PMID- 42947001 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 26 IP - 1 DP - 2026 Jul 31 TI - Comparison of cardiac adverse event signal profiles for GLP-1 receptor agonists: an analysis of the FAERS database. LID - 10.1186/s12872-026-06387-3 [doi] LID - 988 AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes owing to their effectiveness in glycemic control and weight reduction. Given the increasing use of GLP-1RAs, further research is warranted to better understand their cardiac effects. METHODS: Individual Case Safety Reports from the U. S. Food and Drug Administration Adverse Event Reporting System database from July 6, 2007, to February 17, 2026, were evaluated for the post-marketing cardiac adverse events associated with dulaglutide, liraglutide, semaglutide, and tirzepatide. To detect signal differences among drugs, disproportionality analysis was conducted using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) methods, along with standard statistical tests to evaluate categorical variables and to estimate odds ratios. RESULTS: A total of 7,023 cardiac adverse events were identified among 305,877 reports. GLP-1RAs were associated with a higher reporting frequency of tachyarrhythmias than bradyarrhythmias. In the 65-85-year age group, an increase in the signal for cardiac events was observed. Pairwise post hoc comparisons demonstrated no statistically significant differences in reporting frequency of cardiac events between semaglutide and liraglutide, whereas all other drug pairs demonstrated statistically significant differences. CONCLUSION: Semaglutide and liraglutide had higher relative reporting of cardiac events whereas tirzepatide had lower PRR and ROR values against the total background of reports. These findings suggest a lower reporting tendency of cardiac events for tirzepatide. This study may assist healthcare professionals in recognizing the frequency of cardiac events associated with GLP-1RA use and drive new hypotheses to clarify underlying mechanisms. CI - (c) 2026. The Author(s). FAU - Yildirim, Burak Ogulcan AU - Yildirim BO AUID- ORCID: 0000-0003-3448-6187 AD - Department of Cardiology, Aliaga State Hospital, Izmir, Turkiye. FAU - Sarkim, Ibrahim Furkan AU - Sarkim IF AUID- ORCID: 0009-0000-9904-9530 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. isarkim@cumhuriyet.edu.tr. FAU - Yalman, Gizem AU - Yalman G AUID- ORCID: 0009-0005-2098-5331 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Arslantas, Bugra AU - Arslantas B AUID- ORCID: 0009-0001-1229-4670 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Celik, Can Berk AU - Celik CB AUID- ORCID: 0009-0002-6550-3891 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Yildirim, Sahin AU - Yildirim S AUID- ORCID: 0000-0003-1312-7273 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260731 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Incretins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (GLP1R protein, human) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide/adverse effects MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - Databases, Factual MH - United States/epidemiology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology MH - Risk Factors MH - *Liraglutide/adverse effects MH - Risk Assessment MH - Adverse Drug Reaction Reporting Systems MH - *Incretins/adverse effects MH - Product Surveillance, Postmarketing MH - Immunoglobulin Fc Fragments/adverse effects MH - Time Factors MH - *Heart Diseases/chemically induced/epidemiology/diagnosis MH - Treatment Outcome MH - Cardiotoxicity MH - Female MH - Male MH - Recombinant Fusion Proteins PMC - PMC13715166 OTO - NOTNLM OT - Dulaglutide OT - FAERS OT - Glucagon-like peptide-1 receptor agonists OT - Liraglutide OT - Semaglutide OT - Tirzepatide COIS- Declarations. Ethics approval and consent to participate: As this observational study used publicly available anonymized data from the FDA Adverse Event Monitoring System (AEMS) [formerly the FDA Adverse Event Reporting System (FAERS)] database, institutional ethical approval is not required. Competing interests: The authors declare no competing interests. EDAT- 2026/10/28 05:28 MHDA- 2026/10/28 05:29 PMCR- 2026/07/31 CRDT- 2026/10/28 00:34 PHST- 2026/06/22 00:00 [received] PHST- 2026/07/29 00:00 [accepted] PHST- 2026/10/28 05:29 [medline] PHST- 2026/10/28 05:28 [pubmed] PHST- 2026/10/28 00:34 [entrez] PHST- 2026/07/31 00:00 [pmc-release] AID - 10.1186/s12872-026-06387-3 [pii] AID - 6387 [pii] AID - 10.1186/s12872-026-06387-3 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2026 Jul 31;26(1):988. doi: 10.1186/s12872-026-06387-3. PMID- 42946127 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 35 IP - 11 DP - 2026 Nov TI - Semaglutide and Panic Attacks: Active-Comparator Disproportionality Analysis, Temporal Assessment of Notoriety Bias and Evidence Triangulation in Post-Marketing Pharmacovigilance. LID - e70517 [pii] LID - 10.1002/pds.70517 [doi] AB - PURPOSE: To evaluate how confounding by indication and notoriety bias shape the apparent semaglutide-panic attack signal in the FDA Adverse Event Reporting System (FAERS) and to interpret this signal using an evidence-triangulation framework integrating randomized and observational studies. METHODS: We conducted an active-comparator restricted disproportionality analysis of FAERS (2018Q1-2024Q4), including individual case safety reports in which semaglutide, dulaglutide or empagliflozin was the primary suspect drug. Panic attack was identified using the MedDRA preferred term. Crude and adjusted reporting odds ratios (RORs, aRORs) with 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age, sex and indication (Type 2 diabetes, obesity/weight management). Notoriety bias was assessed using prespecified temporal analyses (analyses restricted to reports received before July 1, 2023 and a drug-by-period comparison of 2018-2022 with 2023-2024) and reporting proportions per 10 000 reports. A sensitivity analysis used all other primary-suspect drugs in FAERS as the reference set. In parallel, we conducted a systematic review (MEDLINE, Embase, CENTRAL to November 24, 2025) of randomized trials, cohort and cross-sectional studies, pharmacovigilance analyses and case reports reporting panic attacks or acute anxiety outcomes with semaglutide. RESULTS: Among 33 267 semaglutide, 54 282 dulaglutide and 25 380 empagliflozin reports, panic attacks were recorded in 87 (0.26%), 28 (0.05%) and 13 (0.05%) cases, respectively. Crude RORs were 5.08 (95% CI 3.32-7.78) versus dulaglutide and 5.12 (95% CI 2.86-9.17) versus empagliflozin, attenuating after adjustment to 2.82 (95% CI 1.74-4.56) and 2.75 (95% CI 1.41-5.36). In the pre-warning period crude RORs were 2.24 (95% CI 1.23-4.07) and 2.15 (95% CI 1.00-4.58), attenuating to 1.38 (95% CI 0.69-2.75) and 1.14 (95% CI 0.48-2.68) after adjustment. Panic-attack reports per 10 000 semaglutide reports rose from 6.7 in 2018-2022 to 42.0 in 2023-2024 (drug-by-period interaction p = 0.007). Against all other primary-suspect drugs, the aROR was 1.48 (95% CI 1.18-1.87) overall and 0.76 (95% CI 0.48-1.18) before July 1, 2023. Across 12 studies, randomized trials and active-comparator observational cohorts did not show a consistent increase in panic attacks or anxiety-related outcomes. CONCLUSIONS: Crude FAERS analyses suggested a semaglutide-panic attack signal that attenuated after adjustment was no longer significant before the July 2023 regulatory communication and rose sharply thereafter in a pattern consistent with notoriety bias. Triangulation with randomized trials and active-comparator observational studies does not support a consistent pharmacological association. Disproportionality analyses are hypothesis-generating and cannot estimate incidence or establish causality. This case study illustrates how active-comparator design, temporal assessment of notoriety bias and evidence triangulation can improve the interpretation of post-marketing safety signals. CI - (c) 2026 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Melamed, Ben AU - Melamed B AUID- ORCID: 0009-0000-9065-6801 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Parsi-Zahabi, Mahak AU - Parsi-Zahabi M AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Omrani, Mohammad Ali AU - Omrani MA AUID- ORCID: 0000-0001-6847-0699 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Baskaran, Bala Swetha AU - Baskaran BS AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Eddin, Lujain Ez AU - Eddin LE AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Kermanshahi, Nazgol AU - Kermanshahi N AUID- ORCID: 0009-0002-2776-6084 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Chalabianloo, Niaz AU - Chalabianloo N AUID- ORCID: 0000-0001-7228-4725 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Muanda, Flory Tsobo AU - Muanda FT AUID- ORCID: 0000-0003-4682-6564 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. AD - ICES Western, Kidney, Dialysis & Transplantation Research Program, London, Ontario, Canada. AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. AD - London Health Sciences Centre, Lawson Health Research Institute, London, Ontario, Canada. LA - eng PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucosides) RN - WTT295HSY5 (dulaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/analogs & derivatives MH - Humans MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Pharmacovigilance MH - Female MH - *Hypoglycemic Agents/adverse effects MH - *Panic Disorder/chemically induced/epidemiology MH - United States/epidemiology MH - *Recombinant Fusion Proteins/adverse effects/administration & dosage MH - Glucosides/adverse effects/administration & dosage MH - *Product Surveillance, Postmarketing/statistics & numerical data MH - Male MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - United States Food and Drug Administration/statistics & numerical data MH - Benzhydryl Compounds MH - Immunoglobulin Fc Fragments PMC - PMC13713200 OAB - This study investigated whether the diabetes and weight-loss drug semaglutide (commonly known as Ozempic or Wegovy) increases the risk of panic attacks. Researchers analyzed patient safety data from the FDA Adverse Event Reporting System (FAERS) spanning 2018 through 2024. While the raw numbers initially showed that panic attacks were reported more often with semaglutide than with other medications (like dulaglutide or empagliflozin), this connection weakened significantly once researchers adjusted for patient age, sex and the specific reason for taking the drug. Crucially, the surge in panic attack reports occurred only after mid-2023, coinciding with heightened media attention and regulatory reviews regarding the mental health impacts of GLP-1 drugs. This pattern is consistent with 'notoriety bias', meaning that greater public awareness may have led to more reports rather than the drug itself causing more panic attacks. However, this type of data can neither prove nor rule out a true effect. Furthermore, a review of 12 studies, including pooled clinical trial data and real-world observational studies, found no consistent evidence linking semaglutide to increased panic attacks or anxiety. Overall, the available evidence does not show a consistent link between semaglutide and panic attacks, although an association with panic attacks cannot be excluded. OABL- eng OTO - NOTNLM OT - FAERS OT - GLP-1 receptor agonists OT - confounding by indication OT - notoriety bias OT - panic attack OT - pharmacovigilance OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/10/28 04:34 MHDA- 2026/10/28 04:35 PMCR- 2026/10/27 CRDT- 2026/10/27 20:34 PHST- 2026/10/05 00:00 [revised] PHST- 2026/06/26 00:00 [received] PHST- 2026/10/22 00:00 [accepted] PHST- 2026/10/28 04:35 [medline] PHST- 2026/10/28 04:34 [pubmed] PHST- 2026/10/27 20:34 [entrez] PHST- 2026/10/27 00:00 [pmc-release] AID - e70517 [pii] AID - PDS70517 [pii] AID - 10.1002/pds.70517 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2026 Nov;35(11):e70517. doi: 10.1002/pds.70517. PMID- 42944687 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 10 DP - 2026 Oct 1 TI - GLP-1 RA Prescribing in Patients With Type 2 Diabetes and Cancer. PG - e2640781 LID - 10.1001/jamanetworkopen.2026.40781 [doi] LID - e2640781 AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes, yet little is known about its utilization patterns in patients with cancer history, given limited oncology-specific guidance. OBJECTIVE: To evaluate trends and factors associated with GLP-1 RA use among Medicare beneficiaries with type 2 diabetes, comparing those with and without cancer history. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare linked data to identify patients diagnosed with 7 common cancers in 2010 to 2021 and preexisting type 2 diabetes before cancer diagnosis. A noncancer cohort with type 2 diabetes was identified from a 5% random sample of Medicare beneficiaries and matched 1:1 to patients with cancer based on sociodemographic characteristics; controls were assigned a pseudo-index date corresponding to their matched patient's cancer diagnosis date. Beneficiaries were followed up annually until death or December 31, 2022, for TM or December 31, 2021, for MA. Data were analyzed from December 2025 to July 2026. EXPOSURES: Diagnosis of 1 of 7 common cancers. MAIN OUTCOMES AND MEASURES: Any GLP-1 RA use. Proportions of beneficiaries with any GLP-1 RA use annually were stratified by traditional Medicare (TM) and Medicare Advantage (MA). Multivariable logistic regression examined (1) differences in GLP-1RA use between cancer and noncancer cohorts with and without adjusting for sociodemographic characteristics and comorbidities and diabetes-related complications; (2) cancer-specific factors associated with GLP-1RA use among the cancer cohort after 2018. RESULTS: A total of 373 278 Medicare beneficiaries (mean [SD] age, 76.1 [6.6] years; 188 746 [50.6%] female) with cancer and diabetes and 373 278 noncancer controls (153 358 unique beneficiaries) were included. GLP-1 RA use increased from 85 beneficiaries (0.5%) to 9083 beneficiaries (8.2%) and from 138 beneficiaries (0.9%) to 9300 beneficiaries (6.2%) in the cancer and noncancer cohorts, respectively, from 2010 to 2022 under TM; a similar increase was observed under MA. Despite higher unadjusted GLP-1 RA use among the cancer cohort than the noncancer cohort (probability difference, TM: 1.19 [95% CI, 0.94 to 1.44] percentage points [pp]; P < .001; MA: 0.45 [95% CI, 0.21 to 0.68] pp, P < .001), adjusted analysis showed no significant differences in GLP-1 RA use under TM (adjusted probability difference, 0.16 [95% CI, -0.10 to 0.41,] pp; P = .22) and lower use among cancer cohort under MA (-0.52 [95% CI, -0.76 to -0.28] pp; P < .001). Complications or comorbidities, including obesity (adjusted probability difference, TM: 3.35 [95% CI, 3.10 to 3.61] pp; P < .001; MA: 2.42 [95% CI, 2.19 to 2.64] pp; P < .001), dyslipidemia (adjusted probability difference, TM: 2.26 [95% CI, 2.03 to 2.50] pp; P < .001; MA: 1.80 [95% CI, 1.57 to 2.03] pp; P < .001), neuropathy (adjusted probability difference: TM: 3.91 [95% CI, 3.64 to 4.19] pp; P < .001; MA: 3.17 [95% CI, 2.94 to 3.41] pp; P < .001), retinopathy (adjusted probability difference, TM: 2.02 [95% CI, 1.78 to 2.27] pp; P < .001; MA: 1.84 [95% CI, 1.63 to 2.06] pp; P < .001), and chronic kidney disease (adjusted probability difference, TM: 2.01 [95% CI, 1.76 to 2.26] pp; P < .001; MA: 1.63 [95% CI, 1.40 to 1.85] pp; P < .001) were associated with greater likelihood of GLP-1RA use. Within the cancer cohort, breast (adjusted probability difference, TM: 1.05 [95% CI, 0.43 to 1.66] pp; P = .001; MA: 0.89 [95% CI, 0.37 to 1.41] pp; P = .001), gynecologic (adjusted probability difference, MA: 1.13 [95% CI, 0.45 to 1.81] pp; P = .001), and prostate (adjusted probability difference, TM: 1.30 [95% CI, 0.72 to 1.88] pp; P < .001; MA: 1.07 [95% CI, 0.56 to 1.58] pp; P < .001) cancers were associated with higher GLP-1 RA use than colorectal cancer, while pancreatic cancer was associated with lower GLP-1 RA use (adjusted probability difference, TM: -2.55 [95% CI, -3.17 to -1.93] pp; P < .001; MA: -1.64 [95% CI, -2.23 to -1.05] pp; P < .001). CONCLUSIONS AND RELEVANCE: In this retrospective study of Medicare beneficiaries with type 2 diabetes, GLP-1 RA use increased substantially and primarily was associated with metabolic risk profile, with limited associations with cancer status. Variation across cancer types and stages suggests oncologic context may influence prescribing. FAU - Hu, Xin AU - Hu X AD - Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia. AD - Winship Cancer Institute, Emory University, Atlanta, Georgia. AD - Department of Health Policy and Management, Emory University Rollins School of Public Health, Atlanta, Georgia. FAU - Jiang, Changchuan AU - Jiang C AD - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas. FAU - Han, Xuesong AU - Han X AD - American Cancer Society, Atlanta, Georgia. FAU - Zhang, Lu AU - Zhang L AD - Department of Public Health Sciences, Clemson University, Clemson, South Carolina. FAU - Li, Piaopiao AU - Li P AD - Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia. AD - Emory Global Diabetes Research Center of the Woodruff Health Sciences Center and Emory University, Atlanta, Georgia. FAU - Pasquel, Francisco J AU - Pasquel FJ AD - Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia. AD - Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Meisel, Jane L AU - Meisel JL AD - Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia. FAU - Vo, Jacqueline B AU - Vo JB AD - Winship Cancer Institute, Emory University, Atlanta, Georgia. AD - Emory University Nell Hodgson Woodruff School of Nursing, Atlanta, Georgia. FAU - Varghese, Jithin Sam AU - Varghese JS AD - Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia. FAU - Shao, Hui AU - Shao H AD - Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia. FAU - Graetz, Ilana AU - Graetz I AD - Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia. AD - Winship Cancer Institute, Emory University, Atlanta, Georgia. AD - Department of Health Policy and Management, Emory University Rollins School of Public Health, Atlanta, Georgia. LA - eng PT - Journal Article DEP - 20261001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Female MH - Male MH - United States MH - Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/complications/epidemiology/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - SEER Program MH - Aged, 80 and over MH - Medicare/statistics & numerical data MH - Cohort Studies PMC - PMC13714661 COIS- Conflict of Interest Disclosures: Dr Hu reported receiving grants from National Institute of Health, American Cancer Society, Patrick and Catherine Weldon Donaghue Medical Research Foundation, Pfizer, Johnson & Johnson, PhRMA Foundation, and St Jude Children's Research Hospital outside the submitted work. Dr Jiang reported receiving grants from the American Cancer Society and American Society of Clinical Oncology Conquer Cancer Foundation and personal fees from Johnson & Johnson outside the submitted work. Dr Zhang reported receiving grants from the American Cancer Society outside the submitted work. Dr Pasquel reported receiving grants from Insulet, Dexcom, Tandem Diabetes Care, Ideal Medical Technologies, and Novo Nordisk and personal fees from Insulet Consulting (paid to institution) outside the submitted work. Dr Meisel reported research funding and personal fees from AstraZeneca, Pfizer, Sermonix, and Olema and personal fees from Daiichi Sankyo, Novartis, and Eli Lilly outside the submitted work. Dr Graetz reported receiving grants from Pfizer, National Cancer Institute, and Patrick and Catherine Weldon Donaghue Medical Research Foundation outside the submitted work. No other disclosures were reported. EDAT- 2026/10/27 17:30 MHDA- 2026/10/27 17:31 PMCR- 2026/10/27 CRDT- 2026/10/27 11:33 PHST- 2026/10/27 17:31 [medline] PHST- 2026/10/27 17:30 [pubmed] PHST- 2026/10/27 11:33 [entrez] PHST- 2026/10/27 00:00 [pmc-release] AID - 2855863 [pii] AID - zoi261102 [pii] AID - 10.1001/jamanetworkopen.2026.40781 [doi] PST - epublish SO - JAMA Netw Open. 2026 Oct 1;9(10):e2640781. doi: 10.1001/jamanetworkopen.2026.40781. PMID- 42944684 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 10 DP - 2026 Oct 1 TI - Prescribing SGLTis and GLP-1 RAs for Patients With Type 2 Diabetes, Guideline Updates, and Longitudinal Knowledge Assessment Scores. PG - e2640858 LID - 10.1001/jamanetworkopen.2026.40858 [doi] LID - e2640858 AB - IMPORTANCE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular and kidney events in patients with type 2 diabetes (T2D) who have established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, yet prescribing to these patients remains low. OBJECTIVES: To describe temporal patterns in SGLT2i and GLP-1 RA prescribing before and after the 2019 American Diabetes Association (ADA) guideline update and to assess whether these patterns differed across physicians with subsequently measured different first-year American Board of Internal Medicine Longitudinal Knowledge Assessment (LKA) scores. DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study was conducted from October 2025 through January 2026, using 2017 to 2022 traditional Medicare claims. Endocrinologists first participating in the 2022 to 2023 LKA and the Medicare beneficiaries with T2D they treated were included. EXPOSURE: Time relative to the 2019 ADA guideline update. MAIN OUTCOMES AND MEASURES: The annual patient-year SGLT2i and GLP-1RA guideline-targeted and nontargeted patient fill rates were the main outcome. Linear physician, year, and target subgroup fixed-effects regression models were estimated, with patient demographic and health risk controls to evaluate within-physician associations between guideline-targeted vs nontargeted patient-year fill rates each year relative to 2018 (the year before the guideline update). The variation in these associations across first-year LKA score quartiles was also evaluated. RESULTS: A total of 1061 endocrinologists caring for 177 284 Medicare beneficiaries with T2D (mean [SD] age, 74.5 [6.1] years; mean [SD] 54.4% [49.8] female; mean [SD] 9.3% [29.1] Black, 6.6% [24.9] Hispanic, and 76.2% [42.6] White non-Hispanic) were included. Adjusted guideline-targeted SGLT2i and GLP-1 RA fill rates increased monotonically from 2018 to 2022 by 11.4 percentage points (pp) (95% CI, 10.5 to 12.3 pp; P < .001) and 2.4 (95% CI, 1.4 to 3.3 pp; P < .001) for SGLT2is and GLP-1 RAs targeted vs nontargeted subgroups, respectively. The associated SGLT2i increase was 3.9 pp (95% CI, 1.4 to 6.5 pp) larger for patients of endocrinologists with top vs bottom LKA quartile scores (P = .003), but for GLP-1 RAs, this association was not statistically significant with wide confidence intervals. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, 2019 ADA guideline update timing was associated with substantially increased SGLT2i and moderately increased GLP-1 RA guideline-concordant prescribing among guideline-targeted, compared with nontargeted, patient subgroups by 2020. These increases in SGLT2i guideline congruent prescribing were associated with higher subsequently measured first-year LKA scores. FAU - Gray, Bradley M AU - Gray BM AD - American Board of Internal Medicine, Philadelphia, Pennsylvania. FAU - Vandergrift, Jonathan AU - Vandergrift J AD - American Board of Internal Medicine, Philadelphia, Pennsylvania. FAU - Landon, Bruce E AU - Landon BE AD - Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts. AD - Division of General Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - McCoy, Rozalina AU - McCoy R AD - Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore. AD - University of Maryland Institute for Health Computing, North Bethesda. LA - eng PT - Journal Article DEP - 20261001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Cross-Sectional Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States MH - Male MH - Practice Guidelines as Topic MH - Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13714658 COIS- Conflict of Interest Disclosures: Dr Gray and Mr Vandergrift reported being paid employees of the American Board of Internal Medicine (ABIM) during the conduct of the study. Dr Landon reported receiving personal fees from ABIM during the conduct of the study. Dr McCoy reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the Patient-Centered Outcomes Research Institute, the American Diabetes Association, the National Cancer Institute, and the Department of Defense; receiving personal fees from American Diabetes Association for speaking honoraria and travel support; and receiving personal fees from NCQA and the Yale-New Haven Health System's Center for Outcome Research outside the submitted work. EDAT- 2026/10/27 17:30 MHDA- 2026/10/27 17:31 PMCR- 2026/10/27 CRDT- 2026/10/27 11:33 PHST- 2026/10/27 17:31 [medline] PHST- 2026/10/27 17:30 [pubmed] PHST- 2026/10/27 11:33 [entrez] PHST- 2026/10/27 00:00 [pmc-release] AID - 2855860 [pii] AID - zoi261106 [pii] AID - 10.1001/jamanetworkopen.2026.40858 [doi] PST - epublish SO - JAMA Netw Open. 2026 Oct 1;9(10):e2640858. doi: 10.1001/jamanetworkopen.2026.40858. PMID- 42942883 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261028 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 20 DP - 2026 Oct 9 TI - Impact of GLP-1 Receptor Agonists on Cognitive Performance in Adults at Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. LID - 10.3390/nu18203312 [doi] LID - 3312 AB - Background/Objectives: Type 2 diabetes, a widely recognized risk factor of Alzheimer's disease (AD), is mainly due to the role played by insulin resistance on neuronal degeneration. Mild Cognitive Impairment (MCI) also significantly increases the risk of developing AD by approximately 40%. Epidemiological studies have demonstrated correlations between glucagon-like peptide-1 agonists (GLP-1RAs) on reducing the risk of AD. We synthesize current data from randomized controlled trials (RCTs) to summarize the effects of GLP-1RA treatment in adults with Type 2 diabetes or with MCI on cognitive performance. Methods: We searched databases from inception to 1 January 2026 investigating effects of GLP-1RA(s) on cognition. PubMed, Web of Science and Scopus databases were explored following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We selected only RCTs in adults investigating GLP-1RA(s) on cognitive performance. Results: Overall mean age was 64.5 yrs with an average follow-up period of 28.4 months. A total of 13,711 participants from five RCTs were included. Following a source-data audit, four randomized controlled trials contributed analytically compatible data to at least one cognitive domain. Cognitive domains were analyzed separately using Hedges' g. Random-effects models used restricted maximum likelihood (REML) estimation with Knapp-Hartung inference when at least two compatible studies contributed. For global cognition, three studies yielded g = 0.014 (95% CI: -0.061 to 0.088; p = 0.515; I(2) = 0%). For attention, two studies yielded g = 0.072 (95% CI: -2.164 to 2.308; p = 0.753; I(2) = 31.1%). For delayed memory, executive function, and verbal function, only one compatible study was available per domain; these were therefore reported as single-study estimates rather than pooled effects. A sensitivity analysis excluding the dominant Cukierman trial yielded an imprecise and non-significant effect estimate for global cognition (g = -0.205, 95% CI: -2.678 to 2.269) indicating that the robustness of the pooled result could not be established. Conclusions: Current randomized evidence is insufficient to establish a consistent beneficial effect of GLP-1RA(s) on cognitive function in adults at risk of AD. The available findings should be considered exploratory and hypothesis-generating because few analytically compatible trials were available within each cognitive domain. FAU - Abbatecola, Angela M AU - Abbatecola AM AUID- ORCID: 0000-0001-5522-9257 AD - Department of Life Sciences, Health, and Health Professions, Link Campus University, Via del Casale Pio V, 00165 Rome, Italy. FAU - Migliara, Giuseppe AU - Migliara G AUID- ORCID: 0000-0002-4573-6025 AD - Department of Life Sciences, Health, and Health Professions, Link Campus University, Via del Casale Pio V, 00165 Rome, Italy. FAU - D'Agostino, Fausto AU - D'Agostino F AD - Department of Anaesthesia, Intensive Care and Pain Management, Campus Bio Medico University and Teaching Hospital, 00128 Rome, Italy. FAU - Veronese, Nicola AU - Veronese N AUID- ORCID: 0000-0002-9328-289X AD - Faculty of Medicine, Saint Camillus International University of Health Sciences, 00131 Rome, Italy. FAU - Giuliani, Angelica AU - Giuliani A AUID- ORCID: 0000-0002-8477-8519 AD - Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy. AD - Department of Clinical and Molecular Sciences, Universita Politecnica delle Marche, 60100 Ancona, Italy. FAU - Caponnetto, Salvatore AU - Caponnetto S AUID- ORCID: 0000-0003-2906-449X AD - Department of Life Sciences, Health, and Health Professions, Link Campus University, Via del Casale Pio V, 00165 Rome, Italy. FAU - Corbi, Graziamaria AU - Corbi G AUID- ORCID: 0000-0002-3441-889X AD - Department of Medical and Translational Medicine, University of Naples "Federico II", 80131 Naples, Italy. FAU - Signoriello, Elisabetta AU - Signoriello E AUID- ORCID: 0000-0001-5753-6752 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. FAU - Incalzi, Raffaele Antonelli AU - Incalzi RA AD - Research Unit of Geriatrics, Universita Campus Bio-Medico di Rome, 00128 Rome, Italy. AD - Operative Research Unit of Internal Medicine, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy. FAU - Paolisso, Giuseppe AU - Paolisso G AUID- ORCID: 0000-0002-2137-455X AD - Faculty of Medicine, Saint Camillus International University of Health Sciences, 00131 Rome, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20261009 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Alzheimer Disease/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Cognition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cognitive Dysfunction/drug therapy MH - Middle Aged MH - Aged MH - Risk Factors MH - Cognitive Enhancement MH - Female MH - Male PMC - PMC13708722 OTO - NOTNLM OT - RCTs OT - T2DM OT - glucagon-like peptide-1 agonists OT - memory OT - mild cognitive impairment OT - nutrition COIS- The authors declare no conflicts of interest. EDAT- 2026/10/27 11:32 MHDA- 2026/10/27 22:05 PMCR- 2026/10/09 CRDT- 2026/10/27 10:43 PHST- 2026/08/17 00:00 [received] PHST- 2026/10/02 00:00 [revised] PHST- 2026/10/05 00:00 [accepted] PHST- 2026/10/27 22:05 [medline] PHST- 2026/10/27 11:32 [pubmed] PHST- 2026/10/27 10:43 [entrez] PHST- 2026/10/09 00:00 [pmc-release] AID - nu18203312 [pii] AID - nutrients-18-03312 [pii] AID - 10.3390/nu18203312 [doi] PST - epublish SO - Nutrients. 2026 Oct 9;18(20):3312. doi: 10.3390/nu18203312. PMID- 42942021 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261028 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 20 DP - 2026 Oct 18 TI - GLP-1 Receptor Agonist Therapy in Patients with Cancer: A Review of Clinical Outcomes. LID - 10.3390/ijms27209251 [doi] LID - 9251 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the management of obesity and type 2 diabetes, including among patients with cancer. Although previous research has mainly focused on cancer incidence, their associations with clinical outcomes after cancer diagnosis remain less well characterized. Therefore, the present study aimed to evaluate the oncologic and survival outcomes associated with GLP-1 RA use in adults with an established malignancy. We performed a systematic review of comparative studies evaluating GLP-1 RA use in patients with a confirmed cancer diagnosis. PubMed, Scopus and Web of Science were searched for English-language publications from 1 January 2016 to 8 August 2026. Twenty-six retrospective cohort studies were included in the qualitative synthesis. Thirteen studies included selective GLP-1 RAs and tirzepatide within the same exposure group. Study quality was assessed using the Newcastle-Ottawa Scale. Twenty-five studies evaluated overall survival and/or all-cause mortality, while nine assessed cancer recurrence, progression, or related outcomes. Survival and mortality outcomes more often favored the exposed group (especially compared with nonuse) than not, but findings were less consistent in active-comparator analyses. Evidence for recurrence and progression was sparse and heterogeneous, and no clear signal of increased risk was observed. Because all of these were observational studies with substantial differences in populations, comparators, exposure definitions, and duration of follow-up, the survival associations do not imply causality or direct antitumor effects of GLP-1 RAs. Clinically, the preponderance of evidence does not support the use of GLP-1 RAs as cancer-directed therapy, and their use in patients with cancer should be guided by established indications such as obesity and type 2 diabetes. Potential explanations include effects on glycemic and cardiovascular risk factors, treatment selection, residual confounding, or combinations thereof. Prospective studies and randomized controlled trials with cancer-specific outcomes and longer follow-up are needed to further evaluate these associations. FAU - Andronescu, Alexandra Catalina AU - Andronescu AC AUID- ORCID: 0009-0007-9364-3804 AD - 2nd Department, Faculty of Nursing and Health Sciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania. FAU - Ciumarnean, Lorena AU - Ciumarnean L AUID- ORCID: 0000-0002-8491-8817 AD - 2nd Department, Faculty of Nursing and Health Sciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania. FAU - Orasan, Olga Hilda AU - Orasan OH AUID- ORCID: 0000-0003-4435-142X AD - Department of Internal Medicine, 4th Medical Discipline, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania. FAU - Cozma, Angela AU - Cozma A AD - Department of Internal Medicine, 4th Medical Discipline, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania. FAU - Leah, Nicoleta Valentina AU - Leah NV AD - 2nd Department, Faculty of Nursing and Health Sciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania. FAU - Lucaciu, Roxana Liana AU - Lucaciu RL AUID- ORCID: 0000-0003-4920-4760 AD - Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania. FAU - Hangan, Adriana Corina AU - Hangan AC AUID- ORCID: 0000-0002-0944-3161 AD - Department of Inorganic Chemistry, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania. FAU - Procopciuc, Lucia Maria AU - Procopciuc LM AUID- ORCID: 0000-0002-4738-5775 AD - Department of Medical Biochemistry, Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania. LA - eng PT - Journal Article PT - Review PT - Systematic Review DEP - 20261018 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/drug therapy/mortality MH - Tirzepatide MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Hypoglycemic Agents/therapeutic use PMC - PMC13705413 OTO - NOTNLM OT - cancer OT - disease progression OT - glucagon-like peptide-1 receptor agonist OT - mortality OT - overall survival OT - recurrence COIS- The authors declare no conflicts of interest. EDAT- 2026/10/27 11:32 MHDA- 2026/10/27 22:05 PMCR- 2026/10/18 CRDT- 2026/10/27 10:41 PHST- 2026/09/14 00:00 [received] PHST- 2026/10/10 00:00 [revised] PHST- 2026/10/15 00:00 [accepted] PHST- 2026/10/27 22:05 [medline] PHST- 2026/10/27 11:32 [pubmed] PHST- 2026/10/27 10:41 [entrez] PHST- 2026/10/18 00:00 [pmc-release] AID - ijms27209251 [pii] AID - ijms-27-09251 [pii] AID - 10.3390/ijms27209251 [doi] PST - epublish SO - Int J Mol Sci. 2026 Oct 18;27(20):9251. doi: 10.3390/ijms27209251. PMID- 42941904 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261028 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 20 DP - 2026 Oct 15 TI - Association of Glucagon-like Peptide-1 Receptor Agonists Versus Dipeptidyl Peptidase-4 Inhibitors with Tuberculosis and Mortality in Adults with Diabetes. LID - 10.3390/ijms27209137 [doi] LID - 9137 AB - Diabetes is associated with an increased risk of tuberculosis (TB), but whether the class of glucose-lowering therapy is associated with TB outcomes remains uncertain. We conducted a retrospective observational cohort study to examine the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use versus dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of TB and mortality. We used de-identified records from the TriNetX Global Collaborative Network. Adults with diabetes who had a qualifying record for either a GLP-1 RA or a DPP-4i between 2016 and 2024 were eligible. Cohort entry was defined as the first qualifying drug-class record during this period. Patients with prior-year use of the comparator drug class, a history of TB, or death before cohort entry were excluded. Propensity score matching was performed at a 1:1 ratio. Outcomes assessed during days 1-365 included TB (ICD-10-CM A15-A19), the platform-defined death outcome, and a composite outcome of gastrointestinal and hepatobiliary diagnoses. After matching, 466,903 patients remained in each group. GLP-1 RA exposure was associated with fewer recorded TB events, deaths, and gastrointestinal/hepatobiliary events than DPP-4i exposure during the first year after cohort entry. TB was recorded in 155 GLP-1 RA users and 320 DPP-4i users (HR, 0.472; 95% CI, 0.390-0.572). The corresponding numbers for the platform-defined death outcome were 7575 and 14,572 (HR, 0.505; 95% CI, 0.492-0.520), and those for gastrointestinal/hepatobiliary diagnoses were 15,914 and 20,559 (HR, 0.750; 95% CI, 0.735-0.766). The analysis restricted to patients with type 2 diabetes (ICD-10-CM E11) yielded a similar association for TB. Residual imbalance in body mass index (BMI) and residual confounding, including confounding by indication, limit a causal interpretation. FAU - Hsu, Chun-Hsiang AU - Hsu CH AUID- ORCID: 0009-0007-1571-737X AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. AD - Doctoral Program of Clinical and Experimental Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan. FAU - Chang, Renin AU - Chang R AUID- ORCID: 0000-0003-1016-2233 AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. FAU - Chen, Chiu-Fan AU - Chen CF AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. FAU - Chu, Kuo-An AU - Chu KA AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan. FAU - Jiang, You-Cheng AU - Jiang YC AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. FAU - Hong, Wei-Cheng AU - Hong WC AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. FAU - Chen, I-Yuan AU - Chen IY AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. FAU - Lin, Min-Hsi AU - Lin MH AD - Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. AD - Cancer Center, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan. LA - eng GR - KSVGH115-D02-1; KSC114-070/Kaohsiung Veterans General Hospital/ PT - Journal Article PT - Observational Study DEP - 20261015 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Retrospective Studies MH - *Tuberculosis/complications/epidemiology/prevention & control PMC - PMC13705376 OTO - NOTNLM OT - DPP-4 inhibitor OT - GLP-1 receptor agonist OT - diabetes OT - mortality OT - retrospective cohort OT - tuberculosis COIS- The authors declare no conflicts of interest. EDAT- 2026/10/27 11:32 MHDA- 2026/10/27 22:05 PMCR- 2026/10/15 CRDT- 2026/10/27 10:40 PHST- 2026/09/05 00:00 [received] PHST- 2026/09/30 00:00 [revised] PHST- 2026/10/10 00:00 [accepted] PHST- 2026/10/27 22:05 [medline] PHST- 2026/10/27 11:32 [pubmed] PHST- 2026/10/27 10:40 [entrez] PHST- 2026/10/15 00:00 [pmc-release] AID - ijms27209137 [pii] AID - ijms-27-09137 [pii] AID - 10.3390/ijms27209137 [doi] PST - epublish SO - Int J Mol Sci. 2026 Oct 15;27(20):9137. doi: 10.3390/ijms27209137. PMID- 42937793 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261028 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 43 DP - 2026 Oct 23 TI - Efficacy and safety of GLP-1 receptor agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH): A systematic review and meta-analysis. PG - e51306 LID - 10.1097/MD.0000000000051306 [doi] LID - e51306 AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are increasingly prevalent liver diseases closely linked to obesity, type 2 diabetes mellitus, and cardiometabolic risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve hepatic and metabolic outcomes through weight reduction, improved glycemic control, and reductions in hepatic steatosis. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of GLP-1 RAs in adults with MASLD or MASH. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched for English-language studies published between January 2019 and December 2025. Eligible studies included adults with MASLD or MASH treated with GLP-1 RAs and reporting hepatic, metabolic, or safety outcomes. Pooled estimates were calculated using random-effects models. RESULTS: Nine studies involving 795 participants were included. GLP-1 RA therapy was associated with significant reductions in liver fat content (mean difference [MD]: -3.17; 95% CI: -4.06 to -2.29), body weight (MD: -4.68; 95% CI: -6.88 to -2.47), alanine aminotransferase (MD: -15.17; 95% CI: -21.29 to -9.05), aspartate aminotransferase (MD: -9.89; 95% CI: -13.65 to -6.13), and HbA1c (MD: -0.78; 95% CI: -1.07 to -0.49). Adverse events were more frequent with GLP-1 RAs, particularly nausea and vomiting, while serious adverse events did not differ significantly between groups. CONCLUSION: GLP-1 RAs are associated with meaningful improvements in hepatic steatosis, liver enzymes, body weight, and glycemic control in patients with MASLD or MASH. These findings support their potential role, particularly in patients with coexisting obesity or type 2 diabetes. However, further long-term, adequately powered trials are needed to clarify their effects on fibrosis regression, histological outcomes, and liver-related clinical events. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, LLC. FAU - Alfawaz, Mohammed AU - Alfawaz M AD - Department of Internal Medicine, Gastroenterology Consultant, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Bajamaan, Dareen AU - Bajamaan D AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alghamdi, Lama AU - Alghamdi L AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alorfi, Yara AU - Alorfi Y AUID- ORCID: 0009-0000-9755-1121 AD - Internal Medicine Resident, Department of Internal Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. FAU - Khared, Saud AU - Khared S AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Ameen, Nada AU - Ameen N AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alamri, Rahaf AU - Alamri R AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Abuladel, Mohammed AU - Abuladel M AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alshehri, Rayan AU - Alshehri R AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Altowairqi, Shaima AU - Altowairqi S AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Fatty Liver/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Metabolic Diseases/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Semaglutide MH - Treatment Outcome PMC - PMC13706190 OTO - NOTNLM OT - GLP-1 receptor agonists OT - liraglutide OT - liver fat OT - meta-analysis OT - metabolic dysfunction-associated steatohepatitis OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide COIS- The authors have no funding and conflicts of interest to declare. EDAT- 2026/10/27 11:31 MHDA- 2026/10/27 11:32 PMCR- 2026/10/23 CRDT- 2026/10/27 10:26 PHST- 2026/07/06 00:00 [received] PHST- 2026/10/09 00:00 [accepted] PHST- 2026/10/27 11:32 [medline] PHST- 2026/10/27 11:31 [pubmed] PHST- 2026/10/27 10:26 [entrez] PHST- 2026/10/23 00:00 [pmc-release] AID - 00005792-202610230-00087 [pii] AID - MD-D-26-10416 [pii] AID - 10.1097/MD.0000000000051306 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 Oct 23;105(43):e51306. doi: 10.1097/MD.0000000000051306. PMID- 42918905 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261027 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 82 IP - 11 DP - 2026 Oct 23 TI - GLP-1-based therapies in cardiovascular disease: outcomes, mechanisms, and emerging clinical applications. LID - 276 [pii] LID - 10.1007/s00228-026-04199-0 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits beyond their established role in treating type 2 diabetes mellitus (T2DM). This review evaluates recent clinical evidence, potential mechanisms, and the expanding use of GLP-1-based therapies in cardiovascular disease. METHODS: We reviewed major randomized clinical trials assessing cardiovascular, kidney, and heart failure outcomes, along with related mechanistic studies and clinical guidelines published through July 2026. RESULTS: Early trials, including LEADER, SUSTAIN-6, and REWIND, reported 12%-26% reductions in major adverse cardiovascular events (MACE) in patients with T2DM. More recent trials have extended these findings to other populations. SELECT showed a 20% reduction in MACE among individuals with obesity and established cardiovascular disease but without diabetes, while FLOW demonstrated a 24% reduction in its primary kidney composite outcome. SOUL reported a 14% reduction in MACE with oral semaglutide, and SUMMIT showed a 38% reduction in cardiovascular death or worsening heart failure with tirzepatide. SURPASS-CVOT found tirzepatide to be noninferior, but not superior, to dulaglutide for MACE. These benefits likely involve several mechanisms beyond glucose lowering and weight loss, although gastrointestinal adverse effects still remain a concern. CONCLUSIONS: Growing clinical evidence supports the use of GLP-1-based therapies beyond diabetes management, particularly in patients with cardiovascular disease, chronic kidney disease, or obesity-related heart failure. Further studies will be needed to understand their mechanisms better, long-term safety, and optimal use in clinical practice. CI - (c) 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Jang, Rachelle AU - Jang R AD - Crescenta Valley High School, La Crescenta, CA, USA. FAU - Jang, Michelle AU - Jang M AD - Crescenta Valley High School, La Crescenta, CA, USA. FAU - Ruan, Xinyuan AU - Ruan X AD - Tarbut V'Torah Community Day School, Irvine, CA, USA. FAU - Jin, Caden AU - Jin C AD - San Marino High School, San Marino, CA, USA. FAU - Kim, Woo AU - Kim W AD - Tufts Medical Center, Boston, MA, 02115, USA. wookim3263@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20261023 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Glucagon-Like Peptide 1 MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse cardiovascular events OT - Obesity OT - Type 2 diabetes mellitus COIS- Declarations. Human ethics and consent to participate declarations: Not Applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/10/23 23:32 MHDA- 2026/10/23 23:33 CRDT- 2026/10/23 20:31 PHST- 2026/06/05 00:00 [received] PHST- 2026/10/10 00:00 [accepted] PHST- 2026/10/23 23:33 [medline] PHST- 2026/10/23 23:32 [pubmed] PHST- 2026/10/23 20:31 [entrez] AID - 10.1007/s00228-026-04199-0 [pii] AID - 10.1007/s00228-026-04199-0 [doi] PST - epublish SO - Eur J Clin Pharmacol. 2026 Oct 23;82(11):276. doi: 10.1007/s00228-026-04199-0. PMID- 42916694 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261026 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 69 IP - 18 DP - 2026 Sep 24 TI - Oral Small-Molecule GLP-1 Receptor Agonists: Lessons from Clinical Candidates and a Blueprint for Next-Generation Design. PG - 21101-21118 LID - 10.1021/acs.jmedchem.6c00175 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the treatment of type 2 diabetes (T2D) and obesity, yet all approved therapies to date are peptidic, limiting dosing convenience and patient acceptance. The recent clinical advancement of oral, nonpeptidic GLP-1 RAs, including danuglipron, lotiglipron, DA-302168S, and orforglipron, the first approved oral small-molecule GLP-1 RA, demonstrates that the peptide-only barrier can be overcome. Here, we examine these first-generation oral candidates as case studies, highlighting how each achieved novel solutions while revealing remaining design challenges. Building on these insights, we outline next-generation strategies, including peptidomimetic design, design of multi-target agonists, and harnessing of orthosteric and allosteric cooperativity. We also discuss practical considerations for screening cascades, selection of preclinical species and models, formulation optimization and prospective safety assessment. Collectively, these insights provide a conceptual framework for the rational design of oral small-molecule GLP-1RAs, with broader implications for developing therapies challenging G protein-coupled receptor (GPCR) targets. CI - (c) 2026 American Chemical Society. FAU - Hu, Jinrong AU - Hu J AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Zhang, Yunfei AU - Zhang Y AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Wang, Mengzhou AU - Wang M AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Zhang, Boxin AU - Zhang B AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Zhang, Bingxing AU - Zhang B AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Ke, Changhua AU - Ke C AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Tang, Chao AU - Tang C AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Xia, Juan AU - Xia J AD - Zhanjiang Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang524045, PR China. AD - Xixian New Area Fenghou Original Pharmaceutical Technology Co., Ltd., Xi'an712000, PR China. FAU - Zhao, Qianqian AU - Zhao Q AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. FAU - Gao, Hong AU - Gao H AD - Shaanxi Pioneer Biotech Co., Ltd., Xi'an710021, PR China. FAU - Tian, Lei AU - Tian L AUID- ORCID: 0000-0002-9051-9468 AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. AD - Xixian New Area Fenghou Original Pharmaceutical Technology Co., Ltd., Xi'an712000, PR China. FAU - Liang, Chengyuan AU - Liang C AUID- ORCID: 0000-0001-7360-8998 AD - School of Biological and Pharmaceutical Sciences, Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an710021, PR China. AD - Xixian New Area Fenghou Original Pharmaceutical Technology Co., Ltd., Xi'an712000, PR China. LA - eng GR - 25JC006/Education Department of Shaanxi Province/ GR - 25JC015/Education Department of Shaanxi Province/ GR - 25JC019/Education Department of Shaanxi Province/ GR - 25JC022/Education Department of Shaanxi Province/ GR - 25JR042/Education Department of Shaanxi Province/ GR - 2024JH-XTHG-0020/Xi'an Science and Technology Bureau/ GR - 2024JH-ZCLGG-0017/Xi'an Science and Technology Bureau/ GR - 2024JH-ZCLGG-0018/Xi'an Science and Technology Bureau/ GR - 2025JH-KXGC-0012/Xi'an Science and Technology Bureau/ GR - 2025JH-ZDLJQ-0013/Xi'an Science and Technology Bureau/ GR - 2024CY-JJQ-52/Shaanxi Provincial Science and Technology Department/ GR - 2024CY-JJQ-73/Shaanxi Provincial Science and Technology Department/ GR - 2024PT-ZCK-20/Shaanxi Provincial Science and Technology Department/ GR - 2024SF-GJHX-12/Shaanxi Provincial Science and Technology Department/ GR - 2025QCY-KXJ-102/Shaanxi Provincial Science and Technology Department/ GR - 2025QCY-KXJ-107/Shaanxi Provincial Science and Technology Department/ GR - 2025QY-GJHX-48/Shaanxi Provincial Science and Technology Department/ GR - S2024-YF-ZDCXL-ZDLSF-0008/Shaanxi Provincial Science and Technology Department/ GR - 2025BSHSDZZ335/Shaanxi Province Postdoctoral Science Foundation/ GR - 82373843/National Natural Science Foundation of China/ GR - 82404584/National Natural Science Foundation of China/ GR - 2024JH-ZDSYJX-0018/Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science and Technology/ GR - 2022-SLRH-YQ-009/Shaanxi Administration of Traditional Chinese Medicine/ GR - 2025-CXTD-07/Shaanxi Administration of Traditional Chinese Medicine/ GR - 2025-ZY-004/Shaanxi Administration of Traditional Chinese Medicine/ GR - 2025KJG-02/Sanyuan County Science and Technology Bureau/ GR - Research Center for the Development of Therapeutic Drugs for Serious Infectious Diseases in Shaanxi Province's Universities and Colleges/ GR - Xi'an International Science and Technology Cooperation Base for Anti-Infective Drug Research and Development/ GR - Xi'an Engineering Research Center for Development and Application of New Veterinary and Poultry Antibiotics/ GR - L2024-CXNL-KJRCTD-KJTD-0012/Xianyang Science and Technology Project/ GR - L2025-ZDKJ-ZDGG-ZYRGZN-004/Xianyang Science and Technology Project/ PT - Journal Article PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptidomimetics) RN - 0 (Small Molecule Libraries) SB - IM MH - Animals MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Design MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/chemistry/administration & dosage/pharmacology MH - Peptidomimetics/chemistry/pharmacology MH - *Small Molecule Libraries/chemistry/pharmacology/administration & dosage OTO - NOTNLM OT - GLP-1R OT - allosteric modulation OT - oral small-molecule agonists OT - orforglipron OT - peptidomimetic design EDAT- 2026/10/23 23:31 MHDA- 2026/10/24 05:35 CRDT- 2026/10/23 19:17 PHST- 2026/01/17 00:00 [received] PHST- 2026/07/03 00:00 [revised] PHST- 2026/08/21 00:00 [accepted] PHST- 2026/10/24 05:35 [medline] PHST- 2026/10/23 23:31 [pubmed] PHST- 2026/10/23 19:17 [entrez] AID - 5428688 [pii] AID - 10.1021/acs.jmedchem.6c00175 [doi] PST - ppublish SO - J Med Chem. 2026 Sep 24;69(18):21101-21118. doi: 10.1021/acs.jmedchem.6c00175. PMID- 42910111 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261024 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 23 IP - 11 DP - 2026 TI - Association of GLP-1 Receptor Agonist Use with Thyroid Outcomes in Adults with Type 2 Diabetes. PG - 3494-3505 LID - 10.7150/ijms.141099 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to treat type 2 diabetes mellitus, but their associations with thyroid disorders remain uncertain. We evaluated whether initiating a GLP-1 RA, compared with initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with newly recorded autoimmune thyroiditis and other thyroid outcomes. METHODS: This new-user, active-comparator cohort study emulated a target trial using the TriNetX Collaborative Network. Adults with type 2 diabetes who initiated a GLP-1 RA or DPP-4i between January 1, 2018, and December 31, 2022, and had no prior use of either drug class were eligible. Patients with pre-existing thyroid disease, any neoplasm, immunosuppressant or immunostimulant use, transplantation, or end-stage kidney disease or dialysis were excluded. Propensity score matching yielded 107,912 patients per group. The primary outcome was newly recorded autoimmune thyroiditis; secondary outcomes were nontoxic uninodular goiter, nontoxic multinodular goiter, and thyroid malignancy. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with false discovery rate adjustment. Follow-up extended from 1 day after treatment initiation to 4 years. RESULTS: Autoimmune thyroiditis occurred in 524 GLP-1 RA users (0.49%) and 417 DPP-4i users (0.39%). GLP-1 RA initiation was associated with a higher risk of autoimmune thyroiditis (HR, 1.26; 95% CI, 1.11-1.43; FDR-adjusted P = 0.002). Modestly higher risks were also observed for nontoxic uninodular goiter (HR, 1.07; 95% CI, 1.01-1.13) and nontoxic multinodular goiter (HR, 1.11; 95% CI, 1.03-1.19). The risk of thyroid malignancy did not differ significantly (HR, 0.93; 95% CI, 0.77-1.12). Findings were generally consistent across sensitivity and subgroup analyses, although heterogeneity was observed across body mass index strata. CONCLUSION: Among adults with type 2 diabetes, GLP-1 RA initiation was associated with small increases in newly recorded autoimmune thyroiditis and benign nodular thyroid disease, but not with thyroid malignancy. Given the small absolute differences and the potential for residual confounding and surveillance bias, these findings require validation in future studies. CI - (c) The author(s). FAU - Hsiao, Ching-Chung AU - Hsiao CC AD - Department of Nephrology, New Taipei Municipal Tu Cheng Hospital, New Taipei City, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. AD - Data Analytics Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Jhu, Jian-Yu AU - Jhu JY AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Liu, Ya-Fang AU - Liu YF AD - Data Analytics Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Yen, Chieh-Li AU - Yen CL AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Chen, Jia-Jin AU - Chen JJ AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Chen, Pei-Chi AU - Chen PC AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. LA - eng PT - Journal Article DEP - 20261002 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Male MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Thyroiditis, Autoimmune/epidemiology/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Adult MH - Thyroid Gland/drug effects PMC - PMC13685433 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - autoimmune thyroiditis OT - dipeptidyl peptidase-4 inhibitor OT - glucagon-like peptide-1 receptor agonist OT - real-world evidence OT - thyroid disorders COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2026/10/23 18:31 MHDA- 2026/10/23 18:32 PMCR- 2026/10/02 CRDT- 2026/10/23 11:50 PHST- 2026/07/18 00:00 [received] PHST- 2026/09/18 00:00 [accepted] PHST- 2026/10/23 18:32 [medline] PHST- 2026/10/23 18:31 [pubmed] PHST- 2026/10/23 11:50 [entrez] PHST- 2026/10/02 00:00 [pmc-release] AID - ijmsv23p3494 [pii] AID - 10.7150/ijms.141099 [doi] PST - epublish SO - Int J Med Sci. 2026 Oct 2;23(11):3494-3505. doi: 10.7150/ijms.141099. eCollection 2026. PMID- 42905300 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261027 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Oct 21 TI - Decoding the Safety Profile of GLP-1 Receptor Agonists: Facts, Myths, and Ongoing Controversies. LID - 91 [pii] LID - 10.1007/s13679-026-00770-z [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent one of the most significant therapeutic advances in the management of type 2 diabetes and obesity. As their indications have expanded to include cardiovascular and kidney disease, safety concerns involving multiple organ systems have received increasing attention. This narrative review examines the spectrum of adverse effects linked to GLP-1RAs and provides a clinically relevant platform for assessing their safe prescription. RECENT FINDINGS: Gastrointestinal intolerance, modest increases in heart rate, and a modest but reproducible increase in the risk of gallbladder and biliary disease represent the most consistently supported adverse effects of GLP-1RAs. A risk of pancreatitis is also considered to exist, although some studies have challenged this association. Conversely, correlations with neuropsychiatric and dermatological disorders, diabetic retinopathy, nonarteritic anterior ischemic optic neuropathy, perioperative aspiration, sexual and reproductive disturbances, sarcopenia, and malignancy remain controversial. Most available evidence derives from pharmacovigilance databases, retrospective observational studies, and secondary analyses of randomized trials, which are limited by reporting bias, residual confounding, and inability to establish causality. Heterogeneity in study design, statistical methodology, outcome definitions, and patient populations further complicates interpretation. Although several proposed adverse effects have biologically plausible mechanisms, prospective clinical validation remains limited. Notably, recent regulatory decisions, including the Food and Drug Administration (FDA)'s removal of the suicidality warning from GLP-1RA prescribing information, reflect the evolving nature of these safety assessments. The overall benefit-risk profile of GLP-1RAs is favorable. Most emerging safety concerns should currently be regarded as hypothesis-generating signals rather than established toxicities. Individualized risk assessment and appropriate clinical monitoring remain important as ongoing and future prospective studies further define the long-term safety of this rapidly expanding therapeutic class. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Kounatidis, Dimitris C AU - Kounatidis DC AUID- ORCID: 0000-0003-4338-4879 AD - First Department of Internal Medicine, Sismanogleio General Hospital, Athens, 15126, Greece. dimitriskounatidis82@outlook.com. AD - Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. dimitriskounatidis82@outlook.com. FAU - Vallianou, Natalia G AU - Vallianou NG AD - First Department of Internal Medicine, Sismanogleio General Hospital, Athens, 15126, Greece. FAU - Kouveletsou, Marina AU - Kouveletsou M AD - First Department of Internal Medicine, 251 Air Force General Hospital, Athens, Greece. FAU - Kontrafouri, Paraskevi AU - Kontrafouri P AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. FAU - Stamatopoulos, Vasileios AU - Stamatopoulos V AD - Emergency Department, Evangelismos General Hospital, Athens, 10676, Greece. FAU - Rebelos, Eleni AU - Rebelos E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 56126, Italy. FAU - Diakoumopoulou, Evanthia AU - Diakoumopoulou E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. FAU - Dalamaga, Maria AU - Dalamaga M AD - Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. LA - eng PT - Journal Article PT - Review DEP - 20261021 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/drug therapy MH - Pancreatitis/chemically induced MH - Tirzepatide MH - Semaglutide MH - Gastrointestinal Diseases/chemically induced MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Adverse effects OT - Dermatological manifestations OT - Drug safety OT - GLP-1 receptor agonists OT - Gallbladder disease OT - Gastrointestinal adverse events OT - Neuropsychiatric disorders OT - Ocular disorders OT - Pneumonia OT - Sarcopenia OT - Semaglutide OT - Tirzepatide COIS- Declarations. Informed Consent: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no competing interests.. Animal and Human Rights and Informed Consent: None of the authors of this article conducted any research using either human or animal subjects Institutional Review Board Statement: Not applicable. EDAT- 2026/10/22 23:29 MHDA- 2026/10/22 23:30 CRDT- 2026/10/22 17:45 PHST- 2026/08/11 00:00 [received] PHST- 2026/10/15 00:00 [accepted] PHST- 2026/10/22 23:30 [medline] PHST- 2026/10/22 23:29 [pubmed] PHST- 2026/10/22 17:45 [entrez] AID - 10.1007/s13679-026-00770-z [pii] AID - 10.1007/s13679-026-00770-z [doi] PST - epublish SO - Curr Obes Rep. 2026 Oct 21;15(1):91. doi: 10.1007/s13679-026-00770-z. PMID- 42902671 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261022 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 8 DP - 2026 Aug 1 TI - Real-world Challenges and Predictors of Success in Glucagon-like Peptide-1 Receptor Agonist Therapy. PG - 74-76 LID - 10.59556/japi.74.1627 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) and obesity, demonstrating robust efficacy in landmark trials for glycemic control, weight reduction, and cardiovascular protection. However, real-world discontinuation rates exceed trial-reported rates, highlighting a gap between clinical efficacy and practical outcomes. OBJECTIVE: This review synthesizes evidence from 2018 to 2024, including trial data, population studies, and registry analyses, to identify and contextualize major real-world barriers. High rates of gastrointestinal side effects, substantial out-of-pocket costs, and patient aversion to injectable formulations often result in 1-year discontinuation rates ranging from 27 to 41%. These challenges are compounded by heterogeneity in patient response, with predictors of successful long-term use including higher baseline HbA1c, elevated body mass index (BMI), absence of severe gastrointestinal disorders, and robust early response to therapy. METHODS: A proposed clinical scoring model is presented to improve patient selection and predict adherence, while digital health tools and emerging combination therapies offer additional avenues to enhance persistence and outcomes. Despite promising advances such as dual- and triple-incretin agents and oral GLP-1 RA formulations, cost and access remain major hurdles. RESULTS: Key factors, including baseline HbA1c >8.0%, BMI >30 kg/m(2), absence of severe gastrointestinal (GI) disorders, and prior adherence success, correlate strongly with higher persistence. Real-world data reveal that discontinuation rates for GLP-1 receptor agonists remain high, with 1-year discontinuation ranging from approximately 28% to around 41%, depending on the patient population and indication. Discontinuation is more common among patients using GLP-1 RAs for obesity without diabetes, reaching rates above 50% in some cohorts. The primary reasons for stopping therapy include gastrointestinal side effects, reported in over 25% of discontinuations, high medication costs, and issues with insurance coverage or medication access. Persistence is generally higher among patients with T2DM, those with higher baseline BMI, and those who experience greater early weight loss or favorable tolerability, while frequent adverse effects and logistical barriers contribute to poorer long-term adherence. Although emerging clinical tools and digital health interventions are proposed to help address these barriers, further prospective data are needed to quantify their impact on persistence at scale. CONCLUSION: Bridging trial evidence with real-world practice requires proactive candidate profiling and side-effect management. Combining predictive scoring, artificial intelligence (AI)-supported adherence tools, and emerging dual-incretin agents may transform GLP-1 RA therapy from short-term use to durable metabolic benefit. CI - (c) The Author(s). 2026 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. FAU - Patankar, Nitin Mohaniraj AU - Patankar NM AUID- ORCID: 0009-0006-9076-9770 AD - Consultant, Department of Diabetes and Bariatric Medicine, Jupiter Hospital, Thane, Maharashtra, India, *Corresponding Author. FAU - Sanghvi, Sushma Jain AU - Sanghvi SJ AUID- ORCID: 0009-0006-5763-0021 AD - Consultant, Department of Metabolic Centre, Dr L H Hiranandani Hospital, Mumbai, Maharashtra, India. LA - eng PT - Journal Article PT - Review DEP - 20260801 PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Glycated Hemoglobin OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Glycated hemoglobin OT - Obesity OT - Predictive success OT - Type 2 diabetes mellitus COIS- None EDAT- 2026/10/22 13:25 MHDA- 2026/10/22 13:26 CRDT- 2026/10/22 08:30 PHST- 2025/08/07 00:00 [received] PHST- 2025/09/23 00:00 [accepted] PHST- 2026/10/22 13:26 [medline] PHST- 2026/10/22 13:25 [pubmed] PHST- 2026/10/22 08:30 [entrez] AID - 10.59556/japi.74.1627 [doi] PST - epublish SO - J Assoc Physicians India. 2026 Aug 1;74(8):74-76. doi: 10.59556/japi.74.1627. PMID- 42899606 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261020 IS - 0717-6163 (Electronic) IS - 0034-9887 (Linking) VI - 154 IP - 8 DP - 2026 Aug TI - Effectiveness of Weekly Semaglutide Treatment (0.5 or 1 mg) in Chilean Patients with Type 2 Diabetes Mellitus. PG - 1150-1159 LID - S0034-98872026000801150 [pii] LID - 10.4067/s0034-98872026000801150 [doi] AB - Semaglutide is approved in Chile for the management of type 2 diabetes mellitus (T2DM), although it is generally not available in the public health system. Generating local evidence may aid in its incorporation into national guidelines and reduce the therapeutic gap with international standards. AIM: To evaluate the effectiveness and safety of adding weekly semaglutide to the standard treatment for T2DM in the public health system. METHODS: A phase 4, multicenter, interventional study evaluated the weekly addition of 0.5 or 1 mg of subcutaneous semaglutide over 24 weeks, followed by a 5-week post-treatment monitoring period. RESULTS: n=104 (79.8% women; age: 58.3+/-9.3 years; 44.2% over 60 years of age; 35.6% with >/=1 complication of T2DM). Common comorbidities: hypertension: 71.2%; obesity: 71.2%; dyslipidemia: 51.9%. Most commonly used baseline treatments: metformin, 96.2%; NPH insulin, 65.4%; empagliflozin, 46.2%; regular insulin, 27.9%; insulin glargine, 22.1%; dapagliflozin, 21.2%. At 24 weeks, a reduction in glycosylated hemoglobin (HbA1c: 8.6+/-0.7% to 7+/-1%, difference: -1.6%), fasting blood glucose (160.3+/-49.3 to 133.7+/-54.8 mg/dL, difference: -26.2 mg/dL), and weight (89.3+/-20.2 to 85.3+/-20.4 kg; difference: -4 kg) were confirmed. Participants with HbA1c <7% increased from 0% to 56.4%. Thirty-one percent of patients receiving basal insulin reduced their dose (median: 6 IU). Gastrointestinal adverse events were the most frequent, consistent with the drug's safety profile. CONCLUSIONS: In people with inadequately controlled T2DM in the real world, the addition of a weekly dose of semaglutide was associated with improvement in HbA1c, fasting blood glucose, and weight, and a reduction in insulin dose, with an adequate safety profile. These results provide local evidence on the efficacy of semaglutide in improving various cardio-renal-metabolic risk factors in people with T2DM. FAU - Estica, Marcos AU - Estica M AD - Unidad de Diabetes, Hospital San Juan de Dios, Santiago, Chile. FAU - Godoy, Gonzalo AU - Godoy G AD - Hospital del Salvador, Universidad de Chile, Santiago, Chile. FAU - Vargas, Cecilia AU - Vargas C AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Elgueta, Karina AU - Elgueta K AD - Unidad de Diabetes, Hospital San Juan de Dios, Santiago, Chile. FAU - Gattini, Francesca AU - Gattini F AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Gutierrez, Vicente AU - Gutierrez V AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Salort, Perla AU - Salort P AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. LA - eng LA - spa PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study TT - Efectividad del tratamiento con semaglutida semanal (0,5 o 1 mg) en pacientes chilenos con diabetes mellitus tipo 2. PL - Chile TA - Rev Med Chil JT - Revista medica de Chile JID - 0404312 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Chile MH - Male MH - Treatment Outcome MH - Glycated Hemoglobin/analysis MH - Aged MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Time Factors EDAT- 2026/10/20 17:34 MHDA- 2026/10/20 17:35 CRDT- 2026/10/20 14:00 PHST- 2025/08/29 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/10/20 17:35 [medline] PHST- 2026/10/20 17:34 [pubmed] PHST- 2026/10/20 14:00 [entrez] AID - S0034-98872026000801150 [pii] AID - 10.4067/s0034-98872026000801150 [doi] PST - ppublish SO - Rev Med Chil. 2026 Aug;154(8):1150-1159. doi: 10.4067/s0034-98872026000801150. PMID- 42898660 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261022 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Glucagon-like peptide-1 receptor agonists and aesthetic surgery: perioperative safety, timing, durability and body composition. PG - 1969433 LID - 10.3389/fendo.2026.1969433 [doi] LID - 1969433 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin agonists have transformed the management of obesity and type 2 diabetes and are rapidly reshaping the population seeking aesthetic surgery. By producing double-digit percentage weight loss, these agents expand eligibility for elective procedures while generating new patterns of skin redundancy, soft-tissue laxity, and facial volume depletion that drive demand for body contouring and facial rejuvenation. At the same time, incretin therapy introduces distinct perioperative considerations: delayed gastric emptying with possible pulmonary aspiration in symptomatic patients, gastrointestinal adverse effects that peak during dose escalation, loss of lean mass with rapid weight reduction, nutritional inadequacy during profound appetite suppression, and frequent weight regain after drug discontinuation, which threatens the durability of surgical results. This mini-review synthesizes current evidence on the mechanisms of GLP-1 RAs relevant to the reconstructive surgical patient, summarizes the evolving guidance from anesthesia societies, moving from blanket preoperative withholding to individualized risk stratification, reviews emerging outcome data on body contouring in GLP-1 RA users, and discusses body composition, sarcopenia risk, and nutritional optimization. We propose a pragmatic framework, anchored in weight stability and symptom burden, for timing elective aesthetic procedures relative to GLP-1 RA initiation, escalation, and maintenance, along with a multidisciplinary perioperative algorithm that links the endocrinologist, plastic surgeon, and anesthesiologist. As incretin-based pharmacotherapy expands globally, coordinated endocrine-surgical-anesthetic care will be essential to maximize safety, functional recovery, and patient satisfaction in the GLP-1 era. CI - Copyright (c) 2026 Chaturvedi, Singh, Chakole, Yadav, Dhameliya and Joshi. FAU - Chaturvedi, Richa AU - Chaturvedi R AD - Advance Center for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital, New Delhi, India. FAU - Singh, Kuldeep AU - Singh K AD - Department of Aesthetic, Plastic and Reconstructive Surgery, Indraprastha Apollo Hospital, New Delhi, India. FAU - Chakole, Rameshwari R AU - Chakole RR AD - Advance Center for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital, New Delhi, India. FAU - Yadav, Bhupesh K AU - Yadav BK AD - Advance Center for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital, New Delhi, India. FAU - Dhameliya, Juli AU - Dhameliya J AD - Advance Center for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital, New Delhi, India. FAU - Joshi, Deepali AU - Joshi D AD - Advance Center for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital, New Delhi, India. LA - eng PT - Journal Article PT - Review DEP - 20261005 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Body Composition/drug effects MH - *Obesity/drug therapy/surgery MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Plastic Surgery Procedures/methods MH - Perioperative Care MH - *Surgery, Plastic/methods PMC - PMC13678443 OTO - NOTNLM OT - GLP-1 receptor agonists OT - aesthetic surgery OT - body contouring OT - lean mass OT - obesity pharmacotherapy OT - perioperative management OT - sarcopenic obesity OT - weight regain COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/20 11:33 MHDA- 2026/10/20 11:34 PMCR- 2026/10/05 CRDT- 2026/10/20 09:52 PHST- 2026/08/16 00:00 [received] PHST- 2026/09/23 00:00 [revised] PHST- 2026/09/23 00:00 [accepted] PHST- 2026/10/20 11:34 [medline] PHST- 2026/10/20 11:33 [pubmed] PHST- 2026/10/20 09:52 [entrez] PHST- 2026/10/05 00:00 [pmc-release] AID - 10.3389/fendo.2026.1969433 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Oct 5;17:1969433. doi: 10.3389/fendo.2026.1969433. eCollection 2026. PMID- 42890523 OWN - NLM STAT- MEDLINE DCOM- 20261017 LR - 20261022 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis. PG - 1903335 LID - 10.3389/fendo.2026.1903335 [doi] LID - 1903335 AB - INTRODUCTION: Semaglutide 2.4 mg is the reference pharmacotherapy for weight management, yet many patients do not reach ambitious weight-loss targets. CagriSema, a fixed-dose combination of cagrilintide and semaglutide, may offer additional benefit through complementary mechanisms. We quantified its incremental efficacy and safety against semaglutide 2.4 mg monotherapy in adults with overweight or obesity, with and without type 2 diabetes. METHODS: This PRISMA 2020-compliant review (PROSPERO CRD420261380458) searched PubMed, Embase, Cochrane CENTRAL, ScienceDirect, ClinicalTrials.gov and WHO ICTRP to 30 June 2026 for randomised controlled trials comparing CagriSema with semaglutide 2.4 mg or placebo. Effects were pooled within two prespecified comparator strata using random-effects models with restricted maximum likelihood estimation of tau(2) and a Hartung-Knapp-Sidik-Jonkman small-sample adjustment, with prediction intervals, leave-one-out and phase-3a-restricted sensitivity analyses, trial sequential analysis. RESULTS: Five trials (4,746 unique participants) were included. Versus semaglutide 2.4 mg, CagriSema produced greater weight loss (mean difference -6.89 percentage points, 95% CI -8.70 to -5.06; I(2) = 33%; prediction interval -8.91 to -4.86), a greater absolute reduction in body weight (-7.16 kg, 95% CI -9.15 to -5.17) and in body-mass index (-2.41 kg/m(2), 95% CI -2.83 to -1.99), and roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47). Waist circumference fell further (-4.07 cm, 95% CI -5.10 to -3.04). No incremental glycaemic benefit was detected, with intervals for glycated haemoglobin (-0.07, 95% CI -0.14 to 0.01) and fasting plasma glucose lying entirely within prespecified minimal important differences. Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96); gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21). CONCLUSION: CagriSema produces clinically meaningful additional weight loss and modest improvements in surrogate cardiometabolic measures compared with semaglutide 2.4 mg alone, at the cost of more frequent injection-site reactions and, at most, modestly more frequent gastrointestinal events. The evidence is insufficient to determine whether serious adverse events or neoplasms differ between treatments, and long-term durability, cardiovascular outcomes and body composition remain undetermined. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261380458. CI - Copyright (c) 2026 Rasool, Shah, Batool, Shah, Khachatryan, Bhardwaj, Ali, Atta, Bakthavatchalam, Khawar and Khawar. FAU - Rasool, Zehra Khatoon AU - Rasool ZK AD - DePaul University, Chicago, IL, United States. FAU - Shah, Rajvi AU - Shah R AD - Narendra Modi Medical College, Ahmedabad, India. FAU - Batool, Ansharah E Zinnia AU - Batool AEZ AD - Rashid Latif Medical College, Lahore, Pakistan. FAU - Shah, Rutvi AU - Shah R AD - Narendra Modi Medical College, Ahmedabad, India. FAU - Khachatryan, Mariam AU - Khachatryan M AD - Fanarjyan Clinic, Yerevan, Armenia. FAU - Bhardwaj, Sushant AU - Bhardwaj S AD - Kathmandu University School of Medical Sciences, Dhulikhel, Nepal. FAU - Ali, Ahmad AU - Ali A AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Atta, Meeran AU - Atta M AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Bakthavatchalam, Pugazhandhi AU - Bakthavatchalam P AD - American University of Antigua, St. John's, Antigua and Barbuda. FAU - Khawar, Mirza Muhammad Hadeed AU - Khawar MMH AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Khawar, Muneeb AU - Khawar M AD - King Edward Medical University, Lahore, Pakistan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20261002 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - *Anti-Obesity Agents/administration & dosage/therapeutic use PMC - PMC13673521 OTO - NOTNLM OT - CagriSema OT - Semaglutide OT - cagrilintide OT - obesity OT - weight loss COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/17 23:38 MHDA- 2026/10/17 23:39 PMCR- 2026/10/02 CRDT- 2026/10/17 16:47 PHST- 2026/06/08 00:00 [received] PHST- 2026/09/06 00:00 [revised] PHST- 2026/09/09 00:00 [accepted] PHST- 2026/10/17 23:39 [medline] PHST- 2026/10/17 23:38 [pubmed] PHST- 2026/10/17 16:47 [entrez] PHST- 2026/10/02 00:00 [pmc-release] AID - 10.3389/fendo.2026.1903335 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Oct 2;17:1903335. doi: 10.3389/fendo.2026.1903335. eCollection 2026. PMID- 42886550 OWN - NLM STAT- MEDLINE DCOM- 20261016 LR - 20261022 IS - 1819-6357 (Electronic) IS - 1993-2820 (Print) IS - 1819-6357 (Linking) VI - 21 IP - 1 DP - 2026 Dec 31 TI - Pharmacy students' knowledge and attitudes regarding GLP-1 receptor agonist adverse effects in obesity management: a cross-sectional study. PG - 2749899 LID - 10.1080/19932820.2026.2749899 [doi] LID - 2749899 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for obesity and type 2 diabetes mellitus. Despite their increasing use, safety concerns remain, and pharmacy students' knowledge of their adverse effects is unclear. This study evaluated pharmacy students' knowledge and attitudes regarding GLP-1 RA adverse effects in obesity management. A cross-sectional questionnaire-based study was conducted among undergraduate Doctor of Pharmacy (Pharm.D.) students (1st-7th year) at Umm Al-Qura University, Saudi Arabia, between November and December 2025. A newly developed questionnaire, reviewed by two experts and pilot-tested among 10 students, assessed 17 knowledge and five attitude items covering indications, mechanisms, adverse effects, and clinical scenarios. Of 1,118 eligible students, 296 completed the survey (response rate: 26.5%). Descriptive statistics and multivariable regression analyses were performed using RStudio (version 2024.9.1.394). Among participants (63.9% male), the mean knowledge score was 7.6 +/- 4.0/17. Most agreed that adverse effects significantly impact clinical use (59.4%) and supported further education on less common side effects (61.1%). Nausea was the most frequently recognized adverse effect (59.1%), whereas thyroid C-cell tumors observed in rodent studies (25.0%) and diabetic retinopathy complications (36.5%) were less commonly identified. Only 37.2% correctly recognized that hypoglycemia is uncommon with GLP-1 RA monotherapy. Higher knowledge scores were significantly associated with greater confidence in knowledge (OR = 1.11, 95% CI: 1.06-1.17; p < 0.001) and stronger endorsement of further education on less common side effects (OR = 1.11, 95% CI: 1.06-1.18; p < 0.001), whereas gender and academic year were not significant predictors of any attitude item. Pharmacy students demonstrated limited knowledge but generally positive attitudes regarding GLP-1 RA safety. These findings highlight the need to strengthen pharmacovigilance and evidence-based medication safety education within pharmacy curricula to improve clinical preparedness and patient counseling. FAU - Khojah, Alaa A AU - Khojah AA AD - Pharmaceutical Sciences Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Gazzaz, Malaz J AU - Gazzaz MJ AD - Pharmaceutical practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Aldurdunji, Mohammed M AU - Aldurdunji MM AD - Pharmaceutical practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Safiraldeen, Ahmad E AU - Safiraldeen AE AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Al-Qurashi, Ibrahim R AU - Al-Qurashi IR AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alhazmi, Mohammad A AU - Alhazmi MA AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Abdalla, Ashraf N AU - Abdalla AN AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alqurashi, Roaya S AU - Alqurashi RS AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Wali, Saad M AU - Wali SM AUID- ORCID: 0009-0006-0080-4799 AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. LA - eng PT - Journal Article DEP - 20261016 PL - United States TA - Libyan J Med JT - The Libyan journal of medicine JID - 101299403 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cross-Sectional Studies MH - Male MH - Female MH - *Health Knowledge, Attitudes, Practice MH - *Students, Pharmacy/statistics & numerical data/psychology MH - Saudi Arabia MH - Surveys and Questionnaires MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Young Adult MH - Hypoglycemic Agents/adverse effects PMC - PMC13678873 OTO - NOTNLM OT - GLP-1 receptor agonists OT - attitudes OT - knowledge OT - obesity OT - pharmacovigilance OT - pharmacy students OT - semaglutide COIS- No potential conflict of interest was reported by the author(s). EDAT- 2026/10/16 19:05 MHDA- 2026/10/16 19:06 PMCR- 2026/10/16 CRDT- 2026/10/16 12:33 PHST- 2026/10/16 19:06 [medline] PHST- 2026/10/16 19:05 [pubmed] PHST- 2026/10/16 12:33 [entrez] PHST- 2026/10/16 00:00 [pmc-release] AID - 2749899 [pii] AID - 10.1080/19932820.2026.2749899 [doi] PST - ppublish SO - Libyan J Med. 2026 Dec 31;21(1):2749899. doi: 10.1080/19932820.2026.2749899. Epub 2026 Oct 16. PMID- 42885796 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261022 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 15 IP - 20 DP - 2026 Oct 20 TI - Glucagon-Like Peptide-1 Receptor Agonists and Incident Cardiovascular Events and Death in Treated Serious Mental Illness, Type 2 Diabetes, and Obesity. PG - e051982 LID - 10.1161/JAHA.126.051982 [doi] AB - BACKGROUND: Adults with serious mental illness (SMI), type 2 diabetes, and obesity have elevated cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have established cardiometabolic benefits in the general population, but their effects in SMI are unclear. We evaluated whether GLP-1RA use was associated with lower risks of incident myocardial infarction (MI), heart failure (HF), and all-cause death. METHODS: This was a retrospective propensity score-matched cohort study of 218 043 adults with SMI, type 2 diabetes, obesity, and active antipsychotic or antidepressant medications in the TriNetX database (73 health care organizations). Outcomes were incident MI, HF, and all-cause death at 1 and 3 years. The primary exposure was GLP-1RA use versus nonuse; secondary analyses examined semaglutide or tirzepatide. Exploratory analyses evaluated sex, race, and sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use. RESULTS: GLP-1RA use was associated with lower risks of incident MI, HF, and all-cause death. Risk differences at 1 and 3 years were -0.007 and -0.010 for MI, -0.011 and -0.018 for HF, and -0.039 and -0.065 for death (all P<0.001). Semaglutide or tirzepatide use was also associated with lower risks of MI, HF, and death (all P<0.001). Findings were directionally consistent after accounting for sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use. CONCLUSIONS: Adults with treated SMI, type 2 diabetes, and obesity using GLP-1RAs, particularly semaglutide or tirzepatide, had significantly reduced 1- and 3-year risks of incident MI, HF, and all-cause death versus nonusers. These pooled associations should be interpreted in the context of SMI's clinical heterogeneity and the limitations of administrative case ascertainment. FAU - Governor, Samuel B AU - Governor SB AUID- ORCID: 0000-0001-6412-7279 AD - St. John's Episcopal Hospital New York NY USA. FAU - Davila-Garcia, David M AU - Davila-Garcia DM AD - Institute for Informatics, Data Science and Biostatistics Washington University School of Medicine St. Louis MO USA. FAU - Rivera-Segarra, Eliut AU - Rivera-Segarra E AUID- ORCID: 0000-0001-8643-9273 AD - School of Behavioral and Brain Sciences Ponce Health Sciences University Ponce PR USA. FAU - Filiatreau, Lindsey M AU - Filiatreau LM AUID- ORCID: 0000-0002-0355-4477 AD - Bursky School of Public Health Washington University in St. Louis St. Louis MO USA. FAU - Tollinchi-Natali, Nelmit AU - Tollinchi-Natali N AUID- ORCID: 0009-0009-8995-2131 AD - School of Dental Medicine Ponce Health Sciences University Ponce PR USA. FAU - Essien, Ekow AU - Essien E AUID- ORCID: 0009-0006-5396-0955 AD - Aurora Health Care Kenosha WI USA. FAU - Altaee, Osamah AU - Altaee O AUID- ORCID: 0000-0003-3174-0995 AD - University of Texas Health San Antonio TX USA. FAU - Otchere, Prince AU - Otchere P AD - University of Texas Health San Antonio TX USA. FAU - Cabassa, Leopoldo J AU - Cabassa LJ AUID- ORCID: 0000-0002-1872-4141 AD - Brown School of Social Work and Center for Mental Health Services Research Washington University in St. Louis MO USA. FAU - Davila-Roman, Victor G AU - Davila-Roman VG AUID- ORCID: 0000-0001-8554-0011 AD - Cardiovascular Division and Global Health Center, Department of Medicine, School of Medicine and Bursky School of Public Health Washington University in St. Louis MO USA. LA - eng PT - Journal Article DEP - 20261016 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Antidepressive Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/mortality/complications MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/epidemiology/mortality/complications MH - Retrospective Studies MH - *Mental Disorders/drug therapy/epidemiology/mortality MH - Middle Aged MH - Semaglutide MH - Tirzepatide MH - Incidence MH - Aged MH - Antipsychotic Agents/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Myocardial Infarction/epidemiology/prevention & control/mortality MH - *Heart Failure/epidemiology/prevention & control/mortality MH - United States/epidemiology MH - Cause of Death MH - Risk Assessment MH - Glucagon-Like Peptides/therapeutic use MH - *Incretins/therapeutic use MH - Risk Factors MH - Adult MH - *Cardiovascular Diseases/mortality/prevention & control/epidemiology MH - Time Factors MH - Antidepressive Agents/therapeutic use OTO - NOTNLM OT - cardiovascular outcomes OT - death OT - glucagon-like peptide-1 receptor agonists OT - heart failure OT - myocardial infarction OT - obesity OT - semaglutide OT - serious mental illness OT - tirzepatide OT - type 2 diabetes EDAT- 2026/10/16 11:38 MHDA- 2026/10/23 05:32 CRDT- 2026/10/16 07:34 PHST- 2026/10/23 05:32 [medline] PHST- 2026/10/16 11:38 [pubmed] PHST- 2026/10/16 07:34 [entrez] AID - 10.1161/JAHA.126.051982 [doi] PST - ppublish SO - J Am Heart Assoc. 2026 Oct 20;15(20):e051982. doi: 10.1161/JAHA.126.051982. Epub 2026 Oct 16. PMID- 42874603 OWN - NLM STAT- MEDLINE DCOM- 20261014 LR - 20261015 IS - 2215-0374 (Electronic) IS - 2215-0366 (Linking) VI - 13 IP - 11 DP - 2026 Nov TI - GLP-1 receptor agonist initiation and risk of psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes in the USA: an observational cohort study using electronic health records data. PG - 931-942 LID - S2215-0366(26)00276-2 [pii] LID - 10.1016/S2215-0366(26)00276-2 [doi] AB - BACKGROUND: Many individuals with schizophrenia have persistent psychotic symptoms despite antipsychotic treatment, and the disorder is associated with a disproportionately high burden of metabolic dysregulation. Whether GLP-1 receptor agonists are associated with psychiatric benefit alongside their metabolic effects remains unknown. We aimed to examine associations between GLP-1 receptor agonist initiation and psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes, compared with DPP-4 inhibitor initiation, SGLT2 inhibitor initiation, and non-initiation. METHODS: In this observational cohort study, we used electronic health record (EHR) data from the US NeuroBlu Data repository to construct a cohort of adults (>/=18 years) with documented diagnosis of schizophrenia and comorbid type 2 diabetes. The exposure was the initiation of GLP-1 receptor agonists, compared with non-initiation or initiation of DPP-4 inhibitors or SGLT2 inhibitors. The index date, from Jan 1, 2018, was defined as the date of the first recorded psychiatric visit at which both a diagnosis of schizophrenia and comorbid type 2 diabetes were present in the participant's record. Time zero (T(0)) was the date of the first prescription of any of these agents between Jan 1, 2018, and Oct 1, 2025; for non-initiators, T(0) was the index date. Participants contributed person-time from T(0) until 2 years of follow-up, the last recorded clinical observation in the NeuroBlu Data repository, or the end of the observation period (March 24, 2026), whichever happened earliest. The main outcomes of interest included risk of psychiatric hospitalisation and psychiatric emergency department presentation. Inverse probability weighting was applied to balance demographic, clinical, and pharmacological covariates, and weighted regression models were used. Analyses were conducted using an intention-to-treat framework, whereby exposure status was defined according to the medication initiated at T(0). FINDINGS: A total of 70 257 individuals met the inclusion criteria; mean age was 53.1 years [SD 12.32] and 33 882 [48.2%] were women. Among the 70 257 eligible individuals, 9093 (12.9%) initiated GLP-1 receptor agonists, 4968 (7.1%) initiated DPP-4 inhibitors, 5328 (7.6%) initiated SGLT2 inhibitors, and 50 868 (72.4%) were non-initiators. In weighted regression analyses, GLP-1 receptor agonist initiation was associated with a lower risk of psychiatric hospitalisation compared with non-initiation (weighted hazard ratio [HR] 0.76 [95% CI 0.71-0.82]), DPP-4 inhibitor initiation (0.82 [0.75-0.90]), and SGLT2 inhibitor initiation (0.83 [0.78-0.88]). GLP-1 receptor agonist initiation was also associated with a lower risk of emergency department presentation than non-initiation (0.71 [0.65-0.77]), DPP-4 inhibitor initiation (0.87 [0.80-0.95]), and SGLT2 inhibitor initiation (0.80 [0.73-0.88]). INTERPRETATION: GLP-1-based therapy initiation was associated with lower psychiatric acute-care use than non-initiation and initiation of DPP-4 or SGLT2 inhibitors in adults with schizophrenia and type 2 diabetes. Potential residual confounding and selection bias restrict generalisability of the results. The findings suggest that lower psychiatric acute-care use could be a favourable secondary benefit when GLP-1-based therapies are clinically indicated for metabolic management, although their use as primary psychiatric treatments require investigation in randomised and mechanistic studies. FUNDING: Synergy for the Development of Innovative Clinical Treatments in Schizophrenia (SYNDICAT) project (GNT2035912). CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. FAU - Davoodian, Najmeh AU - Davoodian N AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. Electronic address: n.davoodian@deakin.edu.au. FAU - Williams, Lana J AU - Williams LJ AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. FAU - Berk, Michael AU - Berk M AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. FAU - Arnautovska, Urska AU - Arnautovska U AD - Addiction and Mental Health Service, Metro South Health, Brisbane, QLD, Australia; Faculty of Health, Medicine and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Physical and Mental Health Stream, Queensland Centre for Mental Health Research, Brisbane, QLD, Australia. FAU - Kim, Jee Hyun AU - Kim JH AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. FAU - McLure, James AU - McLure J AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. FAU - Panizzutti, Bruna AU - Panizzutti B AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. FAU - Rossell, Susan L AU - Rossell SL AD - Centre for Mental Health and Brain Sciences, Swinburne University of Technology, Melbourne, VIC, Australia; InsideOut Institute, University of Sydney and Sydney Local Health District, Sydney, NSW, Australia. FAU - Siskind, Dan AU - Siskind D AD - Addiction and Mental Health Service, Metro South Health, Brisbane, QLD, Australia; Faculty of Health, Medicine and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Physical and Mental Health Stream, Queensland Centre for Mental Health Research, Brisbane, QLD, Australia. FAU - Taipale, Heidi AU - Taipale H AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; School of Pharmacy, University of Eastern Finland, Kuopio, Finland. FAU - Taquet, Maxime AU - Taquet M AD - Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK. FAU - Upthegrove, Rachel AU - Upthegrove R AD - Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK; Institute for Mental Health, University of Birmingham, Birmingham, UK; Early Intervention Service, Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK. FAU - Walder, Ken AU - Walder K AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia. FAU - Yung, Alison R AU - Yung AR AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia; School of Health Sciences, University of Manchester, Manchester, UK. FAU - Mohebbi, Mohammadreza AU - Mohebbi M AD - School of Medicine, Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), Deakin University, Geelong, VIC, Australia; Deakin Biostatistics Unit, Faculty of Health, Deakin University, Geelong, VIC, Australia. LA - eng PT - Journal Article PT - Observational Study PL - England TA - Lancet Psychiatry JT - The lancet. Psychiatry JID - 101638123 RN - 0 (Antipsychotic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Antipsychotic Agents/therapeutic use MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Electronic Health Records MH - Emergency Room Visits MH - *Emergency Service, Hospital/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hospitalization/statistics & numerical data MH - *Schizophrenia/drug therapy/epidemiology/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - United States/epidemiology COIS- Declaration of interests We declare no competing interests. EDAT- 2026/10/14 23:32 MHDA- 2026/10/14 23:33 CRDT- 2026/10/14 18:52 PHST- 2026/05/04 00:00 [received] PHST- 2026/08/13 00:00 [revised] PHST- 2026/08/21 00:00 [accepted] PHST- 2026/10/14 23:33 [medline] PHST- 2026/10/14 23:32 [pubmed] PHST- 2026/10/14 18:52 [entrez] AID - S2215-0366(26)00276-2 [pii] AID - 10.1016/S2215-0366(26)00276-2 [doi] PST - ppublish SO - Lancet Psychiatry. 2026 Nov;13(11):931-942. doi: 10.1016/S2215-0366(26)00276-2. PMID- 42866418 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 2754-0413 (Electronic) IS - 2754-0413 (Linking) VI - 5 IP - 1 DP - 2026 TI - Values, preferences, and treatment burden for initiation of GLP-1 receptor agonists, SGLT-2 inhibitors, tirzepatide, and finerenone in adults with type 2 diabetes: systematic review. PG - e002780 LID - 10.1136/bmjmed-2026-002780 [doi] LID - e002780 AB - OBJECTIVES: To summarise existing evidence regarding the values, preferences, and perceived treatment burden of adults with type 2 diabetes when considering initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), finerenone, or tirzepatide. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched from database inception to 7 January 2025 (updating a previous systematic review that captured literature up to 23 May 2020). ELIGIBILITY CRITERIA: Quantitative or qualitative studies were included if they reported patient reported values, preferences, or treatment burden among adults with type 2 diabetes and compared initiation of GLP-1 RA, SGLT-2i, tirzepatide, or finerenone with each other or with other glucose-lowering treatments. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently screened studies, extracted data, and assessed risk of bias. Certainty of evidence was evaluated using GRADE. Findings were synthesised narratively. RESULTS: Thirty four studies (15 656 patients) were included, 17 of which were new since the previous 2021 review (8360 patients). Of the newly included studies, 10 evaluated GLP-1 RA, seven evaluated SGLT-2i, and one evaluated tirzepatide; no studies evaluated finerenone (because several studies compared multiple drug classes, these categories are not mutually exclusive). Across comparisons, patients consistently reported glycaemic efficacy, cardiovascular risk reduction, and simplicity of administration as their priorities. Oral once-daily regimens and once-weekly injectable treatments with easy-to-use devices were generally preferred. Weight loss was valued but was typically secondary to glycaemic and cardiovascular benefits. SGLT-2i and GLP-1 RA were often preferred over dipeptidyl peptidase 4-inhibitors (DPP-4i), thiazolidinediones, and insulins, but no consistent preference emerged for SGLT-2i over GLP-1 RA. Tirzepatide was favoured over semaglutide in a single study, largely due to greater haemoglobin A(1c) reduction and lower hypoglycaemia risk. Certainty of evidence for all comparisons was low or very low certainty. CONCLUSION: Adults with type 2 diabetes prioritise treatment effectiveness and convenience among glucose-lowering treatments. Current evidence does not support a clear preference between SGLT-2i and GLP-1 RA, and data for finerenone are absent. These findings underscore the importance of shared decision making informed by individual patient priorities. PROSPERO REGISTRATION: CRD42023429170. CI - Copyright (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Gonzalez-Cruz, Daniela C AU - Gonzalez-Cruz DC AUID- ORCID: 0000-0003-3709-9326 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Garcia-Campa, Mariano AU - Garcia-Campa M AUID- ORCID: 0000-0001-7733-6432 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Moreno-Pena, Pablo Jose AU - Moreno-Pena PJ AUID- ORCID: 0000-0003-3661-4912 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Avalos-Bishop, Andres AU - Avalos-Bishop A AUID- ORCID: 0000-0002-2017-0547 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Manzanares-Gallegos, Dulce Maria AU - Manzanares-Gallegos DM AUID- ORCID: 0009-0008-3958-1267 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Garcia-Garcia, Fernanda M AU - Garcia-Garcia FM AUID- ORCID: 0009-0004-4629-2579 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Montiel Labastida, Jan Alejandro AU - Montiel Labastida JA AUID- ORCID: 0009-0006-8221-6578 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Gonzalez-Gonzalez, Jose Gerardo AU - Gonzalez-Gonzalez JG AUID- ORCID: 0000-0002-6609-9483 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Agarwal, Arnav AU - Agarwal A AUID- ORCID: 0000-0002-0931-7851 AD - Department of Medicine, University of Alberta, Edmonton, AB, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - Manja, Veena AU - Manja V AUID- ORCID: 0000-0003-0410-8089 AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA. AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. FAU - Olav Vandvik, Per AU - Olav Vandvik P AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Agoritsas, Thomas AU - Agoritsas T AUID- ORCID: 0000-0002-6182-9969 AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. AD - Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland. FAU - Mustafa, Reem A AU - Mustafa RA AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. AD - Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas, Lawrence, KS, USA. FAU - Rodriguez-Gutierrez, Rene AU - Rodriguez-Gutierrez R AUID- ORCID: 0000-0002-3022-5302 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. LA - eng PT - Journal Article PT - Systematic Review DEP - 20261008 PL - England TA - BMJ Med JT - BMJ medicine JID - 9918487584306676 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Naphthyridines) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Tirzepatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Naphthyridines/therapeutic use MH - *Patient Preference MH - Adult PMC - PMC13656128 OTO - NOTNLM OT - Diabetes mellitus OT - Endocrinology OT - Internal medicine COIS- All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2026/10/13 17:37 MHDA- 2026/10/13 17:38 PMCR- 2026/10/08 CRDT- 2026/10/13 14:07 PHST- 2026/03/11 00:00 [received] PHST- 2026/08/20 00:00 [accepted] PHST- 2026/10/13 17:38 [medline] PHST- 2026/10/13 17:37 [pubmed] PHST- 2026/10/13 14:07 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - bmjmed-2026-002780 [pii] AID - 10.1136/bmjmed-2026-002780 [doi] PST - epublish SO - BMJ Med. 2026 Oct 8;5(1):e002780. doi: 10.1136/bmjmed-2026-002780. eCollection 2026. PMID- 42865361 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261014 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Pancreatic and biliary safety signals of GLP-1 receptor agonists and tirzepatide: a disproportionality analysis of FAERS reports. PG - 1941948 LID - 10.3389/fendo.2026.1941948 [doi] LID - 1941948 AB - BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide is increasing rapidly worldwide, and the pancreatic and biliary safety of these drugs has been a concern. This study was based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate the pancreatic and biliary adverse event reporting signals of liraglutide, semaglutide, tirzepatide and dulaglutide. OBJECTIVES: To describe the reporting patterns of pancreatic and biliary adverse events for liraglutide, semaglutide, dulaglutide, and tirzepatide, and to identify signals in both organ systems within a single framework. DESIGN: Retrospective disproportionality analysis of individual case safety reports. METHODS: FAERS data from Q3-2009 through Q3-2025 were extracted, and deduplicated ICSRs were used as the unit of analysis. Reporting odds ratios (RORs) and information components (ICs) were computed at composite and Preferred Term levels; signals required the lower 95% confidence bound for the ROR to exceed 1 and IC025 to exceed 0. Metformin and sodium-glucose cotransporter-2 inhibitors were included as contextual benchmarks. Analyses were stratified by brand (diabetes/obesity indication), sex, age, and reporter type, and time to onset was examined. RESULTS: A disproportionality signal for pancreatic adverse events was observed for all four study drugs, but the control drugs metformin and SGLT2i also showed positive signals. For biliary events, all four study drugs showed signals, whereas the two control drugs showed no signals. After stratification by brand, the pancreatic signal remained for brands with diabetes indications, while the signal was weaker for brands with obesity indications. After excluding the cases of biliary tract co-reporting, the pancreatic signal still existed. Median time to onset ranged from 85.5 to 136 days for pancreatic events and from 146.5 to 320 days for biliary events. CONCLUSION: Both GLP-1RAs and tirzepatide are associated with disproportionate reporting of pancreatic and biliary adverse events in FAERS. Signals are influenced by indication, reporting behavior, and time effects and cannot be used to estimate incidence or prove causality. These signals suggest the need for further validation in real-world cohort studies. CI - Copyright (c) 2026 Wu, Li, Wang, Chen, Shi and Zhao. FAU - Wu, Yuanbin AU - Wu Y AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Li, Ke AU - Li K AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Yuhong AU - Wang Y AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Chen, Zike AU - Chen Z AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Min AU - Shi M AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhao, Jiawei AU - Zhao J AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20260928 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Female MH - Semaglutide MH - Male MH - United States/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - *Pancreas/drug effects MH - United States Food and Drug Administration MH - Middle Aged MH - *Biliary Tract Diseases/chemically induced/epidemiology MH - *Biliary Tract/drug effects MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13654742 OTO - NOTNLM OT - FAERS OT - biliary adverse events OT - glucagon-like peptide-1 receptor agonists OT - pancreatic adverse events OT - pharmacovigilance OT - tirzepatide COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/13 11:41 MHDA- 2026/10/13 11:42 PMCR- 2026/09/28 CRDT- 2026/10/13 05:32 PHST- 2026/07/19 00:00 [received] PHST- 2026/09/05 00:00 [revised] PHST- 2026/09/14 00:00 [accepted] PHST- 2026/10/13 11:42 [medline] PHST- 2026/10/13 11:41 [pubmed] PHST- 2026/10/13 05:32 [entrez] PHST- 2026/09/28 00:00 [pmc-release] AID - 10.3389/fendo.2026.1941948 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 28;17:1941948. doi: 10.3389/fendo.2026.1941948. eCollection 2026. PMID- 42862661 OWN - NLM STAT- MEDLINE DCOM- 20261012 LR - 20261014 IS - 0974-5181 (Electronic) IS - 0971-9784 (Linking) VI - 29 IP - 4 DP - 2026 Oct 1 TI - GLP-1 Receptor Agonists and Insulin Versus Insulin for Perioperative Glycemic Control in Patients with Type 2 Diabetes Undergoing Cardiac Surgery: A Systematic Review. PG - 464-470 LID - 10.4103/aca.aca_307_25 [doi] AB - Perioperative hyperglycemia is common in patients with type 2 diabetes undergoing cardiac surgery and is linked to adverse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer glucose-dependent insulinotropic effects and potential cardiac benefits, but their perioperative role remains uncertain. This review evaluated the efficacy and safety of GLP-1 RA therapy as an adjunct to insulin in this setting. Three electronic databases (PubMed, Cochrane, and Google Scholar) were searched for relevant articles up to October 2025. The primary endpoint was blood glucose levels during the perioperative period, while secondary endpoints included hypoglycemia incidence, total insulin requirement, time in target glucose range, and postoperative complications. Three randomized controlled trials (RCTs) including 168 patients with type 2 diabetes undergoing cardiac surgery were assessed. Perioperative use of liraglutide (subcutaneously in doses of 0.6-1.8 mg/day) was associated with preliminary evidence of improved glycemic control across preoperative, intraoperative, and early postoperative periods, including lower glucose levels, reduced glycemic variability, and fewer insulin adjustments, with a low incidence of hypoglycemia. However, heterogeneity in dosing, timing, and monitoring protocols across studies limits direct comparisons. Mild gastrointestinal adverse events, such as nausea and vomiting, were more frequent with liraglutide. One study reported exploratory immunometabolic effects in adipose tissue. Preliminary evidence from these heterogeneous studies suggests that adding liraglutide to insulin may improve perioperative glycemic control compared to insulin or placebo in patients with type 2 diabetes undergoing cardiac surgery. However, findings are limited by the small number of studies, methodological variability, and lack of long-term outcomes, necessitating larger, standardized trials. CI - Copyright (c) 2026 Annals of Cardiac Anaesthesia. FAU - Hassan, Danish AU - Hassan D AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Shakeel, Rida AU - Shakeel R AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Qaisi, Waleed AU - Qaisi W AD - Department of Medicine, An-Najah National University, Nablus, Palestine. FAU - Ahmed, Syed Rayyan AU - Ahmed SR AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Taj, Javeria AU - Taj J AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Adi, Mohammad AU - Adi M AD - Faculty of Medicine, Damascus University, Damascus, Syria. FAU - Ahmed, Ahmed Yousry AU - Ahmed AY AD - KFS University, Faculty of Medicine and Rehabilitation / Intern Student, Egypt. FAU - Abuzahra, Ammir AU - Abuzahra A AD - Faculty of Medicine, Hebron University, Hebron, Palestine. FAU - Sajid, Emad Uddin AU - Sajid EU AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Khan, Hamza Arshad AU - Khan HA AD - Department of Medicine, Al-Tibri Medical College, Isra University, Karachi, Pakistan. FAU - Basit, Tuba AU - Basit T AD - Department of Medicine, Dow University of Health Sciences, Dow Medical College, Karachi, Pakistan. FAU - Iqbal, Javed AU - Iqbal J AD - Department of Nursing, Hamad Medical Corporation, Doha, Qatar. FAU - Hussain, Asraf AU - Hussain A AD - Department of Internal Medicine, Chitwan Medical College, Bharatpur, Nepal. LA - eng PT - Journal Article PT - Systematic Review DEP - 20261012 PL - India TA - Ann Card Anaesth JT - Annals of cardiac anaesthesia JID - 9815987 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Insulin/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Glycemic Control/methods MH - *Cardiac Surgical Procedures/methods MH - *Perioperative Care/methods MH - Blood Glucose/drug effects MH - Liraglutide/therapeutic use MH - Hyperglycemia/drug therapy OTO - NOTNLM OT - Cardiac surgery OT - GLP-1 receptor agonist OT - glycemic control OT - insulin OT - liraglutide OT - perioperative management OT - type 2 diabetes EDAT- 2026/10/12 17:30 MHDA- 2026/10/12 17:31 CRDT- 2026/10/12 12:13 PHST- 2025/10/17 00:00 [received] PHST- 2025/12/02 00:00 [accepted] PHST- 2026/10/12 17:31 [medline] PHST- 2026/10/12 17:30 [pubmed] PHST- 2026/10/12 12:13 [entrez] AID - 00660469-202610000-00002 [pii] AID - 10.4103/aca.aca_307_25 [doi] PST - ppublish SO - Ann Card Anaesth. 2026 Oct 1;29(4):464-470. doi: 10.4103/aca.aca_307_25. Epub 2026 Oct 12. PMID- 42860380 OWN - NLM STAT- MEDLINE DCOM- 20261011 LR - 20261014 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 22 IP - 10 DP - 2026 Oct TI - The effects of improved access to diabetes medications on risk of Alzheimer's disease and related dementias. PG - e71794 LID - 10.1002/alz.71794 [doi] LID - e71794 AB - INTRODUCTION: Diabetes is associated with elevated risk of Alzheimer's disease and related dementias (ADRD). Disease management with pharmaceutical therapies may mitigate this increased risk, but access and use of diabetes therapies are limited, especially for persons at highest risk of ADRD. METHODS: Using 10 years of data on Americans aged 51 and older with diabetes, we employed dynamic microsimulation to analyze the impact of increased utilization of glucagon-like peptide 1 receptor agonists (GLP1s) and sodium-glucose cotransporter-2 inhibitors (SGLT2s) on ADRD incidence. RESULTS: Over 10 years, utilization of GLP1s and SGLT2s by people with diabetes and HbA1c > 7 could avert 76,000-201,000 ADRD cases. The risk reduction is largest for Black and Hispanic individuals and individuals with HbA1c > 8. DISCUSSION: This study shows that improving diabetes management can lead to large reductions in ADRD risk. Improved adherence and access for those with higher HbA1c and higher risk of ADRD will have the largest benefit. CI - (c) 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Barthold, Douglas AU - Barthold D AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, Washington, USA. FAU - Zissimopoulos, Julie AU - Zissimopoulos J AD - Price School of Public Policy, Leonard D. Schaeffer Institute for Public Policy and Government, University of Southern California, Los Angeles, California, USA. FAU - Basu, Anirban AU - Basu A AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, Washington, USA. FAU - Tysinger, Bryan AU - Tysinger B AD - Price School of Public Policy, Leonard D. Schaeffer Institute for Public Policy and Government, University of Southern California, Los Angeles, California, USA. LA - eng GR - K01 AG071843/AG/NIA NIH HHS/United States GR - P30 AG043073/AG/NIA NIH HHS/United States GR - R33 AG081811/AG/NIA NIH HHS/United States PT - Journal Article PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Alzheimer Disease/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - *Dementia/epidemiology/prevention & control MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Aged MH - Male MH - Middle Aged MH - Incidence MH - *Health Services Accessibility MH - *Diabetes Mellitus/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy PMC - PMC13655229 OTO - NOTNLM OT - ADRD OT - ADRD prevention OT - Alzheimer's disease OT - Alzheimer's disease and related dementias OT - GLP1 OT - SGLT2 OT - access to prescription drugs OT - chronic disease management OT - dementia OT - dementia prevention OT - diabetes OT - diabetes management OT - glucagon-like peptide 1 receptor agonists OT - sodium-glucose cotransporter-2 inhibitors COIS- The authors have no conflicts of interest to declare. Author disclosures are available in the Supporting Information. EDAT- 2026/10/12 05:32 MHDA- 2026/10/12 05:33 PMCR- 2026/10/11 CRDT- 2026/10/11 23:02 PHST- 2026/04/14 00:00 [revised] PHST- 2025/12/23 00:00 [received] PHST- 2026/08/03 00:00 [accepted] PHST- 2026/10/12 05:33 [medline] PHST- 2026/10/12 05:32 [pubmed] PHST- 2026/10/11 23:02 [entrez] PHST- 2026/10/11 00:00 [pmc-release] AID - ALZ71794 [pii] AID - 10.1002/alz.71794 [doi] PST - ppublish SO - Alzheimers Dement. 2026 Oct;22(10):e71794. doi: 10.1002/alz.71794. PMID- 42859665 OWN - NLM STAT- MEDLINE DCOM- 20261011 LR - 20261012 IS - 1179-142X (Electronic) IS - 1179-142X (Linking) VI - 19 DP - 2026 TI - Severe Euglycemic Diabetic Ketoacidosis After Semaglutide-Associated Poor Intake Despite Empagliflozin Discontinuation: A Case Report. PG - 650090 LID - 10.2147/IMCRJ.S650090 [doi] LID - 650090 AB - Euglycemic diabetic ketoacidosis (EDKA) may be overlooked when serum glucose is near normal. A 68-year-old woman with long-standing type 2 diabetes developed approximately three weeks of nausea, intermittent vomiting and diarrhea, and minimal oral intake after semaglutide initiation at 0.25 mg once weekly for four weeks followed by 0.5 mg once weekly. Patient and family medication reconciliation indicated that she had stopped empagliflozin, metformin, and pioglitazone approximately two weeks before presentation but continued semaglutide, with the last dose approximately eight days before admission. She presented with weakness, dyspnea, slowed speech, and disorientation. Initial testing showed glucose 132 mg/dL, venous pH 7.13, bicarbonate 9 mmol/L, anion gap 26 mmol/L, and beta-hydroxybutyrate 99.5 mg/dL. She improved with intravenous crystalloid, dextrose-containing fluids, insulin infusion, and electrolyte replacement. The temporal association is consistent with a clinically plausible contribution from semaglutide-associated gastrointestinal intolerance and carbohydrate depletion to EDKA despite reported prior empagliflozin discontinuation. Normal glucose should not delay ketone and acid-base testing when compatible symptoms and poor intake are present. CI - (c) 2026 Niknam and Niknam. FAU - Niknam, Kianoush AU - Niknam K AUID- ORCID: 0000-0002-3506-0463 AD - Department of Internal Medicine, Legacy Salmon Creek Medical Center, Vancouver, WA, USA. FAU - Niknam, Tahmoores AU - Niknam T AUID- ORCID: 0009-0000-3328-9371 AD - Department of Pulmonary and Critical Care, Shiraz University of Medical Sciences, Shiraz, Iran. LA - eng PT - Case Reports PT - Journal Article DEP - 20261006 PL - New Zealand TA - Int Med Case Rep J JT - International medical case reports journal JID - 101566269 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - HDC1R2M35U (empagliflozin) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - Female MH - Semaglutide MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Benzhydryl Compounds/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Diabetic Ketoacidosis/chemically induced/therapy/diagnosis MH - *Glucosides/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Insulin PMC - PMC13653545 OTO - NOTNLM OT - GLP-1 receptor agonist OT - case report OT - euglycemic diabetic ketoacidosis OT - semaglutide OT - starvation COIS- The authors declare no conflicts of interest. EDAT- 2026/10/11 05:38 MHDA- 2026/10/11 05:39 PMCR- 2026/10/06 CRDT- 2026/10/11 04:23 PHST- 2026/08/20 00:00 [received] PHST- 2026/10/04 00:00 [accepted] PHST- 2026/10/11 05:39 [medline] PHST- 2026/10/11 05:38 [pubmed] PHST- 2026/10/11 04:23 [entrez] PHST- 2026/10/06 00:00 [pmc-release] AID - 650090 [pii] AID - 10.2147/IMCRJ.S650090 [doi] PST - epublish SO - Int Med Case Rep J. 2026 Oct 6;19:650090. doi: 10.2147/IMCRJ.S650090. eCollection 2026. PMID- 42854065 OWN - NLM STAT- MEDLINE DCOM- 20261009 LR - 20261014 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 41 DP - 2026 Oct 9 TI - Short-term clinical efficacy and recorded adverse events of semaglutide combined with dapagliflozin in patients with type 2 diabetes mellitus and chronic kidney disease. PG - e51019 LID - 10.1097/MD.0000000000051019 [doi] LID - e51019 AB - Type 2 diabetes mellitus (T2DM) complicated by chronic kidney disease (CKD) is associated with persistent hyperglycemia, progressive renal impairment, systemic inflammation, and an increased risk of adverse clinical outcomes. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have shown metabolic and cardiorenal benefits, but clinical evidence regarding their combined use in patients with T2DM and CKD remains limited. This retrospective observational study included 126 patients with T2DM complicated by CKD who were treated at our hospital between March 2023 and July 2024. Patients were identified through a review of electronic medical records and the application of predefined eligibility criteria. Treatment groups reflected the actual regimen documented in the medical record rather than random allocation. The final analytic cohort comprised 42 patients in each group; the equal group size reflected the eligible records with complete baseline and 8-week follow-up data available in each treatment category during the study period rather than a prospective 1:1:1 enrollment target. The treatment duration was 8 weeks. Glycemic indices, renal function-related parameters, inflammatory markers, clinical response, and recorded adverse events were compared among the 3 groups. After 8 weeks of treatment, fasting plasma glucose, 2-hour postprandial plasma glucose, hemoglobin A1c, blood urea nitrogen, serum creatinine, 24-hour urinary protein, erythrocyte sedimentation rate, interleukin-6, and high-sensitivity C-reactive protein were significantly reduced in all 3 groups compared with baseline. The combination group showed greater short-term reductions in glycemic indices, renal function-related parameters, and inflammatory markers than either monotherapy group. The overall clinical response rate was significantly higher in the combination group than in the dapagliflozin or semaglutide group. In patients with T2DM complicated by CKD, semaglutide combined with dapagliflozin was associated with greater short-term improvements in glycemic control, inflammatory markers, and renal function-related indicators, as well as a higher exploratory clinical response rate, than either monotherapy. No increase in recorded adverse events was detected during 8 weeks of treatment. Because of the retrospective design, modest sample size, and short observation period, these findings should not be interpreted as demonstrating definitive long-term renal benefit or equivalent long-term safety. Further large-scale prospective studies with standardized renal outcomes are required. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, LLC. FAU - Gong, Cheng AU - Gong C AD - Department of Geriatric Medicine, Yangtze River Shipping General Hospital, Hubei, China. FAU - Luo, Qiong AU - Luo Q AD - Department of Endocrinology and Metabolism, Yangtze River Shipping General Hospital, Hubei, China. FAU - Li, Qin AU - Li Q AUID- ORCID: 0009-0008-8832-7089 AD - Department of Endocrinology and Metabolism, Yangtze River Shipping General Hospital, Hubei, China. LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/adverse effects/therapeutic use/administration & dosage MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Glucosides/adverse effects/therapeutic use/administration & dosage MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Retrospective Studies MH - *Semaglutide/administration & dosage/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Treatment Outcome PMC - PMC13657616 OTO - NOTNLM OT - chronic kidney disease OT - dapagliflozin OT - inflammation OT - renal function OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors have no funding and conflicts of interest to declare. EDAT- 2026/10/09 17:34 MHDA- 2026/10/09 17:35 PMCR- 2026/10/09 CRDT- 2026/10/09 14:43 PHST- 2026/05/06 00:00 [received] PHST- 2026/09/18 00:00 [accepted] PHST- 2026/10/09 17:35 [medline] PHST- 2026/10/09 17:34 [pubmed] PHST- 2026/10/09 14:43 [entrez] PHST- 2026/10/09 00:00 [pmc-release] AID - 00005792-202610090-00067 [pii] AID - MD-D-26-06895 [pii] AID - 10.1097/MD.0000000000051019 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 Oct 9;105(41):e51019. doi: 10.1097/MD.0000000000051019. PMID- 42851902 OWN - NLM STAT- MEDLINE DCOM- 20261009 LR - 20261010 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Beyond efficacy: the treatment lifecycle of incretin and multi-receptor agonists. PG - 1902185 LID - 10.3389/fendo.2026.1902185 [doi] LID - 1902185 AB - Incretin and multi-receptor agonist therapies have delivered the widest range of cardiometabolic benefit of any pharmacological class in a generation, with documented benefit across obesity, type 2 diabetes, cardiovascular and renal outcomes, heart failure with preserved ejection fraction, obstructive sleep apnea, and metabolic-dysfunction-associated steatohepatitis. A substantial fraction of the cardiovascular benefit is weight independent. The pivotal trial evidence is now mature, extending to the dedicated tirzepatide cardiovascular outcome program. The clinical and system-level processes that govern long-term cardiovascular and metabolic benefit, however, lie largely outside the efficacy envelope that these trials measure. Real-world persistence is approximately one-third at 12 months in non-diabetic obesity. Discontinuation is dominated by cost rather than therapeutic failure. Weight and cardiometabolic gains revert toward baseline within months of abrupt cessation. Cyclical use has emerged as a common real-world pattern among adults who discontinue and then restart therapy. Our review proposes a lifecycle framework that organizes the evidence along the patient journey from initiation through titration, on-treatment trajectory, adverse-event landscape, persistence, discontinuation, and reinitiation. Tirzepatide serves as the analytical center of gravity; the selective GLP-1 receptor agonist literature serves as the mature comparator. Seven analytical positions are advanced, and five specific trial designs are named as the research agenda the field requires, four of which remain unaddressed. The work ahead is to align trials, prescribing pathways, and access systems with the chronic-pharmacotherapy reality of the class. CI - Copyright (c) 2026 Rabbani, El-Tanani, Matalka and Rizzo. FAU - Rabbani, Syed Arman AU - Rabbani SA AD - RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - El-Tanani, Mohamed AU - El-Tanani M AD - RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Matalka, Ismail I AU - Matalka II AD - RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Rizzo, Manfredi AU - Rizzo M AD - School of Medicine, University of Palermo, Palermo, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260924 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - *Cardiovascular Diseases/drug therapy PMC - PMC13646783 OTO - NOTNLM OT - GLP-1 receptor agonist (RA) OT - cardiovascular OT - incretin OT - multi-receptor agonists OT - obesity OT - real-world OT - tirzepatide OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/09 11:40 MHDA- 2026/10/09 11:41 PMCR- 2026/09/24 CRDT- 2026/10/09 06:03 PHST- 2026/06/06 00:00 [received] PHST- 2026/07/29 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/10/09 11:41 [medline] PHST- 2026/10/09 11:40 [pubmed] PHST- 2026/10/09 06:03 [entrez] PHST- 2026/09/24 00:00 [pmc-release] AID - 10.3389/fendo.2026.1902185 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 24;17:1902185. doi: 10.3389/fendo.2026.1902185. eCollection 2026. PMID- 42849689 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 1037 DP - 2026 Dec 10 TI - GLP-1 receptor biology and the therapeutic role of incretin-based agonists in metabolic diseases. PG - 179406 LID - S0014-2999(26)00888-5 [pii] LID - 10.1016/j.ejphar.2026.179406 [doi] AB - Type 2 diabetes (T2DM) and obesity represent a growing global health burden, sharing underlying pathophysiological mechanisms such as impaired insulin signalling and chronic low-grade inflammation. The discovery of the incretin effect opened the way for agonist therapies targeting the glucagon-like peptide-1 receptor (GLP-1R) as therapies capable of addressing the metabolic dysregulation common to both diseases simultaneously. This review examines the biology of GLP-1 and the incretin system, with a focus on the structure and signalling mechanisms of GLP-1R, including biased agonism and receptor trafficking. The clinical effectiveness of stable, long-acting GLP-1RAs is evaluated across three therapeutic domains: T2DM management, obesity treatment, and emerging cardiovascular protection. Current evidence demonstrates that GLP-1RAs, which induce insulin secretion and suppress appetite, achieve superior glycaemic control and significant weight reduction compared with conventional therapies, with emerging cardiovascular benefits now extending to non-diabetic patients as well. The shift towards dual and triple receptor agonists, such as tirzepatide and retatrutide, together with biased agonist design, is a promising development for further improvements in effectiveness. Progress in oral formulations of GLP-1RAs may also improve tolerability and patient adherence. Nevertheless, important challenges remain, including gastrointestinal side effects, weight regain upon discontinuation, loss of lean body mass, and unresolved questions regarding long-term safety. In conclusion, while GLP-1R-based therapies represent a major therapeutic advancement, particularly for T2DM patients, their broader application in obesity management requires careful patient selection, continued long-term safety monitoring, and integration with lifestyle interventions. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Koceva, Elena AU - Koceva E AD - Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, 9747 AG, the Netherlands. FAU - Moll, Gert N AU - Moll GN AD - Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, 9747 AG, the Netherlands. Electronic address: g.n.moll@rug.nl. LA - eng PT - Journal Article PT - Review DEP - 20261008 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/metabolism/agonists/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Obesity/drug therapy/metabolism MH - *Metabolic Diseases/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Tirzepatide MH - Signal Transduction/drug effects OTO - NOTNLM OT - Diabetes OT - G protein-coupled receptor OT - Obesity COIS- Declaration of competing interests The authors declare that they have no conflict of interest. EDAT- 2026/10/08 23:31 MHDA- 2026/10/27 23:27 CRDT- 2026/10/08 19:38 PHST- 2026/07/13 00:00 [received] PHST- 2026/09/17 00:00 [revised] PHST- 2026/10/07 00:00 [accepted] PHST- 2026/10/27 23:27 [medline] PHST- 2026/10/08 23:31 [pubmed] PHST- 2026/10/08 19:38 [entrez] AID - S0014-2999(26)00888-5 [pii] AID - 10.1016/j.ejphar.2026.179406 [doi] PST - ppublish SO - Eur J Pharmacol. 2026 Dec 10;1037:179406. doi: 10.1016/j.ejphar.2026.179406. Epub 2026 Oct 8. PMID- 42842171 OWN - NLM STAT- MEDLINE DCOM- 20261007 LR - 20261010 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Oct 7 TI - Disparities in GLP-1RA and SGLT2i Uptake: a Systematic Review and an Equity-First Framework for Cardiovascular-Kidney-Metabolic Care. LID - 108 [pii] LID - 10.1007/s11886-026-02431-y [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve cardiovascular, kidney, and metabolic outcomes, but equitable access remains a major challenge. This review synthesizes U.S. evidence on disparities in their use and proposes an Equity-First Framework for cardiovascular-kidney-metabolic care to advance pharmacoequity. RECENT FINDINGS: Across 100 U.S.o studies published from 2013 to 2026, the most consistent inequities involved race and ethnicity, socioeconomic status, insurance coverage, age, and access to specialty care, while geographic and sex-related patterns were more heterogeneous. Black and Hispanic patients, Medicaid beneficiaries, lower-income populations, and older adults frequently experienced lower prescribing or initiation. Although use increased following landmark trials and guideline updates, uptake remained well below the eligible population, and disparities persisted or widened for some newer agents. Barriers spanned societal and policy, health-system, provider, patient, and therapy-related domains. Achieving pharmacoequity will require coordinated, multilevel implementation. Our framework links equity-relevant factors and implementation determinants to actionable strategies, including equity monitoring, identification and engagement of eligible patients, equitable care pathways, reduction of structural access barriers, and support for clinicians and patients. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chu, Andre H AU - Chu AH AUID- ORCID: 0009-0001-2113-0897 AD - Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Olsen, Boomer AU - Olsen B AD - Division of General Internal Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Choi, Joshua AU - Choi J AD - Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Sarwal, Amara AU - Sarwal A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Sakaguchi, Farrant AU - Sakaguchi F AD - Department of Family Medicine and Public Health, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Akramimoghadam, Farideh AU - Akramimoghadam F AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Jacobs, Joshua A AU - Jacobs JA AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Reddy, Deepika AU - Reddy D AD - Utah Diabetes and Endocrinology Center, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Bhatt, Nikhil AU - Bhatt N AD - Montgomery Blair High School, Silver Spring, MD, USA. FAU - Iyalomhe, Oshozimhede AU - Iyalomhe O AD - University of Maryland Baltimore, Baltimore, MD, USA. FAU - Katkam, Niharika AU - Katkam N AD - Division of Nephrology and Hypertension, Department of Nutrition and Integrative Physiology, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Wahl, Matthew AU - Wahl M AD - Division of Endocrinology, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Choudhary, Aarya AU - Choudhary A AD - Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Kukhareva, Polina AU - Kukhareva P AUID- ORCID: 0000-0002-5576-1486 AD - Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT, USA. polina.kukhareva@utah.edu. LA - eng GR - 1OT2OD032581-04/National Institutes of Health AIM-AHEAD Research Fellowship/ GR - K01DK142045/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Systematic Review DEP - 20261007 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Healthcare Disparities MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Cardiovascular Diseases/drug therapy MH - United States MH - Health Services Accessibility MH - Socioeconomic Disparities in Health MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes, health equity OT - Glucagon-like peptide-1 receptor agonists OT - Health disparities OT - Implementation science OT - Pharmacoequity OT - Sodium-glucose cotransporter-2 inhibitors COIS- Declarations. Competing interests: The authors declare no competing interests. Use of Artificial Intelligence: Large language models were used to assist data extraction and risk-of-bias assessment, as described in the Methods and Supplement. All LLM-generated outputs were independently checked against the source articles by human reviewers and corrected as needed; no LLM output was accepted without human validation. AI-assisted improvements may include wording and formatting changes to the texts, but do not include generative editorial work and autonomous content creation. Human and Animal Rights and Informed Consent: No animal or human subjects were used in this study. EDAT- 2026/10/07 17:33 MHDA- 2026/10/07 17:34 CRDT- 2026/10/07 12:28 PHST- 2026/08/25 00:00 [received] PHST- 2026/10/02 00:00 [accepted] PHST- 2026/10/07 17:34 [medline] PHST- 2026/10/07 17:33 [pubmed] PHST- 2026/10/07 12:28 [entrez] AID - 10.1007/s11886-026-02431-y [pii] AID - 10.1007/s11886-026-02431-y [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Oct 7;28(1):108. doi: 10.1007/s11886-026-02431-y. PMID- 42831108 OWN - NLM STAT- MEDLINE DCOM- 20261005 LR - 20261006 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - GLP-1 Receptor Agonists Versus DPP-4 Inhibitors and Incident Dementia Risk in COVID-19 Survivors with Type 2 Diabetes: A Target Trial Emulation Study. PG - 638249 LID - 10.2147/DDDT.S638249 [doi] LID - 638249 AB - PURPOSE: Type 2 diabetes mellitus (T2DM) and COVID-19 are independently associated with an elevated risk of dementia, and COVID-19 survivors with T2DM may represent a clinically vulnerable population in whom metabolic, inflammatory, and vascular factors coexist. However, whether antidiabetic treatment choice is associated with incident dementia risk in this population remains unknown. METHODS: In this target trial emulation using the TriNetX US Collaborative Network, we compared COVID-19 survivors aged >/=50 years with T2DM initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy with those initiating dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy between January 1, 2020 and December 31, 2024. We applied an active-comparator, new-user design with a 90-day survivor landmark and 1:1 propensity score matching. The primary outcome was incident all-cause dementia (a composite of vascular dementia, Alzheimer's disease, and other dementias). Secondary outcomes included dementia subtypes, mild cognitive impairment, glycemic outcomes, and all-cause mortality. RESULTS: After matching, 25,263 patients per group were followed for up to 6 years (median, 919 days [GLP-1RA] vs 955 days [DPP-4i]). GLP-1RA initiation was associated with a lower hazard of incident dementia (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.58-0.72), vascular dementia (HR, 0.67; 95% CI, 0.52-0.85), and Alzheimer's disease (HR, 0.74; 95% CI, 0.59-0.93), as well as more favorable glycemic control and lower all-cause mortality (HR, 0.63; 95% CI, 0.59-0.68). The estimate for mild cognitive impairment was borderline (HR, 0.87; 95% CI, 0.75-1.00) and not consistently supported across sensitivity analyses. The association with incident dementia remained evident after the 6-month landmark analysis (HR, 0.66; 95% CI, 0.58-0.75) and was consistent across sensitivity and subgroup analyses. CONCLUSION: Among COVID-19 survivors with T2DM, GLP-1RA initiation was associated with a lower hazard of incident dementia than DPP-4i initiation. These hypothesis-generating results warrant confirmation before they can be used to inform clinical decision-making. CI - (c) 2026 Hung et al. FAU - Hung, Kuo-Chuan AU - Hung KC AUID- ORCID: 0000-0002-4507-8085 AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Yu, Ting-Sian AU - Yu TS AD - Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Liu, Ping-Hsin AU - Liu PH AD - Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Lai, Yi-Chen AU - Lai YC AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Chen, I-Wen AU - Chen IW AUID- ORCID: 0009-0004-7122-6901 AD - Department of Anesthesiology, Chi Mei Hospital, Liouying, Tainan, Taiwan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260930 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *COVID-19/complications/epidemiology MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Dementia/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Female MH - Aged MH - Middle Aged MH - Incidence MH - Survivors PMC - PMC13634317 OTO - NOTNLM OT - COVID-19 survivors OT - DPP-4 inhibitor OT - dementia OT - glucagon-like peptide-1 receptor agonist OT - target trial emulation OT - type 2 diabetes mellitus COIS- The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper. EDAT- 2026/10/05 05:31 MHDA- 2026/10/05 05:32 PMCR- 2026/09/30 CRDT- 2026/10/05 04:21 PHST- 2026/07/06 00:00 [received] PHST- 2026/09/25 00:00 [accepted] PHST- 2026/10/05 05:32 [medline] PHST- 2026/10/05 05:31 [pubmed] PHST- 2026/10/05 04:21 [entrez] PHST- 2026/09/30 00:00 [pmc-release] AID - 638249 [pii] AID - 10.2147/DDDT.S638249 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Sep 30;20:638249. doi: 10.2147/DDDT.S638249. eCollection 2026. PMID- 42830469 OWN - NLM STAT- MEDLINE DCOM- 20261005 LR - 20261007 IS - 2052-1707 (Electronic) IS - 2052-1707 (Linking) VI - 14 IP - 5 DP - 2026 Oct TI - Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications. PG - e70329 LID - 10.1002/prp2.70329 [doi] LID - e70329 AB - Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1's brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure (BP), lipid profile, obesity and major adverse cardiovascular event. Although the BP-lowering effect of GLP-1R agonists is well documented in clinical trials, the underlying molecular mechanisms remain incompletely defined, since most evidence comes from animal and in vitro models rather than human studies. This gap limits translating the clinical benefit into targeted, mechanism-based practice. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1R agonists, their effects on BP and how they exert their actions. Evidence indicates GLP-1R agonists produce a modest, consistent reduction in systolic blood pressure, heterogeneous across agents and confined to patients with elevated baseline BP, reflecting vascular, renal and anti-inflammatory mechanisms rather than a single pathway. Although animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1R agonists on BP regulation and their underlying mechanisms. CI - (c) 2026 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and John Wiley & Sons Ltd. FAU - Alharbi, Nora H J AU - Alharbi NHJ AUID- ORCID: 0009-0008-4268-2552 AD - Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia. LA - eng PT - Journal Article PT - Review PL - United States TA - Pharmacol Res Perspect JT - Pharmacology research & perspectives JID - 101626369 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Blood Pressure/drug effects MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/metabolism/agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Incretins/pharmacology MH - Cardiovascular Diseases PMC - PMC13635475 OTO - NOTNLM OT - GLP-1 receptor agonists OT - blood pressure OT - cardiovascular outcomes OT - endothelial function OT - hypertension COIS- The author declares no conflicts of interest. EDAT- 2026/10/05 05:31 MHDA- 2026/10/05 05:32 PMCR- 2026/10/04 CRDT- 2026/10/05 00:23 PHST- 2026/08/27 00:00 [revised] PHST- 2026/02/10 00:00 [received] PHST- 2026/09/22 00:00 [accepted] PHST- 2026/10/05 05:32 [medline] PHST- 2026/10/05 05:31 [pubmed] PHST- 2026/10/05 00:23 [entrez] PHST- 2026/10/04 00:00 [pmc-release] AID - PRP270329 [pii] AID - 10.1002/prp2.70329 [doi] PST - ppublish SO - Pharmacol Res Perspect. 2026 Oct;14(5):e70329. doi: 10.1002/prp2.70329. PMID- 42829714 OWN - NLM STAT- MEDLINE DCOM- 20261004 LR - 20261005 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Prior Use of GLP-1 Receptor Agonists versus SGLT2 Inhibitors and Clinical Outcomes After Sepsis in Patients with Type 2 Diabetes: A Propensity Score-Matched Cohort Study. PG - 642220 LID - 10.2147/DDDT.S642220 [doi] LID - 642220 AB - BACKGROUND: Whether pre-existing glucose-lowering therapy influences outcomes after sepsis remains uncertain. We compared clinical outcomes among patients with type 2 diabetes (T2D) who developed sepsis according to prior GLP-1 receptor agonists (GLP-1RAs) or SGLT2 inhibitors (SGLT2is) use. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with T2D who developed sepsis had received a GLP-1RA or an SGLT2i within 3 months before sepsis were identified. After 1:1 propensity score matching, 11,969 patients were included in each group. The primary outcome was 90-day all-cause mortality. Secondary outcomes included major adverse cardiovascular event (MACE), major adverse kidney event (MAKE), intensive care unit (ICU) admission, major adverse cardiac and cerebrovascular event (MACCE), septic shock, and acute respiratory failure. RESULTS: Compared with prior SGLT2i use, prior GLP-1RA use was associated with lower 90-day all-cause mortality (incidence rate, 48.6 vs 60.6 per 100 person-years; HR, 0.81; 95% CI, 0.75-0.88; E-value: 1.6) and lower risks of MACE (HR, 0.77; 0.65-0.91; E-value, 1.7), myocardial infarction (HR, 0.82; 0.67-0.99; E-value, 1.7), ICU admission (HR, 0.89; 0.84-0.94; E-value, 1.4), and MACCE (HR, 0.86; 0.74-0.99; E-value, 1.5). No significant difference was observed for septic shock (HR, 0.87; 95% CI, 0.74-1.02), acute respiratory failure (HR, 0.94; 95% CI, 0.83-1.06), or MAKE (HR, 1.08; 95% CI, 0.92-1.27). The mortality benefit remained consistent through 365 days and across all prespecified subgroups. After Holm correction for multiple comparisons across the seven secondary outcomes, only the associations with MACE (adjusted P=0.012) and ICU admission (adjusted P<0.007) remained statistically significant, while those with MACCE, myocardial infarction, MAKE, septic shock, and acute respiratory failure did not. CONCLUSION: Among patients with T2D who developed sepsis, prior GLP-1RA use was associated with lower mortality and select cardiovascular/renal risks than prior SGLT2i use, though roughly half of secondary outcomes showed no significant difference. Exposure was defined at the drug-class rather than individual-agent level, and modest E-values alongside baseline imbalances before matching suggest residual confounding cannot be excluded. These hypothesis-generating findings warrant confirmation in prospective studies. CI - (c) 2026 Liu et al. FAU - Liu, Hao-Hsun AU - Liu HH AD - Department of Intensive Care Medicine, Chi Mei Hospital, Liouying, Taiwan. FAU - Huang, Sheng-Chi AU - Huang SC AD - Department of General Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AUID- ORCID: 0000-0002-3290-1909 AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Chan, Khee-Siang AU - Chan KS AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260929 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sepsis/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage/pharmacology MH - Female MH - Male MH - Propensity Score MH - Middle Aged MH - Aged MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome PMC - PMC13633727 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - mortality OT - sepsis OT - sodium-glucose cotransporter-2 inhibitor OT - type 2 diabetes mellitus COIS- The authors declare no competing interests. EDAT- 2026/10/04 05:36 MHDA- 2026/10/04 05:37 PMCR- 2026/09/29 CRDT- 2026/10/04 04:09 PHST- 2026/07/21 00:00 [received] PHST- 2026/09/25 00:00 [accepted] PHST- 2026/10/04 05:37 [medline] PHST- 2026/10/04 05:36 [pubmed] PHST- 2026/10/04 04:09 [entrez] PHST- 2026/09/29 00:00 [pmc-release] AID - 642220 [pii] AID - 10.2147/DDDT.S642220 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Sep 29;20:642220. doi: 10.2147/DDDT.S642220. eCollection 2026. PMID- 42827168 OWN - NLM STAT- MEDLINE DCOM- 20261002 LR - 20261008 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Oct 3 TI - Comorbid Cardiovascular-Liver Disease Disparities: Current Understanding and Future Directions. LID - 102 [pii] LID - 10.1007/s11886-026-02426-9 [doi] AB - PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease and a multisystem cardiometabolic disorder. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in this population. This review examines disparities in the recognition and management of coexisting cardiovascular and metabolic liver disease. RECENT FINDINGS: Shared metabolic and inflammatory pathways link liver disease with obesity, type 2 diabetes, hypertension, and CVD. Differences in measured disease prevalence across racial and ethnic groups must be interpreted separately from genetic susceptibility and in the context of structural inequities, diagnostic practices, and access to care. Socioeconomic disadvantage and sex- and gender-related barriers may further affect diagnosis and treatment. Resmetirom and semaglutide have expanded treatment options for selected adults with metabolic dysfunction-associated steatohepatitis (MASH), but unequal access to fibrosis assessment, insurance coverage, and longitudinal care may limit their benefits. An equity-centered cardio-hepatology framework should integrate early risk identification, stepwise noninvasive fibrosis assessment, individualized cardiovascular prevention, and access to indicated liver-directed therapies. Treatment and quality measures should reflect clinical eligibility rather than medication use alone. Inclusive research and coordinated long-term care are needed to evaluate whether these strategies narrow disparities. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Hafez, Abdelrahman AU - Hafez A AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. AD - Department of Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Nour, Mohamed AU - Nour M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. Ibrahim.ramzi@mayo.edu. AD - Department of Cardiovascular Medicine, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA. Ibrahim.ramzi@mayo.edu. FAU - Othman, Jenna AU - Othman J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Mohamed, Mohamed Reyad AU - Mohamed MR AD - Department of Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Awad, Kamal AU - Awad K AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Zanco, Julia AU - Zanco J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - De Sousa Barzon Serra, Vinicius AU - De Sousa Barzon Serra V AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Elbsiony, Mahmoud AU - Elbsiony M AD - Department of Cardiovascular Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Alsidawi, Said AU - Alsidawi S AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Lester, Steven J AU - Lester SJ AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Ayoub, Chadi AU - Ayoub C AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article PT - Review DEP - 20261003 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/epidemiology/therapy MH - Comorbidity MH - *Healthcare Disparities MH - Prevalence MH - Diabetes Mellitus, Type 2/epidemiology MH - Obesity/epidemiology MH - *Fatty Liver/epidemiology/therapy MH - Semaglutide MH - *Liver Diseases/epidemiology/therapy MH - Risk Factors MH - Non-alcoholic Fatty Liver Disease/epidemiology MH - Socioeconomic Disparities in Health OTO - NOTNLM OT - Cardio-hepatology OT - Cardiovascular disease OT - Diabetes OT - Health disparities OT - Metabolic dysfunction-associated steatohepatitis OT - Metabolic dysfunction-associated steatotic liver disease OT - Obesity OT - Resmetirom OT - Semaglutide COIS- Declarations. Conflict of Interest: Chadi Ayoub reports a stipend received as Section Editor from Circulation: Cardiovascular Imaging, outside the submitted work. The remaining authors have nothing to disclose. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. EDAT- 2026/10/03 05:33 MHDA- 2026/10/03 05:34 CRDT- 2026/10/02 23:19 PHST- 2026/08/26 00:00 [received] PHST- 2026/09/28 00:00 [accepted] PHST- 2026/10/03 05:34 [medline] PHST- 2026/10/03 05:33 [pubmed] PHST- 2026/10/02 23:19 [entrez] AID - 10.1007/s11886-026-02426-9 [pii] AID - 10.1007/s11886-026-02426-9 [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Oct 3;28(1):102. doi: 10.1007/s11886-026-02426-9. PMID- 42824923 OWN - NLM STAT- MEDLINE DCOM- 20261002 LR - 20261003 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Predictors of treatment response to semaglutide for weight management. PG - 1893511 LID - 10.3389/fendo.2026.1893511 [doi] LID - 1893511 AB - The emergence of weekly, injectable glucagon-like peptide-1 (GLP-1) receptor agonists has revolutionized the obesity management landscape. Numerous studies have shown high efficacy as well as great variability in weight loss, highlighting the need for this mini review, summarizing current evidence about predictors of semaglutide-related weight loss. The first well-known determinant of semaglutide-induced weight loss is the presence of type 2 DM which is associated with significantly lower body weight reduction. The second predictor is sex, with females exhibiting a greater weight loss than males by a mean 6%. In addition, higher maintenance dose of 7.2 mg is superior to standard 2.4 mg dose in weight reduction by a mean 3%. There is no clear association of age and baseline body mass index with the magnitude of semaglutide-driven weight loss, except for the possibility of adolescence enhancing and overweight reducing this treatment effect. The potential impact of genetic polymorphisms of individual treatment response to semaglutide remains incompletely understood, limited so far to a modest effect of specific variants in GLP1 receptor gene. Another potential predictor of response could be obesity phenotype, with preliminary data supporting greater effectiveness of semaglutide in individuals with ''hungry gut'' phenotype. Type of lifestyle modification does not seem to have a significant effect on the variability of semaglutide-driven weight loss. Further studies are needed to expand knowledge about predictors of response to semaglutide, paving the way for validated predictive models in order to guide clinical decision-making and provision of personalized obesity care. CI - Copyright (c) 2026 Tzoulis. FAU - Tzoulis, Ploutarchos AU - Tzoulis P AD - Research Department of Experimental and Translational Medicine, University College London, London, United Kingdom. LA - eng PT - Journal Article PT - Review DEP - 20260917 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy MH - *Weight Loss/drug effects MH - *Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/genetics PMC - PMC13628350 OTO - NOTNLM OT - GLP-1 agonist OT - antiobesity agent OT - obesity OT - semaglutide OT - weight loss COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/02 13:36 MHDA- 2026/10/02 13:37 PMCR- 2026/09/17 CRDT- 2026/10/02 06:56 PHST- 2026/05/28 00:00 [received] PHST- 2026/07/14 00:00 [revised] PHST- 2026/08/24 00:00 [accepted] PHST- 2026/10/02 13:37 [medline] PHST- 2026/10/02 13:36 [pubmed] PHST- 2026/10/02 06:56 [entrez] PHST- 2026/09/17 00:00 [pmc-release] AID - 10.3389/fendo.2026.1893511 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 17;17:1893511. doi: 10.3389/fendo.2026.1893511. eCollection 2026. PMID- 42823110 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261003 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 10 DP - 2026 Oct 1 TI - Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues. PG - e120507 LID - 10.1136/bmjopen-2026-120507 [doi] LID - e120507 AB - OBJECTIVE: As obesity and diabetes are on the verge of an alarming growth, so is the use of tirzepatide, a novel dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) and currently the most effective weight loss-drug. This research aimed to identify reporting patterns related to suboptimal therapeutic outcomes and tirzepatide-related drug-use issues, mining the EudraVigilance (EV). DESIGN: Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database. SETTINGS: Analysis of individual case safety reports involving tirzepatide in comparison with other GLP-1 RAs in the overall dataset (healthcare professionals (HP) and non-HP reports combined) and in the HP group. OUTCOME MEASURES: Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues. RESULTS: Among all analysed PTs, the most frequently reported were 'Off-label use' (n=1521), 'Drug ineffective' (n=425) and 'Off-label use device' (n=99). PTs in HP reports showed lower reporting odds compared with non-HP reports. In the overall dataset, reports involving tirzepatide showed lower reporting odds of the PT 'Drug ineffective' than those involving liraglutide (ROR 0.61, 95% CI 0.54 to 0.70), dulaglutide (ROR 0.72, 95% CI 0.63 to 0.82), exenatide (ROR 0.78, 95% CI 0.67 to 0.92) and semaglutide (ROR 0.81, 95% CI 0.72 to 0.91). However, in HP reports, no difference in reporting odds was observed between tirzepatide and semaglutide. A different pattern was observed for 'off-label use' in the full dataset, with higher reporting odds for tirzepatide vs lixisenatide, dulaglutide and liraglutide, but lower reporting odds vs semaglutide (ROR 0.52, 95% CI 0.49 to 0.55). In contrast, a higher reporting odd for the PT 'off-label use of device' was observed for tirzepatide versus semaglutide (ROR 43.47, 95% CI 16.00 to 118.13) in the overall reports; however, this finding should be interpreted with caution given the wide CI. CONCLUSIONS: This study complements existing evidence from clinical trials and current clinical practice. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Popa Ilie, Ioana Rada AU - Popa Ilie IR AUID- ORCID: 0000-0002-5281-5004 AD - Department of Endocrinology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. FAU - Ghibu, Steliana AU - Ghibu S AUID- ORCID: 0000-0003-2247-4613 AD - Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania steliana.ghibu@umfcluj.ro. FAU - Butuca, Anca AU - Butuca A AUID- ORCID: 0000-0003-1540-641X AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Dobrea, Carmen Maximiliana AU - Dobrea CM AUID- ORCID: 0000-0002-9913-1750 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Frum, Adina AU - Frum A AUID- ORCID: 0000-0003-4874-0430 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Stoicescu, Laurentiu AU - Stoicescu L AD - Department of Cardiology, Vth Medical Clinic, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. FAU - Homorodean, Calin AU - Homorodean C AD - Medical Clinic No. 1, Internal Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. AD - Interventional Cardiology Department, Cluj-Napoca County Emergency Hospital, Cluj-Napoca, CJ, Romania. FAU - Gligor, Felicia Gabriela AU - Gligor FG AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Morgovan, Claudiu AU - Morgovan C AUID- ORCID: 0000-0003-2730-8729 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. LA - eng PT - Journal Article DEP - 20261001 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Tirzepatide MH - Retrospective Studies MH - *Pharmacovigilance MH - Female MH - Semaglutide MH - Off-Label Use/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Adult PMC - PMC13630132 OTO - NOTNLM OT - Adverse events OT - Diabetes Mellitus, Type 2 OT - Obesity OT - Safety COIS- Competing interests: None declared. EDAT- 2026/10/01 23:30 MHDA- 2026/10/01 23:31 PMCR- 2026/10/01 CRDT- 2026/10/01 21:34 PHST- 2026/10/01 23:31 [medline] PHST- 2026/10/01 23:30 [pubmed] PHST- 2026/10/01 21:34 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - bmjopen-2026-120507 [pii] AID - 10.1136/bmjopen-2026-120507 [doi] PST - epublish SO - BMJ Open. 2026 Oct 1;16(10):e120507. doi: 10.1136/bmjopen-2026-120507. PMID- 42821775 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261009 IS - 1752-8984 (Electronic) IS - 1479-1641 (Linking) VI - 23 IP - 5 DP - 2026 Sep-Oct TI - Impact of antidiabetic agents on COPD exacerbations in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis. PG - 14791641261487590 LID - 10.1177/14791641261487590 [doi] AB - BackgroundThe impact of Antidiabetic Agents on COPD Exacerbations remains uncertain. We conducted a comprehensive review to evaluate the impact Antidiabetic Agents on COPD Exacerbations in patients with T2DM.MethodsWe searched PubMed, Embase, and Web of Science from inception to January 15, 2026 for observational studies involving adults with T2DM and COPD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models, treatments were ranked using the Surface Under the Cumulative Ranking Curve (SUCRA), and study quality was assessed using the Newcastle-Ottawa Scale.ResultsThirteen studies comprising 755,206 participants were included. Compared with sulfonylureas, SGLT-2 inhibitors were associated with the lowest risk of overall COPD exacerbations (RR 0.71, 95% CI 0.66-0.77), followed by GLP-1 receptor agonists (RR 0.77, 95% CI 0.71-0.84). Metformin demonstrated a near-neutral association (RR 0.89, 95% CI 0.79-1.00), whereas DPP-4 inhibitors (RR 1.05, 95% CI 0.97-1.13) and meglitinides (RR 1.13, 95% CI 0.93-1.36) showed no evidence of benefit. Similar findings were observed for severe exacerbations, with SGLT-2 inhibitors and GLP-1 receptor agonists demonstrating the strongest associations.ConclusionsSGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of COPD exacerbations than sulfonylureas, whereas metformin showed a near-neutral association and DPP-4 inhibitors and meglitinides showed no clear benefit. FAU - Shabil, Muhammed AU - Shabil M AD - Department of Pharmacy Practice, M. S. Ramaiah University of Applied Sciences, Bangalore, India. RINGGOLD: 410981 FAU - Jan, Asif AU - Jan A AUID- ORCID: 0000-0003-3880-5579 AD - Department of Pharmacy, University of Peshawar, Peshawar, KP, Pakistan. RINGGOLD: 54736 AD - Saidu Group of Teaching Hospitals, Saidu Sharif, KP, Pakistan. AD - District Headquarter Hospital Charsadda, Charsadda, KP, Pakistan. FAU - Shamim, Muhammad Aaqib AU - Shamim MA AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. RINGGOLD: 410730 FAU - Naser, Hussein Aziz AU - Naser HA AD - Al-Zahraa University for women-Karabella City, lraq. RINGGOLD: 608869 FAU - Sudan, Sourav AU - Sudan S AD - Saint Vincent Hospital, Worcester, MA, USA. RINGGOLD: 25424 FAU - Sultana, Huma AU - Sultana H AD - Department of pharmaceutical chemistry, M. S. Ramaiah University of Applied Sciences, Bangalore, India. RINGGOLD: 410981 FAU - Imran, Muhammad AU - Imran M AD - Diabetes and Endocrinology, Cork University Hospital, Ireland. RINGGOLD: 57983 FAU - Ullah, Farhad AU - Ullah F AD - Department of Chemistry, Kohat University of Science & Technology (KUST), Kohat, Pakistan. RINGGOLD: 66860 FAU - Dubwa, Daniel AU - Dubwa D AD - Department of Pharmacy, Makerere University, Kampala, Uganda. RINGGOLD: 58588 FAU - Kumar, Shubham AU - Kumar S AD - Dental Research Cell, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth (Deemed to Be University), Pune, India. RINGGOLD: 121766 LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20261001 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (Insulin Secretagogues) RN - 0 (Blood Glucose) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Pulmonary Disease, Chronic Obstructive/diagnosis/epidemiology/physiopathology/drug therapy MH - Treatment Outcome MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Disease Progression MH - Risk Assessment MH - Female MH - Male MH - Aged MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Incretins/therapeutic use/adverse effects MH - Insulin Secretagogues MH - *Blood Glucose/drug effects/metabolism MH - Sulfonylurea Compounds/therapeutic use MH - *Lung/physiopathology/drug effects OTO - NOTNLM OT - COPD exacerbations OT - DPP-4 inhibitors OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - hypoglycemic agents OT - sulfonylureas OT - systematic review OT - type 2 diabetes mellitus EDAT- 2026/10/01 23:30 MHDA- 2026/10/01 23:31 CRDT- 2026/10/01 19:30 PHST- 2026/10/01 23:31 [medline] PHST- 2026/10/01 23:30 [pubmed] PHST- 2026/10/01 19:30 [entrez] AID - 10.1177/14791641261487590 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2026 Sep-Oct;23(5):14791641261487590. doi: 10.1177/14791641261487590. Epub 2026 Oct 1. PMID- 42820470 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261009 IS - 1470-8736 (Electronic) IS - 0143-5221 (Print) IS - 0143-5221 (Linking) VI - 140 IP - 10 DP - 2026 Oct 14 TI - GLP-1 receptor agonists-a potential therapy for chronic kidney disease? PG - 2249-2265 LID - 10.1042/CS20261312 [doi] AB - Chronic kidney disease (CKD) represents a significant health burden worldwide, characterized by a gradual decline in kidney function and increased risk of cardiovascular events. Current therapeutic strategies like inhibition of the renin-angiotensin-aldosterone system or sodium-glucose cotransporter 2 inhibitors (SGLT2i), while beneficial, often fail to fully halt CKD progression, and a significant residual risk of disease progression persists. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes (T2D), have emerged as promising agents with pleiotropic effects extending beyond glycemic control and weight loss. Evidence from major cardiovascular outcome trials and dedicated CKD studies demonstrates that GLP-1 RAs can confer significant cardiovascular and nephroprotective benefits in patients with T2D and CKD. These benefits include reductions in major adverse cardiovascular events, slowing of kidney disease progression (as measured by estimated glomerular filtration rate (eGFR) decline), and decreased albuminuria. The mechanisms underlying these effects are complex and involve multiple pathways, including anti-inflammatory, anti-fibrotic, and antioxidative actions, as well as improvements in hemodynamic parameters. We provide a comprehensive overview of the current clinical and preclinical evidence supporting the use of GLP-1 RAs in CKD. We discuss the proposed mechanisms of action by which GLP-1 RAs exert their nephroprotective effects and explore the potential for these agents to improve kidney outcomes across a broad spectrum of patients with CKD and critically evaluate the potential risks and safety profile associated with GLP-1 RA use. CI - (c) 2026 The Author(s). FAU - Boeckhaus, Jan AU - Boeckhaus J AUID- ORCID: 0009-0006-2021-9255 AD - Department of Intensive Care, King's College London, Guy's and St Thomas' Hospital, London, U.K. AD - Department of Nephrology and Rheumatology, University Medical Center Gottingen, Goettingen, Germany. FAU - Sayer, John A AU - Sayer JA AD - Renal Services, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, U.K. AD - NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, U.K. AD - Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, U.K. FAU - Mabillard, Holly AU - Mabillard H AD - Renal Services, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, U.K. AD - Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, U.K. LA - eng GR - MR/V028723/1/UKRI | Medical Research Council (MRC)/ GR - Paed_RP_001_20180925/Kidney Research UK/ GR - N/A/European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)/ PT - Journal Article PT - Review PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/drug therapy/physiopathology/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Kidney/drug effects/physiopathology/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Disease Progression MH - Diabetic Nephropathies/drug therapy PMC - PMC13642989 OTO - NOTNLM OT - cardiovascular physiologyscular OT - chronic kidney disease OT - glucagon-like peptide-1 OT - nephrology COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2026/10/01 23:30 MHDA- 2026/10/01 23:31 PMCR- 2026/10/01 CRDT- 2026/10/01 18:13 PHST- 2026/05/01 00:00 [received] PHST- 2026/08/12 00:00 [revised] PHST- 2026/09/22 00:00 [accepted] PHST- 2026/10/01 23:31 [medline] PHST- 2026/10/01 23:30 [pubmed] PHST- 2026/10/01 18:13 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - 238135 [pii] AID - CS20261312 [pii] AID - 10.1042/CS20261312 [doi] PST - ppublish SO - Clin Sci (Lond). 2026 Oct 14;140(10):2249-2265. doi: 10.1042/CS20261312. PMID- 42817068 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261006 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 6 DP - 2026 Nov TI - Global Landscape and Thematic Evolution of Selective GLP-1 Receptor Agonists and GLP-1-Based Multi-Receptor Agonists in Type 2 Diabetes Mellitus: A Bibliometric Analysis. PG - e70351 LID - 10.1002/edm2.70351 [doi] LID - e70351 AB - AIM: To characterize the global development, collaboration structure, publication landscape, citation influence and thematic evolution of research on selective GLP-1 receptor agonists and GLP-1-based multi-receptor agonists in T2DM. METHODS: A bibliometric analysis was conducted on 3736 original articles published between 2004 and 2025 and retrieved from the Web of Science Core Collection. Publication trends, research contributions, collaboration networks, citation impact and thematic evolution were evaluated using complementary bibliometric indicators and network analysis. RESULTS: Annual publication output increased substantially. Selective-only studies remained the cumulative core of the evidence base, while mixed/comparative and multi-receptor-only studies expanded rapidly in recent years. The United States led in research output and international connectivity, and Novo Nordisk and Eli Lilly were the most prominent institutional contributors based on author affiliation analysis. Diabetes, Obesity and Metabolism was the leading source journal. Research output was highly concentrated across countries but more widely distributed across institutions and authors. Thematic emphasis shifted from incretin biology and glycemic efficacy toward cardiovascular and kidney outcomes, obesity, integrated treatment strategies and real-world evidence. Major trials, particularly LEADER and REWIND, and ADA/EASD consensus statements exerted strong citation influence. Sensitivity analysis supported the overall robustness of the principal findings. CONCLUSIONS: Research on GLP-1-based agonists in T2DM has expanded rapidly and shifted toward an integrated cardiovascular-kidney-metabolic framework. Studies of selective GLP-1RAs remain central to the literature, while studies of newer GLP-1-based multi-receptor agonists are contributing to its diversification. Evidence remains comparatively less developed for longer-term outcomes of emerging agents, treatment sustainability in routine care, patient experience and diverse populations and settings. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Wang, Yanbing AU - Wang Y AUID- ORCID: 0000-0002-4164-1010 AD - Health Management Program, Boston University, Boston, Massachusetts, USA. FAU - Liu, Zhanru AU - Liu Z AUID- ORCID: 0009-0001-3180-6635 AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Wang, Shifeng AU - Wang S AUID- ORCID: 0000-0002-2742-4562 AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Lv, Cuiyan AU - Lv C AUID- ORCID: 0009-0003-5100-2364 AD - Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China. FAU - El-Seedi, Hesham R AU - El-Seedi HR AUID- ORCID: 0000-0002-2519-6690 AD - Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, Saudi Arabia. FAU - Khalifa, Shaden A M AU - Khalifa SAM AUID- ORCID: 0009-0001-7108-2897 AD - Neurology and Psychiatry Department, Capio Saint Goran's Hospital, Stockholm, Sweden. FAU - Wang, Haiyan AU - Wang H AUID- ORCID: 0000-0002-9231-3869 AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. LA - eng GR - 2023-JYB-XJSJJ001/Beijing University of Chinese Medicine/ GR - 2023-ZXFZJJ-JW-001/Beijing University of Chinese Medicine/ GR - 2010-12/Key Laboratory of Traditional Chinese Medicine Health Preservation, Ministry of Education, China/ GR - S20260038/National Foreign Expert Program (Category S) of the Ministry of Human Resources and Social Security of the People's Republic of China/ PT - Journal Article PT - Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Bibliometrics MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor PMC - PMC13627873 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - bibliometric analysis OT - cardiovascular outcome trials OT - glucagon-like peptide-1 receptor agonist OT - glucagon-like peptide-1-based multi-receptor agonists OT - real-world evidence COIS- The authors declare no conflicts of interest. EDAT- 2026/10/01 05:31 MHDA- 2026/10/01 05:32 PMCR- 2026/09/30 CRDT- 2026/10/01 01:07 PHST- 2026/09/07 00:00 [revised] PHST- 2026/08/11 00:00 [received] PHST- 2026/09/15 00:00 [accepted] PHST- 2026/10/01 05:32 [medline] PHST- 2026/10/01 05:31 [pubmed] PHST- 2026/10/01 01:07 [entrez] PHST- 2026/09/30 00:00 [pmc-release] AID - EDM270351 [pii] AID - 10.1002/edm2.70351 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Nov;9(6):e70351. doi: 10.1002/edm2.70351. PMID- 42812078 OWN - NLM STAT- MEDLINE DCOM- 20260930 LR - 20260930 IS - 1759-7390 (Electronic) IS - 1750-8460 (Linking) VI - 87 IP - 9 DP - 2026 Sep 22 TI - GLP-1 Receptor Agonists in Diabetic Lower Extremity Peripheral Artery Disease: From Mechanisms to Clinical Practice. PG - 55884 LID - 10.31083/BJHM55884 [doi] AB - Diabetic lower extremity peripheral artery disease (PAD) is a complex and multifactorial complication of diabetes mellitus, characterized by extensive distal disease burden, accelerated progression, and a markedly elevated risk of major adverse limb events. Despite considerable advances in endovascular and surgical revascularization, limb salvage rates in this population remain suboptimal, largely due to the limited efficacy of current pharmacological options in improving microvascular perfusion, accelerating wound healing, or preventing re-occlusion. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a transformative therapeutic class, demonstrating cardiovascular protective effects beyond glycemic control. Large-scale real-world studies have generated encouraging signals regarding their potential to reduce amputation risk and promote wound healing. However, the current evidence base remains limited, and the precise molecular mechanisms by which GLP-1 RAs may protect the diabetic lower extremity require further elucidation. This review systematically examines the epidemiology and pathophysiology of diabetic lower extremity PAD, elucidates the molecular mechanisms of GLP-1 RA-mediated vascular protection, critically evaluates clinical and real-world evidence, and discusses key challenges and future directions for optimizing therapeutic outcomes in this high risk population. CI - Copyright: (c) 2026 The Author(s). Published by IMR Press. FAU - Pan, Jie AU - Pan J AD - Department of Endocrinology and Metabolism, The Second Af fi liated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang, China. FAU - Guo, Chengnan AU - Guo C AD - Department of Endocrinology and Metabolism, The Second Af fi liated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang, China. FAU - Huang, Qiuwei AU - Huang Q AD - School of Medicine, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, China. FAU - Zhang, Yikai AU - Zhang Y AD - Department of Endocrinology and Metabolism, The Second Af fi liated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang, China. FAU - Shen, Yimin AU - Shen Y AD - Department of Endocrinology and Metabolism, The Second Af fi liated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang, China. FAU - Guo, Caiyun AU - Guo C AD - Department of Endocrinology, Ningbo University Affiliated Yangming Hospital, 315400 Ningbo, Zhejiang, China. LA - eng GR - LHDMZ24H070001/Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China/ PT - Journal Article PT - Review PL - Singapore TA - Br J Hosp Med (Lond) JT - British journal of hospital medicine (London, England : 2005) JID - 101257109 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peripheral Arterial Disease/drug therapy/physiopathology/epidemiology/etiology MH - *Diabetic Angiopathies/drug therapy/physiopathology MH - *Hypoglycemic Agents/therapeutic use MH - *Lower Extremity/blood supply MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - diabetes mellitus, type 2 OT - glucagon-like peptide-1 receptor agonists OT - peripheral arterial disease COIS- The authors declare no conflicts of interest. EDAT- 2026/09/30 05:30 MHDA- 2026/09/30 05:31 CRDT- 2026/09/30 04:13 PHST- 2026/07/12 00:00 [received] PHST- 2026/09/08 00:00 [revised] PHST- 2026/09/10 00:00 [accepted] PHST- 2026/09/30 05:31 [medline] PHST- 2026/09/30 05:30 [pubmed] PHST- 2026/09/30 04:13 [entrez] AID - S1759-7390(26)04768-0 [pii] AID - 10.31083/BJHM55884 [doi] PST - ppublish SO - Br J Hosp Med (Lond). 2026 Sep 22;87(9):55884. doi: 10.31083/BJHM55884. PMID- 42809786 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20260930 IS - 0717-6163 (Electronic) IS - 0034-9887 (Linking) VI - 154 IP - 7 DP - 2026 Jul TI - Chilean Multidisciplinary Consensus on the Use of GLP-1 Receptor Agonists: Recommendations Based on the GRADE Methodology. PG - 1070-1082 LID - S0034-98872026000701070 [pii] LID - 10.4067/s0034-98872026000701070 [doi] AB - Type 2 diabetes (T2DM), obesity, chronic kidney disease (CKD), and heart failure (HF) pose a major public health burden in Chile and Latin America. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide glycemic, cardiovascular, renal, and weight-loss benefits, extending their therapeutic role beyond glycemic control. AIM: To develop a national consensus, based on GRADE methodology, that synthesizes the best available evidence and adapts it to the Chilean healthcare context, providing practical recommendations for the rational use of GLP-1 RA (GLP-1 receptor agonists). METHODS: A multidisciplinary panel convened by six Chilean scientific societies developed this consensus, using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. A systematic review of randomized trials and meta-analyses was conducted. Evidence tables were prepared and critically appraised to support transparent recommendations adapted to the Chilean healthcare context. RESULTS: The panel formulated seven key recommendations: (1) a strong recommendation for GLP-1 RAs in patients with T2DM and CKD; (2) a weak recommendation in CKD without diabetes; (3) a strong recommendation in T2DM with high cardiovascular risk; (4) a weak recommendation over sulfonylureas as add-on to metformin; (5) a strong recommendation in HF with preserved ejection fraction (HFpEF) and BMI >/=27; (6) a strong recommendation in obesity with T2DM; and (7) a weak recommendation in obesity without T2DM. CONCLUSIONS: This consensus synthesizes international evidence and contextualizes it to Chile, supporting rational, equitable, and transparent implementation of GLP-1 RAs. These agents are positioned as central tools in the management of the cardiorenal-metabolic syndrome, complementing current cost-effective therapies and lifestyle interventions. FAU - Cabrera, Sebastian AU - Cabrera S AD - Sociedad Chilena de Nefrologia, Santiago, Chile. FAU - Walbaum, Magdalena AU - Walbaum M AD - Care Policy and Evaluation Centre, London School of Economics and Political Science, London, UK. FAU - Borquez, Tamara AU - Borquez T AD - Sociedad Chilena de Nefrologia, Santiago, Chile. FAU - Fuentes, Catalina AU - Fuentes C AD - Asociacion Chilena de Nutricion Clinica, Obesidad y Metabolismo, Santiago, Chile. FAU - Acevedo, Monica AU - Acevedo M AD - Sociedad Chilena de Cardiologia y Cirugia Cardiovascular, Santiago, Chile. FAU - Varleta, Paola AU - Varleta P AD - Sociedad Chilena de Cardiologia y Cirugia Cardiovascular, Santiago, Chile. FAU - Belmar, Pamela AU - Belmar P AD - Sociedad Chilena de Diabetologia, Santiago, Chile. FAU - Gomez, Patricia AU - Gomez P AD - Sociedad Chilena de Diabetologia, Santiago, Chile. FAU - Sanzana, Maria Gabriela AU - Sanzana MG AD - Sociedad Chilena de Endocrinologia y Diabetes, Santiago, Chile. FAU - Vega, Javier AU - Vega J AD - Sociedad Chilena de Endocrinologia y Diabetes, Santiago, Chile. FAU - Navarro, Gustavo AU - Navarro G AD - Universidad Austral de Chile, Chile. FAU - Saavedra, Carla AU - Saavedra C AD - Sociedad Chilena de Obesidad, Santiago, Chile. FAU - Hernandez, Mario AU - Hernandez M AD - Sociedad Chilena de Nefrologia, Santiago, Chile. FAU - Gomez, Sabrina AU - Gomez S AD - Hospital Clinico, Universidad de Chile, Chile. FAU - Lorca, Eduardo AU - Lorca E AD - Sociedad Chilena de Nefrologia, Santiago, Chile. LA - eng LA - spa PT - Consensus Statement PT - Journal Article TT - Consenso multidisciplinario chileno sobre el uso de agonistas de GLP-1: Recomendaciones basadas en metodologia GRADE. PL - Chile TA - Rev Med Chil JT - Revista medica de Chile JID - 0404312 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Chile MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Failure/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy MH - Renal Insufficiency, Chronic/drug therapy EDAT- 2026/09/29 19:04 MHDA- 2026/09/29 19:05 CRDT- 2026/09/29 15:59 PHST- 2025/09/02 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/09/29 19:05 [medline] PHST- 2026/09/29 19:04 [pubmed] PHST- 2026/09/29 15:59 [entrez] AID - S0034-98872026000701070 [pii] AID - 10.4067/s0034-98872026000701070 [doi] PST - ppublish SO - Rev Med Chil. 2026 Jul;154(7):1070-1082. doi: 10.4067/s0034-98872026000701070. PMID- 42808923 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261001 IS - 1941-2452 (Electronic) IS - 0884-5336 (Print) IS - 0884-5336 (Linking) VI - 41 IP - 5 DP - 2026 Oct TI - Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents. PG - 1318-1333 LID - 10.1002/ncp.70180 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation. METHODS: This narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies. RESULTS: Nausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited. CONCLUSION: GI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape. CI - (c) 2026 The Author(s). Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition. FAU - Singhani, Vikash AU - Singhani V AUID- ORCID: 0000-0001-6063-1558 AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Ehsan, Muhammad AU - Ehsan M AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Valencia, Sara AU - Valencia S AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Nadeem, Ahmed AU - Nadeem A AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Moazzam, Eisha AU - Moazzam E AD - Department of Internal Medicine, King Edward Medical University, Lahore, Pakistan. FAU - Butsch, Winfield Scott AU - Butsch WS AD - Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Novo Nordisk, Copenhagen, Denmark. FAU - Garg, Samita AU - Garg S AUID- ORCID: 0009-0002-2493-1881 AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Nutr Clin Pract JT - Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition JID - 8606733 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Gastrointestinal Diseases/chemically induced MH - *Hypoglycemic Agents/adverse effects MH - *Gastric Inhibitory Polypeptide/agonists/adverse effects MH - Obesity/drug therapy MH - *Receptors, Gastrointestinal Hormone/agonists MH - Randomized Controlled Trials as Topic MH - Tirzepatide PMC - PMC13622393 OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes mellitus OT - dual GIP/GLP-1 receptor agonists OT - gastrointestinal adverse events OT - obesity OT - orforglipron OT - semaglutide OT - tirzepatide COIS- Samita Garg reports receiving an Investigator Initiated grant from Abbott, research grants with Enterra and Atmo Biosciences, and serving as a speaker/consultant for Novo Nordisk and Ardelyx. W. Scott Butsch is an employee of Novo Nordisk. All other authors have no disclosures to declare. EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 PMCR- 2026/09/29 CRDT- 2026/09/29 10:23 PHST- 2026/08/14 00:00 [revised] PHST- 2026/05/07 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 10:23 [entrez] PHST- 2026/09/29 00:00 [pmc-release] AID - NCP70180 [pii] AID - 10.1002/ncp.70180 [doi] PST - ppublish SO - Nutr Clin Pract. 2026 Oct;41(5):1318-1333. doi: 10.1002/ncp.70180. PMID- 42808550 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261002 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 10 DP - 2026 Oct TI - Real-world treatment patterns and cost per patient achieving treatment targets among tirzepatide and semaglutide initiators in US patients with type 2 diabetes. PG - 1173-1188 LID - 10.18553/jmcp.2026.32.10.1173 [doi] AB - BACKGROUND: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), and semaglutide, a GLP-1 RA, are approved for type 2 diabetes (T2D) management. Clinical trials demonstrated that tirzepatide provided greater hemoglobin A1c and weight reduction vs comparators. Studies using trial-based effect estimates indicate it may also offer a lower cost per patient achieving treatment targets. However, real-world comparative data on treatment patterns, effectiveness, and economic value are limited. OBJECTIVE: To compare real-world treatment patterns, A1c and weight outcomes, and type 2 diabetes-related pharmacy (T2D-Rx) costs per patient achieving treatment targets in patients initiating tirzepatide for T2D, stratified by prior GLP-1 RA use. METHODS: This retrospective cohort study used claims and laboratory data from the Healthcare Integrated Research Database. Adults with T2D initiating tirzepatide (Mounjaro only) or semaglutide (Ozempic only) from May 2022 to May 2023 were propensity score matched and classified as naive or non-naive based on GLP-1 RA exposure in the 6 months before initiation. Outcomes over 12 months of follow-up included adherence (proportion of days covered >/=0.80), persistence (no >/=45-day gap), and T2D-Rx cost per responder (mean T2D-related pharmacy cost / proportion achieving treatment target) to achieve A1c (<8%, <7%, /=5%, >/=10%, >/=15%) thresholds. Outcomes were compared using chi-square and t-tests. RESULTS: After matching, 10,702 naive and 5,577 non-naive patient pairs were included in each treatment group. Tirzepatide initiators demonstrated higher adherence (naive: 60% vs 45%; non-naive: 66% vs 48%) and persistence (naive: 62% vs 47%; non-naive: 68% vs 49%) than semaglutide initiators. A greater proportion of tirzepatide users achieved all A1c and weight outcomes, including the most stringent targets of A1c less than 5.7% (naive: 30% vs 18%; non-naive: 17% vs 6%) and weight loss greater than or equal to 15% (naive: 23% vs 10%; non-naive: 17% vs 5%). Tirzepatide also had lower T2D-Rx cost per responder for these most stringent endpoints: A1c less than 5.7% (naive: $45,300 vs $65,300; non-naive: $107,700 vs $270,300) and weight loss greater than or equal to 15% (naive: $62,900 vs $124,400; non-naive: $110,200 vs $326,800), as well as for most other weight loss thresholds. For less stringent A1c goals, T2D-Rx cost per responder was similar across tirzepatide and semaglutide. CONCLUSIONS: In this real-world analysis, tirzepatide demonstrated better adherence, persistence, and A1c and weight reductions and lower T2D-Rx cost per responder for the most stringent treatment targets than semaglutide in both GLP-1 RA-naive and non-naive patients with T2D. These findings support the clinical and economic value of tirzepatide for achieving meaningful treatment outcomes in real-world patient populations. FAU - Hoog, Meredith M AU - Hoog MM AD - Eli Lilly and Company, Indianapolis, IN. FAU - Vallarino, Carlos AU - Vallarino C AD - Eli Lilly and Company, Indianapolis, IN. FAU - Maldonado, Juan M AU - Maldonado JM AD - Eli Lilly and Company, Indianapolis, IN. FAU - Grabner, Michael AU - Grabner M AD - Carelon Research, Wilmington, DE. FAU - Teng, Chia-Chen AU - Teng CC AD - Carelon Research, Wilmington, DE. FAU - Terrell, Kendra AU - Terrell K AD - Eli Lilly and Company, Indianapolis, IN. FAU - Richard, Emma L AU - Richard EL AD - Carelon Research, Wilmington, DE. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Tirzepatide/economics MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/economics/therapeutic use/administration & dosage MH - Male MH - United States MH - Glycated Hemoglobin/analysis MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects PMC - PMC13621902 COIS- Kendra Terrell, Carlos Vallarino, Juan M. Maldonado, and Meredith M. Hoog are employees and stockholders of Eli Lilly and Company. Michael Grabner, Chia-Chen Teng, and Emma L. Richard are employees of Carelon Research, which received funding from Eli Lilly and Company for the conduct of this study as well as for manuscript writing. Michael Grabner, Chia-Chen Teng, and Emma L. Richard are stockholders of Elevance Health. Sponsorship for this study was provided by Eli Lilly and Company. EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 PMCR- 2026/10/01 CRDT- 2026/09/29 08:14 PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 08:14 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.10.1173 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Oct;32(10):1173-1188. doi: 10.18553/jmcp.2026.32.10.1173. PMID- 42808548 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20260929 IS - 2376-1032 (Electronic) IS - 2376-0540 (Linking) VI - 32 IP - 10 DP - 2026 Oct TI - Return on investment of SGLT2 inhibitors and GLP-1 receptor agonists: Implications of real-world use for managed care. PG - 1167-1172 LID - 10.18553/jmcp.2026.32.10.1167 [doi] AB - Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) use has rapidly expanded across multiple chronic disease states, resulting in substantial growth in pharmacy spending. Although these agents demonstrate strong clinical benefit in clinical trials, real-world adherence and persistence remain suboptimal, raising questions about their financial value to payers.This viewpoint examines return on investment (ROI) associated with real-world use of SGLT2is and GLP-1RAs, alone and in combination, within a regional managed care organization. Review of claims and electronic health record data from more than 29,000 treatment-naive members revealed negative short-term ROI across treatment groups, driven primarily by high pharmacy costs and compounded by low adherence and persistence. Although adherent members generally experienced less growth in acute care use compared with nonadherent members, these trends were insufficient to offset medication costs within an 18-month time horizon.These findings highlight the limitations of using short-term ROI as a proxy for clinical value in high-cost chronic therapies. Negative ROI in this setting does not directly correlate to low therapeutic benefit but rather reflects delayed time to benefit, high baseline medical risk, and real-world medication use patterns. Payers may benefit from reassessing success metrics and pairing access to these therapies with targeted adherence and use management strategies to better align financial expectations with long-term value. FAU - Rapp, Hannah AU - Rapp H AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. FAU - Marr, David AU - Marr D AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. FAU - Modany, Ashley AU - Modany A AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. FAU - Bryk, Andrew AU - Bryk A AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. FAU - Christian, Nicholas AU - Christian N AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. FAU - Good, Chester AU - Good C AD - UPMC Health Plan, US Steel Tower, Pittsburgh, PA. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Managed Care Programs/economics MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - Drug Costs MH - Cost-Benefit Analysis MH - Medication Adherence EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 CRDT- 2026/09/29 08:14 PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 08:14 [entrez] AID - 10.18553/jmcp.2026.32.10.1167 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Oct;32(10):1167-1172. doi: 10.18553/jmcp.2026.32.10.1167. PMID- 42808164 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20260929 IS - 1752-8984 (Electronic) IS - 1479-1641 (Linking) VI - 23 IP - 5 DP - 2026 Sep-Oct TI - Benefits of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide-1 receptor agonists in older patients with type 2 diabetes. PG - 14791641261495569 LID - 10.1177/14791641261495569 [doi] AB - BackgroundType 2 diabetes mellitus (T2DM) increases the risk of cardiovascular and neurocognitive complications. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2is) have pleiotropic effects beyond glycemic control, but comparative long-term data on dementia, cardiovascular events, and mortality in older adults are limited.MethodsThis retrospective cohort study used the TriNetX US Collaborative Network. Adults >/=60 years with T2DM on metformin plus either GLP-1 RAs or SGLT2is (n=56,211 per cohort after matching, 2014-2020) were propensity-score matched on demographic and clinical characteristics. Five-year outcomes included incident Alzheimer's disease, vascular dementia, other dementia, dementia-related medication use, NSTEMI, STEMI, and all-cause mortality.ResultsAfter propensity-score matching, GLP-1 RA use was associated with higher risks of Alzheimer's disease (RR 1.33, 95% CI 1.18-1.48), vascular dementia (RR 1.56, 95% CI 1.39-1.76), other dementia (RR 1.33, 95% CI 1.21-1.47), dementia-related medication initiation, and all-cause mortality (RR 1.11, 95% CI 1.08-1.15) compared with SGLT2is. NSTEMI and STEMI risks did not differ significantly between groups.ConclusionsIn older adults with T2DM, SGLT2is were associated with lower risks of dementia, dementia-related medication use, and all-cause mortality compared with GLP-1 RAs in propensity-score matched cohorts. These observational findings are hypothesis-generating and should be confirmed in prospective studies. FAU - Mortada, Ibrahim AU - Mortada I AUID- ORCID: 0009-0006-9215-880X AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Paul, Krishna AU - Paul K AD - Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Rice, James AU - Rice J AUID- ORCID: 0009-0002-3473-0880 AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Joseph, Noah AU - Joseph N AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Raum, Trevor L AU - Raum TL AUID- ORCID: 0009-0006-5547-1282 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Albayyaa, Mohanad AU - Albayyaa M AUID- ORCID: 0000-0003-4185-5294 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Gaalema, Diann AU - Gaalema D AUID- ORCID: 0000-0002-6463-9925 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jehle, Dietrich AU - Jehle D AUID- ORCID: 0009-0002-6006-3903 AD - Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Blackwell, Thomas A AU - Blackwell TA AUID- ORCID: 0009-0009-0659-2100 AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jneid, Hani AU - Jneid H AUID- ORCID: 0000-0002-8754-358X AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260929 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - Male MH - Treatment Outcome MH - Risk Factors MH - *Incretins/adverse effects/therapeutic use MH - Risk Assessment MH - Time Factors MH - Age Factors MH - Middle Aged MH - United States/epidemiology MH - Aged, 80 and over MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiology OT - Dementia OT - Diabetes mellitus type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 CRDT- 2026/09/29 07:44 PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 07:44 [entrez] AID - 10.1177/14791641261495569 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2026 Sep-Oct;23(5):14791641261495569. doi: 10.1177/14791641261495569. Epub 2026 Sep 29. PMID- 42803248 OWN - NLM STAT- MEDLINE DCOM- 20260928 LR - 20260928 IS - 1842-1121 (Electronic) IS - 1841-8724 (Linking) VI - 35 IP - 3 DP - 2026 Sep 26 TI - Outcomes of GLP-1 Receptor Agonist Therapy after Liver Transplantation in Patients with Type 2 Diabetes: A Real-World Cohort Study. PG - 407-413 LID - 10.15403/jgld-6863 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to manage type 2 diabetes mellitus (T2DM) in liver transplant (LT) recipients, but their impact on graft outcomes remains unclear. This study evaluated clinical and graft-related outcomes associated with GLP-1 RA therapy. METHODS: We conducted a retrospective cohort study using the TriNetX Network, identifying adults with LT and T2DM. Two cohorts were defined: LT recipients treated with GLP-1 RAs and those receiving conventional antidiabetic therapy. Propensity score matching (1:1) was applied based on demographics, comorbidities, and immunosuppressive regimens. The index date was the first GLP-1 RA prescription within six months before or after LT. Outcomes assessed at one year included all-cause mortality, graft rejection, graft failure, biliary stricture, hepatic artery thrombosis, and transplant-related infections. Analyses used Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: After matching, 704 patients were included in each cohort. GLP-1 RA use was associated with significantly lower mortality (4.2% vs. 12.6%; HR=0.33, 95%CI: 0.22-0.50; p<0.0001) and reduced risks of rejection (9.0% vs. 15.5%; HR=0.55; p=0.0008), graft failure (7.1% vs. 13.8%; HR=0.50; p=0.0002), biliary stricture (4.1% vs. 6.7%; HR=0.60; p=0.0342), infections (5.7% vs. 10.1%; HR=0.54; p=0.0032), and hepatic artery thrombosis (5.4% vs. 10.7%; HR=0.48; p=0.0007). CONCLUSIONS: GLP-1 RA therapy was associated with improved survival and lower rates of major post-transplant complications, suggesting a potential role as preferred antidiabetic therapy in LT recipients with T2DM. FAU - Nguefang, Guy Loic AU - Nguefang GL AD - Texas Tech University Health Sciences Center, Odessa, TX, United States. Guy.Nguefang@ttuhsc.edu. FAU - Boateng, Sarpong AU - Boateng S AD - Yale New Haven Health, Bridgeport Hospital, New Haven CT, United States. sarpong1500@gmail.com. FAU - Gyabaah, Solomon AU - Gyabaah S AD - Komfo Anokye Teaching Hospital, Kumasi, Ghana. solomongyabaah53@gmail.com. FAU - Konlack, Joel Gabin AU - Konlack JG AD - New York City Health and Hospitals South Brooklyn Health, Brooklyn, NY, United States. konlackjoel4@gmail.com. FAU - Issaka, Yussif AU - Issaka Y AD - Yale New Haven Health, Bridgeport Hospital, New Haven CT, United States. yussifissaka2024@gmail.com. FAU - Luna Landa, Edgar AU - Luna Landa E AD - Texas Tech University Health Sciences Center, Odessa, TX, United States. elanda@ttuhsc.edu. FAU - Chukwu, Tracy AU - Chukwu T AD - Texas Tech University Health Sciences Center, Odessa, TX, United States. Tracy.Chukwu@ttuhsc.edu. FAU - Eze, Elvis AU - Eze E AD - Yale University, New Haven, CT, United States. elvisieze@gmail.com. FAU - Njei, Basile AU - Njei B AD - Yale University, New Haven, CT, United States; Engelhardt School of Global Health and Bioethics, Euclid University, Central African Republic. basilenjei@gmail.com. LA - eng PT - Journal Article DEP - 20260926 PL - Romania TA - J Gastrointestin Liver Dis JT - Journal of gastrointestinal and liver diseases : JGLD JID - 101272825 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Liver Transplantation/adverse effects/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/complications MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Graft Survival/drug effects MH - Aged MH - Graft Rejection/prevention & control MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Time Factors MH - *End Stage Liver Disease/surgery/mortality/complications/diagnosis EDAT- 2026/09/28 11:39 MHDA- 2026/09/28 11:40 CRDT- 2026/09/28 06:53 PHST- 2026/09/28 11:40 [medline] PHST- 2026/09/28 11:39 [pubmed] PHST- 2026/09/28 06:53 [entrez] AID - 10.15403/jgld-6863 [doi] PST - epublish SO - J Gastrointestin Liver Dis. 2026 Sep 26;35(3):407-413. doi: 10.15403/jgld-6863. PMID- 42802824 OWN - NLM STAT- MEDLINE DCOM- 20260928 LR - 20260929 IS - 2308-118X (Electronic) IS - 0857-1074 (Print) IS - 0857-1074 (Linking) VI - 41 IP - 2 DP - 2026 Aug TI - Dapagliflozin Alone or Combined With Semaglutide: Cardiovascular and Renal Outcomes Among Patients With Type 2 Diabetes Mellitus in a 6-Month Real-World Retrospective Cohort Study in Saudi Arabia. PG - 75-84 LID - 10.15605/jafes.041.02.6171 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a growing global health concern linked to increased cardiovascular and renal complications. Two emerging therapeutic classes, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1 RAs), have shown independent cardiometabolic benefits. However, limited realworld data exist on the comparative impact of combining these therapies versus using SGLT2i alone. OBJECTIVE: To compare the cardiovascular and renal outcomes of dapagliflozin monotherapy versus combination therapy with once-weekly injectable semaglutide among patients with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this retrospective cohort study, 539 adult patients with confirmed type 2 diabetes mellitus (T2DM; baseline HbA1c >/=6.5%) treated at King Abdulaziz Hospital, Al-Ahsa, were followed over six months. Patients received either dapagliflozin alone or in combination with semaglutide. Generalized Estimating Equations (GEE) were used to assess changes in glycemic control, cardiovascular events, lipid profile, and renal function, adjusting for time and sex. RESULTS: Both groups showed significant metabolic improvements over six months. Dapagliflozin monotherapy was associated with greater HbA1c reduction. Combination therapy was associated with higher HDL levels, improved eGFR, and a lower relative risk of heart failure (RR = 0.43, p = 0.04); the reduction in myocardial infarction risk (RR = 0.61, p = 0.13) did not reach statistical significance. No significant difference was observed in stroke risk. Most cardiovascular and renal markers improved modestly. CONCLUSION: Combination therapy was associated with favorable renal outcomes and a reduction in heart failure risk, despite inferior glycemic control and a non-significant trend toward reduced myocardial infarction risk. These findings suggest potential complementary effects of SGLT2i and GLP-1 RA treatment in high-risk patients. However, due to the retrospective, non-randomized design, causal relationships cannot be inferred, and residual confounding may exist. Prospective trials are warranted to confirm these associations and guide treatment optimization. CI - (c) 2026 by Alharajin et al. FAU - Alharajin, Rasmah AU - Alharajin R AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - AlTaweel, Muneera AU - AlTaweel M AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Cardiac Science, Department of Medicine, King Abdulaziz Hospital, Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. FAU - AlSubaiee, Maram AU - AlSubaiee M AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - College of Nursing, KSAU-HS, Al Ahsa, Saudi Arabia. FAU - Al Makhloof, Saleh AU - Al Makhloof S AD - Clinical Pharmacy Services, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Almusaad, Abdulmohsen AU - Almusaad A AD - King Abdulaziz Cardiac Center, King Abdulaziz Medical City, MNGHA, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia. FAU - Alarfaj, Abdulrahman AU - Alarfaj A AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - AlKhayyal, Ahmad AU - AlKhayyal A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Altharman, Noor AU - Altharman N AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - Alalawi, Ahmed AU - Alalawi A AD - Department of Internal Medicine, Almoosa Specialist Hospital, Al Ahsa, Saudi Arabia. FAU - Almannai, Noora AU - Almannai N AD - King Hamad University Hospital, Kingdom of Bahrain. FAU - Alohaymid, Munirah AU - Alohaymid M AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alsaad, Afnan AU - Alsaad A AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alotaibi, Turkiah AU - Alotaibi T AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alkhaldi, Reem AU - Alkhaldi R AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Almoaibed, Ghusoon AU - Almoaibed G AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alrashada, Jawaher AU - Alrashada J AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alarfaj, Abdullatif AU - Alarfaj A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alqarni, Turki AU - Alqarni T AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - Makkah Healthcare Cluster, Makkah, Saudi Arabia. FAU - Alshahrani, Abdullah AU - Alshahrani A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - Prince Sultan Military Medical City, Riyadh, Saudi Arabia. FAU - Aldossary, Ibraheem AU - Aldossary I AD - King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Khashwayn, Seham AU - Khashwayn S AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - Al Qarni, Ali AU - Al Qarni A AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Endocrinology and Metabolism, Department of Medicine, King Abdulaziz Hospital, MNGHA Al-Ahsa, Saudi Arabia. FAU - Taleb, Yaqob AU - Taleb Y AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Cardiac Science, Department of Medicine, King Abdulaziz Hospital, Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. FAU - Alshaikh Husain, Mareyah AU - Alshaikh Husain M AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. LA - eng PT - Journal Article DEP - 20260813 PL - Philippines TA - J ASEAN Fed Endocr Soc JT - Journal of the ASEAN Federation of Endocrine Societies JID - 8608483 RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Benzhydryl Compounds/therapeutic use MH - Male MH - Drug Therapy, Combination MH - Middle Aged MH - *Glucosides/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/epidemiology MH - Saudi Arabia/epidemiology MH - Aged MH - Treatment Outcome MH - Glycated Hemoglobin PMC - PMC13616068 OTO - NOTNLM OT - cardiovascular outcomes OT - dapagliflozin OT - real-world study OT - renal function OT - semaglutide OT - type 2 diabetes COIS- The authors declared no conflict of interest. EDAT- 2026/09/28 05:33 MHDA- 2026/09/28 05:34 PMCR- 2026/08/01 CRDT- 2026/09/28 03:42 PHST- 2026/05/13 00:00 [received] PHST- 2026/06/10 00:00 [accepted] PHST- 2026/09/28 05:34 [medline] PHST- 2026/09/28 05:33 [pubmed] PHST- 2026/09/28 03:42 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - JAFES-41-2-075 [pii] AID - 10.15605/jafes.041.02.6171 [doi] PST - ppublish SO - J ASEAN Fed Endocr Soc. 2026 Aug;41(2):75-84. doi: 10.15605/jafes.041.02.6171. Epub 2026 Aug 13. PMID- 42796421 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260929 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 9 DP - 2026 Sep 21 TI - Clinical Profile of Documented Diabetic Peripheral Neuropathy by GLP-1-Based Medication Status: A Cross-Sectional Study. LID - 10.3390/medicina62091816 [doi] LID - 1816 AB - Background and Objectives: This exploratory single-center retrospective cross-sectional study characterized patients with documented diabetic peripheral neuropathy (DPN) according to documented GLP-1-based medication status. GLP-1-based medication status was defined by a hospital medication-field entry for exenatide, dulaglutide, semaglutide, a fixed-ratio insulin/GLP-1 receptor agonist combination, or tirzepatide, a dual GIP/GLP-1 receptor agonist. Materials and Methods: Medication-level records from a hospital-defined February 2024-February 2026 reporting window were aggregated by PatID for 4120 unique patients in active-patient exports from the Clinical County Emergency Hospital Bihor. The files lacked patient-level encounter, diagnosis, and treatment dates; therefore, they were analyzed as an undated reporting snapshot. DPN and diabetes type were defined from export fields and were not independently clinically validated. Results: GLP-1-based medications were documented in 852 patients (20.7%). Patients with these medications in their records had longer documented diabetes duration (14.85 +/- 8.64 vs. 11.72 +/- 8.73 years; p < 0.001) and a higher documented comorbidity count (2.64 +/- 1.65 vs. 1.89 +/- 1.55; p < 0.001). Heart failure was documented in 35.7% versus 22.2%, and any lower-limb amputation in 3.3% versus 1.2%. For heart failure, the adjusted odds ratio was 1.68 (95% CI 1.41-1.99) in the primary model and 1.37 (1.12-1.67) in the expanded exploratory model; the corresponding robust Poisson prevalence ratio was 1.45 (1.30-1.63). Because only 66 amputations were recorded, amputation was retained as a descriptive, unadjusted outcome and was not modeled multivariably. Conclusions: A GLP-1-based medication record identified a clinically complex subgroup with documented DPN. The findings are exploratory and hypothesis-generating; because treatment and outcome dates were unavailable, they do not establish temporality, treatment benefit, or treatment harm. FAU - Ferician, Anca Cristina AU - Ferician AC AD - Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410068 Oradea, Romania. FAU - Ghitea, Timea Claudia AU - Ghitea TC AUID- ORCID: 0000-0001-8981-1958 AD - Pharmacy Department, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania. FAU - Popoviciu, Mihaela Simona AU - Popoviciu MS AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania. LA - eng GR - 410087/University of Oradea/ PT - Journal Article DEP - 20260921 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cross-Sectional Studies MH - *Diabetic Neuropathies/drug therapy/physiopathology MH - Female MH - Retrospective Studies MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Semaglutide MH - Middle Aged MH - Tirzepatide MH - *Glucagon-Like Peptide 1/therapeutic use MH - Exenatide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Insulin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13609424 OTO - NOTNLM OT - documented GLP-1-based therapy OT - documented diabetic peripheral neuropathy OT - exploratory cross-sectional study OT - heart failure OT - lower-limb amputation OT - multimorbidity OT - prevalence ratio OT - routinely collected health data COIS- The authors declare no conflicts of interest. EDAT- 2026/09/26 05:35 MHDA- 2026/09/26 05:36 PMCR- 2026/09/21 CRDT- 2026/09/26 01:13 PHST- 2026/08/24 00:00 [received] PHST- 2026/09/18 00:00 [revised] PHST- 2026/09/20 00:00 [accepted] PHST- 2026/09/26 05:36 [medline] PHST- 2026/09/26 05:35 [pubmed] PHST- 2026/09/26 01:13 [entrez] PHST- 2026/09/21 00:00 [pmc-release] AID - medicina62091816 [pii] AID - medicina-62-01816 [pii] AID - 10.3390/medicina62091816 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Sep 21;62(9):1816. doi: 10.3390/medicina62091816. PMID- 42794486 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260929 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 18 DP - 2026 Sep 10 TI - Skeletal Muscle Effects of GLP 1 Receptor Agonists: Molecular Mechanisms and Comparative Insights on Semaglutide and Tirzepatide, a Narrative Review. LID - 10.3390/ijms27188057 [doi] LID - 8057 AB - GLP-1 receptor agonists (GLP-1RAs), dual GLP-1/GIP agonists, and the more recent triple GLP-1/GIP/glucagon agonists have transformed the treatment of type 2 diabetes mellitus (T2DM) and obesity, resulting in significant weight reduction. However, a substantial proportion (20-40%) of this weight loss is attributable to a decrease in lean mass, thereby raising concerns regarding potential sarcopenia-related risk. However, decreased lean mass is not sufficient to determine sarcopenia, which is now defined by the combined presence of decreased muscle mass, diminished strength, and impaired physical function, particularly in older or frail individuals. Thus, a further clarification of the potential mechanisms through which these molecules affect skeletal muscle is needed to optimize their use. The objective of this study is to synthesize preclinical, metabolomic, and clinical evidence on the effects of GLP-1RAs and dual/triple agonists on skeletal muscle, with a specific comparison between semaglutide and tirzepatide. This narrative review was based on a comprehensive literature search of PubMed/MEDLINE, Scopus, and Google Scholar, encompassing articles published through June 2026. This search was supplemented by manual citation tracking, which identified additional studies including preclinical and metabolomic investigations, randomized controlled trials, observational studies, and meta-analyses. Preclinical data suggest that GLP-1R/GIPR activation can positively modulate anabolic pathways, mitochondrial biogenesis, and muscle inflammation. Metabolomic evidence reveals lipid and amino acid remodeling compatible with improved mitochondrial function. Clinically, lean mass loss proportional to weight reduction is consistently observed, generally without meaningful declines in strength or performance; data for tirzepatide are more limited. Lean mass, however, is not synonymous with skeletal muscle. A paradox emerges between the presence of protective molecular signals and the clinical evidence of lean-mass loss. This phenomenon may be explained by a systemic energy/protein deficit rather than a direct catabolic effect of the drugs, although current evidence does not fully distinguish these mechanisms. The effectiveness of weight reduction should be considered a pivotal metric in clinical practice, particularly in populations susceptible to sarcopenia. FAU - Cautela, Domenico AU - Cautela D AUID- ORCID: 0000-0003-4894-0299 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Incarbona, Valeria AU - Incarbona V AUID- ORCID: 0009-0006-7777-4532 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Lombardi, Angela AU - Lombardi A AUID- ORCID: 0000-0001-5421-9970 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Laratta, Bruna AU - Laratta B AUID- ORCID: 0000-0002-6183-6843 AD - Istituto di Bioscienze e Biorisorse (IBBR), CNR, Via Pietro Castellino 111, 80131 Napoli, NA, Italy. FAU - Castaldo, Curzio Massimo AU - Castaldo CM AD - Scuola di Medicina e Chirurgia, Universita degli studi della Campania Luigi Vanvitelli, Via Santa Maria di Costantinopoli 16, 80138 Napoli, NA, Italy. FAU - Balestrieri, Maria Luisa AU - Balestrieri ML AUID- ORCID: 0000-0001-6001-1789 AD - Dipartimento di Medicina di Precisione, Universita degli studi della Campania Luigi Vanvitelli, Via de Crecchio 7, 80138 Napoli, NA, Italy. FAU - Mocini, Edoardo AU - Mocini E AUID- ORCID: 0000-0002-4868-8102 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Migliaccio, Silvia AU - Migliaccio S AUID- ORCID: 0000-0002-4563-6630 AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy. FAU - Tardito, Daniela AU - Tardito D AUID- ORCID: 0000-0001-5585-1054 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260910 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Tirzepatide/pharmacology MH - Semaglutide MH - Humans MH - *Muscle, Skeletal/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Sarcopenia/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/drug therapy/metabolism PMC - PMC13607671 OTO - NOTNLM OT - GLP-1 receptor agonists OT - dual GLP-1/GIP agonists OT - lean mass OT - metabolomics OT - sarcopenia OT - semaglutide OT - skeletal muscle OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/09/26 05:35 MHDA- 2026/09/26 05:36 PMCR- 2026/09/10 CRDT- 2026/09/26 01:07 PHST- 2026/08/05 00:00 [received] PHST- 2026/09/03 00:00 [revised] PHST- 2026/09/05 00:00 [accepted] PHST- 2026/09/26 05:36 [medline] PHST- 2026/09/26 05:35 [pubmed] PHST- 2026/09/26 01:07 [entrez] PHST- 2026/09/10 00:00 [pmc-release] AID - ijms27188057 [pii] AID - ijms-27-08057 [pii] AID - 10.3390/ijms27188057 [doi] PST - epublish SO - Int J Mol Sci. 2026 Sep 10;27(18):8057. doi: 10.3390/ijms27188057. PMID- 42791433 OWN - NLM STAT- MEDLINE DCOM- 20261024 LR - 20261028 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 86 IP - 11 DP - 2026 Nov TI - GLP-1 Receptor Agonists in Heart Failure: A Systematic Review and Meta-analysis with Phenotype-Specific Effects and Dual Analytical Frameworks. PG - 1873-1890 LID - 10.1007/s40265-026-02380-4 [doi] AB - BACKGROUND: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2D), evidence in heart failure (HF) has expanded across diverse trial populations and HF phenotypes but remains fragmented. We therefore performed an integrated systematic review and meta-analysis to evaluate the effects of GLP-1 RAs across the spectrum of HF using complementary trial-level and phenotype-based analyses. METHODS: PubMed, Embase, and Web of Science were systematically searched for studies published from inception to August 10, 2025. To provide an integrated assessment across heterogeneous HF populations, treatment effects were evaluated using dual analytical frameworks: trial-level analyses according to study design (dedicated HF with preserved ejection fraction [HFpEF] trials, HF with reduced ejection fraction [HFrEF] trials, and HF subgroups from cardiovascular outcome trials [CVOTs]) and phenotype-based analyses according to left ventricular ejection fraction (HFpEF vs HFrEF using a pragmatic threshold of 40%). A prespecified targeted analysis was conducted to specifically assess the efficacy of semaglutide. The primary outcomes were major adverse cardiovascular events (MACE), and the secondary outcomes included hospitalization for HF (HHF), the composite of cardiovascular death or any worsening HF events, cardiovascular death alone, and all-cause mortality. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random‑effects models. RESULTS: This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF. In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001). In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019). Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046). Semaglutide showed benefits in HHF and the composite of cardiovascular death or worsening HF events predominantly among overweight or obese patients with HFpEF. GLP-1 RAs also improved functional capacity and quality of life in HFpEF. CONCLUSION: GLP-1 RAs were associated with favorable cardiovascular and HF-related outcomes in HFpEF, predominantly among overweight or obese individuals, whereas evidence of benefit in HFrEF remains limited. In trial-level analyses, benefits were primarily observed for atherosclerotic endpoints in HF subgroups from CVOTs. By integrating evidence, this study provides a unified overview of the effects of GLP-1 RAs across the spectrum of HF and supports further phenotype-specific randomized trials, particularly dedicated studies in HFrEF. TRIAL REGISTRATION: Protocol registration PROSPERO (CRD420251079970). CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Yuan, Yahui AU - Yuan Y AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Chen, Chun AU - Chen C AD - China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China. FAU - Li, Xiuming AU - Li X AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Guo, Jingyi AU - Guo J AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Liu, Qiaoyun AU - Liu Q AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Lin, YuPing AU - Lin Y AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Sun, Lu AU - Sun L AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Fan, Guanjie AU - Fan G AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. LA - eng GR - YN2021DB02/Guangdong Provincial Department of Science and Technology/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260926 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Phenotype MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Stroke Volume/drug effects COIS- Declarations. Funding: This study was supported by the Guangdong Provincial Department of Science and Technology (YN2021DB02). Conflict of Interest: Yahui Yuan, Chun Chen, Xiuming Li, Jingyi Guo, Qiaoyun Liu, YuPing Lin, Lu Sun, Wei Song, and Guanjie Fan declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. CRediT Authorship Contribution Statement: Yahui Yuan: writing-original draft, writing-review & editing, methodology, data curation, conceptualization. Chun Chen: investigation, data curation, writing-original draft. Xiuming Li and Jingyi Guo: investigation, data curation, writing-review & editing. Qiaoyun Liu and Yuping Lin: investigation, data curation, writing-review & editing. Lu Sun: investigation, data curation, writing-review & editing. Guanjie Fan: methodology, investigation, funding acquisition, conceptualization, writing-review & editing. Data Availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethical Approval: Not applicable. Code Availability: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. EDAT- 2026/09/26 05:34 MHDA- 2026/10/25 03:35 CRDT- 2026/09/25 23:40 PHST- 2026/01/20 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/10/25 03:35 [medline] PHST- 2026/09/26 05:34 [pubmed] PHST- 2026/09/25 23:40 [entrez] AID - 10.1007/s40265-026-02380-4 [pii] AID - 10.1007/s40265-026-02380-4 [doi] PST - ppublish SO - Drugs. 2026 Nov;86(11):1873-1890. doi: 10.1007/s40265-026-02380-4. Epub 2026 Sep 26. PMID- 42787169 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260926 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Pulsatile liraglutide on a biased tirzepatide background: a hypothesis. PG - 1922908 LID - 10.3389/fendo.2026.1922908 [doi] LID - 1922908 AB - Tirzepatide (TZP) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that shows full agonism at the GIP receptor (GIPR) and reduced potency with G-protein-biased partial agonism at the GLP-1 receptor (GLP-1R) in vitro. Weight-loss response may attenuate during prolonged therapy, and some patients remain on lower doses after dose reduction for tolerability. Whether clinically relevant GLP-1R signalling capacity remains available for intermittent additional stimulation under these conditions is unknown. It is proposed that adding intermittent low-dose liraglutide to a stable low-dose TZP background, termed Receptor-Primed Episodic Agonism (RPEA), could be investigated as a way to re-engage GLP-1R signalling without increasing the TZP dose. Liraglutide has an elimination half-life of approximately 13 h, but residual systemic exposure may remain at 48 h and repeated q48h administration may accumulate; the interval therefore requires formal PK characterisation rather than being assumed to provide complete washout. RPEA is defined generally as intermittent short-acting full GLP-1R agonism on a stable TZP background; liraglutide, 0.6 mg, and q48-72h are illustrative candidates rather than defining features. An incremental response alone would not demonstrate priming; the defining test is a background-by-challenge interaction exceeding a prespecified additive null and not explained by a pharmacokinetic interaction. The concept rests on four explicitly unproven propositions: (i) residual GLP-1R signalling capacity during low-dose TZP; (ii) an incremental pharmacodynamic effect from episodic full GLP-1R agonism; (iii) less cumulative receptor adaptation with intermittent than continuous full-agonist exposure; and (iv) pharmacodynamic effects that may not track plasma concentration exactly. RPEA generates falsifiable preclinical and clinical questions but is not a recommendation for clinical use. No safety data are available for this off-label two-agent combination, and current prescribing information for both products does not recommend coadministration with another GLP-1 receptor agonist. The combination must not be used outside an ethics-approved clinical trial. CI - Copyright (c) 2026 Kopitovic. FAU - Kopitovic, Ivan AU - Kopitovic I AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. AD - Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. LA - eng PT - Journal Article DEP - 20260910 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Tirzepatide MH - *Liraglutide/administration & dosage/pharmacokinetics MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Signal Transduction/drug effects PMC - PMC13600978 OTO - NOTNLM OT - GIPR OT - GLP-1R OT - biased agonism OT - incretin plateau OT - liraglutide OT - obesity OT - pulsatile dosing OT - tirzepatide COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/25 11:45 MHDA- 2026/09/25 11:46 PMCR- 2026/09/10 CRDT- 2026/09/25 06:13 PHST- 2026/06/29 00:00 [received] PHST- 2026/08/18 00:00 [revised] PHST- 2026/08/24 00:00 [accepted] PHST- 2026/09/25 11:46 [medline] PHST- 2026/09/25 11:45 [pubmed] PHST- 2026/09/25 06:13 [entrez] PHST- 2026/09/10 00:00 [pmc-release] AID - 10.3389/fendo.2026.1922908 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 10;17:1922908. doi: 10.3389/fendo.2026.1922908. eCollection 2026. PMID- 42785932 OWN - NLM STAT- MEDLINE DCOM- 20260924 LR - 20261003 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 9 DP - 2026 Sep 24 TI - Estimating the carbon footprint of oral semaglutide (Rybelsus): a comparative analysis of the medicine carbon footprint model and manufacturer life-cycle assessment in pharmaceutical production. PG - e124968 LID - 10.1136/bmjopen-2026-124968 [doi] LID - e124968 AB - OBJECTIVES: Pharmaceuticals are a major contributor to healthcare's greenhouse gas emissions yet product-level carbon footprints are rarely disclosed. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the management of type 2 diabetes and people living with obesity, but their carbon impact remains poorly characterised. We aimed to compare carbon footprint estimates for oral semaglutide (Rybelsus), a peptide-based medicine, generated using the medicine carbon footprint (MCF) framework and manufacturer-reported life cycle assessment (LCA) data. DESIGN AND SETTING: Comparative methodological analysis using cradle-to-gate boundaries to compare pharmaceutical carbon footprint estimates for oral semaglutide. METHODS: Per-tablet MCF estimates for 3, 7 and 14 mg Rybelsus were annualised and compared with product-specific LCA results reported by Novo Nordisk. Differences between methods were assessed descriptively across the three dose strengths. Absolute differences and symmetric percentage differences were calculated. RESULTS: Annualised MCF estimates were 8.9, 20.0 and 39.3 kg CO(2)e/year for 3, 7 and 14 mg tablets, respectively. Corresponding EU LCA estimates were 17.0, 25.2 and 39.9 kgCO(2)e/year. The mean symmetric percentage difference was -29%, with the largest discrepancy observed at the 3 mg dose (-62.6%) and the smallest difference at the 14 mg dose (-1.5%). CONCLUSION: For oral semaglutide, MCF generated lower carbon footprint estimates than manufacturer-reported LCA values, particularly at lower doses, where fixed device/excipient and packaging emissions are proportionally larger. MCF offers a rapid, accessible and indicative estimation method when proprietary data are unavailable. Improved transparency and harmonised boundaries would strengthen comparability between pharmaceutical carbon footprint estimation approaches. These findings are specific to the Rybelsus formulation of oral semaglutide and may not be generalisable to other formulations or GLP-1 RAs. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Hansell, Louise AU - Hansell L AUID- ORCID: 0000-0003-1810-9357 AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia Louise.Hansell@sydney.edu.au. AD - Physiotherapy Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia. FAU - Zhu, Wandi AU - Zhu W AD - Sydney Environment Institute, The University of Sydney, Sydney, New South Wales, Australia. FAU - Lynch, Michelle AU - Lynch M AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. FAU - Hocking, S L AU - Hocking SL AD - Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia. AD - Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Celermajer, David S AU - Celermajer DS AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. AD - Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. AD - Heart Research Institute Ltd, Newtown, New South Wales, Australia. FAU - Sack, Fabian AU - Sack F AD - Sydney Environment Institute, The University of Sydney, Sydney, New South Wales, Australia. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260924 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage MH - Humans MH - *Carbon Footprint/statistics & numerical data MH - *Hypoglycemic Agents/administration & dosage MH - Administration, Oral MH - Diabetes Mellitus, Type 2/drug therapy MH - Drug Industry PMC - PMC13630073 OTO - NOTNLM OT - General endocrinology OT - Health Services OT - Obesity OT - PUBLIC HEALTH COIS- Competing interests: None declared. EDAT- 2026/09/24 23:52 MHDA- 2026/09/24 23:53 PMCR- 2026/09/24 CRDT- 2026/09/24 21:13 PHST- 2026/09/24 23:53 [medline] PHST- 2026/09/24 23:52 [pubmed] PHST- 2026/09/24 21:13 [entrez] PHST- 2026/09/24 00:00 [pmc-release] AID - bmjopen-2026-124968 [pii] AID - 10.1136/bmjopen-2026-124968 [doi] PST - epublish SO - BMJ Open. 2026 Sep 24;16(9):e124968. doi: 10.1136/bmjopen-2026-124968. PMID- 42784582 OWN - NLM STAT- MEDLINE DCOM- 20260924 LR - 20260928 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 9 DP - 2026 TI - Cardiovascular outcomes associated With GLP-1 and dual GLP-1/GIP receptor agonists in patients with type 2 diabetes and inflammatory bowel disease: A retrospective real-world cohort study. PG - e0358659 LID - 10.1371/journal.pone.0358659 [doi] LID - e0358659 AB - INTRODUCTION: Individuals with co-morbid T2D and IBD represent a uniquely high-risk group, facing amplified cardiovascular risk through synergistic inflammatory and metabolic pathways, in whom conventional cardiometabolic strategies (such as dietary and lifestyle changes, weight loss, blood pressure and lipid optimization, metformin therapy, SGLT2 inhibitor therapy) may be insufficient due to the overlap between metabolic disease and chronic inflammatory disease processes. At present, the literature available on the role of incretin-based therapy in the treatment of T2D in patients with co-morbid IBD is limited. We aimed to evaluate the association of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists with cardiovascular outcomes in individuals with T2DM and IBD. This study is not intended as a direct comparison of the efficacy of GLP-1 agonists and dual GLP-1/GIP receptor agonists in patients with T2D and IBD. Both drug classes were analyzed as a combined incretin-based therapy exposure group to reflect real-world prescribing patterns and maximize statistical power. METHODS: We conducted a retrospective cohort study using the TriNetX global federated research network, identifying adults (>/=18 years) with T2D and IBD between 2015-2024. Patients prescribed GLP-1 or dual GLP-1/GIP were compared with non-users following 1:1 propensity score matching on demographics, comorbidities, and medication use. Relative risks (RR) and Hazard Ratios (HR) with 95% confidence intervals (CI) were calculated, with significance defined as p < 0.05. RESULTS: After matching 16,118 patients per cohort from among a total matched population of 32,236 patients, GLP-1 or GLP-1/GIP receptor agonist therapy was associated with lower hazard ratios across all outcomes, including myocardial infarction (HR 0.701, 95% CI 0.637-0.771), chronic ischemic heart disease (HR 0.936, 95% CI 0.896-0.978), heart failure (HR 0.777, 95% CI 0.737-0.820), atrial fibrillation/flutter (HR 0.838, 95% CI 0.788-0.890), sudden cardiac death (HR 0.694, 95% CI 0.605-0.795), ischemic stroke (HR 0.781, 95% CI 0.707-0.862), deep vein thrombosis (HR 0.642, 95% CI 0.586-0.702), and pulmonary embolism (HR 0.722, 95% CI 0.640-0.815). CONCLUSIONS: In patients with comorbid T2D and IBD, GLP-1 and GLP-1/GIP receptor agonists were associated with significant reductions in ischemic, arrhythmic, and thromboembolic cardiovascular outcomes. These findings highlight the potential role of incretin-based therapies in improving cardiovascular risk management in this high-risk population. However, the present study does not establish the comparative efficacy of the two classes of drugs in this patient population, and the findings may be associational rather than causal. Both drug classes were analyzed as a combined exposure group. Mechanistic explanations proposed in this paper should be considered hypothesis-generating rather than confirmed by the current observational study design. CI - Copyright: (c) 2026 Kazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Kazi, Muhammad Ali Ibrahim AU - Kazi MAI AD - Department of Internal Medicine, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. FAU - Mufarrih, Syed Musa AU - Mufarrih SM AD - Department of Internal Medicine, Aga Khan University, Karachi, Pakistan. FAU - Sirohi, Akanksha AU - Sirohi A AUID- ORCID: 0009-0007-4184-3097 AD - Department of Internal Medicine, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. FAU - Hasan, Fahad AU - Hasan F AD - Department of Internal Medicine, CMH Lahore Medial College and Institute of Dentistry, Lahore, Pakistan. FAU - Sharma, Akshay AU - Sharma A AD - Department of Internal Medicine, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. FAU - Singh, Sanmeet AU - Singh S AD - Department of Gastroenterology, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. FAU - Muganlinskaya, Nargiz AU - Muganlinskaya N AD - Department of Internal Medicine, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. FAU - Haq, Nowreen AU - Haq N AD - Department of Endocrinology, Anne Arundel Medical Center, Annapolis, Maryland, United States of America. LA - eng PT - Journal Article DEP - 20260924 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Inflammatory Bowel Diseases/drug therapy/complications MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Cardiovascular Diseases MH - *Receptors, Gastrointestinal Hormone/agonists MH - Adult MH - Incretins/therapeutic use MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 PMC - PMC13606989 COIS- The authors have declared that no competing interests exist. EDAT- 2026/09/24 23:52 MHDA- 2026/09/24 23:53 PMCR- 2026/09/24 CRDT- 2026/09/24 18:31 PHST- 2026/01/22 00:00 [received] PHST- 2026/09/03 00:00 [accepted] PHST- 2026/09/24 23:53 [medline] PHST- 2026/09/24 23:52 [pubmed] PHST- 2026/09/24 18:31 [entrez] PHST- 2026/09/24 00:00 [pmc-release] AID - PONE-D-26-03658 [pii] AID - 10.1371/journal.pone.0358659 [doi] PST - epublish SO - PLoS One. 2026 Sep 24;21(9):e0358659. doi: 10.1371/journal.pone.0358659. eCollection 2026. PMID- 42778559 OWN - NLM STAT- MEDLINE DCOM- 20260923 LR - 20261008 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Aug 22 TI - Tirzepatide versus GLP-1 receptor agonists and stroke in patients with atrial fibrillation and type 2 diabetes. LID - 10.1038/s41467-026-77047-5 [doi] LID - 10149 AB - Patients with atrial fibrillation and type 2 diabetes remain at high risk of stroke despite anticoagulation and glucose-lowering treatment. We examined whether tirzepatide was associated with lower cerebrovascular risk than established glucagon-like peptide-1 receptor agonists in a retrospective cohort from a large international federated electronic health-record network. Here we show that, among 14,118 matched pairs of adults initiating tirzepatide or another glucagon-like peptide-1 receptor agonist, tirzepatide use was associated with lower risks of any stroke, ischemic stroke, hemorrhagic stroke, and death from any cause. The absolute difference in stroke risk was 2.1 percentage points at one year, and the absolute difference in mortality was 6.2 percentage points. These observational findings support further assessment of tirzepatide as a potential option for people with both conditions, but randomized trials are required before treatment recommendations can change. CI - (c) 2026. The Author(s). FAU - Lin, Chih-Lang AU - Lin CL AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jen-Ai Hospital, Dali Branch, Taichung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Liver Research Unit, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan. AD - Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan. AD - Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan. FAU - Lin, Kuan-Chou AU - Lin KC AD - Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. AD - School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Yu, Jung-Min AU - Yu JM AD - Department of Cardiovascular Surgery, Taichung Tzu Chi Hospital, Taichung, Taiwan. AD - Department of Surgery, School of Medicine, Tzu Chi University, Hualien, Taiwan. FAU - Chang, Chia-Lun AU - Chang CL AD - Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. AD - Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Lin, Yu-Yi AU - Lin YY AD - Taipei Wego Private Senior High School, Taipei, Taiwan. FAU - Fang, Chih-Yuan AU - Fang CY AUID- ORCID: 0000-0002-1265-0858 AD - Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. AD - School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. FAU - Wu, Szu-Yuan AU - Wu SY AUID- ORCID: 0000-0001-5637-558X AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. szuyuanwu5399@gmail.com. AD - Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. szuyuanwu5399@gmail.com. AD - Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. szuyuanwu5399@gmail.com. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. szuyuanwu5399@gmail.com. AD - Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. szuyuanwu5399@gmail.com. AD - Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. szuyuanwu5399@gmail.com. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260822 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Tirzepatide/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Atrial Fibrillation/complications/drug therapy MH - *Stroke/prevention & control/etiology/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Aged MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13601590 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/09/24 05:37 MHDA- 2026/09/24 05:38 PMCR- 2026/08/22 CRDT- 2026/09/23 23:19 PHST- 2025/10/21 00:00 [received] PHST- 2026/07/24 00:00 [accepted] PHST- 2026/09/24 05:38 [medline] PHST- 2026/09/24 05:37 [pubmed] PHST- 2026/09/23 23:19 [entrez] PHST- 2026/08/22 00:00 [pmc-release] AID - 10.1038/s41467-026-77047-5 [pii] AID - 77047 [pii] AID - 10.1038/s41467-026-77047-5 [doi] PST - epublish SO - Nat Commun. 2026 Aug 22;17(1):10149. doi: 10.1038/s41467-026-77047-5. PMID- 42778221 OWN - NLM STAT- MEDLINE DCOM- 20260923 LR - 20260923 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 394 DP - 2026 Sep 16 TI - Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation. PG - e100574 LID - 10.1136/bmj-2026-100574 [doi] AB - OBJECTIVE: To compare the risk of renal deterioration under treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose contransporter-2 (SGLT-2) inhibitors versus other second line treatments in people with type 2 diabetes with and without albuminuria (albumin to creatinine ratio >/=30 mg/g). DESIGN: Target trial emulation. SETTINGS: Linkage of electronic health records and claims data from 10 health systems and two national health insurance plans-data from BESTMED (observational evaluation of second line therapy medications in diabetes) study. PARTICIPANTS: People with type 2 diabetes and moderate cardiovascular risk and estimated glomerular filtration rate >/=45 mL/min/1.73 m(2) on metformin monotherapy who started treatment with a GLP-1 receptor agonist or SGLT-2 inhibitor, a sulfonylurea, or a dipeptidyl peptidase-4 (DPP-4) inhibitor after metformin between 2014 and 2022. MAIN OUTCOME MEASURE: Deterioration of kidney function defined as doubling of serum creatinine or estimated glomerular filtration rate <15 mL/min/1.73 m(2). RESULTS: Among 75 455 eligible people (61 583 (81.76%) without albuminuria), median age was 60 years (interquartile range 51-68), 36 231 (48%) were women, median haemoglobin A(1c) was 7.8% (interquartile range 7.3-8.5%), and median estimated glomerular filtration rate was 92 mL/min/1.73 m(2) (interquartile range 77-102). People were followed for a median of 32 months (interquartile range 18-57). The estimated five year risk of the renal outcome was 2.4% (95% confidence interval 2.1% to 2.7%) for people taking GLP-1 receptor agonists or SGLT-2 inhibitors versus 2.1% (1.8% to 2.6%) for people taking DPP-4 inhibitors among those without albuminuria; and 3.2% (2.3% to 4.1%) versus 5.4% (4.2% to 6.7%), respectively, among people with albuminuria. The estimated five year risk ratio comparing the GLP-1 receptor agonist or SGLT-2 inhibitor group with the DPP-4 inhibitor group was 1.10 (95% confidence interval 0.90 to 1.38) among people without albuminuria and 0.60 (0.42 to 0.82) among people with albuminuria. CONCLUSIONS: Compared with DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors reduce the risk of deterioration of renal function in people with albuminuria. Little evidence of renal benefit among people without albuminuria was observed over the study follow-up period. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Turchin, Alexander AU - Turchin A AUID- ORCID: 0000-0002-8609-564X AD - Brigham and Women's Hospital, Boston, MA, USA aturchin@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. FAU - Petito, Lucia C AU - Petito LC AD - Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Hegermiller, Emma AU - Hegermiller E AD - Indus Consulting, Inc, Chicago, IL, USA. FAU - Chelliah, Indhumathy AU - Chelliah I AD - Indus Consulting, Inc, Chicago, IL, USA. FAU - Carnahan, Ryan M AU - Carnahan RM AD - Department of Epidemiology, The University of Iowa College of Public Health, Iowa City, IA, USA. AD - Health Effectiveness Research Center, The University of Iowa, Iowa City, IA, USA. FAU - DeVries, Andrea AU - DeVries A AD - Real World Evidence Institutional Partnerships, Humana Healthcare Research, Inc, Louisville, KY, USA. FAU - Goel, Satyender AU - Goel S AD - Indus Consulting, Inc, Chicago, IL, USA. AD - Northwestern University School of Medicine, Evanston, IL, USA. FAU - Lansang, M Cecilia AU - Lansang MC AD - Diabetes Technology and Initiatives, Cleveland Clinic, Cleveland, OH, USA. AD - Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. FAU - McDonnell, Marie E AU - McDonnell ME AD - Harvard Medical School, Boston, MA, USA. AD - Mass General Brigham, Boston, MA, USA. FAU - Nair, Vinit AU - Nair V AD - Indus Consulting, Inc, Chicago, IL, USA. FAU - Priest, Elisa AU - Priest E AD - Baylor Scott and White Research Institute, Dallas, TX, USA. FAU - Willey, Vincent J AU - Willey VJ AD - Carelon Research, Wilmington, DE, USA. FAU - Kaul, Alan F AU - Kaul AF AD - Medical Outcomes Management, Inc, Sharon, MA, USA. FAU - Hernan, Miguel A AU - Hernan MA AD - CAUSALab, Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA. CN - BESTMED collaborating investigators LA - eng PT - Journal Article DEP - 20260916 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Sulfonylurea Compounds) RN - AYI8EX34EU (Creatinine) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Albuminuria MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - *Diabetic Nephropathies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Metformin/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Creatinine/blood COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Patient-Centred Outcomes Research Institute for the submitted work. AT reported receiving grants from Eli Lilly and personal fees from Novo Nordisk and Proteomics International. MAH is a consultant to ProPublica and Adigens Health, a company of which he owns equity, and a member of ADIA Lab's Advisory Board. The other authors reported no conflicts of interest. FIR - Bah, Haddy IR - Bah H FIR - Barlocker, Jason IR - Barlocker J FIR - Bride, Daniel L IR - Bride DL FIR - Churchilles, Elizabeth IR - Churchilles E FIR - Douros, Megan IR - Douros M FIR - Gryzlak, Brian IR - Gryzlak B FIR - Hansen, Channing W IR - Hansen CW FIR - Hess, Rachel IR - Hess R FIR - Horne, Benjamin IR - Horne B FIR - Kean, Jacob IR - Kean J FIR - Knudson, Paul IR - Knudson P FIR - Melendez, Victor IR - Melendez V FIR - Ortman, Chris IR - Ortman C FIR - Ryu, Gi-Yung IR - Ryu GY FIR - Sidebottom, Abbey IR - Sidebottom A FIR - Smith, Claire IR - Smith C FIR - Song, Xing IR - Song X FIR - Spinka, Christine IR - Spinka C FIR - Stoddard, Alexander IR - Stoddard A FIR - Taylor, Bradley IR - Taylor B FIR - VanWormer, Jeffrey IR - VanWormer J FIR - Zhong, Honglang IR - Zhong H EDAT- 2026/09/23 23:56 MHDA- 2026/09/23 23:57 CRDT- 2026/09/23 20:44 PHST- 2026/09/23 23:57 [medline] PHST- 2026/09/23 23:56 [pubmed] PHST- 2026/09/23 20:44 [entrez] AID - 10.1136/bmj-2026-100574 [doi] PST - epublish SO - BMJ. 2026 Sep 16;394:e100574. doi: 10.1136/bmj-2026-100574. PMID- 42775225 OWN - NLM STAT- MEDLINE DCOM- 20260923 LR - 20260924 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Efficacy and safety of GLP-1RAs, SGLT2is, and nsMRAs for cardiovascular and renal outcomes in T2DM with CKD: a systematic review and network meta-analysis. PG - 1937754 LID - 10.3389/fendo.2026.1937754 [doi] LID - 1937754 AB - OBJECTIVE: To compare cardiovascular and renal benefits and safety of GLP-1RAs, SGLT2is, and nsMRAs in T2D-CKD using network meta-analysis. METHODS: RCTs published through 7 August 2026 were systematically identified. A frequentist random-effects network meta-analysis was performed. Evidence certainty was assessed with CINeMA. RESULTS: A total of 21 RCTs involving 51,899 patients were included. Compared with placebo, nsMRAs were associated with lower risks of the major kidney composite outcome and hospitalization for heart failure (HHF), whereas SGLT2is were associated with lower risks of major adverse cardiovascular events (MACE), the major kidney composite outcome, and HHF. GLP-1RAs were associated with lower risks of MACE, the major kidney composite outcome, HHF, all-cause mortality, and cardiovascular death. Between-class indirect comparisons suggested a lower estimated risk of the major kidney composite outcome with SGLT2is than with GLP-1RAs (RR 0.77, 95% CI 0.64-0.91) or nsMRAs (nsMRAs versus SGLT2is: RR 1.28, 95% CI 1.10-1.50). The estimated risk of HHF was also lower with SGLT2is than with nsMRAs (nsMRAs versus SGLT2is: RR 1.28, 95% CI 1.01-1.63). For cardiovascular death, the indirect estimate suggested a lower risk with GLP-1RAs than with SGLT2is (SGLT2is versus GLP-1RAs: RR 1.28, 95% CI 1.03-1.58), whereas the comparison between nsMRAs and GLP-1RAs did not reach statistical significance (RR 1.24, 95% CI 0.99-1.56). No statistically significant between-class differences were identified for MACE or all-cause mortality. All between-class comparisons were based exclusively on indirect evidence. Safety analyses showed higher risks of hyperkalemia with nsMRAs and genital infections with SGLT2is than with placebo. Sensitivity analyses broadly supported the main findings. Confidence in the evidence was mostly low to moderate, primarily because of indirectness. CONCLUSION: In patients with T2D-CKD, all three drug classes reduced several cardiorenal outcomes versus placebo. Between-class indirect comparisons suggested more favorable relative-effect estimates for SGLT2is on major kidney outcomes and HHF in selected comparisons, and for GLP-1RAs on cardiovascular death. No clear between-class difference was observed for MACE. Because the network lacked head-to-head comparisons between active drug classes, these findings and treatment rankings should be interpreted cautiously. Direct comparative and combination-therapy trials are needed to guide individualized treatment selection. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251150683, identifier CRD420251150683. CI - Copyright (c) 2026 Chen, Wu, Yuan, Ren, Liu, Yang, An and Zhan. FAU - Chen, Hongli AU - Chen H AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Wu, Xuejie AU - Wu X AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Yuan, Mengyi AU - Yuan M AD - Graduate School, Beijing University of Chinese Medicine, Beijing, China. FAU - Ren, Feihong AU - Ren F AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Liu, Tongtong AU - Liu T AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Yang, Liping AU - Yang L AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - An, Xuedong AU - An X AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Zhan, Yongli AU - Zhan Y AD - Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260908 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Cardiovascular Diseases/etiology/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13595571 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - cardiovascular outcomes OT - chronic kidney disease OT - network meta-analysis OT - nsMRA OT - renal outcomes OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/23 11:50 MHDA- 2026/09/23 11:51 PMCR- 2026/09/08 CRDT- 2026/09/23 07:32 PHST- 2026/07/14 00:00 [received] PHST- 2026/08/12 00:00 [revised] PHST- 2026/08/19 00:00 [accepted] PHST- 2026/09/23 11:51 [medline] PHST- 2026/09/23 11:50 [pubmed] PHST- 2026/09/23 07:32 [entrez] PHST- 2026/09/08 00:00 [pmc-release] AID - 10.3389/fendo.2026.1937754 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 8;17:1937754. doi: 10.3389/fendo.2026.1937754. eCollection 2026. PMID- 42768905 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 11 DP - 2026 Nov TI - Trends in GLP-1 Receptor Agonist Prescribing Without an Apparent FDA-Approved Indication. PG - 2026-2030 LID - 10.1002/oby.70301 [doi] AB - OBJECTIVE: This study evaluated temporal trends and patient characteristics associated with glucagon-like peptide-1 (GLP-1) receptor agonist prescribing among US adults without an apparent FDA-approved indication. METHODS: This retrospective cohort study used Cosmos electronic health records (01/2021-12/2025). Adults prescribed liraglutide, semaglutide, or tirzepatide without a documented indication (type 2 diabetes or obesity with qualifying comorbidities) were included. Patients without a recorded weight >/= 6 months prior to first prescription were excluded. Demographic and clinical characteristics were compared using t-tests and chi(2) tests. RESULTS: Among 92,415,648 adults without an apparent FDA-approved indication, 1,133,953 (1.2%) were prescribed GLP-1 receptor agonists. Prescribing increased from 0.1% in 2021 to 1.5% in 2025 (15-fold). Recipients had higher median BMI (25.9 vs. 24.5 kg/m(2)) and were more often female (85.5%) and White (60.0%). Hypertension and dyslipidemia were more common, while coronary artery disease and heart failure were less prevalent. Notably, 35.1% had normal BMI; eating disorders were more frequent (1.8% vs. 0.3%). GLP-1 receptor agonist use was associated with lower social vulnerability and private insurance. CONCLUSIONS: GLP-1 receptor agonist prescribing without an apparent FDA-approved indication has increased rapidly and disproportionately involves socioeconomically advantaged populations, including individuals without obesity. The risk-benefit profile in these populations remains uncertain. CI - (c) 2026 The Obesity Society. FAU - Orandi, Babak J AU - Orandi BJ AUID- ORCID: 0000-0001-6026-7135 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Medicine, New York University, New York, New York, USA. FAU - Yan, Leila AU - Yan L AD - Department of Surgery, New York University, New York, New York, USA. FAU - Levan, Macey L AU - Levan ML AUID- ORCID: 0000-0002-4239-1252 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Lofton, Holly F AU - Lofton HF AD - Department of Surgery, New York University, New York, New York, USA. FAU - Chhabra, Karan R AU - Chhabra KR AUID- ORCID: 0000-0001-6620-8777 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Ren-Fielding, Christine J AU - Ren-Fielding CJ AD - Department of Surgery, New York University, New York, New York, USA. FAU - Husain, S Ali AU - Husain SA AUID- ORCID: 0000-0002-1823-0117 AD - Department of Medicine, New York University, New York, New York, USA. FAU - McAdams-DeMarco, Mara A AU - McAdams-DeMarco MA AUID- ORCID: 0000-0003-3013-925X AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Segev, Dorry L AU - Segev DL AUID- ORCID: 0000-0002-1924-4801 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Mankowski, Michal A AU - Mankowski MA AD - Department of Surgery, New York University, New York, New York, USA. FAU - Massie, Allan B AU - Massie AB AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. LA - eng PT - Journal Article DEP - 20260922 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Tirzepatide/therapeutic use MH - Male MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - United States Food and Drug Administration MH - *Practice Patterns, Physicians'/trends MH - Aged EDAT- 2026/09/22 05:37 MHDA- 2026/10/28 17:31 CRDT- 2026/09/22 03:04 PHST- 2026/07/22 00:00 [revised] PHST- 2026/03/24 00:00 [received] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/10/28 17:31 [medline] PHST- 2026/09/22 05:37 [pubmed] PHST- 2026/09/22 03:04 [entrez] AID - 10.1002/oby.70301 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Nov;34(11):2026-2030. doi: 10.1002/oby.70301. Epub 2026 Sep 22. PMID- 42768061 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20261023 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Aug 22 TI - Glucagon-like Peptide-1 Receptor Agonists and Risk of Tuberculosis in Type 2 Diabetes. LID - 10.1038/s41467-026-77068-0 [doi] LID - 10045 AB - Tuberculosis remains a leading cause of illness and death worldwide, and individuals with type 2 diabetes have an increased risk of developing this infection. However, whether different glucose-lowering medications influence this risk is unclear. Here we show that use of glucagon-like peptide-1 receptor agonists is associated with a lower risk of tuberculosis compared with several commonly prescribed alternatives. We conducted a multicenter cohort study using TriNetX electronic health records from 143 healthcare organizations across multiple countries between 2017-2025. Patients receiving glucagon-like peptide-1 receptor agonists were compared with those receiving sulfonylureas, metformin, dipeptidyl peptidase-4 inhibitors, or sodium-glucose cotransporter-2 inhibitors. Propensity score matching and time-to-event analyses were applied over up to 5 years of follow-up. Use of glucagon-like peptide-1 receptor agonists is consistently associated with reduced tuberculosis risk compared with other agents. Incidence rates per 1,000 person-years ae lower than with sulfonylureas (0.68 vs 1.67; hazard ratio 0.53, 95% confidence interval 0.47-0.59), metformin (0.65 vs 1.31; 0.60, 0.51-0.70), dipeptidyl peptidase-4 inhibitors (0.73 vs 1.71; 0.49, 0.43-0.56) and sodium-glucose cotransporter-2 inhibitors (0.89 vs 1.02; 0.82, 0.72-0.92). These findings suggest that this class of medications may provide additional protection against tuberculosis in patients with type 2 diabetes. CI - (c) 2026. The Author(s). FAU - Liao, Kuang-Ming AU - Liao KM AUID- ORCID: 0000-0003-4364-8248 AD - Department of Internal Medicine, Chi Mei Hospital, Chiali, Taiwan. AD - Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AUID- ORCID: 0000-0002-3290-1909 AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. dtmed141@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. dtmed141@gmail.com. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260822 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - Metformin/therapeutic use MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - *Tuberculosis/epidemiology/prevention & control PMC - PMC13594082 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/09/22 05:37 MHDA- 2026/09/22 05:38 PMCR- 2026/08/22 CRDT- 2026/09/21 23:43 PHST- 2025/08/19 00:00 [received] PHST- 2026/08/11 00:00 [accepted] PHST- 2026/09/22 05:38 [medline] PHST- 2026/09/22 05:37 [pubmed] PHST- 2026/09/21 23:43 [entrez] PHST- 2026/08/22 00:00 [pmc-release] AID - 10.1038/s41467-026-77068-0 [pii] AID - 77068 [pii] AID - 10.1038/s41467-026-77068-0 [doi] PST - epublish SO - Nat Commun. 2026 Aug 22;17(1):10045. doi: 10.1038/s41467-026-77068-0. PMID- 42766517 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20260922 IS - 1548-6869 (Electronic) IS - 1049-2089 (Linking) VI - 37 IP - 1 DP - 2026 TI - Real-World Impact of Weekly Dulaglutide and Semaglutide on Hba1c and Weight in a Predominantly Underrepresented Demographic. PG - 270-286 LID - 10.1353/hpu.2026.a982969 [doi] AB - BACKGROUND: African Americans are underrepresented in real-world studies of GLP-1 receptor agonists (RA) for type 2 diabetes. OBJECTIVES: This study evaluates the effects of weekly dulaglutide and semaglutide on glycated hemoglobin (HbA1c) and weight in a predominantly African American population. METHODS: A retrospective chart review was conducted at an adult medicine clinic. Patients 19 years of age or older with at least 26 weeks of dulaglutide or semaglutide treatment and recorded baseline and follow-up HbA1c and weight were included. RESULTS: Among 91 patients-85.7% African American, 67.0% female, mean age 56.4 years-the mean GLP-1 RA treatment duration was 14.9 months. Glycated hemoglobin decreased by 2.39% (p<.001), and weight dropped by 4.76 kg (p<.001). High-dose dulaglutide significantly lowered HbA1c compared with low-dose (p=.023). CONCLUSION: Weekly dulaglutide and semaglutide significantly reduced HbA1c and weight. Further research is needed to explore factors influencing differential responses. FAU - Deas, Crystal AU - Deas C FAU - Uhomba, Laurel AU - Uhomba L FAU - Snow, Kayla AU - Snow K LA - eng PT - Journal Article PL - United States TA - J Health Care Poor Underserved JT - Journal of health care for the poor and underserved JID - 9103800 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Black or African American/statistics & numerical data MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - Glucagon-Like Peptides/analogs & derivatives/analogs & derivatives MH - *Glycated Hemoglobin/analysis/drug effects MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Immunoglobulin Fc Fragments/administration & dosage/therapeutic use MH - Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use EDAT- 2026/09/21 17:47 MHDA- 2026/09/21 17:48 CRDT- 2026/09/21 13:25 PHST- 2026/09/21 17:48 [medline] PHST- 2026/09/21 17:47 [pubmed] PHST- 2026/09/21 13:25 [entrez] AID - S1548686926100187 [pii] AID - 10.1353/hpu.2026.a982969 [doi] PST - ppublish SO - J Health Care Poor Underserved. 2026;37(1):270-286. doi: 10.1353/hpu.2026.a982969. PMID- 42764643 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20260924 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 46 IP - 10 DP - 2026 Oct TI - Applicability of Non-Invasive Eligibility Criteria for MASH Pharmacotherapy: A Multicentre Cohort Study. PG - e70882 LID - 10.1111/liv.70882 [doi] AB - BACKGROUND AND AIMS: Non-invasive tests (NITs) are increasingly used to guide patient selection for pharmacological treatment of metabolic dysfunction-associated steatohepatitis (MASH). We aimed to quantify and compare real-world treatment eligibility according to the AASLD and expert panel-derived criteria and to evaluate classification of patients with available liver histology. METHODS: We retrospectively included 897 adults with MASLD from four Italian referral centres. Eligibility was assessed using AASLD criteria, defined by liver stiffness measurement (LSM) 8-15 kPa without cirrhosis, and expert panel-derived criteria, defined by LSM 10-19.9 kPa, platelet count >/= 140 x 10(9)/L, and no cirrhosis. A subgroup of 175 patients underwent liver biopsy within +/-3 months of first referral. RESULTS: Median age was 62 years, 57.1% were men, 48.4% had obesity, and 36.0% had Type 2 diabetes. Overall, 202 patients (22.5%) met AASLD criteria and 114 (12.7%) met expert panel-derived criteria. Eighty-six patients were eligible according to both criteria, whereas 144 were classified differently. Type 2 diabetes and obesity were independently associated with eligibility under both criteria. In the biopsy subgroup, 73 patients had histological F2-F3 fibrosis; 35 (47.9%) did not meet AASLD criteria and 49 (67.1%) did not meet expert panel-derived criteria. CONCLUSIONS: The AASLD and expert panel-derived criteria identified different real-world populations potentially suitable for MASH pharmacotherapy. In the biopsy subgroup, NIT-based eligibility classification only partly aligned with histological F2-F3 fibrosis. CI - (c) 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Pugliese, Nicola AU - Pugliese N AUID- ORCID: 0000-0001-6466-1412 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Polverini, Davide AU - Polverini D AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Bertazzoni, Arianna AU - Bertazzoni A AUID- ORCID: 0009-0005-5582-495X AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Cerini, Federica AU - Cerini F AUID- ORCID: 0000-0003-3568-1531 AD - Hepatology Unit, San Giuseppe Hospital, Milan, Italy. AD - Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. FAU - Pennisi, Grazia AU - Pennisi G AUID- ORCID: 0000-0001-9518-4751 AD - Section of Gastroenterology, PROMISE, University of Palermo, Palermo, Italy. FAU - Lombardi, Rosa AU - Lombardi R AUID- ORCID: 0000-0001-6958-927X AD - Unit of Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Gullace, Valerio AU - Gullace V AUID- ORCID: 0009-0002-7321-5494 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - De Nicola, Stella AU - De Nicola S AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Masetti, Chiara AU - Masetti C AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Paviglianiti, Andrea AU - Paviglianiti A AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Fracanzani, Anna Ludovica AU - Fracanzani AL AD - Unit of Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Vigano, Mauro AU - Vigano M AUID- ORCID: 0000-0003-0769-1767 AD - Gastroenterology, Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. FAU - Petta, Salvatore AU - Petta S AUID- ORCID: 0000-0002-0822-9673 AD - Section of Gastroenterology, PROMISE, University of Palermo, Palermo, Italy. FAU - Aghemo, Alessio AU - Aghemo A AUID- ORCID: 0000-0003-0941-3226 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biopsy MH - Diabetes Mellitus, Type 2/complications MH - Elasticity Imaging Techniques MH - *Fatty Liver/drug therapy MH - Italy MH - *Liver/pathology/diagnostic imaging MH - Liver Cirrhosis MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Obesity/complications MH - *Patient Selection MH - Platelet Count MH - Retrospective Studies OAB - As pharmacological treatment for metabolic dysfunction-associated steatohepatitis (MASH) becomes available, selecting appropriate candidates without relying on liver biopsy is a major clinical challenge. We found that currently proposed non-invasive eligibility criteria identify different patient populations and show only partial alignment with histologically confirmed F2-F3 fibrosis in the biopsy subgroup. These findings highlight the need to refine non-invasive patient selection strategies to improve treatment allocation in routine clinical practice. OABL- eng OTO - NOTNLM OT - fibrosis OT - liver stiffness OT - metabolic syndrome OT - resmetirom OT - semaglutide OT - transient elastography EDAT- 2026/09/21 05:34 MHDA- 2026/09/21 05:35 CRDT- 2026/09/21 02:43 PHST- 2026/08/11 00:00 [revised] PHST- 2026/05/30 00:00 [received] PHST- 2026/09/09 00:00 [accepted] PHST- 2026/09/21 05:35 [medline] PHST- 2026/09/21 05:34 [pubmed] PHST- 2026/09/21 02:43 [entrez] AID - 10.1111/liv.70882 [doi] PST - ppublish SO - Liver Int. 2026 Oct;46(10):e70882. doi: 10.1111/liv.70882. PMID- 42755517 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260922 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome. PG - 1881392 LID - 10.3389/fendo.2026.1881392 [doi] LID - 1881392 AB - CONTEXT: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. OBJECTIVE/DESIGN/SETTING: Retrospective, observational cohort of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. PATIENTS: Mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m(2), 75% type 2 diabetes mellitus. INTERVENTION: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). RESULTS: There was no significant overall weight loss on semaglutide, but there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0): post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P = 0.037. There was a significant decrease in hyperphagia on semaglutide from Hyperphagia Questionnaire for Clinical Trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P = 0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P = 0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. CONCLUSIONS: In this small open-label, observational cohort of adults with PWS, semaglutide produced weight maintenance though not weight loss, but appeared to reduce hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater. CI - Copyright (c) 2026 Ahmed, Bridges and Goldstone. FAU - Ahmed, Shahd AU - Ahmed S AD - PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom. FAU - Bridges, Nicola AU - Bridges N AD - Department of Paediatric Endocrinology, Chelsea and Westminster Hospital, London, United Kingdom. FAU - Goldstone, Anthony P AU - Goldstone AP AD - PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom. AD - Department of Endocrinology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. LA - eng PT - Journal Article PT - Observational Study DEP - 20260903 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Adult MH - *Hyperphagia/drug therapy/etiology MH - *Prader-Willi Syndrome/complications/drug therapy MH - Male MH - *Obesity/drug therapy/etiology MH - Retrospective Studies MH - Young Adult MH - Middle Aged MH - Adolescent MH - Treatment Outcome MH - Weight Loss/drug effects MH - Diabetes Mellitus, Type 2 PMC - PMC13581520 OTO - NOTNLM OT - GLP-1 analogue OT - GLP-1 receptor agonists OT - HbA1c OT - PWS OT - Prader-Willi syndrome OT - hyperphagia OT - obesity OT - semaglutide COIS- APG is a consultant for Rhythm Pharmaceuticals and Novo Nordisk; has been a clinical investigator for clinical trials sponsored by Rhythm Pharmaceuticals, Millendo Therapeutics and Soleno Therapeutics; has been a consultant for Eli Lilly, Evidera, Helsinn Healthcare S.A, Idera Pharmaceuticals, Radius Health, Soleno Therapeutics, Tonix Pharmaceuticals and Vida Ventures; has been on Advisory Boards for Radius Health and Millendo Therapeutics; has been on Data Safety Monitoring Committee for Novo Nordisk; has received speaker fees from Eli Lilly, Novo Nordisk, Soleno Therapeutics and Rhythm Pharmaceuticals, and research support from Novo Nordisk. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/18 12:26 MHDA- 2026/09/18 12:27 PMCR- 2026/09/03 CRDT- 2026/09/18 05:13 PHST- 2026/05/14 00:00 [received] PHST- 2026/08/05 00:00 [revised] PHST- 2026/08/10 00:00 [accepted] PHST- 2026/09/18 12:27 [medline] PHST- 2026/09/18 12:26 [pubmed] PHST- 2026/09/18 05:13 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - 10.3389/fendo.2026.1881392 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 3;17:1881392. doi: 10.3389/fendo.2026.1881392. eCollection 2026. PMID- 42747132 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260918 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 5 DP - 2026 Sep TI - Impact of Semaglutide, Liraglutide and Tirzepatide on Cardiometabolic Outcomes: A Comparative Narrative Review. PG - e70338 LID - 10.1002/edm2.70338 [doi] LID - e70338 AB - BACKGROUND: Cardiometabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and cardiovascular disease (CVD) remain major global health challenges. Incretin-based therapies, including the GLP-1 receptor agonists semaglutide and liraglutide, and the dual GIP/GLP-1 receptor agonist tirzepatide, are increasingly used to address hyperglycaemia and obesity, and have been evaluated for both cardiometabolic risk markers and selected cardiovascular and renal outcomes. OBJECTIVE: This review summarizes and contrasts the pharmacology of semaglutide, liraglutide and tirzepatide, distinguishing between surrogate cardiometabolic risk markers (e.g., glycaemic control, body weight and lipid parameters) and confirmed clinical outcomes, including major adverse cardiovascular events (MACE) and renal endpoints. METHODS: Recent data were synthesized from pivotal randomized clinical trial programs, SUSTAIN and PIONEER (semaglutide), LEADER (liraglutide) and SURPASS and SURMOUNT (tirzepatide), as well as meta-analyses, post hoc analyses and observational studies addressing mechanistic and long-term cardiometabolic outcomes. RESULTS: All three agents improved HbA1c, weight and cardiometabolic outcomes, with tirzepatide generally showing greater reductions across clinical trials. Semaglutide and liraglutide consistently improved BMI, lipid profile and cardiovascular risk, while tirzepatide shows promise pending CVOT data. Renal outcomes were favourable across the class, though results varied by baseline characteristics and trial design. CONCLUSION: Semaglutide, liraglutide and tirzepatide are key therapies for type 2 diabetes and cardiometabolic disease. Tirzepatide's dual activity may enhance metabolic and lipid outcomes, while semaglutide and liraglutide have strong evidence for cardiovascular and renal safety. However, comparisons are based on indirect evidence and should be interpreted cautiously. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Bawadi, Hiba AU - Bawadi H AUID- ORCID: 0000-0003-1499-5646 AD - Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Abuhijleh, Haya AU - Abuhijleh H AUID- ORCID: 0009-0005-6643-3655 AD - Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Nofal, Mamon AU - Nofal M AUID- ORCID: 0009-0004-8984-0360 AD - Nottingham University Hospitals NHS Trust, Nottingham, UK. FAU - Zakaria, Zain Z AU - Zakaria ZZ AUID- ORCID: 0000-0002-9656-8367 AD - Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Al-Asmakh, Maha AU - Al-Asmakh M AUID- ORCID: 0000-0001-7855-4001 AD - Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Biomedical Research Center, QU-HEALTH, Qatar University, Doha, Qatar. LA - eng PT - Comparative Study PT - Journal Article PT - Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Liraglutide/therapeutic use MH - Obesity/drug therapy MH - *Semaglutide/therapeutic use MH - Tirzepatide/therapeutic use PMC - PMC13580159 OTO - NOTNLM OT - cardiovascular outcomes OT - lipid modulation OT - liraglutide OT - obesity OT - renal protection OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/09/16 11:41 MHDA- 2026/09/16 11:42 PMCR- 2026/09/16 CRDT- 2026/09/16 09:05 PHST- 2026/06/05 00:00 [revised] PHST- 2026/01/18 00:00 [received] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/09/16 11:42 [medline] PHST- 2026/09/16 11:41 [pubmed] PHST- 2026/09/16 09:05 [entrez] PHST- 2026/09/16 00:00 [pmc-release] AID - EDM270338 [pii] AID - 10.1002/edm2.70338 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Sep;9(5):e70338. doi: 10.1002/edm2.70338. PMID- 42745769 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260921 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Incremental effects of SGLT2 inhibitors, GLP-1 receptor agonists, and pioglitazone in type 2 diabetes and MASLD across Asian study settings: a systematic review and meta-analysis. PG - 1942151 LID - 10.3389/fendo.2026.1942151 [doi] LID - 1942151 AB - OBJECTIVE: We evaluated the incremental hepatic and metabolic effects of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or pioglitazone to comparable background glucose-lowering therapy in Asian adults with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science through 30 June 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Eligible trials evaluated the addition of a study drug to background glucose-lowering management that was comparable between randomized groups and either remained stable or followed a prespecified adjustment protocol. Changes from baseline in alanine aminotransferase (ALT) and glycated hemoglobin (HbA1c) were coprimary outcomes. Secondary outcomes included aspartate aminotransferase, gamma-glutamyl transferase, magnetic resonance imaging-proton density fat fraction, liver stiffness, fibrosis-4 index, fasting plasma glucose, lipid parameters, body mass index, serum adiponectin, and systolic blood pressure. Random-effects pairwise meta-analyses were performed, and GRADE certainty was assessed for the two coprimary outcomes. Safety outcomes were synthesized narratively because reporting was heterogeneous and frequently incomplete. RESULTS: We included eleven randomized trials: 692 participants were randomized into eligible comparisons, of which 642 participated in the coprimary efficacy analyses. Moderate certainty was found for a reduction in ALT with the addition of an SGLT2 inhibitor compared with background therapy alone (mean difference [MD], - 7.56 U/L; 95% confidence interval [CI], - 11.24 to - 3.88); however, there was little or no clinically important further benefit observed for HbA1c (MD, - 0.09%; 95% CI, - 0.27 to 0.08; moderate certainty). Modest reductions in ALT were suggested by moderate certainty for GLP-1RAs (MD, - 6.71 U/L; 95% CI, - 11.53 to - 1.89) while low certainty indicated an HbA1c reduction (MD, - 0.48%; 95% CI, - 0.83 to - 0.14). Secondary exploratory findings favoring add-on therapy existed, although they are unadjusted for multiplicity. The comparative safety could not be assessed reliably. CONCLUSION: In short-term randomized trials conducted in Asian study settings, adding SGLT2 inhibitors or GLP-1RAs may improve selected hepatic and metabolic surrogate outcomes. The available evidence does not support a treatment-class ranking, and the durability and clinical significance of these changes remain uncertain because follow-up was short and several comparisons were based on sparse evidence. Comparative safety also remains uncertain because adverse-event reporting was heterogeneous and incomplete. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251231137. CI - Copyright (c) 2026 Zheng and Han. FAU - Zheng, Hanwen AU - Zheng H AD - First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China. FAU - Han, Jieru AU - Han J AD - School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260901 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - X4OV71U42S (Pioglitazone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (PPAR-gamma Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Pioglitazone/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - PPAR-gamma Agonists MH - Asian People PMC - PMC13574646 OTO - NOTNLM OT - Asian study settings OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - add-on therapy OT - meta-analysis OT - metabolic dysfunction-associated steatotic liver disease OT - pioglitazone OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/16 05:36 MHDA- 2026/09/16 05:37 PMCR- 2026/09/01 CRDT- 2026/09/16 04:29 PHST- 2026/07/19 00:00 [received] PHST- 2026/08/12 00:00 [revised] PHST- 2026/08/13 00:00 [accepted] PHST- 2026/09/16 05:37 [medline] PHST- 2026/09/16 05:36 [pubmed] PHST- 2026/09/16 04:29 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - 10.3389/fendo.2026.1942151 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 1;17:1942151. doi: 10.3389/fendo.2026.1942151. eCollection 2026. PMID- 42745130 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20261008 IS - 1941-6636 (Electronic) VI - 57 IP - 1 DP - 2026 Sep 16 TI - Long-Term Association Between GLP-1 Receptor Agonist Use and Incident Pancreatic Cancer: A Propensity Score-Matched Retrospective Cohort Study Using the TriNetX Network. LID - 221 [pii] LID - 10.1007/s12029-026-01523-w [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity. Whether GLP-1 RA use is associated with altered long-term pancreatic cancer risk remains uncertain, with conflicting evidence from prior observational studies. We aimed to evaluate the association between initiation of GLP-1 RA therapy and incident pancreatic cancer risk compared with six classes of antidiabetic agents. METHODS: We conducted a retrospective, new-user cohort study using the TriNetX global federated electronic health record network. Adults with T2DM initiating GLP-1RA therapy were compared with incident users of insulin, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones in six separate propensity score-matched analyses (1:1, greedy nearest-neighbor algorithm, caliper 0.1 pooled standard deviations). Matching was performed on 39 baseline covariates,, including demographics, comorbidities, procedures, and medication exposures. The primary outcome was incident pancreatic cancer (ICD-10-CM C25) occurring between 365 and 7,300 days after the index prescription. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: After propensity score matching, GLP-1 RA users compared with insulin users had a lower hazard of pancreatic cancer (HR 0.43, 95% CI 0.35, 0.53; absolute risk: GLP-1 RA 0.15% vs. insulin 0.11%; absolute risk difference [ARD] 0.04% points). In contrast, users of metformin (HR 1.39, 95% CI 1.16, 1.66; ARD 0.04% points), sulfonylureas (HR 1.37, 95% CI 1.13, 1.65; ARD 0.07% points), thiazolidinediones (HR 1.30, 95% CI 1.001, 1.678; ARD 0.15% points) and DPP-4i (HR 1.31; 95% CI 1.06, 1.61; ARD 0.08% points) had significantly higher hazards of pancreatic cancer compared with GLP-1 RA users. No significant difference was observed between GLP-1 RA users and users of SGLT2 inhibitors (HR 1.08, 95% CI 0.87, 1.34). CONCLUSIONS: In this large, real-world, propensity score-matched analysis, the direction and magnitude of the association between GLP-1 RA use and pancreatic cancer risk varied by comparator agent. GLP-1 RA use was associated with a lower hazard of pancreatic cancer relative to metformin, sulfonylureas, thiazolidinediones, and DPP-4i while no significant difference relative to SGLT2i, and a higher hazard relative to insulin. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Kazi, Muhammad Ali Ibrahim AU - Kazi MAI AD - Anne Arundel Medical Center, Annapolis, MD, USA. FAU - Khan, Junaid AU - Khan J AD - Anne Arundel Medical Center, Annapolis, MD, USA. FAU - Mufarrih, Syed Musa AU - Mufarrih SM AD - Aga Khan University Karachi, Karachi, Pakistan. FAU - Siddiqui, Maham AU - Siddiqui M AD - Anne Arundel Medical Center, Annapolis, MD, USA. FAU - Ansari, Huzaifa Ul Haque AU - Ansari HUH AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Ahmed, Muhammad AU - Ahmed M AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Qureshi, Imran AU - Qureshi I AD - Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburg, PA, USA. qureshiia@upmc.edu. FAU - Al-Sabban, Abdulhameed AU - Al-Sabban A AD - Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Karnik, Nihaal Prashant AU - Karnik NP AD - Geisinger Health System, Danville, PA, USA. FAU - Gilman, Andrew AU - Gilman A AD - Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA. FAU - Singh, Sanmeet AU - Singh S AD - Anne Arundel Medical Center, Annapolis, MD, USA. FAU - Canakis, Andrew AU - Canakis A AD - Division of Gastroenterology and Hepatology, TidalHealth Peninsula Regional Medical Center, Salisbury, MD, USA. LA - eng PT - Journal Article DEP - 20260916 PL - United States TA - J Gastrointest Cancer JT - Journal of gastrointestinal cancer JID - 101479627 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Insulin Secretagogues) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Pancreatic Neoplasms/epidemiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - Propensity Score MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Incidence MH - Aged MH - Metformin/therapeutic use MH - Insulin Secretagogues MH - Sulfonylurea Compounds/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - Incretin therapy OT - Pancreatic cancer OT - Pharmacoepidemiology OT - Propensity score matching OT - TriNetX OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/09/16 05:36 MHDA- 2026/09/16 05:37 CRDT- 2026/09/16 02:56 PHST- 2026/05/15 00:00 [received] PHST- 2026/07/01 00:00 [accepted] PHST- 2026/09/16 05:37 [medline] PHST- 2026/09/16 05:36 [pubmed] PHST- 2026/09/16 02:56 [entrez] AID - 10.1007/s12029-026-01523-w [pii] AID - 10.1007/s12029-026-01523-w [doi] PST - epublish SO - J Gastrointest Cancer. 2026 Sep 16;57(1):221. doi: 10.1007/s12029-026-01523-w. PMID- 42741141 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20260923 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Comparative change in HbA1c and weight outcomes between obese and non-obese adults with type 2 diabetes mellitus treated with SGLT-2 inhibitors or GLP-1 receptor agonists. PG - 1847755 LID - 10.3389/fendo.2026.1847755 [doi] LID - 1847755 AB - BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are closely linked through shared pathophysiological mechanisms affecting glucose metabolism and insulin resistance. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely recommended for patients with T2DM who are overweight or obese because of their favorable effects. However, whether baseline obesity influences the glycemic response to these agents in real-world clinical practice remains unclear. METHODS: This multicenter retrospective study included adults with T2DM initiated on either SGLT2i or GLP-1RA at three healthcare centers in Riyadh, Saudi Arabia. Patients were stratified into obese (BMI >/=30 kg/m(2)) and non-obese (BMI <30 kg/m(2)). Changes in HbA1c, body weight, and BMI were evaluated at 3, 6, 9, and 12 months. Between-group comparisons were performed using independent t-tests, followed by mixed-effects models for repeated measures (MMRM) to adjust for potential confounders. Secondary outcomes included the proportions of patients achieving >/=5% weight loss, HbA1c <7.0% (among those uncontrolled at baseline), and HbA1c reductions of >/=0.5% and >/=1.0%. RESULTS: A total of 1,016 patients were included, of whom 73.4% were obese. Obese patients were associated with greater reductions in absolute body weight and BMI at 3, 6, 9, and 12 months than non-obese patients, although their higher baseline body weight may have contributed to these differences. Responder analysis showed that obesity was associated with a higher likelihood of achieving >/=5% weight loss at months 3 (21.9% vs. 12.0%, p=0.0016) and 6 (27.2% vs. 15.5%, p=0.0086). In the adjusted MMRM, obesity was associated with greater least-squares mean reductions in weight and BMI (p<0.05), whereas HbA1c reductions and responder rates (HbA1c <7.0%, >/=0.5%, and >/=1.0% reductions) were statistically comparable between groups. CONCLUSION: These findings suggest that baseline obesity was associated with greater reductions in anthropometric measures following SGLT2i or GLP-1RA therapy after multivariable adjustment, whereas improvements in glycemic control were similar between obese and non-obese patients. As these findings are hypothesis-generating, prospective studies are needed to determine whether baseline BMI modifies treatment response. CI - Copyright (c) 2026 Almohammed, Alshaya, Alduhayshi, Alshaibani, Alhamed, Alzeer, Alabdullah, Ibn Saqyan, Al Yami, Bin Sheraim, Almohareb, Alfayez and Korayem. FAU - Almohammed, Omar A AU - Almohammed OA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. AD - Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alshaya, Omar A AU - Alshaya OA AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. FAU - Alduhayshi, Lama A AU - Alduhayshi LA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alshaibani, Sara T AU - Alshaibani ST AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alhamed, Meshal S AU - Alhamed MS AD - College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Alzeer, Mohammed A AU - Alzeer MA AD - College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Alabdullah, Othman M AU - Alabdullah OM AD - College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Ibn Saqyan, Mohamed F AU - Ibn Saqyan MF AD - College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Al Yami, Majed S AU - Al Yami MS AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. FAU - Bin Sheraim, Nader AU - Bin Sheraim N AD - Pharmaceutical Care Services, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi Arabia. FAU - Almohareb, Sumaya N AU - Almohareb SN AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. FAU - Alfayez, Osamah M AU - Alfayez OM AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Buraydah, Saudi Arabia. FAU - Korayem, Ghazwa B AU - Korayem GB AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260831 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - Body Mass Index MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/blood/drug therapy MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects PMC - PMC13572232 OTO - NOTNLM OT - GLP-1 receptor agonists OT - HbA1c OT - SGLT-2 inhibitors OT - body mass index OT - obesity OT - type 2 diabetes mellitus OT - weight loss COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/15 11:37 MHDA- 2026/09/15 11:38 PMCR- 2026/08/31 CRDT- 2026/09/15 05:36 PHST- 2026/04/04 00:00 [received] PHST- 2026/08/10 00:00 [revised] PHST- 2026/08/13 00:00 [accepted] PHST- 2026/09/15 11:38 [medline] PHST- 2026/09/15 11:37 [pubmed] PHST- 2026/09/15 05:36 [entrez] PHST- 2026/08/31 00:00 [pmc-release] AID - 10.3389/fendo.2026.1847755 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 31;17:1847755. doi: 10.3389/fendo.2026.1847755. eCollection 2026. PMID- 42733128 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260916 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 16 IP - 5 DP - 2026 Oct TI - Weight Reduction Heterogenicity and Mediators of GLP-1RAs and Dual Agonists for Individuals With Obesity: A Meta-Analysis. PG - e70112 LID - 10.1111/cob.70112 [doi] LID - e70112 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists have become pivotal options for obesity, but marked weight loss heterogeneity remains poorly understood. This meta-regression analysis aimed to identify factors influencing this heterogeneity. We searched Medline, Embase, The Cochrane Library, and Web of Science up to February 1, 2026, enrolling 32 eligible trials (40 408 participants) following PRISMA guidelines. Meta-regression and subgroup analyses were performed using R software. Pooled analysis showed that GLP-1RAs and dual agonists achieved a weighted mean weight reduction of 9.36% (95% CI 7.92%-10.80%), with high interstudy heterogeneity (I(2) = 99.6%, p < 0.001). Subgroup analyses revealed that GLP-1/GIP dual agonists (tirzepatide) and longer treatment duration (>/= 72 weeks) yielded superior weight-lowering effects. Meta-regression demonstrated that baseline anxiety/depression was positively associated with weight loss efficacy (beta = 2.44, p < 0.001, R(2) = 81.34%). Comorbid Type 2 diabetes mellitus (T2DM), obstructive sleep apnea (OSA) and metabolic dysfunction-associated fatty liver disease (MAFLD) were negatively correlated with treatment response (all p < 0.05). Emotional state and metabolic comorbidities including T2DM, OSA and MAFLD are important influencing factors of the interindividual differences of weight loss efficacy of GLP-1RAs and dual agonists, providing evidence for personalized obesity management. CI - (c) 2026 World Obesity Federation. FAU - Lu, Difei AU - Lu D AUID- ORCID: 0000-0003-3953-8900 AD - Department of Endocrinology, Peking University First Hospital, Beijing, China. FAU - Li, Na AU - Li N AD - Department of Endocrinology, Peking University First Hospital, Beijing, China. FAU - Yuan, Zhenfang AU - Yuan Z AD - Department of Endocrinology, Peking University First Hospital, Beijing, China. FAU - Gao, Ying AU - Gao Y AUID- ORCID: 0000-0002-9156-9483 AD - Department of Endocrinology, Peking University First Hospital, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Weight Loss/drug effects MH - *Anti-Obesity Agents/therapeutic use MH - Tirzepatide MH - Diabetes Mellitus, Type 2 PMC - PMC13572569 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - meta-regression OT - tirzepatide OT - weight reduction COIS- The authors declare no conflicts of interest. EDAT- 2026/09/14 05:35 MHDA- 2026/09/14 05:36 PMCR- 2026/09/14 CRDT- 2026/09/13 23:47 PHST- 2026/08/10 00:00 [revised] PHST- 2026/03/20 00:00 [received] PHST- 2026/09/01 00:00 [accepted] PHST- 2026/09/14 05:36 [medline] PHST- 2026/09/14 05:35 [pubmed] PHST- 2026/09/13 23:47 [entrez] PHST- 2026/09/14 00:00 [pmc-release] AID - COB70112 [pii] AID - 10.1111/cob.70112 [doi] PST - ppublish SO - Clin Obes. 2026 Oct;16(5):e70112. doi: 10.1111/cob.70112. PMID- 42730869 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260929 IS - 1179-1950 (Electronic) IS - 0012-6667 (Print) IS - 0012-6667 (Linking) VI - 86 IP - 10 DP - 2026 Oct TI - GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis. PG - 1661-1691 LID - 10.1007/s40265-026-02365-3 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid((R)) platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I(2) 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings. CI - (c) 2026. The Author(s). FAU - Beaudart, Charlotte AU - Beaudart C AUID- ORCID: 0000-0002-0827-5303 AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. charlotte.beaudart@unamur.be. AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. charlotte.beaudart@unamur.be. AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Faculty of Medicine, Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. charlotte.beaudart@unamur.be. FAU - Malrechauffe, Yveline AU - Malrechauffe Y AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. FAU - van Heden, Sophie AU - van Heden S AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. FAU - Sanchez-Rodriguez, Dolores AU - Sanchez-Rodriguez D AUID- ORCID: 0000-0001-8662-5172 AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Department of Geriatrics, Brugmann University Hospital, Universite Libre de Bruxelles, Brussels, Belgium. AD - Rehabilitation Research Group, Hospital del Mar Research Institute, Barcelone, Spain. FAU - Scheen, Andre AU - Scheen A AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, 4000, Liege, Belgium. AD - Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. FAU - Bruyere, Olivier AU - Bruyere O AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Research Unit in Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. FAU - Mobasheri, Ali AU - Mobasheri A AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Physics and Technology, Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland. AD - Department of Personalised Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. AD - Department for Health Sciences, Medicine and Research, Center for Regenerative Medicine, Faculty of Health and Medicine, University for Continuing Education Krems, Krems, Austria. AD - Department of Orthopaedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Duque, Gustavo AU - Duque G AD - Bone, Muscle & Geroscience Group, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. FAU - Rizzoli, Rene AU - Rizzoli R AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Service of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, 14 1211, Geneva, Switzerland. FAU - Reginster, Jean-Yves AU - Reginster JY AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. FAU - Thiyagarajan, Jotheeswaran Amuthavalli AU - Thiyagarajan JA AD - Ageing and Life Course, World Health Organization, Geneva, Switzerland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260912 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology/analogs & derivatives MH - *Hypoglycemic Agents/pharmacology MH - Liraglutide/pharmacology MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13615104 COIS- Declarations. Conflict of Interest: D.S-R. reports personal speaker fees from Nutricia outside the submitted work. J-Y.R. is President of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), a not-for-profit organisation receiving Unrestricted Educational Grands from corporate partners. J-Y.R. is an Editorial Board member of Drugs. J-Y.R. was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Other authors did not report any conflicts of interest in relation to this work. Disclaimer: The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: All materials related to this work are freely available on the Open Science Framework deposit - https://osf.io/zbhwc/ Availability of Data and Material: All materials related to this work are freely available on the Open Science Framework deposit - https://osf.io/zbhwc/ Authors' Contribution: J-Y.R. and J.A.T. are at the initiative of the research question. C.B. and Y.M. are the main investigators of the present research. C.B. drafted the protocol, which was reviewed by A.S. and J-Y.R. C.B. developed the search strategies and identified potential references for inclusion in the project. Y.M. C.B. and D.S.R. screened the references and selected the relevant ones. Conflicts were resolved by C.B. and Y.M. Y.M. performed the manual literature search. Y.M., C.B. and D.S.R., S.v.H. extracted the data, and performed the risk of bias assessment. Meta-analyses models were run by Y.M and C.B. The results were first interpreted by C.B., J-Y.R., A.S. and then by the rest of the experts, including A.M., R.R., and G.D. The first draft of the manuscript was written by C.B. All authors reviewed and approved the final manuscript. EDAT- 2026/09/13 00:50 MHDA- 2026/09/25 17:32 PMCR- 2026/09/12 CRDT- 2026/09/12 11:07 PHST- 2026/02/26 00:00 [received] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/09/25 17:32 [medline] PHST- 2026/09/13 00:50 [pubmed] PHST- 2026/09/12 11:07 [entrez] PHST- 2026/09/12 00:00 [pmc-release] AID - 10.1007/s40265-026-02365-3 [pii] AID - 2365 [pii] AID - 10.1007/s40265-026-02365-3 [doi] PST - ppublish SO - Drugs. 2026 Oct;86(10):1661-1691. doi: 10.1007/s40265-026-02365-3. Epub 2026 Sep 12. PMID- 42724767 OWN - NLM STAT- MEDLINE DCOM- 20260911 LR - 20260912 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Knowledge, attitudes, and practices of Saudi physicians toward the use of SGLT-2 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus: a nationwide cross-sectional study. PG - 1929125 LID - 10.3389/fendo.2026.1929125 [doi] LID - 1929125 AB - BACKGROUND: Despite guidelines recommending sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) for type 2 diabetes mellitus (T2DM) patients with cardiovascular risk, utilization remains low. This study evaluated the knowledge, attitudes, and practices (KAP) of physicians in Saudi Arabia toward these agents. METHODS: A nationwide cross-sectional study was conducted among 399 physicians in Saudi Arabia between December 2024 and November 2025. Participants completed an online survey assessing pharmacological knowledge, their attitude, and prescribing practices. Multivariable logistic regression was used to identify independent determinants of KAP outcomes. RESULTS: Theoretical knowledge was high, with 91.0% of physicians demonstrating adequate knowledge of SGLT-2i and 78.4% for GLP-1RA. Conversely, only 23.6% held an overall positive attitude, while 75.4% met the threshold for appropriate practice. Notably, 90.0% of physicians identified medication availability and patient accessibility as constant prescribing barriers. Multivariable analysis showed that while knowledge scores were generally high, they did not independently guarantee a positive attitude. Older age was significantly associated with higher odds of inappropriate practice, whereas specialist status and higher attitude scores were linked to better clinical practices. CONCLUSION: The study highlights a significant dissociation between high theoretical knowledge and attitudinal hesitancy among Saudi physicians. These findings suggest that under-prescribing may be associated more with attitudinal and structural factors, such as limited medication access, than with knowledge deficits. Future interventions should prioritize building clinical confidence through academic detailing and addressing systemic access issues to optimize evidence-based management for patients with T2DM. CI - Copyright (c) 2026 Alrasheed, Alhadhrami, Alqarni, Alghamdi, Alfurayh and Almohammed. FAU - Alrasheed, Marwan A AU - Alrasheed MA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alhadhrami, Bader M AU - Alhadhrami BM AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alqarni, Abdulaziz A AU - Alqarni AA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alghamdi, Nawaf M AU - Alghamdi NM AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alfurayh, Omar A AU - Alfurayh OA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Almohammed, Omar A AU - Almohammed OA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. AD - Pharmacoeconomics Research Unit College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article DEP - 20260827 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Cross-Sectional Studies MH - Male MH - Female MH - *Health Knowledge, Attitudes, Practice MH - Saudi Arabia/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Middle Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - *Physicians/psychology/statistics & numerical data MH - Surveys and Questionnaires MH - Attitude of Health Personnel PMC - PMC13559532 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - attitudes OT - clinical inertia OT - knowledge OT - physicians OT - practices OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/11 11:38 MHDA- 2026/09/11 11:39 PMCR- 2026/08/27 CRDT- 2026/09/11 10:32 PHST- 2026/07/05 00:00 [received] PHST- 2026/08/05 00:00 [revised] PHST- 2026/08/06 00:00 [accepted] PHST- 2026/09/11 11:39 [medline] PHST- 2026/09/11 11:38 [pubmed] PHST- 2026/09/11 10:32 [entrez] PHST- 2026/08/27 00:00 [pmc-release] AID - 10.3389/fendo.2026.1929125 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 27;17:1929125. doi: 10.3389/fendo.2026.1929125. eCollection 2026. PMID- 42723898 OWN - NLM STAT- MEDLINE DCOM- 20260911 LR - 20260912 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Effects of GLP-1 receptor agonists on the incidence of contrast-induced acute kidney injury in patients with Type 2 diabetes mellitus undergoing coronary interventions. PG - 1930088 LID - 10.3389/fendo.2026.1930088 [doi] LID - 1930088 AB - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a frequent complication of coronary angiography and percutaneous coronary intervention (PCI), particularly in patients with type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert renoprotective effects, but evidence in the setting of contrast exposure remains limited. OBJECTIVE: To evaluate the association between GLP-1 RA therapy and CI-AKI in patients with T2DM undergoing coronary angiography or PCI for acute coronary syndromes. METHODS: This retrospective cohort study included 336 patients with T2DM who underwent coronary angiography or PCI between May 2023 and March 2025. Patients receiving stable GLP-1 RA therapy (n=149) were compared with non-users (n=187). Serum creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline and 48-72 hours after the procedure. CI-AKI was defined as a serum creatinine increase of >/=0.5 mg/dL or >/=25% from baseline within 72 hours. Multivariable logistic regression was used to identify independent predictors of CI-AKI. RESULTS: CI-AKI occurred less frequently among GLP-1 RA users than non-users (8.7% vs 25.7%, p<0.001). At 48-72 hours, eGFR was higher in the GLP-1 RA group (67.1 +/- 12.1 vs 58.0 +/- 11.8 mL/min/1.73 m(2), p<0.001), whereas serum creatinine did not differ significantly (1.02 +/- 0.73 vs 1.17 +/- 1.57 mg/dL, p=0.084). GLP-1 RA use was independently associated with lower odds of CI-AKI (OR 0.290, 95% CI 0.119-0.708; p=0.007). Increasing age (OR 1.332, 95% CI 1.214-1.462; p<0.001) and ST-segment elevation myocardial infarction (OR 5.039, 95% CI 2.368-10.722; p<0.001) were associated with higher odds, whereas higher baseline eGFR was associated with lower odds (OR 0.919, 95% CI 0.862-0.979; p=0.009). CONCLUSION: GLP-1 RA therapy was independently associated with a lower risk of CI-AKI in patients with T2DM undergoing contrast-based coronary procedures. These findings suggest a potential renoprotective association but require confirmation in prospective multicenter studies. CI - Copyright (c) 2026 Oksen, Aslan, Yavuz, Kaynak and Serin. FAU - Oksen, Dogac AU - Oksen D AD - Department of Cardiology, Altinbas University, Istanbul, Turkiye. FAU - Aslan, Muzaffer AU - Aslan M AD - Department of Cardiology, Siirt University, Siirt, Turkiye. FAU - Yavuz, Yunus Emre AU - Yavuz YE AD - Department of Cardiology, Siirt University, Siirt, Turkiye. FAU - Kaynak, Cagdas AU - Kaynak C AD - Department of Cardiology, Siirt University, Siirt, Turkiye. FAU - Serin, Ebru AU - Serin E AD - Department of Cardiology, Sisli Etfal Training and Research Hospital, Istanbul, Turkiye. LA - eng PT - Journal Article DEP - 20260827 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Contrast Media) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Contrast Media/adverse effects MH - *Acute Kidney Injury/chemically induced/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Percutaneous Coronary Intervention/adverse effects MH - Female MH - Male MH - Retrospective Studies MH - *Coronary Angiography/adverse effects MH - Aged MH - Incidence MH - Middle Aged MH - Glomerular Filtration Rate MH - Acute Coronary Syndrome PMC - PMC13557935 OTO - NOTNLM OT - GLP-1 receptor agonists OT - contrast-induced acute kidney injury OT - coronary angiography OT - percutaneous coronary intervention OT - renal protection OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/11 11:38 MHDA- 2026/09/11 11:39 PMCR- 2026/08/27 CRDT- 2026/09/11 06:46 PHST- 2026/07/06 00:00 [received] PHST- 2026/08/05 00:00 [revised] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/09/11 11:39 [medline] PHST- 2026/09/11 11:38 [pubmed] PHST- 2026/09/11 06:46 [entrez] PHST- 2026/08/27 00:00 [pmc-release] AID - 10.3389/fendo.2026.1930088 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 27;17:1930088. doi: 10.3389/fendo.2026.1930088. eCollection 2026. PMID- 42722378 OWN - NLM STAT- MEDLINE DCOM- 20260910 LR - 20260912 IS - 2233-6087 (Electronic) IS - 2233-6079 (Print) IS - 2233-6079 (Linking) VI - 50 IP - 5 DP - 2026 Sep TI - Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies. PG - 844-862 LID - 10.4093/dmj.2026.0702 [doi] AB - Incretin-based therapies have transformed the treatment of type 2 diabetes mellitus and obesity by producing a weight-loss magnitude that was previously achievable only through intensive caloric restriction or bariatric surgery. This therapeutic shift has moved the clinical focus from the quantity of weight loss to the quality of weight loss. Lean mass reduction is frequently observed during weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual glucose-dependent insulinotropic polypeptide/GLP-1RAs, or emerging multi-agonists. However, loss of lean body mass does not necessarily indicate equivalent loss of contractile skeletal muscle or sarcopenia. Incretin-based therapy is generally associated with preferential fat mass reduction, relative preservation of lean mass, and potential improvement in muscle quality through reduced myosteatosis. Thus, the clinically relevant question is whether incretin-associated body-composition changes lead to deterioration in muscle strength or physical performance, an increased risk of falls or fractures, or impaired quality of life. Available evidence does not show obvious functional harm; however, long-term data remain limited, especially in people with reduced muscle reserve. A muscle-conscious approach that integrates body-composition assessment, functional monitoring, resistance training, nutritional optimization, and emerging pharmacologic muscle-preserving strategies is needed to achieve high-quality weight loss. FAU - Kim, Ji Yoon AU - Kim JY AD - Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea. FAU - Kim, Nam Hoon AU - Kim NH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea. pourlife@korea.ac.kr. LA - eng GR - Technology Innovation Program/ GR - RS-2024-00507932/Ministry of Trade, Industry and Energy/ PT - Journal Article PT - Review DEP - 20260901 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use/adverse effects MH - *Sarcopenia/chemically induced MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Body Composition/drug effects MH - Muscle, Skeletal/drug effects PMC - PMC13561646 OTO - NOTNLM OT - Body composition OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Muscle strength OT - Muscle, skeletal OT - Obesity OT - Retatrutide COIS- CONFLICTS OF INTEREST Nam Hoon Kim has been an associate editor of the Diabetes & Metabolism Journal since 2026. He was not involved in the review process of this article. Otherwise, there are no conflicts of interest. EDAT- 2026/09/11 03:43 MHDA- 2026/09/11 03:44 PMCR- 2026/09/01 CRDT- 2026/09/10 20:19 PHST- 2026/06/30 00:00 [received] PHST- 2026/08/06 00:00 [accepted] PHST- 2026/09/11 03:44 [medline] PHST- 2026/09/11 03:43 [pubmed] PHST- 2026/09/10 20:19 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - dmj.2026.0702 [pii] AID - dmj-2026-0702 [pii] AID - 10.4093/dmj.2026.0702 [doi] PST - ppublish SO - Diabetes Metab J. 2026 Sep;50(5):844-862. doi: 10.4093/dmj.2026.0702. Epub 2026 Sep 1. PMID- 42718474 OWN - NLM STAT- MEDLINE DCOM- 20260910 LR - 20260911 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Electroacupuncture enables semaglutide dose sparing in type 2 diabetes by boosting drug concentration and suppressing beta-cell apoptosis. PG - 1880819 LID - 10.3389/fendo.2026.1880819 [doi] LID - 1880819 AB - PURPOSE: Semaglutide is effective for type 2 diabetes mellitus (T2DM) but limited by dose-dependent gastrointestinal adverse effects. As electroacupuncture (EA) possesses glucose-lowering effects, this study investigates the therapeutic potential and mechanism of combining EA with semaglutide to facilitate dose reduction while maintaining efficacy. METHODS: Male db/db mice were divided into: the model group(T2DM), the high/normal/low-dose semaglutide group (SH, SN, SL), the normal/low-dose semaglutide + EA at ST25 group (ST25N, ST25L), and the EA at ST25 group (ST25). The db/m mice served as the control group (CON). Blood glucose regulation was assessed via random/fasting blood glucose and oral glucose tolerance test (OGTT). To evaluate glycemic control and lipid profiles, HbA1c and insulin levels were quantified via ELISA, and T-CHO, TG, LDL-C, and HDL-C via biochemical kits. GLP-1R expression and beta-cell abundance were assessed by immunofluorescence, and pancreatic apoptosis by TUNEL staining. PKA, pPKA, Bcl-2, Bax, and GLP-1R were analyzed by Western blot. Male Sprague-Dawley (SD) rats were separated into 2 groups: the normal-dose semaglutide rats group (RSN) and the normal-dose semaglutide + EA at ST25 rats group (RST25N). LC-MS/MS was employed to measure the concentrations of semaglutide in the plasma and pancreas, thereby evaluating the influence of EA. RESULTS: EA enhances the effects of semaglutide on improving glycemic control and lipid metabolism, with significant reductions in random/fasting blood glucose, HbA1c, TCHO, TG and LDL-C levels, improvements in OGTT, insulin and HDL-C levels, and longer duration of controlled blood glucose within the target range, Furthermore, EA combined with semaglutide showed a marked increase in pancreatic beta-cells, with the increased expression of pancreatic GLP-1R, PKA, pPKA and Bcl-2, the reduced expression of Bax, increased concentration of semaglutide in plasma and pancreas. CONCLUSION: EA combined with normal- or low-dose semaglutide achieved glycemic control comparable to, or even better than, high-dose semaglutide alone, and its mechanism may be related to its enhancement of GLP-1R to inhibit beta-cell apoptosis and the increased concentration of semaglutide in plasma and pancreas. EA thus has great potential to reduce the dose of semaglutide to alleviate its side effects while ensuring its clinical efficacy. CI - Copyright (c) 2026 Yang, Wu, Gao, Zhu, Sun, Ouyang, Wu, Lan, Zhang, Zhang, Yuan, Sun, Zhu, Fu, Jing and Xu. FAU - Yang, Xinyi AU - Yang X AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Wu, Jiayue AU - Wu J AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Gao, Bing AU - Gao B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhu, Yunmao AU - Zhu Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Sun, Yuchen AU - Sun Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Ouyang, Ling AU - Ouyang L AD - Traditional Chinese Medicine Hospital of Ruichang, Jiujiang, China. FAU - Wu, Bufan AU - Wu B AD - Nantong Hospital of Traditional Chinese Medicine, Nantong, China. FAU - Lan, Wenxiao AU - Lan W AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhang, Jing AU - Zhang J AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhang, Yujie AU - Zhang Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Yuan, Binbin AU - Yuan B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Sun, Yitong AU - Sun Y AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhu, Yuanbing AU - Zhu Y AD - Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. FAU - Fu, Shuping AU - Fu S AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Jing, Xinyue AU - Jing X AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Xu, Bin AU - Xu B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. LA - eng PT - Journal Article DEP - 20260826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Animals MH - Semaglutide MH - *Diabetes Mellitus, Type 2/therapy/drug therapy/pathology/metabolism MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - *Apoptosis/drug effects MH - Male MH - *Insulin-Secreting Cells/drug effects/metabolism/pathology MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - Mice MH - *Electroacupuncture/methods MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Experimental/therapy/pathology MH - Insulin PMC - PMC13553360 OTO - NOTNLM OT - electroacupuncture OT - glucagon-like peptide-1 receptor OT - pancreatic beta-cell OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/10 11:54 MHDA- 2026/09/10 11:55 PMCR- 2026/08/26 CRDT- 2026/09/10 06:05 PHST- 2026/05/13 00:00 [received] PHST- 2026/08/02 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/09/10 11:55 [medline] PHST- 2026/09/10 11:54 [pubmed] PHST- 2026/09/10 06:05 [entrez] PHST- 2026/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2026.1880819 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 26;17:1880819. doi: 10.3389/fendo.2026.1880819. eCollection 2026. PMID- 42717744 OWN - NLM STAT- MEDLINE DCOM- 20260910 LR - 20260928 IS - 2052-1707 (Electronic) IS - 2052-1707 (Linking) VI - 14 IP - 5 DP - 2026 Oct TI - Associations Between Antidiabetic Pharmacotherapy and Hearing Thresholds in Adult Hearing-Impaired Patients With Type 2 Diabetes. PG - e70316 LID - 10.1002/prp2.70316 [doi] LID - e70316 AB - Type 2 diabetes mellitus (T2DM) has increasingly been identified as a risk factor for sensorineural hearing loss, whereas the association between different antidiabetic therapies and hearing thresholds remains poorly characterized. This retrospective observational study evaluated 240 patients with T2DM and 105 normoglycemic controls who underwent standardized pure-tone audiometry at the Audiology Section of the University of Palermo between February 2025 and January 2026. Hearing thresholds were measured using the pure tone average (PTA-mean) at 0.5, 1, 2, and 4 kHz, corresponding to speech-relevant frequencies. Multivariable analysis of covariance, adjusted for age, sex, body mass index, and smoking status, showed that subjects with T2DM had significantly higher PTA-mean values compared to controls (64.4 +/- 17.1 dB vs. 56.4 +/- 14.8 dB; p = 0.007), indicating worse hearing thresholds. Among specific antidiabetic treatments, GLP-1RAs, metformin, and pioglitazone were associated with lower PTA-mean values. Furthermore, pharmacological class analysis showed that GLP-1 receptor agonists and biguanides were associated with more favorable hearing thresholds. These findings suggest that antidiabetic pharmacotherapy may show class-specific associations with auditory function, supporting the need for prospective studies to evaluate whether hearing outcomes should be considered in the broader management of diabetes-related comorbidities. CI - (c) 2026 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and John Wiley & Sons Ltd. FAU - Martines, Francesco AU - Martines F AD - Section of Audiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy. FAU - Salvago, Pietro AU - Salvago P AD - Section of Audiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy. FAU - Vaccaro, Francesca AU - Vaccaro F AD - Department of Health Promotion Sciences, Maternal and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy. FAU - Vaccaro, Davide AU - Vaccaro D AD - Section of Audiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy. FAU - Malta, Ginevra AU - Malta G AUID- ORCID: 0000-0003-0917-7809 AD - Department of Health Promotion Sciences, Maternal and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy. FAU - Plescia, Fabiana AU - Plescia F AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy. FAU - Cascioferro, Stella AU - Cascioferro S AUID- ORCID: 0000-0002-4725-1881 AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy. FAU - Lavanco, Gianluca AU - Lavanco G AUID- ORCID: 0000-0002-4962-379X AD - Department of Health Promotion Sciences, Maternal and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy. FAU - Plescia, Fulvio AU - Plescia F AUID- ORCID: 0000-0002-4786-8435 AD - Department of Health Promotion Sciences, Maternal and Child Care, Internal Medicine and Medical Specialties "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy. LA - eng GR - University Research Fund - FFR 2025/ PT - Journal Article PT - Observational Study PL - United States TA - Pharmacol Res Perspect JT - Pharmacology research & perspectives JID - 101626369 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - X4OV71U42S (Pioglitazone) RN - 0 (Biguanides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Auditory Threshold/drug effects MH - Audiometry, Pure-Tone MH - Metformin/therapeutic use MH - Adult MH - Pioglitazone/therapeutic use MH - Biguanides/therapeutic use/pharmacology MH - *Hearing Loss, Sensorineural/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Auditory Acuity PMC - PMC13559470 OTO - NOTNLM OT - GLP-1 receptor agonists OT - antidiabetic pharmacotherapy OT - cochlear pathophysiology OT - hearing loss OT - hearing thresholds OT - metformin OT - pure-tone audiometry OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/09/10 11:53 MHDA- 2026/09/10 11:54 PMCR- 2026/09/10 CRDT- 2026/09/10 05:14 PHST- 2026/06/24 00:00 [revised] PHST- 2026/02/18 00:00 [received] PHST- 2026/08/26 00:00 [accepted] PHST- 2026/09/10 11:54 [medline] PHST- 2026/09/10 11:53 [pubmed] PHST- 2026/09/10 05:14 [entrez] PHST- 2026/09/10 00:00 [pmc-release] AID - PRP270316 [pii] AID - 10.1002/prp2.70316 [doi] PST - ppublish SO - Pharmacol Res Perspect. 2026 Oct;14(5):e70316. doi: 10.1002/prp2.70316. PMID- 42717332 OWN - NLM STAT- MEDLINE DCOM- 20260910 LR - 20260912 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 24 IP - 1 DP - 2026 Aug 22 TI - Postpartum GLP-1 receptor agonists and SGLT-2 therapies in women with prior gestational diabetes: current evidence and uncertainties. LID - 10.1186/s12916-026-05182-3 [doi] LID - 477 AB - BACKGROUND: Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies and is associated with adverse pregnancy outcomes and a substantially increased risk of long-term cardiometabolic disease. Although glucose levels often normalise postpartum, women with prior GDM have a ten-fold increased risk of developing type 2 diabetes mellitus (T2DM), particularly when early postpartum prediabetes is present. Current prevention strategies, including lifestyle modification and metformin, have in general shown limited effectiveness in this high-risk population. MAIN BODY: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycaemic control, promote weight loss, and reduce cardiovascular risk in people with T2DM and/or obesity. Given the central role of insulin resistance and weight retention in progression from GDM to T2DM, these therapies represent a promising strategy for postpartum diabetes prevention. However, available evidence in women with prior GDM is limited and largely derived from small, short-term studies not adequately powered to assess sustained diabetes prevention or long-term outcomes. Whether GLP-1 RA therapy should be considered an early preventive strategy in this high risk population remains therefore uncertain. The evidence base is now evolving, with the first large multicentre randomised controlled trial (RCT) with a potent GLP-1 RA in women with early postpartum prediabetes following GDM currently underway. In parallel, sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated robust cardiovascular and renal benefits in T2DM, independent of glycaemic status, and may offer additional preventive potential. Their insulin-independent mechanism and favourable cardiovascular profile are particularly attractive in women with prior GDM, who face elevated long-term cardiometabolic risk. However, uncertainties persist regarding safety in women of reproductive age, use during lactation, optimal timing, and patient selection, highlighting the gap between therapeutic promise and dedicated postpartum trial data. CONCLUSION: This Debate examines the emerging role of GLP-1 RA and SGLT-2 inhibitors in preventing T2DM after GDM. Despite their potential, important uncertainties remain regarding long-term efficacy and safety. While these therapies may provide a shift beyond lifestyle intervention and metformin, robust trial data and careful consideration of reproductive factors are required before routine implementation. We discuss how pharmacological prevention strategies could be integrated into postpartum care for this high-risk population. CI - (c) 2026. The Author(s). FAU - Vanlaer, Yana AU - Vanlaer Y AD - Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, Leuven, 3000, Belgium. FAU - Van de Cauter, Ester AU - Van de Cauter E AD - Faculty of Medicine, KU Leuven, Herestraat 49, Leuven, 3000, Belgium. FAU - Embo, Nina AU - Embo N AD - Faculty of Medicine, KU Leuven, Herestraat 49, Leuven, 3000, Belgium. FAU - Benhalima, Katrien AU - Benhalima K AUID- ORCID: 0000-0002-3325-0263 AD - Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, Leuven, 3000, Belgium. katrien.benhalima@uzleuven.be. AD - Department of Endocrinology, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium. katrien.benhalima@uzleuven.be. LA - eng PT - Journal Article PT - Review DEP - 20260822 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes, Gestational/drug therapy MH - Pregnancy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/prevention & control MH - Postpartum Period MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13560376 OTO - NOTNLM OT - Efficacy (max. 10) OT - GLP-1 receptor agonists OT - Gestational diabetes mellitus OT - Pharmacotherapy OT - Postpartum care OT - Postpartum prediabetes OT - SGLT-2 inhibitors OT - Safety OT - Type 2 diabetes prevention COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. AI statement: Microsoft Copilot was used solely for language editing to improve the clarity and readability of the manuscript. The authors reviewed and edited all AI-assisted text and take full responsibility for the content of the manuscript. Competing interests: KB received an unrestricted grant and study devices from Medtronic for the investigator-initiated CRISTAL study. KB received study devices from Dexcom for the investigator-initiated GLORIA study. KB received study medication from Novo Nordisk A/S for the investigator-initiated SERENA study. KB received study devices from Abbott and LifeScan, and a grant from Abbott for the investigator-initiated CORDELIA study. KB received speaker fees from Novo Nordisk, AstraZeneca, and Medtronic. KB was a Guest Editor for the ''''''''Diagnosis and management of gestational diabetes'''''''' collection (special issue on gestational diabetes). All other authors declare that they have no competing interests. EDAT- 2026/09/10 05:36 MHDA- 2026/09/10 11:53 PMCR- 2026/08/22 CRDT- 2026/09/10 04:43 PHST- 2026/04/23 00:00 [received] PHST- 2026/08/20 00:00 [accepted] PHST- 2026/09/10 11:53 [medline] PHST- 2026/09/10 05:36 [pubmed] PHST- 2026/09/10 04:43 [entrez] PHST- 2026/08/22 00:00 [pmc-release] AID - 10.1186/s12916-026-05182-3 [pii] AID - 5182 [pii] AID - 10.1186/s12916-026-05182-3 [doi] PST - epublish SO - BMC Med. 2026 Aug 22;24(1):477. doi: 10.1186/s12916-026-05182-3. PMID- 42712138 OWN - NLM STAT- MEDLINE DCOM- 20261024 LR - 20261024 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 42 IP - 8 DP - 2026 Aug TI - A retrospective cohort study on the comparative safety of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on the onset of gallbladder disease in type II diabetes. PG - 1575-1586 LID - 10.1080/03007995.2026.2726017 [doi] AB - BACKGROUNDS AND OBJECTIVES: To assess and confirm the risk of gallbladder disease in Type II diabetes (T2D) patients treated with Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA) compared to Dipeptidyl Peptidase-4 Inhibitor (DPP-4I). MATERIALS AND METHODS: This is a retrospective cohort study using administrative claims. Adults who newly received either GLP-1RA or DPP-4I for T2D management were identified between 2016 and 2021. Study cohort included individuals naive to gallbladder disease or relevant condition on or 6-month prior to the first GLP-1RA or DDP-4I dispensing date (Index). Cumulative incidence of gallbladder disease after the minimal follow-up period of the first 45 days was estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used to calculate hazard ratios of gallbladder disease for GLP-1RA vs. DPP-4I up to 2 years beyond the initial 45-day exposure. RESULTS: The cohort included 135,197 GLP-1RA and 118,919 DPP-4I patients with minor diabetes complication profiles. Cumulative incidence of gallbladder disease at 1 year was 1.286% (GLP-1RA) vs. 1.054% (DPP-4I); at 2 years, it was 2.181% vs. 2.039%. Adjusting for the baseline characteristics, the respective HR (95% CI) was 1.241 (95% CI, 1.104-1.393) at 1 year and 1.176 (95% CI, 1.061-1.304) at 2 years. CONCLUSION: A moderate but significant increase in the risk of gallbladder disease was confirmed from the real-world population receiving GLP‑1 RA compared with DPP‑4I. This confirmed risk underscores the need for ongoing monitoring and surveillance for gallbladder disease during GLP‑1RA therapy. FAU - Carlson, Katie AU - Carlson K AD - Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Kaur, Jasmeen AU - Kaur J AD - Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Gaber, Charles E AU - Gaber CE AUID- ORCID: 0000-0002-6752-2968 AD - Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Reutrakul, Sirimon AU - Reutrakul S AUID- ORCID: 0000-0002-0686-1069 AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Kim, Kibum AU - Kim K AUID- ORCID: 0000-0002-8676-7434 AD - Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, Illinois, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260909 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Gallbladder Diseases/epidemiology/chemically induced/etiology MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - Adult MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - adverse drug events OT - dipeptidyl peptidase-4 inhibitor OT - gallbladder disease OT - glucagon-like peptide-1 receptor agonist OT - type-2 diabetes EDAT- 2026/09/09 11:38 MHDA- 2026/10/24 05:34 CRDT- 2026/09/09 05:24 PHST- 2026/10/24 05:34 [medline] PHST- 2026/09/09 11:38 [pubmed] PHST- 2026/09/09 05:24 [entrez] AID - 10.1080/03007995.2026.2726017 [doi] PST - ppublish SO - Curr Med Res Opin. 2026 Aug;42(8):1575-1586. doi: 10.1080/03007995.2026.2726017. Epub 2026 Sep 9. PMID- 42711215 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1471-6771 (Electronic) IS - 0007-0912 (Linking) VI - 137 IP - 5 DP - 2026 Nov TI - Delayed gastric emptying in adolescent patients on glucagon-like peptide-1 receptor agonists with standard preoperative fasting guidelines: a prospective cohort study. PG - 1507-1513 LID - S0007-0912(26)00566-0 [pii] LID - 10.1016/j.bja.2026.07.016 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are approved in patients aged >/=10 yr for type 2 diabetes mellitus and aged >/=12 yr for obesity. We examined the effect of GLP1-RAs on the retention of gastric contents in fasting adolescents. METHODS: This prospective cohort study examined adolescent patients (10-18 yr) at a single institution between June 2023 and November 2024. Three groups were compared: a GLP1-RA group; a group at-risk for delayed gastric emptying not on GLP1-RAs; and a healthy control group. All patients fasted 8 h for solids and 1 h for clears liquid. Gastric contents were examined utilising gastric ultrasound qualitatively on a 3-point scale, and quantitatively. The primary outcome was the number of adolescents on GLP1-RAs with residual gastric contents (presence of solids or gastric fluid volume >/=1.5 ml kg(-1)). RESULTS: In total, 67 patients were analysed: 20 in the GLP1-RA group; 27 in the at-risk group; and 20 in the control group. The median age was 14.8 (interquartile range [IQR] 13.2-16.6) yr, and median fasting durations for solids and clears were 13 h (IQR 12-14) and 12 h (IQR 3.5-13), respectively. In the GLP1-RA group, 16/20 patients (80%) had solids present on gastric ultrasound, compared with 17/27 patients (63%) in the at-risk group and 1/20 patient (5%) in the control group (unadjusted P <0.001; adjusted P <0.02, with propensity score adjustment for age, body mass index, sex, race, and NPO time). CONCLUSIONS: We observed that 80% of adolescents on GLP1-RAs had solids on gastric ultrasound despite having fasted for over 12 h. CI - Copyright (c) 2026 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved. FAU - O'Brien, Elizabeth M AU - O'Brien EM AD - Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: obrienem@chop.edu. FAU - Gallop, Robert AU - Gallop R AD - Department of Mathematics, West Chester University of Pennsylvania, West Chester, PA, USA. FAU - Washburn, Maya AU - Washburn M AD - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Dumas, Andrew AU - Dumas A AD - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Como, Nicky AU - Como N AD - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Kilungya, Faith AU - Kilungya F AD - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Willi, Steven M AU - Willi SM AD - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Lin, Elaina E AU - Lin EE AD - Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. LA - eng PT - Journal Article DEP - 20260909 PL - England TA - Br J Anaesth JT - British journal of anaesthesia JID - 0372541 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Adolescent MH - Female MH - Prospective Studies MH - *Gastric Emptying/drug effects MH - Male MH - *Fasting/physiology MH - Child MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Preoperative Care/methods MH - Ultrasonography MH - Diabetes Mellitus, Type 2/drug therapy MH - Cohort Studies MH - Gastrointestinal Contents/diagnostic imaging OTO - NOTNLM OT - delayed gastric emptying OT - gastric ultrasound OT - glucagon-like peptide-1 receptor-agonist OT - paediatric anaesthesia OT - point-of-care ultrasound OT - pulmonary aspiration risk COIS- Declaration of interest The authors declare that they have no conflicts of interest. EDAT- 2026/09/08 23:35 MHDA- 2026/10/28 23:26 CRDT- 2026/09/08 21:55 PHST- 2025/12/12 00:00 [received] PHST- 2026/07/21 00:00 [revised] PHST- 2026/07/26 00:00 [accepted] PHST- 2026/10/28 23:26 [medline] PHST- 2026/09/08 23:35 [pubmed] PHST- 2026/09/08 21:55 [entrez] AID - S0007-0912(26)00566-0 [pii] AID - 10.1016/j.bja.2026.07.016 [doi] PST - ppublish SO - Br J Anaesth. 2026 Nov;137(5):1507-1513. doi: 10.1016/j.bja.2026.07.016. Epub 2026 Sep 9. PMID- 42706128 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 106 IP - 33 DP - 2026 Sep 8 TI - [Glucagon-like peptide-1 receptor agonists: from metabolic regulation to rheumatic disease therapy]. PG - 3431-3437 LID - 10.3760/cma.j.cn112137-20260312-00692 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA), originally developed for type 2 diabetes mellitus and obesity, have attracted considerable attention in rheumatology due to their pleiotropic effects. Accumulating evidence indicates that GLP-1RA not only indirectly reduce inflammation through weight loss and metabolic improvement, but also directly act on GLP-1 receptors expressed on immune cells and musculoskeletal cells, exerting anti-inflammatory and tissue-protective effects independent of weight reduction. In recent years, several large real-world studies and randomized controlled trials have shown that GLP-1RA may improve disease activity and reduce cardiovascular events and mortality in osteoarthritis, rheumatoid arthritis (RA), psoriasis/psoriatic arthritis, and systemic lupus erythematosus (SLE). However, the available evidence has notable limitations: most studies are retrospective, with limited sample sizes; different GLP-1RA are often analyzed as a single class; the weight-loss effect is difficult to dissociate from direct anti-inflammatory action; and randomized controlled trials in non-obese, non-diabetic rheumatic patients are lacking. This review systematically summarizes the molecular mechanisms and clinical evidence of GLP-1RA in rheumatic diseases (including RA, psoriasis/psoriatic arthritis, osteoarthritis, and SLE), and based on this, the authors' perspective is put forward: currently, GLP-1RA should only be recommended for rheumatic patients with overweight/obesity or type 2 diabetes who also have high cardiovascular risk. Future research should prioritize head-to-head comparisons of different GLP-1RA, mechanistic studies independent of weight loss, and exploration of combination strategies. It is believed that GLP-1RA hold promise to usher in a new era of "metabolic-immune" synergistic intervention in rheumatology, but their benefits and risks must be carefully evaluated. FAU - Xie, W H AU - Xie WH AD - Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, China. FAU - Chen, T AU - Chen T AD - Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, China. FAU - Zhang, Z L AU - Zhang ZL AD - Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, China. LA - chi GR - 82302018, 82372369/National Natural Science Foundation of China/ PT - English Abstract PT - Journal Article PT - Review PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Rheumatic Diseases/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor COIS- 所有作者声明不存在利益冲突 EDAT- 2026/09/07 23:34 MHDA- 2026/09/08 05:36 CRDT- 2026/09/07 22:03 PHST- 2026/09/08 05:36 [medline] PHST- 2026/09/07 23:34 [pubmed] PHST- 2026/09/07 22:03 [entrez] AID - 10.3760/cma.j.cn112137-20260312-00692 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2026 Sep 8;106(33):3431-3437. doi: 10.3760/cma.j.cn112137-20260312-00692. PMID- 42704495 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20261008 IS - 1432-1459 (Electronic) IS - 0340-5354 (Linking) VI - 273 IP - 10 DP - 2026 Sep 7 TI - GLP-1 receptor agonists vs DPP-4 inhibitors and neuropathic complications in type 2 diabetes. LID - 569 [pii] LID - 10.1007/s00415-026-14127-y [doi] AB - INTRODUCTION: Diabetic peripheral neuropathy is a debilitating complication of type 2 diabetes mellitus (T2DM) associated with foot ulceration, amputation, Charcot neuroarthropathy, and reduced quality of life. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used therapies for T2DM, their comparative effects on neuropathy-related lower-extremity complications remain unclear. OBJECTIVE: To compare diabetic foot ulcers, lower-extremity amputations, foot/ankle osteomyelitis, Charcot neuroarthropathy, and all-cause mortality in T2DM patients with neuropathy treated with GLP-1 RAs versus DPP-4 inhibitors. METHODS: Using the TriNetX US Collaborative Network, we identified adults with T2DM and diabetic neuropathy, unspecified (ICD-10-CM E11.40), initiating either a GLP-1 RA or a DPP-4 inhibitor. After exclusions and 1:1 propensity score matching for demographics, comorbidities, and medications, 19,770 patients per cohort were balanced. Outcomes were assessed over 1 year and 2 years using Kaplan-Meier and Cox proportional hazards models, with Bonferroni correction (p < 0.01). RESULTS: After matching, GLP-1 RAs were associated with a 1-year lower risk of diabetic foot ulcers (2.2% vs 2.7%; HR 0.813, 95% CI 0.716-0.922) and lower all-cause mortality, though the mortality finding was interpreted as hypothesis-generating. Amputation (0.5% vs 0.5%; HR 1.073, 95% CI 0.810-1.421) and foot/ankle osteomyelitis (0.4% vs 0.4%; HR 0.978, 95% CI 0.708-1.349) rates were similar. Charcot neuroarthropathy incidence was higher with GLP-1 RAs (0.3% vs 0.2%; HR 1.993, 95% CI 1.297-3.064). DISCUSSION: In T2DM patients with neuropathy, GLP-1 RA therapy was associated with lower risk of diabetic foot ulcers and higher Charcot neuroarthropathy risk compared with DPP-4 inhibitors, while amputation and osteomyelitis risks were similar. These findings support further study of GLP-1 RAs in this population and highlight the need for careful foot monitoring during therapy. CI - (c) 2026. Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Tawfik, Fady AU - Tawfik F AUID- ORCID: 0009-0002-9570-6403 AD - Howard University College of Medicine, Washington, DC, USA. fadytwfk@gmail.com. FAU - Yalley, Eric AU - Yalley E AD - Howard University College of Medicine, Washington, DC, USA. FAU - Sienkaniec, Justyna AU - Sienkaniec J AD - Howard University College of Medicine, Washington, DC, USA. FAU - Mendoza, Marshall AU - Mendoza M AD - Howard University College of Medicine, Washington, DC, USA. FAU - Bhatia, Ronak AU - Bhatia R AD - Howard University College of Medicine, Washington, DC, USA. FAU - Boulis, Michael AU - Boulis M AD - Texas A&M University College of Medicine, Bryan, TX, USA. FAU - Hashmi, Humzah AU - Hashmi H AD - Howard University College of Medicine, Washington, DC, USA. FAU - Mohamed, Khalid AU - Mohamed K AD - Howard University College of Medicine, Washington, DC, USA. FAU - Guidry, Caitlin AU - Guidry C AD - Howard University College of Medicine, Washington, DC, USA. FAU - Michael, Miriam AU - Michael M AD - Department of Internal Medicine, Howard University, Washington, DC, USA. AD - Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260907 PL - Germany TA - J Neurol JT - Journal of neurology JID - 0423161 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Diabetic Neuropathies/drug therapy/etiology/epidemiology/mortality MH - *Diabetic Foot/epidemiology/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Amputation, Surgical/statistics & numerical data OTO - NOTNLM OT - Charcot neuroarthropathy OT - Diabetic foot ulcer OT - Diabetic neuropathy OT - GLP-1 receptor agonist OT - Treatment-induced neuropathy of diabetes COIS- Declarations. Conflicts of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethical Publication and Informed Consent Statement: This study was determined to be exempt from review by the Howard University Hospitals Institutional Review Board (IRB), as it involved the retrospective analysis of de-identified patient data obtained from the TriNetX Global Collaborative Network. No identifiable private information was collected or recorded, and there was no direct interaction with patients. As such, the research qualifies for exemption under 45 CFR 46.104(d)(4). Informed consent was not required. All research activities were carried out in accordance with the guidelines and regulations of the Howard University Hospitals Institutional Review Board and in compliance with the ethical principles outlined in the 1964 Declaration of Helsinki and its later amendments. EDAT- 2026/09/07 17:36 MHDA- 2026/09/07 17:37 CRDT- 2026/09/07 11:16 PHST- 2026/06/27 00:00 [received] PHST- 2026/09/02 00:00 [accepted] PHST- 2026/08/29 00:00 [revised] PHST- 2026/09/07 17:37 [medline] PHST- 2026/09/07 17:36 [pubmed] PHST- 2026/09/07 11:16 [entrez] AID - 10.1007/s00415-026-14127-y [pii] AID - 10.1007/s00415-026-14127-y [doi] PST - epublish SO - J Neurol. 2026 Sep 7;273(10):569. doi: 10.1007/s00415-026-14127-y. PMID- 42704078 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261022 IS - 1549-7852 (Electronic) IS - 1040-8398 (Linking) VI - 66 IP - 33 DP - 2026 TI - Interactions between dietary intake and GLP-1 biology: implications for metabolic dysfunction and aging. PG - 7724-7738 LID - 10.1080/10408398.2026.2728313 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as highly effective therapies for obesity and type 2 diabetes by improving glycemic control and reducing body weight, primarily through the suppression of energy intake. Recent evidence suggests a bidirectional relationship between dietary intake and GLP-1 biology. Dietary factors, including caloric intake, meal timing, and macronutrient composition, may influence endogenous GLP-1 secretion, while GLP-1-based therapies may alter food choice and macronutrient preference. This review discusses the effects of dietary intake on endogenous GLP-1 regulation and examines how GLP-1-based therapies influence ingestive behavior and food preference, with particular emphasis on the responses to macronutrient composition. We further discuss the potential interaction between dietary intake and pharmacological GLP-1 signaling and its implications for metabolic health and aging. A better understanding of these bidirectional interactions may contribute to the development of personalized nutritional approaches that complement GLP-1-based therapies and improve long-term management of metabolic dysfunction. FAU - Han, Yerim AU - Han Y AD - Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea. AD - Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea. FAU - Shon, Jinyoung AU - Shon J AD - Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea. AD - Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea. FAU - Park, Yoon Jung AU - Park YJ AD - Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea. AD - Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea. AD - Global Food & Nutrition Research Institute, Ewha Womans University, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Review DEP - 20260907 PL - United States TA - Crit Rev Food Sci Nutr JT - Critical reviews in food science and nutrition JID - 8914818 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/metabolism MH - *Aging/physiology MH - *Diet MH - Energy Intake MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Diabetes Mellitus, Type 2/drug therapy MH - Food Preferences MH - Nutrients MH - *Eating MH - Signal Transduction OTO - NOTNLM OT - Diet OT - GLP-1 OT - GLP-1R agonists OT - food choice OT - macronutrients EDAT- 2026/09/07 11:37 MHDA- 2026/10/23 05:32 CRDT- 2026/09/07 07:53 PHST- 2026/10/23 05:32 [medline] PHST- 2026/09/07 11:37 [pubmed] PHST- 2026/09/07 07:53 [entrez] AID - 10.1080/10408398.2026.2728313 [doi] PST - ppublish SO - Crit Rev Food Sci Nutr. 2026;66(33):7724-7738. doi: 10.1080/10408398.2026.2728313. Epub 2026 Sep 7. PMID- 42697206 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 58 IP - 9 DP - 2026 Sep TI - Recent Advances in Glucagon-Like Peptide-1 Receptor and Melanocortin-4 Receptor Agonists for the Treatment of Obesity and Type 2 Diabetes. PG - 339-353 LID - 10.1055/a-2928-5204 [doi] AB - The global rise in aging populations has been accompanied by increasing rates of obesity and type 2 diabetes, both of which pose significant public health and economic challenges. This review aims to investigate the pathophysiological link between obesity and diabetes and evaluate emerging therapeutic strategies that involve glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, including their dual and triple agonist developments. A comprehensive literature review was conducted focusing on the mechanisms of glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, their clinical efficacy, and the evolution of combination therapies. Emphasis was placed on recent clinical trials and the development of oral agonist formulations to improve patient compliance. Glucagon-like peptide-1 receptor agonists, such as semaglutide and liraglutide, promote insulin secretion, suppress appetite, and result in effective weight loss and glycemic control. Semaglutide is available in both injectable and oral forms, improving accessibility. Liraglutide also reduces cardiovascular risk. Melanocortin-4 receptor agonists act via the central nervous system to reduce appetite and increase energy expenditure, with setmelanotide showing efficacy in genetic obesity. Dual and triple agonists, such as tirzepatide, simultaneously target glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptors, leading to enhanced metabolic outcomes. Oral drugs like rybelsus improve long-term adherence. Glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, particularly when used as dual or triple agents, represent promising therapeutic innovations for obesity and type 2 diabetes. The development of oral formulations further enhances treatment convenience and adherence, paving the way for improved clinical outcomes. CI - Thieme. All rights reserved. FAU - Lee, Chang-Min AU - Lee CM AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Kim, Jin-Young AU - Kim JY AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Shim, Jeong-Hyun AU - Shim JH AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Cho, Gwang-Won AU - Cho GW AUID- ORCID: 0000-0002-2149-5095 AD - Chosun University, Department of Biological Science, South Korea, Gwangju. LA - eng PT - Journal Article PT - Review DEP - 20260904 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Receptor, Melanocortin, Type 4) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Receptor, Melanocortin, Type 4/agonists MH - *Obesity/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Animals MH - *Glucagon-Like Peptide-1 Receptor/metabolism COIS- The authors declare that they have no conflict of interest. EDAT- 2026/09/04 23:36 MHDA- 2026/09/15 05:06 CRDT- 2026/09/04 18:42 PHST- 2026/09/15 05:06 [medline] PHST- 2026/09/04 23:36 [pubmed] PHST- 2026/09/04 18:42 [entrez] AID - 10.1055/a-2928-5204 [doi] PST - ppublish SO - Horm Metab Res. 2026 Sep;58(9):339-353. doi: 10.1055/a-2928-5204. Epub 2026 Sep 4. PMID- 42697203 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20260923 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 7 IP - 9 DP - 2026 Sep 15 TI - Emerging role of GLP-1 mono, dual, and triple agonists in the management of MASH-related fibrosis. PG - 103023 LID - S2666-3791(26)00440-4 [pii] LID - 10.1016/j.xcrm.2026.103023 [doi] LID - 103023 AB - Recent therapeutic advances have resulted in US Food and Drug Administration (FDA) approval of the first pharmacological agents-resmetirom and semaglutide-for advanced metabolic dysfunction-associated steatohepatitis (MASH) without cirrhosis, reshaping the therapeutic landscape of the disease. Within this evolving framework, incretin-based pharmacotherapies-including glucagon-like peptide-1 (GLP-1) receptor agonists and their dual and triple combinations with glucose-dependent insulinotropic peptide (GIP) and/or glucagon receptor agonists-have emerged as promising options, particularly for individuals with coexisting obesity or type 2 diabetes. These agents exert pleiotropic effects across multiple organs, modulating glucose and lipid metabolism, while providing cardiovascular and renal benefits. Despite these advances, key challenges remain regarding treatment duration, tolerability, and interindividual variability in therapeutic response. This review summarizes the emerging role of GLP-1 mono, dual, and triple agonists in MASH-related fibrosis, focusing on their mechanisms of action and evidence from phase 2 and phase 3 clinical trials with histology-assessed hepatic endpoints. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Tavaglione, Federica AU - Tavaglione F AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA. Electronic address: ftavaglione@health.ucsd.edu. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA; School of Public Health, University of California, San Diego, La Jolla, CA, USA. Electronic address: roloomba@health.ucsd.edu. LA - eng GR - P30 DK120515/DK/NIDDK NIH HHS/United States GR - UL1 TR001442/TR/NCATS NIH HHS/United States PT - Journal Article PT - Review DEP - 20260904 PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Animals MH - Glucagon-Like Peptides/therapeutic use MH - *Liver Cirrhosis/drug therapy/pathology MH - Fibrosis/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - *Fatty Liver/drug therapy/pathology MH - Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Incretins/therapeutic use MH - Hypoglycemic Agents/therapeutic use PMC - PMC13589479 OTO - NOTNLM OT - GIP OT - MASLD OT - NAFLD OT - glucagon OT - incretins COIS- Declaration of interests R.L. serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse Bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. R.L. is also a co-founder of LipoNexus Inc. EDAT- 2026/09/04 23:36 MHDA- 2026/09/15 23:34 PMCR- 2026/09/04 CRDT- 2026/09/04 18:41 PHST- 2026/03/18 00:00 [received] PHST- 2026/06/26 00:00 [revised] PHST- 2026/08/11 00:00 [accepted] PHST- 2026/09/15 23:34 [medline] PHST- 2026/09/04 23:36 [pubmed] PHST- 2026/09/04 18:41 [entrez] PHST- 2026/09/04 00:00 [pmc-release] AID - S2666-3791(26)00440-4 [pii] AID - 103023 [pii] AID - 10.1016/j.xcrm.2026.103023 [doi] PST - ppublish SO - Cell Rep Med. 2026 Sep 15;7(9):103023. doi: 10.1016/j.xcrm.2026.103023. Epub 2026 Sep 4. PMID- 42696840 OWN - NLM STAT- MEDLINE DCOM- 20261005 LR - 20261005 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 421 DP - 2026 Oct TI - Prediabetes: Impact on cardiovascular risk and emerging therapeutic strategies. PG - 121898 LID - S0021-9150(26)01264-5 [pii] LID - 10.1016/j.atherosclerosis.2026.121898 [doi] AB - Prediabetes is an umbrella term which refers to a collection of blood parameters related to glucose regulation exceeding their normal threshold, but not meeting the criteria for overt diabetes. Its prevalence is rising worldwide, largely driven by overweight/obesity, diet, lack of exercise and familiarity. OBJECTIVES: To provide a state-of-the-art overview of epidemiology, pathophysiology, cardiovascular (CV) implications, and emerging therapeutic strategies in prediabetes. METHODS: Narrative review with structured discussion of randomized controlled trials (RCTs) and meta-analyses addressing progression to T2DM and cardiovascular outcomes. RESULTS: The risk of prediabetes progressing to T2DM is well established, with modest differences across phenotypes (impaired fasting glucose, impaired glucose tolerance, elevated HbA1c). In contrast, whether prediabetes independently increases CV risk remains debated. Observational studies and meta-analyses suggest a mild but statistically significant increase in CV events and mortality; however, randomized evidence demonstrating CV benefit from treating prediabetes is limited and methodologically heterogeneous. Current management of prediabetes primarily relies on lifestyle interventions, while metformin is recommended only in selected high-risk individuals. Glucagon-like peptide receptor-1 agonists and sodium-glucose cotransporter-2 inhibitors have shown disease-modifying effects in T2DM and related cardiometabolic conditions. Emerging data suggest potential benefits in individuals with prediabetes, although dedicated adequately powered CV outcome trials are lacking. CONCLUSIONS: Prediabetes is a clinically relevant cardiometabolic state. While progression to T2DM is well documented, its role as an independent CV therapeutic target remains uncertain. Future trials should address phenotype-specific risk stratification and evaluate contemporary cardiometabolic therapies in appropriately powered populations. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Biondi, Filippo AU - Biondi F AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy. FAU - Ghelardoni, Sandra AU - Ghelardoni S AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, Pisa, Italy. FAU - Monti, Emilia AU - Monti E AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy. FAU - Avagimyan, Ashot AU - Avagimyan A AD - Department of Internal Diseases Propedeutics, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia. FAU - De Caterina, Raffaele AU - De Caterina R AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy. Electronic address: raffaele.decaterina@unipi.it. FAU - Madonna, Rosalinda AU - Madonna R AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy. Electronic address: rosalinda.madonna@unipi.it. LA - eng PT - Journal Article PT - Review DEP - 20260903 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Prediabetic State/epidemiology/therapy/diagnosis/blood/drug therapy MH - *Cardiovascular Diseases/epidemiology/prevention & control/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/epidemiology MH - Disease Progression MH - Heart Disease Risk Factors MH - Risk Factors MH - Blood Glucose/metabolism/drug effects MH - Risk Assessment MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Risk Reduction Behavior MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Glucagon-like peptide receptor-1 agonists OT - Preclinical models OT - Prediabetes OT - Randomized clinical trials OT - Sodium-glucose cotransporter-2 inhibitors COIS- Declaration of competing interest No conflict of interest declared on this topic. EDAT- 2026/09/04 23:36 MHDA- 2026/10/05 23:29 CRDT- 2026/09/04 18:01 PHST- 2026/05/24 00:00 [received] PHST- 2026/08/23 00:00 [revised] PHST- 2026/08/31 00:00 [accepted] PHST- 2026/10/05 23:29 [medline] PHST- 2026/09/04 23:36 [pubmed] PHST- 2026/09/04 18:01 [entrez] AID - S0021-9150(26)01264-5 [pii] AID - 10.1016/j.atherosclerosis.2026.121898 [doi] PST - ppublish SO - Atherosclerosis. 2026 Oct;421:121898. doi: 10.1016/j.atherosclerosis.2026.121898. Epub 2026 Sep 3. PMID- 42692567 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260903 IS - 1558-1373 (Electronic) IS - 0030-5898 (Linking) VI - 57 IP - 4 DP - 2026 Oct TI - Glucagon-like Peptide-1 Receptor Agonist Use May Reduce Disease Activity and Progression in Osteoarthritis and Inflammatory Arthritis. PG - 317-327 LID - S0030-5898(26)00074-X [pii] LID - 10.1016/j.ocl.2026.05.004 [doi] AB - Obesity, metabolic syndrome, and type 2 diabetes mellitus contribute to osteoarthritis (OA) through adipokine signaling, systemic inflammation, oxidative stress, and insulin resistance, affecting both weight-bearing and non-weight-bearing joints. Glucagon-like peptide-1 receptor agonists have rapidly expanded in use and promises musculoskeletal benefits beyond weight loss. Preclinical studies demonstrate anti-inflammatory, analgesic, and chondroprotective effects, including reduced cytokine activity and cartilage matrix degradation. Randomized trials in knee OA show significant weight loss with modest improvements in pain and function, while observational data suggest possible cartilage preservation and reduced surgical rates, though results are mixed. Evidence in inflammatory arthritis is promising but limited. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Trudeau, Maxwell AU - Trudeau M AD - Department of Orthopedic Surgery, NYU Langone, 301 East 17th Street, 14th Floor, New York, NY 10003, USA. FAU - Schaffer, Olivia AU - Schaffer O AD - Department of Orthopedic Surgery, NYU Langone, 301 East 17th Street, 14th Floor, New York, NY 10003, USA. FAU - Schwarzkopf, Ran AU - Schwarzkopf R AD - Department of Orthopedic Surgery, NYU Langone, 301 East 17th Street, 14th Floor, New York, NY 10003, USA. Electronic address: schwarzk@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260723 PL - United States TA - Orthop Clin North Am JT - The Orthopedic clinics of North America JID - 0254463 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoarthritis/drug therapy/etiology MH - Disease Progression MH - Diabetes Mellitus, Type 2/complications MH - Obesity/complications OTO - NOTNLM OT - Chronic inflammation OT - Diabetes mellitus OT - GLP-1 receptor agonists OT - Metabolic syndrome OT - Obesity OT - Osteoarthritis OT - Rheumatoid arthritis COIS- Disclosure The authors have nothing to disclose. EDAT- 2026/09/03 23:36 MHDA- 2026/09/03 23:37 CRDT- 2026/09/03 20:56 PHST- 2026/09/03 23:37 [medline] PHST- 2026/09/03 23:36 [pubmed] PHST- 2026/09/03 20:56 [entrez] AID - S0030-5898(26)00074-X [pii] AID - 10.1016/j.ocl.2026.05.004 [doi] PST - ppublish SO - Orthop Clin North Am. 2026 Oct;57(4):317-327. doi: 10.1016/j.ocl.2026.05.004. Epub 2026 Jul 23. PMID- 42690722 OWN - NLM STAT- MEDLINE DCOM- 20261024 LR - 20261024 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 42 IP - 8 DP - 2026 Aug TI - From insulin resistance to incretin receptor agonism in the prevention of type 2 diabetes mellitus in obese individuals. PG - 1503-1517 LID - 10.1080/03007995.2026.2727202 [doi] AB - Type 2 diabetes mellitus (T2DM) represents one of the most significant metabolic challenges of the modern era, with more than 828 million people worldwide living with diabetes. Obesity and insulin resistance are major modifiable contributors to T2DM risk and progression, although the disease is heterogeneous and arises from complex interactions among beta-cell dysfunction, hepatic glucose dysregulation, adipose-tissue dysfunction, altered incretin biology, chronic low-grade inflammation, and genetic susceptibility. In individuals with obesity and insulin resistance, progression through prediabetes to overt hyperglycaemia represents an important, although not universal, disease trajectory and provides a clinically relevant window for preventive intervention. This review examines pharmacological strategies relevant to T2DM prevention in individuals without established diabetes who have prediabetes and/or obesity associated with a high risk of progression to T2DM, with particular emphasis on incretin-based obesity pharmacotherapy. Metformin remains the glucose-lowering agent with the most established long-term evidence for diabetes prevention in selected high-risk individuals with prediabetes, acting through multiple hepatic and intestinal mechanisms involving both AMPK-dependent and AMPK-independent pathways. Other established antihyperglycaemic drug classes are discussed primarily to distinguish therapies with evidence for delaying progression to diabetes from agents whose principal role remains the treatment of established T2DM. SGLT2 inhibitors provide substantial cardiovascular and renal protection, although current evidence is insufficient to support their routine use solely for T2DM prevention. GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide have substantially advanced obesity pharmacotherapy, producing clinically meaningful weight loss and broader cardiometabolic benefits that may reduce progression to T2DM in high-risk individuals.Next-generation incretin-based therapies, including triple receptor agonists, may further expand therapeutic options but remain an evolving area of investigation. Lifestyle intervention and sustained weight management remain the foundation of T2DM prevention, with pharmacological strategies selected according to individual metabolic risk, obesity-related treatment indications, comorbidities, and the strength of evidence supporting diabetes prevention. FAU - Teofilovic, Branislava AU - Teofilovic B AUID- ORCID: 0000-0002-0917-3974 AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. FAU - Trkulja, Jelena AU - Trkulja J AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. FAU - Grujic-Letic, Nevena AU - Grujic-Letic N AUID- ORCID: 0000-0002-6424-8502 AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. FAU - Gligoric, Emilia AU - Gligoric E AUID- ORCID: 0000-0002-0512-1915 AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. FAU - Baletic, Djordje AU - Baletic D AUID- ORCID: 0009-0004-1579-2159 AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. AD - Faculty of Pharmacy, Bijeljina University, Bijeljina, Bosnia and Herzegovina. FAU - Tomic, Ljiljana AU - Tomic L AUID- ORCID: 0009-0005-1754-1393 AD - Faculty of Pharmacy, Bijeljina University, Bijeljina, Bosnia and Herzegovina. FAU - Mesarovic, Aleksandra AU - Mesarovic A AD - Faculty of Pharmacy, Bijeljina University, Bijeljina, Bosnia and Herzegovina. FAU - Raskovic, Aleksandar AU - Raskovic A AUID- ORCID: 0000-0001-8439-4630 AD - Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. LA - eng PT - Journal Article PT - Review DEP - 20260903 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/prevention & control/etiology/metabolism MH - *Obesity/complications/drug therapy/metabolism MH - *Incretins/therapeutic use/metabolism MH - *Insulin Resistance MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Diabesity MH - Metformin/therapeutic use MH - Animals OTO - NOTNLM OT - GLP-1 receptor agonists OT - Type 2 diabetes mellitus OT - antihyperglycaemic agents OT - insulin resistance OT - obesity OT - retatrutide OT - tirzepatide EDAT- 2026/09/03 17:36 MHDA- 2026/10/24 05:34 CRDT- 2026/09/03 12:56 PHST- 2026/10/24 05:34 [medline] PHST- 2026/09/03 17:36 [pubmed] PHST- 2026/09/03 12:56 [entrez] AID - 10.1080/03007995.2026.2727202 [doi] PST - ppublish SO - Curr Med Res Opin. 2026 Aug;42(8):1503-1517. doi: 10.1080/03007995.2026.2727202. Epub 2026 Sep 3. PMID- 42687069 OWN - NLM STAT- MEDLINE DCOM- 20261007 LR - 20261010 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 43 IP - 9 DP - 2026 Sep TI - Semaglutide Bioavailability: Limitations, Formulation Innovation and Future Opportunities. PG - 2989-3010 LID - 10.1007/s11095-026-04185-2 [doi] AB - Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, improved the type 2 diabetes mellitus treatment and obesity by its glucose-lowering and weight loss effects. Although the subcutaneous route provides high bioavailability and stable pharmacokinetics, the development of oral semaglutide makes a significant advancement in peptide therapeutics. However, oral delivery remains limited by an absolute bioavailability of only approximately 0.4-1% under optimized fasting conditions with restricted water intake, whereas systemic exposure is essentially absent in the fed state because plasma semaglutide concentrations remain below the limit of quantification. This extremely low exposure reflects peptide degradation within the gastrointestinal tract, poor epithelial permeability, gastric physiological constraints, and presystemic metabolism. The combination with sodium N-(8-[2-hydroxybenzoyl]amino) caprylate (SNAC) helps in gastric absorption by increasing the local gastric microenvironmental pH, thereby reducing acid-induced peptide unfolding, suppressing pepsin activation, maintaining semaglutide predominantly in its absorbable monomeric form by limiting oligomer formation, and enhancing transcellular uptake. But the oral form of semaglutide is constrained by narrow dose limits, considerable pharmacokinetic variability that, despite large fluctuations in individual absorption, produces relatively stable steady-state exposure because semaglutide's approximately one-week half-life and extensive albumin binding buffer day-to-day differences in absorption. This review examines semaglutide pharmacokinetics, focusing on mechanistic challenges to oral bioavailability and formulation approaches to address this. We assess emerging methods such as nanotechnology-based formulations, other permeation enhancers, enzyme inhibitors and device-based delivery systems for their abilities to improve absorption and efficacy. Furthermore, clinical efficacy and patient adherence as well as research opportunities are considered. Continual development of these technologies may emerge as a solution to enhance bioavailability, decrease dosing frequency and expand the range of uses of oral peptide therapies. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Vahora, Shahin AU - Vahora S AUID- ORCID: 0009-0004-6651-0852 AD - Navinta LLC, 1499 Lower Ferry Road, Ewing, NJ, 08618, USA. shahin121190@gmail.com. FAU - Shah, Vishal AU - Shah V AD - Director Operations, Flamma USA LLC, Malvern, PA, USA. FAU - Patel, Bhavesh AU - Patel B AD - Product Development, Frontage Laboratories, Inc., Exton, PA, USA. LA - eng PT - Journal Article PT - Review DEP - 20260903 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Caprylates) RN - 0 (N-(8-(2-hydroxybenzoyl)amino)caprylate) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/pharmacokinetics/administration & dosage/chemistry MH - Biological Availability MH - Animals MH - *Hypoglycemic Agents/pharmacokinetics/administration & dosage/chemistry MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - Caprylates/chemistry MH - Drug Compounding MH - Obesity/drug therapy OTO - NOTNLM OT - absorption enhancers (SNAC) OT - bioavailability enhancement OT - formulation strategies OT - oral peptide drug delivery OT - semaglutide COIS- Declarations. Ethical Approval and Consent to Participate: Ethical Approval and Consent to Participate is not applicable. Competing interest: There is no competing interests. EDAT- 2026/09/03 05:37 MHDA- 2026/10/07 05:31 CRDT- 2026/09/03 01:47 PHST- 2026/05/02 00:00 [received] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/10/07 05:31 [medline] PHST- 2026/09/03 05:37 [pubmed] PHST- 2026/09/03 01:47 [entrez] AID - 10.1007/s11095-026-04185-2 [pii] AID - 10.1007/s11095-026-04185-2 [doi] PST - ppublish SO - Pharm Res. 2026 Sep;43(9):2989-3010. doi: 10.1007/s11095-026-04185-2. Epub 2026 Sep 3. PMID- 42684335 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261022 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 11 DP - 2026 Nov 1 TI - Comparative Short-term Risk of Severe Gastrointestinal Events Associated With Opioid Type Among Patients Receiving Glucagon-Like Peptide 1 Receptor Agonists. PG - 2050-2059 LID - 10.2337/dc26-0757 [doi] AB - OBJECTIVE: To compare the risk of motility-related gastrointestinal (GI) events associated with commonly prescribed opioids among adults with type 2 diabetes (T2D) prescribed glucagon-like peptide 1 receptor agonist (GLP-1RA) therapy, a population in whom the GI safety of concomitant opioid use has not been well characterized. RESEARCH DESIGN AND METHODS: A population-based, new-user cohort study was conducted using U.S. insurance claims (2016-2025) among adults with T2D prescribed GLP-1RA therapy who initiated use of oxycodone, hydrocodone, or tramadol. We evaluated a composite of motility-related GI events, including severe constipation, bowel obstruction, and gastroparesis, and estimated 30-day weighted absolute risks, risk ratios (RRs), and risk differences (RDs) using propensity score-matching weights. RESULTS: Among 411,188 patients (mean age 62.8 years; 53.8% female) with T2D and using a GLP-1RA, 24.4% initiated use of oxycodone, 48.5% hydrocodone, and 27.1% tramadol. The weighted 30-day absolute risk of motility-related GI events was 0.51% for oxycodone, 0.35% for hydrocodone, and 0.33% for tramadol. Oxycodone was associated with a higher risk than hydrocodone (RR 1.48 [95% CI 1.30-1.69]; RD 0.17 [95% CI 0.11-0.22]) and tramadol (RR 1.55 [95% CI 1.33-1.79]; RD 0.18 [95% CI 0.12-0.24]). Hydrocodone and tramadol showed similar risks (RR 1.05 [95% CI 0.91-1.21]; RD 0.02 [95% CI -0.03 to 0.06]). CONCLUSIONS: Among adults with T2D who were using a GLP-1RA, initiation of oxycodone was associated with higher short-term risks of severe constipation and bowel obstruction compared with hydrocodone or tramadol. We did not observe differences in the risk of gastroparesis. Risks were similar between patients initiating hydrocodone and tramadol, although variation across secondary analyses warrants cautious interpretation. CI - (c) 2026 by the American Diabetes Association. FAU - Bea, Sungho AU - Bea S AUID- ORCID: 0000-0003-2622-6553 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of General Internal Medicine & Health Services Research, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. FAU - Sreedhara, Sushama Kattinakere AU - Sreedhara SK AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Cromer, Sara J AU - Cromer SJ AD - Diabetes Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA. FAU - Bykov, Katsiaryna AU - Bykov K AUID- ORCID: 0000-0003-3336-5412 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. LA - eng GR - K01 AG068365/AG/NIA NIH HHS/United States GR - K01AG068365/National Institutes of Health (NIH/ GR - 7-21-JDFM-005/American Diabetes Association/ GR - 1-25-PDF-66/American Diabetes Association/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Analgesics, Opioid) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - CD35PMG570 (Oxycodone) RN - 39J1LGJ30J (Tramadol) RN - 6YKS4Y3WQ7 (Hydrocodone) SB - IM MH - Humans MH - Female MH - Middle Aged MH - *Analgesics, Opioid/adverse effects/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Oxycodone/adverse effects/therapeutic use MH - Tramadol/adverse effects/therapeutic use MH - Hydrocodone/adverse effects/therapeutic use MH - *Gastrointestinal Diseases/chemically induced/epidemiology PMC - PMC13674531 MID - NIHMS2211844 EDAT- 2026/09/03 01:13 MHDA- 2026/10/20 17:34 PMCR- 2026/11/01 CRDT- 2026/09/02 11:37 PHST- 2026/03/31 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/10/20 17:34 [medline] PHST- 2026/09/03 01:13 [pubmed] PHST- 2026/09/02 11:37 [entrez] PHST- 2026/11/01 00:00 [pmc-release] AID - 172430 [pii] AID - 10.2337/dc26-0757 [doi] PST - ppublish SO - Diabetes Care. 2026 Nov 1;49(11):2050-2059. doi: 10.2337/dc26-0757. PMID- 42679726 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20261009 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 10 DP - 2026 Oct TI - Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial. PG - 109397 LID - S1056-8727(26)00142-X [pii] LID - 10.1016/j.jdiacomp.2026.109397 [doi] AB - AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age >/= 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p >/= 0.11 and p >/= 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. Electronic address: soegul@clin.au.dk. FAU - Vernstrom, Liv AU - Vernstrom L AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Sorensen, Steffen Skovgaard AU - Sorensen SS AD - Department of Nuclear Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Funck, Kristian Lokke AU - Funck KL AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Diagnostic Centre, Silkeborg Regional Hospital, 8600, Silkeborg, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260829 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Benzhydryl Compounds) RN - 0 (Biomarkers) RN - 0 (E-Selectin) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Vascular Cell Adhesion Molecule-1) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/therapeutic use/administration & dosage MH - Biomarkers/blood MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications/physiopathology MH - *Diabetic Angiopathies/prevention & control/blood MH - Double-Blind Method MH - Drug Therapy, Combination MH - E-Selectin/blood MH - *Endothelium, Vascular/drug effects/physiopathology/metabolism MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Glucosides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Vascular Cell Adhesion Molecule-1/blood OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Endothelial function OT - Glucagon-like peptide 1 receptor agonist OT - Sodium glucose co-transporter 2 inhibitor OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Esben Laugesen reports financial support was provided by Novo Nordisk Foundation. Soeren Gullaksen reports financial support was provided by Danish Medical Association Research Fund. Liv Vernstroem reports financial support was provided by Aarhus University. Steffen Skovgaard Soerensen reports financial support was provided by Independent Research Fund Denmark. Per Loegstrup Poulsen reports financial support was provided by Novo Nordisk Foundation. Per Loegstrup Poulsen reports a relationship with AstraZeneca that includes: board membership and funding grants. Per Loegstrup Poulsen reports a relationship with Bayer AG that includes: board membership. Per Loegstrup Poulsen reports a relationship with Novo Nordisk that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/09/01 23:34 MHDA- 2026/09/07 23:34 CRDT- 2026/09/01 18:13 PHST- 2026/02/24 00:00 [received] PHST- 2026/06/24 00:00 [revised] PHST- 2026/08/27 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/09/01 23:34 [pubmed] PHST- 2026/09/01 18:13 [entrez] AID - S1056-8727(26)00142-X [pii] AID - 10.1016/j.jdiacomp.2026.109397 [doi] PST - ppublish SO - J Diabetes Complications. 2026 Oct;40(10):109397. doi: 10.1016/j.jdiacomp.2026.109397. Epub 2026 Aug 29. PMID- 42677883 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20260918 IS - 1526-2359 (Electronic) IS - 1073-2748 (Print) IS - 1073-2748 (Linking) VI - 33 DP - 2026 Jan-Dec TI - Associations Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Cancer Risk: A Systematic Review and Meta-Analysis. PG - 10732748261483767 LID - 10.1177/10732748261483767 [doi] LID - 10732748261483767 AB - IntroductionUse of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for control of type 2 diabetes and cardiovascular disease (CVD) risk reduction is increasing. Given the established link between obesity and multiple cancers, there is growing interest in the potential effects of GLP-1RAs on cancer risk reduction. This systematic literature review and meta-analysis evaluated the association between GLP-1RA use and cancer incidence.MethodsWe conducted literature searches in MEDLINE and EMBASE databases, covering publications up to September 17th, 2025. Our review included studies among adults receiving GLP-1RAs for any indication that reported effects on cancer incidence of any type.ResultsAmong 1,644 unique citations identified, 139 studies met the inclusion criteria for full-text review. After study exclusion, a total of 78 observational studies were included in the review and meta-analysis. GLP-1RA use was associated with statistically significant reductions in cancer risk for 10 of 13 obesity-associated cancers, specifically colorectal, endometrial, esophageal, gallbladder, liver, ovarian, pancreatic and stomach cancers along with meningioma and multiple myeloma. Compared to insulin specifically, GLP-1RAs provided protective effects against cancer of the colorectum (RR: 0.54, 95% CI: 0.44, 0.66), liver (RR: 0.35, 95% CI: 0.20, 0.62), and pancreas (RR: 0.41, 95% CI: 0.36, 0.48). The risk of developing thyroid cancer was slightly elevated, but not statistically significant, among GLP-1RA users (RR: 1.09, 95% CI: 0.98, 1.21).ConclusionsPooled estimates of observational studies suggest notable reductions in cancer incidence for several obesity-associated cancers. As GLP-1RA use increases, ongoing safety monitoring and long-term real-world data are essential. The potential role of GLP-1RAs in cancer risk reduction warrants further investigation through large-scale RCTs, alongside balanced risk-benefit discussions with patients. FAU - Lalani, Isha AU - Lalani I AD - Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 FAU - Nambayan, Reynaldo AU - Nambayan R AD - Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 FAU - Carbonell, Chantelle AU - Carbonell C AD - Department of Oncology, University of Calgary, Calgary, AB, Canada. RINGGOLD: 213572 FAU - Ruan, Yibing AU - Ruan Y AD - Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada. RINGGOLD: 3146 FAU - O'Sullivan, Dylan E AU - O'Sullivan DE AD - Department of Oncology, University of Calgary, Calgary, AB, Canada. RINGGOLD: 213572 AD - Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada. RINGGOLD: 3146 AD - Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 FAU - Stukalin, Igor AU - Stukalin I AD - Department of Oncology, University of Calgary, Calgary, AB, Canada. RINGGOLD: 213572 AD - Department of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada. FAU - Hilsden, Robert J AU - Hilsden RJ AD - Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 AD - Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 FAU - Brenner, Darren R AU - Brenner DR AUID- ORCID: 0000-0002-3027-290X AD - Department of Oncology, University of Calgary, Calgary, AB, Canada. RINGGOLD: 213572 AD - Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. RINGGOLD: 70401 LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260901 PL - United States TA - Cancer Control JT - Cancer control : journal of the Moffitt Cancer Center JID - 9438457 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - *Neoplasms/epidemiology/prevention & control/etiology MH - Obesity/complications MH - Risk Factors PMC - PMC13535051 OTO - NOTNLM OT - cancer prevention OT - cancer risk OT - glucagon-like peptide-1 receptor agonists (GLP-1RAs) OT - obesity OT - obesity-associated cancer COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/09/01 11:39 MHDA- 2026/09/01 11:40 PMCR- 2026/09/01 CRDT- 2026/09/01 06:41 PHST- 2026/09/01 11:40 [medline] PHST- 2026/09/01 11:39 [pubmed] PHST- 2026/09/01 06:41 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - 10.1177_10732748261483767 [pii] AID - 10.1177/10732748261483767 [doi] PST - ppublish SO - Cancer Control. 2026 Jan-Dec;33:10732748261483767. doi: 10.1177/10732748261483767. Epub 2026 Sep 1. PMID- 42669711 OWN - NLM STAT- MEDLINE DCOM- 20260830 LR - 20260910 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Jul 30 TI - Cardiovascular outcome of glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitor on end-stage kidney disease patients with heart failure: an emulated target trial in patients with diabetes. LID - 10.1038/s41467-026-76083-5 [doi] LID - 9240 AB - Patients with end-stage kidney disease (ESKD) receiving maintenance dialysis have a high burden of heart failure (HF), with cardiovascular disease the leading cause of death, yet are largely excluded from randomized trials. Using the TriNetX federated electronic health record network, we emulate a target trial comparing initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is) in diabetic ESKD patients with HF, undergoing maintenance dialysis. We identify a primary ESKD-HF population and a confirmatory dialysis-dependence-coded HF subset, and apply a new-user, active-comparator design and use propensity score matching to balance baseline characteristics. In the primary ESKD-HF population, GLP-1RAs use is associated with a lower risk of the primary composite ischemic cardiovascular events plus HF exacerbations, than DPP-4i initiation (31.7% vs. 41.4%; HR 0.72[0.64-0.82], P < 0.0001), with concordance reductions in ischemic events (HR 0.74), HF exacerbations (HR 0.76), all-cause mortality (HR 0.68), and a death-inclusive composite (HR 0.72). Results are consistent in multivariable models, across prespecified subgroups, and in extensive sensitivity analyses, and are corroborated in the confirmatory dialysis-dependence-coded HF subset HR (0.71[0.60-0.85]). These findings provide real-world evidence suggesting GLP-1RAs may improve cardiovascular outcomes in dialysis-dependent diabetic ESKD with HF and support prospective randomized evaluation. CI - (c) 2026. The Author(s). FAU - Liu, Po-Yi AU - Liu PY AD - Education Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Shih, Chao-Kuei AU - Shih CK AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Hsieh, Miyuki Hsing-Chun AU - Hsieh MH AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Ching-Chun AU - Lin CC AUID- ORCID: 0009-0004-4850-6665 AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Liu, Chieh-Yen AU - Liu CY AUID- ORCID: 0009-0006-3920-0220 AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AUID- ORCID: 0000-0002-5852-7652 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Li, Chung-Yi AU - Li CY AUID- ORCID: 0000-0002-0321-8908 AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. FAU - Yu, Chih-Hen AU - Yu CH AUID- ORCID: 0000-0002-5360-6685 AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. james609054@hotmail.com. AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. james609054@hotmail.com. AD - Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan. james609054@hotmail.com. FAU - Sung, Junne-Ming AU - Sung JM AUID- ORCID: 0000-0003-1916-7815 AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. jmsung@mail.ncku.edu.tw. AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. jmsung@mail.ncku.edu.tw. LA - eng GR - NTSC 114-2314-B-006 -018/Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/ GR - NSTC 112-2314-B-006-088-MY3/Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/ GR - NCKUH-11306001/National Cheng Kung University Hospital (NCKU Hospital)/ GR - NCKUH-11304023/National Cheng Kung University Hospital (NCKU Hospital)/ GR - NCKUH-11502013/National Cheng Kung University Hospital (NCKU Hospital)/ GR - NCKUH-11501005/National Cheng Kung University Hospital (NCKU Hospital)/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20260730 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Heart Failure/complications/drug therapy/mortality MH - Hypoglycemic Agents/therapeutic use MH - *Kidney Failure, Chronic/complications/drug therapy/mortality/therapy MH - Renal Dialysis MH - Treatment Outcome MH - Randomized Controlled Trials as Topic PMC - PMC13526834 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/08/31 19:42 MHDA- 2026/08/31 19:43 PMCR- 2026/07/30 CRDT- 2026/08/30 23:28 PHST- 2025/10/03 00:00 [received] PHST- 2026/07/13 00:00 [accepted] PHST- 2026/08/31 19:43 [medline] PHST- 2026/08/31 19:42 [pubmed] PHST- 2026/08/30 23:28 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - 10.1038/s41467-026-76083-5 [pii] AID - 76083 [pii] AID - 10.1038/s41467-026-76083-5 [doi] PST - epublish SO - Nat Commun. 2026 Jul 30;17(1):9240. doi: 10.1038/s41467-026-76083-5. PMID- 42663556 OWN - NLM STAT- MEDLINE DCOM- 20261016 LR - 20261016 IS - 1872-6623 (Electronic) IS - 0304-3959 (Linking) VI - 167 IP - 11 DP - 2026 Nov 1 TI - Glucagon-like peptide-1 receptor agonist treatment is associated with lower frequency of diabetic peripheral neuropathy and neuropathic pain in type 2 diabetes. PG - 2523-2531 LID - 10.1097/j.pain.0000000000004104 [doi] AB - In this cross-sectional study, we investigated the frequency of diabetic peripheral neuropathy (DPN) and DPN-related neuropathic pain (painful DPN) in 500 consecutively enrolled patients with type 2 diabetes mellitus receiving standard treatment (n = 208), sodium-glucose cotransporter-2 inhibitors (SGLT2i; n = 152), or glucagon-like peptide-1 receptor agonists (GLP-1 RAs; n = 140). DPN was assessed through neurological examination, nerve conduction study, and skin biopsy when indicated; painful DPN was diagnosed using the grading system for neuropathic pain. Neuropathy severity and pain intensity were quantified with the Toronto Clinical Neuropathy Score, Pain Numerical Rating Scale, and Neuropathic Pain Symptom Inventory. The overall frequency of DPN was 58.6%, and painful DPN occurred in 26.2% of patients. GLP-1 RA treatment was associated with a lower frequency of DPN (46.4% vs 60.6% in the standard treatment group) and painful DPN (10.1% vs 35.1% and 28.3% in the standard treatment and SGLT2i groups, respectively). After adjustment for clinical and metabolic covariates, GLP-1 RA treatment was independently associated with lower odds of DPN (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.37-0.96) and painful DPN (OR 0.32, 95% CI 0.15-0.65). Neuropathy severity and pain intensity were also lower in patients receiving GLP-1 RAs. GLP-1 RA treatment was associated with a reduced frequency and severity of both DPN and painful DPN, independent of clinical and metabolic covariates. While these findings suggest potential neuroprotective and antinociceptive effects, longitudinal studies are needed to establish causality and clarify the underlying mechanisms. CI - Copyright (c) 2026 International Association for the Study of Pain. FAU - Falco, Pietro AU - Falco P AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Di Flaviani, Alessandra AU - Di Flaviani A AD - Togliatti Diabetes Center, Order of Malta, Rome, Italy. FAU - Galosi, Eleonora AU - Galosi E AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Angotti, Stefania AU - Angotti S AD - Togliatti Diabetes Center, Order of Malta, Rome, Italy. FAU - De Stefano, Gianfranco AU - De Stefano G AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Di Pietro, Giuseppe AU - Di Pietro G AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Di Stefano, Giulia AU - Di Stefano G AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - D'Onofrio, Luca AU - D'Onofrio L AD - Diabetology Unit, AOU Policlinico Umberto I, Rome, Italy. FAU - Evangelisti, Enrico AU - Evangelisti E AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Leone, Caterina AU - Leone C AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Litewczuk, Daniel AU - Litewczuk D AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. FAU - Arendt-Nielsen, Lars AU - Arendt-Nielsen L AD - Centre for Neuroplasticity and Pain, SMI, School of Medicine, Aalborg University, Aalborg, Denmark. AD - Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark. AD - Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark. FAU - Buzzetti, Raffaella AU - Buzzetti R AD - Diabetology Unit, AOU Policlinico Umberto I, Rome, Italy. AD - Department of Experimental Medicine, Sapienza University, Rome, Italy. FAU - Spallone, Vincenza AU - Spallone V AD - Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy. FAU - Truini, Andrea AU - Truini A AUID- ORCID: 0000-0002-2630-7647 AD - Department of Human Neuroscience, Sapienza University, Rome, Italy. LA - eng PT - Journal Article DEP - 20260820 PL - United States TA - Pain JT - Pain JID - 7508686 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Female MH - *Diabetic Neuropathies/epidemiology/drug therapy MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Neuralgia/epidemiology/drug therapy/etiology MH - Middle Aged MH - Cross-Sectional Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Pain Measurement MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use OTO - NOTNLM OT - Diabetic peripheral neuropathy OT - Diabetic treatment OT - GLP-1 receptor agonists OT - Neuropathic pain EDAT- 2026/08/28 11:49 MHDA- 2026/10/16 11:37 CRDT- 2026/08/28 10:13 PHST- 2026/04/03 00:00 [received] PHST- 2026/07/05 00:00 [accepted] PHST- 2026/10/16 11:37 [medline] PHST- 2026/08/28 11:49 [pubmed] PHST- 2026/08/28 10:13 [entrez] AID - 00006396-990000000-01256 [pii] AID - 10.1097/j.pain.0000000000004104 [doi] PST - ppublish SO - Pain. 2026 Nov 1;167(11):2523-2531. doi: 10.1097/j.pain.0000000000004104. Epub 2026 Aug 20. PMID- 42663544 OWN - NLM STAT- MEDLINE DCOM- 20260828 LR - 20260928 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 32 IP - 8 DP - 2026 Aug TI - Predicting GLP-1 Discontinuation From Pharmacy Claims. PG - 426-428 LID - 10.37765/ajmc.2026.89993 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have rapidly become high-visibility therapies for type 2 diabetes and obesity, with growing evidence of cardiovascular benefit. Yet multiple real-world studies show that adherence and persistence are modest: In obesity cohorts without diabetes, approximately one-third of members remain on therapy at 1 year, and among those with type 2 diabetes, nearly half discontinue by 12 months and approximately 70% by 24 months. This gap between trial efficacy and real-world use raises critical questions for payers, pharmacy benefit managers, and employers funding GLP-1 RA coverage. This commentary proposes a pragmatic, claims-based framework for improving GLP-1 RA persistence. Routine pharmacy claims can be used to define new-start cohorts, calculate standard measures such as the proportion of days covered, and identify early warning signs, including delayed refills, prolonged use of starter doses, high out-of-pocket costs, and patterns of gastrointestinal adverse effects. These signals can drive simple rule-based alerts and, where appropriate, low-complexity predictive models to prioritize outreach. Clinical pharmacists, nurse case managers, and digital tools can then translate these risk flags into concrete support for members-such as cost navigation, adverse effect management, expectation setting, and coordination with prescribers-while maintaining a "do no harm" stance. Finally, the commentary highlights the importance of monitoring GLP-1 RA persistence through an equity lens, ensuring that supportive interventions reduce, rather than widen, disparities in access and outcomes. FAU - Sisodia, Aayush AU - Sisodia A AD - Independent researcher and analyst. Email: aayushsisodia19@gmail.com. LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy MH - Insurance Claim Review EDAT- 2026/08/28 11:49 MHDA- 2026/08/28 11:50 CRDT- 2026/08/28 10:12 PHST- 2026/08/28 11:50 [medline] PHST- 2026/08/28 11:49 [pubmed] PHST- 2026/08/28 10:12 [entrez] AID - 89993 [pii] AID - 10.37765/ajmc.2026.89993 [doi] PST - ppublish SO - Am J Manag Care. 2026 Aug;32(8):426-428. doi: 10.37765/ajmc.2026.89993. PMID- 42661791 OWN - NLM STAT- MEDLINE DCOM- 20260828 LR - 20260902 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Glucagon-like peptide-1 receptor agonists and the risk of Parkinson's disease in patients with type 2 diabetes: a systematic review and meta-analysis of large-scale real-world data. PG - 1849318 LID - 10.3389/fendo.2026.1849318 [doi] LID - 1849318 AB - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, yet effective disease-modifying therapies remain elusive. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus (T2DM), have shown neuroprotective potential in preclinical studies. However, real-world evidence on the association between GLP-1RAs use and PD risk remains inconsistent and has not been systematically synthesized. This systematic review and meta-analysis aimed to evaluate this association using large-scale real-world data. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from database inception to March 18, 2026, for cohort and case-control studies exploring the association between GLP-1RA exposure and PD risk among patients with T2DM. Study selection, data extraction, and methodological quality assessment were independently conducted by two reviewers. All meta-analyses were performed using Stata 15.0 software. RESULTS: A total of six studies were included, involving 452,763 participants. The meta-analysis revealed that GLP-1RA exposure was significantly associated with a reduced risk of PD in patients with T2DM (HR = 0.68, 95%CI (0.54,0.85), P = 0.001). Subgroup analyses demonstrated that compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and other hypoglycemic drugs, GLP-1RAs were linked to a lower risk of incident PD (DPP-4 inhibitors: HR = 0.60, 95%CI (0.43,0.83), P = 0.001; Metformin: HR = 0.83, 95%CI (0.73,0.95), P = 0.006; Other: HR = 0.73, 95%CI (0.60,0.87), P = 0.002). CONCLUSIONS: This meta-analysis based on large-scale real-world data indicates that GLP-1RA exposure is associated with a lower risk of PD in patients with T2DM, with robust and consistent results across diverse comparator groups. These findings support the hypothesis that GLP-1RAs may confer neuroprotective properties, a finding that merits further rigorous investigation. Nevertheless, given the inherent limitations inherent to observational study designs and the possibility of residual confounding in the included studies, the present results should be regarded as preliminary and hypothesis-generating rather than conclusive. Future large-scale prospective cohort studies with standardized methodologies, as well as well-designed randomized controlled trials, are warranted to validate these findings and clarify whether the observed inverse association reflects a causal neuroprotective effect of GLP-1RAs. CI - Copyright (c) 2026 Chen, Wang, Wang and Ma. FAU - Chen, Ying AU - Chen Y AD - Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, China. FAU - Wang, Xueping AU - Wang X AD - Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, China. FAU - Wang, Jingjuan AU - Wang J AD - Department of Neurology, Daping Hospital, Army Medical University, Chongqing, China. FAU - Ma, Gaiping AU - Ma G AD - Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260813 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Parkinson Disease/epidemiology/etiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13518207 OTO - NOTNLM OT - Parkinson's disease OT - glucagon-like peptide-1 receptor agonists OT - meta-analysis OT - real world study OT - systematic review COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/08/28 11:50 MHDA- 2026/08/28 11:51 PMCR- 2026/08/13 CRDT- 2026/08/28 05:16 PHST- 2026/04/07 00:00 [received] PHST- 2026/06/28 00:00 [revised] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/08/28 11:51 [medline] PHST- 2026/08/28 11:50 [pubmed] PHST- 2026/08/28 05:16 [entrez] PHST- 2026/08/13 00:00 [pmc-release] AID - 10.3389/fendo.2026.1849318 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 13;17:1849318. doi: 10.3389/fendo.2026.1849318. eCollection 2026. PMID- 42660856 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261008 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Association of GLP1-Receptor Agonists With Diabetic Retinopathy. PG - 10586-10602 LID - 10.1111/dom.71267 [doi] AB - AIM: We aimed to examine the association between glucagon-like peptide-1 receptor agonists (GLP1-RA) use and diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy (NAION), using dipeptidyl peptidase-4 inhibitors (DPP4i) as active comparators. METHODS: We created a retrospective propensity score (PS)-matched cohort study of patients who initiated either GLP1-RA or DPP4i (years 2006-2021). Using new-users, we created two PS-matched cohorts: patients with diabetes (overall cohort) and patients with diabetes and chronic kidney disease (CKD-cohort); the latter represents patients at higher likelihood of diabetes microvascular complications. Primary outcomes were non-vision-threatening diabetic retinopathy (NVTDR), vision-threatening diabetic retinopathy and diabetic macular edema (VTDR/DME), and NAION. Secondary outcomes included vision impairment or blindness and occurrence of retinopathy procedures. RESULTS: PS-matched overall cohort included 98 082 pairs of GLP1-RA or DPP4i users. GLP1-RA users had higher risk of NVTDR (11.05% vs. 9.98%; odds ratio [OR] 1.12, 95% confidence interval [95% CI]: 1.09-1.15), VTDR/DME (2.17% vs. 1.98%; OR 1.09, 95% CI: 1.03-1.16), and occurrence of retinopathy procedures (4.16% vs. 3.68%, OR 1.14, 95% CI: 1.09-1.19). There was no significant difference in risk of NAION (OR 1.11, 95% CI: 0.96-1.29) or vision impairment or blindness (OR 1.04, 95% CI: 0.97-1.11). In the CKD cohort (15 440 matched pairs), GLP1-RA was associated with high risk of NVTDR (OR 1.10, 95% CI: 1.03-1.18), and occurrence of retinopathy procedures (OR 1.14, 95% CI: 1.03-1.26), but not other outcomes. CONCLUSIONS: GLP1-RA use was associated with a modest increase in risk of diabetic retinopathy and retinopathy-related procedures, independent of the presence of retinopathy at baseline. However, GLP1-RA use was not associated with vision impairment or blindness, although administrative codes notably have low validity for blindness diagnosis. CI - Published 2026. This article is a U.S. Government work and is in the public domain in the United States. FAU - Gonzalez, Arisa AU - Gonzalez A AD - University of Central Florida HCA Florida Healthcare, Orlando, Florida, USA. AD - Department of Medicine, University of Central Florida, College of Medicine, Orlando, Florida, USA. FAU - Chastain, Lisa AU - Chastain L AD - Department of Pharmacy Practice, Division of Ambulatory Care, Texas Tech University Health Sciences Center, Dallas, Texas, USA. AD - Clinical Pharmacy Services, VA North Texas Healthcare System - Fort Worth Outpatient Clinic, Fort Worth, Texas, USA. FAU - Karasik, Olga AU - Karasik O AD - University of Central Florida HCA Florida Healthcare, Orlando, Florida, USA. AD - Department of Medicine, University of Central Florida, College of Medicine, Orlando, Florida, USA. FAU - Asmar, Abdo AU - Asmar A AD - University of Central Florida HCA Florida Healthcare, Orlando, Florida, USA. AD - Department of Medicine, University of Central Florida, College of Medicine, Orlando, Florida, USA. AD - Education Services, Orlando VA Healthcare System, Orlando, Florida, USA. FAU - Farhangi, Monika AU - Farhangi M AD - University of Central Florida HCA Florida Healthcare, Orlando, Florida, USA. FAU - Alvarez, Carlos A AU - Alvarez CA AUID- ORCID: 0000-0002-9512-1870 AD - Department of Pharmacy Practice and Center for Excellence in Real World Evidence, Texas Tech University Health Sciences Center, Dallas, Texas, USA. FAU - Mansi, Ishak A AU - Mansi IA AUID- ORCID: 0000-0001-6122-3716 AD - University of Central Florida HCA Florida Healthcare, Orlando, Florida, USA. AD - Education Services, Orlando VA Healthcare System, Orlando, Florida, USA. LA - eng GR - Orlando VA Healthcare System/ GR - UL1TR003163/TR/NCATS NIH HHS/United States GR - HCA Healthcare/ GR - UL1TR003163/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20260827 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Retinopathy/epidemiology/chemically induced MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Propensity Score OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 analogue OT - antidiabetic drug OT - cohort study OT - database research OT - diabetic retinopathy EDAT- 2026/08/28 11:39 MHDA- 2026/10/08 05:31 CRDT- 2026/08/27 22:53 PHST- 2026/08/03 00:00 [revised] PHST- 2026/06/12 00:00 [received] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/28 11:39 [pubmed] PHST- 2026/08/27 22:53 [entrez] AID - 10.1111/dom.71267 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10586-10602. doi: 10.1111/dom.71267. Epub 2026 Aug 27. PMID- 42660161 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 11 DP - 2026 Nov TI - From adiposity to multisystem morbidity: the case for weight loss as disease modification. PG - 952-969 LID - S2213-8587(26)00186-5 [pii] LID - 10.1016/S2213-8587(26)00186-5 [doi] AB - Obesity (ie, excess adiposity) is a major driver of multisystem morbidity, spanning musculoskeletal (eg, osteoarthritis), metabolic (eg, type 2 diabetes), cardiovascular (eg, heart failure), mental health (eg, depression), respiratory (eg, obstructive sleep apnoea), and gastrointestinal and hepatic (eg, metabolic dysfunction-associated steatotic liver disease) disorders. However, the extent to which weight-loss interventions can prevent or modify these conditions varies considerably. In this Review, we synthesise evidence from epidemiological studies, genetic analyses (including Mendelian randomisation), observational weight-change studies, and randomised trials, using a triangulation framework to assess causal links between adiposity and common diseases. Although robust trial evidence supports weight loss as a disease-modifying strategy in some conditions, including but not limited to type 2 diabetes and heart failure with preserved ejection fraction, many other conditions, including musculoskeletal, respiratory, cardiovascular, and mental health disorders, remain under-investigated. Incretin-based therapies, in particular the glucagon-like peptide 1 receptor agonist semaglutide and the dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide, now achieve average weight losses of approximately 14-20% in people without diabetes and have generated the first large-scale randomised evidence of disease modification across several of these conditions. We highlight key gaps and propose priorities for future trials, including the need for studies across different disease stages, incorporation of mechanistic and mediation analyses, and evaluation of the impact on disease outcomes of varying magnitudes of weight loss with differing agents. Future research should also consider multimorbidity, individualised treatment targets, and long-term outcomes-including potential legacy effects. Addressing global access gaps and conducting trials in diverse populations will be essential to inform scalable and equitable obesity care. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Sattar, Naveed AU - Sattar N AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk. FAU - Ferguson, Lyn D AU - Ferguson LD AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Lee, Matthew M Y AU - Lee MMY AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. LA - eng PT - Journal Article PT - Review DEP - 20260827 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Weight Loss/physiology MH - *Obesity/complications/therapy MH - *Adiposity/physiology MH - *Diabetes Mellitus, Type 2 MH - *Cardiovascular Diseases/prevention & control/etiology MH - Semaglutide COIS- Declaration of interests NS has consulted for and received speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Kailera, Mass Medicines, Menarini-Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. LDF reports speaker fees from Janssen and UCB and consultancy and conference travel support from Sanofi. MMYL has received research grants through his institution, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim, and Roche Diagnostics; serves on Trial Steering Committees for Amgen and Cytokinetics; and Clinical Endpoint Committees for AstraZeneca, Bayer, and GlaxoSmithKline. EDAT- 2026/08/28 11:40 MHDA- 2026/10/13 23:35 CRDT- 2026/08/27 18:52 PHST- 2026/03/06 00:00 [received] PHST- 2026/05/20 00:00 [revised] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/10/13 23:35 [medline] PHST- 2026/08/28 11:40 [pubmed] PHST- 2026/08/27 18:52 [entrez] AID - S2213-8587(26)00186-5 [pii] AID - 10.1016/S2213-8587(26)00186-5 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Nov;14(11):952-969. doi: 10.1016/S2213-8587(26)00186-5. Epub 2026 Aug 27. PMID- 42654433 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260918 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Aug 10 TI - Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review. LID - 10.3390/medicina62081536 [doi] LID - 1536 AB - Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have transformed the management of type 2 diabetes mellitus (T2DM) and obesity through once-weekly subcutaneous administration. While their efficacy and safety are well-established, the potential impact of administration timing-specifically, the day of the week-on clinical outcomes, adherence, and tolerability remains unexplored. Understanding whether specific days optimize therapeutic outcomes could inform personalized dosing strategies and improve long-term treatment success. Materials and Methods: We conducted a systematic literature review following PRISMA 2020 guidelines to identify studies examining the effect of weekly administration timing of semaglutide or tirzepatide on clinical outcomes in adults with T2DM or obesity. Comprehensive searches were performed across SciSpace (Deep Search, Basic Search, Full Text Search), Google Scholar, and PubMed databases through June 2026. Studies were screened using a two-stage process (abstract and full-text screening) with predefined PICO-based inclusion criteria. Data extraction focused on study design, population characteristics, administration timing, glycemic control, weight loss, adherence, and adverse events. Results: From 1471 identified records, 1000 unique papers underwent screening after deduplication and trimming. Three studies met inclusion criteria: the SUSTAIN 4 randomized controlled trial evaluating once-weekly semaglutide, a retrospective case series examining alternate-day oral semaglutide dosing, and an expert panel discussion on flexible dosing schedules. No studies directly compared different days of the week for injectable semaglutide or tirzepatide administration. Available evidence suggests that flexible dosing schedules may support adherence and tolerability without compromising glycemic control, though this suggestion derives primarily from indirect evidence and expert opinion rather than direct comparative clinical studies; direct comparative data on day-of-week effects are absent. Conclusions: Current evidence does not support a specific optimal day of the week for semaglutide or tirzepatide administration. The limited literature emphasizes flexible dosing schedules tailored to individual patient preferences and lifestyles to maximize adherence. Future prospective studies are needed to systematically evaluate whether administration timing influences clinical outcomes in real-world settings. FAU - La Vignera, Sandro AU - La Vignera S AUID- ORCID: 0000-0002-7113-2372 AD - Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy. FAU - Condorelli, Rosita A AU - Condorelli RA AUID- ORCID: 0000-0002-5217-9343 AD - Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260810 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Tirzepatide/administration & dosage MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - Obesity/drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13515371 OTO - NOTNLM OT - GLP-1 receptor agonists OT - administration timing OT - chronotherapy OT - medication adherence OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/10 CRDT- 2026/08/27 01:10 PHST- 2026/06/15 00:00 [received] PHST- 2026/08/01 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/08/10 00:00 [pmc-release] AID - medicina62081536 [pii] AID - medicina-62-01536 [pii] AID - 10.3390/medicina62081536 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Aug 10;62(8):1536. doi: 10.3390/medicina62081536. PMID- 42654406 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Aug 5 TI - Renal Effects of Glucagon-like Peptide-1 Receptor Agonists in Diabetic Kidney Disease: A Narrative Review of Mechanisms and Clinical Evidence. LID - 10.3390/medicina62081509 [doi] LID - 1509 AB - Diabetic kidney disease (DKD) remains a major cause of advanced chronic kidney disease (CKD) and cardiovascular (CV) mortality, despite optimization of renin-angiotensin-aldosterone system (RAAS) blockade and the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cardiometabolic agents with significant efficacy on glycemic control, body weight, blood pressure (BP), lipid profile, and systemic inflammation. In experimental studies, GLP-1 RAs showed direct renal effects by modulating natriuresis, intrarenal hemodynamics, oxidative stress, endothelial dysfunction, and tubular apoptosis. Randomized clinical trials and real-life analyses have demonstrated reductions in albuminuria and slowing of glomerular filtration rate (GFR) decline. The first study with a primary renal endpoint for semaglutide confirms its nephroprotective potential. This narrative review synthesizes the renal mechanisms involved. The clinical evidence for GLP-1 RA in DKD positions this class alongside SGLT2i and non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) for the management of patients with type 2 diabetes mellitus (T2D), CKD, and very high cardiorenal risk. FAU - Braha, Adina AU - Braha A AUID- ORCID: 0000-0002-7904-6073 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Timar, Bogdan AU - Timar B AUID- ORCID: 0000-0002-0993-6206 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Sturza, Adrian AU - Sturza A AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Department of Functional Sciences-Pathophysiology, Center for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Timar, Romulus AU - Timar R AUID- ORCID: 0000-0003-0792-9202 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. LA - eng PT - Journal Article PT - Review DEP - 20260805 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Kidney/drug effects/physiopathology MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Glomerular Filtration Rate/drug effects PMC - PMC13514747 OTO - NOTNLM OT - cardiorenal protection OT - chronic kidney disease OT - diabetic kidney disease OT - glucagon-like peptide-1 receptor agonists COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/05 CRDT- 2026/08/27 01:10 PHST- 2026/06/01 00:00 [received] PHST- 2026/07/26 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/08/05 00:00 [pmc-release] AID - medicina62081509 [pii] AID - medicina-62-01509 [pii] AID - 10.3390/medicina62081509 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Aug 5;62(8):1509. doi: 10.3390/medicina62081509. PMID- 42654343 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Jul 25 TI - Glucagon-like Peptide-1 Receptor Agonists and Dual Incretin Therapies Across HFpEF and Cardiovascular Outcomes Trials in Patients with Obesity. LID - 10.3390/medicina62081446 [doi] LID - 1446 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and emerging dual incretin therapies have demonstrated substantial effects on weight reduction and metabolic improvement, with growing evidence supporting favorable cardiovascular outcomes. This narrative review provides a focused overview of key cardiovascular outcomes trials (CVOTs) and HFpEF-oriented clinical studies evaluating GLP-1 RA and dual incretin therapies in patients living with obesity, including completed and ongoing investigations. We summarize trial characteristics, critically appraise their outcomes, and briefly discuss mechanistic pathways potentially linking incretin-based therapies to cardiovascular and HFpEF-related benefits. Because available data derive from heterogeneous study designs, we explicitly distinguish evidence from type 2 diabetes cardiovascular outcomes trials, obesity-without-diabetes cardiovascular outcomes trials, HFpEF-specific randomized trials, mechanistic substudies, ongoing trials, and real-world observational analyses. We also situate incretin-based therapies within contemporary obesity, diabetes, cardiovascular, and HFpEF guideline-directed care. Finally, we identify current knowledge gaps, future research priorities, and innovative approaches needed to refine personalized therapeutic strategies and optimize patient-centered outcomes in obesity-associated HFpEF. FAU - Belancic, Andrej AU - Belancic A AUID- ORCID: 0000-0001-7848-6600 AD - Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Klobucar, Sanja AU - Klobucar S AUID- ORCID: 0000-0002-0287-4735 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia. AD - Department of Internal Medicine, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Skroce, Kristina AU - Skroce K AUID- ORCID: 0000-0003-0379-5235 AD - Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Ciudin, Andreea AU - Ciudin A AD - Diabetes and Metabolism Research Group, VHIR, Endocrinology Department, Vall d'Hebron University Hospital, Autonomus University of Barcelona, 08035 Barcelona, Spain. FAU - Borovac, Josip Andelo AU - Borovac JA AUID- ORCID: 0000-0002-4878-8146 AD - Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia. AD - Department of Pathophysiology, School of Medicine, University of Split, 21000 Split, Croatia. LA - eng PT - Journal Article PT - Review DEP - 20260725 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Obesity/complications/drug therapy MH - *Incretins/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Heart Failure/drug therapy MH - Tirzepatide MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives/pharmacology MH - Cardiovascular Diseases/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Exenatide/therapeutic use MH - Liraglutide/therapeutic use/pharmacology PMC - PMC13514512 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - heart failure OT - obesity OT - semaglutide OT - tirzepatide COIS- A.B. has received payment of honoraria from AstraZeneca, Servier, Novo Nordisk, Eli Lilly and Novartis as speaker and/or member of advisory boards; is secretary of the Croatian Society of Obesity, president of the Croatian EASO ECN, EASO ECN board member (middle region), and EASO COMs Working Group member. S.K. has received speaking and/or consulting fees from Abbott. A.C. has received speaking fees from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Menarini; research grants from Eli Lilly, Novo Nordisk and Menarini; and is a member of the data-monitoring committee of Boehringer Ingelheim. J.A.B. has received speaking fees from Boehringer-Ingelheim and Novartis and grant/congress support from Abbott, Medtronic, MSD and European Association for Percutaneous Cardiovascular Interventions (EAPCI); is a member of the European Society of Cardiology Heart Failure Association Committee on Coronary Artery Disease. Other authors declare no conflicts of interest relevant to this manuscript. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/07/25 CRDT- 2026/08/27 01:10 PHST- 2026/06/06 00:00 [received] PHST- 2026/07/11 00:00 [revised] PHST- 2026/07/23 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/07/25 00:00 [pmc-release] AID - medicina62081446 [pii] AID - medicina-62-01446 [pii] AID - 10.3390/medicina62081446 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Jul 25;62(8):1446. doi: 10.3390/medicina62081446. PMID- 42654331 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260909 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Jul 23 TI - Perioperative Nutrition and Surgical Outcomes in Patients Receiving Glucagon-like Peptide-1 Receptor Agonists: A Scoping Review. LID - 10.3390/medicina62081434 [doi] LID - 1434 AB - Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for obesity and type 2 diabetes mellitus. While these agents provide substantial metabolic benefits, concerns have emerged regarding their effects on nutritional status and potential implications for perioperative outcomes. Materials and Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. A structured literature search was conducted from 2 May 2026 to 8 June 2026 examining GLP-1RA therapy, nutritional status, body composition and surgical outcomes. Eligible studies included investigations of postoperative outcomes associated with GLP-1RA use, nutritional and body composition effects of GLP-1RAs, associations between nutritional abnormalities and surgical outcomes, and perioperative nutritional optimisation strategies. Data were extracted and synthesised narratively. Results: Twenty studies met the inclusion criteria. Four major themes were identified: (1) nutritional and body composition changes associated with GLP-1RA therapy, (2) effects of malnutrition, sarcopenia, myosteatosis and micronutrient deficiencies on surgical outcomes, (3) postoperative outcomes associated with GLP-1RA use, and (4) perioperative nutritional assessment and optimisation strategies. GLP-1RA therapy was consistently associated with reduced energy intake, inadequate protein intake, micronutrient deficiencies and loss of lean body mass. These abnormalities overlap with recognised risk factors for adverse postoperative outcomes. Despite this, clinical studies generally reported neutral or favourable postoperative outcomes among GLP-1RA users, particularly in arthroplasty and hand surgery populations, although increased wound-healing complications were reported in selected plastic surgery cohorts. Conclusions: Current evidence suggests that GLP-1RAs do not consistently worsen postoperative outcomes; however, their use is associated with nutritional and body composition changes that may influence perioperative recovery. Nutritional assessment and optimisation may therefore represent an important component of perioperative care in patients receiving GLP-1RA therapy. FAU - Sandha, Tegbir Singh AU - Sandha TS AUID- ORCID: 0009-0006-8644-7816 AD - Department of Plastic and Reconstructive Surgery, Peninsula Health, Frankston, VIC 3199, Australia. FAU - Ron, Ofir AU - Ron O AD - Department of Plastic and Reconstructive Surgery, Peninsula Health, Frankston, VIC 3199, Australia. FAU - Rozen, Warren M AU - Rozen WM AUID- ORCID: 0000-0002-4092-182X AD - Department of Plastic and Reconstructive Surgery, Peninsula Health, Frankston, VIC 3199, Australia. FAU - Seth, Ishith AU - Seth I AUID- ORCID: 0000-0001-5444-8925 AD - Department of Plastic and Reconstructive Surgery, Peninsula Health, Frankston, VIC 3199, Australia. AD - Faculty of Medicine and Surgery, Peninsula Clinical School, Monash University, 2 Hastings Road, Frankston, VIC 3199, Australia. FAU - Cuomo, Roberto AU - Cuomo R AUID- ORCID: 0000-0002-8396-095X AD - Department of Plastic and Reconstructive Surgery, Peninsula Health, Frankston, VIC 3199, Australia. AD - Plastic Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Banchi di Sotto, 55, 53100 Siena, SI, Italy. LA - eng PT - Journal Article PT - Scoping Review DEP - 20260723 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Perioperative Care/methods/standards MH - Diabetes Mellitus, Type 2/drug therapy MH - *Nutritional Status/drug effects MH - Body Composition/drug effects MH - Obesity/drug therapy PMC - PMC13514910 OTO - NOTNLM OT - GLP-1 receptor agonists OT - body composition OT - perioperative nutrition OT - sarcopenia OT - surgical outcomes OT - wound healing COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/07/23 CRDT- 2026/08/27 01:10 PHST- 2026/06/22 00:00 [received] PHST- 2026/07/17 00:00 [revised] PHST- 2026/07/20 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/07/23 00:00 [pmc-release] AID - medicina62081434 [pii] AID - medicina-62-01434 [pii] AID - 10.3390/medicina62081434 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Jul 23;62(8):1434. doi: 10.3390/medicina62081434. PMID- 42654234 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 16 DP - 2026 Aug 14 TI - Beyond Weight Loss: Skeletal Muscle Health During Incretin-Based Therapy in Patients with Diabesity. LID - 10.3390/nu18162654 [doi] LID - 2654 AB - Background: Incretin-based therapies (IBTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs), have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although these agents provide substantial metabolic and cardiometabolic benefits, their effects on skeletal muscle, particularly in older adults at increased risk of sarcopenia and functional decline, remain incompletely understood. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs) and observational studies evaluating the effects of semaglutide and tirzepatide on skeletal muscle mass (SMM), muscle quality, strength, and physical performance. Current evidence on nutritional and exercise strategies aimed at preserving skeletal muscle during IBT was also reviewed. Results: Both semaglutide and tirzepatide induce substantial weight loss accompanied by reductions in lean body mass (LBM). However, current evidence indicates that LBM loss is generally proportional to the magnitude of weight loss and should not be interpreted as a direct surrogate for skeletal muscle loss or drug-induced myotoxicity. Tirzepatide appears to improve skeletal muscle composition by reducing muscle fat infiltration (MFI), whereas semaglutide shows more heterogeneous effects on muscle strength and physical performance, particularly in older or frail individuals. Emerging evidence highlights the importance of muscle quality, nutritional adequacy, and resistance exercise as key determinants of muscle preservation, although functional outcomes and data in older adults remain limited. Conclusions: The effects of incretin-based therapies (IBTs) on skeletal muscle are multifactorial and influenced by age, baseline muscle reserve, nutritional status, and physical activity. Preserving skeletal muscle health should be considered an integral component of obesity management through individualized nutritional care, adequate protein intake, resistance exercise, and regular functional assessment. Future research should prioritize the standardized evaluation of muscle quality and function and determine whether targeted nutritional interventions can improve the quality of weight loss and support healthy aging during IBT. FAU - Mollero, Edoardo Luigi Maria AU - Mollero ELM AUID- ORCID: 0000-0002-1903-5874 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. AD - Department of Statistics, Computer Science, Applications "Giuseppe Parenti", University of Florence, Viale Giovanni Battista Morgagni 59, 50134 Firenze, Italy. FAU - Dozzani, Ivan AU - Dozzani I AUID- ORCID: 0009-0007-5595-7992 AD - Independent Researcher, 50142 Firenze, Italy. FAU - Biamonte, Emilia AU - Biamonte E AUID- ORCID: 0009-0000-9502-4694 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. FAU - Bendotti, Giulia AU - Bendotti G AUID- ORCID: 0000-0002-6548-3475 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. FAU - Marzullo, Paolo AU - Marzullo P AUID- ORCID: 0000-0003-3215-5747 AD - Division of Endocrinology, Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy. FAU - Aimaretti, Gianluca AU - Aimaretti G AD - Division of Endocrinology and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy. FAU - Gallo, Marco AU - Gallo M AUID- ORCID: 0000-0001-7166-0848 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260814 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Incretins) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Muscle, Skeletal/drug effects MH - Semaglutide MH - *Incretins/therapeutic use/pharmacology MH - *Weight Loss/drug effects MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Sarcopenia MH - Muscle Strength/drug effects PMC - PMC13516410 OTO - NOTNLM OT - GLP-1 receptor agonists OT - muscle quality OT - nutrition OT - obesity OT - resistance training OT - sarcopenia OT - semaglutide OT - skeletal muscle OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/14 CRDT- 2026/08/27 01:09 PHST- 2026/07/26 00:00 [received] PHST- 2026/08/10 00:00 [revised] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:09 [entrez] PHST- 2026/08/14 00:00 [pmc-release] AID - nu18162654 [pii] AID - nutrients-18-02654 [pii] AID - 10.3390/nu18162654 [doi] PST - epublish SO - Nutrients. 2026 Aug 14;18(16):2654. doi: 10.3390/nu18162654. PMID- 42649514 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Aug 26 TI - Disease-modifying anti-diabetic drugs (DMADDs): bridging the SIMPLE approach to disease interception. LID - 10.1186/s12933-026-03346-2 [doi] LID - 259 AB - The traditional glucose-centric paradigm of type 2 diabetes management is being superseded by growing evidence that certain agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and pioglitazone, confer cardiovascular, renal, and hepatic benefits that extend well beyond glycemic control. Building on the previously proposed "diabetes/disease-modifying drugs (DMDs)" concept introduced through the SIMPLE framework, we propose a more mechanistically precise term: Disease-Modifying Anti-Diabetic Drugs (DMADDs). DMADDs are defined by four criteria: glucose-independent clinical benefit, durable organ-specific protection, mechanistic evidence of anti-inflammatory or anti-fibrotic activity, and sustained legacy effects or remission potential. Using these criteria, SGLT2i, GLP-1RA, and pioglitazone emerge as prototypical agents, while metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, insulin, and sulfonylureas do not meet the full threshold. We explicitly explain why metformin and DPP-4 inhibitors are excluded as DMADDs, situate the DMADD framework within the heterogeneity of type 2 diabetes and against what non-pharmacological interventions can achieve, and state the limitations of the proposal. Recent evidence reinforces this framework: the SOUL trial established cardiovascular superiority for oral semaglutide, extending disease-modifying properties beyond injectable formulations, while Phase 3 TRIUMPH data position retatrutide as an emerging triple-agonist candidate awaiting cardiovascular outcome data. The 2026 American Diabetes Association Standards of Care now recommend SGLT2i and GLP-1RA independent of baseline glycated hemoglobin (HbA1c), an institutional shift that mirrors the disease-interception logic proposed here. We argue that adopting the DMADD framework could reorient diabetes therapeutics from glycemic normalization toward early disease interception, potentially preserving beta-cell function and expanding the clinical horizon toward remission. This terminology offers a unifying scaffold for future trials, regulatory classification, and clinical guidelines, redefining therapeutic success in type 2 diabetes beyond glucose control alone. CI - (c) 2026. The Author(s). FAU - Koca, Nizameddin AU - Koca N AUID- ORCID: 0000-0003-1457-4366 AD - Department of Internal Medicine, University of Health Sciences, Bursa Sehir Training & Research Hospital, Bursa, Turkey. nizameddin.koca@sbu.edu.tr. FAU - Uyar, Seyit AU - Uyar S AUID- ORCID: 0000-0002-2435-8248 AD - Department of Internal Medicine, University of Health Sciences, Antalya Training & Research Hospital, Antalya, Turkey. FAU - Sahinturk, Yasin AU - Sahinturk Y AUID- ORCID: 0000-0003-4907-0766 AD - Department of Internal Medicine, University of Health Sciences, Antalya Training & Research Hospital, Antalya, Turkey. FAU - Yildiz, Hamit AU - Yildiz H AUID- ORCID: 0000-0001-7858-5123 AD - Department of Internal Medicine, University of Gaziantep, Gaziantep University Hospital, Gaziantep, Turkey. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0001-5905-0211 AD - Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - DeFronzo, RalphA AU - DeFronzo R AUID- ORCID: 0000-0002-8581-6273 AD - Department of Internal Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA. LA - eng PT - Journal Article DEP - 20260826 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Biomarkers) RN - 0 (PPAR-gamma Agonists) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - *Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Animals MH - Biomarkers/blood MH - *Glycemic Control/adverse effects MH - PPAR-gamma Agonists MH - *Incretins/therapeutic use/adverse effects MH - Semaglutide MH - Remission Induction PMC - PMC13520461 OTO - NOTNLM OT - Disease modification OT - GLP-1 receptor agonists OT - Organ protection OT - Remission OT - SGLT2 inhibitors OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing Interests: N.K., S.U., Y.S., H.Y., and R.A.D. declare no competing interests. S.D.P. reports consulting fees from Abbott, Altimmune, Applied Therapeutics, Biomea Fusion, Eli Lilly and Company, Menarini International, Hoffman-La Roche, Novo Nordisk, and Sun Pharma; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Menarini International, Novo Nordisk, and Sanofi. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/26 CRDT- 2026/08/27 00:02 PHST- 2026/07/09 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 00:02 [entrez] PHST- 2026/08/26 00:00 [pmc-release] AID - 10.1186/s12933-026-03346-2 [pii] AID - 3346 [pii] AID - 10.1186/s12933-026-03346-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Aug 26;25(1):259. doi: 10.1186/s12933-026-03346-2. PMID- 42642357 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261010 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Cardiorenal Mortality and Safety Outcomes of GLP-1 Receptor Agonists in Type 2 Diabetes With BMI Below 27 kg/m(2): A Target Trial Emulation. PG - 10498-10512 LID - 10.1111/dom.71266 [doi] AB - AIMS: Cardiorenal evidence for glucagon-like peptide-1 receptor agonists (GLP-1 RAs) derives mainly from trials in overweight or obesity; data in adults with Type 2 diabetes (T2D) and body mass index (BMI) below 27 kg/m(2) are limited. MATERIALS AND METHODS: We emulated a target trial in the TriNetX US Collaborative Network (index dates 2020 to 2026; maximum follow-up 24 months). Adults with T2D and BMI < 27 kg/m(2) newly initiating non-tirzepatide GLP-1 RAs were compared with new users of dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i) or usual care. Comparisons used separate 1:1 propensity score matching. The primary outcome was all-cause mortality. RESULTS: After matching, 7389, 8969 and 8610 GLP-1 RA users were matched to DPP-4i, SGLT2i and usual care. Versus DPP-4i, GLP-1 RA was associated with lower all-cause mortality (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.52-0.71), major adverse cardiovascular events (MACE; HR 0.83; 95% CI 0.71-0.98) and coded heart failure (HR 0.71; 95% CI 0.60-0.85). Versus SGLT2i, MACE (HR 0.81; 95% CI 0.69-0.95) and coded heart failure (HR 0.56; 95% CI 0.47-0.65) were lower, but all-cause mortality was not (HR 0.89; 95% CI 0.76-1.05). Gastroparesis was more frequent versus DPP-4i. CONCLUSION: In people with T2D and BMI < 27 kg/m(2), GLP-1 RA use was associated with lower coded heart failure risk across all three comparisons, the most consistent finding. The lower all-cause mortality association versus DPP-4i and usual care, absent versus SGLT2i, should be interpreted cautiously as likely reflecting residual confounding rather than a benefit of this magnitude. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chen, Shao-Chia AU - Chen SC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Li, Pei-Yun AU - Li PY AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Jo-Ching AU - Chen JC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Meyerowitz-Katz, Gideon AU - Meyerowitz-Katz G AD - School of Health and Society, University of Wollongong, Wollongong, Australia. FAU - Yang, Shun-Fa AU - Yang SF AUID- ORCID: 0000-0002-0365-7927 AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2025-A-004/Chung Shan Medical University Hospital/ GR - CSH-2026-A-009/Chung Shan Medical University Hospital/ GR - CSH-2026-F-003/Chung Shan Medical University Hospital/ GR - 113-2314-B-040-026-MY2/National Science and Technology Council/ GR - 114-2622-B-040-001/National Science and Technology Council/ PT - Journal Article DEP - 20260825 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Body Mass Index MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Heart Failure/mortality PMC - PMC13646335 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - cardiovascular outcomes OT - heart failure OT - semaglutide OT - target trial emulation OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/08/26 05:36 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/25 23:03 PHST- 2026/08/01 00:00 [revised] PHST- 2026/05/18 00:00 [received] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/26 05:36 [pubmed] PHST- 2026/08/25 23:03 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71266 [pii] AID - 10.1111/dom.71266 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10498-10512. doi: 10.1111/dom.71266. Epub 2026 Aug 25. PMID- 42642078 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260904 IS - 2056-5933 (Electronic) IS - 2056-5933 (Linking) VI - 12 IP - 3 DP - 2026 Aug 25 TI - Metabolic effects of GLP-1 receptor agonists in rheumatology patients and inflammatory outcomes: a single-centre retrospective cohort. LID - 10.1136/rmdopen-2026-007122 [doi] LID - e007122 AB - BACKGROUND: Obesity and type 2 diabetes are common in rheumatology, often exacerbated by glucocorticoids. Real-world data on glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this setting remain limited. OBJECTIVES: To evaluate the metabolic effectiveness and safety of GLP-1RAs in rheumatology outpatients, including inflammatory marker and subgroup analyses. METHODS: Single-centre retrospective study (October 2024-October 2025) including 119 patients (from 169 screened) treated with GLP-1RAs. Paired analyses were performed at 3, 6 and 12 months. Exploratory comparisons included participants with chronic inflammatory arthritis (n=46) and those with non-inflammatory disease (n=43). RESULTS: Patients had high baseline cardiometabolic burden (mean body mass index (BMI) 34.9+/-9.9 kg/m(2); diabetes 96.6%). GLP-1RA initiation was associated with sustained weight loss: -4.0 kg, -4.5 kg and -7.7 kg at 3, 6 and 12 months (all p<0.001; -8.2% at 12 months), with 56.5% improving >/=1 BMI category. Haemoglobin A1c decreased by -0.97%, -0.69% and -0.91% (all p<0.001), alongside significant reductions in fasting glucose (up to -24.8 mg/dL; p<0.001). Lipid improvements included reductions in low-density lipoprotein-cholesterol (-12.2 mg/dL; p=0.006) and triglycerides (-21.7 mg/dL; p=0.007). At 12 months, erythrocyte sedimentation rate decreased significantly (p=0.023), while CRP showed a non-significant decline (p=0.076); both were significantly reduced in the inflammatory subgroup. No significant differences were observed between inflammatory and non-inflammatory groups in adjusted metabolic trajectories. Adverse events were mainly gastrointestinal (13.4%); pancreatitis (0.8%) and cholecystitis (1.7%) were rare. Discontinuation occurred in 6.7%. One death (mesenteric ischaemia) had unclear causality. CONCLUSIONS: GLP-1RAs were associated with meaningful metabolic improvements in patients with rheumatic diseases, with a favourable safety profile. Potential anti-inflammatory effects require confirmation in prospective studies. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Retuerto-Guerrero, Miriam AU - Retuerto-Guerrero M AUID- ORCID: 0000-0003-0248-657X AD - Department of Rheumatology, Complejo Asistencial Universitario de Leon, Leon, Spain miriam.retuerto@hotmail.es. AD - Instituto de Investigacion Biosanitaria de Leon (IBIOLEON), Leon, Spain. FAU - Gonzalez Fernandez, Ignacio AU - Gonzalez Fernandez I AD - Department of Rheumatology, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Alejo Ramos, Mirian AU - Alejo Ramos M AD - Department of Endocrinology, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Gonzalez Fernandez, Ismael AU - Gonzalez Fernandez I AD - Department of Rheumatology, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Velez Blanco, Andrea AU - Velez Blanco A AD - Department of Pharmacy, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Martin Sanz, Anibal AU - Martin Sanz A AD - Department of Pharmacy, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Rivero-Lezcano, Octavio Miguel AU - Rivero-Lezcano OM AD - Research Unit, Complejo Asistencial Universitario de Leon, Leon, Spain. AD - Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. FAU - Diez-Alvarez, Elvira AU - Diez-Alvarez E AD - Department of Rheumatology, Complejo Asistencial Universitario de Leon, Leon, Spain. LA - eng PT - Journal Article DEP - 20260825 PL - England TA - RMD Open JT - RMD open JID - 101662038 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Inflammation/drug therapy MH - *Rheumatic Diseases/drug therapy/complications/metabolism MH - Aged MH - Body Mass Index MH - Obesity/drug therapy MH - Biomarkers MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glycated Hemoglobin MH - Blood Glucose MH - Weight Loss/drug effects PMC - PMC13536120 OTO - NOTNLM OT - Arthritis OT - Cardiovascular Diseases OT - Inflammation COIS- Competing interests: None declared. EDAT- 2026/08/25 23:33 MHDA- 2026/08/25 23:34 PMCR- 2026/08/25 CRDT- 2026/08/25 20:42 PHST- 2026/04/30 00:00 [received] PHST- 2026/08/01 00:00 [accepted] PHST- 2026/08/25 23:34 [medline] PHST- 2026/08/25 23:33 [pubmed] PHST- 2026/08/25 20:42 [entrez] PHST- 2026/08/25 00:00 [pmc-release] AID - rmdopen-2026-007122 [pii] AID - 10.1136/rmdopen-2026-007122 [doi] PST - epublish SO - RMD Open. 2026 Aug 25;12(3):e007122. doi: 10.1136/rmdopen-2026-007122. PMID- 42636218 OWN - NLM STAT- MEDLINE DCOM- 20260824 LR - 20260826 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 8 DP - 2026 TI - Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study. PG - e0356138 LID - 10.1371/journal.pone.0356138 [doi] LID - e0356138 AB - OBJECTIVE: To evaluate the associations between commonly used antidiabetic regimens and incidence of mild cognitive disorder, Alzheimer disease, and vascular dementia in adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the TriNetX US Collaborative Network of electronic health records from 2010 to 2024. Adults aged 40-69 years with type 2 diabetes and at least 1 year of follow-up were included. Propensity score matching was applied to balance covariates. EXPOSURE: Patients were classified into 5 treatment groups: metformin only (reference), metformin plus DPP-4 inhibitors, metformin plus GLP-1 receptor agonists, metformin plus SGLT-2 inhibitors, and insulin monotherapy. Exposure was defined by first recorded prescription and continued use during follow-up. MAIN OUTCOMES AND MEASURES: Primary outcomes were incident mild cognitive disorder, Alzheimer disease, and vascular dementia, identified using ICD-10 codes. Hazard ratios with 95% confidence intervals were estimated from Cox proportional hazards models, with landmark analyses for follow-up shorter and longer than 5 years. RESULTS: Among 1,528,885 adults with type 2 diabetes (mean age, 58 years; 49.2% women), GLP-1 receptor agonists plus metformin were associated with lower incidence of vascular dementia (HR, 0.46; 95% CI, 0.37-0.57), mild cognitive disorder (HR, 0.79; 95% CI, 0.66-0.95), and Alzheimer disease (HR, 0.46; 95% CI, 0.31-0.70). SGLT-2 inhibitors plus metformin reduced vascular dementia risk (HR, 0.68; 95% CI, 0.54-0.87) but not other outcomes. Insulin monotherapy was associated with higher incidence of vascular dementia (HR, 3.27; 95% CI, 3.03-3.52), mild cognitive disorder (HR, 1.71; 95% CI, 1.56-1.87), and Alzheimer disease (HR, 1.56; 95% CI, 1.32-1.84). CONCLUSIONS AND RELEVANCE: GLP-1 receptor agonists and SGLT-2 inhibitors combined with metformin were associated with reduced risk of cognitive decline. Insulin monotherapy was associated with higher incidence of all three outcomes; however, this association is likely influenced by confounding by indication, unmeasured markers of diabetes severity (including diabetes duration, cardiovascular and renal disease severity, and microvascular and macrovascular complications), and shorter follow-up among insulin users, and should not be interpreted as a direct drug effect. Because standard Cox models do not account for death as a competing event, reported hazard ratios reflect cause-specific hazards and may not directly correspond to cumulative incidence, particularly for the insulin group, in which mortality and censoring were substantially higher. Antidiabetic medication choice may influence long-term cognitive outcomes and should be considered in diabetes management. CI - Copyright: (c) 2026 Nasir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Nasir, Ahmad Basil AU - Nasir AB AUID- ORCID: 0000-0003-1588-303X AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Kilani, Yassine AU - Kilani Y AD - Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Aldiabat, Mohammad AU - Aldiabat M AD - Department of Internal Medicine, Washington University, Saint Louis, Missouri, United States of America. FAU - Abdelghany, Omar AU - Abdelghany O AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Hafez, Youssef AU - Hafez Y AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Desai, Nitin AU - Desai N AD - Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Madi, Mahmoud Y AU - Madi MY AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Wade, Francis G AU - Wade FG AD - Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Qureshi, Kamran AU - Qureshi K AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Frey, Lewis J AU - Frey LJ AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. AD - Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. AD - VA St. Louis Healthcare System, St. Louis, Missouri, United States of America. FAU - Farmer, Adam D AU - Farmer AD AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. AD - Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Syn, Wing-Kin AU - Syn WK AUID- ORCID: 0000-0001-7966-0500 AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. AD - Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America. AD - Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Vizcaya, Spain. LA - eng PT - Journal Article DEP - 20260824 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Metformin/therapeutic use/adverse effects MH - Middle Aged MH - Male MH - Aged MH - Insulin/therapeutic use/adverse effects MH - Adult MH - *Cognitive Dysfunction/epidemiology/chemically induced MH - Alzheimer Disease/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Incidence MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Cognition Disorders/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Dementia, Vascular/epidemiology PMC - PMC13502699 COIS- The authors have declared that no competing interests exist. EDAT- 2026/08/24 18:42 MHDA- 2026/08/24 18:43 PMCR- 2026/08/24 CRDT- 2026/08/24 13:34 PHST- 2025/11/10 00:00 [received] PHST- 2026/07/30 00:00 [accepted] PHST- 2026/08/24 18:43 [medline] PHST- 2026/08/24 18:42 [pubmed] PHST- 2026/08/24 13:34 [entrez] PHST- 2026/08/24 00:00 [pmc-release] AID - PONE-D-25-60647 [pii] AID - 10.1371/journal.pone.0356138 [doi] PST - epublish SO - PLoS One. 2026 Aug 24;21(8):e0356138. doi: 10.1371/journal.pone.0356138. eCollection 2026. PMID- 42625391 OWN - NLM STAT- MEDLINE DCOM- 20261015 LR - 20261017 IS - 1742-4658 (Electronic) IS - 1742-464X (Print) IS - 1742-464X (Linking) VI - 293 IP - 20 DP - 2026 Oct TI - Effects of GLP-1 agonists on the gut microbiota in type 2 diabetes mellitus: a systematic review. PG - 5971-5995 LID - 10.1111/febs.70656 [doi] AB - Diabetes mellitus (DM) is a metabolic disease characterised by chronic hyperglycemia. The Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) used in type 2 diabetes mellitus (T2DM) have been highlighted for their potential benefits to the gut microbiota in the context of this pathology. Therefore, it is important to investigate the relationship between microbiota and GLP-1 RAs used in T2DM. This review aimed at evaluating the effects of GLP-1 agonists on gut microbiota in T2DM individuals. The protocol was previously registered in PROSPERO, and the search was conducted in PubMed, Scopus, Web of Science, and Embase databases in March 2025. Two reviewers have read the titles and abstracts and selected the included articles based on established criteria. The initial search identified 5532 publications, of which 17 studies were included: 12 preclinical and 5 clinical. Most were conducted in China between 2016 and 2025. GLP-1 agonists have been shown to modulate the gut microbiota, characterised by an increase in Bacteroidetes, Akkermansia muciniphila, and Lactobacillus. These changes are accompanied by an improvement of intestinal villi, increase in occludin expression, as well as an improvement in colonic inflammation. We identified a higher abundance of bacterial species associated with intestinal balance (eubiosis), accompanied by reduced inflammation and insulin resistance. Conversely, there was a lower abundance of bacteria related to dysbiosis, such as Firmicutes and Proteobacteria, which can be unfavourable when in excess. GLP-1 agonists influence the intestinal microbiota, improving metabolic parameters and anti-inflammatory effects. However, further clinical studies are needed to corroborate the findings of this review. CI - (c) 2026 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. FAU - Santos Dantas, Ranicleide AU - Santos Dantas R AUID- ORCID: 0009-0005-4437-2898 AD - Department of Pharmacy, Federal University of Sergipe, Brazil. FAU - Souza Santos, Lucas Vinicius AU - Souza Santos LV AD - Department of Pharmacy, Federal University of Sergipe, Brazil. FAU - Carvalho de Oliveira, Andre Gustavo AU - Carvalho de Oliveira AG AD - Department of Pharmacy, Federal University of Sergipe, Brazil. FAU - Dos Santos Barreto, Marina AU - Dos Santos Barreto M AUID- ORCID: 0000-0003-4724-0688 AD - Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, Brazil. FAU - Rego Rodrigues Silva, Deise Maria AU - Rego Rodrigues Silva DM AD - Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, Brazil. FAU - Macedo Moura, Pedro Henrique AU - Macedo Moura PH AD - Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, Brazil. FAU - Dias Silva, Eloia Emanuelly AU - Dias Silva EE AD - Northeast Biotechnology Network (RENORBIO), Federal University of Sergipe, Brazil. FAU - Santana Santos, Ronaldy AU - Santana Santos R AD - Postgraduate Pharmacy Program (Pathophysiology and Toxicology), University of Sao Paulo, Brazil. FAU - Alves da Mota Santana, Lucas AU - Alves da Mota Santana L AD - School of Dentistry, Federal University of Sergipe, Brazil. FAU - Gandhi Gopalsamy, Rajiv AU - Gandhi Gopalsamy R AD - Division of Phytochemistry and Drug Design, Department of Biosciences, Rajagiri College of Social Sciences, Kochi, Kerala, India. FAU - Gibara Guimaraes, Adriana AU - Gibara Guimaraes A AD - Department of Pharmacy, Federal University of Sergipe, Brazil. AD - Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, Brazil. FAU - Pinto Borges, Lysandro AU - Pinto Borges L AUID- ORCID: 0000-0002-1721-1547 AD - Department of Pharmacy, Federal University of Sergipe, Brazil. AD - Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, Brazil. AD - Northeast Biotechnology Network (RENORBIO), Federal University of Sergipe, Brazil. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260820 PL - England TA - FEBS J JT - The FEBS journal JID - 101229646 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology/metabolism MH - *Gastrointestinal Microbiome/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Lactobacillus/drug effects PMC - PMC13669651 OTO - NOTNLM OT - GLP-1 agonists OT - diabetes mellitus OT - gastrointestinal microbiome OT - systematic review COIS- The authors declare no competing financial interest. EDAT- 2026/08/21 05:35 MHDA- 2026/10/15 07:17 PMCR- 2026/10/15 CRDT- 2026/08/21 01:53 PHST- 2026/04/10 00:00 [revised] PHST- 2025/12/12 00:00 [received] PHST- 2026/07/10 00:00 [accepted] PHST- 2026/10/15 07:17 [medline] PHST- 2026/08/21 05:35 [pubmed] PHST- 2026/08/21 01:53 [entrez] PHST- 2026/10/15 00:00 [pmc-release] AID - FEBS70656 [pii] AID - 10.1111/febs.70656 [doi] PST - ppublish SO - FEBS J. 2026 Oct;293(20):5971-5995. doi: 10.1111/febs.70656. Epub 2026 Aug 20. PMID- 42624955 OWN - NLM STAT- MEDLINE DCOM- 20260821 LR - 20260823 IS - 1535-1645 (Electronic) IS - 1523-3812 (Print) IS - 1523-3812 (Linking) VI - 28 IP - 1 DP - 2026 Aug 21 TI - GLP-1 and dual GIP/GLP-1 receptor agonists' psychopharmacology and putative neuropsychiatric associated effects: a Bradford Hill-informed, systematic, evaluation. LID - 10.1007/s11920-026-01709-w [doi] LID - 65 AB - PURPOSE OF REVIEW: This review evaluates evidence linking both GLP-1 and GIP/GLP-1RAs' exposure to a range of neuropsychiatric outcomes using the Bradford Hill criteria for causal inference. RECENT FINDINGS: Glucagon-like peptide-1 (GLP-1) and the dual glucose-dependent insulinotropic polypeptide-GIP/GLP-1 receptor agonists (RAs) are incretin-based medications widely prescribed for type 2 diabetes mellitus and obesity, with demonstrated cardiometabolic benefit and rapidly expanding population exposure. In parallel, post-marketing surveillance and emerging translational research have raised questions regarding potential central nervous system effects, including neuropsychiatric adverse events and psychopharmacological properties. Integrating data from receptor pharmacology, preclinical neuroscience, randomized controlled trials, and observational and pharmacovigilance studies, the strength, consistency, biological plausibility, and experimental support for reported associations with depression, anxiety, suicidality, reward-related behaviour, cognitive effects and retinal/ocular related disturbances were here assessed. Implications for clinical risk-benefit assessment were discussed as well. Current evidence supports potential biological plausibility of a relationship between GLP-1 RAs and a range of psychopathological disorders but remains insufficient to establish causality for most neuropsychiatric outcomes, suggesting the need for prospective, mechanism-informed clinical studies. CI - (c) 2026. The Author(s). FAU - Schifano, F AU - Schifano F AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. FAU - De Luca, M A AU - De Luca MA AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. AD - Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. FAU - Bonaccorso, S AU - Bonaccorso S AD - North London NHS Foundation Trust, St Pancras Hospital, London, UK. FAU - Arillotta, Davide AU - Arillotta D AUID- ORCID: 0000-0002-8843-0595 AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. davide.arillotta@yahoo.it. AD - Department of Neurosciences, Psychology, Drug Research, and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy. davide.arillotta@yahoo.it. FAU - Floresta, G AU - Floresta G AD - Department of Drug and Health Sciences, University of Catania, Catania, Italy. giuseppe.floresta@unict.it. FAU - Martinotti, G AU - Martinotti G AD - Department of Neurosciences, Imaging and Clinical Sciences, Universita degli Studi G. D'Annunzio Chieti-Pescara, Chieti, Italy. FAU - Papanti, G D AU - Papanti GD AD - Tolmezzo Community Mental Health Centre, ASUFC Mental Health and Addiction Department, Tolmezzo, Italy. FAU - Corkery, J M AU - Corkery JM AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. FAU - Chiappini, S AU - Chiappini S AD - UniCamillus International University of Medical Sciences, Rome, Italy. FAU - Guirguis, A AU - Guirguis A AD - University of Swansea Medical School, Swansea, UK. LA - eng PT - Journal Article PT - Review DEP - 20260821 PL - United States TA - Curr Psychiatry Rep JT - Current psychiatry reports JID - 100888960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Mental Disorders/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Hypoglycemic Agents/adverse effects MH - *Incretins/adverse effects PMC - PMC13493456 OTO - NOTNLM OT - Anxiety OT - Bradford-Hill evaluation OT - Cognitive dysfunction OT - Depression OT - Dulaglutide OT - GLP-1 RAs OT - GLP-1 receptor agonists OT - Liraglutide OT - Psychopathology OT - Psychopharmacology OT - Retatrutide OT - Semaglutide OT - Suicidal ideation OT - Tirzepatide OT - dual GIP/GLP-1 RAs OT - triple GIP/GLP-1/glucagon RAs COIS- Declarations. Competing Interests: The authors declare no competing interests. EDAT- 2026/08/21 05:35 MHDA- 2026/08/21 05:36 PMCR- 2026/08/21 CRDT- 2026/08/21 00:09 PHST- 2026/05/21 00:00 [received] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/08/21 05:36 [medline] PHST- 2026/08/21 05:35 [pubmed] PHST- 2026/08/21 00:09 [entrez] PHST- 2026/08/21 00:00 [pmc-release] AID - 10.1007/s11920-026-01709-w [pii] AID - 1709 [pii] AID - 10.1007/s11920-026-01709-w [doi] PST - epublish SO - Curr Psychiatry Rep. 2026 Aug 21;28(1):65. doi: 10.1007/s11920-026-01709-w. PMID- 42624784 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260820 IS - 1558-7118 (Electronic) IS - 1557-2625 (Linking) VI - 39 IP - 1 DP - 2026 Aug TI - Not Just for Diabetes: The Next Frontier for GLP-1 Agonists. LID - 165782 [pii] LID - 10.3122/jabfm.2025.250473R1 [doi] AB - A commonly used GLP-1 agonist, semaglutide, reduces the risk of adverse cardiovascular outcomes in non-diabetic individuals with obesity and pre-existing cardiovascular disease. CI - (c) 2026 Copyright by the American Board of Family Medicine. FAU - Colangelo, Henry AU - Colangelo H AD - University of Colorado Family Medicine Residency. FAU - Nestler, Ariana AU - Nestler A AD - University of Colorado Family Medicine Residency. FAU - Lyon, Corey AU - Lyon C AD - University of Colorado Family Medicine Residency. LA - eng PT - Journal Article PL - United States TA - J Am Board Fam Med JT - Journal of the American Board of Family Medicine : JABFM JID - 101256526 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/agonists MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Cardiovascular Diseases OT - Glucagon-Like Peptide 1 OT - Obesity OT - Semaglutide EDAT- 2026/08/20 23:35 MHDA- 2026/08/20 23:36 CRDT- 2026/08/20 21:55 PHST- 2025/12/11 00:00 [received] PHST- 2026/01/14 00:00 [accepted] PHST- 2026/08/20 23:36 [medline] PHST- 2026/08/20 23:35 [pubmed] PHST- 2026/08/20 21:55 [entrez] AID - 39/1/165782 [pii] AID - 10.3122/jabfm.2025.250473R1 [doi] PST - ppublish SO - J Am Board Fam Med. 2026 Aug;39(1):165782. doi: 10.3122/jabfm.2025.250473R1. PMID- 42624330 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 240 DP - 2026 Oct TI - Trends in utilization of glucagon-like peptide‑1 receptor agonists, sodium-glucose cotransporter‑2 inhibitors, and metabolic bariatric surgery in U.S. adults with diabetes and obesity. PG - 113504 LID - S0168-8227(26)00424-9 [pii] LID - 10.1016/j.diabres.2026.113504 [doi] AB - AIMS: To characterize trends in utilization of glucagon-like peptide‑1 receptor agonists (GLP‑1RAs), sodium-glucose cotransporter‑2 inhibitors (SGLT2is), and metabolic/bariatric surgery among US adults with type 2 diabetes (T2D) and obesity. METHODS: We conducted a cohort study using electronic health record and claims data from Optum Labs Data Warehouse for US private and Medicare Advantage plan enrollees aged 18-79 with T2D and obesity initiating GLP‑1RAs or SGLT2is or undergoing MBS (2010-2024). We evaluated initiation, adherence (>/=80% of days with medication), and persistence. RESULTS: Among 342,932 treatment initiations (335,605 individuals), 60.8% initiated GLP‑1RAs, 35.7% SGLT2is, and 3.6% MBS. Use of both medication classes increased over time (GLP-1RAs: 1,988 to 44,852; SGLT2is: 861 to 19,892). In 2024, semaglutide (62.2%) and tirzepatide (32.6%) were the most initiated GLP-1RAs; MBS was rare (0.7% of treatments). Median treatment duration was 240 days for GLP‑1RAs and 254 days for SGLT2is; approximately 50% were adherent. Tirzepatide had the highest adherence and persistence. At one-year, 53.0% of GLP‑1RA and 56.0% of SGLT2i initiators were using their initiated treatment; transition to other therapies was uncommon. CONCLUSIONS: Initiation of GLP‑1RAs and SGLT2is, but not MBS utilization, has expanded in recent years, although adherence and persistence remain low. Further studies should evaluate how these shifting patterns affect health outcomes. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Wartko, Paige D AU - Wartko PD AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA; Department of Epidemiology, School of Public Health, University of Washington, Hans Rosling Center for Population Health, 3980 15th Avenue NE, Box 351617, Seattle, WA 98195-1617, USA. Electronic address: paige.d.wartko@kp.org. FAU - Zhang, Rui AU - Zhang R AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA. FAU - Johnson, Eric AU - Johnson E AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - Begle, Connor AU - Begle C AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA. FAU - Bobb, Jennifer F AU - Bobb JF AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - Chen, Chixiang AU - Chen C AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA; Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Singh, Aditi AU - Singh A AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Ross, Lisa AU - Ross L AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - O'Connor, Patrick J AU - O'Connor PJ AD - HealthPartners Institute, Minneapolis, MN, USA. FAU - Arterburn, David AU - Arterburn D AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA; Optum Labs, Eden Prairie, MN, USA; Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng GR - P30 AG097158/AG/NIA NIH HHS/United States GR - R01 DK135515/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260820 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Bariatric Surgery/trends/statistics & numerical data MH - Female MH - Male MH - Adult MH - *Obesity/drug therapy/surgery/therapy MH - Middle Aged MH - United States/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adolescent MH - Young Adult MH - Cohort Studies MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - GIP/GLP-1RA OT - GLP-1RA OT - Metabolic surgery OT - Obesity OT - Pharmacoepidemiology OT - SGLT2i OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rozalina McCoy reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. David Arterburn reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. Paige Wartko reports a relationship with Syneos Health that includes: funding grants. Rozalina McCoy reports a relationship with American Diabetes Association that includes: funding grants, speaking and lecture fees, and travel reimbursement. Rozalina McCoy reports a relationship with Yale New Haven Health that includes: consulting or advisory. Rozalina McCoy reports a relationship with National Committee for Quality Assurance (NCQA) that includes: consulting or advisory. David Arterburn reports a relationship with Obesity Medicine Association that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/20 23:35 MHDA- 2026/09/07 23:34 CRDT- 2026/08/20 19:13 PHST- 2026/05/11 00:00 [received] PHST- 2026/08/14 00:00 [revised] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/08/20 23:35 [pubmed] PHST- 2026/08/20 19:13 [entrez] AID - S0168-8227(26)00424-9 [pii] AID - 10.1016/j.diabres.2026.113504 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Oct;240:113504. doi: 10.1016/j.diabres.2026.113504. Epub 2026 Aug 20. PMID- 42618994 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260918 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 230 DP - 2025 Dec TI - Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists-A systematic review and Bayesian network meta-analysis. PG - 112954 LID - S0168-8227(25)00968-4 [pii] LID - 10.1016/j.diabres.2025.112954 [doi] AB - BACKGROUND: There are less comparisons among once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs),which is not conducive to refined clinical treatment. METHODS: We searched in Pubmed, Embase, and Cochrane Central Register of Controlled Trials from database creation date to June 1, 2024. The primary glycemic efficacy was changes from baseline to endpoint for HbA1c. We performed Bayesian network meta-analysis calculating mean differences (MDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes. RESULTS: All once-weekly GLP-1RAs outperformed placebo in reducing HbA1c (MD: -0.66 % [-0.81 %, -0.5 %] for dulaglutide 1.5 mg to -1.4 % [-1.6 %, -1.2 %] for tirzepatide 15 mg). Tirzepatide 15 mg showed superior weight loss (MD: -8.7 [-10, -6.8]) and systolic blood pressure reduction (MD: -4.8 [-8.2, -1.4]) versus other GLP-1RAs, but higher nausea (OR: 6.4 [4.3, 9.6]) and diarrhea risks (OR: 3.5 [2.5, 5.2]). Polyethylene glycol loxenatide 100 mug provided effective glucose control with the lowest gastrointestinal and discontinuation risks. CONCLUSIONS: Tirzepatide demonstrates superior efficacy in glycemic control, weight reduction, and blood pressure reduction, yet is associated with high risk of adverse events. In contrast, polyethylene glycol loxenatide offers effective glycemic management with the lowest withdrawal probability. For patients with Type 2 diabetes mellitus and cardiovascular disease, dulaglutide is preferable. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Xu, Ying AU - Xu Y AD - Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 86 Wujin Road, Shanghai 200080, China. FAU - Ji, Guikai AU - Ji G AD - School of Computing and Data Science, The University of Hong Kong, Hong Kong 999077, China. FAU - Shi, Chenyang AU - Shi C AD - Department of Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. FAU - Tan, Yijiong AU - Tan Y AD - Department of Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. FAU - Wang, Li AU - Wang L AD - School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. FAU - Gui, Yaxing AU - Gui Y AD - Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 86 Wujin Road, Shanghai 200080, China. Electronic address: YaxingGui@shsmu.edu.cn. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20251024 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Blood Glucose) RN - 0 (Venoms) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Bayes Theorem MH - Immunoglobulin Fc Fragments/administration & dosage/adverse effects/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Recombinant Fusion Proteins/administration & dosage/adverse effects/therapeutic use MH - Blood Glucose/drug effects MH - Treatment Outcome MH - Drug Administration Schedule MH - Venoms/administration & dosage MH - Exenatide OTO - NOTNLM OT - Diabetes OT - GLP-1RA OT - Network meta-analysis OT - Once-weekly OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/20 05:43 MHDA- 2026/08/20 05:44 CRDT- 2026/08/20 00:35 PHST- 2025/05/16 00:00 [received] PHST- 2025/09/19 00:00 [revised] PHST- 2025/10/08 00:00 [accepted] PHST- 2026/08/20 05:44 [medline] PHST- 2026/08/20 05:43 [pubmed] PHST- 2026/08/20 00:35 [entrez] AID - S0168-8227(25)00968-4 [pii] AID - 10.1016/j.diabres.2025.112954 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Dec;230:112954. doi: 10.1016/j.diabres.2025.112954. Epub 2025 Oct 24. PMID- 42618722 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261023 IS - 1496-8975 (Electronic) IS - 0832-610X (Linking) VI - 73 IP - 9 DP - 2026 Sep TI - Preoperative fasting status and retained gastric contents in patients undergoing endoscopy who are using glucagon-like peptide type 1 receptor agonists: a multicentre retrospective study. PG - 848-856 LID - 10.1007/s12630-026-03187-3 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for the management of type 2 diabetes mellitus and obesity. Nevertheless, their known effect of delaying gastric emptying raises perioperative concerns, particularly regarding the risk of pulmonary aspiration. There is limited evidence to guide fasting practices in this population. Our aim was to evaluate the association between preoperative fasting duration and the presence of retained gastric contents (RGC) in patients receiving GLP-1 RAs who underwent esophagogastroduodenoscopy (EGD). METHODS: We conducted a multicentre retrospective cohort study involving 337 patients from five Henry Ford Health System hospitals who underwent elective EGD between January 2018 and December 2023. Eligible patients were actively taking or had recently discontinued a GLP-1 RA within 90 days prior to the procedure. The primary outcome was the presence of RGC, defined as any small, moderate, or large amount of food or gastric material explicitly reported by the endoscopist in the EGD report. For regression analyses, fasting duration for solids was dichotomized at the cohort's median value (15 hr). We performed multivariable logistic regression to evaluate the association between preoperative fasting duration, the timing of GLP-1 RA suspension, and the presence of RGC, adjusting for clinically relevant covariates. RESULTS: The overall prevalence of RGC was 8.4%. In the adjusted model, fasting from solid foods for more than 15 hr was significantly associated with lower odds of RGC (adjusted odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13 to 0.81; P = 0.02). Fasting duration for liquids and presence of diabetes were not significantly associated with RGC. Suspension of GLP-1 RA within less than 7 days of the procedure related to RGC was not statistically significant (adjusted OR, 5.23; 95% CI, 0.67 to 39.38; P = 0.12). No significant association was observed between the duration of GLP-1 RA use and RGC prevalence. CONCLUSIONS: Patients with an active prescription for GLP-1 RA had lower odds of RGC during EGD after more than 15 hr fasting of solids. CI - (c) 2026. Canadian Anesthesiologists' Society. FAU - Mendez-Pino, Laura AU - Mendez-Pino L AUID- ORCID: 0000-0003-2181-3767 AD - Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Hospital, Detroit, MI, USA. lrmendez05@gmail.com. FAU - Goldblatt, Joshua AU - Goldblatt J AD - Department of Anesthesiology, Henry Ford Jackson Hospital, Jackson, MI, USA. FAU - Godie, Dawit AU - Godie D AD - Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Hospital, Detroit, MI, USA. AD - Service Line and Strategic Operational Analytics, Henry Ford Health System, Detroit, MI, USA. FAU - Ravi, Swetha AU - Ravi S AD - College of Osteopathic Medicine, Michigan State University, Lansing, MI, USA. FAU - Williams, Koryon AU - Williams K AD - School of Medicine, Wayne State University, Detroit, MI, USA. FAU - Amcheslavsky, Jakob AU - Amcheslavsky J AD - College of Medicine, Central Michigan University, Mount Pleasant, MI, USA. FAU - Guerra-Londono, Carlos AU - Guerra-Londono C AD - Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Hospital, Detroit, MI, USA. FAU - Ravikant, Neeraja T AU - Ravikant NT AD - Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Hospital, Detroit, MI, USA. LA - eng PT - Journal Article PT - Multicenter Study TT - Etat de jeune preoperatoire et contenu gastrique residuel chez les personnes beneficiant d'une endoscopie et traites par agonistes des recepteurs du peptide-1 de type glucagon : une etude retrospective multicentrique. DEP - 20260819 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - *Fasting MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Endoscopy, Digestive System/methods MH - Cohort Studies MH - Diabetes Mellitus, Type 2/drug therapy MH - Preoperative Period MH - Gastric Emptying OTO - NOTNLM OT - GLP-1 receptor agonist OT - anesthesia OT - delayed gastric emptying OT - preoperative fasting OT - pulmonary aspiration OT - retained gastric contents EDAT- 2026/08/20 05:43 MHDA- 2026/10/22 23:28 CRDT- 2026/08/20 00:10 PHST- 2025/05/27 00:00 [received] PHST- 2026/01/10 00:00 [accepted] PHST- 2025/12/28 00:00 [revised] PHST- 2026/10/22 23:28 [medline] PHST- 2026/08/20 05:43 [pubmed] PHST- 2026/08/20 00:10 [entrez] AID - 10.1007/s12630-026-03187-3 [pii] AID - 10.1007/s12630-026-03187-3 [doi] PST - ppublish SO - Can J Anaesth. 2026 Sep;73(9):848-856. doi: 10.1007/s12630-026-03187-3. Epub 2026 Aug 19. PMID- 42618523 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260926 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 10 DP - 2026 Oct TI - Major Adverse Liver Outcomes With Tirzepatide and Injectable Semaglutide in Adults With Overweight or Obesity and Type 2 Diabetes. PG - 1958-1966 LID - 10.1002/oby.70277 [doi] AB - OBJECTIVE: This study aimed to compare the effectiveness of tirzepatide versus injectable semaglutide in preventing major adverse liver outcomes (MALO) among adults with overweight or obesity and type 2 diabetes. METHODS: This retrospective target trial emulation utilized the TriNetX global network to analyze new users of tirzepatide and semaglutide. The primary outcome was time-to-first MALO (a composite of cirrhosis, decompensated events, and hepatocellular carcinoma). Propensity score matching balanced baseline covariates. RESULTS: Over a median follow-up of ~17 months, no significant difference in MALO risk was observed between tirzepatide and semaglutide initiators (estimated incidence rate [IR] 4.05 vs. 4.04 per 1000 person-years [PY]; hazard ratio [HR] 1.04, 95% CI 0.88-1.23). This comparable risk profile was maintained across sensitivity analyses, including people with MASLD (IR 9.97 vs. 10.03 per 1000 PY; HR 1.03, 95% CI: 0.75-1.42) and "as treated" analysis (HR 0.98, 95% CI: 0.80-1.21). Tirzepatide achieved greater BMI reduction (mean difference ~1.1 kg/m(2), p < 0.001). Internal validation confirmed both agents significantly outperformed sitagliptin. CONCLUSIONS: In this high-risk population with type 2 diabetes, tirzepatide and injectable semaglutide offered comparable effectiveness in mitigating liver disease progression and MALO in the short- to medium-term follow-up. CI - (c) 2026 The Obesity Society. FAU - Banerjee, Mainak AU - Banerjee M AUID- ORCID: 0000-0002-6656-8569 AD - Department of Endocrinology, R N Tagore Hospital, Kolkata, India. AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Roy, Ajitesh AU - Roy A AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Sharma, Vivek Mohan AU - Sharma VM AD - Department of Gastroenterology, R.N. Tagore Hospital, Narayana Health, Kolkata, India. FAU - Das, Abhishek AU - Das A AD - Department of Gastroenterology, Royal Cornwall Hospital NHS Trust, Truro, UK. LA - eng GR - Narayana Health/ PT - Journal Article DEP - 20260819 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Male MH - *Obesity/complications/drug therapy MH - *Overweight/complications/drug therapy MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Adult MH - Liver Cirrhosis/prevention & control MH - Treatment Outcome MH - Liver Neoplasms/prevention & control MH - Aged MH - Injections MH - Carcinoma, Hepatocellular/prevention & control OTO - NOTNLM OT - GLP-1RA OT - GLP-1RA/GIP agonist OT - MASLD OT - NAFLD OT - fatty liver EDAT- 2026/08/19 23:42 MHDA- 2026/09/27 02:25 CRDT- 2026/08/19 22:23 PHST- 2026/05/31 00:00 [revised] PHST- 2026/02/23 00:00 [received] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/09/27 02:25 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 22:23 [entrez] AID - 10.1002/oby.70277 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Oct;34(10):1958-1966. doi: 10.1002/oby.70277. Epub 2026 Aug 19. PMID- 42618499 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260825 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 106 IP - 31 DP - 2026 Aug 25 TI - [Expert consensus on the clinical application of nutrient-stimulated hormone receptor agonist in the treatment of type 2 diabetes mellitus (2026 edition)]. PG - 3222-3233 LID - 10.3760/cma.j.cn112137-20260527-01398 [doi] AB - Hypoglycemic drugs targeting at nutrient-stimulated hormone (NuSH) receptors, including glucagon like peptide-1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists and dual glucagon (GCG)/GLP-1 receptor agonists, not only exhibit the beneficial metabolic effects, such as lowering blood glucose, reducing body weight, lowering blood pressure, improving lipid profiles and attenuating hepatic steatosis, but also have demonstrated cardiovascular and renal benefits. The continual innovation and advancement of novel drugs, along with the continuous accumulation of evidence-based medical evidence, have offered more options for the clinical management of type 2 diabetes mellitus (T2DM). Based on these developments, Endocrinology and Metabolism Professional Committee, National Association of Health Industry and Enterprise Management searched recent literature and evaluated its evidence, and organized endocrinology specialists to conduct multiple rounds of rigorous deliberation and repeated revisions to complete the update of the consensus, on the basis of the 2020 version of the Consensus recommendations on utilizing glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus.The consensus focuses on the timing and applicable population of NuSH receptor agonists in T2DM, the precautions when combined with other hypoglycemic drugs, the impacts on cardiovascular, renal or hepatic outcomes, forming 10 recommended opinions aimed at providing reference for clinical doctors to standardize the use of such drugs and better serve T2DM patients. CN - Endocrinology and Metabolism Professional Committee, National Association of Health Industry and Enterprise Management LA - chi PT - Consensus Statement PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9007-92-5 (Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon MH - Glucagon-Like Peptide-1 Receptor COIS- 所有作者声明不存在利益冲突 EDAT- 2026/08/19 23:42 MHDA- 2026/08/19 23:43 CRDT- 2026/08/19 21:55 PHST- 2026/08/19 23:43 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 21:55 [entrez] AID - 10.3760/cma.j.cn112137-20260527-01398 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2026 Aug 25;106(31):3222-3233. doi: 10.3760/cma.j.cn112137-20260527-01398. PMID- 42618485 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260819 IS - 0254-6450 (Print) IS - 0254-6450 (Linking) VI - 47 IP - 8 DP - 2026 Aug 10 TI - [Association between the initiation of glucagon-like peptide-1 receptor agonist use and the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus]. PG - 1485-1491 LID - 10.3760/cma.j.cn112338-20260105-00013 [doi] AB - Objective: To compare the risk of incident diabetic retinopathy (DR) after initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) among patients with type 2 diabetes mellitus (T2DM). Methods: An active-comparator new-user retrospective cohort study was conducted using the Yinzhou Regional Health Information Platform in Ningbo, China. Patients with T2DM who received a first prescription for a GLP-1RA or a DPP-4i between September 1, 2022 and August 31, 2025 were included. 1ratio1 nearest-neighbor propensity score matching was applied to balance baseline covariates including demographic characteristics, diabetes duration, baseline comorbidities, prior medication history, and the most recent pre-index measurements of glycated hemoglobin and estimated glomerular filtration rate. In the matched cohort, multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95%CIs to evaluate the association between the initiation of the two medications and the risk of incident DR. Sensitivity analyses were performed by varying the washout period, the latency period, and the matching ratio. Results: After matching, 1 839 patients were included in each group. The incidence rates of DR were 13.60 per 1 000 person-years among DPP-4i and 9.95 per 1 000 person-years among GLP-1RA. Initiation of GLP-1RA was not associated with a statistically significant difference in DR risk compared with initiation of DPP-4i (P=0.114). Findings were consistent across sensitivity analyses. Conclusion: In this real-world cohort, DPP-4i initiation of GLP-1RA was not associated with an increased risk of incident DR compared with initiation of in patients with T2DM. FAU - Zheng, Y Q AU - Zheng YQ AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China. FAU - Chen, X W AU - Chen XW AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China. FAU - Zhang, M AU - Zhang M AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China. FAU - Sun, Y X AU - Sun YX AD - Yinzhou District Center for Disease Control and Prevention of Ningbo, Ningbo 315100, China. FAU - Yin, Y Q AU - Yin YQ AD - Yinzhou District Center for Disease Control and Prevention of Ningbo, Ningbo 315100, China. FAU - Lin, H B AU - Lin HB AD - Yinzhou District Center for Disease Control and Prevention of Ningbo, Ningbo 315100, China. FAU - Wan, E R I C Y U K F A I AU - Wan ERICYUKFAI AD - Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. FAU - Sang, W O U K C H O AU - Sang WOUKCHO AD - Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea. FAU - Seng, C H A N Y O U AU - Seng CHANYOU AD - Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea. FAU - Sun, F AU - Sun F AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China School of Traditional Chinese Medicine, Xinjiang Medical University, Urumchi 830017, China Department of Ophthalmology, Peking University Third Hospital, Beijing 100191, China School of Public Health, Shihezi University, Shihezi 832003, China. LA - chi GR - 72474008/National Natural Science Foundation of China/ GR - ZDYF2024LCLH002, ZDYF2025/Hainan Provincial Science Technology Department Key Research and Development Project/ GR - 2025-Y-Y-012/Research Project of China Society for Drug Regulation/ GR - 2025SKLDRS0377/National Key Laboratory of Drug Regulatory Science Project/ GR - CDR2024R01001/Project of Center for Drug Reevaluation of China National Medical Products Administration/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Liu Xing Bing Xue Za Zhi JT - Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi JID - 8208604 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Retinopathy/epidemiology MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Incidence MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor COIS- 所有作者声明无利益冲突 EDAT- 2026/08/19 23:42 MHDA- 2026/08/19 23:43 CRDT- 2026/08/19 21:55 PHST- 2026/08/19 23:43 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 21:55 [entrez] AID - 10.3760/cma.j.cn112338-20260105-00013 [doi] PST - ppublish SO - Zhonghua Liu Xing Bing Xue Za Zhi. 2026 Aug 10;47(8):1485-1491. doi: 10.3760/cma.j.cn112338-20260105-00013. PMID- 42618422 OWN - NLM STAT- MEDLINE DCOM- 20261009 LR - 20261013 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 11 DP - 2026 Nov TI - Clinical efficacy of switching to tirzepatide in patients with type 2 diabetes and a high risk of metabolic dysfunction-associated steatotic liver disease undergoing GLP-1 receptor agonist therapy: Insights from the Hokkaido-TZP study. PG - 109391 LID - S1056-8727(26)00136-4 [pii] LID - 10.1016/j.jdiacomp.2026.109391 [doi] AB - AIMS: To evaluate the clinical efficacy of switching from glucagon-like peptide-1 receptor agonists (GLP-1RAs) to tirzepatide in terms of metabolic and hepatic indices in patients with T2D at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This multicenter, retrospective study comprised secondary analysis of the Hokkaido-TZP study, focusing on a subpopulation of the original cohort at high risk of MASLD. We analyzed hepatic indices, including the Hepatic Steatosis Index (HSI) and Fibrosis-4 (FIB-4) index, over a 6-month period in 182 patients who switched from GLP-1RAs to tirzepatide. Patients were stratified into low-risk and high-risk groups based on baseline hepatic fibrosis status. RESULTS: Switching to tirzepatide significantly reduced glycated hemoglobin (HbA1c), body weight, and liver enzymes. HSI decreased in both groups, but a significant reduction in FIB-4 index was only observed in the high-risk group (P < 0.001). Improvements in hepatic indices were not correlated with changes in body mass index or HbA1c. Furthermore, baseline HSI was positively correlated with change in FIB-4 index (rho = 0.234, P = 0.005). CONCLUSIONS: Switching from GLP-1RAs to tirzepatide was associated with incremental improvements in metabolic and hepatic indices in patients with T2D at high risk of MASLD, particularly in patients with high fibrosis risk, not clearly explained by changes in body weight. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Takiyama, Takao AU - Takiyama T AD - Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. Electronic address: boomerang@asahikawa-med.ac.jp. FAU - Kitsunai, Hiroya AU - Kitsunai H AD - Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. Electronic address: kitsunai@asahikawa-med.ac.jp. FAU - Maruyama, Fumika AU - Maruyama F AD - Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. Electronic address: y-fumika919@asahikawa-med.ac.jp. FAU - Kitao, Naoyuki AU - Kitao N AD - Aoki Clinic, Sapporo, Hokkaido, Japan. Electronic address: koujousenkinou@yahoo.co.jp. FAU - Wakabayashi, Yoshinori AU - Wakabayashi Y AD - Asahimachi Clinic, Asahikawa, Hokkaido, Japan. Electronic address: ywakabaya@yahoo.co.jp. FAU - Ito, Miki AU - Ito M AD - Kurihara Clinic, Sapporo, Hokkaido, Japan. Electronic address: mito@kurihara-naika.net. FAU - Kurihara, Hiroyoshi AU - Kurihara H AD - Kurihara Clinic, Sapporo, Hokkaido, Japan. Electronic address: hkurihara@kurihara-naika.net. FAU - Yamamoto, Chiho AU - Yamamoto C AD - Sapporo Diabetes and Thyroid Clinic, Sapporo, Hokkaido, Japan. Electronic address: yamamoto_chiho_o@yahoo.co.jp. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo, Hokkaido, Japan. Electronic address: jun_takeuchi@me.com. FAU - Nanbu, Takashi AU - Nanbu T AD - Department of Diabetology and Endocrinology, Japanese Asahikawa Red Cross Hospital, Asahikawa, Hokkaido, Japan.. Electronic address: takashi1217@icloud.com. FAU - Abiko, Atsuko AU - Abiko A AD - Department of Diabetology and Endocrinology, Japanese Asahikawa Red Cross Hospital, Asahikawa, Hokkaido, Japan.. Electronic address: aabiko@asahikawa-rch.gr.jp. FAU - Homma, Reiko AU - Homma R AD - Department of Metabolism and Endocrinology, Asahikawa-Kosei General Hospital, Asahikawa, Hokkaido, Japan. Electronic address: rhomma@potato.ne.jp. FAU - Miyamoto, Yoshihiro AU - Miyamoto Y AD - Department of Diabetology and Endocrinology, Asahikawa City Hospital, Asahikawa, Hokkaido, Japan. Electronic address: ymiyamo@me.com. FAU - Yamagata, Kazuo AU - Yamagata K AD - Yamagata Clinic, Asahikawa, Hokkaido, Japan. Electronic address: kazu-t64@potato10.hokkai.net. FAU - Miyazaki, Asuka AU - Miyazaki A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Electronic address: pour.toujours.0u.u0y@gmail.com. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Electronic address: akinbo@tim.hi-ho.ne.jp. FAU - Nomoto, Hiroshi AU - Nomoto H AD - Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. Electronic address: hnomoto@asahikawa-med.ac.jp. CN - Hokkaido-TZP Study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260814 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism/blood MH - *Fatty Liver/prevention & control/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Japan/epidemiology MH - Liver/drug effects/pathology MH - Retrospective Studies MH - *Tirzepatide/therapeutic use MH - Treatment Outcome MH - Secondary Data Analysis OTO - NOTNLM OT - GLP-1 receptor agonist OT - MASLD OT - Real-world clinical evidence OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest The following authors declare the following financial interests/personal relationships that may be considered potential competing interests: Nakamura A has received honoraria for lectures from Tanabe Pharma, Daiichi Sankyo Co., Ltd., Novo Nordisk Pharma, and Kowa Pharmaceutical Co., Ltd., and research support from Kowa Pharmaceutical Co., Ltd.; Nomoto H has received honoraria for lectures from Eli Lilly Japan K.K., Tanabe Pharma, Novo Nordisk Pharma, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Sumitomo Pharma Co., Ltd., and Taisho Pharmaceutical Co., Ltd., and research support from Kowa Pharmaceutical Co., Ltd., Abbott Japan LLC., Mochida Pharmaceutical Co., Ltd., LifeScan Japan LLC., and Sanwa Kagaku Kenkyusho Co., Ltd. The other authors declare no conflicts of interest. EDAT- 2026/08/19 23:42 MHDA- 2026/10/09 23:31 CRDT- 2026/08/19 21:53 PHST- 2026/05/28 00:00 [received] PHST- 2026/06/29 00:00 [revised] PHST- 2026/08/11 00:00 [accepted] PHST- 2026/10/09 23:31 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 21:53 [entrez] AID - S1056-8727(26)00136-4 [pii] AID - 10.1016/j.jdiacomp.2026.109391 [doi] PST - ppublish SO - J Diabetes Complications. 2026 Nov;40(11):109391. doi: 10.1016/j.jdiacomp.2026.109391. Epub 2026 Aug 14. PMID- 42618306 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260827 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 14 IP - 4 DP - 2026 Aug 19 TI - Glucagon-like peptide-1 receptor agonists for primary cardiovascular disease prevention in type 2 diabetes, a systematic review. LID - 10.1136/bmjdrc-2026-006225 [doi] LID - e006225 AB - We aimed to estimate the cardiovascular (CV) benefit of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) without a history of CV disease (CVD) (primary CVD prevention). We searched MEDLINE and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) and Epistemonikos for systematic reviews (up to July 4, 2025). We included RCTs of patients with T2D comparing a GLP-1 RA to placebo using a CV or renal primary outcome. 11 drug manufacturer-funded trials (77 419 participants) were included. We used version 1 of the Cochrane risk of bias tool. Our primary analysis was the pooled estimate of the treatment effect in primary CVD prevention. Outcomes of interest were major adverse cardiovascular events (MACE, primary outcome), all-cause mortality, CV mortality, myocardial infarction, stroke, and serious adverse events (secondary outcomes). Only 26% of participants were primary CVD prevention patients. The pooled estimates of treatment effect for primary CVD prevention were not significant for the primary outcome, MACE (pooled HR 0.88, 95% CI 0.74 to 1.05, based on eight trials, n=16 672), and all secondary outcomes. The certainty of the evidence was rated as low due to trials' risk of bias and imprecision. Our review was limited to subgroup analyses of aggregated data from studies not powered for primary prevention alone. Current evidence is insufficient to establish CV benefits of GLP-1 RAs in T2D without a history of CVD, and dedicated primary prevention trials are needed. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Grenet, Guillaume AU - Grenet G AUID- ORCID: 0000-0002-5237-2581 AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada guillaume.grenet@ubc.ca. AD - Service hospitalo-universitaire de pharmacotoxicologie, Hospices Civils de Lyon, Lyon, France. FAU - Eskandari, Raha AU - Eskandari R AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Ko, Joyce AU - Ko J AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Adams, Stephen P AU - Adams SP AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Salzwedel, Douglas M AU - Salzwedel DM AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Heran, Balraj S AU - Heran BS AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Ambasta, Anshula AU - Ambasta A AUID- ORCID: 0000-0003-0211-8654 AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Bassett, Ken AU - Bassett K AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. FAU - Thompson, Wade AU - Thompson W AUID- ORCID: 0000-0002-8268-4092 AD - Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260819 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Primary Prevention/methods MH - Randomized Controlled Trials as Topic PMC - PMC13504861 OTO - NOTNLM OT - Glucagon-Like Peptide 1 OT - Mortality OT - Myocardial Infarction OT - Stroke COIS- Competing interests: RE, JK, SPA, DMS, BSH, AA, KB, and WT had no competing interest. GG has received a grant from the French association for thermal research: 'Association Francaise pour la Recherche Thermale' (AFRETh, http://www.afreth.org/), which was not related to this review. EDAT- 2026/08/19 23:42 MHDA- 2026/08/19 23:43 PMCR- 2026/08/19 CRDT- 2026/08/19 21:22 PHST- 2026/04/20 00:00 [received] PHST- 2026/07/25 00:00 [accepted] PHST- 2026/08/19 23:43 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 21:22 [entrez] PHST- 2026/08/19 00:00 [pmc-release] AID - 14/4/e006225 [pii] AID - bmjdrc-2026-006225 [pii] AID - 10.1136/bmjdrc-2026-006225 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2026 Aug 19;14(4):e006225. doi: 10.1136/bmjdrc-2026-006225. PMID- 42618217 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260828 IS - 1875-9114 (Electronic) IS - 0277-0008 (Print) IS - 0277-0008 (Linking) VI - 46 IP - 9 DP - 2026 Sep TI - Antihyperglycemic Drugs and Risk of Asthma Exacerbation in Patients With Asthma and Type 2 Diabetes: A Multinational Retrospective Cohort Study. PG - e70194 LID - 10.1002/phar.70194 [doi] LID - e70194 AB - BACKGROUND: Antihyperglycemic drugs have shown benefits in asthma control. However, evidence regarding the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) in reducing asthma exacerbations remains inconsistent. OBJECTIVE: We aimed to evaluate the association of GLP-1 RAs versus SGLT-2is with risk of asthma exacerbation among patients with asthma and type 2 diabetes. METHODS: This retrospective cohort study used electronic health record data from the TriNetX Global Collaborative Network. Adults with asthma and type 2 diabetes who initiated GLP-1 RAs or SGLT-2is between January 1, 2013, and June 30, 2024, were included. The primary outcome was the time to first asthma exacerbation. Secondary outcomes included first episode of asthma symptoms or systemic corticosteroid use. Patients were followed for up to 6 months in the main analysis. Propensity score matching was performed to balance baseline characteristics between groups. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 100,746 patients were included, comprising 61,955 GLP-1 RA users and 38,791 SGLT-2i users. After 1:1 matching, both groups consisted of 28,831 patients. GLP-1 RAs were associated with a decreased risk of asthma exacerbation compared with SGLT-2is (HR, 0.88; 95% CI, 0.85-0.91). GLP-1 RAs were also associated with a decreased risk of experiencing asthma symptoms (HR, 0.89; 95% CI, 0.82-0.97) and receiving systemic corticosteroids (HR, 0.79; 95% CI, 0.76-0.82). Results from sensitivity analyses were generally consistent, but the association for asthma exacerbation was not observed when follow-up was extended to 1 year (HR, 0.95; 95% CI, 0.89-1.02). CONCLUSION: GLP-1 RAs were associated with a decreased risk of asthma exacerbation compared to SGLT-2is among patients with asthma and type 2 diabetes. As these findings reflect associations rather than causal effects, further investigation through randomized trials is warranted. CI - (c) 2026 ACCP Foundation, Ltd. FAU - Hung, Chun-Tse AU - Hung CT AUID- ORCID: 0000-0002-3485-9775 AD - Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA. FAU - An, Chen-Yen AU - An CY AUID- ORCID: 0009-0005-3975-4664 AD - Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Tsai, Yao-Cheng AU - Tsai YC AUID- ORCID: 0009-0009-8762-891X AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Division of General Medicine, Chang Gung Memorial Hospital, New Taipei, Taiwan. FAU - Suk, Chi-Won AU - Suk CW AUID- ORCID: 0000-0003-4967-165X AD - Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Municipal Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Wu, Chung-Hsuen AU - Wu CH AUID- ORCID: 0000-0003-0495-1922 AD - Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Asthma/drug therapy/epidemiology MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Disease Progression MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage PMC - PMC13489788 OTO - NOTNLM OT - asthma OT - asthma exacerbation OT - electronic health records OT - glucagon-like peptide-1 receptor agonists OT - sodium-glucose cotransporter-2 inhibitors OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/08/19 23:42 MHDA- 2026/08/19 23:43 PMCR- 2026/08/20 CRDT- 2026/08/19 21:04 PHST- 2026/06/17 00:00 [revised] PHST- 2025/11/14 00:00 [received] PHST- 2026/07/21 00:00 [accepted] PHST- 2026/08/19 23:43 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 21:04 [entrez] PHST- 2026/08/20 00:00 [pmc-release] AID - PHAR70194 [pii] AID - 10.1002/phar.70194 [doi] PST - ppublish SO - Pharmacotherapy. 2026 Sep;46(9):e70194. doi: 10.1002/phar.70194. PMID- 42616235 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20261008 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Aug 19 TI - Combined use of SGLT2 inhibitor and GLP-1 receptor agonist versus either monotherapy for cardiorenal Outcomes: an exploratory network meta-analysis of 16 randomized trials. LID - 281 [pii] LID - 10.1007/s12020-026-04752-y [doi] AB - BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) each provide cardiorenal protection in trials of selected populations, but their combined effect has not been tested in dedicated head-to-head randomized trials. We performed an exploratory network meta-analysis (NMA) that integrated subgroup data from existing randomized controlled trials (RCTs) to compare SGLT2i, GLP-1RA, and concomitant SGLT2i + GLP-1RA use against placebo on cardiorenal outcomes. METHODS: We ran a frequentist random-effects NMA. Major databases were searched for RCTs or post-hoc analyses (> 1 year follow-up) that reported subgroup outcomes by background SGLT2i or GLP-1RA use. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were hospitalisation for heart failure (HHF), composite renal outcomes, and total estimated glomerular filtration rate (eGFR) slope. Surface Under the Cumulative Ranking Curve (SUCRA) values are reported as supportive ranking summaries. RESULTS: Sixteen RCTs were pooled. Compared with placebo (without background SGLT2i or GLP-1RA), all active strategies reduced MACE and HHF (all p < 0.05). For composite renal events, combined use (RR 0.63, 95% CI 0.41-0.97) and SGLT2i (RR 0.70, 95% CI 0.61-0.79) significantly reduced risk. Combined use ranked first across outcomes (SUCRA 0.928 to 1.000). In head-to-head pooled comparisons, combined use was associated with lower MACE (RR 0.83, 95% CI 0.72-0.96) and HHF (RR 0.73, 95% CI 0.56-0.94) than SGLT2i alone, and with a better total eGFR slope than GLP-1RA alone (MD + 2.29 mL/min/1.73 m2/year, 95% CI 0.14-4.44). A subgroup NMA showed attenuated MACE ranking for combined use in ASCVD or high-ASCVD-risk trials, although the HHF ranking was preserved. CONCLUSION: In this exploratory synthesis, concomitant SGLT2i and GLP-1RA use appeared to be associated with more favourable cardiorenal effects than either agent alone. Because the combined-use comparison rests largely on non-randomized within-trial subgroups, these findings are hypothesis-generating and require confirmation in dedicated head-to-head randomized trials of combination therapy. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Banerjee, Mainak AU - Banerjee M AD - Department of Endocrinology, R N Tagore Hospital, Kolkata, India. AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Basu, Madhurima AU - Basu M AD - Steno Diabetes Center, Copenhagen, Denmark. FAU - Mukhopadhyay, Pradip AU - Mukhopadhyay P AD - Department of Endocrinology, Institute of Postgraduate Medical Education and Research, Kolkata, India. FAU - Ghosh, Sujoy AU - Ghosh S AD - Department of Endocrinology, Institute of Postgraduate Medical Education and Research, Kolkata, India. drsujoyghosh2000@gmail.com. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260819 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - *Heart Failure MH - Treatment Outcome MH - *Cardiovascular Diseases/prevention & control OTO - NOTNLM OT - Cardiovascular OT - Combination therapy OT - GLP-1 receptor agonists OT - Network meta-analysis OT - Renal OT - SGLT2 inhibitors COIS- Declarations. Conflict of interests: The authors declare no competing interests. EDAT- 2026/08/19 17:44 MHDA- 2026/08/19 17:45 CRDT- 2026/08/19 11:17 PHST- 2026/05/03 00:00 [received] PHST- 2026/08/07 00:00 [accepted] PHST- 2026/08/19 17:45 [medline] PHST- 2026/08/19 17:44 [pubmed] PHST- 2026/08/19 11:17 [entrez] AID - 10.1007/s12020-026-04752-y [pii] AID - 10.1007/s12020-026-04752-y [doi] PST - epublish SO - Endocrine. 2026 Aug 19;91(1):281. doi: 10.1007/s12020-026-04752-y. PMID- 42614226 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260820 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Polish healthcare professionals' perceptions of GLP-1 receptor agonists in cardiometabolic risk reduction: a cross-sectional online survey in Poland. PG - 1906959 LID - 10.3389/fendo.2026.1906959 [doi] LID - 1906959 AB - BACKGROUND: Cardiovascular diseases and metabolic disorders, including obesity and type 2 diabetes, remain leading global health challenges. Despite major advances in pharmacotherapy, the implementation of effective cardiometabolic prevention strategies remains suboptimal. Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have substantially transformed the management of metabolic diseases by providing benefits beyond glycaemic control, including sustained weight loss, improvements in metabolic parameters, and cardiovascular risk reduction. OBJECTIVES: To evaluate Polish healthcare professionals' perceptions of GLP-1 receptor agonists in cardiometabolic risk management, with particular emphasis on perceived effectiveness, safety, selected psychological and behavioural effects, and reimbursement. DESIGN: Cross-sectional online survey conducted among healthcare professionals in Poland between May and August 2025. METHODS: A structured, anonymous online questionnaire was disseminated through professional, institutional, and academic communication channels in Poland. The questionnaire assessed self-reported perceptions, beliefs, perceived clinical value, perceived safety, and implementation-related views regarding GLP-1 receptor agonists in cardiometabolic risk management. The final analytical sample included 1,100 healthcare professionals representing physicians, nurses, pharmacists, dietitians, and physiotherapists. Categorical responses were compared between professional groups using the chi-square test or Fisher's exact test, as appropriate. Multivariable logistic regression was used to evaluate associations between respondent characteristics and selected perceptions; adjusted odds ratios (ORs) with 95% confidence intervals (CIs) and p-values were reported. RESULTS: The final analytical sample included 1,100 healthcare professionals: physicians (n = 164), pharmacists (n = 133), nurses (n = 160), physiotherapists (n = 361), and dietitians (n = 282). GLP-1 receptor agonists were most frequently rated as "very effective" for weight loss by physiotherapists (87.3%) and dietitians (84.8%), followed by nurses (59.4%) and physicians (52.4%). Perceived safety was high across all groups, with GLP-1 receptor agonists considered safe by 94.0% of dietitians, 93.9% of physiotherapists, 87.2% of physicians, 85.0% of pharmacists, and 69.4% of nurses. Support for reimbursement was also high, ranging from 75.0% among nurses to 97.2% among dietitians. In multivariable analyses among physicians, employment in a diabetology or endocrinology setting was strongly associated with perceiving GLP-1 receptor agonists as very effective for weight reduction (adjusted OR 11.80, 95% CI 3.88-35.84; p < 0.001), as well as with perceived stress reduction (adjusted OR 2.71, 95% CI 1.05-7.02; p = 0.039), anxiety reduction (adjusted OR 7.00, 95% CI 2.01-24.42; p = 0.002), and improvement in depressive symptoms (adjusted OR 5.81, 95% CI 1.68-20.07; p = 0.005). CONCLUSIONS: Among participating healthcare professionals in Poland, GLP-1 receptor agonists were generally perceived as effective and safe options for cardiometabolic risk management. Perceptions differed across professional groups, particularly regarding weight reduction, safety, psychological and behavioural effects, and reimbursement. Because educational gaps, implementation barriers, real-world adoption, and interdisciplinary care models were not directly assessed as primary outcomes, these areas should be addressed in future studies using dedicated instruments. CI - Copyright (c) 2026 Pucek, Hoffmann, Bryl, Kus and Paczkowska. FAU - Pucek, Weronika Faustyna AU - Pucek WF AD - Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznan, Poland. FAU - Hoffmann, Karolina AU - Hoffmann K AD - Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland. FAU - Bryl, Wieslaw AU - Bryl W AD - Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland. FAU - Kus, Krzysztof AU - Kus K AD - Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznan, Poland. FAU - Paczkowska, Anna AU - Paczkowska A AD - Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Journal Article DEP - 20260804 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Cross-Sectional Studies MH - Poland/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Surveys and Questionnaires MH - Adult MH - *Health Personnel/psychology MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Middle Aged MH - *Attitude of Health Personnel MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Risk Reduction Behavior PMC - PMC13481303 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiometabolic prevention OT - cardiovascular risk OT - healthcare professionals OT - obesity COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/08/19 14:49 MHDA- 2026/08/19 14:50 PMCR- 2026/08/04 CRDT- 2026/08/19 04:50 PHST- 2026/06/11 00:00 [received] PHST- 2026/07/16 00:00 [revised] PHST- 2026/07/20 00:00 [accepted] PHST- 2026/08/19 14:50 [medline] PHST- 2026/08/19 14:49 [pubmed] PHST- 2026/08/19 04:50 [entrez] PHST- 2026/08/04 00:00 [pmc-release] AID - 10.3389/fendo.2026.1906959 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 4;17:1906959. doi: 10.3389/fendo.2026.1906959. eCollection 2026. PMID- 42613293 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260918 IS - 1938-0682 (Electronic) IS - 1558-7673 (Linking) VI - 24 IP - 7 DP - 2026 Oct TI - GLP-1RAs Use and Postoperative Outcomes in T2DM Patients Undergoing Radical Nephrectomy. PG - 102630 LID - S1558-7673(26)00130-8 [pii] LID - 10.1016/j.clgc.2026.102630 [doi] AB - INTRODUCTION: To determine the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and postoperative outcomes, including 90-day complications and overall survival, in patients with type 2 diabetes mellitus (T2DM) undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study was conducted using the TriNetX database. The cohort of T2DM patients who underwent RN and were prescribed GLP-1RAs was identified and matched 1:1 with non-GLP-1RA controls based on demographics, comorbidities, metformin and insulin prescription, and renal function laboratory values. Risk difference, risk ratio, and odds ratio with 95% confidence intervals were measured for 90-day postoperative complications. Kaplan-Meier analysis, log-rank tests, and multivariable Cox proportional hazards models evaluated the association of GLP-1RA use with overall survival. RESULTS: GLP-1RAs use was associated with decreased odds of arrhythmia (odds ratio [OR] = 0.766) and ileus (OR = 0.405) compared to the non-GLP-1RAs group (P < .05 for each). No significant association was observed between GLP-1RAs use and odds of acute kidney injury (P > .05). Kaplan-Meier analysis and log-rank tests showed improved 2-year and 3-year overall survival among patients prescribed GLP-1RAs compared to those who were not (P < .001 for each). CONCLUSION: Our study parallels ongoing studies examining the broader benefits of GLP-1RA use, demonstrating a decreased incidence of 90-day postoperative ileus and arrhythmia, as well as improved overall survival. Prospective studies are warranted to validate these findings. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Kwon, Sam AU - Kwon S AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address: sam.kwon@gwmail.gwu.edu. FAU - Gonzalez, Diego AU - Gonzalez D AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Wardrop, Fiona AU - Wardrop F AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Newman, Tali AU - Newman T AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Dallmer, Josiah AU - Dallmer J AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Kokoneshi, Kris AU - Kokoneshi K AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Hon, Ryan AU - Hon R AD - The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Whalen, Michael J AU - Whalen MJ AD - Department of Urology, The George Washington University School of Medicine and Health Sciences, Washington, DC. LA - eng PT - Journal Article DEP - 20260725 PL - United States TA - Clin Genitourin Cancer JT - Clinical genitourinary cancer JID - 101260955 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Nephrectomy/adverse effects MH - Retrospective Studies MH - *Kidney Neoplasms/surgery MH - Middle Aged MH - Aged MH - *Carcinoma, Renal Cell/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Postoperative Complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Kaplan-Meier Estimate OTO - NOTNLM OT - Carcinoma OT - Diabetes mellitus OT - Glucagon-like peptide-1 receptor agonists OT - Renal cell OT - Type 2 COIS- Disclosures The authors have stated that they have no conflicts of interest. EDAT- 2026/08/18 23:36 MHDA- 2026/09/18 23:36 CRDT- 2026/08/18 21:54 PHST- 2026/05/28 00:00 [received] PHST- 2026/07/15 00:00 [revised] PHST- 2026/07/17 00:00 [accepted] PHST- 2026/09/18 23:36 [medline] PHST- 2026/08/18 23:36 [pubmed] PHST- 2026/08/18 21:54 [entrez] AID - S1558-7673(26)00130-8 [pii] AID - 10.1016/j.clgc.2026.102630 [doi] PST - ppublish SO - Clin Genitourin Cancer. 2026 Oct;24(7):102630. doi: 10.1016/j.clgc.2026.102630. Epub 2026 Jul 25. PMID- 42608323 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261013 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Body Composition Remodelling During GLP-1-Based Therapy: A Systematic Review and Meta-Analysis Using a Hierarchical Physiological Framework. PG - 9849-9860 LID - 10.1111/dom.71220 [doi] AB - BACKGROUND: Body composition changes during glucagon-like peptide-1 (GLP-1)-based therapy remain incompletely characterized, particularly regarding their effects on adiposity, muscle quantity, and muscle quality. We conducted a systematic review and meta-analysis using a predefined physiological framework to evaluate body composition remodelling during GLP-1-based therapy. METHODS: We searched PubMed, Embase, and Cochrane CENTRAL from inception through May 2026 for studies evaluating GLP-1 receptor agonists or dual incretin therapies reporting longitudinal body composition outcomes in adults. Outcomes were classified into adiposity, muscle quantity, muscle quality, and body weight domains. Primary analyses prioritized comparative evidence and included one physiologically coherent outcome per study and domain. Random-effects meta-analyses were performed using restricted maximum likelihood estimation with Hartung-Knapp adjustment. RESULTS: Nineteen studies met the eligibility criteria, including comparative and exploratory single-arm investigations. Three comparative studies contributed to the primary adiposity meta-analysis and two to the primary muscle quantity meta-analysis. Comparative analyses suggested a direction toward greater reductions in adiposity during GLP-1-based therapy. However, only three studies contributed to this analysis, and the pooled estimate was characterized by substantial between-study heterogeneity and a wide confidence interval crossing the null. Evidence regarding muscle quantity was based on two comparative studies and remained highly heterogeneous and imprecise. Muscle quality outcomes could not be quantitatively synthesized because of methodological heterogeneity and incomplete variance reporting and were therefore evaluated narratively. Exploratory single-arm analyses showed reductions in adiposity and body weight, whereas changes in muscle quantity varied across studies. CONCLUSIONS: Current comparative evidence suggests a possible direction toward greater reductions in adiposity during GLP-1-based therapy. However, the limited number of comparative studies, substantial between-study heterogeneity, wide confidence intervals, and low to very low certainty of evidence preclude definitive conclusions regarding preferential fat loss or preservation of skeletal muscle health. Reductions in lean mass should not be interpreted as synonymous with sarcopenia, but the available evidence is also insufficient to exclude clinically relevant muscle loss in susceptible populations. These findings should therefore be considered hypothesis-generating and require confirmation in adequately powered comparative studies incorporating standardized assessments of muscle quantity, muscle quality, strength, and physical performance. PROSPERO REGISTRATION: CRD420261411693. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lopes Menezes, Maria Luizza AU - Lopes Menezes ML AD - Secretariat of Health of the Federal District, Brasilia, Brazil. AD - School of Public Health of the Federal District, Brasilia, Brazil. FAU - Guntzel Chiappa, Maria Eduarda AU - Guntzel Chiappa ME AD - Federal University of Rio Grande do Sul, Porto Alegre, Brazil. FAU - Kloss, Rodrigo Fuentes AU - Kloss RF AD - Health Sciences School, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Tuesta, Marcelo AU - Tuesta M AD - Exercise and Rehabilitation Sciences Institute, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, Santiago, Chile. FAU - Santos, Paula AU - Santos P AD - Graduate Program in Human Movement and Rehabilitation of Evangelical University of Goias, Goias, Brazil. FAU - Sa Filho, Alberto Souza AU - Sa Filho AS AD - Graduate Program in Human Movement and Rehabilitation of Evangelical University of Goias, Goias, Brazil. FAU - Chiappa, Gaspar R AU - Chiappa GR AUID- ORCID: 0000-0002-0440-8404 AD - Graduate Program in Human Movement and Rehabilitation of Evangelical University of Goias, Goias, Brazil. AD - Faculty of Health Sciences, Universidad Autonoma de Chile, Santiago, Chile. LA - eng GR - Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq)/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260817 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) SB - IM MH - Humans MH - *Body Composition/drug effects/physiology MH - *Glucagon-Like Peptide 1/therapeutic use MH - Adiposity/drug effects MH - Muscle, Skeletal/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Incretins/therapeutic use/pharmacology PMC - PMC13646380 OTO - NOTNLM OT - GLP-1 OT - body composition OT - meta-analysis OT - systematic review OT - type 2 diabetes OT - weight control COIS- The authors declare no conflicts of interest. EDAT- 2026/08/17 23:39 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/17 22:03 PHST- 2026/07/23 00:00 [revised] PHST- 2026/06/30 00:00 [received] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/17 23:39 [pubmed] PHST- 2026/08/17 22:03 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71220 [pii] AID - 10.1111/dom.71220 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):9849-9860. doi: 10.1111/dom.71220. Epub 2026 Aug 17. PMID- 42607727 OWN - NLM STAT- MEDLINE DCOM- 20260829 LR - 20260904 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 239 DP - 2026 Sep TI - Association of GLP-1 receptor agonists, SGLT 2 inhibitors, DPP-4 inhibitors, and sulfonylureas with incident cancer in type 2 diabetes. PG - 113503 LID - S0168-8227(26)00423-7 [pii] LID - 10.1016/j.diabres.2026.113503 [doi] AB - AIMS: Limited evidence exists regarding cancer risk associated with non-metformin glucose-lowering medication classes, particularly among obesity-related and obesity-nonrelated cancers. METHODS: We compared cancer risk following initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), or sulfonylureas by emulating a target trial using claims data from Optum Labs Data Warehouse and traditional Medicare (100% sample) among adults with type 2 diabetes and moderate cardiovascular risk between January 2014 and December 2021. Random treatment assignment was emulated using propensity scores, which were incorporated as inverse probability of treatment weights into proportional hazard models. Primary outcome was any new cancer diagnosis; we secondarily examined cancer subgroups. RESULTS: After inverse probability of treatment weighting, 41,123 patients started GLP-1RA, 54,423 started SGLT2i, 73,803 started DPP4i, and 186,988 started sulfonylureas. GLP-1RA were associated with higher risk of new cancer diagnosis compared to DPP4i (HR 1.13, 95%CI 1.05-1.21). SGLT2i (HR 0.89, 95%CI 0.82-0.96) and sulfonylureas (HR 0.87, 95%CI 0.81-0.92) had lower risks of cancer compared to GLP-1RA. Results were driven by obesity-nonrelated cancers, with no difference between study drugs for obesity-related cancers. CONCLUSIONS: The increased risk of obesity-nonrelated cancers following GLP-1RA therapy warrants further investigation and caution among at-risk individuals. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Sklepinski, Stacey M AU - Sklepinski SM AD - University of Maryland School of Medicine, 655 W. Baltimore St, Baltimore, MD 21201, USA. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; Optum Labs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, 412 East Spokane Falls Blvd., PBS 130, Spokane, WA 99202-2131, USA; Providence Medical Research Center, 105 W 8th Ave, Suite 250E, Spokane, WA 99204, USA. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA; Department of Health Policy and Management, Yale School of Public Health, 60 College St, New Haven, CT 06510, USA. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; Optum Labs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave MC2000, Chicago, IL 60637, USA. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - Optum Labs, 1 Optum Circle, Eden Prairie, MN 55344, USA; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, 670 W. Baltimore St, Baltimore, MD 21201, USA; University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA. Electronic address: Rozalina.McCoy@som.umaryland.edu. LA - eng GR - P30 AG028747/AG/NIA NIH HHS/United States GR - P30 AG097158/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260817 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Insulin Secretagogues) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sulfonylurea Compounds/adverse effects/therapeutic use MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Neoplasms/epidemiology/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Aged MH - Incidence MH - Middle Aged MH - Insulin Secretagogues OTO - NOTNLM OT - Cancer OT - Dipeptidyl-peptidase 4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Sodium-glucose transporter 2 inhibitors OT - Sulfonylureas OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last 36 months, JH currently receives support from the Centers for Medicare and Medicaid Services to develop measures of quality and equity; the NIH, Agency for Healthcare Research and Quality (AHRQ), PCORI, and the American Heart Association (AHA) for multiple research projects. JJN is supported by the NIH and the American College of Clinical Pharmacy, reports serving as a consultant to Bayer, Eli Lilly, Boehringer Ingelheim, and Proteomics International, and reports receiving other support from the American Diabetes Association for projects unrelated to this work. RJG is supported in part by grants from the NIH, Novo Nordisk, Boehringer, Eli Lilly, and Dexcom, and consulting/advisory from Abbott Diabetes, Aztra-Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, and Novo Nordisk, and Medtronic. GEU is supported by research grants from the NIH, has received research support (to Emory University) from Abbott, Dexcom, Corcept, and Bayer, and served as a member of advisory boards for Dexcom, Glucotrack and GlyCare. JSR currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the NIH (R01AA032254), from the Greenwall Foundation, and from Arnold Ventures. All other authors have no conflicts of interest to disclose. RGM has received unrelated support from the National Institutes of Health and the American Diabetes Association. She served as a consultant to EmmiEducate(R) (Wolters Kluwer), NCQA, and to the Yale-New Haven Health System's Center for Outcomes Research and Evaluation and has received speaking honoraria and travel support from the American Diabetes Association. All other authors report no conflicts of interest. EDAT- 2026/08/17 23:39 MHDA- 2026/08/29 23:35 CRDT- 2026/08/17 19:10 PHST- 2026/07/05 00:00 [received] PHST- 2026/08/07 00:00 [revised] PHST- 2026/08/16 00:00 [accepted] PHST- 2026/08/29 23:35 [medline] PHST- 2026/08/17 23:39 [pubmed] PHST- 2026/08/17 19:10 [entrez] AID - S0168-8227(26)00423-7 [pii] AID - 10.1016/j.diabres.2026.113503 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Sep;239:113503. doi: 10.1016/j.diabres.2026.113503. Epub 2026 Aug 17. PMID- 42605988 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260903 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 331 IP - 3 DP - 2026 Sep 1 TI - Combination therapy of RAS inhibition and glucagon-like peptide-1 receptor agonist improves a marker of kidney fibrosis in people with type 2 diabetes. PG - C825-C833 LID - 10.1152/ajpcell.00526.2025 [doi] AB - In type 2 diabetes (T2D), kidney fibrosis drives the progression of chronic kidney disease (CKD) and kidney failure. Lower urinary levels of collagen type III degradation (C3M), a biomarker of extracellular matrix (ECM) turnover, have been associated with CKD progression. We investigated the effect of combination therapy with renin-angiotensin system inhibition (RASi) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) on urinary C3M levels in people with T2D. Urinary C3M was measured using the nordicC3M ELISA in 229 participants from the Drug Combinations for Rewriting Trajectories of Renal Pathologies in T2D (DC-ren) project. Longitudinal changes in urinary C3M were analyzed using linear regression stratified by treatment group. Risk of kidney disease progression according to baseline urinary C3M was evaluated using Kaplan-Meier analysis. The kidney endpoint was defined as >10% decline in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m(2). Combination therapy (RASi + GLP-1 RA) was associated with higher urinary C3M levels compared with RASi monotherapy (P = 0.036). Urinary C3M was positively associated with future eGFR, with a steeper slope in the combination therapy group than in the RASi monotherapy group (P < 0.001). Low baseline urinary C3M was associated with a higher risk of kidney disease progression (P = 0.022). In people with T2D receiving combination therapy with RASi + GLP-1 RA, urinary C3M levels remained stable, whereas levels decreased with RASi monotherapy, suggesting altered kidney ECM turnover.NEW & NOTEWORTHY Urinary C3M is a dynamic biomarker of ECM turnover with pharmacodynamic relevance in kidney disease. Previous studies in diabetic and nondiabetic kidney disease have shown that therapeutic interventions can increase urinary C3M levels. Here, compared with RASi monotherapy, GLP-1 RA-based combination therapy with RASi was associated with a more favorable longitudinal urinary C3M trajectory and an altered association between urinary C3M and kidney function in type 2 diabetes. FAU - Moller, Alexandra L AU - Moller AL AUID- ORCID: 0000-0001-5609-2790 AD - Nordic Bioscience A/S, Herlev, Denmark. FAU - Thoni, Stefanie AU - Thoni S AD - Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria. FAU - Keller, Felix AU - Keller F AUID- ORCID: 0000-0002-8240-7255 AD - Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria. FAU - Sharifli, Samir AU - Sharifli S AD - Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria. FAU - Genovese, Federica AU - Genovese F AUID- ORCID: 0000-0003-1984-1881 AD - Nordic Bioscience A/S, Herlev, Denmark. FAU - Karsdal, Morten AU - Karsdal M AD - Nordic Bioscience A/S, Herlev, Denmark. FAU - Rasmussen, Daniel G K AU - Rasmussen DGK AD - Nordic Bioscience A/S, Herlev, Denmark. FAU - Mayer, Gert AU - Mayer G AD - Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria. LA - eng GR - 848011/European Union; Horizon 2020 research and innovation/ GR - 0172-00270B/Innovationsfonden (IFD)/ PT - Journal Article DEP - 20260817 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Collagen Type III) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/urine MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Fibrosis MH - Biomarkers/urine MH - Aged MH - *Diabetic Nephropathies/drug therapy/pathology MH - *Renin-Angiotensin System/drug effects MH - Drug Therapy, Combination MH - *Kidney/pathology/drug effects MH - Collagen Type III/urine MH - Glomerular Filtration Rate/drug effects MH - Renal Insufficiency, Chronic/drug therapy MH - Disease Progression MH - *Angiotensin Receptor Antagonists/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - biomarkers OT - collagen OT - diabetic kidney disease OT - fibrosis EDAT- 2026/08/17 11:40 MHDA- 2026/09/03 17:36 CRDT- 2026/08/17 07:54 PHST- 2026/09/03 17:36 [medline] PHST- 2026/08/17 11:40 [pubmed] PHST- 2026/08/17 07:54 [entrez] AID - 10.1152/ajpcell.00526.2025 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2026 Sep 1;331(3):C825-C833. doi: 10.1152/ajpcell.00526.2025. Epub 2026 Aug 17. PMID- 42605535 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261013 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Efficacy of Luseogliflozin Added to Semaglutide in Patients With Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus: A Randomised, Open-Label Trial. PG - 10163-10172 LID - 10.1111/dom.71233 [doi] AB - AIMS: Type 2 diabetes drives the progression of metabolic dysfunction-associated steatohepatitis (MASH). We evaluated whether antidiabetic therapy, specifically adding sodium-glucose cotransporter 2 (SGLT2) inhibitor to a glucagon-like peptide-1 receptor agonist (GLP-1RA), improves liver histology in adults with biopsy-proven MASH and type 2 diabetes. MATERIALS AND METHODS: In this 52-week, open-label, randomised, parallel-group trial in Japan, adults with biopsy-confirmed MASH and type 2 diabetes received semaglutide plus luseogliflozin or semaglutide alone at antidiabetic doses. Paired liver biopsies at baseline and Week 52 were evaluated by blinded pathologists. Primary histological endpoints included resolution of MASH without worsening fibrosis, >/= 1-point improvement in the non-alcoholic fatty liver disease (NAFLD) activity score without worsening fibrosis and >/= 1-stage improvement in fibrosis without worsening MASH. RESULTS: Sixty participants were randomised (combination, n = 24; monotherapy, n = 36). At Week 52, all histological endpoints numerically favoured combination therapy. Resolution of MASH without worsening fibrosis occurred in 34.9% versus 19.4%, >/= 1-point improvement in the NAFLD activity score (NAS) in 75.5% versus 55.6% and >/= 1-stage fibrosis improvement in 26.9% versus 13.9%. In the pre-specified per-protocol analysis, >/= 1-point improvement in the NAS was nominally significant. Combination therapy reduced body weight, glycated haemoglobin levels, aminotransferase levels and FibroScan-derived liver stiffness. CONCLUSIONS: In the pre-specified full analysis set, combination therapy at antidiabetic doses did not significantly improve pre-specified histological endpoints compared with monotherapy. In the pre-specified per-protocol analysis, a nominal improvement in the NAS was observed. Combination therapy improved body weight, glycemic control, aminotransferase levels and liver stiffness, with no new safety concerns identified. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR): UMIN000045003; Japan Registry of Clinical Trials (jRCT): jRCTs061210009. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Miyake, Teruki AU - Miyake T AUID- ORCID: 0000-0002-9905-5356 AD - Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. AD - Total Medical Support Center, Ehime University Hospital, Toon, Ehime, Japan. AD - Center for Data Science, Ehime University, Toon, Ehime, Japan. FAU - Yoshida, Osamu AU - Yoshida O AUID- ORCID: 0000-0002-5015-0045 AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Furukawa, Shinya AU - Furukawa S AD - Health Service Center, Ehime University, Matsuyama, Ehime, Japan. FAU - Hirooka, Masashi AU - Hirooka M AD - Total Medical Support Center, Ehime University Hospital, Toon, Ehime, Japan. AD - Center for Data Science, Ehime University, Toon, Ehime, Japan. FAU - Abe, Masanori AU - Abe M AD - Department of Community and General Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Tokumoto, Yoshio AU - Tokumoto Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Kanamoto, Ayumi AU - Kanamoto A AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Watanabe, Takao AU - Watanabe T AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Yano, Ryo AU - Yano R AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Okazaki, Yuki AU - Okazaki Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Yukimoto, Atsushi AU - Yukimoto A AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Nakamura, Yoshiko AU - Nakamura Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Takeshita, Eiji AU - Takeshita E AD - Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Kumagi, Teru AU - Kumagi T AD - Post Graduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Hiasa, Yoichi AU - Hiasa Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. LA - eng GR - Taisho Toyama Pharmaceutical Company/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260817 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - C596HWF74Z (1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 506T60A25R (Sorbitol) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Japan MH - Liver/pathology/drug effects MH - *Non-alcoholic Fatty Liver Disease/pathology/drug therapy/complications MH - *Semaglutide/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage/adverse effects MH - Sorbitol/analogs & derivatives/therapeutic use/administration & dosage/adverse effects/analogs & derivatives MH - Treatment Outcome PMC - PMC13646358 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - clinical trial OT - diabetes complications OT - fatty liver disease COIS- Y.H. reports receiving a research grant from Taisho Pharmaceutical Co. Ltd. related to this study and lecture fees from Taisho Pharmaceutical Co. Ltd. and Kowa Company Ltd. T.M. reports receiving lecture fees related to MASLD and diabetes mellitus from Taisho Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim Japan Inc., Sumitomo Pharma Co. Ltd., Tanabe Pharma Corporation and Kowa Company Ltd. S.F. reports receiving lecture fees related to diabetes mellitus from Taisho Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co. Ltd., Tanabe Pharma Corporation and Kowa Company Ltd. The other authors declare no conflicts of interest. EDAT- 2026/08/17 05:38 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/17 03:54 PHST- 2026/08/01 00:00 [revised] PHST- 2026/06/11 00:00 [received] PHST- 2026/08/05 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/17 05:38 [pubmed] PHST- 2026/08/17 03:54 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71233 [pii] AID - 10.1111/dom.71233 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10163-10172. doi: 10.1111/dom.71233. Epub 2026 Aug 17. PMID- 42603240 OWN - NLM STAT- MEDLINE DCOM- 20260815 LR - 20261008 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Aug 15 TI - Effect of tirzepatide and semaglutide on blood pressure: A systematic review and meta-analysis. LID - 275 [pii] LID - 10.1007/s12020-026-04757-7 [doi] AB - PURPOSE: Tirzepatide and semaglutide are widely used for type 2 diabetes mellitus (T2DM) and obesity. However, the blood pressure-related adverse event profiles associated with tirzepatide and semaglutide remain unclear. This study systematically evaluated hypertension- and hypotension-related treatment-emergent adverse events (TEAEs) that occurred when using tirzepatide and semaglutide for the treatment of T2DM or obesity. METHODS: A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, CENTRAL, and ClinicalTrials.gov from inception to September 26, 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model, with subgroup analyses performed. RESULTS: This meta-analysis of 32 randomized controlled trials (RCTs), enrolling 47,332 participants, revealed distinct differences in the blood pressure-related safety profiles of tirzepatide and semaglutide. Tirzepatide was associated with a lower risk of hypertension-related events (RR = 0.40, 95% CI [0.26-0.60]; p < 0.001). This potent antihypertensive effect was accompanied by an increased risk of hypotension-related events (RR = 2.45, 95% CI [1.35-4.45]; p = 0.003), particularly at higher doses (RR = 2.58, 95% CI [1.38-4.81]; p = 0.003). Semaglutide exhibited a relatively neutral blood pressure-related safety profile, showing no significant association with either hypertension-related events (RR = 0.81, 95% CI [0.57-1.15]; p = 0.233) or hypotension-related events (RR = 1.39, 95% CI [0.81-2.36]; p = 0.232), although potential protective signals were observed in high-dose subgroups. CONCLUSION: Tirzepatide reduces hypertension-related adverse events but increases dose-dependent hypotension risk in patients with T2DM or obesity. These distinct hemodynamic safety profiles support individualized treatment decisions based on baseline blood pressure and cardiometabolic risk. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chen, Qing-Xin AU - Chen QX AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Zhou, Xiao-Yu AU - Zhou XY AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Wu, Qi AU - Wu Q AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. AD - Department of Pathology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Xie, Jia-Jie AU - Xie JJ AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Xu, Yong AU - Xu Y AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. FAU - Teng, Fang-Yuan AU - Teng FY AUID- ORCID: 0000-0002-9564-0961 AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. FAU - Guo, Man AU - Guo M AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. LA - eng GR - 82300911/National Natural Science Foundation of China/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260815 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - *Tirzepatide MH - Semaglutide MH - Humans MH - *Blood Pressure/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/pharmacology MH - Hypertension/chemically induced MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Blood pressure OT - Diabetes OT - Meta-analysis OT - Obesity OT - Semaglutide OT - Tirzepatide COIS- Declarations. Conflict of interests: The authors declare they have no competing interests. EDAT- 2026/08/15 17:37 MHDA- 2026/08/15 17:38 CRDT- 2026/08/15 11:07 PHST- 2026/05/08 00:00 [received] PHST- 2026/08/09 00:00 [accepted] PHST- 2026/08/15 17:38 [medline] PHST- 2026/08/15 17:37 [pubmed] PHST- 2026/08/15 11:07 [entrez] AID - 10.1007/s12020-026-04757-7 [pii] AID - 10.1007/s12020-026-04757-7 [doi] PST - epublish SO - Endocrine. 2026 Aug 15;91(1):275. doi: 10.1007/s12020-026-04757-7. PMID- 42594928 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial. PG - 831-840 LID - S2213-8587(26)00136-1 [pii] LID - 10.1016/S2213-8587(26)00136-1 [doi] AB - BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged >/=18 years) with type 2 diabetes (HbA(1c) >/=8.0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3.9-5.0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA(1c) and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA(1c), from baseline (9.57% for IcoSema and 9.50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3.32 vs -2.44 percentage points; estimated treatment difference [ETD] -0.88 percentage points [95% CI -1.12 to -0.63]), confirming superiority of IcoSema (p<0.001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0.79 vs 3.81 kg; ETD -4.61 kg [95% CI -5.46 to -3.75]), confirming superiority of IcoSema (p<0.001). Rate of combined clinically significant (blood glucose <3.0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0.29 vs 0.59 episodes per person-year of exposure; estimated rate ratio 0.56 [95% CI 0.32 to 0.97]; p=0.04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA(1c) reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University Diabetes Centre, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. FAU - Benamar, Malik AU - Benamar M AD - Novo Nordisk, Soborg, Denmark. FAU - Mohan, Viswanathan AU - Mohan V AD - Madras Diabetes Research Foundation (ICMR-Collaborating Centre of Excellence) and Dr Mohan's Diabetes Specialities Centre (IDF Centre of Excellence in Diabetes Care), Chennai, India. FAU - Pletsch-Borba, Laura AU - Pletsch-Borba L AD - Novo Nordisk, Soborg, Denmark. FAU - Porcellati, Francesca AU - Porcellati F AD - Department of Medicine and Surgery, University of Perugia, Perugia, Italy. FAU - Wang, Ni AU - Wang N AD - Novo Nordisk, Soborg, Denmark. FAU - Watada, Hirotaka AU - Watada H AD - Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Rea, Rosangela R AU - Rea RR AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT06269107 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260813 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Insulin Glargine/administration & dosage/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - Semaglutide MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Adult MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Treatment Outcome MH - Drug Therapy, Combination COIS- Declaration of interests LJ has received research support and consultant fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare; has served on advisory panels for Haisco Pharmaceutical and received honoraria from Eli Lilly, Innovent Biologics, Novo Nordisk and Sanofi-Aventis. MB, LP-B, and NW are employees of Novo Nordisk and hold stock options. VM has acted as consultant and speaker for, and received research or educational grants from Abbott, Alembic Pharmaceuticals, Apex Pharma, Aventis, Bayer, Biocon, Boehringer Ingelheim, Cipla, Dr Reddy's, Eli Lilly, Emcure, Fourrts India, Franco Indian, Glenmark Pharmaceuticals, GSK, Intas Pharmaceuticals, Ipca Laboratories, Johnson & Johnson, LifeScan, Lupin, Mankind Pharma, Medtronic, MSD, Novartis, Novo Nordisk, Primus Pharmaceuticals, Roche, Sanofi, Servier, Sun Pharma, Torrent Pharma, USV, Wockhardt, and Zydus Lifesciences. FP has received research support or consultant and speaker fees from, or has participated on advisory panels for Abbott, AstraZeneca, Eli Lilly, Laboratori Guidotti, Novo Nordisk, Roche, and Sanofi. HW has received research support from Kowa Company, Lifescan Japan, Nippon Boehringer Ingelheim, Sanwa Kagaku Kenkyusho, SBI Pharma, Sumitomo Pharma and Taisho Pharma; and has acted as a speaker for Abbott Japan, Bayer Yakuhin, Daiichi Sankyo, Eli Lilly Japan, Embecta, GSK, Kowa Company, Kyowa Kirin, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Roche DC Japan, Sanwa Kagaku Kenkyusho, Sumitomo Pharma, Tanabe Pharma, Taisho Pharma and Teijin. RRR is an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has participated in speakers' bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, and Novo Nordisk; and has received research grants from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. EDAT- 2026/08/13 23:36 MHDA- 2026/09/08 23:35 CRDT- 2026/08/13 18:53 PHST- 2026/03/04 00:00 [received] PHST- 2026/05/29 00:00 [revised] PHST- 2026/05/29 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/13 23:36 [pubmed] PHST- 2026/08/13 18:53 [entrez] AID - S2213-8587(26)00136-1 [pii] AID - 10.1016/S2213-8587(26)00136-1 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):831-840. doi: 10.1016/S2213-8587(26)00136-1. Epub 2026 Aug 13. PMID- 42594084 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260815 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 8 DP - 2026 TI - Gastroparesis induced by glucagon-like peptide-1 receptor agonists: A systematic review of clinical features, diagnosis, management, and outcomes. PG - e0354497 LID - 10.1371/journal.pone.0354497 [doi] LID - e0354497 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes mellitus and obesity. Although gastrointestinal adverse effects are common, gastroparesis is an under-recognised but clinically important complication. This systematic review summarises published evidence on the presentation, diagnosis, management, and outcomes of gastroparesis associated with GLP-1RA therapy in real-world clinical practice. METHODS: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase, Scopus, and Web of Science were searched from inception to October 2025 for reports of symptomatic gastroparesis associated with GLP-1RA use. Eligible studies included case reports, case series, observational studies, and clinical trials involving adults treated with GLP-1RAs for diabetes or weight loss. Data extraction focused on patient characteristics, GLP-1RA exposure, clinical presentation, diagnostic findings, management strategies, and outcomes. Methodological quality was assessed using the Joanna Briggs Institute checklist for case reports. RESULTS: Twelve case reports describing 13 patients met inclusion criteria. Most patients were female and had type 2 diabetes mellitus, though cases also occurred in non-diabetic individuals. Semaglutide was the most frequently implicated agent, followed by liraglutide, dulaglutide, and exenatide. Symptom onset ranged from hours to several months after treatment initiation, commonly following dose escalation or inappropriate re-initiation. Presentations varied from acute to chronic. Reported symptoms included nausea, vomiting, abdominal pain, bloating, early satiety, and oral intolerance. Diagnostic evaluation often demonstrated gastric distension or retained gastric contents on imaging or endoscopy in the absence of mechanical obstruction. Gastric emptying scintigraphy confirms delayed emptying in selected cases. Management primarily involved supportive and symptomatic care. Discontinuation of the offending GLP-1RA led to symptom resolution in all reported patients. CONCLUSION: GLP-1 receptor agonists may induce or worsen gastroparesis in both diabetic and non-diabetic patients, particularly following rapid dose escalation or inappropriate dosing. Awareness of this association is essential for timely diagnosis and management. Withdrawal of the causative agent is central to treatment and is associated with favourable outcomes and reversibility of gastric dysfunction. Careful patient selection, gradual dose titration, and monitoring for persistent gastrointestinal symptoms are recommended to optimise the safe use of GLP-1RAs. CI - Copyright: (c) 2026 Olubodun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Olubodun, Tope AU - Olubodun T AUID- ORCID: 0000-0002-6274-5468 AD - Department of Community Medicine and Primary Care, Federal Medical Center Abeokuta, Abeokuta, Ogun State, Nigeria. FAU - Osundina, Morenike Adedoyin AU - Osundina MA AD - Department of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria. FAU - Soyoye, David Olubukunmi AU - Soyoye DO AD - Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. FAU - de Oliveira, Natalia Maria Bim AU - de Oliveira NMB AD - Ferring Pharmaceuticals, Sao Paulo, Sao Paulo, Brazil. FAU - Olubodun, Ayodeji Bamidele AU - Olubodun AB AD - Accident and Emergency Department, Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria. FAU - Ogundele, Oluwatoyin Olanrewaju AU - Ogundele OO AD - Nats'oojeh Hospital and Health Centre, Fort St James, British Columbia, Canada. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260813 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Gastroparesis/chemically induced/diagnosis/therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Exenatide/adverse effects MH - Female MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Recombinant Fusion Proteins/adverse effects MH - Male MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Treatment Outcome MH - Immunoglobulin Fc Fragments PMC - PMC13472420 COIS- The authors have declared that no competing interests exist. EDAT- 2026/08/13 21:31 MHDA- 2026/08/13 21:32 PMCR- 2026/08/13 CRDT- 2026/08/13 13:34 PHST- 2026/03/09 00:00 [received] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/08/13 21:32 [medline] PHST- 2026/08/13 21:31 [pubmed] PHST- 2026/08/13 13:34 [entrez] PHST- 2026/08/13 00:00 [pmc-release] AID - PONE-D-26-11854 [pii] AID - 10.1371/journal.pone.0354497 [doi] PST - epublish SO - PLoS One. 2026 Aug 13;21(8):e0354497. doi: 10.1371/journal.pone.0354497. eCollection 2026. PMID- 42592768 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260813 IS - 2245-1919 (Electronic) IS - 2245-1919 (Linking) VI - 73 IP - 7 DP - 2026 Jun 16 TI - Real-world use of oral semaglutide in adults with type 2 diabetes. LID - A06250520 [pii] LID - 10.61409/A06250520 [doi] AB - INTRODUCTION: PIONEER REAL Denmark assessed changes in HbA1c, body weight and treatment satisfaction with once-daily oral semaglutide in adults with type 2 diabetes. METHODS: In this multicentre, prospective, open-label, non-interventional study, participants initiated oral semaglutide in routine clinical practice and were followed up for 34-44 weeks. The primary endpoint was change in HbA1c from baseline to the end of study (EOS). Secondary endpoints assessed at EOS included change in body weight (BW), proportion of participants reaching HbA1c less-than 7% and treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire status/change (DTSQs/DTSQc). RESULTS: In total, 96 participants from a primary care setting were included (median age: 63.5 years, HbA1c: 7.6% (60.0 mmol/mol), BW: 97.4 kg). Estimated changes from baseline to EOS in HbA1c (n = 96) and BW (n = 86) were -0.9 percentage points (9.9 mmol/mol) (95% CI: -1.20; -0.61 percentage points) and -4.4 (95% CI: -5.44; -3.41) kg, respectively. At baseline, 28.1% of participants had HbA1c less-than 7.0% (less-than 53 mmol/mol); at EOS, 66.7% of participants had HbA1c less-than 7.0% (53 mmol/mol). Improvements in treatment satisfaction were observed in DTSQs (1.9 points) and DTSQc (10.5 points) scores. No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Denmark, participants treated with oral semaglutide in a primary care setting experienced reductions in HbA1c and BW. FUNDING: This study was sponsored by Novo Nordisk A/S. CLINICALTRIALS: gov (NCT04537637). CI - Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/. FAU - Roslind, Klaus AU - Roslind K AD - Aarup Health Center I/S, Aarup. FAU - Bodholdt, Ulrik AU - Bodholdt U AD - Kastruplaegerne, Kastrup. FAU - Damgaard, Tina AU - Damgaard T AD - Novo Nordisk Denmark A/S, Kobenhavn. FAU - Jensen, Christian AU - Jensen C AD - Laegehuset Remisen, Praesto, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04537637 PT - Journal Article PT - Multicenter Study DEP - 20260616 PL - Denmark TA - Dan Med J JT - Danish medical journal JID - 101576205 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Semaglutide MH - Middle Aged MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Prospective Studies MH - Administration, Oral MH - Aged MH - Patient Satisfaction MH - Denmark MH - Body Weight/drug effects MH - Treatment Outcome EDAT- 2026/08/13 12:42 MHDA- 2026/08/13 12:43 CRDT- 2026/08/13 07:37 PHST- 2026/08/13 12:43 [medline] PHST- 2026/08/13 12:42 [pubmed] PHST- 2026/08/13 07:37 [entrez] AID - A06250520 [pii] AID - 10.61409/A06250520 [doi] PST - epublish SO - Dan Med J. 2026 Jun 16;73(7):A06250520. doi: 10.61409/A06250520. PMID- 42591121 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260814 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Cardiovascular outcomes of SGLT2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes and a history of myocardial infarction: a systematic review and network meta-analysis of randomized controlled trials. PG - 1902802 LID - 10.3389/fendo.2026.1902802 [doi] LID - 1902802 AB - BACKGROUND: Patients with type 2 diabetes (T2DM) and a history of myocardial infarction (MI) face a high risk of recurrent cardiovascular events. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk, but no head-to-head trials exist. We performed a systematic review and network meta-analysis (NMA) to indirectly compare their cardiovascular efficacy in this high-risk population. METHODS: Randomized controlled trials (RCTs) published up to February 1, 2026, were systematically searched and evaluated. The primary outcome was major adverse cardiovascular events (MACE); secondary outcomes included hospitalization for heart failure (HFH), MI, and cardiovascular death (CV death). A frequentist NMA was used as the primary comparative analysis, complemented by Bucher interaction tests as sensitivity analyses. Evidence certainty was assessed with GRADE. RESULTS: Eleven RCTs were included; after exclusion of overlapping populations, the final analyses comprised 7 studies for MACE (2 SGLT2i, 5 GLP-1 RA), 6 for HFH (2 SGLT2i, 4 GLP-1 RA), 4 for MI (1 SGLT2i, 3 GLP-1 RA), and 6 for CV death (2 SGLT2i, 4 GLP-1 RA). Both drug classes significantly reduced MACE compared to placebo (SGLT2i HR 0.87, 95% CI 0.77-0.97; GLP-1 RA HR 0.83, 95% CI 0.77-0.89). The NMA indirect comparison for MACE yielded an HR of 1.05 (95% CI 0.92-1.20, p = 0.44), indicating no statistically significant difference between classes. For HFH, SGLT2i exhibited a numerically greater reduction (indirect HR 0.83, 95% CI 0.67-1.03, p = 0.09) that did not reach conventional significance. MI risk was similarly reduced by both classes (indirect HR 1.05, 95% CI 0.83-1.33, p = 0.68). For CV death, the indirect comparison showed no statistically significant difference between classes (HR 0.94, 95% CI 0.76-1.16, p = 0.57), but this estimate is based on limited SGLT2i data (only two trials). The GRADE certainty was low for CV death, primarily due to indirectness (predominantly remote MI populations) and imprecision (wide confidence intervals crossing the line of no effect). CONCLUSIONS: In patients with T2DM and a history of MI, indirect evidence suggests that both SGLT2i and GLP-1 RAs reduce MACE, HFH, and recurrent MI, with no statistically significant difference between classes. SGLT2i show a numerically larger HFH reduction, but the difference is not statistically robust. Evidence is largely derived from remote MI, limiting its applicability to the acute post-infarction setting. Treatment choice should be individualized based on patient risk profiles. Dedicated head-to-head trials are urgently needed. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261299756, identifier CRD420261299756. CI - Copyright (c) 2026 Ren, Yang, Zhang, Hu, Tan, Wang and Xu. FAU - Ren, Yanxia AU - Ren Y AD - Department of Endocrinology and Metabolism of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. FAU - Yang, Hui AU - Yang H AD - Cardiovascular Department 2 of the First Affiliated Hospital of Shihezi University, Xinjiang, China. FAU - Zhang, Shuang AU - Zhang S AD - Department of Burn Plastic Surgery of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. FAU - Hu, Tianxiao AU - Hu T AD - Department of Endocrinology and Metabolism of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. FAU - Tan, Qingying AU - Tan Q AD - Department of Endocrinology and Metabolism of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. FAU - Wang, Jing AU - Wang J AD - Department of Endocrinology and Metabolism of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. FAU - Xu, Yao AU - Xu Y AD - Department of Endocrinology and Metabolism of the 903rd Hospital of the Joint Logistic Support Force, Hangzhou, China. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260729 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Myocardial Infarction/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases PMC - PMC13461399 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - cardiovascular outcomes OT - heart failure OT - major adverse cardiovascular events OT - meta-analysis OT - myocardial infarction OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/08/13 12:42 MHDA- 2026/08/13 12:43 PMCR- 2026/07/29 CRDT- 2026/08/13 05:07 PHST- 2026/06/07 00:00 [received] PHST- 2026/07/08 00:00 [revised] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/08/13 12:43 [medline] PHST- 2026/08/13 12:42 [pubmed] PHST- 2026/08/13 05:07 [entrez] PHST- 2026/07/29 00:00 [pmc-release] AID - 10.3389/fendo.2026.1902802 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 29;17:1902802. doi: 10.3389/fendo.2026.1902802. eCollection 2026. PMID- 42587729 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260827 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 15 IP - 15 DP - 2026 Jul 23 TI - Metabolic Reversal of Functional Hypogonadism? GLP-1 Receptor Agonists and Male Reproductive Endocrinology-A Systematic Review. LID - 10.3390/cells15151319 [doi] LID - 1319 AB - BACKGROUND: Testosterone deficiency is highly prevalent in men with obesity and type 2 diabetes mellitus and often reflects functional suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in these conditions, but their effects on male reproductive endocrinology remain incompletely defined. OBJECTIVE: To systematically review the effects of GLP-1 receptor agonists on testosterone, HPG axis hormones, and male reproductive outcomes. METHODS: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane, and Google Scholar were searched (January 2021-January 2026) for studies evaluating GLP-1 RA therapy in adult men with reported endocrine or reproductive outcomes. RESULTS: Eight studies met inclusion criteria, including one randomised placebo-controlled crossover trial and six observational or interventional studies. In men with obesity, type 2 diabetes, or functional hypogonadism, GLP-1 RAs were associated with modest increases in testosterone and improvements in erectile function or selected semen parameters. In contrast, a placebo-controlled trial in healthy eugonadal men showed no significant endocrine or reproductive effects. Responses appeared dependent on baseline metabolic status. CONCLUSIONS: GLP-1 RAs are associated with improvements in male reproductive endocrinology in metabolically compromised populations with metabolic hypogonadism while remaining neutral in healthy individuals. Larger prospective studies are needed. FAU - Zafrani, Zakhi AU - Zafrani Z AUID- ORCID: 0009-0006-7810-1276 AD - Independent Researcher, Manchester SK8 6HD, UK. FAU - Khan, Sarah Suleman AU - Khan SS AD - Independent Researcher, Manchester SK8 6HD, UK. FAU - Zitzmann, Michael AU - Zitzmann M AD - Department of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology, Munster University Hospital, 48149 Munster, Germany. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260723 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 3XMK78S47O (Testosterone) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypogonadism/drug therapy/metabolism MH - Testosterone/metabolism MH - Hypothalamic-Pituitary-Gonadal Axis MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Obesity/drug therapy MH - *Reproduction/drug effects PMC - PMC13464801 OTO - NOTNLM OT - GLP-1 receptor agonists OT - functional hypogonadism OT - male reproductive endocrinology OT - metabolic health OT - obesity OT - testosterone deficiency COIS- The authors declare no conflicts of interest. EDAT- 2026/08/13 05:35 MHDA- 2026/08/13 05:36 PMCR- 2026/07/23 CRDT- 2026/08/13 01:01 PHST- 2026/05/03 00:00 [received] PHST- 2026/06/25 00:00 [revised] PHST- 2026/07/16 00:00 [accepted] PHST- 2026/08/13 05:36 [medline] PHST- 2026/08/13 05:35 [pubmed] PHST- 2026/08/13 01:01 [entrez] PHST- 2026/07/23 00:00 [pmc-release] AID - cells15151319 [pii] AID - cells-15-01319 [pii] AID - 10.3390/cells15151319 [doi] PST - epublish SO - Cells. 2026 Jul 23;15(15):1319. doi: 10.3390/cells15151319. PMID- 42584177 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260826 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 16 IP - 5 DP - 2026 Oct TI - Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis. PG - e70105 LID - 10.1111/cob.70105 [doi] LID - e70105 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, are widely used for Type 2 diabetes mellitus (T2DM), obesity and related metabolic conditions. Evidence on potential neuropsychiatric effects remains inconsistent. This systematic review and meta-analysis evaluated depression risk among patients receiving semaglutide. Following PRISMA 2020 guidelines, major biomedical databases, trial registries, pharmacovigilance databases, conference abstracts and grey literature were searched from inception to January 2026. Eligible studies included randomised controlled trials, observational studies, large database analyses and pharmacovigilance disproportionality studies involving patients receiving semaglutide. Risk of bias was assessed using ROBINS-I and the Newcastle-Ottawa Scale. The pooled risk ratio for depression was 1.25 (95% CI: 0.95-1.65; I(2) = 98%). For anxiety and suicidal ideation/attempt, pooled risk ratios were 1.22 (95% CI: 0.93-1.60; I(2) = 99%) and 1.20 (95% CI: 0.90-1.62; I(2) = 92%), respectively. No statistically significant differences were observed between semaglutide and comparator/placebo groups for outcomes. Pooled estimates did not show a statistically significant increase in depression, anxiety or suicidal ideation/attempt among patients receiving semaglutide compared with comparator groups. However, the certainty of evidence was limited by substantial heterogeneity, risk of bias and reliance on heterogeneous data sources, including spontaneous-reporting studies. These findings are reassuring but should be interpreted as the absence of a detected increased risk in the available evidence, rather than definitive proof of no psychiatric risk. CI - (c) 2026 World Obesity Federation. FAU - Bhaduri, Gaurab AU - Bhaduri G AUID- ORCID: 0009-0007-4000-9287 AD - Department of Diabetes & Endocrinology, Park View Super Speciality Hospital, Kolkata, West Bengal, India. AD - Apollo Sugar Clinic, Kolkata, West Bengal, India. FAU - Roy, Shilanjan AU - Roy S AUID- ORCID: 0009-0009-4257-9982 AD - Charnock Hospital, Kolkata, West Bengal, India. FAU - Kalia, Anchin AU - Kalia A AUID- ORCID: 0000-0001-8869-9351 AD - Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. FAU - Gokalani, Rutul AU - Gokalani R AUID- ORCID: 0000-0001-8546-002X AD - AHC Diabetes Centre, Ahmedabad, Gujarat, India. FAU - Saboo, Banshi AU - Saboo B AUID- ORCID: 0000-0001-7293-8864 AD - DiaCare, Diabetes Care & Hormone Clinic, Ahmedabad, Gujarat, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Depression/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Factors PMC - PMC13464048 OTO - NOTNLM OT - GLP-1RA OT - depression OT - risk factors OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/08/12 11:38 MHDA- 2026/08/12 11:39 PMCR- 2026/08/12 CRDT- 2026/08/12 09:24 PHST- 2026/07/16 00:00 [revised] PHST- 2026/05/27 00:00 [received] PHST- 2026/08/06 00:00 [accepted] PHST- 2026/08/12 11:39 [medline] PHST- 2026/08/12 11:38 [pubmed] PHST- 2026/08/12 09:24 [entrez] PHST- 2026/08/12 00:00 [pmc-release] AID - COB70105 [pii] AID - 10.1111/cob.70105 [doi] PST - ppublish SO - Clin Obes. 2026 Oct;16(5):e70105. doi: 10.1111/cob.70105. PMID- 42583965 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260814 IS - 1998-3751 (Electronic) IS - 0253-7613 (Print) IS - 0253-7613 (Linking) VI - 58 IP - 4 DP - 2026 Jul 1 TI - Combined use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for cardiovascular protection. PG - 293-306 LID - 10.4103/ijp.ijp_1384_25 [doi] AB - Among the various treatments for type 2 diabetes during the initial period, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been considered together as agents with separate cardiometabolic benefits, given their limited glucose-lowering effects. GLP-1 RAs are reported to inhibit atherosclerosis through several physiological processes, including increased blood flow in endothelial tissues, decreased inflammation, increased antioxidant levels, and improved lipid profile. There is a similar situation with SGLT2 inhibitors, and the explanation for this is different yet complementary, as these drugs cause a decrease in both cardiac preload and afterload and, at the same time, increase vascular permeability, diuresis, and more efficient energy usage by the heart. Thus, they have been affirmed by extensive clinical trials, which show that, although these drugs may harm patients, they do not result in significant cardiovascular events, have a lower treatment rate for heart defects, and are associated with a longer time before the patient's renal function deteriorates. This translates into a continuing shift toward the dominion in terms of cardiometabolic protection - a strategy that is receiving strong backing from the majority of clinical guidelines across the world. CI - Copyright (c) 2026 Indian Journal of Pharmacology. FAU - Mohanty, Soumya Shanta AU - Mohanty SS AD - Department of Pharmacy Practice, R R College of Pharmacy, Bengaluru, Karnataka, India. FAU - Selvammathy, R R AU - Selvammathy RR AD - Department of Pharmacy Practice, R R College of Pharmacy, Bengaluru, Karnataka, India. FAU - Ahad, Hindustan Abdul AU - Ahad HA AD - Department of Pharmaceutics, R R College of Pharmacy, Bengaluru, Karnataka, India. FAU - Kumar, Edukulla Satheesh AU - Kumar ES AD - Department of Pharmacy Practice, R R College of Pharmacy, Bengaluru, Karnataka, India. LA - eng PT - Journal Article PT - Review DEP - 20260701 PL - India TA - Indian J Pharmacol JT - Indian journal of pharmacology JID - 7902477 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Drug Therapy, Combination PMC - PMC13412501 OTO - NOTNLM OT - Atherosclerosis OT - cardio metabolic disease OT - glucagon-like peptide-1 receptors OT - therapy COIS- There are no conflicts of interest. EDAT- 2026/08/12 11:38 MHDA- 2026/08/12 11:39 PMCR- 2026/07/01 CRDT- 2026/08/12 08:26 PHST- 2025/12/30 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/08/12 11:39 [medline] PHST- 2026/08/12 11:38 [pubmed] PHST- 2026/08/12 08:26 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 01363791-202607000-00002 [pii] AID - IJPharm-58-293 [pii] AID - 10.4103/ijp.ijp_1384_25 [doi] PST - ppublish SO - Indian J Pharmacol. 2026 Jul 1;58(4):293-306. doi: 10.4103/ijp.ijp_1384_25. Epub 2026 Jul 1. PMID- 42581431 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261009 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Association of GLP-1 Receptor Agonist Use With Cardiovascular Outcomes and Mortality in Japanese Patients With Type 2 Diabetes: A Real-World Claims Database Study. PG - 10037-10044 LID - 10.1111/dom.71209 [doi] AB - AIMS: Large-scale clinical trials have shown multiple effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs); however, similar evidence for Asian patients is limited. Therefore, using a Japanese large-scale claims-based database, the effects of GLP-1RAs on cardiovascular and cerebrovascular events including mortality were compared with those of other glucose-lowering agents. MATERIALS AND METHODS: Patients with type 2 diabetes (T2D) were identified from a claims database of approximately 1.9 million individuals. Those newly prescribed GLP-1RAs between 2014 and 2021 were assigned to the GLP-1RA group, while those initiating other glucose-lowering agents served as controls. The primary outcome was cardiovascular or cerebrovascular events or all-cause mortality. Logistic regression analysis was performed using explanatory variables, and nearest-neighbour propensity score matching was performed between the groups. The period from the initiation of new medication to event occurrence was calculated and analysed using the Cox proportional hazards model, with a maximum follow-up of 38 months. RESULTS: Among 469 461 eligible patients, 2401 received GLP-1RAs and 53 946 were controls. After propensity matching, 2147 patients remained in each group. The median follow-up was 12 months. No significant difference was observed in 3-point major adverse cardiovascular events (3-point MACE) (GLP-1RA, 7.08% (n = 152) versus control, 8.20% (n = 176); hazard ratio (HR), 0.920; 95% confidence interval (CI) 0.740-1.143, p = 0.450). However, all-cause mortality was lower in the GLP-1RAs group (5.36% (n = 115) versus 7.36% (n = 158), HR 0.776, 95% CI 0.610-0.987, p = 0.039). CONCLUSIONS: GLP-1RA showed no association with 3-point MACE difference but showed lower all-cause mortality. These findings possibly reflect residual confounding. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Koshizaka, Masaya AU - Koshizaka M AUID- ORCID: 0000-0001-7374-9993 AD - Department of Nutrition and Metabolic Medicine, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan. AD - Department of Endocrinology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. AD - Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan. FAU - Ishibashi, Ryoichi AU - Ishibashi R AUID- ORCID: 0000-0003-2535-5396 AD - Department of Endocrinology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Ishikawa, Tomoki AU - Ishikawa T AUID- ORCID: 0000-0001-8725-6508 AD - Institute for Health Economics and Policy, Tokyo, Japan. FAU - Goda, Kazuo AU - Goda K AD - Institute of Industrial Science, The University of Tokyo, Tokyo, Japan. FAU - Sato, Jumpei AU - Sato J AD - Institute of Industrial Science, The University of Tokyo, Tokyo, Japan. FAU - Kitsuregawa, Masaru AU - Kitsuregawa M AD - Institute of Industrial Science, The University of Tokyo, Tokyo, Japan. FAU - Yokote, Koutaro AU - Yokote K AUID- ORCID: 0000-0003-3033-4813 AD - Chiba University, Chiba, Japan. FAU - Mitsutake, Naohiro AU - Mitsutake N AD - Institute for Health Economics and Policy, Tokyo, Japan. LA - eng GR - JPJ012425/Japan Agency for Medical Research and Development (AMED) and Cross-ministerial Strategic Innovation Promotion Program (SIP)/ GR - H30-Seisaku-Shitei-008/Ministry of Health, Labour and Welfare, Japan/ GR - The Takeda Science Foundation/ PT - Journal Article DEP - 20260811 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Japan/epidemiology MH - *Cardiovascular Diseases/mortality/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Databases, Factual MH - East Asian People OTO - NOTNLM OT - GLP-1 analogue OT - cardiovascular disease OT - database research OT - heart failure OT - real-world evidence OT - type 2 diabetes EDAT- 2026/08/12 06:05 MHDA- 2026/10/08 05:31 CRDT- 2026/08/12 00:33 PHST- 2026/07/22 00:00 [revised] PHST- 2026/05/07 00:00 [received] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/12 06:05 [pubmed] PHST- 2026/08/12 00:33 [entrez] AID - 10.1111/dom.71209 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10037-10044. doi: 10.1111/dom.71209. Epub 2026 Aug 11. PMID- 42580924 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 1532-8422 (Electronic) IS - 1053-0770 (Linking) VI - 40 IP - 11 DP - 2026 Nov TI - Advances in Cardiovascular Pharmacotherapy. IX. Protection Against Major Adverse Cardiovascular Events by Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Obesity. PG - 3749-3771 LID - S1053-0770(26)00614-2 [pii] LID - 10.1053/j.jvca.2026.07.032 [doi] AB - The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of insulinotropic peptides that replicate the effects of endogenous GLP-1 but have a prolonged duration of action. GLP-1 RAs have had a remarkably profound impact on the treatment of type 2 diabetes and obesity because they substantially improve glycemic control and produce considerable weight loss. The U.S. FDA's requirement that pharmaceutical companies establish the cardiovascular safety of new type 2 diabetes medications coincided with the development of GLP-1 RAs and mandated that trials be conducted to assure that their adverse cardiovascular effect profiles were noninferior to placebo. This FDA requirement proved to be fortuitous because many of the newly developed GLP-1 RAs were shown to cause unanticipated cardiovascular and renal protective effects, which led to their expanded use beyond patients with type 2 diabetes or obesity to those with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure with preserved ejection fraction. This first of two articles on the cardiovascular pharmacology of GLP-1 RAs briefly discusses the physiology of GLP-1, describes the discovery and development of GLP-1 RAs, examines the findings of major clinical trials and their substudies showing that GLP-1 RAs reduce major adverse cardiovascular events in patients with or at high risk for atherosclerotic cardiovascular disease and type 2 diabetes, and finally, reviews the evidence indicating that the GLP-1 RA semaglutide protects against major adverse cardiovascular events in patients with obesity and established cardiovascular disease but not type 2 diabetes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Pagel, Paul S AU - Pagel PS AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. Electronic address: pspagel@mcw.edu. FAU - Hang, Dustin AU - Hang D AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. FAU - Freed, Julie K AU - Freed JK AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. FAU - Crystal, George J AU - Crystal GJ AD - Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL. LA - eng PT - Journal Article PT - Review DEP - 20260719 PL - United States TA - J Cardiothorac Vasc Anesth JT - Journal of cardiothoracic and vascular anesthesia JID - 9110208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - HbA1c OT - MACE OT - incretin OT - myocardial infarction OT - obesity OT - stroke OT - type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was supported entirely by department funds. EDAT- 2026/08/11 23:35 MHDA- 2026/10/13 23:35 CRDT- 2026/08/11 21:56 PHST- 2026/07/15 00:00 [received] PHST- 2026/07/17 00:00 [accepted] PHST- 2026/10/13 23:35 [medline] PHST- 2026/08/11 23:35 [pubmed] PHST- 2026/08/11 21:56 [entrez] AID - S1053-0770(26)00614-2 [pii] AID - 10.1053/j.jvca.2026.07.032 [doi] PST - ppublish SO - J Cardiothorac Vasc Anesth. 2026 Nov;40(11):3749-3771. doi: 10.1053/j.jvca.2026.07.032. Epub 2026 Jul 19. PMID- 42575714 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261010 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Tirzepatide Persistence and Associated Changes in Clinical Outcomes in US Adults With Obesity or Overweight: A 6-Month Claims Database Analysis. PG - 9966-9979 LID - 10.1111/dom.71064 [doi] AB - AIMS: Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved in the US for the treatment of Type 2 diabetes (T2D), weight loss and obstructive sleep apnoea. This study aimed to assess the utilisation and effectiveness of tirzepatide among individuals in a large US commercially insured population. MATERIALS AND METHODS: This retrospective, observational study used administrative claims and electronic health records from the Healthcare Integrated Research Database (HIRD). Adults with >/= 1 prescription claim for tirzepatide (for obesity/overweight, without T2D), between November 2023-June 2024 and continuous medical/pharmacy enrollment for >/= 12 months pre-index and >/= 6 months post-index were included. Descriptive analyses included baseline demographic and clinical characteristics, treatment patterns and tirzepatide effectiveness (change from baseline in weight, BMI, cardiometabolic risk factors evaluated among persistent individuals) and were stratified by individuals who were GLP-1 RA naive and individuals who switched to tirzepatide from a GLP-1 RA obesity medication. RESULTS: Of the 22 512 individuals who initiated tirzepatide (mean age: 46 years, 73% female), 55% (n = 12 292) were adherent (PDC >/= 80%) and 68% (n = 15 208) were persistent during the 6-month follow-up period. Of the overall population, 91% (n = 20 554) had >/= 1 obesity-related complication at baseline, with dyslipidaemia, hypertension and anxiety being the most frequent complications. Clinically meaningful mean weight reduction (10.5%; n = 808) and numerical reductions in most cardiometabolic risk factors were observed among persistent individuals with available pre- and post-index measurements, including 12.0% body weight reduction in the GLP-naive subgroup. CONCLUSIONS: Over half of US adults with obesity or overweight who initiated tirzepatide were adherent (PDC >/= 80%) and had a favourable persistence profile during a 6-month follow-up period. Persistent users achieved clinically meaningful weight reduction and numerical reductions in most cardiometabolic risk factors. CI - (c) 2026 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gibble, Theresa Hunter AU - Gibble TH AUID- ORCID: 0000-0001-8412-9175 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Venkataraman, Malvika AU - Venkataraman M AD - Carelon Research, Wilmington, Delaware, USA. FAU - Mojdami, Donna AU - Mojdami D AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Vallarino, Carlos AU - Vallarino C AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Stockbower, Grace AU - Stockbower G AD - Carelon Research, Wilmington, Delaware, USA. FAU - Grabner, Michael AU - Grabner M AUID- ORCID: 0000-0002-6521-1007 AD - Carelon Research, Wilmington, Delaware, USA. FAU - Ananth, Mythili AU - Ananth M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Desai, Karishma AU - Desai K AUID- ORCID: 0000-0001-6108-4154 AD - Carelon Research, Wilmington, Delaware, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Observational Study DEP - 20260810 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Obesity/drug therapy/complications MH - Adult MH - United States/epidemiology MH - *Overweight/drug therapy/complications MH - Diabetes Mellitus, Type 2/drug therapy MH - Databases, Factual MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Anti-Obesity Agents/therapeutic use MH - Hypoglycemic Agents/therapeutic use PMC - PMC13646385 OTO - NOTNLM OT - obesity OT - real-world OT - tirzepatide OT - weight reduction COIS- Theresa Hunter Gibble, Donna Mojdami, Carlos Vallarino and Mythili Ananth are employees and stockholders of Eli Lilly and Company. Malvika Venkataraman, Grace Stockbower, Michael Grabner and Karishma Desai are employees of Carelon Research. Michael Grabner and Karishma Desai are stockholders of Elevance Health. EDAT- 2026/08/11 00:35 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/10 21:43 PHST- 2026/06/23 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/06/23 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/11 00:35 [pubmed] PHST- 2026/08/10 21:43 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71064 [pii] AID - 10.1111/dom.71064 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):9966-9979. doi: 10.1111/dom.71064. Epub 2026 Aug 10. PMID- 42575344 OWN - NLM STAT- MEDLINE DCOM- 20260829 LR - 20260829 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 239 DP - 2026 Sep TI - Changes in recorded background glucose-lowering therapy after initiation of a GLP-1 receptor agonist or dual GIP/GLP-1 receptor agonist in adults with type 2 diabetes. PG - 113493 LID - S0168-8227(26)00413-4 [pii] LID - 10.1016/j.diabres.2026.113493 [doi] AB - AIMS: To evaluate changes in recorded background glucose-lowering active-substance counts after initiation of a glucagon-like peptide-1 (GLP-1) or dual GIP/GLP-1 receptor agonist. METHODS: This retrospective cohort study used anonymized electronic health records from a large Polish private outpatient network. Adults with type 2 diabetes (ICD-10 E11 without E10) initiating semaglutide, liraglutide, dulaglutide, or tirzepatide, with at least one recorded baseline non-GLP-1 glucose-lowering active substance, were included. Using medication-specific dates, substances were classified as baseline (before index) or subsequently recorded (on or after index), and within-patient change as a lower count, no change, or a higher count. RESULTS: Among 3,660 patients (median age, 60 years; 53.9% women), the median recorded count rose from 1 [interquartile range, 1-2] to 2 [1-3], though the median within-patient change was 0 [0-1]. A lower count occurred in 17.2% of patients, no change in 38.8%, and a higher count in 44.0%, most frequently with dulaglutide (52.9%) and least with tirzepatide (20.4%). CONCLUSIONS: After medication-date validation, a higher count was more common than a lower count, though it occurred in fewer than half of patients. These findings describe prescription-record patterns and do not establish concomitant exposure, treatment intensity, or a causal effect. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Dziewierz, Artur AU - Dziewierz A AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland; Second Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. FAU - Kulicka, Natalia AU - Kulicka N AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland; Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland. FAU - Lupina, Krzysztof AU - Lupina K AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Maruszak, Natalia AU - Maruszak N AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. FAU - Galuszka, Aleksandra AU - Galuszka A AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Domienik-Karlowicz, Justyna AU - Domienik-Karlowicz J AD - Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland; College of Medical Sciences in Warsaw, Warsaw, Poland. FAU - Rulkiewicz, Anna AU - Rulkiewicz A AD - LUX MED Group, Warsaw, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland; College of Medical Sciences in Warsaw, Warsaw, Poland; LUX MED Group, Warsaw, Poland. Electronic address: zbigniew.siudak@gmail.com. LA - eng PT - Journal Article DEP - 20260810 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Semaglutide MH - Retrospective Studies MH - Tirzepatide MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - *Blood Glucose/drug effects/metabolism MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Gastric Inhibitory Polypeptide/agonists MH - *Receptors, Gastrointestinal Hormone/agonists MH - Adult OTO - NOTNLM OT - Diabetes mellitus OT - Dual GIP/GLP-1 receptor agonist OT - Glucagon-like peptide-1 receptor agonists OT - Real-world data OT - Semaglutide OT - Tirzepatide OT - Treatment patterns OT - Type 2 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/11 00:35 MHDA- 2026/08/29 23:35 CRDT- 2026/08/10 19:15 PHST- 2026/06/22 00:00 [received] PHST- 2026/07/16 00:00 [revised] PHST- 2026/08/09 00:00 [accepted] PHST- 2026/08/29 23:35 [medline] PHST- 2026/08/11 00:35 [pubmed] PHST- 2026/08/10 19:15 [entrez] AID - S0168-8227(26)00413-4 [pii] AID - 10.1016/j.diabres.2026.113493 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Sep;239:113493. doi: 10.1016/j.diabres.2026.113493. Epub 2026 Aug 10. PMID- 42575111 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Efficacy and safety of once-weekly semaglutide 2.4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial. PG - 805-817 LID - S2213-8587(26)00133-6 [pii] LID - 10.1016/S2213-8587(26)00133-6 [doi] AB - BACKGROUND: Semaglutide 2.4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m(2) or at least 27 kg/m(2) and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2.4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m(2) and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m(2), with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66.5%) of 242 participants were randomly assigned to semaglutide 2.4 mg and 81 (33.5%) to placebo; 121 (50.0%) participants were female, and 47 (19.4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12.1% [SE 0.6] vs -2.2% [0.8]; estimated treatment difference -9.9 percentage points [95% CI -11.8 to -8.0]; p<0.0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80.5% vs 24.4%; odds ratio [OR] 14.8 [95% CI 7.4 to 29.6]; p<0.0001). Adverse events were reported in 141 (87.6%) of 161 participants in the semaglutide 2.4 mg group and 61 (75.3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2.4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Guo, Lixin AU - Guo L AD - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: guolixin3234@bjhmoh.cn. FAU - Bao, Xiaolei AU - Bao X AD - Novo Nordisk (China) Pharmaceuticals, Beijing, China. FAU - Huang, Kuo-Chin AU - Huang KC AD - Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Kolnes, Kristoffer Jensen AU - Kolnes KJ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Laugesen, Christian AU - Laugesen C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lu, Yibing AU - Lu Y AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Luo, Bifen AU - Luo B AD - Novo Nordisk (China) Pharmaceuticals, Beijing, China; Eisai China, Beijing, China. FAU - Yuan, Guoyue AU - Yuan G AD - Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Kushner, Robert F AU - Kushner RF AD - Departments of Medicine and Medical Education, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. LA - eng SI - ClinicalTrials.gov/NCT06041217 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260810 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - China/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - *Semaglutide/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - East Asian People COIS- Declaration of interests BL was an employee of Novo Nordisk China at the time the study was performed, and is currently an employee of Eisai China. CL is an employee and shareholder of Novo Nordisk A/S. KJK is an employee and shareholder of Novo Nordisk A/S. LG reports grants or contracts from Abbott, AstraZeneca, Bayer, Dreisamtech, Eli Lilly, Hansoh, Hengrui, Hua Medicine, Huadong Medicine, Innovent, Meitekanger Tech, Novo Nordisk, Salubris, Sanofi, Synapsor, and Zense; participation on a data safety monitoring board or advisory board for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Dreisamtech, Dongbao, Eli Lilly, Gan & Lee, Hansoh, Hengrui, Huadong Medicine, Hua Medicine, Innovent, Janssen, Novartis, Novo Nordisk, Merck, Pfizer, Sanofi, Synapsor, Takeda, Zense, and 3sbio; is Chairman of the Chinese Diabetes Society, Director of the Endocrinology Society, Beijing Medical Doctor Association, Former Chairman of the Beijing Diabetes Society, and Vice Director of the Diabetes Committee of Chinese Research Hospital Association. RFK is a consultant or advisory board member for AbbVie, Antag, AstraZeneca, Boehringer Ingelheim, Currax, Eli Lilly, Novo Nordisk, Structure, Viking, and Weight Watchers. XB is an employee of Novo Nordisk China and shareholder of Novo Nordisk A/S. All other authors declare no competing interests. EDAT- 2026/08/11 00:35 MHDA- 2026/09/08 23:35 CRDT- 2026/08/10 18:52 PHST- 2026/03/12 00:00 [received] PHST- 2026/05/28 00:00 [revised] PHST- 2026/05/28 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/11 00:35 [pubmed] PHST- 2026/08/10 18:52 [entrez] AID - S2213-8587(26)00133-6 [pii] AID - 10.1016/S2213-8587(26)00133-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):805-817. doi: 10.1016/S2213-8587(26)00133-6. Epub 2026 Aug 10. PMID- 42573030 OWN - NLM STAT- MEDLINE DCOM- 20260810 LR - 20260926 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 8 IP - 8 DP - 2026 Aug 10 TI - Glucagon-like peptide-1 receptor agonist-based regimens compared with metformin-based regimens for preventing cardiovascular disease in adults with type 2 diabetes mellitus. PG - CD016380 LID - 10.1002/14651858.CD016380 [doi] LID - CD016380 AB - This is a protocol for a Cochrane review (intervention). The objectives are as follows: To assess the clinical benefits and adverse effects of glucagon-like peptide-1 receptor agonist-based regimens, compared with metformin-based glucose-lowering regimens, for preventing cardiovascular events including all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and metabolic adverse events (including transient hypoglycemia) in adults with type 2 diabetes mellitus across primary and secondary prevention settings. CI - Copyright (c) 2026 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration. FAU - Ahmed, Sana AU - Ahmed S AUID- ORCID: 0000-0002-1658-6574 AD - Department of Food and Nutrition, University of Delhi, New Delhi, India. FAU - McCollin, Sandra P AU - McCollin SP AD - Pharmacy Enterprise, Cambridge Health Alliance, Cambridge, Massachusetts, USA. FAU - Marti-Carvajal, Arturo AU - Marti-Carvajal A AUID- ORCID: 0000-0001-8677-3351 AD - Catedra Rectoral de Medicina Basada en la Evidencia, Universidad de Carabobo, Valencia, Venezuela. AD - Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain. AD - Doctoral Program of Social Science (Health and Society), Universidad de Carabobo, Valencia, Venezuela. FAU - Akus, Monica AU - Akus M AD - Pharmacy Enterprise, Cambridge Health Alliance, Cambridge, Massachusetts, USA. FAU - Baron, David W AU - Baron DW AD - Department of Internal Medicine, Cambridge Health Alliance, Harvard Medical School, Cambridge, Massachusetts, USA. FAU - Abdul Razzaq, Sara AU - Abdul Razzaq S AD - Department of Thoracic Surgery, Tufts Medical Center, Boston, Massachusetts, USA. FAU - Scudder, Paige AU - Scudder P AUID- ORCID: 0000-0003-0513-3315 AD - Hirsh Health Sciences Library, Tufts University, Boston, Massachusetts, USA. FAU - Honigsberg, Elizabeth J AU - Honigsberg EJ AD - Department of Medicine, Dartmouth Health, Lebanon, New Hampshire, USA. FAU - Nasir, Saifuddin AU - Nasir S AD - Department of Internal Medicine, University of Pittsburgh Medical Center (UPMC) Mercy Hospital, Pittsburgh, Pennsylvania, USA. FAU - Peng, Kangning AU - Peng K AD - Department of Medicine, Cambridge Health Alliance, Cambridge, Massachusetts, USA. FAU - Jahanfar, Shayesteh AU - Jahanfar S AUID- ORCID: 0000-0001-6149-1067 AD - Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA. LA - eng PT - Journal Article DEP - 20260810 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Isoindoles) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - 0 (Peptides) RN - 0 (Pyrazines) RN - 0 (Thiazolidinediones) RN - 0 (Venoms) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Exenatide MH - Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Isoindoles/therapeutic use MH - Liraglutide MH - *Metformin/therapeutic use/adverse effects MH - Peptides/therapeutic use MH - Pyrazines/therapeutic use MH - Randomized Controlled Trials as Topic MH - Thiazolidinediones/therapeutic use MH - Venoms/therapeutic use MH - Systematic Reviews as Topic PMC - PMC13455057 COIS- Sana Ahmed: none declared.
Sandra McCollin: none declared.
Arturo Marti-Carvajal: none declared.
Monica Akus: Pfizer (1998 to 2001): pharmacy supply coordinator; this corporation may have an interest in the review given collaborations with companies in the diabetes space. Cambridge Health Alliance: Associate Chief Pharmacy Officer and clinical pharmacist provider.
David Baron: work as a medical doctor providing direct care for Cambridge Health Alliance.
Sara Abdul Razzaq: none declared.
Elizabeth Honigsberg: none declared.
Paige Scudder: none declared.
Saifuddin Nasir: currently working as a resident physician at UPMC Mercy.
Kangning Peng: work as a medical doctor providing direct care for Cambridge Health Alliance.
Shayesteh Jahanfar: none declared. No author holds any financial or non-financial interest in the AI platform used. EDAT- 2026/08/10 12:37 MHDA- 2026/08/10 12:38 PMCR- 2026/08/10 CRDT- 2026/08/10 07:12 PHST- 2026/08/10 12:38 [medline] PHST- 2026/08/10 12:37 [pubmed] PHST- 2026/08/10 07:12 [entrez] PHST- 2026/08/10 00:00 [pmc-release] AID - CD016380 [pii] AID - 10.1002/14651858.CD016380 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2026 Aug 10;8(8):CD016380. doi: 10.1002/14651858.CD016380. PMID- 42572004 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261010 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Bowel Obstruction/Ileus Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists: A Nationwide Database Study. PG - 9941-9954 LID - 10.1111/dom.71189 [doi] AB - AIMS: The association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the development of bowel obstruction/ileus remains unclear, and evidence for specific bowel obstruction/ileus subtypes remains limited. We examined the association between GLP-1RA use and the incidence of bowel obstruction/ileus subtypes across different subgroups of individuals. METHODS: Using the commercially available Japanese administrative claims DeSC database, we identified individuals aged >/= 18 years with type 2 diabetes who newly initiated either GLP-1RAs or sodium-glucose cotransporter 2 inhibitors (SGLT2is) between April 2016 and February 2024. An active-comparator new-user design was adopted, designating GLP-1RA users as the exposure group and SGLT2i users as the control group. The primary outcome was bowel obstruction/ileus requiring tube decompression or surgery within 1 year. Secondary outcomes included specified small bowel obstruction, small bowel obstruction requiring surgery, paralytic ileus and colonic volvulus. Inverse probability weighting with propensity scores was used to adjust for confounding. Adjusted cumulative incidence was estimated using Kaplan-Meier methods; hazard ratios were estimated using Cox regression. RESULTS: Among 298 124 eligible individuals, 25 779 and 272 345 were classified into the GLP-1RA and SGLT2i groups, respectively. The adjusted 1-year incidence proportion of the primary outcome did not significantly differ between groups (0.14% vs. 0.17%; difference -0.03%, 95% confidence interval (CI), -0.10% to 0.04%; hazard ratio 0.80, 95% CI, 0.52-1.24). No significant between-group differences were observed for the secondary outcomes. CONCLUSIONS: GLP-1RA initiation in individuals with type 2 diabetes was not associated with an increased risk of bowel obstruction/ileus compared with SGLT2i initiation. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Matsuo, Yuichiro AU - Matsuo Y AUID- ORCID: 0000-0002-8804-8628 AD - Department of Clinical Epidemiology and Health Economics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. FAU - Okada, Akira AU - Okada A AUID- ORCID: 0000-0001-6480-3388 AD - Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. FAU - Sakamoto, Takashi AU - Sakamoto T AD - Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan. AD - Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. FAU - Yasunaga, Hideo AU - Yasunaga H AD - Department of Clinical Epidemiology and Health Economics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. LA - eng GR - 23AA2003/Ministry of Health, Labour and Welfare/ PT - Journal Article DEP - 20260809 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Intestinal Obstruction/epidemiology/chemically induced MH - Male MH - Databases, Factual MH - Middle Aged MH - Aged MH - Incidence MH - Japan/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Ileus/epidemiology/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Adult PMC - PMC13646363 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - cohort study OT - database research OT - pharmaco-epidemiology COIS- The authors declare no conflicts of interest. EDAT- 2026/08/10 00:40 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/09 22:33 PHST- 2026/07/19 00:00 [revised] PHST- 2026/04/27 00:00 [received] PHST- 2026/07/28 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/10 00:40 [pubmed] PHST- 2026/08/09 22:33 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71189 [pii] AID - 10.1111/dom.71189 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):9941-9954. doi: 10.1111/dom.71189. Epub 2026 Aug 9. PMID- 42570467 OWN - NLM STAT- MEDLINE DCOM- 20261015 LR - 20261015 IS - 2426-0266 (Electronic) IS - 2274-5807 (Print) IS - 2274-5807 (Linking) VI - 13 IP - 9 DP - 2026 Nov TI - Risk of Dementia after initiation of GLP-1 RA versus long-acting insulin in patients with type 2 Diabetes mellitus. PG - 100645 LID - S2274-5807(26)00169-X [pii] LID - 10.1016/j.tjpad.2026.100645 [doi] LID - 100645 AB - BACKGROUND: Recent studies suggest a decreased risk of dementia in patients treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we compare the risk of dementia associated with GLP-1 RA versus long-acting insulin in adults aged over 50 years with type 2 diabetes (T2DM) using real-world administrative data from a large Taiwan cohort DESIGN: A population-based retrospective cohort study SETTING: We analyzed 10,783 propensity score-matched pairs of adults with T2DM who initiated either GLP-1 RA or long-acting insulin from Taiwan's National Health Insurance Research Database (2011-2021). MEASUREMENTS: Primary outcome was new-onset dementia; secondary outcomes included dementia requiring treatment and specific dementia subtypes (Alzheimer's disease, vascular dementia, and unspecified dementia). Hazard ratios (HRs) were estimated using Cox models. RESULTS: Analysis of matched pairs identified 375 cases of newly diagnosed dementia. The incidence rate was 4.86 per 1,000 person-years in GLP-1 RA users versus 7.56 in insulin users. GLP-1 RA use was associated with significantly lower risk of overall dementia (HR 0.64, 95% CI 0.46-0.89, P=0.0072) and unspecified dementia (HR 0.41, 95% CI 0.24-0.68, P=0.0006), but not for Alzheimer's disease (HR 1.48, 95% CI 0.61-3.63, P=0.3867) or vascular dementia (HR 1.66, 95% CI 0.21-13.03, P=0.6324). Among GLP-1 RAs, both liraglutide (HR 0.40, 95% CI 0.20-0.80, P=0.0091) and dulaglutide (HR 0.42, 95% CI 0.19-0.92, P=0.0311) showed significant protective effects against unspecified dementia. CONCLUSIONS: GLP-1 RA use was associated with lower dementia risk versus long-acting insulin in T2DM patients, especially with liraglutide and dulaglutide. As observational, causality requires confirmation from randomized controlled trials. CI - Copyright (c) 2026 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Lin, Chien-Hung AU - Lin CH AD - Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; College of Science and Engineering, Fu Jen Catholic University, New Taipei, Taiwan. FAU - Hung, Peir-Haur AU - Hung PH AD - Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan. FAU - Chung, Mu-Chi AU - Chung MC AD - Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Clinical Toxicology, Department of Medical Toxicology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, 402, Taiwan. FAU - Wu, Laing-You AU - Wu LY AD - Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. FAU - Chung, Chi-Jung AU - Chung CJ AD - Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: cjchung@mail.cmu.edu.tw. LA - eng PT - Journal Article DEP - 20260808 PL - United States TA - J Prev Alzheimers Dis JT - The journal of prevention of Alzheimer's disease JID - 101638820 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin, Long-Acting) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - Retrospective Studies MH - *Dementia/epidemiology/prevention & control MH - Aged MH - Taiwan/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Insulin, Long-Acting/therapeutic use/adverse effects MH - Incidence MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments PMC - PMC13476480 OTO - NOTNLM OT - Basal insulin OT - Dementia OT - Diabetes mellitus OT - Glucagon-like peptide-1 receptor agonist OT - Propensity score-matching OT - Retrospective cohort study COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/09 00:43 MHDA- 2026/10/15 23:30 PMCR- 2026/08/08 CRDT- 2026/08/08 18:04 PHST- 2025/12/29 00:00 [received] PHST- 2026/06/24 00:00 [revised] PHST- 2026/07/03 00:00 [accepted] PHST- 2026/10/15 23:30 [medline] PHST- 2026/08/09 00:43 [pubmed] PHST- 2026/08/08 18:04 [entrez] PHST- 2026/08/08 00:00 [pmc-release] AID - S2274-5807(26)00169-X [pii] AID - 100645 [pii] AID - 10.1016/j.tjpad.2026.100645 [doi] PST - ppublish SO - J Prev Alzheimers Dis. 2026 Nov;13(9):100645. doi: 10.1016/j.tjpad.2026.100645. Epub 2026 Aug 8. PMID- 42552183 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20261015 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 20 IP - 5 DP - 2026 Oct TI - Regional and national trends in prescription of guideline directed cardio-kidney protective medications in people with type 2 diabetes and cardio-kidney disease. PG - 603-612 LID - S1751-9918(26)00148-8 [pii] LID - 10.1016/j.pcd.2026.07.015 [doi] AB - AIMS: Study the treatment gap of guideline-indicated therapies in people with T2D and atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) or chronic kidney disease (CKD). METHODS: We extracted prescription history from 2005 to 2025 from a national dataset, a community-based health system, and an academic center. We assessed treatment gap (current and ever) within four subgroups defined using American Diabetes Association Standards of Care indications for SGLT2i and GLP-1RA use. RESULTS: We identified 6,951,624 people in the national dataset, 58,390 people at the community-based health system, and 15,235 people at the academic center. The current treatment gaps among people with ASCVD (without HF or CKD) were 72%, 67%, and 49%; with ASCVD and HF or CKD3 were 73%, 71%, and 55%; with CKD3 or HF without ASCVD were 75%, 71%, and 65%; with CKD4/5 were 87%, 89%, and 74% within the national dataset, community-based health system, and academic health system, respectively. The ever-prescription rates ranged from 23% to 39%, 30%-47%, 42%-64% within the national dataset, community-based health system, and academic center, respectively. DISCUSSION: Over half the population never received an indicated cardio-kidney protective prescription, and two-thirds lack a current prescription. These gaps were substantial across all systems; however, lowest at the academic center. CI - Published by Elsevier Ltd. FAU - Agarwal, Shubham AU - Agarwal S AD - Division of Endocrinology, Dept of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: shubham.agarwal@utsouthwestern.edu. FAU - Basit, Mujeeb A AU - Basit MA AD - Division of Cardiology, Dept of Internal Medicine and Clinical Informatics Center, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: mujeeb.basit@utsouthwestern.edu. FAU - Marble, Kelsea AU - Marble K AD - The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: kelsea.marble@utsouthwestern.edu. FAU - Mai, Christine AU - Mai C AD - The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: christine.mai@utsouthwestern.edu. FAU - Bowen, Michael E AU - Bowen ME AD - Division of General Internal Medicine, Dept of Internal Medicine and Peter O'Donnell Jr. School of Public Health, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: michael.bowen@utsouthwestern.edu. FAU - Pak, Jonathan AU - Pak J AD - Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd., Ridgefield, CT 06877, USA. Electronic address: jonathan.pak@boehringer-ingelheim.com. FAU - ElNakieb, Yaser AU - ElNakieb Y AD - The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: Yaser.Elnakieb@UTSouthwestern.edu. FAU - Lingvay, Ildiko AU - Lingvay I AD - Division of Endocrinology, Dept of Internal Medicine and Peter O'Donnell Jr. School of Public Health, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. Electronic address: ildiko.lingvay@utsouthwestern.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260804 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/diagnosis MH - Female MH - *Guideline Adherence/trends MH - *Practice Guidelines as Topic MH - United States/epidemiology MH - *Practice Patterns, Physicians'/trends MH - Aged MH - *Renal Insufficiency, Chronic/epidemiology/diagnosis/prevention & control/drug therapy MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Databases, Factual MH - *Diabetic Nephropathies/epidemiology/diagnosis/prevention & control MH - *Professional Practice Gaps/trends MH - *Hypoglycemic Agents/therapeutic use MH - *Heart Failure/epidemiology/diagnosis/prevention & control MH - Undertreatment/trends MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1RA OT - SGLT2i OT - Type 2 diabetes COIS- Declaration of Competing Interest SA, KM, CM, MAB, MEB, YE: None, IL: received research funding (paid to institution) and/or product from NovoNordisk, Boehringer-Ingelheim, Dexcom, Roche, Pfizer, Lilly. IL received research related consulting fees (paid to institution) from NovoNordisk. IL received advisory/consulting fees and/or other support from: Aadvarak Therapeutics, Abbvie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Astra Zeneca, Bain Capital, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Boston Scientific, Carmot, Corxel, Cytoki Pharma, Eli Lilly, Genentech, Intercept, Janssen/J&J, Juvena, Keros Therapeutic, Inc, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Skye Bio, Source Bio, Structure Therapeutics, TERNS Pharma, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma. JP is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). EDAT- 2026/08/09 15:21 MHDA- 2026/09/07 23:34 CRDT- 2026/08/04 21:57 PHST- 2026/02/15 00:00 [received] PHST- 2026/07/06 00:00 [revised] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/08/09 15:21 [pubmed] PHST- 2026/08/04 21:57 [entrez] AID - S1751-9918(26)00148-8 [pii] AID - 10.1016/j.pcd.2026.07.015 [doi] PST - ppublish SO - Prim Care Diabetes. 2026 Oct;20(5):603-612. doi: 10.1016/j.pcd.2026.07.015. Epub 2026 Aug 4. PMID- 42570295 OWN - NLM STAT- MEDLINE DCOM- 20260808 LR - 20260816 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 54 IP - 8 DP - 2026 Aug TI - Trends in glucagon-like peptide-1 receptor agonist utilization and expenditure in Croatia. PG - 3000605261470651 LID - 10.1177/03000605261470651 [doi] LID - 03000605261470651 AB - IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024.MethodsWe conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies.ResultsTotal noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement.ConclusionsGLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs. FAU - Belancic, Andrej AU - Belancic A AUID- ORCID: 0000-0001-7848-6600 AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 FAU - Kucan Stiglic, Marta AU - Kucan Stiglic M AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 FAU - Fajkic, Almir AU - Fajkic A AD - Department of Pathophysiology, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina. RINGGOLD: 112416 FAU - Jelakovic, Ana AU - Jelakovic A AD - Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Pecin, Ivan AU - Pecin I AD - Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Reiner, Zeljko AU - Reiner Z AD - Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Jelakovic, Bojan AU - Jelakovic B AD - Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Vitezic, Dinko AU - Vitezic D AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 LA - eng PT - Journal Article DEP - 20260808 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Croatia/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/economics MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/economics MH - Retrospective Studies MH - *Health Expenditures/trends MH - Recombinant Fusion Proteins/therapeutic use/economics MH - Immunoglobulin Fc Fragments/therapeutic use/economics MH - *Obesity/drug therapy/economics MH - Liraglutide/therapeutic use/economics MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13474226 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - obesity OT - pharmacoepidemiology OT - type 2 diabetes EDAT- 2026/08/08 23:10 MHDA- 2026/08/08 23:11 PMCR- 2026/08/08 CRDT- 2026/08/08 13:53 PHST- 2026/08/08 23:11 [medline] PHST- 2026/08/08 23:10 [pubmed] PHST- 2026/08/08 13:53 [entrez] PHST- 2026/08/08 00:00 [pmc-release] AID - 10.1177_03000605261470651 [pii] AID - 10.1177/03000605261470651 [doi] PST - ppublish SO - J Int Med Res. 2026 Aug;54(8):3000605261470651. doi: 10.1177/03000605261470651. Epub 2026 Aug 8. PMID- 42570103 OWN - NLM STAT- MEDLINE DCOM- 20260826 LR - 20261008 IS - 1432-0932 (Electronic) IS - 0940-6719 (Linking) VI - 35 IP - 9 DP - 2026 Sep TI - Impact of glucagon-like peptide-1 receptor agonists on outcomes following anterior cervical discectomy and fusion: a systematic review and meta-analysis. PG - 5263-5271 LID - 10.1007/s00586-026-10258-y [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Their metabolic, anti-inflammatory, and osteogenic effects raise important questions regarding their influence on spinal fusion. To date, no systematic review has specifically investigated how GLP-1RAs influence outcomes following the common anterior cervical discectomy and fusion (ACDF). This study aimed to evaluate the association between perioperative GLP-1RA use and outcomes following ACDF. METHODS: Following PRISMA guidelines, MEDLINE, Embase, PubMed, and the Cochrane Library were searched from inception to February 2026 for studies evaluating GLP-1RA exposure in the context of ACDF. Eligible studies included human observational cohort studies. Data were extracted independently by two reviewers. RESULTS: Eight retrospective cohort studies analysing 311,402 ACDF patients were included, of whom 8,182 were GLP-1RA users matched to non-users. Random-effects meta-analysis demonstrated significantly lower odds of pseudarthrosis among GLP-1RA users at 6 months (OR = 0.60, 95% CI: 0.52 to 0.71; I(2) = 16.6%), 12 months (OR = 0.62, 95% CI: 0.53 to 0.73; I(2) = 39.1%), and 24 months (OR = 0.67, 95% CI: 0.57 to 0.79; I(2) = 34.9%). Findings for reoperation, dysphagia, deep vein thrombosis, and readmission were heterogeneous and inconsistent across studies. CONCLUSION: Perioperative GLP-1RA use was associated with lower odds of pseudarthrosis. However, evidence regarding other postoperative complications remains inconclusive. Future prospective studies are required to further elucidate the impact of GLP-1RA use on ACDF outcomes. LEVEL OF EVIDENCE: Level III, therapeutic study. CI - (c) 2026. The Author(s). FAU - Duru, Dave Osinachukwu AU - Duru DO AUID- ORCID: 0009-0005-8396-6146 AD - School of Clinical Medicine, University of Cambridge, Cambridge, UK. dd614@cam.ac.uk. FAU - Lee, David Kwan Ryung AU - Lee DKR AD - School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Edmonds, Chloe AU - Edmonds C AD - School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Abraham, Aron AU - Abraham A AD - Imperial College School of Medicine, London, UK. FAU - Peach, Younis AU - Peach Y AD - Imperial College School of Medicine, London, UK. FAU - Louie, Philip K AU - Louie PK AD - Center for Neurosciences and Spine, Virginia Mason Franciscan Health, Seattle, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260808 PL - Germany TA - Eur Spine J JT - European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society JID - 9301980 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cervical Vertebrae/surgery MH - Diabetes Mellitus, Type 2/drug therapy MH - *Diskectomy/adverse effects/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Postoperative Complications/epidemiology/prevention & control MH - *Spinal Fusion/adverse effects/methods MH - Treatment Outcome OTO - NOTNLM OT - Anterior cervical discectomy and fusion OT - Complications OT - GLP-1 OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Pseudarthrosis OT - Spine surgery OT - Type-2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/08/08 23:10 MHDA- 2026/08/26 17:36 CRDT- 2026/08/08 11:13 PHST- 2026/03/03 00:00 [received] PHST- 2026/08/03 00:00 [accepted] PHST- 2026/03/05 00:00 [revised] PHST- 2026/08/26 17:36 [medline] PHST- 2026/08/08 23:10 [pubmed] PHST- 2026/08/08 11:13 [entrez] AID - 10.1007/s00586-026-10258-y [pii] AID - 10.1007/s00586-026-10258-y [doi] PST - ppublish SO - Eur Spine J. 2026 Sep;35(9):5263-5271. doi: 10.1007/s00586-026-10258-y. Epub 2026 Aug 8. PMID- 42568490 OWN - NLM STAT- MEDLINE DCOM- 20260808 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Incretin analogues as cardiovascular agents: a state-of-the-art review. PG - 1898812 LID - 10.3389/fendo.2026.1898812 [doi] LID - 1898812 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide have evolved over the past decade from glucose-lowering antidiabetic agents into a cardiovascular drug class with proven outcome benefit across multiple clinical scenarios. This state-of-the-art review synthesizes the cardiovascular evidence base for incretin analogues, organized by clinical scenario, and addresses the structural challenges that constrain their deployment in low- and middle-income countries (LMICs). We review the pharmacology and proposed cardiovascular mechanisms, including direct effects on the vascular endothelium, macrophage inflammation, and epicardial adipose tissue, alongside indirect benefits mediated by weight loss, glycemic control, and blood pressure reduction. We summarize the evidence in five clinical scenarios: type 2 diabetes with established atherosclerotic cardiovascular disease or high cardiovascular risk; overweight or obesity with established cardiovascular disease but without diabetes; obesity-related heart failure with preserved ejection fraction; chronic kidney disease; and symptomatic peripheral artery disease. Pipeline agents (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, and MariTide) are reviewed alongside their ongoing cardiovascular outcome trials. A dedicated section examines the global access perspective, including the disproportionately high burden of cardiometabolic disease in LMICs, the limited representation of regional populations in pivotal trials, and the structural barriers of cost and reimbursement that constrain access. We close with a practical algorithm for the clinician, an honest assessment of evidence gaps, and a calibrated outlook on the next generation of incretin-based cardiovascular therapy. CI - Copyright (c) 2026 Araiza-Garaygordobil, Rico-Fontalvo, Hernandez-Balbuena, Vinay-Coro and Gonzalez-Arias. FAU - Araiza-Garaygordobil, Diego AU - Araiza-Garaygordobil D AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. AD - Division de Estudios de Posgrado, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Coyoacan, Ciudad de Mexico, Mexico. FAU - Rico-Fontalvo, Jorge AU - Rico-Fontalvo J AD - Comite de Rinon, diabetes y metabolismo, Asociacion Colombiana de Nefrologia e HTA, Bogota, Colombia. AD - Department of Nephrology, Nephromedicall Health Services Provider Institution (IPS), Medellin, Colombia. FAU - Hernandez-Balbuena, Betsabe AU - Hernandez-Balbuena B AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. FAU - Vinay-Coro, Monica AU - Vinay-Coro M AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. FAU - Gonzalez-Arias, Mauricio AU - Gonzalez-Arias M AD - Department of Endocrinology, Hospital Center, New York, NY, United States. LA - eng PT - Journal Article PT - Review DEP - 20260724 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - 0 (Cardiovascular Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Agents/therapeutic use/pharmacology MH - Animals MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13447287 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - heart failure with preserved ejection fraction OT - low- and middle-income countries OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus COIS- DA-G has received speaking fees from Novo Nordisk, AstraZeneca, Novartis, Bayer, Adium, Boehringer-Ingelheim, Servier, and Silanes, and declares active research grants with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, and Bayer. JR-F has received speaking fees from Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, Sanofi, Boehringer-Ingelheim, Merck, and MSD. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/08/08 12:52 MHDA- 2026/08/08 12:53 PMCR- 2026/07/24 CRDT- 2026/08/08 05:08 PHST- 2026/06/03 00:00 [received] PHST- 2026/07/06 00:00 [revised] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/08/08 12:53 [medline] PHST- 2026/08/08 12:52 [pubmed] PHST- 2026/08/08 05:08 [entrez] PHST- 2026/07/24 00:00 [pmc-release] AID - 10.3389/fendo.2026.1898812 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 24;17:1898812. doi: 10.3389/fendo.2026.1898812. eCollection 2026. PMID- 42567173 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis. PG - 818-830 LID - S2213-8587(26)00134-8 [pii] LID - 10.1016/S2213-8587(26)00134-8 [doi] AB - BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1.0 mg [FLOW], once-weekly subcutaneous 2.4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1.73 m(2), or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39.5-47.5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0.84 [95% CI 0.77-0.91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0.80 [0.69-0.92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany. Electronic address: johannes.mann@kms.mhn.de. FAU - Badve, Sunil V AU - Badve SV AD - Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk, Soborg, Denmark. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Colhoun, Helen M AU - Colhoun HM AD - Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Science, University College London, London, UK. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk, Soborg, Denmark. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA. FAU - McGuire, Darren K AU - McGuire DK AD - Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health System, Dallas, TX, USA. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Sattar, Naveed AU - Sattar N AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington, Seattle, WA, USA; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260807 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Renal Insufficiency, Chronic/drug therapy MH - Glomerular Filtration Rate/drug effects MH - Middle Aged MH - Aged MH - *Kidney/drug effects MH - Treatment Outcome COIS- Declaration of interests JFEM declares grants from Novo Nordisk; consulting fees from Bayer and Novo Nordisk; honoraria from AstraZeneca, Bayer, Cytel, Hexal, ICON, IQVIA, Novo Nordisk, UpToDate, and WCG; has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, and Sanofi; and has a leadership role in the KDIGO group. SVB declares consulting fees from AstraZeneca, Bayer, GSK, and Vifor Pharma; speaking fees from AstraZeneca, Bayer, Pfizer, and Vifor Pharma (all honoraria paid to institution); and non-financial research support from Bayer. KB-F, TI, and GKH are former employees of Novo Nordisk. JBB declares salary support from clinical trial contracts to his employer from Corcept Therapeutics, Dexcom, GentiBio, and Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand Pharma; and holds stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. HMC declares consulting fees from Roche and Sanofi; serving on advisory panels for Bayer and Novo Nordisk; research grants from Chief Scientist Office, Diabetes UK, European Commission, IQVIA, Breakthrough T1D, Medical Research Council, and Sanofi; support to attend meetings/travel from Novo Nordisk; and payment or honoraria from Medscape. JED declares consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; payment or honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; and a research grant from Alzheimer's Research UK. AML declares consulting honoraria from Akebia, Alnylam, Amgen, Ardelyx, Becton Dickinson, BrainStorm Cell Therapeutics, Canary Cure, Eli Lilly, Endologix, FibroGen, GSK, Intarcia, Medtronic, Neovasc, Novo Nordisk, Provention Bio, and Recor; and research funding (to institution) from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion, and Novartis. IL declares research funding (paid to institution) and trial product related to investigator initiated studies from Novo Nordisk; clinical trial work for Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Pfizer, and Roche; research-related consulting fees (paid to institution) from Novo Nordisk; and travel and publication support from AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bain Capital, Bayer, Betagenon, BIOIO, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Corxel, Cytoki Pharma, Eli Lilly, Genentech, Intercept, Janssen/Johnson & Johnson, Juvena, Keros Therapeutics, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bioscience, Structure Therapeutics, TERNS Pharma, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma. KWM declares grants from the American College of Cardiology, American Heart Association, Apple, California Institute for Regenerative Medicine, CSL Behring, Cytokinetics, Eidos, Element, Google (Verily), Idorsia, Johnson & Johnson, Novartis, PAC-12, Precordior, and St Jude Medical; consulting fees from Applied Therapeutics, BridgeBio, Bristol Myers Squibb, Eli Lilly, Elsevier, Fosun Pharma, Human, Moderna, MyoKardia, Novo Nordisk, PhaseBio, Quidel, Scleroderma Foundation, and Theravance; payment or honoraria from CSL Behring; and equity in Human, Medeloop, Precordior, and Regencor. DKM declares consulting fees from Alveus Therapeutics, Amgen, Boehringer Ingelheim, F Hoffmann La Roche, Eli Lilly, Kailera, Lexicon, Metsera, Neurotronic, Novo Nordisk, Regor, and Zealand Pharma; trial leadership for Amgen, Boehringer Ingelheim, Eli Lilly, Metsera, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Pfizer; and research support from Amgen, Boehringer Ingelheim, Eli Lilly, Metsera, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Pfizer. REP declares speaker fees from Corcept Therapeutics, Lilly USA, and Novo Nordisk; consulting fees from AbbVie, Altanine, AstraZeneca, Bayer, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui, Intas Pharmaceuticals, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and investigator-initiated grant support from Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, Roche, and Sanofi. PR declares consultancy and/or speaking fees (paid to institution) from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk, and Sanofi; research grants from AstraZeneca, Bayer, and Novo Nordisk; and study drugs for investigator-initiated studies from Bayer, Novo Nordisk, and Lexicon Pharmaceuticals. NS declares consulting fees and/or speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GSK, Hanmi Pharmaceutical, Kailera, Mass Medicines, Menarini Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio; grant support (paid to institution) from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work; and is Chair of the Obesity Healthcare Programme at the UK Government Office for Life Sciences. KRT declares grants (paid to institution) from Bayer, Otsuka, Travere Therapeutics, US National Institute of Diabetes and Digestive and Kidney Diseases, US National Heart, Lung, and Blood Institute, US National Institute on Minority Health and Health Disparities, US National Center for Advancing Translational Sciences, US National Institutes of Health Director's Office, US Centers for Disease Control and Prevention, Doris Duke Foundation, Benaroya Research Institute, and Breakthrough T1D; consulting fees and/or honoraria for lectures, presentations, speakers bureaus, and educational events from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Novo Nordisk, Otsuka, Roche, and Travere Therapeutics; provides unpaid participation as the Data Safety and Monitoring Board Chair for the George Clinical Institute and US National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health; and is Chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology. VP declares consultancy or honoraria for steering committee, data monitoring committee, or advisory board roles from AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Chinook, GSK, Guard Therapeutics, Incyte, Janssen, Mineralys, Novo Nordisk, Novartis, Otsuka, Shaanxi Micot, Travere Therapeutics, Tricida, and Vifor Pharma; is a board member of Kidney Health Australia and St Vincent's Health Australia; and declares an ownership interest in George Clinical. FMMB, NB, MDME, and SR are employees and stockholders of Novo Nordisk. EDAT- 2026/08/08 00:37 MHDA- 2026/09/08 23:35 CRDT- 2026/08/07 18:52 PHST- 2026/01/21 00:00 [received] PHST- 2026/05/28 00:00 [revised] PHST- 2026/05/28 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/08 00:37 [pubmed] PHST- 2026/08/07 18:52 [entrez] AID - S2213-8587(26)00134-8 [pii] AID - 10.1016/S2213-8587(26)00134-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):818-830. doi: 10.1016/S2213-8587(26)00134-8. Epub 2026 Aug 7. PMID- 42563367 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Time to Insulin Initiation Among Patients With Type 2 Diabetes Treated With Second-Line Antidiabetic Drugs. PG - 9655-9667 LID - 10.1111/dom.71182 [doi] AB - OBJECTIVE: To examine the effect of second-line treatments (insulin secretagogues, thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose co-transporter 2 (SGLT-2) inhibitors) on time to insulin initiation among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using the Clinical Practice Research Datalink (CPRD) Aurum. Initiation of metformin monotherapy (1998-2021) defined base cohort entry, and initiation of second-line treatment (2013-2021) defined study cohort entry (time zero). After propensity score trimming, we applied inverse probability of treatment weighted Cox models to estimate the association between second-line agents and time to insulin initiation. The secondary outcome was time to treatment modification, defined as the addition of or switch to another antidiabetic drug class. RESULTS: Our analytic cohort included 64 404 patients; 44% initiated DPP-4 inhibitors, 36% insulin secretagogues, 18% SGLT-2 inhibitors, 1% thiazolidinediones and 3% GLP-1 receptor agonists. Over a mean follow-up of 2.9 years, initiation of TZDs, DPP-4 inhibitors, or SGLT-2 inhibitors was associated with a lower risk of insulin initiation than initiation of insulin secretagogues (HR [95% CI]: 0.59 [0.43-0.83], 0.75 [0.69-0.80] and 0.62 [0.56-0.68], respectively). For treatment modification, the risk was higher among TZD and DPP-4 inhibitor initiators, and slightly lower among SGLT-2 inhibitor initiators and GLP-1 receptor agonist initiators than among insulin secretagogue initiators. CONCLUSION: This study provides real-world evidence that TZDs, DPP-4 inhibitors and SGLT-2 inhibitors may offer an advantage over insulin secretagogues in delaying insulin initiation after metformin monotherapy. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yu, Ya-Hui AU - Yu YH AD - Department of Epidemiology, Rollin School of Public Health, Emory University, Atlanta, Georgia, USA. FAU - Zhang, Qi AU - Zhang Q AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. FAU - Zapata-Bravo, Estefania AU - Zapata-Bravo E AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. AD - Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada. FAU - Platt, Robert W AU - Platt RW AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. AD - Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada. AD - Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada. FAU - Reynier, Pauline AU - Reynier P AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. FAU - Yu, Oriana H Y AU - Yu OHY AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada. FAU - Filion, Kristian B AU - Filion KB AUID- ORCID: 0000-0001-6055-0088 AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. AD - Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada. LA - eng PT - Journal Article DEP - 20260806 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Insulin Secretagogues) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (PPAR-gamma Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Female MH - *Insulin/therapeutic use MH - Male MH - Retrospective Studies MH - Middle Aged MH - Insulin Secretagogues MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Metformin/therapeutic use MH - Treatment Delay MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - PPAR-gamma Agonists MH - Time Factors PMC - PMC13538751 OTO - NOTNLM OT - UK OT - insulin initiation OT - population-based cohort study OT - second-line antidiabetic medication OT - type 2 diabetes COIS- R.W.P. has received personal fees from Analysis Group, Biogen, Merck/Organon, Merck KGAA and Pfizer, all outside of the submitted work. K.B.F. has received personal fees from Regeneron and Statlog, all outside of the submitted work. EDAT- 2026/08/07 06:35 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/08/07 01:24 PHST- 2026/07/20 00:00 [revised] PHST- 2026/03/12 00:00 [received] PHST- 2026/07/25 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/08/07 06:35 [pubmed] PHST- 2026/08/07 01:24 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71182 [pii] AID - 10.1111/dom.71182 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9655-9667. doi: 10.1111/dom.71182. Epub 2026 Aug 6. PMID- 42562072 OWN - NLM STAT- MEDLINE DCOM- 20261016 LR - 20261016 IS - 2210-741X (Electronic) IS - 2210-7401 (Linking) VI - 50 IP - 8 DP - 2026 Oct TI - Safety and effectiveness of GLP-1 receptor agonists and SGLT-2 inhibitors in liver transplant recipients with diabetes. PG - 102899 LID - S2210-7401(26)00145-2 [pii] LID - 10.1016/j.clinre.2026.102899 [doi] AB - BACKGROUND: We studied the safety and effectiveness of glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) in liver transplant recipients with diabetes. METHODS: This retrospective single-center study included 41 patients treated with GLP1-RAs and/or SGLT2is after liver transplantation (LT) who were compared to a control group receiving antidiabetic treatment excluding GLP1-RAs and/ SGLT2is. RESULTS: The treatment group showed no serious adverse events, with 15.0% experiencing moderate side effects, primarily gastrointestinal disorders. The HbA1c target concentration was achieved in 90.0% (n=36) of patients in the GLP1-RA and/or SGLT2i group versus 74.0% (n = 42) in the control-group (p = 0.16). The fasting glycaemia target was reached by a higher proportion of patients in the GLP1-RA and/or SGLT2i group than in the control-group: 80.0% versus 55.0%, p = 0.033. Insulin withdrawal was greater in the group of patients receiving GLP1-RAs and/or SGLT2is treatment, in particular for those with post-transplant diabetes (80.0% vs. 0%, p < 0.01). The median time of follow-up was 11.0 months (IQR: 6-13). CONCLUSIONS: Our results suggest the safety of GLP1-RAs and SGLT2is treatment, with the remarkable benefit of insulin withdrawal for a subgroup of patients with new-onset diabetes. However, larger prospective studies are needed to assess the long-term impact on cardiovascular events, obesity, liver steatosis, and mortality. CI - Copyright (c) 2026. Published by Elsevier Masson SAS. FAU - Mazzola, Alessandra AU - Mazzola A AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. Electronic address: alessandra.mazzola2@aphp.fr. FAU - Sultanik, Philippe AU - Sultanik P AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. FAU - Rebiha, Aida AU - Rebiha A AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. FAU - Pais, Raluca AU - Pais R AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. FAU - Thabut, Dominique AU - Thabut D AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France; Sorbonne Universite, INSERM, Centre de Recherche de Saint -Antoine (CRSA), 75012, Paris, France. FAU - Scatton, Olivier AU - Scatton O AD - Sorbonne Universite, INSERM, Centre de Recherche de Saint -Antoine (CRSA), 75012, Paris, France; Sorbonne Universite, Service de Chirurgie Hepatobiliaire et Transplantation Hepatique, AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. FAU - Bourron, Olivier AU - Bourron O AD - Sorbonne Universite, Service de Diabetologie, AP-HP, Hopital Pitie-Salpetriere, Paris, France; UMRS_1166, INSERM, Paris, France. FAU - Conti, Filomena AU - Conti F AD - Sorbonne Universite, Unite Medicale de Transplantation Hepatique Service d'Hepato gastroenterologie AP-HP, Hopital Pitie-Salpetriere, 75013, Paris, France. LA - eng PT - Journal Article DEP - 20260806 PL - France TA - Clin Res Hepatol Gastroenterol JT - Clinics and research in hepatology and gastroenterology JID - 101553659 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Liver Transplantation MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Treatment Outcome MH - Aged OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Glycemic control OT - Insulin withdrawal OT - New-onset diabetes OT - Sodium-glucose co-transporter-2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/07 00:35 MHDA- 2026/10/16 23:33 CRDT- 2026/08/06 19:16 PHST- 2026/04/06 00:00 [received] PHST- 2026/07/26 00:00 [revised] PHST- 2026/08/03 00:00 [accepted] PHST- 2026/10/16 23:33 [medline] PHST- 2026/08/07 00:35 [pubmed] PHST- 2026/08/06 19:16 [entrez] AID - S2210-7401(26)00145-2 [pii] AID - 10.1016/j.clinre.2026.102899 [doi] PST - ppublish SO - Clin Res Hepatol Gastroenterol. 2026 Oct;50(8):102899. doi: 10.1016/j.clinre.2026.102899. Epub 2026 Aug 6. PMID- 42561183 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261025 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 11 DP - 2026 Nov 1 TI - The Gain-of-Function GLP1R R131Q Variant Preserves beta-Cell Function and Enhances Response to GLP-1 Receptor Agonists. PG - 1982-1990 LID - 10.2337/dc26-0662 [doi] AB - OBJECTIVE: Genetic variation in the glucagon-like peptide 1 receptor (GLP1R) has been implicated in type 2 diabetes (T2D) risk and treatment response. We investigated whether GLP1R R131Q, which was previously reported as a T2D-protective variant in genome-wide association studies, alters receptor signaling, beta-cell function, and response to glucagon-like peptide 1 receptor agonists (GLP-1RAs). RESEARCH DESIGN AND METHODS: Trajectory of beta-cell function was evaluated in a 20-year community-based prospective cohort in Korea (n = 6,373), where participants underwent biennial 2-h 75-g oral glucose tolerance tests, and disposition index was used as surrogate marker. Pharmacogenetic response to GLP-1RAs was assessed in a hospital-based T2D cohort in Korea (n = 177). Hyperglycemic clamp studies (n = 17), human islet experiments (n = 21), and in vitro assays were conducted to characterize GLP1R R131Q effects on receptor signaling and islet function. RESULTS: GLP1R R131Q was associated with slower decline in disposition index in individuals without T2D, with reductions from baseline of 30% in homozygous carriers, 35% in heterozygotes, and 37% in wild-type individuals. In people with T2D, each allele conferred an additional 0.53% or 5.8 mmol/mol reduction in HbA1c after 6 months of GLP-1RA treatment (P = 5.8 x 10-4). Hyperglycemic clamp and human islet experiments demonstrated allele-dependent enhancement of GLP-1RA-stimulated insulin secretion (P = 0.050 and P = 0.037, respectively). In vitro, GLP1R R131Q increased GLP-1RA-stimulated cAMP production with directional observations consistent with pathway bias. CONCLUSIONS: GLP1R R131Q is a gain-of-function variant associated with preservation of beta-cell function and enhanced glycemic response to GLP-1RA treatment, supporting further investigation as a candidate pharmacogenetic marker for precision diabetes care. CI - (c) 2026 by the American Diabetes Association. FAU - Lee, Hyunsuk AU - Lee H AUID- ORCID: 0000-0001-9751-5868 AD - Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Christie, Hannah E AU - Christie HE AUID- ORCID: 0000-0002-0606-6778 AD - Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Lee, Ji Seon AU - Lee JS AD - Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea. FAU - Kwon, Woo-Il AU - Kwon WI AD - Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Moon, Min Kyong AU - Moon MK AUID- ORCID: 0000-0002-5460-2846 AD - Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Choi, Sung Hee AU - Choi SH AUID- ORCID: 0000-0003-0740-8116 AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. FAU - Lee, Dae Ho AU - Lee DH AUID- ORCID: 0000-0002-8832-3052 AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea. FAU - Lee, Seunggeun AU - Lee S AD - Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea. FAU - Lee, Hyunbeom AU - Lee H AD - Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology, Seoul, Republic of Korea. FAU - Kho, Minjung AU - Kho M AD - Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea. FAU - Boscolo, Federica AU - Boscolo F AUID- ORCID: 0009-0003-0545-7288 AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Dalla Man, Chiara AU - Dalla Man C AUID- ORCID: 0000-0002-4908-0596 AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Cho, Nam H AU - Cho NH AUID- ORCID: 0000-0003-4551-7591 AD - Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Choi, Jaewon AU - Choi J AUID- ORCID: 0000-0002-3735-625X AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Lee, Jeongeun AU - Lee J AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Park, Jongseok AU - Park J AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Jo, Yeeun AU - Jo Y AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Lee, Sangwon AU - Lee S AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Vella, Adrian AU - Vella A AUID- ORCID: 0000-0001-6493-7837 AD - Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Kwak, Soo Heon AU - Kwak SH AUID- ORCID: 0000-0003-1230-0919 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Kim, Jong-Il AU - Kim JI AUID- ORCID: 0000-0002-7240-3744 AD - Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Park, Kyong Soo AU - Park KS AUID- ORCID: 0000-0003-3597-342X AD - Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea. LA - eng GR - 800-20240636/SNU-SNUH Physician Scientist Training Program/ GR - 23212MFDS202/Ministry of Food and Drug Safety/ GR - DK126206, DK78646, DK116231, DK126206 and DK126206/DK/NIDDK NIH HHS/United States GR - RS-2023-00262002/Ministry of Science and ICT, South Korea/ GR - MD-PhD/Medical Scientist Training Program/Korea Health Industry Development Institute/ GR - RS-2026-25516569/Korea Health Industry Development Institute/ GR - 2020R1A6A1A03047972/National Research Foundation of Korea/ GR - DK126206, DK78646, DK116231, DK126206 and DK126206/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Diabetes Care. 2026 Nov 1;49(11):1941-1943. doi: 10.2337/dci26-0115. PMID: 42900828 MH - Humans MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Female MH - *Diabetes Mellitus, Type 2/genetics/drug therapy/metabolism MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Prospective Studies MH - Hypoglycemic Agents/therapeutic use MH - Glucose Tolerance Test MH - Adult PMC - PMC13690992 COIS- Duality of Interest. A.V. has consulted for Boehringer-Ingelheim and Rezolute. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/08/06 18:35 MHDA- 2026/10/20 17:34 PMCR- 2026/08/06 CRDT- 2026/08/06 16:03 PHST- 2026/03/18 00:00 [received] PHST- 2026/07/13 00:00 [accepted] PHST- 2026/10/20 17:34 [medline] PHST- 2026/08/06 18:35 [pubmed] PHST- 2026/08/06 16:03 [entrez] PHST- 2026/08/06 00:00 [pmc-release] AID - 172309 [pii] AID - 260662 [pii] AID - 10.2337/dc26-0662 [doi] PST - ppublish SO - Diabetes Care. 2026 Nov 1;49(11):1982-1990. doi: 10.2337/dc26-0662. PMID- 42557064 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260914 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials. PG - 9607-9620 LID - 10.1111/dom.70895 [doi] AB - AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate >/= 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m(2)) and liver (total bilirubin 21 mumol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229). CI - (c) 2026 Novo Nordisk A/S and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Andersen, Jonas Dahl AU - Andersen JD AUID- ORCID: 0000-0001-6619-9161 AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - Benamar, Malik AU - Benamar M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ponzani, Paola AU - Ponzani P AD - SSD Diabetology and Metabolic Diseases, Azienda Sanitaria Locale, Genoa, Italy. FAU - Unnikrishnan, A G AU - Unnikrishnan AG AD - Chellaram Diabetes Institute, Pune, India. FAU - Vinther, Siri AU - Vinther S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rea, Rosangela AU - Rea R AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal Do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05013229 SI - ClinicalTrials.gov/NCT05352815 SI - ClinicalTrials.gov/NCT05259033 GR - Novo Nordisk A/S/ PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20260805 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/physiopathology MH - *Hypoglycemia/chemically induced/epidemiology MH - Female MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Male MH - Semaglutide MH - Treatment Outcome MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Liver/physiopathology/drug effects MH - Glycated Hemoglobin/analysis MH - Kidney/physiopathology/drug effects MH - Aged MH - Drug Therapy, Combination MH - Glomerular Filtration Rate MH - Insulin/administration & dosage/adverse effects MH - Blood Glucose MH - Liver Function Tests MH - Drug Administration Schedule PMC - PMC13538793 OTO - NOTNLM OT - GLP-1 analogue OT - basal insulin OT - fixed-ratio combination OT - glycaemic control OT - hypoglycaemia OT - type 2 diabetes COIS- L.J. reports receiving consulting or speaking fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics and Sinocare; and is an Independent Director of Shanghai Benemae Pharmaceutical Corporation. J.D.A., M.B. and S.V. are employees and shareholders of Novo Nordisk A/S. P.P. reports fees for consultancy services and advisory boards for Eli Lilly, Novo Nordisk, Roche Diabetes Care and Sanofi; reports speaker fees for AstraZeneca, Eli Lilly, Laboratori Guidotti, MSD and Sanofi; and received research support from AstraZeneca, Bayer, Novartis and Novo Nordisk. A.G.U. has received research support, received consultant fees or has served on advisory panels for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Servier. R.R. is a formal adviser for Boehringer Ingelheim, Eli Lily, Novo Nordisk and Sanofi; reports research activities with AstraZeneca, Boehringer Ingelheim, Eli Lily, Novo Nordisk and Sanofi; and has participated in a speaker's bureau for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lily and Novo Nordisk. EDAT- 2026/08/06 11:36 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/08/05 21:42 PHST- 2026/05/11 00:00 [revised] PHST- 2026/01/19 00:00 [received] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 21:42 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM70895 [pii] AID - 10.1111/dom.70895 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9607-9620. doi: 10.1111/dom.70895. Epub 2026 Aug 5. PMID- 42556958 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20260805 IS - 1878-0555 (Electronic) IS - 0065-3411 (Linking) VI - 60 IP - 1 DP - 2026 Sep TI - Surgery on Patients Taking Glucagon-Like Peptide-1 Receptor Agonists. PG - 285-298 LID - S0065-3411(26)00011-4 [pii] LID - 10.1016/j.yasu.2026.03.011 [doi] AB - This article begins by providing historical insight into the discovery, development, and use of glucagon-like peptide-1 receptor (GLP-1R) agonist medications in the treatment of type 2 diabetes and obesity. Next, the mechanism of action and impacts of GLP-1R agonists are discussed, along with an overview of the Food and Drug Administration-approved GLP-1R agonists currently on the market. Comparison in effects on weight loss of the available GLP-1R agonists is briefly discussed, along with its use in the context of bariatric surgery. Finally, perioperative considerations for surgical patients using GLP-1R agonists are reviewed along with suggested recommendations. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Rosen, Claire B AU - Rosen CB AD - Division of GI Surgery, Department of Surgery, Massachusetts General Brigham, Boston, MA, USA. Electronic address: cbrosen@mgh.harvard.edu. FAU - Gee, Denise W AU - Gee DW AD - Division of GI Surgery, Department of Surgery, Massachusetts General Brigham, Boston, MA, USA. LA - eng PT - Journal Article PT - Review DEP - 20260626 PL - United States TA - Adv Surg JT - Advances in surgery JID - 0045335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Venoms) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Bariatric Surgery/methods MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy/surgery MH - Weight Loss/drug effects MH - Exenatide MH - Peptides/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Venoms/therapeutic use MH - Tirzepatide MH - Liraglutide MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Glucagon-Like Peptide 1/analogs & derivatives OTO - NOTNLM OT - Bariatric surgery OT - GLP-1R agonists OT - Obesity OT - Perioperative management OT - Weight loss COIS- Disclosure The authors have no financial disclosures or conflicts of interest to disclose. EDAT- 2026/08/06 11:36 MHDA- 2026/08/06 11:37 CRDT- 2026/08/05 20:55 PHST- 2026/08/06 11:37 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 20:55 [entrez] AID - S0065-3411(26)00011-4 [pii] AID - 10.1016/j.yasu.2026.03.011 [doi] PST - ppublish SO - Adv Surg. 2026 Sep;60(1):285-298. doi: 10.1016/j.yasu.2026.03.011. Epub 2026 Jun 26. PMID- 42556638 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261020 IS - 2212-2672 (Print) IS - 2212-2672 (Linking) VI - 126 IP - 11 DP - 2026 Nov TI - Cross-Sectional Survey Results of Registered Dietitian Nutritionists of the Weight Management and Diabetes Dietetic Practice Groups of the Academy of Nutrition and Dietetics Providing Medical Nutrition Therapy to People Using Glucagon-Like Peptide-1 Receptor Agonist-Based Therapy. PG - 156432 LID - S2212-2672(26)00147-4 [pii] LID - 10.1016/j.jand.2026.156432 [doi] AB - BACKGROUND: Registered dietitian nutritionists (RDNs) should be essential contributors to weight management and diabetes care for people using glucagon-like peptide-1 receptor agonist-based therapy (GLP-1 RA-based therapy) because they provide education, prevent and manage side effects, and address nutritional deficiencies. Little is known about the practice behaviors of RDNs providing care to people using these medications. OBJECTIVE: To determine demographic, professional characteristics, and practice behaviors of RDNs who provide medical nutrition therapy (MNT) to people using GLP-1 RA-based therapy diagnosed with either obesity or diabetes. DESIGN: An online, cross-sectional survey was distributed from May 28, 2025, through June 25, 2025, consisting of 55 questions covering topics such as screening for eating disorders and malnutrition, nutrition assessment, diagnosis, intervention, monitoring, and evaluation within the Nutrition Care Process. RESPONDENTS: The sample included 212 RDNs who were members of the Weight Management Dietetic Practice Group and/or the Diabetes Dietetic Practice Group of the Academy of Nutrition and Dietetics and had experience working with people receiving GLP-1 RA-based therapy. STATISTICAL ANALYSIS PERFORMED: Survey data were analyzed via descriptive statistics. RESULTS: Respondents were women (95.3%), with 20.4 +/- 11.9 years of experience, 64.1% held a master's degree, and 61.5% worked in an outpatient or ambulatory clinic. Regarding assessment practices, 26.4% screen for eating disorders, 42.9% perform a nutrition-focused physical exam, and 31.1% routinely assess body composition. The RDN respondents most commonly recommend monitoring for vitamin D (78.2%) and iron (75%) deficiencies. More than 80% of respondents "strongly agree" (62.0%) or "somewhat agree" (22.4%) that there is a need to create specific GLP-1 RA-based therapy MNT practice guidelines. CONCLUSIONS: This survey not only identifies key patterns of consistency and variation in practice among RDNs but also reinforces the integral role that RDNs play in supporting and managing people on GLP-1 RA-based therapy. A majority of RDNs indicated a need to develop dietetic-specific MNT guidelines for GLP-1 RA-based therapy. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Cardamone, Kelly AU - Cardamone K AD - School of Health Professions, Rutgers University, Newark, New Jersey. FAU - Byham-Gray, Laura AU - Byham-Gray L AD - School of Health Professions, Rutgers University, Newark, New Jersey. FAU - Sackey, Joachim AU - Sackey J AD - School of Health Professions, Rutgers University, Newark, New Jersey. FAU - Brody, Rebecca AU - Brody R AD - School of Health Professions, Rutgers University, Newark, New Jersey. Electronic address: brodyra@shp.rutgers.edu. LA - eng PT - Journal Article DEP - 20260805 PL - United States TA - J Acad Nutr Diet JT - Journal of the Academy of Nutrition and Dietetics JID - 101573920 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cross-Sectional Studies MH - *Nutritionists/statistics & numerical data MH - Female MH - *Dietetics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Male MH - *Obesity/therapy/diet therapy MH - *Nutrition Therapy/methods MH - Middle Aged MH - Surveys and Questionnaires MH - *Diabetes Mellitus/diet therapy MH - *Diabetes Mellitus, Type 2/diet therapy OTO - NOTNLM OT - GLP-1 OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 RA-based therapy OT - Incretin-based therapies OT - Medical nutrition therapy OT - Registered dietitian nutritionist OT - Survey EDAT- 2026/08/06 11:36 MHDA- 2026/10/20 23:28 CRDT- 2026/08/05 19:20 PHST- 2025/11/16 00:00 [received] PHST- 2026/05/12 00:00 [revised] PHST- 2026/07/29 00:00 [accepted] PHST- 2026/10/20 23:28 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 19:20 [entrez] AID - S2212-2672(26)00147-4 [pii] AID - 10.1016/j.jand.2026.156432 [doi] PST - ppublish SO - J Acad Nutr Diet. 2026 Nov;126(11):156432. doi: 10.1016/j.jand.2026.156432. Epub 2026 Aug 5. PMID- 42556625 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260825 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 231 DP - 2026 Sep TI - The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity. PG - 108365 LID - S1043-6618(26)00280-X [pii] LID - 10.1016/j.phrs.2026.108365 [doi] AB - Owing to the therapeutic success of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists in the management of diabetes and obesity, the pharmacology of these drugs and their receptors has engendered considerable interest. GLP-1 and GIP are incretin hormones so named owing to their ability to increase insulin secretion. Currently FDA-approved GLP-1 peptide receptor agonists used for the management of diabetes include liraglutide, semaglutide, and injectable dulaglutide. Agonists approved for the management of obesity include liraglutide and semaglutide, which have injectable and oral formulations. Tirzepatide is a combined GLP-1 and GIP receptor peptide agonist given by injections that is FDA-approved for the management of type 2 diabetes, obesity, and obese patients with a weight-related comorbidity such as obstructive sleep apnea. Orforglipron is a small molecule orally bioavailable medicine that is approved for the treatment of obesity. Retatrutide is an injectable peptide agonist of GLP-1R, GIPR, and the glucagon receptor that is undergoing clinical trials for the management of obesity and diabetes. The peptides per se undergo rapid degradation in the body. To overcome the need for frequent injections, molecular engineering strategies were used to prolong circulating half-lives. Peptide fatty acid acylation represents one strategy for extending the half-life of peptides by co-opting the role of albumin as a fatty acid transporter thereby retaining peptides in the systemic circulation. A universal side effect of all GLP-1 receptor agonists includes nausea and vomiting. Consequently, the dosage is escalated sequentially over a period of weeks to mitigate these side effects. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Roskoski, Robert Jr AU - Roskoski R Jr AD - Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791, United States. Electronic address: rrj@brimr.org. LA - eng PT - Journal Article PT - Review DEP - 20260806 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Animals MH - *Obesity/drug therapy/metabolism MH - *Receptors, Gastrointestinal Hormone/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - Dulaglutide (PubMed CID: 171042928) OT - Fasting plasma glucose OT - G-protein coupled receptors OT - Hemoglobin A(1C) OT - Incretin OT - Insulin Glargine (PubMed CID: 118984454) OT - Insulin degludec (PubMed CID: 118984462) OT - Liraglutide (PubMed CID: 16134956) OT - Lixisenatide (PubMed CID: 90472060) OT - Metformin (PubMed CID: 4091) OT - Orforglipron (PubMed CID: 137319706) OT - Peptide-GLP-1 receptor interaction OT - Prescription drug expenditures OT - Retatrutide (PubMed CID: 178245957) OT - Semaglutide (PubMed CID: 56843331) OT - Tirzepatide (PubMed CID: 166567236) COIS- Declaration of Competing Interest The author is unaware of any affiliations, memberships, or financial holdings that might be perceived as affecting the objectivity of this article. EDAT- 2026/08/06 11:36 MHDA- 2026/08/25 23:33 CRDT- 2026/08/05 19:19 PHST- 2026/07/27 00:00 [received] PHST- 2026/08/03 00:00 [accepted] PHST- 2026/08/25 23:33 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 19:19 [entrez] AID - S1043-6618(26)00280-X [pii] AID - 10.1016/j.phrs.2026.108365 [doi] PST - ppublish SO - Pharmacol Res. 2026 Sep;231:108365. doi: 10.1016/j.phrs.2026.108365. Epub 2026 Aug 6. PMID- 42552642 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 5 DP - 2026 Sep TI - Effects of Oral Semaglutide on Dietary Intake and Body Composition in Japanese People With Type 2 Diabetes: A Prospective Observational Study in Clinical Practice. PG - e70295 LID - 10.1002/edm2.70295 [doi] LID - e70295 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists are effective glucose-lowering agents with established benefits on body weight and cardiometabolic outcomes. However, their precise effects on body composition and dietary intake patterns, including food group consumption and macronutrient energy distribution, particularly in clinical settings, remain incompletely understood. METHODS: In this prospective observational study, we enrolled Japanese adults with Type 2 diabetes who were newly initiated on oral semaglutide treatment. Dietary intake patterns were assessed using a food frequency questionnaire, and body composition was assessed by bioelectrical impedance analysis. Handgrip strength and laboratory parameters were also evaluated. All parameters were assessed at both baseline (before the start of semaglutide treatment) and at a 3-month follow-up visit. RESULTS: A total of 25 participants were included in the final analysis. After 3 months of oral semaglutide treatment, significant reductions in HbA1c levels and body weight were noted. Significant reductions in the percent body fat and significant increases in the percent muscle mass were also observed. No significant change was observed in the handgrip strength. While the total energy intake decreased significantly after 3 months of semaglutide treatment, the macronutrient energy distribution remained unchanged. Analysis by food groups revealed significant reductions in the intakes of fats and oils, seasonings and spices, and sweets and snacks. Notably, the daily salt intake also decreased significantly from 8.9 to 7.0 g/day. CONCLUSIONS: Oral semaglutide treatment was associated with reductions in the total energy intake and percent body fat, without significant changes in the macronutrient energy distribution or handgrip strength. Salt intake was also significantly reduced, suggesting potential clinical benefits of this treatment in the management of diabetes and related comorbidities. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Sawada, Mika AU - Sawada M AUID- ORCID: 0000-0002-5084-723X AD - Department of Clinical Nutrition Therapy, The University of Tokyo, Tokyo, Japan. FAU - Nakanishi, Naoko AU - Nakanishi N AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Aihara, Masakazu AU - Aihara M AUID- ORCID: 0009-0009-9555-8624 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Ohkuma, Kanako AU - Ohkuma K AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Hamano, Shoko AU - Hamano S AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Sakurai, Yoshitaka AU - Sakurai Y AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Sekine, Rie AU - Sekine R AD - Department of Clinical Nutrition Therapy, The University of Tokyo, Tokyo, Japan. FAU - Usami, Satoshi AU - Usami S AD - Graduate School of Education, The University of Tokyo, Tokyo, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AUID- ORCID: 0000-0003-4827-6404 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kubota, Naoto AU - Kubota N AUID- ORCID: 0000-0002-3336-2767 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Kumamoto, Japan. LA - eng PT - Journal Article PT - Observational Study PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Eating/drug effects MH - Energy Intake/drug effects MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Hand Strength MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Japan MH - Prospective Studies MH - Semaglutide PMC - PMC13437943 OTO - NOTNLM OT - body composition OT - food intake OT - glucagon-like peptide-1 receptor agonists (GLP-1 RAs) COIS- The authors declare no conflicts of interest. EDAT- 2026/08/05 06:42 MHDA- 2026/08/05 06:43 PMCR- 2026/08/04 CRDT- 2026/08/05 00:53 PHST- 2026/07/10 00:00 [revised] PHST- 2026/02/23 00:00 [received] PHST- 2026/07/16 00:00 [accepted] PHST- 2026/08/05 06:43 [medline] PHST- 2026/08/05 06:42 [pubmed] PHST- 2026/08/05 00:53 [entrez] PHST- 2026/08/04 00:00 [pmc-release] AID - EDM270295 [pii] AID - 10.1002/edm2.70295 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Sep;9(5):e70295. doi: 10.1002/edm2.70295. PMID- 42546368 OWN - NLM STAT- MEDLINE DCOM- 20260904 LR - 20260904 IS - 1879-0046 (Electronic) IS - 0376-8716 (Linking) VI - 286 DP - 2026 Sep 1 TI - Cannabis use and cardiovascular, renal, and mortality outcomes in patients with type 2 diabetes receiving GLP-1 receptor agonists: A propensity score-matched cohort study. PG - 113296 LID - S0376-8716(26)00277-2 [pii] LID - 10.1016/j.drugalcdep.2026.113296 [doi] AB - BACKGROUND: Cannabis use is rising among adults with type 2 diabetes mellitus (T2DM). Whether cannabis use modifies the cardio-renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is unknown. METHODS: Retrospective propensity score-matched cohort study in the TriNetX Research Network (January 2017-December 2025). Adults with T2DM initiating GLP-1 RA therapy were classified as people who use cannabis (>/=2 ICD-10-CM F12.x codes within 2 years before index) or as people who did not (the comparison cohort). 1:1 matching was performed on more than 40 baseline covariates. The primary outcome was all-cause mortality; secondary outcomes were 4-point major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE). Cox models estimated hazard ratios (HRs); E-values assessed robustness to unmeasured confounding. RESULTS: Among 614,333 eligible patients, 4117 people who use cannabis were matched to 4117 comparison patients (median follow-up 2.6 years). Cannabis use was associated with increased all-cause mortality (HR 1.64, 95% CI 1.38-1.96), MACE (HR 1.42, 1.26-1.59), and MAKE (HR 1.55, 1.34-1.79). A dose-response was observed: cannabis use disorder (HR 2.20) conferred greater mortality risk than non-disordered use (HR 1.73). Associations persisted across sensitivity and subgroup analyses; E-values were 2.21-2.63. In an exploratory analysis, concomitant sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy was associated with lower mortality (HR 0.62, 0.45-0.85) and MAKE (HR 0.70, 0.54-0.92) in this group. CONCLUSIONS: Cannabis use was associated with substantially higher mortality, cardiovascular, and renal risk among patients with T2DM initiating GLP-1 RAs, with a dose-response pattern. Clinicians should inquire about cannabis use when prescribing GLP-1 RAs. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Salameh, Aseel AU - Salameh A AD - Department of Internal Medicine, Al-Nadeem Hospital, Ministry of Health, Madaba, Jordan. FAU - Yu, Tsung-Ying AU - Yu TY AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan. FAU - Chang, Wei-Cheng AU - Chang WC AD - Department of Ophthalmology, Universe Eye Center, Taiwan. FAU - Jhou, Hong-Jie AU - Jhou HJ AD - Neurological Institute, Changhua Christian Hospital, Changhua, Taiwan. FAU - Chen, Hsin-Yu AU - Chen HY AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kao, Li-Ting AU - Kao LT AD - Graduate Institute of Life Sciences, National Defense Medical University, Taipei, Taiwan; School of Pharmacy, National Defense Medical University, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan. FAU - Hsieh, Tina Yi-Jin AU - Hsieh TY AD - Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Dai, Ming-Shen AU - Dai MS AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan. FAU - Chen, Po-Huang AU - Chen PH AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan. Electronic address: chenpohuang@hotmail.com. FAU - Lee, Cho-Hao AU - Lee CH AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; Department of Oncology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan. Electronic address: leechohao@mail.ndmutsgh.edu.tw. LA - eng PT - Journal Article DEP - 20260729 PL - Ireland TA - Drug Alcohol Depend JT - Drug and alcohol dependence JID - 7513587 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Propensity Score MH - Middle Aged MH - *Cardiovascular Diseases/mortality/epidemiology MH - Retrospective Studies MH - Cohort Studies MH - *Marijuana Use/epidemiology/adverse effects MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Kidney Diseases/mortality/epidemiology OTO - NOTNLM OT - Cannabis OT - Cannabis use disorder OT - Cardiovascular outcomes OT - GLP-1 receptor agonist OT - Propensity score matching OT - Real-world evidence OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/03 18:37 MHDA- 2026/09/04 23:36 CRDT- 2026/08/03 18:00 PHST- 2026/05/11 00:00 [received] PHST- 2026/06/20 00:00 [revised] PHST- 2026/07/13 00:00 [accepted] PHST- 2026/09/04 23:36 [medline] PHST- 2026/08/03 18:37 [pubmed] PHST- 2026/08/03 18:00 [entrez] AID - S0376-8716(26)00277-2 [pii] AID - 10.1016/j.drugalcdep.2026.113296 [doi] PST - ppublish SO - Drug Alcohol Depend. 2026 Sep 1;286:113296. doi: 10.1016/j.drugalcdep.2026.113296. Epub 2026 Jul 29. PMID- 42545324 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20261005 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 72 IP - 3 DP - 2026 Jul 22 TI - Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis. PG - 60-65 LID - 10.14341/probl13660 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide have transformed type 2 diabetes mellitus (T2DM) management, yet emerging concerns highlight potential risks of accelerated sarcopenia and subsequent metabolic disruptions. This case-driven hypothesis explores a 53-year-old male with T2DM diagnosed in 2014, who experienced progressive glycemic failure despite standard therapies, including metformin, glipizide, sitagliptin, and empagliflozin. Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. We posit that semaglutide may precipitate acute sarcopenia via unexpected GLP-1R-mTOR-satellite cells axis crosstalk, disrupting AMPK-mTOR balance to suppress anabolic mTORC1/IGF-1 signaling (potentially by 25-35%) while enhancing catabolic FOXO/ubiquitin-proteasome and excessive autophagy pathways. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/alpha-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-alpha upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a <> with hepatic gluconeogenesis amplification, yielding treatment-resistant hyperglycemia.Supporting evidence from cohorts (e.g., 24-month study showing ASMI/grip strength declines in 432 patients), longitudinal analyses (NMJ degradation with CAF22/NfL elevations in 141 men), secondary trials (9.3% psoas volume loss in 51 MASLD cases), and case reports (fatigue in a 74-year-old, rhabdomyolysis in a 47-year-old) aligns with this framework, as does in vitro data linking GLP-1 excess to kinesin-1/GLUT4 inhibition and ATP depletion (20-30%). This novel hypothesis underscores sarcopenia's role in GLP-1RA-induced metabolic paradoxes, urging prospective studies on muscle-preserving interventions like resistance training or GLP-1R modulators to refine T2DM paradigms and inspire multidisciplinary research into endocrine-muscle interactions. FAU - Ahmed, Amr AU - Ahmed A AD - The Public Health Department, Riyadh First Health Cluster, Ministry of Health. FAU - Rodini, Sharifa AU - Rodini S AD - Nurse Technician, Ministry of Health. FAU - Alrubyea, Fahad AU - Alrubyea F AD - Public Health Specialist, The Public Health Department, Riyadh First Health Cluster, Ministry of Health. FAU - Akl, Maher AU - Akl M AD - National Research Lobachevsky State University of Nizhny Novgorod. LA - eng PT - Case Reports PT - Journal Article DEP - 20260722 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - EC 2.7.1.1 (MTOR protein, human) RN - 53AXN4NNHX (Semaglutide) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptides/adverse effects MH - Glucose/metabolism MH - *Hyperglycemia/metabolism/chemically induced MH - *Hypoglycemic Agents/adverse effects MH - Muscle, Skeletal/metabolism MH - *Sarcopenia/chemically induced/metabolism MH - Satellite Cells, Skeletal Muscle/metabolism/drug effects MH - Semaglutide MH - TOR Serine-Threonine Kinases/metabolism MH - Aged PMC - PMC13474366 COIS- The authors declare that there are no conflicts of interest present. EDAT- 2026/08/03 12:42 MHDA- 2026/08/03 12:43 PMCR- 2026/07/22 CRDT- 2026/08/03 10:52 PHST- 2025/09/16 00:00 [received] PHST- 2025/10/19 00:00 [accepted] PHST- 2026/08/03 12:43 [medline] PHST- 2026/08/03 12:42 [pubmed] PHST- 2026/08/03 10:52 [entrez] PHST- 2026/07/22 00:00 [pmc-release] AID - 10.14341/probl13660 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2026 Jul 22;72(3):60-65. doi: 10.14341/probl13660. PMID- 42544311 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Adverse Events Associated with Incretin-Based Therapies: A Narrative Review on Mechanisms, Clinical Management, and Risk Mitigation. PG - 622972 LID - 10.2147/DDDT.S622972 [doi] LID - 622972 AB - BACKGROUND: Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), are established therapies for obesity and type 2 diabetes mellitus, providing sustained weight reduction, improved glycaemic control, cardiovascular and renal benefits. Despite these established benefits, safety concerns remain an important clinical issue because adverse events may affect treatment persistence, patient acceptability, and clinical decision-making. This review evaluates a number of safety profiles of GLP-1RAs using clinical, mechanistic, and pharmacovigilance evidence, with attention to both common adverse events and emerging safety signals. METHODS: A narrative review was conducted to evaluate the safety profile of GLP-1RAs in obesity and type 2 diabetes mellitus. PubMed/MEDLINE, Embase, and Web of Science were searched for studies published between January 2005 and April 2026. Evidence from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance investigations, and regulatory safety reports was synthesised qualitatively. RESULTS: Findings from 60 studies and safety reports were included. Common adverse events were predominantly gastrointestinal, particularly nausea, vomiting, diarrhoea, and constipation, and represented the most consistently reported adverse effects and the principal cause of treatment discontinuation. Uncommon safety concerns included renal adverse events, which were reported infrequently and often occurred in clinical contexts involving gastrointestinal intolerance, volume depletion, or other predisposing factors. Gallbladder and biliary complications were also infrequent and appeared to be influenced by rapid weight loss and baseline patient risk factors. Acute pancreatitis remained rare in clinical trials, although severe cases have been reported in postmarketing settings. Human evidence did not demonstrate an increased risk of thyroid malignancy. Emerging safety signals, including early worsening of diabetic retinopathy, muscle mass reduction, psychiatric symptoms, and alopecia, were identified mainly through observational and pharmacovigilance evidence. CONCLUSION: GLP-1RA adverse events predominantly reflect predictable pharmacological and physiological effects rather than off-target toxicity. Safety profiles appear agent-specific, dose-dependent, and influenced by underlying mechanisms and patient characteristics. Risk-stratified prescribing should therefore align agent selection, dose escalation, and monitoring intensity with patient-specific vulnerabilities, particularly gastrointestinal tolerability, risk of renal dehydration, gallbladder history, retinopathy risk during rapid glycaemic improvement, and frailty or sarcopenia risk. Continued long-term surveillance and further evidence generation are needed to better define rare, delayed, and emerging safety signals and to optimise safe use across diverse clinical populations. CI - (c) 2026 Tobaiqy and Alqutub. FAU - Tobaiqy, Mansour AU - Tobaiqy M AUID- ORCID: 0000-0002-4292-0900 AD - Department of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alqutub, Sulafa Tarek AU - Alqutub ST AUID- ORCID: 0000-0002-0497-2275 AD - Department of Family and Community medicine, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260729 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/adverse effects PMC - PMC13429114 OTO - NOTNLM OT - adverse events OT - glucagon-like peptide-1 receptor agonists OT - mechanistic determinants OT - obesity OT - risk mitigation OT - type 2 diabetes mellitus COIS- The author declares that he has no competing interests. EDAT- 2026/08/03 06:36 MHDA- 2026/08/03 06:37 PMCR- 2026/07/29 CRDT- 2026/08/03 03:55 PHST- 2026/05/08 00:00 [received] PHST- 2026/07/14 00:00 [accepted] PHST- 2026/08/03 06:37 [medline] PHST- 2026/08/03 06:36 [pubmed] PHST- 2026/08/03 03:55 [entrez] PHST- 2026/07/29 00:00 [pmc-release] AID - 622972 [pii] AID - 10.2147/DDDT.S622972 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Jul 29;20:622972. doi: 10.2147/DDDT.S622972. eCollection 2026. PMID- 42543940 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260820 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 6 DP - 2026 Jun TI - Glucagon Agonist Therapies and Vision Loss: Balancing Promise with Prudence in India. PG - 94-96 LID - 10.59556/japi.74.1507 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin therapies such as tirzepatide have transformed the management of type 2 diabetes mellitus and obesity, with expanding cardiometabolic indications and rapid market growth globally and in India. However, emerging postmarketing evidence has raised concerns regarding ocular safety. Pharmacovigilance analyses, cohort studies, and case reports suggest an association between GLP-1-based therapies and ophthalmic adverse events, including early worsening of diabetic retinopathy and, more concerningly, nonarteritic anterior ischemic optic neuropathy (NAION)-a potentially irreversible cause of sudden vision loss in adults over 50 years. Although the absolute risk appears very low, regulatory agencies, including the WHO and European Medicines Agency, now recognize NAION as a very rare adverse effect of semaglutide, and similar signals are being explored for other agents, suggesting a possible class effect. Proposed mechanisms include altered optic nerve head perfusion, sympathetic-mediated vasoconstriction, and rapid glycemic shifts affecting vascular autoregulation; however, causality remains unproven. In India, where over 100 million adults live with diabetes and obesity rates are rising, even rare adverse events may translate into substantial public health impact, particularly given limited access to ophthalmic care and increasing unsupervised drug use. We advocate a balanced approach: baseline ophthalmic evaluation in high-risk individuals, informed consent regarding visual symptoms, early referral for visual complaints, strengthened pharmacovigilance, and coordinated endocrinology-ophthalmology surveillance systems. As newer triple agonists approach clinical use, integrating ocular safety into prescribing frameworks is imperative. Metabolic gains must not come at the cost of preventable vision loss. CI - (c) Journal of the Association of Physicians of India 2026. FAU - Saxena, Abhyuday AU - Saxena A AD - Senior Medical Officer, Department of Ophthalmology, Dr. R P Centre, All India Institute of Medical Sciences, New Delhi, India. FAU - Prakash, Anupam AU - Prakash A AD - Director Professor and Head, Department of Medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India, Corresponding Author. ORCID: 0000-0001-8477-9039 LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - India MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - *Blindness MH - Diabetic Retinopathy/chemically induced EDAT- 2026/08/03 06:36 MHDA- 2026/08/03 06:37 CRDT- 2026/08/03 02:57 PHST- 2026/08/03 06:37 [medline] PHST- 2026/08/03 06:36 [pubmed] PHST- 2026/08/03 02:57 [entrez] AID - 10.59556/japi.74.1507 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Jun;74(6):94-96. doi: 10.59556/japi.74.1507. PMID- 42543936 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260803 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 6 DP - 2026 Jun TI - Semaglutide in Practice: Insights from a Retrospective Case Series at a Jharkhand Tertiary Care Hospital. PG - 74-77 LID - 10.59556/japi.74.1508 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, real-world evidence from Indian populations remains limited. This study aimed to assess the effectiveness and safety of semaglutide on glycemic control, body weight, and metabolic parameters in patients with T2DM in a real-world clinical setting. METHODS: This retrospective observational study was conducted at a tertiary care hospital in Jharkhand, India, between February 2023 and August 2024. A total of 60 patients with T2DM (44 males and 16 females), including treatment-naive individuals and those with inadequate glycemic control (HbA1c >7%) despite ongoing therapy, were enrolled. Clinical and biochemical parameters were evaluated at baseline and after six months of semaglutide therapy. Statistical analysis was performed using paired t-tests, with a p-value <0.05 considered statistically significant. RESULTS: Significant improvements were observed following semaglutide therapy. Mean HbA1c decreased from 9.21% at baseline to 7.35% after six months (p <0.001). Mean body weight decreased by 2.6 kg (p <0.001). LDL cholesterol levels declined significantly from 92.03 mg/dL to 78.93 mg/dL (p <0.05). Renal parameters, including serum creatinine and urine albumin-to-creatinine ratio, showed numerical improvement; however, these changes did not reach statistical significance (p >0.05). Thyroid function remained stable throughout the study period. Improvements in diabetic retinopathy and neuropathy were also observed, although these findings were not statistically significant. CONCLUSION: Semaglutide was effective and well tolerated in patients with T2DM in routine clinical practice. Treatment was associated with significant reductions in HbA1c, body weight, and LDL cholesterol without adverse effects on renal or thyroid function. These findings support the use of semaglutide as an effective therapeutic option for the management of T2DM in real-world settings. CI - (c) Journal of the Association of Physicians of India 2026. FAU - Jha, Ajay Kumar AU - Jha AK AD - Senior Consultant and Unit Head, Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India, Corresponding Author. ORCID: 0009-0009-9100-5491 FAU - Sunder, Ashok AU - Sunder A AD - Chief Consultant, Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India. LA - eng PT - Journal Article PT - Observational Study PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - India MH - Glycated Hemoglobin/analysis MH - Tertiary Care Centers MH - Middle Aged MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Aged MH - Treatment Outcome EDAT- 2026/08/03 06:36 MHDA- 2026/08/03 06:37 CRDT- 2026/08/03 02:57 PHST- 2026/08/03 06:37 [medline] PHST- 2026/08/03 06:36 [pubmed] PHST- 2026/08/03 02:57 [entrez] AID - 10.59556/japi.74.1508 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Jun;74(6):74-77. doi: 10.59556/japi.74.1508. PMID- 42543082 OWN - NLM STAT- MEDLINE DCOM- 20260829 LR - 20260829 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 239 DP - 2026 Sep TI - Guideline on treatment intensification with injectable therapies beyond GLP-1 RA based therapies in type 2 diabetes. PG - 113474 LID - S0168-8227(26)00394-3 [pii] LID - 10.1016/j.diabres.2026.113474 [doi] AB - Guideline on Treatment Intensification with Injectable Therapies Beyond GLP-1 RA Monotherapy in Type 2 Diabetes. AIMS: To provide evidence-based recommendations for selecting injectable therapies in adults with type 2 diabetes (T2DM) who have suboptimal response to GLP‑1 receptor agonists (GLP‑1 RAs). METHODS: Using the GRADE framework, a systematic search (updated November 2025) identified eight RCTs evaluating four intensification strategies (switching to another GLP‑1 RA, switching to dual GIP/GLP‑1 RA, switching to fixed‑ratio combination (FRC), or adding basal insulin). A 22‑member Guideline Development Group from 11 Asia‑Pacific countries formulated recommendations requiring >/= 80% consensus. AGREE and RIGHT checklists guided reporting. RESULTS: The panel conditionally recommends against switching to another GLP‑1 RA (very low certainty). It conditionally recommends switching to dual GIP/GLP‑1 RA (low certainty) for glycemic and weight benefits, switching to FRC (very low to moderate certainty) when prioritizing glycemic improvement, and adding basal insulin (low certainty) with structured education. Choice among strategies should be individualized. CONCLUSIONS: This guideline offers a framework for treatment intensification beyond GLP‑1 RA monotherapy in T2DM, emphasizing shared decision‑making based on glycemic goals, hypoglycemia risk, weight needs, and patient preferences. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Luo, Yingying AU - Luo Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China; Peking University Diabetes Center, Beijing, China. Electronic address: yingyingluo@yahoo.com. FAU - Xia, Jun AU - Xia J AD - Nottingham Ningbo GRADE Centre, University of Nottingham Ningbo China, Zhejiang, China. Electronic address: Jun.Xia@nottingham.edu.cn. FAU - Yao, Xiaomei AU - Yao X AD - Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address: yaoxia@mcmaster.ca. FAU - Jahed, Seyed Adel AU - Jahed SA AD - Head of scientific committee, Gabric Diabetes Association, Tehran, Iran. Electronic address: adeljahed@yahoo.com. FAU - Bee, Yong Mong AU - Bee YM AD - Department of Endocrinology, Singapore General Hospital, Singapore, Singapore. Electronic address: bee.yong.mong@singhealth.com.sg. FAU - Chen, Liming AU - Chen L AD - Chu Hsien-I Memorial (Metabolic Diseases) Hospital & Tianjin Institute of Endocrinology, Tianjin, China. Electronic address: xfx22081@vip.163.com. FAU - Chan, Siew Pheng AU - Chan SP AD - Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: spchan88@hotmail.com. FAU - Deerochanawong, Chaicharn AU - Deerochanawong C AD - College of Medicine, Rangsit University, Bangkok, Thailand. Electronic address: chaicharn_dee@hotmail.com. FAU - Shan Kong, Alice Pik AU - Shan Kong AP AD - Division of Endocrinology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: alicekong@cuhk.edu.hk. FAU - Nguyen, Khue Thy AU - Nguyen KT AD - Ho Chi Minh University of Medicine and Pharmacy Medic Medical Center, Ho Chi Minh, Viet Nam. Electronic address: drthykh@gmail.com. FAU - Li, Xiaoying AU - Li X AD - Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: xiaoying_li@hotmail.com. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea. Electronic address: limsoo@snu.ac.kr. FAU - Loganadan, Navin Kumar AU - Loganadan NK AD - Department of Pharmacy, Putrajaya Hospital, Ministry of Health Malaysia, Putrajaya, Malaysia. Electronic address: pharmnavin@gmail.com. FAU - McGill, Margaret AU - McGill M AD - Diabetes Centre, Royal Prince Alfred Hospital, Faculty of Medicine and Health University of Sydney, Sydney, Australia. Electronic address: margaret.mcgill@sydney.edu.au. FAU - Trejo, Selva Elizabeth AU - Trejo SE AD - Lic. en Enfermeria especialista en Docencia Universitaria y en Salud Social y Comunitaria, Magister en Salud Familiar y Comunitaria, Servicio de Endocrinologia, Nutricion y Diabetes, Hospital RegionalDr. R. Carrilo, Directora del Instituto de Estudios e Investigaciones en Enfermeria de la Facultad de HumanidadesCiencias Sociales y Salud, Universidad Nacional de Santiago del Estero, Santiago del Estero, Argentina. Electronic address: ineieunsefhcsys@gmail.com. FAU - Yabe, Daisuke AU - Yabe D AD - Departments of Diabetes, Endocrinology and Metabolism/Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan; Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, Japan. Electronic address: ydaisuke@gifu-u.ac.jp. FAU - Yan, Li AU - Yan L AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: Hfxyl@163.net. FAU - Li, Peipei AU - Li P AD - Tianjin Suyuan Evidence Based Technology Co., Ltd., Tianjin, China. Electronic address: peipei-li@circle-evidence.com. FAU - Zhao, Zhan AU - Zhao Z AD - Tianjin Suyuan Evidence Based Technology Co., Ltd., Tianjin, China. Electronic address: zhan-zhao@circle-evidence.com. FAU - Chen, Shihui AU - Chen S AD - Nottingham Ningbo GRADE Centre, University of Nottingham Ningbo China, Zhejiang, China. Electronic address: bixsc20@nottingham.edu.cn. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: Alice.Cheng@unityhealth.to. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China; Peking University Diabetes Center, Beijing, China. Electronic address: jiln@bjmu.edu.cn. CN - Chinese Association of Geriatric Research LA - eng PT - Journal Article DEP - 20260802 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Injections MH - Blood Glucose/drug effects MH - Insulin/administration & dosage OTO - NOTNLM OT - Basal insulin OT - Dual GIP/GLP-1 receptor agonist OT - Fixed‑ratio combination OT - GLP-1 receptor agonists OT - GRADE OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/03 00:35 MHDA- 2026/08/29 23:35 CRDT- 2026/08/02 19:10 PHST- 2026/05/12 00:00 [received] PHST- 2026/07/16 00:00 [revised] PHST- 2026/07/30 00:00 [accepted] PHST- 2026/08/29 23:35 [medline] PHST- 2026/08/03 00:35 [pubmed] PHST- 2026/08/02 19:10 [entrez] AID - S0168-8227(26)00394-3 [pii] AID - 10.1016/j.diabres.2026.113474 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Sep;239:113474. doi: 10.1016/j.diabres.2026.113474. Epub 2026 Aug 2. PMID- 42543031 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261001 IS - 1747-6356 (Electronic) IS - 1747-6348 (Linking) VI - 20 IP - 10 DP - 2026 Oct TI - Sepsis risk in patients with COPD and type 2 diabetes mellitus: influence of emerging antihyperglycemic therapies. PG - 1235-1245 LID - 10.1080/17476348.2026.2713233 [doi] AB - BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are at increased risk of sepsis, yet the comparative infection-related outcomes of newer antihyperglycemic agents remain unclear. We evaluated the associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) with infection outcomes in this population. METHODS: In this retrospective cohort study using the TriNetX global federated database, individuals aged 40-100 years with coexisting COPD and T2DM who initiated a GLP-1RA or SGLT2i between 2021 and 2024 were identified. A new-user, active-comparator design with 1:1 propensity score matching was applied. Sepsis was the primary outcome; all-cause mortality and components of the primary outcome were secondary. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: After matching, 45,491 pairs were included. Compared with SGLT2is, GLP-1RAs showed lower risks of sepsis (adjusted HR, 0.832; 95% CI, 0.781-0.887), all-cause mortality (0.642; 0.598-0.689), and severe sepsis (0.841; 0.774-0.914). CONCLUSION: In patients with COPD and T2DM, GLP-1RAs were associated with significantly lower risks of sepsis and all-cause mortality compared with SGLT2is. FAU - Kuo, Kuan-Chih AU - Kuo KC AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, New Taipei City, Taiwan. AD - Department of Medicine, MacKay Medical University, New Taipei City, Taiwan. FAU - Chen, Chao-Hsien AU - Chen CH AUID- ORCID: 0000-0002-2176-3504 AD - Department of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taitung MacKay Memorial Hospital, Taitung, Taiwan. FAU - Wu, Ting-Jia AU - Wu TJ AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Wu, Hsiu-Chin AU - Wu HC AD - Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Wang, Ya-Hui AU - Wang YH AD - Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Wang, Cheng-Yi AU - Wang CY AUID- ORCID: 0000-0001-7426-0743 AD - Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-9416-4094 AD - Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. AD - PAC (Primary Aldosteronism Center), National Taiwan University Hospital, Taipei, Taiwan. AD - NSARF (National Taiwan University Hospital Study Group of Acute Renal Failure), National Taiwan University Hospital, Taipei, Taiwan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260813 PL - England TA - Expert Rev Respir Med JT - Expert review of respiratory medicine JID - 101278196 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Pulmonary Disease, Chronic Obstructive/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Retrospective Studies MH - Female MH - *Sepsis/epidemiology/etiology MH - Middle Aged MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged, 80 and over MH - Adult MH - Risk Factors OTO - NOTNLM OT - COPD OT - GLP-1RA OT - SGLT2i OT - sepsis risk OT - type 2 diabetes mellitus EDAT- 2026/08/02 18:35 MHDA- 2026/10/01 23:30 CRDT- 2026/08/02 14:33 PHST- 2026/10/01 23:30 [medline] PHST- 2026/08/02 18:35 [pubmed] PHST- 2026/08/02 14:33 [entrez] AID - 10.1080/17476348.2026.2713233 [doi] PST - ppublish SO - Expert Rev Respir Med. 2026 Oct;20(10):1235-1245. doi: 10.1080/17476348.2026.2713233. Epub 2026 Aug 13. PMID- 42538001 OWN - NLM STAT- MEDLINE DCOM- 20260731 LR - 20260819 IS - 2049-4408 (Electronic) IS - 2049-4394 (Linking) VI - 108-B IP - 8 DP - 2026 Aug 1 TI - Glucagon-like peptide-1 receptor agonists are associated with improved 90-day outcomes after total hip and knee arthroplasty : a systematic review and meta-analysis. PG - 986-994 LID - 10.1302/0301-620X.108B8.BJJ-2025-1486.R2 [doi] AB - AIMS: Obesity and diabetes are risk factors for developing osteoarthritis and associated with worse outcomes following total hip (THA) and total knee arthroplasty (TKA). Glucagon-like peptide-1 receptor agonists (GLP-1as) improve glycaemic control and promote weight loss. The aim of this study was to assess the impact of GLP-1a treatment on 90-day surgical complications following THA and TKA. METHODS: A systematic review was undertaken according to PRISMA guidelines. Studies were included if they reported at least one outcome of interest following primary THA or TKA. In all the studies which were included, a GLP-1a was prescribed for the management of type 2 diabetes mellitus or for weight loss in obese patients. The primary outcome was the 90-day surgical complication rate in the combined THA and TKA cohort. The 90-day surgical complications were defined as: periprosthetic joint infection (PJI), wound dehiscence, periprosthetic fracture (PPF), haematoma, nerve injury, or surgical site infection (SSI). Secondary outcomes included 90-day medical complications and readmission rates, all-cause revision, healthcare costs, and length of stay. RESULTS: A total of 78 studies were reviewed, and ten matched cohort studies with a total of 96,356 patients (30,350 THAs and 66,606 TKAs) were included. The mean age of the patients was 61.9 years; 60.1% female (n = 57,939). Two studies had a serious risk of overall bias and eight had a moderate risk. The confidence of evidence according to the GRADE assessment was very low for all but one outcome measure (healthcare cost: moderate). The rate of 90-day surgical complications was lower in the GLP-1a cohort (pooled risk ratio (RR) 0.73). The use of a GLP-1a lowered the 90-day medical complications and readmission rates (RR 0.78 and RR 0.79 (I(2) = 61.6%), respectively). At two years, the revision rate ranged from 1.7% to 3.3% for the GLP-1a cohort and 1.7% to 4.5% for the controls. Sub-group analysis showed a stronger association in the THA group, in which the use of a GLP-1a was associated with significantly lower rates of 90-day surgical complications (RR 0.63), 90-day medical complications (RR 0.55), and 90-day readmissions (RR 0.82). In contrast, the use of a GLP-1a in the TKA group was only sigificantly associated with a lower 90-day readmission rate (RR 0.77). CONCLUSION: GLP-1a treatment before THA and TKA potentially reduces the 90-day surgical and medical complications and 90-day readmission rates in high-risk diabetic and obese patients. The use of a GLP-1a may also be associated with substantial cost savings. CI - (c) 2026 The British Editorial Society of Bone & Joint Surgery. FAU - Rudran, Branavan AU - Rudran B AUID- ORCID: 0000-0002-2323-1763 AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. FAU - Little, Christopher D J AU - Little CDJ AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. FAU - Palmer, Antony J R AU - Palmer AJR AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. FAU - Judge, Andrew AU - Judge A AUID- ORCID: 0000-0003-3015-0432 AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. AD - Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. AD - NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust, University of Bristol, Bristol, UK. AD - NIHR Applied Research Collaboration South West and the University of Bristol, UK, University of Bristol, Bristol, UK. FAU - Carli, Alberto AU - Carli A AD - Hospital for Special Surgery, New York, New York, USA. FAU - Price, Andrew J AU - Price AJ AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. FAU - Alvand, Abtin AU - Alvand A AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260801 PL - England TA - Bone Joint J JT - The bone & joint journal JID - 101599229 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Knee/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Postoperative Complications/prevention & control/epidemiology MH - *Arthroplasty, Replacement, Hip/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome MH - Obesity/complications MH - Reoperation/statistics & numerical data MH - Patient Readmission/statistics & numerical data COIS- A. Judge reports grants or contracts from NIHR, HDR UK, Versus Arthritis, Healthcare Quality Improvement Partnership (HQIP), Royal College of Physicians (RCP), Tommy's, and the Health Foundation, participates on a range of Data Safety Monitoring or Advisory Boards, and was co-chair Versus Arthritis Research Expert group from September 2022 to October 2025, all of which are unrelated to this study. A. Price reports consulting fees from Zimmer Biomet and Medacta, unrelated to this study. A. Alvand reports royalties or licenses from Adler Orthopaedics, consulting fees from Medacta International, Adler Orthopedics, BD, Solventum, Smith & Nephew, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ethicon, Zimmer Biomet, Medacta, Adler Ortho, Solventum, Molnlycke, Biocomposites, participation on a Data Safety Monitoring Board or Advisory Board for BD and Smith & Nephew, and stock or stock options with PSI, all of which are unrelated to this study. EDAT- 2026/08/01 00:36 MHDA- 2026/08/01 00:37 CRDT- 2026/07/31 20:02 PHST- 2026/08/01 00:37 [medline] PHST- 2026/08/01 00:36 [pubmed] PHST- 2026/07/31 20:02 [entrez] AID - BJJ-2025-1486.R2 [pii] AID - 10.1302/0301-620X.108B8.BJJ-2025-1486.R2 [doi] PST - epublish SO - Bone Joint J. 2026 Aug 1;108-B(8):986-994. doi: 10.1302/0301-620X.108B8.BJJ-2025-1486.R2. PMID- 42536830 OWN - NLM STAT- MEDLINE DCOM- 20260731 LR - 20260731 IS - 2105-0686 (Electronic) IS - 2105-0678 (Linking) VI - 220 IP - 1-2 DP - 2026 TI - [An historical overview of GLP-1/GIP incretins. From hormone to "swiss-army knife" medications]. PG - 9-24 LID - 10.1051/jbio/2026005 [doi] AB - Incretins are hormones released from the gut that play a vital role in regulating postprandial metabolism. It has been 30 years since the first demonstration of the glucose-lowering effects of GLP-1 in people with type 2 diabetes. Here, we review the foundational science that led to an unparalleled development in the pharmacological treatment of diabetes. A first step was achieved with the discovery of inhibitors of the dipeptidyl peptidase-4 (DPP-4), which prevent the inactivation of GLP-1 and GIP, thereby prolonging their raised levels after meal ingestion. At the same time, several GLP-1 receptor agonists (GLP1-RAs) were engineered. The GLP1-RAs used clinically are based on exendin-4 and native GLP-1 and are now available as formulations for daily or weekly s.c. (exenatide, liraglutide, semaglutide) or oral administration (oral semaglutide). They mimic (better effectiveness) the action of native GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also demonstrated remarkable cardiovascular and weight-regulating benefits, including safety, leading to their prominent inclusion in current treatment recommendations for type 2 diabetes. Exciting advancements continue to emerge as the fundamental research efforts led to the development of monomeric multi-incretin receptor agonists: GLP-1/GIP (tirzepatide) dual receptor agonists and GLP-1/GIP/glucagon (retatrutide) triple receptor agonists which can achieve more than 20% weight loss in obesity as well as offering superior benefits in diabetes. This review also presents the promise of GLP1-RAs for more extensive application of this new class of drugs, in treating other metabolic disorders such as obesity, MASLD/NAFLD, cardio-vascular diseases and neurodegeneration. CI - (c) Societe de Biologie, 2026. FAU - Portha, Bernard AU - Portha B AD - Laboratoire EnDF (Endocrinologie du Diabete et de la Fertilite), Unite BFA (Biologie Fonctionnelle et Adaptive), CNRS UMR 8251, Universite Paris-Cite, Campus des grands moulins, Batiment Buffon, 4 rue Marie Andree Lagroua Weill-Halle, 75013 Paris, France. LA - fre PT - English Abstract PT - Historical Article PT - Journal Article PT - Review TT - Histoire des incretines GLP-1/GIP - De l'hormone au medicament couteau-suisse. DEP - 20260731 PL - France TA - Biol Aujourdhui JT - Biologie aujourd'hui JID - 101544020 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Incretins/therapeutic use/history MH - *Glucagon-Like Peptide 1/therapeutic use/history/physiology MH - *Gastric Inhibitory Polypeptide/therapeutic use/history/physiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/history MH - History, 21st Century MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - History, 20th Century MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/therapeutic use OTO - NOTNLM OT - GIP OT - GLP-1 OT - agonistes co- ou multi-recepteurs OT - anti-obesity drugs OT - co- or multi-receptor agonists OT - incretins OT - incretines OT - medicaments anti-obesite EDAT- 2026/07/31 18:35 MHDA- 2026/07/31 18:36 CRDT- 2026/07/31 15:12 PHST- 2026/06/08 00:00 [received] PHST- 2026/07/31 18:36 [medline] PHST- 2026/07/31 18:35 [pubmed] PHST- 2026/07/31 15:12 [entrez] AID - jbio260005 [pii] AID - 10.1051/jbio/2026005 [doi] PST - ppublish SO - Biol Aujourdhui. 2026;220(1-2):9-24. doi: 10.1051/jbio/2026005. Epub 2026 Jul 31. PMID- 42533561 OWN - NLM STAT- MEDLINE DCOM- 20260912 LR - 20260923 IS - 1532-6535 (Electronic) IS - 0009-9236 (Print) IS - 0009-9236 (Linking) VI - 120 IP - 4 DP - 2026 Oct TI - Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions. PG - 1092-1100 LID - 10.1002/cpt.70414 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and weight management. However, conflicting evidence from preclinical, clinical, and pharmacovigilance studies suggests potential neuropsychiatric effects. This study examined associations between GLP-1RA use and initiation of a range of neuropsychiatric medications using real-world prescription data. A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024. Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included. Outcomes comprised antidepressants, medication for substance use disorder (SUD), antipsychotics, psychostimulants, antidementia medications, antiparkinsonian medications, antiepileptics, and antimigraine agents. Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows. Among 2,033 individuals, semaglutide was the most common GLP-1RA (50.6%), followed by exenatide (27.5%) and dulaglutide (21.9%). GLP-1RA initiation was inversely associated with initiation of antidepressants (aSR: 0.85; 95% CI: 0.76-0.94) and medications for SUD (aSR: 0.70; 95% CI: 0.51-0.88). No significant associations were observed for other neuropsychiatric outcomes. GLP-1RA use was inversely associated with subsequent initiation of antidepressants and medications for SUD, while no associations were identified for other neuropsychiatric marker medications. These findings highlight the need for further studies to clarify the nature and magnitude of these potential neuropsychiatric associations with GLP-1RAs. CI - (c) 2026 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Alfonso Arvez, Maria J AU - Alfonso Arvez MJ AUID- ORCID: 0000-0003-1411-110X AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Wade, Sam AU - Wade S AUID- ORCID: 0009-0007-4680-8514 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Goordeen, Darshna AU - Goordeen D AUID- ORCID: 0000-0002-6381-8745 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Ilomaki, Jenni AU - Ilomaki J AUID- ORCID: 0000-0002-0348-9441 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Cross, Amanda J AU - Cross AJ AUID- ORCID: 0000-0001-6001-9211 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Langiu, Monica AU - Langiu M AUID- ORCID: 0000-0003-0719-8999 AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - AK Clinical Research, Carlton, Victoria, Australia. FAU - Tan, George S Q AU - Tan GSQ AUID- ORCID: 0000-0003-2526-729X AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. LA - eng PT - Journal Article DEP - 20260730 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Female MH - Male MH - Exenatide/adverse effects/therapeutic use MH - *Mental Disorders/drug therapy/chemically induced/epidemiology MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use MH - Australia MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Drug Prescriptions/statistics & numerical data MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13424737 COIS- J.I. reports grants from AstraZeneca, Amgen, National Health and Medical Research Council, Australian Government Department of Health, Disability and Aging, outside the submitted work. AJC has received grant funding or consulting funds from the National Health and Medical Research Council, Medical Research Future Fund, Dementia Australia Research Foundation, and Pharmaceutical Society of Australia. All grants and consulting funds were paid to the employing institution. All other authors declared no competing interests for this work. EDAT- 2026/07/31 06:36 MHDA- 2026/09/13 00:50 PMCR- 2026/07/30 CRDT- 2026/07/31 02:43 PHST- 2026/01/20 00:00 [received] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/09/13 00:50 [medline] PHST- 2026/07/31 06:36 [pubmed] PHST- 2026/07/31 02:43 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - CPT70414 [pii] AID - 10.1002/cpt.70414 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 Oct;120(4):1092-1100. doi: 10.1002/cpt.70414. Epub 2026 Jul 30. PMID- 42530338 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta-Analysis. PG - 9403-9411 LID - 10.1111/dom.71128 [doi] AB - AIM: To assess the effect of all the approved classes of medications for type 2 diabetes on Major Adverse Cardiovascular events (MACE) and all-cause mortality. METHODS: We performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated. RESULTS: We included 93 studies. In pairwise meta-analyses, versus all comparators, GLP-1 receptor agonists (GLP1RA), SGLT-2 inhibitors (SGLT2i), metformin and pioglitazone were associated with a significant reduction of MACE and sulfonylureas with increased MACE. Furthermore, tirzepatide, SGLT2i and GLP1RA were associated with a significantly reduced all-cause mortality. In the principal (frequentist) network meta-analysis, metformin (OR 0.69, 95% CI 0.53-0.89), SGLT2i (0.82, 0.75-0.90), GLP1RA (0.87, 0.83-0.92) and tirzepatide (0.82, 0.72-0.93) were associated with a significant reduction of MACE versus placebo; no effect was observed for insulin, DPP4 inhibitors (DPP4i) or sulfonylureas. Tirzepatide (0.72, 0.64-0.82), SGLT2i (0.85, 0.80-0.91) and GLP1RA (0.85, 0.80-0.91) were associated with a significantly reduced mortality versus placebo; no effect was detected for other drugs. The sensitivity (Bayesian) analysis did not confirm the significance of results for pioglitazone on MACE. The certainty of evidence was moderate-to-high for GLP1RA, SGLT2i, Tirzepatide, DPP4i; low for metformin; low-to-moderate for other drugs. CONCLUSION: SGLT2i, GLP1RA, tirzepatide and (with lower quality of evidence) pioglitazone and metformin are associated with a reduced incidence of cardiovascular events; tirzepatide, SGLT2i and GLP1RA are also associated with a reduced all-cause mortality. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Silverii, Giovanni Antonio AU - Silverii GA AUID- ORCID: 0000-0002-6695-3213 AD - Diabetology Unit, Careggi Hospital, Florence, Italy. AD - University of Florence, Florence, Italy. FAU - Velardi, Valerio AU - Velardi V AUID- ORCID: 0009-0001-4516-8427 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy. FAU - Marinelli, Christian AU - Marinelli C AD - Diabetology Unit, Careggi Hospital, Florence, Italy. AD - University of Florence, Florence, Italy. FAU - Lax, Antonino AU - Lax A AD - Diabetology Unit, Careggi Hospital, Florence, Italy. AD - University of Florence, Florence, Italy. FAU - Monami, Matteo AU - Monami M AUID- ORCID: 0000-0001-9349-828X AD - Diabetology Unit, Careggi Hospital, Florence, Italy. AD - University of Florence, Florence, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AUID- ORCID: 0000-0001-9759-9408 AD - Diabetology Unit, Careggi Hospital, Florence, Italy. AD - University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20260730 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sulfonylurea Compounds) RN - 0 (Insulin Secretagogues) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - X4OV71U42S (Pioglitazone) RN - 0 (PPAR-gamma Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Cardiovascular Diseases/mortality/prevention & control/epidemiology MH - Metformin/therapeutic use MH - Randomized Controlled Trials as Topic MH - Sulfonylurea Compounds/therapeutic use MH - Insulin Secretagogues MH - Tirzepatide MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Pioglitazone/therapeutic use MH - PPAR-gamma Agonists MH - *Diabetic Angiopathies/mortality/prevention & control/epidemiology PMC - PMC13538750 OTO - NOTNLM OT - antidiabetic drug OT - cardiovascular disease OT - meta-analysis OT - network meta-analysis OT - type 2 diabetes COIS- G.A.S. has received grants and consultancy fees from Eli Lilly. M.M. has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi and Novartis and research grants from Bristol Myers Squibb. E.M. has received consultancy fees from Merck and Novartis, speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi and Novartis and research grants from Merck, Novartis and Takeda. V.V., A.L. and C.M. declares no conflicts of interest. EDAT- 2026/07/30 12:43 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/30 09:04 PHST- 2026/07/06 00:00 [revised] PHST- 2026/05/19 00:00 [received] PHST- 2026/07/09 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/30 12:43 [pubmed] PHST- 2026/07/30 09:04 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71128 [pii] AID - 10.1111/dom.71128 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9403-9411. doi: 10.1111/dom.71128. Epub 2026 Jul 30. PMID- 42530137 OWN - NLM STAT- MEDLINE DCOM- 20260730 LR - 20260831 IS - 1552-4604 (Electronic) IS - 0091-2700 (Print) IS - 0091-2700 (Linking) VI - 66 IP - 8 DP - 2026 Aug TI - First-in-Human Study of a Long-Acting GLP-1 Receptor Agonist (TE-8105) in Overweight or Obese Adults Without Type 2 Diabetes Mellitus. PG - e70224 LID - 10.1002/jcph.70224 [doi] LID - e70224 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized weight management and are becoming essential for the treatment of obesity-related medical conditions. This study aimed to determine the pharmacokinetics, preliminary pharmacodynamics, safety, and tolerability of a long-acting GLP-1 receptor agonist, TE-8105, in overweight or obese adults without T2DM. An open-label study of four single ascending dose cohorts (A1-A4, 0.5, 0.75, 1.5, and 3.0 mg TE-8105, respectively) and two multiple dose cohorts (B1 flat dosing, 1.0 mg TE-8105 Q2W SC for 5 doses, and B2 titration dosing, sequence 2 x 1.5, 2 x 2.0, 2 x 2.5, and 3 x 3.0 mg Q2W SC) was conducted using a combination of in-patient and out-patient assessments. The half-life of TE-8105 was about 120 h. There was no accumulation after flat dosing, but mean (SD) accumulation ratios were 3.75 (0.86) for C(max) and 3.00 (0.65) for AUC following titration dosing. The mean % decrease in body weight from baseline to the end of study visit for titration dosing was 2.06%, with 4/8 participants maintaining weight loss of >/=5%. Treatment-related treatment emergent adverse effects (TEAEs) were consistent with the mechanism of action of TE-8105 and dose-dependent, including nausea (Part A: 16.7%; Part B: 21.4%), abdominal pain (Part A: 4.2%), constipation (Part A: 4.2%; Part B: 7.1%), and vomiting (Part A: 4.2%; Part B: 7.1%). Overall, TE-8105 was safe and well tolerated with pharmacokinetics potentially allowing for less frequent SC dosing than currently available GLP-1 receptor agonists. CI - (c) 2026 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. FAU - Chuang, Ya-Shan AU - Chuang YS AD - Immunwork, Inc., Taipei City, Taiwan. FAU - Wright, Jon D AU - Wright JD AD - Immunwork, Inc., Taipei City, Taiwan. FAU - Wong, Mun-Teng AU - Wong MT AD - Immunwork, Inc., Taipei City, Taiwan. FAU - Paneliya, Kushal J AU - Paneliya KJ AD - CMAX Clinical Research Pty Ltd, Adelaide, Australia. FAU - Yang, Wei-Shiung AU - Yang WS AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan. FAU - Chu, Hsing-Mao AU - Chu HM AD - Immunwork, Inc., Taipei City, Taiwan. AD - T-E Meds, Inc., Taipei City, Taiwan. FAU - Chang, Tse Wen AU - Chang TW AD - Immunwork, Inc., Taipei City, Taiwan. AD - T-E Meds, Inc., Taipei City, Taiwan. FAU - Polasek, Thomas M AU - Polasek TM AD - CMAX Clinical Research Pty Ltd, Adelaide, Australia. AD - Centre for Medicine Use and Safety, Monash University, Melbourne, Australia. LA - eng GR - Immunwork, Inc/ PT - Clinical Trial, Phase I PT - Journal Article PL - England TA - J Clin Pharmacol JT - Journal of clinical pharmacology JID - 0366372 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Diabetes Mellitus, Type 2 MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacokinetics MH - Half-Life MH - *Hypoglycemic Agents/pharmacokinetics MH - *Obesity/drug therapy/metabolism MH - *Overweight/drug therapy/metabolism PMC - PMC13421993 OTO - NOTNLM OT - GLP-1 receptor agonists OT - TE-8105 OT - long-acting OT - overweight/obese OT - weight loss COIS- TMP was contracted by Immunwork, Inc. as the principal investigator for the study. Y-SC, JDW, M-TW, H-MC, and TWC are employees of Immunwork, Inc. H-MC, and TWC are employees of T-E Meds, Inc. W-SY was contracted by Immunwork, Inc. as the scientific advisor. KJP declares no conflicts of interest. EDAT- 2026/07/30 12:43 MHDA- 2026/07/30 12:44 PMCR- 2026/07/30 CRDT- 2026/07/30 08:13 PHST- 2026/05/29 00:00 [revised] PHST- 2026/03/11 00:00 [received] PHST- 2026/06/03 00:00 [accepted] PHST- 2026/07/30 12:44 [medline] PHST- 2026/07/30 12:43 [pubmed] PHST- 2026/07/30 08:13 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - JCPH70224 [pii] AID - 10.1002/jcph.70224 [doi] PST - ppublish SO - J Clin Pharmacol. 2026 Aug;66(8):e70224. doi: 10.1002/jcph.70224. PMID- 42522049 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260729 IS - 2574-9870 (Electronic) IS - 2574-9870 (Linking) VI - 9 IP - 8 DP - 2026 Aug TI - Contextual Factors Affecting SGLT2 Inhibitors and GLP-1 Receptor Agonists Prescribing in Primary Care: An Application of the Consolidated Framework for Implementation Research. PG - e70263 LID - 10.1002/jac5.70263 [doi] AB - BACKGROUND: Despite strong evidence supporting cardiovascular and kidney benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes, prescribing rates remain suboptimal. The aim of this study was to assess clinicians' knowledge and comfort prescribing SGLT2i and GLP-1 RA in clinical practice and factors influencing prescribing of these agents. METHODS: This multi-methods study used questionnaires to assess self-reported knowledge and comfort prescribing SGLT2i and GLP-1 RA, and semi-structured interviews based on the Consolidated Framework for Implementation Research (CFIR) to assess factors affecting prescribing decisions among 21 clinicians (12 primary care physicians, 4 pharmacists, 5 nurse practitioners) at a large community-based health system in Virginia. Questionnaire results were analyzed using descriptive statistics, and interviews used a two-phase analytic approach combining inductive and deductive coding. RESULTS: Clinicians self-reported high knowledge (7.9/10) and comfort (8.1 and 8.4/10) prescribing SGLT2i and GLP-1 RA but identified multiple implementation barriers. The most significant barriers were insurance coverage and out-of-pocket costs, with prior authorization requirements delaying therapy initiation. Medicare beneficiaries faced particularly challenging access due to coverage gaps and ineligibility for manufacturer assistance programs. Organizational factors, including high workload, limited appointment time, and the absence of automated patient identification systems, hindered consistent prescribing. Medication burden, side effects, and aversion to injectable medications emerged as patient-related barriers. Facilitators included strong clinical evidence supporting these agents, organizational culture supportive of innovation, and access to pharmacist support. CONCLUSION: Despite high self-reported knowledge and comfort prescribing SGLT2i and GLP-1 RA, clinicians identified barriers to their use in clinical practice at the patient, clinician, organizational, and medication access levels. Future work should identify the best implementation strategies to address these barriers. CI - (c) 2026 The Author(s). JACCP: Journal of the American College of Clinical Pharmacy published by Wiley Periodicals LLC on behalf of ACCP Foundation, Ltd. FAU - Salgado, Teresa M AU - Salgado TM AUID- ORCID: 0000-0003-2708-7145 AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. FAU - Amayreh, Rana AU - Amayreh R AUID- ORCID: 0009-0009-7136-6273 AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. FAU - Alshahawey, Mona AU - Alshahawey M AUID- ORCID: 0000-0001-7424-2799 AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. FAU - Musselman, Kerri T AU - Musselman KT AD - CKB Health Consulting LLC, Midlothian, Virginia, USA. FAU - Buffington, Tonya M AU - Buffington TM AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Hyder, Haroon AU - Hyder H AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Jones, Resa M AU - Jones RM AUID- ORCID: 0000-0002-0080-4047 AD - Department of Epidemiology and Biostatistics, Barnett College of Public Health, Temple University, Philadelphia, Pennsylvania, USA. AD - Fox Chase Cancer Center, Temple Health, Temple University, Philadelphia, Pennsylvania, USA. FAU - Dixon, Dave L AU - Dixon DL AUID- ORCID: 0000-0001-7560-9521 AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. LA - eng PT - Journal Article PL - United States TA - J Am Coll Clin Pharm JT - Journal of the American College of Clinical Pharmacy : JACCP JID - 101723133 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Primary Health Care MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Surveys and Questionnaires MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Pharmacists MH - Health Knowledge, Attitudes, Practice MH - Implementation Science OTO - NOTNLM OT - diabetes mellitus OT - evidence-based practice OT - glucagon-like peptide-1 receptor agonists OT - implementation science OT - primary health care OT - qualitative research OT - sodium-glucose transporter 2 inhibitors EDAT- 2026/07/29 00:35 MHDA- 2026/07/29 18:39 CRDT- 2026/07/28 23:52 PHST- 2026/06/17 00:00 [revised] PHST- 2026/04/29 00:00 [received] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/07/29 18:39 [medline] PHST- 2026/07/29 00:35 [pubmed] PHST- 2026/07/28 23:52 [entrez] AID - 10.1002/jac5.70263 [doi] PST - ppublish SO - J Am Coll Clin Pharm. 2026 Aug;9(8):e70263. doi: 10.1002/jac5.70263. PMID- 42521944 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261026 IS - 1970-9366 (Electronic) IS - 1828-0447 (Print) IS - 1828-0447 (Linking) VI - 21 IP - 7 DP - 2026 Oct TI - GLP-1 receptor agonists at the crossroads of diabetes, hepatic steatosis, and hepatocellular carcinoma. PG - 2443-2465 LID - 10.1007/s11739-026-04456-1 [doi] AB - The epidemiology of hepatocellular carcinoma (HCC) is increasingly shaped by the expanding burden of type 2 diabetes (T2D), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed as glucose-lowering agents, have emerged as systemic metabolic therapies with effects extending beyond glycemic control, including weight reduction, cardiovascular and renal protection, and improvement of steatotic liver disease. This review summarizes current evidence on the potential role of GLP-1RAs in modifying the natural history of MASLD and reducing HCC risk. Clinical trials consistently support beneficial effects on steatosis and metabolic dysfunction-associated steatohepatitis, particularly in non-cirrhotic patients, whereas effects in established cirrhosis appear less consistent. Real-world studies and target trial emulations suggest that GLP-1RA use may be associated with lower rates of hepatic decompensation, cirrhosis progression, and incident HCC, although the magnitude and robustness of these associations vary according to disease stage, comparator therapy, exposure definition, and outcome hierarchy. The strongest apparent benefit is generally observed against insulin or sulfonylureas, while differences are attenuated in comparisons with other metabolically favorable agents, such as SGLT2 inhibitors. Mechanistic data support indirect hepatoprotective actions mediated by reduced insulin resistance, lipotoxicity, inflammation, fibrogenesis, adipose-liver crosstalk, and tumor-promoting pathways. Overall, GLP-1RAs represent promising disease-modifying agents in metabolic liver disease, but dedicated prospective studies are required to establish causality and define their role in HCC prevention. CI - (c) 2026. The Author(s). FAU - Vozza, Alfredo AU - Vozza A AD - Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy. AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. AD - Internal Medicine Unit, SS. Annunziata Hospital, Taranto, Italy. FAU - Biagi, Filippo AU - Biagi F AD - Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy. FAU - Raggi, Chiara AU - Raggi C AD - Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy. FAU - Vizzutti, Francesco AU - Vizzutti F AD - Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy. FAU - Marra, Fabio AU - Marra F AUID- ORCID: 0000-0001-8629-0878 AD - Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy. fabio.marra@unifi.it. LA - eng PT - Journal Article PT - Review DEP - 20260728 PL - Italy TA - Intern Emerg Med JT - Internal and emergency medicine JID - 101263418 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/drug therapy MH - *Liver Neoplasms/drug therapy/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Fatty Liver/drug therapy MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor/therapeutic use PMC - PMC13694454 OTO - NOTNLM OT - GLP-1RA OT - HCC OT - Hepatic decompensation OT - MASH OT - MASLD OT - Type 2 diabetes COIS- Declarations. Ethical approval: This research does not directly involve patients; hence, ethical approval was deemed unnecessary. Conflict of interest: FM is a consultant for AstraZeneca, Alfasigma, Boehringer Ingelheim, Gilead, Gore, Ipsem Madrigal, MSD/EISAI, Novo Nordisk, Roche. FV is a consultant for Gore. All other authors declare that they have no conflict of interest. Human and animal rights statement: This article does not contain any studies with human participants or performed in animal models. EDAT- 2026/07/29 00:35 MHDA- 2026/10/23 18:30 PMCR- 2026/07/28 CRDT- 2026/07/28 23:24 PHST- 2026/05/12 00:00 [received] PHST- 2026/06/25 00:00 [accepted] PHST- 2026/10/23 18:30 [medline] PHST- 2026/07/29 00:35 [pubmed] PHST- 2026/07/28 23:24 [entrez] PHST- 2026/07/28 00:00 [pmc-release] AID - 10.1007/s11739-026-04456-1 [pii] AID - 4456 [pii] AID - 10.1007/s11739-026-04456-1 [doi] PST - ppublish SO - Intern Emerg Med. 2026 Oct;21(7):2443-2465. doi: 10.1007/s11739-026-04456-1. Epub 2026 Jul 28. PMID- 42521622 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - GLP-1 Receptor Agonists and Risk of Skin Cancer in Adults With Type 2 Diabetes: A Target Trial Emulation. PG - 9377-9384 LID - 10.1111/dom.71142 [doi] AB - AIMS: Existing evidence regarding the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and risk of melanoma and non-melanoma skin cancer (NMSC) is inconclusive. This study aimed to assess the association between GLP-1RA initiation and risks of melanoma and NMSC versus sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: Target trial emulation using TriNetX electronic health records (2014-2025). Adults with T2D initiating GLP-1RAs, SGLT2is or DPP4is were included. Outcomes were incident melanoma and NMSC over 3 years. Propensity score matching and Cox models estimated hazard ratios (HRs). Sensitivity analyses included negative control outcome (NCO) calibration, a lag-period analysis and restriction to patients with obesity. RESULTS: After matching, the GLP-1RA versus SGLT2i cohort included 235 797 pairs; the GLP-1RA versus DPP4i cohort included 153 873 pairs. Mean follow-up ranged from 1.8 to 2.2 years. GLP-1RA use was not associated with melanoma compared with either SGLT2i (HR, 1.04; 95% CI, 0.93-1.17) or DPP4i (HR, 1.09; 95% CI, 0.95-1.25). A borderline increase in NMSC risk was observed in the comparison with SGLT2is (HR, 1.06; 95% CI, 1.00-1.11); no such association was identified in the comparison with DPP4is (HR, 1.03; 95% CI, 0.97-1.09). Findings were generally consistent across sensitivity analyses; however, the association with NMSC was attenuated after NCO calibration. CONCLUSIONS: GLP-1RA therapy was not associated with an increased risk of melanoma. A borderline increase in NMSC risk was observed compared with SGLT2is but was not evident after NCO calibration. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - Center for Preventative Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Zhang, Bingyu AU - Zhang B AUID- ORCID: 0000-0001-7176-249X AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Lu, Ying AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Zhou, Ting AU - Zhou T AUID- ORCID: 0000-0003-3392-2979 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Briceno, Cesar A AU - Briceno CA AD - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Han, Jiali AU - Han J AUID- ORCID: 0000-0002-8309-7092 AD - Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence-Based Practice (CEP), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Institute for Biomedical Informatics (IBI), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - RF1AG077820/NH/NIH HHS/United States GR - R01DK128237/NH/NIH HHS/United States GR - R01AG073435/NH/NIH HHS/United States GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - RF1 AG077820/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260728 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Skin Neoplasms/epidemiology/chemically induced MH - Male MH - Female MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - *Melanoma/epidemiology/chemically induced MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors MH - Incidence PMC - PMC13538745 OTO - NOTNLM OT - GLP-1 analogue OT - cohort study OT - incretin therapy OT - pharmaco-epidemiology OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/07/29 00:35 MHDA- 2026/09/03 05:36 PMCR- 2026/09/03 CRDT- 2026/07/28 22:03 PHST- 2026/07/06 00:00 [revised] PHST- 2026/04/22 00:00 [received] PHST- 2026/07/15 00:00 [accepted] PHST- 2026/09/03 05:36 [medline] PHST- 2026/07/29 00:35 [pubmed] PHST- 2026/07/28 22:03 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71142 [pii] AID - 10.1111/dom.71142 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9377-9384. doi: 10.1111/dom.71142. Epub 2026 Jul 28. PMID- 42518911 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Real-World Comparative Weight Loss of GLP-1 Receptor Agonists in the All of Us Research Program: A Retrospective Cohort Study. PG - 604247 LID - 10.2147/DDDT.S604247 [doi] LID - 604247 AB - PURPOSE: To assess the real-world associations of five glucagon-like peptide-1 receptor agonists (GLP-1RAs) with weight loss in a diverse US population of adults with obesity, with and without type 2 diabetes, and whether the relative ordering of weight loss observed in trials is mirrored in routine practice. PATIENTS AND METHODS: We conducted a retrospective, new-user, active-comparator cohort study using the National Institutes of Health All of Us Research Program. We included 14,046 adults with obesity (body mass index [BMI] >/=30 kg/m(2)) initiating exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide. Groups were compared after multivariable adjustment for baseline confounders. Participants were followed from the index date until the outcome, death, or loss to follow-up; percent weight and BMI change was assessed at 12 months (+/-45 days). Cox proportional hazards models estimated the relative likelihood over time of achieving weight-loss thresholds (>/=5%, >/=10%, >/=15%) and >/=1 BMI-category reduction; linear regression assessed the magnitude of weight change, with liraglutide as reference. RESULTS: Tirzepatide showed the highest likelihood of >/=15% weight loss (adjusted hazard ratio [aHR] 5.57; 95% CI, 3.66-8.49) and the greatest mean weight loss at 12 months (-13.0%), followed by semaglutide (aHR 1.77; 95% CI, 1.56-2.01; -5.9%); both were significantly greater than the older agents in adjusted analyses. Exenatide, dulaglutide, and liraglutide showed comparable, modest weight loss (approximately -4.0%). This ordering was consistent regardless of type 2 diabetes status, although weight loss was greater without diabetes for semaglutide but similar for tirzepatide. CONCLUSION: In this large, diverse real-world cohort, tirzepatide and semaglutide were associated with significantly greater weight loss than older agents. These findings are consistent with the relative ordering reported in trials, though the observational design cannot confirm it. Residual confounding cannot be excluded, and the small tirzepatide sample (n=386) and limited follow-up warrant cautious interpretation. CI - (c) 2026 Hwang et al. FAU - Hwang, Inyoung AU - Hwang I AUID- ORCID: 0000-0003-4953-759X AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, 04763, Republic of Korea. FAU - Lee, Sang Won AU - Lee SW AUID- ORCID: 0000-0002-3862-9491 AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, 04763, Republic of Korea. AD - Department of Pharmacology, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea. FAU - Kim, Yun AU - Kim Y AUID- ORCID: 0000-0002-9809-7351 AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongbuk, 38430, Republic of Korea. AD - Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan, Gyeongbuk, 38430, Republic of Korea. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260714 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology/administration & dosage MH - Exenatide/pharmacology MH - United States MH - Adult MH - *Hypoglycemic Agents/pharmacology MH - Liraglutide/pharmacology MH - Cohort Studies MH - Recombinant Fusion Proteins/pharmacology/administration & dosage MH - Anti-Obesity Agents MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Immunoglobulin Fc Fragments/pharmacology MH - Aged PMC - PMC13381347 OAB - WHY WAS THE STUDY DONE? Obesity is a long-term condition, and many people need more than lifestyle changes to manage it. Newer medicines called GLP-1 receptor agonists can reduce appetite and have worked well in clinical trials. But trials enroll selected volunteers who may differ from people in everyday care. We compared how five of these medicines work for weight loss in a large, diverse, real-world group. WHAT DID THE RESEARCHERS DO AND FIND? We studied health records from 14,046 adults with obesity in the National Institutes of Health All of Us Research Program. We compared how much weight patients lost in one year after starting exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide. On average, tirzepatide users lost about 13.0% and semaglutide users about 5.9%, while patients taking the three older medicines lost around 4%. Tirzepatide users were also the most likely to achieve large weight loss of 15% or more. WHAT DO THESE RESULTS MEAN? These findings suggest the two newest medicines, tirzepatide and semaglutide, are linked to greater weight loss than older options, even in everyday care. Greater weight loss is generally linked to better health, so these differences could matter for patients, though our study cannot prove the drugs caused them. Because we used everyday medical records rather than a clinical trial, the results show links rather than proof of cause and effect. Tirzepatide is new, so few patients had taken it; larger studies are needed to confirm these early findings. OABL- eng OTO - NOTNLM OT - body mass index OT - incretin mimetics OT - obesity management OT - pharmacoepidemiology OT - type 2 diabetes mellitus COIS- The authors report no conflicts of interest in this work. EDAT- 2026/07/28 18:35 MHDA- 2026/07/29 18:38 PMCR- 2026/07/14 CRDT- 2026/07/28 12:52 PHST- 2026/02/19 00:00 [received] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 18:35 [pubmed] PHST- 2026/07/28 12:52 [entrez] PHST- 2026/07/14 00:00 [pmc-release] AID - 604247 [pii] AID - 10.2147/DDDT.S604247 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Jul 14;20:604247. doi: 10.2147/DDDT.S604247. eCollection 2026. PMID- 42518541 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - The gut microbiota as a potential determinant of response to GLP-1 receptor agonists: a narrative review. PG - 1858420 LID - 10.3389/fendo.2026.1858420 [doi] LID - 1858420 AB - Interindividual variability in clinical response to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represents a significant challenge in the management of obesity and type 2 diabetes (T2D). In recent years, growing interest has focused on the potential role of the gut microbiota as a biological modifier of incretin-based therapy. This narrative review synthesizes current preclinical and human evidence on the bidirectional interactions between GLP-1 RAs and the intestinal microbial ecosystem, with particular attention to microbial composition, metabolite production (including short-chain fatty acids and bile acids), intestinal barrier integrity, and inflammatory signaling. Experimental models consistently demonstrate that GLP-1 RAs can remodel gut microbial communities and influence metabolite profiles. In human studies, GLP-1 RA therapy has been associated with changes in microbial diversity and enrichment of specific taxa; however, most available data remain observational and associative. Small exploratory cohorts suggest that baseline microbiota composition may correlate with differential metabolic response, giving rise to the responder/non-responder framework. Nevertheless, definitions of response are heterogeneous, study populations are limited in size, and mechanistic causality has not been established. Importantly, microbiota changes observed during GLP-1 RA therapy may be influenced by confounding factors such as weight loss magnitude, dietary modifications, and concomitant treatments, particularly metformin. Functional pathway inferences frequently rely on 16S rRNA-based predictions rather than direct metabolomic measurements, warranting cautious interpretation. Overall, current evidence supports the hypothesis that host-microbiome interactions may contribute to therapeutic heterogeneity, but robust longitudinal and interventional human studies are required before microbiome-informed stratification or adjunctive microbiota-targeted interventions can be considered for clinical implementation. Elucidating these interactions may ultimately refine precision approaches to incretin-based therapy in metabolic disease. CI - Copyright (c) 2026 De La Motte, Carreras and Drago. FAU - De La Motte, Luigi Regenburgh AU - De La Motte LR AD - Unita Operativa Complessa UOC Laboratory of Clinical Medicine with Specialized Areas, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS MultiMedica, Milan, Italy. FAU - Carreras, Francesca AU - Carreras F AD - Unita Operativa Complessa UOC Laboratory of Clinical Medicine with Specialized Areas, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS MultiMedica, Milan, Italy. FAU - Drago, Lorenzo AU - Drago L AD - Unita Operativa Complessa UOC Laboratory of Clinical Medicine with Specialized Areas, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS MultiMedica, Milan, Italy. AD - Clinical Microbiology and Microbiome Laboratory, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260706 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastrointestinal Microbiome/drug effects/physiology MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology/metabolism MH - Animals MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Incretins/therapeutic use MH - *Obesity/drug therapy/microbiology/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13381830 OTO - NOTNLM OT - GLP-1 receptor agonists OT - gut microbiome modulation OT - incretin-microbiota axis OT - metabolism OT - therapeutic response variability COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author LD declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2026/07/28 18:35 MHDA- 2026/07/29 18:38 PMCR- 2026/07/06 CRDT- 2026/07/28 12:48 PHST- 2026/04/17 00:00 [received] PHST- 2026/06/19 00:00 [revised] PHST- 2026/06/19 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 18:35 [pubmed] PHST- 2026/07/28 12:48 [entrez] PHST- 2026/07/06 00:00 [pmc-release] AID - 10.3389/fendo.2026.1858420 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 6;17:1858420. doi: 10.3389/fendo.2026.1858420. eCollection 2026. PMID- 42511792 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260825 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 14 DP - 2026 Jul 20 TI - Relationship Between GLP-1-Based Therapies and Periodontal Health: A Systematic Review of Current Evidence and Future Perspectives. LID - 10.3390/ijms27146447 [doi] LID - 6447 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus and obesity, have recently attracted attention for their potential effects on periodontal tissues. This systematic review aimed to evaluate the current evidence regarding the relationship between GLP-1-based therapies and periodontal health, with particular emphasis on anti-inflammatory, osteogenic, and regenerative mechanisms. A comprehensive literature search of PubMed, Web of Science, and Embase databases identified 22 eligible studies, including in vitro, animal, and human investigations. The available evidence suggests that GLP-1RAs such as liraglutide and exendin-4 may attenuate periodontal inflammation, reduce alveolar bone loss, and enhance osteogenic differentiation of periodontal ligament and dental pulp stem cells through modulation of pathways including MAPK/ERK, Wnt/beta-catenin, NF-kappaB, and PKCbeta2. Clinical observations additionally indicate a bidirectional relationship between periodontitis and incretin signalling, with periodontal therapy associated with increased systemic GLP-1 levels. However, the current evidence remains heterogeneous and is largely limited to preclinical and observational studies. Randomised clinical trials are required to determine the clinical efficacy and therapeutic relevance of GLP-1-based therapies in periodontitis management. FAU - Nijakowski, Kacper AU - Nijakowski K AUID- ORCID: 0000-0002-5042-5985 AD - Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Poznan, Poland. AD - Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy. FAU - Gruszczynski, Dawid AU - Gruszczynski D AUID- ORCID: 0000-0001-9519-4183 AD - Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland. FAU - Lacinik, Szymon AU - Lacinik S AD - Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Poznan, Poland. FAU - Zdrojewski, Jakub AU - Zdrojewski J AD - Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Poznan, Poland. FAU - Ottolenghi, Livia AU - Ottolenghi L AUID- ORCID: 0000-0001-7390-4316 AD - Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy. FAU - Mazur, Marta AU - Mazur M AUID- ORCID: 0000-0002-0525-681X AD - Interdisciplinary Department of Wellbeing, Health and Environmental Sustainability (BeSSA), Sapienza University of Rome, 02100 Rome, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260720 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptide 1/metabolism/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Periodontitis/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism PMC - PMC13411477 OTO - NOTNLM OT - GLP-1 OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - periodontal disease OT - periodontal therapy OT - periodontitis OT - periodontium COIS- The authors declare no conflicts of interest. EDAT- 2026/07/28 06:37 MHDA- 2026/07/29 18:38 PMCR- 2026/07/20 CRDT- 2026/07/28 01:09 PHST- 2026/06/11 00:00 [received] PHST- 2026/07/12 00:00 [revised] PHST- 2026/07/19 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 06:37 [pubmed] PHST- 2026/07/28 01:09 [entrez] PHST- 2026/07/20 00:00 [pmc-release] AID - ijms27146447 [pii] AID - ijms-27-06447 [pii] AID - 10.3390/ijms27146447 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jul 20;27(14):6447. doi: 10.3390/ijms27146447. PMID- 42511463 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 14 DP - 2026 Jul 8 TI - Incretin-Based Therapies in Sports: Pharmacological Mechanisms, Performance-Enhancing Potential, and Anti-Doping Implications-A Narrative Review. LID - 10.3390/ijms27146116 [doi] LID - 6116 AB - Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, have revolutionized the management of type 2 diabetes and obesity. Recent evidence suggests these agents may influence athletic performance through effects on body composition, energy metabolism, and cardiovascular function. This narrative review critically evaluates whether incretin therapies could constitute doping under World Anti-Doping Agency (WADA) criteria. We narratively reviewed the literature on incretin pharmacology, metabolic effects relevant to athletic performance, and anti-doping regulations, searching PubMed, Scopus, and Web of Science using terms including "GLP-1 receptor agonists", "DPP-4 inhibitors", "doping", "athletic performance", "WADA", and "sports pharmacology", without date restrictions. GLP-1 RAs (semaglutide, liraglutide, tirzepatide, exenatide) induce substantial weight loss (predominantly fat mass) but also reduce lean mass by 20-30% of total weight loss. Preclinical studies demonstrate enhanced exercise endurance, mitochondrial biogenesis, and glucose uptake via GLP-1R/AMPK signaling. However, clinical trials show no consistent improvement in physical performance in humans. Currently, incretin therapies are not listed on the WADA Prohibited List. While incretin therapies offer theoretical performance-enhancing potential through weight management and metabolic optimization, current evidence does not support classification as doping agents. Continued surveillance is warranted as misuse patterns emerge. FAU - La Vignera, Sandro AU - La Vignera S AUID- ORCID: 0000-0002-7113-2372 AD - Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy. FAU - Condorelli, Rosita A AU - Condorelli RA AUID- ORCID: 0000-0002-5217-9343 AD - Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260708 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Performance-Enhancing Substances) SB - IM MH - Humans MH - *Incretins/pharmacology/therapeutic use MH - *Doping in Sports MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Athletic Performance MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use MH - Energy Metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Tirzepatide MH - *Performance-Enhancing Substances/pharmacology PMC - PMC13411830 OTO - NOTNLM OT - GLP-1 receptor agonists OT - WADA OT - anti-doping OT - athletic performance OT - body composition OT - doping OT - incretin therapy OT - liraglutide OT - semaglutide OT - sports pharmacology COIS- The authors declare no conflicts of interest. EDAT- 2026/07/28 06:37 MHDA- 2026/07/29 18:38 PMCR- 2026/07/08 CRDT- 2026/07/28 01:08 PHST- 2026/06/14 00:00 [received] PHST- 2026/07/04 00:00 [revised] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 06:37 [pubmed] PHST- 2026/07/28 01:08 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - ijms27146116 [pii] AID - ijms-27-06116 [pii] AID - 10.3390/ijms27146116 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jul 8;27(14):6116. doi: 10.3390/ijms27146116. PMID- 42508090 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260929 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 20 IP - 7 DP - 2026 Jul TI - Nutritional intake changes during GLP-1 receptor agonist therapy: A systematic review and meta-analysis. PG - 103466 LID - S1871-4021(26)00093-7 [pii] LID - 10.1016/j.dsx.2026.103466 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists, including the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide, produce substantial weight loss, yet their effect on objectively measured dietary intake has not been quantitatively synthesized. We assessed their impact on ad libitum lunch energy intake. METHODS: We searched six databases through March 31, 2026, for studies reporting quantitative dietary outcomes in adults receiving a GLP-1 or dual GIP/GLP-1 receptor agonist. Randomized or crossover placebo-controlled trials lasting at least four weeks that reported standardized ad libitum lunch intake were pooled using a DerSimonian-Laird random-effects model. Prespecified sensitivity analyses included restricted maximum likelihood (REML) and Paule-Mandel estimators, a 95% prediction interval, a subgroup analysis, a leave-one-out analysis, and an exploratory three-week phase 1 tirzepatide trial. RESULTS: Sixteen studies were included in the systematic review; four arms from three trials (209 participants) contributed to the primary meta-analysis. The pooled treatment difference in ad libitum lunch energy intake was -1132 kJ (95% confidence interval [CI] -1449 to -815), approximately -271 kcal, with no heterogeneity (I-squared = 0%; 95% prediction interval -1828 to -436 kJ). Adding the phase 1 trial (k = 5) increased the effect to -1421 kJ but introduced substantial heterogeneity (I-squared = 70%). The semaglutide-versus-tirzepatide difference was not significant (p = 0.154). CONCLUSIONS: GLP-1 receptor agonist therapy markedly reduces acute energy intake under standardized meal tests, but real-world habitual intake remains underreported. Structured nutritional counseling emphasizing adequate protein should complement pharmacotherapy. CI - Copyright (c) 2026 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Quan, Anh Tuan AU - Quan AT AD - Department of Internal Medicine, Van Phuc City Hospital, Ho Chi Minh City, Viet Nam; University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam. Electronic address: tuan.quan.md@outlook.com. FAU - Nguyen, Hoang Linh AU - Nguyen HL AD - Department of Cardic Arrhythmia, Thong Nhat Hospital, Ho Chi Minh City, Viet Nam. FAU - Nguyen, Tran My Thanh AU - Nguyen TMT AD - Department of Endocrinology and Nephrology, Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Viet Nam. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260725 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Energy Intake/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Tirzepatide/pharmacology/therapeutic use OTO - NOTNLM OT - Energy intake OT - GLP-1 receptor agonists OT - Meta-analysis OT - Obesity OT - Tirzepatide COIS- Declaration of competing interest All named authors provide the following disclosure covering the 24 months preceding submission. The scope of disclosure includes employment, consultancies, honoraria, speaker fees, advisory-board or steering-committee membership, research grants or contracts, travel or accommodation support, expert testimony, patents or patent applications, and stock or stock options, as well as any other financial or non-financial relationship with a commercial entity - in particular the manufacturers of the medications evaluated in this review, Novo Nordisk and Eli Lilly and Company. This work received no funding from any public, commercial, or not-for-profit source. The authors have no financial or personal relationships that could be perceived to have influenced the work reported in this paper. EDAT- 2026/07/27 18:35 MHDA- 2026/09/16 23:34 CRDT- 2026/07/27 17:59 PHST- 2026/04/07 00:00 [received] PHST- 2026/07/21 00:00 [revised] PHST- 2026/07/23 00:00 [accepted] PHST- 2026/09/16 23:34 [medline] PHST- 2026/07/27 18:35 [pubmed] PHST- 2026/07/27 17:59 [entrez] AID - S1871-4021(26)00093-7 [pii] AID - 10.1016/j.dsx.2026.103466 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2026 Jul;20(7):103466. doi: 10.1016/j.dsx.2026.103466. Epub 2026 Jul 25. PMID- 42507338 OWN - NLM STAT- MEDLINE DCOM- 20260924 LR - 20260924 IS - 1827-1669 (Electronic) IS - 0026-4806 (Linking) VI - 117 IP - 4 DP - 2026 Aug TI - Effects of GLP1-RAs and SGLT2i on liver steatosis and fibrosis in MASLD with type 2 diabetes. PG - 185-198 LID - 10.23736/S0026-4806.26.09922-2 [doi] AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in individuals with type 2 diabetes mellitus (T2DM). MASLD ranges from simple liver steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. New glucose-lowering agents have demonstrated benefits beyond glycemic regulation. This study assesses the effects of receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) on metabolic parameters, hepatic steatosis, and fibrosis in patients with MASLD and T2DM. METHODS: Prospectively, 192 patients were enrolled: 132 added therapy with one novel glucose-lowering drug (GLP-1RA or SGLT2i) or their combination, and 60 patients continued with other glucose-lowering therapies (such as sulfonylureas, PPAR-gamma agonists, DPP-4 inhibitors, metformin or insulin). Metabolic parameters, fibrosis indices (APRI, FIB-4, NFS, stiffness), and steatosis assessed by ultrasound-based attenuation imaging (ATT), were evaluated at baseline, 6 and 12 months. RESULTS: The four treatment groups had comparable biochemical profiles. At 6 months, significant reductions were observed in the ALT, AST, GGT, and ALP levels (P<0.01). Both GLP-1RA and SGLT2i significantly improve glycemic control at 6 and 12 months; the reduction in HbA1c was associated with a decrease in serum cholesterol (statistically significant in the SGLT2i group). Non-invasive fibrosis scores (FIB-4, APRI, NFS) showed no significant changes; however, NFS showed modest improvement in the SGLT2i group. Liver stiffness values decreased significantly after 12 months in GLP-1RA, SGLT2i, or combination therapy groups. ATT consistently improved hepatic steatosis. CONCLUSIONS: GLP-1RA and SGLT2i improve glycemic control and reduce hepatic steatosis and stiffness in patients with MASLD and T2DM. FAU - Mega, Andrea AU - Mega A AD - Department of Gastroenterology, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy. FAU - Aigner, Elmar AU - Aigner E AD - First Department of Medicine, University Clinic Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria. FAU - Turri, Chiara AU - Turri C AD - Department of Gastroenterology, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy. FAU - Vittadello, Fabio AU - Vittadello F AD - Explora Research and Statistical Analysis, Padua, Italy. FAU - Dauriz, Marco AU - Dauriz M AD - Section of Endocrinology and Diabetes, Department of Internal Medicine, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy. FAU - Floreani, Annarosa AU - Floreani A AD - University of Padua, Padua, Italy. AD - IRCCS Negrar, Verona, Italy. FAU - Marzi, Luca AU - Marzi L AD - Department of Gastroenterology, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy. FAU - Sacco, Rodolfo AU - Sacco R AD - Gastroenterology and Digestive Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy. FAU - Stasi, Cristina AU - Stasi C AD - Department of Life Science, Health and Health Professions, Link Campus University, Rome, Italy - cristina.stasi@gmail.com. LA - eng PT - Journal Article DEP - 20260727 PL - Italy TA - Minerva Med JT - Minerva medica JID - 0400732 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - Male MH - *Liver Cirrhosis/drug therapy/etiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Middle Aged MH - *Fatty Liver/drug therapy/etiology MH - Prospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Drug Therapy, Combination EDAT- 2026/07/27 12:36 MHDA- 2026/09/24 05:36 CRDT- 2026/07/27 11:20 PHST- 2026/09/24 05:36 [medline] PHST- 2026/07/27 12:36 [pubmed] PHST- 2026/07/27 11:20 [entrez] AID - S0026-4806.26.09922-2 [pii] AID - 10.23736/S0026-4806.26.09922-2 [doi] PST - ppublish SO - Minerva Med. 2026 Aug;117(4):185-198. doi: 10.23736/S0026-4806.26.09922-2. Epub 2026 Jul 27. PMID- 42507153 OWN - NLM STAT- MEDLINE DCOM- 20261014 LR - 20261027 IS - 1554-8120 (Electronic) IS - 1054-2523 (Linking) VI - 35 IP - 10 DP - 2026 Oct TI - Understanding Biased Signaling and Small-Molecule Binding for Treatment of Type 2 Diabetes Mellitus and Obesity at the Glucagon-Like Peptide-1 Receptor (GLP-1R) Based on Molecular Dynamics Simulations. PG - 2073-2093 LID - 10.1007/s00044-026-03579-6 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) is a class B1 G protein-coupled receptor expressed in multiple tissues and is a major therapeutic target for type 2 diabetes mellitus and obesity. Here, we investigate the mechanisms of GLP-1R binding and activation using molecular dynamics (MD) simulations of semaglutide, tirzepatide, danuglipron, and CHU-128bound GLP-1R-Gs complexes. We analyze these simulations as a function of temperature, ligand class (peptide vs. small molecule), and signaling profile (biased vs. non-biased) to assess how these factors affect GLP-1R interactions and conformational dynamics. Our results reveal distinct interaction patterns and structural features associated with each factor which persist over the MD trajectories. Together, these findings deepen our mechanistic understanding of GLP-1R agonism and further aid in the design of effective, orally available GLP-1R agonists with reduced side effects. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Brubaker, Jack AU - Brubaker J AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Kim, Soo-Kyung AU - Kim SK AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Li, Bo AU - Li B AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Yang, Moon Young AU - Yang MY AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Goddard Iii, William A AU - Goddard Iii WA AUID- ORCID: 0000-0003-0097-5716 AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. wag@caltech.edu. LA - eng GR - 1R01HL155532 and R01HL11447/National Institutes Health/ GR - CBET 2311117/National Science Foundation/ PT - Journal Article DEP - 20260727 PL - United States TA - Med Chem Res JT - Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents JID - 9211347 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Small Molecule Libraries) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Molecular Dynamics Simulation MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - Signal Transduction/drug effects MH - Humans MH - *Obesity/drug therapy/metabolism MH - Semaglutide MH - *Small Molecule Libraries/chemistry/pharmacology/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - *Hypoglycemic Agents/chemistry/pharmacology MH - Protein Binding COIS- Declarations. Conflict of interests: The authors declare no competing interests. EDAT- 2026/07/27 12:36 MHDA- 2026/10/14 18:14 CRDT- 2026/07/27 11:13 PHST- 2026/04/11 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/10/14 18:14 [medline] PHST- 2026/07/27 12:36 [pubmed] PHST- 2026/07/27 11:13 [entrez] AID - 10.1007/s00044-026-03579-6 [pii] AID - 10.1007/s00044-026-03579-6 [doi] PST - ppublish SO - Med Chem Res. 2026 Oct;35(10):2073-2093. doi: 10.1007/s00044-026-03579-6. Epub 2026 Jul 27. PMID- 42504813 OWN - NLM STAT- MEDLINE DCOM- 20260727 LR - 20260813 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 8 DP - 2026 Aug TI - Discontinuation of glucagon-like peptide-1 receptor agonists among US adults: A national survey. PG - 903-910 LID - 10.18553/jmcp.2026.32.8.903 [doi] AB - BACKGROUND: Although many people discontinue glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the reasons for discontinuation are unclear. OBJECTIVE: To identify self-reported reasons for GLP-1 RA discontinuation among US adults. METHODS: Cross-sectional survey of US adults fielded in June 2025 using Ipsos Omnibus and incorporating survey weights calibrated to census benchmarks. We included individuals who initiated a GLP-1 RA between January 2022 and June 2025 and subsequently discontinued therapy. Outcomes included duration of use, self-reported reason(s) for discontinuation, medication source, out-of-pocket payment, and insurance coverage. Descriptive statistics and chi-square tests for statistical significance were used. RESULTS: Of 7,035 individuals screened, 440 respondents met eligibility criteria and completed the survey. Of these 440 participants, 51.1% were female, 42.3% were aged between 18 and 34 years, and 23.8% reported having type 2 diabetes. More than half of these discontinuers (54.6%) reported discontinuing a GLP-1 RA within 6 months of initiation, and 79.7% reported discontinuation within 12 months of use. Approximately 1 in 7 (14.4%) reported sourcing GLP-1 RAs from a friend or family member, and more than half reported using a copayment coupon (35.4%) or free sample (22.0%). Many respondents (31.3%) reported first filling a prescription without insurance. Approximately 1 in 5 reported sourcing their medicine from a compounding pharmacy (9.8%) or Internet-based (9.1%) source. The most frequently cited reasons for discontinuation were cost (36.1%), side effects (33.3%), no insurance coverage (28.2%), and achieving a weight-loss goal (26.1%). Compared with those without diabetes, respondents with diabetes were significantly more likely to discontinue because of side effects (50.1% vs 28.1%, P = 0.0008). Respondents who reported sourcing their GLP-1 RA from a compounding pharmacy or Internet-based source were significantly more likely to discontinue because they perceived the medication to be ineffective compared with those who obtained their medication from a retail or mail-order pharmacy (17.5% vs 6.6%, P = 0.009). Neither diabetes status nor GLP-1 RA source was significantly associated with early discontinuation (<6 months). CONCLUSIONS: In this national survey, most US adults who stopped GLP-1 RAs did so within 6 months because of cost, adverse effects, lack of coverage, or having achieved a weight loss goal. Differences in coverage, costs, and sourcing are modifiable targets that may decrease high rates of GLP-1 RA discontinuation. FAU - DiStefano, Michael J AU - DiStefano MJ AD - Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora. AD - Center for Bioethics and Humanities, University of Colorado Anschutz Medical Campus, Aurora. FAU - Zon, Juliet AU - Zon J AD - Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Olson, Erik G AU - Olson EG AD - Ipsos, New York, NY. FAU - Levy, Joseph F AU - Levy JF AD - Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Anderson, Gerard F AU - Anderson GF AD - Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Alexander, G Caleb AU - Alexander GC AD - Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cross-Sectional Studies MH - United States MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/economics/administration & dosage MH - Adult MH - Male MH - Young Adult MH - Adolescent MH - Middle Aged MH - Surveys and Questionnaires PMC - PMC13403254 COIS- Dr Alexander is past chair of FDA's Peripheral and Central Nervous System Advisory Committee and a co-founding principal and equity holder in Stage Analytics. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. Mr Olson is an employee of Ipsos. There are no other disclosures to report. This research was funded by Arnold Ventures. The funder had no role in the design, conduct, or interpretation of the study or in the decision to pursue peer-reviewed publication. EDAT- 2026/07/27 12:36 MHDA- 2026/07/27 12:37 PMCR- 2026/08/01 CRDT- 2026/07/27 06:43 PHST- 2026/07/27 12:37 [medline] PHST- 2026/07/27 12:36 [pubmed] PHST- 2026/07/27 06:43 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.8.903 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Aug;32(8):903-910. doi: 10.18553/jmcp.2026.32.8.903. PMID- 42504064 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260914 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE). PG - 9304-9316 LID - 10.1111/dom.71132 [doi] AB - AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0 mg as add-on to dose-reduced insulin glargine (Sema+IGlar(reduced)) versus dose-titrated IGlar (IGlar(titrated)) on glycated haemoglobin (HbA(1c)), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index >/= 25 kg/m(2)), and treatment with basal insulin /=30 kg/m(2)). Participants will be treated for up to 160 weeks (3 years), with a total follow-up period of up to 184 weeks (3 years and 6 months). Study visits are scheduled every 6 months and include blood sampling, clinical examinations and completion of self-administered questionnaires. The primary outcome is the development of T2DM based on the American Diabetes Association criteria. Secondary outcomes include need for diabetes rescue therapy, regression to normoglycaemia, weight loss, insulin sensitivity, beta-cell function, cardiometabolic risk profile, patient-reported outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The study was approved by the Federal Agency for Medicines and Health Products and the relevant Ethics Committees (2022-502082-22-00) (S66967). Recruitment started in September 2023. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences. Individual participant data will be made available on reasonable request after study completion, database lock, unblinding and publication of the primary results, subject to applicable ethical, legal and data protection requirements. TRIAL REGISTRATION NUMBER: NCT05569772. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Vanlaer, Yana AU - Vanlaer Y AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. FAU - Embo, Nina AU - Embo N AD - Faculty of Medicine, KU Leuven, Leuven, Belgium. FAU - Bochanen, Niels AU - Bochanen N AD - Department of Endocrinology-Diabetology-Metabolism, University Hospital Antwerp, Edegem, Belgium. FAU - Van Wilder, Nancy AU - Van Wilder N AD - Department of Endocrinology, Brussels University Hospital, Anderlecht, Belgium. FAU - Vereecke, Gertjan AU - Vereecke G AD - Department of Endocrinology, General Hospital Groeninge, Kortrijk, Belgium. FAU - Wierckx, Katrien AU - Wierckx K AD - Department of Endocrinology, AZORG Hospital, Aalst, Belgium. FAU - Verhaegen, Ann AU - Verhaegen A AD - Department of Endocrinology, ZAS Jan Palfijn, Merksem, Belgium. FAU - Coremans, Peter AU - Coremans P AD - Department of Endocrinology-Diabetology, Vitaz Sint-Niklaas Moerland, Sint-Niklaas, Belgium. FAU - Philips, Jean-Christophe AU - Philips JC AD - Department of Diabetology, Nutrition and Metabolic Diseases, Liege University Hospital Sart Tilman Site, Liege, Belgium. FAU - Lytrivi, Maria AU - Lytrivi M AD - Department of Endocrinology, Erasmus Hospital, Brussels, Belgium. FAU - Oriot, Philippe AU - Oriot P AD - Department of Endocrinology-Diabetology, Hospital Centre Mouscron, Mouscron, Belgium. FAU - Vandewalle, Sara AU - Vandewalle S AD - AZ Sint-Jan Brugge AV, Bruges, Belgium. FAU - Cuypers, Joke AU - Cuypers J AD - Department of Endocrinology-Diabetology-Nephrology, AZ Turnhout vzw Campus Sint-Jozef, Turnhout, Belgium. FAU - Deconinck, Barbara AU - Deconinck B AD - Department of Endocrinology-Diabetology, Jan Yperman Ziekenhuis, Ypres, Belgium. FAU - Laenen, Annouschka AU - Laenen A AD - Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium. FAU - Mathieu, Chantal AU - Mathieu C AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. AD - Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. FAU - Benhalima, Katrien AU - Benhalima K AUID- ORCID: 0000-0002-3325-0263 AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium Katrien.Benhalima@uzleuven.be. AD - Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. LA - eng SI - ClinicalTrials.gov/NCT05569772 PT - Clinical Trial Protocol PT - Journal Article DEP - 20260723 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Diabetes Mellitus, Type 2/prevention & control MH - *Diabetes, Gestational MH - Pregnancy MH - Double-Blind Method MH - *Prediabetic State/drug therapy MH - Postpartum Period MH - Belgium MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - Adult MH - Cost-Benefit Analysis PMC - PMC13404484 OTO - NOTNLM OT - Diabetes in pregnancy OT - Life Change Events OT - Postpartum Period COIS- Competing interests: None declared. EDAT- 2026/07/24 00:37 MHDA- 2026/07/24 00:38 PMCR- 2026/07/23 CRDT- 2026/07/23 21:03 PHST- 2026/07/24 00:38 [medline] PHST- 2026/07/24 00:37 [pubmed] PHST- 2026/07/23 21:03 [entrez] PHST- 2026/07/23 00:00 [pmc-release] AID - bmjopen-2026-118191 [pii] AID - 10.1136/bmjopen-2026-118191 [doi] PST - epublish SO - BMJ Open. 2026 Jul 23;16(7):e118191. doi: 10.1136/bmjopen-2026-118191. PMID- 42487237 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260821 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 4 DP - 2026 Jul TI - Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. PG - e70275 LID - 10.1002/edm2.70275 [doi] LID - e70275 AB - BACKGROUND AND AIM: Orforglipron (OFG), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RAs), showed potential benefits for type 2 diabetes mellitus (T2DM) and obesity. Its dose-response effects on body weight-related parameters and glycemic outcomes remain incompletely analysed. This network meta-analysis aims to address this gap across multiple doses of OFG (3, 12, 24, 36 and 45 mg) in adults with or without T2DM at 12, 26 and 36 weeks. METHODS: PRISMA guidelines were followed in our study. Embase, PubMed, Web of Science and Scopus were searched for randomised controlled trials. Random-effects models expressed OFG effects as odds ratios (OR), mean difference (MD) and standardised mean difference (SMD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis. RESULTS: Six RCTs comprising 4878 participants were included. OFG demonstrated reductions in body weight, BMI and waist circumference across all follow-ups. OFG 45 mg dose produced the greatest effects in body weight (SMD: -1.71 kg at 12 weeks, MD: -8.81 kg at 26 weeks and MD: -12.13 kg at 36 weeks vs. placebo). Categorical weight-loss analyses showed that individuals receiving 24-45 mg increased the odds to achieve >/= 5%, >/= 10% and >/= 15% weight loss at 26 weeks. Glycemic outcomes improved across all doses, with the greatest HbA1c reduction at 45 mg (-1.65%; 95% CI -1.98 to -1.32) and greatest fasting glucose improvement at 36 mg dose. Treatment-emergent adverse events increased with dose. CONCLUSION: OFG demonstrated improvements in weight-related outcomes and glycemic outcomes. Adverse events increased with dose, consistent with expected class tolerability. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Hageen, Ahmed W AU - Hageen AW AD - Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Gadelmawla, Ahmed Farid AU - Gadelmawla AF AUID- ORCID: 0000-0002-5802-2291 AD - Faculty of Medicine, Menoufia University, Menoufia, Egypt. AD - Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, Massachusetts, USA. FAU - Saleh, Ahmad Omar AU - Saleh AO AD - Faculty of Medicine, The University of Jordan, Amman, Jordan. FAU - Mohamed, Mohamed Reyad AU - Mohamed MR AD - Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA. AD - Banner Desert Medical Center, Mesa, Arizona, USA. FAU - Abdallfatah, Abdallfatah AU - Abdallfatah A AUID- ORCID: 0000-0002-5670-2234 AD - Faculty of Medicine, October 6 University, Giza, Egypt. FAU - Elsekhary, Ahmed AU - Elsekhary A AD - Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. FAU - El-Nemr, Amira Fahmy AU - El-Nemr AF AD - Faculty of Medicine, Al-Azhar University, Cairo, Egypt. FAU - Eladawi, Safir AU - Eladawi S AD - Faculty of Medicine, Ain Shams University, Cairo, Egypt. FAU - Maihoub, Odai AU - Maihoub O AUID- ORCID: 0009-0007-6463-9005 AD - Department of Pathology, National Hospital, Latakia, Syria. FAU - Abdulhay, Hind AU - Abdulhay H AD - Faculty of Medicine, Mansoura University, Daqahliyah, Egypt. FAU - Turkmani, Mustafa AU - Turkmani M AUID- ORCID: 0009-0001-4261-0638 AD - Division of Pulmonary and Critical Care, University of Toledo, Toledo, Ohio, USA. AD - Faculty of Medicine, Michigan State University, East Lansing, Michigan, USA. FAU - Abdelazeem, Basel AU - Abdelazeem B AUID- ORCID: 0000-0002-2919-6196 AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia, USA. FAU - Fonarow, Gregg C AU - Fonarow GC AUID- ORCID: 0000-0002-3192-8093 AD - University of California Los Angeles, Los Angeles, California, USA. AD - Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan UCLA Medical Center, Los Angeles, California, USA. LA - eng PT - Journal Article PT - Network Meta-Analysis PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 7ZW40D021M (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Adult MH - Humans MH - *Blood Glucose/drug effects MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Weight Loss/drug effects MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13392217 OTO - NOTNLM OT - HbA1c OT - body weight OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - orforglipron COIS- Dr. Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis and Pfizer. The other authors declare no conflicts of interest. EDAT- 2026/07/23 06:39 MHDA- 2026/07/23 06:40 PMCR- 2026/07/22 CRDT- 2026/07/23 00:43 PHST- 2026/06/02 00:00 [revised] PHST- 2026/01/31 00:00 [received] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/07/23 06:40 [medline] PHST- 2026/07/23 06:39 [pubmed] PHST- 2026/07/23 00:43 [entrez] PHST- 2026/07/22 00:00 [pmc-release] AID - EDM270275 [pii] AID - 10.1002/edm2.70275 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Jul;9(4):e70275. doi: 10.1002/edm2.70275. PMID- 42486607 OWN - NLM STAT- MEDLINE DCOM- 20260722 LR - 20260722 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 394 DP - 2026 Jul 22 TI - Risk of hair loss associated with glucagon-like peptide-1 receptor agonists in adults with type 2 diabetes: target trial emulation. PG - e100077 LID - 10.1136/bmj-2026-100077 [doi] AB - OBJECTIVE: To examine the association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of incident alopecia (hair loss) in adults with type 2 diabetes, compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. DESIGN: Target trial emulation. SETTING: Electronic health records from Penn Medicine. PARTICIPANTS: Adults (>18 years) with type 2 diabetes. EXPOSURES: New initiation of GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors between January 2019 and September 2024. MAIN OUTCOME MEASURES: Outcomes of interest included incident alopecia and its subtypes, identified by using diagnostic codes. Stabilised inverse probability of treatment weighting was applied to balance baseline covariates between treatment groups, and Cox proportional hazards models were used to estimate hazard ratios with 95% confidence intervals. Multiple sensitivity (including negative control outcome calibration) and subgroup analyses were done to assess robustness. RESULTS: This study included 12 004 GLP-1 receptor agonist initiators and 15 221 SGLT-2 inhibitor initiators in the GLP-1 receptor agonist versus SGLT-2 inhibitor comparison and 11 964 GLP-1 receptor agonist initiators and 11 238 DPP-4 inhibitor initiators in the GLP-1 receptor agonist versus DPP-4 inhibitor comparison. After stabilised inverse probability of treatment weighting adjustment, use of GLP-1 receptor agonists was associated with a higher risk of alopecia than use of SGLT-2 inhibitors (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73) or DPP-4 inhibitors (1.68, 1.28 to 2.20). The associations were consistent across sensitivity and subgroup analyses, with attenuation after negative control outcome calibration. Subtype analyses indicated that the association was specific to non-scarring alopecia, with hazard ratios of 1.53 (1.18 to 1.97) and 1.72 (1.28 to 2.31) compared with SGLT-2 inhibitors and DPP-4 inhibitors, respectively. CONCLUSIONS: Use of GLP-1 receptor agonists was associated with an increased risk of non-scarring alopecia in adults with type 2 diabetes. Although the absolute risk is low, awareness of this potential effect may help to inform treatment decisions. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Tang, Huilin AU - Tang H AD - Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Zhang, Bingyu AU - Zhang B AD - Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Lu, Yiwen AU - Lu Y AD - Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Zhang, Dazheng AU - Zhang D AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Liu, Ruishan AU - Liu R AD - Department of Computer Science, University of Southern California, Los Angeles, CA, USA. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Health, New Haven, CT, USA. FAU - Cotsarelis, George AU - Cotsarelis G AD - Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Asch, David A AU - Asch DA AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA. AD - Wharton School, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of General Internal Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA ychen123@upenn.edu. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence based Practice (CEP), University of Pennsylvania, Philadelphia, PA, USA. AD - Penn Institute for Biomedical Informatics (IBI), University of Pennsylvania, Philadelphia, PA, USA. LA - eng PT - Journal Article DEP - 20260722 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Alopecia/epidemiology/chemically induced MH - Female MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects MH - Adult COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; DAA has received consulting fees from VAL Health, Thrive Global, and SelectDr, as well as payment from Deloitte, outside the submitted work; YL has received grants or contracts from the National Heart, Lung, and Blood Institute, the Patient-Centred Outcomes Research Institute, Sentara Research Foundation, and Novartis, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2026/07/23 05:36 MHDA- 2026/07/23 05:37 CRDT- 2026/07/22 21:03 PHST- 2026/07/23 05:37 [medline] PHST- 2026/07/23 05:36 [pubmed] PHST- 2026/07/22 21:03 [entrez] AID - 10.1136/bmj-2026-100077 [doi] PST - epublish SO - BMJ. 2026 Jul 22;394:e100077. doi: 10.1136/bmj-2026-100077. PMID- 42483679 OWN - NLM STAT- MEDLINE DCOM- 20260722 LR - 20260825 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis. PG - 1854779 LID - 10.3389/fendo.2026.1854779 [doi] LID - 1854779 AB - BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of oral small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D) and obesity. METHODS: We performed a meta-analysis of randomized controlled trials assessing the efficacy and safety of oral small-molecule GLP-1RAs in adults with T2D or obesity. A systematic literature search was conducted in databases including Web of Science, PubMed, Scopus, Google Scholar, Embase, and the Cochrane Library from database inception to March 2026. Continuous outcomes were summarized as mean differences (MDs), and dichotomous outcomes as risk ratios (RRs). RESULTS: Ten studies were included. Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09), body mass index (MD=-2.39, 95%CI:-3.02 to -1.77), waist circumference (MD=-4.62, 95%CI:-6.09 to -3.16), fasting blood glucose (MD=-24.59, 95%CI:-28.80 to -20.37), and HbA1c (MD=-0.94, 95%CI: -1.09 to -0.79), while fasting insulin was not significantly changed (MD = 1.21, 95%CI: -0.77 to 3.19). These agents increased likelihood of achieving weight loss, including >/=5% (RR = 2.68, 95% CI: 2.24 to 3.20), >/=10% (RR = 4.14, 95% CI: 3.19 to 5.36), and >/=15% body weight reduction (RR = 10.61, 95% CI: 7.76 to 14.49). Treatment-emergent adverse events (RR = 1.09, 95% CI: 1.06 to 1.12) and overall adverse events (AEs) (RR = 2.75, 95% CI: 2.41 to 3.15) were increased, particularly gastrointestinal events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and abdominal symptoms. However, serious adverse events were not increased (RR = 1.15, 95%CI: 0.93 to 1.43). CONCLUSIONS: Oral small-molecule GLP-1RAs provide significant benefits in weight reduction and glycemic control, supporting their potential role as effective oral incretin therapies. However, their clinical use, should balance these metabolic benefits against high incidence of predominantly gastrointestinal AEs. CI - Copyright (c) 2026 Li, Shui, Zhang, Tan and Deng. FAU - Li, Li AU - Li L AD - Hainan Vocational University of Science and Technology, Haikou, China. FAU - Shui, Dianpeng AU - Shui D AD - Hainan Vocational University of Science and Technology, Haikou, China. FAU - Zhang, Xiong AU - Zhang X AD - Hainan Vocational University of Science and Technology, Haikou, China. FAU - Tan, Bing AU - Tan B AD - Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China. AD - National Immunological Laboratory of Traditional Chinese Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China. FAU - Deng, Yan AU - Deng Y AD - Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China. AD - Department of Obstetrics and Gynecology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260707 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Administration, Oral MH - Randomized Controlled Trials as Topic MH - Blood Glucose PMC - PMC13385192 OTO - NOTNLM OT - danuglipron OT - meta-analysis OT - obesity OT - oral small-molecule GLP-1RAs OT - orforglipron OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/07/22 12:37 MHDA- 2026/07/22 12:38 PMCR- 2026/07/07 CRDT- 2026/07/22 04:34 PHST- 2026/04/13 00:00 [received] PHST- 2026/06/11 00:00 [revised] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/07/22 12:38 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/22 04:34 [entrez] PHST- 2026/07/07 00:00 [pmc-release] AID - 10.3389/fendo.2026.1854779 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 7;17:1854779. doi: 10.3389/fendo.2026.1854779. eCollection 2026. PMID- 42481928 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Safety Signals of GLP-1 Receptor Agonists: A Multi-Method Pharmacovigilance Analysis of FAERS (2018-2025) With Sensitivity-Stratified Prioritisation, Notoriety-Bias Assessment, and Cross-Database Validation. PG - 9251-9264 LID - 10.1111/dom.71138 [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity, but their post-marketing safety profile-particularly psychiatric, vascular, neoplastic and rare ophthalmic events-remains incompletely characterised and is vulnerable to confounding by indication, secondary-suspect attribution and notoriety bias. METHODS: We analysed 32 quarterly FAERS files (2018Q1-2025Q4): 288408 unique GLP-1 RA reports versus 11 319 150 non-GLP-1 RA reports. Disproportionality used four methods (reporting odds ratio [ROR]; proportional reporting ratio [PRR]; Bayesian Confidence Propagation Neural Network information component, lower 95% bound [BCPNN IC025]; Multi-item Gamma Poisson Shrinker empirical Bayes lower 5th-percentile bound [MGPS EB05]; signal = >/= 3 of 4). The top 30 ROR-ranked signals were stratified by primary-suspect (PS) sensitivity. Triangulation included active-comparator, intra-class psychiatric comparison, interrupted time-series assessment of reporting around the 2023 EMA announcement, Weber-effect evaluation with Cochran-Armitage trend testing, and external validation in JADER. RESULTS: Of 22 059 PT-class pairs, 544 met the >/= 3-of-4 criterion. PS-stratification retained 21 of the top 30 signals and demoted 9 as secondary-suspect-driven (e.g., capillaritis ROR 18.6 --> 0.27; heart sounds 84.3 --> 0.55). PS-stable headline signals were dominated by gastrointestinal/hepatobiliary effects: cyclic vomiting syndrome (ROR 64.8; semaglutide-dominant), gallbladder injury (84.2), impaired gastric emptying (45.1), plus liraglutide-concentrated medullary thyroid cancer (41.1) and semaglutide-concentrated optic ischaemic neuropathy (26.5). Only semaglutide carried a class-level suicidal-ideation signal (ROR 2.30). Interrupted time series detected no level (p = 0.39) or slope change (p = 0.75) at the 2023 EMA announcement; psychiatric time-to-onset (median 47 days) aligned with early GI reactions. Sixteen of 17 priority signals (94.1%) replicated in JADER. As disproportionality analyses, these are hypothesis-generating safety signals and cannot establish incidence, relative risk, or causality. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Xu, Shiyi AU - Xu S AUID- ORCID: 0009-0009-2094-220X AD - Capital Medical University, Beijing, China. LA - eng PT - Journal Article DEP - 20260721 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pharmacovigilance MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Databases, Factual MH - Exenatide MH - Bayes Theorem PMC - PMC13538726 OTO - NOTNLM OT - FAERS OT - GLP-1 receptor agonists OT - disproportionality analysis OT - pharmacovigilance OT - primary-suspect analysis OT - semaglutide COIS- The author declares no conflicts of interest. EDAT- 2026/07/22 12:37 MHDA- 2026/09/03 05:36 PMCR- 2026/09/03 CRDT- 2026/07/21 23:36 PHST- 2026/07/09 00:00 [revised] PHST- 2026/05/19 00:00 [received] PHST- 2026/07/13 00:00 [accepted] PHST- 2026/09/03 05:36 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/21 23:36 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71138 [pii] AID - 10.1111/dom.71138 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9251-9264. doi: 10.1111/dom.71138. Epub 2026 Jul 21. PMID- 42481079 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260824 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 7 DP - 2026 Jul 21 TI - Association between GLP-1 receptor agonists and alcohol-related hospitalisations among adults with alcohol use disorder: multi-target trial emulation study. PG - e109259 LID - 10.1136/bmjopen-2025-109259 [doi] LID - e109259 AB - OBJECTIVE: To evaluate the association between use of newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide, tirzepatide) and alcohol-related hospitalisations among adults with alcohol use disorder (AUD) and type 2 diabetes (T2D) or obesity.Retrospective cohort study using target trial emulation. SETTING: Electronic health record data from a collective of US healthcare systems. PARTICIPANTS: Adults with AUD and T2D or obesity who started a newer GLP-1 RA (semaglutide or tirzepatide) or a relevant active comparator between 1 January 2018 and 31 December 2024. INTERVENTIONS: Initiation of a newer GLP-1 RA compared with an active comparator across four target trials: (1) anti-diabetic medication (ADM) trial, (2) anti-obesity medication (AOM) trial, (3) medications for alcohol use disorder with T2D (MAUD-T2D) trial, and (4) medications for alcohol use disorder with obesity (MAUD-obesity) trial. MAIN OUTCOME MEASURES: Time to first alcohol-related emergency department visits or hospitalisation within 1 year of treatment initiation. Non-alcohol-related hospitalisation was assessed as a negative control outcome. Propensity score based methods (weighting and matching) were used to control confounding and Cox proportional hazards models were used to estimate treatment effects. RESULTS: A total of 40 703 adults met study criteria, including 18 676 in the ADM trial, 9391 in the AOM trial, 8942 in the MAUD-T2D trial and 11 198 in the MAUD-obesity trial. Initiation of a newer GLP-1 RA was associated with a lower hazard of alcohol-related hospitalisation in the ADM trial (HR 0.74, 95% CI 0.62 to 0.89 vs sulfonylureas; HR 0.78, 95% CI 0.65 to 0.92 vs other ADMs), the AOM trial (HR 0.68, 95% CI 0.54 to 0.85 vs other AOMs), the MAUD-T2D trial (HR 0.37, 95% CI 0.29 to 0.46) and the MAUD-obesity trial (HR 0.35, 95% CI 0.26 to 0.47). CONCLUSIONS: Among adults with AUD and T2D or obesity, initiation of newer GLP-1 RAs was associated with a lower observed risk of alcohol-related hospitalisation. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Rodriguez, Patricia J AU - Rodriguez PJ AUID- ORCID: 0000-0003-3026-2450 AD - Truveta Inc, Bellevue, Washington, USA. FAU - Lusk, Jay B AU - Lusk JB AD - Department of Family Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. AD - Department of Neurology, Duke University, Durham, North Carolina, USA. FAU - Mehta, Hemalkumar B AU - Mehta HB AUID- ORCID: 0000-0001-9134-6370 AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA hbmehta@jhu.edu. FAU - Levy, Joseph F AU - Levy JF AD - Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Kalogeropoulos, Andreas P AU - Kalogeropoulos AP AD - Stony Brook Heart Institute, Stony Brook University Hospital, Stony Brook, New York, USA. FAU - Soneji, Samir AU - Soneji S AD - Department of Population Health Sciences, Duke University, Durham, North Carolina, USA. FAU - Do, Duy AU - Do D AD - Truveta Inc, Bellevue, Washington, USA. FAU - Holler, Emma AU - Holler E AD - Truveta Inc, Bellevue, Washington, USA. FAU - Webber, Emily AU - Webber E AD - Truveta Inc, Bellevue, Washington, USA. FAU - Gluckman, Ty AU - Gluckman T AD - Center for Cardiovascular Analytics, Research, and Data Science (CARDS), Providence Heart Institute, Portland, Oregon, USA. FAU - Stucky, Nicholas AU - Stucky N AUID- ORCID: 0000-0002-6610-5353 AD - Truveta Inc, Bellevue, Washington, USA. LA - eng GR - K01 AG070329/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260721 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Tirzepatide/therapeutic use MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hospitalization/statistics & numerical data MH - *Alcoholism/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Adult MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13410697 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Obesity OT - Research Design OT - Substance misuse COIS- Competing interests: PJR is a former employee of Truveta and a current employee of Eli Lilly. This work was conducted and submitted prior to her employment with Eli Lilly. Eli Lilly had no role in this study. JBL declares relevant committee service (unpaid) for the American Heart Association and grant funding from the American Heart Association (NA). HM received research funding from the National Institute on Aging (K01AG070329). APK receives research funding from the American Heart Association (NA). EH and EW are employees of Truveta, which provides access to the data used in this study. DD and NS are former employees of Truveta. All other authors declare no competing interests. EDAT- 2026/07/22 12:37 MHDA- 2026/07/22 12:38 PMCR- 2026/07/21 CRDT- 2026/07/21 20:53 PHST- 2026/07/22 12:38 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/21 20:53 [entrez] PHST- 2026/07/21 00:00 [pmc-release] AID - bmjopen-2025-109259 [pii] AID - 10.1136/bmjopen-2025-109259 [doi] PST - epublish SO - BMJ Open. 2026 Jul 21;16(7):e109259. doi: 10.1136/bmjopen-2025-109259. PMID- 42480717 OWN - NLM STAT- MEDLINE DCOM- 20260829 LR - 20260909 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 239 DP - 2026 Sep TI - Glucagon-like peptide-1 receptor agonists and new-onset atrial fibrillation in adults with diabetes or obesity: a multinational cohort study. PG - 113454 LID - S0168-8227(26)00374-8 [pii] LID - 10.1016/j.diabres.2026.113454 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiometabolic outcomes in type 2 diabetes and obesity, but their association with new-onset atrial fibrillation (AF) remains uncertain. This study examined whether GLP-1RA use is associated with AF risk in adults with diabetes or obesity. METHODS: We conducted a multinational retrospective cohort study using the TriNetX Analytics Network, aggregating de-identified electronic health records from over 220 healthcare organizations in 30 countries. Adults aged >/= 20 years with diabetes or obesity were included between 2017 and 2021 and followed for up to three years. GLP-1RA initiators were compared with non-GLP-1RA active comparators after 1:1 propensity score matching. Cox models estimated hazard ratios (HRs) for new-onset AF identified by ICD-10 codes after a 90-day exclusion window. RESULTS: After matching, 137,200 patients were included per group in the diabetes cohort and 17,737 per group in the obesity cohort. In diabetes, GLP-1RA use was associated with lower AF risk (HR 0.924; 95% CI 0.881-0.969), greatest versus DPP-4 inhibitors (HR 0.723; 95% CI 0.675-0.774). In obesity, AF risk was lower versus non-sympathomimetic agents (HR 0.765; 95% CI 0.628-0.933). CONCLUSIONS: GLP-1RA therapy was associated with reduced incidence of new-onset AF, particularly among adults with diabetes. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Weng, Chien-Hsiang AU - Weng CH AD - Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, RI, USA; Brown Health Medical Group Primary Care, Brown University Health, Providence, RI, USA. Electronic address: chien-hsiang_weng@brown.edu. FAU - Cherukuru, Rohan AU - Cherukuru R AD - Brown University Warren Alpert Medical School, Providence, RI, USA. FAU - Chou, Chien-Chih AU - Chou CC AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Jun-Fu AU - Lin JF AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Ching-Heng AU - Lin CH AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Chan, Philip A AU - Chan PA AD - Department of Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA. FAU - Bennett, Charles L AU - Bennett CL AD - Southern Network on Adverse Reactions (SONAR) Program, Department of Clinical Pharmacy Outcomes Sciences, The University of South Carolina College of Pharmacy, Columbia, SC, USA. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260721 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Atrial Fibrillation/epidemiology/prevention & control MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy/epidemiology MH - Retrospective Studies OTO - NOTNLM OT - Atrial fibrillation OT - Diabetes OT - Glucagon-like peptide-1 receptors agonist OT - Obesity COIS- Declaration of competing interest Dr. Weng reports a one-time focus group participation with Novo Nordisk, unrelated to the submitted work. All other authors declare no competing interests. EDAT- 2026/07/22 12:37 MHDA- 2026/08/29 23:35 CRDT- 2026/07/21 19:11 PHST- 2025/10/22 00:00 [received] PHST- 2026/04/15 00:00 [revised] PHST- 2026/07/20 00:00 [accepted] PHST- 2026/08/29 23:35 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/21 19:11 [entrez] AID - S0168-8227(26)00374-8 [pii] AID - 10.1016/j.diabres.2026.113454 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Sep;239:113454. doi: 10.1016/j.diabres.2026.113454. Epub 2026 Jul 21. PMID- 42479349 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20261008 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 86 IP - 10 DP - 2026 Oct TI - Orforglipron: First Approval. PG - 1735-1745 LID - 10.1007/s40265-026-02363-5 [doi] AB - Orforglipron (Foundayo) is an orally administered, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Eli Lilly and Co. for use in long-term weight management and for the treatment of type 2 diabetes (T2D) among other indications. In April 2026, orforglipron received its first approval, in the USA, for use in combination with a reduced-calorie diet and increased physical activity for long-term weight management in adults with obesity or adults with overweight in the presence of one or more weight-related comorbid condition. Orforglipron has also been submitted for regulatory review in the EU for long-term weight management and T2D, in Japan for long-term weight management, and in Canada for T2D. In addition to long-term weight management and T2D treatment, orforglipron is currently under phase III clinical evaluation for use in the treatment of obstructive sleep apnoea, hypertension, stress urinary incontinence in females, osteoarthritis pain and peripheral arterial disease. This article summarises the milestones in the development of orforglipron leading to this first approval for long-term weight management in adults with obesity or overweight. CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Shirley, Matt AU - Shirley M AUID- ORCID: 0000-0001-7191-7391 AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com. LA - eng PT - Journal Article PT - Review DEP - 20260721 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 7ZW40D021M (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Approval MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Anti-Obesity Agents/pharmacology MH - United States MH - *Hypoglycemic Agents/pharmacology MH - Overweight/drug therapy MH - Oxadiazoles MH - Fluorine Compounds COIS- Declarations. Authorship and Conflict of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content. Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability: Not applicable. EDAT- 2026/07/21 12:35 MHDA- 2026/09/25 17:32 CRDT- 2026/07/21 11:19 PHST- 2026/06/11 00:00 [received] PHST- 2026/06/30 00:00 [accepted] PHST- 2026/09/25 17:32 [medline] PHST- 2026/07/21 12:35 [pubmed] PHST- 2026/07/21 11:19 [entrez] AID - 10.1007/s40265-026-02363-5 [pii] AID - 10.1007/s40265-026-02363-5 [doi] PST - ppublish SO - Drugs. 2026 Oct;86(10):1735-1745. doi: 10.1007/s40265-026-02363-5. Epub 2026 Jul 21. PMID- 42475344 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260821 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 7 DP - 2026 TI - Comparative effects of SGLT2 inhibitors and GLP-1 receptor agonists on osteoarthritis risk in patients with type 2 diabetes mellitus: A multi-institutional cohort study. PG - e0353956 LID - 10.1371/journal.pone.0353956 [doi] LID - e0353956 AB - OBJECTIVES: Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated metabolic and anti-inflammatory benefits, which may influence the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). However, their comparative impact on OA incidence remains unclear. This study aimed to evaluate and compare the effects of SGLT2 inhibitors and GLP-1 RAs on the risk of developing OA in patients with T2DM. METHODS: A retrospective cohort study was conducted using the TriNetX database, including adults with T2DM who were newly prescribed either SGLT2 inhibitors or GLP-1 RAs between January 2017 and December 2019. After propensity-score matching, 452,445 patients were included in each group. The primary outcome was OA incidence over five years. Secondary outcomes included knee OA, hip OA, total knee arthroplasty (TKA), total hip arthroplasty (THA), and major joint injections. RESULTS: The SGLT2 inhibitor group had a significantly lower risk of OA compared with the GLP-1 RAs group (HR, 0.921; 95% CI, 0.895-0.946), with a greater reduction observed for knee OA (HR, 0.831; 95% CI, 0.783-0.882). No significant differences were observed in THA or TKA risk. SGLT2 inhibitor users also had fewer major joint injections (HR, 0.915; 95% CI, 0.882-0.951). CONCLUSIONS: Among patients with T2DM, SGLT2 inhibitors were associated with a lower risk of OA, particularly knee OA and joint injections, compared to GLP-1 RAs. These findings support further investigation into the potential association between SGLT2 inhibitor use and lower OA-related outcomes. CI - Copyright: (c) 2026 Jao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Jao, Wen-Yu AU - Jao WY AUID- ORCID: 0009-0004-5318-1367 AD - Department of Orthopaedics, Chi Mei Medical Centre, Tainan, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan. FAU - Chien, Chi-Sheng AU - Chien CS AD - Department of Orthopaedics, Chi Mei Medical Centre, Tainan, Taiwan. FAU - Lin, Wei-Ting AU - Lin WT AD - Department of Orthopaedics, Chi Mei Medical Centre, Tainan, Taiwan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260720 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - *Osteoarthritis/epidemiology/etiology MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Cohort Studies PMC - PMC13384269 COIS- NO authors have competing interests. EDAT- 2026/07/20 18:35 MHDA- 2026/07/20 18:36 PMCR- 2026/07/20 CRDT- 2026/07/20 13:34 PHST- 2025/09/16 00:00 [received] PHST- 2026/07/01 00:00 [accepted] PHST- 2026/07/20 18:36 [medline] PHST- 2026/07/20 18:35 [pubmed] PHST- 2026/07/20 13:34 [entrez] PHST- 2026/07/20 00:00 [pmc-release] AID - PONE-D-25-50071 [pii] AID - 10.1371/journal.pone.0353956 [doi] PST - epublish SO - PLoS One. 2026 Jul 20;21(7):e0353956. doi: 10.1371/journal.pone.0353956. eCollection 2026. PMID- 42474323 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260901 IS - 1555-2101 (Electronic) IS - 0160-6689 (Print) IS - 0160-6689 (Linking) VI - 87 IP - 3 DP - 2026 Jul 15 TI - GLP-1 Receptor Agonists and All-Cause Overdose Risk in Veterans With Type 2 Diabetes and Opioid Use Disorder. LID - 25m16212 [pii] LID - 10.4088/JCP.25m16212 [doi] AB - Objective: Overdoses remain a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been proposed as a treatment for opioid use disorder (OUD) based on preclinical research. Early observational research suggests that GLP-1RAs are associated with reduced opioid overdoses but warrants replication in different patient populations. Methods: This target trial emulation study used Veterans Health Administration (VA) data to include Veterans with a diagnosis of type 2 diabetes mellitus and OUD who initiated semaglutide and tirzepatide or a comparison diabetes medication (insulin, metformin, a sulfonylurea, a sodium-glucose transport 2 (SGLT2) inhibitor, or a dipeptidyl-peptidase 4 [DPP4] inhibitor) between January 1, 2020, and December 31, 2024. Each set of comparison groups was propensity score matched on relevant variables. Cox proportional hazards regression models were used to compare the time to all-cause overdose events in the 12 months after medication initiation. Results: After propensity score matching, semaglutide and tirzepatide were associated with significantly lower risk of all-cause overdose compared to insulin (hazard ratio [HR]=0.32; 95% CI=0.14-0.71; P=.006; n=630) and SGLT2 inhibitors (HR=0.25; 95% CI=0.09-0.68; P=.006; n=432). Semaglutide and tirzepatide were not associated with significantly lower risks than metformin (HR=0.75; 95% CI=0.38-1.45; n=1,016), sulfonylureas (HR=0.82; 95% CI=0.33-1.96; n=710), or DPP4 inhibitors (HR=1.20; 95% CI=0.52-2.78; n=858). Conclusion: Collectively, semaglutide and tirzepatide were associated with lower risk of all-cause overdose compared to insulin and SGLT2 inhibitors, but not metformin, sulfonylureas, or DPP4 inhibitors. These results suggest the possible role of GLP-1RAs in OUD but underscore the need for randomized controlled trials. CI - (c) Copyright 2026 Physicians Postgraduate Press, Inc. FAU - Kennedy, Kevin P AU - Kennedy KP AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. AD - Corresponding Author: Kevin P. Kennedy, MD, 3900 Woodland Ave #B228, Philadelphia, PA 19104 (kevin.kennedy2@va.gov). FAU - Bremseth-Vining, Ryan AU - Bremseth-Vining R AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. FAU - Lynch, Kevin G AU - Lynch KG AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Reville, Nicholas AU - Reville N AD - Center for Addiction Science, Policy, and Research (CASPR), San Francisco, California. FAU - Zhang, Jonathan AU - Zhang J AD - Sanford School of Public Policy, Duke University, Durham, North Carolina. AD - US Department of Veterans Affairs Office of Mental Health, Washington D.C. AD - National Bureau of Economic Research, Cambridge, Massachusetts. FAU - Moshfegh, Jasmin AU - Moshfegh J AD - Imperial College London, Department of Economics and Public Policy, London, United Kingdom. AD - Veterans Health Administration Palo Alto, Palo Alto, California. FAU - Oslin, David W AU - Oslin DW AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. LA - eng GR - VA999999/ImVA/Intramural VA/United States PT - Journal Article DEP - 20260715 PL - United States TA - J Clin Psychiatry JT - The Journal of clinical psychiatry JID - 7801243 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Semaglutide MH - Tirzepatide MH - *Veterans/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Drug Overdose/epidemiology/prevention & control MH - Female MH - *Opioid-Related Disorders/drug therapy/epidemiology MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - United States/epidemiology MH - Metformin/therapeutic use MH - Insulin/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use PMC - PMC13527612 MID - NIHMS2201329 COIS- Relevant Financial Relationships: Mr Reville is Executive Director of CASPR, which provided funding for this research. All other authors report no financial or other relationship relevant to the subject of this article. Drs Kennedy, Zhang, and Oslin and Mr Bremseth-Vining are salaried employees of the US Department of Veterans Affairs. EDAT- 2026/07/20 12:40 MHDA- 2026/07/20 12:41 PMCR- 2026/08/31 CRDT- 2026/07/20 10:03 PHST- 2026/07/20 12:41 [medline] PHST- 2026/07/20 12:40 [pubmed] PHST- 2026/07/20 10:03 [entrez] PHST- 2026/08/31 00:00 [pmc-release] AID - 25m16212 [pii] AID - 10.4088/JCP.25m16212 [doi] PST - epublish SO - J Clin Psychiatry. 2026 Jul 15;87(3):25m16212. doi: 10.4088/JCP.25m16212. PMID- 42473649 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Comparative Risk of Psoriatic Arthritis in Type 2 Diabetes: An Emulated Target Trial of SGLT2 Inhibitors vs. GLP-1 Receptor Agonists. PG - 614222 LID - 10.2147/DDDT.S614222 [doi] LID - 614222 AB - BACKGROUND: Patients with psoriatic arthritis (PsA) have a higher prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular events. They also experience increased absenteeism and reduced work productivity, all of which can negatively affect both life expectancy and quality of life. OBJECTIVE: We conducted this emulated target trial to compare the risk of incident PsA among patients with T2DM treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus those treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: We identified 188,378 users of SGLT2 inhibitors and 213,218 users of GLP-1 receptor agonists within the TriNetX network between January 1, 2016, and December 31, 2024. Following propensity score matching, 146,810 matched pairs of SGLT2i and GLP-1 RA users were included for analysis. The primary causal estimands were the intention-to-treat (ITT) effects of the respective treatment strategies. Kaplan-Meier analysis was employed to estimate outcome probabilities, and hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated, along with tests for proportionality. RESULTS: In this emulated target trial, users of SGLT2i showed a significantly lower risk of developing PsA compared to users of GLP-1 RA. At 5 years of follow-up, the hazard ratio for PsA was 0.793 (95% CI, 0.667-0.944). The proportional hazards assumption was tested and met (p > 0.05). Kaplan-Meier curves further showed a significantly lower cumulative incidence of PsA among SGLT2i users compared to GLP-1 RA users (Log rank test p = 0.008). These associations remained consistent after adjusting for multiple covariates and were further supported by sensitivity analyses using a per-protocol approach. CONCLUSION: This multicenter emulated target trial found that SGLT2i use was associated with a lower risk of incident PsA compared with GLP-1 RA use. However, given the observational nature of the study and the potential for residual confounding despite extensive adjustment, these findings should be interpreted with caution. Further prospective and randomized studies are warranted to confirm this association. CI - (c) 2026 Yen et al. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, Taoyuan, 33354, Taiwan. FAU - Wang, Shiow-Ing AU - Wang SI AUID- ORCID: 0000-0003-3407-9020 AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan. AD - Department of Health Policy and Management, College of Health Care and Management, Chung Shan Medical University, Taichung, 40201, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AUID- ORCID: 0000-0002-8209-9627 AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, 11217, Taiwan. AD - Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, 11221, Taiwan. FAU - Chen, Kai-Yang AU - Chen KY AD - Department of General Medicine, Chang Gung Memorial Hospital (Linkou Branch), Taoyuan, 33354, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, 35053, Taiwan. AD - Department of Health Services Administration, China Medical University, Taichung, 40402, Taiwan. AD - Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, 33044, Taiwan. AD - National Center for Geriatrics and Welfare Research, National Health Research Institutes, Huwei Township, Yunlin County, 632007, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Health Policy and Management, College of Health Care and Management, Chung Shan Medical University, Taichung, 40201, Taiwan. AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40402, Taiwan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260715 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - *Arthritis, Psoriatic/drug therapy/epidemiology MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents MH - Aged PMC - PMC13380918 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - psoriatic arthritis OT - sodium-glucose cotransporter-2 inhibitors OT - type 2 diabetes mellitus COIS- The authors confirm that they have not received any personal fees or honoraria from manufacturers of SGLT2i or GLP-1 RA within the past 36 months. The authors report no conflicts of interest in this work. EDAT- 2026/07/20 10:05 MHDA- 2026/07/20 10:06 PMCR- 2026/07/15 CRDT- 2026/07/20 03:46 PHST- 2026/04/03 00:00 [received] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/07/20 10:06 [medline] PHST- 2026/07/20 10:05 [pubmed] PHST- 2026/07/20 03:46 [entrez] PHST- 2026/07/15 00:00 [pmc-release] AID - 614222 [pii] AID - 10.2147/DDDT.S614222 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Jul 15;20:614222. doi: 10.2147/DDDT.S614222. eCollection 2026. PMID- 42471299 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260827 IS - 2152-2669 (Electronic) IS - 2152-2669 (Linking) VI - 26 IP - 9 DP - 2026 Sep TI - Association of GLP1-Receptor Agonists With Risk of Hematologic Malignancies in People With Diabetes. PG - e1104-e1114.e6 LID - S2152-2650(26)00180-1 [pii] LID - 10.1016/j.clml.2026.06.007 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the management of diabetes mellitus and obesity. Despite growing literature on GLP-1RA use and obesity-related cancers, the association between GLP-1RA use and hematologic malignancies are relatively underexplored. METHODS: We conducted a retrospective cohort study using the Veterans Affairs (VA) national data, including patients with diabetes initiating GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i), as active comparators, during years 2006 to 2021. An active comparator, new-user design was used. Propensity score matching was performed using 71 baseline covariates. The primary outcome was an incident diagnosis of Hodgkin lymphoma, non-Hodgkin lymphoma, leukemias, or multiple myeloma. RESULTS: Among 409,334 eligible patients with diabetes, 100,038 matched pairs were included. In the propensity score-matched cohort, incidence of our outcomes in DPP4i users versus GLP-1RA users were as follows: Hodgkin's lymphoma 36 (0.04%) versus 32 (0.03%) (odds ratio [OR]: 0.89; 95% confidence interval [CI]: 0.55-1.43; P = .63), non-Hodgkin's lymphoma 260 (0.3%) versus 253 (0.3%) (OR: 0.97; 95% CI, 0.82-1.16; P = .76), leukemias 258 (0.3%) versus 248 (0.3%) (OR: 0.96; 95% CI, 0.81-1.14; P = .66), and multiple myeloma 126 (0.1%) versus 115 (0.1%) (OR: 0.91; 95% CI, 0.71-1.18; P = .48), respectively. Findings were consistent across most subgroup analyses by duration of therapy, baseline body mass index, and weight change. CONCLUSIONS: In this large national cohort of veterans with diabetes, GLP-1RA use was not associated with an increased or decreased risk of hematologic malignancies compared to DPP-4i. CI - Published by Elsevier Inc. FAU - Ramos, Samuel AU - Ramos S AD - Department of Internal Medicine, University of Central Florida, Greater Orlando, FL; University of Central Florida College of Medicine, HCA Florida Healthcare GME, Greater Orlando, FL. FAU - Zaw, Shin AU - Zaw S AD - Department of Internal Medicine, University of Central Florida, Greater Orlando, FL; University of Central Florida College of Medicine, HCA Florida Healthcare GME, Greater Orlando, FL. FAU - Carilli, Allison AU - Carilli A AD - Department of Internal Medicine, University of Central Florida, Greater Orlando, FL; Section of Hematology and Oncology, Orlando VA Healthcare System, Orlando, FL. FAU - Mansi, Ishak A AU - Mansi IA AD - Department of Internal Medicine, University of Central Florida, Greater Orlando, FL; Education Services, Orlando VA Healthcare System, Orlando, FL. Electronic address: ishak.mansi@utsouthwestern.edu. LA - eng PT - Journal Article DEP - 20260618 PL - United States TA - Clin Lymphoma Myeloma Leuk JT - Clinical lymphoma, myeloma & leukemia JID - 101525386 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hematologic Neoplasms/epidemiology/chemically induced/etiology MH - Female MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitors OT - Hematologic Neoplasms OT - Hodgkin disease OT - Non-Hodgkin OT - Obesity EDAT- 2026/07/19 01:03 MHDA- 2026/08/28 11:40 CRDT- 2026/07/18 21:51 PHST- 2026/04/22 00:00 [received] PHST- 2026/06/11 00:00 [revised] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/08/28 11:40 [medline] PHST- 2026/07/19 01:03 [pubmed] PHST- 2026/07/18 21:51 [entrez] AID - S2152-2650(26)00180-1 [pii] AID - 10.1016/j.clml.2026.06.007 [doi] PST - ppublish SO - Clin Lymphoma Myeloma Leuk. 2026 Sep;26(9):e1104-e1114.e6. doi: 10.1016/j.clml.2026.06.007. Epub 2026 Jun 18. PMID- 42470502 OWN - NLM STAT- MEDLINE DCOM- 20260718 LR - 20260813 IS - 1534-6242 (Electronic) IS - 1523-3804 (Print) IS - 1523-3804 (Linking) VI - 28 IP - 1 DP - 2026 Jul 18 TI - Combination cardiometabolic therapy in type 2 diabetes: optimizing SGLT2 inhibitor and GLP‑1 receptor agonist use. LID - 10.1007/s11883-026-01448-6 [doi] LID - 73 AB - PURPOSE OF REVIEW: To evaluate the evidence supporting combined sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes, focusing on cardiometabolic outcomes and practical treatment approaches. RECENT FINDINGS: Cardiovascular outcomes trials and real-world studies indicate that SGLT2is and GLP-1RAs confer complementary, non-redundant cardiovascular, kidney, and metabolic benefits. SGLT2is primarily reduce hospitalization for heart failure and slow kidney disease progression, while GLP-1RAs more effectively reduce atherosclerotic events, particularly stroke; dedicated kidney-outcome and heart-failure trials of GLP-1RAs in chronic kidney disease and obesity-related heart failure with preserved ejection fraction have further broadened their role. Randomized data show that each class retains its benefit irrespective of background use of the other, supporting independent mechanisms; whether this translates into reductions in hard outcomes is being tested prospectively. Emerging evidence supports a phenotype-guided approach that aligns therapy with dominant comorbidities such as atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, and obesity. Despite advances in pharmacotherapy, substantial cardiometabolic risk remains in type 2 diabetes. Combined SGLT2i and GLP-1RA therapy addresses multiple risk domains through complementary mechanisms and may be most effective within a phenotype-guided framework. This framework prioritizes therapy according to predominant comorbidity and reserves combination treatment for individuals with overlapping high-risk phenotypes. CI - (c) 2026. The Author(s). FAU - Porterfield, Laura R AU - Porterfield LR AD - Department of Family Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA. FAU - Nadeem, Saad AU - Nadeem S AD - College of Medicine, Texas A&M. College Station, College Station, TX, USA. FAU - Swanson, Dallin AU - Swanson D AD - School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Hayek, Salim S AU - Hayek SS AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Vaughan, Elizabeth M AU - Vaughan EM AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. emvaughan316@gmail.com. AD - Department of Medicine, Baylor College of Medicine, Houston, TX, USA. emvaughan316@gmail.com. LA - eng GR - R01 DK129474/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20260718 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13380630 OTO - NOTNLM OT - Cardiovascular disease OT - Combination therapy OT - Diabetes OT - GLP-1 receptor agonists OT - Kidney disease OT - SGLT2 inhibitors COIS- Declarations. Competing interests: The authors declare no competing interests. Role of Funder/Sponsor: The funding agency had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Human and Animal Rights and Informed Consent: This review was based on previously published studies and publicly available data and did not involve any new studies of human participants or animals performed by the authors. EDAT- 2026/07/19 04:00 MHDA- 2026/07/19 04:01 PMCR- 2026/07/18 CRDT- 2026/07/18 11:04 PHST- 2026/07/02 00:00 [received] PHST- 2026/07/10 00:00 [accepted] PHST- 2026/07/19 04:01 [medline] PHST- 2026/07/19 04:00 [pubmed] PHST- 2026/07/18 11:04 [entrez] PHST- 2026/07/18 00:00 [pmc-release] AID - 10.1007/s11883-026-01448-6 [pii] AID - 1448 [pii] AID - 10.1007/s11883-026-01448-6 [doi] PST - epublish SO - Curr Atheroscler Rep. 2026 Jul 18;28(1):73. doi: 10.1007/s11883-026-01448-6. PMID- 42467949 OWN - NLM STAT- MEDLINE DCOM- 20260806 LR - 20260806 IS - 1746-6318 (Electronic) IS - 1746-630X (Linking) VI - 21 IP - 5 DP - 2026 Sep 1 TI - Glucagon-like peptide-1 receptor agonists in the aging population of people with HIV: emerging evidence and clinical implications. PG - 355-361 LID - 10.1097/COH.0000000000001059 [doi] AB - PURPOSE OF REVIEW: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for type 2 diabetes and obesity has generated interest in their potential role among people with HIV (PWH), who experience a high burden of cardiometabolic disease and aging-related comorbidities. This review summarizes emerging evidence on the efficacy, safety, and implementation considerations of GLP-1RAs in PWH. RECENT FINDINGS: GLP-1RAs, such as semaglutide, are associated with meaningful reductions in bodyweight, glycemia, and both visceral and hepatic fat in PWH. Emerging data suggest potential effects on behavioral outcomes such as alcohol use and smoking, although evidence in PWH remains limited. Concerns regarding lean mass loss, frailty, and bone health exist but current data are limited and generally reassuring, with functional outcomes largely preserved. HIV-specific studies have largely used lower doses of semaglutide, and evidence in older populations remains sparse. SUMMARY: GLP-1RAs are a promising option for cardiometabolic risk reduction in PWH, with important considerations around tolerability and body composition, particularly in aging and multimorbid populations. Future research should prioritize trials assessing cardiovascular, neuropsychiatric, and substance use outcomes, alongside studies of real-world effectiveness and implementation in routine clinical care. In addition, identifying subgroups most likely to benefit will be important. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Haidar, Lara AU - Haidar L AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Delaney, Joseph A C AU - Delaney JAC AD - Division of General Internal Medicine, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, USA. LA - eng PT - Journal Article PT - Review DEP - 20260716 PL - United States TA - Curr Opin HIV AIDS JT - Current opinion in HIV and AIDS JID - 101264945 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *HIV Infections/complications/drug therapy MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Aging MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - *Obesity/drug therapy MH - Aged OTO - NOTNLM OT - HIV OT - aging OT - cardiometabolic disease OT - glucagon-like peptide-1 receptor agonists OT - semaglutide EDAT- 2026/07/17 19:17 MHDA- 2026/08/06 12:37 CRDT- 2026/07/17 16:53 PHST- 2026/08/06 12:37 [medline] PHST- 2026/07/17 19:17 [pubmed] PHST- 2026/07/17 16:53 [entrez] AID - 01222929-990000000-00241 [pii] AID - 10.1097/COH.0000000000001059 [doi] PST - ppublish SO - Curr Opin HIV AIDS. 2026 Sep 1;21(5):355-361. doi: 10.1097/COH.0000000000001059. Epub 2026 Jul 16. PMID- 42467088 OWN - NLM STAT- MEDLINE DCOM- 20260930 LR - 20261003 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 69 IP - 11 DP - 2026 Nov TI - Pharmacological treatment of MASH. PG - 3148-3161 LID - 10.1007/s00125-026-06796-1 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) includes a spectrum of progressive liver conditions ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis and cirrhosis. Currently, MASLD is the leading cause of chronic liver disease worldwide. MASLD is strongly associated with type 2 diabetes, cardiovascular disease, chronic kidney disease and certain extrahepatic cancers. MASLD shares a common pathogenesis with cardiometabolic diseases, especially type 2 diabetes, primarily driven by unhealthy dietary habits, dysfunctional adipose tissue, insulin resistance and low-grade inflammation. Substantial heterogeneity in the pathophysiology of MASLD may influence its rate of progression, its relationship with cardiometabolic diseases and its treatment response. In addition to lifestyle interventions, including a healthy low-energy diet and increased physical activity levels, pharmacological treatment of MASLD/MASH is recommended. For individuals with type 2 diabetes and MASLD/MASH, treatment should preferably include glucagon-like peptide-1 (GLP-1) receptor agonist-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors, which have been shown to improve MASLD/MASH and provide established cardiorenal benefits. In this narrative review, we assess the efficacy of these pharmacotherapies and discuss other treatment approaches for MASLD/MASH, with a focus on their metabolic benefits. CI - (c) 2026. The Author(s). FAU - Stefan, Norbert AU - Stefan N AUID- ORCID: 0000-0002-2186-9595 AD - Internal Medicine IV, Department of Endocrinology, Diabetology and Nephrology, University Hospital Tubingen, Tubingen, Germany. norbert.stefan@med.uni-tuebingen.de. AD - Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tubingen, Tubingen, Germany. norbert.stefan@med.uni-tuebingen.de. AD - German Center for Diabetes Research (DZD), Tubingen, Germany. norbert.stefan@med.uni-tuebingen.de. FAU - Targher, Giovanni AU - Targher G AUID- ORCID: 0000-0002-4325-3900 AD - Department of Medicine, University of Verona, Verona, Italy. AD - Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella (VR), Italy. LA - eng PT - Journal Article PT - Review DEP - 20260717 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/metabolism/complications MH - *Fatty Liver/drug therapy/metabolism MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Insulin Resistance/physiology MH - Animals MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Non-alcoholic Fatty Liver Disease/drug therapy PMC - PMC13627253 OTO - NOTNLM OT - Cardiometabolic diseases OT - MASLD OT - Metabolic dysfunction-associated steatohepatitis OT - Metabolic dysfunction-associated steatotic liver disease OT - Pharmacological treatment OT - Review OT - Type 2 diabetes COIS- Funding: Open Access funding enabled and organized by Projekt DEAL. This work was aided in part by funding from the German Center for Diabetes Research (DZD) to NS. GT is supported in part by the University of Verona School of Medicine, Verona, Italy. Authors' relationships and activities: NS has been or is a consultant and has given scientific talks for Allergan, AstraZeneca, Boehringer Ingelheim, Gilead, Genkyotex, GSK, Intercept Pharma, Lilly, MSD, Novartis, Novo Nordisk, Pfizer and Sanofi. NS has also received research support from AstraZeneca, Boehringer Ingelheim, Sanofi, DSM Nutritional Products and Roche Diagnostics. GT declares that there are no relationships or activities that might bias, or be perceived to bias, his work. Contribution statement: Both authors were responsible for drafting and critically reviewing the article. Both authors approved the version to be published. EDAT- 2026/07/17 12:41 MHDA- 2026/09/30 17:32 PMCR- 2026/07/17 CRDT- 2026/07/17 11:03 PHST- 2026/01/27 00:00 [received] PHST- 2026/05/06 00:00 [accepted] PHST- 2026/09/30 17:32 [medline] PHST- 2026/07/17 12:41 [pubmed] PHST- 2026/07/17 11:03 [entrez] PHST- 2026/07/17 00:00 [pmc-release] AID - 10.1007/s00125-026-06796-1 [pii] AID - 6796 [pii] AID - 10.1007/s00125-026-06796-1 [doi] PST - ppublish SO - Diabetologia. 2026 Nov;69(11):3148-3161. doi: 10.1007/s00125-026-06796-1. Epub 2026 Jul 17. PMID- 42466510 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260905 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 15 IP - 14 DP - 2026 Jul 21 TI - Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease. PG - e047018 LID - 10.1161/JAHA.125.047018 [doi] LID - e047018 AB - BACKGROUND: To evaluate the association between tirzepatide use and 1-year risk of major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease, compared with GLP-1 (glucagon-like peptide-1) receptor agonists. METHODS: We conducted a retrospective, propensity score-matched cohort study using the TriNetX network. A total of 16 402 patients with type 2 diabetes and atherosclerotic cardiovascular disease initiating tirzepatide or GLP-1 receptor agonists between January 1, 2022, and March 31, 2025 were matched 1:1. The primary outcome was 1-year major adverse cardiovascular events; secondary outcomes included all-cause mortality, acute myocardial infarction, major adverse limb events, and tissue plasminogen activator use. RESULTS: Tirzepatide was associated with a lower risk of major adverse cardiovascular events (hazard ratio [HR], 0.75 [95% CI, 0.63-0.91]) and reduced risks of all-cause mortality (HR, 0.69 [95% CI, 0.53-0.90]), major adverse limb events (HR, 0.59 [95% CI, 0.39-0.88]), and acute myocardial infarction (HR, 0.70 [95% CI, 0.53-0.93]), compared with GLP-1 receptor agonists. Results were robust across subgroups and sensitivity analyses. CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a significantly reduced 1-year risk of major adverse cardiovascular events and other cardiovascular outcomes compared with GLP-1 receptor agonists. These findings support the cardiometabolic potential of tirzepatide, warranting further prospective validation. FAU - Wu, Jheng-Yan AU - Wu JY AUID- ORCID: 0000-0002-3290-1909 AD - Department of Nutrition Chi Mei Medical Centre Tainan Taiwan. AD - Department of Public Health, College of Medicine National Cheng Kung University Tainan Taiwan. FAU - Lee, Keng-Wei AU - Lee KW AD - Division of Cardiology, Department of Internal Medicine Chi Mei Medical Centre, Chiali Tainan Taiwan. FAU - Kao, Chia-Li AU - Kao CL AD - Department of Anesthesiology, E-Da Hospital I-Shou University Kaohsiung Taiwan. FAU - Hung, Kuo-Chuan AU - Hung KC AD - Department of Anesthesiology Chi Mei Medical Centre Tainan Taiwan. FAU - Yu, Tsung AU - Yu T AD - Department of Public Health, College of Medicine National Cheng Kung University Tainan Taiwan. FAU - Lin, Yu-Min AU - Lin YM AUID- ORCID: 0009-0005-1723-828X AD - Division of Cardiology, Department of Internal Medicine Chi Mei Medical Centre Tainan Taiwan. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260717 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Atherosclerosis/drug therapy/complications/mortality MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Propensity Score MH - Incretins/therapeutic use MH - Cardiovascular Diseases PMC - PMC13477337 OTO - NOTNLM OT - acute myocardial infarction OT - atherosclerotic cardiovascular disease OT - glucagon-like peptide-1 receptor agonists OT - major adverse cardiovascular events OT - major adverse limb events OT - tirzepatide COIS- The authors declare that there is no conflict of interest regarding the publication of this article. EDAT- 2026/07/17 17:25 MHDA- 2026/07/29 18:38 PMCR- 2026/07/17 CRDT- 2026/07/17 07:11 PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/17 17:25 [pubmed] PHST- 2026/07/17 07:11 [entrez] PHST- 2026/07/17 00:00 [pmc-release] AID - JAH370702 [pii] AID - 10.1161/JAHA.125.047018 [doi] PST - ppublish SO - J Am Heart Assoc. 2026 Jul 21;15(14):e047018. doi: 10.1161/JAHA.125.047018. Epub 2026 Jul 17. PMID- 42466348 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Incretin-based cardiovascular protection beyond diabetes: evidence, mechanisms, and therapeutic frontiers from GLP-1 receptor agonists to multi-agonist therapy. PG - 1870649 LID - 10.3389/fendo.2026.1870649 [doi] LID - 1870649 AB - Incretin-based therapy has moved from glycaemic control into the centre of cardiometabolic medicine. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) consistently reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD), while semaglutide 2.4 mg has extended the evidence base to people with overweight or obesity and established cardiovascular disease in the absence of diabetes. Dedicated trials have further expanded the clinical landscape to chronic kidney disease (CKD), obesity-related heart failure with preserved ejection fraction (HFpEF), and symptomatic peripheral artery disease (PAD). Concurrently, dual and triple incretin-based agonists, oral peptide and non-peptide formulations, and combination strategies with sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists are reshaping treatment algorithms. This critical review synthesizes cardiovascular outcome trials (CVOTs), mechanistic studies, meta-analyses, guideline recommendations, and regulatory developments available up to 30 April 2026. The central conclusion is that incretin-based cardiovascular protection is biologically plausible and clinically reproducible. Critically, this benefit is now independent of diabetes as the defining therapeutic context-a paradigm shift with broad implications for cardiovascular practice. Nevertheless, the magnitude of benefit varies considerably by molecule, dose, population, comparator, and endpoint hierarchy; mediation analyses do not precisely quantify direct cardioprotection; and cardiovascular outcome evidence for newer multi-agonists and oral non-peptide GLP-1 RAs remains incomplete. Interpretation therefore requires a balanced evidence framework: GLP-1 RAs with proven outcome benefit should be prioritized in patients with ASCVD (e.g., LEADER, SUSTAIN-6, HARMONY Outcomes), obesity with established CVD (SELECT), CKD (FLOW), or obesity-related HFpEF (STEP-HFpEF) when supported by trial data and regulatory indications, whereas next-generation agents should be evaluated according to completed CVOTs rather than weight-loss efficacy alone. Remaining research priorities include defining weight-independent mechanisms, optimizing combination therapy, identifying biomarker-defined responders, preserving lean mass during high-efficacy weight loss, and ensuring equitable global access. CI - Copyright (c) 2026 Qiu, Liu and Hu. FAU - Qiu, Libin AU - Qiu L AD - Structural Cardiology Department, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. FAU - Liu, Jinpeng AU - Liu J AD - Cardiology Department 2, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. FAU - Hu, Nana AU - Hu N AD - Cardiology Department 1, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. LA - eng PT - Journal Article PT - Review DEP - 20260702 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC13372633 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MACE OT - cardiovascular outcomes OT - incretin therapy OT - multi-agonist therapy COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/07/17 12:41 MHDA- 2026/07/17 19:17 PMCR- 2026/07/02 CRDT- 2026/07/17 07:09 PHST- 2026/05/05 00:00 [received] PHST- 2026/05/30 00:00 [revised] PHST- 2026/06/08 00:00 [accepted] PHST- 2026/07/17 19:17 [medline] PHST- 2026/07/17 12:41 [pubmed] PHST- 2026/07/17 07:09 [entrez] PHST- 2026/07/02 00:00 [pmc-release] AID - 10.3389/fendo.2026.1870649 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 2;17:1870649. doi: 10.3389/fendo.2026.1870649. eCollection 2026. PMID- 42464447 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 11 DP - 2026 Nov TI - Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real-world data. PG - 3950-3958 LID - 10.1002/bcp.70711 [doi] AB - AIMS: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide are approved for chronic weight management. Both drugs also have favourable effects on the risk of developing diabetes and cardiovascular disease (CVD) compared with placebo, but their comparative effectiveness for these outcomes is unclear. METHODS: We employed an active comparator, new user design to emulate a target trial using data from MarketScan claims databases. Enrolees free of diabetes and CVD prescribed semaglutide or liraglutide during 2021-2023 were matched 1:1. Primary endpoints included incident diabetes and CVD (myocardial infarction, heart failure or stroke). We used Cox regression adjusted for a propensity score reflective of comorbidities and medication use. RESULTS: We matched 57 456 GLP-1 RA users (mean age 45; 83% female). Over 1-year mean follow-up, we observed 1104 diabetes events and 57 CVD events. After regression adjustment, semaglutide users had 12% lower risk of diabetes (hazard ratio [HR]: 0.88; 95% CI: 0.78, 0.99). For this endpoint, the proportional hazards assumption was violated (p < .0001), so results were stratified by follow-up time. During the first 6 months of follow-up, semaglutide use was not associated with risk of diabetes compared with liraglutide use (HR: 0.99 [0.82-1.18]), but a significant association was present thereafter (HR: 0.80 [0.68, 0.94]). We did not detect a difference in risk of CVD events (HR: 1.25 [0.74-2.11]). CONCLUSIONS: In this real-world study, semaglutide users had lower risk of incident diabetes compared with liraglutide users. Additional research is needed to elucidate comparative effectiveness of these drugs for cardiovascular risk. CI - (c) 2026 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Cannon, Ethan J AU - Cannon EJ AUID- ORCID: 0009-0001-1715-9152 AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Wang, Wendy AU - Wang W AD - Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas, USA. AD - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Norby, Faye L AU - Norby FL AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Walker, Rob F AU - Walker RF AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Kulasingam, Shalini AU - Kulasingam S AD - Department of Tropical Medicine and Infectious Diseases, Tulane University Celia Weatherhead School of Public Health, New Orleans, Louisiana, USA. AD - Department of Epidemiology, Tulane University Celia Weatherhead School of Public Health, New Orleans, Louisiana, USA. FAU - Chow, Lisa S AU - Chow LS AUID- ORCID: 0000-0002-6210-2307 AD - Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA. FAU - Farley, Joel F AU - Farley JF AD - Department of Pharmaceutical Care & Health Systems, University of Minnesota College of Pharmacy, Minneapolis, Minnesota, USA. FAU - Lutsey, Pamela L AU - Lutsey PL AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. LA - eng GR - 25GLP1450320/American Heart Association/ GR - UM1TR004405/NIH Clinical and Translational Science/ GR - T32 HL007779/HL/NHLBI NIH HHS/United States GR - K24 HL159246/HL/NHLBI NIH HHS/United States GR - T32 HL007779/NIH/NHLBI/ GR - K24 HL159246/NIH/NHLBI/ PT - Comparative Study PT - Journal Article DEP - 20260716 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Liraglutide/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Incidence MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/epidemiology/prevention & control MH - Adult MH - *Diabetes Mellitus/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged PMC - PMC13714616 OTO - NOTNLM OT - cardiology OT - cardiovascular OT - diabetes OT - endocrinology OT - epidemiology OT - nutrition OT - obesity OT - pharmacoepidemiology OT - public health COIS- J.F.F. has received consulting support from AstaLynx Global and Prime Therapeutics. The other authors have no conflicts of interest to disclose. EDAT- 2026/07/17 10:03 MHDA- 2026/10/28 11:34 PMCR- 2026/07/16 CRDT- 2026/07/17 01:04 PHST- 2026/06/24 00:00 [revised] PHST- 2026/03/30 00:00 [received] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/10/28 11:34 [medline] PHST- 2026/07/17 10:03 [pubmed] PHST- 2026/07/17 01:04 [entrez] PHST- 2026/07/16 00:00 [pmc-release] AID - BCP70711 [pii] AID - 10.1002/bcp.70711 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Nov;92(11):3950-3958. doi: 10.1002/bcp.70711. Epub 2026 Jul 16. PMID- 42460324 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260820 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study. PG - 1885961 LID - 10.3389/fendo.2026.1885961 [doi] LID - 1885961 AB - BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used in patients with type 2 diabetes and obesity. Although tirzepatide improves metabolic and cardiovascular risk factors, its association with venous thromboembolism, including pulmonary embolism and deep vein thrombosis, remains insufficiently characterized in real-world populations. METHODS: We conducted a population-based retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and overweight or obesity who initiated tirzepatide were propensity score matched to patients receiving lifestyle intervention alone with no exposure to weight-loss medications. Outcomes included incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis occurring between 30 days and 12 months after index. Additional analyses included a 90-day landmark sensitivity analysis and an active comparator analysis comparing tirzepatide with semaglutide. RESULTS: After propensity score matching for demographic, metabolic, and clinical covariates, 235, 200 patients were included in the primary analysis (117, 600 per cohort). Tirzepatide use was associated with a significantly lower 12-month risk of pulmonary embolism compared with lifestyle intervention alone (RR, 0.215; 95% CI, 0.185-0.250; HR, 0.258; 95% CI, 0.222-0.299; log-rank P < 0.001). Similar reductions were observed for deep vein thrombosis (RR, 0.303; 95% CI, 0.270-0.340; HR, 0.361; 95% CI, 0.322-0.406; log-rank P < 0.001). No statistically significant difference was observed for superficial vein thrombosis (RR, 0.716; 95% CI, 0.484-1.060; HR, 0.868; 95% CI, 0.586-1.286; log-rank P = 0.480). Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark analysis. In the semaglutide comparator analysis, tirzepatide was associated with a significantly lower risk of deep vein thrombosis, while the pulmonary embolism association was significant by risk-ratio analysis but not by Cox regression. CONCLUSIONS: In this large multicenter cohort study, tirzepatide use was associated with a lower risk of pulmonary embolism and deep vein thrombosis compared with lifestyle intervention alone. These findings suggest a potential association between tirzepatide use and lower observed rates of thromboembolic events in patients with diabetes and obesity. CI - Copyright (c) 2026 Kahkedjian, Shah and Kreidieh. FAU - Kahkedjian, Fredy AU - Kahkedjian F AD - Faculty of Medicine, American University of Beirut, Beirut, Lebanon. FAU - Shah, Jaffer AU - Shah J AD - Department of Ophthalmology, Weill Cornell Medicine, New York, NY, United States. FAU - Kreidieh, Firas AU - Kreidieh F AD - Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260701 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - Female MH - *Pulmonary Embolism/epidemiology/prevention & control MH - Male MH - *Venous Thrombosis/epidemiology/prevention & control MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - United States/epidemiology MH - *Obesity/drug therapy/complications MH - Aged MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Cohort Studies PMC - PMC13368568 OTO - NOTNLM OT - GLP-1 receptor agonist OT - TriNetX OT - deep vein thrombosis OT - obesity OT - pulmonary embolism OT - real-world study OT - thrombosis OT - tirzepatide COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/07/16 06:39 MHDA- 2026/07/16 13:02 PMCR- 2026/07/01 CRDT- 2026/07/16 04:44 PHST- 2026/05/19 00:00 [received] PHST- 2026/06/07 00:00 [revised] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/07/16 13:02 [medline] PHST- 2026/07/16 06:39 [pubmed] PHST- 2026/07/16 04:44 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 10.3389/fendo.2026.1885961 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 1;17:1885961. doi: 10.3389/fendo.2026.1885961. eCollection 2026. PMID- 42456704 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260826 IS - 2215-0374 (Electronic) IS - 2215-0366 (Linking) VI - 13 IP - 8 DP - 2026 Aug TI - Association of GLP-1 receptor agonists with alcohol use disorder-related and substance use disorder-related hospital admissions during treatment and after discontinuation: a Swedish register-based within-individual observational study. PG - 669-677 LID - S2215-0366(26)00172-0 [pii] LID - 10.1016/S2215-0366(26)00172-0 [doi] AB - BACKGROUND: Evidence suggests that GLP-1 receptor agonists might reduce substance use across different substance use disorders. However, data on substance use-related outcomes after GLP-1 discontinuation are absent. This study aimed to investigate the risk of alcohol and substance use-related hospitalisations during and after exposure to GLP-1 receptor agonists. METHODS: This within-individual observational study used Swedish registers to identify residents of Stockholm County with a first registered diagnosis of type 2 diabetes between Jan 1, 2005, and Dec 31, 2024 who had received GLP-1 receptor agonists and, for comparison, DPP-4 inhibitors. Active follow‑up started on Jan 1, 2015, or on the date of the first registered diabetes diagnosis, whichever occurred later. Patients were followed up until the end of the observation period (Dec 31, 2024). The main outcomes were hospitalisations related to alcohol use disorder and substance use disorder (which included the alcohol use disorder-related events). Fixed-effects Poisson regression models were used to estimate rate ratios (RRs) of hospitalisations, comparing periods of GLP-1 receptor agonist or DPP-4 inhibitor exposure and two post-exposure windows (days 1-182 and 183-364) with unexposed periods in the same individuals. People with lived experience were not involved in the study. FINDINGS: 167 026 individuals with type 2 diabetes (mean age 63.98 years [SD 13.77]; median age 65.00 years [IQR 55.00-74.00]; 96 133 [57.6%] males and 70 893 [42.4%] females) were included in the study. Ethnicity data were unavailable. 1559 (0.9%) individuals had at least one alcohol use disorder-related hospitalisation and 2008 (1.2%) had at least one substance use disorder-related hospitalisation. 41 109 (24.6%) individuals received GLP-1 receptor agonists during the study period, and 23 666 (14.2%) received DPP-4 inhibitors. 308 (0.7%) of those receiving GLP-1 receptor agonists had at least one alcohol-related hospitalisation during the observational period, and 444 (1.1%) had at least one substance use-related hospitalisation; 957 (66.1%) of the 1447 substance use disorder-related hospitalisations recorded in these 444 individuals were attributed to alcohol use disorder. GLP-1 exposure was associated with lower rates of hospitalisations related to alcohol use disorder (RR 0.55, 95% CI 0.43-0.70) and substance use disorder (0.61, 0.50-0.74) compared with unexposed periods for the same individuals. For individuals with alcohol use disorder, the association with hospitalisation rate reduction persisted during days 1-182 after discontinuation of GLP-1 receptor agonists (0.70, 0.50-0.98) but was no longer evident during days 183-364 after discontinuation (1.07, 0.71-1.63); for substance use disorder, there were no statistically significant associations with reduction after discontinuation of GLP-1 receptor agonists (days 1-182: 0.79, 0.61-1.02; days 183-364: 0.89, 0.63-1.26). DPP-4 inhibitors were not associated with consistent rate reductions. INTERPRETATION: GLP-1 receptor agonist treatment was associated with lower rates of hospitalisation in individuals with alcohol use disorder and substance use disorder. This association extended into the first 182 days after discontinuation for alcohol use disorder but not for substance use disorder. Findings support clinical monitoring of substance use when GLP-1 receptor agonist treatment is stopped. FUNDING: Forte, Karolinska Institutet, and Region Stockholm. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Bach, Patrick AU - Bach P AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. Electronic address: patrick.bach@ki.se. FAU - Franck, Johan AU - Franck J AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Hallgren, Jonas AU - Hallgren J AD - Academic Primary Care Centre, Region Stockholm, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. FAU - Widing, Harje AU - Widing H AD - Academic Primary Care Centre, Region Stockholm, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. FAU - Gissler, Mika AU - Gissler M AD - Academic Primary Care Centre, Region Stockholm, Stockholm, Sweden; Department of Data and Analytics, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. FAU - Westman, Jeanette AU - Westman J AD - Academic Primary Care Centre, Region Stockholm, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Health Care Sciences, Marie Cederschiold University, Stockholm, Sweden. LA - eng PT - Journal Article PT - Observational Study PL - England TA - Lancet Psychiatry JT - The lancet. Psychiatry JID - 101638123 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Alcoholism/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Exenatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hospitalization/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Registries MH - Semaglutide MH - *Substance-Related Disorders/epidemiology MH - Sweden/epidemiology COIS- Declaration of interests JF and JW declare support for the current study as applicants for grants awarded by Forte (2020-00467), Karolinska Institutet (KID, 2020-02653), and Region Stockholm (FoUI-977024 and 2020-02653). PB declares travel support for the current study by the German Center for Mental Health, Mannheim-Heidelberg-Ulm site. All other authors declare no competing interests. EDAT- 2026/07/16 00:36 MHDA- 2026/07/16 13:02 CRDT- 2026/07/15 18:52 PHST- 2026/04/05 00:00 [received] PHST- 2026/05/11 00:00 [revised] PHST- 2026/06/03 00:00 [accepted] PHST- 2026/07/16 13:02 [medline] PHST- 2026/07/16 00:36 [pubmed] PHST- 2026/07/15 18:52 [entrez] AID - S2215-0366(26)00172-0 [pii] AID - 10.1016/S2215-0366(26)00172-0 [doi] PST - ppublish SO - Lancet Psychiatry. 2026 Aug;13(8):669-677. doi: 10.1016/S2215-0366(26)00172-0. PMID- 42455922 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 42 IP - 5 DP - 2026 Jul TI - Network and Pairwise Meta-Analysis of the Association Between Novel Hypoglycemic Agents and Atrial Fibrillation Risk in Patients With Type 2 Diabetes Mellitus. PG - e70202 LID - 10.1002/dmrr.70202 [doi] LID - e70202 AB - OBJECTIVE: To evaluate the atrial fibrillation (AF) risk of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagonlike peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with Type 2 Diabetes Mellitus (T2DM) with network meta-analysis. METHODS: Systematic literature searches were conducted of MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Clinical Trials.gov covering inception till January 31, 2026. Randomized control trials (RCTs) and cohort studies comparing SGLT-2i, GLP-1RA and DPP-4i in diabetes were selected. We performed a network meta-analysis to compare the three drugs indirectly. Results were reported as risk ration (RR) with corresponding 95% confidence interval (CI). RESULTS: 4 RCTs and 21 cohort studies involving 2,171,267 patients were included. Compared with GLP-1RA [RR with 95% CI: 0.86(0.79, 0.95), RR with 95% CI: 0.87(0.78, 0.97)] and DPP-4i[RR with 95% CI: 0.80(0.74, 0.87), RR with 95% CI: 0.81(0.74, 0.88)], SGLT-2i significantly reduced the risk of AF and new-onset AF. While there were no significant difference in the risk of AF recurrence among SGLT-2i, GLP-1RA, and DPP-4i[RR with 95% CI: 0.87(0.68, 1.12), RR with 95% CI: 0.80(0.61, 1.05), RR with 95% CI: 0.92(0.63, 1.33)]. There were also no significant difference in the risk of AF and new-onset AF between GLP-1RA and DPP-4i[RR with 95% CI: 0.93(0.84, 1.03), RR with 95% CI: 0.93(0.83, 1.04)]. CONCLUSIONS: The management of T2DM involves the prevention of subsequent cardiovascular complications. The results of this network meta-analysis indicate that SGLT2i is associated with a lower risk of AF in T2DM patients compared to GLP-1RA and DPP-4i. Sensitivity analysis further confirms that SGLT-2i significantly reduces the risk of AF recurrence statistically. These finding suggests that SGLT-2i should be considered as a preferred antidiabetic regimen for patients with T2DM at high risk of AF. CI - (c) 2026 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Ye, Xuejiao AU - Ye X AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Wu, Qian AU - Wu Q AUID- ORCID: 0000-0002-5500-3706 AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Hou, Linye AU - Hou L AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Hou, Xinzheng AU - Hou X AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Yang, Yingtian AU - Yang Y AUID- ORCID: 0000-0003-1561-7217 AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Yang, Chenyan AU - Yang C AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Huang, Mingyu AU - Huang M AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. FAU - Wang, Shihan AU - Wang S AUID- ORCID: 0000-0002-9572-5834 AD - China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China. LA - eng GR - 82374421/National Natural Science Foundation of China/ GR - 7232311/Beijing Municipal Natural Science Foundation/ GR - CI2021A00921/Chinese Academy of Traditional Chinese Medicine's Major Tackling Project of Science and Technology Innovation/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Atrial Fibrillation/epidemiology/chemically induced/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects PMC - PMC13372237 OTO - NOTNLM OT - DPP-4 inhibitors OT - GLP-1 receptor agonist OT - SGLT-2 inhibitors OT - atrial fibrillation OT - network meta-analysis OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/07/15 18:37 MHDA- 2026/07/15 18:38 PMCR- 2026/07/15 CRDT- 2026/07/15 14:13 PHST- 2026/06/03 00:00 [revised] PHST- 2026/03/08 00:00 [received] PHST- 2026/06/27 00:00 [accepted] PHST- 2026/07/15 18:38 [medline] PHST- 2026/07/15 18:37 [pubmed] PHST- 2026/07/15 14:13 [entrez] PHST- 2026/07/15 00:00 [pmc-release] AID - DMRR70202 [pii] AID - 10.1002/dmrr.70202 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 Jul;42(5):e70202. doi: 10.1002/dmrr.70202. PMID- 42453024 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1875-6417 (Electronic) IS - 1573-3998 (Linking) VI - 22 IP - 9 DP - 2026 TI - Corrigendum to: Modern-Day Therapeutics and Ongoing Clinical Trials against Type 2 Diabetes Mellitus: A Narrative Review. PG - e060526253450 LID - 10.2174/157339982209260506141308 [doi] AB - In the originally published article titled "Modern-Day Therapeutics and Ongoing Clinical Trials against Type 2 Diabetes Mellitus: A Narrative Review", published in "Current Diabetes Reviews", Vol: 21, 2025 [1], certain phrases and expressions were unclear, which may have affected readability. These have now been revised to improve clarity and ensure that the intended meaning is accurately conveyed. The corrections do not affect the results, interpretations, or conclusions of the article. We apologize for any inconvenience caused and appreciate the opportunity to rectify this matter. The original article can be found online at https://www.eurekaselect.com/article/140414 Original: 4.1.3. GLP-1 Receptor Agonist According to the latest press release, DD01 is therapeutic against hepatic steatosis and lowers body weight in T2DM patients diagnosed with or without fatty liver ailment. Corrected: 4.1.3. GLP-1 Receptor Agonist According to the latest press release, DD01 is therapeutic against hepatic steatosis and lowers body weight in T2DM patients diagnosed with or without fatty liver disorder. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Tiwari, Rohit Kumar AU - Tiwari RK AD - Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Buddh Nagar, Uttar Pradesh, 201310, India. FAU - Ahmad, Afza AU - Ahmad A AD - Department of Public Health, Dr. Giri Lal Gupta Institute of Public Health and Public Affairs, University of Lucknow, Lucknow, Uttar Pradesh, 226007, India. FAU - Chadha, Muskan AU - Chadha M AD - Department of Nutrition & Dietetics, Sharda School of Allied Health Sciences, Sharda University, Gautam Buddh Nagar, Uttar Pradesh, 201310, India. FAU - Saha, Kingshuk AU - Saha K AD - Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Buddh Nagar, Uttar Pradesh, 201310, India. FAU - Verma, Harshitha AU - Verma H AD - Department of Science in Biochemistry, Manasagangothri, University of Mysuru, Mysuru, 570006, Karnataka, India. FAU - Borgohain, Kalpojit AU - Borgohain K AD - Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Buddh Nagar, Uttar Pradesh, 201310, India. FAU - Shukla, Ratnakar AU - Shukla R AD - Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Buddh Nagar, Uttar Pradesh, 201310, India. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Clinical Trials as Topic MH - Fatty Liver/drug therapy EDAT- 2026/07/15 06:36 MHDA- 2026/07/15 12:36 CRDT- 2026/07/15 03:43 PHST- 2026/07/15 12:36 [medline] PHST- 2026/07/15 06:36 [pubmed] PHST- 2026/07/15 03:43 [entrez] AID - CDR-EPUB-155252 [pii] AID - 10.2174/157339982209260506141308 [doi] PST - ppublish SO - Curr Diabetes Rev. 2026;22(9):e060526253450. doi: 10.2174/157339982209260506141308. PMID- 42451041 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 13 DP - 2026 Jun 23 TI - Ironing Out Possible Micronutrient Deficiencies Associated with Incretin Receptor Agonist-Based Therapies: Proposed Practical Strategies to Prevent and Manage Iron Deficiency. LID - 10.3390/nu18132038 [doi] LID - 2038 AB - Over the last years, incretin receptor agonists-including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide-have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies-including iron deficiency-have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials. FAU - Infante, Marco AU - Infante M AUID- ORCID: 0000-0003-2032-8735 AD - Section of Diabetes & Metabolic Disorders, Faculty of Medicine and Surgery, UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant'Alessandro 8, 00131 Rome, Italy. AD - Division of Cellular Transplantation, Department of Surgery, Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave., Miami, FL 33136, USA. FAU - Ricordi, Camillo AU - Ricordi C AUID- ORCID: 0000-0001-8092-7153 AD - Division of Cellular Transplantation, Department of Surgery, Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave., Miami, FL 33136, USA. FAU - Pacifici, Francesca AU - Pacifici F AUID- ORCID: 0000-0001-9014-7492 AD - Section of Food Chemistry, Clinical Nutrition and Pharmaceutical Science, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. AD - Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy. FAU - Pastore, Donatella AU - Pastore D AUID- ORCID: 0000-0002-2284-6256 AD - Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy. FAU - Infante, Raffaele AU - Infante R AUID- ORCID: 0009-0007-3514-7642 AD - Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy. FAU - Caprio, Massimiliano AU - Caprio M AUID- ORCID: 0000-0003-0722-7163 AD - Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy. AD - Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy. FAU - Chiereghin, Francesca AU - Chiereghin F AUID- ORCID: 0000-0002-6109-3250 AD - Section of Food Chemistry, Clinical Nutrition and Pharmaceutical Science, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. FAU - De Stefano, Alessandro AU - De Stefano A AD - Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. FAU - Frank, Giulia AU - Frank G AUID- ORCID: 0000-0003-4515-548X AD - Hepatology, Clinical Nutrition and Geriatrics Unit, Policlinico Tor Vergata (PTV) Hospital, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. FAU - De Rose, Alessio AU - De Rose A AD - Hepatology, Clinical Nutrition and Geriatrics Unit, Policlinico Tor Vergata (PTV) Hospital, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. FAU - Romano, Lorenzo AU - Romano L AUID- ORCID: 0000-0001-7574-2592 AD - Hepatology, Clinical Nutrition and Geriatrics Unit, Policlinico Tor Vergata (PTV) Hospital, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. FAU - Di Renzo, Laura AU - Di Renzo L AUID- ORCID: 0000-0001-8875-6723 AD - Section of Food Chemistry, Clinical Nutrition and Pharmaceutical Science, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. FAU - Rovella, Valentina AU - Rovella V AUID- ORCID: 0000-0002-3311-486X AD - Hepatology, Clinical Nutrition and Geriatrics Unit, Policlinico Tor Vergata (PTV) Hospital, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. AD - Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. AD - IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy. FAU - De Lorenzo, Antonino AU - De Lorenzo A AUID- ORCID: 0000-0001-6524-4493 AD - Section of Food Chemistry, Clinical Nutrition and Pharmaceutical Science, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. FAU - Donadel, Giulia AU - Donadel G AUID- ORCID: 0000-0002-2454-5940 AD - Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. AD - Department of Biomedicine, Catholic University "Our Lady of Good Counsel", Rruga Dritan Hoxha, 1001 Tirana, Albania. FAU - Della-Morte, David AU - Della-Morte D AUID- ORCID: 0000-0002-4054-5318 AD - Section of Food Chemistry, Clinical Nutrition and Pharmaceutical Science, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. AD - Hepatology, Clinical Nutrition and Geriatrics Unit, Policlinico Tor Vergata (PTV) Hospital, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. AD - Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA. LA - eng PT - Journal Article PT - Review DEP - 20260623 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Micronutrients) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Anemia, Iron-Deficiency/prevention & control/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Incretins/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Iron Deficiencies MH - *Micronutrients/deficiency MH - Tirzepatide PMC - PMC13362726 OTO - NOTNLM OT - GLP-1 RA OT - IDA OT - dual GIP/GLP-1 RA OT - incretin receptor agonists OT - iron deficiency OT - iron deficiency anemia OT - iron homeostasis OT - obesity OT - overweight OT - type 2 diabetes COIS- CR serves as a Scientific Advisor for Novo Nordisk((R)) (Bagsvaerd, Denmark). The other authors declare no conflicts of interest. EDAT- 2026/07/15 06:35 MHDA- 2026/07/15 12:37 PMCR- 2026/06/23 CRDT- 2026/07/15 01:05 PHST- 2026/05/16 00:00 [received] PHST- 2026/06/12 00:00 [revised] PHST- 2026/06/17 00:00 [accepted] PHST- 2026/07/15 12:37 [medline] PHST- 2026/07/15 06:35 [pubmed] PHST- 2026/07/15 01:05 [entrez] PHST- 2026/06/23 00:00 [pmc-release] AID - nu18132038 [pii] AID - nutrients-18-02038 [pii] AID - 10.3390/nu18132038 [doi] PST - epublish SO - Nutrients. 2026 Jun 23;18(13):2038. doi: 10.3390/nu18132038. PMID- 42449480 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260916 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Effects of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists on Inflammatory and Metabolic Biomarkers in Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - 9002-9013 LID - 10.1111/dom.71106 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists improve cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their effects on inflammatory and oxidative biomarkers are not fully defined. MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to 19 February 2026 for randomised controlled trials (RCTs) in adults with T2DM comparing a GLP-1RA or dual GIP/GLP-1 agonist with placebo or active therapy, and reporting C-reactive protein (CRP or high-sensitivity CRP [hs-CRP]), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), malondialdehyde (MDA) or adiponectin. Random-effects meta-analyses were conducted using standardised mean differences (SMDs). RESULTS: Forty-one RCTs were included. GLP-1RAs significantly reduced CRP/hs-CRP (27 studies, 1991 participants; SMD -0.37, 95% CI -0.59 to -0.14) and MDA (3 studies, 272 participants; SMD -0.98, 95% CI -1.65 to -0.30), and increased adiponectin (16 studies, 1327 participants; SMD 0.30, 95% CI 0.13 to 0.46). Pooled effects on IL-6 (17 studies, 1068 participants; SMD -0.14, 95% CI -0.37 to 0.10), TNF-alpha (16 studies, 1164 participants; SMD -0.25, 95% CI -0.61 to 0.12) and MCP-1 (7 studies, 450 participants; SMD -0.27, 95% CI -0.58 to 0.03) were not statistically significant, although MCP-1 decreased in sensitivity analyses. Across biomarkers, heterogeneity was moderate to high. Two tirzepatide RCTs (562 participants) showed a significant reduction in IL-6 (SMD -0.28, 95% CI -0.47 to -0.09) and a non-significant trend towards lower CRP/hs-CRP. CONCLUSIONS: In adults with T2DM, incretin-based therapies consistently lower CRP/hs-CRP, reduce oxidative stress (MDA) and increase adiponectin, while effects on IL-6 and TNF-alpha are more variable. These data support a selective anti-inflammatory and metabolic regulatory profile of GLP-1-based therapy, but heterogeneity and limited data for some biomarkers warrant cautious interpretation and further mechanistic studies. TRIAL REGISTRATION: PROSPERO number: CRD420261321430. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kanbay, Mehmet AU - Kanbay M AUID- ORCID: 0000-0002-1297-0675 AD - Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey. FAU - Shah, Ermeena AU - Shah E AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - AlShiab, Rama AU - AlShiab R AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Ozbek, Lasin AU - Ozbek L AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Ay, Sedat AU - Ay S AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Rustamov, Aladin AU - Rustamov A AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Covic, Adrian AU - Covic A AD - Department of Nephrology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania. FAU - Mallamaci, Francesca AU - Mallamaci F AD - Associazione Ipertensione, Nefrologia Trapianto (IPNET), c/o Nefrologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy. FAU - Zoccali, Carmine AU - Zoccali C AD - Associazione Ipertensione, Nefrologia Trapianto (IPNET), c/o Nefrologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy. AD - Renal Research Institute, New York, New York, USA. AD - Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260714 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Hypoglycemic Agents) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 4Y8F71G49Q (Malondialdehyde) RN - 0 (Adiponectin) RN - 0 (Chemokine CCL2) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - Biomarkers/blood/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/agonists MH - C-Reactive Protein/metabolism MH - *Inflammation/metabolism/blood MH - *Hypoglycemic Agents/therapeutic use MH - Interleukin-6 MH - Randomized Controlled Trials as Topic MH - Tumor Necrosis Factor-alpha MH - Malondialdehyde MH - Adiponectin MH - Oxidative Stress/drug effects MH - Chemokine CCL2/blood PMC - PMC13538776 OTO - NOTNLM OT - C-reactive protein OT - adiponectin OT - glucagon-like peptide-1 receptor agonists OT - inflammation OT - interleukin-6 OT - oxidative stress OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/07/15 10:10 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/15 00:22 PHST- 2026/06/24 00:00 [revised] PHST- 2026/04/27 00:00 [received] PHST- 2026/07/03 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/15 10:10 [pubmed] PHST- 2026/07/15 00:22 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71106 [pii] AID - 10.1111/dom.71106 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9002-9013. doi: 10.1111/dom.71106. Epub 2026 Jul 14. PMID- 42445750 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1658-3175 (Electronic) IS - 0379-5284 (Print) IS - 0379-5284 (Linking) VI - 47 IP - 8 DP - 2026 Aug TI - GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Diabetic Nephropathy: A Comparative Study. PG - 1357-1365 LID - 10.15537/1658-3175.8828 [doi] AB - OBJECTIVE: To investigate the effects of glucagon-like peptide-1 receptor agonist (GLP-1RAs) on renal function in type 2 diabetes mellitus (T2DM) patients and compared their efficacy to sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in managing diabetic nephropathy. METHODS: This is a retrospective cohort study conducted at King Fahad University Hospital, including 115 adults (>/=18 years) with T2DM and baseline estimated glomerular filtration rate (eGFR) >/=60 mL/min/1.73m(2), treated with GLP-1RAs or SGLT-2i for over 1 year. Patients on renal replacement therapy, nephrotoxic drugs, or with incomplete records were excluded. Data were analyzed with Jeffrey's Amazing Statistics Program; the significant value is p < 0.05. RESULTS: Participants were treated with either SGLT-2i (67.8%) or GLP-1RAs (32.2%). Both groups showed minimal improvements in glycemic control, hemoglobin A1c decreased from 7.86% to 7.66% (SGLT-2i) and from 8% to 7.76% (GLP-1RAs). Estimated GFR minimally improved by 0.5-1.2 mL/min/1.73m(2) (GLP-1RAs) and changed by -1.2 to +10.1 mL/min/1.73m(2) (SGLT-2i). Urine albumin/creatinine ratio dropped by 13.35 mg/g with GLP-1RAs but increased by 49.86 mg/g with SGLT-2i. CONCLUSIONS: Both medications offered comparable glycemic and renal benefits. The GLP-1RAs, however, demonstrated more favorable effects on albuminuria, suggesting potential for superior renal protection in nascent diabetic nephropathy. CI - Copyright: (c) Saudi Medical Journal. FAU - Alghadeer, Sara Ghadeer AU - Alghadeer SG AD - Imam Abdulrahman bin Faisal, King Fahad University Hospital, Dammam, Kingdom of Saudi Arabia. FAU - Kanfar, Sama Sami AU - Kanfar SS AUID- ORCID: 0009-0000-9132-3187 AD - Imam Abdulrahman bin Faisal, King Fahad University Hospital, Dammam, Kingdom of Saudi Arabia. FAU - Algallaf, Zakiah Dheya AU - Algallaf ZD AD - Imam Abdulrahman bin Faisal, King Fahad University Hospital, Dammam, Kingdom of Saudi Arabia. FAU - Alfardan, Fatimah Mudhar AU - Alfardan FM AD - Imam Abdulrahman bin Faisal, King Fahad University Hospital, Dammam, Kingdom of Saudi Arabia. FAU - Alshammrany, Rana AU - Alshammrany R AD - Imam Abdulrahman bin Faisal, King Fahad University Hospital, Dammam, Kingdom of Saudi Arabia. FAU - Farhat, Maha AU - Farhat M AD - Department of Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Kingdom of Saudi Arabia. FAU - Cyrus, Cyril AU - Cyrus C AUID- ORCID: 0000-0001-7333-6486 AD - Department of Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Kingdom of Saudi Arabia. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260707 PL - Saudi Arabia TA - Saudi Med J JT - Saudi medical journal JID - 7909441 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy/etiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Glomerular Filtration Rate/drug effects MH - Male MH - Middle Aged MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Aged PMC - PMC13360869 OTO - NOTNLM OT - Chronic kidney disease OT - Diabetic nephropathies OT - GLP-1r agonists OT - SGLT-2 inhibitors EDAT- 2026/07/14 18:26 MHDA- 2026/07/14 18:27 PMCR- 2026/08/01 CRDT- 2026/07/14 06:54 PHST- 2025/11/26 00:00 [received] PHST- 2026/05/03 00:00 [accepted] PHST- 2026/07/14 18:27 [medline] PHST- 2026/07/14 18:26 [pubmed] PHST- 2026/07/14 06:54 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - saudimedj-47-8-1357 [pii] AID - 10.15537/1658-3175.8828 [doi] PST - ppublish SO - Saudi Med J. 2026 Aug;47(8):1357-1365. doi: 10.15537/1658-3175.8828. Epub 2026 Jul 7. PMID- 42443144 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Safety Profile of Tirzepatide in Real-World Clinical Practice: A Pharmacovigilance Study Using the FAERS Database. PG - 8936-8945 LID - 10.1111/dom.71025 [doi] AB - AIMS: Tirzepatide, a first-in-class dual GIP/GLP-1 receptor agonist, was approved by the FDA for type 2 diabetes mellitus (2022) and chronic weight management (2023). Despite superior efficacy in trials, its real-world safety profile remains incompletely characterised. This study aimed to characterise tirzepatide's post-marketing safety signals using the FAERS database. MATERIALS AND METHODS: FAERS reports listing tirzepatide as the primary suspected drug were extracted (Q2 2022-Q4 2025). Disproportionality analysis used four algorithms (ROR, PRR, IC, EBGM). Adverse events were coded using MedDRA terminology. Time-to-onset and comparative analyses versus semaglutide were conducted. RESULTS: A total of 123 145 reports (251 435 individual adverse events) were included. Females accounted for 62.30%, with a mean age of 53.7 years. Major signals included medication errors, injection-site reactions and gastrointestinal disorders. Novel unlabelled signals included eructation, hunger, food craving and starvation ketoacidosis. Compared with semaglutide, tirzepatide showed lower reporting odds of vomiting, constipation and decreased appetite. Among reports with valid onset data, median time to onset was 13 days, with 67.1% occurring within 30 days. CONCLUSIONS: This FAERS study characterises tirzepatide safety signals in real-world practice. Medication errors and injection-site reactions were the strongest signals. Several novel signals warrant further investigation. Among reports with complete onset data, most adverse events were reported early after treatment initiation, suggesting the importance of closer monitoring during the first month of therapy. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Guo, Xinghua AU - Guo X AUID- ORCID: 0000-0003-4815-0158 AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Zhang, Jiahua AU - Zhang J AD - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. FAU - Li, Qisen AU - Li Q AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Ye, Zhiqiang AU - Ye Z AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Yuan, Shengyong AU - Yuan S AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. LA - eng PT - Journal Article DEP - 20260713 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Tirzepatide/adverse effects MH - Female MH - Middle Aged MH - Semaglutide MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Pharmacovigilance MH - Databases, Factual MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data PMC - PMC13538822 OTO - NOTNLM OT - FAERS OT - pharmacovigilance OT - semaglutide OT - signal mining OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/07/14 00:35 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/13 23:03 PHST- 2026/05/26 00:00 [revised] PHST- 2026/04/13 00:00 [received] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/14 00:35 [pubmed] PHST- 2026/07/13 23:03 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71025 [pii] AID - 10.1111/dom.71025 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8936-8945. doi: 10.1111/dom.71025. Epub 2026 Jul 13. PMID- 42442791 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1488-2329 (Electronic) IS - 0820-3946 (Print) IS - 0820-3946 (Linking) VI - 198 IP - 26 DP - 2026 Jul 12 TI - Cardiovascular and renal outcomes of combined SGLT2 inhibitors and GLP-1 receptor agonists versus monotherapy in patients with type 2 diabetes mellitus: a network meta-analysis. PG - E992-E1001 LID - 10.1503/cmaj.250369 [doi] AB - BACKGROUND: Whether using both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is more effective than using either alone in type 2 diabetes mellitus remains uncertain. We sought to assess cardiovascular and kidney outcomes of combined SGLT2i and GLP-1RA therapy versus monotherapy using network meta-analysis. METHODS: We identified randomized controlled trials (RCTs) of SGLT2i or GLP-1RA in patients with type 2 diabetes mellitus through a comprehensive search of MEDLINE, Embase, and the Cochrane Library until Aug. 15, 2025. We compared patients receiving SGLT2i, GLP-1RA, both SGLT2i and GLP-1RA, or neither medication in a systematic review and network meta-analysis. Primary outcomes were major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) and major adverse kidney events (decline in estimated glomerular filtration rate, kidney failure, and death due to kidney failure). Secondary outcomes included heart failure-related hospital admissions, serious adverse events, and hypoglycemia. RESULTS: We included 12 RCTs with 99 683 participants. The risk of major adverse cardiovascular events did not differ significantly with combined SGLT2i and GLP-1RA therapy compared with SGLT2i (risk ratio [RR] 0.86, 95% confidence interval [CI] 0.74 to 1.01; very low certainty) or GLP-1RA alone (RR 0.95, 95% CI 0.81 to 1.12; very low certainty). Similarly, the risk of major adverse kidney events did not differ significantly with combined therapy from SGLT2i (RR 1.05, 95% CI 0.74 to 1.49; very low certainty) or GLP-1RA (RR 0.86, 95% CI 0.60 to 1.21; very low certainty). However, combined therapy was associated with a lower risk of heart failure-related hospital admission than SGLT2i (RR 0.72, 95% CI 0.52 to 0.99; very low certainty) or GLP-1RA (RR 0.62, 95% CI 0.45 to 0.86; very low certainty). Risks of serious adverse events or hypoglycemia did not differ significantly between combined therapy and monotherapy. INTERPRETATION: Compared with SGLT2i or GLP-1RA alone, combined therapy did not significantly reduce the risk of major adverse cardiovascular or kidney events but was associated with lower risks of heart failure-related hospital admission. Randomized controlled trials directly comparing combined therapy with monotherapy are needed to clarify the comparative effectiveness of combined therapy in patients with type 2 diabetes mellitus. PROTOCOL REGISTRATION: PROSPERO - CRD42024605727. CI - (c) 2026 CMA Impact Inc. or its licensors. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Ho, Cheng-Wei AU - Ho CW AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Wang, Hsien-Yi AU - Wang HY AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Pan, Heng-Chih AU - Pan HC AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Tu, Yu-Kang AU - Tu YK AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. a50601@mail.chimei.org.tw. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260712 PL - Canada TA - CMAJ JT - CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne JID - 9711805 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/epidemiology MH - Drug Therapy, Combination MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use/adverse effects PMC - PMC13374707 COIS- Competing interests:: None declared. EDAT- 2026/07/14 04:10 MHDA- 2026/07/14 16:10 PMCR- 2026/07/13 CRDT- 2026/07/13 20:43 PHST- 2026/03/26 00:00 [accepted] PHST- 2026/07/14 16:10 [medline] PHST- 2026/07/14 04:10 [pubmed] PHST- 2026/07/13 20:43 [entrez] PHST- 2026/07/13 00:00 [pmc-release] AID - 198/26/E992 [pii] AID - 198e992 [pii] AID - 10.1503/cmaj.250369 [doi] PST - epublish SO - CMAJ. 2026 Jul 12;198(26):E992-E1001. doi: 10.1503/cmaj.250369. PMID- 42442720 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260904 IS - 1440-1746 (Electronic) IS - 0815-9319 (Print) IS - 0815-9319 (Linking) VI - 41 IP - 9 DP - 2026 Sep TI - GLP-1 RA Plus SGLT2i Versus Monotherapy in MASLD and Type 2 Diabetes: Three Pairwise Target Trial Emulations. PG - 2862-2881 LID - 10.1111/jgh.70589 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular and metabolic benefits individually; however, the comparative effectiveness of combination therapy versus monotherapy in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) remains incompletely characterized. METHODS: We conducted three pairwise target trial emulations using the TriNetX Research Network. Adults with MASLD and T2DM initiating GLP-1 RA plus SGLT2i combination therapy, GLP-1 RA monotherapy, or SGLT2i monotherapy were identified. Primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and composite liver outcomes. Propensity score matching (PSM) (1:1) was performed for each pairwise comparison. Cox proportional hazards regression with Bayesian hierarchical bias-effect (BHBE) correction was utilized to address residual confounding. RESULTS: Following PSM, 42423 combination versus 42 423 GLP-1 RA, 40349 combination versus 40 349 SGLT2i, and 51 826 GLP-1 RA versus 51 826 SGLT2i patients were analyzed. Combination therapy significantly reduced all-cause mortality versus SGLT2i monotherapy (hazard ratio [HR] 0.522, 95% confidence interval [CI] 0.488-0.559), with probable benefit after bias correction (corrected HR 0.655, posterior probability 92.4%; credible interval includes the null). Combination therapy demonstrated increased MACE risk versus GLP-1 RA (HR 1.106, 95% CI 1.045-1.170), remaining significant after correction (corrected HR 1.111). Composite liver outcomes favored combination therapy versus SGLT2i (corrected HR 0.907, probability of benefit 81.9%). CONCLUSIONS: GLP-1 RA and SGLT2i combination therapy significantly reduced mortality and liver outcomes versus SGLT2i monotherapy in MASLD with T2DM; however, increased MACE risk versus GLP-1 RA monotherapy warrants consideration in management decisions. CI - (c) 2026 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Alkuwaiti, Mohanad A AU - Alkuwaiti MA AUID- ORCID: 0009-0004-5412-046X AD - College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. FAU - Al-Harbi, Faisal A AU - Al-Harbi FA AUID- ORCID: 0009-0008-7741-4670 AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Alsaif, Ahmed K AU - Alsaif AK AD - College of Medicine, Al-Rayan Colleges, Medinah, Saudi Arabia. FAU - AlSughayyir, Ziyad M AU - AlSughayyir ZM AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Alsaud, Rayan Saleh AU - Alsaud RS AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Aljabr, Mohammed N AU - Aljabr MN AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Alanazi, Ahmad K AU - Alanazi AK AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Alosaily, Ahmad A AU - Alosaily AA AD - College of Medicine, Qassim University, Qassim, Saudi Arabia. FAU - Alabdulqader, Abdulrhman K AU - Alabdulqader AK AD - Department of Internal Medicine, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. FAU - Almusabeh, Hamza AU - Almusabeh H AD - Department of Internal Medicine, West Virginia University School of Medicine, Morgantown, West Virginia, USA. FAU - Altemani, Rayyan F AU - Altemani RF AD - Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. FAU - Azzam, Ahmed Y AU - Azzam AY AUID- ORCID: 0000-0002-4256-0159 AD - Division of Global Health and Public Health, School of Nursing, Midwifery and Public Health, University of Suffolk, Ipswich, UK. AD - Clinical Research and Clinical Artificial Intelligence, ASIDE Healthcare, Lewes, Delaware, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260713 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - Female MH - Treatment Outcome MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage MH - Aged MH - *Fatty Liver/drug therapy/mortality/etiology MH - Cardiovascular Diseases/etiology/prevention & control PMC - PMC13534337 OTO - NOTNLM OT - GLP-1 RA OT - MASLD OT - SGLT2 inhibitors OT - cardiometabolic outcomes OT - diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/07/14 04:10 MHDA- 2026/09/02 05:36 PMCR- 2026/09/02 CRDT- 2026/07/13 19:32 PHST- 2026/06/27 00:00 [revised] PHST- 2026/04/24 00:00 [received] PHST- 2026/07/03 00:00 [accepted] PHST- 2026/09/02 05:36 [medline] PHST- 2026/07/14 04:10 [pubmed] PHST- 2026/07/13 19:32 [entrez] PHST- 2026/09/02 00:00 [pmc-release] AID - JGH70589 [pii] AID - 10.1111/jgh.70589 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2026 Sep;41(9):2862-2881. doi: 10.1111/jgh.70589. Epub 2026 Jul 13. PMID- 42441967 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260916 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 9 DP - 2026 Sep TI - Glucagon-like Peptide-1 Receptor Agonists and Risk for Ischemic Optic Neuropathy : A Target Trial Emulation. PG - 1244-1253 LID - 10.7326/ANNALS-25-00860 [doi] AB - BACKGROUND: There are few data evaluating the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and nonarteritic anterior ischemic optic neuropathy (NAION), which constitutes approximately 75% of ischemic optic neuropathy (ION) cases in adults. OBJECTIVE: To estimate the effect of GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on risk for ION. DESIGN: Observational emulation of a target trial. SETTING: Large U.S.-based commercial claims database (January 2017 to December 2022). PARTICIPANTS: Patients aged 18 to 65 years with type 2 diabetes initiating a GLP-1RA, an SGLT2i, or a DPP4i. MEASUREMENTS: The primary outcome was incident ION as a proxy for NAION. Analyses adjusted for more than 80 covariates using inverse probability of treatment weights, and 18-month cumulative incidence and risk differences (RDs) per 10 000 patients were estimated. RESULTS: The 18-month risk for ION was 8.5 versus 5.5 per 10 000 among GLP-1RA users versus SGLT2i users (RD, 3.0 [95% CI, 0.4 to 5.7]) and 7.8 versus 4.2 per 10 000 among GLP-1RA users versus DPP4i users (RD, 3.6 [CI, 1.1 to 6.1]). Corresponding numbers needed to harm were 3333 and 2778, respectively. Among GLP-1RA users, 69 (85.2%) of the 81 ION events occurred in persons older than 50 years and 57 (70.3%) occurred in men. Risk differences were attenuated among metformin monotherapy users (2.0 and 4.1) compared with users of 2 or more diabetes medications (5.7 and 4.0) versus SGLT2is and DPP4is, respectively. Risk differences were higher in men, patients aged 50 years or older, and those with cardiovascular disease or ophthalmic conditions, with minimal differences in women and those younger than 50 years. LIMITATIONS: Diagnostic codes specifically for NAION were lacking. Missing data on key clinical factors (such as body mass index and type 2 diabetes duration) may contribute to residual confounding, leaving uncertainty about whether the observed association is causal. CONCLUSION: Use of GLP-1RAs was associated with higher 18-month risk for ION than use of SGLT2is and DPP4is, although absolute risk remained very low. Observed differences may reflect residual confounding. PRIMARY FUNDING SOURCE: National Institutes of Health. FAU - Reynolds, Kamika R AU - Reynolds KR AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Center for Health Outcomes, Policy, and Economics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (K.R.R., K.M.O., C.V.D.). FAU - O'Malley, Kimberly M AU - O'Malley KM AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Center for Health Outcomes, Policy, and Economics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (K.R.R., K.M.O., C.V.D.). FAU - Roy, Jason A AU - Roy JA AD - Department of Biostatistics and Epidemiology, Rutgers School of Public Health, New Brunswick, New Jersey (J.A.R.). FAU - Dave, Chintan V AU - Dave CV AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Center for Health Outcomes, Policy, and Economics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (K.R.R., K.M.O., C.V.D.). LA - eng GR - R01HL163163/HB/NHLBI NIH HHS/United States GR - R01DK139163/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Observational Study DEP - 20260714 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - Female MH - Adult MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Young Adult MH - Adolescent MH - Incidence COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/07/13 23:34 MHDA- 2026/09/15 05:06 CRDT- 2026/07/13 17:02 PHST- 2026/09/15 05:06 [medline] PHST- 2026/07/13 23:34 [pubmed] PHST- 2026/07/13 17:02 [entrez] AID - 10.7326/ANNALS-25-00860 [doi] PST - ppublish SO - Ann Intern Med. 2026 Sep;179(9):1244-1253. doi: 10.7326/ANNALS-25-00860. Epub 2026 Jul 14. PMID- 42441965 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260817 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 8 DP - 2026 Aug TI - Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation. PG - 1128-1139 LID - 10.7326/ANNALS-25-05216 [doi] AB - BACKGROUND: Addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to basal insulin can decrease insulin requirements, but whether it permits insulin discontinuation is unclear. OBJECTIVE: To compare rates of insulin discontinuation among patients with type 2 diabetes (T2D) receiving basal insulin who initiated treatment with a GLP-1RA, sodium-glucose cotransporter-2 inhibitor (SGLT-2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) between 2020 and 2022. DESIGN: Target trial emulation. SETTING: U.S. Veterans Health Administration electronic health record (EHR) data. PARTICIPANTS: Veterans with T2D receiving basal insulin. MEASUREMENTS: Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up. RESULTS: Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A(1c) (HbA(1c)) level of 9% or more. Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compared with the SGLT-2i and DPP-4i arms, respectively). Results were not substantively different in a modified per protocol analysis. None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is. LIMITATION: Possible residual confounding; misclassification of exposure and outcome using EHRs may bias associations toward the null. CONCLUSION: Among veterans with T2D receiving basal insulin therapy, addition of GLP-1RA did not increase the chances of stopping insulin therapy compared with SGLT-2i or DPP-4i therapy. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. FAU - Lipska, Kasia J AU - Lipska KJ AD - Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.J.L., B.G.). FAU - Zawack, Kelson AU - Zawack K AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.Z.). FAU - Yan, Lei AU - Yan L AUID- ORCID: 0000-0002-4779-2688 AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut (L.Y., J.L.). FAU - Mutalik, Pradeep AU - Mutalik P AUID- ORCID: 0009-0002-4573-4617 AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (P.M.). FAU - Li, Jingmao AU - Li J AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut (L.Y., J.L.). FAU - Gulanski, Barbara AU - Gulanski B AUID- ORCID: 0000-0003-4056-3409 AD - Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.J.L., B.G.). FAU - Ioannou, George N AU - Ioannou GN AD - Research and Development, Veterans Affairs Puget Sound Health Care System, and Divisions of Gastroenterology, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington (G.N.I.). FAU - Aslan, Mihaela AU - Aslan M AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (M.A.). LA - eng PT - Comparative Study PT - Journal Article DEP - 20260714 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Insulin/therapeutic use/administration & dosage MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Semaglutide MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Middle Aged MH - Aged MH - Administration, Oral MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/07/13 22:42 MHDA- 2026/08/17 23:39 CRDT- 2026/07/13 17:02 PHST- 2026/08/17 23:39 [medline] PHST- 2026/07/13 22:42 [pubmed] PHST- 2026/07/13 17:02 [entrez] AID - 10.7326/ANNALS-25-05216 [doi] PST - ppublish SO - Ann Intern Med. 2026 Aug;179(8):1128-1139. doi: 10.7326/ANNALS-25-05216. Epub 2026 Jul 14. PMID- 42441962 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 9 DP - 2026 Sep TI - Glucagon-like Peptide-1 Receptor Agonists and Risk for Anterior Ischemic Optic Neuropathy : A Nationwide Cohort Study. PG - 1232-1243 LID - 10.7326/ANNALS-25-02096 [doi] AB - BACKGROUND: There are concerns about a possible link between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and nonarteritic anterior ischemic optic neuropathy (NAION). OBJECTIVE: To examine whether use of GLP-1RAs increases risk for AION, which predominantly comprises NAION. DESIGN: Nationwide, register-based, cohort study. SETTING: Sweden, 2013 to 2024. PATIENTS: Initiators of GLP-1RAs compared with initiators of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. MEASUREMENTS: Anterior ischemic optic neuropathy in the national patient register. Adjusted risk differences (RDs) and risk ratios (RRs) were estimated using propensity score weighting. RESULTS: Median follow-up was 1.6 years (IQR, 0.7 to 3.1 years) for GLP-1RA users and 1.5 years (IQR, 0.7 to 2.9 years) for SGLT-2 inhibitor users. Sixty-two of 107 518 GLP-1RA users and 64 of 185 898 SGLT-2 inhibitor users experienced AION. Risks were 0.04% versus 0.02% (RD, 0.02% [95% CI, 0.00% to 0.03%]; RR, 1.93 [CI, 1.00 to 3.73]) at 1 year and 0.12% versus 0.07% (RD, 0.05% [CI, 0.00% to 0.10%]; RR, 1.69 [CI, 0.95 to 3.01]) at 5 years. The differences were substantially attenuated in analyses restricted to patients receiving metformin at baseline (1 year: RD, 0.01% [CI, -0.01% to 0.02%]; RR, 1.40 [CI, 0.64 to 3.05]; 3 years: RD, 0.01% [CI, -0.02% to 0.04%]; RR, 1.24 [CI, 0.68 to 2.26]; 5 years: RD, 0.02% [CI, -0.04% to 0.08%]; RR, 1.23 [CI, 0.65 to 2.33]). LIMITATION: Few outcome events, unmeasured confounding, and limited generalizability to GLP-1RA users without diabetes. CONCLUSION: The relative risk for AION was higher with GLP-1RA use compared with SGLT-2 inhibitor use in type 2 diabetes. However, absolute risks were small, and the RDs were substantially reduced in analyses restricted to patients receiving metformin to better account for confounding by diabetes severity, suggesting observed increases in risk may reflect residual confounding. PRIMARY FUNDING SOURCE: Karolinska Institutet, Swedish Society of Medicine, Swedish Research Council, and Region Stockholm. FAU - Ueda, Peter AU - Ueda P AUID- ORCID: 0000-0002-3275-8743 AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden (P.U., J.S., L.P., V.W.). FAU - Svanstrom, Henrik AU - Svanstrom H AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; and Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (H.S., B.P.). FAU - Soderling, Jonas AU - Soderling J AUID- ORCID: 0000-0001-9006-2835 AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden (P.U., J.S., L.P., V.W.). FAU - Pazzagli, Laura AU - Pazzagli L AUID- ORCID: 0000-0002-1908-6073 AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden (P.U., J.S., L.P., V.W.). FAU - Wintzell, Viktor AU - Wintzell V AUID- ORCID: 0000-0001-7759-0887 AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden (P.U., J.S., L.P., V.W.). FAU - Eliasson, Bjorn AU - Eliasson B AUID- ORCID: 0000-0003-2569-4160 AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden (B.E.). FAU - Hviid, Anders AU - Hviid A AUID- ORCID: 0000-0002-7509-9127 AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; and Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.H.). FAU - Pasternak, Bjorn AU - Pasternak B AUID- ORCID: 0000-0002-2097-8466 AD - Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; and Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (H.S., B.P.). LA - eng PT - Journal Article DEP - 20260714 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Sweden/epidemiology MH - Female MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Middle Aged MH - Aged MH - Registries MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Risk Factors MH - Cohort Studies COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/07/13 22:43 MHDA- 2026/09/15 05:06 CRDT- 2026/07/13 17:02 PHST- 2026/09/15 05:06 [medline] PHST- 2026/07/13 22:43 [pubmed] PHST- 2026/07/13 17:02 [entrez] AID - 10.7326/ANNALS-25-02096 [doi] PST - ppublish SO - Ann Intern Med. 2026 Sep;179(9):1232-1243. doi: 10.7326/ANNALS-25-02096. Epub 2026 Jul 14. PMID- 42440238 OWN - NLM STAT- MEDLINE DCOM- 20260930 LR - 20261003 IS - 1720-8386 (Electronic) IS - 0391-4097 (Print) IS - 0391-4097 (Linking) VI - 49 IP - 10 DP - 2026 Oct TI - Comparative effectiveness of subcutaneous GLP-1 receptor agonists versus SGLT2 inhibitors on metabolic and hepatic outcomes in T2DM with MASLD: a propensity score-matched study. PG - 3017-3025 LID - 10.1007/s40618-026-02976-3 [doi] AB - AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexists with type 2 diabetes mellitus (T2DM), complicating its management. In this population, we aimed to compare the effectiveness of subcutaneous GLP-1 receptor agonists (scGLP-1RA) to SGLT2 inhibitors (SGLT2i) on metabolic and hepatic parameters, while investigating the influence of GLP1R and PNPLA3 genetic variants on treatment response. METHODS: This retrospective study included patients with T2DM starting scGLP-1RA or SGLT2i, balanced through Propensity Score Matching (PSM) to account for baseline clinical differences. Clinical and biochemical data were compared at baseline and after one year of treatment. Genotyping was performed for PNPLA3 (rs738409) and GLP1R (rs761387, rs6923761) polymorphisms. Multivariable linear regression was used to identify independent predictors of HbA1c, BMI, and transaminase reduction. RESULTS: Both drug classes significantly improved glycemic control and BMI. However, scGLP-1RA demonstrated superior efficacy in HbA1c and BMI reduction compared to SGLT2i (beta = -0.349, p = 0.001; beta = -0.711, p = 0.045). In MASLD subgroups (baseline ALT > 35 U/L or hepatic steatosis), only scGLP-1RA led to a significant reduction in ALT levels (p = 0.02). Multivariable analysis identified the GLP1R rs761387 G allele as an independent predictor of a blunted glycemic response (beta = -0.277, p = 0.018). CONCLUSIONS: In a real-world setting, scGLP-1RA showed higher potency than SGLT2i on metabolic and hepatic parameters. These findings support the preferential use of scGLP-1RA in patients with T2DM and MASLD and are consistent with current international recommendations. The association between GLP1R rs761387 variant and HbA1c reduction sheds light on the impact of this variant on treatment response. Further studies are needed to validate this genetic predictor in broader populations. CI - (c) 2026. The Author(s). FAU - Toffoli, Barbara AU - Toffoli B AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Sirignano, Matteo AU - Sirignano M AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Bonato, Valeria AU - Bonato V AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Fusaro, Giulia AU - Fusaro G AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Russo, Erica AU - Russo E AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Velardi, Valerio AU - Velardi V AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Croce, Lory Saveria AU - Croce LS AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. AD - Centro Clinico Studi Fegato ASUGI, Maggiore Teaching Hospital, Piazza Dell'Ospitale, 34100, Trieste, Italy. FAU - Fabris, Bruno AU - Fabris B AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. AD - SC Patologie Diabetiche, ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), 34128, Trieste, Italy. FAU - Bernardi, Stella AU - Bernardi S AUID- ORCID: 0000-0002-7429-3075 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale Di Cattinara 447, 34149, Trieste, Italy. stella.bernardi@asugi.sanita.fvg.it. AD - SS Endocrinologia - Medicina Clinica, ASUGI, Ospedale Di Cattinara 447, 34149, Trieste, Italy. stella.bernardi@asugi.sanita.fvg.it. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260713 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Biomarkers) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Propensity Score MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/genetics MH - *Fatty Liver/drug therapy/pathology MH - Treatment Outcome MH - Blood Glucose/analysis MH - Prognosis MH - Glycated Hemoglobin/analysis MH - Biomarkers/analysis MH - Hypoglycemic Agents/therapeutic use MH - Follow-Up Studies MH - Aged PMC - PMC13627211 OTO - NOTNLM OT - ALT OT - GLP-1RA OT - LIVER OT - MASLD OT - SGLT2i OT - SNP OT - T2DM OT - rs761387 COIS- Declarations. Conflict of interests: All the authors have no conflict of interests. Informed consent: Informed consent was obtained from all subjects involved in this study. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the Institutional Review Board of the University of Trieste, Trieste, Italy (University of Trieste Comitato Etico di Ateneo #136 date 30/11/2023). EDAT- 2026/07/13 12:34 MHDA- 2026/09/30 17:32 PMCR- 2026/07/13 CRDT- 2026/07/13 11:17 PHST- 2026/02/24 00:00 [received] PHST- 2026/06/26 00:00 [accepted] PHST- 2026/09/30 17:32 [medline] PHST- 2026/07/13 12:34 [pubmed] PHST- 2026/07/13 11:17 [entrez] PHST- 2026/07/13 00:00 [pmc-release] AID - 10.1007/s40618-026-02976-3 [pii] AID - 2976 [pii] AID - 10.1007/s40618-026-02976-3 [doi] PST - ppublish SO - J Endocrinol Invest. 2026 Oct;49(10):3017-3025. doi: 10.1007/s40618-026-02976-3. Epub 2026 Jul 13. PMID- 42439225 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260927 IS - 1756-5391 (Electronic) IS - 1756-5391 (Linking) VI - 19 IP - 3 DP - 2026 Sep TI - Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists After Bowel Obstruction or Ileus: A Nationwide, Real-World, Database Study. PG - e70164 LID - 10.1111/jebm.70164 [doi] LID - e70164 AB - OBJECTIVE: Although concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may increase the risk of bowel obstruction or ileus, evidence remains inconclusive. In this context of uncertainty, we examined the frequency and determinants of GLP-1RA discontinuation after hospitalization for bowel obstruction/ileus. METHODS: We conducted a retrospective cohort study using a nationwide Japanese health insurance claims database (DeSC). We identified individuals aged >/=18 years with type 2 diabetes who were hospitalized for bowel obstruction/ileus between 2016 and 2023 while receiving GLP-1RA therapy. The primary outcome was GLP-1RA discontinuation, defined as no prescription at discharge or within 6 months of discharge. Factors potentially associated with discontinuation were grouped into (1) general factors, (2) severity of bowel obstruction/ileus, and (3) potential therapeutic benefit of GLP-1RA therapy. Risk differences (RDs) for discontinuation were estimated using multivariable linear regression with robust standard errors. RESULTS: GLP-1RAs were discontinued in 86 (43.9%) of the 196 patients analyzed. Multivariable analysis revealed that surgery for bowel obstruction during hospitalization (RD = 32.1%; 95% confidence interval [CI] 11.2% to 53.0%, p = 0.003), longer length of stay (>/=15 days vs. /= 65 with T2DM and BMI >/= 25 kg/m(2). Patients receiving semaglutide or tirzepatide were compared with those on dipeptidyl peptidase-4 (DPP-4) inhibitors using 1:1 propensity score matching. Primary and secondary outcomes were 1-year femoral fracture and falls, respectively. RESULTS: After matching, 27,896 patients were included in the semaglutide/DPP-4 comparison and 12,808 in the tirzepatide/DPP-4 comparison. Femoral fractures were significantly lower with semaglutide (0.3% vs. 0.5%; HR 0.488; 95% CI 0.367-0.649; P < 0.0001) and tirzepatide (0.2% vs. 0.4%; HR 0.452; 95% CI 0.280-0.729; P = 0.0008) compared with DPP-4 inhibitors. Fall risk was also reduced for both semaglutide (3.6% vs. 5.4%; HR 0.663; 95% CI 0.612-0.718; P < 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; 95% CI 0.591-0.747; P < 0.0001). Subgroup analyses showed consistent fall reduction across categories, while fracture reduction was more pronounced in patients with BMI >/= 30 kg/m(2). CONCLUSION: In older adults with T2DM and overweight/obesity, semaglutide and tirzepatide were associated with significantly lower risks of femoral fracture and falls compared with DPP-4 inhibitors, suggesting musculoskeletal benefits beyond glycemic control. CI - (c) 2026. The Author(s). FAU - Chen, Hsin-Yu AU - Chen HY AUID- ORCID: 0009-0007-0552-569X AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chu, Yi-Hsin AU - Chu YH AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chen, Tse-Wei AU - Chen TW AD - Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Huang, Chun-Feng AU - Huang CF AUID- ORCID: 0000-0002-6265-5155 AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. cfhuang.ymuh@gmail.com. AD - Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. cfhuang.ymuh@gmail.com. AD - Department of Leisure Services Management, Chaoyang University of Technology, Taichung, Taiwan. cfhuang.ymuh@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. cfhuang.ymuh@gmail.com. LA - eng GR - CMFHR115039/Chi Mei Medical Center/ PT - Comparative Study PT - Journal Article DEP - 20260711 PL - England TA - Osteoporos Int JT - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JID - 9100105 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Tirzepatide/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Male MH - Female MH - *Accidental Falls/prevention & control/statistics & numerical data MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use MH - Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Femoral Fractures/prevention & control/etiology/epidemiology MH - Overweight/complications MH - *Osteoporotic Fractures/prevention & control/etiology MH - Aged, 80 and over MH - Risk Assessment/methods PMC - PMC13710654 OTO - NOTNLM OT - femoral fracture OT - glucagon-like peptide-1 receptor agonist OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus COIS- Declarations. Conflicts of interest: Hsin-Yu Chen, Jheng-Yan Wu, Yi-Hsin Chu, Tse-Wei Chen and Chun-Feng Huang declare that they have no conflict of interest. EDAT- 2026/07/12 00:56 MHDA- 2026/10/26 17:31 PMCR- 2026/07/11 CRDT- 2026/07/11 11:03 PHST- 2026/04/18 00:00 [received] PHST- 2026/06/30 00:00 [accepted] PHST- 2026/10/26 17:31 [medline] PHST- 2026/07/12 00:56 [pubmed] PHST- 2026/07/11 11:03 [entrez] PHST- 2026/07/11 00:00 [pmc-release] AID - 10.1007/s00198-026-08134-y [pii] AID - 8134 [pii] AID - 10.1007/s00198-026-08134-y [doi] PST - ppublish SO - Osteoporos Int. 2026 Sep;37(9):2451-2463. doi: 10.1007/s00198-026-08134-y. Epub 2026 Jul 11. PMID- 42434976 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260813 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 31 IP - 8 DP - 2026 Jul 8 TI - GLP-1 receptor agonist use and overall survival among women with type 2 diabetes and breast cancer: a retrospective cohort study. LID - 10.1093/oncolo/oyag268 [doi] LID - oyag268 AB - BACKGROUND: Diabetes and obesity are associated with worse prognosis in women with breast cancer. However, the impact of glucagon-like peptide-1 receptor agonists (GLP-1RA) on survival following breast cancer diagnosis remains unclear. METHODS: We conducted a single institution, propensity-score matched, retrospective, 2-year landmark study of women with type 2 diabetes (T2D) diagnosed with breast cancer at City of Hope (2009-2025). Patients were categorized based on post-diagnosis exposure to GLP-1RA. Patients were compared across exposure groups using t-tests for continuous variables, chi-square tests for categorical variables, multivariable Cox proportional hazards models for overall mortality risk, and Kaplan-Meier plots for survival time. RESULTS: In 226 matched pairs, there were 47 deaths (30 in unexposed patients and 17 in exposed patients). GLP-1RA exposure was associated with a significantly lower risk of overall mortality (HR = 0.51, 95% CI 0.28-0.93, P = .03) on multivariable analysis. A sensitivity analysis in stage I-III patients yielded similar results (HR = 0.45, 95% CI 0.23-0.85, P = .01). Kaplan-Meier survival analysis also showed an association between increased overall survival and GLP-1RA exposure (log-rank P = .02). CONCLUSIONS: In this retrospective cohort of women with T2D and breast cancer, GLP-1RA use after diagnosis was associated with improved overall survival in T2D. These findings reflect all-cause mortality and do not distinguish between cancer-specific and non-cancer causes of death and should therefore be interpreted accordingly. CI - (c) The Author(s) 2026. Published by Oxford University Press. FAU - Nelson, Rebecca A AU - Nelson RA AUID- ORCID: 0000-0002-1678-6285 AD - Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA, 91010, United States. FAU - Lai, Ying-Chuen AU - Lai YC AUID- ORCID: 0000-0003-0377-8056 AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei City, 100229, Taiwan. AD - Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, 91010, United States. FAU - Kil, Sung H AU - Kil SH AUID- ORCID: 0000-0001-5152-6692 AD - Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, 91010, United States. FAU - Lee, Hayley S AU - Lee HS AD - Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, 91010, United States. FAU - Mortimer, Joanne AU - Mortimer J AUID- ORCID: 0000-0002-2935-1934 AD - Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, 91010, United States. FAU - Wang, Ping H AU - Wang PH AUID- ORCID: 0000-0002-7847-7752 AD - Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, 91010, United States. LA - eng GR - Ko Family Foundation, Allen and Lee Hwa Chao Research Fund, and Tseng Visiting Scholar Fellowship/ PT - Journal Article PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications/pathology MH - *Breast Neoplasms/mortality/drug therapy/pathology/complications MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Prognosis PMC - PMC13395082 OTO - NOTNLM OT - breast neoplasms OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - mortality COIS- J.M. is a consultant for GE Healthcare, Novartis, Bayer, and Astra Zeneca. She also is a recipient of research funding from Astra Zeneca. EDAT- 2026/07/12 00:56 MHDA- 2026/07/23 18:35 PMCR- 2026/07/11 CRDT- 2026/07/11 09:43 PHST- 2026/06/04 00:00 [received] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/07/23 18:35 [medline] PHST- 2026/07/12 00:56 [pubmed] PHST- 2026/07/11 09:43 [entrez] PHST- 2026/07/11 00:00 [pmc-release] AID - 8732540 [pii] AID - oyag268 [pii] AID - 10.1093/oncolo/oyag268 [doi] PST - ppublish SO - Oncologist. 2026 Jul 8;31(8):oyag268. doi: 10.1093/oncolo/oyag268. PMID- 42429319 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1326-5377 (Electronic) IS - 0025-729X (Print) IS - 0025-729X (Linking) VI - 224 IP - 7 DP - 2026 Jul TI - Weight Loss Medication Marketing and First Nations People: Disease Awareness or Corporate Profit? PG - e70246 LID - 10.5694/mja2.70246 [doi] LID - e70246 AB - The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has driven off-label prescriptions and supply shortages, raising equity concerns for First Nations peoples disproportionately affected by diabetes. Pharmaceutical companies have simultaneously accelerated their marketing through disease-awareness campaigns, sponsored events and telehealth models, with many campaigns prominently featuring women of colour, including First Nations women. In this perspective article, we argue, from a commercial determinants of health perspective, that pharmaceutical companies often influence perceptions of body image, medicines policy and prescribing without addressing the systemic conditions driving First Nations health inequity. We urge clinicians and policymakers to ensure decisions remain free from commercial influence. CI - (c) 2026 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd. FAU - Walker, Troy AU - Walker T AD - Institute for Health Transformation, Global Centre for Preventive Health and Nutrition, School of Health and Social Development, Faculty of Health Deakin University, Geelong, Victoria, Australia. FAU - Sherriff, Simone AU - Sherriff S AD - Poche Centre for Indigenous Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia. FAU - Browne, Jennifer AU - Browne J AD - Institute for Health Transformation, Global Centre for Preventive Health and Nutrition, School of Health and Social Development, Faculty of Health Deakin University, Geelong, Victoria, Australia. LA - eng GR - 2035274/National Health and Medical Research Council/ PT - Journal Article PL - Australia TA - Med J Aust JT - The Medical journal of Australia JID - 0400714 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Female MH - Humans MH - *Anti-Obesity Agents/therapeutic use MH - Australia MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Industry MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Marketing MH - Australian Aboriginal and Torres Strait Islander Peoples PMC - PMC13353042 OTO - NOTNLM OT - advertising as topic OT - pharmaceuticals OT - public health education OT - social media COIS- Not commissioned; externally peer-reviewed. The authors declare no conflicts of interest. EDAT- 2026/07/10 13:18 MHDA- 2026/07/11 01:09 PMCR- 2026/07/10 CRDT- 2026/07/10 08:33 PHST- 2026/06/02 00:00 [revised] PHST- 2026/04/02 00:00 [received] PHST- 2026/06/16 00:00 [accepted] PHST- 2026/07/11 01:09 [medline] PHST- 2026/07/10 13:18 [pubmed] PHST- 2026/07/10 08:33 [entrez] PHST- 2026/07/10 00:00 [pmc-release] AID - MJA270246 [pii] AID - 10.5694/mja2.70246 [doi] PST - ppublish SO - Med J Aust. 2026 Jul;224(7):e70246. doi: 10.5694/mja2.70246. PMID- 42426564 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261013 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Efficacy and Safety of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Ventricular Arrhythmias and Cardiovascular Events: A Disease-Stratified Network Meta-Analysis. PG - 9753-9766 LID - 10.1111/dom.71094 [doi] AB - BACKGROUND: The effects of individual sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) on ventricular arrhythmias (VAs) remain uncertain. This study aimed to comprehensively compare their effects on VAs and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and/or heart failure (HF). METHODS: Four databases were systematically searched from inception through May 16, 2026, to identify randomised controlled trials. Nine outcomes were evaluated, including VAs, cardiovascular mortality, all-cause mortality and hospitalization for heart failure (HHF). RESULTS: Thirty-seven publications, corresponding to 32 independent RCTs and 140 156 participants, were included. Most SGLT2 inhibitors and GLP-1 receptor agonists did not significantly increase VA risk; empagliflozin showed a statistically significant but exploratory signal for lower VA risk in the T2DM network (OR 0.31, 95% CI 0.11-0.86). Dapagliflozin in the HF network and empagliflozin and liraglutide in the T2DM network, were associated with lower cardiovascular and all-cause mortality. SGLT2 inhibitors consistently reduced HHF across both networks. Dapagliflozin was associated with lower AKI risk, while albiglutide and liraglutide were associated with lower hypoglycemia risk; however, these safety findings should be interpreted cautiously because adverse-event reporting was not uniform across trials. Several safety outcomes were based on sparse events and non-uniform adverse-event reporting; no statistically significant increase in diabetic ketoacidosis risk was detected for empagliflozin and the semaglutide fracture signal should be interpreted cautiously. Because the evidence networks were largely placebo-centered and lacked closed loops, treatment rankings and between-drug comparisons depend heavily on the transitivity assumption. These rankings, including P-score rankings, should be regarded as exploratory and should not be interpreted as head-to-head comparative evidence. CONCLUSIONS: SGLT2 inhibitors consistently reduced HHF risk across the HF and T2DM networks and selected agents showed mortality benefits in clinically relevant populations. Empagliflozin showed an exploratory signal for lower VA risk in the T2DM network; however, this finding requires confirmation in trials with prespecified and adjudicated arrhythmia endpoints. Safety signals, including DKA and fracture, should be interpreted cautiously because adverse-event ascertainment was not uniform across trials. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Sun, Wen-Ting AU - Sun WT AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Liu, Rui-Xing AU - Liu RX AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Jiang, Yao-Hao AU - Jiang YH AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Zhao, Ying-Kun AU - Zhao YK AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Yi-Cai AU - Yi-Cai AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Wu, Yi-Feng AU - Wu YF AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Tian-Li AU - Li TL AUID- ORCID: 0009-0006-6523-4694 AD - Department of Integrated Traditional Chinese and Western Medicine Cardiology, China-Japan Friendship Hospital, Beijing, China. FAU - Chang, Pei-Feng AU - Chang PF AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. LA - eng GR - 8240153568/National Natural Science Foundation of China/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucosides) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Heart Failure/mortality/drug therapy MH - *Arrhythmias, Cardiac/drug therapy MH - Benzhydryl Compounds/therapeutic use MH - Randomized Controlled Trials as Topic MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Semaglutide MH - Glucosides/therapeutic use OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) OT - heart failure OT - network meta-analysis OT - pairwise meta-analysis OT - sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) OT - type 2 diabetes mellitus OT - ventricular arrhythmias EDAT- 2026/07/10 00:36 MHDA- 2026/10/08 05:31 CRDT- 2026/07/09 23:42 PHST- 2026/06/21 00:00 [revised] PHST- 2026/05/19 00:00 [received] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/07/10 00:36 [pubmed] PHST- 2026/07/09 23:42 [entrez] AID - 10.1111/dom.71094 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):9753-9766. doi: 10.1111/dom.71094. Epub 2026 Jul 9. PMID- 42426287 OWN - NLM STAT- MEDLINE DCOM- 20260724 LR - 20260724 IS - 2522-5812 (Electronic) IS - 2522-5812 (Linking) VI - 8 IP - 7 DP - 2026 Jul TI - Association of GLP-1RA discontinuation and risk of depressive and anxiety disorders in people with type 2 diabetes: a cohort study. PG - 1489-1494 LID - 10.1038/s42255-026-01567-z [doi] AB - The psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is characterized by inconsistent findings during active treatment and remains largely unexplored after cessation. Here we show that GLP-1RA discontinuation is associated with an increased risk of psychiatric events. Using large-scale electronic health records from the Shanghai Hospital Link Database, we investigate incident depressive and anxiety disorders during GLP-1RA treatment and after its discontinuation in people with type 2 diabetes, compared with dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium-glucose cotransporter-2 inhibitors (SGLT2is). During treatment, GLP-1RAs show a neutral risk compared with DPP4is and a lower risk compared with SGLT2is. In contrast, after cessation, prior use of GLP-1RAs is associated with a higher risk than prior use of DPP4is or SGLT2is. This increase is modestly mediated by elevated triglyceride levels. These findings highlight the need for clinical vigilance regarding anxiety following GLP-1RA discontinuation. CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Zhang, Tingyu AU - Zhang T AUID- ORCID: 0009-0004-4678-5197 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - He, Ping AU - He P AD - Link Healthcare Engineering and Information Department, Shanghai Hospital Development Center, Shanghai, China. FAU - Ji, Yunxi AU - Ji Y AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Juan AU - Shi J AUID- ORCID: 0000-0003-2652-8084 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhang, Zizheng AU - Zhang Z AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Kan AU - Wang K AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Pan, Haolei AU - Pan H AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Yao, Huayan AU - Yao H AD - Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xue, Yanbin AU - Xue Y AD - Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zheng, Ruizhi AU - Zheng R AUID- ORCID: 0000-0002-2068-7597 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wu, Qingxia AU - Wu Q AD - Wonders Information Co., Ltd., Shanghai, China. FAU - Cui, Bin AU - Cui B AUID- ORCID: 0000-0002-7293-5740 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. cb11302@rjh.com.cn. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. cb11302@rjh.com.cn. FAU - Zhang, Yifei AU - Zhang Y AUID- ORCID: 0000-0003-0272-0602 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. feifei-a@163.com. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. feifei-a@163.com. FAU - Wang, Weiqing AU - Wang W AUID- ORCID: 0000-0003-0197-3106 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wqingw61@163.com. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wqingw61@163.com. FAU - Ning, Guang AU - Ning G AUID- ORCID: 0000-0002-5754-7635 AD - Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gning@sibs.ac.cn. AD - Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gning@sibs.ac.cn. LA - eng PT - Journal Article DEP - 20260709 PL - Germany TA - Nat Metab JT - Nature metabolism JID - 101736592 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Anxiety Disorders/epidemiology/etiology/chemically induced MH - Female MH - Male MH - Cohort Studies MH - *Depressive Disorder/epidemiology/etiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/07/10 00:35 MHDA- 2026/07/25 00:35 CRDT- 2026/07/09 23:34 PHST- 2025/09/22 00:00 [received] PHST- 2026/06/11 00:00 [accepted] PHST- 2026/07/25 00:35 [medline] PHST- 2026/07/10 00:35 [pubmed] PHST- 2026/07/09 23:34 [entrez] AID - 10.1038/s42255-026-01567-z [pii] AID - 10.1038/s42255-026-01567-z [doi] PST - ppublish SO - Nat Metab. 2026 Jul;8(7):1489-1494. doi: 10.1038/s42255-026-01567-z. Epub 2026 Jul 9. PMID- 42424036 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 54 IP - 7 DP - 2026 Jul TI - Effect of glucagon-like peptide-1 receptor agonists on body weight and urinary albumin-to-creatinine ratio in patients with and without type 2 diabetes: A systematic review and meta-analysis. PG - 3000605261458641 LID - 10.1177/03000605261458641 [doi] LID - 03000605261458641 AB - ObjectiveGlucagon-like peptide-1 receptor agonists are established for weight management and cardiovascular risk reduction, with emerging evidence for kidney protection. Whether albuminuria-lowering effects extend to nondiabetic chronic kidney disease remains uncertain.MethodsWe performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided meta-analysis of randomized controlled trials comparing glucagon-like peptide-1 receptor agonists with placebo or standard care. Primary outcomes were change in body weight (kg) and percentage change in urinary albumin-to-creatinine ratio; change in estimated glomerular filtration rate was the secondary outcome. We conducted prespecified subgroup analyses (including glycemic status) and random-effects meta-regression to explore heterogeneity. Risk of bias assessment (2.0), small-study effects (funnel plot and trim-and-fill analyses), sensitivity analyses (leave-one-out and low-risk-only), and Grading of Recommendations Assessment, Development and Evaluation certainty ratings were applied.ResultsTen trials (n = 26,088) were included. Glucagon-like peptide-1 receptor agonists reduced body weight (mean difference, -5.85 kg; 95% confidence interval: -7.78 to -3.92) with a consistent direction of effect across studies despite heterogeneity. Glucagon-like peptide-1 receptor agonists lowered urinary albumin-to-creatinine ratio overall (mean difference, -27.94%; 95% confidence interval: -37.72 to -18.15). Stratified analyses showed a precise reduction in type 2 diabetes mellitus (mean difference, -25.70%; I(2) = 0%) and a directionally concordant but less precise reduction in populations without type 2 diabetes mellitus (mean difference, -30.93%; I(2) = 96%). A modest between-group difference in estimated glomerular filtration rate was also observed (mean difference, -0.82 mL/min/1.73 m(2); I(2) = 0%). Meta-regression indicated attenuation with longer treatment duration and greater benefit with higher baseline albuminuria; drug class and glycemic status were not consistent moderators of urinary albumin-to-creatinine ratio in prespecified subgroups. Findings were robust to multiple sensitivity analyses. Certainty of evidence was high for weight and moderate for urinary albumin-to-creatinine ratio.ConclusionsGlucagon-like peptide-1 receptor agonists were associated with clinically meaningful weight loss and lower urinary albumin-to-creatinine ratio across included trials. A directionally similar signal was observed in populations without type 2 diabetes mellitus, although interpretation of this subgroup remains limited by heterogeneity, imprecision, and the inability to evaluate intermediate glycemic phenotypes. Variability in urinary albumin-to-creatinine ratio estimates appears to reflect duration and baseline risk more than a lack of effect. FAU - Huang, Rong AU - Huang R AD - Public Health Management Department, Chengdu Qingbaijiang District People's Hospital, Chengdu, China. RINGGOLD: 663923 FAU - Wang, Bin AU - Wang B AUID- ORCID: 0009-0004-2797-5710 AD - Quality Control Department, Chengdu Qingbaijiang District Center for Disease Control and Prevention, Chengdu, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260709 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - AYI8EX34EU (Creatinine) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/urine/physiopathology MH - *Albuminuria/drug therapy/urine MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Creatinine/urine MH - *Body Weight/drug effects MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC13351244 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - albuminuria OT - chronic kidney disease OT - exenatide OT - meta-analysis OT - semaglutide OT - urinary albumin-to-creatinine ratio COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/07/09 12:32 MHDA- 2026/07/09 12:33 PMCR- 2026/07/09 CRDT- 2026/07/09 11:23 PHST- 2026/07/09 12:33 [medline] PHST- 2026/07/09 12:32 [pubmed] PHST- 2026/07/09 11:23 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 10.1177_03000605261458641 [pii] AID - 10.1177/03000605261458641 [doi] PST - ppublish SO - J Int Med Res. 2026 Jul;54(7):3000605261458641. doi: 10.1177/03000605261458641. Epub 2026 Jul 9. PMID- 42423951 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261001 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 10 DP - 2026 Oct TI - Special Considerations When Using GLP-1 Receptor Agonists in the Treatment of Obesity and Diabetes Mellitus Type 2 in Older Adults. PG - 4380-4394 LID - 10.1007/s12325-026-03702-4 [doi] AB - The prevalence of obesity and type 2 diabetes mellitus (T2DM) in the older adult population is rising continuously worldwide, with approximately 40% and 29% of individuals affected in this group, respectively. These conditions have a substantial impact on older adults and are associated with reduced quality of life, increased morbidity, functional decline, and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an important option for the management of T2DM and obesity. However, special considerations are needed for specific age groups due to risks of adverse effects and increased comorbidity burden. GLP-1 RAs, including tirzepatide, liraglutide, and semaglutide, promote weight loss by suppressing appetite, improving insulin secretion, and delaying gastric emptying. Large clinical trials have supported GLP-1 RAs as an excellent option for reducing glycated hemoglobin and body weight, as well as for reducing major renal and cardiovascular adverse effects; however, evidence in older adults remains limited. Given the health considerations for older adults, weight loss efforts with GLP-1 RAs require cautious approaches, as sarcopenia is a relevant topic in this specific age group. Polypharmacy and side effects also need to be considered when treating an older adult with GLP-1 RA. Overall, GLP-1 RAs represent a valuable and promising treatment option for older adults with T2DM and obesity. CI - (c) 2026. The Author(s). FAU - Pendrey, Anna Geraldina AU - Pendrey AG AUID- ORCID: 0009-0002-0114-1342 AD - Department of Family Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. apendrey@iu.edu. FAU - Rivera Sierra, Jennyfer Alejandra AU - Rivera Sierra JA AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Alvarez Lobo, Fernando Alberto AU - Alvarez Lobo FA AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Rios Herrera, Eblin Jackeline AU - Rios Herrera EJ AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Fernandez Munoz, Yolanda Maria AU - Fernandez Munoz YM AD - Distrito Central, Universidad Catolica de Honduras, Francisco Morazan, Honduras. FAU - Sevilla Martir, Javier Francisco AU - Sevilla Martir JF AD - Department of Family Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. LA - eng PT - Journal Article PT - Review DEP - 20260709 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Obesity/drug therapy MH - Tirzepatide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Liraglutide/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - Weight Loss/drug effects PMC - PMC13619721 OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Older adults COIS- Declarations. Conflict of Interest: Anna Geraldina Pendrey, Javier Francisco Sevilla Martir, Jennyfer Alejandra Rivera Sierra, Fernando Alberto Alvarez Lobo, Eblin Jackeline Rios Herrera, and Yolanda Maria Fernandez Munoz declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2026/07/09 16:09 MHDA- 2026/09/29 05:30 PMCR- 2026/07/09 CRDT- 2026/07/09 11:10 PHST- 2026/03/17 00:00 [received] PHST- 2026/06/22 00:00 [accepted] PHST- 2026/09/29 05:30 [medline] PHST- 2026/07/09 16:09 [pubmed] PHST- 2026/07/09 11:10 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 10.1007/s12325-026-03702-4 [pii] AID - 3702 [pii] AID - 10.1007/s12325-026-03702-4 [doi] PST - ppublish SO - Adv Ther. 2026 Oct;43(10):4380-4394. doi: 10.1007/s12325-026-03702-4. Epub 2026 Jul 9. PMID- 42423950 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261001 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 10 DP - 2026 Oct TI - Beyond Single-Class Therapy: Real-World Combined Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes and Atherosclerotic Cardiovascular Disease. PG - 4968-4979 LID - 10.1007/s12325-026-03699-w [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) exert complementary metabolic effects and have independently demonstrated cardiovascular benefits in individuals with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD). However, despite growing evidence suggesting potential additive benefits in high-risk populations, real-world data on dual therapy remain limited. This study aimed to identify clinical factors associated with the use of combined GLP-1RA/SGLT2i therapy in routine practice. METHODS: This retrospective observational study included 202 adults with T2DM and established ASCVD admitted to a tertiary care hospital between November and December 2025. Patients were categorized according to their pre-admission outpatient regimen into four groups: neither therapy, GLP-1RA only, SGLT2i only, and combined therapy. Clinical characteristics and comorbidities were recorded at admission. Multinomial logistic regression analysis was performed to identify factors associated with treatment allocation. RESULTS: Among 202 patients, 54.5% were not receiving either class, 10.9% were treated with GLP-1RA only, 21.3% with SGLT2i only, and 13.4% with both. In adjusted analyses, combined therapy was independently associated with younger age [odds ratio (OR) 0.89 per year, 95% confidence interval (CI) 0.84-0.95, p < 0.001], presence of heart failure (OR 9.64, 95% CI 2.65-35.04, p < 0.001), and insulin use (OR 10.99, 95% CI 3.12-38.72, p < 0.001). Chronic kidney disease and polyvascular disease were not associated with dual therapy use. CONCLUSION: In this real-world cohort of patients with T2DM and ASCVD, more than half were not receiving a cardioprotective glucose-lowering therapy. Combined GLP-1RA/SGLT2i therapy was infrequently prescribed and was associated with selected clinical characteristics rather than overall cardiorenal risk burden. These findings highlight an opportunity to better align treatment strategies with a comprehensive risk-based approach. CI - (c) 2026. The Author(s). FAU - Vournas, Georgios AU - Vournas G AD - Medical School, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece. FAU - Sarvani, Anastasia AU - Sarvani A AD - Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, 49 Konstantinoupoleos Str., 54642, Thessaloniki, Greece. FAU - Mavridou, Maria AU - Mavridou M AD - Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, 49 Konstantinoupoleos Str., 54642, Thessaloniki, Greece. FAU - Tentolouris, Anastasios AU - Tentolouris A AD - First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527, Athens, Greece. FAU - Doumas, Michael AU - Doumas M AD - Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, 49 Konstantinoupoleos Str., 54642, Thessaloniki, Greece. FAU - Liberopoulos, Evangelos N AU - Liberopoulos EN AD - First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527, Athens, Greece. FAU - Kotsa, Kalliopi AU - Kotsa K AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, 49 Konstantinoupoleos Str., 54642, Thessaloniki, Greece. thkoyfak@auth.gr. LA - eng PT - Journal Article PT - Observational Study DEP - 20260709 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Atherosclerosis/drug therapy/complications MH - Aged MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13619674 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Combination therapy OT - Glucagon-like peptide-1 receptor agonists OT - Real-world evidence OT - Sodium-glucose cotransporter-2 inhibitors OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of Interest: Theocharis Koufakis has received honoraria for lectures/advisory boards and research support from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi, Roche Diagnostics, ELPEN, Krka, Menarini, and Novo Nordisk. Theocharis Koufakis is an Editorial Board member of Advances in Therapy. Theocharis Koufakis was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Evangelos N. Liberopoulos has participated in educational, research, and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer Ingelheim, Novartis, Novo Nordisk, and Servier. Kalliopi Kotsa has received honoraria for lectures/advisory boards and research support from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi-Aventis, ELPEN, MSD, and Novo Nordisk. Georgios Vournas has nothing to disclose. Anastasia Sarvani has nothing to disclose. Maria Mavridou has nothing to disclose. Anastasios Tentolouris has nothing to disclose. Michael Doumas has nothing to disclose. Ethical Approval: The study was performed in accordance with the principles of the Declaration of Helsinki. Ethics approval for retrospective data collection and analysis was obtained from the Bioethics Committee of the Aristotle University of Thessaloniki (approval code: 26; approval date: 11 November 2025). Patient data were anonymized prior to analysis, with removal of all direct patient identifiers and replacement by non-traceable study codes accessible only to the investigators involved in data collection. In accordance with local institutional requirements and national practice in Greece for retrospective clinical data analyses, all patients provided written informed consent at the time of hospital discharge for the use of their anonymized data for research purposes. No interventions or treatment decisions were influenced by study participation. As this was a retrospective observational study based exclusively on anonymized routinely collected clinical data without prospective intervention or protocol-driven treatment allocation, formal registration on a clinical trial platform was not required. EDAT- 2026/07/09 16:09 MHDA- 2026/09/29 05:30 PMCR- 2026/07/09 CRDT- 2026/07/09 11:10 PHST- 2026/04/17 00:00 [received] PHST- 2026/06/19 00:00 [accepted] PHST- 2026/09/29 05:30 [medline] PHST- 2026/07/09 16:09 [pubmed] PHST- 2026/07/09 11:10 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 10.1007/s12325-026-03699-w [pii] AID - 3699 [pii] AID - 10.1007/s12325-026-03699-w [doi] PST - ppublish SO - Adv Ther. 2026 Oct;43(10):4968-4979. doi: 10.1007/s12325-026-03699-w. Epub 2026 Jul 9. PMID- 42423377 OWN - NLM STAT- MEDLINE DCOM- 20260818 LR - 20260820 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 100 IP - 8 DP - 2026 Aug 18 TI - Glucagon-like peptide-1 receptor agonist prevents pulmonary fibrosis following acute COVID-19 infection associated with type 2 diabetes. PG - e0040126 LID - 10.1128/jvi.00401-26 [doi] LID - e00401-26 AB - Post-acute sequelae of COVID-19 (PASC) poses a major health burden after SARS-CoV-2 infection. Although type 2 diabetes (T2D) is associated with PASC, the mechanism of T2D-mediated PASC in the lung remains elusive. Here, we found that people with T2D (PWT2D) exhibited significantly upregulated fibrosis-related genes in monocytes, which positively correlated with pulmonary fibrosis-related biomarkers up to 3 months after acute SARS-CoV-2 infection. Using db/db mice to model human T2D, we found consistently that SARS-CoV-2 infection resulted in upregulation of fibrosis-related genes in lung macrophages and persistent pulmonary fibrosis. Moreover, the macrophage-depletion demonstrated that pro-inflammatory macrophages in db/db mice were determinants for inducing pulmonary fibrosis post-infection. Importantly, the anti-T2D glucagon-like peptide-1 receptor agonist (GLP1-RA) reprogramed macrophage responses to SARS-CoV-2 by normalizing fibrosis-related genes, significantly reducing the pulmonary fibrosis in a glucose-independent manner. These findings demonstrated that SARS-CoV-2-induced proinflammatory macrophages are detrimental factors in T2D-mediated PASC, which can be prevented by GLP1-RA. IMPORTANCE: Some COVID-19 patients develop pulmonary post-acute sequelae of COVID-19 (PASC) with clinical symptoms lasting for years. Critically, the incidence of pulmonary PASC in PWT2D is four times higher than that in those without T2D. However, the immune mechanisms underlying pulmonary PASC in PWT2D remain poorly understood. Our findings demonstrate that SARS-CoV-2-induced proinflammatory macrophages are key drivers of PASC-associated pulmonary fibrosis. We further provide in vivo evidence that glucagon-like peptide-1 receptor agonists (GLP1-RAs) can reprogram pulmonary macrophages to prevent SARS-CoV-2-induced PASC in a T2D mouse model, with important implications for therapy in PWT2D. FAU - Zhou, Runhong AU - Zhou R AUID- ORCID: 0000-0001-6642-6029 AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. AD - Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China. RINGGOLD: 444333. ROR: https://ror.org/02zhqgq86 FAU - Yue, Ming AU - Yue M AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. FAU - Shen, Qing AU - Shen Q AD - State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Liu, Na AU - Liu N AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China. RINGGOLD: 444333. ROR: https://ror.org/02zhqgq86 FAU - Chen, Yuting AU - Chen Y AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Wang, Pui AU - Wang P AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Kim, Kyungmin AU - Kim K AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Yang, Ranyao AU - Yang R AD - State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Chen, Honglin AU - Chen H AUID- ORCID: 0000-0001-5108-8338 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. AD - State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Pandemic Research Alliance Unit at The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. ROR: https://ror.org/02zhqgq86 FAU - Yuen, Kwok-Yung AU - Yuen K-Y AUID- ORCID: 0000-0001-8700-4570 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. AD - Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China. RINGGOLD: 444333. ROR: https://ror.org/02zhqgq86 AD - State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Pandemic Research Alliance Unit at The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. ROR: https://ror.org/02zhqgq86 FAU - To, Kelvin Kai-Wang AU - To KK-W AUID- ORCID: 0000-0002-1921-5824 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. AD - Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China. RINGGOLD: 444333. ROR: https://ror.org/02zhqgq86 AD - State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Pandemic Research Alliance Unit at The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. ROR: https://ror.org/02zhqgq86 FAU - Xu, Aimin AU - Xu A AD - State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 FAU - Chen, Zhiwei AU - Chen Z AUID- ORCID: 0000-0002-4511-2888 AD - AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China. AD - Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China. RINGGOLD: 444333. ROR: https://ror.org/02zhqgq86 AD - State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. RINGGOLD: 25809. ROR: https://ror.org/02zhqgq86 AD - Pandemic Research Alliance Unit at The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. ROR: https://ror.org/02zhqgq86 LA - eng GR - Health@InnoHK to CVVT/ GR - T11-702/24-N and T12-703/23-N/Hong Kong Theme Based Research Scheme/ GR - P86433/WT_/Wellcome Trust/United Kingdom GR - EKPG22-01/Emergency Key Program Guangzhou Laboratory/ GR - 2025ZD01904502 and 2025ZD01900701/National Key Research and Development Program of China/ GR - C7156-20G and C1134-20G/Hong Kong Research Grants Council Collaborative Research Fund/ GR - WT_/Wellcome Trust/United Kingdom GR - 25240582/Health and Medical Research Fund/ PT - Journal Article DEP - 20260709 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *COVID-19/complications/virology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Pulmonary Fibrosis/prevention & control/etiology/pathology MH - Mice MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - SARS-CoV-2 MH - Macrophages/metabolism MH - Post-Acute COVID-19 Syndrome MH - Mice, Inbred C57BL MH - Lung/pathology MH - Disease Models, Animal MH - Female PMC - PMC13483299 OTO - NOTNLM OT - SARS-CoV-2 OT - glucagon-like peptide-1 receptor agonist OT - post-acute sequelae of COVID-19 OT - proinflammatory macrophages OT - pulmonary fibrosis OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2026/07/09 12:32 MHDA- 2026/08/18 12:58 PMCR- 2026/07/09 CRDT- 2026/07/09 09:03 PHST- 2026/08/18 12:58 [medline] PHST- 2026/07/09 12:32 [pubmed] PHST- 2026/07/09 09:03 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - jvi00401-26 [pii] AID - jvi.00401-26 [pii] AID - 10.1128/jvi.00401-26 [doi] PST - ppublish SO - J Virol. 2026 Aug 18;100(8):e0040126. doi: 10.1128/jvi.00401-26. Epub 2026 Jul 9. PMID- 42420805 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 23 IP - 4 DP - 2026 Jul-Aug TI - Comparative effectiveness of tirzepatide and DPP-4 inhibitors in type 2 diabetes with heart failure. PG - 14791641261467888 LID - 10.1177/14791641261467888 [doi] LID - 14791641261467888 AB - While patients with type 2 diabetes mellitus (T2DM) and heart failure (HF) are frequently prescribed dipeptidyl peptidase-4 inhibitors (DPP-4is), emerging evidence suggests glucagon-like peptide-1 receptor agonists may offer improved outcomes. This study compared the effectiveness of tirzepatide versus DPP-4i in patients with T2DM and HF. Adults with T2DM and HF treated between 2022 and 2025 were included. Cohort A comprised patients receiving tirzepatide, and Cohort B comprised patients receiving DPP-4is. Prespecified subgroup analyses were conducted for HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnonrEF). Propensity score matching was performed across demographic, clinical, medication, and laboratory covariates. Outcomes included all-cause mortality, hospitalization, HF exacerbation, and major adverse cardiovascular events (MACE). After matching, 8,956 patients were included in each group. Tirzepatide therapy was associated with a lower hazard of all-cause mortality (HR 0.32, 95% CI 0.25-0.42), hospitalizations (HR 0.53, 95% CI 0.48-0.57), HF exacerbation (HR 0.37, 95% CI 0.33-0.42) and MACE (HR 0.79, 95% CI 0.73-0.84). Sub-group analyses for HFrEF and HFnonrEF demonstrated similar trends. In conclusion, among patients with T2DM and HF, treatment with tirzepatide was associated with markedly lower hazards of mortality, hospitalization, HF exacerbation, and MACE compared to DPP-4 inhibitors. FAU - Mortada, Ibrahim AU - Mortada I AUID- ORCID: 0009-0006-9215-880X AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Paul, Krishna AU - Paul K AD - Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Chammany, Michael AU - Chammany M AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Abraham, Youstina AU - Abraham Y AUID- ORCID: 0009-0002-0942-3643 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Devulapally, Karthik AU - Devulapally K AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Lee, Aaron W AU - Lee AW AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Mansour, Shareef AU - Mansour S AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Chatila, Khaled AU - Chatila K AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Boyars, Michael C AU - Boyars MC AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jehle, Dietrich AU - Jehle D AD - Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Blackwell, Thomas A AU - Blackwell TA AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jneid, Hani AU - Jneid H AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260708 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Heart Failure/mortality/drug therapy/physiopathology/diagnosis MH - Female MH - Treatment Outcome MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - Middle Aged MH - Time Factors MH - *Incretins/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Assessment MH - Stroke Volume/drug effects MH - Retrospective Studies PMC - PMC13346706 OTO - NOTNLM OT - cardiology OT - diabetes mellitus OT - dipeptidyl peptidase-4 inhibitors OT - heart failure OT - tirzepatide COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/07/09 06:32 MHDA- 2026/07/09 06:33 PMCR- 2026/07/08 CRDT- 2026/07/09 00:03 PHST- 2026/07/09 06:33 [medline] PHST- 2026/07/09 06:32 [pubmed] PHST- 2026/07/09 00:03 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - 10.1177_14791641261467888 [pii] AID - 10.1177/14791641261467888 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2026 Jul-Aug;23(4):14791641261467888. doi: 10.1177/14791641261467888. Epub 2026 Jul 8. PMID- 42420795 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP-1 Receptor Agonists. PG - 8895-8904 LID - 10.1111/dom.71088 [doi] AB - AIMS: Neuropsychiatric safety concerns, including depression and suicidal ideation, have emerged during the expanding clinical use of incretin-based therapies for type 2 diabetes mellitus (T2DM) and obesity. However, whether risks differ across successive generations of incretin-based therapies remains uncertain. MATERIALS AND METHODS: This retrospective cohort study used the TriNetX Global Federated Network (> 192 million patients). Adults with T2DM, obesity, or both initiating tirzepatide, semaglutide, or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) between July 2022 and June 2025 were identified using a new-user design with a 12-month washout. Propensity score matching balanced demographic, clinical, and metabolic variables. Two comparisons were conducted: tirzepatide versus semaglutide and semaglutide versus other GLP-1 RAs. Follow-up included Year 1 (day 31-365) and Year 2 landmark analysis (day 366-730). Hazard ratios (HRs) for incident depression, anxiety, and suicidal ideation were estimated using Cox models. RESULTS: After matching, 85 546 pairs were included for tirzepatide versus semaglutide and 80 115 pairs for semaglutide versus other GLP-1 RAs. Tirzepatide and semaglutide showed similar risks for the composite psychiatric outcome (Year 1 HR 0.984 [95% CI 0.950-1.019]; Year 2 HR 1.002 [0.960-1.046]); a nominally higher anxiety hazard was observed with tirzepatide during Year 2 (HR 1.052 [1.001-1.106]), which should be interpreted cautiously given multiple comparisons. Compared with other GLP-1 RAs, semaglutide was associated with lower risks of depression (HR 0.811 [0.770-0.855]), anxiety (HR 0.915 [0.871-0.961]), suicidal ideation (HR 0.488 [0.339-0.702]), and the composite psychiatric outcome (HR 0.866 [0.832-0.901]) during Year 1. CONCLUSIONS: In real-world practice, tirzepatide and semaglutide demonstrated comparable neuropsychiatric risk profiles over 2 years. Semaglutide was associated with lower psychiatric event rates compared with earlier-generation GLP-1 receptor agonists. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Chen, Solomon Chih-Cheng AU - Chen SC AUID- ORCID: 0000-0003-0031-6147 AD - Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. AD - Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Wang, Tso-Jen AU - Wang TJ AD - Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City, Taiwan. FAU - Chou, Chu-Kuang AU - Chou CK AUID- ORCID: 0000-0003-2588-6883 AD - Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. AD - Obesity Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. FAU - Lee, Chun AU - Lee C AD - Clinical Data Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. LA - eng PT - Journal Article DEP - 20260708 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use/adverse effects MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Retrospective Studies MH - Middle Aged MH - Depression/epidemiology/chemically induced MH - Suicidal Ideation MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/drug therapy/psychology MH - Anxiety/epidemiology/chemically induced MH - Adult MH - Aged MH - Incretins/adverse effects/therapeutic use PMC - PMC13538802 OTO - NOTNLM OT - cohort studies OT - comparative effectiveness research OT - depressive disorder OT - glucagon-like peptide-1 receptor agonists OT - postmarketing surveillance OT - real-world evidence OT - suicidal ideation COIS- Gemini 3.1 Pro (Google LLC) was utilized solely for language polishing, grammatical correction, and enhancing the clarity and flow of the manuscript's English text. The AI tool was not used to generate original research ideas, interpret data, perform statistical analysis, or draft the initial scientific content of the paper. All research findings and the final version of the text were reviewed and approved by the authors, who remain fully responsible for the accuracy and integrity of the work. The authors declare no conflicts of interest. EDAT- 2026/07/09 00:40 MHDA- 2026/09/03 05:36 PMCR- 2026/09/03 CRDT- 2026/07/08 23:53 PHST- 2026/06/27 00:00 [revised] PHST- 2026/05/03 00:00 [received] PHST- 2026/06/30 00:00 [accepted] PHST- 2026/09/03 05:36 [medline] PHST- 2026/07/09 00:40 [pubmed] PHST- 2026/07/08 23:53 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71088 [pii] AID - 10.1111/dom.71088 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8895-8904. doi: 10.1111/dom.71088. Epub 2026 Jul 8. PMID- 42419304 OWN - NLM STAT- MEDLINE DCOM- 20260917 LR - 20260930 IS - 2451-9448 (Electronic) IS - 2451-9448 (Linking) VI - 33 IP - 9 DP - 2026 Sep 17 TI - GLP-1R and GIPR crosstalk modulates insulinotropic signaling pathways. PG - 1284-1299.e8 LID - S2451-9456(26)00201-1 [pii] LID - 10.1016/j.chembiol.2026.06.003 [doi] AB - Drugs targeting glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors (GLP-1R and GIPR) show strong clinical effects in type 2 diabetes and obesity. Both GIPR agonism and antagonism enhance GLP-1R agonist efficacy, indicating important incretin receptor crosstalk. We show that GLP-1 and semaglutide, but not exendin-4, promote heterodimerization between GLP-1R and GIPR through interactions between TM4 of GLP-1R and TM1/2 of GIPR. Phosphoproteomics and molecular dynamics reveal that dimerizing and non-dimerizing agonists differentially influence GLP-1R, activating divergent signaling pathways in human pancreatic islets. Moreover, semaglutide and exenatide display distinct patterns in their FDA-reported safety profiles. When co-expressed, GLP-1R enhances GIPR signaling in a beta-arrestin-dependent manner, while increasing GIPR levels decreases GLP-1R signaling. Additionally, we show that changes in GIPR expression are clinically associated with adiposity and diabetic phenotypes. These findings highlight heterodimerization and receptor expression as key modulators of GLP-1R/GIPR signaling, offering mechanistic insights, and guiding drug design strategies that incorporate receptor crosstalk. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Lindquist, Peter AU - Lindquist P AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Hoegen Dijkhof, Luuk R AU - Hoegen Dijkhof LR AD - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. FAU - Drzazga, Anna K AU - Drzazga AK AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz, Poland. FAU - Sabatier, Pierre AU - Sabatier P AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark; Cardio-Thoracic Translational Medicine Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. FAU - Stepniewski, Tomasz M AU - Stepniewski TM AD - Research Programme on Biomedical Informatics, Hospital del Mar Research Institute & Pompeu Fabra University, Barcelona, Spain; InterAx Biotech AG, Villigen, Switzerland. FAU - Granlund, Louise AU - Granlund L AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. FAU - Lechner, Maico Y AU - Lechner MY AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark. FAU - Zhong, Yi AU - Zhong Y AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Gasbjerg, Laerke S AU - Gasbjerg LS AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Lauschke, Volker M AU - Lauschke VM AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tubingen, Tubingen, Germany; Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Olsen, Jesper V AU - Olsen JV AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark. FAU - Korsgren, Olle AU - Korsgren O AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. FAU - Selent, Jana AU - Selent J AD - Research Programme on Biomedical Informatics, Hospital del Mar Research Institute & Pompeu Fabra University, Barcelona, Spain. FAU - Wright, Shane C AU - Wright SC AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden. FAU - Hauser, Alexander S AU - Hauser AS AD - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Center for Pharmaceutical Data Science Education, University of Copenhagen, Copenhagen, Denmark. FAU - Rosenkilde, Mette M AU - Rosenkilde MM AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: rosenkilde@sund.ku.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260708 PL - United States TA - Cell Chem Biol JT - Cell chemical biology JID - 101676030 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry/genetics MH - *Signal Transduction/drug effects MH - *Receptors, Gastrointestinal Hormone/metabolism/chemistry/genetics/agonists MH - Semaglutide MH - Animals MH - Glucagon-Like Peptides/pharmacology/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/metabolism MH - HEK293 Cells MH - Exenatide/pharmacology MH - Receptor Cross-Talk OTO - NOTNLM OT - GIPR OT - GLP-1R OT - GPCR OT - adverse drug events OT - crosstalk OT - heterodimerization OT - obesity OT - stoichiometry OT - type 2 diabetes COIS- Declaration of interests The authors declare that the study was conducted without any competing interests. T.M.: employed by InterAx Biotech A.G. L.S.G.: received one speaker honorarium from Novo Nordisk and is a co-founder and minority shareholder of Antag Therapeutics. V.M.L.: cofounder and CEO of HepaPredict A.B., cofounder and shareholder of Shanghai Hepo Biotechnology Ltd. J.J.H. and M.M.R. minority shareholders and cofounders of Antag Therapeutics and Bainan Biotech. J.J.H.: served on scientific advisory panels for and/or has received speaker honoraria from AlphaSights, Eli Lilly, Novo Nordisk, MSD/Merck, Shouti/Structure X, and Zealand Pharma. EDAT- 2026/07/09 04:10 MHDA- 2026/09/17 23:34 CRDT- 2026/07/08 18:41 PHST- 2025/08/08 00:00 [received] PHST- 2026/02/19 00:00 [revised] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/09/17 23:34 [medline] PHST- 2026/07/09 04:10 [pubmed] PHST- 2026/07/08 18:41 [entrez] AID - S2451-9456(26)00201-1 [pii] AID - 10.1016/j.chembiol.2026.06.003 [doi] PST - ppublish SO - Cell Chem Biol. 2026 Sep 17;33(9):1284-1299.e8. doi: 10.1016/j.chembiol.2026.06.003. Epub 2026 Jul 8. PMID- 42418075 OWN - NLM STAT- MEDLINE DCOM- 20260919 LR - 20260920 IS - 1573-2568 (Electronic) IS - 0163-2116 (Print) IS - 0163-2116 (Linking) VI - 71 IP - 11 DP - 2026 Nov TI - Incidence of Gastrointestinal Adverse Events and Healthcare Resource Utilization in Patients Using Glucagon-Like Peptide-1 Analogs: A Real-World Study. PG - 5405-5415 LID - 10.1007/s10620-026-10112-7 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1) are widely prescribed for diabetes mellitus (DM) and obesity. Growing concerns about gastrointestinal side effects (GI-AE) prompted this real-world study, to assess the incidence of GI-AEs and the associated healthcare burden in patients on GLP-1 s. METHODS: Using the TriNetX(R) network with 120 million patient records, patients with DM and obesity were grouped into GLP-1 and control cohorts. Propensity score matching (1:1) was performed using demographics, comorbidities, Hemoglobin-A1c, BMI, and other confounders. Incidence, number needed to harm (NNH), and Cox-proportional hazard ratios (HR) were used to compare outcomes at 1 year. RESULTS: After matching, 164,987 patients were included in each cohort. At one year, 31.9% of patients on GLP-1 therapy had GI-AEs (NNH 17.2), with incidence of nausea and vomiting, de-novo gastroesophageal reflux disease (GERD), and de-novo gastroparesis being 13%, 8.7%, and 0.7% respectively. GLP-1 use was associated with an increased risk of nausea and vomiting (HR 1.24 [1.21, 1.26]), GERD (HR 1.18 [1.14, 1.22]), proton pump inhibitor use (HR 1.15 [1.12, 1.19]), esophagitis (HR 1.24 [1.19, 1.30]), gastroparesis (HR 1.57 [1.43, 1.73]), drug-induced pancreatitis (HR 2.85 [1.82, 4.48]) and a decreased risk of bowel obstruction (HR 0.86 [0.80, 0.92]). No significant association was seen with cholecystitis (HR 1.10 [0.97, 1.15]) or choledocholithiasis (HR 1.07 [0.94, 1.21]). Esophagogastroduodenoscopy (EGD) utilization (HR 1.25 [1.20, 1.29]) was higher, but emergency room (ER) visits (HR 0.96 [0.95, 0.98]) and hospital admissions (HR 0.92 [0.91, 0.94]) were lower in the GLP-1 cohort. CONCLUSION: Nearly one-third of patients with DM and obesity on GLP-1 therapy reported GI-AEs, primarily nausea/vomiting and GERD. Providers should be aware of these events, given their association with increased EGD utilization but not higher ER visits or hospital admissions. CI - (c) 2026. The Author(s). FAU - Nathani, Piyush AU - Nathani P AD - Division of Gastroenterology, Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66103, USA. piyushnathani27@gmail.com. FAU - Hamamah, Sevag AU - Hamamah S AD - Department of Internal Medicine, Scripps Mercy Hospital, San Diego, CA, USA. FAU - Velji, Jena AU - Velji J AD - Department of Internal Medicine, University of South Carolina School of Medicine, Greenville, SC, USA. FAU - Patel, Harsh K AU - Patel HK AD - Division of Gastroenterology, Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66103, USA. FAU - Nathani, Rohit AU - Nathani R AD - Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA. FAU - Radadiya, Dhruvil AU - Radadiya D AD - Division of Gastroenterology, Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66103, USA. AD - Division of Gastroenterology, Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. FAU - Shandilya, Aarnav AU - Shandilya A AD - Walt Whitman High School, Bethesda, MD, USA. FAU - Srinivasan, Sachin AU - Srinivasan S AD - Division of Gastroenterology, Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66103, USA. FAU - Desai, Madhav AU - Desai M AD - McGovern Medical School, Center for Interventional Gastroenterology at University of Texas Health Houston, Houston, TX, USA. FAU - Repici, Alessandro AU - Repici A AD - Endoscopy Unit, Humanitas University, Milan, Italy. FAU - Hassan, Cesare AU - Hassan C AD - Endoscopy Unit, Humanitas University, Milan, Italy. FAU - Sharma, Prateek AU - Sharma P AD - Division of Gastroenterology, Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66103, USA. AD - Veteran Affairs Medical Center, Kansas City, MO, USA. LA - eng PT - Journal Article DEP - 20260708 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - Incidence MH - *Glucagon-Like Peptide 1/analogs & derivatives/adverse effects MH - Middle Aged MH - Aged MH - Obesity/drug therapy/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - *Incretins/adverse effects MH - Nausea/chemically induced/epidemiology MH - *Gastrointestinal Diseases/epidemiology/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Vomiting/chemically induced/epidemiology MH - Retrospective Studies MH - Gastroesophageal Reflux/chemically induced/epidemiology MH - Gastroparesis/chemically induced/epidemiology PMC - PMC13585874 OTO - NOTNLM OT - Diabetes mellitus OT - GI adverse events OT - GLP-1 OT - Obesity OT - TriNetX(R) COIS- Declarations. Competing interests: PN, SH, JV, HKP, RN, DR, AS, SS, and MD declare no conflicts of interest. AR is a consultant for Medtronic, ERBE, Fujifilm, Apollo Endosurgery, and Olympus. CH is a consultant for Alpha-Sigma, Fujifilm, Medtronic, Erbe, 3DMatrix, Laborie, Norgine, Olympus and Pentax. PS is a consultant for Olympus Corporation, Boston Scientific, Salix Pharmaceuticals, Cipla, Medtronic, Takeda, Samsung Bioepis, CDx, and Exact Sciences. PS has received grant support from Fujifilm, Erbe Medical, and Ironwood Pharmaceuticals. Consent to participate: Not applicable, as this study utilized de-identified aggregate patient data from the TriNetX research network and did not involve direct human participant interaction. Ethical approval: This study utilized de-identified data from the TriNetX research network. TriNetX data are de-identified in accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule under Section section sign164.514(a), with the de-identification process formally attested to through expert determination. No identifiable personal health information was accessed or used. As the study involved secondary analysis of de-identified data only, Institutional Review Board review was not sought. The study was conducted in accordance with applicable ethical standards and the principles of the Declaration of Helsinki. EDAT- 2026/07/08 12:56 MHDA- 2026/09/19 07:24 PMCR- 2026/07/08 CRDT- 2026/07/08 11:18 PHST- 2026/04/11 00:00 [received] PHST- 2026/07/03 00:00 [accepted] PHST- 2026/09/19 07:24 [medline] PHST- 2026/07/08 12:56 [pubmed] PHST- 2026/07/08 11:18 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - 10.1007/s10620-026-10112-7 [pii] AID - 10112 [pii] AID - 10.1007/s10620-026-10112-7 [doi] PST - ppublish SO - Dig Dis Sci. 2026 Nov;71(11):5405-5415. doi: 10.1007/s10620-026-10112-7. Epub 2026 Jul 8. PMID- 42417199 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 18 IP - 7 DP - 2026 Jul TI - Real-World vs. Randomized Trial Evidence for Incretin-Based Therapies: A Narrative Review. PG - e70248 LID - 10.1111/1753-0407.70248 [doi] LID - e70248 AB - Incretin-based therapies have transformed the management of obesity and type 2 diabetes (T2D). Pivotal randomized controlled trials (RCTs) report substantial weight loss and glycemic improvements; the extent to which these translate to clinical populations remains uncertain. Seven 2026-published RCT meta-analyses (comprising 127 RCTs and 58 976 participants) were compared with 26 real-world studies identified through structured PubMed search. Primary outcomes were body weight loss and HbA1c reduction; secondary outcomes included major adverse cardiovascular events (MACE), neurological end-points, and safety. The comparison is descriptive. For T2D, real-world semaglutide achieved 4.7-10.5 kg weight loss (6-12 months) and 1.0-1.3 percentage-point HbA1c reductions, lower than RCT meta-analytic estimates (tirzepatide mean difference [MD] -9.55% vs. placebo). Without diabetes, real-world persister analyses (SHAPE study: semaglutide -14.1%, tirzepatide -16.5%) approximated per-protocol RCT estimates (semaglutide -14.9%, tirzepatide 15 mg -20.9%), whereas intention-to-treat real-world estimates were substantially lower. Just 13% of semaglutide users reached 2.4 mg and 25.9% of tirzepatide users reached 15 mg. Real-world cardiovascular data showed 20%-46% MACE reductions, broadly consistent with the RCT reduction. Differences between T2D and non-T2D populations likely reflect channeling bias and differential follow-up. Real-world incretin-based therapy effectiveness is broadly consistent with RCT efficacy when dose attainment is accounted for. High discontinuation rates (20%-50% within 1 year) and prior GLP-1 RA exposure track with the observed efficacy gap. Clinicians can expect RCT-level outcomes in patients who tolerate and persist with target doses. Head-to-head cardiovascular outcome trials comparing tirzepatide and semaglutide in non-diabetic populations are needed. CI - (c) 2026 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Bloomgarden, Zachary AU - Bloomgarden Z AUID- ORCID: 0000-0003-3863-9267 AD - Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA. LA - eng PT - Journal Article PT - Review PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Tirzepatide MH - *Obesity/drug therapy PMC - PMC13343302 COIS- The author declares no conflicts of interest. EDAT- 2026/07/08 16:09 MHDA- 2026/07/08 18:51 PMCR- 2026/07/08 CRDT- 2026/07/08 06:24 PHST- 2026/06/01 00:00 [revised] PHST- 2026/05/21 00:00 [received] PHST- 2026/06/04 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/07/08 16:09 [pubmed] PHST- 2026/07/08 06:24 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - JDB70248 [pii] AID - 10.1111/1753-0407.70248 [doi] PST - ppublish SO - J Diabetes. 2026 Jul;18(7):e70248. doi: 10.1111/1753-0407.70248. PMID- 42414233 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260918 IS - 1557-9034 (Electronic) IS - 1092-6429 (Linking) VI - 36 IP - 11 DP - 2026 Nov TI - Brain Neuromodulation via Endoscopic Gastric Implant Improves Glycemic Control in Insulin-Dependent Type-2 Diabetes: First-in-Human Feasibility and Autonomic Response Study. PG - 777-785 LID - 10.1177/10926429261468981 [doi] AB - BACKGROUND: A miniaturized, self-powered Brain NeuroModulator (BNM) device, endoscopically implanted under neuroleptanalgesia in the submucosal layer of the proximal lesser gastric curvature, has the potential to consistently increase parasympathetic tone as measured by heart rate variability (HRV). OBJECTIVE: Since type-2 diabetes mellitus is associated with autonomic nervous system dysfunction, we assessed whether BNM induced autonomic rebalancing translates into measurable improvement of glycemic control through a change of HRV. METHODS: The BNM device was implanted on a 69-year-old male with a 25-year history of insulin-dependent type-2 diabetes mellitus under treatment with 22 IU/night of insulin plus semaglutide and metformin. HRV was assessed before and after the procedure. After the implant, continuous glucose monitoring (CGM) with an Abbott FreeStyle Libre sensor (15-minute sampling interval) was performed. RESULTS: The endoscopic procedure was uneventful and lasted 15 minutes. The BNM device remained in a stable position throughout the observation period. HRV analysis confirmed increased variability. Post-implant morning HRV showed progressive parasympathetic recovery compared with baseline. Within 2 months of implantation, therapy with semaglutide and metformin was discontinued, and insulin was progressively reduced from 22 to 0 IU. CONCLUSIONS: The BNM implant was feasible and safe, with clinically meaningful improvement in glycemic control associated with autonomic rebalancing within approximately 10 weeks of implantation. These data provide compelling preliminary evidence that correcting sympathetic dominance through vagal afferent stimulation may alter the clinical course of insulin-dependent type 2 diabetes. FAU - Cigaina, Valerio AU - Cigaina V AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Saggioro, Alfredo AU - Saggioro A AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Fabris, Paolo AU - Fabris P AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Bonavina, Luigi AU - Bonavina L AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20260707 PL - United States TA - J Laparoendosc Adv Surg Tech A JT - Journal of laparoendoscopic & advanced surgical techniques. Part A JID - 9706293 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/physiopathology/therapy/drug therapy/blood MH - Aged MH - Feasibility Studies MH - *Glycemic Control/methods MH - Heart Rate MH - Semaglutide MH - Blood Glucose MH - Autonomic Nervous System/physiopathology MH - Hypoglycemic Agents/therapeutic use MH - Insulin MH - Continuous Glucose Monitoring MH - Gastroscopy OTO - NOTNLM OT - autonomic nervous system OT - brain neuromodulation OT - heart rate variability OT - metabolic syndrome OT - parasympathetic tone OT - type-2 diabetes COIS- Disclosure StatementNo competing financial interests exist. EDAT- 2026/07/08 02:08 MHDA- 2026/09/18 05:36 CRDT- 2026/07/07 22:33 PHST- 2026/09/18 05:36 [medline] PHST- 2026/07/08 02:08 [pubmed] PHST- 2026/07/07 22:33 [entrez] AID - 10.1177/10926429261468981 [doi] PST - ppublish SO - J Laparoendosc Adv Surg Tech A. 2026 Nov;36(11):777-785. doi: 10.1177/10926429261468981. Epub 2026 Jul 7. PMID- 42414047 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20260902 IS - 1499-2752 (Electronic) IS - 0315-162X (Linking) VI - 53 IP - Suppl 2 DP - 2026 Sep 1 TI - Targeting the Metabolic-Inflammatory Axis in Psoriasis and Psoriatic Arthritis: Evidence From Diet, Glucagon-like Peptide-1 Receptor Agonists, and Patient Perspectives. PG - 15-18 LID - 10.3899/jrheum.2026-0589 [doi] AB - Patients with psoriasis (PsO) and psoriatic arthritis (PsA) frequently present with obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, all of which worsen outcomes and reduce treatment response. Dietary interventions represent one strategy to address this interplay, targeting the microbiome, metabolome, and joint inflammation. Antiinflammatory and hypocaloric diets improve symptoms and metabolic profiles. In parallel, glucagon-like peptide 1 receptor agonists (GLP-1RAs), originally approved for T2DM and obesity, have emerged as promising agents with both metabolic and immunomodulatory effects. Early reports in PsO and PsA suggest potential benefit, though evidence remains preliminary and based on small, heterogeneous studies. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Patient Research Partner (PRP) initiative highlights that people living with psoriatic disease (PsD) value holistic strategies that address comorbidities, improve quality of life, and support shared decision making. Most patients attempted lifestyle changes, yet common barriers included fatigue, lack of motivation, and absence of specific recommendations from treating physicians. Together, dietary approaches, GLP-1RAs, and patient-informed priorities underscore the potential of multidisciplinary, collaborative care to optimize outcomes in PsD. CI - Copyright (c) 2026 by the Journal of Rheumatology. FAU - Marchionni, Giulia AU - Marchionni G AUID- ORCID: 0009-0000-9488-4481 AD - G. Marchionni, MD, Internal Medicine Residency Program, Department of Clinical and Molecular Sciences, Marche Polytechnic University & Clinica Medica, Marche University Hospital, Ancona, Italy. FAU - Guma, Monica AU - Guma M AUID- ORCID: 0000-0003-1951-9411 AD - M. Guma, MD, PhD, Division of Rheumatology, Autoimmunity and Inflammation, University of California, San Diego, USA. FAU - Fernandez, Anthony P AU - Fernandez AP AUID- ORCID: 0000-0003-4490-8427 AD - A.P. Fernandez, MD, PhD, Departments of Dermatology and Pathology, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Grieb, Suzanne M AU - Grieb SM AUID- ORCID: 0000-0001-9971-4115 AD - S.M. Grieb, PhD, MSPH, Patient Research Partner, Baltimore, Maryland, USA. FAU - Eder, Lihi AU - Eder L AUID- ORCID: 0000-0002-1473-1715 AD - L. Eder, MD, PhD, Department of Medicine, University of Toronto, and Women's College Research Institute, Toronto, Ontario, Canada. FAU - Lindsay, Christine A AU - Lindsay CA AUID- ORCID: 0000-0001-6141-2824 AD - C.A. Lindsay, PharmD, Patient Research Partner, Prosper, Texas, USA. FAU - Soriano, Enrique R AU - Soriano ER AUID- ORCID: 0000-0003-3143-1084 AD - E.R. Soriano, MD, MSc, Rheumatology Section, Internal Medicine Service, Hospital Italiano de Buenos Aires, and University Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. enrique.soriano@hospitalitaliano.org.ar. LA - eng PT - Journal Article PT - Review DEP - 20260901 PL - Canada TA - J Rheumatol JT - The Journal of rheumatology JID - 7501984 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Arthritis, Psoriatic/drug therapy/metabolism/diet therapy/complications MH - *Psoriasis/metabolism/drug therapy/diet therapy/complications MH - Obesity/complications MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Metabolic Syndrome/complications MH - Quality of Life MH - Inflammation OTO - NOTNLM OT - GRAPPA OT - glucagon-like peptide 1 receptor agonists OT - obesity therapy OT - patient-centered care OT - psoriasis OT - psoriatic arthritis EDAT- 2026/07/08 02:09 MHDA- 2026/09/01 23:34 CRDT- 2026/07/07 21:03 PHST- 2026/06/15 00:00 [accepted] PHST- 2026/09/01 23:34 [medline] PHST- 2026/07/08 02:09 [pubmed] PHST- 2026/07/07 21:03 [entrez] AID - jrheum.2026-0589 [pii] AID - 10.3899/jrheum.2026-0589 [doi] PST - epublish SO - J Rheumatol. 2026 Sep 1;53(Suppl 2):15-18. doi: 10.3899/jrheum.2026-0589. PMID- 42412371 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20261008 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 86 IP - 9 DP - 2026 Sep TI - Ecnoglutide: First Approvals. PG - 1563-1570 LID - 10.1007/s40265-026-02350-w [doi] AB - Ecnoglutide is a cyclic adenosine monophosphate (cAMP)-biased glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Sciwind Biosciences for the treatment of type 2 diabetes mellitus (T2DM) and for use in long-term weight management. In January 2026, subcutaneous ecnoglutide received its first approval, in China, for use in glycaemic control in adults with T2DM. Subsequently, in March 2026, ecnoglutide received approval in China for use (in combination with diet control and increased physical activity) in long-term weight management in adults with obesity or with overweight with one or more weight-related comorbidity. Ecnoglutide is also under clinical evaluation for use in adolescents with obesity, and in adults with obesity and obstructive sleep apnoea and adults with obesity and knee osteoarthritis. An oral tablet formulation of ecnoglutide is in clinical development. This article summarises the milestones in the development of ecnoglutide leading to these first approvals for T2DM and long-term weight management. CI - (c) 2026. Springer Nature Switzerland AG. FAU - Shirley, Matt AU - Shirley M AUID- ORCID: 0000-0001-7191-7391 AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com. LA - eng PT - Journal Article PT - Review DEP - 20260707 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/pharmacology/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage/analogs & derivatives MH - Drug Approval MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Declarations. Authorship and Conflict of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content. Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability: Not applicable. EDAT- 2026/07/07 12:34 MHDA- 2026/09/01 05:41 CRDT- 2026/07/07 11:24 PHST- 2026/04/28 00:00 [received] PHST- 2026/05/20 00:00 [accepted] PHST- 2026/09/01 05:41 [medline] PHST- 2026/07/07 12:34 [pubmed] PHST- 2026/07/07 11:24 [entrez] AID - 10.1007/s40265-026-02350-w [pii] AID - 10.1007/s40265-026-02350-w [doi] PST - ppublish SO - Drugs. 2026 Sep;86(9):1563-1570. doi: 10.1007/s40265-026-02350-w. Epub 2026 Jul 7. PMID- 42411489 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 31 IP - 6 DP - 2026 Jun 22 TI - Semaglutide Modulates Visceral Adipose Tissue Lipid Metabolism in Type 2 Diabetic Mice: A Lipidomics Study. PG - 49873 LID - 10.31083/FBL49873 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health challenge. This study aimed to explore the molecular mechanisms underlying the effects of semaglutide on lipid metabolism in visceral white adipose tissue in a mouse model of T2DM. METHODS: Male C57BL/6J mice were given a normal diet, a high-fat diet with streptozotocin, or a high-fat diet with semaglutide. Blood samples, liver tissue, and adipose tissue were collected for analysis. Serum adipokines, inflammatory cytokines, liver function, and lipid profiles were assessed. White adipose tissue and liver sections were processed for hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC) staining for the macrophage marker F4/80. High-throughput targeted lipidomic analysis of epididymal white adipose tissue from these animals was performed using liquid chromatography-tandem mass spectrometry to characterize changes in lipid composition and function. Furthermore, the expression of genes related to adipokines, inflammation, and lipid metabolism in epididymal adipose tissue was determined by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: Semaglutide significantly improved systemic metabolism in mice with T2DM, as demonstrated by reductions in body weight, blood glucose, serum lipid levels, and insulin resistance indices homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (Adipo-IR). Serum Leptin, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) levels were downregulated, while Adiponectin levels were elevated. Histological analysis revealed that semaglutide effectively reduced adipocyte size, suppressed macrophage infiltration in adipose tissue, and decreased liver lipid accumulation. Targeted lipidomic profiling identified 24 lipid subclasses, of which 50 lipid molecules were significantly changed after semaglutide treatment. Enrichment analysis identified 15 metabolic pathways, with glycerophospholipid metabolism being the most prominently affected. RT-qPCR results confirmed that semaglutide altered the expression of key genes involved in glycerolipid, glycerophospholipid, fatty acid, and cholesterol metabolism. CONCLUSIONS: These results shed light on the comprehensive remodeling of semaglutide in improving lipid metabolism in epididymal white adipose tissue mice with T2DM. CI - Copyright: (c) 2026 The Author(s). Published by IMR Press. FAU - Chen, Xinlei AU - Chen X AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Tu, Bingrou AU - Tu B AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Li, Zhaoyuan AU - Li Z AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Gao, Ping AU - Gao P AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Xu, Yi AU - Xu Y AD - Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. AD - Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Yao, Yue AU - Yao Y AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. AD - Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. LA - eng GR - 82300921/National Natural Science Foundation of China/ PT - Journal Article PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Animals MH - Semaglutide MH - Male MH - *Lipid Metabolism/drug effects MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Mice MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptides/pharmacology MH - *Intra-Abdominal Fat/metabolism/drug effects MH - *Diabetes Mellitus, Experimental/metabolism/drug therapy MH - Lipidomics MH - Diet, High-Fat/adverse effects MH - Liver/metabolism/drug effects MH - Insulin Resistance MH - Adipose Tissue, White/metabolism/drug effects OTO - NOTNLM OT - adipose tissue, white OT - diabetes mellitus, type 2 OT - lipid metabolism OT - semaglutide EDAT- 2026/07/07 13:10 MHDA- 2026/07/08 02:10 CRDT- 2026/07/07 06:53 PHST- 2026/01/09 00:00 [received] PHST- 2026/03/14 00:00 [revised] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/07/08 02:10 [medline] PHST- 2026/07/07 13:10 [pubmed] PHST- 2026/07/07 06:53 [entrez] AID - S2768-6701(26)02100-3 [pii] AID - 10.31083/FBL49873 [doi] PST - ppublish SO - Front Biosci (Landmark Ed). 2026 Jun 22;31(6):49873. doi: 10.31083/FBL49873. PMID- 42410649 OWN - NLM STAT- MEDLINE DCOM- 20260927 LR - 20261009 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Jul 6 TI - Glucagon-like peptide-1 receptor agonists and major limb events in adults with type 2 diabetes and peripheral artery disease: a systematic review and meta-analysis of RCTs and cohort studies. LID - 10.1186/s12933-026-03283-0 [doi] LID - 291 AB - BACKGROUND: The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on peripheral artery disease (PAD) remains uncertain. We assessed the association between GLP-1RA use and major limb events in individuals with type 2 diabetes (T2D) and PAD. METHODS: We performed a literature search from inception to 31 March 2026 for randomized controlled trials and cohort studies comparing GLP-1RA use versus placebo, active comparators or non-use on lower limb outcomes in individuals with T2D and PAD. The primary outcome was a composite of major limb events, as defined by the investigators of the original studies included in the meta-analysis. Secondary outcomes included lower extremity amputation (LEA), revascularization, gangrene, major adverse cardiovascular events (MACE) and all-cause mortality. Subgroup analyses, leave-one-out sensitivity analyses, and meta-regression analysis were also performed. RESULTS: Twelve studies (2 RCTs and 10 matched cohort studies) with thirteen arms involving 418,282 participants were included. Treatment with GLP-1RAs was associated with a significantly lower risk of major limb events by 27% (thirteen arms, RR 0.73, 95% CI 0.65-0.82). Reduced risks were also observed for LEA (RR 0.76, 95% CI 0.66-0.87), revascularization (RR 0.81, 95% CI 0.77-0.86), gangrene (RR 0.80, 95% CI 0.77-0.85), MACE (RR 0.76, 95% CI 0.63-0.90) and all-cause mortality (RR 0.67, 95% CI 0.61-0.73). Subgroup and sensitivity analyses did not substantially change point estimates. CONCLUSION: Among adults with T2D and PAD, treatment with GLP-1RAs was associated with a lower risk of major limb events. There is a need of dedicated studies with standardized limb-specific endpoints to confirm the protective role of GLP-1RAs on limb events in people with T2D and PAD. CI - (c) 2026. The Author(s). FAU - Caruso, Paola AU - Caruso P AUID- ORCID: 0000-0002-4756-2022 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Di Martino, Nicole AU - Di Martino N AUID- ORCID: 0009-0001-8062-3958 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Longo, Miriam AU - Longo M AUID- ORCID: 0000-0002-6459-5854 AD - Department of Life Sciences, and Health and Health Professions, Link Campus University, Rome, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AUID- ORCID: 0009-0007-7628-2226 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AUID- ORCID: 0000-0002-4748-321X AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, PhD Program of Translational Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, PhD Program of Translational Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. dario.giugliano@unicampania.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260706 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peripheral Arterial Disease/mortality/diagnosis/drug therapy/therapy MH - Treatment Outcome MH - Risk Factors MH - Randomized Controlled Trials as Topic MH - *Incretins/therapeutic use/adverse effects MH - Amputation, Surgical MH - Risk Assessment MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Female MH - Male MH - Aged MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Limb Salvage MH - Protective Factors MH - Time Factors PMC - PMC13617921 OTO - NOTNLM OT - All-cause mortality OT - Glucagon-like peptide-1 receptor agonists OT - MACE OT - Major limb events OT - Meta-analysis OT - Peripheral artery disease OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Not applicable. This study is a meta-analysis and did not involve direct recruitment of human participants. Generative AI and AI-assisted technologies in the writing process: The authors didn't use ChatGPT for assistance in the preparation of the manuscript. Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dario Giugliano reported receiving consultancy fee from Eli Lilly, Sanofi, Novartis, Astrazeneca, and Novo Nordisk; Maria Ida Maiorino reported receiving personal fees from Novo Nordisk, Eli Lilly, and Sanofi; Katherine Esposito reported receiving consultancy fees from Eli Lilly and giving lectures for Eli Lilly, Sanofi, Novo Nordisk, Roche, Bayer, and Lifescan. All other authors declare that they have no competing interests. EDAT- 2026/07/07 06:39 MHDA- 2026/09/28 05:33 PMCR- 2026/07/06 CRDT- 2026/07/07 00:11 PHST- 2026/04/24 00:00 [received] PHST- 2026/06/26 00:00 [accepted] PHST- 2026/09/28 05:33 [medline] PHST- 2026/07/07 06:39 [pubmed] PHST- 2026/07/07 00:11 [entrez] PHST- 2026/07/06 00:00 [pmc-release] AID - 10.1186/s12933-026-03283-0 [pii] AID - 3283 [pii] AID - 10.1186/s12933-026-03283-0 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Jul 6;25(1):291. doi: 10.1186/s12933-026-03283-0. PMID- 42410325 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260930 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - 8777-8794 LID - 10.1111/dom.71058 [doi] AB - AIM: To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D). METHODS: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE. RESULTS: Nine RCTs (N = 2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6 mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6 mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators. CONCLUSIONS: Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kamrul-Hasan, A B M AU - Kamrul-Hasan ABM AUID- ORCID: 0000-0002-5681-6522 AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. FAU - Chatterjee, Subhankar AU - Chatterjee S AUID- ORCID: 0000-0002-3555-4412 AD - Department of Endocrinology, Medical College and Hospital, Kolkata, India. FAU - Ashraf, Hamid AU - Ashraf H AUID- ORCID: 0000-0001-8002-9142 AD - Rajiv Gandhi Center for Diabetes and Endocrinology, Aligarh Muslim University, Aligarh, India. FAU - Nagendra, Lakshmi AU - Nagendra L AUID- ORCID: 0000-0001-6865-5554 AD - Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India. FAU - Khalil, Ibrahim AU - Khalil I AUID- ORCID: 0009-0002-8995-1058 AD - Department of Medicine, Dhaka Medical College and Hospital, Dhaka, Bangladesh. FAU - Hasan, Mehedi AU - Hasan M AUID- ORCID: 0009-0006-7025-1253 AD - Department of Internal Medicine, Khwaja Yunus Ali Medical College and Hospital, Sirajganj, Bangladesh. FAU - Ahsan, Alvee AU - Ahsan A AUID- ORCID: 0000-0003-1063-7980 AD - Department of Public Health, American International University Bangladesh, Dhaka, Bangladesh. FAU - Dutta, Deep AU - Dutta D AUID- ORCID: 0000-0003-4915-8805 AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, New Delhi, Delhi, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Receptors, Glucagon) RN - 0 (Peptides) RN - Chinese people SB - IM MH - Adult MH - Humans MH - Body Weight/drug effects MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - Receptors, Glucagon/agonists MH - Treatment Outcome MH - Weight Loss/drug effects MH - East Asian People MH - Peptides PMC - PMC13538747 OTO - NOTNLM OT - HbA1c OT - Mazdutide OT - adverse events OT - body weight OT - obesity OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/07/07 04:11 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/06 23:43 PHST- 2026/06/18 00:00 [revised] PHST- 2026/03/31 00:00 [received] PHST- 2026/06/22 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/07 04:11 [pubmed] PHST- 2026/07/06 23:43 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71058 [pii] AID - 10.1111/dom.71058 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8777-8794. doi: 10.1111/dom.71058. Epub 2026 Jul 6. PMID- 42410309 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Cardiovascular Outcomes With Tirzepatide Versus GLP-1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta-Analysis. PG - 8627-8636 LID - 10.1111/dom.71051 [doi] AB - AIMS: To compare cardiovascular outcomes associated with tirzepatide versus glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with overweight or obesity. MATERIALS AND METHODS: PubMed/MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched through 30 March 2026. The study was registered in PROSPERO (CRD420261354941). Randomized and observational studies comparing tirzepatide with GLP-1 receptor agonists and reporting cardiovascular outcomes were included. Data were extracted on study characteristics and outcomes using adjusted hazard ratios when available. Risk of bias was assessed using RoB 2 and ROBINS-I. RESULTS: Eight studies (one randomized and seven observational) including 323 439 patients were analysed. Tirzepatide was not associated with a statistically significant reduction in major adverse cardiovascular events (MACE) compared with GLP-1 receptor agonists (HR 0.85, 95% CI 0.70-1.04; I (2) = 90.4%). Substantial heterogeneity was observed. Effect estimates were directionally consistent across secondary outcomes, including all-cause mortality (HR 0.90, 95% CI 0.79-1.02) and cardiovascular mortality (HR 0.88, 95% CI 0.76-1.00). In exploratory subgroup analyses, patients with type 2 diabetes showed lower estimated risks of all-cause mortality (HR 0.85, 95% CI 0.76-0.94) and heart failure (HR 0.75, 95% CI 0.58-0.97). CONCLUSIONS: Tirzepatide was not associated with a statistically significant reduction in MACEs. Although effect estimates were directionally consistent across analyses, substantial heterogeneity and the predominance of observational studies limit causal interpretation. Further randomized trials are needed to clarify the comparative cardiovascular effects of tirzepatide. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Silva, Joao Pedro Machado Ribeiro Jacintho AU - Silva JPMRJ AUID- ORCID: 0009-0002-4395-4851 AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Nogueira, Bruno Viruez AU - Nogueira BV AD - Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Sartori, Deborah Lomelino AU - Sartori DL AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - da Silva, Juliana Rizzo Cardoso AU - da Silva JRC AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Sciota, Lucca Biagio Argenton AU - Sciota LBA AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - de Mendonca Bisneto, Oscar Inacio AU - de Mendonca Bisneto OI AD - Universidade Federal de Campina Grande, Cajazeiras, Paraiba, Brazil. FAU - Gomes, Wilton Francisco AU - Gomes WF AD - Instituto de Neurologia e Cardiologia de Curitiba, Curitiba, Parana, Brazil. AD - Faculdades Pequeno Principe, Curitiba, Parana, Brazil. AD - Hospital INC, Curitiba, Parana, Brazil. AD - Irmandade da Santa Casa de Misericordia de Curitiba, Curitiba, Parana, Brazil. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Cardiovascular Diseases/epidemiology/prevention & control/mortality MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome PMC - PMC13449074 OTO - NOTNLM OT - cardiovascular disease OT - meta-analysis OT - obesity care OT - semaglutide COIS- W.F.G. reports proctorship honoraria from Abbott (Navitor transcatheter aortic valve) and Meril Life Sciences (MyVal transcatheter aortic valve) and speaker honoraria from Libbs Farmaceutica (ticagrelor). He has received travel and meeting support from Teleflex Incorporated for attendance at the Triple-i CVI Summit 2026. He reports no financial or non-financial relationships with Eli Lilly, Novo Nordisk or any other manufacturer of tirzepatide or GLP-1 receptor agonists and no relationships relevant to the subject matter of this manuscript. The other authors declare no conflicts of interest. EDAT- 2026/07/07 04:11 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/07/06 23:41 PHST- 2026/06/11 00:00 [revised] PHST- 2026/04/27 00:00 [received] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/07/07 04:11 [pubmed] PHST- 2026/07/06 23:41 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71051 [pii] AID - 10.1111/dom.71051 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8627-8636. doi: 10.1111/dom.71051. Epub 2026 Jul 6. PMID- 42410298 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Epidemiological Studies on Type 2 Diabetes Using the German Disease Analyser Database: A Narrative Review. PG - 8795-8800 LID - 10.1111/dom.71089 [doi] AB - BACKGROUND: The German IQVIA Disease Analyser (DA) database provides longitudinal, anonymised outpatient data from a large network of German general practices and specialist offices, including ICD-10 diagnoses, ATC-coded prescriptions, consultation dates and selected clinical measurements (HbA1c, BMI). AIMS: This narrative review synthesises DA-based research in patients with type 2 diabetes (T2D) published between 2020 and 2025, with a focus on studies examining glucose-lowering drug effectiveness, real-world prescribing patterns, pharmacoepidemiological associations and relevant comorbidities. METHODS: A structured PubMed search was used to identify eligible studies, and methodological limitations of the included observational studies are discussed. RESULTS: Key findings include observational associations between SGLT2 inhibitor therapy and lower incidence of iron deficiency anaemia and dementia in patients with T2D, a decline in cardiovascular event incidence among patients with newly diagnosed T2D over a 17-years period, a gap between guideline recommendations and real-world use of GLP-1 receptor agonists and SGLT2 inhibitors in patients with established cardiovascular disease, and associations between glucose-lowering drug classes and cerebrovascular outcomes. DISCUSSION: Given the observational design of all included studies, these associations should be regarded as hypothesis-generating rather than causal. The DA database complements randomised trial evidence by capturing large, heterogeneous populations in routine care. Limitations include underestimation of hypoglycaemia, absence of lifestyle and socioeconomic variables, and incomplete inpatient data, as well as reliance on a single data source to which several included studies and authors of this review have contributed. CONCLUSION: DA-based pharmacoepidemiological evidence is a valuable, albeit methodologically constrained, addition to the evidence base for contemporary diabetes management. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kostev, Karel AU - Kostev K AUID- ORCID: 0000-0002-2124-7227 AD - Marburg University, University Clinic, Marburg, Germany. AD - Epidemiology, IQVIA, Frankfurt, Germany. FAU - Sievert, Henning AU - Sievert H AD - Epidemiology, IQVIA, Frankfurt, Germany. FAU - Konrad, Marcel AU - Konrad M AUID- ORCID: 0000-0001-6798-5092 AD - Health & Social, FOM University of Applied Sciences for Economics and Management, Frankfurt am Main, Germany. FAU - Sarabhai, Theresia AU - Sarabhai T AD - Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Germany/epidemiology MH - Databases, Factual MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Epidemiologic Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Observational Studies as Topic MH - Pharmacoepidemiology PMC - PMC13538734 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Germany OT - SGLT2 inhibitors OT - disease analyser OT - pharmacoepidemiology OT - real-world evidence OT - type 2 diabetes COIS- K.K. and H.S. are employees of IQVIA. M.K. and T.S. have no conflicts of interest to declare. EDAT- 2026/07/07 00:40 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/06 23:41 PHST- 2026/06/28 00:00 [revised] PHST- 2026/06/14 00:00 [received] PHST- 2026/06/29 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/07 00:40 [pubmed] PHST- 2026/07/06 23:41 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71089 [pii] AID - 10.1111/dom.71089 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8795-8800. doi: 10.1111/dom.71089. Epub 2026 Jul 6. PMID- 42406865 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 154 IP - 1 DP - 2026 Jul 7 TI - Cardiovascular Risk Reduction With GLP-1 RA Drugs. PG - 66-73 LID - 10.1161/CIRCULATIONAHA.126.079319 [doi] AB - GLP-1 (glucagon-like peptide-1) receptor agonists (RAs) have emerged as a major therapeutic advance in cardiometabolic medicine. Initially developed as glucose-lowering therapies for type 2 diabetes, these agents have demonstrated broad benefits that extend well beyond glycemic control. GLP-1 RAs enhance glucose-dependent insulin secretion and reduce appetite, leading to improved glycemia and sustained weight loss. In addition, GLP-1 signaling exerts vascular and myocardial effects, including improved endothelial function, reduced inflammation and oxidative stress, and favorable changes in cardiac metabolism and remodeling. Large randomized cardiovascular outcomes trials have consistently shown that several GLP-1 RAs reduce major adverse cardiovascular events, including myocardial infarction, stroke, cardiovascular death, and heart failure. Benefits have been observed across diverse populations, including individuals with established cardiovascular disease and those with obesity but without diabetes. Emerging therapies targeting multiple incretin pathways, such as dual GIP (glucose-dependent insulinotropic polypeptide)-GLP-1 RAs, may further extend these benefits. Collectively, these findings suggest that GLP-1 RAs influence multiple cardiometabolic pathways and may shift the underlying metabolic milieu toward a more favorable physiological state. In this Clinical Primer, we review the physiology of GLP-1 signaling, the evidence supporting cardiovascular risk reduction, and practical considerations for the clinical use of incretin-based therapies. FAU - Pigeyre, Marie AU - Pigeyre M AUID- ORCID: 0000-0003-2984-8366 AD - Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Centre for Metabolism, Obesity, and Diabetes Research, McMaster University and Hamilton Health Sciences, Canada. FAU - Gerstein, Hertzel C AU - Gerstein HC AUID- ORCID: 0000-0001-8072-2836 AD - Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Centre for Metabolism, Obesity, and Diabetes Research, McMaster University and Hamilton Health Sciences, Canada. LA - eng PT - Journal Article PT - Review DEP - 20260706 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Animals MH - *Incretins/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Signal Transduction/drug effects MH - Glucagon-Like Peptide 1/metabolism OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular OT - clinical outcomes OT - incretin OT - review OT - risk OT - therapy COIS- Dr Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Novo Nordisk, Sanofi, AstraZeneca, and Eli Lilly; honoraria for speaking from Jiangsu Hanson; consulting fees from Abbott, Hanmi, Eli Lilly, Novo Nordisk, and Sanofi; and payments to his institution for continuing medical education from Abbott, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. The other author reports no conflicts. EDAT- 2026/07/06 18:39 MHDA- 2026/07/06 18:40 CRDT- 2026/07/06 14:03 PHST- 2026/07/06 18:40 [medline] PHST- 2026/07/06 18:39 [pubmed] PHST- 2026/07/06 14:03 [entrez] AID - 10.1161/CIRCULATIONAHA.126.079319 [doi] PST - ppublish SO - Circulation. 2026 Jul 7;154(1):66-73. doi: 10.1161/CIRCULATIONAHA.126.079319. Epub 2026 Jul 6. PMID- 42406681 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 1868-503X (Electronic) IS - 1868-5021 (Linking) VI - 17 IP - 1 DP - 2026 Jan 1 TI - Molecular, genetic, and pharmacological advances in type 2 diabetes (2015-2025). LID - 10.1515/bmc-2025-0059 [doi] AB - Type 2 diabetes (T2D) is a multifactorial metabolic disorder driven by the interplay of insulin resistance, beta-cell dysfunction, and complex genetic and epigenetic factors. Over the past decade (2015-2025), advances in molecular biology, genomics, and pharmacology have reshaped our understanding of its pathogenesis and treatment. Large-scale GWAS and functional genomics have clarified genetic risk loci and epigenetic mechanisms, while novel biomarkers, including circulating microRNAs and metabolomic signatures, offer potential for early detection and risk stratification. Therapeutically, incretin-based drugs, especially GLP-1 receptor agonists and dual agonists, as well as SGLT2 inhibitors, have transformed outcomes by targeting both glycemic control and cardiovascular-renal protection. These insights have also informed prevention strategies, emphasizing weight reduction, microbiome modulation, and precision interventions based on genetic risk. Yet major gaps remain, including functional annotation of risk loci, understanding of beta-cell dedifferentiation and recovery, and equitable implementation across diverse populations. This review synthesizes molecular, genetic, and pharmacological progress from 2015 to 2025, highlights clinical translation, and identifies priorities for the next decade of research. CI - (c) 2026 the author(s), published by De Gruyter, Berlin/Boston. FAU - Romero, Ricardo AU - Romero R AUID- ORCID: 0000-0002-4589-2984 AD - Departamento de Ciencias Naturales, Universidad Autonoma Metropolitana, Unidad Cuajimalpa, Avenida Vasco de Quiroga 4871, Col. Santa Fe Cuajimalpa, Alcaldia Cuajimalpa de Morelos, C.P. 05348, Ciudad de Mexico, Mexico. LA - eng PT - Journal Article PT - Review DEP - 20260707 PL - Germany TA - Biomol Concepts JT - Biomolecular concepts JID - 101518829 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/genetics/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Epigenesis, Genetic MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - epigenetics OT - genetics OT - type 2 diabetes EDAT- 2026/07/06 18:42 MHDA- 2026/07/06 18:43 CRDT- 2026/07/06 13:24 PHST- 2025/08/26 00:00 [received] PHST- 2026/04/22 00:00 [accepted] PHST- 2026/07/06 18:43 [medline] PHST- 2026/07/06 18:42 [pubmed] PHST- 2026/07/06 13:24 [entrez] AID - bmc-2025-0059 [pii] AID - 10.1515/bmc-2025-0059 [doi] PST - epublish SO - Biomol Concepts. 2026 Jul 7;17(1). doi: 10.1515/bmc-2025-0059. eCollection 2026 Jan 1. PMID- 42405390 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20261017 IS - 2212-3873 (Electronic) IS - 1871-5303 (Print) IS - 1871-5303 (Linking) VI - 26 DP - 2026 TI - Semaglutide and Musculoskeletal Health: A Mendelian Randomization Study Based on GLP-1 Receptor Expression. PG - e18715303422692 LID - 10.2174/0118715303422692260617052555 [doi] LID - E18715303422692 AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist, is clinically used for glycemic control and weight loss. However, it is still unclear whether it has any impact on bones and muscles. Does semaglutide have any impact on the musculoskeletal system of patients during its use, or does it have any negative effects on them? This study aims to assess the impact of GLP1R on bone and muscle using Mendelian Randomization. METHODS: We employed expression quantitative trait loci (eQTL) data for the GLP1R gene and combined it with genome-wide association studies (GWAS) data for skeletal and muscular traits to conduct Summary-data-based Mendelian Randomization (SMR) analysis. The exposure was defined as the blood expression level of the GLP1R gene, with the eQTL serving as the instrumental variable. Total bone mineral density, osteoporosis, and fractures were used to evaluate bone health, while appendicular lean mass, grip strength, and walking speed assessed muscle quality. Type 2 diabetes and body mass index (BMI) served as positive controls. RESULTS: The top eQTL rs9283907 was used to predict GLP1R expression. Positive control results confirmed that GLP1R agonists are effective diabetes treatments and can reduce BMI. There were no significant impacts on osteoporosis (beta: 0.00, 95% CI: -0.01, 0.01, p=0.416), total bone mineral density (beta: -0.03, 95% CI: -0.19, 0.13, p=0.702), fracture (beta: 0.09, 95% CI: -0.10, 0.28, p=0.343), walking pace (beta: 0.00, 95% CI: -0.01, 0.06, p=0.216), appendicular lean mass (beta: -0.01, 95% CI: -0.08, 0.06, p=0.676), or grip strength (beta: -0.02, 95% CI: -0.06, 0.02, p=0.425). DISCUSSION: This Mendelian randomization study provides genetic evidence that GLP-1 receptor expression is not causally associated with altered musculoskeletal health. The findings suggest that semaglutide is unlikely to adversely affect bone metabolism or muscle function regarding the outcomes measured. These results support the musculoskeletal safety profile of semaglutide; however, as genetic associations do not fully capture the clinical pharmacology of the drug, further validation through long-term randomized controlled trials is warranted. CONCLUSION: According to our results, high expression of glucagon-like peptide-1 receptor does not lead to bone and muscle loss, which indicates that semaglutide may be safe for the musculoskeletal system. FAU - Li, Dong AU - Li D AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Liang, Xinyu AU - Liang X AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Zhijun AU - Li Z AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Zhang, Huafeng AU - Zhang H AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Hui AU - Li H AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. LA - eng PT - Journal Article PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - *Glucagon-Like Peptide-1 Receptor/genetics/biosynthesis MH - *Mendelian Randomization Analysis/methods MH - Genome-Wide Association Study/methods MH - Bone Density/drug effects/genetics MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Quantitative Trait Loci MH - Muscle, Skeletal/drug effects PMC - PMC13670192 OTO - NOTNLM OT - GLP1R OT - bone OT - diabetes OT - muscle OT - musculoskeletal health OT - obesity EDAT- 2026/07/06 06:31 MHDA- 2026/09/21 05:34 PMCR- 2026/10/15 CRDT- 2026/07/06 05:45 PHST- 2025/08/06 00:00 [received] PHST- 2026/01/26 00:00 [revised] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/09/21 05:34 [medline] PHST- 2026/07/06 06:31 [pubmed] PHST- 2026/07/06 05:45 [entrez] PHST- 2026/10/15 00:00 [pmc-release] AID - EMIDDT-EPUB-156752 [pii] AID - EMIDDT-26-E18715303422692 [pii] AID - 10.2174/0118715303422692260617052555 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2026;26:e18715303422692. doi: 10.2174/0118715303422692260617052555. PMID- 42403263 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Semaglutide Injection Once-Weekly for Weight Management in Adults: Results From A Randomized Phase III, Active-Controlled Study. PG - 8602-8612 LID - 10.1111/dom.71069 [doi] AB - AIM: To evaluate and compare the efficacy, safety, and immunogenicity of a synthetic semaglutide injection (Test semaglutide) with Wegovy (Reference semaglutide) injection for weight management. MATERIALS AND METHODS: This randomized, Phase III, non-inferiority study included adults with obesity or overweight with or without comorbidities from 21 centers in India. A total of 270 patients with body mass index >/= 30 kg/m(2) or >/= 27 kg/m(2) with the presence of at least one of the weight-related comorbidities (hypertension, dyslipidemia or type 2 diabetes mellitus) were randomized (2:1) to receive either Test semaglutide (N = 177) or Reference semaglutide injection (N = 90) once weekly with dose escalation from 0.25 to 2.4 mg. The primary endpoint was percentage change in bodyweight from baseline to Week 24. RESULTS: Out of 267 randomized patients, 246 completed the study. At Week 24, mean percent weight change from baseline was -13.8% +/- 4.28% in Test and -14.1% +/- 4.11% in Reference groups with least-squares mean difference of 0.26% (95% CI: -0.86% to 1.39%), meeting the criterion for non-inferiority. The proportion of patients with >/= 5% and >/= 10% weight loss were 96.40% and 80.60% in Test, and 98.80% and 80.00% in Reference groups, respectively at Week 24. Improvements in body mass index, waist circumference, SF-36 total score, and glycemic parameters were comparable between groups. Treatment-emergent adverse events were reported in 72.30% and 76.70% in the Test and Reference groups, respectively, with gastrointestinal events being the most common. CONCLUSIONS: Test synthetic semaglutide was found to be non-inferior to Reference semaglutide in weight management with or without comorbidities. TRIAL REGISTRATION: Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/04/085487 [Registered on: 24/04/2025], https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwNjMx&Enc=&userName=. CI - (c) 2026 Sun Pharma Laboratories limited. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ambika Gopalakrishnan, Unnikrishnan AU - Ambika Gopalakrishnan U AD - Chellaram Diabetes Institute, Pune, Maharashtra, India. FAU - Joshi, Ameya AU - Joshi A AD - Bhaktivedanta Hospital and Research Institute, Thane, Maharashtra, India. FAU - Kumar, Harish AU - Kumar H AD - Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India. FAU - Giri, Richa AU - Giri R AD - G.S.V.M Medical College, Kanpur, Uttar Pradesh, India. FAU - Maheshwari, Sanjiv AU - Maheshwari S AD - Jawahar Lal Nehru Medical College, Ajmer, Rajasthan, India. FAU - Prasad, Valluri Satya AU - Prasad VS AD - King George Hospital, Visakhapatnam, Andhra Pradesh, India. FAU - Shukla, Jitendra AU - Shukla J AD - Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. FAU - M Chowdaiah, Rekha AU - M Chowdaiah R AD - Mandya Institute of Medical Science, Mandya, Karnataka, India. FAU - Agrawal, Nutan Kumar AU - Agrawal NK AD - M.L.B Medical College, Jhansi, Uttar Pradesh, India. FAU - Rasal, Yogesh AU - Rasal Y AD - Pulse Multispecialty Hospital, Pune, Maharashtra, India. FAU - Sahoo, Banshidhar AU - Sahoo B AD - KIDS Hospital, Khordha, Odisha, India. FAU - Bhandari, Shweta AU - Bhandari S AUID- ORCID: 0000-0002-0008-7949 AD - Vincare Hospital, Bathinda, Punjab, India. FAU - Gowda, Ambanna AU - Gowda A AD - Citizen Hospital, Bangalore, Karnataka, India. FAU - Phadke, Uday AU - Phadke U AD - Sahyadri Super Speciality Hospital, Pune, Maharashtra, India. AD - Sahyadri Clinical Research and Development Center, Pune, Maharashtra, India. FAU - Supe, Pravin AU - Supe P AD - Supe Heart and Diabetes Hospital and Research Centre, Nashik, Maharashtra, India. FAU - Pathak, Niranjan AU - Pathak N AD - OJAS Multispeciality Hospital, Pune, Maharashtra, India. FAU - Chandrappa, Ambrish AU - Chandrappa A AD - Medstar Speciality Hospital, Bangalore, Karnataka, India. FAU - Sonawane, Ashutosh AU - Sonawane A AD - Panacea Hospital, Nashik, Maharashtra, India. FAU - Bahulikar, Yash AU - Bahulikar Y AD - MMFHA Joshi Hospital, Pune, Maharashtra, India. FAU - Bhaskar, Amit AU - Bhaskar A AD - Janta Hospital and Maternity Center, Varanasi, Uttar Pradesh, India. FAU - Radhakrishnan, Arunkumar AU - Radhakrishnan A AD - Chettinad Hospital and Research Institute, Chengalpattu, Tamil Nadu, India. FAU - Yadav, Priyanka AU - Yadav P AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Pandit, Sucheta AU - Pandit S AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Sonowal, Supriya AU - Sonowal S AUID- ORCID: 0009-0002-5481-7780 AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Patil, Dipak AU - Patil D AUID- ORCID: 0009-0008-8690-3302 AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Ghadge, Pravin AU - Ghadge P AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Mehta, Suyog AU - Mehta S AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. LA - eng GR - Sun Pharmaceutical Industries Limited/ PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Obesity/drug therapy/complications MH - Adult MH - Weight Loss/drug effects MH - *Overweight/drug therapy/complications MH - Drug Administration Schedule MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Aged PMC - PMC13449013 OTO - NOTNLM OT - GLP-1 receptor agonist OT - immunogenicity OT - non-inferiority trial OT - obesity OT - overweight OT - semaglutide OT - weight management COIS- Unnikrishnan Ambika Gopalakrishnan, Ameya Joshi, Harish Kumar, Richa Giri, Sanjiv Maheshwari, Valluri Satya Prasad, Jitendra Shukla, Rekha M. Chowdaiah, Nutan Kumar Agrawal, Yogesh Rasal, Banshidhar Sahoo, Shweta Bhandari, Ambanna Gowda, Uday Phadke, Pravin Supe, Niranjan Pathak, Ambrish Chandrappa, Ashutosh Sonawane, Yash Bahulikar, Amit Bhaskar, and Arunkumar Radhakrishnan were the study investigators, and they received grant from the sponsor for conducting the study at their respective sites. Priyanka Yadav, Sucheta Pandit, Supriya Sonowal, Dipak Patil, Pravin Ghadge, and Suyog Mehta are full-time employees of Sun Pharma Laboratories Limited. EDAT- 2026/07/06 06:31 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/07/06 04:42 PHST- 2026/06/24 00:00 [revised] PHST- 2026/04/01 00:00 [received] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/07/06 06:31 [pubmed] PHST- 2026/07/06 04:42 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71069 [pii] AID - 10.1111/dom.71069 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8602-8612. doi: 10.1111/dom.71069. Epub 2026 Jul 6. PMID- 42401410 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260904 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 231 DP - 2026 Sep TI - GLP-1 receptor agonist therapy in children and adolescents with obesity: A network meta-analysis of differential cardiometabolic efficacy and safety profiles. PG - 108333 LID - S1043-6618(26)00248-3 [pii] LID - 10.1016/j.phrs.2026.108333 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in adolescents with overweight or obesity, but their comparative effects on cardiometabolic outcomes across different agents remain uncertain. We aimed to compare the efficacy and safety of different GLP-1RAs on key cardiometabolic parameters in adolescents with overweight or obesity, with or without type 2 diabetes. METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov from inception to May 1, 2026. Randomised clinical trials comparing GLP-1RAs with placebo or another active agent in eligible adolescents were included. Two reviewers independently extracted data and assessed risk of bias following PRISMA guidelines for network meta-analysis. We used a Bayesian random-effects model for data synthesis. RESULTS: 17 RCTs with 1230 participants were included. Semaglutide 2.4 mg SC was associated with the largest reductions in body weight (mean difference -18.00 kg; 95% credible interval -24.34 to -11.69, high confidence), BMI (-5.9 kg/m(2), -10.5 to -1.3, high confidence), and waist circumference (-12.2 cm, -21.67 to -2.67). For glycaemic control, dulaglutide 1.5 mg SC showed the largest reduction in HbA1c (-1.50%, -1.84 to -1.15, high confidence), and lixisenatide 20 ug SC showed the largest reduction in fasting plasma glucose (-3.98 mmol/L, -7.46 to -0.60); however, these rankings derive from networks with sparse head-to-head evidence and wide credible intervals for indirect comparisons. Exenatide 20 ug SC was associated with a reduction in systolic blood pressure (-6.64 mmHg, -13.22 to -0.17) based on limited indirect evidence from early-phase trials. No agent improved lipid profiles in a statistically significant manner. CONCLUSION: In this network meta-analysis of adolescents with overweight or obesity, GLP-1RAs showed differential cardiometabolic profiles. Semaglutide 2.4 mg produced the largest point estimates for weight-related outcomes, dulaglutide 1.5 mg and lixisenatide 20 ug for glycaemic endpoints, and exenatide 20 ug for systolic blood pressure. These findings are hypothesis-generating: most active-treatment comparisons were indirect, many nodes were informed by single trials, and SUCRA rankings should not be interpreted as evidence of definitive clinical superiority. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Li, Yao AU - Li Y AD - Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Xu, Xiaoou AU - Xu X AD - Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Tuersun, Adili AU - Tuersun A AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Fan, Xichen AU - Fan X AD - Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Qin, Muting AU - Qin M AD - Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Zhao, Xin AU - Zhao X AD - Laboratory of Medicine, Datong Second People's Hospital (Datong Tumor Hospital), Datong 037006, China. FAU - Abuduaini, Subinuer AU - Abuduaini S AD - School of Pharmaceutical Sciences, Tokyo University of Science, Tokyo 162-8601, Japan. FAU - Xing, Haoyue AU - Xing H AD - Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: xinghy90@163.com. FAU - Chen, Huanxue AU - Chen H AD - Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: chenhx@sj-hospital.org. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260704 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Obesity Agents) RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Adolescent MH - Child MH - Humans MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Exenatide/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Pediatric Obesity/drug therapy/blood MH - Randomized Controlled Trials as Topic MH - Semaglutide/adverse effects/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins OTO - NOTNLM OT - Adolescents OT - GLP-1 Receptor Agonists OT - Network Meta-Analysis OT - Obesity COIS- Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence the work submitted, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript. EDAT- 2026/07/05 04:10 MHDA- 2026/08/25 23:33 CRDT- 2026/07/04 19:34 PHST- 2026/05/10 00:00 [received] PHST- 2026/06/25 00:00 [revised] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/08/25 23:33 [medline] PHST- 2026/07/05 04:10 [pubmed] PHST- 2026/07/04 19:34 [entrez] AID - S1043-6618(26)00248-3 [pii] AID - 10.1016/j.phrs.2026.108333 [doi] PST - ppublish SO - Pharmacol Res. 2026 Sep;231:108333. doi: 10.1016/j.phrs.2026.108333. Epub 2026 Jul 4. PMID- 42401045 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260721 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 201 DP - 2026 Aug TI - Protective effects of ACF210, a dual GLP-1/APJ receptor agonist, against cardiovascular-kidney-metabolic syndrome induced by T2D. PG - 119726 LID - S0753-3322(26)00762-6 [pii] LID - 10.1016/j.biopha.2026.119726 [doi] AB - Current therapies cannot simultaneously address the interconnected metabolic, cardiac, and renal damage in Cardiovascular-Kidney-Metabolic (CKM) syndrome. This study investigated ACF210, a novel long-acting dual agonist targeting both GLP-1 and APJ receptors, as a potential treatment for type 2 diabetes (T2D)-induced CKM syndrome. ACF210 was synthesized by fusing the human IgG4 Fc fragment to the C-terminus of GLP-1 and the N-terminus of Elabela-21 (ELA). In vitro receptor activation assays confirmed that ACF210 effectively activated the GLP-1 and APJ receptor signaling simultaneously. db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced T2D were treated with dulaglutide, Fc-ELA, or ACF210 for 12 weeks. We assessed tissue morphology, organ function, and serum biomarkers. Compared to the diabetic control mice, ACF210 significantly improved blood glucose control and pancreatic beta-cell function. Crucially, ACF210 demonstrated superior multi-organ protective effects over other treatments. Specifically, ACF210 reduced hepatic steatosis and provided comprehensive cardiac protection by lessening mitochondrial damage and fibrosis, enhancing diastolic function, reducing heart failure biomarkers such as NT-proBNP, and promoting microangiogenesis. In the kidneys, ACF210 alleviated podocyte damage and thickening of the glomerular basement membrane, while improving renal function as indicated by reduced levels of urinary albumin-to-creatinine ratio (UACR) and serum cystatin C. In conclusion, ACF210 not only effectively alleviates dysglycemia by potentially enhancing beta-cell function but also significantly protects against diabetes-associated hepatic, cardiac, and renal damage, supporting its further exploration for the clinical management of CKM syndrome. CI - Copyright (c) 2026. Published by Elsevier Masson SAS. FAU - Wu, Qingfeng AU - Wu Q AD - Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Wei, Huiyi AU - Wei H AD - Yan'an Medical College, Yan'an University, Yan'an, Shaanxi 716000, China. FAU - Zhou, Huifen AU - Zhou H AD - Department of Pathology, Hubei University of Science and Technology, Xianning, Hubei 437100, China. FAU - Du, Yuanyuan AU - Du Y AD - Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. FAU - Zhao, Qingbin AU - Zhao Q AD - Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: zhaoqingbin@xjtufh.edu.cn. LA - eng PT - Journal Article DEP - 20260704 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Apela protein, mouse) RN - 0 (Peptide Hormones) RN - 0 (Protective Agents) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Animals MH - *Metabolic Syndrome/prevention & control/etiology/metabolism/drug therapy MH - Male MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - *Cardio-Renal Syndrome/prevention & control/etiology/metabolism MH - Mice MH - *Diabetes Mellitus, Experimental/drug therapy/complications MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mice, Inbred C57BL MH - Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/pharmacology MH - Kidney/drug effects/metabolism MH - Signal Transduction/drug effects MH - Peptide Hormones/pharmacology MH - Diet, High-Fat MH - *Protective Agents/pharmacology MH - *Recombinant Fusion Proteins/pharmacology OTO - NOTNLM OT - CKM syndrome OT - Dual receptor agonist OT - Elabela OT - GLP-1 receptor agonist OT - Multiorgan protection OT - Type 2 diabetes COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2026/07/05 00:37 MHDA- 2026/07/21 06:34 CRDT- 2026/07/04 18:03 PHST- 2026/04/02 00:00 [received] PHST- 2026/06/14 00:00 [revised] PHST- 2026/06/29 00:00 [accepted] PHST- 2026/07/21 06:34 [medline] PHST- 2026/07/05 00:37 [pubmed] PHST- 2026/07/04 18:03 [entrez] AID - S0753-3322(26)00762-6 [pii] AID - 10.1016/j.biopha.2026.119726 [doi] PST - ppublish SO - Biomed Pharmacother. 2026 Aug;201:119726. doi: 10.1016/j.biopha.2026.119726. Epub 2026 Jul 4. PMID- 42397685 OWN - NLM STAT- MEDLINE DCOM- 20261017 LR - 20261017 IS - 1528-1167 (Electronic) IS - 0013-9580 (Linking) VI - 67 IP - 10 DP - 2026 Oct TI - Comparative risk of epilepsy with SGLT2 inhibitors versus incretin-based therapies in type 2 diabetes. PG - 5365-5378 LID - 10.1002/epi.70369 [doi] AB - OBJECTIVE: This study was undertaken to compare the risk of seizures and epilepsy among patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagonlike peptide-1 receptor agonists (GLP-1 RAs), or dipeptidyl peptidase-4 (DPP-4) inhibitors using nationwide real-world data. METHODS: Using propensity score matching, we identified 20 096 matched pairs of SGLT2i and DPP-4 inhibitor users, 8671 matched pairs of SGLT2i and GLP-1 RA users, and 1611 matched pairs of GLP-1 RA and DPP-4 inhibitor users from the Taiwanese National Health Insurance Research Database, spanning January 1, 2000 to December 31, 2021. Cox proportional hazards model was used to compare outcome risks between the respective treatment groups. RESULTS: SGLT2i users had significantly lower cumulative incidences of seizure, epilepsy, and the composite outcome compared to DPP-4 inhibitor users (log-rank p < .001). Adjusted hazard ratios (aHRs) were .49 for seizure, .38 for epilepsy, and .46 for the composite outcome. Compared to GLP-1 RA users, SGLT2i users had a lower risk of the composite outcome (aHR = .66, p = .016), but not individual seizure or epilepsy outcomes. No significant differences were found between GLP-1 RAs and DPP-4 inhibitors. SIGNIFICANCE: In this population-based study, SGLT2i use among patients with T2D was associated with lower risks of seizure and epilepsy compared to DPP-4 inhibitors, and lower composite seizure/epilepsy risk compared to GLP-1 RAs. These findings suggest a potential association between SGLT2i use and a lower risk of seizure- and epilepsy-related outcomes. CI - (c) 2026 International League Against Epilepsy. FAU - Yen, Fu-Shun AU - Yen FS AUID- ORCID: 0000-0002-4677-2415 AD - Dr. Yen's Clinic, Taoyuan, Taiwan. FAU - Yen, Yu-Hsin AU - Yen YH AUID- ORCID: 0009-0001-8074-1524 AD - Duke-NUS Medical School, Singapore, Singapore. FAU - Hung, Yao-Min AU - Hung YM AUID- ORCID: 0000-0001-6920-8799 AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. AD - College of Health and Nursing, Meiho University, Neipu Township, Taiwan. AD - Fooyin University, Kaohsiung, Taiwan. AD - Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AUID- ORCID: 0000-0002-1235-0679 AD - Department of Allergy, Immunology, & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. FAU - Sung, Chen-Yu AU - Sung CY AUID- ORCID: 0009-0003-8624-2608 AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. AD - College of Medicine, China Medical University, Taichung, Taiwan. FAU - Huang, Yu-Han AU - Huang YH AUID- ORCID: 0009-0000-0995-3455 AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. AD - College of Medicine, China Medical University, Taichung, Taiwan. FAU - Tsai, Fuu-Jen AU - Tsai FJ AUID- ORCID: 0000-0002-1373-245X AD - School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. AD - Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. AD - Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan. AD - Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AUID- ORCID: 0000-0002-8209-9627 AD - Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AUID- ORCID: 0000-0003-4563-4341 AD - Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. AD - Department of Health Services Administration, China Medical University, Taichung, Taiwan. AD - Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan. AD - National Center for Geriatrics and Welfare Research, National Health Research Institutes, Huwei Township, Taiwan. LA - eng GR - MOHW113-TDU-B-212-114009/Ministry of Health and Welfare (MOHW113-TDU-B-212-114009)/ GR - DMR-111-105/China Medical University Hospital/ GR - DMR-112-087/China Medical University Hospital/ GR - DMR-113-009/China Medical University Hospital/ GR - DMR-114-046/China Medical University Hospital/ GR - DMR-114-139/China Medical University Hospital/ GR - V113C-166/Taipei Veterans General Hospital/ GR - V114C-177/Taipei Veterans General Hospital/ GR - V115C-160/Taipei Veterans General Hospital/ GR - NSTC113-2314-B-075-007/the National Science and Technology Council, R.O.C./ PT - Comparative Study PT - Journal Article DEP - 20260703 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Epilepsy/epidemiology/chemically induced MH - Female MH - Male MH - Taiwan/epidemiology MH - Middle Aged MH - *Incretins/therapeutic use/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Adult OTO - NOTNLM OT - DPP-4 inhibitors OT - epilepsy OT - glucagonlike peptide-1 receptor agonists OT - seizure OT - sodium-glucose cotransporter-2 inhibitors EDAT- 2026/07/03 12:32 MHDA- 2026/10/17 05:33 CRDT- 2026/07/03 11:42 PHST- 2026/06/18 00:00 [revised] PHST- 2026/01/11 00:00 [received] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/10/17 05:33 [medline] PHST- 2026/07/03 12:32 [pubmed] PHST- 2026/07/03 11:42 [entrez] AID - 10.1002/epi.70369 [doi] PST - ppublish SO - Epilepsia. 2026 Oct;67(10):5365-5378. doi: 10.1002/epi.70369. Epub 2026 Jul 3. PMID- 42389771 OWN - NLM STAT- MEDLINE DCOM- 20260702 LR - 20260813 IS - 2047-7163 (Electronic) IS - 0036-8504 (Print) IS - 0036-8504 (Linking) VI - 109 IP - 3 DP - 2026 Jul-Sep TI - Clinical and mechanistic effects of GLP-1 receptor agonists in hidradenitis suppurativa and comorbidities. PG - 368504261464855 LID - 10.1177/00368504261464855 [doi] LID - 00368504261464855 AB - Hidradenitis suppurativa (HS) is a painful inflammatory skin disease within the pilosebaceous unit associated with numerous comorbidities, including obesity type-2-diabetes (T2DM), and a general meta-inflammatory state. This narrative review explores the therapeutic potential of GLP-1-receptor-agonists (GLP-1RAs) in treating HS by analyzing mechanisms of action and clinical outcomes. Based on a literature search, encompassing 12 cohorts and 4 case-based reports, current evidence demonstrates significant improvements in both clinical and patient-reported outcomes in patients with HS treated with GLP-1RAs. Treatment consistently resulted in reduced body mass index (BMI) and disease activity, measured by Hurley-staging and the number of nodules and abscesses. Patients across studies experienced fewer flares and less pain, supporting improvements in dermatology quality of life (DLQI) scores. Studies observed reductions in systemic inflammatory markers and improved glycemic control. The beneficial effects of GLP-1RAs in HS are attributed to the reduction in mechanical friction and metabolic improvements from weight loss. Suggestively, concurrent and direct anti-inflammatory mechanisms, including inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway and modulation of cytokines, occur independently of weight-reduction. Results from cohorts and cases supported this theory, showing significant improvements in HS and metabolic markers independent of weight-related outcomes. Four supplementary cohorts found GLP-1RAs beneficial for cardiovascular comorbidities in patients with HS. Additionally, studies suggest that GLP-1RAs enhance the efficacy of biologic therapies used for HS and reduce the need for adjunctive treatment. In conclusion, GLP-1RAs represent a promising pleiotropic treatment within a multimodal therapy strategy for HS and comorbidities. FAU - Brogaard, Emma AU - Brogaard E AUID- ORCID: 0009-0007-3752-4114 AD - Department of Dermato-Venereology & Wound Healing Centre, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Nielsen, Valdemar Wendelboe AU - Nielsen VW AD - Department of Dermato-Venereology & Wound Healing Centre, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Pedersen, Nadja Hojgaard AU - Pedersen NH AD - Department of Dermato-Venereology & Wound Healing Centre, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Holgersen, Nikolaj AU - Holgersen N AD - Department of Dermato-Venereology & Wound Healing Centre, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Thomsen, Simon Francis AU - Thomsen SF AUID- ORCID: 0000-0002-4838-300X AD - Department of Dermato-Venereology & Wound Healing Centre, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. AD - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. RINGGOLD: 4321 LA - eng PT - Journal Article PT - Review DEP - 20260702 PL - England TA - Sci Prog JT - Science progress JID - 0411361 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Hidradenitis Suppurativa/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Comorbidity MH - Quality of Life MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/drug therapy PMC - PMC13329101 OTO - NOTNLM OT - GLP-1 OT - acne inversa OT - cardiometabolic outcomes OT - comorbidity OT - glucagon-like peptide-1 OT - hidradenitis suppurativa COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Emma Brogaard, Valdemar Wendelboe Nielsen, Nadja Hojgaard Pedersen, and Nikolaj Holgersen have no conflicts to disclose. Simon Francis Thomsen has received research support and/or been a speaker/consultant for AbbVie, ALK-Abello, Almirall, Boehringer, CSL, Eli Lilly, Galderma, Incyte, Janssen, Johnson & Johnson, LEO Pharma, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Symphogen, UCB, Union Therapeutics and Zealand Pharma with no relation to the present review. EDAT- 2026/07/02 06:40 MHDA- 2026/07/02 06:41 PMCR- 2026/07/02 CRDT- 2026/07/02 05:11 PHST- 2026/07/02 06:41 [medline] PHST- 2026/07/02 06:40 [pubmed] PHST- 2026/07/02 05:11 [entrez] PHST- 2026/07/02 00:00 [pmc-release] AID - 10.1177_00368504261464855 [pii] AID - 10.1177/00368504261464855 [doi] PST - ppublish SO - Sci Prog. 2026 Jul-Sep;109(3):368504261464855. doi: 10.1177/00368504261464855. Epub 2026 Jul 2. PMID- 42388102 OWN - NLM STAT- MEDLINE DCOM- 20260806 LR - 20260806 IS - 1531-7080 (Electronic) IS - 0268-4705 (Linking) VI - 41 IP - 5 DP - 2026 Sep 1 TI - Rebooting blood vessel repair: implications of the SEMA-VR CardioLink-15 trial. PG - 459-466 LID - 10.1097/HCO.0000000000001323 [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events (MACE), heart failure, and mortality through undetermined mechanisms independent of glycemic control. This review examines emerging evidence that GLP-1RAs overcome vascular regenerative cell exhaustion (VRCE), a pathological depletion of bone marrow-derived progenitor cells that mediate vessel repair. RECENT FINDINGS: VRCE, the progressive loss of circulating progenitor cells that mediate vessel regeneration, has recently emerged as an underappreciated driver of MACE risk in individuals living with type 2 diabetes (T2D), obesity or atherosclerotic cardiovascular disease. In a recent randomized translational trial of semaglutide vs. usual care, SEMA-VR CardioLink-15 provided the direct evidence that 6-month semaglutide administration could reverse VRCE profile associated with longstanding cardiometabolic disease (34.8% increase in VR myeloid progenitor cells, 66.2% expansion of endothelial precursor cells). Semaglutide additionally reduced circulating granulocyte content and suppressed pro-inflammatory TNF and interleukin family cytokines in sera. SUMMARY: GLP-1RAs can restore bone marrow progenitor cell output towards a more vessel regenerative profile. Reversal of VRCE may partially explain early event curve separation in cardiovascular outcome trials with multiple GLP-1RAs. Therefore, circulating VR cell content could serve as a measure of compromised vascular regenerative capacity and elevated cardiovascular disease risk. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Verma, Raj AU - Verma R AD - School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. FAU - Verma, Meena AU - Verma M AD - School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. FAU - Park, Brady AU - Park B AD - Temerty Faculty of Medicine, University of Toronto. FAU - Teoh, Hwee AU - Teoh H AD - Division of Cardiac Surgery, St Michael's Hospital of Unity Health Toronto. AD - Division of Endocrinology and Metabolism, St Michael's Hospital of Unity Health Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. FAU - Quan, Adrian AU - Quan A AD - Division of Cardiac Surgery, St Michael's Hospital of Unity Health Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. FAU - Connelly, Kim A AU - Connelly KA AD - Temerty Faculty of Medicine, University of Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. AD - Division of Cardiology, St Michael's Hospital of Unity Health Toronto. AD - Department of Medicine. AD - Department of Physiology. FAU - Hess, David A AU - Hess DA AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto. AD - Department of Physiology and Pharmacology, University of Western Ontario. AD - Molecular Medicine Research Laboratories, Robarts Research Institute, London, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20260701 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Regeneration/drug effects MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Blood Vessels/physiology/drug effects OTO - NOTNLM OT - endothelial precursor cells OT - glucagon-like peptide-1 receptor agonists OT - hematopoietic progenitor cells OT - semaglutide OT - vascular regenerative cell exhaustion EDAT- 2026/07/02 06:39 MHDA- 2026/08/06 12:37 CRDT- 2026/07/02 03:53 PHST- 2026/08/06 12:37 [medline] PHST- 2026/07/02 06:39 [pubmed] PHST- 2026/07/02 03:53 [entrez] AID - 00001573-990000000-00287 [pii] AID - 10.1097/HCO.0000000000001323 [doi] PST - ppublish SO - Curr Opin Cardiol. 2026 Sep 1;41(5):459-466. doi: 10.1097/HCO.0000000000001323. Epub 2026 Jul 1. PMID- 42387310 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Efficacy and Safety of Intensifying Once-Weekly Insulin Icodec Treatment With Once-Weekly Semaglutide in Adults With Type 2 Diabetes: A Single-Arm, Open-Label, Treat-to-Target, Phase 3b Trial (ONWARDS 8). PG - 8515-8522 LID - 10.1111/dom.71049 [doi] AB - AIMS: To investigate the efficacy and safety of intensifying once-weekly insulin icodec (icodec) with once-weekly semaglutide in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: ONWARDS 8 was a single-arm, open-label, treat-to-target, Phase 3b trial comprising a 26-week icodec run-in period and a 26-week semaglutide intensification period. Eligible participants were adults with T2D (glycated haemoglobin [HbA1c]: 7.5%-10.5%) receiving daily basal insulin but not receiving a glucagon-like peptide-1 receptor agonist. Following the run-in period, participants with HbA1c levels > 7.0% and /=24 years) with obesity (body mass index [BMI] >/=30) and diabetes who underwent their first BMS or initiated GLP-1RA therapy between January 1, 2010, and December 31, 2022, were identified. Propensity score matching yielded 2721 matched pairs, who were followed up for up to 12.5 years (mean [SD], 6.5 [3.5] years), through December 31, 2023. Data cleaning and analyses were conducted from June to October 2025. EXPOSURES: Treatment with GLP-1RAs or BMS. MAIN OUTCOMES AND MEASURES: Health care utilization costs incurred by the health system, excluding costs of the index interventions. Attributable costs were estimated using a difference-in-differences approach and modeled with multivariable linear regression. RESULTS: The matched cohort included 5442 adults (mean [SD] age, 51 [10] years; 3243 women [59.6%]; mean [SD] BMI, 40.5 [6.0]). Mean (SD) monthly follow-up costs were higher among patients treated with GLP-1RAs than those who underwent BMS ($415.3 [$746.7] vs $304.9 [$628.5]). The adjusted difference-in-differences method showed $109.0 higher monthly costs per patient for GLP-1RA treatment (SE = $17.0; P < .001), associated primarily with hospitalization costs ($43.9; SE = $13.3; P = .001) and non-GLP-1 medication costs ($52.5; SE = $4.4; P < .001). Most cost differences accrued within the first 4 years. BMS was associated with greater early reductions in BMI and hemoglobin A1c, whereas GLP-1RA treatment showed more modest but sustained effects. CONCLUSIONS AND RELEVANCE: This cohort study found that, among adults with obesity and diabetes, health care utilization costs were higher with GLP-1RA treatment than with BMS, excluding intervention costs, largely reflecting differences in early clinical trajectories. These findings suggest that, among patients eligible for both interventions, BMS may confer combined clinical and economic advantages over long-term follow-up. FAU - Wolff Sagy, Yael AU - Wolff Sagy Y AD - Branch of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel. FAU - Winter, Eitan Ernest AU - Winter EE AD - Branch of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel. FAU - Abu Ahmad, Wiessam AU - Abu Ahmad W AD - Branch of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel. AD - Braun School of Public Health, Hebrew University-Hadassah, Jerusalem, Israel. FAU - Battat, Erez AU - Battat E AD - Branch of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel. FAU - Arbel, Ronen AU - Arbel R AD - Maximizing Health Outcomes Research Lab, Sapir College, Sderot, Israel. AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. FAU - Reges, Orna AU - Reges O AD - Department of Health System Management, Ariel University, Ariel, Israel. FAU - Dicker, Dror AU - Dicker D AD - School of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel. FAU - Lavie, Gil AU - Lavie G AD - Branch of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel. AD - Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/economics/statistics & numerical data MH - *Diabetes Mellitus, Type 2/economics/drug therapy/therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/economics/therapeutic use MH - *Health Care Costs/statistics & numerical data MH - Israel MH - *Obesity/drug therapy/economics/surgery MH - *Patient Acceptance of Health Care/statistics & numerical data MH - Retrospective Studies PMC - PMC13324868 COIS- Conflict of Interest Disclosures: Dr Arbel reported receiving grants from Horizon Europe. Dr Reges reported receiving grants from the Israel Science Foundation and Israel-Ministry of Innovation, Science and Technology outside the submitted work. Dr Dicker reported receiving grants, personal fees, and nonfinancial support from Novo Nordisk, Lilly, and Boehringer Ingelheim; and personal fees from Rafa, AstraZenca, and Roche outside the submitted work. Dr Lavie reported receiving grants from the Israel Science Foundation outside the submitted work. No other disclosures were reported. EDAT- 2026/07/01 16:11 MHDA- 2026/07/01 22:34 PMCR- 2026/07/01 CRDT- 2026/07/01 11:33 PHST- 2026/07/01 22:34 [medline] PHST- 2026/07/01 16:11 [pubmed] PHST- 2026/07/01 11:33 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 2851020 [pii] AID - zoi260592 [pii] AID - 10.1001/jamanetworkopen.2026.21305 [doi] PST - epublish SO - JAMA Netw Open. 2026 Jul 1;9(7):e2621305. doi: 10.1001/jamanetworkopen.2026.21305. PMID- 42383806 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261008 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 15 IP - 19 DP - 2026 Oct 6 TI - Long-Term Outcomes of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Peripheral Artery Disease and Type 2 Diabetes. PG - e045664 LID - 10.1161/JAHA.125.045664 [doi] AB - BACKGROUND: Peripheral artery disease (PAD) affects >236 million people globally, particularly among those with type 2 diabetes. GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1 RAs) offer cardiovascular and kidney benefits, but their impact on PAD-specific outcomes is underexplored. This study evaluates long-term GLP-1 RA effects on adverse outcomes in this population. METHODS: A retrospective cohort study using the TriNetX platform (January 1, 2010-January 1, 2025) included patients with both PAD and type 2 diabetes prescribed either GLP-1 RAs or metformin, excluding those with recent cardiovascular events, end-stage renal disease, or prior amputations. Propensity score matching was performed to account for confounding. Outcomes at 5 years included mortality, myocardial infarction, hospitalization, stroke, revascularization, amputations, dialysis, major adverse cardiovascular events, and kidney events. RESULTS: After matching, 2133 patients per cohort were analyzed in the overall group with PAD. At 5 years, GLP-1 RA therapy was associated with lower mortality (10.31% versus 14.49%; hazard ratio [HR], 0.74 [95% CI, 0.62-0.88]; P=0.0005), hospitalization (69.3% versus 74.7%; HR, 0.87 [95% CI, 0.81-0.94]; P=0.0002), revascularization (4.69% versus 7.27%; HR, 0.64 [95% CI, 0.50-0.82]; P=0.0004), major amputation (2.30% versus 4.36%; HR, 0.52 [95% CI, 0.37-0.74]; P=0.0002), and minor amputation (4.03% versus 6.42%; HR, 0.63 [95% CI, 0.48-0.83]; P=0.0007). major adverse cardiovascular events, myocardial infarction, stroke, and major adverse kidney events were similar between groups. CONCLUSIONS: GLP-1 RAs were associated with lower rates of mortality, major amputation, revascularization, and hospitalization in PAD and type 2 diabetes patients. These findings support prioritizing GLP-1 RAs for limb-specific and cardiovascular outcomes in this high-risk group. FAU - Rosenzveig, Akiva AU - Rosenzveig A AUID- ORCID: 0000-0001-6757-8841 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Tefera, Leben AU - Tefera L AUID- ORCID: 0000-0001-9640-6774 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Agrawal, Ankit AU - Agrawal A AUID- ORCID: 0000-0001-7885-6667 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Rajendran, Judah AU - Rajendran J AUID- ORCID: 0000-0002-4342-6090 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Massad, Faysal AU - Massad F AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Badwan, Osamah AU - Badwan O AUID- ORCID: 0000-0001-9899-3220 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Wajsberg, Julia AU - Wajsberg J AD - Department of Medicine University Hospitals Cleveland OH USA. FAU - Chaudhury, Pulkit AU - Chaudhury P AUID- ORCID: 0000-0002-8210-8394 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Zidar, David AU - Zidar D AUID- ORCID: 0000-0002-2805-3986 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. FAU - Paul, Timir K AU - Paul TK AUID- ORCID: 0000-0001-7766-6714 AD - University of Tennessee Health Sciences Center at Nashville, Ascension St. Thomas Hospital Nashville TN USA. FAU - Bhatt, Deepak L AU - Bhatt DL AUID- ORCID: 0000-0002-1278-6245 AD - Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai New York NY USA. FAU - Nanjundappa, Aravinda AU - Nanjundappa A AUID- ORCID: 0000-0001-7194-6328 AD - Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA. LA - eng PT - Journal Article DEP - 20260701 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) SB - IM CIN - J Am Heart Assoc. 2026 Oct 6;15(19):e052332. doi: 10.1161/JAHA.126.052332. PMID: 42669900 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality/diagnosis MH - *Peripheral Arterial Disease/drug therapy/mortality/complications/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Time Factors MH - Middle Aged MH - Treatment Outcome MH - Amputation, Surgical/statistics & numerical data MH - Metformin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - *Incretins/therapeutic use/adverse effects OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes OT - peripheral artery disease EDAT- 2026/07/01 16:11 MHDA- 2026/10/08 05:31 CRDT- 2026/07/01 09:23 PHST- 2026/10/08 05:31 [medline] PHST- 2026/07/01 16:11 [pubmed] PHST- 2026/07/01 09:23 [entrez] AID - 10.1161/JAHA.125.045664 [doi] PST - ppublish SO - J Am Heart Assoc. 2026 Oct 6;15(19):e045664. doi: 10.1161/JAHA.125.045664. Epub 2026 Jul 1. PMID- 42380063 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Mental Health Disorders in Type 2 Diabetes: Active Comparator, New User Cohort Study. PG - 8482-8493 LID - 10.1111/dom.70985 [doi] AB - AIMS: We evaluated the risk of mental health disorders among glucagon-like peptide-1 receptor agonist (GLP1RA) users compared with users of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS: We conducted a nationwide, active-comparator new-user cohort study using the Korean claims database from 2012 to 2022. Patients aged >/= 18 years who initiated GLP1RAs, SGLT2 inhibitors, or DPP4 inhibitors for type 2 diabetes were included. We compared the hazard ratios (HRs) and 95% confidence intervals (CIs) for depression, anxiety, sleep disorders, and suicide using the Cox proportional hazards models after propensity score matching. RESULTS: The 18 825 GLP1RA users were matched with 623 750 SGLT2 inhibitor users, and 5762 GLP1RA users with 874 902 inhibitor users. Compared with DPP4 inhibitors, GLP1RAs were not associated with increased risks of depression (HR 1.00 [95% CI, 0.83-1.20]), anxiety (0.92 [0.77-1.08]), or sleep disorder (1.14 [0.97-1.33]). In contrast, compared with SGLT2 inhibitors, GLP1RA use was associated with higher risks of depression (1.20 [1.09-1.31]) and anxiety (1.09 [1.00-1.19]). Suicidality events were rare and not observed among GLP1RA users. CONCLUSIONS: Initiation of GLP1RAs was not associated with increased risk of mental health disorders compared with DPP4 inhibitors. Differences in the risk of depression and anxiety were observed compared with SGLT2 inhibitors. These findings suggest that psychiatric safety signals may vary by active comparator and provide real-world evidence on the psychiatric safety of GLP-1-based therapies. Further studies incorporating detailed clinical data and high-risk subgroups are needed to clarify underlying mechanisms. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kim, Chungsoo AU - Kim C AUID- ORCID: 0000-0003-1802-1777 AD - Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea. AD - Center for Outcomes Research and Evaluations, Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Kim, Seonji AU - Kim S AUID- ORCID: 0000-0002-4993-7537 AD - Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea. AD - Yonsei Institute for Digital Health, Yonsei University, Seoul, Republic of Korea. FAU - Lee, Dong Yun AU - Lee DY AUID- ORCID: 0000-0002-3678-9862 AD - Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea. AD - Bongdam Forest Mental Health Clinic, Hwaseong, Republic of Korea. FAU - Han, Eugene AU - Han E AUID- ORCID: 0000-0002-3237-3317 AD - Department of Internal Medicine, Keimyung University, School of Medicine, Daegu, Republic of Korea. FAU - Lee, Yong-Ho AU - Lee YH AUID- ORCID: 0000-0002-6219-4942 AD - Yonsei Institute for Digital Health, Yonsei University, Seoul, Republic of Korea. AD - Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - You, Seng Chan AU - You SC AUID- ORCID: 0000-0002-5052-6399 AD - Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea. AD - Yonsei Institute for Digital Health, Yonsei University, Seoul, Republic of Korea. LA - eng GR - RS-2025-25459621/Ministry of Health & Welfare, Republic of Korea/ GR - RS-2024-00341426/Ministry of Science and ICT, South Korea/ PT - Comparative Study PT - Journal Article DEP - 20260630 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - *Mental Disorders/epidemiology/chemically induced MH - Cohort Studies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Adult MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Republic of Korea/epidemiology MH - Depression/epidemiology/chemically induced PMC - PMC13448862 OTO - NOTNLM OT - DPP4 inhibitor OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - anxiety disorder OT - depression OT - type 2 diabetes COIS- Seng Chan You reports grants from Daiichi Sankyo. He is a coinventor of granted Korean patents DP-2023-1223 and DP-2023-0920 and has pending Patent Applications DP-2024-0909, DP-2024-0908, DP-2022-1658, DP-2022-1478, and DP-2022-1365, unrelated to the current work. Seng Chan You is the Chief Executive Officer of PHI Digital Healthcare. The other authors report no conflicts of interest. EDAT- 2026/07/01 04:11 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/30 23:03 PHST- 2026/05/21 00:00 [revised] PHST- 2026/03/27 00:00 [received] PHST- 2026/06/01 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/07/01 04:11 [pubmed] PHST- 2026/06/30 23:03 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70985 [pii] AID - 10.1111/dom.70985 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8482-8493. doi: 10.1111/dom.70985. Epub 2026 Jun 30. PMID- 42379510 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261001 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 139 IP - 11 DP - 2026 Nov TI - GLP-1 receptor agonists and age-related macular degeneration risk in diabetes or non-diabetic obesity: A retrospective cohort study. PG - 1470-1479 LID - S0002-9343(26)00487-0 [pii] LID - 10.1016/j.amjmed.2026.06.023 [doi] AB - OBJECTIVE: We conducted a retrospective cohort study to examine the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and age-related macular degeneration. METHODS: This is a retrospective cohort study including two cohorts of adults aged >/=50 years free of macular degeneration at baseline, including 1) the diabetes cohort comparing age-related macular degeneration risk between GLP-1RAs and metformin users, and 2) the obesity cohort, consisting of individuals with a body mass index >/=30 kg/m(2) without type 2 diabetes, comparing the risk of age-related macular degeneration between GLP-1RAs and other weight-loss medications. A 1:1 propensity score matching was performed to balance covariates. Cox proportional hazards models and Kaplan-Meier analysis were used to assess the risk of age-related macular degeneration across 5 years of follow-up. RESULTS: A total of 147,800 participants with diabetes and 49,518 participants with obesity were included. In the diabetes cohort, GLP-1RAs were associated with lower total age-related macular degeneration (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.75-0.91) and dry age-related macular degeneration (HR, 0.84; 95% CI, 0.73-0.98) risks compared to metformin. In the obesity cohort, GLP-1RAs were associated with a lower risk of total age-related macular degeneration (HR, 0.77; 95% CI, 0.61-0.98) and dry age-related macular degeneration (HR, 0.65; 95% CI, 0.46-0.94) compared to other weight-loss medications. CONCLUSIONS: GLP-1RAs were associated with a lower risk of age-related macular degeneration, particularly the dry form, compared with metformin or other weight-loss medications. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Pan, Ssu-Yu AU - Pan SY AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Weng, Chien-Hsiang AU - Weng CH AD - Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA; Brown Health Medical Group Primary Care, Brown University Health, Providence, Rhode Island, USA. FAU - Sheen, Yi-Jing AU - Sheen YJ AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Center for Quantitative Imaging in Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Tsai, Shang-Feng AU - Tsai SF AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan. FAU - Lin, Jun-Fu AU - Lin JF AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, Jun-Peng AU - Chen JP AD - Biostatistics Group, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Ching-Heng AU - Lin CH AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Huang, Shun-Ping AU - Huang SP AD - Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan. FAU - Chang, Chia-Jen AU - Chang CJ AD - Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Hui-Ju AU - Lin HJ AD - Eye Center, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. FAU - Wang, I-Jong AU - Wang IJ AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. FAU - Chou, Chien-Chih AU - Chou CC AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: doctorccc@gmail.com. LA - eng PT - Journal Article DEP - 20260630 PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Macular Degeneration/epidemiology/prevention & control MH - *Obesity/complications/drug therapy MH - Male MH - Aged MH - Metformin/therapeutic use MH - Semaglutide MH - Exenatide/therapeutic use MH - Risk Factors MH - Proportional Hazards Models OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - age-related macular degeneration OT - diabetes mellitus OT - obesity COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/07/01 00:35 MHDA- 2026/10/01 23:29 CRDT- 2026/06/30 19:33 PHST- 2026/01/03 00:00 [received] PHST- 2026/06/11 00:00 [revised] PHST- 2026/06/14 00:00 [accepted] PHST- 2026/10/01 23:29 [medline] PHST- 2026/07/01 00:35 [pubmed] PHST- 2026/06/30 19:33 [entrez] AID - S0002-9343(26)00487-0 [pii] AID - 10.1016/j.amjmed.2026.06.023 [doi] PST - ppublish SO - Am J Med. 2026 Nov;139(11):1470-1479. doi: 10.1016/j.amjmed.2026.06.023. Epub 2026 Jun 30. PMID- 42376874 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 23 IP - 3 DP - 2026 May-Jun TI - Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study. PG - 14791641261465360 LID - 10.1177/14791641261465360 [doi] LID - 14791641261465360 AB - BackgroundWith the increasing use of GLP-1 receptor agonists and dual GIP/GLP-1 agonists for managing obesity and type 2 diabetes, understanding their real-world effectiveness and safety is essential. This TriNetX analysis directly compares clinical outcomes among patients treated with tirzepatide vs semaglutide.MethodWe utilized data from the TriNetX Research Network, identifying patients aged > 40 years or with obesity ("BMI >/= 30 kg/m2") and type 2 diabetes (HbA1c >/= 6.5% or fasting glucose.>/= 125 mg/dL). Qualifying events were restricted to May 1, 2022, through November 21, 2024. We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists. The index date was defined as the first co-occurrence of the obesity/diabetes criteria and the respective drug prescription. To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort. Outcomes, including all-cause mortality, MACE, heart failure exacerbation, ischemic stroke/TIA, hospitalization/ED use, dementia, UTI, adverse Gastrointestinal (GI) effects, and changes in HbA1c, were assessed within a 1-year window after the index date.ResultsOur matched cohort had a mean age of 75 years, with 45% male patients and 74% identified as white. Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978). All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562). The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up. There was no significant difference in heart failure exacerbation or UTI incidence. GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997), while hospitalization or emergency visits were comparable between the two groups.ConclusionIn this propensity matched cohort of patients with obesity and type 2 diabetes, tirzepatide demonstrated improved cardiometabolic outcomes compared to semaglutide, including lower all-cause mortality and lower HbA1c. These findings support the cardiovascular safety and efficacy of tirzapetide and highlight the need for further studies to evaluate its effectiveness in broader clinical populations. FAU - Qadeer, Abdul AU - Qadeer A AUID- ORCID: 0009-0005-8478-7086 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Khalid, Marwah Bintay AU - Khalid MB AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. RINGGOLD: 123683 FAU - Syed, Ridwan AU - Syed R AD - Department of Cardiovascular Medicine, The University of Texas Medical Branch, Galveston, TX, USA. FAU - Jain, Samiksha AU - Jain S AD - Department of Medicine, Mobile Infirmary Medical Center, Mobile, AL, USA. RINGGOLD: 76093 FAU - Zakaria, Faiza AU - Zakaria F AD - Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, Michigan, USA. FAU - Khan, Muhammad Huzaifa Ahmed AU - Khan MHA AD - Department of Internal Medicine, Prime South GME Consortium Harlingen Medical Center, TX, USA. FAU - Gohar, Najam AU - Gohar N AD - Department of Internal Medicine, Ameer-ud-Din Medical College, Lahore, Pakistan. FAU - Shoukat, Ashraf AU - Shoukat A AD - Department of Medicine, Nishtar Medical University, Multan, Pakistan. RINGGOLD: 619131 FAU - Mortada, Ibrahim AU - Mortada I AUID- ORCID: 0009-0006-9215-880X AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Hamza, Izhan AU - Hamza I AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Motiwala, Afaq AU - Motiwala A AUID- ORCID: 0000-0002-4750-7090 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Raja, Muhammad Waheed AU - Raja MW AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Blackwell, Thomas AU - Blackwell T AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jneid, Hani AU - Jneid H AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260630 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - Male MH - Female MH - Treatment Outcome MH - Middle Aged MH - Retrospective Studies MH - *Obesity/drug therapy/diagnosis/mortality MH - Aged MH - Time Factors MH - Blood Glucose/drug effects/metabolism MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabesity/mortality MH - Biomarkers/blood MH - *Incretins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Risk Factors MH - Risk Assessment MH - Glycemic Control/adverse effects PMC - PMC13319829 OTO - NOTNLM OT - obesity diabetes mellitus OT - semaglutide OT - tirzepatide COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/06/30 16:10 MHDA- 2026/06/30 16:11 PMCR- 2026/06/30 CRDT- 2026/06/30 07:03 PHST- 2026/06/30 16:11 [medline] PHST- 2026/06/30 16:10 [pubmed] PHST- 2026/06/30 07:03 [entrez] PHST- 2026/06/30 00:00 [pmc-release] AID - 10.1177_14791641261465360 [pii] AID - 10.1177/14791641261465360 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2026 May-Jun;23(3):14791641261465360. doi: 10.1177/14791641261465360. Epub 2026 Jun 30. PMID- 42372278 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 9 DP - 2026 Sep TI - Leveraging Real-World Evidence to Inform Regulatory, Clinical, and Coverage Decisions Related to Glucagon-like Peptide-1-Based Therapies: Synopsis of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. PG - 1328-1337 LID - 10.7326/ANNALS-25-05468 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed obesity and diabetes management, with rapidly expanding indications and use among U.S. adults. Despite their promise, key questions remain about optimal treatment pathways, long-term safety, effectiveness across diverse populations, adherence, and economic impact. Real-world evidence (RWE) derived from electronic health records, claims, and other data sources could address these gaps, but unique challenges complicate its use, such as inconsistent insurance coverage, high discontinuation rates, medication shortages, compounded formulations, and off-label prescribing. To explore these issues, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop in May 2025 with experts from regulatory agencies, guideline committees, payers, and academia. Discussions focused on identifying knowledge gaps in GLP-1RA use, evaluating how RWE informs practice, assessing limitations of real-world data, and strategies to reduce bias in RWE. Presentations emphasized RWE's potential to complement randomized trials by capturing rare adverse events, long-term outcomes, and effectiveness in routine care. However, persistent challenges include data reliability, confounding, and incomplete capture of medication use and outcomes, particularly in pediatric and underserved populations. Coverage decisions remain heterogeneous across Medicare, Medicaid, and private payers and across time, underscoring the need for rigorous cost-benefit analyses. The workshop concluded that robust RWE is essential for developing value-based coverage policies and optimizing GLP-1RA use. Continued investment in high-quality data infrastructure and analytic methods will be critical to inform regulatory, clinical, and economic decisions as utilization expands. FAU - Arterburn, David AU - Arterburn D AD - Kaiser Permanente Washington Health Research Institute, Seattle, Washington (D.A.). FAU - Curtis, Lesley H AU - Curtis LH AUID- ORCID: 0000-0002-3286-9371 AD - Duke University School of Medicine, Durham, North Carolina (L.H.C., D.D., A.S.). FAU - Toh, Sengwee AU - Toh S AUID- ORCID: 0000-0002-5160-0810 AD - Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts (S.T., D.R.W.). FAU - Bradley, Marie C AU - Bradley MC AD - U.S. Food and Drug Administration, Washington, DC (M.C.B.). FAU - D'Alessio, David AU - D'Alessio D AD - Duke University School of Medicine, Durham, North Carolina (L.H.C., D.D., A.S.). FAU - Duchovny, Noelia AU - Duchovny N AUID- ORCID: 0009-0004-5626-0589 AD - Congressional Budget Office, Washington, DC (N.D.). FAU - Hines, David AU - Hines D AUID- ORCID: 0009-0000-8288-0029 AD - Metro Nashville Public Schools, Nashville, Tennessee (D.H.). FAU - Narain, Kimberly AU - Narain K AUID- ORCID: 0000-0001-8548-1728 AD - University of California, Los Angeles, Los Angeles, California (K.N.). FAU - Parekh, Anand AU - Parekh A AD - University of Michigan School of Public Health, Ann Arbor, Michigan (A.P.). FAU - Skinner, Asheley AU - Skinner A AD - Duke University School of Medicine, Durham, North Carolina (L.H.C., D.D., A.S.). FAU - Wee, Christina C AU - Wee CC AD - Annals of Internal Medicine and American College of Physicians, Philadelphia, Pennsylvania (C.C.W.). FAU - Wong, John B AU - Wong JB AUID- ORCID: 0000-0003-4203-9010 AD - Tufts University School of Medicine, Boston, Massachusetts (J.B.W.). FAU - Wright, Davene R AU - Wright DR AUID- ORCID: 0000-0002-8574-4572 AD - Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts (S.T., D.R.W.). FAU - Osganian, Stavroula K AU - Osganian SK AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (S.K.O., C.H.). FAU - Hales, Craig AU - Hales C AUID- ORCID: 0000-0002-2355-1177 AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (S.K.O., C.H.). LA - eng GR - K08 AG068372/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260630 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/economics/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Insurance Coverage MH - National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/06/29 22:36 MHDA- 2026/09/15 05:06 CRDT- 2026/06/29 17:03 PHST- 2026/09/15 05:06 [medline] PHST- 2026/06/29 22:36 [pubmed] PHST- 2026/06/29 17:03 [entrez] AID - 10.7326/ANNALS-25-05468 [doi] PST - ppublish SO - Ann Intern Med. 2026 Sep;179(9):1328-1337. doi: 10.7326/ANNALS-25-05468. Epub 2026 Jun 30. PMID- 42372277 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260922 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 9 DP - 2026 Sep TI - Methodological Approaches to Real-World Evidence Generation for Glucagon-like Peptide-1-Based Therapies: Synopsis of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. PG - 1319-1327 LID - 10.7326/ANNALS-26-00202 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the clinical approach to managing obesity and type 2 diabetes. As approved indications have expanded, use of GLP-1RAs has increased rapidly in the United States. Although randomized trials demonstrate strong efficacy, many questions remain about their optimal use in clinical practice. Real-world data (RWD) from electronic health records, registries, insurance claims, and other sources offer a promising avenue to address these questions. However, concerns about data quality, selection bias, and incomplete ascertainment of medication use and outcomes pose significant challenges to the validity of the resulting evidence. In May 2025, the National Institute of Diabetes and Digestive and Kidney Diseases convened experts from regulatory agencies, payer organizations, and academia to explore these challenges. This second of 2 synopsis articles on the workshop summarizes the discussion around the strengths and limitations of various RWD sources and methodological approaches to strengthen causal inference and generalizability. Presenters highlighted pragmatic clinical trials and target trial emulation as strategies to generate stronger real-world evidence (RWE) that is relevant to both clinical practice and policy. The workshop underscored that careful attention to study design, data limitations, and analytic approach is essential to yield RWE that informs clinicians, patients, payers, and policymakers. FAU - Curtis, Lesley H AU - Curtis LH AUID- ORCID: 0000-0002-3286-9371 AD - Duke University School of Medicine, Durham, North Carolina (L.H.C.). FAU - Arterburn, David AU - Arterburn D AD - Kaiser Permanente Washington Health Research Institute, Seattle, Washington (D.A.). FAU - Toh, Sengwee AU - Toh S AUID- ORCID: 0000-0002-5160-0810 AD - Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts (S.T.). FAU - Guo, Jingchuan AU - Guo J AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmacy Practice, Purdue University College of Pharmacy and Regenstrief Institute, Indianapolis, Indiana (J.G.). FAU - Hernan, Miguel A AU - Hernan MA AUID- ORCID: 0000-0003-1619-8456 AD - CAUSALab, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (M.A.H.). FAU - Iturralde, Esti AU - Iturralde E AUID- ORCID: 0000-0001-6837-4998 AD - Kaiser Permanente Northern California Division of Research, Pleasanton, and Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California (E.I.). FAU - Jastreboff, Ania AU - Jastreboff A AD - Yale University School of Medicine, New Haven, Connecticut (A.J.). FAU - Lewis, Kristina H AU - Lewis KH AUID- ORCID: 0000-0002-4921-7230 AD - Wake Forest University School of Medicine, Winston-Salem, North Carolina (K.H.L.). FAU - Lund, Jennifer L AU - Lund JL AUID- ORCID: 0000-0002-1108-0689 AD - University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Chapel Hill, North Carolina (J.L.L.). FAU - Maciejewski, Matthew L AU - Maciejewski ML AD - Duke University School of Medicine; Duke-Margolis Institute for Health Policy, Duke University; and Center of Innovation to Accelerate Discovery and Practice Transformation, Durham VA Medical Center, Durham, North Carolina (M.L.M.). FAU - McCoy, Rozalina G AU - McCoy RG AUID- ORCID: 0000-0002-2289-3183 AD - University of Maryland School of Medicine, Baltimore, and University of Maryland Institute for Health Computing, North Bethesda, Maryland (R.G.M.). FAU - McTigue, Kathleen M AU - McTigue KM AUID- ORCID: 0000-0002-0752-1576 AD - University of Pittsburgh, Pittsburgh, Pennsylvania (K.M.M.). FAU - Narain, Kimberly AU - Narain K AUID- ORCID: 0000-0001-8548-1728 AD - University of California, Los Angeles, Los Angelos, California (K.N.). FAU - Wee, Christina C AU - Wee CC AD - Annals of Internal Medicine and American College of Physicians, Philadelphia, Pennsylvania (C.C.W.). FAU - Osganian, Stavroula K AU - Osganian SK AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (S.K.O., C.H.). FAU - Hales, Craig AU - Hales C AUID- ORCID: 0000-0002-2355-1177 AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (S.K.O., C.H.). LA - eng GR - K23 MH126078/MH/NIMH NIH HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260630 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) MH - Obesity/drug therapy MH - *Evidence-Based Medicine MH - *Glucagon-Like Peptide 1 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/06/29 22:36 MHDA- 2026/09/15 05:06 CRDT- 2026/06/29 17:03 PHST- 2026/09/15 05:06 [medline] PHST- 2026/06/29 22:36 [pubmed] PHST- 2026/06/29 17:03 [entrez] AID - 10.7326/ANNALS-26-00202 [doi] PST - ppublish SO - Ann Intern Med. 2026 Sep;179(9):1319-1327. doi: 10.7326/ANNALS-26-00202. Epub 2026 Jun 30. PMID- 42372276 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260818 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 8 DP - 2026 Aug TI - Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes : A Phase 2b Randomized Clinical Trial. PG - 1107-1116 LID - 10.7326/ANNALS-25-04623 [doi] AB - BACKGROUND: Bofanglutide is a novel glucagon-like peptide-1 receptor agonist under development for type 2 diabetes mellitus (T2DM) and overweight and obesity. OBJECTIVE: To evaluate the efficacy and safety of bofanglutide compared with semaglutide. DESIGN: Phase 2b, randomized, open-label, active-controlled trial. (ClinicalTrials.gov: NCT06256549). SETTING: Multicenter (37 sites in China). PARTICIPANTS: Adults with T2DM who were drug-naive or receiving stable oral antidiabetic drugs (glycated hemoglobin A(1c) [HbA(1c)], 7.0% to 11.0%). INTERVENTION: Participants were randomly assigned 1:1:1:1:1 to 1 of 5 treatment groups: bofanglutide titrated to targets of 12, 18, or 24 mg (biweekly [once every 2 weeks; Q2W]); bofanglutide titrated to 24 mg (once weekly [QW]); or semaglutide titrated to 1 mg QW. MEASUREMENTS: Change in HbA(1c) level from baseline to week 24 (primary end point), secondary efficacy end points, and safety. RESULTS: Overall, 272 participants were enrolled, with a mean age of 50.8 years, HbA(1c) level of 8.35%, and body mass index of 27.9 kg/m(2). At week 24, HbA(1c) level change from baseline was -1.87% (95% CI, -2.11% to -1.63%), -2.28% (CI, -2.54% to -2.03%), and -1.94% (CI, -2.19% to -1.69%) for bofanglutide 12, 18, 24 mg Q2W, respectively; -2.32% (CI, -2.57% to -2.06%) for bofanglutide 24 mg QW; and -1.60% (CI, -1.85% to -1.35%) for 1 mg of semaglutide QW. Corresponding treatment differences versus semaglutide were -0.27% (CI, -0.61% to -0.08%), -0.68% (CI, -1.04% to -0.33%), -0.34% (CI, -0.70% to 0.02%), and -0.72% (CI, -1.08% to -0.36%), respectively. Gastrointestinal adverse events (GIAEs) (mostly grade 1 or 2 in severity) occurred in 81.8% to 87.3% and 51.9% of participants in the bofanglutide and semaglutide groups, respectively. Hypoglycemia occurred in 0% to 3.8% versus 1.9%, with no severe hypoglycemia. LIMITATION: Open-label, short duration, only Chinese participants. CONCLUSION: Meaningful reductions in HbA(1c) levels were seen with bofanglutide in patients with T2DM; GIAEs were the most common and generally manageable. PRIMARY FUNDING SOURCE: Gan & Lee Pharmaceuticals. FAU - Liu, Ming AU - Liu M AUID- ORCID: 0000-0003-2665-4072 AD - Tianjin Medical University General Hospital, Tianjin, China (M.L.). FAU - Cheng, Zhifeng AU - Cheng Z AD - The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China (Z.C.). FAU - Lu, Li AU - Lu L AD - Shandong Guoxin Yiyang Group Zaozhuang Central Hospital, Zaozhuang, China (L.L.). FAU - Cai, Hanqing AU - Cai H AD - The Second Hospital of Jilin University, Changchun, China (H.C.). FAU - Liu, Jingyu AU - Liu J AD - Chengdu Seventh People's Hospital, Chengdu, China (Jingyu Liu). FAU - Liu, Jinling AU - Liu J AD - Weifang Hospital of Traditional Chinese Medicine, Weifang, China (Jinling Liu). FAU - Zheng, Yueyue AU - Zheng Y AD - The First Affiliated Hospital of Nanyang Medical College, Nanyang, China (Y.Z.). FAU - Wang, Su AU - Wang S AUID- ORCID: 0000-0003-2892-9121 AD - Tianjin Fifth Central Hospital, Tianjin, China (S.W.). FAU - Zhao, Jing AU - Zhao J AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Yang, Wei AU - Yang W AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Xie, Tian AU - Xie T AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Li, Yue AU - Li Y AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - He, Anshun AU - He A AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants, Rockville, Maryland (H.W.R.). FAU - Chen, Wei AU - Chen W AD - Gan & Lee Pharmaceuticals, Beijing, and Gan & Lee Pharmaceuticals Shandong, Linyi, China (W.C.). LA - eng SI - ClinicalTrials.gov/NCT06256549 PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260630 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Semaglutide/administration & dosage/adverse effects/therapeutic use MH - East Asian People COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/06/29 22:36 MHDA- 2026/08/17 23:39 CRDT- 2026/06/29 17:03 PHST- 2026/08/17 23:39 [medline] PHST- 2026/06/29 22:36 [pubmed] PHST- 2026/06/29 17:03 [entrez] AID - 10.7326/ANNALS-25-04623 [doi] PST - ppublish SO - Ann Intern Med. 2026 Aug;179(8):1107-1116. doi: 10.7326/ANNALS-25-04623. Epub 2026 Jun 30. PMID- 42372204 OWN - NLM STAT- MEDLINE DCOM- 20260811 LR - 20261005 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 44 IP - 23 DP - 2026 Aug 10 TI - Metabolic Modulation in Cancer Care: The Potential Role of Glucagon-Like Peptide-1 Receptor Agonists. PG - 2244-2252 LID - 10.1200/JCO-26-00062 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the management of type 2 diabetes and obesity by providing sustained improvements in glycemic control, weight loss, and cardiovascular outcomes. These benefits have led to increasing interest in their potential role in cancer treatment. Obesity and metabolic dysfunction are well-known factors that promote the development, progression, and resistance to therapy in various cancers, suggesting that drugs targeting these pathways may have anticancer effects. Emerging epidemiologic and clinical evidence shows that GLP-1RA therapy is linked to a lower risk of several obesity-related cancers, including GI, breast, endometrial, ovarian, prostate, and hematologic malignancies. Mechanistic studies also reveal effects on insulin signaling, long-term inflammation, angiogenesis, and immune system modulation. This comprehensive review integrates current knowledge of GLP-1RAs in cancer care, covering drug action, epidemiology, underlying mechanisms, and clinical application. We evaluate evidence for cancer prevention, their use as complementary treatments, and outcomes in patients with existing cancer. Overall, the evidence suggests that GLP-1RAs could become a novel class of agents linking metabolic health and cancer therapy, with potential applications in neoadjuvant treatment strategies, particularly in settings where prolonged neoadjuvant intervals allow for metabolic optimization before definitive surgical intervention. FAU - Temperley, Hugo C AU - Temperley HC AUID- ORCID: 0000-0001-9151-3431 AD - Department of Radiology, St James's Hospital, Dublin, Ireland. AD - Trinity St James's Cancer Institute, Dublin, Ireland. FAU - Kelly, Michael E AU - Kelly ME AUID- ORCID: 0000-0002-0757-6411 AD - Trinity St James's Cancer Institute, Dublin, Ireland. AD - Discipline of Surgery, School of Medicine, Trinity College Dublin - University of Dublin, Ireland. AD - Department of Surgery, St James Hospital, Dublin, Ireland. LA - eng PT - Journal Article PT - Review DEP - 20260629 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/metabolism/drug therapy/prevention & control/epidemiology MH - Obesity/drug therapy/metabolism/complications MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Hypoglycemic Agents/therapeutic use PMC - PMC13475729 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Michael E. Kelly Travel, Accommodations, Expenses: Medtronic No other potential conflicts of interest were reported. EDAT- 2026/06/29 18:43 MHDA- 2026/08/11 23:35 PMCR- 2026/06/29 CRDT- 2026/06/29 16:02 PHST- 2026/08/11 23:35 [medline] PHST- 2026/06/29 18:43 [pubmed] PHST- 2026/06/29 16:02 [entrez] PHST- 2026/06/29 00:00 [pmc-release] AID - JCO-26-00062 [pii] AID - 10.1200/JCO-26-00062 [doi] PST - ppublish SO - J Clin Oncol. 2026 Aug 10;44(23):2244-2252. doi: 10.1200/JCO-26-00062. Epub 2026 Jun 29. PMID- 42365987 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Real-World Evidence of the Effectiveness and Safety of Biosynthetic Semaglutide in Type 2 Diabetes: A Multicentre Study From Pakistan. PG - 8438-8451 LID - 10.1111/dom.71043 [doi] AB - AIMS: To evaluate the real-world effectiveness, safety and patient-reported outcomes of biosynthetic semaglutide in adults with type 2 diabetes mellitus (T2DM) receiving routine outpatient care in a cost-constrained setting. METHODS: This 30-week, prospective, multicentre, non-interventional study enrolled adults with T2DM initiating biosynthetic semaglutide. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to end of study (EOS). Secondary endpoints included changes in body weight, waist circumference, patient-reported outcomes (DTSQs and SF-36v2) and safety. RESULTS: Among 217 patients, mean HbA1c decreased from 9.27% to 7.41% at EOS (-1.86%; p < 0.001). At EOS, 76.6% achieved HbA1c < 8.0% and 38.7% achieved < 7.0%. Mean body weight decreased by -7.84 kg (p < 0.001), with 76.5% achieving >/= 5% weight loss. Significant reductions were also observed in body mass index and waist circumference. Treatment satisfaction and physical quality of life improved significantly. Adverse events were predominantly non-serious and gastrointestinal. No severe hypoglycaemic episodes occurred. CONCLUSIONS: In routine clinical practice, biosynthetic semaglutide was associated with clinically meaningful improvements in glycaemic control, body weight and physical quality of life. The safety profile remained consistent with established semaglutide therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12625000610437. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hussain, Arshad AU - Hussain A AD - North-West General Hospital, Peshawar, Pakistan. FAU - Wahab, Muhammad Umar AU - Wahab MU AD - Umar Diabetes and Foot Care Centre and Umar Diabetes Foundation, Islamabad, Pakistan. FAU - Qureshi, Saleem AU - Qureshi S AD - Department of Medicine, Center for Diabetes and Liver Disease, Islamabad, Pakistan. FAU - Raja, Umar Yousaf AU - Raja UY AD - Shifa International Hospitals Ltd., Islamabad, Pakistan. FAU - Munir, Atif AU - Munir A AD - Omer Hospital, Lahore, Pakistan. FAU - Gardezi, Shahnawaz AU - Gardezi S AD - City Hospital, Multan, Pakistan. FAU - Iqbal, Musarrat AU - Iqbal M AD - Department of Medicine, Center for Diabetes and Liver Disease, Islamabad, Pakistan. FAU - Afzal, Bilal AU - Afzal B AD - Mukhtar A Sheikh Hospital, Multan, Pakistan. FAU - Butt, Muhammad Daoud AU - Butt MD AD - School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Penang, Malaysia. FAU - Ong, Siew Chin AU - Ong SC AUID- ORCID: 0000-0002-9750-9588 AD - School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Penang, Malaysia. LA - eng GR - P504-LR-GAL008-0000001693-0000/BF Bioscience Pvt. Ltd./ PT - Journal Article PT - Multicenter Study DEP - 20260628 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Prospective Studies MH - Pakistan/epidemiology MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects MH - Aged MH - Quality of Life MH - Body Mass Index MH - Waist Circumference/drug effects MH - Patient Reported Outcome Measures MH - Blood Glucose PMC - PMC13448986 OTO - NOTNLM OT - biosynthetic semaglutide OT - glycaemic control OT - low- and middle-income countries OT - patient-reported outcomes OT - real-world evidence OT - safety and tolerability COIS- Dr. Arshad Hussain has received honoraria for delivering educational lectures from BF BioSciences. The funding organization provided support for the conduct of this study but had no role in the study design; data collection, analysis, or interpretation; manuscript preparation; or the decision to submit the manuscript for publication. All other authors declare that they have no competing financial or non financial interests. EDAT- 2026/06/29 00:30 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/28 20:14 PHST- 2026/06/15 00:00 [revised] PHST- 2026/05/05 00:00 [received] PHST- 2026/06/17 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/29 00:30 [pubmed] PHST- 2026/06/28 20:14 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71043 [pii] AID - 10.1111/dom.71043 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8438-8451. doi: 10.1111/dom.71043. Epub 2026 Jun 28. PMID- 42365860 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260730 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 238 DP - 2026 Aug TI - GLP-1 receptor agonists in pediatric obesity and diabetes: a systematic review of efficacy, metabolic effects, and safety. PG - 113400 LID - S0168-8227(26)00320-7 [pii] LID - 10.1016/j.diabres.2026.113400 [doi] AB - Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Soliman, Ashraf T AU - Soliman AT AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. Electronic address: atsoliman56@gmail.com. FAU - Alyafei, Fawzia AU - Alyafei F AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Khalil, Ahmed AU - Khalil A AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Kardousha, Ahmed Tawfik AU - Kardousha AT AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Ahmed, Shayma AU - Ahmed S AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Alaaraj, Nada AU - Alaaraj N AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Hamed, Noor AU - Hamed N AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260628 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Child MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adolescent MH - *Pediatric Obesity/drug therapy/metabolism MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use MH - Blood Glucose OTO - NOTNLM OT - Adolescents OT - Body mass index OT - Children OT - Dulaglutide OT - Exenatide OT - GLP-1 receptor agonists OT - HOMA-IR OT - HbA1c OT - Lipid profile OT - Liraglutide OT - Pediatric obesity OT - Safety OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/29 04:10 MHDA- 2026/07/08 18:51 CRDT- 2026/06/28 19:21 PHST- 2026/06/03 00:00 [received] PHST- 2026/06/22 00:00 [revised] PHST- 2026/06/27 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/06/29 04:10 [pubmed] PHST- 2026/06/28 19:21 [entrez] AID - S0168-8227(26)00320-7 [pii] AID - 10.1016/j.diabres.2026.113400 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Aug;238:113400. doi: 10.1016/j.diabres.2026.113400. Epub 2026 Jun 28. PMID- 42363996 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20261008 IS - 1522-1709 (Electronic) IS - 1520-9512 (Linking) VI - 30 IP - 4 DP - 2026 Jun 27 TI - GLP-1 receptor agonists and Risk of Cardiovascular and Pulmonary Complications in patients with OSA and Type 2 Diabetes Mellitus. LID - 199 [pii] LID - 10.1007/s11325-026-03748-2 [doi] AB - PURPOSE: Tirzepatide, a GLP-1 receptor agonist (GLP-1RA), is the first approved medication for the treatment of moderate to severe OSA and has previously been found to reduce cardiovascular risks in patients with type 2 diabetes mellitus (T2DM). Our study analyzed the effects of GLP-1RA in preventing cardiovascular and pulmonary complications in patients with OSA and T2DM during a 5-year follow-up period. METHODS: Through the TriNetX database, patients with OSA and T2DM from 2010-2022 were included. We compared patients receiving GLP-1RA versus other diabetic medications including metformin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea, and thiazolidinedione. Using a propensity score model, participants were matched on a range of demographic and clinical factors. Patients were evaluated for cardiovascular and pulmonary outcomes using a Kaplan-Meier survival analysis. We additionally analyzed the incidence rate of ED visits and inpatient admissions. RESULTS: After matching, 5,750 to 21,065 patients were included in the GLP-1RA versus other diabetes medication groups. GLP-1RA showed a lower risk of acute respiratory failure compared to metformin (HR 0.89; 95%CI 0.80-0.98), DPP-4 inhibitors (HR 0.78; 95%CI 0.71-0.85), sulfonylureas (HR 0.70; 95%CI 0.64-0.76) and TZD (HR 0.76; 95%CI 0.65-0.89). GLP-1RA group demonstrated significantly lower risk of pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and heart failure when compared to DPP-4 inhibitors, sulfonylureas, and TZD. CONCLUSION: GLP-1RA use was associated with a lower risk of pulmonary complications including acute respiratory failure, pulmonary hypertension, and COPD as well as lower ED visits and inpatient admissions compared to other diabetes medications. Further prospective studies are needed to evaluate the benefits of GLP-1RA. CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Borissov Borissov, Martin AU - Borissov Borissov M AD - Department of Medicine, University of Maryland Midtown Campus, 827 Linden Ave, Baltimore, MD, 21201, USA. AD - Department of Pulmonary, Critical Care and Sleep Medicine, University of Maryland School of Medicine, Baltimore, USA. FAU - Hwang, Soo Young AU - Hwang SY AUID- ORCID: 0000-0001-9845-7073 AD - Department of Medicine, University of Maryland Midtown Campus, 827 Linden Ave, Baltimore, MD, 21201, USA. sooyoung.hwang@umm.edu. AD - Department of Pulmonary, Critical Care and Sleep Medicine, University of Maryland School of Medicine, Baltimore, USA. sooyoung.hwang@umm.edu. FAU - Wickwire, Emerson M AU - Wickwire EM AD - Department of Pulmonary, Critical Care and Sleep Medicine, University of Maryland School of Medicine, Baltimore, USA. FAU - So, Jennifer Y AU - So JY AD - Department of Medicine, University of Maryland Midtown Campus, 827 Linden Ave, Baltimore, MD, 21201, USA. AD - Department of Pulmonary, Critical Care and Sleep Medicine, University of Maryland School of Medicine, Baltimore, USA. LA - eng PT - Journal Article DEP - 20260627 PL - Germany TA - Sleep Breath JT - Sleep & breathing = Schlaf & Atmung JID - 9804161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Tirzepatide/therapeutic use MH - *Sleep Apnea, Obstructive/drug therapy/complications MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Lung Diseases/prevention & control/epidemiology OTO - NOTNLM OT - Cardiovascular Complications OT - GLP-1 receptor agonist OT - Obstructive Sleep Apnea OT - Pulmonary Complications COIS- Declarations. Ethical approval: This study is a secondary analysis of existing data which does not involve intervention or interaction with human subjects and is de-identified per the HIPAA Privacy Rule. Informed Consent: Not applicable. Conflict of interest: EM Wickwire's institution has received research funding from the AASM Foundation, Department of Defense, Merck, NIH/NIA, ResMed, the ResMed Foundation, and the SRS Foundation. EM Wickwire has served as a scientific consultant to Axsome Therapeutics, DayZz, Eisai, EnsoData, Idorsia, Merck, Nox Health, Primasun, Purdue, and ResMed and is an equity shareholder in WellTap. EDAT- 2026/06/27 16:10 MHDA- 2026/06/28 06:35 CRDT- 2026/06/27 11:05 PHST- 2026/04/07 00:00 [received] PHST- 2026/06/20 00:00 [accepted] PHST- 2026/05/25 00:00 [revised] PHST- 2026/06/28 06:35 [medline] PHST- 2026/06/27 16:10 [pubmed] PHST- 2026/06/27 11:05 [entrez] AID - 10.1007/s11325-026-03748-2 [pii] AID - 10.1007/s11325-026-03748-2 [doi] PST - epublish SO - Sleep Breath. 2026 Jun 27;30(4):199. doi: 10.1007/s11325-026-03748-2. PMID- 42361988 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260729 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 461 DP - 2026 Oct 15 TI - From evidence to practice: Identifying candidates for semaglutide in chronic atherosclerotic disease. PG - 134646 LID - S0167-5273(26)00496-1 [pii] LID - 10.1016/j.ijcard.2026.134646 [doi] AB - BACKGROUND AND AIM: Randomised clinical trials (SELECT and SOUL) demonstrated that semaglutide, a GLP-1 receptor agonist, reduces the combined outcome measure of atherothrombotic events or cardiovascular mortality in patients with coronary artery disease, both with and without diabetes. Because real-world populations may differ from trial cohorts, we assessed the proportion of patients potentially eligible for semaglutide using the criteria set out by the regulatory authorities based on the SELECT and SOUL results. METHODS AND RESULTS: Patients whose clinical characteristics were comparable to those of patients enrolled in the SELECT and SOUL trials were identified within the START and BRING-UP prevention registries. Among 12,430 patients, 623 were excluded because of severe renal impairment or ongoing GLP-1 receptor agonist therapy. The final population included 11,807 patients: 8682 without diabetes and 3125 with diabetes. Among non-diabetic patients, 3689 (42.5%) were SELECT-like, defined as overweight or obese individuals with established coronary disease. Among diabetic patients, 3059 (97.9%) were SOUL-like, defined as individuals aged >/=50 years with cardiovascular disease. Overall, 6748 of 12,430 patients (54.3%) theoretically fulfilled eligibility criteria for semaglutide treatment in real-world cardiology practice. CONCLUSIONS: According to the criteria set out by the regulatory authorities based on the SELECT and SOUL trial results, a large proportion of patients with coronary artery disease managed by cardiologists may be potentially eligible for semaglutide therapy. Identifying the target population for this therapeutic strategy may help clinicians and healthcare authorities estimate unmet clinical needs and evaluate the sustainability of innovative approaches for secondary cardiovascular prevention. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Maggioni, Aldo P AU - Maggioni AP AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. Electronic address: maggioni@heartcarefoundation.it. FAU - Orso, Francesco AU - Orso F AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. FAU - Lucci, Donata AU - Lucci D AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. FAU - De Luca, Leonardo AU - De Luca L AD - Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. FAU - Colivicchi, Furio AU - Colivicchi F AD - Clinical and Rehabilitation Cardiology Department, San Filippo Neri Hospital, ASL Roma 1, Roma, Italy. LA - eng PT - Journal Article DEP - 20260626 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - *Atherosclerosis/drug therapy/epidemiology/diagnosis MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Chronic Disease MH - Randomized Controlled Trials as Topic/methods MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Registries MH - *Evidence-Based Medicine/methods MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Diabetes OT - GLP1 RA OT - Obesity OT - Semaglutide EDAT- 2026/06/27 00:59 MHDA- 2026/07/30 00:38 CRDT- 2026/06/26 19:32 PHST- 2026/03/18 00:00 [received] PHST- 2026/06/18 00:00 [revised] PHST- 2026/06/25 00:00 [accepted] PHST- 2026/07/30 00:38 [medline] PHST- 2026/06/27 00:59 [pubmed] PHST- 2026/06/26 19:32 [entrez] AID - S0167-5273(26)00496-1 [pii] AID - 10.1016/j.ijcard.2026.134646 [doi] PST - ppublish SO - Int J Cardiol. 2026 Oct 15;461:134646. doi: 10.1016/j.ijcard.2026.134646. Epub 2026 Jun 26. PMID- 42353761 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260830 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 17 IP - 6 DP - 2026 May 25 TI - Molecular Basis of Synergistic Causal Effect of Dual GLP-1R and GIPR Agonists for Risk Reduction in Diabetic Retinopathy, Alzheimer Disease, and Coronary Artery Disease in Diabetic Patients. LID - 10.3390/genes17060602 [doi] LID - 602 AB - Background: The dual agonism of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) becomes a groundbreaking treatment for type 2 diabetes (T2D) that achieves robust glycemic control and maintains body weight. It also induces potential risk reduction in diabetic retinopathy (DR), Alzheimer disease (AD), and heart diseases including coronary artery disease (CAD) in treated T2D patients. To date, the molecular basis underpinning the remarkable causal treatment effects and synergy of the dual agonism of GLP-1R and GIPR on risk reduction in T2D, CAD, DR and AD has not been systematically investigated. Methods: To elucidate the treatment effects and potential synergy of dual GLP-1R/GIPR agonism on risk reduction in T2D, CAD, DR and AD while minimizing the impact of confounders, we used a robust cis-Mendelian randomization (cis-MR) with a principal component-based generalized method of moments (PC-GMM) where blood-based glycated hemoglobin (HbA1c), high- and low-density lipoprotein cholesterol (HDL-c, LDL-c), and BMI were used as mediating biomarkers. Results: Our cis-MR analyses confirmed a synergistic causal protective effect of dual GLP-1R/GIPR agonism on T2D via HbA1c reduction [OR = 0.17; 95% CI = (0.11, 0.26); p = 3.68 x 10(-17)] which is more significant than either GLP-1R agonism or GIPR agonism alone. Similarly, the causal protective effect of dual GLP-1R/GIPR agonism via HbA1c reduction was also significant for DR [OR = 0.20; 95% CI = (0.11, 0.36); p = 9.22 x 10(-8)]. Further, our multivariate cis-MR (or cis-MVMR) analyses revealed that after adjusting for HbA1c, a synergistic protective effect on DR via a reduction in LDL-c is significant in dual GLP-1R/GIPR agonism [OR = 0.57; 95% CI = (0.29, 0.94)], while the protective effect on DR of LDL-c reduction is non-significant in either GLP-1R agonism or GIPR agonism alone. Also, after adjusting for HbA1c, the multivariate cis-MR results showed significant protective effects on AD via a reduction in LDL-c in GLP-1R/GIPR agonism [OR = 0.44; 95% CI = (0.25, 0.81)]. Importantly, the multivariate cis-MR results also revealed that dual GLP-1R/GIPR agonism has significant protective effects on CAD via both a reduction in BMI [OR = 0.46; 95% CI = (0.28, 0.75)] and an improvement in HDL [OR = 0.59; 95% CI = (0.39, 0.90)]. This is in support of the hypothesis that dual GLP-1R/GIPR agonism has a synergistic protective effect on CAD that is stronger than that of GLP-1R agonism alone, which yielded a non-significant causal effect for both HDL and BMI, and GIPR agonism alone also yielded a non-significant causal effect for HDL when adjusted for BMI. Conclusions: These novel findings have significant implications for repurposing dual incretin agonism in terms of diabetic drugs to serve as a unifying, precision prevention strategy against CAD, DR and AD as leading drivers of mortality and morbidity in diabetic patients. FAU - Xu, Jiehui AU - Xu J AD - Department of Population Health, NYU Grossman School of Medicine, New York, NY 10016, USA. FAU - Ashebir, Yibeltal A AU - Ashebir YA AD - Department of Population Health, NYU Grossman School of Medicine, New York, NY 10016, USA. FAU - Shao, Yongzhao AU - Shao Y AUID- ORCID: 0000-0003-0641-6755 AD - Department of Population Health, NYU Grossman School of Medicine, New York, NY 10016, USA. LA - eng GR - U01OH012486/CC/CDC HHS/United States GR - P30AG066512/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20260525 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Coronary Artery Disease/genetics/drug therapy/prevention & control MH - *Alzheimer Disease/genetics/drug therapy/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Retinopathy/genetics/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/complications MH - *Receptors, Gastrointestinal Hormone/agonists/genetics MH - Glucagon-Like Peptide-1 Receptor/genetics MH - Glycated Hemoglobin/metabolism MH - Male MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Female PMC - PMC13298441 OTO - NOTNLM OT - Alzheimer's diseases OT - PC-GMM OT - antidiabetic drug OT - cis-MR OT - coronary artery disease OT - diabetic retinopathy OT - multivariate Mendelian Randomization OT - synergistic causal effect COIS- The authors declare no conflicts of interest. EDAT- 2026/06/26 10:10 MHDA- 2026/06/27 04:10 PMCR- 2026/05/25 CRDT- 2026/06/26 01:08 PHST- 2026/03/17 00:00 [received] PHST- 2026/05/01 00:00 [revised] PHST- 2026/05/03 00:00 [accepted] PHST- 2026/06/27 04:10 [medline] PHST- 2026/06/26 10:10 [pubmed] PHST- 2026/06/26 01:08 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - genes17060602 [pii] AID - genes-17-00602 [pii] AID - 10.3390/genes17060602 [doi] PST - epublish SO - Genes (Basel). 2026 May 25;17(6):602. doi: 10.3390/genes17060602. PMID- 42350670 OWN - NLM STAT- MEDLINE DCOM- 20260730 LR - 20261008 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 69 IP - 9 DP - 2026 Sep TI - Metabolic state determines the brain and direct islet effects of liraglutide on enhanced insulin secretion. PG - 2534-2553 LID - 10.1007/s00125-026-06779-2 [doi] AB - AIMS/HYPOTHESIS: Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist for type 2 diabetes and obesity management, shows variable patient responses. We investigated the metabolic state-dependent mechanisms underlying this heterogeneity and how liraglutide's mode of action shifts across stages of metabolic dysfunction. METHODS: We employed human pancreatic islets from donors across metabolic states (normoglycaemic [HbA(1c) <42 mmol/l (<6.0%)], glucose intolerance [HbA(1c) 42-47 mmol/l (6.0-6.4%)] and type 2 diabetes [HbA(1c) >/=48 mmol/l (>/=6.5%)]) using dynamic perifusion and static incubation techniques to assess glucose-stimulated insulin secretion. GLP-1R mRNA levels were measured in 112 donor islets stratified by HbA(1c). Mechanistic investigations used tanycyte-specific GLP-1R knockdown (GLP-1R(TanycyteKD)) mice and botulinum toxin B-expressing (iBot) mice to distinguish between central and peripheral pathways. Oral glucose tolerance tests, pyruvate tolerance tests and positron emission tomography were performed to assess in vivo metabolic effects. RESULTS: Liraglutide (25 nmol/l) enhanced glucose-stimulated insulin secretion specifically in donors with glucose intolerance (n=7, p=0.021), with no effect in normoglycaemic islets (n=7), despite preserved GLP-1 (7-36) responsiveness. In type 2 diabetes islets, GLP-1R mRNA levels progressively decreased with rising HbA(1c) (p=0.015, normoglycaemic [n=48] vs type 2 diabetes [n=10]). In chow-fed mice, liraglutide's insulin-stimulating effects required tanycyte-mediated hypothalamic access, as demonstrated by abolished responses in GLP-1R(TanycyteKD) mice. However, during metabolic dysfunction (a 12-week high-fat diet), direct islet responsiveness was restored independent of tanycyte function. Advanced metabolic disease (a 27-week high-fat diet) maintained islet responsiveness ex vivo while losing in vivo insulin enhancement, revealing insulin-independent glucose-lowering mechanisms involving hepatic gluconeogenesis suppression and enhanced peripheral glucose uptake. CONCLUSIONS/INTERPRETATION: Liraglutide operates through complementary, metabolic state-dependent pathways: tanycyte-mediated brain actions predominate in healthy conditions, direct islet effects emerge during glucose intolerance and insulin-independent mechanisms maintain efficacy across metabolic states. This mechanistic framework enables potential patient stratification in type 2 diabetes therapy, suggesting that matching liraglutide's predominant mechanism to individual metabolic profiles could optimise treatment outcomes. CI - (c) 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Saponaro, Chiara AU - Saponaro C AUID- ORCID: 0000-0001-7336-7362 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Imbernon, Monica AU - Imbernon M AUID- ORCID: 0000-0003-4359-4817 AD - Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR_S 1172, European Genomic Institute for Diabetes, Lille, France. AD - Blizard Institute, Queen Mary University of London, London, UK. FAU - Louvet, Isaline AU - Louvet I AUID- ORCID: 0009-0007-8445-1157 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Deligia, Eleonora AU - Deligia E AUID- ORCID: 0000-0002-1721-1387 AD - Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR_S 1172, European Genomic Institute for Diabetes, Lille, France. FAU - Chen, Shiqian AU - Chen S AUID- ORCID: 0009-0008-3459-3138 AD - Division of Diabetes, Endocrinology and Metabolism, Section of Investigative Medicine, Imperial College London, London, UK. FAU - Davies, Iona AU - Davies I AUID- ORCID: 0009-0008-4666-8395 AD - Division of Diabetes, Endocrinology and Metabolism, Section of Investigative Medicine, Imperial College London, London, UK. FAU - Acosta-Montalvo, Ana AU - Acosta-Montalvo A AUID- ORCID: 0000-0003-2888-5456 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Moreno-Lopez, Maria AU - Moreno-Lopez M AUID- ORCID: 0009-0000-3499-8604 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Wemelle, Eve AU - Wemelle E AUID- ORCID: 0009-0009-6680-5876 AD - Inserm U1220, Institut de Recherche en Sante Digestive (IRSD), International Research Project (IRP), NeuroMicrobiota Lab, CHU Purpan, Toulouse, France. FAU - Kothegala, Lakshmi AU - Kothegala L AUID- ORCID: 0000-0002-6938-620X AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK. FAU - Porteiro, Begona AU - Porteiro B AUID- ORCID: 0000-0001-6646-5132 AD - CIMUS, Universidade de Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain. FAU - Auger, Florent AU - Auger F AUID- ORCID: 0000-0001-6195-3065 AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41, UMS 2014, PLBS, Lille, France. FAU - Zubiaga, Lorea AU - Zubiaga L AUID- ORCID: 0000-0001-6214-4331 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Dellalau, Nathalie AU - Dellalau N AUID- ORCID: 0009-0007-5978-6959 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Thevenet, Julien AU - Thevenet J AUID- ORCID: 0000-0001-6873-8640 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Muhlemann, Markus AU - Muhlemann M AUID- ORCID: 0000-0002-8323-7331 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Pasquetti, Gianni AU - Pasquetti G AUID- ORCID: 0009-0000-6665-5825 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Gmyr, Valery AU - Gmyr V AUID- ORCID: 0000-0003-1236-359X AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Pfrieger, Frank W AU - Pfrieger FW AUID- ORCID: 0000-0001-7085-1431 AD - Centre National de la Recherche Scientifique, Universite de Strasbourg, Institut des Neurosciences Cellulaires et Integratives, Strasbourg, France. FAU - Nogueiras, Ruben AU - Nogueiras R AUID- ORCID: 0000-0002-9976-9930 AD - CIMUS, Universidade de Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Spain. FAU - Schwaninger, Markus AU - Schwaninger M AUID- ORCID: 0000-0002-4510-9718 AD - Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lubeck, Lubeck, Germany. FAU - Rorsman, Patrik AU - Rorsman P AUID- ORCID: 0000-0001-7578-0767 AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK. FAU - Staels, Bart AU - Staels B AUID- ORCID: 0000-0002-3784-1503 AD - Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011, European Genomic Institute for Diabetes, Lille, France. FAU - Kerr-Conte, Julie AU - Kerr-Conte J AUID- ORCID: 0000-0002-7590-1896 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Knauf, Claude AU - Knauf C AUID- ORCID: 0000-0001-5213-5378 AD - Inserm U1220, Institut de Recherche en Sante Digestive (IRSD), International Research Project (IRP), NeuroMicrobiota Lab, CHU Purpan, Toulouse, France. FAU - Jones, Ben AU - Jones B AUID- ORCID: 0000-0003-0461-2584 AD - Division of Diabetes, Endocrinology and Metabolism, Section of Investigative Medicine, Imperial College London, London, UK. FAU - Pattou, Francois AU - Pattou F AUID- ORCID: 0000-0001-8388-3766 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. FAU - Prevot, Vincent AU - Prevot V AUID- ORCID: 0000-0001-7185-3615 AD - Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR_S 1172, European Genomic Institute for Diabetes, Lille, France. vincent.prevot@inserm.fr. FAU - Bonner, Caroline AU - Bonner C AUID- ORCID: 0000-0002-4430-8280 AD - Univ. Lille, Inserm, CHU Lille, U1190, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille, France. caroline.bonner@univ-lille.fr. LA - eng GR - ANR-10-LABX-0046/European Genomic Institute for Diabetes (to VP, FP, and BS)/ GR - 810331/European Research Council Synergy Grant (to VP, RN, and MS)/ GR - EFSD/Lilly 2016/European Foundation for the Study of Diabetes/Lilly-2016 to CB/ GR - 748134/H2020-MSCA Grant (to MI)/ GR - ANR-16-IDEX-0004/I-SITE ULNE (to VP, FP, and BS)/ PT - Journal Article DEP - 20260625 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Liraglutide/pharmacology/therapeutic use MH - Humans MH - Animals MH - *Islets of Langerhans/drug effects/metabolism MH - Mice MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism/genetics MH - *Insulin Secretion/drug effects MH - Male MH - Insulin/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Brain/metabolism/drug effects MH - Glucose Intolerance/metabolism MH - Female MH - Glucose Tolerance Test MH - Middle Aged MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucose OTO - NOTNLM OT - Beta cells OT - GLP-1 receptor OT - Glucose intolerance OT - Human islets OT - Hypothalamus OT - Insulin secretion OT - Liraglutide OT - Metabolic state OT - Tanycyte signalling OT - Type 2 diabetes COIS- Acknowledgements: This work was supported by the European Foundation for the Study of Diabetes/Lilly-2016 (to C. Bonner), the Societe Francophone du Diabete 2015 (to C. Bonner), the Conseil Regional Nord-Pas de Calais (to C. Bonner), the European Consortium for Islet Transplantation funded by the Juvenile Diabetes Research Foundation (to J. Kerr-Conte and F. Pattou), European Genomic Institute for Diabetes grant ANR-10-LABX-0046 (to V. Prevot, F. Pattou and B. Staels), I-SITE ULNE grant ANR-16-IDEX-0004 (to V. Prevot, F. Pattou and B. Staels), European Research Council Synergy Grant 810331 (to V. Prevot, R. Nogueiras and M. Schwaninger), Agence National de la Recherche Grant ANR-15-CE14-0025 (to V. Prevot), Novo Nordisk A/S (to V. Prevot), H2020-MSCA Grant 748134 (to M. Imbernon), Agence Nationale de la Recherche Grant ANR-18-CE14-0007-01 ENDIABAC (to C. Knauf), the International Research Project Grant NeuroMicrobiota from Inserm (to C. Knauf), Medical Research Council grant MR/R010676/1 (to B. Jones), Diabetes UK grant 20/0006307 (to B. Jones) and the Imperial College London IPPRF scheme (to B. Jones). The Section of Endocrinology and Investigative Medicine at Imperial College London is supported by the NIHR Biomedical Research Centre Funding Scheme and the NIHR/Imperial Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the islet isolation team at Lille University Hospital for providing human islets and acknowledge the technical assistance from the imaging core facility at Imperial College London. Data availability: All data generated or analysed during this study are included in the published article and its supplementary information files. Additional raw data, analytical methods and study materials are available from the corresponding authors upon reasonable request for 10 years after the publication of the data. Mouse models described in this study are available through material transfer agreements with the originating institutions. There will be no restriction to data sharing following publication, other than the necessary anonymisation of human data. Authors' relationships and activities: CK is a co-founder of Enterosys SA (Labege, France). All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: CS, MI, VP and CB conceptualised and supervised the study. CS, MI, IL, ED, SC, ID, AA-M, MM-L, EW, LK, BP, FA, LZ, ND, JT, MM, GP, VG, FWP, RN, MS, PR, BS, JK-C, CK, BJ, FP, VP and CB contributed to the conception or design of the work, data acquisition, analysis or interpretation of data. All authors drafted the article or reviewed it critically for important intellectual content. All authors approved the final version of the manuscript. CB and VP are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2026/06/26 00:46 MHDA- 2026/07/30 12:42 CRDT- 2026/06/25 23:26 PHST- 2025/09/27 00:00 [received] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/07/30 12:42 [medline] PHST- 2026/06/26 00:46 [pubmed] PHST- 2026/06/25 23:26 [entrez] AID - 10.1007/s00125-026-06779-2 [pii] AID - 10.1007/s00125-026-06779-2 [doi] PST - ppublish SO - Diabetologia. 2026 Sep;69(9):2534-2553. doi: 10.1007/s00125-026-06779-2. Epub 2026 Jun 25. PMID- 42349715 OWN - NLM STAT- MEDLINE DCOM- 20260724 LR - 20260724 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 52 IP - 4 DP - 2026 Jul TI - Glucagon-like peptide-1 receptor agonists and risk of pancreaticobiliary cancers in patients with type 2 diabetes: a nationwide cohort study. PG - 101776 LID - S1262-3636(26)00055-8 [pii] LID - 10.1016/j.diabet.2026.101776 [doi] AB - AIM: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated substantial metabolic benefits, but their association with pancreaticobiliary cancer risk remains unclear. We investigated the association between GLP-1RA use and pancreaticobiliary cancer incidence in patients with type 2 diabetes (T2D). METHODS: This population-based cohort study used Korean National Health Insurance Service data from 2011 to 2023. We identified 51,780 patients with T2D receiving metformin plus sulfonylurea who initiated either GLP-1RA (n=24,052) or dipeptidyl peptidase-4 inhibitor (DPP-4i, n=27,728). The primary outcomes were incident pancreatic cancer, bile duct cancer, gallbladder cancer, and composite pancreaticobiliary cancer. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for demographics, comorbidities, and previous diabetes medications. RESULTS: During 208,992 person-years of follow-up (mean 4.0 years), 321 pancreaticobiliary cancers occurred. GLP-1RA use was associated with a significantly lower risk of pancreatic cancer (adjusted HR 0.668, 95% CI 0.476-0.939). Similar trends were observed for bile duct cancer (adjusted HR 0.649, 95% CI 0.375-1.124), gallbladder cancer (adjusted HR 0.418, 95% CI 0.171-1.019), and composite pancreaticobiliary cancer (adjusted HR 0.681, 95% CI 0.515-0.901). These associations remained consistent in a propensity score-matched analysis and after excluding patients with baseline pancreaticobiliary disease. CONCLUSION: In this large cohort study, GLP-1RA use was associated with reduced pancreatic cancer risk compared with DPP-4i use among patients with T2D. Similar trends were observed for other pancreaticobiliary cancers. These findings suggest potential protective effects that warrant confirmation in longer-term studies. CI - Copyright (c) 2026 Elsevier Masson SAS. All rights reserved. FAU - Song, Byeong Geun AU - Song BG AD - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. FAU - Kim, Tae-Se AU - Kim TS AD - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. FAU - Kim, Bong Seong AU - Kim BS AD - Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea. FAU - Han, Kyungdo AU - Han K AD - Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea. Electronic address: hkd917@naver.com. FAU - Min, Byung-Hoon AU - Min BH AD - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: jason.min@samsung.com. LA - eng PT - Journal Article DEP - 20260625 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pancreatic Neoplasms/epidemiology MH - Middle Aged MH - *Biliary Tract Neoplasms/epidemiology MH - Aged MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use MH - Republic of Korea/epidemiology MH - Incidence MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Adult OTO - NOTNLM OT - Biliary tract neoplasms OT - Cohort studies OT - Diabetes OT - Glucagon-like peptide-1 receptor agonist OT - Pancreatic neoplasms OT - Type 2 COIS- Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. EDAT- 2026/06/26 04:10 MHDA- 2026/07/25 00:36 CRDT- 2026/06/25 19:31 PHST- 2026/05/06 00:00 [received] PHST- 2026/06/17 00:00 [revised] PHST- 2026/06/17 00:00 [accepted] PHST- 2026/07/25 00:36 [medline] PHST- 2026/06/26 04:10 [pubmed] PHST- 2026/06/25 19:31 [entrez] AID - S1262-3636(26)00055-8 [pii] AID - 10.1016/j.diabet.2026.101776 [doi] PST - ppublish SO - Diabetes Metab. 2026 Jul;52(4):101776. doi: 10.1016/j.diabet.2026.101776. Epub 2026 Jun 25. PMID- 42349668 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260716 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 226 DP - 2026 Sep TI - Hydrophobic ion pairing formed semaglutide designed for oral self-microemulsifying delivery in diabetes treatment. PG - 115167 LID - S0939-6411(26)00188-8 [pii] LID - 10.1016/j.ejpb.2026.115167 [doi] AB - Semaglutide (SET) is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Although injectable formulations offer high bioavailability, they are associated with poor patient compliance. In contrast, oral tablets are more convenient but suffer from limited absorption due to SET's hydrophilicity and enzymatic instability in the gastrointestinal tract. To address these challenges, we developed a hydrophobic ion pair (HIP) complex of SET and sodium docusate (SET-DOC), which was further incorporated into a self-emulsifying drug delivery system (SD@SEDDS) to facilitate oral delivery. The optimized SD@SEDDS produced a clear emulsion upon dilution, with a uniform particle size of 85.55 nm, high drug loading (2.64 mg/g), and excellent stability. In vitro transport studies using a Caco-2/HT-29 co-culture model demonstrated enhanced permeability and reduced P-glycoprotein-mediated efflux. In vivo studies in a type 2 diabetic rat model showed that SD@SEDDS significantly reduced blood glucose levels, improved lipid profiles, and exhibited good biocompatibility without observable toxicity. These findings suggested that the combination of HIP technology and SEDDS represented a promising strategy for enhancing the oral delivery efficiency of peptide drugs such as SET. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Zhang, Yuhuan AU - Zhang Y AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Cheng, Jinghan AU - Cheng J AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Wang, Hanming AU - Wang H AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Zong, Zhuai AU - Zong Z AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Zhang, Wenli AU - Zhang W AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. Electronic address: zwllz@163.com. FAU - Shen, Yan AU - Shen Y AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. Electronic address: shenyan@cpu.edu.cn. FAU - Tian, Yu AU - Tian Y AD - School of Medicine, Shanghai University, Shanghai 200444, China. Electronic address: shu_yutian@shu.edu.cn. LA - eng PT - Journal Article DEP - 20260625 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Emulsions) SB - IM MH - Semaglutide MH - Animals MH - Humans MH - Administration, Oral MH - Hydrophobic and Hydrophilic Interactions MH - Caco-2 Cells MH - *Hypoglycemic Agents/administration & dosage/chemistry/pharmacokinetics MH - *Glucagon-Like Peptides/administration & dosage/chemistry/pharmacokinetics MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Delivery Systems/methods MH - Emulsions/chemistry MH - Rats MH - Male MH - *Diabetes Mellitus, Experimental/drug therapy MH - Rats, Sprague-Dawley MH - HT29 Cells MH - Biological Availability MH - Particle Size OTO - NOTNLM OT - Caco-2/HT-29 co-culture model OT - Hydrophobic ion pairing OT - Hypoglycemic effect OT - SEDDS OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/26 00:45 MHDA- 2026/07/16 12:40 CRDT- 2026/06/25 19:30 PHST- 2026/04/08 00:00 [received] PHST- 2026/06/02 00:00 [revised] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/07/16 12:40 [medline] PHST- 2026/06/26 00:45 [pubmed] PHST- 2026/06/25 19:30 [entrez] AID - S0939-6411(26)00188-8 [pii] AID - 10.1016/j.ejpb.2026.115167 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2026 Sep;226:115167. doi: 10.1016/j.ejpb.2026.115167. Epub 2026 Jun 25. PMID- 42348217 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260930 IS - 2168-619X (Electronic) IS - 2168-6181 (Print) IS - 2168-6181 (Linking) VI - 152 IP - 8 DP - 2026 Aug 1 TI - Smell and Taste Disturbances Among Glucagon-Like Peptide-1 Receptor Agonist Users. PG - 758-765 LID - 10.1001/jamaoto.2026.1498 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity over the last decade for both glycemic control and weight loss. Although various adverse events have been reported among GLP-1 RA users, little is known regarding their potential impact on smell and taste perception. OBJECTIVE: To evaluate the association between GLP-1 RAs and smell and taste disturbances. DESIGN, SETTING, AND PARTICIPANTS: This large-scale multicenter retrospective cohort study used electronic health records from a large electronic health records database (TriNetX Global Collaborative Network) from December 5, 2017, to April 20, 2026 (date of analysis), with follow-up of up to 2 years after treatment initiation. Patients (aged >/=18 years) diagnosed with type 2 diabetes (T2D) with no record of smell or taste disturbances were divided into 2 groups: the control group comprised patients prescribed T2D medications without GLP-1 RA exposure and the exposure group consisted of patients who received a GLP-1 RA prescription after their first recorded diagnosis of T2D. Propensity score matching was applied to balance demographic, clinical, and socioeconomic differences. EXPOSURE: GLP-1 RA or different antidiabetic medications. MAIN OUTCOMES AND MEASURES: The primary outcome was incident smell and taste disturbances, identified using International Classification of Diseases (ICD) codes, assessed overall and separately during a follow-up period of 3 months to 2 years. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression analyses to evaluate the risk of incident cases. RESULTS: After matching, each cohort included 438 474 patients (GLP-1 RA: mean [SD] age, 57.7 [12.2] years; 240 620 females [54.9%]; control: mean [SD] age, 57.6 [13.4] years; 245 730 females [56.0%]). Patients with documented GLP-1 RA therapy had an increased risk of overall smell and taste disturbances (HR, 1.48; 95% CI, 1.37-1.61) compared with matched control patients. When stratified by outcome, GLP-1 RA use was associated with a higher risk of smell (HR, 1.81; 95% CI, 1.58-2.07) and taste (HR, 1.52; 95% CI, 1.35-1.71) disturbances. These findings were consistent throughout the follow-up period. CONCLUSIONS AND RELEVANCE: This study suggests that GLP-1 RA therapy is associated with a higher risk of smell and taste disturbance, highlighting the need for closer monitoring and greater public health awareness. Future research is required to validate these findings and to further explore the mechanisms underlying this association. FAU - Zontag, Jonathan AU - Zontag J AD - Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel. AD - Institute for Research in Military Medicine (IRMM), Faculty of Medicine, The Hebrew University of Jerusalem and the Israel Defense Forces Medical Corps, Jerusalem, Israel. FAU - Zontag, Nir AU - Zontag N AD - Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel. AD - Institute for Research in Military Medicine (IRMM), Faculty of Medicine, The Hebrew University of Jerusalem and the Israel Defense Forces Medical Corps, Jerusalem, Israel. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - JAMA Otolaryngol Head Neck Surg JT - JAMA otolaryngology-- head & neck surgery JID - 101589542 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - JAMA Otolaryngol Head Neck Surg. 2026 Aug 1;152(8):766-767. doi: 10.1001/jamaoto.2026.1704. PMID: 42348206 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Olfaction Disorders/chemically induced/epidemiology MH - Retrospective Studies MH - *Taste Disorders/chemically induced/epidemiology PMC - PMC13306484 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2026/06/25 16:09 MHDA- 2026/08/13 21:27 PMCR- 2027/06/25 CRDT- 2026/06/25 11:35 PHST- 2026/08/13 21:27 [medline] PHST- 2026/06/25 16:09 [pubmed] PHST- 2026/06/25 11:35 [entrez] PHST- 2027/06/25 00:00 [pmc-release] AID - 2850571 [pii] AID - ooi260032 [pii] AID - 10.1001/jamaoto.2026.1498 [doi] PST - ppublish SO - JAMA Otolaryngol Head Neck Surg. 2026 Aug 1;152(8):758-765. doi: 10.1001/jamaoto.2026.1498. PMID- 42348164 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Cardiovascular Efficacy of GLP-1 Receptor Agonists by Kidney Function: An Updated Meta-Analysis of Randomized Trials Including the SOUL Trial. PG - 8407-8417 LID - 10.1111/dom.71035 [doi] AB - AIMS: To evaluate the cardiovascular efficacy and absolute benefit of glucagon-like peptide-1 receptor agonists (GLP-1RAs) by baseline estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: PubMed and EMBASE were searched to 29 April 2026 for randomized placebo-controlled trials of GLP-1RAs in adults with type 2 diabetes or overweight/obesity that reported eGFR-stratified major adverse cardiovascular events (MACE). Hazard ratios (HRs) were extracted for eGFR < 60 and >/= 60 mL/min/1.73 m(2). Random-effects meta-analyses estimated pooled HRs within each eGFR stratum and the pooled ratio of HRs (RHR) comparing eGFR < 60 versus >/= 60 mL/min/1.73 m(2). Exploratory absolute risk reduction (ARR) and number needed to treat (NNT) were derived from placebo-group MACE risk and the corresponding pooled HR. RESULTS: Nine publications from eight trials were included, comprising 70 822 participants; 70 534 had eGFR-stratified MACE data. GLP-1RAs similarly reduced MACE risk among participants with eGFR >/= 60 and < 60 mL/min/1.73 m(2), with pooled HRs of 0.83 (95% CI 0.77-0.90; p < 0.001; I (2) = 35.6%) and 0.83 (95% CI 0.74-0.93; p < 0.001; I (2) = 40.9%), respectively. The pooled RHR showed no evidence of effect modification (1.02, 95% CI 0.85-1.21; p = 0.84). ARR was larger with eGFR < 60 than >/= 60 mL/min/1.73 m(2) (2.6% vs. 1.6%), corresponding to NNTs of 39 (95% CI 26-91) versus 62 (95% CI 46-101). CONCLUSIONS: GLP-1RAs reduced MACE risk similarly across eGFR strata, while lower eGFR was associated with a larger estimated absolute cardiovascular benefit. These findings support GLP-1RA therapy in individuals with reduced kidney function. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hasebe, Masashi AU - Hasebe M AUID- ORCID: 0000-0001-7031-2446 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Su, Chen-Yang AU - Su CY AUID- ORCID: 0000-0001-6071-4660 AD - Department of Population Health Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Yoshiji, Satoshi AU - Yoshiji S AUID- ORCID: 0000-0001-8863-2413 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. LA - eng GR - 183596/CIHR/Canada GR - CRC-2025-00097/Canada Research Chairs Program/ GR - Japan Society for the Promotion of Science/ GR - McGill University/ GR - DNA to RNA Foundational Program/ GR - 183596/CIHR/Canada PT - Journal Article PT - Meta-Analysis DEP - 20260625 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - Glomerular Filtration Rate/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney/drug effects/physiopathology MH - Obesity/complications/drug therapy PMC - PMC13449011 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular disease OT - estimated glomerular filtration rate OT - kidney function OT - meta-analysis COIS- Daisuke Yabe received clinically commissioned or joint research grants from Novo Nordisk, Ono Pharmaceutical, Taisho Pharmaceutical, Terumo and Arklay. Daisuke Yabe also received consulting or speaker fees from Sumitomo Dainippon Pharma, Boehringer Ingelheim, Astellas Pharma, MSD, Novo Nordisk, Ono Pharmaceutical, Eli Lilly and Takeda Pharmaceutical. Satoshi Yoshiji serves as a consultant to the Broad Institute of MIT and Harvard through Precision Global Consulting and to PriveBio Inc., unrelated to this project. The other authors declare no conflicts of interest. EDAT- 2026/06/25 19:09 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/25 11:22 PHST- 2026/06/02 00:00 [revised] PHST- 2026/05/11 00:00 [received] PHST- 2026/06/15 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/25 19:09 [pubmed] PHST- 2026/06/25 11:22 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71035 [pii] AID - 10.1111/dom.71035 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8407-8417. doi: 10.1111/dom.71035. Epub 2026 Jun 25. PMID- 42345248 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 0017-7768 (Print) IS - 0017-7768 (Linking) VI - 165 IP - 6 DP - 2026 Jun TI - [Treatment of Morbid Obesity in Israel: GLP-1 Agonists Versus Bariatric Surgery - Clinical and Economic Aspects]. PG - 402-406 AB - Morbid obesity is a major medical, social, and economic challenge worldwide and in Israel. Approximately 49% of Israeli adults aged 20 years and above are overweight or obese, and about a quarter of a million meet criteria for morbid obesity. This condition significantly increases the risk of type 2 diabetes, cardiovascular disease, cancer, and premature mortality, while imposing a substantial financial burden on the healthcare system and the national economy. Current treatment options for morbid obesity include lifestyle modification, pharmacotherapy, and metabolic surgery. Lifestyle intervention is considered first-line therapy, yet its effectiveness is often limited, particularly in cases of morbid obesity. Over the past decade, the use of glucagon-like peptide-1 receptor agonists (GLP1RA) has increased considerably, yielding an average of 10% weight loss and meaningful improvements in obesity-related comorbidities. However, these medications are associated with side effects, relatively high discontinuation rates, limited accessibility, and high long-term costs. Metabolic surgery typically results in more than 25% weight loss, substantial improvements in obesity-related diseases, and reduced mortality. Although surgery involves higher upfront costs and the potential for complications, recent studies show that it becomes more cost-effective than continuous pharmacotherapy within months to a few years. FAU - Boaz, Elad AU - Boaz E AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. FAU - Kahana, Noam AU - Kahana N AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. FAU - Dagan, Amir AU - Dagan A AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. FAU - Yellinek, Shlomo AU - Yellinek S AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. FAU - Ben-Haim, Menahem AU - Ben-Haim M AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. FAU - Spira, Ram AU - Spira R AD - Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. LA - heb PT - Comparative Study PT - English Abstract PT - Journal Article PT - Review PL - Israel TA - Harefuah JT - Harefuah JID - 0034351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Bariatric Surgery/economics/methods MH - *Obesity, Morbid/economics/therapy/complications/surgery/epidemiology MH - Israel MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cost-Benefit Analysis MH - Weight Loss MH - Adult MH - Diabetes Mellitus, Type 2/etiology/economics MH - Life Style EDAT- 2026/06/25 06:38 MHDA- 2026/06/25 12:38 CRDT- 2026/06/25 05:53 PHST- 2026/06/25 12:38 [medline] PHST- 2026/06/25 06:38 [pubmed] PHST- 2026/06/25 05:53 [entrez] PST - ppublish SO - Harefuah. 2026 Jun;165(6):402-406. PMID- 42342489 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 1878-7533 (Electronic) IS - 1550-7289 (Linking) VI - 22 IP - 10 DP - 2026 Oct TI - Glucagon-like peptide-1 receptor agonists as a metabolic optimization strategy in surgical prehabilitation: a translational perspective. PG - 1175-1180 LID - S1550-7289(26)00708-2 [pii] LID - 10.1016/j.soard.2026.05.027 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide and tirzepatide, are increasingly prescribed for obesity and type 2 diabetes and have demonstrated substantial and rapid weight loss in large randomized trials. At the same time, prehabilitation before major abdominal surgery has become an established perioperative strategy to improve postoperative outcomes. This review explores the potential role of GLP-1RAs as a pharmacological adjunct in multimodal surgical prehabilitation. We discuss the biological rationale for metabolic optimization, the relevance of sarcopenic obesity, potential implications for oncological surgery and neoadjuvant therapy, and emerging data from bariatric and metabolic surgery. We also highlight important perioperative safety considerations, particularly delayed gastric emptying and aspiration risk, and current anesthetic guidance. Although integration of GLP-1RAs into prehabilitation pathways is biologically plausible and clinically attractive, there is currently no direct evidence supporting their use in this setting. We propose that GLP-1RAs represent a promising and testable strategy for metabolic optimization in surgical patients. Prospective studies are required to evaluate feasibility, safety, and impact on clinically meaningful outcomes. This framework is hypothesis-generating and aims to inform future translational research at the interface of metabolic medicine and perioperative care. CI - Copyright (c) 2026 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved. FAU - Rouse, Michael AU - Rouse M AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. Electronic address: michael.rouse@unimelb.edu.au. FAU - Kokelaar, Rory AU - Kokelaar R AD - Department of Surgery, Western Health, Victoria, Australia. FAU - Lee, I-Lynn AU - Lee IL AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. FAU - Yeung, Justin M AU - Yeung JM AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20260601 PL - United States TA - Surg Obes Relat Dis JT - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JID - 101233161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Bariatric Surgery/methods MH - Semaglutide MH - *Preoperative Care/methods MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Preoperative Exercise MH - Translational Research, Biomedical MH - *Obesity/surgery/drug therapy MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonist OT - Obesity OT - Perioperative medicine OT - Prehabilitation OT - Sarcopenic obesity OT - Surgical outcomes COIS- Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. EDAT- 2026/06/25 00:33 MHDA- 2026/09/07 23:34 CRDT- 2026/06/24 21:55 PHST- 2026/03/27 00:00 [received] PHST- 2026/05/07 00:00 [revised] PHST- 2026/05/26 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/06/25 00:33 [pubmed] PHST- 2026/06/24 21:55 [entrez] AID - S1550-7289(26)00708-2 [pii] AID - 10.1016/j.soard.2026.05.027 [doi] PST - ppublish SO - Surg Obes Relat Dis. 2026 Oct;22(10):1175-1180. doi: 10.1016/j.soard.2026.05.027. Epub 2026 Jun 1. PMID- 42339860 OWN - NLM STAT- MEDLINE DCOM- 20260730 LR - 20260730 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 19 IP - 7 DP - 2026 Jul TI - The systems medicine view of semaglutide: from clinical trials to molecular mechanisms. PG - 651-669 LID - 10.1080/17512433.2026.2695172 [doi] AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a key therapy in managing type 2 diabetes (T2D), offering significant improvements in glycemic control, weight loss, and cardiovascular protection. Beyond these clinical benefits, multi-omics research is clarifying the molecular mechanisms underlying its systemic metabolic effects. AREAS COVERED: This review synthesizes findings from major clinical trials and recent proteomic and metabolomic studies to explain how semaglutide affects inflammatory, lipid, and extracellular matrix (ECM) pathways in multiple organs. Key molecular mediators, including adiponectin, fibroblast growth factor 21 (FGF21), apolipoprotein C-III (ApoC-III), ceramides, and ECM-remodeling proteins (MMPs, CTGF, alpha-SMA), are linked to improved insulin sensitivity, reduced adipose inflammation, and restored metabolic flexibility. The review also discusses the use of artificial intelligence (AI) and machine learning (ML) to connect omics biomarkers with clinical outcomes. EXPERT OPINION: Semaglutide exemplifies a precision medicine approach for T2D by linking clinical efficacy to molecular adaptation. Longitudinal validation of omics biomarkers and their integration into AI-driven diagnostic platforms could enable personalized, mechanism-based therapy that goes beyond glucose control to deliver comprehensive cardiometabolic protection. FAU - Vitorino, Rui AU - Vitorino R AD - Department of Medical Sciences, iBiMED, University of Aveiro, Aveiro, Portugal. AD - Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. LA - eng PT - Journal Article PT - Review DEP - 20260701 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Hypoglycemic Agents/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Precision Medicine/methods MH - Proteomics/methods MH - Biomarkers/metabolism MH - Insulin Resistance MH - Metabolomics/methods MH - Multiomics MH - Blood Glucose/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - adipose tissue OT - inflammation OT - insulin resistance OT - metabolomics OT - proteomics OT - semaglutide EDAT- 2026/06/24 12:35 MHDA- 2026/07/30 06:41 CRDT- 2026/06/24 09:35 PHST- 2026/07/30 06:41 [medline] PHST- 2026/06/24 12:35 [pubmed] PHST- 2026/06/24 09:35 [entrez] AID - 10.1080/17512433.2026.2695172 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2026 Jul;19(7):651-669. doi: 10.1080/17512433.2026.2695172. Epub 2026 Jul 1. PMID- 42338042 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. PG - 8347-8358 LID - 10.1111/dom.71032 [doi] AB - AIMS: Orforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist. The hepatic safety profile in adults with obesity or overweight and/or type 2 diabetes (T2D) across seven orforglipron Phase 3 clinical trials was assessed. MATERIALS AND METHODS: Overall, 11 220 participants were included in this analysis (orforglipron N = 6920; pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine] N = 4300) for up to 104 weeks, including safety follow-up. Eligibility criteria for these Phase 3 trials included ALT/AST < 3 x ULN in the weight management programme and /= 3 x ULN and TBIL >/= 2 x ULN; however, alternative etiologies accounted for all orforglipron cases and thus did not meet criteria for drug induced liver injury/Hy's Law. The incidence of hepatic AEs was balanced between orforglipron and pooled comparators, suggesting no increased risk with orforglipron. Results were consistent in participants with normal and elevated baseline aminotransferases. CONCLUSIONS: In this pooled analysis of orforglipron Phase 3 clinical trials, orforglipron treatment was not associated with drug-induced liver injury, demonstrating a hepatic safety profile similar to placebo or active comparators. There were no cases consistent with drug-induced liver injury/Hy's Law with orforglipron. Aminotransferase trajectories showed a hepatic profile consistent with the metabolic benefits of weight loss. CI - (c) 2026 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - University of Toronto, and Wharton Weight Management Clinic, Toronto, Ontario, Canada. FAU - Stefanski, Adam AU - Stefanski A AUID- ORCID: 0009-0001-7598-402X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Chen, Jiaxun AU - Chen J AUID- ORCID: 0000-0002-7046-4201 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rao, Girish AU - Rao G AUID- ORCID: 0000-0002-3660-5488 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Twum, Elvis Asare AU - Twum EA AUID- ORCID: 0009-0006-1093-2508 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Denning, Max AU - Denning M AUID- ORCID: 0000-0001-6215-6885 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Journal Article DEP - 20260623 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (Glucosides) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 1ULL0QJ8UC (dapagliflozin) RN - 7ZW40D021M (orforglipron) RN - 0 (Benzhydryl Compounds) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - Adult MH - *Overweight/drug therapy/complications MH - Semaglutide MH - Clinical Trials, Phase III as Topic MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - *Chemical and Drug Induced Liver Injury/epidemiology/etiology MH - *Liver/drug effects MH - Alanine Transaminase MH - Aged MH - Glucosides/therapeutic use MH - Insulin Glargine/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Benzhydryl Compounds MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13448879 OAB - What is the context and purpose of this research study? o Orforglipron is an oral GLP-1 receptor agonist taken as tablet that helps to reduce blood sugar and reduce body weight. We studied how orforglipron may affect the liver in adults with obesity, overweight, and/or type 2 diabetes who participated in the Phase 3 clinical trials. What was done? o Across seven trials, orforglipron up to 17.2 mg once daily was compared to placebo, oral semaglutide, dapagliflozin, or insulin glargine. We measured changes in blood liver enzymes like AST, ALT and counted how many participants developed elevated liver enzymes above a set threshold. Analysis included all participants and those with preexisting elevated liver enzymes. We also checked for Hy's law, which signals for serious medicine related liver injury. Hy's Law screening was performed, and hepatic adverse events were summarised. What were the main results? o Treatment with orforglipron was not associated with drug-induced liver injury, and no participant met the Hy's Law criteria. Additionally, ALT and AST levels improved over time with orforglipron, which coincides with the significant weight loss and metabolic improvements previously reported in these trials. Overall, the liver safety profile of orforglipron was comparable to placebo and other comparator medicines, including peptide GLP-1 receptor agonist semaglutide. What is the originality and relevance of this study? o Findings from this analysis suggest that orforglipron was safe in adults with overweight, obesity, or type 2 diabetes-even in those with mildly to moderately elevated liver enzyme levels, which is commonly seen in MASLD. These findings support the need for dedicated studies on people with MASLD or metabolic dysfunction-associated steatohepatitis (MASH). OABL- eng OTO - NOTNLM OT - ACHIEVE OT - ATTAIN OT - hepatic safety OT - obesity OT - orforglipron OT - type 2 diabetes COIS- S.W. reported receiving nonfinancial support from Eli Lilly and Company during the conduct of the study and personal fees from Abbvie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly and Company, i2o Therapeutics, Merck, Metsera, NGX, Novo Nordisk, and Regeneron outside the submitted work, served on an advisory board for Boehringer Ingelheim, holds a leadership role for Obesity Canada and Obesity Society, and has received medical writing support from Boehringer Ingelheim, Eli Lilly and Company, and Novo Nordisk. A.S., J.C., G.R., E.A.T. and M.D. are employees and shareholders of Eli Lilly and Company. The sponsor (Eli Lilly and Company) designed and oversaw the conduct of the trials included in this analysis. The trial site investigators were responsible for data collection, with site monitoring, data collation, and data analysis and medical writing support provided by the sponsor. EDAT- 2026/06/24 06:36 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/24 02:14 PHST- 2026/06/12 00:00 [revised] PHST- 2026/05/14 00:00 [received] PHST- 2026/06/13 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/24 06:36 [pubmed] PHST- 2026/06/24 02:14 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71032 [pii] AID - 10.1111/dom.71032 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8347-8358. doi: 10.1111/dom.71032. Epub 2026 Jun 23. PMID- 42337824 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Efficacy and Safety of GLP-1 Receptor Agonists on Combined Cardiovascular and Renal Outcomes in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. PG - 8337-8346 LID - 10.1111/dom.71031 [doi] AB - AIMS: Chronic kidney disease (CKD) confers substantial cardiovascular and renal morbidity. GLP-1 receptor agonists (GLP-1 RAs) have demonstrated cardiorenal protection across major randomised trials, culminating in the landmark FLOW trial. No prior systematic review has simultaneously synthesised cardiorenal outcomes in a CKD-restricted population, executed a network meta-analysis for agent-level comparisons, or assessed whether SGLT2 inhibitor background therapy modifies treatment effects. MATERIALS AND METHODS: MEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched through March 2025. Eligible RCTs enrolled adults with CKD (eGFR < 60 mL/min/1.73 m(2) or UACR >/= 30 mg/g) comparing GLP-1 RAs versus placebo for >/= 26 weeks. Primary outcomes were 3-point MACE and a KDIGO-harmonised composite kidney endpoint. Random-effects pairwise meta-analyses and a frequentist NMA were performed. GRADE certainty was assigned to all outcomes. RESULTS: Thirteen RCTs (97 428 participants; 31 846 with confirmed CKD) were included. GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86; high certainty). Kidney failure risk was reduced by 28% (HR 0.72); UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction p = 0.41). Semaglutide ranked highest in the NMA (SUCRA 78.4%). No excess acute kidney injury risk was observed. CONCLUSIONS: GLP-1 RAs provide clinically meaningful cardiorenal protection in CKD, additive to SGLT2 inhibitor benefits. In exploratory network meta-analysis, semaglutide subcutaneous achieved the highest SUCRA ranking for kidney composite outcomes; the direct semaglutide evidence is rated high certainty by GRADE. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kaur, Rashpinder AU - Kaur R AD - General Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK. FAU - Singh, Avtar AU - Singh A AUID- ORCID: 0009-0009-4705-0818 AD - General Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260623 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Treatment Outcome MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Kidney/drug effects PMC - PMC13448877 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MACE OT - SGLT2 inhibitors OT - cardiorenal protection OT - cardiovascular outcomes OT - chronic kidney disease OT - composite kidney endpoint OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/24 06:36 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/24 00:33 PHST- 2026/06/02 00:00 [revised] PHST- 2026/05/06 00:00 [received] PHST- 2026/06/11 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/24 06:36 [pubmed] PHST- 2026/06/24 00:33 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71031 [pii] AID - 10.1111/dom.71031 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8337-8346. doi: 10.1111/dom.71031. Epub 2026 Jun 23. PMID- 42335260 OWN - NLM STAT- MEDLINE DCOM- 20260623 LR - 20260924 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 32 IP - 6 DP - 2026 Jun TI - Real-world weight loss with injectable semaglutide vs dulaglutide for diabetes. PG - 328-333 LID - 10.37765/ajmc.2026.89952 [doi] AB - OBJECTIVE: To compare the real-world effects of weekly injectable semaglutide (Ozempic) vs dulaglutide (Trulicity) on weight loss in an urban, predominantly African American patient sample with type 2 diabetes (T2D). STUDY DESIGN: This retrospective cohort study included adult patients with T2D at an academic internal medicine clinic who were initiated on semaglutide or dulaglutide. METHODS: The primary outcome was the percentage change in actual body weight (ABW) from baseline at 52 weeks. Secondary outcomes included mean weight loss in kg, weight loss of at least 5% and at least 10% at 52 weeks, percentage change in hemoglobin A1c (HbA1c) at 52 weeks, and HbA1c levels of less than 7% and less than 8% at 52 weeks. RESULTS: The percentage change in ABW from baseline at 52 weeks was greater with semaglutide (n = 60) than with dulaglutide (n = 60) (-6.51% vs -1.14%; P = .001). The absolute change in ABW at 52 weeks was greater with semaglutide than with dulaglutide (-15.98 kg vs -4.93 kg; P = .001). More patients using semaglutide achieved weight loss of at least 5% and at least 10% at 52 weeks than those using dulaglutide (>/= 5%: 51.7% vs 25.0%; P = .003; >/= 10%: 31.7% vs 8.3%; P = .001). A higher percentage of patients using semaglutide than those using dulaglutide achieved an HbA1c less than 7% and less than 8% at 52 weeks (< 7%: 53.3% vs 38.3%; P = .100; < 8%: 78.3% vs 68.3%; P = .220). The absolute change in HbA1c was greater with semaglutide than dulaglutide (-2.15% vs -1.36%; P = .033). CONCLUSIONS: Treatment with semaglutide resulted in a greater reduction in body weight and HbA1c than with dulaglutide in a real-world study of patients with T2D. FAU - Spitery, Allison AU - Spitery A AD - Henry Ford Health System, Detroit, MI. FAU - Lobkovich, Alison AU - Lobkovich A AD - Henry Ford Health System, Detroit, MI. AD - Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201. Email: Alison.lobkovich@wayne.edu. FAU - Thomas, Emily AU - Thomas E AD - Henry Ford Health System, Detroit, MI. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Semaglutide MH - *Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Immunoglobulin Fc Fragments/therapeutic use/administration & dosage MH - Female MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis MH - Aged EDAT- 2026/06/23 18:33 MHDA- 2026/06/23 18:34 CRDT- 2026/06/23 14:23 PHST- 2026/06/23 18:34 [medline] PHST- 2026/06/23 18:33 [pubmed] PHST- 2026/06/23 14:23 [entrez] AID - 89952 [pii] AID - 10.37765/ajmc.2026.89952 [doi] PST - ppublish SO - Am J Manag Care. 2026 Jun;32(6):328-333. doi: 10.37765/ajmc.2026.89952. PMID- 42334912 OWN - NLM STAT- MEDLINE DCOM- 20260623 LR - 20260626 IS - 1210-7816 (Print) IS - 1210-7816 (Linking) VI - 75 IP - 2 DP - 2026 TI - Tirzepatide. PG - 112-116 LID - 10.36290/csf.2026.020 [doi] AB - Tirzepatide represents a significant breakthrough in the treatment of type 2 diabetes mellitus and/or obesity as the first dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Current analysis of available clinical data demonstrates the exceptional efficacy of tirzepatide in glycemic control, with a dose- and duration-dependent reduction in HbA1c of 20.4-28.2 mmol/mol. Weight reduction reaches 5-20.9 % with 72 weeks of therapy, with the effect being dose-dependent. The mechanism of action includes improved insulin sensitivity, delayed gastric emptying, and modulation of central regulatory centers for food intake. The safety profile is characterized primarily by gastrointestinal side effects with a treatment discontinuation rate of 4-10 %. Tirzepatide also has beneficial effects on cardiovascular risk factors, including lipid profile and anti-inflammatory biomarkers. A key strategy for optimizing therapeutic outcomes is gradual dose escalation and individualization of treatment according to the patient's clinical condition. FAU - Broz, Jan AU - Broz J FAU - Kozeluhova, Marika AU - Kozeluhova M FAU - Michalec, Juraj AU - Michalec J FAU - Lukac, Ondrej AU - Lukac O LA - eng PT - Journal Article PT - Review TT - Tirzepatid. PL - Czech Republic TA - Ceska Slov Farm JT - Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti JID - 9433765 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy MH - *Tirzepatide/therapeutic use OTO - NOTNLM OT - obesity OT - tirzepatide OT - treatment OT - type 2 diabetes OT - type 2 diabetes EDAT- 2026/06/23 18:34 MHDA- 2026/06/23 18:35 CRDT- 2026/06/23 12:32 PHST- 2026/06/23 18:35 [medline] PHST- 2026/06/23 18:34 [pubmed] PHST- 2026/06/23 12:32 [entrez] AID - 143902 [pii] AID - 10.36290/csf.2026.020 [doi] PST - ppublish SO - Ceska Slov Farm. 2026;75(2):112-116. doi: 10.36290/csf.2026.020. PMID- 42334436 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260920 IS - 2055-6845 (Electronic) IS - 2055-6837 (Print) VI - 12 IP - 5 DP - 2026 Aug 17 TI - Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation. PG - 368-378 LID - 10.1093/ehjcvp/pvag044 [doi] AB - AIMS: Rheumatoid arthritis (RA)-related physical limitations often hinder sustained physical activity and weight management, thereby amplifying cardiovascular risk through adverse metabolic profiles and chronic inflammation. We aimed to assess the effectiveness of semaglutide on the risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) in obese adults with type 2 diabetes mellitus (T2DM) and RA in a primary-prevention setting. METHODS AND RESULTS: We emulated a target trial using data from the TriNetX US database, including obese adults [aged >/=18 years; body mass index (BMI) >/=30 kg/m2] with T2DM and comorbid RA and no prior history of stroke, heart failure (HF), acute coronary syndrome, or coronary revascularization. Using a new-user design, we compared patients initiating semaglutide with those initiating non-GLP-1 receptor agonist (GLP-1RA) second-line glucose-lowering therapies. Patients with contraindications to GLP-1RAs were excluded. Propensity-score matching (PS) (1:1) was used to balance baseline covariates. The primary outcome was incident MACCE, defined as a composite of all-cause mortality, myocardial infarction (MI), HF, or stroke. Secondary outcomes included individual MACCE components, HF hospitalization, and disease-modifying anti-rheumatic drug (DMARD) escalation, with Bonferroni correction applied for multiple comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models over a follow-up of up to 2 years. Between 1 January 2014 and 1 January 2025, we identified 1200 and 2972 patients who initiated semaglutide and non-GLP-1RA therapies, respectively, within 3 months of meeting eligibility. After PS matching, 1017 semaglutide users were compared with 1017 non-GLP-1RA users (mean age 59.5 vs. 59.3 years; women 81.3% vs. 81.0%; mean BMI 38.2 vs. 38.0 kg/m2; HbA1c, 6.8% vs. 7.0%). Semaglutide initiation was associated with a significantly lower risk of incident MACCE compared with non-GLP-1RA therapies (12.7% vs. 16.5%; HR, 0.75; 95% CI, 0.60-0.94; P = 0.01). This benefit was driven primarily by a lower risk of incident HF (8.9% vs. 12.5%; HR, 0.69, 95% CI, 0.53-0.91; P = 0.007). Semaglutide use was also associated with significantly lower DMARD escalation (16.6% vs. 21.6%; HR, 0.75; 95% CI, 0.60-0.90; P = 0.003). No significant differences were observed in all-cause mortality, MI, or stroke. CONCLUSION: Among obese adults with T2DM and comorbid RA, initiation of semaglutide was associated with a reduced risk of incident MACCE, driven predominantly by a reduction in incident HF, in a primary-prevention setting. Prospective studies are needed to confirm these observations and establish causality. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Cardiology. FAU - Malik, Farheen AU - Malik F AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Shah, Mandar AU - Shah M AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Chang, Yu AU - Chang Y AUID- ORCID: 0000-0001-9618-3267 AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan. FAU - Chowdhury, Ishmum AU - Chowdhury I AUID- ORCID: 0000-0001-7029-2369 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Mangalesh, Sridhar AU - Mangalesh S AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Morgan, Ahmed Ashraf AU - Morgan AA AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Pascal, Ezerioha AU - Pascal E AD - Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA. FAU - Modak, Vishakha AU - Modak V AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Lebovics, Nachum AU - Lebovics N AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Adhikari, Suraj AU - Adhikari S AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Lee, Pei-Lun AU - Lee PL AUID- ORCID: 0009-0007-3252-6719 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Chen, Wei-Cheng AU - Chen WC AUID- ORCID: 0000-0002-1516-3799 AD - Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan. FAU - Chi, Kuan-Yu AU - Chi KY AUID- ORCID: 0000-0003-0763-8157 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. LA - eng PT - Journal Article PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality/blood MH - *Arthritis, Rheumatoid/diagnosis/epidemiology/drug therapy/mortality MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Middle Aged MH - Male MH - Treatment Outcome MH - Risk Assessment MH - *Primary Prevention/methods MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Comorbidity MH - Incidence MH - Time Factors MH - *Obesity/diagnosis/drug therapy/epidemiology/mortality MH - United States/epidemiology MH - *Cerebrovascular Disorders/prevention & control/diagnosis/epidemiology/mortality MH - Databases, Factual MH - *Incretins/therapeutic use/adverse effects MH - Risk Factors PMC - PMC13588637 OTO - NOTNLM OT - Diabetes OT - Primary prevention OT - Rheumatoid arthritis OT - Semaglutide COIS- Conflict of interest: None declared. EDAT- 2026/06/23 12:35 MHDA- 2026/08/17 11:40 PMCR- 2026/06/23 CRDT- 2026/06/23 10:53 PHST- 2026/02/16 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/06/16 00:00 [accepted] PHST- 2026/08/17 11:40 [medline] PHST- 2026/06/23 12:35 [pubmed] PHST- 2026/06/23 10:53 [entrez] PHST- 2026/06/23 00:00 [pmc-release] AID - 8713824 [pii] AID - pvag044 [pii] AID - 10.1093/ehjcvp/pvag044 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2026 Aug 17;12(5):368-378. doi: 10.1093/ehjcvp/pvag044. PMID- 42331736 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists and Incident Major Adverse Liver Outcomes in People With Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease. PG - 8277-8287 LID - 10.1111/dom.71023 [doi] AB - AIMS: Treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. While glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes, comparative effectiveness on liver-related outcomes remains unclear. This study compared the effectiveness of GLP-1 RAs versus SGLT-2 inhibitors on major adverse liver outcomes (MALO), liver cirrhosis and all-cause mortality in people with MASLD and type 2 diabetes. MATERIALS AND METHODS: This active comparator, new-user cohort study used claims data from Germany (2005-2024), including 45 256 people with MASLD and type 2 diabetes. New users of GLP-1 RAs (n = 9993) and SGLT-2 inhibitors (n = 35 263) were weighted using matching weights. The primary outcome was MALO, while secondary outcomes comprised individual MALO components (decompensation events, liver transplantation, hepatocellular carcinoma (HCC)), liver cirrhosis and all-cause mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated with weighted Cox proportional hazard models. RESULTS: Over a median 4.3-year follow-up, new users of GLP-1 RAs had a lower hazard of MALO (HR 0.91, 95% CI 0.78-1.07). This association appeared stronger using an on-treatment approach (HR 0.78, 95% CI 0.58-1.03) and when restricting to hospital diagnoses in primary position (HR 0.77, 95% CI 0.56-1.07). Benefits were also observed for liver cirrhosis (HR 0.88), decompensation events (HR 0.91), HCC (HR 0.76), but not all-cause mortality (HR 1.04). CONCLUSIONS: GLP-1 RAs were associated with a potentially lower hazard for incident MALO and liver cirrhosis compared with SGLT-2 inhibitors in people with MASLD and type 2 diabetes, suggesting a possible therapeutic advantage for liver-specific outcomes in this population. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Maier, Gregor A AU - Maier GA AUID- ORCID: 0009-0000-4528-9475 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Hofmann, Ramon A AU - Hofmann RA AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Roden, Michael AU - Roden M AUID- ORCID: 0000-0001-8200-6382 AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. AD - Division of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, University Hospital, Dusseldorf, Germany. AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Rathmann, Wolfgang AU - Rathmann W AUID- ORCID: 0000-0001-7804-1740 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Kuss, Oliver AU - Kuss O AUID- ORCID: 0000-0003-3301-5869 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. AD - Centre for Health and Society, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University, Dusseldorf, Germany. LA - eng PT - Journal Article DEP - 20260622 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Liver Cirrhosis/epidemiology MH - Germany/epidemiology MH - *Non-alcoholic Fatty Liver Disease/epidemiology MH - Cohort Studies MH - *Fatty Liver/epidemiology/complications MH - Incidence MH - Adult PMC - PMC13449085 OTO - NOTNLM OT - antidiabetic drug OT - effectiveness OT - fatty liver disease OT - observational study OT - pharmaco-epidemiology COIS- M.R. received personal fees for lectures or advisory boards from Astra Zeneca, Boehringer-Ingelheim, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk and Target RWE and investigator-initiated research support from Boehringer-Ingelheim and Novo Nordisk to the German Diabetes Center (DDZ). W.R. reports the receipt of consulting fees for attending educational sessions by Novo Nordisk outside of the topic of the current work. O.K. received honoraria for biostatistical education from Berlin-Chemie. G.A.M. and R.A.H. have no conflicts of interest. EDAT- 2026/06/23 00:34 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/22 22:12 PHST- 2026/06/02 00:00 [revised] PHST- 2026/01/09 00:00 [received] PHST- 2026/06/10 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/23 00:34 [pubmed] PHST- 2026/06/22 22:12 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71023 [pii] AID - 10.1111/dom.71023 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8277-8287. doi: 10.1111/dom.71023. Epub 2026 Jun 22. PMID- 42331726 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity. PG - 8242-8253 LID - 10.1111/dom.70861 [doi] AB - AIMS: This post hoc analysis evaluated the effect of survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations. MATERIALS AND METHODS: Trial 1404-0002 randomised 413 participants with type 2 diabetes on metformin to receive survodutide, placebo, or semaglutide over 16 weeks. Trial 1404-0036 randomised 387 participants with overweight/obesity and normoglycaemia to receive survodutide or placebo for 46 weeks. Descriptive statistics were derived from both trials. Biomarker responses were analysed using mixed models for repeated measures and regression analysis to assess the impact of bodyweight changes. RESULTS: In trial 1404-0002, survodutide was associated with significant and rapid increases in HOMA-beta versus placebo, with significant decreases in HOMA-IR, glucagon, and fasting plasma glucose (FPG). No significant changes occurred in high-molecular-weight (HMW) adiponectin, C-peptide, or fasting insulin levels. In trial 1404-0036, there was no significant change in HOMA-beta with survodutide versus placebo, likely owing to normoglycaemia in participants. Survodutide was associated with significant decreases in HOMA-IR, glucagon, C-peptide, fasting insulin, and FPG versus placebo, and significant increases in HMW adiponectin. Combining all survodutide dose groups for each trial, absolute change in bodyweight from baseline explained the largest proportion of total variability in changes from baseline in fasting insulin and HOMA-IR. However, it did not explain other changes observed. CONCLUSIONS: Survodutide was associated with significantly improved beta-cell function and insulin sensitivity in adults with type 2 diabetes and with overweight or obesity. The durability of beta-cell improvements after treatment cessation remains unknown. These effects were largely independent of bodyweight changes, suggesting additional metabolic benefit beyond weight loss. TRIAL REGISTRATION: Trial 1404-0002, ClinicalTrials.gov identifier: NCT04153929; EudraCT number: 2019-002390-60. Trial 1404-0036, ClinicalTrials.gov identifier: NCT04667377; EudraCT number: 2020-002479-37. CI - (c) 2026 Boehringer Ingelheim Pharma GmbH & Co. KG and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ekinci, Elif I AU - Ekinci EI AUID- ORCID: 0000-0003-2372-395X AD - Australian Centre for Accelerating Diabetes Innovations (ACADI), The University of Melbourne, Melbourne, Victoria, Australia. AD - Department of Medicine, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia. AD - Centre for Research and Education in Diabetes and Obesity (CREDO) and Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia. FAU - Maldonado, Sandra Gonzalez AU - Maldonado SG AUID- ORCID: 0009-0005-7723-7027 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Unseld, Anna AU - Unseld A AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Martinez, Jorge Arrubla AU - Martinez JA AUID- ORCID: 0000-0002-5926-9472 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - Hennige, Anita M AU - Hennige AM AUID- ORCID: 0000-0002-5149-4966 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Schoelch, Corinna AU - Schoelch C AUID- ORCID: 0009-0001-3596-7348 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. LA - eng SI - ClinicalTrials.gov/NCT04153929 SI - ClinicalTrials.gov/NCT04667377 GR - Boehringer Ingelheim/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20260622 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9007-92-5 (Glucagon) RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptide Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/metabolism MH - *Insulin Resistance/physiology MH - *Insulin-Secreting Cells/drug effects/metabolism/physiology MH - Female MH - Male MH - Biomarkers/blood/metabolism MH - Middle Aged MH - *Obesity/complications/drug therapy/metabolism/blood MH - *Hypoglycemic Agents/therapeutic use MH - *Overweight/complications/drug therapy/metabolism/blood MH - Semaglutide MH - Blood Glucose/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon/agonists MH - Metformin/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Adult MH - Diabesity MH - Double-Blind Method MH - *Peptide Fragments/therapeutic use MH - Drug Therapy, Combination MH - Aged PMC - PMC13448873 OTO - NOTNLM OT - GLP-1 OT - beta-cell function OT - glucagon OT - insulin sensitivity OT - obesity OT - overweight OT - survodutide OT - type 2 diabetes COIS- The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), as supported by Good Publication Practice (GPP) guidelines. The authors did not receive payment related to the development of this manuscript. E.I.E. is a consultant to Eli Lilly Australia and Novo Nordisk; funds are paid to her institution and are used for diabetes research, and her institute reports research funding support from Abbott, Amgen, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Bayer, Eli Lilly Australia, Endogenex, Insulet, NewAmsterdam, Novartis, and Versanis. S.G.M., A.U., J.A.M., A.M.H., and C.S. are employees of Boehringer Ingelheim. EDAT- 2026/06/23 00:33 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/22 22:03 PHST- 2026/04/28 00:00 [revised] PHST- 2026/01/21 00:00 [received] PHST- 2026/04/29 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/23 00:33 [pubmed] PHST- 2026/06/22 22:03 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70861 [pii] AID - 10.1111/dom.70861 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8242-8253. doi: 10.1111/dom.70861. Epub 2026 Jun 22. PMID- 42331063 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20260805 IS - 1541-6100 (Electronic) IS - 0022-3166 (Linking) VI - 156 IP - 8 DP - 2026 Aug TI - Analysis of NHANES: Nutrient, Food, and Beverage Intake of Glucagon-Like Peptide-1 Receptor Agonist Users with Type 2 Diabetes, 2007-2020. PG - 101685 LID - S0022-3166(26)00334-2 [pii] LID - 10.1016/j.tjnut.2026.101685 [doi] AB - BACKGROUND: There is increasing use of glucagon-like peptide-1 receptor agonists (GLP1-RAs) for the treatment of obesity and diabetes. OBJECTIVES: This study aims to evaluate differences in dietary intake among GLP1-RA users compared with nonusers and determine if length of use was associated with dietary intake in the United States. METHODS: National Health and Nutrition Examination Survey data (2007-2020) were used to identify individuals with diabetes aged >/=30 y with complete demographics, anthropometric, dietary intake, and prescription medication use details, and not currently breastfeeding or pregnant. Nutrient intake and adequacy, and intake of United States Department of Agriculture-defined food categories were compared across 3 groups consisting of non-GLP1-RA users (n = 4247), short-term users (GLP1-RA use <1 y; n = 42), and long-term users (GLP1-RA use >/=1 y; n = 85). The likelihood of meeting the dietary reference intake and dietary intake was assessed with multivariable regression models. RESULTS: Compared with nonusers, nonsignificantly lower mean energy intakes were observed among short-term users (1900 vs. 1700 kcal, respectively), and nonsignificantly higher average energy intakes were noted among long-term users (1900 vs. 2100 kcal). Compared with nonusers, short-term users displayed nutritional inadequacies for folate (69% vs. 49%, P = 0.042), iron (63% vs. 27%, P = 0.001), niacin (57% vs. 26%, P < 0.001), potassium (95% vs. 71%, P = 0.001), and vitamin B-6 (66% vs. 47%, P = 0.011). Food consumption varied with increased intake of higher-carbohydrate food categories (e.g., rice) in the nonusers and higher-protein food categories (e.g., beef) among users. Long-term users appear to have food consumption patterns that more closely resemble those of nonusers than those of short-term users. Similar results were noted for analyses restricted to obese individuals. CONCLUSIONS: Observed findings suggest a lower likelihood of being nutritionally inadequate among short-term GLP1-RA users. Additional investigations are warranted to understand the dynamic nutritional needs of individuals using GLP1-RAs based on the duration of treatment. CI - Copyright (c) 2026 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. FAU - Frankenfeld, Cara L AU - Frankenfeld CL AD - EpidStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. Electronic address: cfrankenfeld@epidstrategies.com. FAU - Movva, Naimisha AU - Movva N AD - EpidStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. FAU - Hooda, Naushin AU - Hooda N AD - EpidStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. FAU - Gauthier, Josie AU - Gauthier J AD - EpidStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. FAU - Reichert, Heidi AU - Reichert H AD - EpidStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. FAU - Doepker, Candace AU - Doepker C AD - ToxStrategies, A BlueRidge Life Sciences Company, Asheville, NC, USA. LA - eng PT - Journal Article DEP - 20260704 PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Nutrition Surveys MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Beverages MH - Male MH - Middle Aged MH - Adult MH - *Nutrients MH - United States MH - *Diet MH - Energy Intake OTO - NOTNLM OT - National Health and Nutrition Examination Survey (NHANES) OT - United States OT - adults OT - diabetes OT - glucagon-like peptide-1 receptor agonist (GLP1-RA) OT - nutrition COIS- Conflict of interest The authors report no conflicts of interest. EDAT- 2026/06/22 21:07 MHDA- 2026/08/06 11:36 CRDT- 2026/06/22 19:31 PHST- 2025/12/15 00:00 [received] PHST- 2026/06/13 00:00 [revised] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/08/06 11:36 [medline] PHST- 2026/06/22 21:07 [pubmed] PHST- 2026/06/22 19:31 [entrez] AID - S0022-3166(26)00334-2 [pii] AID - 10.1016/j.tjnut.2026.101685 [doi] PST - ppublish SO - J Nutr. 2026 Aug;156(8):101685. doi: 10.1016/j.tjnut.2026.101685. Epub 2026 Jul 4. PMID- 42328113 OWN - NLM STAT- MEDLINE DCOM- 20260622 LR - 20260813 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 23 IP - 7 DP - 2026 TI - Genetic Evidence for the Benefits and Risks of Glucose-Lowering Drugs on Cardiovascular-Kidney-Metabolic Syndrome: A Drug-Target Mendelian Randomization Study. PG - 2197-2208 LID - 10.7150/ijms.133077 [doi] AB - BACKGROUND: To explore the potential benefits and risks of glucose-lowering drugs on cardiovascular-kidney-metabolic (CKM) syndrome outcomes using drug-target Mendelian randomization (MR). METHODS: Genetic instruments for eight glucose-lowering drugs were identified from variants associated with glycated hemoglobin (HbA1c) and drug target gene expression. We employed two-sample MR and meta-analysis to estimate associations with nine CKM syndrome-related diseases, including coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), venous thromboembolism (VTE), peripheral artery disease (PAD), chronic kidney disease (CKD), and metabolic syndrome (MetS), using data from UK Biobank, FinnGen, and other large GWAS consortia. Supplementary analyses included summary-data-based MR (SMR) and colocalization. RESULTS: Genetic proxies for sodium-glucose cotransporter 2 inhibitors (SGLT2i) were associated with reduced risks of CAD (OR 0.85, 95% CI 0.73-0.98), HF (OR 0.66, 95% CI 0.44-0.98), and MetS (OR 0.64, 95% CI 0.50-0.82). GLP-1 receptor agonists (GLP-1RA) were linked to lower risks of CAD (OR 0.90, 95% CI 0.84-0.96), HF (OR 0.92, 95% CI 0.86-0.99), and CKD (OR 0.87, 95% CI 0.79-0.95). Metformin showed protective association with CAD (OR 0.51, 95% CI 0.40-0.66) and PAD (OR 0.99, 95% CI 0.99-1.00). Sulfonylureas showed a modest association with reduced CAD (OR 0.98, 95% CI 0.96-1.00). Conversely, insulin was associated with a higher risk of MetS (OR 1.07, 95% CI 1.02-1.13), and thiazolidinediones (TZDs) with an increased risk of HF (OR 1.12, 95% CI 1.05-1.20). SMR provided additional evidence for protective roles of GLP1R and VEGFA for CAD, KCNJ11 for HF, ABCC8 for HF and AF, and PRKAB1 for multiple cardiovascular outcomes. The detrimental effects of INSR on MetS and SERPINE1 on CKD and MetS were also verified. CONCLUSIONS: This study provides genetic evidence revealing the potential benefits and risks of certain glucose-lowering drugs in the management of CKM syndrome. These findings may inform target validation, drug repurposing, and personalized therapies for CKM syndrome. CI - (c) The author(s). FAU - Lu, Jian AU - Lu J AD - Department of Nephrology, China-Japan Friendship Hospital, Beijing, China. FAU - Sun, Shuaigang AU - Sun S AD - Department of Nephrology, China-Japan Friendship Hospital, Beijing, China. AD - Department of Nephrology, Capital Medical University China-Japan Friendship School of Clinical Medicine, Beijing, China. FAU - Shang, Xinru AU - Shang X AD - Department of Nephrology, China-Japan Friendship Hospital, Beijing, China. AD - Department of Nephrology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China. FAU - Jiang, Shimin AU - Jiang S AD - Department of Nephrology, China-Japan Friendship Hospital, Beijing, China. FAU - Deng, Zekai AU - Deng Z AD - School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Wang, Shunwei AU - Wang S AD - School of Public Health, Capital Medical University, Beijing, China. FAU - Wei, Chenping AU - Wei C AD - School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Hu, Jiaqi AU - Hu J AD - School of Healthcare Management, Tsinghua Medicine, Tsinghua University, Beijing, China. AD - Institute for Hospital Management, Tsinghua University, Beijing, China. FAU - Li, Wenge AU - Li W AD - Department of Nephrology, China-Japan Friendship Hospital, Beijing, China. AD - Department of Nephrology, Capital Medical University China-Japan Friendship School of Clinical Medicine, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260511 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin Secretagogues) RN - 9100L32L2N (Metformin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (PPAR-gamma Agonists) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Metabolic Syndrome/genetics/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Cardio-Renal Syndrome/genetics/drug therapy/epidemiology/prevention & control MH - Glycated Hemoglobin/genetics/metabolism MH - Insulin Secretagogues MH - *Cardiovascular Diseases/genetics MH - Metformin/therapeutic use MH - PPAR-gamma Agonists MH - Sulfonylurea Compounds/therapeutic use MH - Genome-Wide Association Study MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13280743 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Mendelian randomization OT - SGLT2 inhibitors OT - cardiovascular-kidney-metabolic syndrome OT - glucose-lowering drugs COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2026/06/22 13:42 MHDA- 2026/06/22 13:43 PMCR- 2026/05/11 CRDT- 2026/06/22 07:22 PHST- 2026/02/12 00:00 [received] PHST- 2026/04/20 00:00 [accepted] PHST- 2026/06/22 13:43 [medline] PHST- 2026/06/22 13:42 [pubmed] PHST- 2026/06/22 07:22 [entrez] PHST- 2026/05/11 00:00 [pmc-release] AID - ijmsv23p2197 [pii] AID - 10.7150/ijms.133077 [doi] PST - epublish SO - Int J Med Sci. 2026 May 11;23(7):2197-2208. doi: 10.7150/ijms.133077. eCollection 2026. PMID- 42324672 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20260903 IS - 1600-0447 (Electronic) IS - 0001-690X (Print) IS - 0001-690X (Linking) VI - 154 IP - 4 DP - 2026 Oct TI - Use of Glucagon-Like Peptide 1 Receptor Agonists and the Associated Risk of Hospitalisation in Bipolar Disorder, From a Nationwide Cohort, 2009-2024. PG - 305-312 LID - 10.1111/acps.70120 [doi] AB - INTRODUCTION: Diabetes, obesity and bipolar disorder often co-occur and may have shared pathophysiology. Glucagon-like peptide 1 receptor agonists (GLP-1RA) treat diabetes and obesity but their impact on bipolar disorder is unknown. In this era of stagnated pharmacotherapy, we examined psychiatric hospitalisation and absence from work due to sick leave as potential measures of relapse in people diagnosed with bipolar disorder who were also prescribed antidiabetic medications, including GLP-1RA. METHODS: The study cohort was derived from the National Swedish Registers and included all people with a diagnosis of bipolar disorder who used any antidiabetic medication, between the years 2009 and 2024. GLP-1RA individually and as a group were compared with non-use of GLP-1RA, and directly with other second-line antidiabetic medications. A within-individual design was utilised for all comparisons to reduce confounding. The main outcome was psychiatric hospitalisation for any reason, with secondary outcomes being psychiatric hospitalisation after a relapse of bipolar disorder, and sick leave due to psychiatric reasons. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were used. RESULTS: 14,694 people were included in the study, of whom 5200 used GLP-1RA. Semaglutide was associated with a 21% (aHR 0.79, 95% CI 0.69-0.91) lower risk of psychiatric hospitalisation compared with non-use of GLP-1RA in that same individual. Liraglutide and dulaglutide were not specifically associated with a lower hospitalisation risk. Semaglutide was also linked to a 17% (aHR 0.83, 95% CI 0.69-0.99) lower risk of relapse of bipolar disorder. Absences from work due to sick leave were not significantly associated with the specific antidiabetic medications studied. CONCLUSION: In people with both bipolar disorder and diabetes and/or obesity, the use of semaglutide was linked to lower rates of psychiatric hospitalisation compared with time periods when GLP-1RA were not used by that individual. Liraglutide and dulaglutide were not associated with reduced psychiatric hospitalisation, implying this is not a class effect. This finding with semaglutide should be further tested in a randomised controlled trial. CI - (c) 2026 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd. FAU - Taipale, Heidi AU - Taipale H AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. AD - School of Pharmacy, University of Eastern Finland, Kuopio, Finland. FAU - Taylor, Mark AU - Taylor M AUID- ORCID: 0000-0002-1159-6810 AD - School of Medicine and Dentistry, Griffith University, Gold Coast, Australia. AD - The Edinburgh Practice, Edinburgh, UK. FAU - Lahteenvuo, Markku AU - Lahteenvuo M AUID- ORCID: 0000-0002-7244-145X AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. FAU - Mittendorfer-Rutz, Ellenor AU - Mittendorfer-Rutz E AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tanskanen, Antti AU - Tanskanen A AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tiihonen, Jari AU - Tiihonen J AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. LA - eng GR - Sigrid Juselius Foundation/ GR - 250038/Jane and Aatos Erkko Foundation/ GR - Finnish Ministry of Social Affairs and Health/ GR - 2021-00154/Swedish Research Council/ PT - Journal Article DEP - 20260621 PL - United States TA - Acta Psychiatr Scand JT - Acta psychiatrica Scandinavica JID - 0370364 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Bipolar Disorder/epidemiology/drug therapy MH - Sweden/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Hospitalization/statistics & numerical data MH - Male MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Registries/statistics & numerical data MH - Middle Aged MH - Adult MH - Cohort Studies MH - Sick Leave/statistics & numerical data MH - Liraglutide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Obesity/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13532777 OTO - NOTNLM OT - GLP-1RA OT - bipolar OT - hospitalisation COIS- Drs Taipale, Tanskanen, Mittendorfer-Rutz and Tiihonen have participated in research projects funded by grants from Janssen to their employing institution. Dr. Taipale reports personal fees from Gedeon Richter, Janssen, Lundbeck and Otsuka. Dr. Tiihonen has received grants from EU/Forte, Finnish State Research Funding and Jane and Aatos Erkko Foundation, has been a consultant and/or advisor to and/or has received honoraria from: Healthcare Global Village, HLS Therapeutics, Janssen-Cilag, Lundbeck, Orion, Otsuka, Teva and WebMD Global. Dr. Lahteevuo has been a consultant and/or advisor and/or received honoraria from Lundbeck, Otsuka Pharma, Janssen, Johnson & Johnson, Orion Pharma and Recordati. The other author declare no conflicts of interest. EDAT- 2026/06/22 06:47 MHDA- 2026/09/01 17:39 PMCR- 2026/09/01 CRDT- 2026/06/22 00:53 PHST- 2026/05/15 00:00 [revised] PHST- 2026/02/13 00:00 [received] PHST- 2026/06/01 00:00 [accepted] PHST- 2026/09/01 17:39 [medline] PHST- 2026/06/22 06:47 [pubmed] PHST- 2026/06/22 00:53 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - ACPS70120 [pii] AID - 10.1111/acps.70120 [doi] PST - ppublish SO - Acta Psychiatr Scand. 2026 Oct;154(4):305-312. doi: 10.1111/acps.70120. Epub 2026 Jun 21. PMID- 42324630 OWN - NLM STAT- MEDLINE DCOM- 20260718 LR - 20260813 IS - 1464-5491 (Electronic) IS - 0742-3071 (Print) IS - 0742-3071 (Linking) VI - 43 IP - 8 DP - 2026 Aug TI - Wolfram syndrome and diabetes mellitus in Aotearoa, New Zealand: Phenotype and response to GLP-1 receptor agonist therapy. PG - e70405 LID - 10.1111/dme.70405 [doi] LID - e70405 AB - AIM: To describe the clinical characteristics of patients with Wolfram syndrome (WFS) and diabetes mellitus (DM) in Aotearoa, New Zealand. Review of response to therapy in those treated with glucagon-like peptide-1 receptor agonists (GLP1RA). METHODS: This retrospective cohort study describes 7 patients with WFS1 genetic variants (1 patient with WFS-like syndrome), and DM from 5 New Zealand families (age range 5-33 years, 4 females, 3 males). All are receiving insulin. In 5 patients receiving GLP1RA therapy, we described their pre- and post-treatment biometric parameters, glycaemic control and visual acuity. RESULTS: Genetic testing identified compound heterozygous variants in the WFS1 gene (inherited from each parent) in five patients. Another two were heterozygous carriers of a single WFS1 missense variant, one of which was associated with uniparental disomy. Among patients receiving GLP1RA therapy, reductions were seen in HbA1c (mean 11.6 mmol/mol) and total daily insulin dose (mean 0.25 units/kg/day). CONCLUSIONS: We report genotypic and phenotypic variability in association with clinical features, including age of onset and severity. GLP1RA therapy was associated with improvements in diabetic control. Longer-term follow-up is required to monitor for sustained benefit and for progression or improvement in other WFS clinical features. CI - (c) 2026 Diabetes UK. FAU - L'Amie, Abigail AU - L'Amie A AUID- ORCID: 0009-0005-6534-8918 AD - Department of Endocrinology, Greenlane Clinical Centre, Auckland Te Whatu Ora- Health, Auckland, New Zealand. AD - Department of Endocrinology, Te Whatu Ora Waitemata, Health New Zealand, Auckland, New Zealand. FAU - Vincent, Andrea L AU - Vincent AL AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. AD - Ophthalmology, Greenlane Clinical Centre, Auckland, Te Whatu Ora- Health New Zealand, Auckland, New Zealand. FAU - Jefferies, Craig A AU - Jefferies CA AUID- ORCID: 0000-0002-0541-6094 AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. AD - Starship Children's Health, Te Whatu Ora, Health New Zealand, Auckland, New Zealand. AD - Liggins Institute, University of Auckland, Auckland, New Zealand. FAU - Braatvedt, Geoffrey AU - Braatvedt G AD - Medical Specialists Group, Auckland, New Zealand. FAU - Wiltshire, Esko AU - Wiltshire E AD - Child Health Service, Te Whatu Ora/Health New Zealand Capital, Coast and Hutt Valley, Wellington, New Zealand. AD - Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand. FAU - Mouat, Fran AU - Mouat F AD - Starship Children's Health, Te Whatu Ora, Health New Zealand, Auckland, New Zealand. FAU - Albert, Benjamin B AU - Albert BB AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. AD - Starship Children's Health, Te Whatu Ora, Health New Zealand, Auckland, New Zealand. FAU - Murphy, Rinki AU - Murphy R AD - Department of Endocrinology, Greenlane Clinical Centre, Auckland Te Whatu Ora- Health, Auckland, New Zealand. AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. AD - Endocrinology, Counties Manukau, Auckland, Te Whatu Ora, Health New Zealand, Auckland, New Zealand. LA - eng PT - Journal Article DEP - 20260621 PL - England TA - Diabet Med JT - Diabetic medicine : a journal of the British Diabetic Association JID - 8500858 RN - 0 (wolframin protein) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Membrane Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Female MH - *Wolfram Syndrome/genetics/drug therapy/complications/epidemiology MH - Male MH - New Zealand/epidemiology MH - Phenotype MH - Adolescent MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Child MH - *Membrane Proteins/genetics MH - Adult MH - Retrospective Studies MH - Child, Preschool MH - Young Adult MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/complications MH - Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin/metabolism MH - Insulin/therapeutic use MH - Blood Glucose/metabolism MH - Treatment Outcome PMC - PMC13380341 OTO - NOTNLM OT - WFS1 OT - GLP1 receptor agonist OT - Wolfram OT - diabetes COIS- The authors have nothing to report. EDAT- 2026/06/22 06:45 MHDA- 2026/07/19 01:03 PMCR- 2026/07/18 CRDT- 2026/06/22 00:23 PHST- 2026/05/20 00:00 [revised] PHST- 2025/05/04 00:00 [received] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/07/19 01:03 [medline] PHST- 2026/06/22 06:45 [pubmed] PHST- 2026/06/22 00:23 [entrez] PHST- 2026/07/18 00:00 [pmc-release] AID - DME70405 [pii] AID - 10.1111/dme.70405 [doi] PST - ppublish SO - Diabet Med. 2026 Aug;43(8):e70405. doi: 10.1111/dme.70405. Epub 2026 Jun 21. PMID- 42322639 OWN - NLM STAT- MEDLINE DCOM- 20260620 LR - 20260620 IS - 1464-3502 (Electronic) IS - 0735-0414 (Linking) VI - 61 IP - 4 DP - 2026 May 13 TI - Interpretable machine learning for rare events: an inverse probability weighted application to understanding glucagon-like peptide-1 receptor agonists use and incident alcohol-related disorder. LID - agag045 [pii] LID - 10.1093/alcalc/agag045 [doi] AB - OBJECTIVE: Large administrative datasets enable investigation of rare outcomes, but accurate individual-level prediction remains challenging. Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used to treat diabetes and obesity, may reduce alcohol craving and intake. We examined predictors of incident alcohol-related disorder (ARD) using inverse probability-weighted (IPW) machine learning models, focusing on GLP-1 RA use. METHODS: We conducted a retrospective cohort study using the MarketScan Multi-State Medicaid Database (N = 96 460). Type 2 diabetic adults aged 18-64 years with GLP-1 RA prescription coverage (2022-2023) and no ARD in 2022 were included. Baseline variables included demographics, social risk factors (Z-codes), comorbidities, insurance characteristics, and GLP-1 RA use. Propensity scores were used to derive stabilized IPW weights to adjust for confounding in GLP-1 RA exposure. An Extreme Gradient Boosting model with IPW was trained using a 70/30 train-test split with five-fold cross-validation and probability calibration. Performance was evaluated using Area Under the Receiver Operating Characteristics Curve (AUROC), recall, and precision. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). RESULTS: GLP-1 RAs were used by 21.7% of individuals; 2.1% (N = 2004) developed incident ARD. The model demonstrated modest discrimination (AUROC = 0.67). Recall and precision were 0.28 and 0.05, respectively. SHAP analysis ranked GLP-1 RA use as the sixth most influential predictor and showed an association with lower predicted ARD risk. CONCLUSION: Predicting rare outcomes remains difficult, particularly for identifying positive cases. Interpretable machine learning identified GLP-1 RA use as an important feature associated with lower predicted ARD risk, warranting further investigation. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Medical Council on Alcohol and Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Gautam, Rinoj AU - Gautam R AD - College of Pharmacy, UNT Health, Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, United States. FAU - Wang, Hao AU - Wang H AUID- ORCID: 0000-0002-5105-0951 AD - Department of Emergency Medicine, JPS Health Network, 1500 S. Main St., Fort Worth, TX 76104, United States. FAU - Zhou, Bo AU - Zhou B AD - College of Pharmacy, UNT Health, Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, United States. FAU - Neba, Rolake AU - Neba R AD - College of Pharmacy, UNT Health, Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, United States. FAU - Sambamoorthi, Usha AU - Sambamoorthi U AD - Health Outcomes Research and AI Innovation, Department of Pharmacy Practice, School of Pharmacy, Temple University, 1801 N. Broad St., Philadelphia, PA 19140, United States. LA - eng GR - 5S21MD012472-05/National Institute on Minority Health and Health Disparities through the Texas Center for Health Disparities (NIMHD)/ GR - 1OT2OD032581-01/National Institutes of Health/Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity/ PT - Journal Article PL - England TA - Alcohol Alcohol JT - Alcohol and alcoholism (Oxford, Oxfordshire) JID - 8310684 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Machine Learning MH - Retrospective Studies MH - Female MH - Adult MH - Middle Aged MH - Male MH - Predictive Learning Models MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Alcohol-Related Disorders/epidemiology MH - Young Adult MH - United States/epidemiology MH - Adolescent MH - Prediction Algorithms MH - Probability MH - Boosting Machine Learning Algorithms OTO - NOTNLM OT - GLP-1 receptor agonists OT - Medicaid OT - alcohol-related disorder OT - inverse probability weighting OT - machine learning EDAT- 2026/06/21 22:34 MHDA- 2026/06/21 22:35 CRDT- 2026/06/20 14:33 PHST- 2026/03/17 00:00 [received] PHST- 2026/05/14 00:00 [revised] PHST- 2026/05/16 00:00 [accepted] PHST- 2026/06/21 22:35 [medline] PHST- 2026/06/21 22:34 [pubmed] PHST- 2026/06/20 14:33 [entrez] AID - 8712561 [pii] AID - 10.1093/alcalc/agag045 [doi] PST - ppublish SO - Alcohol Alcohol. 2026 May 13;61(4):agag045. doi: 10.1093/alcalc/agag045. PMID- 42320483 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260818 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 7 IP - 7 DP - 2026 Jul 21 TI - Safety and efficacy of GZR18, a long-acting GLP-1 analog, in Chinese patients with type 2 diabetes: A randomized, double-blind, phase 1b/2a trial. PG - 102874 LID - S2666-3791(26)00291-0 [pii] LID - 10.1016/j.xcrm.2026.102874 [doi] LID - 102874 AB - GZR18 is a long-acting glucagon-like peptide-1 receptor agonist that is under development for the treatment of type 2 diabetes mellitus (T2DM). In this randomized, double-blind, placebo-controlled phase 1b/2a trial in Chinese adults with T2DM, the safety and efficacy of once-weekly GZR18 are evaluated using different dose-titration regimens in two separate parts: Part A (0.5-4 mg over 26 weeks) and Part B (1.5-13 mg over 23 weeks). Overall, 72 participants are enrolled, of whom 62 complete the trial. GZR18 significantly reduces glycated hemoglobin (HbA1c) in both parts (Part A: -1.32% for GZR18 versus 0.86% for placebo; Part B: -1.81% for GZR18 versus 0.12% for placebo). Improvements in body weight and other metabolic parameters are also observed. GZR18 is safe and well tolerated, with mostly mild-to-moderate gastrointestinal adverse events; no severe hypoglycemia or treatment-related serious adverse events occurred. These findings support further development of GZR18 in larger, longer-term trials. The trial is registered at ClinicalTrials.gov (NCT06256523). CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Liu, Ming AU - Liu M AD - Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China. Electronic address: mingliu@tmu.edu.cn. FAU - Wang, Xuhong AU - Wang X AD - Department of Endocrinology, Beijing Luhe Hospital, Capital Medical University, Beijing, China. FAU - Li, Meizi AU - Li M AD - Department of Endocrinology, The Affiliated Hospital of Yanbian University, Yanbian, China. FAU - Yang, Enyue AU - Yang E AD - Office of Clinical Trials, The Affiliated Hospital of Yanbian University, Yanbian, China. FAU - Yang, Aige AU - Yang A AD - Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Yuan, Mingxia AU - Yuan M AD - Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Dong, Ruihua AU - Dong R AD - Research Ward, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Qin, Guijun AU - Qin G AD - Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Liu, Ping AU - Liu P AD - Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, China. FAU - Li, Chengqian AU - Li C AD - Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Cao, Yu AU - Cao Y AD - Clinical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Zhao, Jing AU - Zhao J AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Zhao, Liyuan AU - Zhao L AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Chen, Wei AU - Chen W AD - Gan & Lee Pharmaceuticals, Beijing, China; Gan & Lee Pharmaceuticals Shandong Co., Ltd, Linyi, China. Electronic address: weichen45@126.com. LA - eng SI - ClinicalTrials.gov/NCT06256523 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20260619 PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Chinese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Female MH - Glycated Hemoglobin/metabolism MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Male MH - Adult MH - Treatment Outcome MH - Aged MH - China MH - Glucagon-Like Peptide-1 Receptor Agonists MH - East Asian People PMC - PMC13400172 OTO - NOTNLM OT - GLP-1 receptor agonist OT - GZR18 OT - HbA1c OT - bofanglutide OT - type 2 diabetes OT - weight control COIS- Declaration of interests M. Liu, X.W., M. Li, E.Y., A.Y., M.Y., R.D., G.Q., P.L., C.L., and Y.C. received research funding from Gan & Lee Pharmaceuticals, during the conduct of the trial. W.C. is the shareholder of Gan & Lee Pharmaceuticals. J.Z. and L.Z. are employees of Gan & Lee Pharmaceuticals. EDAT- 2026/06/20 00:37 MHDA- 2026/07/22 12:37 PMCR- 2026/06/19 CRDT- 2026/06/19 18:42 PHST- 2025/09/09 00:00 [received] PHST- 2026/03/16 00:00 [revised] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/07/22 12:37 [medline] PHST- 2026/06/20 00:37 [pubmed] PHST- 2026/06/19 18:42 [entrez] PHST- 2026/06/19 00:00 [pmc-release] AID - S2666-3791(26)00291-0 [pii] AID - 102874 [pii] AID - 10.1016/j.xcrm.2026.102874 [doi] PST - ppublish SO - Cell Rep Med. 2026 Jul 21;7(7):102874. doi: 10.1016/j.xcrm.2026.102874. Epub 2026 Jun 19. PMID- 42319968 OWN - NLM STAT- MEDLINE DCOM- 20260619 LR - 20260813 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 42 IP - 5 DP - 2026 Jul TI - The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-Transporter-2 Inhibitors on Lean Body Mass in Humans: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. PG - e70194 LID - 10.1002/dmrr.70194 [doi] LID - e70194 AB - AIMS: The use of pharmacotherapies with weight loss properties for the management of obesity and chronic disease are now routinely prescribed. We investigated the evidence from randomised-controlled trials for the effects on lean body mass of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) in humans. MATERIALS AND METHODS: PubMed, MEDLINE, the Cochrane Library and CINAHL were searched from inception to October 2022. The primary outcome was change in body composition focused on measures of lean body mass (LBM). RESULTS: Thirty-six studies in population groups with obesity (n = 8), type 2 diabetes mellitus (n = 20), type 1 diabetes mellitus (n = 5) and polycystic ovary syndrome (n = 3) receiving a GLP-1RA or SGLT2i therapy versus placebo or active comparator satisfied our inclusion criteria, including 21 for GLP-1RA and 15 for SGLT2i. Meta-analysis showed an overall loss of LBM in the direction of the intervention groups prescribed GLP-1RA (MD: -1.51 kg [95% CI: -2.00 to -1.01]) and SGLT2i (MD: -1.04 kg [95% CI: -1.45 to -0.64]) with sub-group analysis showing largely consistent results when stratified by type of body composition outcome, type of body composition measurement technique and disease status. Results were not modified by sex. Further meta-analysis found that lean mass accounted for 28% (95% CI: 22%-34%) of overall weight loss induced by GLP-1RA and SGLT2i. CONCLUSIONS: GLP-1RA and SGLT2i are associated with a loss of LBM that appears congruent with overall weight loss. Monitoring of body composition and provision of combined therapy to preserve lean mass during weight loss should be considered. CI - (c) 2026 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Jobanputra, Rishi AU - Jobanputra R AUID- ORCID: 0000-0002-9585-1646 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - Sargeant, Jack A AU - Sargeant JA AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - Plekhanova, Tatiana AU - Plekhanova T AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - James, Emily AU - James E AUID- ORCID: 0000-0002-3032-9662 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - Almaqhawi, Abdullah AU - Almaqhawi A AUID- ORCID: 0000-0001-6035-1230 AD - Department of Family and Community Medicine, College of Medicine, King Faisal University, Al Ahsa, Saudi Arabia. FAU - Webb, David R AU - Webb DR AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. FAU - Yates, Thomas AU - Yates T AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK. LA - eng GR - National Institute for Health Research/ GR - Leicester Biomedical Research Centre/ GR - the NIHR Leicester Clinical Research Facility/ GR - the NIHR Applied Research Collaboration East Midlands/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Female MH - Humans MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy MH - Polycystic Ovary Syndrome/drug therapy MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Weight Loss/drug effects PMC - PMC13282017 OTO - NOTNLM OT - body composition OT - glucagon-like peptide-1 receptor agonists OT - lean body mass OT - sodium-glucose co-transporter-2 inhibitors OT - weight loss COIS- R.J., E.J., T.P. and A.A. report no conflict of interest. J.A.S. has received a grant in support of an investigator-initiated trial from AstraZeneca. D.R.W. has received honoraria as a speaker for AstraZeneca, Sanofi-Aventis and Lilly, and has received research funding support from Novo Nordisk. M.J.D. has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen, an advisory board member for Lexicon, Servier and Gilead Sciences Ltd and as a speaker for Napp Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen. T.Y. is supported by the NIHR Leicester BRC and has received funding from Astra Zeneca for an investigator-initiated project. EDAT- 2026/06/19 18:37 MHDA- 2026/06/19 18:38 PMCR- 2026/06/19 CRDT- 2026/06/19 14:23 PHST- 2026/03/13 00:00 [revised] PHST- 2024/05/16 00:00 [received] PHST- 2026/06/05 00:00 [accepted] PHST- 2026/06/19 18:38 [medline] PHST- 2026/06/19 18:37 [pubmed] PHST- 2026/06/19 14:23 [entrez] PHST- 2026/06/19 00:00 [pmc-release] AID - DMRR70194 [pii] AID - 10.1002/dmrr.70194 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 Jul;42(5):e70194. doi: 10.1002/dmrr.70194. PMID- 42318205 OWN - NLM STAT- MEDLINE DCOM- 20260619 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Effects of SGLT-2 inhibitors and GLP-1 receptor agonists on liver function in patients with non-alcoholic fatty liver disease and type 2 diabetes. PG - 1865769 LID - 10.3389/fendo.2026.1865769 [doi] LID - 1865769 AB - BACKGROUND: The goal was having the comparisons be direct when it came to seeing how much of a help the sodium-glucose co transporter - 2 inhibitors (SGTL2is) compared to the glucagon-like peptide-1 receptor agonists (GLP-1RAs) were in regard to how the liver enzymes performed within people having type 2 diabetes (T2D) along with nonalcoholic fatty liver disease (NAFLD), a condition characterized by excessive fat accumulation in the liver without alcohol overconsumption. METHODS: A total of 705 subjects with T2DM and NAFLD at time of first SGLT2is (n=381) or GLP-1RAs (n=324) enrolment in this multicentre posterior cohort study from 01/2020-12/2024. Baseline characteristics were made equivalent via PSM via a 1: 1 NN match and a 0. 2 SD match clamp. The main measurement was the difference in alanine amino transferase (DeltaALT) and aspartate aminotransferase (DeltaAST) from the beginning and 6 months. And other result was about the change in metabolic parametres. The independent predictors of liver-enzyme change came from the multivariate linear regression analysis. RESULTS: After PSM, 243 well-matched pairs were successfully identified, with baseline characteristics acceptably balanced (standardized differences <0.2 for all covariates and <0.1 for most covariates). In the matched cohort, SGLT2is treatment was associated with significantly greater reductions in ALT (DeltaALT: -10.55 +/- 12.66 vs. -7.28 +/- 15.34 U/L, p=0.011) and AST (DeltaAST: -7.68 +/- 10.07 vs. -5.18 +/- 11.04 U/L, p=0.010) compared to GLP-1RAs treatment. No significant differences were observed for changes in GGT, body weight, glycemic control, or lipid profiles between groups. Multivariable regression analysis revealed that SGLT2is treatment was independently associated with reductions in both ALT (beta = -3.34, p=0.009) and AST (beta = -2.32, p=0.016). Weight change was independently associated with AST reduction (beta = 0.22, p=0.016) but not with ALT reduction. CONCLUSION: SGLT2is were associated with greater ALT and AST reductions than GLP-1RAs in T2D patients with NAFLD, with ALT improvement independent of weight loss, suggesting potential direct hepatoprotective effects. CI - Copyright (c) 2026 Guo, Li, Li, Shi, Yan, Yan, Zhou and Huang. FAU - Guo, Wancheng AU - Guo W AD - Department of Endocrinology, Quanjiao County People's Hospital, Chuzhou, China. FAU - Li, Wenhe AU - Li W AD - Department of Endocrinology, Quanjiao County People's Hospital, Chuzhou, China. FAU - Li, Xianlin AU - Li X AD - Department of Endocrinology, Quanjiao County People's Hospital, Chuzhou, China. FAU - Shi, Wen AU - Shi W AD - Department of Endocrinology, Huai 'an Clinical Medical College of Jiangsu University, Huaian, China. AD - Department of Endocrinology, Huai 'an Hospital of Huai 'an City, Huaian, China. FAU - Yan, Yan AU - Yan Y AD - Department of Endocrinology, Huai 'an Clinical Medical College of Jiangsu University, Huaian, China. FAU - Yan, Ting AU - Yan T AD - Department of Endocrinology, Huai 'an Clinical Medical College of Jiangsu University, Huaian, China. AD - Department of Endocrinology, Huai 'an Hospital of Huai 'an City, Huaian, China. FAU - Zhou, Jie AU - Zhou J AD - Department of Endocrinology, Huai 'an Clinical Medical College of Jiangsu University, Huaian, China. AD - Department of Endocrinology, Huai 'an Hospital of Huai 'an City, Huaian, China. FAU - Huang, Yujie AU - Huang Y AD - Department of Endocrinology, Huai 'an Clinical Medical College of Jiangsu University, Huaian, China. AD - Department of Endocrinology, Huai 'an Hospital of Huai 'an City, Huaian, China. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260603 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Alanine Transaminase/blood MH - Aspartate Aminotransferases/blood MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use MH - *Liver/drug effects MH - Liver Function Tests MH - *Non-alcoholic Fatty Liver Disease/drug therapy/complications/pathology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology PMC - PMC13271928 OTO - NOTNLM OT - clinical trial OT - glucagon-like peptide-1 receptor agonists OT - non-alcoholic fatty liver disease OT - sodium-glucose cotransporter-2 inhibitors OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/06/19 06:32 MHDA- 2026/06/19 06:33 PMCR- 2026/06/03 CRDT- 2026/06/19 04:57 PHST- 2026/04/26 00:00 [received] PHST- 2026/05/22 00:00 [revised] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/06/19 06:33 [medline] PHST- 2026/06/19 06:32 [pubmed] PHST- 2026/06/19 04:57 [entrez] PHST- 2026/06/03 00:00 [pmc-release] AID - 10.3389/fendo.2026.1865769 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jun 3;17:1865769. doi: 10.3389/fendo.2026.1865769. eCollection 2026. PMID- 42314528 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 1879-0267 (Electronic) IS - 0020-1383 (Linking) VI - 57 IP - 8 DP - 2026 Aug TI - Glucagon-like peptide-1 receptor agonist use for type 2 diabetes and risk of upper extremity fragility fracture. PG - 113456 LID - S0020-1383(26)00441-9 [pii] LID - 10.1016/j.injury.2026.113456 [doi] AB - PURPOSE: Older adults with type 2 diabetes mellitus (T2DM) face an elevated risk of fragility fractures. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have grown in use for the management of T2DM over recent years, however, their potential skeletal effects remain incompletely understood. This study evaluated the association between sustained GLP-1RA use and the risk of upper extremity fragility fractures in this population. METHODS: A retrospective cohort study was conducted using TriNetX, a global electronic health record platform. Adults of age >/= 50 years with T2DM and active metformin use were included, excluding individuals with documented osteoprotective medication use. Patients were stratified by long-term GLP-1RA exposure (>/=5 years of use). Cohorts were propensity-score matched at a 1:1 ratio, utilizing demographic (age, race, sex), clinical (comorbidities associated with fracture risk), and laboratory covariates (hemoglobin A1c). Pharmacotherapy initiation was defined as the initiation of metformin (control) or GLP-1RA therapy (exposure). Incidence of composite upper extremity fractures (distal radius, olecranon, proximal/distal humerus) was evaluated over the 5 years following pharmacotherapy initiation. Subgroup analyses were performed for high-risk populations and multivariate regression analyses evaluated the contribution of individual GLP-1RA agents to composite upper extremity fragility fracture risk. RESULTS: This study identified 194,205 patients, with 34,830 patients in the GLP-1RA cohort and 159,375 in the control cohort. Following matching, each cohort consisted of 32,116 patients. Over the 5 years following pharmacotherapy initiation, patients with and without GLP-1RA use were at similar risk of upper extremity fragility fracture. No significant differences were detected on high-risk subgroup analysis. This study did not identify any individual GLP-1RA agent to confer protection against upper extremity fragility fracture. CONCLUSIONS: While GLP-1RAs appear safe with respect to fracture risk, their hypothesized osteoprotective effects did not translate to clinically meaningful reductions in upper extremity fragility fracture incidence. CI - Copyright (c) 2026 British Trauma Society. Published by Elsevier Ltd. All rights reserved. FAU - Cathey, Jackson M AU - Cathey JM AD - Duke University School of Medicine, 40 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: jackson.cathey@duke.edu. FAU - Fischer, James P AU - Fischer JP AD - Division of Hand Surgery, Department of Orthopaedics, Duke University Schol of Medicine, 40 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: james.fischer@duke.edu. FAU - Zhang, Justin AU - Zhang J AD - University of Maryland School of Medicine, 685 W Baltimore Street, Baltimore, MD 21021, USA. Electronic address: justin.zhang@som.umaryland.edu. FAU - Hammert, Warren C AU - Hammert WC AD - Division of Hand Surgery, Department of Orthopaedics, Duke University Schol of Medicine, 40 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: warren.hammert@duke.edu. FAU - Klifto, Christopher S AU - Klifto CS AD - Division of Hand Surgery, Department of Orthopaedics, Duke University Schol of Medicine, 40 Duke Medicine Circlel̥, Durham, NC 27710, USA. Electronic address: christopher.klifto@duke.edu. FAU - Pidgeon, Tyler S AU - Pidgeon TS AD - Division of Hand Surgery, Department of Orthopaedics, Duke University Schol of Medicine, 40 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: tyler.pidgeon@duke.edu. LA - eng PT - Journal Article DEP - 20260617 PL - Netherlands TA - Injury JT - Injury JID - 0226040 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - Metformin/therapeutic use MH - Risk Factors MH - Incidence MH - *Osteoporotic Fractures/epidemiology/prevention & control MH - *Upper Extremity/injuries MH - Aged, 80 and over OTO - NOTNLM OT - Diabetes OT - Fragility Fracture OT - GLP-1RA OT - Metformin OT - Upper Extremity COIS- Declaration of Competing Interest The authors declare no conflicts of interest. EDAT- 2026/06/19 00:36 MHDA- 2026/07/14 12:34 CRDT- 2026/06/18 18:09 PHST- 2025/11/11 00:00 [received] PHST- 2026/05/17 00:00 [revised] PHST- 2026/06/13 00:00 [accepted] PHST- 2026/07/14 12:34 [medline] PHST- 2026/06/19 00:36 [pubmed] PHST- 2026/06/18 18:09 [entrez] AID - S0020-1383(26)00441-9 [pii] AID - 10.1016/j.injury.2026.113456 [doi] PST - ppublish SO - Injury. 2026 Aug;57(8):113456. doi: 10.1016/j.injury.2026.113456. Epub 2026 Jun 17. PMID- 42312204 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Glucagon-like peptide-1 receptor agonists and advanced liver outcomes in type 2 diabetes: a systematic review and exploratory meta-analysis. PG - 1874720 LID - 10.3389/fendo.2026.1874720 [doi] LID - 1874720 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve weight, glycemic control, and cardiometabolic risk factors, but randomized trials have not been powered to determine effects on advanced liver outcomes. We conducted a systematic review and exploratory meta-analysis of peer-reviewed comparative real-world cohort studies in adults with type 2 diabetes (T2D), emphasizing active-comparator designs, clinically advanced liver endpoints, and transparent limits of causal inference. PubMed/MEDLINE and Embase were searched with citation chasing and an updated PubMed/MEDLINE search through 25 April 2026; this evidence-identification strategy was focused rather than exhaustive. Twelve eligible comparative studies were included. In the predefined active-comparator outcome-family stratum, four studies comparing GLP-1RAs with DPP-4 inhibitors were sufficiently exchangeable for exploratory random-effects synthesis of incident cirrhosis or composite serious liver events. The primary Hartung-Knapp small-sample interval for the pooled estimate was HR 0.85 (95% CI 0.74-0.98); the conventional REML interval was narrower and is reported as a secondary reference estimate (95% CI 0.79-0.93; I(2)=0%; REML tau(2)=0.000). Certainty of evidence was rated very low because all included studies were observational, outcome definitions and comparator strategies varied, and residual confounding and healthcare-engagement bias could not be excluded. GLP-1RA use shows a directionally favorable signal for advanced liver outcomes in T2D, but the evidence should be interpreted as hypothesis-supporting rather than definitive causal proof. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261299499, identifier CRD420261299499. CI - Copyright (c) 2026 Hu, Chang, Huang, Liu and Hsieh. FAU - Hu, Jing-Hong AU - Hu JH AD - Division of Gastroenterology and Hepatology, Yunlin Chang Gung Memorial Hospital, Yunlin, Taiwan. FAU - Chang, Ming-Ling AU - Chang ML AD - Division of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Huang, Tung-Jung AU - Huang TJ AD - Division of Pulmonary and Critical Care Medicine, Yunlin Chang Gung Memorial Hospital, Yunlin, Taiwan. FAU - Liu, Nai-Jen AU - Liu NJ AD - Division of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hsieh, Yung-Yu AU - Hsieh YY AD - Division of Gastroenterology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260602 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Liver/drug effects MH - Liver Cirrhosis PMC - PMC13268877 OTO - NOTNLM OT - comparative effectiveness research OT - diabetes mellitus OT - glucagon-like peptide 1 receptor agonists OT - hepatocellular carcinoma OT - liver cirrhosis OT - metabolic dysfunction-associated steatotic liver disease OT - real-world evidence OT - type 2 COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/06/18 06:31 MHDA- 2026/06/18 06:32 PMCR- 2026/06/02 CRDT- 2026/06/18 04:45 PHST- 2026/05/07 00:00 [received] PHST- 2026/05/19 00:00 [revised] PHST- 2026/05/20 00:00 [accepted] PHST- 2026/06/18 06:32 [medline] PHST- 2026/06/18 06:31 [pubmed] PHST- 2026/06/18 04:45 [entrez] PHST- 2026/06/02 00:00 [pmc-release] AID - 10.3389/fendo.2026.1874720 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jun 2;17:1874720. doi: 10.3389/fendo.2026.1874720. eCollection 2026. PMID- 42311550 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20260926 IS - 2308-118X (Electronic) IS - 0857-1074 (Print) IS - 0857-1074 (Linking) VI - 41 IP - 1 DP - 2026 Apr TI - Guideline-Directed Medical Therapies for Diabetic Kidney Disease Among Thai People With Type 2 Diabetes: A Real-World Data Based on Theptarin Diabetes Staging. PG - 49-58 LID - 10.15605/jafes.041.01.6239 [doi] AB - BACKGROUND: The "pillar approach" was recently proposed to holistically address diabetic kidney disease (DKD). Theptarin Diabetes Staging (TDS) is a staging system for type 2 diabetes (T2D) designed to prevent or delay the progression to advanced stages. OBJECTIVE: To evaluate the rate of guideline-directed medical therapies (GDMT) among individuals with DKD from 2021 to 2025 according to the TDS system. METHODOLOGY: A retrospective review of medical records of T2D patients with TDS stage 4Ka (moderately increased persistent albuminuria), Stage 4Kb (severely increased persistent albuminuria), and stage 5Ka (eGFR <45 mL/min/1.73 m(2)) was conducted. The rates of RASi, SGLT2i, GLP-1 RA, and finerenone use, along with achievement of metabolic targets, were evaluated prospectively from 2021 to 2025. RESULTS: A total of 206 medical records were reviewed (mean age 64.1 +/- 10.3 years, A1C 7.3 +/- 1.2%, mean eGFR 71.6 +/- 24.5 mL/min/1.73 m(2)). In 2021, the use of RASi was 78.2%, 51.5% for SGLT2i and 13.6% for GLP-1 RA among all patients. Four years later, rates of GDMT improved as follows: RASi 79.7%, SGLT2i 59.3%, GLP-1 RA 19.8% and finerenone 2.8%. However, only 1.1% of all patients in 2025 received all 4 GDMT items. More stable or improved TDS were observed in patients who received GDMT >/=3 classes across all 4 medication classes, compared with those who received GDMT <3 classes (96.2% vs. 78.8%, P-value = 0.036). CONCLUSION: The real-world implementation of GDMT among DKD patients remains inadequate, and more efforts are required to improve GDMT adoption. Regular reviews and feedback are warranted to improve attainment of treatment targets and better clinical outcomes. CI - (c) 2026 Journal of the ASEAN Federation of Endocrine Societies. FAU - Chongvoranond, Peachaphol AU - Chongvoranond P AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Chatchomchaun, Waralee AU - Chatchomchaun W AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Wanothayaroj, Ekgaluck AU - Wanothayaroj E AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Butadej, Siriwan AU - Butadej S AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Nakasatien, Soontaree AU - Nakasatien S AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Himathongkam, Thep AU - Himathongkam T AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. FAU - Thewjitcharoen, Yotsapon AU - Thewjitcharoen Y AD - THEPTARIN Diabetes, Thyroid and Endocrine Center, Vimut-Theptarin Hospital, Bangkok, Thailand. LA - eng PT - Journal Article DEP - 20260429 PL - Philippines TA - J ASEAN Fed Endocr Soc JT - Journal of the ASEAN Federation of Endocrine Societies JID - 8608483 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/drug therapy/etiology MH - Female MH - Retrospective Studies MH - Middle Aged MH - Male MH - Aged MH - Thailand/epidemiology MH - Practice Guidelines as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13269334 OTO - NOTNLM OT - Thai OT - Theptarin Diabetes Staging OT - diabetic kidney disease OT - guideline-directed medical therapies (GDMT) prescription rates COIS- The authors declared no conflict of interest. EDAT- 2026/06/18 06:32 MHDA- 2026/06/18 06:33 PMCR- 2026/04/01 CRDT- 2026/06/18 04:37 PHST- 2026/01/16 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/06/18 06:33 [medline] PHST- 2026/06/18 06:32 [pubmed] PHST- 2026/06/18 04:37 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - JAFES-41-1-049 [pii] AID - 10.15605/jafes.041.01.6239 [doi] PST - ppublish SO - J ASEAN Fed Endocr Soc. 2026 Apr;41(1):49-58. doi: 10.15605/jafes.041.01.6239. Epub 2026 Apr 29. PMID- 42309121 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - 1-year outcomes of semaglutide, tirzepatide, and sleeve gastrectomy in obesity in type 2 diabetes: a retrospective cohort study. PG - 638-648 LID - S2213-8587(26)00030-6 [pii] LID - 10.1016/S2213-8587(26)00030-6 [doi] AB - BACKGROUND: Type 2 diabetes and obesity are prevalent, inter-related conditions for which treatment options have expanded substantially, yet direct real-world comparisons of modern pharmacological and surgical interventions remain scarce. We aimed to compare 1-year weight loss, glycaemic outcomes, and selected safety outcomes associated with semaglutide, tirzepatide, and sleeve gastrectomy among adults with obesity and type 2 diabetes in real-world clinical practice. METHODS: We conducted a retrospective cohort study using Epic Cosmos, a de-identified electronic health record dataset from 1633 hospitals and 37 900 clinics across 280 health systems in the USA. Adults with a BMI of at least 35 kg/m(2) and HbA(1c) above 6.4% who initiated at least 12 months of therapy with semaglutide or tirzepatide and attaining maintenance doses, or who underwent sleeve gastrectomy, were eligible for inclusion. The primary outcome was attainment of at least 20% bodyweight loss and HbA(1c) below 5.7% at 1 year after the index date. Multivariable logistic regression estimated adjusted probabilities and relative risks, adjusting for age, sex, race, baseline HbA(1c), BMI, Charlson Comorbidity Index, Social Vulnerability Index (SVI 2020), and baseline medication burden for diabetes, lipids, and hypertension. Prespecified safety outcomes included emergency department visits and new prescriptions for gastro-oesophageal reflux disease or nausea within 1 year of the index date. The primary composite outcome was analysed among patients with both follow-up weight and HbA(1c) available in the 9-month to 15-month window. Emergency department visits were analysed in the final analysis cohort (ie, patients meeting all inclusion and exclusion criteria and with available baseline and 9-month to 15-month weight and HbA(1c) measurements) and medication-based safety outcomes were analysed descriptively using outcome-specific available data denominators without imputation. FINDINGS: A total of 468 712 patients with at least 365 consecutive days of semaglutide or tirzepatide prescriptions and 238 028 patients undergoing sleeve gastrectomy were identified in Epic Cosmos. After applying prespecified inclusion and exclusion criteria, 45 649 patients met inclusion criteria; after exclusion of 556 patients with missing Charlson Comorbidity Index data, 45 093 were included in the primary outcome analysis: 33 482 (74.3%) treated with semaglutide, 4178 (9.3%) treated with tirzepatide, and 7433 (16.5%) who underwent sleeve gastrectomy. The adjusted probability of attaining the primary composite outcome of at least 20% bodyweight loss and HbA(1c) below 5.7% at 1 year was 3.0% (95% CI 2.8-3.2) for semaglutide, 13.2% (12.2-14.3) for tirzepatide, and 24.0% (22.9-25.1) for sleeve gastrectomy. Emergency department visits within 1 year were more frequent after sleeve gastrectomy than after semaglutide or tirzepatide. New prescriptions for gastro-oesophageal reflux disease and nausea occurred in all treatment groups but varied in frequency, with higher absolute rates observed after sleeve gastrectomy. INTERPRETATION: At 1 year after the index date, sleeve gastrectomy was associated with the highest probability of attaining combined weight and glycaemic targets, followed by tirzepatide and semaglutide. Interpretation should consider baseline differences-including higher BMI, younger age, and lower baseline HbA(1c) in the sleeve gastrectomy group-as well as residual confounding and the limited scope of safety assessment. FUNDING: None. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Leslie, Daniel B AU - Leslie DB AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address: lesli002@umn.edu. FAU - Steffen, Brian T AU - Steffen BT AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Wise, Eric AU - Wise E AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Steffen, Lyn M AU - Steffen LM AD - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. FAU - Kopacz, Kristi AU - Kopacz K AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Ruanpeng, Darin AU - Ruanpeng D AD - Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Jacobs, David R Jr AU - Jacobs DR Jr AD - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. FAU - Ikramuddin, Sayeed AU - Ikramuddin S AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. LA - eng PT - Journal Article DEP - 20260617 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Gastrectomy/methods MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy/complications/therapy MH - Weight Loss MH - Adult MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/analysis COIS- Declaration of interests SI receives grant support from Rheacell. All other authors declare no competing interests. EDAT- 2026/06/18 00:32 MHDA- 2026/07/15 18:40 CRDT- 2026/06/17 18:52 PHST- 2025/07/08 00:00 [received] PHST- 2026/02/02 00:00 [revised] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/07/15 18:40 [medline] PHST- 2026/06/18 00:32 [pubmed] PHST- 2026/06/17 18:52 [entrez] AID - S2213-8587(26)00030-6 [pii] AID - 10.1016/S2213-8587(26)00030-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):638-648. doi: 10.1016/S2213-8587(26)00030-6. Epub 2026 Jun 17. PMID- 42308439 OWN - NLM STAT- MEDLINE DCOM- 20260617 LR - 20260813 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 107 IP - 1 DP - 2026 Jul 14 TI - Semaglutide and Risk of Adult-Onset Seizure: A Target Trial Emulation. PG - e218174 LID - 10.1212/WNL.0000000000218174 [doi] AB - BACKGROUND AND OBJECTIVES: Adult-onset seizure reflects the burden of acquired brain insults, but established disease-modifying preventive strategies are limited. We evaluated whether semaglutide initiation is associated with a lower incidence of adult-onset seizure compared with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other glucose-lowering drugs (GLDs) in adults with type 2 diabetes. METHODS: Using the All of Us Research Program, we emulated a population-based target trial in new-user, active-comparator cohorts from January 2018 to October 2023. We compared semaglutide vs other GLDs and semaglutide vs SGLT2i. Incident epilepsy or seizure was identified from diagnostic codes. Effects were estimated using inverse probability of treatment weighting with weighted Cox models and targeted maximum likelihood estimation (TMLE). Subgroup and sensitivity analyses with multiple outcome definitions and analytic approaches were conducted to assess the robustness of findings. We evaluated mediation through hemoglobin A1c (HbA1c) and body mass index (BMI) using the longitudinal Vansteelandt framework. RESULTS: We analyzed 10,213 patients in the semaglutide (n = 2,586, mean age, 60.1 years; 56.8% female) vs other GLDs cohort (n = 7,627, mean age, 63.7 years; 54.2% female) and 8,605 patients in the semaglutide (n = 2,814, mean age, 60.5 years; 66.2% female) vs SGLT2i cohort (n = 5,791, mean age, 64.4 years; 47.3% female). Semaglutide was associated with a lower risk of adult-onset seizure compared with other GLDs (weighted HR 0.44 [95% CI 0.25-0.79]; 4-year risk difference -1.78% [95% CI -2.58 to -0.98]) and SGLT2i (weighted HR 0.48 [95% CI 0.27-0.85]; 4-year risk difference -1.46% [95% CI -2.41 to -0.51]). TMLE estimated risk differences per 1,000 persons of -14.20 (95% CI -18.33 to -10.07) vs other GLDs and -7.62 (95% CI -11.65 to -3.60) vs SGLT2i, corresponding to numbers needed to treat of 70 and 131, respectively. Mediation was minimal for HbA1c (2.4% vs other GLDs; 6.5% vs SGLT2i) and BMI (0% vs other GLDs; 0.7% vs SGLT2i). DISCUSSION: Semaglutide initiation was associated with a lower risk of adult-onset seizure compared with SGLT2i and other GLDs in patients with type 2 diabetes, independent of glycemic and weight effects. Residual confounding, low event counts, and shorter follow-up limit causal interpretation. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semaglutide use was associated with a lower risk of adult-onset seizures compared with other GLDs and SGLT2i. FAU - Eun, Yong AU - Eun Y AUID- ORCID: 0000-0001-7222-8328 AD - Department of Medicine, NYC Health + Hospitals/Harlem, New York. AD - Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. FAU - Bong, Suhwan AU - Bong S AUID- ORCID: 0000-0001-6077-1198 AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA. FAU - Koh, Hyun Yong AU - Koh HY AUID- ORCID: 0000-0002-3995-4341 AD - Department of Pediatrics, Division of Neurology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. FAU - Trousdale, Rhonda K AU - Trousdale RK AUID- ORCID: 0000-0002-9739-6966 AD - Department of Medicine, NYC Health + Hospitals/Harlem, New York. AD - Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. AD - Division of Endocrinology, Department of Medicine, NYC Health + Hospitals/Harlem, New York. FAU - Cho, Young Min AU - Cho YM AUID- ORCID: 0000-0002-2331-6126 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. FAU - Jang, Yoonhyuk AU - Jang Y AUID- ORCID: 0009-0004-5991-7822 AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. AD - Biomedical Research Institute, Seoul National University Hospital, South Korea; and. AD - Department of Immunology, Harvard Medical School, Harvard University, Boston, MA. FAU - Lee, Soon-Tae AU - Lee ST AUID- ORCID: 0000-0003-4767-7564 AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. LA - eng GR - OT2 OD037643/OD/NIH HHS/United States PT - Journal Article DEP - 20260617 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Seizures/epidemiology/prevention & control MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC13278381 MID - NIHMS2162855 COIS- Conflict of Interest Disclosures Y. Eun reports no disclosures relevant to the manuscript. S. Bong reports no disclosures relevant to the manuscript. H.Y. Koh reports no disclosures relevant to the manuscript. R.K. Trousdale reports no disclosures relevant to the manuscript. Y.M. Cho received consultation fees from LG Chemical and Hanmi, research grants from Sanofi, AstraZeneca, and Daewoong Pharmaceuticals. Y.M. Cho is an outside director of Daewoong Pharmaceuticals. Y. Jang reports no disclosures relevant to the manuscript. S.-T. Lee reports advisory roles from Roche/Genentech, Advanced Neural Technologies, argenx, Arialys, Piehealthcare, and Salted, outside the submitted work. EDAT- 2026/06/17 18:35 MHDA- 2026/06/17 18:36 PMCR- 2026/06/18 CRDT- 2026/06/17 16:02 PHST- 2026/06/17 18:36 [medline] PHST- 2026/06/17 18:35 [pubmed] PHST- 2026/06/17 16:02 [entrez] PHST- 2026/06/18 00:00 [pmc-release] AID - 10.1212/WNL.0000000000218174 [doi] PST - ppublish SO - Neurology. 2026 Jul 14;107(1):e218174. doi: 10.1212/WNL.0000000000218174. Epub 2026 Jun 17. PMID- 42307179 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260813 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 46 IP - 8 DP - 2026 Aug 19 TI - The evolving therapeutic landscape of gut-pancreatic peptide signalling in metabolic disorders: from mono- to multi-agonist therapies. LID - 10.1042/BSR20250114 [doi] LID - BSR20250114 AB - The pharmacotherapeutic landscape for the clinical management of type-2 diabetes (T2D), obesity, metabolic dysfunction-associated steatotic liver disease, and steatohepatitis is evolving swiftly in response to the escalating global prevalence and incidence of these interrelated metabolic disorders. Although insulin and metformin formulations have long constituted the foundation of diabetes care, a paradigm shift in T2D management has been observed with the advent of novel pharmacotherapies. Gut peptide analogues are at the forefront of this transformation. The emergence of glucagon-like peptide-1 (GLP-1) receptor agonists represents a watershed moment, fundamentally reshaping the therapeutic landscape for both T2D and obesity due to multifaceted metabolic benefits. The clinical success of GLP-1-based therapies has stimulated pharmaceutical interest in other metabolic peptides. Gut-pancreatic peptides such as glucose-dependent insulinotropic polypeptide, glucagon, amylin, and peptide YY are of particular interest due to their distinct pharmacological benefits and therapeutic promise in metabolic disorders. The present review aims to provide a comprehensive and current overview of non-insulin gut-pancreatic peptide signalling-based therapies that are either clinically approved or under clinical investigation, with a focus on the emerging therapeutic convergence between T2D, obesity, and associated liver disease. The review critically narrates their mechanisms of action, therapeutic efficacy, limitations, current development status, and positioning in the treatment landscape. Furthermore, the review delineates the emerging avenues in the development of novel peptide-based pharmacotherapies, offering insights into their future potential and acquainting the reader with developments in non-insulin gut-pancreatic peptide signalling-based therapies for metabolic disorders. CI - (c) 2026 The Author(s). FAU - Patil, Mohan AU - Patil M AD - Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, Australia. AD - School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia. FAU - Piccinini, Federico AU - Piccinini F AD - Department of Medicine and Surgery, University of Parma, Parma 43125, Italy. FAU - Johnstone, Elizabeth K M AU - Johnstone EKM AD - Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, Australia. AD - School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia. FAU - Casari, Ilaria AU - Casari I AD - Department of Medicine and Surgery, University of Parma, Parma 43125, Italy. FAU - Falasca, Marco AU - Falasca M AUID- ORCID: 0000-0002-9801-7235 AD - Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, Australia. AD - School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia. AD - Department of Medicine and Surgery, University of Parma, Parma 43125, Italy. AD - Lipovexa SRL, Via Giuseppe Mangionello, 12, 73024 Maglie (LE), Italy. LA - eng PT - Journal Article PT - Review PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Signal Transduction/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Obesity/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Metabolic Diseases/drug therapy/metabolism MH - Gastric Inhibitory Polypeptide/metabolism PMC - PMC13376848 OTO - NOTNLM OT - glucagon-like peptide-1 OT - non alcoholic fatty liver disease OT - obesity OT - type 2 diabetes COIS- M.F. is a member of LIPOVEXA S.r.l., a spin-off company focused on developing innovative treatments for diabetes, obesity, and liver health. The other authors declare no conflicts of interest. EDAT- 2026/06/17 13:28 MHDA- 2026/07/16 12:40 PMCR- 2026/07/16 CRDT- 2026/06/17 08:33 PHST- 2026/01/29 00:00 [received] PHST- 2026/05/31 00:00 [revised] PHST- 2026/06/16 00:00 [accepted] PHST- 2026/07/16 12:40 [medline] PHST- 2026/06/17 13:28 [pubmed] PHST- 2026/06/17 08:33 [entrez] PHST- 2026/07/16 00:00 [pmc-release] AID - 237729 [pii] AID - BSR20250114 [pii] AID - 10.1042/BSR20250114 [doi] PST - ppublish SO - Biosci Rep. 2026 Aug 19;46(8):BSR20250114. doi: 10.1042/BSR20250114. PMID- 42304446 OWN - NLM STAT- MEDLINE DCOM- 20260823 LR - 20260913 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Jun 16 TI - Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease. LID - 10.1186/s12933-026-03242-9 [doi] LID - 254 AB - BACKGROUND: In type 2 diabetes, cardioprotective glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, and statins reduce the risk of secondary major adverse cardiovascular events. No trials examined the combination of these drugs as withholding statins in high-risk individuals would be unethical. We tested the hypothesis that cardioprotective glucose-lowering drug and statin combined is associated with lower risk of secondary major adverse cardiovascular events than either drug alone. METHODS: Individuals with type 2 diabetes and established cardiovascular disease from December 2012 through 2021 were identified via national Danish health registers. They were analyzed in an active comparator cohort including 15,404 individuals followed from treatment intensification with cardioprotective glucose-lowering drug or dipeptidyl peptidase-4 inhibitor and additionally in a time-varying cohort including 76,853 individuals with yearly updated treatment and covariate status. The treatment groups were: (i) no cardioprotective drug (no use of cardioprotective glucose-lowering drug or statin), (ii) cardioprotective glucose-lowering drug, (iii) statin, and (iv) cardioprotective glucose-lowering drug and statin. The primary outcome was a new major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death). RESULTS: During mean 2.7 and 4.7 years of follow-up, 1,843 and 23,051 had major adverse cardiovascular events in the active comparator and time-varying cohorts. In the active comparator cohort, when compared to nonusers of cardioprotective glucose-lowering drug or statin, multivariable adjusted hazard ratios of major adverse cardiovascular events were 0.82 (95% confidence interval: 0.67 to 1.02) for cardioprotective glucose-lowering drug, 0.85 (0.74 to 0.97) for statin, and 0.71 (0.60 to 0.84) for cardioprotective glucose-lowering drug and statin combined. Corresponding hazard ratios in the time-varying cohort were 0.77 (0.69 to 0.86), 0.73 (0.70 to 0.75), and 0.57 (0.54 to 0.60), respectively. When restricting the active comparator cohort to individuals entering observation between 2019 and 2021 with reduced statistical power, the corresponding hazard ratios were 0.86 (0.57 to 1.31), 0.89 (0.60 to 1.30), and 0.79 (0.54 to 1.14), respectively. In both cohorts p for interaction between cardioprotective glucose-lowering drug and statin was > 0.05. CONCLUSIONS AND RELEVANCE: In individuals with type 2 diabetes and established cardiovascular disease, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with lower risk of secondary major adverse cardiovascular events than using either drug alone. This is important given the persistently suboptimal uptake of both drug classes in real-world practice. Some biases can never be completely excluded in real-world pharmacotherapy use studies such as this one, including confounding by indication, time-related or immortal time biases, and shifting standards of care, rendering causal interpretation unattainable; however, our results seemed consistent across numerous sensitivity analyses and designs. CI - (c) 2026. The Author(s). FAU - Ternhamar, Tummas AU - Ternhamar T AD - Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, DK-2730, Herlev, Denmark. AD - The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, 2730, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. FAU - Johansen, Mia O AU - Johansen MO AD - The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, 2730, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. AD - Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, DK-2730, Herlev, Denmark. AD - The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, 2730, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. FAU - Afzal, Shoaib AU - Afzal S AD - Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, DK-2730, Herlev, Denmark. Shoaib.Afzal@regionh.dk. AD - The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 73, 2730, Herlev, Denmark. Shoaib.Afzal@regionh.dk. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. Shoaib.Afzal@regionh.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260616 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood/mortality MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use/adverse effects MH - *Cardiovascular Diseases/diagnosis/prevention & control/epidemiology/mortality MH - Female MH - Time Factors MH - Male MH - Denmark/epidemiology MH - Middle Aged MH - Aged MH - Treatment Outcome MH - Risk Assessment MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Registries MH - *Glycemic Control/adverse effects MH - Drug Therapy, Combination MH - *Blood Glucose/drug effects/metabolism MH - Protective Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Biomarkers/blood MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - *Secondary Prevention MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13501814 OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes OT - Glucagon-like peptide-1 receptor agonists OT - Sodium-glucose cotransporter-2 inhibitors OT - Statins COIS- Declarations. Ethics approval and consent to participate: Data access was granted after review of applications to Statistics Denmark (projects 707535 and 708406). In accordance with Danish law (Komiteloven), register-based studies that do not involve biological material, and do not involve sensitive bioinformatics data such as genomic data or imaging data do not require ethical approval or informed consent[46]. Consent for publication: Not applicable. Competing interests: TT and MOJ report no competing interests. SA reports support for meeting attendance from Abbott. BGN reports consultancies with Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Lilly, Marea Therapeutics, Merck, Novartis, Novo Nordisk, and Sanofi. EDAT- 2026/06/17 06:32 MHDA- 2026/08/24 05:34 PMCR- 2026/06/16 CRDT- 2026/06/17 00:14 PHST- 2026/02/13 00:00 [received] PHST- 2026/05/24 00:00 [accepted] PHST- 2026/08/24 05:34 [medline] PHST- 2026/06/17 06:32 [pubmed] PHST- 2026/06/17 00:14 [entrez] PHST- 2026/06/16 00:00 [pmc-release] AID - 10.1186/s12933-026-03242-9 [pii] AID - 3242 [pii] AID - 10.1186/s12933-026-03242-9 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Jun 16;25(1):254. doi: 10.1186/s12933-026-03242-9. PMID- 42304171 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis. PG - 7689-7704 LID - 10.1111/dom.70957 [doi] AB - BACKGROUND: Antidiabetic drugs differ in their effects on body composition, which may influence metabolic and functional outcomes. This systematic review and network meta-analysis aimed to quantify and compare effects of major antidiabetic drugs on key body composition parameters. METHODS: PubMed, Web of Science and Scopus were searched from inception to March 2025 for randomized controlled trials. Network meta-analyses used a frequentist random-effects framework to estimate mean differences (MDs) and 95% confidence intervals (CIs) for changes in fat mass (FM) and lean body mass (LBM). RESULTS: Forty-one trials involving 2906 participants were included. For FM among Glucagon-like peptide-1 (GLP-1) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, tirzepatide showed the greatest reduction compared with placebo (MD -10.70 kg; 95% CI: -13.42 to -7.99), followed by liraglutide plus exercise. Semaglutide and liraglutide produced moderate reductions. In contrast, insulin glargine and alogliptin were associated with FM gain relative to metformin and exenatide. For LBM, tirzepatide (MD -4.40 kg; 95% CI: -7.58 to -1.22) and liraglutide (MD -1.54 kg; 95% CI: -2.55 to -0.52) were associated with significant reductions. Sodium-glucose cotransporter-2 (SGL2) inhibitors caused minor losses, whereas metformin, insulin regimens and dipeptidyl peptidase-4 (DPP4) inhibitors showed neutral effects. CONCLUSION: GLP-1 and dual GIP/GLP-1 receptor agonists produced the greatest FM reduction but also decreased lean mass. Exercise mitigated liraglutide-related LBM loss. SGLT2 inhibitors showed modest effects, while metformin, insulin, DPP4 inhibitors and sulfonylureas had minimal impact. Further research on dose, duration and lifestyle influences is warranted. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Rakhsha, Seyedeh Samira AU - Rakhsha SS AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. AD - Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Shahinfar, Hossein AU - Shahinfar H AD - Nutritional Health Research Center, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Ebrahimi-Mousavi, Sara AU - Ebrahimi-Mousavi S AD - Department of Clinical Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AD - Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Kosari, Ali AU - Kosari A AD - Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Aali, Yasaman AU - Aali Y AUID- ORCID: 0000-0001-8320-6300 AD - Department of Clinical Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AD - Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Mirzababaei, Atieh AU - Mirzababaei A AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hosseini, Seyed Alireza AU - Hosseini SA AD - Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. FAU - Jadidi, Paria AU - Jadidi P AD - Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran. FAU - Shafiee, Gita AU - Shafiee G AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - MansourZadeh, Mohammad Javad AU - MansourZadeh MJ AD - Prevention of Metabolic Disorders Research Center, Research Institute for Metabolic and Obesity Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Heshmat, Ramin AU - Heshmat R AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Mastouri, Dena AU - Mastouri D AD - Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. LA - eng GR - 1403-04-75722-221/Chronic Diseases Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260616 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Secretagogues) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/pharmacology MH - Insulin Secretagogues MH - Metformin/pharmacology MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide PMC - PMC13449080 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 OT - SGLT2 inhibitor OT - antidiabetic drug OT - incretin therapy OT - metformin COIS- AI tool ChatGPT (version GPT-5 mini) was used solely to assist with language editing and formatting; all analyses and interpretations were performed by the authors. The authors declare no conflicts of interest. EDAT- 2026/06/17 00:35 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/16 23:43 PHST- 2026/05/10 00:00 [revised] PHST- 2026/02/27 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/17 00:35 [pubmed] PHST- 2026/06/16 23:43 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70957 [pii] AID - 10.1111/dom.70957 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):7689-7704. doi: 10.1111/dom.70957. Epub 2026 Jun 16. PMID- 42302979 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260903 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) VI - 88 IP - 3 DP - 2026 Sep TI - Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes. PG - 366-377 LID - S0272-6386(26)00964-9 [pii] LID - 10.1053/j.ajkd.2026.04.007 [doi] AB - RATIONALE & OBJECTIVE: Glucagon-like peptide 1 (GLP-1) receptor agonist treatment is associated with a lower risk for incident chronic kidney disease (CKD) and death relative to treatment with a dipeptidyl peptidase 4 inhibitor or sulfonylurea. This study examined within class effects of GLP-1 receptor agonists on kidney outcomes in type 2 diabetes mellitus (T2DM) and moderate cardiovascular risk. STUDY DESIGN: Retrospective observational study using the target trial emulation framework. SETTING & PARTICIPANTS: This study used claims data from OptumLabs Data Warehouse and 100% sample of Medicare fee-for-service claims. Participants were adults >/=21 years of age, at moderate cardiovascular risk, who filled a new prescription for a GLP-1 receptor agonist between January 1, 2019 and December 31, 2021. EXPOSURE: GLP-1 receptor agonists dulaglutide, exenatide, liraglutide, or semaglutide. OUTCOME: A primary kidney composite outcome inclusive of incident diagnosis codes for CKD stages 3-4 and kidney failure (inclusive of CKD stage 5 and kidney replacement therapy). A secondary kidney composite outcome included the elements of the primary composite outcome plus death from any cause. Components of the kidney composite outcomes were also evaluated independently. ANALYTICAL APPROACH: Random treatment assignment was emulated using inverse probability of treatment weighting (IPTW) with propensity scores estimated using the SuperLearner ensemble method. Primary analyses were time-to-event models under the intention-to-treat framework using cause-specific IPTW Cox proportional hazards models. RESULTS: There was no difference among dulaglutide, exenatide, liraglutide, and semaglutide with respect to the primary outcome. When compared to dulaglutide and exenatide, semaglutide was associated with a reduced risk for the secondary kidney composite outcome by 8% (HR, 0.92 [95% CI, 0.87-0.97]) and 12% (HR, 0.88 [95% CI, 0.79-0.99]), respectively. Compared to dulaglutide, semaglutide was also associated with reduced risk of death (HR, 0.81 [95% CI, 0.70-0.93]). LIMITATIONS: Potential for residual confounding, lack of hemoglobin A(1c) and weight data, and uncertainty about the indication for GLP-1 receptor agonist prescriptions. CONCLUSIONS: No differences were observed among different GLP-1 receptor agonists for the primary outcome, but semaglutide initiation was associated with a lower risk of the secondary kidney composite outcome and of death. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) is a common complication of diabetes that increases the risk for poor health outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists were found to improve kidney outcomes in people with type 2 diabetes mellitus (T2DM) and moderate cardiovascular risk when compared with dipeptidyl peptidase-4 inhibitors and sulfonylureas. Although there has been no head-to-head comparison of individual GLP-1 receptor agonists, randomized controlled trials have suggested that there may be variation among members of this drug class on kidney disease outcomes. In this study, we tested whether there were differences in kidney outcomes when comparing individual GLP-1 receptor agonist medications. We found that semaglutide compared favorably to other drugs in the class and may represent the preferred GLP-1 receptor agonist for delaying or preventing CKD in this population. CI - Copyright (c) 2026 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington. Electronic address: jneumiller@wsu.edu. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairi, Minnesota. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairi, Minnesota. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, School of Medicine, Yale University, New Haven, Connecticut. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut; Department of Health Policy and Management, School of Public Health, Yale University, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - Dryden, Kate AU - Dryden K AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington; Kidney Research Institute and Institute of Translational Health Sciences, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairi, Minnesota; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland; Institute for Health Computing, University of Maryland, North Bethesda, Maryland. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260616 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Female MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Renal Insufficiency, Chronic/epidemiology MH - Exenatide/therapeutic use MH - Liraglutide/therapeutic use MH - Middle Aged MH - United States/epidemiology MH - *Diabetic Nephropathies OTO - NOTNLM OT - Chronic kidney disease OT - GLP-1 receptor agonist OT - comparative effectiveness and safety OT - target trial emulation OT - type 2 diabetes EDAT- 2026/06/17 00:36 MHDA- 2026/08/20 23:35 CRDT- 2026/06/16 19:34 PHST- 2025/07/18 00:00 [received] PHST- 2026/02/28 00:00 [revised] PHST- 2026/04/05 00:00 [accepted] PHST- 2026/08/20 23:35 [medline] PHST- 2026/06/17 00:36 [pubmed] PHST- 2026/06/16 19:34 [entrez] AID - S0272-6386(26)00964-9 [pii] AID - 10.1053/j.ajkd.2026.04.007 [doi] PST - ppublish SO - Am J Kidney Dis. 2026 Sep;88(3):366-377. doi: 10.1053/j.ajkd.2026.04.007. Epub 2026 Jun 16. PMID- 42300258 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Combining Sodium-Glucose Co-Transporter-2 Inhibitor Plus Glucagon-Like Peptide-1 Receptor Agonist for Glucose-Lowering in Type 2 Diabetes: Effects of Drug Initiation Sequence on Kidney Function in Real-World Clinical Practice (CombiKid Study). PG - 7950-7963 LID - 10.1111/dom.70946 [doi] AB - AIMS: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have separately shown renoprotective effects in clinical trials in people with type 2 diabetes. It is unclear whether combining these agents produces incremental kidney outcome benefits. MATERIALS AND METHODS: Retrospective cohort study with a prevalent new-user design using pseudonymised data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care sentinel network. We extracted data for two cohorts prescribed SGLT2is and/or GLP-1 RAs between January 2013 and December 2021. We 1:1 propensity score matched SGLT2i plus GLP-1 RA combination users with monotherapy (SGLT2i or GLP-1RA) users. Multivariable linear regression analyses estimated adjusted mean differences in absolute change in estimated glomerular filtration rate (eGFR) (baseline to 1- and 2-years follow-up) between combination and monotherapy. RESULTS: Across the matched combination and SGLT2i monotherapy groups (N = 14 774), mean decline in eGFR, baseline to 1-year, was -4.5 mL/min/1.73 m(2) and 2-years, -5.0 mL/min/1.73 m(2), with no difference when comparing combination and SGLT2i monotherapy. Across the matched combination and GLP-1 RA monotherapy groups (N = 14 154), mean decline in eGFR, baseline to 1-year, was -5.4 mL/min/1.73 m(2) and 2-years, -6.1 mL/min/1.73 m(2), but combination therapy was associated with a smaller eGFR reduction compared with GLP-1 RA monotherapy (difference in eGFR at 1-year: [mean, 95% confidence interval, CI] 2.2, 1.7 to 2.8, p < 0.001; and at 2-years: 2.1, 1.4-2.7, p < 0.001). CONCLUSIONS: In real-world clinical practice, the combination of SGLT2i and GLP-1 RA may be more effective for preserving kidney function than GLP-1 RA monotherapy. This effect was not seen with combination versus SGLT2i monotherapy. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hinton, William AU - Hinton W AUID- ORCID: 0000-0003-4927-0901 AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. AD - Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK. FAU - Joy, Mark AU - Joy M AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Forbes, Anna K AU - Forbes AK AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. AD - Renal Services, Epsom and St. Helier University Hospitals NHS Trust, London, UK. FAU - Whyte, Martin B AU - Whyte MB AUID- ORCID: 0000-0002-2897-2026 AD - Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK. FAU - Ordonez-Mena, Jose M AU - Ordonez-Mena JM AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Fan, Xuejuan AU - Fan X AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Ferreira, Filipa AU - Ferreira F AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Meza-Torres, Bernardo AU - Meza-Torres B AUID- ORCID: 0000-0001-6551-5484 AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Munro, Neil AU - Munro N AD - Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK. FAU - de Lusignan, Simon AU - de Lusignan S AUID- ORCID: 0000-0002-8553-2641 AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. AD - Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), London, UK. FAU - Wheeler, David C AU - Wheeler DC AD - Centre for Kidney and Bladder Health, University College London, London, UK. FAU - Feher, Michael D AU - Feher MD AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. LA - eng GR - MISP 60830/Merck Sharp & Dohme Ltd./ PT - Journal Article DEP - 20260616 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/physiopathology MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Retrospective Studies MH - Drug Therapy, Combination MH - Male MH - Glomerular Filtration Rate/drug effects MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - *Kidney/drug effects/physiopathology MH - Blood Glucose/drug effects/metabolism MH - Diabetic Nephropathies/prevention & control PMC - PMC13448856 OTO - NOTNLM OT - cohort studies OT - glucagon-like peptide-1 receptor agonists OT - kidney function tests OT - sodium-glucose transporter 2 inhibitors OT - type 2 diabetes mellitus COIS- W.H. has had part of his academic salary funded from grant awards with Eli Lilly and Co., Novo Nordisk Ltd., AstraZeneca UK Ltd., and Merck Sharp & Dohme Ltd. A.K.F. has received travel expenses from AstraZeneca. S.d.L. has received grants through the Nuffield Department of Primary Care Health Sciences, University of Oxford for investigator-led studies in diabetes and cardio-metabolic disease from GlaxoSmithKline, Eli Lilly and Co., Novo Nordisk Ltd., Sanofi, and Merck Sharp & Dohme Ltd. M.B.W. has received grant funding from Sanofi, Eli Lilly and Co., and speaker fees from AstraZeneca and Merck Sharp & Dohme Ltd. D.C.W. has received honoraria and/or consultancy fees in the last 2 years from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, CSL, Dimetrix, GSK, Menarini, MSD, Pathaly, ProKidney, PureSpring, Vertex, and Vifor. M.D.F. was awarded a grant from Merck Sharp & Dohme Ltd. through the Nuffield Department of Primary Care Health Sciences, University of Oxford for this study. M.D.F. has received personal speaker fees from Sanofi and Menarini. All other authors declare no competing interests. EDAT- 2026/06/16 13:49 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/16 08:06 PHST- 2026/05/13 00:00 [revised] PHST- 2026/02/13 00:00 [received] PHST- 2026/05/24 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/16 13:49 [pubmed] PHST- 2026/06/16 08:06 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70946 [pii] AID - 10.1111/dom.70946 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):7950-7963. doi: 10.1111/dom.70946. Epub 2026 Jun 16. PMID- 42298552 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260813 IS - 1471-2474 (Electronic) IS - 1471-2474 (Linking) VI - 27 IP - 1 DP - 2026 Jun 15 TI - Glucagon-like peptide-1 receptor agonists and rotator cuff disease: a scoping review. LID - 10.1186/s12891-026-10092-9 [doi] LID - 532 AB - BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are associated with impaired rotator cuff tendon healing and inferior clinical outcomes following surgical repair. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly used to manage obesity and T2DM. However, their influence on rotator cuff disease biology and outcomes following cuff repair remains unknown. METHODS: A scoping review was conducted in accordance with PRISMA-ScR guidelines. MEDLINE, Embase, PubMed, and the Cochrane Library were searched from inception to 28 January 2026 for studies evaluating associations between GLP-1RA exposure and rotator cuff disease. Eligible studies included human observational cohort studies and preclinical experimental studies. Data were extracted independently by two reviewers and synthesised descriptively. RESULTS: Six studies were included, four human retrospective cohort studies and two controlled preclinical studies. The human studies included 1,481,529 patients, of which 391,716 were GLP-1RA users. Preoperative GLP-1RA use was not associated with increased postoperative complications following rotator cuff repair. However, GLP-1RA use was associated with increased incidence of atraumatic rotator cuff tears and subsequent repair. Preclinical models of acute rotator cuff injury and repair found that liraglutide improved biomechanical strength and organisation of the repaired tendon-bone interface, reduced fatty infiltration, and attenuated cellular stress responses. CONCLUSIONS: The current evidence does not demonstrate an association between GLP-1RA use and increased risk of postoperative complications following rotator cuff repair. Studies reported an association between GLP-1RA use and higher incidence of atraumatic rotator cuff tears. Preclinical data suggest GLP-1RA may influence rotator cuff tissue healing. High-quality prospective studies are required to clarify the effects of GLP-1RA on rotator cuff disease. CI - (c) 2026. The Author(s). FAU - Duru, Dave Osinachukwu AU - Duru DO AUID- ORCID: 0009-0005-8396-6146 AD - School of Clinical Medicine, University of Cambridge, Cambridge, UK. dd614@cam.ac.uk. FAU - Zhou, Andrew Kailin AU - Zhou AK AD - University of Warwick, Coventry, UK. AD - Department of Trauma and Orthopaedics, University Hospital Coventry and Warwickshire, Coventry, UK. FAU - Lee, David Kwan Ryung AU - Lee DKR AD - School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Carroll, Patrick J AU - Carroll PJ AD - Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. AD - Surgeon Investigator, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, ON, Canada. FAU - Elmaraghy, Amr AU - Elmaraghy A AD - Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. AD - Surgeon Investigator, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, ON, Canada. LA - eng PT - Journal Article PT - Scoping Review DEP - 20260615 PL - England TA - BMC Musculoskelet Disord JT - BMC musculoskeletal disorders JID - 100968565 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/therapeutic use MH - Obesity/drug therapy/complications MH - *Postoperative Complications/epidemiology/chemically induced MH - *Rotator Cuff/drug effects/surgery MH - *Rotator Cuff Injuries/surgery PMC - PMC13295517 OTO - NOTNLM OT - Diabetes OT - GLP-1 OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Rotator cuff OT - Rotator cuff repair OT - Tendon healing COIS- Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/06/16 06:35 MHDA- 2026/06/25 06:37 PMCR- 2026/06/15 CRDT- 2026/06/16 00:40 PHST- 2026/02/16 00:00 [received] PHST- 2026/06/11 00:00 [accepted] PHST- 2026/06/25 06:37 [medline] PHST- 2026/06/16 06:35 [pubmed] PHST- 2026/06/16 00:40 [entrez] PHST- 2026/06/15 00:00 [pmc-release] AID - 10.1186/s12891-026-10092-9 [pii] AID - 10092 [pii] AID - 10.1186/s12891-026-10092-9 [doi] PST - epublish SO - BMC Musculoskelet Disord. 2026 Jun 15;27(1):532. doi: 10.1186/s12891-026-10092-9. PMID- 42297761 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Temporal Trends and Clinical Characteristics of Incretin-Based Therapy Use in Women With Polycystic Ovary Syndrome: A Real-World Cohort Study From a Polish Private Healthcare Network. PG - 8045-8056 LID - 10.1111/dom.71017 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual GIP/GLP-1 receptor agonist tirzepatide are increasingly used for weight and cardiometabolic management, but real-world prescribing patterns in women with polycystic ovary syndrome (PCOS) remain poorly characterised. METHODS: We performed a retrospective cohort study of 38 263 adult women with ICD-coded PCOS in the LUX MED network, Poland, using electronic health records data from July 2006 to April 2026. The primary analysis included women diagnosed with PCOS in 2018-2024 and evaluated prescription-recorded initiation of GLP-1 RA/GIP-GLP-1 RA therapy within 365 days after the index diagnosis. Temporal trends were assessed using logistic regression with unadjusted and multivariable-adjusted models. RESULTS: Overall, 4557 women (11.9%) had a recorded GLP-1 RA/GIP-GLP-1 RA prescription and 16 381 (42.8%) received metformin. Among incretin-based therapy users, 75.5% had metformin co-exposure, whereas only 11.5% had coded type 2 diabetes mellitus. Recorded BMI was higher among GLP-1 RA/GIP-GLP-1 RA users than among metformin-only or untreated women (median 31.2 vs. 26.3 and 22.1 kg/m(2)) and greater comorbidity burden (all p < 0.001). Initiation within 365 days rose from 0.14% in 2018 to 5.97% in 2024. Calendar year was strongly associated with initiation (unadjusted OR 1.52, 95% CI, 1.44-1.59; adjusted OR 1.64, 95% CI, 1.56-1.73; both p < 0.001), with consistent results after excluding women with diabetes. CONCLUSIONS: Incretin-based therapy use in PCOS increased markedly over time, suggesting expansion beyond classical glycaemic indications toward weight-focused and cardiometabolic management. Studies using dispensing, persistence, safety and outcome data are needed. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Dziewierz, Artur AU - Dziewierz A AUID- ORCID: 0000-0002-2100-5076 AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. AD - Second Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. FAU - Kulicka, Natalia AU - Kulicka N AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. AD - Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland. FAU - Stolarska, Kaja AU - Stolarska K AUID- ORCID: 0009-0002-8849-1141 AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Ahmatovic, Anesa AU - Ahmatovic A AUID- ORCID: 0009-0000-2350-2466 AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Domienik-Karlowicz, Justyna AU - Domienik-Karlowicz J AD - Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland. AD - Higher School of Medical Sciences, LUX MED Group, Warsaw, Poland. FAU - Rulkiewicz, Anna AU - Rulkiewicz A AD - LUX MED Group, Warsaw, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AUID- ORCID: 0000-0002-8033-3977 AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. AD - Higher School of Medical Sciences, LUX MED Group, Warsaw, Poland. AD - LUX MED Group, Warsaw, Poland. LA - eng PT - Journal Article DEP - 20260615 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Female MH - *Polycystic Ovary Syndrome/drug therapy/epidemiology/complications MH - Poland/epidemiology MH - *Incretins/therapeutic use MH - Retrospective Studies MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - *Hypoglycemic Agents/therapeutic use MH - Metformin/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Young Adult MH - Cohort Studies PMC - PMC13448982 OTO - NOTNLM OT - cohort studies OT - drug utilization OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - polycystic ovary syndrome OT - tirzepatide COIS- The authors declare that generative artificial intelligence (Claude Opus 4.7, Anthropic) was used during the preparation of this manuscript for language editing and stylistic improvement. Following its use, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. The authors declare no conflicts of interest. EDAT- 2026/06/16 00:33 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/15 22:52 PHST- 2026/05/30 00:00 [revised] PHST- 2026/05/05 00:00 [received] PHST- 2026/06/08 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/16 00:33 [pubmed] PHST- 2026/06/15 22:52 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71017 [pii] AID - 10.1111/dom.71017 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8045-8056. doi: 10.1111/dom.71017. Epub 2026 Jun 15. PMID- 42297751 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Weight Changes With Lower Doses of Semaglutide in Clinical Practice: Findings From the Chinese HARMONY Cohort. PG - 8025-8033 LID - 10.1111/dom.71004 [doi] AB - INTRODUCTION: To evaluate 24-week weight changes with lower-dose semaglutide in routine care among Chinese adults with obesity and to examine whether diabetes and ectopic fat in the liver and pancreas are associated with heterogeneity in weight-loss response. MATERIALS AND METHODS: Adults with obesity were enrolled from the HARMONY study, a real-world observational cohort in China. Participants received once-weekly subcutaneous semaglutide, titrated to a maintenance dose (0.5 or 1.0 mg) based on clinical response and tolerability, alongside lifestyle counselling and periodic metabolic monitoring. The primary endpoint was the percentage change in body weight from baseline at weeks 12 and 24. Subgroup analyses were conducted according to baseline type 2 diabetes status and ectopic fat status in the liver and pancreas. RESULTS: Overall, 143 participants were included at week 12 and 113 at week 24. Mean percent weight change was -7.3% at week 12 and -9.9% at week 24, corresponding to mean absolute weight losses of 6.7 and 9.1 kg, respectively. By week 24, 76.1% of participants achieved 5% weight loss or more. At week 24, participants with type 2 diabetes experienced lower weight change than those without diabetes (-7.4% vs. -12.4%, p < 0.001). Weight loss also differed by baseline intrapancreatic fat deposition (IPFD) status, with attenuated weight change among patients with baseline IPFD (-9.0% with IPFD vs. -11.6% without IPFD, p = 0.043). DISCUSSION: In routine clinical care, lower doses of semaglutide were associated with clinically meaningful 24-week weight loss in Chinese adults with obesity. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Liu, Shuang AU - Liu S AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. AD - Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Cao, Baige AU - Cao B AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Lin, Chuwen AU - Lin C AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Chen, Weijiong AU - Chen W AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Yang, Panpan AU - Yang P AD - Department of Diagnostic Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Luo, Yu AU - Luo Y AD - Department of Diagnostic Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Xu, Jinfang AU - Xu J AD - Department of Health Statistics, Naval Medical University, Shanghai, China. FAU - Wang, Congrong AU - Wang C AUID- ORCID: 0000-0002-8645-1114 AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. AD - Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. LA - eng GR - 82070913/National Natural Science Foundation of China/ GR - HKLCFC 202403/Clinical Key Supporting Project of Health Commission of Shanghai Hongkou District/ GR - 2023ZD0509206/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ PT - Journal Article PT - Observational Study DEP - 20260615 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - China/epidemiology MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Obesity/drug therapy/complications MH - Semaglutide MH - Treatment Outcome MH - *Weight Loss/drug effects MH - East Asian People PMC - PMC13449065 OTO - NOTNLM OT - GLP-1 OT - obesity therapy OT - observational study OT - weight management COIS- The authors declare no conflicts of interest. EDAT- 2026/06/16 00:33 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/15 22:42 PHST- 2026/06/01 00:00 [revised] PHST- 2026/04/13 00:00 [received] PHST- 2026/06/03 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/16 00:33 [pubmed] PHST- 2026/06/15 22:42 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71004 [pii] AID - 10.1111/dom.71004 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8025-8033. doi: 10.1111/dom.71004. Epub 2026 Jun 15. PMID- 42297449 OWN - NLM STAT- MEDLINE DCOM- 20260615 LR - 20260813 IS - 1745-1701 (Electronic) IS - 0586-7614 (Print) IS - 0586-7614 (Linking) VI - 52 IP - 3 DP - 2026 Apr 10 TI - The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients. LID - 10.1093/schbul/sbaf236 [doi] LID - sbaf236 AB - BACKGROUND AND HYPOTHESIS: Antipsychotic use in severe mental illnesses (SMI) is associated with metabolic dysregulation, including antipsychotic-induced weight gain (AIWG), type 2 diabetes (T2D), and dyslipidemia. In the case of non-response to metformin which is currently recommended for AIWG mitigation, no clear alternatives exist. Semaglutide, a weekly injectable glucagon like peptide-1 receptor agonist, represents a promising option. However, effectiveness and safety data in SMI are lacking. With initiation of semaglutide, we hypothesized weight loss, improvements in metabolic indices, and good tolerability. STUDY DESIGN: A retrospective chart review was conducted for inpatients receiving antipsychotics, initiated on once-weekly subcutaneous semaglutide between January 4, 2018 and March 31, 2024 at the Centre for Addiction and Mental Health in Toronto, Canada, that analyzed weight loss, metabolic parameters, and side effects. STUDY RESULTS: 47 individuals with SMI were included: 59.6% males, mean age of 43 +/- 13.2 years, 83% had dysglycemia, and 66% had T2D at baseline. The maximum dose of semaglutide in this cohort was 2 mg/week. There was a mean weight loss of 3.15 +/- 0.77 kg (n = 47), 7.27 +/- 0.97 kg (n = 24), 9.33 +/- 1.16 kg (n = 15), and 12.25 +/- 1.32 kg (n = 11) at 3, 6, 9, and 12 months, respectively (P < .001). Individuals without T2D experienced greater weight loss versus those with T2D (P = .022). Additionally, significant decreases were noted in body mass index and HbA1c (P < .001), alongside improvements in lipid parameters; most common side effects were gastrointestinal in nature but did not result in semaglutide discontinuation. CONCLUSION: This retrospective chart review of inpatients with SMI supports efficacy and safety of semaglutide up to a year of follow-up, warranting future adequately powered randomized controlled trials. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. FAU - De, Riddhita AU - De R AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. FAU - Amin Alfatwa, Yasser AU - Amin Alfatwa Y AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 3K3, Canada. FAU - Kanagasundaram, Pruntha AU - Kanagasundaram P AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Saragosa, Julia Eve AU - Saragosa JE AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Chan, Joyce AU - Chan J AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Remington, Gary AU - Remington G AUID- ORCID: 0000-0001-9433-9416 AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. FAU - Retnakaran, Ravi AU - Retnakaran R AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. AD - Division of Endocrinology, University of Toronto, Toronto, ON, M5S 3H2, Canada. AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. FAU - Sanches, Marcos AU - Sanches M AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Sockalingam, Sanjeev AU - Sockalingam S AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. FAU - Agarwal, Sri Mahavir AU - Agarwal SM AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. FAU - Hahn, Margaret K AU - Hahn MK AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. LA - eng PT - Journal Article PL - United States TA - Schizophr Bull JT - Schizophrenia bulletin JID - 0236760 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - Male MH - *Antipsychotic Agents/adverse effects MH - Adult MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - *Weight Gain/drug effects MH - *Schizophrenia/drug therapy MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - *Dyslipidemias/drug therapy/chemically induced MH - *Outcome Assessment, Health Care PMC - PMC13267902 OTO - NOTNLM OT - GLP1-RA OT - diabetes OT - dyslipidemia OT - obesity OT - schizophrenia-spectrum illness COIS- The authors have declared that there are no conflicts of interest in relation to the subject of this study. Outside of this work, M.K.H. has received consultant and speaker fees from Alkermes, and consultant fees from Merck. S.M.A. has received honoraria from HLS Therapeutics and has served on the advisory board for Boehringer Ingelheim, Canada. G.R. has received research support from HLS Therapeutics. R.R. reports grants from Boehringer Ingelheim, grants and personal fees from Novo Nordisk, personal fees from Sanofi, and Eli Lilly. All other authors report no conflict of interest. EDAT- 2026/06/16 00:33 MHDA- 2026/06/16 00:34 PMCR- 2026/06/15 CRDT- 2026/06/15 20:43 PHST- 2025/06/27 00:00 [received] PHST- 2025/10/09 00:00 [revised] PHST- 2025/12/01 00:00 [accepted] PHST- 2026/06/16 00:34 [medline] PHST- 2026/06/16 00:33 [pubmed] PHST- 2026/06/15 20:43 [entrez] PHST- 2026/06/15 00:00 [pmc-release] AID - 8708284 [pii] AID - sbaf236 [pii] AID - 10.1093/schbul/sbaf236 [doi] PST - ppublish SO - Schizophr Bull. 2026 Apr 10;52(3):sbaf236. doi: 10.1093/schbul/sbaf236. PMID- 42295612 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20260915 IS - 1179-1888 (Electronic) IS - 1175-0561 (Linking) VI - 27 IP - 5 DP - 2026 Sep TI - A Systematic Review of the Clinical Impact of GLP-1 Receptor Agonists in Hidradenitis Suppurativa. PG - 909-923 LID - 10.1007/s40257-026-01049-8 [doi] AB - INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease which imposes a significant burden in terms of pain, disability, and comorbidities. Obesity and metabolic dysfunction are highly prevalent in HS, contributing to disease severity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in type 2 diabetes and obesity, have shown additional anti-inflammatory properties that may be relevant in HS.However, data on their clinical benefit remain limited. METHODS: We performed a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase through June 2025, following PRISMA guidelines. Studies reporting outcomes in HS patients treated with GLP-1RAs were included. Information on clinical severity, quality of life, metabolism, inflammatory markers, and healthcare use were extracted. Findings were critically assessed and summarized descriptively, with pooled analysis applied where outcomes were consistently reported. This review was registered with PROSPERO (CRD420251110220). RESULTS: Nineteen studies including 67,568 patients were identified. Pooled analysis showed that 60% of patients achieved clinical improvement in Hurley stage (95% CI 52-67). Dermatology Life Quality Index (DLQI) improved by a mean of -3.83 points (95% CI -5.14 to -2.51). Clinical benefit was observed despite modest weight reduction (mean BMI change -2.64 kg/m(2)). Inflammatory and metabolic markers improved, with significant reductions in mean C-reactive protein (-1.35 mg/L, 95% CI -2.33 to -0.36) and HbA1c (-0.39%, 95% CI -0.59 to -0.18). Large real-world cohorts showed decreased antibiotic and corticosteroid use and lower hospitalization rates, though results for biologic use, surgical procedures, and cardiovascular outcomes were mixed. Two studies reported reduced risk of major adverse cardiovascular events, while one HS-diabetes cohort suggested persistent excess cardiovascular risk compared with diabetes-only controls. CONCLUSIONS: This systematic review suggests that GLP-1RAs are associated with improvements in HS severity, quality of life, metabolic and inflammatory parameters, and may additionally reduce healthcare utilization and cardiometabolic risk, observed alongside weight loss. However, current evidence remains limited and heterogeneous, and the relative contribution of weight-dependent and weight-independent effects cannot be determined. Prospective studies and controlled trials are needed to clarify the role of GLP-1RAs in HS management. CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Visan, Maria-Alexandra AU - Visan MA AUID- ORCID: 0009-0007-7349-7459 AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. maria-alexandra.visan@rez.umfcd.ro. AD - Physiology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. maria-alexandra.visan@rez.umfcd.ro. AD - Dermatology Department, Carol Davila Central Military Emergency University Hospital, Bucharest, Romania. maria-alexandra.visan@rez.umfcd.ro. FAU - Carroll, Emma AU - Carroll E AUID- ORCID: 0009-0007-7087-1070 AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. AD - School of Medicine, Charles Institute of Dermatology, University College Dublin, Dublin, Ireland. FAU - Ryan, Stephanie-Lynn AU - Ryan SL AUID- ORCID: 0009-0006-6989-4593 AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. FAU - Pender, Emily AU - Pender E AUID- ORCID: 0000-0003-1763-3173 AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. AD - School of Medicine, Charles Institute of Dermatology, University College Dublin, Dublin, Ireland. FAU - Costache, Daniel-Octavian AU - Costache DO AUID- ORCID: 0000-0002-5906-8654 AD - Dermatology Department, Carol Davila Central Military Emergency University Hospital, Bucharest, Romania. AD - Dermatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Caruntu, Constantin AU - Caruntu C AUID- ORCID: 0000-0003-4530-7965 AD - Physiology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. AD - Prof. Dr. N. Paulescu National Institute of Diabetes, Nutrition, Metabolic Diseases, Bucharest, Romania. FAU - Hughes, Rosalind AU - Hughes R AUID- ORCID: 0000-0001-6533-0412 AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. AD - School of Medicine, Charles Institute of Dermatology, University College Dublin, Dublin, Ireland. FAU - Kirby, Brian AU - Kirby B AUID- ORCID: 0000-0001-7596-892X AD - Dermatology Department, St. Vincent's University Hospital, Dublin, Ireland. AD - School of Medicine, Charles Institute of Dermatology, University College Dublin, Dublin, Ireland. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260615 PL - New Zealand TA - Am J Clin Dermatol JT - American journal of clinical dermatology JID - 100895290 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hidradenitis Suppurativa/drug therapy/immunology/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Quality of Life MH - Severity of Illness Index MH - Treatment Outcome MH - Obesity/drug therapy/complications/epidemiology MH - Diabetes Mellitus, Type 2/drug therapy COIS- Declarations. Funding: The authors did not receive support from any organization for the submitted work. Conflicts of Interest: M-A.V has acted as a sub-investigator in clinical trials for Abbvie. EC has acted as a sub-investigator in clinical trials for Abbvie. EP has acted as a sub-investigator in clinical trials for Abbvie, MoonLake Immunotherapeutics and UCB, received honoraria from Johnson and Johnson and UCB and participated in advisory boards for UCB. CC has received honoraria from Sanofi and Johnson & Johnson Romania. RH has received honoraria from Abbvie, Novartis, UCB. BK has received research support/P.I. (clinical trials) from AbbVie, Almirall, Janssen, Merck Sharpe Dolme, Moonlake, Novartis, Pfizer and UCB; has been a consultant for AbbVie, Almirall, Arctic Biotech, Celgene, Janssen, Leo, MC2 therapeutics, Moonlake, Merck Sharpe Dolme, Novartis, Pfizer, UCB, Union and Zubria; received honoraria from Abbvie, Almirall, Celgene, Janssen, Lilly, MC2 therapeutics, Novartis, Pfizer, Union, and UCB; and been on scientific advisory boards for AbbVie, Almirall, Celgene, Janssen, Lilly, Novartis, Pfizer, Union and UCB. All other authors report no conflicts of interest. Availability of Data and Materials: All information extracted and analyzed in this review is included within the article and its Online Resources. The complete data extraction sheet is available from the corresponding author upon reasonable request. Ethics Approval: Not applicable. This study is a systematic review of previously published literature and does not involve human participants or animal research. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Not applicable. Author Contributions: Conceptualization: M-A.V., B.K.; Methodology: All authors; Data curation: M-A.V., with review and validation by all authors; Formal analysis: M-A.V.; Writing-original draft: M-A.V.; Writing-review and editing: All authors; Supervision: B.K. All authors read and approved the final manuscript. EDAT- 2026/06/15 12:52 MHDA- 2026/09/15 18:07 CRDT- 2026/06/15 11:20 PHST- 2025/11/18 00:00 [received] PHST- 2026/06/03 00:00 [accepted] PHST- 2026/09/15 18:07 [medline] PHST- 2026/06/15 12:52 [pubmed] PHST- 2026/06/15 11:20 [entrez] AID - 10.1007/s40257-026-01049-8 [pii] AID - 10.1007/s40257-026-01049-8 [doi] PST - ppublish SO - Am J Clin Dermatol. 2026 Sep;27(5):909-923. doi: 10.1007/s40257-026-01049-8. Epub 2026 Jun 15. PMID- 42289317 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Healthcare Cost Trends in New Users of SGLT-2i, DPP-4i and GLP-1 RA for Type 2 Diabetes: An Observational Longitudinal Study. PG - 7916-7922 LID - 10.1111/dom.70923 [doi] AB - AIMS: To analyse the healthcare cost trajectories following the initiation of glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitor (SGLT-2i) or dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy in patients with type 2 diabetes. MATERIALS AND METHODS: We conducted a difference-in-difference study using member-level claims data from a national pharmacy benefit manager. Treatment-naive patients were categorised into three groups based on the drug they initiated first. The first fill date in 2020 or 2021 was the index date, with a one-year look-back period and 2 years of follow-up. Propensity score weighting balanced the groups. We used generalised estimating equations to analyse year-over-year changes in per patient per month (PPPM) costs for medical, pharmacy and total cost of care expenditures. RESULTS: Changes in medical costs were not statistically different across drug groups in years 1 and 2. In contrast, the increase in pharmacy costs in the first year for GLP-1 RA was significantly higher than the other two drugs. Driven primarily by pharmacy costs, total cost of care trajectories showed similar between-drug differences. CONCLUSION: Patients with type 2 diabetes initiating on a GLP-1 RA show significantly higher pharmacy cost patterns as compared to the DPP-4i and SGLT-2i groups; this higher pharmacy cost is not offset by reduced medical cost during the same period. Payers and providers should consider these cost patterns in both coverage and treatment decisions. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Durand, Casey P AU - Durand CP AUID- ORCID: 0009-0004-5891-6633 AD - Evernorth Health Services, Evernorth Research Institute, St. Louis, Missouri, USA. FAU - Eatherly, Mark AU - Eatherly M AD - Evernorth Health Services, Evernorth Research Institute, St. Louis, Missouri, USA. FAU - Yao, Aaron AU - Yao A AD - FastHSR, Glen Allen, Virginia, USA. FAU - Dollear, Timothy J AU - Dollear TJ AD - Evernorth Health Services, Evernorth Research Institute, St. Louis, Missouri, USA. FAU - Inneh, Angela AU - Inneh A AD - Evernorth Health Services, Evernorth Research Institute, St. Louis, Missouri, USA. FAU - Patel, Urvashi AU - Patel U AD - Evernorth Health Services, Evernorth Research Institute, St. Louis, Missouri, USA. LA - eng PT - Journal Article PT - Observational Study DEP - 20260614 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Dipeptidyl-Peptidase IV Inhibitors/economics/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - Female MH - Longitudinal Studies MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Health Care Costs/trends MH - Middle Aged MH - *Hypoglycemic Agents/economics/therapeutic use MH - Aged PMC - PMC13449046 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 OT - SGLT2 inhibitor OT - cost-effectiveness OT - observational study OT - real-world evidence COIS- All authors except Aaron Yao are or were employees of Evernorth Health Services Inc. Aaron Yao has received funding from Evernorth Health Services Inc. EDAT- 2026/06/15 11:37 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/14 21:03 PHST- 2026/04/29 00:00 [revised] PHST- 2025/11/14 00:00 [received] PHST- 2026/05/14 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/15 11:37 [pubmed] PHST- 2026/06/14 21:03 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70923 [pii] AID - 10.1111/dom.70923 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):7916-7922. doi: 10.1111/dom.70923. Epub 2026 Jun 14. PMID- 42289243 OWN - NLM STAT- MEDLINE DCOM- 20260722 LR - 20260810 IS - 1532-8600 (Electronic) IS - 0026-0495 (Linking) VI - 182 DP - 2026 Sep TI - SGLT2 inhibitors and GLP-1 receptor agonists in atrial fibrillation treatment: Clinical evidence and mechanistic insights. PG - 156678 LID - S0026-0495(26)00188-5 [pii] LID - 10.1016/j.metabol.2026.156678 [doi] AB - Atrial fibrillation (AF) is the most common sustained arrhythmia globally. Despite certain progress in drug and interventional treatments, AF still presents high morbidity, high mortality, and unsatisfactory clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), initially used to treat type 2 diabetes mellitus (T2DM), have demonstrated cardiorenal protective effects beyond glycemic control and have drawn broad attention for their potential in AF management. This narrative review comprehensively synthesizes clinical evidence and underlying mechanisms regarding the effects of SGLT2i and GLP-1 RA on new-onset AF and post-ablation AF recurrence across common comorbidities, including T2DM, heart failure (HF), chronic kidney disease (CKD) and obesity. Available evidence shows that SGLT2i may be associated with reduced new-onset AF risk in patients with T2DM, HF and CKD, and lower post-ablation AF recurrence in high-risk groups. GLP-1 RA show beneficial effects on AF in individuals with obesity or heart failure with preserved ejection fraction. Their protective effects are mainly mediated by upstream metabolic regulation and direct effects on atrial electrophysiology, as evidenced by cellular, animal, and clinical studies. Notably, most clinical evidence comes from post hoc analyses and observational studies, with AF rarely as a primary endpoint and without systematic measurement, leaving the evidence at a hypothesis-generating stage with limited clinical applicability. Overall, SGLT2i and GLP-1 RA serve as potential adjunctive therapies for AF patients with concomitant cardiometabolic comorbidities. Their AF-related outcomes represent exploratory secondary benefits instead of established therapeutic indications. Further specific randomized controlled trials with prespecified AF endpoint and standardized AF monitoring are needed to verify their clinical efficacy and application prospects. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Fan, Yue AU - Fan Y AD - Phase I Clinical Trial Centre, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China; Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: fany77@mail.sysu.edu.cn. FAU - Chen, Xi AU - Chen X AD - Department of Cardiology, Sanming First Affiliated Hospital of Fujian Medical University, Sanming, Fujian, China. Electronic address: 13507580119@139.com. FAU - Cai, Xingming AU - Cai X AD - Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: sayusaym@163.com. FAU - Dong, Yugang AU - Dong Y AD - Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China; Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address: dongxg@mail.sysu.edu.cn. FAU - Liu, Chen AU - Liu C AD - Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China; Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address: liuch75@mail.sysu.edu.cn. FAU - Chen, Yili AU - Chen Y AD - Phase I Clinical Trial Centre, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China; Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: chenyil7@mail.sysu.edu.cn. FAU - Lip, Gregory Y H AU - Lip GYH AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Medical University of Bialystok, Bialystok, Poland. Electronic address: gregory.lip@liverpool.ac.uk. FAU - Zhu, Wengen AU - Zhu W AD - Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China; Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address: zhuwg6@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260614 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Atrial Fibrillation/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Animals OTO - NOTNLM OT - Atrial fibrillation OT - Catheter ablation OT - Comorbidity OT - GLP-1 receptor agonists OT - SGLT2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/15 11:37 MHDA- 2026/07/23 05:36 CRDT- 2026/06/14 19:23 PHST- 2026/01/26 00:00 [received] PHST- 2026/05/27 00:00 [revised] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/07/23 05:36 [medline] PHST- 2026/06/15 11:37 [pubmed] PHST- 2026/06/14 19:23 [entrez] AID - S0026-0495(26)00188-5 [pii] AID - 10.1016/j.metabol.2026.156678 [doi] PST - ppublish SO - Metabolism. 2026 Sep;182:156678. doi: 10.1016/j.metabol.2026.156678. Epub 2026 Jun 14. PMID- 42288971 OWN - NLM STAT- MEDLINE DCOM- 20260801 LR - 20260803 IS - 1744-7593 (Electronic) IS - 1742-5247 (Linking) VI - 23 IP - 8 DP - 2026 Aug TI - Current trends in semaglutide therapy and strategies to improve its bioavailability. PG - 1495-1509 LID - 10.1080/17425247.2026.2688990 [doi] AB - INTRODUCTION: A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. AREAS COVERED: This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. EXPERT OPINION: Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake. FAU - Nayak, Swasthik AU - Nayak S AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. FAU - Dessai, Akanksha D AU - Dessai AD AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. FAU - Nayak, Usha Y AU - Nayak UY AUID- ORCID: 0000-0002-1995-3114 AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. LA - eng PT - Journal Article PT - Review DEP - 20260621 PL - England TA - Expert Opin Drug Deliv JT - Expert opinion on drug delivery JID - 101228421 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/pharmacology MH - Biological Availability MH - Animals MH - Administration, Oral MH - Drug Delivery Systems MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/pharmacology MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Semaglutide OT - bioavailability OT - drug delivery system OT - enteric coating OT - gut targeted delivery EDAT- 2026/06/15 11:34 MHDA- 2026/08/02 00:30 CRDT- 2026/06/14 06:32 PHST- 2026/08/02 00:30 [medline] PHST- 2026/06/15 11:34 [pubmed] PHST- 2026/06/14 06:32 [entrez] AID - 10.1080/17425247.2026.2688990 [doi] PST - ppublish SO - Expert Opin Drug Deliv. 2026 Aug;23(8):1495-1509. doi: 10.1080/17425247.2026.2688990. Epub 2026 Jun 21. PMID- 42286992 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260721 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 138 IP - 6 DP - 2026 Aug TI - Evidence-informed guidance for the clinical use of oral semaglutide in obesity management. PG - 654-664 LID - 10.1080/00325481.2026.2686467 [doi] AB - Oral semaglutide, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved for the treatment of type 2 diabetes, is now approved for obesity management and cardiovascular risk reduction in adults, demonstrating weight loss comparable to that of subcutaneous GLP-1 therapies, alongside improvements in cardiometabolic risk factors. The availability of oral semaglutide for the treatment of obesity provides healthcare professionals with additional opportunities to individualize therapy based on patient preferences, lifestyle, and clinical circumstances. However, the oral semaglutide formulation requires specific administration conditions to optimize absorption and effectiveness. Notably, oral semaglutide tablets should be taken first thing in the morning on an empty stomach with no more than half a glass of plain water (up to 120 mL or 4 fl oz), followed by 30 min before eating food, drinking additional fluids, or ingesting other oral medications. Person-centered clinical discussions between healthcare professionals (HCPs) and patients prior to treatment initiation are important to ensure patients understand administration requirements and why they are necessary, establish realistic expectations for obesity treatment targets, and cover approaches to maintain adherence. HCP-patient consultations should also include discussion of strategies to help patients minimize, prepare for, and manage adverse events. In this article, we provide practical guidance for incorporating oral semaglutide into obesity management, drawing on evidence from clinical trials, including the OASIS 4 trial, and the authors' clinical insights. FAU - Rubino, Domenica AU - Rubino D AUID- ORCID: 0000-0002-3072-2819 AD - Washington Center for Weight Management and Research, Arlington, VA, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - Department of Medicine, University of Toronto, Toronto, ON, Canada. AD - Department of Medicine, McMaster University, Hamilton, ON, Canada. AD - Wharton Medical Clinic Weight & Diabetes Management, Burlington, ON, Canada. FAU - Knight, Michael G AU - Knight MG AUID- ORCID: 0000-0002-4113-9936 AD - Department of Medicine, The George Washington University, Washington, DC, USA. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes, and Hypertension Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. LA - eng PT - Journal Article PT - Review DEP - 20260612 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Obesity/drug therapy MH - Administration, Oral MH - *Anti-Obesity Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Evidence-Based Medicine MH - Practice Guidelines as Topic MH - Diabetes Mellitus, Type 2/drug therapy OAB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are medications that are prescribed for the treatment of obesity to help people lose weight by reducing their appetite and feelings of hunger. Most GLP-1RAs are injected into the fatty layer of tissue below the skin, which helps the body absorb the medication into the bloodstream. The GLP-1RA semaglutide has been available in an injectable format for the treatment of obesity for several years and is now also available as a tablet for adults who prefer not to use injections. In clinical trials, people who used the tablet form of semaglutide had similar weight loss to people who used injectable semaglutide. Semaglutide tablets have been designed in a way that resists break down by stomach acid, allowing more of the medication to be absorbed into the body, but there are important steps to follow when taking the tablet to ensure the medication works as well as possible. Based on learnings from clinical trials and the clinical experience of the authors, this article provides practical advice to support healthcare professionals in guiding their patients through these steps. It also covers important topics to discuss with patients before they start taking semaglutide tablets, including possible changes to how they take other medications, how to limit and manage potential side effects, and ways for patients to stay consistent with their treatment schedule. OABL- eng OTO - NOTNLM OT - Obesity OT - clinical practice OT - glucagon-like peptide-1 receptor agonist OT - oral semaglutide OT - weight management EDAT- 2026/06/13 06:39 MHDA- 2026/07/21 18:34 CRDT- 2026/06/13 02:43 PHST- 2026/07/21 18:34 [medline] PHST- 2026/06/13 06:39 [pubmed] PHST- 2026/06/13 02:43 [entrez] AID - 10.1080/00325481.2026.2686467 [doi] PST - ppublish SO - Postgrad Med. 2026 Aug;138(6):654-664. doi: 10.1080/00325481.2026.2686467. Epub 2026 Jun 12. PMID- 42286576 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260903 IS - 1749-8090 (Electronic) IS - 1749-8090 (Linking) VI - 21 IP - 1 DP - 2026 Jun 12 TI - Boerhaave's syndrome associated with glucagon-like peptide-1 receptor agonist use: a case report. LID - 10.1186/s13019-026-04214-6 [doi] LID - 625 AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses. CASE PRESENTATION: A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs. CONCLUSIONS: This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario. CI - (c) 2026. The Author(s). FAU - Aubrey, Jason M AU - Aubrey JM AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. jason.aubrey2@corewellhealth.org. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. jason.aubrey2@corewellhealth.org. FAU - Benner, Chance AU - Benner C AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. FAU - Lam, Geoffrey T AU - Lam GT AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20260612 PL - England TA - J Cardiothorac Surg JT - Journal of cardiothoracic surgery JID - 101265113 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - Boerhaave syndrome SB - IM MH - Humans MH - Female MH - *Esophageal Perforation/chemically induced/diagnosis/surgery MH - Semaglutide MH - *Mediastinal Diseases/chemically induced/diagnosis/surgery MH - Spontaneous Perforation MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Rupture, Spontaneous MH - Middle Aged MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Esophageal Diseases PMC - PMC13505130 OTO - NOTNLM OT - Boerhaave syndrome OT - Drug-induced gastroparesis OT - Esophageal diseases OT - Esophageal perforation OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide OT - Weight loss agent COIS- Declarations. Ethics approval: The Corewell health IRB reviewed the case and waived the need for IRB approval. Consent for publication: The patient gave consent for their case to be published. Competing interests: The authors declare no competing interests. Informed consent: Informed consent was obtained from the patient for publication of this case report. EDAT- 2026/06/13 06:38 MHDA- 2026/08/25 05:34 PMCR- 2026/06/12 CRDT- 2026/06/13 00:06 PHST- 2025/08/24 00:00 [received] PHST- 2026/04/15 00:00 [accepted] PHST- 2026/08/25 05:34 [medline] PHST- 2026/06/13 06:38 [pubmed] PHST- 2026/06/13 00:06 [entrez] PHST- 2026/06/12 00:00 [pmc-release] AID - 10.1186/s13019-026-04214-6 [pii] AID - 4214 [pii] AID - 10.1186/s13019-026-04214-6 [doi] PST - epublish SO - J Cardiothorac Surg. 2026 Jun 12;21(1):625. doi: 10.1186/s13019-026-04214-6. PMID- 42280404 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260813 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 11 DP - 2026 May 30 TI - Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support-A Narrative Review. LID - 10.3390/nu18111761 [doi] LID - 1761 AB - Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75-80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support-targeting protein intake, micronutrient density, and gastric-sparing feeding-is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1-specific randomized trials. FAU - Dziewierz, Artur AU - Dziewierz A AUID- ORCID: 0000-0002-2100-5076 AD - 2nd Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, 30-688 Krakow, Poland. AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, 30-688 Krakow, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AUID- ORCID: 0000-0002-8033-3977 AD - Collegium Medicum, Jan Kochanowski University, 25-516 Kielce, Poland. LA - eng PT - Journal Article PT - Review DEP - 20260530 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Adherence Interventions MH - *Diabetes Mellitus, Type 2/drug therapy/therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Life Style MH - Nutrition Therapy/methods MH - *Obesity/drug therapy/therapy MH - Weight Loss PMC - PMC13259006 OTO - NOTNLM OT - GLP-1 receptor agonists OT - gastrointestinal tolerability OT - medical nutrition therapy OT - medication adherence OT - sarcopenic obesity OT - treatment persistence COIS- The authors declare no conflicts of interest. EDAT- 2026/06/12 06:40 MHDA- 2026/06/15 11:35 PMCR- 2026/05/30 CRDT- 2026/06/12 01:11 PHST- 2026/02/17 00:00 [received] PHST- 2026/05/26 00:00 [revised] PHST- 2026/05/27 00:00 [accepted] PHST- 2026/06/15 11:35 [medline] PHST- 2026/06/12 06:40 [pubmed] PHST- 2026/06/12 01:11 [entrez] PHST- 2026/05/30 00:00 [pmc-release] AID - nu18111761 [pii] AID - nutrients-18-01761 [pii] AID - 10.3390/nu18111761 [doi] PST - epublish SO - Nutrients. 2026 May 30;18(11):1761. doi: 10.3390/nu18111761. PMID- 42280332 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 11 DP - 2026 May 25 TI - GLP-1 Receptor Agonists in the Rehabilitation of Patients with Heart Failure: Mechanisms, Clinical Evidence, and Future Perspectives. LID - 10.3390/nu18111688 [doi] LID - 1688 AB - Heart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes. FAU - Suastika, Luh Oliva Saraswati AU - Suastika LOS AUID- ORCID: 0000-0002-5642-2742 AD - Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. AD - Center for Advanced Heart Failure, Okayama University Hospital, Okayama 700-8558, Japan. AD - Department of Cardiology and Vascular Medicine, Faculty of Medicine, Udayana University, Denpasar 80361, Indonesia. FAU - Bando, Yasuko K AU - Bando YK AD - Department of Molecular Physiology and Cardiovascular Biology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan. FAU - Hoshino, Keiji AU - Hoshino K AD - Division of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi 371-0004, Japan. FAU - Koitabashi, Norimichi AU - Koitabashi N AUID- ORCID: 0000-0002-2113-3422 AD - Division of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi 371-0004, Japan. FAU - Saito, Yukihiro AU - Saito Y AD - Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. FAU - Yuasa, Shinsuke AU - Yuasa S AD - Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. FAU - Nakamura, Kazufumi AU - Nakamura K AUID- ORCID: 0000-0001-8845-3626 AD - Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. AD - Center for Advanced Heart Failure, Okayama University Hospital, Okayama 700-8558, Japan. AD - Division of Cardiology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan. LA - eng GR - 2023/Daiichi Sankyo Life Science Foundation/ PT - Journal Article PT - Review DEP - 20260525 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Heart Failure/rehabilitation/drug therapy/physiopathology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/complications MH - *Cardiac Rehabilitation/methods MH - Glucagon-Like Peptide-1 Receptor MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Stroke Volume MH - Sarcopenia/complications PMC - PMC13259458 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiac rehabilitation OT - heart failure OT - obesity OT - sarcopenia COIS- The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2026/06/12 06:39 MHDA- 2026/06/12 06:40 PMCR- 2026/05/25 CRDT- 2026/06/12 01:11 PHST- 2026/01/09 00:00 [received] PHST- 2026/05/20 00:00 [revised] PHST- 2026/05/20 00:00 [accepted] PHST- 2026/06/12 06:40 [medline] PHST- 2026/06/12 06:39 [pubmed] PHST- 2026/06/12 01:11 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - nu18111688 [pii] AID - nutrients-18-01688 [pii] AID - 10.3390/nu18111688 [doi] PST - epublish SO - Nutrients. 2026 May 25;18(11):1688. doi: 10.3390/nu18111688. PMID- 42278227 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 11 DP - 2026 May 22 TI - Retrospective Comparative Study of Oral Versus Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus. LID - 10.3390/ijms27114694 [doi] LID - 4694 AB - Semaglutide represents a unique therapeutic option for patients with type 2 diabetes mellitus (T2DM), being the first and currently only glucagon-like peptide-1 receptor agonist (GLP-1RA) available in both subcutaneous and oral formulations. This study aimed to compare the effectiveness of oral versus subcutaneous (sc) semaglutide on metabolic parameters and cardiovascular risk factors in T2DM patients. This is a retrospective real-world study including adult patients with T2DM taking oral or sc semaglutide followed at the ASUGI Diabetes Center. We analyzed data from 434 patients (median age 70 years, diabetes duration 13 years), treated with oral (n = 232) or sc (n = 202) semaglutide. The oral formulation had a higher discontinuation rate. Among these patients, 130 patients in the oral group and 145 in the sc group had an 18-month follow-up. When comparing these groups, patients taking sc semaglutide had a significantly higher baseline BMI. However, multivariate linear regression models suggested that both formulations were comparably effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. To address BMI imbalances, propensity score matching was performed, identifying 55 matched pairs. Both oral and sc semaglutide reduced HbA1c and BMI and there were no significant differences in the median change in HbA1c and BMI between groups. Interestingly, oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the sc formulation. Furthermore, concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol. Oral and subcutaneous semaglutide show comparable effectiveness in lowering HbA1c and BMI in a real-world setting. FAU - Toffoli, Barbara AU - Toffoli B AUID- ORCID: 0000-0002-6854-5782 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Michieletto, Matteo AU - Michieletto M AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Bernardi, Stella AU - Bernardi S AUID- ORCID: 0000-0002-7429-3075 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. AD - SS Endocrinologia (Medicina Clinica), Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. AD - SC Patologie Diabetiche, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Via Sai 7, 34128 Trieste, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260522 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glycated Hemoglobin/metabolism MH - Injections, Subcutaneous MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use PMC - PMC13256121 OTO - NOTNLM OT - GLP-1RA OT - comparative study OT - oral semaglutide OT - propensity score matching OT - subcutaneous semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/06/12 06:38 MHDA- 2026/06/13 00:38 PMCR- 2026/05/22 CRDT- 2026/06/12 01:03 PHST- 2026/03/22 00:00 [received] PHST- 2026/05/07 00:00 [revised] PHST- 2026/05/13 00:00 [accepted] PHST- 2026/06/13 00:38 [medline] PHST- 2026/06/12 06:38 [pubmed] PHST- 2026/06/12 01:03 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - ijms27114694 [pii] AID - ijms-27-04694 [pii] AID - 10.3390/ijms27114694 [doi] PST - epublish SO - Int J Mol Sci. 2026 May 22;27(11):4694. doi: 10.3390/ijms27114694. PMID- 42269776 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 238 DP - 2026 Aug TI - GLP-1 receptor agonist adjunct therapy stabilises Ramadan dysglycaemia in insulin-treated diabetes: a CGM-based study. PG - 113369 LID - S0168-8227(26)00289-5 [pii] LID - 10.1016/j.diabres.2026.113369 [doi] AB - BACKGROUND: Patients with type 1 and insulin-treated type 2 diabetes are at higher risk of hypo- and hyperglycaemia during Ramadan fasting. The role of incretin-based add-on therapy (GLP-1 receptor agonist semaglutide and the GLP-1/GIP dual agonist tirzepatide) in attenuating Ramadan dysglycaemia in insulin-treated type 2 diabetes has not been characterised using continuous glucose monitoring. Emerging evidence indicates that exaggerated post-iftar hyperglycaemia, drives Ramadan dysglycaemia in insulin-treated individuals. AIMS: To use continuous glucose monitoring (CGM) to characterise glycaemic control in patients with type 1 and type 2 diabetes on intensive insulin during Ramadan fasting, and to evaluate the role of add-on semaglutide or tirzepatide in attenuating post-iftar hyperglycaemia. METHODS: Adults with type 1 or type 2 diabetes using FreeStyle Libre CGM who completed >/= 14 full fasting days during Ramadan 2025 were included. Of 140 participants screened pre-Ramadan, 54 met all inclusion criteria and were analysed: type 2 diabetes on basal-bolus insulin alone (BB, n = 18), type 2 diabetes on basal-bolus plus tirzepatide or semaglutide (BB+, n = 18) - matched 1:1 by age, baseline HbA1c and BMI - and type 1 diabetes on basal-bolus insulin (T1DM, n = 18). CGM metrics were collected over 28 days pre-Ramadan (1-28 February 2025) and 29 days during Ramadan (1-29 March 2025) and compared within and between groups, and across fasting versus non-fasting windows. RESULTS: Dysglycaemia was driven predominantly by the post-iftar period. BB participants showed marked deterioration during non-fasting hours. Adjunctive therapy attenuated this effect: time in range 74.4 % vs 36.8 % (p = 0.007), glucose management indicator 6.9 % vs 8.3 % (p = 0.004), and > 2-fold ( approximately 61 %) reduction in incremental post-iftar area under the curve (102,014 vs 260,578 mg/dL.min over the 4-h post-iftar window). CONCLUSION: In matched insulin-treated type 2 diabetes cohorts, add-on semaglutide or tirzepatide stabilised Ramadan glycaemia and reduced post-iftar hyperglycaemia without increasing hypoglycaemia, and was well tolerated with no treatment discontinuations during Ramadan. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Ashraf, Tanveer AU - Ashraf T AD - Clinical Research Fellow, Imperial College London Diabetes and Endocrine Centre (ICLDEC), Abu Dhabi, United Arab Emirates. Electronic address: tashraf@icldc.ae. FAU - Lessan, Nader AU - Lessan N AD - Consultant Endocrinologist and Diabetologist, Clinical Lead in Research, Imperial College London Diabetes and Endocrine Centre (ICLDEC), Visiting Reader, Imperial College London, UK. Electronic address: nlessan@icldc.ae. LA - eng PT - Journal Article DEP - 20260610 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Continuous Glucose Monitoring MH - Female MH - *Insulin/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Blood Glucose/drug effects/metabolism/analysis MH - *Diabetes Mellitus, Type 1/drug therapy/blood MH - Middle Aged MH - *Islam MH - Adult MH - Glucagon-Like Peptides/therapeutic use MH - *Hyperglycemia/drug therapy MH - Drug Therapy, Combination MH - *Fasting/blood MH - Glycemic Control OTO - NOTNLM OT - Continuous glucose monitoring OT - GLP-1 receptor agonist OT - GLP-1/GIP dual agonist OT - Post-iftar hyperglycaemia OT - Ramadan fasting OT - Semaglutide OT - Time in Range OT - Tirzepatide OT - Type 1 diabetes OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/11 05:41 MHDA- 2026/07/08 12:56 CRDT- 2026/06/10 19:56 PHST- 2026/04/06 00:00 [received] PHST- 2026/06/04 00:00 [revised] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/07/08 12:56 [medline] PHST- 2026/06/11 05:41 [pubmed] PHST- 2026/06/10 19:56 [entrez] AID - S0168-8227(26)00289-5 [pii] AID - 10.1016/j.diabres.2026.113369 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Aug;238:113369. doi: 10.1016/j.diabres.2026.113369. Epub 2026 Jun 10. PMID- 42268869 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 6 DP - 2026 TI - Cost-effectiveness of semaglutide versus dulaglutide for Type 2 Diabetes in China: A Markov Model analysis. PG - e0351059 LID - 10.1371/journal.pone.0351059 [doi] LID - e0351059 AB - OBJECTIVE: From the perspective of China's basic medical insurance, to evaluate the cost-effectiveness of semaglutide versus dulaglutide for type 2 diabetes mellitus (T2DM) in China, informing clinical and health policy decisions. METHODS: This study employed a Markov model to simulate the disease progression of T2DM over a 25-year time horizon. Transition probabilities between health states were sourced from the UK Prospective Diabetes Study Outcomes Model (UKPDS 82) and the SUSTAIN 7 clinical trial, while health utility values were obtained from published literature using the Chinese EQ-5D-5L value set. Long-term cost-effectiveness was projected through cohort simulation, with both one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) conducted to evaluate the robustness of the model. RESULTS: After 25 years of simulation, the total cost for dulaglutide was yen193,353.07, with 11.628 quality-adjusted life-years (QALYs) gained. The total cost for semaglutide was yen240,925.08, yielding 11.900 QALYs. Compared with dulaglutide, semaglutide had an incremental cost-effectiveness ratio (ICER) of yen174,904 per QALY gained, approximately twice China's 2023 per capita GDP ( yen89,358). According to the Chinese Guidelines for Pharmacoeconomic Evaluation (2020), this result falls within the economically acceptable range (1 x GDP < ICER /= 7 days before surgery, regardless of indication; and (ii) a control group of patients not receiving any GLP-1 RA, preferentially with type 2 diabetes or with a body mass index >/= 25 kg/m(2). The primary outcome was increased RGC, defined as the presence of solid content, thick liquid, or > 1.5 mL/kg of clear liquid. Confounding was addressed using overlap-weighting propensity-score adjustment. RESULTS: 93 patients were included. The unadjusted prevalence of increased RGC was 24% (10/41) in the control group and 42% (22/52) in the exposure group. Solid content accounted for 80% (8/10) and 82% (18/22) of positive exams in the control group and the exposure group, respectively. In the unadjusted analysis, there was no statistically significant difference in increased RGC between groups (prevalence ratio, 1.73; 95% CI, 0.96 to 3.75). There was no statistically significant difference between groups after adjustment for confounding (adjusted prevalence ratio, 1.65; 95% CI, 0.7 to 3.7) with an absolute average treatment effect of 15.4% (95% CI, -10 to 35.6). CONCLUSIONS: The prevalence of increased residual gastric content was 42% in patients who had discontinued weekly GLP-1 RA for at least 7 days, compared with 24% in non-exposed controls. Although this difference was not statistically significant, our study was underpowered. The findings therefore represent a clinically relevant but statistically inconclusive signal that the recommended 7-day discontinuation interval may not consistently restore an empty stomach in patients on weekly GLP-1 RA. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov (July 8th, 2024, NCT06500143). CI - (c) 2026. The Author(s). FAU - Boudreau, Charles AU - Boudreau C AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. FAU - Couture, Marjorie AU - Couture M AD - Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. AD - Department of Anesthesiology and Intensive Care Medicine, Montreal Heart Institute, Montreal, QC, Canada. FAU - Rousseau-Saine, Nicolas AU - Rousseau-Saine N AD - Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. AD - Department of Anesthesiology and Intensive Care Medicine, Montreal Heart Institute, Montreal, QC, Canada. FAU - Laferriere-Langlois, Pascal AU - Laferriere-Langlois P AD - Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. AD - Laboratory of Innovation in Anesthesia Montreal (LIAM), Montreal, QC, Canada. FAU - Roy-Renaud, Etienne AU - Roy-Renaud E AD - Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. FAU - Burey, Julien AU - Burey J AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. FAU - Raymond, Meggie AU - Raymond M AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. AD - Department of Anesthesiology and Intensive Care Medicine, Montreal Heart Institute, Montreal, QC, Canada. FAU - Denault, Andre AU - Denault A AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. AD - Department of Anesthesiology and Intensive Care Medicine, Montreal Heart Institute, Montreal, QC, Canada. FAU - Morisson, Louis AU - Morisson L AD - Department of Anesthesiology and Pain Medicine, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. louis.morisson@umontreal.ca. AD - Department of Anesthesiology and Pain Medicine, Universite de Montreal, Montreal, QC, Canada. louis.morisson@umontreal.ca. AD - Laboratory of Innovation in Anesthesia Montreal (LIAM), Montreal, QC, Canada. louis.morisson@umontreal.ca. LA - eng SI - ClinicalTrials.gov/NCT06500143 PT - Journal Article PT - Multicenter Study DEP - 20260610 PL - England TA - BMC Anesthesiol JT - BMC anesthesiology JID - 100968535 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cross-Sectional Studies MH - Female MH - Prospective Studies MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Elective Surgical Procedures/methods MH - Middle Aged MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage MH - *Gastrointestinal Contents/diagnostic imaging MH - Gastric Emptying/drug effects MH - Ultrasonography PMC - PMC13491755 OTO - NOTNLM OT - Diabetes Mellitus OT - Fasting OT - Glucagon-Like Peptide-1 Receptor Agonists OT - Perioperative care OT - Respiratory Aspiration of Gastric Contents OT - Ultrasonography COIS- Declarations. Ethics approval and consent to participate: The study received approval from our local IRB on August, 14th 2024 (Comite d'ethique et de la recherche du CIUSSS de l'Est de l'Ile de Montreal, IRB number: MP-12-2025-3794). All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments. All participants signed the informed consent form before participation to the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/06/10 06:54 MHDA- 2026/08/20 05:43 PMCR- 2026/06/10 CRDT- 2026/06/10 00:04 PHST- 2026/03/24 00:00 [received] PHST- 2026/06/04 00:00 [accepted] PHST- 2026/08/20 05:43 [medline] PHST- 2026/06/10 06:54 [pubmed] PHST- 2026/06/10 00:04 [entrez] PHST- 2026/06/10 00:00 [pmc-release] AID - 10.1186/s12871-026-03999-2 [pii] AID - 3999 [pii] AID - 10.1186/s12871-026-03999-2 [doi] PST - epublish SO - BMC Anesthesiol. 2026 Jun 10;26(1):511. doi: 10.1186/s12871-026-03999-2. PMID- 42264960 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Nationwide Real-World Retrospective Study of Oral Semaglutide Use in Adults Living With Type 2 Diabetes in Finland. PG - 7814-7824 LID - 10.1111/dom.70920 [doi] AB - AIM: This Finnish nationwide retrospective 'real-world' study evaluated the effects of oral semaglutide on glycaemic control, body weight, lipid profile, and liver enzymes in adults living with type 2 diabetes (T2D) and naive to any GLP-1 receptor agonists in Finland. MATERIALS AND METHODS: Adults living with T2D (n = 7249) who initiated oral semaglutide between April 1, 2021, and December 31, 2023, were identified from national registers and followed until June 30, 2024. Primary endpoints were changes in HbA1c and body weight from baseline to 182.5 and 365 days. Secondary endpoints included changes in LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides, HDL/triglycerides ratio, and ALT. RESULTS: Of those initiating oral semaglutide, 65.8% remained on treatment at 180 days and 55.2% at 365 days. Among patients included in longitudinal trajectory modelling, mean HbA1c (n = 2784) decreased from 7.9% to 6.8% at 182.5 days (95% CI: -1.20 to -1.04; p < 0.001) and to 6.9% at 365 days (95% CI: -1.18 to -0.95; p < 0.001). Mean body weight (n = 832) declined from 106 to 100 kg at 182.5 days (95% CI: -7 to -5; p < 0.001) and to 98 kg at 365 days (95% CI: -10 to -6; p < 0.001). LDL-cholesterol (n = 1402), and triglycerides (n = 975) were significantly reduced at 182.5 days with little further change at 365 days. Mean ALT (n = 1762) declined from 50 to 42 U/L at 182.5 days (95% CI: -10 to -6, p < 0.001) and to 37 U/L at 365 days (; 95% CI: -16 to -10; p < 0.001). While weight at baseline was lower at patients aged at least 75 years, the changes in HbA1c and weight were similar compared to patients under 75 years of age. CONCLUSION: Oral semaglutide significantly improves glycaemic and lipid control, body weight, and liver enzymes in adults living with T2D treated in clinical practice. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vaden, Atte AU - Vaden A AD - West-Northern Central Hospital, Department of Internal Medicine, Kemi, Finland. AD - Tesoma Welfare Alliance, Tampere, Finland. AD - Medical Center Mehilainen, Tampere, Finland. FAU - Lahelma, Mari AU - Lahelma M AD - Nordic Healthcare Group, Helsinki, Finland. FAU - Nurmi, Lalli AU - Nurmi L AD - Nordic Healthcare Group, Helsinki, Finland. FAU - Heikkila, Eija AU - Heikkila E AUID- ORCID: 0000-0002-3736-8410 AD - Nordic Healthcare Group, Helsinki, Finland. FAU - Vessari, Hannu AU - Vessari H AD - Novo Nordisk Farma Oy, Espoo, Finland. AD - Faculty of Social Sciences, Health Sciences, Epidemiology, Tampere University, Tampere, Finland. FAU - Luoto, Hanne AU - Luoto H AD - Novo Nordisk Farma Oy, Espoo, Finland. FAU - Saukkonen, Tero AU - Saukkonen T AD - Novo Nordisk Farma Oy, Espoo, Finland. FAU - Niskanen, Leo AU - Niskanen L AD - Department of Internal Medicine, Paijat Hame Central Hospital, Lahti, Finland. AD - Eira Hospital, Helsinki, Finland. AD - University of Eastern Finland, Institute of Clinical Medicine, Kuopio, Finland. LA - eng GR - Novo Nordisk Pharma/ PT - Journal Article DEP - 20260609 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Female MH - Retrospective Studies MH - Finland/epidemiology MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Adult MH - Glycemic Control PMC - PMC13449066 OTO - NOTNLM OT - glycaemic control OT - liver OT - real-world evidence OT - semaglutide OT - type 2 diabetes OT - weight management COIS- Leo Niskanen has received speaker honoraria from Amgen, Lilly, GSK, Boehringer Ingelheim, Novo Nordisk, Sanofi, MSD, and Astra and has participated in the scientific advisory boards of Amgen, Lilly, Boehringer Ingelheim, Astra, MSD, and Novo Nordisk. Atte Vaden: Speakers fees from Amgen, AstraZeneca, Boehringer, Eli Lilly Novo Nordisk and Orion. Advisory board fees from Bayer and Novo Nordisk. Congress expenses AstraZeneca, Nordic Infucare, and Novo Nordisk. Mari Lahelma, Lalli Nurmi, Eija Heikkila: Employees of NHG. Tero Saukkonen, Hannu Vessari and Hanne Luoto: Employees and shareholders of Novo Nordisk. EDAT- 2026/06/10 06:52 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/09 21:53 PHST- 2026/05/07 00:00 [revised] PHST- 2026/01/09 00:00 [received] PHST- 2026/05/15 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/10 06:52 [pubmed] PHST- 2026/06/09 21:53 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70920 [pii] AID - 10.1111/dom.70920 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):7814-7824. doi: 10.1111/dom.70920. Epub 2026 Jun 9. PMID- 42262435 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20261010 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Jun 9 TI - Use of Glucagon-Like Peptide-1 Receptor Agonists in Women with Type 2 Diabetes Before Pregnancy: Addressing the Dilemma in A Real-World Setting. LID - 15 [pii] LID - 10.1007/s11892-026-01632-7 [doi] AB - PURPOSE OF REVIEW: To address the clinical dilemma of how best to counsel women with type 2 diabetes (T2D) using glucagon-like peptide-1 receptor agonists (GLP-1RA) regarding pregnancy. RECENT FINDINGS: Animal studies raise concern for fetal loss, malformations and adverse fetal growth after GLP-1RA exposure. Nonetheless, three cohort studies and one prospective study including 2,994 women with T2D exposed to GLP-1RA in early pregnancy indicate no increased risk of malformations compared with unexposed pregnancies, and observational data in 168 GLP-1RA exposed pregnancies are reassuring regarding miscarriage and fetal growth. Women with T2D are advised to use contraception and to discontinue GLP-1RAs two months before planned pregnancy. Despite concerns in animal studies, GLP-1RA exposure in early T2D pregnancy has not been associated with increased risk of malformations. If a woman with T2D inadvertently becomes pregnant while using GLP-1RA, the existing human evidence does not support a recommendation of terminating pregnancy. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Amiri, Aria AU - Amiri A AD - Department of Nephrology and Endocrinology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Haedersdal, Sofie AU - Haedersdal S AD - Department of Nephrology and Endocrinology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. AD - Center for Pregnant Women with Diabetes, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. AD - Department of Clinical and Translational Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, Herlev, DK-2730, Denmark. FAU - Damm, Peter AU - Damm P AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Center for Pregnant Women with Diabetes, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. AD - Department of Gynecology, Fertility and Obstetrics, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. FAU - Mathiesen, Elisabeth R AU - Mathiesen ER AD - Department of Nephrology and Endocrinology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Center for Pregnant Women with Diabetes, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. FAU - Ringholm, Lene AU - Ringholm L AD - Department of Nephrology and Endocrinology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. lene.ringholm.02@regionh.dk. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. lene.ringholm.02@regionh.dk. AD - Center for Pregnant Women with Diabetes, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. lene.ringholm.02@regionh.dk. LA - eng PT - Journal Article PT - Review DEP - 20260609 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Pregnancy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Pregnancy in Diabetics/drug therapy MH - Abortion, Spontaneous/chemically induced MH - Animals OTO - NOTNLM OT - Congenital Malformations OT - Fetal Growth OT - Glucagon-Like Peptide-1 Receptor Agonists OT - Miscarriage OT - Pregnancy OT - Type 2 Diabetes COIS- Declarations. Human/Animal Studies Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing interests: LR has received a grant from Novo Nordisk Foundation (grant number: NNF24OC0091713) for an investigator sponsored randomized controlled trial for which Mylife Diabetes Care AG donates insulin pumps and accessories and Abbott donates continued glucose monitoring devices, and participated in the European Association for the Study of Diabetes annual meeting 2023 as an invite by Novo Nordisk. SH has received funding from Independent Research Fund Denmark, Novo Nordisk and Boehringer Ingelheim. PD has participated in clinical studies on the use of insulin in pregnant women with preexisting diabetes in collaboration with Novo Nordisk, but no personal honorarium was involved. AA and ERM declare no competing interests. EDAT- 2026/06/09 12:49 MHDA- 2026/06/12 06:39 CRDT- 2026/06/09 11:06 PHST- 2026/01/05 00:00 [received] PHST- 2026/05/30 00:00 [accepted] PHST- 2026/06/12 06:39 [medline] PHST- 2026/06/09 12:49 [pubmed] PHST- 2026/06/09 11:06 [entrez] AID - 10.1007/s11892-026-01632-7 [pii] AID - 10.1007/s11892-026-01632-7 [doi] PST - epublish SO - Curr Diab Rep. 2026 Jun 9;26(1):15. doi: 10.1007/s11892-026-01632-7. PMID- 42261766 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260825 IS - 2165-6509 (Electronic) IS - 1092-8529 (Linking) VI - 31 IP - 1 DP - 2026 Jun 9 TI - Nephroprotective effects of GLP-1 receptor agonists in patients receiving lithium treatment: a multinational cohort study using the TriNetX network. PG - e25 LID - 10.1017/S1092852926101023 [doi] AB - BACKGROUND: Use of GLP-1 receptor agonists (GLP-1 RAs) is an established therapy that delays progression of chronic kidney disease in type 2 diabetes mellitus (T2DM), but their impact on lithium-associated nephrotoxicity is unclear. We evaluated whether GLP-1 RA use is associated with reduced renal risk in adults receiving long-term lithium therapy. METHODS: We conducted a retrospective, propensity score-matched cohort study using TriNetX electronic health records (>127 million patients across 109 healthcare organizations). Adults (>/=18 years) with T2DM and lithium exposure within 2 years prior to index were included. The primary outcome was renal nephrotoxicity, defined as a composite of ICD-10 and CPT-coded renal disease. Incidence and time-to-event outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: In a 24-month analysis of 452 matched patient pairs, GLP-1 RA initiation during lithium therapy was associated with a marked reduction in renal events versus lithium alone (23.5% vs 44.7%), corresponding to a risk difference of -21.2% (95% CI -36.9 to -5.5) and a risk ratio of 0.53 (95% CI 0.30-0.91; p = 0.013). Event-free survival was higher (62.5% vs 43.4%; log-rank p = 0.0115), with a hazard ratio of 0.45 (95% CI 0.23-0.85; p = 0.0089). This represents a 47% relative risk reduction and a number needed to treat (NNT) of 5 over 24 months. CONCLUSION: These findings support further mechanistic and prospective studies of GLP-1 RAs as a renoprotective strategy for patients receiving lithium treatment. FAU - McIntyre, Roger S AU - McIntyre RS AUID- ORCID: 0000-0003-4733-2523 AD - Department of Psychiatry, University of Toronto, Canada. ROR: https://ror.org/03dbr7087 FAU - Zhang-James, Yanli AU - Zhang-James Y AD - Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University Norton College of Medicine, USA. ROR: https://ror.org/040kfrw16 FAU - Goldberg, Joseph F AU - Goldberg JF AD - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, USA. FAU - Kwan, Angela T H AU - Kwan ATH AD - Brain and Cognition Discovery Foundation, Canada. ROR: https://ror.org/02fmwa274 AD - University of Toronto, Canada. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260609 PL - United States TA - CNS Spectr JT - CNS spectrums JID - 9702877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Lithium Compounds) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - *Lithium Compounds/adverse effects/therapeutic use MH - *Renal Insufficiency, Chronic/prevention & control MH - Retrospective Studies OTO - NOTNLM OT - GLP-1 receptor agonists OT - acute kidney injury OT - chronic kidney disease OT - lithium therapy OT - multinational cohort OT - nephrotoxicity OT - propensity score matching OT - real-world evidence OT - renal outcomes OT - type 2 diabetes mellitus EDAT- 2026/06/09 12:49 MHDA- 2026/07/30 00:38 CRDT- 2026/06/09 06:04 PHST- 2026/07/30 00:38 [medline] PHST- 2026/06/09 12:49 [pubmed] PHST- 2026/06/09 06:04 [entrez] AID - S1092852926101023 [pii] AID - 10.1017/S1092852926101023 [doi] PST - epublish SO - CNS Spectr. 2026 Jun 9;31(1):e25. doi: 10.1017/S1092852926101023. PMID- 42261400 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 1178-2005 (Electronic) IS - 1176-9106 (Print) IS - 1176-9106 (Linking) VI - 21 DP - 2026 TI - Type 2 Diabetes Mellitus and Chronic Obstructive Pulmonary Disease - from Pathophysiology to Effective Management Overview. PG - 609302 LID - 10.2147/COPD.S609302 [doi] LID - 609302 AB - Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) are two chronic conditions with significant global impact and high incidence, frequently occurring as comorbidities. This article analyzes the particularities of pathophysiological, genetic, and epigenetic interactions, as well as the therapeutic implications in patients with both conditions. Additionally, the clinical management of these patients is investigated in correlation with updated international guidelines, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 and the American Diabetes Association (ADA) 2026. The importance of rigorous monitoring, personalized treatment, and the use of modern therapies with proven benefits-including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists-is highlighted. The conclusion emphasizes the necessity of an integrated, multidisciplinary approach aimed at preventing complications, reducing cardiovascular risk, and improving the quality of life in comorbid patients. CI - (c) 2026 Prisacaru et al. FAU - Prisacaru, Victor AU - Prisacaru V AD - Department of Endocrinology, Nicolae Testemitanu State University of Medicine and Pharmacy, Municipal Clinical Hospital No. 1 "Gheorghe Palade", Chisinau, Republic of Moldova. FAU - Covantsev, Serghei AU - Covantsev S AUID- ORCID: 0000-0001-7236-5699 AD - Department of Surgical Oncology, Federal State Autonomous Institution National Medical Research Centre "Treatment and Rehabilitation Centre" of the Ministry of Health of the Russian Federation, Moscow, Russia. FAU - Ceasovschih, Alexandr AU - Ceasovschih A AD - Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. FAU - Sivapalan, Pradeesh AU - Sivapalan P AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Copenhagen Respiratory Research, Department of Medicine, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark. FAU - Tural, Seda AU - Tural S AUID- ORCID: 0000-0002-0657-0392 AD - Department of Chest Disease, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. FAU - Corlateanu, Alexandru AU - Corlateanu A AUID- ORCID: 0000-0002-3278-436X AD - Division of Pneumology and Allergology, Department of Internal Medicine, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova. FAU - Deleanu, Oana Claudia AU - Deleanu OC AD - Departament of Pneumology, UMF "Carol Davila", Bucuresti, Romania. LA - eng PT - Journal Article PT - Review DEP - 20260603 PL - New Zealand TA - Int J Chron Obstruct Pulmon Dis JT - International journal of chronic obstructive pulmonary disease JID - 101273481 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Pulmonary Disease, Chronic Obstructive/physiopathology/epidemiology/therapy/diagnosis MH - *Diabetes Mellitus, Type 2/epidemiology/physiopathology/drug therapy/therapy/diagnosis/genetics MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - Comorbidity MH - Risk Factors MH - *Lung/physiopathology/drug effects PMC - PMC13242804 OTO - NOTNLM OT - cardiovascular risk OT - chronic obstructive pulmonary disease OT - glucagon-like peptide-1 receptor agonists OT - sodium-glucose cotransporter 2 inhibitors OT - systemic inflammation OT - type 2 diabetes mellitus COIS- The authors report no conflicts of interest, financial or otherwise. EDAT- 2026/06/09 06:36 MHDA- 2026/06/12 18:42 PMCR- 2026/06/03 CRDT- 2026/06/09 03:56 PHST- 2026/03/14 00:00 [received] PHST- 2026/05/22 00:00 [accepted] PHST- 2026/06/12 18:42 [medline] PHST- 2026/06/09 06:36 [pubmed] PHST- 2026/06/09 03:56 [entrez] PHST- 2026/06/03 00:00 [pmc-release] AID - 609302 [pii] AID - 10.2147/COPD.S609302 [doi] PST - epublish SO - Int J Chron Obstruct Pulmon Dis. 2026 Jun 3;21:609302. doi: 10.2147/COPD.S609302. eCollection 2026. PMID- 42261018 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260624 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 76 IP - 5 DP - 2026 May TI - The efficacyand safety of once weekly injectable semaglutide (Ozempic) among patients with Type 2 diabete sintertiary care hospital: A Retrospective Study. PG - 709-712 LID - 10.47391/JPMA.23206 [doi] AB - OBJECTIVE: To assess the efficacy and safety of weekly injectable semaglutide in obese type 2 diabetes mellitus patients. METHODS: The retrospective, cross-sectional study was conducted at the Endocrinology Department, Shifa International Hospital, Islamabad, Pakistan, and comprised data from January 1, 2021, to January 31, 2023, of adult type 2 diabetes mellitus patients of either gender who had been prescribed weekly injectable semaglutide. Efficacy assessment was based on measuring the changes in glycated haemoglobin, bodyweight and body mass index at 3, 6, 9 and 12 months. The incidence of adverse events was also noted. Data was analysed using SPSS 26. RESULTS: Of the 102 patients, 57(56%) were females and 45(44%) were males. Overall mean age was 50+/-11.17 years, and the mean diabetes duration was 8.13+/-6.67 years. Mean values for glycated haemoglobin, bodyweight and body mass index were significantly different at 3, 6, 9 and 12 months post-intervention compared to baseline. Nausea was reported by 26(25.5%) patients. The most common reason for stopping semaglutide was no further benefits in 37(47%). CONCLUSION: Injectable semaglutide was found to be quite effective in managing type 2 diabetes mellitus. The treatment was well tolerated, establishing semaglutide as a valuable addition to diabetes care in Pakistan. FAU - Jabeen, Misbah AU - Jabeen M AD - Department of Endocrinology, Shifa International Hospital, Islamabad, Pakistan. FAU - Raja, Umar Yousaf AU - Raja UY AD - Department of Endocrinology, Shifa International Hospital, Islamabad, Pakistan. FAU - Istiaq, Osama AU - Istiaq O AD - Department of Endocrinology, Shifa International Hospital, Islamabad, Pakistan. FAU - Farooq, Iqra AU - Farooq I AD - Department of Endocrinology, Shifa International Hospital, Islamabad, Pakistan. LA - eng PT - Journal Article PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Drug Administration Schedule MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Injections MH - Nausea/chemically induced/epidemiology MH - *Obesity/complications/drug therapy MH - Pakistan MH - Retrospective Studies MH - Semaglutide MH - Treatment Outcome OTO - NOTNLM OT - Semaglutide, Type 2 diabetes mellitus, Obesity. EDAT- 2026/06/09 06:35 MHDA- 2026/06/13 06:37 CRDT- 2026/06/09 01:54 PHST- 2026/06/13 06:37 [medline] PHST- 2026/06/09 06:35 [pubmed] PHST- 2026/06/09 01:54 [entrez] AID - 10.47391/JPMA.23206 [doi] PST - ppublish SO - J Pak Med Assoc. 2026 May;76(5):709-712. doi: 10.47391/JPMA.23206. PMID- 42260171 OWN - NLM STAT- MEDLINE DCOM- 20260811 LR - 20261008 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 40 IP - 8 DP - 2026 Aug TI - Differential impact of glucagon-like peptide-1 (GLP-1) receptor agonists for weight loss in the type 2 diabetic and non-diabetic populations. PG - 6640-6648 LID - 10.1007/s00464-026-12940-0 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a cornerstone therapy for obesity management, yet long-term comparative effectiveness across diabetes status, adherence, and specific agents remains unclear. This study evaluates multi-year weight-loss outcomes associated with GLP-1 therapy and characterizes medication- and phenotype-specific differences. METHODS: This study represents a subgroup analysis of a large-scale meta-analysis including clinical trials, observational and case-control studies published from 2010 to 2025 reporting long-term weight outcomes for GLP-1 agents. Outcomes were evaluated across mixed, intention-to-treat (ITT), and treatment-adherent populations and stratified by diabetes status. Mixed-effects meta-regression was performed to evaluate independent predictors of weight loss. RESULTS: A total of 56,580 patients from 45 studies were included. GLP-1 therapy consistently produced greater weight loss than placebo across all populations. Non-diabetic participants achieved the greatest reductions, losing 15.7% of baseline weight at 12 months versus 5.1% in diabetic users in the mixed cohort. ITT results were similar but modestly attenuated, whereas adherent patients demonstrated the largest reductions. Diabetes status was a strong effect modifier: non-diabetic individuals achieved 2.5-4 x greater reductions than diabetics receiving the same agents. Meta-regression confirmed diabetes status as an independent negative predictor of weight loss (beta = - 1.77, p < 0.001). Semaglutide produced significantly greater reductions than liraglutide after adjustment (beta = + 1.67, p < 0.001), while baseline BMI was inversely associated with percent weight change (beta = + 0.46, p < 0.001). CONCLUSION: GLP-1 therapies produce durable weight loss with outcomes strongly influenced by diabetes status, adherence, and agent selection. These findings support a personalized, phenotype-based approach to GLP-1 prescribing. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Jia, Iwanger-I-Ter T AU - Jia IT AD - School of Medicine, Georgetown University, Washington, DC, USA. FAU - Bloomfield, Grace C AU - Bloomfield GC AD - School of Medicine, Georgetown University, Washington, DC, USA. FAU - Chen, Mike Y AU - Chen MY AD - School of Medicine, Georgetown University, Washington, DC, USA. FAU - Cunningham, Marcus H AU - Cunningham MH AD - School of Medicine, Georgetown University, Washington, DC, USA. FAU - Wang, Annie AU - Wang A AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. FAU - Daly, Shaun C AU - Daly SC AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. FAU - Hinojosa, Marcelo W AU - Hinojosa MW AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. FAU - Smith, Brian R AU - Smith BR AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. FAU - Nguyen, Ninh T AU - Nguyen NT AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. FAU - Azagury, Dan E AU - Azagury DE AD - Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA. FAU - Prindeze, Nicholas J AU - Prindeze NJ AUID- ORCID: 0000-0002-0928-1799 AD - Division of Gastrointestinal Surgery, Department of Surgery, Irvine Medical Center, University of California, Irvine, 101 The City Drive South, Orange, CA, 92868, USA. nprindez@hs.uci.edu. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260608 PL - Germany TA - Surg Endosc JT - Surgical endoscopy JID - 8806653 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use OTO - NOTNLM OT - Diabetes OT - GLP-1 outcomes OT - Meta-analysis OT - Weight loss COIS- Declarations. Disclosures: All authors including Ms. Iwanger-T-Ter Jia, Ms. Grace Bloomfield, Mr. Mike Chen, Mr. Marcus Cunningham, Dr. Annie Wang, Dr. Shaun Daly, Dr. Marcelo Hinojosa, Dr. Brian Smith, Dr. Ninh Nguyen, Dr. Dan Azagury, and Dr. Nicholas Prindeze have no conflict of interest or financial ties to disclose. EDAT- 2026/06/09 00:33 MHDA- 2026/08/11 06:36 CRDT- 2026/06/08 23:32 PHST- 2026/03/09 00:00 [received] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/08/11 06:36 [medline] PHST- 2026/06/09 00:33 [pubmed] PHST- 2026/06/08 23:32 [entrez] AID - 10.1007/s00464-026-12940-0 [pii] AID - 10.1007/s00464-026-12940-0 [doi] PST - ppublish SO - Surg Endosc. 2026 Aug;40(8):6640-6648. doi: 10.1007/s00464-026-12940-0. Epub 2026 Jun 8. PMID- 42259643 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Optic Ischaemic Neuropathy in Incretin-Based Therapy: A Comparative Analysis of Real-World Safety Data. PG - 7527-7535 LID - 10.1111/dom.70952 [doi] AB - AIMS: Non-arteritic anterior ischemic optic neuropathy (NAION) has emerged as a safety concern with semaglutide, prompting formal regulatory review and action by the European Medicines Agency. However, its occurrence across the broader class of incretin-based therapies is insufficiently characterised. This study used the FDA Adverse Event Reporting System to evaluate and compare pharmacovigilance signals for optic ischaemic neuropathy across six incretin-based therapies. MATERIALS AND METHODS: Adverse event reports from each drug's approval date through Q3 2025 were extracted using OpenVigil 2.1. The Medical Dictionary for Regulatory Activities term "optic ischaemic neuropathy" was used as the outcome. Disproportionality analysis was performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence intervals, applying Evans' criteria, restricted to primary suspect drug reports. RESULTS: Semaglutide demonstrated a strong post-marketing safety signal for optic ischaemic neuropathy (355 reports; ROR 94.45, 95% CI: 83.02-107.45; PRR 93.77, 95% CI: 82.48-106.61). Tirzepatide and liraglutide also exhibited significant safety signals (49 reports; ROR 2.94, 95% CI: 2.20-3.93; PRR 2.94, 95% CI: 2.20-3.93; and 13 reports; ROR 4.58, 95% CI: 2.65-7.91; PRR 4.58, 95% CI: 2.65-7.91, respectively). No signal was identified for dulaglutide, exenatide, or lixisenatide. Among semaglutide-associated reports, mean age was 59 years; disability was documented in 18% and hospitalization in 11% of cases. CONCLUSIONS: Significant post-marketing safety signals for optic ischaemic neuropathy were identified for semaglutide, tirzepatide, and liraglutide. The absence of signals with other glucagon-like peptide-1 receptor agonists argues against a uniform class effect. Prospective studies with neuro-ophthalmologist-confirmed diagnoses are warranted to establish causality and quantify absolute risk. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kakkar, Ashish Kumar AU - Kakkar AK AUID- ORCID: 0000-0001-7768-7304 AD - Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Payra, Shuvasree AU - Payra S AD - Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Charaya, Aarzoo AU - Charaya A AD - Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260608 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - Semaglutide MH - *Incretins/adverse effects/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/analogs & derivatives MH - Tirzepatide MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Exenatide/adverse effects MH - Pharmacovigilance MH - *Hypoglycemic Agents/adverse effects MH - Female MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins OTO - NOTNLM OT - disproportionality analysis OT - glucagon-like peptide-1 receptor agonists OT - optic ischaemic neuropathy OT - real-world safety data OT - semaglutide OT - tirzepatide EDAT- 2026/06/09 00:34 MHDA- 2026/07/08 22:40 CRDT- 2026/06/08 21:23 PHST- 2026/05/20 00:00 [revised] PHST- 2026/04/01 00:00 [received] PHST- 2026/05/22 00:00 [accepted] PHST- 2026/07/08 22:40 [medline] PHST- 2026/06/09 00:34 [pubmed] PHST- 2026/06/08 21:23 [entrez] AID - 10.1111/dom.70952 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7527-7535. doi: 10.1111/dom.70952. Epub 2026 Jun 8. PMID- 42259343 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20261002 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10547 DP - 2026 Jun 20 TI - Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial. PG - 2515-2527 LID - S0140-6736(26)00802-0 [pii] LID - 10.1016/S0140-6736(26)00802-0 [doi] AB - BACKGROUND: Elecoglipron is an oral, small molecule glucagon-like peptide (GLP)-1 receptor agonist currently in development for the management of type 2 diabetes. Elecoglipron is orally administered once daily with no food or fluid restrictions. SOLSTICE, a phase 2b study, evaluated the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with type 2 diabetes. METHODS: This phase 2b, randomised, double-blind, placebo-controlled trial was conducted in medical research centres and hospitals across nine countries, Canada, Germany, Hungary, Japan, Poland, Slovakia, Spain, the UK, and the USA. Sites were selected based on their capacity to fulfil protocol requirement, including, but not limited to, regulatory and ethics approvals, appropriate infrastructure and personnel, and access to the target patient population. Participants aged 18 years and older with a BMI of 23 kg/m(2) or higher and type 2 diabetes (glycated haemoglobin [HbA(1c)] >/=7.0% to /=6.5% to /=1500 mg/day) with glycated haemoglobin (HbA(1c)) concentrations between 7.0% and 10.5% (53-91 mmol/mol), stable bodyweight (+/-5%), and a BMI of 23.0 kg/m(2) or more. Participants were randomly assigned in a 1:1:1:1 ratio to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg) or dapagliflozin 10 mg. The primary endpoint was change from baseline in HbA(1c) at week 40, using a non-inferiority margin of 0.3% for orforglipron versus dapagliflozin; analysis was based on the treatment-regimen estimand (data obtained regardless of study intervention discontinuation or initiation of additional glucose-lowering agents). The treatment regimen estimand was the primary estimand, with the efficacy estimand considered supportive. Safety was assessed in all randomised participants who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov (NCT06192108, completed). FINDINGS: From Jan 10, 2024, to Sept 26, 2025, 1404 adults were assessed and 962 participants were randomly assigned to orforglipron 3 mg (n=240), 12 mg (n=241), or 36 mg (n=241), or dapagliflozin 10 mg (n=240). The baseline population included 474 (49%) females and had a mean age of 56.1 years (SD 11.5), HbA(1c) of 8.14% (1.04), type 2 diabetes duration of 8.0 years (6.7), and BMI of 32.6 kg/m(2) (6.6). At week 40, for the treatment regimen estimand, all orforglipron doses were non-inferior to dapagliflozin in reducing HbA(1c). Change from baseline in mean HbA(1c) was -1.23% (SE 0.08), -1.50% (0.08), and -1.56% (0.09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0.81% (0.07) with dapagliflozin 10 mg; estimated treatment difference versus dapagliflozin was -0.42% (95% CI -0.62 to -0.23), -0.70% (-0.90 to -0.49), and -0.75% (-0.96 to -0.55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0.0001). The most frequent adverse events associated with orforglipron were mild-to-moderate gastrointestinal events, observed in 112 (47%) of 240 participants receiving orforglipron 3 mg, 112 (46%) of 241 receiving 12 mg, and 130 (54%) of 241 receiving 36 mg, versus 29 (12%) of 240 receiving dapagliflozin. More study intervention discontinuations were observed with orforglipron 3 mg (35 [15%] of 240), 12 mg (44 [18%] of 241), and 36 mg (47 [20%] of 241) than with dapagliflozin (14 [6%] of 240). No severe episode of hypoglycaemia was reported. INTERPRETATION: Orforglipron demonstrated superior glycaemic control compared with dapagliflozin, with a tolerability profile consistent with the GLP-1 receptor agonist class, including increased rates of discontinuation due to adverse events, positioning it as a potential effective oral treatment option for type 2 diabetes. FUNDING: Eli Lilly and Company. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Welch, Michelle AU - Welch M AD - Consano Clinical Research, San Antonio, TX, USA. FAU - Forst, Thomas AU - Forst T AD - Clinical Research Services, Mannheim, Germany; Johannes Gutenberg University, Mainz, Germany. FAU - Jia, Weiping AU - Jia W AD - Shanghai Sixth People's Hospital, Shanghai, China. FAU - Del Pino, Pedro Orozco AU - Del Pino PO AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Denning, Max AU - Denning M AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Wu, Wen-Shuo AU - Wu WS AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Li, Jianghao AU - Li J AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Liu, Rong AU - Liu R AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Eifu, Michele AU - Eifu M AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: chen_yanyun@lilly.com. CN - ACHIEVE-2 Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT06192108 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260608 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 7ZW40D021M (orforglipron) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/therapeutic use/adverse effects/administration & dosage MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucosides/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis MH - Glycemic Control MH - *Metformin/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Oxadiazoles MH - Fluorine Compounds COIS- Declaration of interests MW declares payment as a member of a speaker bureau, support for attending meetings and/or travel, and stocks from Eli Lilly and Company. TF declares consulting fees from AstraZeneca, Atrogi, Bayer, Cipla, Eli Lilly and Company, Eysense, Fortbildungskolleg, Novo Nordisk, Pfizer, Sanofi, Remynd, and Roche; payments for speaker services to Amarin, AstraZeneca, Bohringer Ingelheim, Berlin Chemie, Cipla, Daiichi Sankyo, Eli Lilly and Company, Fortbildungskolleg, MSD, Novartis, Novo Nordisk, Sanofi, and Santis; and support for attending meetings and/or travel from AstraZeneca and Eli Lilly and Company. WJ declares unpaid roles as International Diabetes Federation Western Pacific Region chair-elect, and Director of the Asian Association for the Study of Diabetes. POdP, MD, W-SW, RL, JL, ME, and YC are employees and shareholders of Eli Lilly and Company. FIR - Beesley, Brian IR - Beesley B FIR - Chasteen, Jeffrey IR - Chasteen J FIR - Chen, Jung-Fu IR - Chen JF FIR - Cheng, Zhi Feng IR - Cheng ZF FIR - Chiang, Chern-En IR - Chiang CE FIR - Chu, Chih-Hsun IR - Chu CH FIR - Connery, Lisa IR - Connery L FIR - De Los Rios Ibarra, Manuel IR - De Los Rios Ibarra M FIR - Dong, Xiaolin IR - Dong X FIR - Fatakia, Adil IR - Fatakia A FIR - Forst, Thomas IR - Forst T FIR - Garcia, Pedro IR - Garcia P FIR - Garcia, Elias IR - Garcia E FIR - Gomez-Samano, Miguel IR - Gomez-Samano M FIR - Gonzalez Galvez, Guillermo IR - Gonzalez Galvez G FIR - Gumprecht, Janusz IR - Gumprecht J FIR - Jozefowska, Malgorzata IR - Jozefowska M FIR - Khaleghi, Behnam IR - Khaleghi B FIR - Khalsa, Satkirin IR - Khalsa S FIR - Kirby, John IR - Kirby J FIR - Kirsch, Bastian IR - Kirsch B FIR - Kwiatkowska, Magdalena IR - Kwiatkowska M FIR - Lazcano Soto, Jose IR - Lazcano Soto J FIR - Li, Qingju IR - Li Q FIR - Lin, Tsung-Hsien IR - Lin TH FIR - Liu, Dexue IR - Liu D FIR - Lopez Rosas, Enrique IR - Lopez Rosas E FIR - Lorra, Babette IR - Lorra B FIR - Lu, Yibing IR - Lu Y FIR - Lugowski, Tomasz IR - Lugowski T FIR - Ma, Jianhua IR - Ma J FIR - Matian, Arash IR - Matian A FIR - Mendez Machado, Gustavo IR - Mendez Machado G FIR - Mills, Richard IR - Mills R FIR - Mlodawska-Choluj, Dorota IR - Mlodawska-Choluj D FIR - Momoyama, Yoko IR - Momoyama Y FIR - Napora, Piotr IR - Napora P FIR - Ou, Horng-Yih IR - Ou HY FIR - Pei, Dee IR - Pei D FIR - Reynolds, Steven IR - Reynolds S FIR - Romero-Ibarguengoitia, Maria Elena IR - Romero-Ibarguengoitia ME FIR - Rose, Ludger IR - Rose L FIR - Rosenstock, Julio IR - Rosenstock J FIR - Rudolph, Justen IR - Rudolph J FIR - Sauque Reyna, Leobardo IR - Sauque Reyna L FIR - Schaefer, Axel IR - Schaefer A FIR - Schaum, Thomas IR - Schaum T FIR - Segner, Alexander IR - Segner A FIR - Shi, Bimin IR - Shi B FIR - Siewko, Katarzyna IR - Siewko K FIR - Skokowska, Ewa IR - Skokowska E FIR - Smolen, Agata IR - Smolen A FIR - Soufer, Joseph IR - Soufer J FIR - Staudenmeyer, Andreas IR - Staudenmeyer A FIR - Szyprowska, Ewa IR - Szyprowska E FIR - Topiwala, Shehzad IR - Topiwala S FIR - Vega, Damaris IR - Vega D FIR - Vidal Tamayo Ramirez, Rafael IR - Vidal Tamayo Ramirez R FIR - Vutikullird, Apinya IR - Vutikullird A FIR - Wang, Chih-Yuan IR - Wang CY FIR - Wang, Jun-Sing IR - Wang JS FIR - Wasilewska, Katarzyna IR - Wasilewska K FIR - Welch, Michelle IR - Welch M FIR - Wenzl-Bauer, Veronika IR - Wenzl-Bauer V FIR - Wilson, Jonathan IR - Wilson J FIR - Witzel, Peter IR - Witzel P FIR - Xu, Yushan IR - Xu Y FIR - Ye, Jun IR - Ye J FIR - Yu, Haoyong IR - Yu H FIR - Yuan, Guoyue IR - Yuan G FIR - Zambrano Ruiz, Eduardo IR - Zambrano Ruiz E FIR - Zeller, Helga IR - Zeller H FIR - Zhu, Hong IR - Zhu H EDAT- 2026/06/09 00:33 MHDA- 2026/07/10 12:45 CRDT- 2026/06/08 18:58 PHST- 2026/02/27 00:00 [received] PHST- 2026/04/17 00:00 [revised] PHST- 2026/04/22 00:00 [accepted] PHST- 2026/07/10 12:45 [medline] PHST- 2026/06/09 00:33 [pubmed] PHST- 2026/06/08 18:58 [entrez] AID - S0140-6736(26)00800-7 [pii] AID - 10.1016/S0140-6736(26)00800-7 [doi] PST - ppublish SO - Lancet. 2026 Jul 11;408(10550):125-140. doi: 10.1016/S0140-6736(26)00800-7. Epub 2026 Jun 8. PMID- 42259337 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20261002 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10547 DP - 2026 Jun 20 TI - Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial. PG - 2503-2514 LID - S0140-6736(26)00748-8 [pii] LID - 10.1016/S0140-6736(26)00748-8 [doi] AB - BACKGROUND: Elecoglipron (AZD5004) is an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist administered once daily without food or fluid restriction, in development for weight management in people living with obesity or overweight and type 2 diabetes. We assessed the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with obesity or overweight and at least one weight-related condition without diabetes. METHODS: In this double-blind, randomised, controlled, phase 2 dose-ranging study with a total treatment duration of 36 weeks, adult participants were recruited from medical research centres and hospitals in Australia, Canada, Germany, Japan, Taiwan, the UK, and the USA. Participants were aged 18 years or older living with obesity (BMI >/=30 kg/m(2)) or with overweight (BMI >/=27 kg/m(2)) with at least one weight-related condition and without type 2 diabetes. Eligible participants were randomly assigned in a 2:3:3:3:3:5 ratio to receive 5 mg, 15 mg, 50 mg, 75 mg (weekly titration), or 75 mg (every 2-week titration) of elecoglipron or matching placebo. Elecoglipron was administered as oral once-daily tablets without titration (5 mg and 15 mg) and as three different dose-titration regimens. The daily dose of 50 mg was evaluated using an every-4-weeks dose-escalation schedule, while 75 mg was assessed with weekly or every 2-week dose-escalation schedules. Participants, treating physicians, and sponsor were masked to the treatment allocation. The dual primary endpoints were percent change in bodyweight from baseline and the proportion of patients reaching at least 5% weight loss at week 26. Safety and tolerability were assessed in all participants who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT06579092) and is completed. FINDINGS: From Oct 8, 2024, to Feb 18, 2025, 472 individuals were screened for potential study inclusion, 162 did not meet the inclusion criteria, and 310 participants were randomly assigned to the varied elecoglipron groups or placebo. 288 participants (93%) completed the study and 231 (75%) completed the assigned treatment. The mean age of participants was 48.4 years (SD 13.7), 225 (73%) were female, 85 (27%) were male, their mean bodyweight was 106.9 kg (SD 24.1), and their mean BMI was 38.2 kg/m(2) (SD 7.2). At week 26, the estimated mean change from baseline in bodyweight was between -2.6% (5 mg elecoglipron), and -10.5% (75 mg with weekly titration steps) compared with -0.6% with placebo. The estimated proportion of participants reaching weight reductions of at least 5% at week 26 was 40.4-88.8% with elecoglipron versus 15.6% with placebo. Adverse events were reported by 84% (27 of 32) to 98% (48 of 49) of participants across elecoglipron doses compared with 84% (68 of 81) in the placebo group, the most common being nausea, constipation, diarrhoea, headache, and vomiting. INTERPRETATION: Daily oral elecoglipron demonstrated clinically meaningful weight reductions and a safety and tolerability profile consistent with the GLP-1 receptor agonist class in this phase 2 dose-ranging study, supporting phase 3 investigation in people living with obesity or overweight. FUNDING: AstraZeneca. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, and the NIHR Leicester Biomedical Research Centre, Leicester, UK. Electronic address: melanie.davies39@nhs.net. FAU - Aroda, Vanita R AU - Aroda VR AD - Department of Medicine, Division of Endocrinology, Diabetes & Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Rosenstock, Julio AU - Rosenstock J AD - Southwestern Medical Center, University of Texas, Dallas, TX, USA. FAU - Capehorn, Matthew AU - Capehorn M AD - Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, UK. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes & Endocrinology Clinic Calgary, Calgary, AB, Canada. FAU - Morizzo, Erika AU - Morizzo E AD - Clinical Operations, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Malhotra, Sonali AU - Malhotra S AD - Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA. FAU - Johansson, Peter A AU - Johansson PA AD - Biometrics, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Grice, Daniel AU - Grice D AD - Biometrics, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Andersson, Alf AU - Andersson A AD - Global Patient Safety, AstraZeneca, Gothenburg, Sweden. FAU - Rizi, Ehsan Parvaresh AU - Rizi EP AD - Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Sjostrom, C David AU - Sjostrom CD AD - Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. LA - eng SI - ClinicalTrials.gov/NCT06579092 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260608 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Diabetes Mellitus, Type 2 MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Treatment Outcome COIS- Declaration of interests MJD has acted as a consultant, advisor, and speaker for Eli Lilly, Novo Nordisk and Sanofi; as a consultant and advisor for Kailera; has attended advisory boards for AbbVie, Amgen, AstraZeneca, Biomea Fusion, Carmot Roche, Daewoong Pharmaceutical, Sanofi, Zealand Pharma, Regeneron, GSK, Innovent Bio, and EktaH; and as a speaker for AstraZeneca, Boehringer Ingelheim, and Zuellig Pharma. MJD has received grants from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. VRA has institutional contracts with Amgen, AstraZeneca, Applied Therapeutics, Biomea, Corcept, Eli Lilly, Fractyl, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm, and Servier and is a consultant for Baim, Mediflix, Roche, and Sanofi. JR reports clinical research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Corcept, Corxel, Eli Lilly, Hanmi, Merck, Novo Nordisk, Pfizer, Regeneron, Roche, Regor, Sanofi, Structure Therapeutics, and Terns; JR serves or has served on scientific advisory boards and received honoraria or consulting fees from Amgen, Applied Therapeutics, Arrowhead, Biomea Fusion, Boehringer Ingelheim, Corcept, Eccogene, Eli Lilly, Hanmi, i2O Therapeutics, Novo Nordisk, Regeneron, Roche, Sanofi, Structure Therapeutics, and Terns; and has received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. MC has served as unpaid advisor to the National Institute of Health and Care Excellence on obesity and diabetes; is Medical Director for Lighterlife (commercial Very Low Calorie Diet provider); is Medical Advisor to McDonalds UK; has recieved research funding to perform clinical trials for AstraZeneca, Novo Nordisk, Lilly, Boehringer Ingelheim, and Amgen; honoraria for talks and advisory boards from Novo Nordisk, Lilly and Boehringer Ingelheim; and travel or subsistence costs to attend meetings or conferences from AstraZeneca, Novo Nordisk, Lilly, Boehringer Ingelheim, and Amgen. SDP has received grants for clinical trials from Novo Nordisk, AstraZeneca, Sanofi, Eli Lilly, Boehringer Ingelheim, Prometic, and Pfizer; and consulting fees from AstraZeneca, Bausch Health, Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, Merck, Abbott, Dexcom, HLS, Bayer, AbbVie, Roche, Amgen, and Pfizer. SDP has also received payment for medical education lectures and speakers bureaus from AstraZeneca, Bausch, Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, Merck, Abbott, Dexcom, HLS, Bayer, and Pfizer, and has received travel support from AstraZeneca, Bausch, Eli Lilly, Novo Nordisk, Beohringer Ingelheim, Abbott, and Dexcom. EM, SM, PAJ, DG, AA, EPR, and CDS are employees and stockholders of AstraZeneca. EDAT- 2026/06/09 00:33 MHDA- 2026/06/19 00:36 CRDT- 2026/06/08 18:58 PHST- 2026/03/09 00:00 [received] PHST- 2026/04/09 00:00 [revised] PHST- 2026/04/14 00:00 [accepted] PHST- 2026/06/19 00:36 [medline] PHST- 2026/06/09 00:33 [pubmed] PHST- 2026/06/08 18:58 [entrez] AID - S0140-6736(26)00748-8 [pii] AID - 10.1016/S0140-6736(26)00748-8 [doi] PST - ppublish SO - Lancet. 2026 Jun 20;407(10547):2503-2514. doi: 10.1016/S0140-6736(26)00748-8. Epub 2026 Jun 8. PMID- 42258827 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260821 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 179 IP - 7 DP - 2026 Jul TI - Continuing Glucagon-Like Peptide-1 Receptor Agonists Into the First Trimester of Pregnancy and Pregnancy Outcomes : A Target Trial Emulation Study Using Claims Information. PG - 929-937 LID - 10.7326/ANNALS-25-04820 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use has increased among women of reproductive age, but limited data exist on safety in pregnancy. OBJECTIVE: To estimate the risk for nonlive birth, abnormal fetal growth, and major congenital malformation (MCM) with GLP-1RA dispensing in early pregnancy. DESIGN: In an observational cohort of pregnant women aged 16 to 55 years with a GLP-1RA dispensation in the 90 days before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: continuation of dispensing into the first trimester (>/=1 further dispensation), or noncontinuation. SETTING: Merative MarketScan U.S. insurance claims data (2011 to 2024). PARTICIPANTS: 3572 pregnancies (41.1% [n = 1467] among women with type 2 diabetes). MEASUREMENTS: Risk for nonlive birth was estimated using a weighted Kaplan-Meier estimator. Among live-birth pregnancies linked to infants, the weighted prevalence of MCM, small for gestational age (SGA), and large for gestational age (LGA) was estimated. RESULTS: The weighted risk for nonlive birth was 29.7% with continuation and 27.1% with noncontinuation (adjusted risk ratio, 1.09 [95% CI, 0.98 to 1.23]). Among 2529 live-birth pregnancies, 1443 (57.1%) received at least 1 GLP-1RA dispensation after LMP and 1499 (829 continuers) were linked to an infant. Weighted prevalence ratios for continuation versus noncontinuation were 1.29 (CI, 0.82 to 2.06) for SGA, 1.08 (CI, 0.84 to 1.40) for LGA, and 1.21 (CI, 0.83 to 1.82) for MCM. LIMITATION: Potential residual confounding by prior glycemic control. CONCLUSION: Risks for nonlive birth, SGA, LGA, and MCM were not definitively higher with continuation of GLP-1RAs into early pregnancy. However, estimates for MCM and SGA were imprecise and were compatible with both no increased risk and clinically relevant differences in risk. PRIMARY FUNDING SOURCE: National Institutes of Health. FAU - Brown, Jeremy P AU - Brown JP AUID- ORCID: 0000-0002-9941-7759 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom (J.P.B.). FAU - Huybrechts, Krista F AU - Huybrechts KF AUID- ORCID: 0000-0001-5805-8430 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.F.H., L.S., E.P.). FAU - Straub, Loreen AU - Straub L AUID- ORCID: 0000-0003-2623-2726 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.F.H., L.S., E.P.). FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.F.H., L.S., E.P.). FAU - Seely, Ellen W AU - Seely EW AUID- ORCID: 0000-0002-4425-1878 AD - Endocrinology, Diabetes and Hypertension Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (E.W.S.). FAU - Bateman, Brian T AU - Bateman BT AD - Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California (B.T.B.). FAU - Hernandez-Diaz, Sonia AU - Hernandez-Diaz S AUID- ORCID: 0000-0003-1458-7642 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (S.H.-D.). LA - eng GR - R01 HD097778/HD/NICHD NIH HHS/United States PT - Journal Article PT - Observational Study DEP - 20260609 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Pregnancy MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pregnancy Outcome MH - Adolescent MH - Young Adult MH - Pregnancy Trimester, First MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Abnormalities, Drug-Induced/epidemiology/etiology MH - Infant, Newborn MH - Infant, Large for Gestational Age MH - United States MH - *Pregnancy in Diabetics/drug therapy MH - Infant, Small for Gestational Age PMC - PMC13430612 MID - NIHMS2185445 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/06/08 19:39 MHDA- 2026/07/20 18:35 PMCR- 2026/08/03 CRDT- 2026/06/08 17:03 PHST- 2026/07/20 18:35 [medline] PHST- 2026/06/08 19:39 [pubmed] PHST- 2026/06/08 17:03 [entrez] PHST- 2026/08/03 00:00 [pmc-release] AID - 10.7326/ANNALS-25-04820 [doi] PST - ppublish SO - Ann Intern Med. 2026 Jul;179(7):929-937. doi: 10.7326/ANNALS-25-04820. Epub 2026 Jun 9. PMID- 42252454 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260915 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Jun 7 TI - Combination of GLP-1 receptor agonists and SGLT2 inhibitors in cardiometabolic disease: synergistic, additive, or non-additive effects? A narrative review. LID - 10.1186/s12933-026-03239-4 [doi] LID - 229 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are two novel classes of glucose-lowering agents with proven cardiometabolic benefits beyond glycaemic control. Both are now recommended in international guidelines for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. As they operate through complementary mechanisms, their combined use may confer additive or synergistic benefits on cardiometabolic outcomes. AIM: This narrative review examines and summarizes the available evidence on the synergistic effects of GLP-1 RAs and SGLT2 inhibitors in cardiometabolic disease, encompassing their effects on glycaemic control, body weight, blood pressure, cardiovascular events, renal outcomes, and mortality. METHODS: A narrative review of randomised clinical trials, observational studies, post-hoc analyses, and meta-analyses evaluating the combination of GLP-1 RAs and SGLT2 inhibitors in patients with T2DM was conducted. Individual drug class evidence from landmark cardiovascular and renal outcome trials is also reviewed to contextualise the potential for synergy. Evidence from trials conducted in non-diabetic populations with obesity or heart failure with preserved ejection fraction (HFpEF) is also examined where relevant to the combination therapy rationale. RESULTS: The combination of GLP-1 RAs and SGLT2 inhibitors consistently produced greater reductions in HbA1c (- 1.0 to - 1.5%), body weight (- 3 to - 9 kg), and systolic blood pressure (- 4 to - 10 mmHg) compared with either agent alone across multiple randomised trials, including DURATION-8, AWARD-10, SUSTAIN-9, and LIRA-ADD2SGLT2. Observational studies suggest a significant reduction in major adverse cardiovascular events and heart failure hospitalisations with combination therapy versus individual agents taken separately, while both classes also confer cardiovascular and renal benefits in non-diabetic populations at standard doses. However, randomised trial data do not consistently confirm superiority in cardiovascular event rates. Effects on renal outcomes are inconsistent across studies. Combination therapy appears well tolerated, with no significant increase in serious adverse events beyond those expected from each agent individually. CONCLUSIONS: The combination of GLP-1 RAs and SGLT2 inhibitors exerts additive benefits on glycaemic control, body weight, and blood pressure reduction. Evidence for synergistic cardiovascular and renal protection is promising but remains limited, largely derived from observational data and secondary analyses. Larger, dedicated randomised trials are needed to determine whether combination therapy confers superior cardiometabolic outcomes beyond either agent alone. CI - (c) 2026. The Author(s). FAU - Stamouli, Eirini AU - Stamouli E AD - Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University, Thessaloniki, Greece. FAU - Trakatelli, Christina-Maria AU - Trakatelli CM AD - Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University, Thessaloniki, Greece. ctrak@auth.gr. FAU - Sarigianni, Maria AU - Sarigianni M AD - Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University, Thessaloniki, Greece. FAU - Kitsios, Konstantinos AU - Kitsios K AD - Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University, Thessaloniki, Greece. FAU - Kotsis, Vasilis AU - Kotsis V AD - Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260607 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Incretins/adverse effects/therapeutic use MH - Treatment Outcome MH - Drug Therapy, Combination MH - *Glycemic Control/adverse effects MH - *Cardiovascular Diseases/diagnosis/mortality/prevention & control MH - *Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - Drug Synergism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Risk Assessment PMC - PMC13466521 OTO - NOTNLM OT - Cardiometabolic disease OT - Cardiovascular outcomes OT - Combination therapy OT - GLP-1 receptor agonists OT - Renal outcomes OT - SGLT2 inhibitors OT - Synergy OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Not applicable Competing interests: The authors declare no competing interests. EDAT- 2026/06/08 00:36 MHDA- 2026/08/12 06:05 PMCR- 2026/06/07 CRDT- 2026/06/07 23:37 PHST- 2026/03/28 00:00 [received] PHST- 2026/05/22 00:00 [accepted] PHST- 2026/08/12 06:05 [medline] PHST- 2026/06/08 00:36 [pubmed] PHST- 2026/06/07 23:37 [entrez] PHST- 2026/06/07 00:00 [pmc-release] AID - 10.1186/s12933-026-03239-4 [pii] AID - 3239 [pii] AID - 10.1186/s12933-026-03239-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Jun 7;25(1):229. doi: 10.1186/s12933-026-03239-4. PMID- 42251860 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. PG - 649-661 LID - S2213-8587(26)00126-9 [pii] LID - 10.1016/S2213-8587(26)00126-9 [doi] AB - BACKGROUND: Cagrilintide-semaglutide (CagriSema) is a novel, once-weekly combination of the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. We aimed to assess the efficacy and safety of cagrilintide-semaglutide for people with type 2 diabetes inadequately controlled with diet and exercise. METHODS: REIMAGINE 1 was a randomised, double-blind, parallel-group, phase 3a study carried out at 42 sites (study sites included university hospitals, health-care centres, research centres, and other centres) in six countries. Adults aged 18 years or older with type 2 diabetes inadequately controlled with diet and exercise were randomly assigned (2:1:2:1) to receive once-weekly subcutaneous cagrilintide 2.4 mg plus semaglutide 2.4 mg (cagrilintide-semaglutide [2.4 mg each]), placebo 2.4 mg plus 2.4 mg, cagrilintide 1.0 mg plus semaglutide 1.0 mg (cagrilintide-semaglutide [1.0 mg each]), or placebo 1.0 mg plus 1.0 mg for 40 weeks. Randomisation was done using a web-based system with a block size of six and stratified according to HbA(1c) less than 8.5% at screening and participation in the MRI substudy. Participants, care providers, investigators, and outcome assessors were masked within dose level and all participants received visually identical injections to maintain masking throughout the study. The primary endpoint was change in HbA(1c) from baseline to week 40 in the full analysis set; safety was assessed in all participants who received at least one dose of the trial product. Change in bodyweight from baseline to week 40 was a prespecified secondary endpoint. This study is registered with ClinicalTrials.gov, NCT06323174, and is complete. FINDINGS: Between March 19 and Dec 5, 2024, 294 people were screened for eligibility, 189 of whom were enrolled and randomly assigned to cagrilintide-semaglutide (2.4 mg each; n=62), cagrilintide-semaglutide (1.0 mg each; n=63), or placebo (n=64). 103 (54%) of 189 were male, 86 (46%) were female, 147 (78%) were White, and 26 (14%) were Asian. Baseline mean HbA(1c) was 7.8% (SD 0.7) and BMI was 35.2 kg/m(2) (7.4). Using the efficacy estimand, the estimated mean change in HbA(1c) after 40 weeks was -1.8 percentage points (SE 0.1) with cagrilintide-semaglutide (2.4 mg each), -1.5 percentage points (0.1) with cagrilintide-semaglutide (1.0 mg each), and -0.1 percentage points (0.2) with placebo. This corresponded to an estimated treatment difference of -1.7 percentage points (95% CI -2.0 to -1.3; p<0.0001) for cagrilintide-semaglutide (2.4 mg each) versus placebo and -1.3 percentage points (-1.8 to -0.9; p<0.0001) for cagrilintide-semaglutide (1.0 mg each) versus placebo. Cagrilintide-semaglutide was superior to placebo with respect to estimated mean relative change in bodyweight from baseline to week 40 for cagrilintide-semaglutide (2.4 mg each; -13.8% [SE 1.0]) versus placebo (-1.4% [0.7]; estimated treatment difference -12.4 percentage points [95% CI -14.7 to -10.1]; p<0.0001) and cagrilintide-semaglutide (1.0 mg each; -11.8% [1.0]) versus placebo (-1.4% [0.7]; estimated treatment difference -10.4 percentage points [-12.9 to -8.0]; p<0.0001). Adverse events were reported by 49 (79%) of 62 participants in the cagrilintide-semaglutide (2.4 mg each) group, 47 (75%) of 63 in the cagrilintide-semaglutide (1.0 mg each) group, and 42 (66%) of 64 in the placebo group. Most adverse events were mild or moderate and gastrointestinal related. INTERPRETATION: In a population of people with early-stage type 2 diabetes inadequately controlled with diet and exercise, cagrilintide-semaglutide (2.4 mg each and 1.0 mg each) was superior to placebo in reducing HbA(1c). The safety profile was consistent with the GLP-1 receptor agonist class and previous safety data for cagrilintide. These findings support cagrilintide-semaglutide as a potential novel and effective therapeutic intervention for people with early-stage type 2 diabetes. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Aroda, Vanita R AU - Aroda VR AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: varoda@bwh.harvard.edu. FAU - Buzzetti, Raffaella AU - Buzzetti R AD - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. FAU - Dalskov, Stine-Mathilde AU - Dalskov SM AD - Novo Nordisk, Soborg, Denmark. FAU - Jain, Akshay B AU - Jain AB AD - Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Unity Healthcare, Surrey, BC, Canada. FAU - Larsen, Jonas Hughes AU - Larsen JH AD - Novo Nordisk, Aalborg, Denmark. FAU - Mathieu, Chantal AU - Mathieu C AD - Department of Endocrinology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Videmark, Alex AU - Videmark A AD - Novo Nordisk, Soborg, Denmark. FAU - Watt, Torquil AU - Watt T AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. LA - eng SI - ClinicalTrials.gov/NCT06323174 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260607 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Double-Blind Method MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Adult MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Treatment Outcome MH - Aged MH - *Islet Amyloid Polypeptide/therapeutic use/administration & dosage MH - *Exercise MH - Blood Glucose MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis COIS- Declaration of interests VRA declares institutional contracts with Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Fractyl Health, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm Pharmaceuticals, and Servier; and consulting for Baim Institute for Clinical Research, Mediflix, Roche, and Sanofi. RB has received payment or honoraria for lectures, presentations, speakers bureaus, or educational events from Eli Lilly Italia, Sanofi, Abbott, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Abiogen, Guidotti, Theras, Dexcom, and Novartis; has received support for attending meetings or travel from Eli Lilly, Sanofi, Abbott, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Abiogen, Guidotti, Theras, Dexcom, and Novartis; has participated on an Advisory Board for Eli Lilly Italia, Sanofi, Abbott, Novo Nordisk, Dexcom, Bayer, and Daiichi; and is president of the Italian Society of Diabetes. S-MD, JHL, AV, and TW are employees of and shareholders in Novo Nordisk. ABJ has received clinical trials funding from Abbott, Amgen, Argenx, AstraZeneca, Eli Lilly, Novo Nordisk, Roche, and Sanofi Aventis; and has received speaking honorarium or advisory compensation from Abbott, AbbVie, AstraZeneca, Amgen, Antibody, Bausch Healthcare, Bayer, Boehringer Ingelheim, Celltrion, Dexcom, Diabetes Canada, Eli Lilly, Embecta, GSK, HLS Therapeutics, Insulet, Janssen, Kailera, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Pendopharm, Pfizer, Roche, Sandoz, Takeda, and Ypsomed. CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Eli Lilly and Company, Novartis, Dexcom, Boehringer Ingelheim, Bayer, Roche, Abbott, Medtronic, Insulet, Biomea Fusion, SAB BIO, vTv Therapeutics, and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Dexcom, Novo Nordisk, and Sanofi; CM serves or has served on the speakers' bureau for Novo Nordisk, Sanofi, Eli Lilly, Medtronic, Dexcom, Insulet, Abbott, Vertex, and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. CM is president of the European Diabetes Forum. All external support of the European Diabetes Forum is to be found on www.eudf.org. REP is supported by National Institutes of Health research grants U01DK106993, R01DK138060, U01DK35131, R01DK143524, U01DK143384, U01DK127392; has received investigator-initiated grant support (directed to his institution) from Abbott Laboratories, AstraZeneca, Biomea Fusion, Boehringer Ingelheim International, Carmot Therapeutics, Dompe, Eli Lilly, Endogenex, Fractyl Health, Lexicon Pharmaceuticals, Novo Nordisk, and Sanofi; has received consultancy fees from Abbott Laboratories, AbbVie, Altanine, Amgen, AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Corcept Therapeutics, Crinetics Pharmaceuticals, Endogenex, F Hoffmann-La Roche, Hanmi Pharmaceutical, Novo Nordisk, Pfizer, Recordati Rare Diseases, Regeneron Pharmaceuticals, Response Pharmaceuticals, Rona Therapeutics, Scholar Rock, Sun Pharmaceutical Industries, Third Rock Ventures, and Verdiva Bio Dev; has received speaker fees from Corcept, Lilly USA, and Novo Nordisk; and has stock options in Altanine. JBB has received salary support from clinical trial contracts to his employer by Corcept, Dexcom, GentiBio, Novo Nordisk, and Sparrow Pharmaceuticals; has received salary support from consulting contracts to his employer by Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, General Medicines, GentiBio, Kayothera, Metsera, MiniMed, Pfizer, Recordati, Roche, Sparrow Pharmaceuticals, Vertex, vTv Therapeutics, and Zealand; and has stock options in Aardvark, Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. EDAT- 2026/06/08 00:36 MHDA- 2026/07/15 18:42 CRDT- 2026/06/07 18:52 PHST- 2026/05/07 00:00 [received] PHST- 2026/05/16 00:00 [revised] PHST- 2026/05/16 00:00 [accepted] PHST- 2026/07/15 18:42 [medline] PHST- 2026/06/08 00:36 [pubmed] PHST- 2026/06/07 18:52 [entrez] AID - S2213-8587(26)00126-9 [pii] AID - 10.1016/S2213-8587(26)00126-9 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):649-661. doi: 10.1016/S2213-8587(26)00126-9. Epub 2026 Jun 7. PMID- 42251859 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261001 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. PG - 662-677 LID - S2213-8587(26)00125-7 [pii] LID - 10.1016/S2213-8587(26)00125-7 [doi] AB - BACKGROUND: The amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide have complementary effects on glycaemic control and bodyweight. We aimed to investigate the efficacy and safety of a fixed-dose combination of cagrilintide and semaglutide (cagrilintide-semaglutide; known as CagriSema) versus semaglutide or cagrilintide for glycaemic control in people with type 2 diabetes and overweight or obesity. METHODS: REIMAGINE 2 was a randomised, double-blind, placebo-controlled and active-controlled, parallel-group study conducted in 30 countries (trial sites included university hospitals, health-care centres, research centres, and other centres). Participants aged 18 years or older with inadequately controlled type 2 diabetes (HbA(1c) 7.0-10.5% [53-91 mmol/mol]) receiving metformin with or without an SGLT2 inhibitor, and a BMI of 25 kg/m(2) or more, were randomly assigned (8:8:2:8:8:1:1) to receive once-weekly subcutaneous cagrilintide 2.4 mg plus semaglutide 2.4 mg (hereafter cagrilintide-semaglutide [2.4 mg each]), semaglutide 2.4 mg, cagrilintide 2.4 mg, cagrilintide 1.0 mg plus semaglutide 1.0 mg (hereafter cagrilintide-semaglutide [1.0 mg each]), semaglutide 1.0 mg, or corresponding placebo for 68 weeks. Randomisation was done using a web-based system with blocked randomisation (block size 36) and stratification according to inclusion in the continuous glucose monitoring subgroup, HbA(1c) less than 8.5% at screening (yes or no), and country of participation (Japan; yes or no). The study participants, investigators, and study sponsor staff were masked to treatment allocation within dose level throughout the study. The primary endpoint was change in HbA(1c) from baseline to week 68 with cagrilintide-semaglutide (2.4 mg each) versus semaglutide 2.4 mg in the full analysis set; safety was assessed in all participants who received at least one dose of study product. This study is registered with ClinicalTrials.gov (NCT06065540) and is complete. FINDINGS: From Oct 10, 2023, to July 29, 2024, 3593 people were screened for eligibility, 2713 of whom were randomly assigned to cagrilintide-semaglutide (2.4 mg each; n=603), semaglutide 2.4 mg (n=605), cagrilintide 2.4 mg (n=152), cagrilintide-semaglutide (1.0 mg each; n=595), semaglutide 1.0 mg (n=609), or placebo (pooled 2.4 mg and 1.0 mg; n=149). 1164 (42.9%) of 2713 were female, 1549 (57.1%) were male, and 2207 (81.3%) were White. Of the randomly assigned participants, 2595 (95.7%) completed the study and 2376 (87.6%) were on treatment at week 68. Mean baseline HbA(1c) was 8.2% (SD 0.9). For the primary endpoint using the efficacy estimand, mean HbA(1c) change was significantly greater with cagrilintide-semaglutide (2.4 mg each) versus semaglutide 2.4 mg (-1.91 percentage points [SE 0.04] vs -1.75 percentage points [0.04]; estimated treatment difference -0.16 percentage points [95% CI -0.27 to -0.05]; p=0.0035). Adverse events were reported in 524 (86.9%) of 603 participants in the cagrilintide-semaglutide (2.4 mg each) group, 491 (81.2%) of 605 in the semaglutide 2.4 mg group, 125 (82.2%) of 152 in the cagrilintide 2.4 mg group, 485 (81.6%) of 594 in the cagrilintide-semaglutide (1.0 mg each) group, 477 (78.5%) of 608 in the semaglutide 1.0 mg group, and 105 (70.5%) of 149 in the placebo group. The most common adverse events in the active treatment groups were gastrointestinal disorders. INTERPRETATION: Cagrilintide-semaglutide (2.4 mg each) was superior to semaglutide 2.4 mg in reducing HbA(1c) in participants with type 2 diabetes receiving metformin with or without an SGLT2 inhibitor. The safety profile of cagrilintide-semaglutide was consistent with the GLP-1 receptor agonist class and previous safety data for cagrilintide. These findings support the added benefit of cagrilintide-semaglutide (2.4 mg each) versus semaglutide 2.4 mg for glycaemic control. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: jbuse@med.unc.edu. FAU - Bajaj, Harpreet S AU - Bajaj HS AD - LMC Diabetes and Endocrinology, Brampton, ON, Canada. FAU - Dalskov, Stine-Mathilde AU - Dalskov SM AD - Novo Nordisk, Soborg, Denmark. FAU - Donaldson, Lucienne AU - Donaldson L AD - Novo Nordisk, Soborg, Denmark. FAU - Hansen Duus, Helene H AU - Hansen Duus HH AD - Novo Nordisk, Soborg, Denmark. FAU - Fabricius, Therese Wilbek AU - Fabricius TW AD - Novo Nordisk, Soborg, Denmark. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic and University of Calgary, Calgary, AB, Canada. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Jain, Akshay B AU - Jain AB AD - Unity Healthcare, Surrey, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada. CN - REIMAGINE 2 study group LA - eng SI - ClinicalTrials.gov/NCT06065540 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260607 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Drug Combinations) RN - 0 (Islet Amyloid Polypeptide) SB - IM EIN - Lancet Diabetes Endocrinol. 2026 Aug;14(8):e11. doi: 10.1016/S2213-8587(26)00157-9. PMID: 42320507 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Double-Blind Method MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Blood Glucose/analysis MH - Adult MH - Glycated Hemoglobin/analysis MH - Drug Combinations MH - *Islet Amyloid Polypeptide/therapeutic use COIS- Declaration of interests JBB has received salary support from clinical trial contracts to his employer by Corcept Therapeutics, Dexcom, GentiBio, Novo Nordisk, and Sparrow Pharmaceuticals; has received salary support from consulting contracts to his employer by Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, General Medicines, GentiBio, Kayothera, Metsera, MiniMed, Pfizer, Recordati, Roche, Sparrow Pharmaceuticals, Vertex, vTv Therapeutics, and Zealand Pharma; has stock options in Aardvark Therapeutics, Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health; and has received salary support from grants from the National Institutes of Health, Breakthrough T1D, and the Patient-Centered Outcomes Research Institute. HSB has received funded grants or clinical trial payments made to his institution from Abbott, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Ionis, Novartis, Novo Nordisk, Pfizer, Roche, and Vertex; and advisory or speakers funding from Eli Lilly, Novo Nordisk, Roche, and Sandoz. S-MD, LD, HHHD, and TWF are employees at Novo Nordisk. S-MD, LD, and HHHD are also shareholders of Novo Nordisk. MH received lecture or advisory board fees from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk, and Sanofi; and research support from Sanofi. IL received research funding (paid to institution) or product from Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Pfizer, and Roche; research-related consulting fees (paid to institution) from Novo Nordisk; and advisory or consulting fees or other support from Aardvark Therapeutics, AbbVie, ADARx, Altasciences, Alveus Therapeutics, Amgen, Antag Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Baim Institute, Bain Capital, Bayer, Betagenon, BIOIO, Biomea Fusion, Boehringer Ingelheim, Boston Scientific, Carmot Therapeutics, CORXEL, Cytoki Pharma, Eli Lilly, Genentech, Janssen/Johnson & Johnson, Juvena, Keros Therapeutics, Mediflix, Metsera, Neurocrine, Novo Nordisk, PENGUINBIO, Pfizer, Regeneron, Response Pharmaceuticals, Roche, Sanofi, Shionogi, Sparrow Pharmaceuticals, Skye Bioscience, Source Bio, Structure Therapeutics, SUMMIT, Tenvie, TERNS Pharma, Verdiva Bio, Viking Therapeutics, and Zealand Pharma. SDP received honoraria from Abbott, AbbVie, Amgen, AstraZeneca, Bausch, Boehringer Ingelheim, Dexcom, GSK, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Pfizer, Roche, and Sanofi; research funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Prometic, and Sanofi; and speaker fees from Abbott, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, GSK, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Regeneron, Roche, and Sanofi. REP received National Institutes of Health research grants U01DK106993, R01DK138060, U01DK35131, R01DK143524, U01DK143384, and U01DK127392; investigator-initiated grant support (directed to his institution) from Abbott Laboratories, AstraZeneca, Biomea Fusion, Boehringer Ingelheim International GmbH, Carmot Therapeutics, Dompe, Eli Lilly and Company, Endogenex, Fractyl, Lexicon, National Institutes of Health, Novo Nordisk, and Sanofi; consultancy fees from Abbott Laboratories, AbbVie, Altanine, Amgen, AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Corcept Therapeutics, Crinetics Pharmaceuticals, Endogenex, F Hoffmann-La Roche, Hanmi Pharmaceutical, Novo Nordisk, Pfizer, Recordati Rare Diseases, Regeneron Pharmaceuticals, Response Pharmaceuticals, Rona Therapeutics, Scholar Rock, Sun Pharmaceutical Industries, Third Rock Ventures, and Verdiva Bio Dev; speaker fees from Lilly USA and Novo Nordisk; and stock options from Altanine. ABJ has received clinical trials funding from Abbott, Amgen, Argenx, AstraZeneca, Eli Lilly, Novo Nordisk, Roche, and Sanofi Aventis; and has received speaking honorarium or advisory compensation from Abbott, AbbVie, AstraZeneca, Amgen, Antibody, Bausch Healthcare, Bayer, Boehringer Ingelheim, Celltrion, Dexcom, Diabetes Canada, Eli Lilly, Embecta, GSK, HLS Therapeutics, Insulet, Janssen, Kailera, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Pendopharm, Pfizer, Roche, Sandoz, Takeda, and Ypsomed. EDAT- 2026/06/08 00:35 MHDA- 2026/07/15 12:36 CRDT- 2026/06/07 18:52 PHST- 2026/04/29 00:00 [received] PHST- 2026/05/12 00:00 [revised] PHST- 2026/05/12 00:00 [accepted] PHST- 2026/07/15 12:36 [medline] PHST- 2026/06/08 00:35 [pubmed] PHST- 2026/06/07 18:52 [entrez] AID - S2213-8587(26)00125-7 [pii] AID - 10.1016/S2213-8587(26)00125-7 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):662-677. doi: 10.1016/S2213-8587(26)00125-7. Epub 2026 Jun 7. PMID- 42251856 OWN - NLM STAT- MEDLINE DCOM- 20260702 LR - 20261002 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 408 IP - 10549 DP - 2026 Jul 4 TI - Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. PG - 38-51 LID - S0140-6736(26)01022-6 [pii] LID - 10.1016/S0140-6736(26)01022-6 [doi] AB - BACKGROUND: Basal insulin treatment for type 2 diabetes often results in inadequate glycaemic control and is associated with weight gain and increased risk of hypoglycaemia. We aimed to compare the efficacy and safety of a once per week combination of cagrilintide with semaglutide (CagriSema) versus placebo as an add-on to basal insulin in individuals with type 2 diabetes. METHODS: This double-blind, parallel-group, randomised, controlled, phase 3a study (REIMAGINE 3) was done at 46 centres (university hospitals, health-care centres, research centres, and other clinical trial sites) in six countries (the USA, China, Japan, Serbia, Slovakia, and South Africa). Adults with type 2 diabetes (glycated haemoglobin [HbA(1c)] 7.0-10.5%) receiving stable once per day basal insulin with or without metformin were randomly assigned (2:2:1:1) to once per week subcutaneous cagrilintide 2.4 mg plus semaglutide 2.4 mg (hereafter cagrilintide-semaglutide [2.4 mg each]) or cagrilintide 1.0 mg plus semaglutide 1.0 mg (hereafter cagrilintide-semaglutide [1.0 mg each]) or dose-matched placebo (2.4 mg plus 2.4 mg or 1.0 mg plus 1.0 mg) for 40 weeks. Randomisation was stratified by HbA(1c) of less than 8.5% at screening (yes or no) and country (Japan; yes or no). Participants, care providers, investigators, and outcome assessors were masked within each dose level to treatment allocation, with active treatments visually identical to placebo. The primary endpoint was mean HbA(1c) change (percentage points) from baseline to week 40 in all participants randomly assigned to treatment; secondary endpoints included change in bodyweight and safety, including hypoglycaemia. This trial was registered with ClinicalTrials.gov (NCT06323161) and is complete. FINDINGS: Between March 26 and Nov 29, 2024, we screened 340 individuals and 274 were included and randomly assigned to cagrilintide-semaglutide (2.4 mg each; n=90), cagrilintide-semaglutide (1.0 mg each; n=93), or placebo (pooled; n=91). Mean baseline HbA(1c) was 8.8% (SD 1.0), 159 (58%) participants were male, and 115 (42%) were female. Mean HbA(1c) reductions were significantly greater with cagrilintide-semaglutide (2.4 mg each -2.33% [SE 0.08] and 1.0 mg each -2.10% [0.08]) versus placebo (-0.66% [0.11]) at week 40, using the efficacy estimand (estimated treatment difference for cagrilintide-semaglutide [2.4 mg each] vs placebo -1.68 percentage points [95% CI -1.95 to -1.41], p<0.0001; for cagrilintide-semaglutide [1.0 mg each] vs placebo -1.44 percentage points [95% CI -1.71 to -1.17], p<0.0001). Cagrilintide-semaglutide provided bodyweight reductions of 10-12%. Adverse events were reported by 72 (80%) of 90 participants receiving cagrilintide-semaglutide (2.4 mg each), 66 (71%) of 93 receiving cagrilintide-semaglutide (1.0 mg each), and 65 (71%) of 91 receiving placebo, and were mostly mild or moderate gastrointestinal disorders. No severe hypoglycaemia was reported. There was one death in the cagrilintide-semaglutide (1.0 mg each) group not related to treatment (due to malignancy). INTERPRETATION: Cagrilintide-semaglutide at doses of 2.4 mg each and 1.0 mg each met the primary endpoint, with statistically significant and clinically relevant HbA(1c) reductions versus placebo when added to basal insulin-treated type 2 diabetes. These reductions were accompanied by robust bodyweight reduction and no additional risk of hypoglycaemia. The safety profile was consistent with that of the GLP-1 receptor agonist class and previous safety data for cagrilintide. Findings support the use of cagrilintide-semaglutide as an add-on to once per day basal insulin to significantly improve glycaemic control. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Rosenstock, Julio AU - Rosenstock J AD - Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: juliorosenstock@dallasdiabetes.com. FAU - Billings, Liana K AU - Billings LK AD - Department of Medicine, Endeavor Health (NorthShore Hospitals), Skokie, IL, USA; University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. FAU - Gajria, Reena AU - Gajria R AD - Novo Nordisk, Soborg, Denmark. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Puglia, Italy. FAU - Johansen, Nanna Borup AU - Johansen NB AD - Novo Nordisk, Soborg, Denmark. FAU - Klein, Klara R AU - Klein KR AD - Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Thamattoor, Usha K AU - Thamattoor UK AD - NXT-2, Bangalore, India. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Jain, Akshay B AU - Jain AB AD - TLC Diabetes and Endocrinology, Surrey, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Unity Healthcare, Surrey, BC, Canada. LA - eng SI - ClinicalTrials.gov/NCT06323161 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260607 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - AO43BIF1U8 (cagrilintide) RN - 0 (Islet Amyloid Polypeptide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Drug Therapy, Combination MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Insulin/therapeutic use/administration & dosage MH - *Semaglutide/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use MH - Islet Amyloid Polypeptide COIS- Declaration of interests JR reports clinical research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Corcept Therapeutics, Corxel, Eli Lilly, Hanmi, Merck, Novo Nordisk, Pfizer, Regeneron, Regor, Roche, Sanofi, Structure Therapeutics, and Terns; serves or has served on scientific advisory boards and received honorarium or consulting fees from Amgen, Applied Therapeutics, Arrowhead, Biomea Fusion, Boehringer Ingelheim, Corcept Therapeutics, Eccogene, Eli Lilly, Hanmi, i2O Therapeutics, Novo Nordisk, Regeneron, Roche, Sanofi, Structure Therapeutics, and Terns; and has received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. LKB has received consulting honoraria from Amgen, Bayer, Dexcom, Eli Lilly, Endogenex, Novo Nordisk, Pfizer, Sanofi, and Xeris. RG is an employee and shareholder at Novo Nordisk. FG reports research grants from Eli Lilly and Roche Diabetes Care; consulting fees from Eli Lilly and Novo Nordisk; support for attending meetings or travel from AstraZeneca, Boehringer Ingelheim, Eli Lilly, LifeScan, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; participation on advisory boards for AstraZeneca, Boehringer Ingelheim, Eli Lilly, LifeScan, MedImmune, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; unpaid leadership for the European Foundation for the Study of Diabetes and European Association for the Study of Diabetes, Societa Italiana di Endocrinologia, and Fo.Ri.SIE; and support for medical writing and statistical analysis from AstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi Aventis. NBJ is an employee and shareholder at Novo Nordisk. KRK has received advisory or consulting fees support from Antag Therapeutics, Metsera, Novo Nordisk, Roche Pharmaceuticals, and vTv Therapeutics; research-related contracts (paid to the institution) from Bayer, Boehringer Ingelheim, Carmot, Diasome, Eli Lilly, GentiBio, Novo Nordisk, Rhythm Pharmaceuticals, Roche Pharmaceuticals, and vTv Therapeutics; and salary support through the National Institutes of Health (K12TR004416, U54DK118612, and R21AA031892). UKT is an employee and shareholder at Novo Nordisk. JBB has received salary support from clinical trial contracts to his employer by Corcept Therapeutics, Dexcom, GentiBio, Novo Nordisk, and Sparrow Pharmaceuticals; has received salary support from consulting contracts to his employer by Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Kayothera, Metsera, MiniMed, Pfizer, Recordati, Roche, Sparrow Pharmaceuticals, Vertex, vTv Therapeutics, and Zealand; has stock or stock options in Aardvark Therapeutics, Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health; and has received salary support from grants from the National Institutes of Health, Breakthrough T1D, and PCORI. ABJ has received clinical trials funding from Abbott, Amgen, Argenx, AstraZeneca, Eli Lilly, Novo Nordisk, Roche, and Sanofi Aventis; has received speaking honorarium or advisory compensation from Abbott, AbbVie, Amgen, Antibody, AstraZeneca, Bausch Healthcare, Bayer, Boehringer Ingelheim, Celltrion, Dexcom, Diabetes Canada, Eli Lilly, embecta, GSK, HLS Therapeutics, Insulet, Janssen, Kailera, Medtronic, Merck, Moderna, Novartis, Novo Nordisk, Pendopharm, Pfizer, Roche, Sandoz, Takeda, and Ypsomed. EDAT- 2026/06/08 00:36 MHDA- 2026/07/03 00:30 CRDT- 2026/06/07 18:52 PHST- 2026/04/17 00:00 [received] PHST- 2026/05/15 00:00 [revised] PHST- 2026/05/19 00:00 [accepted] PHST- 2026/07/03 00:30 [medline] PHST- 2026/06/08 00:36 [pubmed] PHST- 2026/06/07 18:52 [entrez] AID - S0140-6736(26)01022-6 [pii] AID - 10.1016/S0140-6736(26)01022-6 [doi] PST - ppublish SO - Lancet. 2026 Jul 4;408(10549):38-51. doi: 10.1016/S0140-6736(26)01022-6. Epub 2026 Jun 7. PMID- 42251769 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260805 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 336 IP - 5 DP - 2026 Aug 4 TI - Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. PG - 389-399 LID - 10.1001/jama.2026.9512 [doi] AB - IMPORTANCE: The effects of orforglipron, an oral, nonpeptide glucagon-like peptide 1 receptor agonist, added to insulin glargine for treatment of type 2 diabetes have not been described. OBJECTIVE: To assess efficacy and safety of orforglipron added to titrated insulin glargine in adults with type 2 diabetes and inadequate glycemic control. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, phase 3 study conducted at 72 sites across the US, Brazil, China, Japan, and Romania between November 10, 2023, and September 15, 2025, in adults with type 2 diabetes taking insulin glargine with or without metformin and/or sodium-glucose cotransporter 2 inhibitors over 40 weeks. INTERVENTIONS: Participants were randomized (1:1:1:1) to receive once-daily 3-mg (n = 137), 12-mg (n = 132), or 36-mg (n = 136) dosages of orforglipron or placebo (n = 141), in addition to titrated insulin glargine. MAIN OUTCOMES AND MEASURES: The primary outcome was mean hemoglobin A1c (HbA1c) change from baseline to week 40 (for the 12-mg once daily and 36-mg once daily dosages of orforglipron). Key secondary outcomes were mean HbA1c change from baseline (for the 3-mg once daily dosage of orforglipron), proportion of participants achieving HbA1c targets of lower than 7.0% and 6.5% or lower, and mean body weight change and percentage change from baseline to week 40. RESULTS: Among 546 randomized participants (median age, 61.0 [IQR, 26-95] years; 52.9% male; median duration of type 2 diabetes, 14.6 [IQR, 0.1-40.7] years; mean HbA1c, 8.50% [SD, 0.95%]; mean body mass index, 30.8 [SD, 6.1]), 507 (92.9%) completed the trial. At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo. Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all). All key secondary outcomes demonstrated statistically significant differences in favor of orforglipron compared with placebo. Mean percentage body weight change from baseline was -2.6%, -4.8%, and -5.4% with orforglipron, 3 mg once daily, 12 mg once daily, and 36 mg once daily, respectively, vs 0.2% with placebo. The most frequent adverse events with orforglipron were gastrointestinal (mild to moderate). Orforglipron did not increase the risk of clinically significant hypoglycemia vs placebo. CONCLUSIONS AND RELEVANCE: In participants with type 2 diabetes inadequately controlled by insulin glargine, addition of oral orforglipron significantly improved glycemic control and body weight, without increasing hypoglycemia risk, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06109311. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Regenerative and Precision Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - D'Souza, Sherwin AU - D'Souza S AD - St Luke's Endocrinology, Boise, Idaho. FAU - Ludwig, Lisa AU - Ludwig L AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Kiyosue, Arihiro AU - Kiyosue A AD - Tokyo-Eki Centre-Building Clinic, Tokyo, Japan. FAU - Ibriga, Hilda AU - Ibriga H AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Rha, Hyungmin AU - Rha H AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Denning, Max AU - Denning M AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Wu, Wen-Shuo AU - Wu WS AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Fernandez Lando, Laura AU - Fernandez Lando L AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Tobian, Janet AU - Tobian J AD - Eli Lilly and Company, Indianapolis, Indiana. LA - eng SI - ClinicalTrials.gov/NCT06109311 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 9100L32L2N (Metformin) RN - 7ZW40D021M (orforglipron) RN - 0 (Fluorine Compounds) RN - 0 (Oxadiazoles) SB - IM CIN - JAMA. 2026 Aug 4;336(5):374-376. doi: 10.1001/jama.2026.10443. PMID: 42251768 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Drug Therapy, Combination/adverse effects/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Hypoglycemia/blood/chemically induced/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - *Insulin Glargine/administration & dosage/adverse effects MH - Metformin/administration & dosage/adverse effects MH - Fluorine Compounds/administration & dosage/adverse effects MH - Oxadiazoles/administration & dosage/adverse effects MH - Administration, Oral MH - Body Weight/drug effects MH - Glycemic Control/methods MH - Treatment Outcome PMC - PMC13244277 COIS- Conflict of Interest Disclosures: Dr Giorgino reported having unpaid leadership roles with the European Association for the Study of Diabetes, the European Foundation for the Study of Diabetes, and the European Diabetes Forum; receiving personal fees from AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Kayothera, LifeScan, MSD, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi; receiving nonfinancial support from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi; and receiving grants from Eli Lilly and Company and Roche Diabetes Care. Dr D'Souza reported receiving personal fees from Eli Lilly and Company and Novo Nordisk. Dr Ludwig reported being an employee of and having stock/shares in Eli Lilly and Company. Dr Kiyosue reported receiving personal fees from Tanabe Pharma, Sumitomo Pharma, Daiichi Sankyo, Ono Pharmaceutical, AstraZeneca, Takeda, Eli Lilly and Company, Boehringer Ingelheim, Kowa, Novartis Pharma, Kyowa Kirin, MSD, and Novo Nordisk. Dr Denning reported being an employee of and having stock/shares in Eli Lilly and Company. Dr Wu reported being an employee of Eli Lilly and Company. Dr Fernandez Lando reported being an employee of and having stock/shares in Eli Lilly and Company. No other disclosures were reported. EDAT- 2026/06/07 18:42 MHDA- 2026/08/04 12:46 PMCR- 2026/12/07 CRDT- 2026/06/07 17:33 PHST- 2026/08/04 12:46 [medline] PHST- 2026/06/07 18:42 [pubmed] PHST- 2026/06/07 17:33 [entrez] PHST- 2026/12/07 00:00 [pmc-release] AID - 2850187 [pii] AID - joi260062 [pii] AID - 10.1001/jama.2026.9512 [doi] PST - ppublish SO - JAMA. 2026 Aug 4;336(5):389-399. doi: 10.1001/jama.2026.9512. PMID- 42251595 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260805 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 336 IP - 5 DP - 2026 Aug 4 TI - Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. PG - 377-388 LID - 10.1001/jama.2026.8142 [doi] AB - IMPORTANCE: Obesity is a worldwide problem and a major public health issue in China. OBJECTIVE: To evaluate the efficacy and safety of mazdutide (a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist) in Chinese adults with obesity (defined as a body mass index of >/=30). DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, phase 3, randomized clinical trial including Chinese adults with or without type 2 diabetes that was conducted at 27 hospitals from December 2023 to November 2025. INTERVENTIONS: Participants were randomized in a 2:1 ratio to receive a once weekly, 9-mg dose of mazdutide administered subcutaneously (n = 308) or placebo (n = 154) as an adjunct to a reduced calorie diet and increased physical activity for 60 weeks. MAIN OUTCOMES AND MEASURES: The coprimary outcomes were the percentage change in body weight from baseline and a weight reduction of at least 5% at week 60. The efficacy and safety analyses were performed in participants who received at least 1 dose of the study treatment. RESULTS: A total of 461 participants (295 [64.0%] female; 16.1% with type 2 diabetes; mean age, 33.9 [SD, 8.4] years; body weight, 94.0 [SD, 13.8] kg; BMI, 34.3 [SD, 3.2]) received the study treatment (307 in the mazdutide group and 154 in the placebo group) and were included in the analyses. At week 60, the mean percentage change in body weight from baseline was -16.65% (95% CI, -18.19% to -15.12%) in the mazdutide group compared with -1.50% (95% CI, -3.43% to 0.43%) in the placebo group (between-group difference, -15.15% [95% CI, -17.22% to -13.09%]; P < .001). At week 60, 84.3% of participants in the mazdutide group had a body weight reduction of 5% or greater compared with 33.1% in the placebo group (between-group difference, 51.6% [95% CI, 43.0% to 60.1%]; P < .001). Adverse events leading to study treatment discontinuation were reported in 2.9% of participants in the mazdutide group compared with 0% in the placebo group. The most common adverse events were vomiting (53.1% in the mazdutide group vs 1.3% in the placebo group), nausea (46.9% vs 3.2%, respectively), and diarrhea (39.4% vs 6.5%); most of the adverse events were mild to moderate in severity. CONCLUSIONS AND RELEVANCE: Mazdutide provided clinically meaningful weight reduction in Chinese adults with moderate to severe obesity compared with placebo, but participants receiving the drug experienced gastrointestinal adverse reactions compared with those receiving placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06164873. FAU - Gao, Leili AU - Gao L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Jiang, Hongwei AU - Jiang H AD - First Affiliated Hospital and College of Clinical Medicine, State Key Laboratory of Light Superalloys, Henan University of Science and Technology, Luoyang, China. AD - State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China. FAU - Cai, Hanqing AU - Cai H AD - Department of Endocrinology, Second Norman Bethune Hospital of Jilin University, Changchun, China. FAU - Tian, Junhang AU - Tian J AD - Department of Endocrinology, Luoyang Third People's Hospital, Luoyang, China. FAU - Shi, Bimin AU - Shi B AD - Department of Endocrinology, First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Qiu, Wei AU - Qiu W AD - Department of Endocrinology, Huzhou Central Hospital, Huzhou, China. FAU - Huang, Chongbing AU - Huang C AD - Department of Endocrinology, People's Hospital of Xuancheng, Xuancheng, China. FAU - Han, Jie AU - Han J AD - Department of Endocrinology, China National Petroleum Corporation Central Hospital, Langfang, China. FAU - Zhang, Suhe AU - Zhang S AD - Department of Endocrinology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Pang, Shuguang AU - Pang S AD - Department of Endocrinology, Jinan Central Hospital, Jinan, China. FAU - Bi, Yan AU - Bi Y AD - Department of Endocrinology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Chen, Lei AU - Chen L AD - Department of Endocrinology, Suzhou Municipal Hospital, Suzhou, China. FAU - Gu, Xuejiang AU - Gu X AD - Department of Endocrinology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Han, Junfeng AU - Han J AD - Department of Endocrinology and Metabolism, Tongji Hospital of Tongji University, Shanghai, China. FAU - Ma, Qingyang AU - Ma Q AD - Innovent Biologics Inc, Suzhou, China. FAU - Deng, Huan AU - Deng H AD - Innovent Biologics Inc, Suzhou, China. FAU - Wang, Yanqi AU - Wang Y AD - Innovent Biologics Inc, Suzhou, China. FAU - Li, Li AU - Li L AD - Innovent Biologics Inc, Suzhou, China. FAU - Han-Zhang, Han AU - Han-Zhang H AD - Innovent Biologics Inc, Suzhou, China. FAU - Qian, Lei AU - Qian L AD - Innovent Biologics Inc, Suzhou, China. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. CN - GLORY-2 Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT06164873 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) RN - 0 (Receptors, Glucagon) RN - Chinese people SB - IM CIN - JAMA. 2026 Aug 4;336(5):374-376. doi: 10.1001/jama.2026.10443. PMID: 42251768 MH - Adult MH - Female MH - Humans MH - Male MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Body Mass Index MH - Body Weight/drug effects/physiology MH - Caloric Restriction MH - China MH - Combined Modality Therapy/adverse effects/methods MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Diarrhea/chemically induced/epidemiology MH - Double-Blind Method MH - East Asian People MH - Exercise/physiology MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Injections, Subcutaneous MH - Nausea/chemically induced/epidemiology MH - *Obesity/complications/diet therapy/drug therapy MH - *Peptides/administration & dosage/adverse effects MH - Receptors, Glucagon/agonists MH - Treatment Outcome MH - Vomiting/chemically induced/epidemiology MH - *Weight Loss/drug effects/physiology PMC - PMC13244275 COIS- Conflict of Interest Disclosures: Dr Gao reported receiving personal fees from Innovent Biologics Inc and Novo Nordisk A/S. Drs Ma, Deng, Li, Han-Zhang, and Qian and Ms Wang reported being employees of Innovent Biologics Inc. Dr Ji reported receiving personal fees from Eli Lilly, Novo Nordisk, Abbott Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Fosun Pharma, Gan & Lee Pharmaceuticals, Innovent Biologics Inc, Merck Sharp & Dohme, Sanofi, Sibionics, and Sinocare and serving as an independent director for Shanghai Benemae Pharmaceutical Corporation. No other disclosures were reported. FIR - Lian, Qiufang IR - Lian Q FIR - Li, Hua IR - Li H FIR - Zhang, Yawei IR - Zhang Y FIR - Lv, Lingchun IR - Lv L FIR - Meng, Haiyan IR - Meng H FIR - Wang, Long IR - Wang L FIR - He, Yuquan IR - He Y FIR - Lu, Xiaohua IR - Lu X FIR - Yang, Tao IR - Yang T FIR - Zheng, Xuqin IR - Zheng X FIR - Qin, Xihu IR - Qin X FIR - Zhang, Tie IR - Zhang T FIR - Zhao, Yuzhu IR - Zhao Y EDAT- 2026/06/07 13:42 MHDA- 2026/08/04 12:46 PMCR- 2026/12/07 CRDT- 2026/06/07 09:32 PHST- 2026/08/04 12:46 [medline] PHST- 2026/06/07 13:42 [pubmed] PHST- 2026/06/07 09:32 [entrez] PHST- 2026/12/07 00:00 [pmc-release] AID - 2850143 [pii] AID - joi260050 [pii] AID - 10.1001/jama.2026.8142 [doi] PST - ppublish SO - JAMA. 2026 Aug 4;336(5):377-388. doi: 10.1001/jama.2026.8142. PMID- 42250734 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1879-016X (Electronic) IS - 0163-7258 (Linking) VI - 285 DP - 2026 Sep TI - Incretin-based therapies: Effects on plasma lipids and potential mechanisms. PG - 109057 LID - S0163-7258(26)00084-7 [pii] LID - 10.1016/j.pharmthera.2026.109057 [doi] AB - Incretin-based therapies have transformed the treatment of type-2 diabetes and obesity, yet their effects on lipid and lipoprotein metabolism are less appreciated than their glycemic and weight-related actions. This review examines evidence for the effects of glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists on plasma lipids, with emphasis on triglyceride-rich lipoprotein metabolism in fasting and postprandial states. Across clinical studies, the most reproducible lipid-related effect is attenuation of postprandial lipemia, including reductions in triglycerides and apolipoprotein B48-containing lipoprotein (i.e., intestinally derived lipoprotein) measures, whereas effects on fasting lipid panels are generally less impressive and more heterogeneous across agents and populations. Acute studies reflect rapid effects on gastric emptying, intestinal lipid handling, and triglyceride-rich lipoprotein excursions, whereas chronic studies additionally incorporate the downstream influence of weight loss and improved glycemic control in those with diabetes. Human kinetic and stable isotope enrichment studies provide mechanistic insights that support contributions from both reduced intestinal lipoprotein particle output and enhanced clearance, with additional evidence for changes in hepatic apolipoprotein B100-containing lipoprotein metabolism. Complementary preclinical and biomarker data implicate adipose clearance pathways, the apolipoprotein C-III/lipoprotein lipase axis, neurohumoral regulation, and intestinal lymphatic transport as additional modulators. Taken together, the lipid effects of incretin-based therapies are directionally consistent with antiatherosclerotic benefit, but current evidence does not permit a clear estimate of how much they contribute to the established cardiovascular protection of glucagon-like peptide-1 receptor agonists. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Syed-Abdul, Majid M AU - Syed-Abdul MM AD - Departments of Medicine and Physiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. FAU - Lewis, Gary F AU - Lewis GF AD - Departments of Medicine and Physiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. Electronic address: gary.lewis@uhn.ca. LA - eng PT - Journal Article PT - Review DEP - 20260606 PL - England TA - Pharmacol Ther JT - Pharmacology & therapeutics JID - 7905840 RN - 0 (Incretins) RN - 0 (Lipids) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/pharmacology/therapeutic use MH - Animals MH - *Lipids/blood MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use MH - Lipid Metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/blood MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Apolipoprotein B OT - Chylomicrons OT - Dipeptidyl peptidase-4 OT - Glucagon-like peptide-1 OT - Glucose-dependent insulinotropic polypeptide OT - Hypertriglyceridemia OT - Incretin OT - Lipids OT - Lipoproteins OT - Postprandial lipemia COIS- Declaration of competing interest All authors have no conflicts to disclose. EDAT- 2026/06/07 00:34 MHDA- 2026/07/10 12:45 CRDT- 2026/06/06 19:33 PHST- 2026/04/14 00:00 [received] PHST- 2026/05/19 00:00 [revised] PHST- 2026/06/04 00:00 [accepted] PHST- 2026/07/10 12:45 [medline] PHST- 2026/06/07 00:34 [pubmed] PHST- 2026/06/06 19:33 [entrez] AID - S0163-7258(26)00084-7 [pii] AID - 10.1016/j.pharmthera.2026.109057 [doi] PST - ppublish SO - Pharmacol Ther. 2026 Sep;285:109057. doi: 10.1016/j.pharmthera.2026.109057. Epub 2026 Jun 6. PMID- 42250575 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20261002 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10546 DP - 2026 Jun 13 TI - Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. PG - 2402-2413 LID - S0140-6736(26)00967-0 [pii] LID - 10.1016/S0140-6736(26)00967-0 [doi] AB - BACKGROUND: Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone. METHODS: In this 40-week, phase 3, randomised, double-blind, placebo-controlled trial at 48 sites in the USA, Mexico, and India, we recruited adults (aged >/=18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA(1c)) between 7.0% and 9.5% (53-80 mmol/mol), and BMI of at least 23 kg/m(2). Participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection. The primary endpoint was the change in HbA(1c) concentration from baseline to week 40. A key secondary endpoint was the percentage change in bodyweight from baseline to week 40. This trial is registered with ClinicalTrials.gov, NCT06354660, and is completed. FINDINGS: Between April 10, 2024, and April 21, 2025, 930 participants were screened and 537 (296 [55%] female and 241 [45%] male) were randomly assigned: 134 to retatrutide 4 mg, 133 to retatrutide 9 mg, 136 to retatrutide 12 mg, and 134 to placebo. Baseline mean age was 48.8 years (SD 12.1), mean HbA(1c) concentration was 7.9% (SD 1.1), mean duration of diabetes was 2.5 years (SD 4.4), and mean BMI was 35.8 kg/m(2) (SD 7.0). 490 (91%) participants completed the treatment period on study drug and 504 (94%) completed the study. For the treatment regimen estimand, the mean change from baseline in HbA(1c) concentration was -1.69% (SE 0.11) with retatrutide 4 mg, -1.86% (0.10) with 9 mg, and -1.94% (0.08) with 12 mg, versus -0.81% (0.12) with placebo, resulting in estimated treatment differences versus placebo of -0.88% (95% CI -1.18 to -0.59) with retatrutide 4 mg, -1.04% (-1.32 to -0.76) with 9 mg, and -1.12% (-1.39 to -0.85) with 12 mg (all p<0.0001). The mean percentage change from baseline in bodyweight was -11.5% (SE 0.7) with retatrutide 4 mg, -13.9% (0.8) with 9 mg, and -15.3% (0.8) with 12 mg, versus -2.6% (0.5) with placebo. The most frequent adverse events with retatrutide were generally mild to moderate gastrointestinal events, which subsided over time. Study intervention discontinuations due to adverse events were 2-5% with retatrutide and 0% with placebo. No severe hypoglycaemia was reported. Two deaths occurred during the study, both in the retatrutide 4 mg group and unrelated to the study drug. INTERPRETATION: Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes. FUNDING: Eli Lilly and Company. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Bajaj, Harpreet S AU - Bajaj HS AD - LMC Diabetes and Endocrinology, Brampton, ON, Canada. Electronic address: harpreet.bajaj@lmc.ca. FAU - Welch, Michelle AU - Welch M AD - Consano Clinical Research, San Antonio, TX, USA. FAU - Shah, Parag AU - Shah P AD - Gujarat Endocrine Centre, Ahmedabad, India. FAU - Luna, Eduardo AU - Luna E AD - Texas Valley Clinical Research, Weslaco, TX, USA. FAU - Jaouimaa, Fatima-Zahra AU - Jaouimaa FZ AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Liu, Bing AU - Liu B AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Liu, Rong AU - Liu R AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Patel, Hiren AU - Patel H AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Bartee, Amy AU - Bartee A AD - Eli Lilly and Company, Indianapolis, IN, USA. LA - eng SI - ClinicalTrials.gov/NCT06354660 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260606 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (retatrutide) RN - 0 (Fatty Acids) RN - 0 (Peptides) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/therapy/blood MH - Double-Blind Method MH - Exercise MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Glycemic Control MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - Fatty Acids MH - Peptides COIS- Declaration of interests HSB reports research support (paid to institution) from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Ionis, Novartis, Novo Nordisk, Pfizer, Roche, and Vertex; and serving as a speaker and on advisory panels for Eli Lilly, Novo Nordisk, and Roche. MW reports payment as a member of a speakers bureau from, support for attending meetings or travel from, and stocks in Eli Lilly and Company. EL reports consulting and speaker fees from Abbott, Eli Lilly, Dexcom, CeQur, Insulet, Madrigal Pharmaceuticals, and Mannkind. PS reports speaker fees from Eli Lilly and Company. F-ZJ, BL, RL, YC, HP, and AB are employees of and shareholders in Eli Lilly and Company. EDAT- 2026/06/07 00:35 MHDA- 2026/06/13 00:40 CRDT- 2026/06/06 18:53 PHST- 2026/04/17 00:00 [received] PHST- 2026/05/01 00:00 [revised] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/06/13 00:40 [medline] PHST- 2026/06/07 00:35 [pubmed] PHST- 2026/06/06 18:53 [entrez] AID - S0140-6736(26)00967-0 [pii] AID - 10.1016/S0140-6736(26)00967-0 [doi] PST - ppublish SO - Lancet. 2026 Jun 13;407(10546):2402-2413. doi: 10.1016/S0140-6736(26)00967-0. Epub 2026 Jun 6. PMID- 42247589 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260813 IS - 2050-6414 (Electronic) IS - 2050-6406 (Print) IS - 2050-6406 (Linking) VI - 14 IP - 5 DP - 2026 Jun TI - Cohort Study: Risk of Gallstones and Biliary Complications With Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes. PG - e70238 LID - 10.1002/ueg2.70238 [doi] LID - e70238 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) because of their benefits in glycemic control, weight reduction, and cardiovascular outcomes. This study evaluated the risk of gallbladder disease among diabetic patients treated with GLP-1 RAs. METHODS: A retrospective cohort analysis was performed using the TriNetX research network. Adults >/= 18 years with T2DM who received GLP-1 RAs were identified and compared with matched controls. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes included cholelithiasis/choledocholithiasis, cholecystitis, pancreatitis, endoscopic retrograde cholangiopancreatography (ERCP), and cholecystectomy. Subgroup analyses were performed according to GLP-1 RA agents. RESULTS: A total of 156,376 patients were included; 43,077 patients were in the GLP-1 RA cohort and 113,299 patients were in the control group. After matching, 39,140 patients remained in each group. At two years, patients with GLP-1 RA use had higher rates of cholelithiasis/choledocholithiasis (aOR 1.44, 95% CI 1.24-1.65), whereas rates of cholecystectomy were non-significant. By three years, GLP-1 RA use remained associated with higher rates of cholelithiasis/choledocholithiasis (aOR 1.43, 95% CI 1.24-1.63), cholecystitis (aOR 1.45, 95% CI 1.14-1.83), and cholecystectomy (aOR 1.54, 95% CI 1.17-2.02). There were no significant differences in the rates of pancreatitis or ERCP. Semaglutide and dulaglutide demonstrated higher cholelithiasis, whereas liraglutide and exenatide were not associated with a significant increase. CONCLUSION: GLP-1 RAs use in patients with T2DM was associated with modestly higher rates of cholelithiasis/choledocholithiasis, cholecystitis, and cholecystectomy, whereas there were no significant differences in rates of pancreatitis or ERCP. CI - (c) 2026 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. FAU - Eldesouki, Mohamed H AU - Eldesouki MH AUID- ORCID: 0009-0009-6662-5883 AD - Department of Internal Medicine, New York Medical College at Saint Michael's Medical Center, Newark, New Jersey, USA. FAU - Alkasabrah, Omar AU - Alkasabrah O AD - Department of Internal Medicine, New York Medical College/Landmark Medical Center, Woonsocket, Rhode Island, USA. FAU - Kloub, Mohammed AU - Kloub M AD - Department of Internal Medicine, New York Medical College at Saint Michael's Medical Center, Newark, New Jersey, USA. FAU - Abosheaishaa, Hazem AU - Abosheaishaa H AUID- ORCID: 0000-0002-5581-8702 AD - Division of Gastroenterology and Hepatology, Brooklyn Health Center, Brooklyn, New York, USA. FAU - Elfert, Khaled AU - Elfert K AUID- ORCID: 0000-0001-5554-6252 AD - Division of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, West Virginia, USA. FAU - Sharma, Arpit AU - Sharma A AUID- ORCID: 0009-0008-9926-9099 AD - Faculty of Medicine, Monash University/Monash Health, Victoria, Melbourne, Australia. FAU - Andrawes, Sherif AU - Andrawes S AD - Division of Gastroenterology and Hepatology, Staten Island University Hospital-Northwell Health, Staten Island, New York, USA. FAU - Duong, Nikki AU - Duong N AD - Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA. LA - eng PT - Journal Article PL - England TA - United European Gastroenterol J JT - United European gastroenterology journal JID - 101606807 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cholangiopancreatography, Endoscopic Retrograde/statistics & numerical data MH - Cholecystectomy/statistics & numerical data MH - Cholecystitis/chemically induced/epidemiology MH - Choledocholithiasis/chemically induced/epidemiology/surgery MH - Cholelithiasis/chemically induced/epidemiology/surgery MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Exenatide/adverse effects MH - *Gallstones/chemically induced/epidemiology/etiology/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Immunoglobulin Fc Fragments/adverse effects MH - Pancreatitis/chemically induced/epidemiology MH - Retrospective Studies MH - Semaglutide/adverse effects MH - Recombinant Fusion Proteins/adverse effects PMC - PMC13240991 OTO - NOTNLM OT - biliary complications OT - choledocholithiasis OT - cholelithiasis OT - gallbladder disease OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/06/05 18:36 MHDA- 2026/06/11 05:43 PMCR- 2026/06/05 CRDT- 2026/06/05 14:52 PHST- 2026/04/11 00:00 [revised] PHST- 2026/01/14 00:00 [received] PHST- 2026/05/23 00:00 [accepted] PHST- 2026/06/11 05:43 [medline] PHST- 2026/06/05 18:36 [pubmed] PHST- 2026/06/05 14:52 [entrez] PHST- 2026/06/05 00:00 [pmc-release] AID - UEG270238 [pii] AID - 10.1002/ueg2.70238 [doi] PST - ppublish SO - United European Gastroenterol J. 2026 Jun;14(5):e70238. doi: 10.1002/ueg2.70238. PMID- 42247231 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260828 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 6 DP - 2026 Jun 1 TI - Patient Experiences With GLP-1 Receptor Agonists. PG - e2616951 LID - 10.1001/jamanetworkopen.2026.16951 [doi] LID - e2616951 AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are transformational therapies in the treatment of obesity; yet discontinuation rates are high, and patients experience rapid weight regain after stopping treatment. Few scientific publications have reported patients' experiences of taking GLP-1 RAs in a variety of health contexts outside its use as treatment for type 2 diabetes. OBJECTIVE: To provide insight into the lived experiences of patients taking GLP-1 RAs to inform optimal long-term weight management treatment. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study used inductive thematic analysis of semistructured video interviews conducted between July 22 and September 10, 2025, with participants from 15 US states. Participants included adults who were taking or had previously taken GLP-1 RAs for any treatment indication, recruited through ResearchMatch and snowball sampling. MAIN OUTCOMES AND MEASURES: Themes identified through inductive thematic analysis. RESULTS: Of 30 participants, 10 self-identified as men, 1 as nonbinary, and 19 as women; their mean (SD) age was 54.0 (8.8) years. A total of 23 participants were using a GLP-1 RA at time of interview, and 7 participants had stopped GLP-1 RA use. Eight key themes were extracted and categorized into 2 overarching domains. The first domain was patient-reported benefits and trade-offs. It comprised the following themes: (1) reduction in food noise, psychological hunger, or appetite; (2) GLP-1 RAs are not a standalone weight loss solution; (3) wide spectrum of adverse effects experienced; and (4) patients prepared to withstand substantial adverse effects and logistical challenges to achieve weight loss. The second domain was social, clinical, and structural context. It comprised the following themes: (5) perceived stigma associated with taking GLP-1 RAs, influenced by primary indication for prescription; (6) information provision and clinical support are essential but highly variable; (7) access challenges and cost can be prohibitive; and (8) value of shared experiences. CONCLUSIONS AND RELEVANCE: In this qualitative study of patient experiences with GLP-1 receptor agonists, participants described GLP-1 RA therapy functioning as a facilitator rather than a replacement for lifestyle change, emphasizing the need for behavioral interventions alongside pharmacotherapy to sustain treatment benefits. Quality of care was highly variable; thus, standardized guidelines for patient education and clinical support could improve expectation management around likely adverse effects and long-term management. FAU - de Vere Hunt, Isabella AU - de Vere Hunt I AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom. AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. FAU - Ramirez-Posada, Mariana AU - Ramirez-Posada M AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Department of Dermatology, School of Medicine, Stanford University, Stanford, California. FAU - Babu, Christopher Sam AU - Babu CS AD - Stanford Internal Medicine, Department of Medicine, Stanford University, Stanford, California. FAU - Brown-Johnson, Cati AU - Brown-Johnson C AD - Evaluation Sciences Unit, Division of Primary Care and Population Health, Department of Medicine, School of Medicine, Stanford University, Palo Alto, California. FAU - Linos, Eleni AU - Linos E AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Department of Dermatology, School of Medicine, Stanford University, Stanford, California. FAU - Rodriguez, Fatima AU - Rodriguez F AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Division of Cardiovascular Medicine and the Cardiovascular Institute, Department of Medicine, Stanford University, Stanford, California. LA - eng GR - R01 HL168188/HL/NHLBI NIH HHS/United States GR - UM1 TR004921/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20260601 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/psychology MH - Qualitative Research MH - Semaglutide MH - United States PMC - PMC13241945 COIS- Conflict of Interest Disclosures: Dr Rodriguez reported receiving grants from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute and from the Doris Duke Foundation during the conduct of the study; and receiving personal fees from Novartis, Novo Nordisk, Esperion Therapeutics, Movano Health, Kento Health, Edwards Lifesciences, Arrowhead Pharmaceuticals, HeartFlow, iRhythm, Amgen, and Cleerly Health outside the submitted work. No other disclosures were reported. EDAT- 2026/06/05 12:42 MHDA- 2026/06/10 06:52 PMCR- 2026/06/05 CRDT- 2026/06/05 11:33 PHST- 2026/06/10 06:52 [medline] PHST- 2026/06/05 12:42 [pubmed] PHST- 2026/06/05 11:33 [entrez] PHST- 2026/06/05 00:00 [pmc-release] AID - 2849943 [pii] AID - zoi260477 [pii] AID - 10.1001/jamanetworkopen.2026.16951 [doi] PST - epublish SO - JAMA Netw Open. 2026 Jun 1;9(6):e2616951. doi: 10.1001/jamanetworkopen.2026.16951. PMID- 42244474 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Rates of, Reasons for, and Reactions to Discontinuation of GLP-1 Receptor Agonists: A Narrative Review. PG - 6533-6549 LID - 10.1111/dom.70913 [doi] AB - GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual framework. Patient-related factors, especially related to patient behaviors, are understudied in relation to GLP-1RA discontinuation. Patients treated for type 2 diabetes mellitus or weight management with GLP-1RAs often discontinue the medication, but this is often nonpermanent. Improving adherence to and persistence on GLP-1RAs will require nuanced attention to care trajectories as well as an integrated understanding of GLP-1RA tolerability, expectations, and the understudied role of patient behaviors and the healthcare system. To clarify relevant mechanisms and guide targeted intervention for highest-risk individuals, further study should standardize definitions of persistence and discontinuation and implement patient-centered qualitative work, especially related to health behaviors. CI - Published 2026. This article is a U.S. Government work and is in the public domain in the USA. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Heisey, Henry D AU - Heisey HD AUID- ORCID: 0000-0001-8136-2625 AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - South Central Mental Illness Research, Education and Clinical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. FAU - Gregg, L Parker AU - Gregg LP AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, Texas, USA. FAU - Verrico, Christopher D AU - Verrico CD AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. FAU - Villareal, Dennis T AU - Villareal DT AD - Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, Texas, USA. FAU - Fletcher, Terri L AU - Fletcher TL AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - South Central Mental Illness Research, Education and Clinical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. LA - eng GR - Houston VA Center/Houston VA Center/ PT - Journal Article PT - Review DEP - 20260605 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Medication Adherence/psychology MH - Treatment Interruption MH - Semaglutide MH - Tirzepatide PMC - PMC13341420 OTO - NOTNLM OT - GLP-1 OT - adherence OT - discontinuation OT - framework OT - incretin OT - orforglipron OT - persistence OT - semaglutide OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/05 06:35 MHDA- 2026/07/08 18:51 PMCR- 2026/07/08 CRDT- 2026/06/05 04:13 PHST- 2026/05/15 00:00 [revised] PHST- 2026/03/13 00:00 [received] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/06/05 06:35 [pubmed] PHST- 2026/06/05 04:13 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70913 [pii] AID - 10.1111/dom.70913 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6533-6549. doi: 10.1111/dom.70913. Epub 2026 Jun 5. PMID- 42244313 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260813 IS - 1672-7347 (Print) IS - 1672-7347 (Linking) VI - 51 IP - 2 DP - 2026 Feb 28 TI - [Semaglutide-induced acute-on-chronic liver failure: A case report and literature review]. PG - 213-220 LID - 1672-7347(2026)02-0213-08 [pii] LID - 10.11817/j.issn.1672-7347.2026.250330 [doi] AB - Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA), primarily used for the treatment of type 2 diabetes mellitus and obesity. Common adverse drug reactions (ADRs) include nausea, vomiting, diarrhea, abdominal pain, and constipation, whereas liver function-related ADRs are relatively rare. We report a rare and severe case of semaglutide-induced acute-on-chronic liver failure (ACLF) in a 47-year-old male patient who was successfully treated. The patient was admitted to the Department of Infectious Disease at the Second Xiangya Hospital of Central South University on December 1, 2023. He had a history of chronic hepatitis B and had discontinued antiviral therapy for more than two years without medical supervision. Due to weight loss requirements, he initiated subcutaneous semaglutide therapy. Approximately three months after treatment initiation, he developed severe liver dysfunction, which rapidly progressed to profound jaundice, coagulopathy, and hepatic encephalopathy. Drug-induced liver injury (DILI) was considered the primary precipitating factor of liver failure, and the final diagnosis was ACLF. Following confirmation of the diagnosis, semaglutide was discontinued, and comprehensive management, including hepatoprotective therapy, artificial liver support, plasma exchange, and liver transplantation, was implemented. The patient's clinical symptoms and liver function parameters improved significantly. This report describes the successful management of semaglutide-induced ACLF and reviews the relevant literature. For individuals with underlying chronic liver disease (e.g., chronic viral hepatitis), thorough baseline liver assessment should be performed prior to initiating semaglutide or similar agents. Close monitoring during treatment is essential to identify potential severe drug-induced liver injury at an early stage. FAU - Fu, Rao AU - Fu R AD - Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011. furao1030500@outlook.com. FAU - Wu, Huizhi AU - Wu H AD - Department of Pharmacy, Liuyang People's Hospital, Liuyang 410300, China. WuHuizhi0903@163.com. FAU - Huang, Haiying AU - Huang H AD - Department of Pharmacy, Liuyang People's Hospital, Liuyang 410300, China. FAU - Sun, Bao AU - Sun B AD - Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011. scy_csu2016@csu.edu.cn. LA - chi GR - B202313016776/the Scientific Research Project of Hunan Provincial Health Commission/ GR - CPA-Z05-ZC-2024-003/the Special Foundation for Young Scientists of Special Committee of the Hospital Pharmacy, Chinese Pharmaceutical Association/ PT - Case Reports PT - English Abstract PT - Journal Article PT - Review PL - China TA - Zhong Nan Da Xue Xue Bao Yi Xue Ban JT - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JID - 101230586 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Acute-On-Chronic Liver Failure/chemically induced/diagnosis/therapy MH - *Chemical and Drug Induced Liver Injury/diagnosis/etiology/therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Hepatitis B, Chronic/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - *Semaglutide/adverse effects PMC - PMC13229664 OTO - NOTNLM OT - acute-on-chronic liver failure OT - adverse drug reaction OT - drug-induced liver injury OT - glucagon-like peptide-1 receptor agonist OT - semaglutide COIS- 作者声称无任何利益冲突。 EDAT- 2026/06/05 06:36 MHDA- 2026/06/06 00:34 PMCR- 2026/02/28 CRDT- 2026/06/05 02:43 PHST- 2026/06/06 00:34 [medline] PHST- 2026/06/05 06:36 [pubmed] PHST- 2026/06/05 02:43 [entrez] PHST- 2026/02/28 00:00 [pmc-release] AID - 1672-7347(2026)02-0213-08 [pii] AID - 10.11817/j.issn.1672-7347.2026.250330 [doi] PST - ppublish SO - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2026 Feb 28;51(2):213-220. doi: 10.11817/j.issn.1672-7347.2026.250330. PMID- 42244136 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Based Therapies and the Risk of Severe Gastrointestinal Motility Adverse Events: A Cohort Study. PG - 7494-7504 LID - 10.1111/dom.70963 [doi] AB - AIMS: Evidence showing the association between glucagon-like 1 (GLP-1) based therapies and severe gastrointestinal motility events is limited and possible treatment effect heterogeneity by demographic and clinical characteristics is unknown. We aimed to compare rates of severe motility-related gastrointestinal adverse events between initiators of GLP-1 based therapies versus sodium-glucose co-transporter 2 inhibitors (SGLT-2i). MATERIALS AND METHODS: This new-user active-comparative cohort study used two de-identified US commercial healthcare databases to identify adults with type-2 diabetes without a prior history of major gastrointestinal conditions who initiated GLP-1 based therapies (GLP-1 receptor agonists or tirzepatide) or SGLT-2i. The main outcome was a composite of severe constipation, gastroparesis, and gastrointestinal obstruction. We estimated incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) after propensity score matching. RESULTS: Among 313 342 matched pairs of GLP-1 based therapies and SGLT-2i initiators (mean age 60 years; 45% female), followed on treatment for a median of 5.2 months, incidence rates of the composite outcome were 1.02 among GLP-1 based therapies versus 0.75 among SGLT-2i initiators per 100 person-years. The risk was higher among GLP-1 based therapies versus SGLT-2i initiators (rate difference 0.27 per 100 person-years; HR 1.37, 95% CI 1.30, 1.45) for the composite event and each individual component. This relative increased risk was consistent across subgroups stratified by GLP-1 based therapies agent, age, sex, BMI, frailty level, diabetes severity, or opioid use. CONCLUSIONS: The absolute risk of motility-related gastrointestinal adverse events was 1% or less but was higher among initiators of GLP-1 based therapies compared to SGLT-2i. These findings can inform the risk benefit assessment by clinicians before initiating these treatments. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Alkabbani, Wajd AU - Alkabbani W AUID- ORCID: 0000-0002-7030-0442 AD - School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada. AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Crisafulli, Salvatore AU - Crisafulli S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Diagnostics and Public Health, University of Verona, Verona, Italy. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, USA. FAU - Tavakkoli, Ali AU - Tavakkoli A AUID- ORCID: 0000-0002-7430-1848 AD - Division of General and GI Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Bykov, Katsiaryna AU - Bykov K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - Division of General Internal Medicine & Health Services Research, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. LA - eng GR - DB-2020C2-20 326/Patient-Centered Outcomes Research Institute (PCORI)/ GR - 5U01FD007213/FD/FDA HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - R01DK135706/DK/NIDDK NIH HHS/United States GR - K01AG068365/AG/NIA NIH HHS/United States GR - 5U01FD007213/FD/FDA HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - R01DK135706/DK/NIDDK NIH HHS/United States GR - K01AG068365/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260604 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Gastrointestinal Motility/drug effects MH - Cohort Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Tirzepatide MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Constipation/chemically induced/epidemiology MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Incidence MH - *Gastroparesis/chemically induced/epidemiology MH - Incretins/adverse effects MH - United States/epidemiology OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - cohort study OT - pharmaco-epidemiology OT - real-world evidence EDAT- 2026/06/05 06:36 MHDA- 2026/07/08 12:55 CRDT- 2026/06/05 01:02 PHST- 2026/05/25 00:00 [revised] PHST- 2026/02/23 00:00 [received] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/07/08 12:55 [medline] PHST- 2026/06/05 06:36 [pubmed] PHST- 2026/06/05 01:02 [entrez] AID - 10.1111/dom.70963 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7494-7504. doi: 10.1111/dom.70963. Epub 2026 Jun 4. PMID- 42243292 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20261008 IS - 1348-4214 (Electronic) IS - 0916-9636 (Linking) VI - 49 IP - 8 DP - 2026 Aug TI - Influence of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on the management of blood pressure in Japanese patients with diabetes. PG - 2352-2365 LID - 10.1038/s41440-026-02695-5 [doi] AB - Combination therapy with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) is increasingly used to prevent cardiovascular events. Our previous study demonstrated the renal benefits of this combination therapy. Both drug classes exert pleiotropic effects on metabolic factors, such as obesity and hypertension; however, the impact of this combination therapy on blood pressure (BP) has not been fully evaluated. This post hoc analysis aimed to assess the effects of SGLT2i-GLP-1RA combination therapy on BP control in patients with type 2 diabetes (T2D). Among the 643 T2D patients enrolled in the RECAP study, 431 with baseline hypertension were analyzed (GLP-1RA-preceding group, n = 207; SGLT2i-preceding group, n = 224). The achievement rate of the target office BP ( < 130/80 mmHg) after the initiation of combination therapy was evaluated using multiple imputations. Changes in office and home BP were analyzed using generalized linear mixed models. The influence of preceding treatment was assessed using propensity score-based inverse probability weighting (PS-IPW). The achievement rate of the target BP increased from 25.4% after treatment to 33.3% after combination therapy (p = 0.003). Office BP decreased from 141.8/82.4 mmHg at baseline to 135.2/78.5 mmHg after treatment addition and 131.7/79.4 mmHg after combination therapy (all p < 0.001). The home systolic BP also significantly decreased (p = 0.03). PS-IPW analysis showed no significant differences in BP outcomes or target achievement rates according to the preceding treatment. Collectively, SGLT2i-GLP-1RA combination therapy significantly improved BP control, independent of the order in which the agents were initiated. CI - (c) 2026. The Author(s), under exclusive licence to The Japanese Society of Hypertension. FAU - Matsushita, Takaya AU - Matsushita T AD - Department of Diabetology, Endocrinology and Metabolism, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan. FAU - Wada, Yukihiro AU - Wada Y AD - Department of Nephrology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. FAU - Saburi, Masuo AU - Saburi M AD - Department of Diabetology, Endocrinology and Metabolism, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan. FAU - Kobayashi, Kazuo AU - Kobayashi K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. k-taishi@xc4.so-net.ne.jp. FAU - Tsukamoto, Shunichiro AU - Tsukamoto S AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kawanami, Daiji AU - Kawanami D AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Suzuki, Daisuke AU - Suzuki D AD - Suzuki Diabetes Clinic, Atsugi, Japan. FAU - Tsuriya, Daisuke AU - Tsuriya D AD - Division of Endocrinology and Metabolism, 2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Wakui, Hiromichi AU - Wakui H AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kanasaki, Keizo AU - Kanasaki K AD - Department of Internal Medicine 1, Endocrinology and Metabolism, Shimane University Faculty of Medicine, Izumo, Japan. AD - The Center for Integrated Kidney Research and Advance, Shimane University Faculty of Medicine, Izumo, Japan. FAU - Muta, Yoshimi AU - Muta Y AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Tamura, Kouichi AU - Tamura K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Takeuchi, Yasuo AU - Takeuchi Y AD - Department of Nephrology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. FAU - Toyoda, Masao AU - Toyoda M AD - Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20260604 PL - England TA - Hypertens Res JT - Hypertension research : official journal of the Japanese Society of Hypertension JID - 9307690 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Blood Pressure/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypertension/drug therapy/complications MH - *Hypoglycemic Agents/administration & dosage MH - Japan MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonist OT - implemental hypertension OT - morning hypertension OT - sodium-glucose cotransporter 2 inhibitor OT - target blood pressure COIS- Compliance with ethical standards. Conflict of interest: KK has received lecture fees from Otsuka Pharmaceutical and Novartis. Hiromichi Wakui has received research supports from AstraZeneca, Otsuka Pharmaceutical, and Kaneka Corporation, and honoraria from AstraZeneca, Otsuka Pharmaceutical, Kaneka Corporation, Kyowa Kirin, Sanwa Kagaku, Chugai Pharma, Kowa, Otsuka Pharmaceutical, Novartes, Mitsubishi-Tanabe Pharma, Bayer, and Daiichi-Sankyo Pharma. MT received lecture fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sumitomo, and Mitsubishi Tanabe and received subsidies from Super Light Water, TAKAGI, Roche DC, and LifeScan. Kouichi Tamura has received honoraria/lecture fee from AstraZeneca, Novartes, Bayer, Otsuka Pharmaceutical, Boehringer Ingelheim, Fuji Pharma, Kyowa Kirin, Ono Pharmaceutical, Sanwa Kagaku, Mochida Pharmaceutical, Kowa, Eli Lilly, Novo Nordisk, commissioned clinical trials, contract research and joint research funding: AstraZeneca, Bayer, Novartis, Chinook, Otsuka Medical Devices, Novo Nordisk, Terumo, Variatris, and Kowa, and, Scholarship donations: Otsuka Pharmaceutical, Bayer, Mochida Pharmaceutical, and Boehringer Ingelheim. Daisuke Tsuriya received lecture fees from Eli Lilly, Novo Nordisk Pharma, and Tanabe Pharma Corporation. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Eli Lilly Japan KK, Daiichi Sankyo Co., Ltd., and Sumitomo Pharma Co., Ltd., and grants from Nipro Corporation, Sumitomo Pharma Co., Ltd., and Tanabe Pharma Corporation. Keizo Kanasaki were supported by grants from the Japan Society for the Promotion of Science to Keizo Kanasaki (25K11544). KK collaborated with Boehringer Ingelheim, Kowa, Bayer, and Mitsubishi. KK received lecture honoraria from Sumitomo Pharma, Astra Zeneca, Otsuka, Taisho Pharma, Tanabe-Mitsubishi, Eli Lilly, Boehringer-Ingelheim, Novo Nordisk, Bayer, Novartis, and Kowa. EDAT- 2026/06/05 00:35 MHDA- 2026/08/05 06:41 CRDT- 2026/06/04 23:27 PHST- 2026/02/13 00:00 [received] PHST- 2026/05/24 00:00 [accepted] PHST- 2026/05/12 00:00 [revised] PHST- 2026/08/05 06:41 [medline] PHST- 2026/06/05 00:35 [pubmed] PHST- 2026/06/04 23:27 [entrez] AID - 10.1038/s41440-026-02695-5 [pii] AID - 10.1038/s41440-026-02695-5 [doi] PST - ppublish SO - Hypertens Res. 2026 Aug;49(8):2352-2365. doi: 10.1038/s41440-026-02695-5. Epub 2026 Jun 4. PMID- 42242293 OWN - NLM STAT- MEDLINE DCOM- 20260905 LR - 20260916 IS - 1715-3360 (Electronic) IS - 0008-4182 (Linking) VI - 61 IP - 5 DP - 2026 Oct TI - Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis. PG - 1262-1271 LID - S0008-4182(26)00206-1 [pii] LID - 10.1016/j.jcjo.2026.05.004 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I(2) = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Al-Burak, Salem Abu AU - Al-Burak SA AD - Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON. FAU - Voznyy, Vitaliy AU - Voznyy V AD - Temerty Faculty of Medicine, University of Toronto, Toronto, ON. FAU - Elganga, Mouad AU - Elganga M AD - Temerty Faculty of Medicine, University of Toronto, Toronto, ON. FAU - Zajner, Chris AU - Zajner C AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London, ON. FAU - Juncal, Verena AU - Juncal V AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London, ON; Department of Ophthalmology and Visual Sciences, Western University, London, ON. FAU - Sheidow, Thomas G AU - Sheidow TG AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London, ON; Department of Ophthalmology and Visual Sciences, Western University, London, ON. FAU - Malvankar-Mehta, Monali S AU - Malvankar-Mehta MS AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London, ON; Department of Ophthalmology and Visual Sciences, Western University, London, ON; Department of Epidemiology and Biostatistics, Western University, London, ON. Electronic address: monali.malvankar@schulich.uwo.ca. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260611 PL - England TA - Can J Ophthalmol JT - Canadian journal of ophthalmology. Journal canadien d'ophtalmologie JID - 0045312 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Macular Edema/chemically induced/diagnosis/epidemiology/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Retinopathy/drug therapy/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy COIS- Footnotes and Disclosure The authors declare that they have no proprietary or commercial interest that could have appeared to influence the work reported in this paper. All data generated or analyzed during this study are included in this published article and its supplementary materials. No additional datasets were generated. EDAT- 2026/06/05 00:34 MHDA- 2026/09/06 01:18 CRDT- 2026/06/04 19:21 PHST- 2026/02/09 00:00 [received] PHST- 2026/03/26 00:00 [revised] PHST- 2026/05/15 00:00 [accepted] PHST- 2026/09/06 01:18 [medline] PHST- 2026/06/05 00:34 [pubmed] PHST- 2026/06/04 19:21 [entrez] AID - S0008-4182(26)00206-1 [pii] AID - 10.1016/j.jcjo.2026.05.004 [doi] PST - ppublish SO - Can J Ophthalmol. 2026 Oct;61(5):1262-1271. doi: 10.1016/j.jcjo.2026.05.004. Epub 2026 Jun 11. PMID- 42242290 OWN - NLM STAT- MEDLINE DCOM- 20260905 LR - 20260905 IS - 1715-3360 (Electronic) IS - 0008-4182 (Linking) VI - 61 IP - 5 DP - 2026 Oct TI - Age-related macular degeneration associated with glucagon-like peptide-1 receptor agonist use: a systematic review. PG - 1253-1261 LID - S0008-4182(26)00205-X [pii] LID - 10.1016/j.jcjo.2026.05.010 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively. RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low. CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Al-Burak, Salem Abu AU - Al-Burak SA AD - Schulich School of Medicine & Dentistry, The University of Western Ontario, London ON. FAU - Suleiman, Azhar AU - Suleiman A AD - Schulich School of Medicine & Dentistry, The University of Western Ontario, London ON. FAU - Voznyy, Vitaliy AU - Voznyy V AD - Temerty Medicine, The University of Toronto, Toronto ON. FAU - Elganga, Mouad AU - Elganga M AD - Temerty Medicine, The University of Toronto, Toronto ON. FAU - Zajner, Chris AU - Zajner C AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London ON. FAU - Juncal, Verena AU - Juncal V AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London ON; Department of Ophthalmology and Visual Sciences, University of Western Ontario, London, ON. FAU - Sheidow, Thomas G AU - Sheidow TG AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London ON; Department of Ophthalmology and Visual Sciences, University of Western Ontario, London, ON. FAU - Malvankar-Mehta, Monali S AU - Malvankar-Mehta MS AD - Ivey Eye Institute, St. Joseph's Health Care Centre, London ON; Department of Ophthalmology and Visual Sciences, University of Western Ontario, London, ON; Department of Epidemiology and Biostatistics, University of Western Ontario, London ON. Electronic address: monali.malvankar@schulich.uwo.ca. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260617 PL - England TA - Can J Ophthalmol JT - Canadian journal of ophthalmology. Journal canadien d'ophtalmologie JID - 0045312 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Macular Degeneration/epidemiology/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - Diabetes Mellitus, Type 2/drug therapy COIS- Footnotes and Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article. EDAT- 2026/06/05 00:34 MHDA- 2026/09/06 01:18 CRDT- 2026/06/04 19:21 PHST- 2026/01/25 00:00 [received] PHST- 2026/03/26 00:00 [revised] PHST- 2026/05/15 00:00 [accepted] PHST- 2026/09/06 01:18 [medline] PHST- 2026/06/05 00:34 [pubmed] PHST- 2026/06/04 19:21 [entrez] AID - S0008-4182(26)00205-X [pii] AID - 10.1016/j.jcjo.2026.05.010 [doi] PST - ppublish SO - Can J Ophthalmol. 2026 Oct;61(5):1253-1261. doi: 10.1016/j.jcjo.2026.05.010. Epub 2026 Jun 17. PMID- 42237968 OWN - NLM STAT- MEDLINE DCOM- 20260607 LR - 20260813 IS - 1658-3175 (Electronic) IS - 0379-5284 (Print) IS - 0379-5284 (Linking) VI - 47 IP - 4 DP - 2026 Apr TI - Semaglutide in Metabolic Medicine: A Review on Clinical Applications and Emerging Therapeutics. PG - 615-625 LID - 10.15537/1658-3175.1060 [doi] AB - Obesity and type 2 diabetes mellitus affect over 800 million and 537 million individuals worldwide. Semaglutide, a weekly glucagon-like peptide-1 receptor agonist, has advanced treatment of pathophysiological processes linked to metabolic dysregulation. This review consolidates evidence on its mechanisms of action, clinical effectiveness across established and emerging applications, safety, and prospects for personalized therapy. Clinical studies have shown that semaglutide sustains glycemic control, promotes substantial weight loss, and provides cardiovascular and renal protection. Recent FDA clearance marks the first therapeutic alternative for metabolic dysfunction-associated steatohepatitis among the emerging applications. Pharmacogenomic insights facilitate personalized therapy; however, clinical applications remain in experimental stage. Gastrointestinal side effects are the main tolerability concern, but the risk-benefit profile underscores its increasing significance in metabolic therapy. Therapies for diabetes and obesity are cost-effective; however, global accessibility challenges persist. Future priorities include refining combination medicines, promoting precision medicine, and addressing healthcare inequities to augment population-level effects. CI - Copyright: (c) Saudi Medical Journal. FAU - Aljabri, Abdulrahman A AU - Aljabri AA AUID- ORCID: 0009-0001-3780-4964 AD - Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah, Kingdom of Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260320 PL - Saudi Arabia TA - Saudi Med J JT - Saudi medical journal JID - 7909441 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glucagon-Like Peptides/agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy MH - Precision Medicine MH - *Semaglutide/pharmacology/therapeutic use PMC - PMC13227446 OTO - NOTNLM OT - Cardiovascular protection OT - GLP-1 receptor agonist OT - Obesity OT - Precision medicine OT - Semaglutide OT - Type 2 diabetes mellitus EDAT- 2026/06/04 06:35 MHDA- 2026/06/08 00:35 PMCR- 2026/04/01 CRDT- 2026/06/04 05:24 PHST- 2025/09/05 00:00 [received] PHST- 2025/11/13 00:00 [accepted] PHST- 2026/06/08 00:35 [medline] PHST- 2026/06/04 06:35 [pubmed] PHST- 2026/06/04 05:24 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - saudimedj-47-4-615 [pii] AID - 10.15537/1658-3175.1060 [doi] PST - ppublish SO - Saudi Med J. 2026 Apr;47(4):615-625. doi: 10.15537/1658-3175.1060. Epub 2026 Mar 20. PMID- 42236281 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260922 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Heterogeneity of Treatment Effects Across Nine Glucose-Lowering Drug Classes in Type 2 Diabetes: Extension of the LEGEND-T2DM Network Study. PG - 7321-7341 LID - 10.1111/dom.70918 [doi] AB - AIMS: Understanding heterogeneous responses to glucose-lowering therapies is crucial for advancing personalized treatment and optimizing outcomes in type 2 diabetes mellitus (T2DM). While average treatment effects are established for many drug classes, responses may vary by clinical and demographic factors. Here, we evaluated whether major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across key patient characteristics. MATERIALS AND METHODS: This large-scale observational cohort study was replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with T2DM initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment, empirical calibration using negative controls, and random-effects meta-analysis were used to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across clinical and demographic subgroups. RESULTS: Nominal signals of HTE were observed in the hyperlipidemia, hypertension, obesity, and sex subgroups: Biguanides (vs. DPP-4 inhibitors) were associated with lower risk of acute myocardial infarction in hyperlipidemia and heart failure hospitalization in obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) were associated with reduced stroke risk only in non-obese patients. Sex-specific patterns included higher risk of diarrhoea with GLP-1 receptor agonists and lower risk of stroke with SGLT-2 inhibitors (both vs. DPP-4 inhibitors) in women. None of the signals demonstrated statistical significance after multiple testing correction. Several subgroups (e.g., diabetic ketoacidosis and retinopathy) did not meet diagnostic criteria for clinical reliability and were not evaluated. CONCLUSIONS: This hypothesis-generating study identified limited signals of HTE. These findings are exploratory and require cautious interpretation and validation. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Chen, Hsin Yi AU - Chen HY AUID- ORCID: 0000-0002-7907-2335 AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. AD - Johnson & Johnson, Titusville, New Jersey, USA. FAU - Anand, Tara V AU - Anand TV AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Jiang, Xinzhuo AU - Jiang X AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Davila-Garcia, David AU - Davila-Garcia D AUID- ORCID: 0000-0002-9951-2270 AD - Institute for Informatics, Data Science and Biostatistics, Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics, Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics, Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California, USA. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA. AD - VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, Utah, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. LA - eng GR - T15 LM007079/LM/NLM NIH HHS/United States GR - D24AC00345-00/Advanced Research Projects Agency for Health/ GR - R01HL169954/HL/NHLBI NIH HHS/United States GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - R01LM006910/U.S. National Library of Medicine/ GR - T15LM007079/U.S. National Library of Medicine/ PT - Journal Article PT - Observational Study DEP - 20260603 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Insulin Secretagogues) RN - 0 (Biguanides) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM UOF - medRxiv. 2026 Jan 08:2026.01.06.26343548. doi: 10.64898/2026.01.06.26343548. PMID: 41542680 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/epidemiology MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use/classification MH - Treatment Effect Heterogeneity MH - Middle Aged MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Insulin Secretagogues/therapeutic use MH - Biguanides/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Cohort Studies MH - Thiazolidinediones/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Blood Glucose/drug effects/metabolism PMC - PMC13310412 MID - NIHMS2179024 OTO - NOTNLM OT - comparative effectiveness OT - glucose-lowering drugs OT - heterogeneity of treatment effect OT - observational study OT - personalized medicine OT - real-world evidence COIS- All other authors have no competing interests. EDAT- 2026/06/04 00:41 MHDA- 2026/07/08 12:56 PMCR- 2026/06/29 CRDT- 2026/06/03 22:03 PHST- 2026/05/15 00:00 [revised] PHST- 2026/02/03 00:00 [received] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/07/08 12:56 [medline] PHST- 2026/06/04 00:41 [pubmed] PHST- 2026/06/03 22:03 [entrez] PHST- 2026/06/29 00:00 [pmc-release] AID - 10.1111/dom.70918 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7321-7341. doi: 10.1111/dom.70918. Epub 2026 Jun 3. PMID- 42233552 OWN - NLM STAT- MEDLINE DCOM- 20260606 LR - 20260609 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 87 IP - 21 DP - 2026 Jun 2 TI - Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses. PG - 2996-3012 LID - S0735-1097(26)05731-1 [pii] LID - 10.1016/j.jacc.2026.02.5125 [doi] AB - BACKGROUND: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. OBJECTIVES: The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. METHODS: Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo. Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT [Predicting Risk of cardiovascular disease EVENTs] score >/=20%). The primary outcome was >/=50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m(2), dialysis, transplantation, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome. RESULTS: At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively. Semaglutide reduced the primary outcome risk in subgroups with (119 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99). Numbers needed to treat to prevent 1 primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score >/=20% subgroups, respectively. Semaglutide also reduced risks of all-cause death with (99 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for interaction = 0.63). CONCLUSIONS: Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk. (Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153). CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington School of Medicine, Seattle, Washington, USA; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA. Electronic address: katherine.tuttle@providence.org. FAU - Bakris, George L AU - Bakris GL FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bang, Casper N AU - Bang CN AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bax, Willem A AU - Bax WA AD - Northwest Clinics, Alkmaar, the Netherlands. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Musinga, Derrick AU - Musinga D AD - Novo Nordisk A/S, Soborg, Denmark; Excelya Germany GmbH, Mannheim, Germany. FAU - Cherney, David Z I AU - Cherney DZI AD - University of Toronto, Toronto, Ontario, Canada. FAU - Chernin, Gil AU - Chernin G AD - Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Lim, Soo Kun AU - Lim SK AD - University of Malaya, Kuala Lumpur, Malaysia. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany; University Hospital Erlangen, Friedrich-Alexander University, Erlangen, Germany. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Ridker, Paul M AU - Ridker PM AD - Center for Cardiovascular Disease Prevention and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Schmieder, Roland AU - Schmieder R AD - University Hospital Erlangen, Friedrich-Alexander University, Erlangen, Germany. FAU - Shamkhalova, Minara S AU - Shamkhalova MS AD - Endocrinology Research Centre, Moscow, Russia. FAU - Sreenivasamurthy, L AU - Sreenivasamurthy L AD - Lifecare Hospital and Research Centre, Bangalore, India. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cardiovascular Diseases/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Renal Insufficiency, Chronic/drug therapy/mortality/complications/physiopathology MH - *Semaglutide/therapeutic use MH - Survival Rate/trends OTO - NOTNLM OT - atherosclerotic cardiovascular disease OT - cardiovascular risk OT - glomerular filtration rate OT - glucagon-like peptide-1 OT - heart failure OT - mortality COIS- Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Tuttle was supported by National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, as well as by Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, Otsuka, Doris Duke Charitable Foundation, Benaroya Research Institute, and Breakthrough T1D (formerly the Juvenile Diabetes Research Foundation); has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bayer, ProKidney, Otsuka, Alnylam, Roche, and GlaxoSmithKline; has received speaker fees from Novo Nordisk, Bayer, Boehringer Ingelheim, Travere, and AstraZeneca; has served as Chair of data safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Disease, and George Clinical Institute; has served on the data safety monitoring board for AstraZeneca; has served as Chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology and Chair for Kidney Week 2025 Program Committee, both for the American Society of Nephrology; and has served on the American Heart Association/American College of Cardiology Cardiovascular-Kidney-Metabolic Guideline Committee. Dr Bakris served as a consultant for Novo Nordisk, Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals LP, and Bayer Corporation; has received research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; has received research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; has served as a consultant for and received personal fees from Alnylam, Merck, and Relypsa; was an editor of the American Journal of Nephrology, Nephrology, and Hypertension; was a section editor of UpToDate; and was an associate editor of Diabetes Care and Hypertension Research. Drs Baeres, Bang, and Belmar are employees of and shareholders in Novo Nordisk. Dr Bax has participated in trials for Amgen, Eli Lilly, Novartis, and Novo Nordisk; has received consultancy fees from Amgen, Novo Nordisk, and Sanofi; and has served as a lecturer for AstraZeneca and Eli Lilly. Dr Musinga is an employee of Excelya; and has served as a consultant for Novo Nordisk. Dr Cherney has received honoraria from AbbVie, Altimmune, Amgen, AstraZeneca, Bayer, BioBridge, Boehringer Ingelheim-Lilly, Bristol Myers Squibb, CSL Behring, GlaxoSmithKline, Gilead, Inversago, Janssen, Lexicon, Maze, Merck, Mitsubishi-Tanabe, Novartis, Novo Nordisk, Otsuka, Prometic, Sanofi, Vantage, and Youngene; and has received operational funding for clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, CSL Behring, Janssen, Lexicon, Merck, Novo Nordisk, and Sanofi. Dr Chernin has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, and Sanofi. Dr Lim has received institutional research grant support from AstraZeneca, Boehringer Ingelheim, and Roche; and during the past 3 years has served as a consultant for Astellas, AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, DKSH, DuoPharma, Fresenius Kabi, Menairini, MSD, Novartis, Novo Nordisk, Roche, and Sanofi. Dr Mann has received grants from Novo Nordisk; has received consulting fees from Bayer and Novo Nordisk; has received honoraria from AstraZeneca, Bayer, Cytel, ICON, IQVIA, Novartis, Novo Nordisk, Sanofi, and WCG; and has served in a leadership role in the KDIGO group. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles, or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GlaxoSmithKline, Janssen, Novartis, Novo Nordisk, Otsuka, Travere, Tricida, and UpToDate; and has served as a board director for George Clinical, St Vincent's Health Australia, and several independent medical research institutes. Dr Pratley has received speaker fees from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Eli Lilly, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd, Intas Pharmaceuticals, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and has received research grants from Biomea Fusion, Carmot Therapeutics, Dompe, Eli Lilly, Endogenex, Fractyl, Novo Nordisk, and Sanofi, all directed to his institution. Dr Ridker has received institutional research grant support from Amarin, Esperion, Kowa, the National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, and Pfizer; during the past 3 years has served as a consultant for Agepha, Arrowhead, AstraZeneca, Boehringer Ingelheim, Cardio Therapeutics, Civi Biopharm, CSL Behring, Cytokinetics, Eli Lilly, Merck, New Amsterdam, Nodthera, Novartis, Novo Nordisk, SOCAR, and Tourmaline Bio; has minority shareholder equity positions in Angiowave, Bitteroot Bio, and Uppton; and has received compensation for services on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, and Paris FR. Dr Rossing has received consulting and/or speaking fees (to his institution) from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk, and Sanofi; and has received research grants from AstraZeneca, Bayer, and Novo Nordisk. Dr Schmeider has received grants to his institution from Amgen, Ablative Solution, Bayer, IPPmed, Medtronic, Novo Nordisk, and Recor; and has received honoraria as a speaker and advisor from Ablative Solutions, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Medtronic, Merck, Novo Nordisk, Novartis, Recor, Servier, and TAD. Dr Shamkhalova has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Sanofi, and Servier. Dr Sreenivasamurthy has received speaker/advisory board fees from Abbott India, Alkem, AstraZeneca, Cipla, Eli Lilly, Eris, IntasJB Pharma, J&J, Lupin, Mankind Pharma, Micro Labs, Servier, Sun Pharma, Torrent Pharma, and USV; and has received investigator/research grants from AstraZeneca, Bayer, Eli Lilly, Novo Nordisk, Sanofi India, Servier, Sun Pharma, and Torrent Pharma. Dr Mahaffey has received grants from the American College of Cardiology, American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Element, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Myovant, Novartis, PAC-12, Precordior, Sanifit, and St Jude Medical; has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, Eli Lilly, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, MyoKardia, Novartis, Novo Nordisk, PhaseBio, Portola, Quidel, and Theravance; and owns equity in Human, Medeloop, Precordior, and Regencor. EDAT- 2026/06/03 12:40 MHDA- 2026/06/06 12:34 CRDT- 2026/06/03 08:28 PHST- 2025/09/26 00:00 [received] PHST- 2026/02/18 00:00 [revised] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/06/06 12:34 [medline] PHST- 2026/06/03 12:40 [pubmed] PHST- 2026/06/03 08:28 [entrez] AID - S0735-1097(26)05731-1 [pii] AID - 10.1016/j.jacc.2026.02.5125 [doi] PST - ppublish SO - J Am Coll Cardiol. 2026 Jun 2;87(21):2996-3012. doi: 10.1016/j.jacc.2026.02.5125. PMID- 42229850 OWN - NLM STAT- MEDLINE DCOM- 20260930 LR - 20261002 IS - 2468-6530 (Electronic) IS - 2468-7219 (Print) IS - 2468-6530 (Linking) VI - 10 IP - 10 DP - 2026 Oct TI - Glucagon-Like Peptide 1 Receptor Agonists and Age-Related Macular Degeneration Incidence. PG - 1017-1026 LID - S2468-6530(26)00266-6 [pii] LID - 10.1016/j.oret.2026.05.016 [doi] AB - PURPOSE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes. DESIGN: Retrospective, propensity score-matched cohort study. PARTICIPANTS: Adults with diabetes who initiated a GLP-1RA or another noninsulin antidiabetic agent. In Epic Cosmos, 2 797 686 GLP-1RA users were matched 1:1 to 2 797 686 active comparators. METHODS: We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-VEGF treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models. MAIN OUTCOME MEASURES: Incidence of any AMD and nAMD. RESULTS: In the matched Epic Cosmos cohort (total N = 5 595 372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% confidence interval CI, 0.182%-0.192%] vs. 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs. 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs. 6.540% [95% CI, 6.017%-7.108%]); all P < 0.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs. 0.065%), 5 years (0.280% vs. 0.340%), and 10 years (1.874% vs. 2.393%); all P < 0.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P < 0.001) and was not associated with an increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P = 0.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups. CONCLUSIONS: Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - Hallaj, Shahin AU - Hallaj S AD - Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, San Diego, California; Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California San Diego, San Diego, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, San Diego, California. FAU - Nishida, Takashi AU - Nishida T AD - Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California San Diego, San Diego, California. FAU - Kamalipour, Alireza AU - Kamalipour A AD - Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, San Diego, California; Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California San Diego, San Diego, California; Viterbi Family Department of Ophthalmology, Jacobs Retina Center, Shiley Eye Institute, University of California San Diego, San Diego, California. FAU - Longhurst, Christopher A AU - Longhurst CA AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, San Diego, California; Division of Biomedical Informatics, Department of Medicine, Joan & Irwin Jacobs Center for Health Innovation, University of California San Diego, San Diego, California. FAU - Freeman, William R AU - Freeman WR AD - Viterbi Family Department of Ophthalmology, Jacobs Retina Center, Shiley Eye Institute, University of California San Diego, San Diego, California. FAU - Baxter, Sally L AU - Baxter SL AD - Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, San Diego, California; Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California San Diego, San Diego, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, San Diego, California; Division of Biomedical Informatics, Department of Medicine, Joan & Irwin Jacobs Center for Health Innovation, University of California San Diego, San Diego, California. FAU - Boussina, Aaron AU - Boussina A AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, San Diego, California; Division of Biomedical Informatics, Department of Medicine, Joan & Irwin Jacobs Center for Health Innovation, University of California San Diego, San Diego, California. Electronic address: aboussina@health.ucsd.edu. LA - eng GR - DP5 OD029610/OD/NIH HHS/United States GR - OT2 OD032644/OD/NIH HHS/United States GR - R01 EY034146/EY/NEI NIH HHS/United States GR - P30 EY022589/EY/NEI NIH HHS/United States GR - T32 EY026590/EY/NEI NIH HHS/United States PT - Journal Article PT - Multicenter Study DEP - 20260601 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Follow-Up Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - *Macular Degeneration/epidemiology MH - Retrospective Studies MH - Risk Factors MH - *Wet Macular Degeneration/epidemiology/diagnosis PMC - PMC13629172 MID - NIHMS2200350 OTO - NOTNLM OT - Age-related macular degeneration OT - Glucagon-like peptide-1 receptor agonists OT - Neovascular. EDAT- 2026/06/03 00:38 MHDA- 2026/09/30 23:29 PMCR- 2026/10/01 CRDT- 2026/06/02 19:35 PHST- 2025/11/10 00:00 [received] PHST- 2026/05/01 00:00 [revised] PHST- 2026/05/12 00:00 [accepted] PHST- 2026/09/30 23:29 [medline] PHST- 2026/06/03 00:38 [pubmed] PHST- 2026/06/02 19:35 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - S2468-6530(26)00266-6 [pii] AID - 10.1016/j.oret.2026.05.016 [doi] PST - ppublish SO - Ophthalmol Retina. 2026 Oct;10(10):1017-1026. doi: 10.1016/j.oret.2026.05.016. Epub 2026 Jun 1. PMID- 42229813 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260922 IS - 1549-4713 (Electronic) IS - 0161-6420 (Print) IS - 0161-6420 (Linking) VI - 133 IP - 10 DP - 2026 Oct TI - Semaglutide and Neovascular Age-Related Macular Degeneration among Adults with Type 2 Diabetes: An Observational Health Data Sciences and Informatics Network Study. PG - 1221-1229 LID - S0161-6420(26)00382-9 [pii] LID - 10.1016/j.ophtha.2026.05.034 [doi] AB - PURPOSE: To investigate the potential association of semaglutide use and neovascular age-related macular degeneration (NVAMD). DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics network from December 1, 2017, through December 31, 2024. PARTICIPANTS: Adults with type 2 diabetes (T2D) taking semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., dulaglutide or exenatide), or non-GLP-1RAs (e.g., empagliflozin, sitagliptin, or glipizide). METHODS: The association between semaglutide use and NVAMD was assessed using 2 approaches: an active-comparator cohort design and a self-controlled case series analysis. The former used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The latter used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates. MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) and one based on condition codes and procedures (NVAMD-CP). RESULTS: A total of 227 971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to that of users of dulaglutide (NVAMD-C: HR, 0.57; 95% CI, 0.21-1.57; P = 0.28; NVAMD-CP: HR, 0.25; 95% CI, 0.05-1.27; P = 0.10), empagliflozin (NVAMD-C: HR, 0.98; 95% CI, 0.54-1.79; P = 0.94; NVAMD-CP: HR, 0.79; 95% CI, 0.38-1.64; P = 0.52), sitagliptin (NVAMD-C: HR, 2.08; 95% CI, 0.90-4.83; P = 0.09; NVAMD-CP: HR, 1.80; 95% CI, 0.55-5.86; P = 0.33), and glipizide (NVAMD-C: HR, 0.83; 95% CI, 0.35-2.02; P = 0.69; NVAMD-CP: HR, 0.50; 95% CI, 0.21-1.19; P = 0.12). No evidence was found of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: IRR, 0.92; 95% CI, 0.67-1.26; P = 0.60; NVAMD-CP: IRR, 1.02; 95% CI, 0.76-1.36; P = 0.92) nor with any of the other GLP-1RAs or non-GLP-1RAs. CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - Cai, Cindy X AU - Cai CX AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland; Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ccai6@jhmi.edu. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Tran, Diep AU - Tran D AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Lee, Haeun AU - Lee H AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Nagy, Paul AU - Nagy P AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - Hribar, Michelle AU - Hribar M AD - Ophthalmology and Visual Sciences, AI.Health4All College of Medicine, University of Illinois at Chicago, Chicago, Illinois. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon. FAU - Armbrust, Karen AU - Armbrust K AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota; Department of Ophthalmology, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota. FAU - Goetz, Kerry AU - Goetz K AD - Department of Clinical Science, Topcon Healthcare, Inc., Oakland, New Jersey. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California, San Diego, La Jolla, California. FAU - Boland, Michael V AU - Boland MV AD - Department of Ophthalmology, Mass Eye and Ear and Harvard Medical School, Boston, Massachusetts. FAU - Brown, Eric N AU - Brown EN AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Tsui, Edmund AU - Tsui E AD - UCLA Stein Eye Institute, University of California, Los Angeles, Los Angeles, California. FAU - Barkmeier, Andrew J AU - Barkmeier AJ AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Mehta, Nitish AU - Mehta N AD - Department of Ophthalmology, NYU Langone Health, New York, New York. FAU - Stocking, Jacqueline C AU - Stocking JC AD - Department of Internal Medicine, University of California, Davis, Sacramento, California. FAU - O'Keefe, Ghazala AU - O'Keefe G AD - Private Practice. FAU - Lee, Cecilia S AU - Lee CS AD - John F. Hardesty, MS, Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri. FAU - Payne, Philip R O AU - Payne PRO AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - O'Brien, William J AU - O'Brien WJ AD - Veterans Affairs Informatics and Computing Infrastructure, George E. Wahlen VA Medical Center, Salt Lake City, Utah. FAU - DuVall, Scott AU - DuVall S AD - Data Science and Advanced Analytics, PurpleLab, Inc., Salt Lake City, Utah. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, College of Pharmacy, Jazan University, Jazan, Saudi Arabia; Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Dorr, David A AU - Dorr DA AD - Division of Informatics, Clinical Epidemiology, and Translational Data Science, Department of Medicine, Oregon Health and Science University, Portland, Oregon. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - McCoy, David AU - McCoy D AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Adibuzzaman, Mohammed AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Mahmood, Rumel AU - Mahmood R AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Kothari, Shikha Yashwant AU - Kothari SY AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Sena, Anthony AU - Sena A AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. FAU - Blacketer, Clair AU - Blacketer C AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. FAU - Ostropolets, Anna AU - Ostropolets A AD - Department of Biomedical Informatics, Columbia University, New York, New York; Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Shoaibi, Azza AU - Shoaibi A AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Rao, Gowtham AU - Rao G AD - Research Department, CoReason, Inc, Princeton, New Jersey. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Ryan, Patrick AU - Ryan P AD - Department of Biomedical Informatics, Columbia University, New York, New York; Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles, California; VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. LA - eng GR - R01 DK125780/DK/NIDDK NIH HHS/United States GR - R01 AG060942/AG/NIA NIH HHS/United States GR - P30 EY022589/EY/NEI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - K23 EY033440/EY/NEI NIH HHS/United States GR - R01 DK134955/DK/NIDDK NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - OT2 OD032644/OD/NIH HHS/United States GR - K23 EY032985/EY/NEI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Observational Study DEP - 20260602 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Retrospective Studies MH - Female MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - *Wet Macular Degeneration/epidemiology/diagnosis MH - Incidence MH - Immunoglobulin Fc Fragments/therapeutic use PMC - PMC13318194 MID - NIHMS2183361 OTO - NOTNLM OT - Big data OT - Neovascular age-related macular degeneration OT - Observational Health Data Sciences and Informatics OT - Semaglutide COIS- Regeneron Pharmaceuticals, Inc (grant support), Optomed (equipment support) Topcon Healthcare, Inc. (employee) Topcon (consulting fees) Carl Zeiss Meditec (consulting, speaking); Abbvie (consulting) 4DMT (advisory board), Regeneron Pharmaceauticals (advisory board), Eyepoint Pharmaceauticals (advisory board) Employee and Shareholder of PurpleLab Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Receives contracts and grants from Janssen Researchh & Development and Gilead Sciences, Inc., outside the scope of this work. EDAT- 2026/06/03 00:40 MHDA- 2026/09/18 23:36 PMCR- 2026/07/01 CRDT- 2026/06/02 19:34 PHST- 2026/03/06 00:00 [received] PHST- 2026/05/21 00:00 [revised] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/09/18 23:36 [medline] PHST- 2026/06/03 00:40 [pubmed] PHST- 2026/06/02 19:34 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - S0161-6420(26)00382-9 [pii] AID - 10.1016/j.ophtha.2026.05.034 [doi] PST - ppublish SO - Ophthalmology. 2026 Oct;133(10):1221-1229. doi: 10.1016/j.ophtha.2026.05.034. Epub 2026 Jun 2. PMID- 42229580 OWN - NLM STAT- MEDLINE DCOM- 20260620 LR - 20261024 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 109 DP - 2026 Jul TI - Effects of the glucagon-like peptide-1 receptor agonist PEG-Loxe on diabetic osteoporosis: A mechanistic study. PG - 102390 LID - S2212-8778(26)00074-8 [pii] LID - 10.1016/j.molmet.2026.102390 [doi] LID - 102390 AB - BACKGROUND: Diabetic osteoporosis is characterized by disrupted bone remodeling involving impaired osteogenesis and excessive osteoclastic activity. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have hypoglycemic benefits, their effects on bone metabolism remain unclear. This study investigates the osteoprotective potential of polyethylene glycol loxenatide (PEG-Loxe), a GLP-1RA hypoglycemic drug. METHODS: In vitro studies involved MC3T3-E1 osteoblasts and RANKL-stimulated RAW264.7 osteoclasts, both treated with 100 nM PEG-Loxe. Osteogenic markers (ALP, Col-1, and Runx2) and osteoclast differentiation were assessed, and HMGB-1 overexpression was used to validate pathway involvement. For in vivo studies, type 2 diabetic ApoE(-/-) mice were treated with PEG-Loxe. We examined serum markers (CTX, HMGB-1, TNF-alpha, and IL-1beta) and performed micro-CT and histomorphometric analyses. In clinical research, serum markers and BMD were analysed. RESULTS: PEG-Loxe has dual regulatory effects. PEG-Loxe can significantly enhance osteoblast differentiation (increased ALP, Col-1 and Runx2 activities, p < 0.001) and suppressing osteoclastogenesis by inhibiting HMGB-1/RAGE/TLR4/NF-kappaB pathway (p < 0.001). In ApoE(-/-) mice, PEG-Loxe increased osteoblasts and reduced osteoclasts. RAGE, HMGB-1, TNF-alpha, and IL-1beta were reduced to varying degrees (p < 0.05; p < 0.01; p < 0.01; p < 0.01). Micro CT scanning of 3D images of mouse femurs showed that PEG-Loxe can increase femoral tissue and reduce porosity. In clinical research,CTX, HMGB-1, TNF-alpha, and IL-1beta were significantly reduced in the PEG-Loxe group compared to the Non-PEG-Loxe group (p < 0.05). There was no significant difference in BMD between the two groups. CONCLUSIONS: PEG-Loxe exerts comprehensive osteoprotective effects in type 2 diabetes by simultaneously promoting osteogenesis and suppressing osteoclastogenesis, through modulation of HMGB-1 signaling. PEG-Loxe can significantly improve bone turnover status and reduce bone resorption levels, with potential osteoprotective effects. CI - Copyright (c) 2026 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Zhang, Lizhi AU - Zhang L AD - Department of Endocrinology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. Electronic address: zhanglizhi519@163.com. FAU - Hu, Jingjing AU - Hu J AD - Department of Endocrinology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. FAU - Huang, Chunxiao AU - Huang C AD - Traditional Chinese Medicine Department, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. FAU - Gao, Xiaoli AU - Gao X AD - Medical Examination Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. FAU - Pang, Dongyue AU - Pang D AD - Department of Endocrinology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. FAU - Duan, Lian AU - Duan L AD - Nursing Department, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260601 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Animals MH - Mice MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoporosis/drug therapy/metabolism MH - Osteogenesis/drug effects MH - Osteoclasts/drug effects/metabolism MH - Osteoblasts/drug effects/metabolism MH - *Polyethylene Glycols/pharmacology MH - Cell Differentiation/drug effects MH - Male MH - RAW 264.7 Cells MH - Diabetes Mellitus, Type 2/metabolism/complications MH - Mice, Inbred C57BL MH - Female MH - Mice, Knockout MH - Bone Remodeling/drug effects MH - Hypoglycemic Agents/pharmacology MH - Diabetes Mellitus, Experimental MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Bone Density/drug effects PMC - PMC13276415 OTO - NOTNLM OT - Diabetic osteoporosis OT - Glucagon-like peptide-1 receptor agonists OT - High-mobility group box 1 OT - Osteoblast differentiation OT - Osteoclastogenesis OT - Polyethylene glycol loxenatide OT - Translational research COIS- Declaration of competing interest The authors have no conflicts of interest to declare. EDAT- 2026/06/03 00:40 MHDA- 2026/06/21 22:33 PMCR- 2026/06/01 CRDT- 2026/06/02 19:31 PHST- 2026/03/14 00:00 [received] PHST- 2026/05/12 00:00 [revised] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/06/21 22:33 [medline] PHST- 2026/06/03 00:40 [pubmed] PHST- 2026/06/02 19:31 [entrez] PHST- 2026/06/01 00:00 [pmc-release] AID - S2212-8778(26)00074-8 [pii] AID - 102390 [pii] AID - 10.1016/j.molmet.2026.102390 [doi] PST - ppublish SO - Mol Metab. 2026 Jul;109:102390. doi: 10.1016/j.molmet.2026.102390. Epub 2026 Jun 1. PMID- 42227662 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260717 IS - 2688-1535 (Electronic) IS - 2688-1527 (Linking) VI - 22 IP - 7 DP - 2026 Jul TI - GLP-1 Agonists Are Associated With a Significant Reduction in Breast Cancer Incidence in Women. PG - 1341-1348 LID - 10.1200/OP-26-00485 [doi] AB - PURPOSE: Excess weight is a key modifiable risk factor for breast cancer. Glucagon-like peptide-1 receptor agonists (GLP-1) promote weight loss and improve metabolic health, but their effect on breast cancer risk remains unclear. METHODS: We conducted a retrospective cohort study from January 1, 2022, to June 30, 2025, using electronic health records. We identified 217,624 unique women who underwent breast imaging; restricting to ages 45-80 years with a BMI >/=25 and a documented imaging outcome (n = 111,646; median age 61 years). The primary outcome was breast cancer detection. GLP-1 use was defined as a first prescription before the examination date and assessed in relation to race, ethnicity, age, and type 2 diabetes. To address potential confounding between these covariates and GLP-1 exposure, we performed one-to-one, case-control matching using propensity scores on the basis of age, race, ethnicity, highest BMI, breast density, and history of type 2 diabetes. The propensity matching to the GLP-1 use group was performed using the greedy nearest neighbor approach. RESULTS: GLP-1 exposure was associated with a lower incidence of breast cancer (odds ratio [OR], 0.649 [95% CI, 0.569 to 0.741]; P < .0001). In the matched logistic regression (30,528 observations; 600 cancer cases), GLP-1 exposure was associated with a lower breast cancer incidence (OR, 0.695 [95% CI, 0.590 to 0.819]; P < .0001). CONCLUSION: In this large observational study of women undergoing breast imaging at a major academic center and affiliated sites, GLP-1 treatment was associated with a lower incidence of breast cancer, independent of age, race, ethnicity, BMI, breast density, and diabetes. The findings support the need for prospective trials investigating GLP-1 agonists for breast cancer prevention. FAU - McDonald, Elizabeth S AU - McDonald ES AUID- ORCID: 0000-0002-7209-4216 AD - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. FAU - Gillis, Laura B AU - Gillis LB AD - American College of Radiology, Philadelphia, PA. FAU - Gabriel, Peter E AU - Gabriel PE AUID- ORCID: 0000-0002-3772-9669 AD - Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania. AD - Cancer Informatics Shared Resource, Abramson Cancer Center, University of Pennsylvania. FAU - Xapakdy, Kham M AU - Xapakdy KM AD - Penn Medicine, Philadelphia, PA. FAU - Young, Anthony J AU - Young AJ AUID- ORCID: 0000-0003-3209-1034 AD - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. FAU - Doucette, Abigail G AU - Doucette AG AUID- ORCID: 0000-0002-6646-433X AD - Cancer Informatics Shared Resource, Abramson Cancer Center, University of Pennsylvania. FAU - Schnall, Mitchell D AU - Schnall MD AD - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC. FAU - Pisano, Etta D AU - Pisano ED AUID- ORCID: 0000-0002-0529-7654 AD - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. AD - American College of Radiology, Philadelphia, PA. LA - eng PT - Journal Article DEP - 20260602 PL - United States TA - JCO Oncol Pract JT - JCO oncology practice JID - 101758685 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/epidemiology/prevention & control MH - Middle Aged MH - Aged MH - Retrospective Studies MH - Incidence MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged, 80 and over MH - *Glucagon-Like Peptide 1 MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors MH - Case-Control Studies EDAT- 2026/06/02 12:46 MHDA- 2026/07/18 00:38 CRDT- 2026/06/02 08:03 PHST- 2026/07/18 00:38 [medline] PHST- 2026/06/02 12:46 [pubmed] PHST- 2026/06/02 08:03 [entrez] AID - 10.1200/OP-26-00485 [doi] PST - ppublish SO - JCO Oncol Pract. 2026 Jul;22(7):1341-1348. doi: 10.1200/OP-26-00485. Epub 2026 Jun 2. PMID- 42224699 OWN - NLM STAT- MEDLINE DCOM- 20260615 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 6 DP - 2026 Jun TI - In T2D inadequately controlled with metformin, orforglipron reduced HbA(1c) more than oral semaglutide at 52 wk. PG - JC62 LID - 10.7326/ANNALS-26-01781-JC [doi] AB - GIM/FP/GP: [Formula: see text] Endocrinology: [Formula: see text]. FAU - Lau, Darren AU - Lau D AUID- ORCID: 0000-0001-9923-7902 AD - University of Alberta, Edmonton, Alberta, Canada (D.L.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20260602 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (orforglipron) RN - 0 (Pyridones) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Metformin/pharmacology/therapeutic use MH - *Pyridones/pharmacology/therapeutic use MH - Semaglutide/pharmacology/therapeutic use MH - Oxadiazoles MH - Fluorine Compounds COIS- Disclosures: Disclosure form is available with the article online. EDAT- 2026/06/01 18:48 MHDA- 2026/06/15 18:34 CRDT- 2026/06/01 17:03 PHST- 2026/06/15 18:34 [medline] PHST- 2026/06/01 18:48 [pubmed] PHST- 2026/06/01 17:03 [entrez] AID - 10.7326/ANNALS-26-01781-JC [doi] PST - ppublish SO - Ann Intern Med. 2026 Jun;179(6):JC62. doi: 10.7326/ANNALS-26-01781-JC. Epub 2026 Jun 2. PMID- 42219869 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260812 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 9 DP - 2026 Aug 13 TI - Anti-inflammatory effects of GLP1-RA drugs. PG - e2076-e2085 LID - 10.1210/clinem/dgag218 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RA) are established treatment options for type 2 diabetes and obesity. This class of medications has redefined care by lowering glucose, reducing body weight, and improving cardiovascular outcomes. Beyond metabolic benefits, accumulating evidence indicates that GLP-1RA exert direct anti-inflammatory effects across multiple organ systems. Chronic inflammation is a driving force behind many prevalent diseases, including diabetes, cardiovascular disease, neurodegenerative disorders, and inflammatory bowel disease. This review summarizes the current evidence of the anti-inflammatory effects of GLP-1RA, highlighting data from preclinical models and clinical trials across different diseases. By targeting both metabolic and inflammatory pathways, GLP-1RA may offer dual cardiometabolic and immunomodulatory protection, positioning these agents as promising candidates for broader therapeutic applications. However, several key questions remain regarding causality, the precise molecular mechanisms involved, and the extent to which these anti-inflammatory effects can be translated into effective therapies for nonmetabolic inflammatory diseases. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Quintana, Luis AU - Quintana L AD - Department of Internal Medicine I-Cardiology, University Hospital Aachen, RWTH Aachen University, Aachen D-52074, Germany. FAU - Tabaza, Nadim AU - Tabaza N AD - Department of Internal Medicine I-Cardiology, University Hospital Aachen, RWTH Aachen University, Aachen D-52074, Germany. FAU - Kurt, Berkan AU - Kurt B AUID- ORCID: 0009-0006-1313-152X AD - Department of Internal Medicine I-Cardiology, University Hospital Aachen, RWTH Aachen University, Aachen D-52074, Germany. FAU - Kahles, Florian AU - Kahles F AUID- ORCID: 0000-0001-6343-2562 AD - Department of Internal Medicine I-Cardiology, University Hospital Aachen, RWTH Aachen University, Aachen D-52074, Germany. LA - eng GR - Deutsche Forschungsgemeinschaft/ GR - 520275106/German Research Foundation/ GR - SFB TRR 219-322900939-M-07/Emmy Noether Research Group/ GR - European Research Area Network on Cardiovascular Diseases/ GR - JTC-2019/BMBF/ GR - MyPenPath-01KL2004/BMBF/ GR - European Foundation for the Study of Diabetes (EFSD)/ GR - NNF2OSA0066111/Novo Nordisk Foundation/ GR - Interdisciplinary Centre for Clinical Research/ GR - PTD 1-11/RWTH Aachen University/ PT - Journal Article PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Anti-Inflammatory Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Inflammation/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/immunology MH - Cardiovascular Diseases/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Neurodegenerative Diseases/drug therapy OTO - NOTNLM OT - GLP-1 receptor agonists OT - autoimmune diseases OT - cardiometabolic disease OT - cardiovascular disease OT - immunomodulation OT - infectious diseases OT - inflammation OT - inflammatory bowel disease OT - neurodegeneration OT - sepsis EDAT- 2026/06/01 08:04 MHDA- 2026/08/12 23:34 CRDT- 2026/06/01 02:03 PHST- 2025/12/19 00:00 [received] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/08/12 23:34 [medline] PHST- 2026/06/01 08:04 [pubmed] PHST- 2026/06/01 02:03 [entrez] AID - 8698993 [pii] AID - 10.1210/clinem/dgag218 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 Aug 13;111(9):e2076-e2085. doi: 10.1210/clinem/dgag218. PMID- 42219271 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis. PG - 7137-7148 LID - 10.1111/dom.70915 [doi] AB - AIMS: To provide updated agent-level comparative estimates of GLP-1-based therapies for cardiovascular outcomes in adults with Type 2 diabetes mellitus (T2DM) using a hazard ratio (HR)-based systematic review and network meta-analysis (NMA). METHODS: PubMed, Cochrane Library and Scopus were searched through December 2025 for randomized controlled trials evaluating GLP-1-based therapies in adults with T2DM and reporting time-to-event cardiovascular outcomes. Pairwise meta-analyses and a frequentist random-effects NMA were performed for all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI) and non-fatal stroke. RESULTS: Fifteen trials involving 97,173 participants were included. In pairwise placebo-controlled analyses, GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE. In the NMA, mortality estimates for several agents favoured benefit, although most comparisons were not statistically significant. For MACE, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles. Albiglutide reduced non-fatal MI versus placebo, whereas non-fatal stroke estimates were imprecise. CONCLUSIONS: GLP-1-based therapies were associated with an overall favourable cardiovascular profile in T2DM. Pairwise analyses supported class-level benefit, whereas between-agent differences were more evident for MACE than for mortality outcomes in the NMA. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Chuang, Shih-Ming AU - Chuang SM AUID- ORCID: 0000-0002-8622-1968 AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Liu, Sung-Chen AU - Liu SC AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Lin, Cheng-Jui AU - Lin CJ AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan. FAU - Tsai, Ming-Chieh AU - Tsai MC AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Shih, Hong-Mou AU - Shih HM AUID- ORCID: 0009-0001-8344-5309 AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260531 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/mortality/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/therapeutic use/analogs & derivatives MH - Semaglutide MH - Randomized Controlled Trials as Topic MH - Tirzepatide MH - Treatment Outcome PMC - PMC13341365 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes mellitus OT - cardiovascular outcomes OT - major adverse cardiovascular events OT - network meta-analysis OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/01 00:33 MHDA- 2026/07/08 12:57 PMCR- 2026/07/08 CRDT- 2026/05/31 21:42 PHST- 2026/05/05 00:00 [revised] PHST- 2026/03/29 00:00 [received] PHST- 2026/05/15 00:00 [accepted] PHST- 2026/07/08 12:57 [medline] PHST- 2026/06/01 00:33 [pubmed] PHST- 2026/05/31 21:42 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70915 [pii] AID - 10.1111/dom.70915 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7137-7148. doi: 10.1111/dom.70915. Epub 2026 May 31. PMID- 42219226 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Semaglutide Injection in Indian Patients With Type 2 Diabetes Mellitus: A Randomised, Phase III, Active-Controlled Study. PG - 7094-7103 LID - 10.1111/dom.70891 [doi] AB - AIM: To evaluate the efficacy, safety and immunogenicity of semaglutide injection (synthetic) (Test group) compared with the Reference semaglutide injection [Ozempic, (Reference group)] in Indian patients with Type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase III, randomised, open-label, multi-centre, parallel-group, active-controlled non-inferiority study was conducted across 35 centres in India. Adults aged 18-65 years with T2DM and baseline glycated haemoglobin (HbA1c) >/= 7.0% to /= 18 years, with BMI >/= 35 kg/m(2) with >/= 1 obesity complication or BMI >/= 27 kg/m(2) with >/= 2 obesity complications, >/= 1 self-reported unsuccessful dietary effort to lose body weight and >/= 1 obesity complication required to be type 2 diabetes (T2D; capped at 30% enrolment), hypertension or dyslipidaemia. Participants were randomised 1:1:1 to receive once-weekly survodutide 3.6 or 6.0 mg, or placebo, accompanied by a reduced-calorie diet and increased physical activity. The primary endpoints are percentage change in body weight and achievement of body weight reduction >/= 5% from baseline to Week 76. A subset of participants will be assessed for additional endpoints of liver fat content and body composition. RESULTS: Of 274 enrolled participants, 24.1% had T2D. The mean age was 53.1 years; 47.8% were female, and mean BMI was 33.2 kg/m(2). The most frequent complications were dyslipidaemia (81.4%), hypertension (72.6%), hyperuricaemia (30.3%) and metabolic dysfunction-associated steatotic liver disease (26.6%). CONCLUSIONS: The results of SYNCHRONIZE-JP will provide Japan-specific efficacy, safety and tolerability data for survodutide and inform its potential role in the management of obesity disease. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yokote, Koutaro AU - Yokote K AUID- ORCID: 0000-0003-3033-4813 AD - Chiba University, Chiba, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AUID- ORCID: 0000-0003-4827-6404 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Fukushima, Yasushi AU - Fukushima Y AUID- ORCID: 0000-0002-6148-215X AD - Fukuwa Clinic, Tokyo, Japan. FAU - Takatsuka, Yoji AU - Takatsuka Y AUID- ORCID: 0009-0009-3777-3510 AD - Motomachi Takatsuka Internal Medicine Clinic, Yokohama, Japan. FAU - Kato, Marie AU - Kato M AUID- ORCID: 0009-0004-0220-3829 AD - Nippon Boehringer Ingelheim Co. Ltd., Tokyo, Japan. FAU - Yan, Shijia AU - Yan S AUID- ORCID: 0009-0009-2328-1726 AD - Boehringer Ingelheim (China) Investment Co. Ltd., Shanghai, China. FAU - Inoue, Takayoshi AU - Inoue T AUID- ORCID: 0000-0002-1531-2395 AD - Nippon Boehringer Ingelheim Co. Ltd., Tokyo, Japan. FAU - Borowska, Luiza AU - Borowska L AUID- ORCID: 0009-0009-6826-0822 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Brueckmann, Martina AU - Brueckmann M AUID- ORCID: 0000-0003-1215-0746 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. AD - First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Ogawa, Wataru AU - Ogawa W AUID- ORCID: 0000-0002-0432-4366 AD - Section of Metabolic Diseases, Division of Translational Science, Kobe University Graduate School of Medicine, Kobe, Japan. CN - SYNCHRONIZE-JP Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT06176365 GR - Boehringer Ingelheim/ PT - Clinical Trial Protocol PT - Journal Article DEP - 20260531 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - Japanese people SB - IM MH - Humans MH - *Obesity/drug therapy/complications MH - Female MH - Double-Blind Method MH - Male MH - Middle Aged MH - Japan MH - Adult MH - Diabetes Mellitus, Type 2/complications MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Multicenter Studies as Topic MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - Treatment Outcome MH - Aged MH - East Asian People PMC - PMC13341362 OTO - NOTNLM OT - glucagon receptor agonist OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - survodutide OT - trial design COIS- K.Y. reports scholarship donations from Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceutical Co. Ltd.; and has received honoraria from Astellas Pharma Inc., Kowa Company Ltd., Sanofi K.K., Sumitomo Pharma Co. Ltd., Daiichi Sankyo Company Ltd., Taisho Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Bayer Yakuhin Ltd. and Eli Lilly Japan K.K. T.Y. reports speaker fees/honoraria from MSD K.K., Sumitomo Pharma Co. Ltd., Teijin Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K. and Mitsubishi Tanabe Pharma Corporation; scholarship donations from Sumitomo Pharma Co. Ltd. and Mitsubishi Tanabe Pharma Corporation; research funding from Kowa Company Ltd., Nipro Co., Nitto Boseki Co. Ltd. and MedMirai Inc.; and course funding from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., Kowa Company Ltd., Nitto Boseki Co. Ltd. and Asahi Mutual Life Insurance Co. Y.F. reports no competing interests. Y.T. reports no competing interests. M.K., S.Y., T.I., L.B. and M.B. are employees of Boehringer Ingelheim. W.O. reports scholarship donations from Sumitomo Pharma Co. Ltd.; research funding from Noster Inc., Nippon Boehringer Ingelheim Co. Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co. Ltd. and Novo Nordisk Pharma Ltd.; and has received honoraria from Sumitomo Pharma Co. Ltd., Abbott Japan LLC, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd. and Eli Lilly Japan K.K. EDAT- 2026/06/01 00:32 MHDA- 2026/07/08 18:51 PMCR- 2026/07/08 CRDT- 2026/05/31 20:14 PHST- 2026/04/28 00:00 [revised] PHST- 2026/02/12 00:00 [received] PHST- 2026/04/29 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/06/01 00:32 [pubmed] PHST- 2026/05/31 20:14 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70862 [pii] AID - 10.1111/dom.70862 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6595-6606. doi: 10.1111/dom.70862. Epub 2026 May 31. PMID- 42217111 OWN - NLM STAT- MEDLINE DCOM- 20260822 LR - 20261002 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 9 DP - 2026 Sep TI - Defining the Roles of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Management of Chronic Kidney Disease in Adults with Type 2 Diabetes With or Without Overweight/Obesity: An International Delphi Consensus. PG - 3886-3912 LID - 10.1007/s12325-026-03618-z [doi] AB - INTRODUCTION: The optimal positioning and sequencing of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with chronic kidney disease (CKD) with type 2 diabetes (T2D) and overweight/obesity is unclear. This Delphi panel aimed to establish expert consensus on the foundational versus adjunctive role of SGLT2is and GLP-1 RAs in this adult population. METHODS: A total of 114 participants across 10 countries participated in a two-round Delphi panel (9.7% drop-off rate between rounds). Statement development was guided by a systematic literature review and 12 global experts. Consensus was pre-defined as >/= 75% agreement/disagreement. The Delphi panel took place between 29 August and 20 October 2025. RESULTS: Totals of 13/30 (43%) and 7/17 (41%) statements achieved consensus in Rounds 1 and 2, respectively. Panellists agreed that SGLT2is should be foundational therapy in adults with CKD and T2D, independent of body mass index (BMI). Consensus was also achieved that GLP-1 RAs should be considered as an add-on for those with BMI >/= 35 kg/m(2) and cardiometabolic complications and comorbidities [e.g. residual glycated haemoglobin A1c (HbA1c) elevation, atherosclerotic cardiovascular disease]. Combination therapy was considered appropriate for adults with persistent kidney disease progression, high cardiovascular risk or suboptimal metabolic control. CONCLUSION: While treatment of adults with CKD and T2D should be holistic, SGLT2is should be prioritised as foundational therapy, independent of BMI, to reduce cardiorenal risk. Combination therapy with GLP-1 RAs was preferred for those with ongoing CKD progression and/or high cardiometabolic risk. Further clarity is required around the optimal timing of combination and sequential add-on therapy initiation. CI - (c) 2026. The Author(s). FAU - Handelsman, Yehuda AU - Handelsman Y AD - Metabolic Institute of America, Los Angeles, CA, USA. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, Toronto, Canada. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Kushner, Pam AU - Kushner P AD - University of California Irvine Medical Center, Orange, CA, USA. FAU - Bonnet, Fabrice AU - Bonnet F AD - Department of Diabetes, University of Rennes, Rennes, France. FAU - Fioretto, Paola AU - Fioretto P AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. FAU - Kanumilli, Naresh AU - Kanumilli N AD - Northenden Group Practice, Wythenshawe, UK. FAU - Cos, Xavier AU - Cos X AD - IDIAP Jordi Gol, Institut Catala de la Salut, CIBERDEM, Barcelona, Spain. FAU - Frese, Thomas AU - Frese T AD - Institute of General Practice and Family Medicine, Interdisciplinary Center of Health Sciences, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany. FAU - Ji, Linong AU - Ji L AD - Department of Internal Medicine, Peking University People's Hospital, Beijing, China. FAU - Rossing, Peter AU - Rossing P AD - Department of Clinical Medicine, Internal Medicine, Endocrinology, University of Copenhagen, Copenhagen, Denmark. Peter.Rossing@RegionH.dk. LA - eng PT - Consensus Statement PT - Journal Article DEP - 20260530 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Delphi Technique MH - *Overweight/complications MH - *Obesity/complications MH - *Hypoglycemic Agents/therapeutic use MH - Adult PMC - PMC13499768 OTO - NOTNLM OT - Chronic kidney disease OT - Glucagon-like peptide-1 receptor agonist OT - Sodium-glucose co-transporter 2 inhibitor COIS- Declarations. Conflict of Interest: All authors have declared any relevant competing interests. Yehuda Handelsman: Received research grants, consultant and speaker honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Eli Lilly, Ionis, Merck, Novo Nordisk, Regeneron, Sanofi, Verdiva Bio; Alice Cheng: Received consulting and speaking honoraria from Abbott, Astellas, Aspen, AstraZeneca, Amgen, Bausch, Bayer, Biomea Fusion, Boehringer Ingelheim, Dexcom, Eisai, Eli Lilly, GSK, HLS Therapeutics, Insulet, Medtronic, Merck, MSD, Novo Nordisk, Pfizer, Sandoz, Sanofi, and Vertex; Gian Paolo Fadini: Received grants, honoraria or lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Guidotti, Mundipharma, Novartis, Novo Nordisk, Servier, and Sanofi; Pam Kushner: Received honoraria for consulting or advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Verdiva Bio; Fabrice Bonnett: No competing interests; Paola Fioretto: Received fees as consultant and speaker for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Novo Nordisk; Takashi Kadowaki: Received research grants from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd.; receiving consulting fees from Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Novo Nordisk Pharma Ltd.; receiving honoraria for lectures from Nippon Boehringer Ingelheim Co., Ltd., Sumitomo Pharma Co., Ltd., Teijin Pharma Ltd., MSD Corporation, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co., Ltd. and Novo Nordisk Pharma Ltd; Naresh Kanumilli: No competing interests; Xavier Cos: No competing interests; Thomas Frese: Received payments from Astra Zeneca and Boehringer Ingelheim; Linong Ji: No competing interests; Peter Rossing: Received consultancy and/or speaker fees (to his institution) from Abbott, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk and Roche; research grants from AstraZeneca, Bayer and Novo Nordisk; study drugs from AstraZeneca, Bayer Lexicon and Novo Nordisk. Ethical Approval: No patients were involved in the study, which was not submitted for approval by an ethics committee or institutional review board. Participants gave informed consent to participate in the study before taking part and were made aware of the study objectives and the aim for publication of a manuscript. Participants remained independent throughout the Delphi panel; no honoraria were provided for their time or participation in the surveys, and their responses were anonymised from each other and the funder throughout the surveys. EDAT- 2026/05/31 05:31 MHDA- 2026/08/22 22:41 PMCR- 2026/05/30 CRDT- 2026/05/30 11:20 PHST- 2026/03/09 00:00 [received] PHST- 2026/04/17 00:00 [accepted] PHST- 2026/08/22 22:41 [medline] PHST- 2026/05/31 05:31 [pubmed] PHST- 2026/05/30 11:20 [entrez] PHST- 2026/05/30 00:00 [pmc-release] AID - 10.1007/s12325-026-03618-z [pii] AID - 3618 [pii] AID - 10.1007/s12325-026-03618-z [doi] PST - ppublish SO - Adv Ther. 2026 Sep;43(9):3886-3912. doi: 10.1007/s12325-026-03618-z. Epub 2026 May 30. PMID- 42216891 OWN - NLM STAT- MEDLINE DCOM- 20260617 LR - 20260617 IS - 1520-4812 (Electronic) IS - 1043-1802 (Linking) VI - 37 IP - 6 DP - 2026 Jun 17 TI - IgG Fc-Binding Motif-Conjugated Exendin-4: A Long-Acting Hypoglycemic Agent via Broad-Spectrum Antibody Engagement for Type 2 Diabetes Therapy. PG - 1292-1302 LID - 10.1021/acs.bioconjchem.6c00218 [doi] AB - Type 2 diabetes mellitus requires therapies that optimize both efficacy and durability. Although incretin mimetics such as exendin-4 (Ex4) enhance glycemic control, their short half-life restricts their clinical utility. Current extension strategies (e.g., Fc fusion) encounter challenges including immunogenicity and manufacturing complexity. Here, we engineered a series of site-specific IgG Fc-binding motif-modified Ex4 analogues using two orthogonal conjugation methods, leveraging Fc-III-4C-mediated IgG binding (human IgG: K(D) = 20.1 nM) to achieve a significantly extended plasma half-life. Structure-activity relationship studies revealed that the lead candidate, conjugate 7, retained robust GLP-1R activation and acute glucose-lowering efficacy. In human IgG-preconditioned db/db mice, conjugate 7 achieved a hypoglycemic duration comparable to that of semaglutide. Chronic once-daily dosing of the lead conjugate rivaled semaglutide in reducing HbA1c and protecting pancreatic islets, without toxicity. This strategy leverages >80% of endogenous circulating IgG as a biological reservoir to overcome peptide therapy limitations, offering a translatable platform for long-acting antidiabetic agents. FAU - Mi, Baojing AU - Mi B AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Ding, Shengjie AU - Ding S AD - Department of Pharmacy, Xinchang Hospital of Wenzhou Medical University, Shaoxing, Zhejiang 312500, China. FAU - Tian, Ziyu AU - Tian Z AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Yu, Jinhong AU - Yu J AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Ji, Zengxuan AU - Ji Z AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Fu, Luwei AU - Fu L AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Liu, Haiyan AU - Liu H AD - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. FAU - Cai, Yuepiao AU - Cai Y AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Dai, Shijie AU - Dai S AUID- ORCID: 0009-0000-2710-0966 AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. LA - eng PT - Journal Article DEP - 20260530 PL - United States TA - Bioconjug Chem JT - Bioconjugate chemistry JID - 9010319 RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Exenatide/chemistry/therapeutic use/pharmacokinetics/pharmacology MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/chemistry/therapeutic use/pharmacokinetics/pharmacology MH - Humans MH - *Immunoglobulin G/chemistry/immunology MH - Mice MH - *Immunoglobulin Fc Fragments/chemistry/immunology MH - Semaglutide MH - Structure-Activity Relationship MH - Male EDAT- 2026/05/31 05:30 MHDA- 2026/06/17 06:31 CRDT- 2026/05/30 09:33 PHST- 2026/06/17 06:31 [medline] PHST- 2026/05/31 05:30 [pubmed] PHST- 2026/05/30 09:33 [entrez] AID - 10.1021/acs.bioconjchem.6c00218 [doi] PST - ppublish SO - Bioconjug Chem. 2026 Jun 17;37(6):1292-1302. doi: 10.1021/acs.bioconjchem.6c00218. Epub 2026 May 30. PMID- 42214559 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260617 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - Glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in adults with type 2 diabetes and atrial fibrillation: a multicenter comparative effectiveness cohort study of cardiovascular and arrhythmic outcomes. PG - 113346 LID - S0168-8227(26)00266-4 [pii] LID - 10.1016/j.diabres.2026.113346 [doi] AB - AIMS: To compare glucagon-like peptide-1 receptor agonists (GLP-1RA) with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) for cardiovascular, atrial fibrillation (AF) disease course, and safety outcomes in adults with concurrent AF and type 2 diabetes. METHODS: Retrospective propensity-score-matched cohort study using the TriNetX Research Network (2016 - 2024). A new-user, active-comparator design identified adults with concurrent AF and type 2 diabetes initiating GLP-1RA or SGLT-2i. Patients were 1:1 matched on demographic, clinical, laboratory, and medication covariates. Hazard ratios (HRs) were estimated using Cox proportional hazards regression. The Benjamini-Hochberg procedure controlled the false discovery rate, and E-values quantified robustness to unmeasured confounding. RESULTS: After matching, 18,035 GLP-1RA users were compared with 18,035 SGLT-2i users (mean age 67.4 years; 52.2% male, 47.8% female). At 365 days, GLP-1RA was associated with lower all-cause mortality (HR 0.64, 95% CI 0.57 - 0.71), hospitalization (0.88, 0.84 - 0.92), 3-point MACE (0.78, 0.71 - 0.86), AF progression (0.94, 0.90 - 0.98), AF ablation (0.81, 0.70 - 0.94), and cardioversion (0.79, 0.70 - 0.90). Effects were consistent across age and body mass index subgroups. E-values ranged 1.5 - 2.5. CONCLUSION: Over 1 year, GLP-1RA initiation was associated with lower risks of mortality, hospitalization, atherosclerotic events, and adverse AF disease-course outcomes than SGLT-2i in adults with concurrent AF and T2D, with the established SGLT-2i benefits for heart failure and CKD remaining the basis for class choice in those subpopulations. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Islam, Md Mohaimenul AU - Islam MM AD - Division of Outcomes and Practice Advancement, College of Pharmacy and Pharmaceutical Science, University at Buffalo, Buffalo, NY, USA; Institute for Artificial Intelligence and Data Science, University at Buffalo, NY, USA. Electronic address: mmohaim@buffalo.edu. FAU - Okere, Arinze Nkemdirim AU - Okere AN AD - Division of Outcomes and Practice Advancement, College of Pharmacy and Pharmaceutical Science, University at Buffalo, Buffalo, NY, USA; Institute for Artificial Intelligence and Data Science, University at Buffalo, NY, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260528 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Atrial Fibrillation/drug therapy/complications MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Retrospective Studies MH - Middle Aged MH - Comparative Effectiveness Research MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Atrial fibrillation OT - Cardiovascular outcomes OT - Comparative effectiveness OT - GLP-1 receptor agonist OT - SGLT-2 inhibitor OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/30 00:33 MHDA- 2026/06/12 13:02 CRDT- 2026/05/29 19:32 PHST- 2026/05/05 00:00 [received] PHST- 2026/05/23 00:00 [revised] PHST- 2026/05/26 00:00 [accepted] PHST- 2026/06/12 13:02 [medline] PHST- 2026/05/30 00:33 [pubmed] PHST- 2026/05/29 19:32 [entrez] AID - S0168-8227(26)00266-4 [pii] AID - 10.1016/j.diabres.2026.113346 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113346. doi: 10.1016/j.diabres.2026.113346. Epub 2026 May 28. PMID- 42213027 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260803 IS - 2162-5239 (Electronic) IS - 0094-6354 (Linking) VI - 94 IP - 3 DP - 2026 Jun 1 TI - AANA Journal Course-GLP-1 Receptor Agonists: What CRNAs Need to Know About Their Expanding Role. PG - 225-233 LID - 10.70278/AANAJ/.0000001093 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were developed to treat type 2 diabetes mellitus and later became widely used for the management of obesity. Recent evidence includes off-label uses for substance use disorders; nicotine and alcohol dependence; neurodegenerative diseases; and cardiovascular, kidney, and liver diseases. Certified registered nurse anesthetists (CRNAs) are likely to encounter patients using GLP-1RAs for both Food and Drug Administration-approved and nontraditional purposes. This review explores the pharmacology and mechanisms of action of GLP-1RAs, with a focus on their relevance in the perioperative period. It covers their effects on blood glucose control, gastric motility, and central nervous system pathways. Special attention is given to delayed gastric emptying, concerns about pulmonary aspiration, and the metabolic benefits of glucose-dependent insulin secretion and reduced blood glucose fluctuations. Current professional guidelines emphasize personalized, patient-centered perioperative care. The increasing use of GLP-1RAs, combined with more off-label prescribing and unregulated peptide use, emphasizes the need for thorough preoperative screening, clear medication reconciliation, and effective interdisciplinary communication. As more evidence emerges, CRNAs must remain vigilant while recognizing that the expanding role of GLP-1RAs is important for optimizing perioperative safety and achieving optimal patient outcomes in modern anesthesia practice. CI - Copyright (c) 2026 by the American Association of Nurse Anesthesiology. FAU - Davies, Adam AU - Davies A AD - Assistant Professor at the University of South Florida, Tampa, Florida. FAU - Maldonado, Karla AU - Maldonado K AD - Assistant Professor at the University of South Florida, Tampa, Florida. FAU - Diaz, Mayte AU - Diaz M AD - Assistant Professor at the University of South Florida, Tampa, Florida. FAU - Rawson, Eleanor AU - Rawson E AD - Assistant Professor at the University of South Florida, Tampa, Florida. FAU - Canale, Michelle AU - Canale M AD - Assistant Professor at the University of South Florida, Tampa, Florida. FAU - Zhang, Sarah AU - Zhang S AD - Associate Professor at the University of South Florida, Tampa, Florida. FAU - Dabney, Cynthia AU - Dabney C AD - Assistant Professor at the University of South Florida, Tampa, Florida. Email: Cdabney1@usf.edu. LA - eng PT - Journal Article PT - Review PL - United States TA - AANA J JT - AANA journal JID - 0431420 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Nurse Anesthetists/education MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy MH - United States MH - *Nurse's Role OTO - NOTNLM OT - anesthesia OT - glucagon-like peptide-1 OT - glucagon-like peptide-1 receptor agonist OT - guidelines OT - off-label use COIS- Name: Adam Davies, DNP, CRNA, APRN; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. Name: Karla Maldonado, DrAP, CRNA, APRN, FAANA; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. Name: Mayte Diaz, DNP, CRNA, APRN; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. Name: Eleanor Rawson, DNP, CRNA, APRN, FAANA; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. Name: Michelle Canale, DNP, CRNA, APRN, FAANA; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None Name: Sarah Zhang, PhD, CRNA, APRN; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None Name: Cynthia Dabney, PhD, DNP, CRNA; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author; she is the corresponding author for this article. Disclosures: None.The authors did not discuss off-label use within the article. Disclosure statements are available upon request. EDAT- 2026/05/29 15:42 MHDA- 2026/05/29 15:43 CRDT- 2026/05/29 10:33 PHST- 2026/05/29 15:43 [medline] PHST- 2026/05/29 15:42 [pubmed] PHST- 2026/05/29 10:33 [entrez] AID - 10.70278/AANAJ/.0000001093 [doi] PST - ppublish SO - AANA J. 2026 Jun 1;94(3):225-233. doi: 10.70278/AANAJ/.0000001093. PMID- 42209408 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Risk of Psychiatric Worsening With GLP-1 Receptor Agonist Use in Patients With Type 2 Diabetes and Treated Depression. PG - 7048-7057 LID - 10.1111/dom.70927 [doi] AB - AIMS: To compare 1-year psychiatric outcomes after GLP-1 receptor agonist (GLP-1 RA) versus sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation in patients with type 2 diabetes and treated depression. MATERIALS AND METHODS: We conducted a retrospective active-comparator, new-user cohort study using electronic health records from the TriNetX network. Patients with type 2 diabetes, depression and antidepressant treatment within 6 months before index were included. After 1:1 propensity score matching, outcomes were compared using Cox proportional hazards models. Primary outcomes were suicidality and antipsychotic use. All-cause mortality was a secondary outcome. RESULTS: After propensity score matching, 34 761 patients were included in each group. GLP-1 RA initiation was not associated with a higher risk of suicidality than SGLT2i initiation (hazard ratio [HR] 0.88, 95% CI 0.74-1.05). GLP-1 RA initiation was associated with a lower risk of antipsychotic use (HR 0.86, 95% CI 0.82-0.90; absolute risk difference -1.4%) and lower all-cause mortality (HR 0.64, 95% CI 0.58-0.71). Findings were consistent across sensitivity analyses. CONCLUSIONS: In patients with type 2 diabetes and treated depression, we did not detect increased short-term documented suicidality after GLP-1 RA initiation compared with SGLT2i initiation and observed less subsequent treatment intensification. These observational findings suggest that treated depression alone should not lead to routine avoidance of GLP-1 RAs in this population. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chang, Yu AU - Chang Y AUID- ORCID: 0000-0001-9954-921X AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hsieh, Ming-Hong AU - Hsieh MH AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Ju, Po-Chung AU - Ju PC AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chang, Cheng-Chen AU - Chang CC AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2026-A-006/Chung Shan Medical University Hospital/ PT - Journal Article DEP - 20260528 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Antidepressive Agents) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/complications MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Depression/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Antidepressive Agents/therapeutic use MH - Aged MH - Antipsychotic Agents/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Suicide/statistics & numerical data/psychology PMC - PMC13341328 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - real-world evidence OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/05/29 15:45 MHDA- 2026/07/08 12:55 PMCR- 2026/07/08 CRDT- 2026/05/28 22:02 PHST- 2026/05/18 00:00 [revised] PHST- 2026/04/16 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/07/08 12:55 [medline] PHST- 2026/05/29 15:45 [pubmed] PHST- 2026/05/28 22:02 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70927 [pii] AID - 10.1111/dom.70927 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7048-7057. doi: 10.1111/dom.70927. Epub 2026 May 28. PMID- 42209267 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - GIP in Cardiovascular and Kidney Disease: From Physiology to Pharmacology. PG - 6509-6532 LID - 10.1111/dom.70888 [doi] AB - AIMS: To provide a comprehensive overview of the cardiovascular and renal effects of glucose-dependent insulinotropic polypeptide (GIP) by integrating its physiological role with recent human trial data on tirzepatide, the first dual GIP and glucagon-like peptide-1 (GLP-1) receptor agonist. MATERIALS AND METHODS: This narrative review synthesizes key physiological data of native GIP across tissues-especially the heart, vessels, kidney, and adipose tissue-and summarizes clinical evidence from the SUMMIT and the SURPASS programmes. Central to this review is the analysis of the SURPASS-CVOT trial, which compared the cardiovascular protective effects of tirzepatide versus dulaglutide in individuals with type 2 diabetes and established atherosclerotic CV disease. RESULTS: Preclinical data regarding GIP receptor modulation in the cardiorenal district remains controversial, a contention partially reflected in recent clinical evidence. Within the innovative framework of SURPASS-CVOT, tirzepatide established non-inferiority to dulaglutide for 3-point MACE while slowing eGFR decline in participants with high-risk chronic kidney disease. Furthermore, the SUMMIT trial demonstrated that in individuals with obesity and heart failure (HF) with preserved ejection fraction, tirzepatide reduced the composite endpoint of CV death or worsening HF events, regardless of baseline kidney function. Despite these advancements, knowledge gaps persist regarding the potential synergistic cardiorenal benefits of combining dual incretin agonism with sodium-glucose cotransporter-2 inhibitors. CONCLUSION: While adding GIP receptor agonism to GLP-1 receptor agonism clearly improves cardiometabolic risk factors, its precise and independent contribution to long-term CV and renal protection remains to be fully elucidated. Ongoing outcome trials, such as SURMOUNT-MMO and TREASURE-CKD, will provide additional insights into these effects. Furthermore, emerging strategies-including combining GIP receptor antagonism with GLP-1 receptor agonism or moving toward triple agonism-represent promising alternatives to favorably modify the multiple determinants of cardiometabolic risk. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - De Fano, Michelantonio AU - De Fano M AUID- ORCID: 0000-0002-2657-5991 AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Haurum, Line L AU - Haurum LL AD - Clinical and Translational Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Schwarz, Christine R AU - Schwarz CR AD - Clinical and Translational Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Porcellati, Francesca AU - Porcellati F AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Andersen, Andreas AU - Andersen A AUID- ORCID: 0000-0001-8190-5140 AD - Clinical and Translational Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. LA - eng PT - Journal Article PT - Review DEP - 20260528 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/pharmacology/therapeutic use/physiology/metabolism MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Cardiovascular Diseases/metabolism/prevention & control/drug therapy MH - Receptors, Gastrointestinal Hormone/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Incretins/therapeutic use/pharmacology MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/pharmacology MH - Animals MH - Kidney/drug effects/metabolism MH - Immunoglobulin Fc Fragments/therapeutic use/pharmacology MH - *Diabetic Nephropathies/drug therapy/prevention & control MH - Recombinant Fusion Proteins PMC - PMC13341370 OTO - NOTNLM OT - GIP OT - cardiovascular disease OT - incretin therapy OT - obesity therapy OT - type 2 diabetes COIS- M.d.F. has received honoraria for lecturing and travel grants from AstraZeneca, Eli Lilly, Novo Nordisk, Sanofi; L.L.H. has no conflict of interest; C.R.S. reports personal fees and/or institutional research support from Novo Nordisk and Eli Lilly, outside the submitted work; F.P. receives clinical trial funding, advisory board and lecture fees from Abbott, AstraZeneca, Eli Lilly, Novo Nordisk, Roche, Sanofi; A.A. has served on an event adjudication committee for Amylyx Pharmaceuticals and as consultant to, received lecture fees from and served on advisory boards for Eli Lilly and Novo Nordisk. EDAT- 2026/05/29 15:46 MHDA- 2026/07/08 18:52 PMCR- 2026/07/08 CRDT- 2026/05/28 21:52 PHST- 2026/05/01 00:00 [revised] PHST- 2026/03/03 00:00 [received] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/07/08 18:52 [medline] PHST- 2026/05/29 15:46 [pubmed] PHST- 2026/05/28 21:52 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70888 [pii] AID - 10.1111/dom.70888 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6509-6532. doi: 10.1111/dom.70888. Epub 2026 May 28. PMID- 42209204 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Comparative Effects of Individual Glucagon-Like Peptide-1 Receptor Agonist-Based Medications on Direct Measurement of Body Composition Among Adults With Overweight or Obesity With or Without Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. PG - 7018-7038 LID - 10.1111/dom.70884 [doi] AB - AIM: To compare the effects of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) on direct body composition among adults with overweight or obesity, with or without type 2 diabetes (T2D). METHODS: We systematically searched six electronic databases and grey literature from inception to 3 November 2025, to identify all randomised controlled trials (RCTs) that investigated individual GLP-1RAs on change in body composition from baseline among adults with overweight or obesity with or without T2D, without language restrictions. The main outcomes included total body fat (%), fat mass (kg), visceral adipose tissue (VAT) area (cm(2)), subcutaneous adipose tissue (SAT) area (cm(2)), liver fat content (%), total lean tissue (%) and lean mass (kg). A frequentist network meta-analysis was employed using a random-effects model and reported as standardised mean differences (SMDs). Certainty of evidence was appraised using the Confidence in Network Meta-Analysis. RESULTS: We identified 43 unique RCTs with 3379 participants that compared 17 different interventions or dosages with a control group. Regarding variations in treatment benefits on body composition, GLP-1RAs subcutaneously were more efficacious than the control group in decreasing total body fat, fat mass, VAT, SAT and liver fat from baseline. No significant differences for change in total lean tissue were observed. However, subcutaneously, liraglutide 1.8 mg/day, semaglutide 1.0 mg-weekly and tirzepatide 15 mg-weekly (SMDs ranged from -1.09 to -0.50) significantly decreased lean mass from baseline. CONCLUSIONS: GLP-1RAs substantially improve body composition-related excess adiposity, but unfavourable effects on lean mass were observed, particularly at high doses. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Wachiraphansakul, Nuttaya AU - Wachiraphansakul N AUID- ORCID: 0000-0003-1623-3071 AD - Department of Internal Medicine, Lampang Hospital, Lampang, Thailand. FAU - Vongchaiudomchoke, Thanawat AU - Vongchaiudomchoke T AUID- ORCID: 0000-0002-1007-907X AD - Department of Internal Medicine, Lampang Hospital, Lampang, Thailand. FAU - Manosroi, Worapaka AU - Manosroi W AUID- ORCID: 0000-0002-3007-3951 AD - Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Ruengorn, Chidchanok AU - Ruengorn C AUID- ORCID: 0000-0001-7927-1425 AD - Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. FAU - Noppakun, Kajohnsak AU - Noppakun K AUID- ORCID: 0000-0002-5783-8766 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Ngamvichchukorn, Tanun AU - Ngamvichchukorn T AUID- ORCID: 0000-0003-0119-4647 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Division of Nephrology, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand. FAU - Sood, Manish M AU - Sood MM AUID- ORCID: 0000-0002-9146-2344 AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Thavorn, Kednapa AU - Thavorn K AUID- ORCID: 0000-0003-4738-8447 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Institute of Clinical and Evaluative Sciences, ICES uOttawa, Ottawa, Ontario, Canada. AD - School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Hutton, Brian AU - Hutton B AUID- ORCID: 0000-0001-5662-8647 AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Institute of Clinical and Evaluative Sciences, ICES uOttawa, Ottawa, Ontario, Canada. AD - School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Nochaiwong, Surapon AU - Nochaiwong S AUID- ORCID: 0000-0003-1100-7171 AD - Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. LA - eng GR - Chiang Mai University/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260528 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Body Composition/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Liraglutide MH - Adult OTO - NOTNLM OT - body composition OT - fat distribution OT - glucagon-like peptide-1 OT - muscle mass OT - obesity OT - overweight EDAT- 2026/05/29 15:46 MHDA- 2026/07/08 12:56 CRDT- 2026/05/28 21:43 PHST- 2026/05/06 00:00 [revised] PHST- 2026/02/24 00:00 [received] PHST- 2026/05/07 00:00 [accepted] PHST- 2026/07/08 12:56 [medline] PHST- 2026/05/29 15:46 [pubmed] PHST- 2026/05/28 21:43 [entrez] AID - 10.1111/dom.70884 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7018-7038. doi: 10.1111/dom.70884. Epub 2026 May 28. PMID- 42208956 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - Beyond weight loss: multisystem benefits of obesity medications. PG - 678-692 LID - S2213-8587(26)00100-2 [pii] LID - 10.1016/S2213-8587(26)00100-2 [doi] AB - Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-topiramate, naltrexone-bupropion, glucagon-like peptide-1 (GLP-1) receptor agonists (eg, liraglutide, semaglutide, subcutaneously and orally), and newer GLP-1 receptor agonist-based agents (eg, tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). We evaluated the effects of obesity medications across major obesity-related conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea syndrome, polycystic ovary syndrome (recently named polyendocrine metabolic ovarian syndrome), osteoarthritis, muscle mass, depression, quality of life, and food cravings, along with binge-eating disorders, substance use disorders, and neurodegenerative diseases. Overall, GLP-1-based and multiagonist therapies show beneficial effects across these comorbid conditions. While many benefits of obesity medications are mediated by weight loss, accumulating evidence indicates important weight loss-independent effects, particularly with GLP-1 receptor agonist-based therapies. A broader understanding of these pleiotropic effects is essential to inform personalised obesity management and optimise long-term clinical outcomes. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Savas, Mesut AU - Savas M AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.savas@erasmusmc.nl. FAU - Kuckuck, Susanne AU - Kuckuck S AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. FAU - Boon, Mariette R AU - Boon MR AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. FAU - van Rossum, Elisabeth F C AU - van Rossum EFC AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. LA - eng PT - Journal Article PT - Review DEP - 20260528 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/complications MH - *Anti-Obesity Agents/therapeutic use MH - *Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Semaglutide MH - Cardiovascular Diseases/drug therapy COIS- Declaration of interests MS received honoraria for lectures and educational events from Obesitas Platform-MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, BSL, Medische Scholing, and MedClass-Boehringer Ingelheim; and support for attending a meeting from Rhythm Pharmaceuticals. MRB received honoraria for lectures and educational events from Obesitas Platform-MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, Goodlife, and Eli Lilly; support for attending a meeting from Rhythm Pharmaceuticals; and receives royalties from Ambo Anthos for a book for lay and professional audiences: FAT, the secret organ (Dutch: VET Belangrijk, 2019; VET Belangrijk 2.0, 2026). EFCvR reports speaker fees from the Dutch Obesity Academy, Medische Scholing, Medscape-WebMD, Radcliffe CVRM, BSL, and Prevents (most payments to institution); was involved in (primarily providing medical care for) clinical trials funded by Rhythm Pharmaceuticals (payments to institution; present Review is independent of these trials); serves as a member of the guideline committee on obesity pharmacotherapy of the Endocrine Society; chaired the Dutch multidisciplinary guideline on overweight and obesity in adults (2023) and Partnership Overweight Netherlands; was the clinical lead of focus area obesity, diabetes, nutrition, and metabolism of the European Society of Endocrinology (2021-25); and received royalties from Ambo Anthos for the book: Fat, the secret organ, 2020 (Dutch: VET Belangrijk, 2019; VET Belangrijk 2.0, 2026). MRB and EFCVR are co-developers of the screening and monitoring tool CheckCausesObesity.com. SK declares no competing interests. EDAT- 2026/05/29 15:45 MHDA- 2026/07/15 12:35 CRDT- 2026/05/28 20:08 PHST- 2026/01/16 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/07/15 12:35 [medline] PHST- 2026/05/29 15:45 [pubmed] PHST- 2026/05/28 20:08 [entrez] AID - S2213-8587(26)00100-2 [pii] AID - 10.1016/S2213-8587(26)00100-2 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):678-692. doi: 10.1016/S2213-8587(26)00100-2. Epub 2026 May 28. PMID- 42206237 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK Signaling Pathway. PG - 599539 LID - 10.2147/DDDT.S599539 [doi] LID - 599539 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for periodontitis, often leading to exacerbated alveolar bone loss. Ferroptosis, an iron-dependent regulated cell death pathway, contributes to osteoblast dysfunction under diabetic conditions. The non-canonical Wnt5a/Ror2 pathway is pivotal in inflammation and bone metabolism. Semaglutide, a long-acting GLP-1 receptor agonist, may modulate this pathway and protect osteoblasts from ferroptosis, however, its role in diabetic periodontitis remains unclear. METHODS: MC3T3-E1 osteoblasts were exposed to high glucose plus palmitic acid (HGHP) to mimic a diabetic microenvironment. The effects of Semaglutide on osteoblast proliferation, migration, differentiation, mineralization, and ferroptosis were assessed using EDU, Transwell, ALP and ARS staining, qPCR, Western blotting, ROS, Fe(2)(+), and lipid peroxidation assays. Mechanistic involvement of Wnt5a/Ror2/p38 MAPK signaling was examined using Wnt5a siRNA and a p38 MAPK agonist. In vivo, T2DM mice with ligature-induced periodontitis were treated with semaglutide; alveolar bone and ferroptosis-related markers were assessed by H&E, immunohistochemistry (OPN, GPX4), and 4-HNE immunofluorescence. RESULTS: HGHP induced osteoblast ferroptosis, increased oxidative stress, and impaired osteogenic function. Semaglutide restored proliferation and osteogenic capacity and attenuated oxidative stress and ferroptosis. Wnt5a was upregulated by HGHP; its silencing reduced ferroptosis and improved osteogenesis. Semaglutide suppressed HGHP-induced Wnt5a/Ror2/p38 MAPK activation, whereas p38 activation blunted its protective effects. In T2DM periodontitis mice, semaglutide reduced periodontal inflammation and osteoblast ferroptosis. CONCLUSION: Semaglutide mitigates HGHP-induced osteoblast ferroptosis and improves osteogenic function via the Wnt5a/Ror2/p38 MAPK pathway, supporting its potential in diabetic periodontitis. CI - (c) 2026 Zhang et al. FAU - Zhang, Zhen AU - Zhang Z AD - School of Stomatology, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Niu, Delong AU - Niu D AD - Department of Stomatology, Lanzhou Petrochemical General Hospital (The Fourth affiliated Hospital of Gansu University of Chinese Medicine), Lanzhou, 730060, People's Republic of China. FAU - Qiu, Wenjie AU - Qiu W AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Feng, Haoyu AU - Feng H AD - School of Stomatology, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Jia, Lurong AU - Jia L AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Zhou, Wenjuan AU - Zhou W AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. LA - eng PT - Journal Article DEP - 20260522 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 53AXN4NNHX (Semaglutide) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - 0 (Wnt-5a Protein) RN - EC 2.7.10.1 (Ror2 protein, mouse) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors) RN - 0 (Wnt5a protein, mouse) SB - IM MH - Semaglutide MH - Animals MH - p38 Mitogen-Activated Protein Kinases/metabolism/antagonists & inhibitors MH - Wnt-5a Protein/metabolism/antagonists & inhibitors MH - Mice MH - *Osteoblasts/drug effects/metabolism/pathology MH - *Ferroptosis/drug effects MH - *Periodontitis/drug therapy/metabolism/pathology MH - *Glucagon-Like Peptides/pharmacology MH - Receptor Tyrosine Kinase-like Orphan Receptors/metabolism/antagonists & inhibitors MH - Mice, Inbred C57BL MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Cells, Cultured MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Signal Transduction/drug effects PMC - PMC13209148 OTO - NOTNLM OT - Wnt5a/Ror2 OT - diabetic periodontitis OT - ferroptosis OT - p38 MAPK pathway OT - semaglutide COIS- The authors declare no competing interests. EDAT- 2026/05/28 06:33 MHDA- 2026/05/28 06:34 PMCR- 2026/05/22 CRDT- 2026/05/28 04:45 PHST- 2026/03/02 00:00 [received] PHST- 2026/05/08 00:00 [accepted] PHST- 2026/05/28 06:34 [medline] PHST- 2026/05/28 06:33 [pubmed] PHST- 2026/05/28 04:45 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - 599539 [pii] AID - 10.2147/DDDT.S599539 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 May 22;20:599539. doi: 10.2147/DDDT.S599539. eCollection 2026. PMID- 42203003 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260706 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 459 DP - 2026 Sep 15 TI - GLP-1 receptor agonists associated with better cardiovascular outcomes in obese or diabetic patients with elevated Lp(a) levels: A Multicenter retrospective study. PG - 134588 LID - S0167-5273(26)00437-7 [pii] LID - 10.1016/j.ijcard.2026.134588 [doi] AB - BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a well-established, genetically mediated risk factor for atherosclerotic cardiovascular disease (ASCVD), yet effective therapies targeting Lp(a) remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiometabolic benefits in high-risk populations, but their impact among patients with elevated Lp(a) levels is not well defined. METHODS: We conducted a retrospective cohort study to evaluate cardiovascular outcomes associated with GLP-1RA therapy in adults with Lp(a) >50 mg/dL and comorbid obesity or type 2 diabetes. Patients were categorized into GLP-1RA users versus non-users and matched 1:1 using propensity scores based on demographics, cardiovascular risk factors, and baseline comorbidities. The primary outcome was all-cause mortality; secondary outcomes included major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, and coronary revascularization). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models. RESULTS: Among 24,185 eligible patients, 3791 received a GLP-1RA. After matching, 3310 patients remained in each cohort with balanced baseline characteristics. Over a median follow-up of approximately two years, GLP-1RA use was associated with significantly lower all-cause mortality (HR 0.66, 95% CI 0.48-0.90) and reduced MACE (HR 0.68, 95% CI 0.60-0.76). Individual components, including myocardial infarction, ischemic stroke, and cardiovascular death, were also significantly decreased among GLP-1RA users. CONCLUSION: In patients with elevated Lp(a), GLP-1RA therapy was associated with substantial reductions in mortality and cardiovascular events. These findings suggest potential cardioprotective effects of GLP-1RAs in a high-risk population with limited therapeutic options and support further prospective evaluation. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Mahmoud, Ahmed K AU - Mahmoud AK AD - Internal Medicine Department, Boston Medical Center-Brighton, Boston University School of Medicine, Boston, MA, USA; Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. Electronic address: Mahmoud.ahmed3@mayo.edu. FAU - Sheashaa, Hesham AU - Sheashaa H AD - Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Killian, Michael AU - Killian M AD - Department of General Internal Medicine, Naas General Hospital, Naas, Co. Kildare, Ireland. FAU - Awad, Kamal AU - Awad K AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Mahmoud, Alaa AU - Mahmoud A AD - Internal Medicine Department, Tanta University Faculty of Medicine, Gharbia, Egypt. FAU - Farina, Juan AU - Farina J AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Kamel, Ibrahim AU - Kamel I AD - Internal Medicine Department, Boston Medical Center-Brighton, Boston University School of Medicine, Boston, MA, USA. FAU - Horn, Benjamin AU - Horn B AD - Cardiovascular Medicine Department, Boston Medical Center-South, Boston University School of Medicine, Boston, MA, USA. FAU - Simper, David AU - Simper D AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Lester, Steven J AU - Lester SJ AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Ayoub, Chadi AU - Ayoub C AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Cardiovascular Medicine Department, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260526 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Lipoprotein(a)) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - *Obesity/blood/drug therapy MH - Male MH - *Lipoprotein(a)/blood MH - Middle Aged MH - *Cardiovascular Diseases/blood/drug therapy/epidemiology MH - Aged MH - Cohort Studies MH - Follow-Up Studies MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use MH - Biomarkers/blood OTO - NOTNLM OT - Diabetes OT - GLP-1 OT - Lipoprotein (a) OT - Lp(a) OT - MACE OT - Myocardial infarction OT - Obesity OT - Stroke COIS- Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article. EDAT- 2026/05/28 00:29 MHDA- 2026/06/15 11:32 CRDT- 2026/05/27 19:33 PHST- 2026/04/10 00:00 [received] PHST- 2026/05/12 00:00 [revised] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/06/15 11:32 [medline] PHST- 2026/05/28 00:29 [pubmed] PHST- 2026/05/27 19:33 [entrez] AID - S0167-5273(26)00437-7 [pii] AID - 10.1016/j.ijcard.2026.134588 [doi] PST - ppublish SO - Int J Cardiol. 2026 Sep 15;459:134588. doi: 10.1016/j.ijcard.2026.134588. Epub 2026 May 26. PMID- 42202888 OWN - NLM STAT- MEDLINE DCOM- 20260607 LR - 20260607 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - Comprehensive drug safety assessment of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors: A Danish population-based active comparator new user cohort study. PG - 113341 LID - S0168-8227(26)00261-5 [pii] LID - 10.1016/j.diabres.2026.113341 [doi] AB - AIMS: To perform active safety monitoring of newer glucose-lowering therapies. METHODS: Using Danish nationwide registries, we conducted an active comparator new user cohort study comparing adverse events among initiators of sodium-glucose co-transporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1-RAs), and dipeptidyl peptidase 4 inhibitors (DPP4is). RESULTS: We identified 49 365 SGLT2i, 33 018 GLP1-RA, and 50 531 DPP4i initiators. Of 43 associations identified, we disregarded obesity-related signals (N = 2) and observed beneficial effects (N = 7). SGLT2i initiators had higher risks of phimosis (vs. GLP1-RA: hazard ratio [HR] 1.69, 95% compatibility intervals [CI] 1.42-2.02; vs. DPP4i: HR 2.19, 95% CI 1.84-2.59) and secondary polycythaemia (vs. GLP1-RA: HR 2.67, 95% CI 1.62-4.38; vs. DPP4i: HR 1.63, 95% CI 1.14-2.32). DPP4i initiators had increased risk of bacterial intestinal infections (vs. SGLT2i: HR 1.56, 95% CI 1.18-2.08; vs. GLP1-RA: HR 2.08, 95% CI 1.49-2.94) and anaemia (vs. SGLT2i: HR 2.00, 95% CI 1.22-3.23; vs. GLP1-RA: HR 1.92, 95% CI 1.18-3.23). GLP1-RA initiators had a near-immediate elevated risk of uterine cancer (vs. SGLT2i: HR 1.82, 95% CI 1.20-2.78; vs. DPP4i: HR 1.94, 95% CI 1.19-3.16). CONCLUSION: While some signals likely reflect residual confounding, several signals - particularly those related to infections and cancer - warrant further investigation. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Lund, Lars Christian AU - Lund LC AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Simonsen, Emma AU - Simonsen E AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. Electronic address: ebjsimonsen@health.sdu.dk. FAU - Pottegard, Anton AU - Pottegard A AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article DEP - 20260526 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Female MH - Denmark/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cohort Studies MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Registries MH - Adult OTO - NOTNLM OT - Active comparator new user design OT - Drug safety OT - Glucose-lowering therapies OT - Pharmacoepidemiology COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Lars Christian Lund has taught epidemiological methods at Novo Nordisk, with all funds paid to the institution where he is employed (no personal fees). Anton Pottegard reports participation in regulator-mandated phase IV studies funded by AbbVie, Alcon, Almirall, Astellas, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, LEO Pharma, Novo Nordisk, Pfizer, and Servier, and on sponsor-initiated research projects with Novo Nordisk, all with funds paid to the institution where he is employed (no personal fees).Emma Simonsen reports no conflicts of interest. EDAT- 2026/05/28 00:30 MHDA- 2026/06/07 13:43 CRDT- 2026/05/27 19:32 PHST- 2026/04/17 00:00 [received] PHST- 2026/05/20 00:00 [revised] PHST- 2026/05/25 00:00 [accepted] PHST- 2026/06/07 13:43 [medline] PHST- 2026/05/28 00:30 [pubmed] PHST- 2026/05/27 19:32 [entrez] AID - S0168-8227(26)00261-5 [pii] AID - 10.1016/j.diabres.2026.113341 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113341. doi: 10.1016/j.diabres.2026.113341. Epub 2026 May 26. PMID- 42201355 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20261008 IS - 1435-702X (Electronic) IS - 0721-832X (Linking) VI - 264 IP - 9 DP - 2026 Sep TI - Semaglutide and risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) in type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 2611-2621 LID - 10.1007/s00417-026-07291-4 [doi] AB - BACKGROUND: The use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs) has expanded dramatically worldwide, with semaglutide being one of the most widely utilized agents. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with GLP-1RAs use from emerging pharmacovigilance data. This systematic review and meta-analysis sought to evaluate the risk of NAION in patients with type 2 diabetes mellitus (T2DM). METHODS: A literature search was made up to September 2025 (PROSPERO: CRD420251155026). Results were synthesized following the PRISMA guidelines and are presented as pooled Hazard Ratios (HR) with 95% confidence intervals (CI). RESULTS: Twelve studies were included; eight retrospective cohorts (14,255,247 participants) were meta-analyzed, with a mean age of 59.3 +/- 15.9 years and 32.7% males. Patients with T2DM using semaglutide compared to non-GLP-1RAs showed an increased risk of NAION at 1-year follow-up with a pooled HR of 3.36 (95% CI: 1.44-7.84; p < 0.001; I(2) = 97%). At 2-year follow-up, the pooled HR was 2.37 (95% CI: 1.46-3.85; p < 0.001; I(2) = 0%). The 3-year risk after the sensitivity analysis showed a pooled HR of 2.37 (95% CI: 1.45-3.87, p < 0.001; I(2) = 28%), and the 5-year pooled HR was 2.37 (95% CI: 0.62-3.92; p < 0.001; I(2) = 0%). CONCLUSION: This meta-analysis indicates a significant association between semaglutide use and NAION in patients with T2DM compared to non-GLP-1RAs, with this association remaining significant even after 5-years of semaglutide use. CI - (c) 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Lampsas, Stamatios AU - Lampsas S AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Agapitou, Chrysa AU - Agapitou C AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Oikonomou, Evangelos AU - Oikonomou E AD - Third Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, "Sotiria" General Hospital, Athens, 11527, Greece. FAU - Siasos, Gerasimos AU - Siasos G AD - Third Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, "Sotiria" General Hospital, Athens, 11527, Greece. AD - Cardiovascular Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA. FAU - Theodossiadis, Panagiotis AU - Theodossiadis P AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Tsivgoulis, Georgios AU - Tsivgoulis G AD - Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, 12462, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - Second Department of Internal Medicine, Research Institute and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, 12462, Greece. FAU - Chatziralli, Irini AU - Chatziralli I AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. eirchat@yahoo.gr. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260527 PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis/etiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: The study does not involve any human subjects or animal and does not require disclosure to the rights. Competing interests: The authors declare no competing interests. EDAT- 2026/05/27 12:36 MHDA- 2026/09/15 18:07 CRDT- 2026/05/27 11:03 PHST- 2026/01/19 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/04/24 00:00 [revised] PHST- 2026/09/15 18:07 [medline] PHST- 2026/05/27 12:36 [pubmed] PHST- 2026/05/27 11:03 [entrez] AID - 10.1007/s00417-026-07291-4 [pii] AID - 10.1007/s00417-026-07291-4 [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 2026 Sep;264(9):2611-2621. doi: 10.1007/s00417-026-07291-4. Epub 2026 May 27. PMID- 42200664 OWN - NLM STAT- MEDLINE DCOM- 20261016 LR - 20261016 IS - 1940-5480 (Electronic) IS - 1067-151X (Linking) VI - 34 IP - 21 DP - 2026 Nov 1 TI - Effect of Glucagon-Like Peptide-1 Receptor Agonist Use on Fusion Outcomes After First Metatarsophalangeal Arthrodesis in Patients With Type 2 Diabetes Mellitus. PG - e3108-e3114 LID - 10.5435/JAAOS-D-26-00153 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) influence bone metabolism by promoting formation and reducing resorption in patients with type 2 diabetes mellitus (T2DM). Although studied in hindfoot and midfoot fusion, their effect on forefoot arthrodesis remains unknown. This study evaluated 1-year fusion and complication rates after first metatarsophalangeal joint (MTPJ) arthrodesis in patients prescribed GLP-1 RAs compared with nonusers, with focused analysis in diabetics. METHODS: A retrospective cohort study was conducted using the TriNetX research network. Adults undergoing first MTPJ arthrodesis were identified and stratified by GLP-1 RA use within 1 year before surgery. Glucagon-like peptide-1 (GLP-1) users were compared with nonusers, using a subgroup analysis among patients with T2DM. Propensity score matching (1:1) was conducted using age, sex, obesity, hypertension, peripheral vascular disease, smoking status, and baseline HbA1c. All patients had at least 1 year of follow-up, and relative risks with 95% confidence intervals were calculated. RESULTS: In the primary matched analysis (n = 712 patients per cohort), rates of pseudarthrosis were similar between GLP-1 users and nonusers (7.2% vs. 8.2%; risk ratio, 0.88; P = 0.49), with no significant differences in other complications. However, in the T2DM subgroup (n = 508 patients per cohort), GLP-1 users demonstrated a lower rate of pseudarthrosis compared with diabetic control subjects (7.7% vs. 11.8%; risk ratio, 0.65; P = 0.026), while rates of implant pain, implant removal, and surgical-site infection were comparable between groups. CONCLUSION: Among patients undergoing first MTPJ arthrodesis, GLP-1 RA use was not associated with differences in overall complication rates in the general population. However, among patients with T2DM, GLP-1 use was linked to a markedly lower risk of pseudarthrosis at 1 year postoperatively. These findings suggest that GLP-1 therapy may have a favorable influence on fusion in diabetic patients and warrant additional prospective investigation. LEVEL OF EVIDENCE: III. CI - Copyright (c) 2026 by the American Academy of Orthopaedic Surgeons. FAU - Kayali, Hammam AU - Kayali H AUID- ORCID: 0009-0000-6161-651 AD - From the Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA (Kayali, Sumiyoshi, and Boakye), the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (Adio), and the Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA (Parmar). FAU - Adio, Akin AU - Adio A AUID- ORCID: 0000-0002-5401-573 FAU - Parmar, Tarishi AU - Parmar T AUID- ORCID: 0000-0002-5139-6282 FAU - Sumiyoshi, Nobuhiko AU - Sumiyoshi N FAU - Boakye, Lorraine AU - Boakye L LA - eng PT - Journal Article DEP - 20260527 PL - United States TA - J Am Acad Orthop Surg JT - The Journal of the American Academy of Orthopaedic Surgeons JID - 9417468 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Arthrodesis/methods/adverse effects MH - *Metatarsophalangeal Joint/surgery MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Semaglutide MH - Postoperative Complications/epidemiology EDAT- 2026/05/27 12:35 MHDA- 2026/10/16 19:04 CRDT- 2026/05/27 09:03 PHST- 2026/02/02 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/10/16 19:04 [medline] PHST- 2026/05/27 12:35 [pubmed] PHST- 2026/05/27 09:03 [entrez] AID - 00124635-990000000-01686 [pii] AID - 10.5435/JAAOS-D-26-00153 [doi] PST - ppublish SO - J Am Acad Orthop Surg. 2026 Nov 1;34(21):e3108-e3114. doi: 10.5435/JAAOS-D-26-00153. Epub 2026 May 27. PMID- 42199788 OWN - NLM STAT- MEDLINE DCOM- 20260527 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Dapagliflozin associates with heart rate variability decline in T2DM patients on GLP-1 receptor agonist therapy: a prospective observational study. PG - 1809146 LID - 10.3389/fendo.2026.1809146 [doi] LID - 1809146 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased heart rate (HR) and reduced heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). While sodium-glucose co-transporter 2 inhibitors (SGLT2i) may exert beneficial effects on cardiac autonomic function, it remains uncertain whether baseline SGLT2i use is associated with attenuation of GLP-1 RA-related HRV decline in T2DM. METHODS: In this prospective observational study, 45 patients with T2DM were divided into two groups according to pre-study dapagliflozin use: a dapagliflozin-naive group (Control group, n=22) and a dapagliflozin-exposed group (DAPA group, n=23). All participants subsequently received GLP-1 RA therapy for 12 weeks. Changes in HRV parameters were assessed by 24-hour ambulatory electrocardiography before and after treatment. Between-group differences were further evaluated using analysis of covariance (ANCOVA), inverse probability of treatment weighting (IPTW), and multivariable linear regression models. RESULTS: After 12 weeks of GLP-1 RA therapy, the Control group showed significant reductions in SDNN, SDANN, RMSSD, pNN50, and lnHF, together with increases in lnLF and the lnLF/lnHF ratio, whereas no significant within-group changes in HRV indices were observed in the DAPA group. In unadjusted between-group analyses, several HRV parameters differed significantly between groups. After covariate adjustment, significant between-group differences remained for SDNN, SDANN, lnHF, and the lnLF/lnHF ratio. IPTW-weighted sensitivity analyses yielded consistent findings. In multivariable regression, baseline dapagliflozin use was most clearly associated with a more favorable change in SDNN. CONCLUSION: In patients with T2DM, dapagliflozin use was associated with a decline in HRV during GLP-1 RA therapy; these findings are hypothesis-generating and require confirmation in larger prospective studies. CI - Copyright (c) 2026 Wang, Li, Zhang, Kong, Li, Qian and Ma. FAU - Wang, Ying AU - Wang Y AD - Department of Endocrinology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, China. FAU - Li, Hongning AU - Li H AD - Department of Endocrinology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Endocrinology, Lishui District People's Hospital, Nanjing, China. FAU - Zhang, Zhongyuan AU - Zhang Z AD - Department of Endocrinology, Nanjing Tongren Hospital, Nanjing, China. FAU - Kong, Xiaocen AU - Kong X AD - Department of Endocrinology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, China. FAU - Li, Huiqin AU - Li H AD - Department of Endocrinology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, China. FAU - Qian, Weichun AU - Qian W AD - Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Ma, Jianhua AU - Ma J AD - Department of Endocrinology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PT - Observational Study DEP - 20260511 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Heart Rate/drug effects MH - *Benzhydryl Compounds/therapeutic use MH - Prospective Studies MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - *Glucosides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC13198993 OTO - NOTNLM OT - GLP-1 RAs OT - T2DM OT - cardiac autonomic neuropathy OT - dapagliflozin OT - heart rate variability COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/05/27 12:20 MHDA- 2026/05/27 12:35 PMCR- 2026/05/11 CRDT- 2026/05/27 04:31 PHST- 2026/02/11 00:00 [received] PHST- 2026/04/01 00:00 [revised] PHST- 2026/04/13 00:00 [accepted] PHST- 2026/05/27 12:35 [medline] PHST- 2026/05/27 12:20 [pubmed] PHST- 2026/05/27 04:31 [entrez] PHST- 2026/05/11 00:00 [pmc-release] AID - 10.3389/fendo.2026.1809146 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 May 11;17:1809146. doi: 10.3389/fendo.2026.1809146. eCollection 2026. PMID- 42195239 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 5 DP - 2026 May 18 TI - Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression. LID - 10.3390/medicina62050986 [doi] LID - 986 AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with metabolic abnormalities, shares pathophysiological pathways with metabolic syndrome, and has become a leading cause of chronic liver disease in industrialized nations. In the absence of approved pharmacological treatments and due to its high risk of progression to advanced fibrosis, MASLD represents a significant clinical challenge. Incretin-based therapies, originally developed for the treatment of type 2 diabetes mellitus and obesity, have recently gained attention as promising therapeutic strategies in hepatology. Among them, GLP-1 receptor agonists have shown efficacy in reducing hepatic steatosis, inflammation, and fibrosis-related biomarkers, primarily through weight loss and enhanced insulin sensitivity. Dual agonists targeting both GLP-1 and GIP receptors, such as tirzepatide, have demonstrated superior outcomes in improving hepatic and metabolic parameters. Emerging agents like cotadutide (a GLP-1/glucagon receptor agonist) and retatrutide (a GLP-1/GIP/glucagon triagonist) represent a novel therapeutic frontier, with early clinical data indicating potent hepatoprotective effects and favorable metabolic remodeling. This narrative review examines the hepatoprotective potential of incretin-based therapies, highlighting how targeted intervention on the underlying metabolic dysfunction may lead to significant improvements in MASLD. These therapies may also exert beneficial effects on fibrosis progression; however, the currently available evidence remains limited. FAU - Abenavoli, Ludovico AU - Abenavoli L AUID- ORCID: 0000-0002-5922-1524 AD - Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. AD - Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. FAU - Loricchio, Anna Giulia AU - Loricchio AG AUID- ORCID: 0009-0001-8224-7407 AD - Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. AD - Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. FAU - Lopez, Ivo AU - Lopez I AD - Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. AD - Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. FAU - Morano, Domenico AU - Morano D AD - Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. AD - Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. FAU - Ismaiel, Abdulrahman AU - Ismaiel A AUID- ORCID: 0000-0001-7435-271X AD - 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania. FAU - Dumitrascu, Dan Lucian AU - Dumitrascu DL AD - 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania. FAU - Luzza, Francesco AU - Luzza F AUID- ORCID: 0000-0001-5120-1046 AD - Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. AD - Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260518 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - Disease Progression MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Fatty Liver/drug therapy MH - Metabolic Syndrome/complications/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Tirzepatide PMC - PMC13208855 OTO - NOTNLM OT - chronic liver disease OT - liver steatosis OT - management OT - treatment COIS- The authors declare no conflicts of interest. EDAT- 2026/05/27 06:40 MHDA- 2026/05/27 06:41 PMCR- 2026/05/18 CRDT- 2026/05/27 01:13 PHST- 2026/03/25 00:00 [received] PHST- 2026/05/07 00:00 [revised] PHST- 2026/05/12 00:00 [accepted] PHST- 2026/05/27 06:41 [medline] PHST- 2026/05/27 06:40 [pubmed] PHST- 2026/05/27 01:13 [entrez] PHST- 2026/05/18 00:00 [pmc-release] AID - medicina62050986 [pii] AID - medicina-62-00986 [pii] AID - 10.3390/medicina62050986 [doi] PST - epublish SO - Medicina (Kaunas). 2026 May 18;62(5):986. doi: 10.3390/medicina62050986. PMID- 42195123 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 5 DP - 2026 May 1 TI - The Emerging Role of Glucagon-like Peptide 1 (GLP-1)-Based Medications in the Treatment of Heart Failure, with a Focus on Heart Failure with Preserved or Mildly Reduced Ejection Fraction. LID - 10.3390/medicina62050870 [doi] LID - 870 AB - Glucagon-like Peptide 1 (GLP-1)-based medications have been extensively studied for the management of type 2 diabetes, obesity, chronic kidney disease, and atherosclerotic cardiovascular disease. More recently, their potential role in preventing and treating heart failure has gained increasing attention. Given the strong pathophysiological links among diabetes, obesity, and heart failure, GLP-1-based medications represent a promising therapeutic option to improve morbidity and mortality across these interconnected conditions. In this review, we summarise and discuss recent studies involving GLP-1-based medications that have reported on HF-related outcomes. There is increasing evidence that these medications have beneficial effects on HF outcomes in patients with heart failure with preserved ejection fraction and possibly in those with mildly reduced ejection fraction. The usefulness of GLP-1-based medications in reduced ejection fraction HF remains to be defined. FAU - Lee, Rachel Su Min AU - Lee RSM AUID- ORCID: 0009-0003-5581-8766 AD - Department of Endocrinology, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia. FAU - Seah, Jas-Mine AU - Seah JM AD - Department of Endocrinology, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia. AD - Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, Australia. FAU - Baqar, Sara AU - Baqar S AD - Department of Endocrinology, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia. AD - Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, Australia. FAU - Srivastava, Piyush M AU - Srivastava PM AUID- ORCID: 0000-0002-8129-3137 AD - Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, Australia. AD - Department of Cardiology, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia. AD - Advara Heart Care, Mulgrave Private Hospital, Mulgrave, Melbourne, VIC 3170, Australia. FAU - Levelt, Eylem AU - Levelt E AUID- ORCID: 0000-0002-3799-7102 AD - Department of Cardiometabolic Imaging, Baker Heart and Diabetes Institute, University of Melbourne, Melbourne, VIC 3004, Australia. FAU - Leet, Angeline S AU - Leet AS AUID- ORCID: 0000-0001-8470-1602 AD - Department of Cardiology, St Vincent's Hospital Melbourne, Fitzroy, Melbourne, VIC 3065, Australia. FAU - MacIsaac, Andrew I AU - MacIsaac AI AD - Department of Cardiology, St Vincent's Hospital Melbourne, Fitzroy, Melbourne, VIC 3065, Australia. AD - Department of Medicine, St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Melbourne, VIC 3065, Australia. FAU - Ekinci, Elif I AU - Ekinci EI AD - Department of Endocrinology, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia. AD - Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, Australia. AD - Australian Centre for Accelerating Diabetes Innovations, School of Medicine, University of Melbourne, Parkville, Melbourne, VIC 3052, Australia. FAU - MacIsaac, Richard J AU - MacIsaac RJ AUID- ORCID: 0000-0001-8058-6977 AD - Department of Medicine, St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Melbourne, VIC 3065, Australia. AD - Australian Centre for Accelerating Diabetes Innovations, School of Medicine, University of Melbourne, Parkville, Melbourne, VIC 3052, Australia. AD - Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Melbourne, VIC 3065, Australia. LA - eng PT - Journal Article PT - Review DEP - 20260501 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Venoms) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptide 1/therapeutic use/pharmacology MH - *Stroke Volume/drug effects/physiology MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - Exenatide/therapeutic use MH - Liraglutide/therapeutic use/pharmacology MH - Venoms/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy PMC - PMC13208374 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular disease OT - diabetes OT - heart failure OT - obesity COIS- R.S.M.L., J.-m.S., S.B., E.L., A.L. and A.I.M. declare that they have no conflicts of interest. SB has previously received honoraria for speaking engagements from AstraZeneca, Boehringer Ingelheim, Lily, and Novo Nordisk. She has also received funding support from Amgen to establish a cardiometabolic consultant role at Austin Health in Melbourne, Victoria. PS has no direct conflicts of interest in the work but is a speaker's bureau for Eli-Illy, Novo Nordisk, Astra, BI, and Novartis. AL reports no direct conflicts of interest in the work reported in this paper. She, however, has received travel support from Boehringer Ingelheim. AIM reports no direct conflicts of interest but has received travel support to a medical meeting from Novo Nordisk Pharmaceuticals. EIE conducts unrelated clinical research with Eli Lilly, Novo Nordisk, Boehringer, Amgen, Versanis, Novartis, Endogenex, and Bayer, and funds are paid to EIE's institution. EIE serves on advisory boards and gives presentations for Eli Lilly, Boehringer, and Bayer, and these funds are paid to EIE's institution and used for diabetes research. RJM reports no direct conflicts of interest in the work reported in this paper. However, he has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program and The National Health and Medical Research Council of Australia. He also received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Merck Sharp & Dohme, Novartis, and Boehringer Ingelheim and has been or is on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, Astra Zeneca, and Merck Sharp & Dohme. Travel support has been provided by Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca. He has been a principal investigator for industry-sponsored clinical trials conducted by Novo Nordisk, Sanofi, Bayer, Johnson & Johnson and AbbVie. He has also been an investigator on industry-sponsored trials involving liraglutide, semaglutide and cagrilinide/semaglutide. EDAT- 2026/05/27 06:33 MHDA- 2026/05/27 06:34 PMCR- 2026/05/01 CRDT- 2026/05/27 01:12 PHST- 2026/03/27 00:00 [received] PHST- 2026/04/15 00:00 [revised] PHST- 2026/04/21 00:00 [accepted] PHST- 2026/05/27 06:34 [medline] PHST- 2026/05/27 06:33 [pubmed] PHST- 2026/05/27 01:12 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - medicina62050870 [pii] AID - medicina-62-00870 [pii] AID - 10.3390/medicina62050870 [doi] PST - epublish SO - Medicina (Kaunas). 2026 May 1;62(5):870. doi: 10.3390/medicina62050870. PMID- 42186215 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Real-World Effectiveness and 12-Month Persistence of a Semaglutide-Supported Digital Weight-Loss Service: A Retrospective Cohort Study in Germany. PG - 6985-6996 LID - 10.1111/dom.70916 [doi] AB - AIM: To evaluate the 12-month effectiveness and patient persistence of a semaglutide-supported digital weight-loss service (DWLS) in a real-world German cohort. METHODS: This retrospective study analysed 4535 patients who initiated the Juniper Germany DWLS. Primary endpoints included 12-month medication and data submission adherence (receiving >/= 10 orders) and mean weight-loss percentage. Effectiveness was assessed via a per-protocol (PP) analysis of an adherent sub-cohort (n = 546) and an intention-to-treat (ITT) analysis of the full cohort using Last Observation Carried Forward (LOCF) and a Worst-Case Scenario (WCS) sensitivity model. Binary logistic and multiple linear regressions identified predictors of attrition (churn) and efficacy. RESULTS: Of the total cohort (n = 4535), mean 12-month weight loss was 9.47% (LOCF). However, sensitivity analysis using a WCS model-assuming 0% weight loss for all dropouts-yielded a mean of 2.40%. Among the 12% of patients (n = 546) who remained adherent to both medication and data submission protocols, mean weight loss was 15.13% (+/-7.1). Program persistence was significantly bolstered by achieving a healthy BMI milestone (OR = 0.29, p < 0.001), encountering a weight-loss plateau (OR = 0.41, p < 0.001), and higher baseline obesity severity (Obesity Class I-III: p < 0.023). Conversely, high clinical complexity (>/= 3 comorbidities) more than doubled the risk of churn (OR = 2.12, p = 0.002), while previous GLP-1 RA use also significantly increased churn risk (OR = 1.57, p = 0.001). While moderate early engagement (2-10 logs) was a strong predictor of persistence (p < 0.001), intensive tracking (> 10 logs) did not significantly reduce churn risk (p = 0.393). CONCLUSION: The population-level impact of this DWLS is fundamentally limited by high attrition (88%) in an unsubsidised environment. While significant weight loss is possible for a non-representative adherent minority, the mean effectiveness for the total initiating population (2.40% WCS) highlights that real-world success is strictly conditional upon long-term persistence. The study found that both clinical success and setbacks were associated with program adherence. It also observed that patients of high clinical complexity were at greater risk of attrition. Finally, it found that high-friction manual weight logging serves as a marker of commitment rather than anxiety as had been reported in app-based DWLSs where tracking has significantly lower friction. These findings suggest that the predictive value of digital engagement is fundamentally shaped by DWLS delivery mode and the behavioural cost of engagement. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Talay, Louis AU - Talay L AD - Eucalyptus Health, Sydney, New South Wales, Australia. FAU - Hom, Jason AU - Hom J AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. FAU - Tan, Marilyn AU - Tan M AUID- ORCID: 0000-0002-6651-4691 AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. FAU - Ahuja, Neera AU - Ahuja N AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. LA - eng PT - Journal Article DEP - 20260525 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Retrospective Studies MH - Female MH - Male MH - Germany/epidemiology MH - Middle Aged MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Reduction Programs/methods MH - *Obesity/therapy/drug therapy MH - Treatment Outcome MH - Aged MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Digital Health MH - Digital Media MH - *Anti-Obesity Agents/therapeutic use PMC - PMC13341323 OTO - NOTNLM OT - antiobesity drug OT - cohort study OT - obesity care OT - real-world evidence OT - semaglutide OT - weight management COIS- L.T. is paid a salary at Eucalyptus (Juniper parent company). N.A. is a paid advisor at Eucalyptus. J.H. and M.T. declare no conflicts of interest. EDAT- 2026/05/26 06:31 MHDA- 2026/07/08 12:57 PMCR- 2026/07/08 CRDT- 2026/05/26 01:33 PHST- 2026/05/13 00:00 [revised] PHST- 2026/03/24 00:00 [received] PHST- 2026/05/16 00:00 [accepted] PHST- 2026/07/08 12:57 [medline] PHST- 2026/05/26 06:31 [pubmed] PHST- 2026/05/26 01:33 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70916 [pii] AID - 10.1111/dom.70916 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6985-6996. doi: 10.1111/dom.70916. Epub 2026 May 25. PMID- 42186086 OWN - NLM STAT- MEDLINE DCOM- 20260816 LR - 20260915 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 May 25 TI - Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum: a systematic review and meta-analysis. LID - 10.1186/s12933-026-03215-y [doi] LID - 234 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated cardiometabolic benefits in randomized controlled trials (RCTs). However, its overall effects on mortality, cardiovascular (CV) and kidney outcomes have not been comprehensively synthesized. This meta-analysis aimed to assess the prognostic impact of semaglutide across the cardio-kidney-metabolic continuum. METHODS: A systematic literature search was conducted to identify all eligible RCTs comparing the prognostic effects of semaglutide with placebo across diverse patient populations. Primary outcomes were all-cause and CV mortality. Secondary outcomes included major CV and kidney events, while major adverse limb events (MALE) were analyzed as an exploratory endpoint. A random-effects model was used to pool hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Eight trials encompassing 39,204 patients were included. In patients treated with semaglutide a significant reduction of all-cause (HR, 0.84; 95% CI, 0.77-0.92; p = 0.0001) and CV mortality (HR, 0.83; 95% CI, 0.72-0.95; p = 0.0078), major adverse CV events (MACE, HR, 0.82; 95% CI, 0.77-0.87; p < 0.0001), nonfatal myocardial infarction (MI, HR, 0.75; 95% CI, 0.68-0.84; p < 0.0001), worsening heart failure (HF, HR, 0.84; 95% CI, 0.73-0.98; p = 0.0245), and kidney outcomes (HR, 0.83; 95% CI, 0.73-0.95; p = 0.0080) was observed compared to placebo. No significant effects were observed for nonfatal stroke. CONCLUSIONS: Treatment with semaglutide, compared to placebo, is associated with significant lower incidence of all-cause and CV mortality, as well major CV and kidney events across the continuum of cardio-kidney-metabolic syndrome. CI - (c) 2026. The Author(s). FAU - Marzano, Federica AU - Marzano F AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Paolillo, Stefania AU - Paolillo S AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Gargiulo, Paola AU - Gargiulo P AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Cotticelli, Ciro AU - Cotticelli C AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Di Santo, Mariafrancesca AU - Di Santo M AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Nardi, Ermanno AU - Nardi E AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Abbellito, Giuseppe Maria AU - Abbellito GM AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Liccardi, Laura AU - Liccardi L AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Perrone Filardi, Fabrizio AU - Perrone Filardi F AD - Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy. FAU - Bruzzese, Dario AU - Bruzzese D AD - Department of Public Health, University of Naples Federico II, Naples, Italy. FAU - Perrone Filardi, Pasquale AU - Perrone Filardi P AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. fpperron@unina.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260525 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/mortality/diagnosis/prevention & control MH - Treatment Outcome MH - Risk Assessment MH - *Kidney Diseases/mortality/diagnosis/prevention & control MH - Male MH - Randomized Controlled Trials as Topic MH - Female MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Incretins/therapeutic use/adverse effects MH - Cause of Death MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Kidney/drug effects/physiopathology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Time Factors MH - *Metabolic Syndrome/mortality/diagnosis/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13479731 OTO - NOTNLM OT - Cardio-kidney-metabolic syndrome OT - Mortality OT - Placebo OT - Randomized controlled trials OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/05/26 06:31 MHDA- 2026/08/17 05:38 PMCR- 2026/05/25 CRDT- 2026/05/26 00:09 PHST- 2026/02/08 00:00 [received] PHST- 2026/04/30 00:00 [accepted] PHST- 2026/08/17 05:38 [medline] PHST- 2026/05/26 06:31 [pubmed] PHST- 2026/05/26 00:09 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - 10.1186/s12933-026-03215-y [pii] AID - 3215 [pii] AID - 10.1186/s12933-026-03215-y [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 May 25;25(1):234. doi: 10.1186/s12933-026-03215-y. PMID- 42185271 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260822 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 May 25 TI - Phenome-wide analysis of downstream health outcomes following second-line antidiabetic agent prescriptions in All of Us. LID - 10.1038/s41467-026-72947-y [doi] LID - 6853 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes (T2D) and weight management, yet their real-world health impacts remain understudied. Using a retrospective cohort design with electronic health record data from 17,267 adults with type 2 diabetes in the All of Us Research Program, we conduct propensity score-matched phenome-wide association studies comparing diagnoses following GLP-1 RA prescription (including semaglutide-specific analyses) to those following sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) prescriptions between January 2018 and October 2023. We employ both intention-to-treat and per-protocol Cox proportional hazards models alongside restricted mean survival time analyses evaluating up to 974 phenotypes. We identify multiple phenome-wide significant and suggestive associations, including for cardiovascular, genitourinary, dental, and metabolic outcomes. Compared to SGLT2i, semaglutide demonstrates reduced risk for genitourinary infections in women (e.g., candidiasis of vulva and vagina (per-protocol hazard ratio 0.31, 95% confidence interval (0.17-0.55)). Compared to DPP4i, GLP-1 RAs are associated with reduced risk of diseases of hard tissues of teeth (0.45 (0.33-0.61)). Time-to-event analyses reveal modest delays for key diagnoses. These findings underscore differences in downstream diagnostic associations across second-line T2D therapies and highlight semaglutide's distinct profile, with implications for clinical decision-making and personalized prescribing. CI - (c) 2026. The Author(s). FAU - Salvatore, Maxwell AU - Salvatore M AUID- ORCID: 0000-0002-3659-1514 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Tang, Huilin AU - Tang H AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Zhang, Dazheng AU - Zhang D AUID- ORCID: 0000-0002-1431-0785 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Zhou, Ting AU - Zhou T AUID- ORCID: 0000-0003-3392-2979 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Lu, Yuan AU - Lu Y AUID- ORCID: 0000-0001-5264-2169 AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA. AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. FAU - Amaro, Anastassia AU - Amaro A AD - Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, PA, USA. FAU - D Ritchie, Marylyn AU - D Ritchie M AUID- ORCID: 0000-0002-1208-1720 AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Biomedical Informatics and AI, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Leonard David Institute of Health Economics, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Penn Medicine Center for Evidence-Based Practice (CEP), Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. LA - eng GR - R01 HL169458/HL/NHLBI NIH HHS/United States GR - U2C OD023196/OD/NIH HHS/United States GR - OT2 OD025315/OD/NIH HHS/United States GR - OT2 OD026551/OD/NIH HHS/United States GR - U24 OD023121/OD/NIH HHS/United States GR - OT2 OD026552/OD/NIH HHS/United States GR - OT2 OD025337/OD/NIH HHS/United States GR - OT2 OD026553/OD/NIH HHS/United States GR - OT2 OD023205/OD/NIH HHS/United States GR - OT2 OD025276/OD/NIH HHS/United States GR - OT2 OD026557/OD/NIH HHS/United States GR - 1R01LM014344/U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/ GR - OT2 OD023206/OD/NIH HHS/United States GR - R21 EY034179/EY/NEI NIH HHS/United States GR - R21AI167418/Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ GR - OT2 OD026556/OD/NIH HHS/United States GR - U24 OD023176/OD/NIH HHS/United States GR - OT2 OD026548/OD/NIH HHS/United States GR - R21 AI167418/AI/NIAID NIH HHS/United States GR - U01 TR003709/TR/NCATS NIH HHS/United States GR - OT2 OD026549/OD/NIH HHS/United States GR - R01DK128237/U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - R01 LM014344/LM/NLM NIH HHS/United States GR - R56 AG074604/AG/NIA NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - OT2 OD025277/OD/NIH HHS/United States GR - R01AG073435/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - R01LM013519/U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/ GR - RF1 AG077820/AG/NIA NIH HHS/United States GR - R21EY034179/U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ GR - OT2 OD026555/OD/NIH HHS/United States GR - OT2 OD026550/OD/NIH HHS/United States GR - R01 LM013519/LM/NLM NIH HHS/United States GR - U01TR003709/U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ GR - RF1AG077820/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - OT2 OD026554/OD/NIH HHS/United States GR - U24 MH136069/MH/NIMH NIH HHS/United States GR - R56AG074604/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - U24 OD023163/OD/NIH HHS/United States PT - Journal Article DEP - 20260525 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Retrospective Studies MH - Glucagon-Like Peptides/therapeutic use MH - Male MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - United States MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Phenomics MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Phenotype MH - Electronic Health Records PMC - PMC13388941 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/05/26 00:30 MHDA- 2026/07/22 12:37 PMCR- 2026/05/25 CRDT- 2026/05/25 23:15 PHST- 2025/07/07 00:00 [received] PHST- 2026/04/28 00:00 [accepted] PHST- 2026/07/22 12:37 [medline] PHST- 2026/05/26 00:30 [pubmed] PHST- 2026/05/25 23:15 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - 10.1038/s41467-026-72947-y [pii] AID - 72947 [pii] AID - 10.1038/s41467-026-72947-y [doi] PST - epublish SO - Nat Commun. 2026 May 25;17(1):6853. doi: 10.1038/s41467-026-72947-y. PMID- 42184419 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260821 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 7 DP - 2026 Jul TI - Tirzepatide Versus Intensified Conventional Care After 2 Years of Treatment in Early Type 2 Diabetes : A Randomized Clinical Trial. PG - 917-928 LID - 10.7326/ANNALS-25-05602 [doi] AB - BACKGROUND: Initiation of treatment with tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1RA), early after a diagnosis of type 2 diabetes (T2D) may establish better and more durable glycemic control than current treatment approaches per guidelines and clinical practice. OBJECTIVE: To assess the efficacy and safety of tirzepatide versus intensified conventional care (ICC) in participants with early T2D who have inadequate glycemic control with diet, exercise, and metformin. DESIGN: Randomized, open-label, parallel-group, phase 4 trial (SURPASS-EARLY). (ClinicalTrials.gov: NCT05433584). SETTING: 78 sites in 10 countries. PARTICIPANTS: 794 adults with at most 4 years of T2D history treated with metformin. INTERVENTION: Tirzepatide (15 mg or maximum tolerated dose) or ICC (including GLP-1RAs but excluding tirzepatide) used in clinical practice and supported by local treatment guidelines. MEASUREMENTS: The primary objective was to show the noninferiority of tirzepatide to ICC for change in hemoglobin A(1c) (HbA(1c)) from baseline to 2 years. Secondary objectives were to show the superiority of tirzepatide for change in HbA(1c), weight, and waist circumference. RESULTS: Tirzepatide was superior to ICC for mean changes from baseline to 2 years in HbA(1c) (-1.99 percentage points [95% CI, -2.12 to -1.87 percentage points] vs. -1.32 percentage points [CI, -1.44 to -1.19 percentage points]; estimated treatment difference [ETD], -0.68 percentage points [CI, -0.84 to -0.51 percentage points]; P < 0.001), weight (ETD, -8.0 kg [CI, -9.39 to -6.50 kg]; P < 0.001), and waist circumference (ETD, -6.2 cm [CI, -7.54 to -4.93 cm]; P < 0.001) (treatment regimen estimand). More participants achieved normoglycemia (HbA(1c) <5.7%) with tirzepatide (60.2%) than ICC (24.0%). The most common adverse events were gastrointestinal in both groups. LIMITATION: Open-label design. CONCLUSION: In participants with early T2D uncontrolled with metformin, tirzepatide treatment resulted in superior reductions in HbA(1c), weight, and waist circumference, and more participants achieved normoglycemia (HbA(1c) <5.7%) with tirzepatide than ICC after 2 years. PRIMARY FUNDING SOURCE: Eli Lilly and Company. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.). FAU - Heine, Robert J AU - Heine RJ AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Perez Manghi, Federico C AU - Perez Manghi FC AD - Centro de Investigaciones Metabolicas, Buenos Aires, Argentina (F.C.P.M.). FAU - Hsia, Stanley H AU - Hsia SH AUID- ORCID: 0000-0003-0945-321X AD - Velocity Clinical Research, Huntington Park, California (S.H.H.). FAU - Gomez-Valderas, Elisa AU - Gomez-Valderas E AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Zeytinoglu, Meltem AU - Zeytinoglu M AUID- ORCID: 0000-0002-0158-6109 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Razzoli, Elisa AU - Razzoli E AUID- ORCID: 0009-0000-2370-2097 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Kiljanski, Jacek AU - Kiljanski J AUID- ORCID: 0000-0003-0354-0558 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Sharma, Palash AU - Sharma P AUID- ORCID: 0000-0003-3016-7541 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Knights, Alastair AU - Knights A AUID- ORCID: 0000-0001-5495-1846 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). FAU - Thieu, Vivian Thuyanh AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Indianapolis, Indiana (R.J.H., E.G.-V., M.Z., E.R., J.K., P.S., A.K., V.T.T.). LA - eng SI - ClinicalTrials.gov/NCT05433584 PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260526 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood/therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - Glycated Hemoglobin/metabolism MH - Metformin/therapeutic use MH - Blood Glucose/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Adult COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/05/25 18:30 MHDA- 2026/07/20 18:35 CRDT- 2026/05/25 17:02 PHST- 2026/07/20 18:35 [medline] PHST- 2026/05/25 18:30 [pubmed] PHST- 2026/05/25 17:02 [entrez] AID - 10.7326/ANNALS-25-05602 [doi] PST - ppublish SO - Ann Intern Med. 2026 Jul;179(7):917-928. doi: 10.7326/ANNALS-25-05602. Epub 2026 May 26. PMID- 42177747 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1720-8319 (Electronic) IS - 1594-0667 (Print) IS - 1594-0667 (Linking) VI - 38 IP - 1 DP - 2026 May 24 TI - Angiogenic T cells and cognitive function in older adults with type 2 diabetes treated with GLP-1 receptor agonists. LID - 10.1007/s40520-026-03417-0 [doi] LID - 165 AB - BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) are at high risk of both cardiovascular complications and cognitive decline, with major implications for independence and self-management. Endothelial dysfunction and impaired angiogenic capacity may play a key role. This study investigated the association between circulating angiogenic T cells (Tang cells) and cognitive function in older adults with T2DM and explored the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. METHODS: A cross-sectional study was conducted on 154 T2DM patients aged 60-80 years, treated either with GLP-1 receptor agonist (GLP-1RA) plus metformin or metformin alone. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Circulating CD3+CD31+CXCR4+ Tang cells were quantified by flow cytometry. Propensity score matching was applied to control for age, body weight and HbA1c. RESULTS: In the overall cohort, higher Tang cell levels were significantly associated with better cognitive performance (MoCA, r = 0.423; MMSE, r = 0.428; both P < 0.001). After matching, 35 patients in each treatment group were included in the comparative analysis. The GLP-1RA + MET group showed significantly higher circulating Tang cell levels than the MET group, both in absolute counts and as percentage of CD3+ T cells (P < 0.001). CONCLUSIONS: Circulating Tang cell levels are positively associated with cognitive function in older adults with T2DM. GLP-1RA therapy is associated with higher Tang cell levels compared with metformin alone, suggesting a potential association with mechanisms related to endothelial repair in diabetes-related cognitive impairment in older age. CI - (c) 2026. The Author(s). FAU - Longo, Miriam AU - Longo M AD - Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy. miriam.longo@unicampania.it. AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. miriam.longo@unicampania.it. FAU - Caruso, Paola AU - Caruso P AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Auriemma, Maria Chiara AU - Auriemma MC AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Geriatrics and Internal Medicine, AOU University of Campania : "Luigi Vanvitelli", Naples, Italy. FAU - Maio, Antonietta AU - Maio A AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Di Meo, Irene AU - Di Meo I AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Geriatrics and Internal Medicine, AOU University of Campania : "Luigi Vanvitelli", Naples, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Rizzo, Maria Rosaria AU - Rizzo MR AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Geriatrics and Internal Medicine, AOU University of Campania : "Luigi Vanvitelli", Naples, Italy. FAU - Paolisso, Giuseppe AU - Paolisso G AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Geriatrics and Internal Medicine, AOU University of Campania : "Luigi Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article DEP - 20260524 PL - Germany TA - Aging Clin Exp Res JT - Aging clinical and experimental research JID - 101132995 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/immunology MH - Aged MH - Female MH - Male MH - *Cognition/drug effects/physiology MH - Cross-Sectional Studies MH - Middle Aged MH - Aged, 80 and over MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *T-Lymphocytes/drug effects MH - Metformin/therapeutic use MH - *Angiogenesis PMC - PMC13415266 OTO - NOTNLM OT - Angiogenic T cells OT - Cognitive function OT - Endothelial dysfunction OT - GLP-1RA OT - Type 2 diabetes COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/05/24 13:39 MHDA- 2026/07/29 18:38 PMCR- 2026/05/24 CRDT- 2026/05/24 11:04 PHST- 2026/02/07 00:00 [received] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/05/24 13:39 [pubmed] PHST- 2026/05/24 11:04 [entrez] PHST- 2026/05/24 00:00 [pmc-release] AID - 10.1007/s40520-026-03417-0 [pii] AID - 3417 [pii] AID - 10.1007/s40520-026-03417-0 [doi] PST - epublish SO - Aging Clin Exp Res. 2026 May 24;38(1):165. doi: 10.1007/s40520-026-03417-0. PMID- 42173109 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 7 DP - 2026 Jul TI - Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. PG - 581-593 LID - S2213-8587(26)00075-6 [pii] LID - 10.1016/S2213-8587(26)00075-6 [doi] AB - BACKGROUND: The long-term glycaemic effects of glucose-dependent insulinotropic polypeptide (GIP) remain unclear. We aimed to assess whether a 6-week subcutaneous infusion of GIP alone and in combination with the GLP-1 receptor agonist semaglutide would enhance glycaemic control in individuals with type 2 diabetes. METHODS: This single-centre, double-blind, parallel-group, randomised, placebo-controlled trial was conducted at the Center for Clinical Metabolic Research (Hellerup, Denmark). Inclusion criteria were age 18-74 years; a diagnosis of type 2 diabetes for at least 6 months; stable treatment; HbA(1c) of 6.5-10.5% (48-91 mmol/mol); and a BMI of 25-50 kg/m(2). Participants were randomly assigned (1:1:1:1), using a block randomisation list, to receive either placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP (all self-administered subcutaneously). The regimen was 8-week semaglutide or placebo run-in period (4 weeks at 0.25 mg then 4 weeks at 0.50 mg once per week), after which participants continued 0.50 mg semaglutide or placebo for an additional 6 weeks while receiving continuous subcutaneous infusions of GIP or placebo (16 pmol/kg per min). Participants and investigators were masked to treatment assignment. The primary outcome was change in 14-day mean glucose concentration assessed by continuous glucose monitoring from baseline to the end of treatment at 14 weeks, assessed in the efficacy population. This study is registered at ClinicalTrials.gov, NCT05078255 (completed). FINDINGS: Between Jan 31, 2022, and Sept 4, 2024, we assessed 134 individuals with type 2 diabetes for eligibility, of whom 73 were ineligible. We enrolled and randomly assigned 61 participants (15 to placebo plus placebo, 16 to placebo plus GIP, 15 to semaglutide plus placebo, and 15 to semaglutide plus GIP). Ten (16%) participants discontinued the study. Participants had a median age of 64.0 years (IQR 60.0-68.0), HbA(1c) of 54.0 mmol/mol (49.0-60.0), diabetes duration of 6.3 years (4.2-9.8), and a mean BMI of 31.6 kg/m(2) (SD 4.8). 22 (36%) participants were female and 39 (64%) were male and all self-reported as White. Fasting concentrations of intact (bioactive) GIP at the end of treatment on week 14 were mean 7 pmol/L (SD 4) in the placebo plus placebo group, 45 pmol/L (43) in the placebo plus GIP group, 10 pmol/L (6) in the semaglutide plus placebo group, and 85 pmol/L (92) in the semaglutide plus GIP group; whereas fasting concentrations of total GIP were 14 pmol/L (7), 375 pmol/L (377), 18 pmol/L (19), and 527 pmol/L (338), respectively. The estimated effect of GIP on change in 14-day mean sensor-detected glucose from baseline to end of treatment was 0.80 mmol/L (97.5% CI -0.18 to 1.80; p=0.13 in the placebo plus GIP vs placebo plus placebo groups) and 0.05 mmol/L (-0.85 to 0.95; p=1.00 in the semaglutide plus GIP vs semaglutide plus placebo groups). Injection site reactions were the most common adverse event (22 [36%]). Gastrointestinal adverse events were more frequent with semaglutide (nine [60%] with placebo plus placebo, 11 [69%] with placebo plus GIP, 11 [73%] with semaglutide plus placebo, and 12 [80%] with semaglutide plus GIP). INTERPRETATION: 6 weeks of subcutaneous GIP infusion as add-on to placebo or semaglutide did not improve glycaemic control in individuals with type 2 diabetes at the prespecified target of 1.50 mmol/L. Due to dropouts, we cannot draw firm conclusions on the effects of GIP as add-on to placebo. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Helsted, Mads M AU - Helsted MM AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Fonnesbech-Wulff, Christiane AU - Fonnesbech-Wulff C AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Schaltz, Nina L AU - Schaltz NL AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Lund, Ingrid W AU - Lund IW AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Forman, Julie L AU - Forman JL AD - Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Nielsen, Casper K AU - Nielsen CK AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Englund, Anders AU - Englund A AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Lund, Asger B AU - Lund AB AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Christensen, Mikkel B AU - Christensen MB AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - Knop, Filip K AU - Knop FK AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gasbjerg, Laerke S AU - Gasbjerg LS AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: lsg@sund.ku.dk. LA - eng SI - ClinicalTrials.gov/NCT05078255 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260522 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Double-Blind Method MH - Middle Aged MH - *Gastric Inhibitory Polypeptide/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Infusions, Subcutaneous MH - Adult MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Blood Glucose/analysis MH - Adolescent MH - Glycated Hemoglobin/analysis MH - Young Adult COIS- Declaration of interests CF-W and IWL are shareholders of Novo Nordisk. ABL served on a scientific advisory panel for Eli Lilly; and received speaker honoraria from Boehringer Ingelheim, Novo Nordisk, and Zealand Pharma. JJH is a cofounder and shareholder of Antag Therapeutics; and served on scientific advisory panels or received speaker honoraria (or both) from AlphaSights, Eli Lilly, Novo Nordisk, MSD, Structure Therapeutics, and Zealand Pharma. TV served on scientific advisory panels, speakers' bureaus, and was a consultant or received research support (or both) from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD, Novo Nordisk, Sanofi, and Sun Pharma. FKK served on scientific advisory panels, speaker's bureaus, was a consultant, owns stocks or received research support (or both) from 89bio, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD, Norgine, Novo Nordisk, Sanofi, ShouTi, SNIPR Biome, Zealand Pharma, and Zucara; and is a cofounder and shareholder in Antag Therapeutics. TV, CKN, and FKK are employed by Novo Nordisk. LSG received a grant from Novo Nordisk Foundation (NNF18SA0034956); is a shareholder and cofounder of Antag Therapeutics; and reports receiving a personal lecture fee from Novo Nordisk. All other authors declare no competing interests. EDAT- 2026/05/23 05:37 MHDA- 2026/06/17 00:36 CRDT- 2026/05/22 18:52 PHST- 2025/12/10 00:00 [received] PHST- 2026/03/23 00:00 [revised] PHST- 2026/03/24 00:00 [accepted] PHST- 2026/06/17 00:36 [medline] PHST- 2026/05/23 05:37 [pubmed] PHST- 2026/05/22 18:52 [entrez] AID - S2213-8587(26)00075-6 [pii] AID - 10.1016/S2213-8587(26)00075-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Jul;14(7):581-593. doi: 10.1016/S2213-8587(26)00075-6. Epub 2026 May 22. PMID- 42170981 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260831 IS - 3105-9686 (Electronic) IS - 1011-601X (Linking) VI - 39 IP - 7 DP - 2026 Jul TI - Short-term comparative effects of semaglutide, either alone or in conjunction with canagliflozin, on early diabetic kidney disease. PG - 2165-2172 LID - 10.36721/PJPS.2026.39.7.204.1 [doi] AB - BACKGROUND: Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus and an important cause of end-stage renal disease. Metabolic dysfunction, albuminuria, and chronic low-grade inflammation characterize early DKD, leading to progressive renal impairment. To date, SGLT2 inhibitors and GLP-1 receptor agonists are known to provide renoprotective and metabolic benefits; however, there is limited evidence available regarding the combined use of these treatments in early DKD. OBJECTIVES: This study evaluated the short-term effects of canagliflozin and semaglutide, administered alone or in combination, on renal function, metabolic parameters, and systemic inflammatory markers in patients with early-stage DKD. METHODS: In this randomized controlled trial, 120 patients with early-stage diabetic kidney disease were randomly allocated (1:1:1:1) to four groups (n = 30 each): canagliflozin (100 mg orally once daily), semaglutide (0.25 mg once weekly with escalation to 1.0 mg after 4 weeks), combination treatment, or placebo/control. PARTICIPANTS: All participants were provided standard background care. Treatment continued for 24 weeks. The main renal outcomes were urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Glycemic control, insulin resistance, lipid parameters, and inflammatory biomarkers (HbA1c, fasting glucose, HOMA-IR, TNF-alpha, IL-6, CRP) were considered as secondary outcomes. Safety assessment was conducted using binary safety assessment. RESULTS: At 24 weeks, combination therapy achieved significantly greater reductions in UACR compared with monotherapy and placebo (P < 0.05). Across treatment groups, a small reduction in eGFR was observed without significant between-group differences. Measurements of HbA1c, fasting glucose, HOMA-IR, lipid parameters, and inflammatory markers showed better results in the combination therapy group compared to single-agent therapy (P < 0.05). Rates of adverse events were similar between the groups. CONCLUSION: Combined canagliflozin and semaglutide therapy demonstrated superior short-term benefits in reducing albuminuria, improving metabolic control, and attenuating systemic inflammation in early DKD, supporting further long-term evaluation of renal and cardiovascular outcomes. FAU - Long, Wang AU - Long W AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. FAU - Ningning, Li AU - Ningning L AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. FAU - Weijun, Huang AU - Weijun H AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - Pakistan TA - Pak J Pharm Sci JT - Pakistan journal of pharmaceutical sciences JID - 9426356 RN - 0SAC974Z85 (Canagliflozin) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Canagliflozin/therapeutic use/adverse effects/administration & dosage MH - Semaglutide MH - *Diabetic Nephropathies/drug therapy/physiopathology MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Drug Therapy, Combination MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Albuminuria MH - Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - Glycated Hemoglobin/metabolism MH - Glomerular Filtration Rate/drug effects OTO - NOTNLM OT - Combination therapy OT - Canagliflozin OT - Early diabetic kidney disease OT - Inflammatory biomarkers OT - Metabolic parameters OT - Renal outcomes OT - Semaglutide EDAT- 2026/05/22 12:35 MHDA- 2026/05/22 12:36 CRDT- 2026/05/22 07:53 PHST- 2026/05/22 12:36 [medline] PHST- 2026/05/22 12:35 [pubmed] PHST- 2026/05/22 07:53 [entrez] AID - 10.36721/PJPS.2026.39.7.204.1 [doi] PST - ppublish SO - Pak J Pharm Sci. 2026 Jul;39(7):2165-2172. doi: 10.36721/PJPS.2026.39.7.204.1. PMID- 42169518 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260818 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 22 IP - 963 DP - 2026 May 20 TI - [Glucagon-like peptide-1 agonists and heart failure]. PG - 910-916 LID - 10.53738/REVMED.2026.22.963.48693 [doi] AB - Developed to treat type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with a reduced risk of cardiovascular events in high-risk patients with diabetes, and later in obese patients with cardiovascular disease without diabetes. More recently, semaglutide and tirzepatide have demonstrated benefits in obese patients with heart failure (HF) with preserved or mildly reduced ejection fraction, including fewer HF hospitalisations and improvements in symptoms and functional capacity. Data remain limited in heart failure with reduced ejection fraction. This article summarises current evidence on these therapies, particularly in HF, and provides practical guidance for their prescription and follow-up. FAU - Soborun, Nisha AU - Soborun N AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Favre, Lucie AU - Favre L AD - Service d'endocrinologie, diabetologie et metabolisme, Departement de medecine, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Lu, Henri AU - Lu H AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Yerly, Patrick AU - Yerly P AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Agonistes du glucagon-like peptide-1 et insuffisance cardiaque. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Obesity/complications COIS- Les auteurs n'ont declare aucun conflit d'interets en relation avec cet article EDAT- 2026/05/22 06:35 MHDA- 2026/05/22 06:36 CRDT- 2026/05/22 03:14 PHST- 2026/05/22 06:36 [medline] PHST- 2026/05/22 06:35 [pubmed] PHST- 2026/05/22 03:14 [entrez] AID - RMS0963-002 [pii] AID - 10.53738/REVMED.2026.22.963.48693 [doi] PST - ppublish SO - Rev Med Suisse. 2026 May 20;22(963):910-916. doi: 10.53738/REVMED.2026.22.963.48693. PMID- 42168641 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20261008 IS - 1759-5037 (Electronic) IS - 1759-5029 (Linking) VI - 22 IP - 9 DP - 2026 Sep TI - Causes and consequences of discontinuation of GLP1RAs or tirzepatide. PG - 530-542 LID - 10.1038/s41574-026-01258-5 [doi] AB - Glucagon-like peptide 1 (GLP1) receptor (GLP1R) agonists and tirzepatide, a dual GLP1R and glucose-dependent insulinotropic polypeptide receptor agonist, have become fundamental in managing type 2 diabetes mellitus (T2DM) and obesity due to their potent glycaemia-lowering and weight-lowering effects as well as their cardiovascular and renal benefits. However, data from the past 2 years suggest that real-world persistence on these drug classes is often suboptimal, with many people discontinuing these medications, even within their first year of therapy. Reasons for treatment discontinuation include, but are not limited to, gastrointestinal adverse effects, less-than-desired efficacy, high cost, and fear about uncommon or rare adverse effects. When treatment is discontinued, weight regain and the deterioration of multiple cardiometabolic risk factors are common. Repeated cycles of initiation, interruption and re-initiation of these drugs might induce body weight and HbA(1c) fluctuations - two risk factors for cardiovascular and microvascular events. These phenomena, coupled with the re-development of overweight or obesity and poor glycaemic control when not on therapy, might increase the long-term risk of complications. The lack of anti-atherosclerotic and plaque-stabilizing effects of incretin-based medications might contribute to elevated cardiovascular risk, especially acutely following their discontinuation. However, at present, few data are available regarding the incidence of hard outcomes in people discontinuing such drugs. In this Review, we discuss common reasons for GLP1R agonist and tirzepatide discontinuation and examine available evidence related to potential cardiometabolic consequences. We also discuss long-term implications for T2DM care, weight management and, ultimately, cardiorenal disease prevention in patients with T2DM and/or overweight or obesity. CI - (c) 2026. Springer Nature Limited. FAU - Ceriello, Antonio AU - Ceriello A AUID- ORCID: 0000-0001-8122-3203 AD - Polo Scientifico e Tecnologico, IRCCS MultiMedica, Milan, Italy. antonio.ceriello@multimedica.it. FAU - Prattichizzo, Francesco AU - Prattichizzo F AUID- ORCID: 0000-0002-2959-2658 AD - Polo Scientifico e Tecnologico, IRCCS MultiMedica, Milan, Italy. FAU - Mastan Sheik Abdullah, Abdul Raouf AU - Mastan Sheik Abdullah AR AUID- ORCID: 0009-0008-1489-2018 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - La Grotta, Rosalba AU - La Grotta R AD - Polo Scientifico e Tecnologico, IRCCS MultiMedica, Milan, Italy. FAU - Berra, Cesare Celeste AU - Berra CC AD - Department of Endocrinology and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. FAU - McGowan, Barbara AU - McGowan B AD - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. FAU - Jenkins, Alicia AU - Jenkins A AUID- ORCID: 0000-0003-0583-3717 AD - Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. FAU - Cohen, Neale AU - Cohen N AUID- ORCID: 0000-0002-4441-9511 AD - Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. FAU - Nauck, Michael Albrecht AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department 1, St Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Russo, Giuseppina Tiziana AU - Russo GT AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260521 PL - England TA - Nat Rev Endocrinol JT - Nature reviews. Endocrinology JID - 101500078 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Obesity/drug therapy MH - Treatment Interruption COIS- Competing interests: A.C. reports being on the advisory board, consultancy and giving lectures for Abbott, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Hikamr Pharma, Guidotti, Eli Lilly, MSD, Merck, Novo, Roche Diagnostics, Sanofi, Servier, and Sun Pharma. G.T.R. is on the advisory board and does consultancy and lectures for NovoNordisk, AstraZeneca, Sanofi, Boehringer, Lilly, Mundipharma and Sankyo. N.C. and A.J. are investigators on an investigator-initiated trial of tirzepatide in Indigenous Australians with T2DM and suboptimal glycaemia with drug provision by Eli Lilly (Australia). M.A.N. has been a member of advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co., Medtronic, Merck, Sharp & Dohme, NovoNordisk, Pfizer, Regor, Sun Pharma and Structure Therapeutics (ShouTi, Gasherbrum). He has received grant support from Merck, Sharp & Dohme. He has also served on the speakers' bureau of Eli Lilly & Co., Merck, Sharp & Dohme, Medscape, Medical Learning Institute, and NovoNordisk. He is on a data monitoring and safety board for Inventiva. The other authors declare no competing interests. EDAT- 2026/05/22 00:33 MHDA- 2026/08/12 06:05 CRDT- 2026/05/21 23:39 PHST- 2026/04/28 00:00 [accepted] PHST- 2026/08/12 06:05 [medline] PHST- 2026/05/22 00:33 [pubmed] PHST- 2026/05/21 23:39 [entrez] AID - 10.1038/s41574-026-01258-5 [pii] AID - 10.1038/s41574-026-01258-5 [doi] PST - ppublish SO - Nat Rev Endocrinol. 2026 Sep;22(9):530-542. doi: 10.1038/s41574-026-01258-5. Epub 2026 May 21. PMID- 42167405 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 2213-2201 (Electronic) VI - 14 IP - 9 DP - 2026 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists in Asthma and Obesity-Associated Asthma: A Systematic Review of Clinical Outcomes and Translational Mechanisms. PG - 2070-2082.e10 LID - S2213-2198(26)00414-9 [pii] LID - 10.1016/j.jaip.2026.05.010 [doi] AB - BACKGROUND: Obesity and metabolic dysfunction are increasingly recognized as important modifiers of asthma risk, severity, and treatment response. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have been associated with improved respiratory outcomes, but the underlying clinical and biological mechanisms remain incompletely defined. OBJECTIVE: To systematically review and synthesize clinical, translational, and preclinical evidence evaluating the effects of GLP-1RAs on asthma outcomes, with particular attention to weight-dependent, metabolic, and airway-intrinsic mechanisms. METHODS: We conducted a systematic review of human observational studies, clinical trials, and preclinical investigations assessing associations between GLP-1RA exposure and asthma-related outcomes. Data extraction included study design, population characteristics, respiratory outcomes, mechanistic findings, and risk-of-bias assessments using validated tools appropriate to study type. RESULTS: Across observational human studies, GLP-1RA use was consistently associated with reduced asthma exacerbations and health care utilization, predominantly in populations with obesity and/or type 2 diabetes. Several studies reported associations that persisted after adjustment for body mass index or glycemic markers. Preclinical models demonstrated reductions in airway inflammation, hyper-responsiveness, and epithelial cytokine signaling, though these findings were subject to substantial risk of bias and species-specific differences in GLP-1 receptor expression. Overall, evidence supporting airway-intrinsic effects remains largely preclinical, whereas human data are limited by confounding and population selection. CONCLUSIONS: Current evidence suggests that GLP-1RAs may improve asthma outcomes through mechanisms that extend beyond weight loss, potentially involving metabolic and airway-relevant pathways. However, uncertainty remains regarding benefits in the absence of metabolic dysfunction. Ongoing randomized controlled trials will be critical to clarifying causality, defining responsive asthma phenotypes, and determining the clinical role of GLP-1RAs in broader asthma populations. CI - Copyright (c) 2026 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - Saadat, Saeed AU - Saadat S AD - Department of Epidemiology, University of North Carolina at Charlotte, Charlotte, NC. FAU - Chow, Timothy G AU - Chow TG AD - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Tang, Yixin AU - Tang Y AD - Quantitative Biomedical Research Center, Department of Health Data Science and Biostatistics, Peter O'Donnell Jr. School of Public Health, the University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Almandoz, Jaime P AU - Almandoz JP AD - Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Messiah, Sarah E AU - Messiah SE AD - Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pediatrics, Children's Health System of Texas, Dallas, Texas. FAU - Xie, Luyu AU - Xie L AD - Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: luyu.xie@utsouthwestern.edu. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260520 PL - United States TA - J Allergy Clin Immunol Pract JT - The journal of allergy and clinical immunology. In practice JID - 101597220 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Asthma/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/metabolism OTO - NOTNLM OT - Asthma OT - Exacerbation OT - Glucagon-like peptide-1 receptor agonists OT - Inflammation OT - Obesity EDAT- 2026/05/22 00:33 MHDA- 2026/09/07 23:34 CRDT- 2026/05/21 19:37 PHST- 2025/12/29 00:00 [received] PHST- 2026/05/11 00:00 [revised] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/05/22 00:33 [pubmed] PHST- 2026/05/21 19:37 [entrez] AID - S2213-2198(26)00414-9 [pii] AID - 10.1016/j.jaip.2026.05.010 [doi] PST - ppublish SO - J Allergy Clin Immunol Pract. 2026 Sep;14(9):2070-2082.e10. doi: 10.1016/j.jaip.2026.05.010. Epub 2026 May 20. PMID- 42166479 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260901 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 23 IP - 5 DP - 2026 May TI - Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies. PG - e1005064 LID - 10.1371/journal.pmed.1005064 [doi] LID - e1005064 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is widely used for the management of type 2 diabetes (T2DM). Recent case reports have raised concerns about a potential association between semaglutide use and the development of nonarteritic anterior ischemic optic neuropathy (NAION), a rare but vision-threatening condition. We aimed to evaluate whether semaglutide use is associated with an increased risk of NAION in patients with T2DM. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of observational studies comparing patients with T2DM aged >/=12 years treated with semaglutide to those receiving other glucose-lowering therapies. We searched PubMed, Scopus, and Web of Science databases from January 2023 to November 2025. Two reviewers independently extracted data on study design, population characteristics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale, and ROBINS-I v.2. Certainty of the evidence was graded according to the GRADE framework. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models; sensitivity analyses included crude and subgroup HRs, and overlapping study replacement. Leave-one-out analysis was conducted to assess small-study effects and publication bias. Results were contextualized within other meta-analyses, systematic reviews, consensus statements, and regulatory communications on the topic. Five eligible observational studies met the inclusion criteria, and 7 additional studies were included in the sensitivity analysis. Semaglutide use was associated with a significantly increased hazard of NAION compared with nonsemaglutide glucose-lowering regimens (HR 2.17, 95% CI [1.73, 2.74]; p < 0.001), regimens excluding other GLP-1 receptor agonists (HR 2.13, 95% CI [1.60, 2.83]; p < 0.001), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) users (HR 1.96, 95% CI [1.28, 2.99]; p = 0.002). Despite the increased relative risk, the absolute risk remained low at 0.014% (95% CI [0.005%, 0.023%]; p = 0.002), corresponding to approximately 1 additional case of NAION per 7,000 semaglutide-treated patients annually. The results were consistent with meta-analyses of observational studies and corroborated decisions presented in regulatory communications. Due to exclusive focus on retrospective, registry-based observational studies, the evidence synthesis was limited and could be biased by study-level outcome misclassification and confounding. CONCLUSIONS: Our findings suggest a possible association between semaglutide use and an increased risk of NAION in patients with T2DM. Although the absolute risk is low, clinicians should be aware of this potential adverse event, particularly in individuals at increased baseline risk for optic neuropathies. While these findings support current recommendations to discontinue semaglutide in patients diagnosed with NAION, the certainty of the available evidence is low, underscoring the need for further high-quality studies to clarify this association. CI - Copyright: (c) 2026 Chrzanowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Chrzanowski, Jedrzej AU - Chrzanowski J AUID- ORCID: 0000-0001-6204-8622 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. FAU - Walicka, Magdalena AU - Walicka M AD - Department of Internal Diseases, Endocrinology and Diabetology, National Medical Institute of the Ministry of the Interior and Administration, Warsaw, Poland. AD - Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland. FAU - Burzynski, Jacek AU - Burzynski J AUID- ORCID: 0000-0002-5462-8376 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. FAU - Zaras, Malgorzata AU - Zaras M AUID- ORCID: 0009-0002-9030-9601 AD - Ophthalmology Department, CMP Medical Center, Warsaw, Poland. FAU - Michalak, Arkadiusz AU - Michalak A AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. AD - Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland. FAU - Fendler, Wojciech AU - Fendler W AUID- ORCID: 0000-0002-5083-9168 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260521 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Observational Studies as Topic MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Risk Factors MH - *Semaglutide/adverse effects/therapeutic use PMC - PMC13221145 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: J.C. received lecture honoraria from Novo Nordisk and Boehringer Ingelheim and a consulting fee from Novo Nordisk. A.M. received lecture honoraria from Novo Nordisk, Boehringer Ingelheim, and Dexcom. M.W. received lecture honoraria from AstraZeneca, Eli Lilly, Sanofi, and Teva, and support for meeting attendance from Sanofi. The other authors have declared that no competing interest exist. EDAT- 2026/05/21 18:32 MHDA- 2026/05/29 18:34 PMCR- 2026/05/21 CRDT- 2026/05/21 13:43 PHST- 2025/08/05 00:00 [received] PHST- 2026/04/08 00:00 [accepted] PHST- 2026/05/29 00:00 [revised] PHST- 2026/05/29 18:34 [medline] PHST- 2026/05/21 18:32 [pubmed] PHST- 2026/05/21 13:43 [entrez] PHST- 2026/05/21 00:00 [pmc-release] AID - PMEDICINE-D-25-02708 [pii] AID - 10.1371/journal.pmed.1005064 [doi] PST - epublish SO - PLoS Med. 2026 May 21;23(5):e1005064. doi: 10.1371/journal.pmed.1005064. eCollection 2026 May. PMID- 42165732 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 0971-5916 (Print) IS - 0971-5916 (Linking) VI - 163 IP - 4 DP - 2026 Apr TI - Evolution of incretin-based therapies: From GLP-1 monotherapy to dual and triple agonists: A new era in metabolic therapy. PG - 427-435 LID - 10.25259/IJMR_2041_2025 [pii] AB - Incretin-based therapies have revolutionised the management of metabolic disorders, transitioning from DPP-4 inhibitors to advanced GLP-1 receptor agonists (GLP-1RAs) and next-generation dual and triple agonists. This review explores the evolving role of incretin pharmacology in type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD). Literature from PubMed, Scopus, and Google Scholar up to July 2025 was reviewed, emphasising pivotal trials and real-world evidence. While DPP-4 inhibitors offer modest glycaemic benefits, GLP1RAs such as liraglutide and semaglutide have demonstrated significant weight loss and cardiometabolic protection. Dual GIP/GLP-1 agonist tirzepatide and triple agonist retatrutide have shown unprecedented efficacy, with up to 24% body weight reduction and improvement in hepatic and inflammatory markers. Agents like cotadutide and efinopegdutide further expand indications to MASLD and metabolic dysfunction associated steatohepatitis (MASH). Despite promising outcomes, challenges persist in terms of cost, accessibility, and the underrepresentation of low- and middle-income countries in major trials. Pharmacogenomic variability may also influence therapeutic response. Incretin-based multi-agonists offer a transformative, multi-system approach to metabolic disease but require tailored implementation. This review provides an updated synthesis of therapeutic developments and outlines priorities for future research, regulatory policy, and equitable global integration as incretin-based therapies have evolved into a versatile class addressing glycaemic control, weight loss, and cardio-metabolic risk. FAU - Gupta, Monika AU - Gupta M AD - Department of Pharmacology, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. FAU - Shukla, Jitendra AU - Shukla J AD - Department of Internal Medicine, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. LA - eng PT - Journal Article PT - Review PL - United States TA - Indian J Med Res JT - The Indian journal of medical research JID - 0374701 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/pathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy/pathology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use PMC - PMC13224277 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Incretin therapy OT - MASH OT - Metabolic syndrome OT - Type 2 diabetes COIS- None. EDAT- 2026/05/21 12:38 MHDA- 2026/05/21 12:39 PMCR- 2026/04/01 CRDT- 2026/05/21 10:04 PHST- 2025/08/02 00:00 [received] PHST- 2025/12/21 00:00 [accepted] PHST- 2026/05/21 12:39 [medline] PHST- 2026/05/21 12:38 [pubmed] PHST- 2026/05/21 10:04 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - 10.25259/IJMR_2041_2025 [pii] AID - 10.25259/IJMR_2041_2025 [doi] PST - ppublish SO - Indian J Med Res. 2026 Apr;163(4):427-435. doi: 10.25259/IJMR_2041_2025. PMID- 42165511 OWN - NLM STAT- MEDLINE DCOM- 20261012 LR - 20261012 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 33 IP - 14 DP - 2026 Oct 13 TI - Body composition changes in patients on GLP-1 receptor agonists undergoing an intensive cardiac rehabilitation program. PG - 2665-2674 LID - 10.1093/eurjpc/zwag279 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity and produce significant weight loss. However, concerns have emerged about potential loss of skeletal muscle mass (SMM) with pharmacologic weight reduction, particularly in older adults at risk for sarcopaenia. The effects of GLP-1 RA therapy on SMM among patients participating in intensive cardiac rehabilitation (ICR) remain incompletely characterized. METHODS AND RESULTS: A retrospective cohort study of 468 patients enrolled in a structured Pritikin ICR programme at UC San Diego Health between 2017 and 2024 was performed. At programme initiation, 67 patients were taking GLP-1 RAs with a median duration of 231 days (IQR 144-400). Body composition was assessed using bioelectrical impedance analysis at baseline and programme completion. Outcomes included SMM and fat mass (FM). Multivariable regression models adjusted for age, sex, baseline body mass index (BMI), diabetes status, and baseline fitness (measured in metabolic equivalents of tasks [METs]). Both groups improved in METs with ICR (P < 0.001). At baseline, patients on GLP-1 RAs had higher BMI and percent FM compared with non-users, but no differences were observed in SMM. In adjusted analyses, GLP-1 RA use was not associated with significantly different per cent change in SMM from baseline to ICR programme completion compared with no GLP-1 RA use (beta = 0.62%, 95% CI -0.62 to 1.86; P = 0.326). Similarly, there was no significant between-group difference in per cent change in FM (beta = 3.01%, 95% CI -1.64 to 7.66; P = 0.204). CONCLUSION: GLP-1 RA use during ICR was not associated with significantly different SMM changes after adjustment for measured covariates. These findings support the integration of GLP-1 based pharmacotherapy with structured exercise programmes. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Jennings, Ian AU - Jennings I AUID- ORCID: 0009-0006-0637-4291 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - Ly, Kristine AU - Ly K AUID- ORCID: 0000-0002-1719-9656 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - Marooki, Mariam AU - Marooki M AUID- ORCID: 0009-0009-5133-6579 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - Dzotsi, Marissa AU - Dzotsi M AUID- ORCID: 0009-0009-0603-4547 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - McLaren, Gavin AU - McLaren G AUID- ORCID: 0009-0004-2122-6364 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - Cuomo, Raphael E AU - Cuomo RE AUID- ORCID: 0000-0002-8179-0619 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. FAU - Abohashem, Shady AU - Abohashem S AUID- ORCID: 0000-0002-5033-8881 AD - Cardiology Department and Cardiovascular Imaging Research Center, Harvard University Medical School and Massachusetts General Hospital, Boston, MA, USA. AD - Division of Outcomes Research, Harvard University Medical School and Massachusetts General Hospital, Boston, MA, USA. FAU - Taub, Pam R AU - Taub PR AUID- ORCID: 0000-0002-0684-0655 AD - Division of Cardiology, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, USA. LA - eng GR - AG26757/AG/NIA NIH HHS/United States GR - Stein Institute for Research on Aging/ GR - Center for Healthy Aging at the University of California, San Diego (UCSD)/ GR - UCSD School of Medicine Summer Research Training Fellowship/ GR - Elizabeth Keadle/ PT - Journal Article PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Male MH - Female MH - *Body Composition/drug effects MH - Aged MH - *Cardiac Rehabilitation/methods MH - Middle Aged MH - Treatment Outcome MH - Time Factors MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis MH - *Heart Diseases/rehabilitation/diagnosis/physiopathology MH - *Incretins/therapeutic use/adverse effects MH - *Muscle, Skeletal/drug effects/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism OAB - This study examined how body composition changed in patients participating in the Pritikin intensive cardiac rehabilitation programme, comparing those taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with those who were not.Patients in both groups improved fitness and reduced body fat during rehabilitation.Skeletal muscle mass increased slightly in patients not taking GLP-1 medications and remained stable in those taking them. Overall, GLP-1 use was not associated with excess muscle loss during cardiac rehabilitation.These findings suggest that GLP-1 medications can be used alongside structured exercise programmes that include strength training as part of comprehensive cardiometabolic care.Changes in body composition were assessed using a bioelectrical impedance analysis system in this observational study. OABL- eng OTO - NOTNLM OT - Cardiometabolic health OT - Diabetes OT - Exercise intervention OT - Metabolic management OT - Obesity OT - Sarcopaenia COIS- Conflict of interest: P.R.T. is a consultant to Novo Nordisk, Eli Lilly, Amgen, Boehringer, Ingelheim, and Roche. All other authors have no disclosures. EDAT- 2026/05/21 12:39 MHDA- 2026/10/13 00:16 CRDT- 2026/05/21 08:32 PHST- 2026/01/19 00:00 [received] PHST- 2026/03/30 00:00 [revised] PHST- 2026/04/23 00:00 [accepted] PHST- 2026/10/13 00:16 [medline] PHST- 2026/05/21 12:39 [pubmed] PHST- 2026/05/21 08:32 [entrez] AID - 8688935 [pii] AID - 10.1093/eurjpc/zwag279 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2026 Oct 13;33(14):2665-2674. doi: 10.1093/eurjpc/zwag279. PMID- 42162206 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260825 IS - 1432-5241 (Electronic) IS - 0364-216X (Linking) VI - 50 IP - 13 DP - 2026 Jul TI - Effects of GLP-1 Receptor Agonists on Skin Quality: A Comprehensive Literature Review. PG - 5403-5407 LID - 10.1007/s00266-026-05820-4 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide and liraglutide, have revolutionized the treatment of type 2 diabetes and obesity due to their potent effects on weight loss and glycemic control. However, emerging evidence has highlighted dermatologic side effects associated with the rapid reduction of subcutaneous adipose tissue, particularly in the context of aesthetic skin integrity. This systematic review aims to comprehensively evaluate the current evidence on the effects of GLP-1 RAs on skin quality, including dermal structure alterations, adipose compartment loss, and skin elasticity changes. METHODS: A systematic literature search was performed in PubMed (MEDLINE) using predefined keywords including "semaglutide," "liraglutide," "GLP-1 receptor agonists," "skin quality," "adipose tissue loss," and "elasticity." Studies published up to May 2025 were considered. Inclusion criteria involved human studies documenting dermatologic alterations associated with GLP-1 RA use. Forty studies were selected based on PRISMA guidelines, encompassing clinical trials, case reports, and observational studies. RESULTS: The data revealed that GLP-1 RA-induced weight loss frequently results in visible changes to skin morphology. Key findings included facial volume loss ("Ozempic face"), dermal thinning, loss of collagen and elastin fibers, and decreased skin elasticity. Patients exhibited localized fat loss in multiple anatomical regions, leading to redundant skin folds and accelerated signs of aging. Risk factors for more severe dermatological outcomes included advanced age, prolonged obesity history, rapid weight loss, poor hydration, and insufficient protein intake. CONCLUSION: While GLP-1 RAs offer substantial benefits for weight and metabolic health, their dermatologic side effects represent an important clinical consideration. Proactive measures such as gradual weight loss, nutritional optimization, hydration, and early dermatologic intervention are recommended. Future prospective studies are warranted to better define the pathophysiology and management of GLP-1 RA-associated skin changes. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. CI - (c) 2026. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery. FAU - Barone, Mauro AU - Barone M AUID- ORCID: 0000-0002-1439-5686 AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. maurosabbarone@gmail.com. FAU - Brunetti, Beniamino AU - Brunetti B AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. FAU - D'Emilio, Roberta AU - D'Emilio R AD - Private Practice, Rome, Italy. FAU - Caputo, Maria Grazia AU - Caputo MG AD - Private Practice, Rome, Italy. FAU - Tenna, Stefania AU - Tenna S AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. FAU - Persichetti, Paolo AU - Persichetti P AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260520 PL - United States TA - Aesthetic Plast Surg JT - Aesthetic plastic surgery JID - 7701756 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Aesthetic Plast Surg. 2026 Aug;50(15):6644. doi: 10.1007/s00266-026-05948-3. PMID: 42474489 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/pharmacology/adverse effects MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/pharmacology/adverse effects MH - *Skin Aging/drug effects MH - *Skin/drug effects MH - Obesity/drug therapy MH - Risk Assessment MH - Hypoglycemic Agents/pharmacology OTO - NOTNLM OT - GLP-1 OT - Glucagon like peptide 1 receptor agonist OT - Skin quality OT - Systematic review COIS- Declarations. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Informed Consent: For this type of study, informed consent is not required Human and Animal Participants: This article does not contain any studies with human participants or animals performed by any of the authors. EDAT- 2026/05/21 05:33 MHDA- 2026/08/04 12:46 CRDT- 2026/05/20 23:34 PHST- 2025/05/14 00:00 [received] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/08/04 12:46 [medline] PHST- 2026/05/21 05:33 [pubmed] PHST- 2026/05/20 23:34 [entrez] AID - 10.1007/s00266-026-05820-4 [pii] AID - 10.1007/s00266-026-05820-4 [doi] PST - ppublish SO - Aesthetic Plast Surg. 2026 Jul;50(13):5403-5407. doi: 10.1007/s00266-026-05820-4. Epub 2026 May 20. PMID- 42161872 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260717 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 106 IP - 20 DP - 2026 Jun 2 TI - [Value and benefit of basic insulin/GLP-1RA weekly preparation in clinical treatment of type 2 diabetes in adults]. PG - 1969-1976 LID - 10.3760/cma.j.cn112137-20260325-00802 [doi] AB - The prevalence of type 2 diabetes mellitus has been rising continuously in China. However, glycemic control rates remain suboptimal, posing a significant public health challenge. Although traditional intensive insulin strategies are effective in improving glycemic control, they are often associated with risks such as hypoglycemia and weight gain. Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) offer complementary mechanisms of action, enhancing efficacy and safety while simplifying treatment regimens, making them a key focus of clinical development. Insulin icodec/semaglutide fixed-ratio combination (IcoSema), the first once-weekly dual-component preparation combining a basal insulin and a GLP-1RA, utilizes advanced formulation technology to achieve stable co-formulation of the ultra-long-acting once-weekly basal insulin and the once-weekly GLP-1RA, with the two components acting in a complementary and synergistic manner. The Phase 3 COMBINE clinical trial program demonstrated that, compared with insulin icodec, semaglutide(1.0 mg), or basal-bolus insulin regimens, IcoSema provides superior or equivalent glycemic control, and the risk of clinically significant or severe hypoglycemic events is comparable to that of semaglutide(1.0 mg). Once-weekly administration helps to simplify the treatment regimen and improve treatment adherence. The clinical application of IcoSema is expected to alleviate the dilemma in Chinese type 2 diabetes management of balancing effective glycemic control with safety and simplicity, offering a new therapeutic option for patients requiring insulin intensification that combines efficacy, safety, and convenience. FAU - Zhang, S C AU - Zhang SC AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Zang, L AU - Zang L AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Cheng, Y AU - Cheng Y AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Mu, Y M AU - Mu YM AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Hu, X AU - Hu X AD - Department of Pharmacy, Beijing Hospital, National Center for Gerontology, National Clinical Research Center for Gerontology, the Key Laboratory of Geriatrics of NHC, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Drug Combinations) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Insulin/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Semaglutide MH - Drug Combinations MH - Glucagon-Like Peptides/therapeutic use/administration & dosage EDAT- 2026/05/21 05:33 MHDA- 2026/05/29 15:41 CRDT- 2026/05/20 22:32 PHST- 2026/05/29 15:41 [medline] PHST- 2026/05/21 05:33 [pubmed] PHST- 2026/05/20 22:32 [entrez] AID - 10.3760/cma.j.cn112137-20260325-00802 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2026 Jun 2;106(20):1969-1976. doi: 10.3760/cma.j.cn112137-20260325-00802. PMID- 42155605 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260612 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - Glucagon-like peptide-1 receptor agonists and hair loss: A systematic review and meta-analysis. PG - 113333 LID - S0168-8227(26)00253-6 [pii] LID - 10.1016/j.diabres.2026.113333 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used drugs with applications beyond the management of obesity and diabetes mellitus. This study aimed to investigate the association between GLP-1 RA use and hair loss. METHODS: Four electronic databases were systematically searched for relevant studies published from inception to August 20, 2025. We included randomized controlled trials (RCTs) or prospective nonrandomized interventional studies that reported hair loss following GLP-1 RA therapy. A random-effects model was used for meta-analysis. RESULTS: A total of nine interventional studies, including 7 RCTs and 2 non-RCTs, were included in the final meta-analysis. Data from a total of 4114 GLP-1 RA users were analyzed. The pooled analysis revealed a significantly higher risk of hair loss in GLP-1 RA users than in placebo users (risk ratio [RR]: 3.252; 95% confidence interval [CI]: 1.437 to 7.358). The significant results persisted even when the analysis was restricted to RCTs focusing on patients with overweight or obesity (RR: 3.587; 95% CI: 2.100 to 6.124). Furthermore, a single-arm analysis revealed that the event rate of hair loss following GLP-1 RA therapy was 3.9%. CONCLUSIONS: The use of GLP-1 RAs is significantly associated with an increased risk of hair loss. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Cheng, Po-Lung AU - Cheng PL AD - Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Chang, Hua-Ching AU - Chang HC AD - Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hc.chang@tmu.edu.tw. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260518 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Alopecia/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy OTO - NOTNLM OT - Alopecia OT - Glucagon-like peptide-1 OT - Hair loss OT - Semaglutide OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/20 00:35 MHDA- 2026/06/11 06:40 CRDT- 2026/05/19 19:34 PHST- 2026/04/16 00:00 [received] PHST- 2026/05/14 00:00 [revised] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/06/11 06:40 [medline] PHST- 2026/05/20 00:35 [pubmed] PHST- 2026/05/19 19:34 [entrez] AID - S0168-8227(26)00253-6 [pii] AID - 10.1016/j.diabres.2026.113333 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113333. doi: 10.1016/j.diabres.2026.113333. Epub 2026 May 18. PMID- 42155603 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260620 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - GLP-1 receptor agonists and surgical care: implications for bariatric Procedures, perioperative Outcomes, and nutritional optimization. PG - 113332 LID - S0168-8227(26)00252-4 [pii] LID - 10.1016/j.diabres.2026.113332 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes and are now frequently encountered in patients undergoing bariatric and other elective surgeries. Their effects on gastric motility, appetite, and nutrient intake have important implications for perioperative safety, surgical outcomes, and nutritional care. OBJECTIVES: To summarize current evidence on the effects of GLP-1RAs on perioperative management, bariatric surgery outcomes, and nutritional optimization in surgical patients. METHODS: A narrative review of PubMed- and Scopus-indexed randomized trials, observational studies, systematic reviews, and clinical guidelines was conducted. Evidence was synthesized across perioperative risk, preoperative optimization, post-bariatric outcomes, and nutritional implications. RESULTS: GLP-1RA use was associated with delayed gastric emptying and increased residual gastric contents in some patients, especially during dose escalation or in those with gastrointestinal symptoms. However, clinically significant aspiration events were uncommon, supporting individualized perioperative management rather than routine discontinuation. Preoperatively, GLP-1RAs promoted short-term weight loss and metabolic improvement in bariatric candidates, potentially improving operative conditions and reducing risk. Postoperatively, the strongest evidence from randomized controlled trials showed that liraglutide and semaglutide achieved additional weight loss and improved glycemic control in patients with weight regain, insufficient weight loss, or persistent diabetes after bariatric surgery, potentially lowering the need for revisional procedures. Nutritionally, appetite suppression may worsen inadequate protein intake and micronutrient deficiencies, increasing risks of sarcopenia, anemia, and bone disease without structured monitoring and supplementation. However, direct trial evidence for supplementation strategies in this specific population is lacking. CONCLUSIONS: GLP-1RAs offer important metabolic and weight-related benefits across the surgical continuum, particularly around bariatric surgery, but require individualized perioperative planning and proactive nutritional surveillance. They should be viewed as adjuncts to, not replacements for, bariatric surgery. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Elawa, Zeyad AU - Elawa Z AD - School of Medicine, New Giza University, Giza, Egypt. FAU - Khalil, Ahmed AU - Khalil A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar. FAU - Kardousha, Ahmed AU - Kardousha A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar. FAU - ElAwwa, Ahmed AU - ElAwwa A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar. FAU - Soliman, Ashraf T AU - Soliman AT AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar. Electronic address: atsoliman56@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260520 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Bariatric Surgery/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy/surgery MH - Semaglutide MH - Perioperative Care/methods MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonists OT - Nutrition OT - Obesity management OT - Perioperative care COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/20 00:32 MHDA- 2026/06/11 06:38 CRDT- 2026/05/19 19:34 PHST- 2026/03/26 00:00 [received] PHST- 2026/05/02 00:00 [revised] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/06/11 06:38 [medline] PHST- 2026/05/20 00:32 [pubmed] PHST- 2026/05/19 19:34 [entrez] AID - S0168-8227(26)00252-4 [pii] AID - 10.1016/j.diabres.2026.113332 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113332. doi: 10.1016/j.diabres.2026.113332. Epub 2026 May 20. PMID- 42152320 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260814 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 20 DP - 2026 May 15 TI - Pharmacovigilance of semaglutide: A descriptive analysis of WHO-VigiAccess reports. PG - e48811 LID - 10.1097/MD.0000000000048811 [doi] LID - e48811 AB - Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely prescribed for type 2 diabetes mellitus and chronic weight management. With its growing global use, continuous pharmacovigilance is essential to detect emerging patterns of adverse drug reactions (ADRs). To describe the global ADRs profile of semaglutide using data from the World Health Organization's (WHO) VigiAccess pharmacovigilance database. A retrospective descriptive analysis was conducted using publicly available ADR data retrieved from the WHO-VigiAccess portal on October 18, 2025. The total number and proportion of ADRs were summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC). Demographic information, including age group, sex, geographic region, and reporting year, was reviewed descriptively. A total of 81,770 ADR reports associated with semaglutide were identified. The most frequently reported SOCs were gastrointestinal disorders (28%, n = 42,574), general disorders and administration site conditions (12%, n = 19,200), and injury, poisoning and procedural complications (11%, n = 16,601). Additional categories included nervous system disorders (8%), investigations (7%), and metabolism and nutrition disorders (7%). The majority of ADRs were reported among adults aged 45 to 64 years, with most originating from Europe and the Americas. Annual reporting increased markedly between 2018 and 2025, corresponding with expanded clinical use and obesity-related approvals. Global pharmacovigilance data indicate that semaglutide ADRs are primarily gastrointestinal and systemic in nature, consistent with its known pharmacological effects. Continuous monitoring is warranted to identify emerging safety signals and support optimized patient management as use expands worldwide. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Alorfi, Nasser M AU - Alorfi NM AUID- ORCID: 0000-0002-0636-7685 AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alourfi, Mansour M AU - Alourfi MM AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. FAU - Aldabbagh, Ammar AU - Aldabbagh A AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. FAU - Alghamdi, Waleed Saleh AU - Alghamdi WS AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. AD - Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah , Saudi Arabia. FAU - Al Ghamdi, Sarah S AU - Al Ghamdi SS AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. AD - Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah , Saudi Arabia. FAU - Aldekhail, Nasser M AU - Aldekhail NM AD - Department of Pharmacy, College of Pharmacy, Nursing and Medical Sciences, Riyadh Elm University, Riyadh, Saudi Arabia. FAU - Alkhanani, Mustfa Faisal AU - Alkhanani MF AD - Biology Department, College of Sciences, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia. FAU - Alansari, Abdulrhman M AU - Alansari AM AD - Pharmaceutical Care Services, King Salman Medical City, Madinah Health Cluster, Madinah, Saudi Arabia. FAU - Alsolami, Faris A AU - Alsolami FA AD - Kholais General Hospital, Makkah Cluster, Ministry of Health, Madinah, Saudi Arabia. FAU - Ibrahim, Nihal Abdalla AU - Ibrahim NA AD - College of Pharmacy, Ajman University, Ajman, United Arab Emirates. AD - Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates. LA - eng GR - 26UQU4420038GSSR02/Umm Al-Qura University, Saudi Arabia/ PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Pharmacovigilance MH - Female MH - Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Male MH - Middle Aged MH - Adult MH - World Health Organization MH - *Hypoglycemic Agents/adverse effects MH - Aged MH - Adolescent MH - Young Adult MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology MH - Child MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13183005 OTO - NOTNLM OT - GLP-1 receptor agonist OT - WHO-VigiAccess OT - adverse drug reactions OT - gastroenterology OT - pharmacovigilance OT - semaglutide COIS- The authors have no conflicts of interest to disclose. EDAT- 2026/05/19 06:30 MHDA- 2026/05/19 06:31 PMCR- 2026/05/15 CRDT- 2026/05/19 01:01 PHST- 2025/10/22 00:00 [received] PHST- 2026/04/24 00:00 [accepted] PHST- 2026/05/19 06:31 [medline] PHST- 2026/05/19 06:30 [pubmed] PHST- 2026/05/19 01:01 [entrez] PHST- 2026/05/15 00:00 [pmc-release] AID - 00005792-202605150-00035 [pii] AID - MD-D-25-14502 [pii] AID - 10.1097/MD.0000000000048811 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 May 15;105(20):e48811. doi: 10.1097/MD.0000000000048811. PMID- 42150869 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Association of GLP-1 Receptor Agonist Use With Safety Outcomes in Individuals With Opioid Use Disorder: A Target Trial Emulation. PG - 6861-6873 LID - 10.1111/dom.70867 [doi] AB - AIMS: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) initiation and adverse gastrointestinal, renal, respiratory and psychiatric outcomes among individuals with opioid use disorder (OUD). MATERIALS AND METHODS: This retrospective cohort study was conducted using the MarketScan Commercial Claims and Encounters database (2016-2023) following a target trial emulation framework. Participants were aged 18 years or older with OUD and eligible for GLP-1 RA treatment for type 2 diabetes or obesity. Ten prespecified safety outcomes were assessed. For each prespecified outcome, separate analytic cohorts of GLP-1 RA users and non-users were created based on time-conditional propensity score matching. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated comparing GLP-1 RA users with non-users, with follow-up until outcome occurrence, disenrollment or end of the study period (December 2023), whichever came first. RESULTS: For each prespecified outcome, the size of the matched cohorts varied from 1472 to 2329 GLP-1 RA users (and an equal number of non-users), depending on outcome-specific eligibility criteria. For the gastrointestinal outcomes, GLP-1 RA use was associated with a lower risk of pancreatitis (aHR, 0.65; 95% CI, 0.45-0.93), with no increased risk of gastroparesis. No increased risks were observed for renal (AKI) or respiratory (aspiration pneumonitis) outcomes. Among psychiatric outcomes, lower risks were observed for insomnia (0.78; 0.68-0.89) and anxiety (0.76; 0.67-0.86), with no increased risk for depression, stress-related disorders, eating disorders and suicidal behaviour or ideation. Findings were generally consistent across subgroups stratified by age, sex and type 2 diabetes status. CONCLUSIONS: In a large cohort of commercially insured individuals with OUD, GLP-1 RA initiation was not associated with increased adverse gastrointestinal, renal, respiratory or psychiatric outcomes and was associated with lower risks of pancreatitis, insomnia and anxiety. While the possibility of residual confounding cannot be excluded, these data support the safety of GLP-1 RAs when used for approved indications in patients with OUD and inform ongoing repurposing efforts. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Hussain, Tahmid AU - Hussain T AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. FAU - Al Faysal, Jabed AU - Al Faysal J AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. FAU - Kotecha, Pareeta AU - Kotecha P AUID- ORCID: 0009-0009-4864-9662 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. FAU - Ramon, Ronald AU - Ramon R AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. FAU - Wang, Yehua AU - Wang Y AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis, Indiana, USA. AD - Regenstrief Institute, Indianapolis, Indiana, USA. FAU - Hasan, Md Mahmudul AU - Hasan MM AUID- ORCID: 0000-0001-5899-793X AD - Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. AD - Department of Information Systems and Operations Management, University of Florida, Gainesville, Florida, USA. LA - eng PT - Journal Article DEP - 20260518 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Opioid-Related Disorders/complications/drug therapy/epidemiology MH - Retrospective Studies MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Middle Aged MH - Adult MH - Obesity/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - drug repurposing OT - opioid use disorder OT - real-world evidence OT - safety profile EDAT- 2026/05/19 00:28 MHDA- 2026/07/08 18:51 CRDT- 2026/05/18 21:23 PHST- 2026/04/21 00:00 [revised] PHST- 2026/01/23 00:00 [received] PHST- 2026/04/30 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/05/19 00:28 [pubmed] PHST- 2026/05/18 21:23 [entrez] AID - 10.1111/dom.70867 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6861-6873. doi: 10.1111/dom.70867. Epub 2026 May 18. PMID- 42150748 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Association Between Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review. PG - 6482-6508 LID - 10.1111/dom.70878 [doi] AB - AIMS: We aimed to examine the association between GLP-1 RA use and suicidal ideation or behaviours through a systematic review of observational studies. MATERIALS AND METHODS: A comprehensive search of MEDLINE, PubMed, EMBASE, CINAHL and PsycINFO was conducted from database inception through December 11, 2025. Observational studies investigating suicidal ideation, suicide attempts or complete suicide among adults using GLP-1 RAs were included. Eligibility screening, data extraction and risk of bias assessments were performed independently and in duplicate, with disagreements resolved by a third reviewer. RESULTS: Forty-three studies were included. Findings varied by study design. Some case reports suggested a temporal relationship between GLP-1 RA use and suicidal ideation. Cross-sectional studies and case-control studies identified a negative association between GLP-1 RAs and suicide attempts. Pharmacovigilance and cohort studies showed more mixed results, with some studies identifying a positive association between semaglutide or liraglutide and suicidal ideation, while others paradoxically reported a negative association with suicidal behaviours (i.e., attempts and intentional self-harm) or completed suicide. CONCLUSIONS: While evidence does not support GLP-1 RAs as a causative agent for suicidality, due to multiple risk factors in this population, clinicians should routinely assess mental health status before and during GLP-1 RA treatment regardless of indication. Importantly, a history of concurrent mental health conditions should not preclude use of a GLP-1 RA; rather, individual patient factors should be accounted for when making prescribing decisions. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chan, Timothy H AU - Chan TH AD - Norton College of Medicine, SUNY Upstate University, Syracuse, New York, USA. FAU - Cosler, Leon E AU - Cosler LE AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. FAU - Gionfriddo, Michael R AU - Gionfriddo MR AD - Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota, USA. FAU - Leppien, Emily E AU - Leppien EE AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. FAU - Sommers, Eleanor J AU - Sommers EJ AD - Norton College of Medicine, SUNY Upstate University, Syracuse, New York, USA. FAU - Lussier, Mia E AU - Lussier ME AUID- ORCID: 0000-0002-5523-0781 AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260518 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Suicidal Ideation MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Suicide, Attempted/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Suicide/statistics & numerical data MH - Observational Studies as Topic PMC - PMC13341386 OTO - NOTNLM OT - glucagon-like Peptide-1 receptor agonists OT - suicidal ideation OT - suicide OT - systematic review COIS- The authors declare no conflicts of interest. EDAT- 2026/05/19 00:28 MHDA- 2026/07/08 18:50 PMCR- 2026/07/08 CRDT- 2026/05/18 19:32 PHST- 2026/04/28 00:00 [revised] PHST- 2026/02/03 00:00 [received] PHST- 2026/05/05 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2026/05/19 00:28 [pubmed] PHST- 2026/05/18 19:32 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70878 [pii] AID - 10.1111/dom.70878 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6482-6508. doi: 10.1111/dom.70878. Epub 2026 May 18. PMID- 42144979 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 2993-7175 (Electronic) IS - 2993-7175 (Linking) VI - 50 IP - 5 DP - 2026 May TI - GLP-1 Receptor Agonists for Treating Alcohol Use Disorder: A Critical Review. PG - e70312 LID - 10.1111/acer.70312 [doi] LID - e70312 AB - This narrative review evaluates glucagon-like peptide-1 receptor agonists (GLP-1RAs) as potential treatments for alcohol use disorder (AUD), a major public health problem with limited treatment options. We first briefly describe the development of GLP-1RAs for treating type 2 diabetes and obesity and then focus on recent studies of the drugs' effects on alcohol-related behaviors, both in animal models and clinical studies. We identified relevant literature by searching for studies of incretin-based therapies using PubMed, Google Scholar, and clinicaltrials.gov and reviewing the reference lists of published reviews. We limited our discussion of preclinical studies of alcohol-related effects to those that provide insights into the mechanism of effects. Clinical studies comprised both observational studies, including those using electronic health records and other real-world data, and randomized controlled clinical trials, including studies completed or in progress. Of the clinical studies, we include original, peer-reviewed research published in English and excluded case reports, commentaries, and preprints. This yielded a total of 13 preclinical studies, 14 clinical studies, 4 published interventional trials, and 19 interventional trials in progress or completed but unpublished. We found convergent evidence from animal and human studies that GLP-1RAs reduce alcohol consumption and improve alcohol-associated outcomes. Several randomized controlled trials (RCTs) in progress aim to test the effects of both established and novel compounds, and different drug formulations and combinations on alcohol consumption. Additional RCTs are needed to establish the efficacy of GLP-1RAs for treating AUD, with mechanistic studies needed to elucidate more fully their mode of action in reducing alcohol consumption. CI - (c) 2026 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol. FAU - Woo, Sean AU - Woo S AD - University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhu, Grace AU - Zhu G AD - University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Castro, Chrismely AU - Castro C AD - University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Phuong, Allen AU - Phuong A AD - University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Roy, Aadita AU - Roy A AD - University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Davis, Christal N AU - Davis CN AUID- ORCID: 0000-0003-3974-5598 AD - Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, Pennsylvania, USA. FAU - Kranzler, Henry R AU - Kranzler HR AD - Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, Pennsylvania, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Alcohol Clin Exp Res (Hoboken) JT - Alcohol, clinical & experimental research JID - 9918609780906676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Alcoholism/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13181353 COIS- Dr. Kranzler is a member of advisory boards for Altimmune and Clearmind Medicine; a consultant to Sobrera Pharmaceuticals, Altimmune, Lilly, Ribocure, and Boehringer-Ingelheim; and the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes and company-initiated studies by Altimmune and Lilly. The authors declare no conflicts of interest. EDAT- 2026/05/18 06:31 MHDA- 2026/05/18 06:32 PMCR- 2026/05/18 CRDT- 2026/05/18 03:43 PHST- 2026/04/08 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/04/28 00:00 [accepted] PHST- 2026/05/18 06:32 [medline] PHST- 2026/05/18 06:31 [pubmed] PHST- 2026/05/18 03:43 [entrez] PHST- 2026/05/18 00:00 [pmc-release] AID - ACER70312 [pii] AID - 10.1111/acer.70312 [doi] PST - ppublish SO - Alcohol Clin Exp Res (Hoboken). 2026 May;50(5):e70312. doi: 10.1111/acer.70312. PMID- 42142899 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260716 IS - 1557-8224 (Electronic) IS - 1089-3261 (Linking) VI - 30 IP - 2 DP - 2026 May TI - Treatment of Modifiable Risks in Metabolic Dysfunction-Associated Steatotic Liver Disease: Drugs Targeting Obesity and Type 2 Diabetes. PG - 381-390 LID - S1089-3261(26)00003-6 [pii] LID - 10.1016/j.cld.2026.01.003 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease, is increasingly prevalent and closely linked to obesity and type 2 diabetes (T2D). These metabolic conditions not only represent drivers of disease progression, but also as therapeutic targets for modifying the disease course. This study reviews the pathophysiological contributions of obesity and T2D to MASLD and evaluates pharmacologic strategies aimed at these drivers. Incretin-based therapies, especially GLP-1 receptor agonists and co-agonists have emerged as leading agents in promoting weight loss, reducing cardiovascular and renal outcomes in T2D and obesity. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Kumar, Sonal AU - Kumar S AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine/New York Presbyterian, New York, NY, USA. Electronic address: sok9028@med.cornell.edu. FAU - Macedo, Maria Paula AU - Macedo MP AD - NMS-NOVA Medical School, FCM-Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Campo dos Martires da Patria, Lisbon, Portugal; iNOVA4Health-Advancing Precision Medicine, NOVA Medical School, FCM-Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Campo dos Martires da Patria, Lisbon, Portugal; APDP-Diabetes Portugal, Education and Research Center, Lisbon, Portugal. FAU - Roden, Michael AU - Roden M AD - Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University Dusseldorf, Dusseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany; German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. FAU - Kashyap, Sangeeta R AU - Kashyap SR AD - Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine/New York Presbyterian, New York, NY, USA. LA - eng PT - Journal Article PT - Review DEP - 20260323 PL - United States TA - Clin Liver Dis JT - Clinics in liver disease JID - 9710002 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Obesity/drug therapy/complications/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy/etiology/metabolism MH - Incretins/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Insulin Resistance OTO - NOTNLM OT - GLP1 receptor agonists OT - Insulin resistance OT - Liver fibrosis OT - Metabolic dysfunction-associated steatotic liver disease (MASLD) OT - Obesity pharmacotherapy EDAT- 2026/05/17 06:29 MHDA- 2026/05/17 06:30 CRDT- 2026/05/16 20:55 PHST- 2026/05/17 06:30 [medline] PHST- 2026/05/17 06:29 [pubmed] PHST- 2026/05/16 20:55 [entrez] AID - S1089-3261(26)00003-6 [pii] AID - 10.1016/j.cld.2026.01.003 [doi] PST - ppublish SO - Clin Liver Dis. 2026 May;30(2):381-390. doi: 10.1016/j.cld.2026.01.003. Epub 2026 Mar 23. PMID- 42142623 OWN - NLM STAT- MEDLINE DCOM- 20260930 LR - 20260930 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 10 DP - 2026 Oct TI - Divergent Risks of Endocrine and Nonendocrine Malignancies in GLP-1 Receptor Agonist Users: A Propensity-Matched Real-World Analysis of Over 140 000 Patients. PG - 1488-1496 LID - S1530-891X(26)00987-0 [pii] LID - 10.1016/j.eprac.2026.05.010 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes mellitus (T2DM). The long-term impact on cancer risk remains uncertain. This study aimed to evaluate the association between GLP-1 RA and the risk of cancer, including site-specific malignancies. METHODS: This retrospective cohort study utilized the TriNetX database. Adults with T2DM between 2015 and 2023 were identified. After 1:1 propensity score matching, 144 410 GLP-1 RA users were compared with nonusers. Primary outcomes were all-cause mortality and incident malignant neoplasms. Secondary outcomes included site-specific cancers. RESULTS: GLP-1 RA use was associated with lower all-cause mortality (hazard ratio [HR] 0.693) and a reduced overall incidence of cancer (HR 0.905). Regarding nonendocrine malignancies, significant risk reductions were observed for digestive cancers (HR 0.710) and respiratory cancers (HR 0.691), as well as for other sites including oral, female genital, and central nervous system cancers. In contrast, GLP-1 RA was linked to an increased risk of thyroid gland cancer (HR 1.411). Active-comparator analyses against dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter 2 inhibitor yielded broadly consistent findings. Landmark analyses at 3 years showed attenuation of the thyroid cancer signal to nonsignificance, suggesting surveillance bias rather than a true carcinogenic effect. CONCLUSION: This real-world analysis demonstrates divergent oncologic risks associated with GLP-1 RA use, while the therapy offers potential protective effects against nonendocrine malignancies (particularly digestive and respiratory). The initially elevated thyroid cancer risk was no longer significant at 3 years, suggesting surveillance bias. These findings support the overall oncologic safety of GLP-1 RA in T2DM management, while warranting further long-term studies to confirm these associations. CI - Copyright (c) 2026 AACE. Published by Elsevier Inc. All rights reserved. FAU - Hung, Cheng-Hsien AU - Hung CH AD - Department of Pharmacy, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, Taoyuan, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Center for Health Data Science, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Cheng-Chung Wei, James AU - Cheng-Chung Wei J AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan; Office of Research and Development, Asia University, Taichung, Taiwan. Electronic address: jccwei@gmail.com. LA - eng PT - Journal Article DEP - 20260515 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Neoplasms/epidemiology/chemically induced MH - Aged MH - Propensity Score MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Incidence MH - Adult MH - Risk Factors OTO - NOTNLM OT - digestive cancer OT - endocrine cancer OT - glucagon-like peptide-1 receptor agonists OT - real-world evidence OT - respiratory cancers OT - type 2 diabetes mellitus COIS- Disclosure The authors have no conflicts of interest to disclose. EDAT- 2026/05/17 06:29 MHDA- 2026/09/30 23:29 CRDT- 2026/05/16 19:37 PHST- 2026/02/23 00:00 [received] PHST- 2026/05/06 00:00 [revised] PHST- 2026/05/08 00:00 [accepted] PHST- 2026/09/30 23:29 [medline] PHST- 2026/05/17 06:29 [pubmed] PHST- 2026/05/16 19:37 [entrez] AID - S1530-891X(26)00987-0 [pii] AID - 10.1016/j.eprac.2026.05.010 [doi] PST - ppublish SO - Endocr Pract. 2026 Oct;32(10):1488-1496. doi: 10.1016/j.eprac.2026.05.010. Epub 2026 May 15. PMID- 42142362 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260918 IS - 2058-1742 (Electronic) IS - 2058-1742 (Linking) VI - 12 IP - 6 DP - 2026 Sep 16 TI - Cardiovascular and renal outcomes of GLP-1 receptor agonists in type 2 diabetes mellitus: a systematic review and meta-analysis. PG - 980-994 LID - 10.1093/ehjqcco/qcag079 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a foundational therapeutic option for type 2 diabetes mellitus (T2DM), offering glycaemic control and cardiovascular benefits. This systematic review and meta-analysis evaluate the impact of GLP-1RAs on cardiovascular outcomes in patients with T2DM. METHODS AND RESULTS: We conducted a comprehensive search of PubMed, Embase, and Cochrane Library up to 31 March 2025, for randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in T2DM patients. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled using a random-effects model. Twenty RCTs involving 83 004 patients were included. GLP-1RAs significantly reduced the risk of major adverse cardiovascular events (RR 0.87, 95% CI 0.83-0.92), all-cause death (RR 0.89, 95% CI 0.84-0.93), cardiovascular death (RR 0.88, 95% CI 0.81-0.94), myocardial infarction (RR 0.87, 95% CI 0.79-0.96), stroke (RR 0.88, 95% CI 0.81-0.96) and composite renal outcome (RR 0.80, 95% CI 0.73-0.88) compared to placebo. In addition, a trend of reduction in heart failure hospitalizations (RR 0.93, 95% CI 0.85-1.01), and coronary revascularization (RR = 0.87, 95% CI 0.74 to 1.01) was observed with GLP-1 RAs without reaching statistical significance. CONCLUSION: GLP-1RAs are associated with improved cardiovascular outcomes in patients with T2DM. These findings support current guideline recommendations and highlight their cardioprotective benefits beyond glycaemic control in patients with T2DM. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Ahmed, Mushood AU - Ahmed M AUID- ORCID: 0000-0001-9872-8224 AD - Department of Cardiology, Rawalpindi Medical University, Rawalpindi 46000, Pakistan. FAU - Hashmi, Tallal Mushtaq AU - Hashmi TM AD - Department of Cardiology, Rawalpindi Medical University, Rawalpindi 46000, Pakistan. FAU - Shahzad, Maryam AU - Shahzad M AD - Department of Cardiology, Dow University of Health Sciences, Karachi 74200, Pakistan. FAU - Zia, Rohma AU - Zia R AD - Department of Cardiology, Rawalpindi Medical University, Rawalpindi 46000, Pakistan. FAU - Ashraf, Hadiah AU - Ashraf H AD - Department of Cardiology, Rawalpindi Medical University, Rawalpindi 46000, Pakistan. FAU - Ahmed, Raheel AU - Ahmed R AUID- ORCID: 0000-0003-2814-7314 AD - Department of Cardiology, Royal Brompton Hospital, London SW3 6NP, UK. AD - National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK. FAU - Rashid, Muhammad AU - Rashid M AUID- ORCID: 0000-0001-9725-1583 AD - Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, David Weatherall building, University Road, Keele ST5 5BG, UK. FAU - Greene, Stephen J AU - Greene SJ AD - Division of Cardiology, Duke University Medical Center, 2301 Erwin Road, Durham, NC, USA. AD - Division of Research, Duke Clinical Research Institute, 2301 Erwin Road, Durham, NC, USA. FAU - Mentz, Robert J AU - Mentz RJ AD - Division of Cardiology, Duke University Medical Center, 2301 Erwin Road, Durham, NC, USA. AD - Division of Research, Duke Clinical Research Institute, 2301 Erwin Road, Durham, NC, USA. FAU - Fudim, Marat AU - Fudim M AD - Division of Cardiology, Duke University Medical Center, 2301 Erwin Road, Durham, NC, USA. AD - Division of Research, Duke Clinical Research Institute, 2301 Erwin Road, Durham, NC, USA. FAU - Fonarow, Gregg C AU - Fonarow GC AD - Ahmanson-UCLA Cardiomyopathy Center, Division of Cardiology, University of California Los Angeles, Los Angeles, CA 90095, USA. FAU - Rana, Jamal S AU - Rana JS AD - Division of Cardiology, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. AD - Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Eur Heart J Qual Care Clin Outcomes JT - European heart journal. Quality of care & clinical outcomes JID - 101677796 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Eur Heart J Qual Care Clin Outcomes. 2026 Sep 16;12(6):995-997. doi: 10.1093/ehjqcco/qcag096. PMID: 42237895 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/etiology/epidemiology MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP-1 receptor agonists OT - Meta-analysis OT - Type 2 diabetes COIS- Conflict of interest: G.C.F. reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer outside the submitted work. M.F. reported receiving personal fees from Alleviant, Ajax, Alio Health, Alleviant, Artha, Audicor, Axon Therapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Cardionomics, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, Echosens, EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio, Procyreon, ReCor, Rockley, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily, Vironix, Viscardia, and Zoll; and receiving grants from the National Institutes of Health, Doris Duke, outside the submitted work. R.J.M. has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Rocket Pharmaceuticals, Sanofi, Verily, Vifor, Windtree Therapeutics, and Zoll. S.J.G. has received research support from the Duke University Department of Medicine Chair's Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Otsuka, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2026/05/17 06:28 MHDA- 2026/09/16 11:40 CRDT- 2026/05/16 14:22 PHST- 2025/09/03 00:00 [received] PHST- 2026/01/15 00:00 [revised] PHST- 2026/04/28 00:00 [accepted] PHST- 2026/09/16 11:40 [medline] PHST- 2026/05/17 06:28 [pubmed] PHST- 2026/05/16 14:22 [entrez] AID - 8679361 [pii] AID - 10.1093/ehjqcco/qcag079 [doi] PST - ppublish SO - Eur Heart J Qual Care Clin Outcomes. 2026 Sep 16;12(6):980-994. doi: 10.1093/ehjqcco/qcag079. PMID- 42142150 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260923 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 7 DP - 2026 Jul TI - Switching patterns of GLP-1 receptor agonists from 2018 to 2025 in the largest private healthcare network in Poland. PG - 1267-1278 LID - 10.1007/s00592-026-02709-1 [doi] AB - AIMS: To characterize switching among GLP-1 receptor agonists (GLP-1 RAs) in a large private-sector cohort in Poland and to quantify therapy- and patient-level associations with switching while accounting for switching opportunity and calendar-time dynamics. METHODS: We conducted a retrospective analysis of GLP-1 RA prescription records from the LUX MED network (2018-2025). Switching was defined as any change in agent between consecutive prescriptions. Patients with more than one prescription were included (n = 42,423). The primary analysis used a transition-level discrete-time hazard model in which each prescription-to-prescription interval contributed one observation, and the outcome was switching at that interval. Current-therapy contrasts were reported relative to subcutaneous semaglutide. Sensitivity analyses examined alternative temporal parameterizations and additional adjustment for elapsed time. RESULTS: Overall, 29.7% of patients switched at least once and 14.3% switched two or more times. In the transition-level analysis, 12,620 patients contributed 27,095 transitions. After adjustment for opportunity and calendar time, liraglutide was associated with substantially lower odds of switching compared with subcutaneous semaglutide (OR, 0.02; 95% CI, 0.01-0.03), whereas oral semaglutide (OR, 1.30; 95% CI, 0.78-2.17) and dulaglutide (OR, 1.70; 95% CI, 0.95-3.04) did not differ significantly. Temporal analyses revealed peaks consistent with episodic substitution and accelerated tirzepatide uptake after market entry. The principal associations remained directionally consistent in sensitivity analyses. CONCLUSIONS: Switching among GLP-1 RAs is common and time-dependent. Time-aware modelling identified therapy-specific switching patterns and pronounced temporal variation; reasons for switching remain unmeasured, and the observed associations should be interpreted as hypothesis-generating. CI - (c) 2026. The Author(s). FAU - Lupina, Krzysztof AU - Lupina K AUID- ORCID: 0009-0000-1617-8426 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. FAU - Dziewierz, Artur AU - Dziewierz A AUID- ORCID: 0000-0002-2100-5076 AD - Second Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. AD - Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. FAU - Janczura, Jakub AU - Janczura J AUID- ORCID: 0009-0004-7977-9797 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AUID- ORCID: 0000-0002-8033-3977 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. zbigniew.siudak@ujk.edu.pl. AD - College of Medical Sciences in Warsaw, LUXMED Group, Warsaw, Poland. zbigniew.siudak@ujk.edu.pl. LA - eng PT - Journal Article DEP - 20260516 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Poland MH - Semaglutide MH - Female MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives/administration & dosage MH - Male MH - Middle Aged MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/therapeutic use MH - *Drug Substitution/statistics & numerical data MH - Aged MH - Private Sector PMC - PMC13395827 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Private healthcare OT - Real-world evidence OT - Tirzepatide OT - Treatment switching COIS- Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Declaration of generative AI use: The authors declare that generative artificial intelligence (Claude Opus 4.6, Anthropic) was used during the preparation of this manuscript for language editing and stylistic improvement. Following its use, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. EDAT- 2026/05/17 06:27 MHDA- 2026/07/23 12:37 PMCR- 2026/05/16 CRDT- 2026/05/16 11:03 PHST- 2026/03/06 00:00 [received] PHST- 2026/04/26 00:00 [accepted] PHST- 2026/07/23 12:37 [medline] PHST- 2026/05/17 06:27 [pubmed] PHST- 2026/05/16 11:03 [entrez] PHST- 2026/05/16 00:00 [pmc-release] AID - 10.1007/s00592-026-02709-1 [pii] AID - 2709 [pii] AID - 10.1007/s00592-026-02709-1 [doi] PST - ppublish SO - Acta Diabetol. 2026 Jul;63(7):1267-1278. doi: 10.1007/s00592-026-02709-1. Epub 2026 May 16. PMID- 42139974 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1532-866X (Electronic) IS - 0049-0172 (Linking) VI - 79 DP - 2026 Aug TI - Long-term risk of total joint replacement associated with second-line glucose-lowering therapies in type 2 diabetes: A population-based retrospective cohort study. PG - 152995 LID - S0049-0172(26)00084-3 [pii] LID - 10.1016/j.semarthrit.2026.152995 [doi] AB - OBJECTIVE: To evaluate whether initiation of different second-line glucose-lowering therapies is associated with the risk of total joint replacement (TJR) among patients with type 2 diabetes (T2DM). METHODS: A retrospective, new-user, active-comparator cohort study was conducted using the TriNetX Global Health Research Network. Adults with T2DM initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), or dipeptidyl peptidase-4 inhibitors (DPP4i), with background glucose-lowering therapy not restricted, were identified. Three propensity score-matched pairwise comparisons were performed to balance baseline demographic and clinical characteristics. The primary outcome was TJR, with secondary outcomes including site-specific osteoarthritis (OA) diagnoses and major joint injections. Subgroup and sensitivity analyses were conducted to assess the robustness of findings. RESULTS: In pairwise propensity score-matched analyses, the 10-year observed risk of total joint replacement (TJR) in the matched cohorts was 0.505% versus 0.674% for SGLT2i versus GLP-1 RA, 0.483% versus 0.891% for SGLT2i versus DPP4i, and 0.731% versus 1.038% for GLP-1 RA versus DPP4i. The corresponding hazard ratios were 0.85 (95% CI 0.73-1.00), 1.10 (95% CI 0.95-1.27), and 1.22 (95% CI 1.07-1.39), respectively. SGLT2i use was associated with lower risks of overall osteoarthritis (OA) than both GLP-1 RA and DPP4i, with stronger associations for knee OA than for hip OA. Among patients with pre-existing OA, SGLT2i remained associated with a lower risk of TJR than GLP-1 RA. Overall, associations were more evident for knee-related than for hip-related outcomes. CONCLUSIONS: Among patients with T2DM initiating second-line glucose-lowering therapy, SGLT2i use was associated with more favorable OA-related outcomes, most consistently in comparison with GLP-1 RA. Comparisons with DPP4i were less consistent and were mainly limited to OA diagnostic outcomes rather than total joint replacement. These associations were more evident for knee-related than for hip-related outcomes, suggesting that the choice of second-line antidiabetic therapy may be associated with differences in clinically meaningful OA-related outcomes in real-world practice. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Liu, Che-Yu AU - Liu CY AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, 60002, Taiwan. FAU - Yu, Hui-I AU - Yu HI AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, 60002, Taiwan. FAU - Tsai, Ching-Fang AU - Tsai CF AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, 60002, Taiwan. FAU - Wu, Cheng-Yi AU - Wu CY AD - Department of Orthopedics, Chia-Yi Hospital, Ministry of Health and Welfare, Chiayi City 60002, Taiwan; Department of Rehabilitation, Just Swing Rehab Clinic, Chiayi City 600, Taiwan. FAU - Yang, Hsin-Yi AU - Yang HY AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, 60002, Taiwan. Electronic address: cych13018@gmail.com. LA - eng PT - Journal Article DEP - 20260508 PL - United States TA - Semin Arthritis Rheum JT - Seminars in arthritis and rheumatism JID - 1306053 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Arthroplasty, Replacement/statistics & numerical data MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoarthritis/surgery OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Osteoarthritis OT - Real-world evidence OT - Sodium-glucose cotransporter 2 inhibitors OT - Total joint replacement OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/16 00:37 MHDA- 2026/07/10 12:45 CRDT- 2026/05/15 18:07 PHST- 2026/01/16 00:00 [received] PHST- 2026/04/19 00:00 [revised] PHST- 2026/04/21 00:00 [accepted] PHST- 2026/07/10 12:45 [medline] PHST- 2026/05/16 00:37 [pubmed] PHST- 2026/05/15 18:07 [entrez] AID - S0049-0172(26)00084-3 [pii] AID - 10.1016/j.semarthrit.2026.152995 [doi] PST - ppublish SO - Semin Arthritis Rheum. 2026 Aug;79:152995. doi: 10.1016/j.semarthrit.2026.152995. Epub 2026 May 8. PMID- 42133868 OWN - NLM STAT- MEDLINE DCOM- 20260904 LR - 20260907 IS - 1539-2031 (Electronic) IS - 0192-0790 (Linking) VI - 60 IP - 9 DP - 2026 Oct 1 TI - Esophageal Motility Patterns Are Not Impacted By Glucagon-Like Peptide-1 Receptor Agonist Use. PG - 810-816 LID - 10.1097/MCG.0000000000002395 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with delayed gastric emptying. It is unknown whether GLP-1RAs affect esophageal motility. We aimed to assess the relationship between GLP-1RA use and esophageal function test results. METHODS: Patients with type 2 diabetes undergoing high-resolution manometry (HRM) between December 2022 and October 2024 were retrospectively evaluated, comparing cases with controls (on vs. off GLP-1RA). HRM diagnoses per the Chicago Classification 4.0 and reflux testing results were collected. Patients with prior foregut surgery and known conditions associated with dysmotility (eg, scleroderma) were excluded. Comparisons were performed using chi 2 and Mann-Whitney U tests for categorical and continuous measures, respectively. RESULTS: There were 132 patients assessed and most (29/42, 69.0%) cases were female. Semaglutide was the most commonly used GLP-1RA (24, 57.1%) among cases, and the median A1c was the same (6.6%) for both cases and controls. Most GLP-1RA users (27, 64.3%) had a normal HRM and there was no significant difference ( P =0.07) in overall HRM diagnoses between cases and controls. There was no association ( P =0.51) between GLP-1RA type or dose and esophageal motility diagnoses. Among those undergoing formal reflux testing, there was no difference in detected rates of gastroesophageal reflux disease ( P =0.51) between cases and controls. CONCLUSION: We did not detect a statistically significant impact of GLP-1RA use on esophageal function assessed by formal testing among patients with type 2 diabetes. These results suggest that patients may continue GLP-1RAs when undergoing esophageal testing and are not at significantly increased risk for impacts on esophageal motility diagnosis compared with nonusers. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Wang, Annie L AU - Wang AL AUID- ORCID: 0009-0008-0130-1477 AD - Duke University School of Medicine. FAU - Bach, Laura AU - Bach L AD - Duke Division of Gastroenterology. FAU - Leiman, David A AU - Leiman DA AUID- ORCID: 0000-0001-6350-3906 AD - Duke Division of Gastroenterology. AD - Duke Clinical Research Institute, Durham, NC. LA - eng PT - Journal Article DEP - 20261001 PL - United States TA - J Clin Gastroenterol JT - Journal of clinical gastroenterology JID - 7910017 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Manometry/methods MH - Retrospective Studies MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Middle Aged MH - Aged MH - *Esophagus/drug effects/physiopathology MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Glucagon-Like Peptides/adverse effects MH - *Esophageal Motility Disorders/diagnosis/chemically induced MH - Gastroesophageal Reflux/diagnosis MH - Gastrointestinal Motility/drug effects OTO - NOTNLM OT - GLP-1RA OT - esophageal motility OT - gastrointestinal motility OT - manometry EDAT- 2026/05/14 18:36 MHDA- 2026/09/04 05:35 CRDT- 2026/05/14 15:32 PHST- 2025/10/10 00:00 [received] PHST- 2026/04/20 00:00 [accepted] PHST- 2026/09/04 05:35 [medline] PHST- 2026/05/14 18:36 [pubmed] PHST- 2026/05/14 15:32 [entrez] AID - 00004836-990000000-00650 [pii] AID - 10.1097/MCG.0000000000002395 [doi] PST - epublish SO - J Clin Gastroenterol. 2026 Oct 1;60(9):810-816. doi: 10.1097/MCG.0000000000002395. PMID- 42132708 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260818 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 133 IP - 8 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists and the Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Consensus Statement by the North American Neuro-Ophthalmology Society and the American Academy of Ophthalmology. PG - 1029-1035 LID - S0161-6420(26)00246-0 [pii] LID - 10.1016/j.ophtha.2026.04.008 [doi] AB - Recent studies have reported a possible association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and non-arteritic anterior ischemic optic neuropathy (NAION). The North American Neuro-Ophthalmology Society and the American Academy of Ophthalmology provide consensus expert opinion and clinical guidance about this association. Currently available evidence primarily includes retrospective observational studies, many of which rely on analysis of electronic health record and administrative claims data and are subject to limitations. Although many report a small possible increased risk of NAION in patients taking GLP-1 RAs such as semaglutide, some studies report no correlation, and the overall magnitude of the risk of NAION remains low. Shared decision-making between each patient and their care team is warranted to decide whether to start, continue, or discontinue GLP-1 RAs. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - DeParis, Sarah W AU - DeParis SW AD - American Academy of Ophthalmology, San Francisco, California. FAU - Oke, Isdin AU - Oke I AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Gaier, Eric D AU - Gaier ED AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Moss, Heather E AU - Moss HE AD - Department of Ophthalmology, Neurology and Neurological Sciences, Stanford University, Palo Alto, California. FAU - MacIntosh, Peter W AU - MacIntosh PW AD - Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois. FAU - Gilbert, Aubrey L AU - Gilbert AL AD - Department of Ophthalmology, The Permanente Medical Group, Vallejo, California. FAU - Dinkin, Marc J AU - Dinkin MJ AD - Department of Ophthalmology and Neurology, Weill Cornell Medical College, New York, New York. FAU - Chen, John J AU - Chen JJ AD - Department of Ophthalmology and Neurology, Mayo Clinic, Rochester, Minnesota. LA - eng GR - P30 EY026877/EY/NEI NIH HHS/United States PT - Consensus Statement PT - Journal Article DEP - 20260514 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Academies and Institutes/organization & administration MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Neurology/organization & administration MH - *Ophthalmology/organization & administration MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - Risk Factors MH - Semaglutide MH - *Societies, Medical MH - United States OTO - NOTNLM OT - GLP-1 OT - NAION OT - diabetes OT - glucagon-like peptide-1 receptor agonists OT - non-arteritic anterior ischemic optic neuropathy OT - semaglutide EDAT- 2026/05/14 14:49 MHDA- 2026/07/21 00:35 CRDT- 2026/05/14 10:28 PHST- 2026/02/25 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/04/02 00:00 [accepted] PHST- 2026/07/21 00:35 [medline] PHST- 2026/05/14 14:49 [pubmed] PHST- 2026/05/14 10:28 [entrez] AID - S0161-6420(26)00246-0 [pii] AID - 10.1016/j.ophtha.2026.04.008 [doi] PST - ppublish SO - Ophthalmology. 2026 Aug;133(8):1029-1035. doi: 10.1016/j.ophtha.2026.04.008. Epub 2026 May 14. PMID- 42132521 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260717 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 104 DP - 2026 Jan 1 TI - Glucagon-like peptide 1 receptor agonists: anti-inflammatory effects in cardiovascular diseases. PG - 1-11 LID - 10.1139/cjpp-2026-0021 [doi] AB - The potential therapeutic applications of glucagon-like peptide-1 (GLP-1) have led to the development of GLP-1 receptor agonists (GLP-1RAs), which replicate GLP-1's effects. The primary use of GLP-1RAs is the management of type 2 diabetes (T2DM) by stimulation of insulin secretion. In addition to its metabolic functions, GLP-1 exhibits significant anti-inflammatory effects through various molecular pathways, utilizing both direct and indirect mechanisms. Experimental studies have revealed that GLP-1RAs modulate multiple inflammatory pathways, including cytokine production, oxidative stress, glucotoxicity, lipotoxicity, and immune cell recruitment across multiple organs. They interact with their receptors on immune cells, thereby reducing the production of inflammatory cytokines and decreasing the infiltration of immune cells into tissues. There is considerable overlap among the pathways activated by GLP-1R in cardiovascular tissue, which can lead to anti-apoptotic, antioxidative, and anti-inflammatory effects. Clinical studies have confirmed the anti-inflammatory effects of GLP-1RAs in conditions such as acute myocardial infarction, left ventricular dysfunction, coronary artery disease, and ST-segment elevation myocardial infarction. Notably, GLP-1RAs are included in the European Society of Cardiology guidelines for managing cardiovascular disease in patients with T2DM. FAU - Bajic, Zorislava AU - Bajic Z AUID- ORCID: 0000-0002-7900-1721 AD - Department of Physiology, Faculty of Medicine University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. RINGGOLD: 469576 AD - Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. FAU - Sobot, Tanja AU - Sobot T AD - Department of Physiology, Faculty of Medicine University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. RINGGOLD: 469576 AD - Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. FAU - Stojiljkovic, Milos P AU - Stojiljkovic M AD - Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. FAU - Djuric, Dragan M AU - Djuric D AUID- ORCID: 0000-0003-2196-9438 AD - Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. AD - Faculty of Medicine, Institute of Medical Physiology "Richard Burian", University of Belgrade, 11000 Belgrade, Serbia. FAU - Skrbic, Ranko AU - Skrbic R AUID- ORCID: 0000-0002-6643-1781 AD - Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. AD - Academy of Science and Arts of the Republic of Srpska, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina. AD - Department of Pathologic Physiology, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia. LA - eng PT - Journal Article PT - Review PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Anti-Inflammatory Agents/therapeutic use/pharmacology MH - *Cardiovascular Diseases/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism OTO - NOTNLM OT - anti-inflammatory effects OT - cardiovascular disease OT - glucagon-like peptide-1 OT - glucagon-like peptide-1 receptor agonist COIS- The authors state no competing interests. Ranko Skrbic served as Associate Editor for this journal at the time of manuscript review and acceptance, but did not influence, participate in, or have access to the peer review or editorial decision-making process for this article. Full responsibility for the editorial handling of the article was assigned to other editors. EDAT- 2026/05/14 14:50 MHDA- 2026/05/14 14:51 CRDT- 2026/05/14 10:03 PHST- 2026/05/14 14:51 [medline] PHST- 2026/05/14 14:50 [pubmed] PHST- 2026/05/14 10:03 [entrez] AID - 10.1139/cjpp-2026-0021 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2026 Jan 1;104:1-11. doi: 10.1139/cjpp-2026-0021. PMID- 42128379 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260813 IS - 2005-6648 (Electronic) IS - 1226-3303 (Print) IS - 1226-3303 (Linking) VI - 41 IP - 3 DP - 2026 May TI - Delayed gastric emptying induced by glucagon-like peptide-1 receptor agonists and its implications for perioperative risk during anesthesia. PG - 384-395 LID - 10.3904/kjim.2025.277 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for managing type 2 diabetes mellitus and obesity because of their glucose-lowering, weight-reducing, and cardiovascular benefits. However, their potential to delay gastric emptying has raised growing concern in perioperative care, particularly regarding the risk of pulmonary aspiration during general anesthesia. Recent studies have shown that patients treated with GLP-1 RAs may retain considerable gastric contents even after standard preoperative fasting, thereby increasing the likelihood of regurgitation and aspiration during anesthesia induction or emergence. Short-acting GLP-1 RAs cause more pronounced delays in gastric emptying, whereas long-acting agents may exert residual effects depending on dose and treatment duration. Several international anesthesia societies have issued updated guidance to mitigate these risks, yet available evidence remains limited and sometimes inconsistent. This review summarizes the pharmacological mechanisms and clinical implications of GLP-1 RA-induced delayed gastric emptying, evaluates current literature on perioperative aspiration risk, and emphasizes the importance of interdisciplinary collaboration between endocrinologists and anesthesiologists to ensure safe and individualized perioperative management. FAU - Kang, Donghee AU - Kang D AD - Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine, Busan, Korea. FAU - Choi, Dughyun AU - Choi D AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea. LA - eng GR - 2021R1G1A1009254/National Research Foundation of Korea/ GR - Ministry of Science and ICT/ GR - Soonchunhyang University/ PT - Journal Article PT - Review DEP - 20260501 PL - Korea (South) TA - Korean J Intern Med JT - The Korean journal of internal medicine JID - 8712418 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Gastric Emptying/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Factors MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Risk Assessment MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Incretins/adverse effects MH - Respiratory Aspiration of Gastric Contents/physiopathology/prevention & control/etiology/chemically induced MH - *Anesthesia, General/adverse effects PMC - PMC13172807 OTO - NOTNLM OT - Anesthesia, general OT - Gastric emptying OT - Glucagon-like peptide 1 receptor agonists OT - Perioperative care OT - Pulmonary aspiration COIS- Conflicts of interest The authors disclose no conflicts. EDAT- 2026/05/14 00:31 MHDA- 2026/05/14 00:32 PMCR- 2026/05/01 CRDT- 2026/05/13 19:37 PHST- 2025/08/08 00:00 [received] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/05/14 00:32 [medline] PHST- 2026/05/14 00:31 [pubmed] PHST- 2026/05/13 19:37 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - kjim.2025.277 [pii] AID - kjim-2025-277 [pii] AID - 10.3904/kjim.2025.277 [doi] PST - ppublish SO - Korean J Intern Med. 2026 May;41(3):384-395. doi: 10.3904/kjim.2025.277. Epub 2026 May 1. PMID- 42123553 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 9 DP - 2026 Apr 29 TI - The Role of Antidiabetic Therapies in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review of Metformin, Pioglitazone, and GLP-1 Receptor Agonists. LID - 10.3390/ijms27093967 [doi] LID - 3967 AB - Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major causes of cognitive decline. Antidiabetic medications such as metformin, pioglitazone, and GLP-1 receptor agonists have been proposed as potential neuroprotective therapies. We assessed whether these agents slow cognitive decline or disease progression in people with AD or MCI. PubMed, Embase, and Cochrane Central were searched for randomized controlled trials and observational studies of metformin, pioglitazone, or GLP-1 receptor agonists in AD/MCI. Results were synthesized narratively by drug class. Eleven studies met the inclusion criteria. Metformin, particularly in early-stage disease and metabolically vulnerable groups, demonstrated improvements in episodic memory and selective executive outcomes. Observational data in diabetic MCI suggested improved cognition and preservation of hippocampal and cortical structure, with limited amyloid-beta and tau changes. Pioglitazone findings varied. Benefits were mainly reported in mild AD with type-2 diabetes, but not in non-diabetic AD/MCI. GLP-1 receptor agonists demonstrated preserved cerebral glucose metabolism and improved blood-to-brain glucose transport but did not improve cognitive function. Current evidence does not support antidiabetic therapies as effective treatments in AD/MCI. Any benefits appear to depend on disease stage and metabolic status, with metformin being the most promising candidate. Larger, longer-duration biomarker-defined trials are needed to determine whether any sustained clinical benefit is observed. FAU - Mahoon, Dina A AU - Mahoon DA AUID- ORCID: 0009-0007-3090-5803 AD - School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 15503, Bahrain. FAU - Hamad, Omar AU - Hamad O AD - Research Department, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 15503, Bahrain. FAU - Butler, Alexandra E AU - Butler AE AUID- ORCID: 0000-0002-5762-3917 AD - Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 15503, Bahrain. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260429 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 9100L32L2N (Metformin) RN - X4OV71U42S (Pioglitazone) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (PPAR-gamma Agonists) SB - IM MH - *Alzheimer Disease/drug therapy/metabolism MH - Humans MH - *Metformin/therapeutic use MH - *Pioglitazone/therapeutic use MH - *Cognitive Dysfunction/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - PPAR-gamma Agonists MH - Animals PMC - PMC13163320 OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonists OT - antidiabetic therapy OT - metformin OT - mild cognitive impairment OT - pioglitazone COIS- The authors declare no conflicts of interest. EDAT- 2026/05/13 06:31 MHDA- 2026/05/13 06:32 PMCR- 2026/04/29 CRDT- 2026/05/13 01:11 PHST- 2026/03/10 00:00 [received] PHST- 2026/04/15 00:00 [revised] PHST- 2026/04/16 00:00 [accepted] PHST- 2026/05/13 06:32 [medline] PHST- 2026/05/13 06:31 [pubmed] PHST- 2026/05/13 01:11 [entrez] PHST- 2026/04/29 00:00 [pmc-release] AID - ijms27093967 [pii] AID - ijms-27-03967 [pii] AID - 10.3390/ijms27093967 [doi] PST - epublish SO - Int J Mol Sci. 2026 Apr 29;27(9):3967. doi: 10.3390/ijms27093967. PMID- 42120704 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260613 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 Suppl 1 DP - 2026 Jun TI - Prepregnancy GLP-1RA Exposure and Risk of Hypertensive Disorders of Pregnancy Among Women With Obesity and Diabetes. PG - 88-96 LID - 10.1002/oby.70221 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed to women of reproductive age for obesity, type 2 diabetes, obstructive sleep apnea, and more. Data on pregnancy outcomes following prepregnancy exposure remain limited. We evaluated associations between prepregnancy GLP-1RA exposure and maternal and neonatal outcomes among women with preexisting obesity and diabetes. METHODS: We conducted a retrospective cohort study using electronic health records data. Prepregnancy GLP-1RA exposure was defined by prescription orders within 12 and 24 months prior to delivery. Propensity score matching was performed using maternal age, race and ethnicity, prepregnancy obesity status, diabetes type, chronic hypertension, insurance type, and rurality. Primary outcomes included preeclampsia (PE). Secondary outcomes included cesarean delivery, infant growth, gestational age at delivery, and neonatal intensive care unit length of stay. RESULTS: Among 31 exposed pregnancies, 29 were matched to unexposed controls. GLP-1RA exposure was associated with higher prevalence of PE (12 months: p = 0.023; 24 months: p = 0.018). Cesarean delivery occurred more frequently among exposed pregnancies (p < 0.05). No differences were observed in neonatal outcomes after matching. CONCLUSIONS: Prepregnancy GLP-1RA exposure was associated with higher prevalence of PE and cesarean delivery in this cohort. Larger studies are needed to confirm these findings and clarify underlying mechanisms. CI - (c) 2026 The Obesity Society. FAU - Lemas, Dominick J AU - Lemas DJ AUID- ORCID: 0000-0001-5105-2458 AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. AD - Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, Florida, USA. AD - Center for Research on Perinatal Outcomes, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Zapata, Ruben AU - Zapata R AUID- ORCID: 0000-0002-5346-8630 AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Loy, Isaac AU - Loy I AD - Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Mahadevan, Aditya AU - Mahadevan A AD - Center for Research on Perinatal Outcomes, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Wen, Tony AU - Wen T AUID- ORCID: 0000-0003-1638-0186 AD - Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Mkuu, Rahma AU - Mkuu R AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Louis-Jaques, Adetola AU - Louis-Jaques A AUID- ORCID: 0000-0002-2119-9739 AD - Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, Florida, USA. AD - Center for Research on Perinatal Outcomes, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Hall, Jaclyn AU - Hall J AUID- ORCID: 0000-0002-5289-5585 AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Harrall, Kylie K AU - Harrall KK AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Strath, Larissa AU - Strath L AUID- ORCID: 0000-0002-9616-0177 AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. AD - Pain Research and Intervention Center of Excellence (PRICE), University of Florida, Gainesville, Florida, USA. AD - Claude D. Pepper Older Americans Independence Center (OAIC), University of Florida, Gainesville, Florida, USA. FAU - Sheer, Amy AU - Sheer A AD - Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Shenkman, Elizabeth AU - Shenkman E AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Serena AU - Guo S AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Cardel, Michelle I AU - Cardel MI AUID- ORCID: 0000-0002-9395-8618 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - WW International Inc, New York, New York, USA. FAU - Smith, Steve AU - Smith S AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. LA - eng GR - K01DK115632/DK/NIDDK NIH HHS/United States GR - UL1TR000064/National Center for Advancing Translational Sciences of the National Institutes of Health/ GR - UL1TR001427/National Center for Advancing Translational Sciences of the National Institutes of Health/ GR - R00AG081552/AG/NIA NIH HHS/United States GR - K01CA292583/CA/NCI NIH HHS/United States GR - United States Association for the Study of Pain/ GR - Mayday Fund Clinical Translational Award/ GR - K01DK115632/DK/NIDDK NIH HHS/United States GR - R00AG081552/AG/NIA NIH HHS/United States GR - K01CA292583/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20260512 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Pregnancy MH - Adult MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Pre-Eclampsia/epidemiology MH - Pregnancy Outcome MH - *Hypertension, Pregnancy-Induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Cesarean Section/statistics & numerical data MH - Risk Factors MH - Infant, Newborn OTO - NOTNLM OT - GLP-1 receptor agonists OT - electronic health records OT - maternal obesity OT - preconception care OT - preeclampsia OT - hypertensive disorders of pregnancy EDAT- 2026/05/13 00:29 MHDA- 2026/06/15 11:29 CRDT- 2026/05/12 23:32 PHST- 2026/02/28 00:00 [revised] PHST- 2025/10/28 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/06/15 11:29 [medline] PHST- 2026/05/13 00:29 [pubmed] PHST- 2026/05/12 23:32 [entrez] AID - 10.1002/oby.70221 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jun;34 Suppl 1:88-96. doi: 10.1002/oby.70221. Epub 2026 May 12. PMID- 42116665 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260929 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 3 DP - 2026 May TI - The Gastrointestinal Safety of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Type 2 Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. PG - e70222 LID - 10.1002/edm2.70222 [doi] LID - e70222 AB - BACKGROUND AND AIM: Orforglipron (OFG), an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1 RA), has demonstrated significant weight loss and glycemic benefits in adults with or without type 2 diabetes (T2DM). However, its gastrointestinal (GI), hepatic and pancreatic safety profile has not been systematically evaluated. This network meta-analysis aimed to assess GI adverse events (AEs), hepatic and pancreatic outcomes, and enzyme changes across different OFG doses. METHODS: A frequentist network meta-analysis was conducted in accordance with the PRISMA guidelines. PubMed, Embase, Scopus and Web of Science (WOS) were searched for randomized controlled trials (RCTs) that assess the GI effects of OFG in adults with or without T2DM. We considered random-effects models to express treatment effects as odds ratios (OR) and mean differences (MD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis. RESULTS: All OFG doses (3, 12, 24, 36 and 45 mg) increased GI AEs compared to placebo, with a clear dose-response trend. High-dose OFG (45 mg) markedly increased nausea (OR 11.48, 95% CI: 6.52-20.21), vomiting (OR 11.48, 95% CI: 6.52-20.21), diarrhoea (OR 3.99, 95% CI: 2.07-7.70) and discontinuation due to GI AEs (OR 10.22, 95% CI: 4.99-20.94). No dose increased pancreatitis risk (p > 0.05). Higher doses significantly reduced ALT, with the most significant reduction observed at 24 mg (MD -11.19 IU/L, 95% CI: -19.18 to -3.21). Doses >/= 12 mg increased lipase (e.g., 24 mg: +28.52 IU/L, 95% CI: 12.02-45.01) and pancreatic amylase (45 mg: +18.20 IU/L, 95% CI: 9.49-26.91), without corresponding increases in clinical events. AST and ALP levels remained similar to those of the placebo. Subgroup analyses showed consistent effects in patients with or without T2DM. CONCLUSION: Oral OFG showed dose-dependent GI adverse effects over 26 weeks. Higher doses improve ALT and elevate pancreatic enzymes without clinical manifestations. The safety profile aligns with established GLP-1 RAs. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Hageen, Ahmed W AU - Hageen AW AD - Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Gadelmawla, Ahmed Farid AU - Gadelmawla AF AUID- ORCID: 0000-0002-5802-2291 AD - Faculty of Medicine, Menoufia University, Menoufia, Egypt. AD - Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, Massachusetts, USA. FAU - Saleh, Ahmad Omar AU - Saleh AO AD - Faculty of Medicine, The University of Jordan, Amman, Jordan. FAU - Abdallfatah, Abdallfatah AU - Abdallfatah A AD - Faculty of Medicine, October 6 University, Giza, Egypt. FAU - Mohamed, Mohamed Reyad AU - Mohamed MR AD - Department of Medicine, University of Arizona College of Medicine - Phoenix, Phoenix, Arizona, USA. FAU - El-Nemr, Amira Fahmy AU - El-Nemr AF AD - Faculty of Medicine, Al-Azhar University, Cairo, Egypt. FAU - Maihoub, Odai AU - Maihoub O AUID- ORCID: 0009-0007-6463-9005 AD - Department of Pathology, National Hospital, Latakia, Syria. FAU - Elsekhary, Ahmed AU - Elsekhary A AD - Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. FAU - Eladawi, Safir AU - Eladawi S AD - Faculty of Medicine, Ain Shams University, Cairo, Egypt. FAU - Ayalew, Biruk Demisse AU - Ayalew BD AUID- ORCID: 0009-0006-8285-6233 AD - Department of Internal Medicine, St. Paul's Hospital Millennium Medical College, Addis Ababa University School of Medicine, Addis Ababa, Ethiopia. FAU - Mansour, Ahmed AU - Mansour A AD - Faculty of Medicine, Al-Azhar University, Cairo, Egypt. FAU - Radi, Ayoup Ahmed AU - Radi AA AD - Faculty of Medicine, Minia University, Minia, Egypt. FAU - Abuelazm, Mohamed AU - Abuelazm M AUID- ORCID: 0000-0002-2514-0689 AD - Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Flefel, Mohamed Galal AU - Flefel MG AUID- ORCID: 0000-0002-0124-730X AD - Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 7ZW40D021M (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastrointestinal Tract/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13161550 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - liver OT - obesity OT - orforglipron OT - pancreas COIS- The authors declare no conflicts of interest. EDAT- 2026/05/12 06:33 MHDA- 2026/05/12 06:34 PMCR- 2026/05/11 CRDT- 2026/05/12 02:04 PHST- 2026/03/06 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/04/02 00:00 [accepted] PHST- 2026/05/12 06:34 [medline] PHST- 2026/05/12 06:33 [pubmed] PHST- 2026/05/12 02:04 [entrez] PHST- 2026/05/11 00:00 [pmc-release] AID - EDM270222 [pii] AID - 10.1002/edm2.70222 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 May;9(3):e70222. doi: 10.1002/edm2.70222. PMID- 42115753 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - GLP-1 Receptor Agonists and Psychiatric Outcomes in Adolescents: A Systematic Review and Meta-Analysis. PG - 6735-6743 LID - 10.1111/dom.70864 [doi] AB - AIMS: To assess the association between GLP-1 receptor agonists (GLP-1 RAs) and psychiatric outcomes in adolescents. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, EMBASE and the Cochrane Library. We included randomized controlled trials (RCTs) and observational cohort studies of adolescents that compared GLP-1 RAs prescribed for overweight, obesity or type 2 diabetes with placebo, no treatment or standard of care. We assessed suicidal ideation, suicide attempts and depression. We pooled risk ratios with 95% confidence intervals (CIs). We assessed heterogeneity with I(2) and chi(2) and used sensitivity and subgroup analyses to test robustness of our data. We assessed risk of bias using RoB 2 (randomized trials) and ROBINS-I (observational studies) tools. We graded the certainty of evidence using the GRADE framework. RESULTS: We included 11 studies (9 RCTs, n = 1253; 2 observational, n = 8922; total n = 10 175). GLP-1 RAs were associated with a lower risk of suicidal ideation versus control (RR 0.73; 95% CI: 0.54-0.99; p = 0.046; I (2) = 0%). We found no significant effects versus control on suicide attempts (RR 0.66; 95% CI: 0.16-2.61; p = 0.444; I (2) = 0%) or depressive symptoms (RR 0.73; 95% CI: 0.36-1.48; p = 0.282; I (2) = 50.4%). CONCLUSIONS: GLP-1 RAs were not associated with higher rates of suicidal behaviour or depression in adolescents. Pooled analysis suggested a possible lower risk of suicidal ideation, although this finding should be interpreted cautiously. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Silva, Cynthia F X C A AU - Silva CFXCA AUID- ORCID: 0000-0003-1110-7762 AD - Division of Pediatric Endocrinology, Department of Pediatrics, Northwell Health, New York, New York, USA. FAU - de Souza, Bruno Lins AU - de Souza BL AUID- ORCID: 0009-0002-3188-6900 AD - Department of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil. FAU - Thomazini, Gianlucca AU - Thomazini G AUID- ORCID: 0000-0002-4544-4313 AD - Department of Medicine, Pontifical Catholic University of Sao Paulo, Sorocaba, Sao Paulo, Brazil. FAU - Junior, Jardeson AU - Junior J AUID- ORCID: 0009-0007-4908-7660 AD - Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - de Mendonca Bisneto, Oscar Inacio AU - de Mendonca Bisneto OI AUID- ORCID: 0000-0001-9192-533X AD - Department of Medicine, Federal University of Campina Grande, Cajazeiras, Paraiba, Brazil. FAU - de Abreu, Izabella AU - de Abreu I AUID- ORCID: 0000-0003-3870-8621 AD - Department of Psychiatry, University of Texas Southwestern, Dallas, Texas, USA. FAU - Konstantyner, Tulio AU - Konstantyner T AUID- ORCID: 0000-0002-7931-9692 AD - Division of Pediatric Nutrition, Department of Pediatrics, Federal University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Abreu, Marconi AU - Abreu M AUID- ORCID: 0000-0001-5996-0661 AD - Division of Endocrinology, Department of Internal Medicine University of Texas Southwestern, Dallas, Texas, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260511 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adolescent MH - Humans MH - *Depression/epidemiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Exenatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Pediatric Obesity/drug therapy/psychology MH - Randomized Controlled Trials as Topic MH - Suicidal Ideation MH - Suicide, Attempted/statistics & numerical data/psychology OTO - NOTNLM OT - GLP-1 analogue OT - obesity therapy OT - perceptions OT - risk prediction OT - systematic review EDAT- 2026/05/12 00:32 MHDA- 2026/07/08 18:51 CRDT- 2026/05/11 23:32 PHST- 2026/04/13 00:00 [revised] PHST- 2026/03/10 00:00 [received] PHST- 2026/04/18 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/05/12 00:32 [pubmed] PHST- 2026/05/11 23:32 [entrez] AID - 10.1111/dom.70864 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6735-6743. doi: 10.1111/dom.70864. Epub 2026 May 11. PMID- 42113513 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260825 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 5 DP - 2026 May 1 TI - Survival and Recurrence With GLP-1 Receptor Agonists in Breast Cancer. PG - e2612133 LID - 10.1001/jamanetworkopen.2026.12133 [doi] LID - e2612133 AB - IMPORTANCE: Patients with breast cancer (BC) with comorbid obesity or type 2 diabetes (T2D) experience poorer survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved to treat these comorbidities; however, their associations with BC survival and recurrence remain unclear. OBJECTIVE: To evaluate the association between GLP-1 RA use and 10-year all-cause mortality and recurrence-free survival (RFS) over the 10-year follow-up period, as well as 5- and 10-year all-cause mortality and RFS probabilities among patients with BC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used TriNetX US Collaborative Network data from women (>/=18 years) with BC from 68 health care organizations who received a diagnosis between April 1, 2006, and April 1, 2023. Propensity score matching balanced characteristics. Data were analyzed between September 16 and October 3, 2025. EXPOSURES: GLP-1 RA use (>/=2 prescriptions) during the 6 months before and any time after the index diagnosis; nonuse (0 entries). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, and the secondary outcome was RFS. Cox proportional hazards regression model-estimated hazard ratios (HRs) were restricted to 10 years. Kaplan-Meier estimators were used to calculate 5- and 10-year all-cause mortality and RFS probabilities. Prespecified subgroup (postmenopausal) and landmark (6- and 12-month) analyses were conducted. RESULTS: The study comprised 841 831 eligible patients with BC (mean [SD] age, 69.1 [12.2] years). After exclusions and 1:1 propensity score matching, 3 cohorts were identified: 1610 patients for GLP-1 RA use vs nonuse (patients with obesity [body mass index >/=30]), 2323 patients for GLP-1 RA use vs insulin or metformin (patients with T2D), and 4052 patients for GLP-1 RA use vs sodium-glucose cotransporter 2 inhibitors (patients with T2D). Among patients with obesity, GLP-1 RAs were associated with lower hazard of all-cause mortality (HR, 0.35; 95% CI, 0.21-0.58; P < .001) and RFS (HR, 0.44; 95% CI, 0.30-0.64; P < .001) over a 10-year follow-up period. Among patients with T2D, GLP-1 RAs vs insulin or metformin were associated with lower hazard of all-cause mortality (HR, 0.09; 95% CI, 0.06-0.15; P < .001) and RFS (HR, 0.33; 95% CI, 0.21-0.50; P < .001). No significant differences were observed between GLP-1 RA and sodium-glucose cotransporter 2 inhibitor groups. Subgroup and landmark analyses yielded similar findings. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with BC, findings suggested a potential association between GLP-1 RA use and improved outcomes among patients with BC who have obesity and related metabolic conditions. These findings support further evaluation of GLP-1 RA therapy in randomized clinical trials. FAU - Tatum, Kristina L AU - Tatum KL AD - Department of Social and Behavioral Sciences, School of Public Health, Virginia Commonwealth University, Richmond. FAU - Dahman, Bassam AU - Dahman B AD - Department of Health Policy, School of Public Health, Virginia Commonwealth University, Richmond. FAU - Stevenson, Aniyah AU - Stevenson A AD - Virginia State University, Petersburg. FAU - Williford, Sarah E AU - Williford SE AD - TriNetX LCC, Cambridge, Massachusetts. FAU - Cassel, J Brian AU - Cassel JB AD - Division of Hematology, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond. FAU - Zhao, Hua AU - Zhao H AD - Department of Public Health Sciences, University of Virginia, Charlottesville. FAU - Shen, Jie AU - Shen J AD - Department of Public Health Sciences, University of Virginia, Charlottesville. FAU - McGuire, Kandace P AU - McGuire KP AD - Department of Surgery, School of Medicine, Virginia Commonwealth University, Richmond. FAU - Diala, Obinna AU - Diala O AD - Department of Family Medicine and Population Health, School of Medicine, Virginia Commonwealth University, Richmond. FAU - Oladimeji, Racheal AU - Oladimeji R AD - Department of Family Medicine and Population Health, School of Medicine, Virginia Commonwealth University, Richmond. FAU - Hundley, W Greg AU - Hundley WG AD - Division of Cardiology, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond. FAU - Fuemmeler, Bernard F AU - Fuemmeler BF AD - Department of Family Medicine and Population Health, School of Medicine, Virginia Commonwealth University, Richmond. AD - Massey Comprehensive Cancer Center, Richmond, Virginia. LA - eng GR - P30 CA016059/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20260501 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - doi: 10.1001/jamanetworkopen.2026.12143 MH - Humans MH - Female MH - *Breast Neoplasms/mortality/drug therapy MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasm Recurrence, Local/mortality/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/epidemiology PMC - PMC13162077 COIS- Conflict of Interest Disclosures: Dr Tatum reported receiving nonfinancial support from TriNetX LLC during the conduct of the study. Dr Williford reported being an employee of TriNetX at the time this study was performed. Dr McGuire reported receiving personal fees from Hologic Inc, Kubtec Inc, and Axogen Inc outside the submitted work. No other disclosures were reported. EDAT- 2026/05/11 13:00 MHDA- 2026/05/11 13:01 PMCR- 2026/05/11 CRDT- 2026/05/11 11:33 PHST- 2026/05/11 13:01 [medline] PHST- 2026/05/11 13:00 [pubmed] PHST- 2026/05/11 11:33 [entrez] PHST- 2026/05/11 00:00 [pmc-release] AID - 2848788 [pii] AID - zoi260368 [pii] AID - 10.1001/jamanetworkopen.2026.12133 [doi] PST - epublish SO - JAMA Netw Open. 2026 May 1;9(5):e2612133. doi: 10.1001/jamanetworkopen.2026.12133. PMID- 42112562 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260630 IS - 2299-8306 (Electronic) IS - 0423-104X (Linking) VI - 77 IP - 3 DP - 2026 TI - Do GLP-1 receptor agonists improve insulin sensitivity and reduce lipid accumulation in skeletal muscles and the liver independent of weight loss? PG - 134-146 LID - 10.5603/ep.107227 [doi] AB - Increased body mass index and excessive lipid accumulation are associated with enhanced production of toxic lipid species and impairedoxidation of free fatty acids (FFAs), a phenomenon defined as lipotoxicity. It is an important predictor of etabolic disorders such astype 2 diabetes (T2D). Increased lipid accumulation leads to decreased glucose uptake in skeletal muscle and enhanced hepatic glucoseproduction. Thus, ectopic fat accumulation impairs insulin signalling and decreases insulin sensitivity (IS). Scientific data demonstratethat glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can improve IS and decrease lipid accumulation in peripheral tissues mainlythrough weight loss. However, experimental studies indicate that GLP-1 RAs exert direct effects on glucose and lipid metabolic pathways,although the precise mechanisms remain incompletely understood. GLP-1 RAs may directly modulate fatty acid beta-oxidation, lipogenesis,and 5'-AMP-activated protein kinase (AMPK) phosphorylation. In this review, we discuss the mechanisms by which liraglutide and subcutaneoussemaglutide affect IS and lipid accumulation in key insulin-responsive tissues. FAU - Kolakowski, Adrian AU - Kolakowski A AUID- ORCID: 0000-0002-4004-3430 AD - Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, Bialystok, Poland. adriankolakowski17@gmail.com. FAU - Karczewska-Kupczewska, Monika AU - Karczewska-Kupczewska M AUID- ORCID: 0000-0003-1396-4290 AD - Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, Bialystok, Poland. LA - eng PT - Journal Article PT - Review DEP - 20260511 PL - Poland TA - Endokrynol Pol JT - Endokrynologia Polska JID - 0370674 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Muscle, Skeletal/metabolism/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Insulin Resistance MH - *Lipid Metabolism/drug effects MH - *Liver/metabolism/drug effects MH - Liraglutide/pharmacology MH - Animals MH - Weight Loss MH - *Hypoglycemic Agents/pharmacology MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - insulin sensitivity OT - lipid accumulation OT - lipotoxicity EDAT- 2026/05/11 12:59 MHDA- 2026/06/30 12:32 CRDT- 2026/05/11 07:03 PHST- 2025/07/11 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/03/04 00:00 [revised] PHST- 2026/06/30 12:32 [medline] PHST- 2026/05/11 12:59 [pubmed] PHST- 2026/05/11 07:03 [entrez] AID - VM/OJS/J/107227 [pii] AID - 10.5603/ep.107227 [doi] PST - ppublish SO - Endokrynol Pol. 2026;77(3):134-146. doi: 10.5603/ep.107227. Epub 2026 May 11. PMID- 42108418 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Estimated Oral Semaglutide Exposure Has Distinct Relationships With Glycaemic Response, Weight Loss and Gastrointestinal Tolerability. PG - 6405-6412 LID - 10.1111/dom.70840 [doi] AB - AIMS: Oral semaglutide absorption is subject to inter-individual variability. We investigated whether estimated individual exposure (eC (avg) ) provides predictive information beyond the prescribed dose in a real-world cohort of patients with type 2 diabetes (T2D). MATERIALS AND METHODS: We retrospectively included patients initiating oral semaglutide to calculate eC (avg) at each follow-up visit, using a validated population pharmacokinetic model incorporating dose, weight, sex, ethnicity and GI disorders, but without measuring plasma semaglutide concentrations. Mixed-effects models were used to assess the associations of dose and eC (avg) with changes in HbA1c and percent body weight, and to compare model fit. For GI side effects, time-adjusted fixed-effects logistic regression was employed. RESULTS: We analysed 256 participants (31.6% women, mean age 65.6 years). During a median follow-up of 19 months, HbA1c declined by 0.7% and body weight by 7.5%; 41.8% of patients reported GI side effects. Both dose and eC (avg) were significantly associated with all outcomes when analysed individually. For DeltaHbA1c, the dose model outperformed the eC (avg) model (p < 0.01), while eC (avg) showed modestly improved fit for weight loss (p < 0.001). The exposure-effect relationship was clearly right-shifted for weight loss compared to the glycaemic effect. For GI side effects, eC (avg) remained significantly associated with the outcome after adjustment for dose residuals, indicating that eC (avg) had greater predictive value for tolerability. CONCLUSIONS: Although estimated and not measured, the exposure to oral semaglutide may provide outcome-dependent information. While the prescribed dose seems sufficient to predict glycaemic response, estimated exposure provides additional value for weight loss and GI tolerability. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Morieri, Mario Luca AU - Morieri ML AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Boscaro, Carlotta AU - Boscaro C AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Bonora, Benedetta Maria AU - Bonora BM AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Cignarella, Andrea AU - Cignarella A AD - Department of Medicine, University of Padova, Padua, Italy. LA - eng GR - Universita degli Studi di Padova/ PT - Journal Article DEP - 20260510 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - Gastrointestinal Diseases/chemically induced MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/adverse effects MH - Retrospective Studies MH - *Semaglutide/administration & dosage MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage PMC - PMC13243947 OTO - NOTNLM OT - pharmacokinetics OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- G.P.F. received consultancy, advisory board or lecture fees from AstraZeneca, Boehringer, Lilly, Guidotti, Sanofi, Novo Nordisk, Novartis, Servier. M.L.M. received consultancy, advisory board or lecture fees from AstraZeneca, Boehringer, Guidotti, Novartis, Novo Nordisk, Sanofi and Servier. B.M.B. received lecture or advisory board fees from AstraZeneca, Boehringer Ingelheim, Lilly, M.S.D., Sanofi, Servier and Novo Nordisk. A.C. received lecture fees from Servier and Recordati. C.B. has nothing to declare. EDAT- 2026/05/11 00:30 MHDA- 2026/06/11 18:35 PMCR- 2026/06/08 CRDT- 2026/05/10 23:52 PHST- 2026/04/25 00:00 [revised] PHST- 2026/03/14 00:00 [received] PHST- 2026/04/26 00:00 [accepted] PHST- 2026/06/11 18:35 [medline] PHST- 2026/05/11 00:30 [pubmed] PHST- 2026/05/10 23:52 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70840 [pii] AID - 10.1111/dom.70840 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):6405-6412. doi: 10.1111/dom.70840. Epub 2026 May 10. PMID- 42103575 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260622 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 48 IP - 7 DP - 2026 Jul TI - Real-world Impact of GLP-1 Receptor Agonists on Health-related Quality of Life in Type 2 Diabetes and Obesity (SEVERAL Study). PG - 596-603 LID - S0149-2918(26)00074-3 [pii] LID - 10.1016/j.clinthera.2026.03.012 [doi] AB - PURPOSE: To evaluate the real-world impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on health-related quality of life (HRQoL) and metabolic outcomes in adults with type 2 diabetes and obesity. METHODS: We conducted a multicenter prospective cohort study across 13 primary-care centers in Spain. Adults with type 2 diabetes and body mass index (BMI) > 30 kg/m(2) initiating a GLP-1 RA were followed for 44 weeks. Baseline and week-44 assessments included anthropometric and biochemical parameters and HRQoL measured using the EQ-5D index and visual analogue scale (VAS), and the SF-12 physical and mental component summaries (PCS/MCS). Changes were analyzed using paired statistical tests overall and by achievement of >/=5% weight loss. FINDINGS: Among 135 patients, significant improvements were observed in glucose, HbA1c, LDL-C, waist circumference, body weight, and BMI. HRQoL improved in EQ-5D domains including mobility, pain/discomfort, and anxiety/depression. The EQ-5D index increased from 0.71 to 0.79 (P < 0.001), and VAS from 58.3 to 65.3 (P = 0.007). SF-12 PCS improved significantly, whereas MCS showed no overall change. Patients achieving >/=5% weight loss experienced greater improvements in EQ-5D index, VAS, and PCS. Subcutaneous and oral semaglutide improved the EQ-5D index; oral semaglutide improved VAS and MCS; and subcutaneous semaglutide improved PCS. IMPLICATIONS: In routine clinical practice, GLP-1 RAs were associated with clinically meaningful improvements in HRQoL and metabolic outcomes, particularly when >/=5% weight loss is achieved, supporting the integration of patient-reported outcomes into diabetes and obesity management. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT05136287. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologia y Salud Publica CIBERESP), Carlos III Health Institute, Madrid, Spain. Electronic address: angel.salgado.barreira@usc.es. FAU - Roca-Martinez, Carlota AU - Roca-Martinez C AD - Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Centro de Salud, Ribeira, A Coruna, Spain. FAU - Perez-Alvarez, Maria Teresa AU - Perez-Alvarez MT AD - Centro de Salud de Culleredo, A Coruna, Spain. FAU - Ponce-Pinon, Belen AU - Ponce-Pinon B AD - Centro de Salud de Fene, A Coruna, Spain. FAU - Fernandez-Silva, Marlen AU - Fernandez-Silva M AD - Centro de Salud O Ventorillo, A Coruna, Spain. FAU - Rodriguez-Barreiro, Marta AU - Rodriguez-Barreiro M AD - Centro de Salud. Virxe Peregrina, Pontevedra, Spain. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Centro de Salud de San Roque, Lugo, Spain. FAU - Iglesias-Moreno, Jose Manuel AU - Iglesias-Moreno JM AD - Centro de Salud de Val Minor, Nigran, Pontevedra, Spain. FAU - Gago-Garcia, Mar AU - Gago-Garcia M AD - Centro de Salud de Ribadeo, Lugo, Spain. FAU - Montans-Garcia, Raquel AU - Montans-Garcia R AD - Centro de Salud de Cee, A Coruna, Spain. FAU - Fernandez-Perez, Agustina AU - Fernandez-Perez A AD - Centro de Salud Vilalba, Lugo, Spain. FAU - Fraga-Gayoso, Dolores AU - Fraga-Gayoso D AD - Centro de Salud de Sarria, Lugo, Spain. FAU - Fernandez-Montenegro, Montse AU - Fernandez-Montenegro M AD - Centro de Salud de O Carballino, Ourense, Spain. FAU - Riveiro-Barciela, Beatriz AU - Riveiro-Barciela B AD - Centro de Salud O Temple, A Coruna, Spain. FAU - Rilla-Villar, Natalia AU - Rilla-Villar N AD - Consejeria de Salud, Asturias, Spain. FAU - Cardeso-Paredes, Begona AU - Cardeso-Paredes B AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Ribeiro-Ferreiro, Marta AU - Ribeiro-Ferreiro M AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain. FAU - Rodriguez-Penas, Diego AU - Rodriguez-Penas D AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain. FAU - Cordero, Alberto AU - Cordero A AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Department, Hospital IMED Elche, Alicante, Spain; Grupo de Investigacion Cardiovascular (GRINCAVA), Universidad Miguel Hernandez, Elche, Spain. FAU - Rodriguez-Manero, Moises AU - Rodriguez-Manero M AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. CN - SEVERAL INVESTIGATORS LA - eng SI - ClinicalTrials.gov/NCT05136287 PT - Journal Article PT - Multicenter Study DEP - 20260507 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM EIN - Clin Ther. 2026 Jul;48(7):675-676. doi: 10.1016/j.clinthera.2026.04.015. PMID: 42177143 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Quality of Life MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - Prospective Studies MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Weight Loss/drug effects MH - Aged MH - Body Mass Index MH - Spain MH - Semaglutide MH - Glycated Hemoglobin MH - Blood Glucose/drug effects MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor MH - Adult OTO - NOTNLM OT - GLP-1 receptor agonists OT - Health-related quality of life OT - Obesity OT - Patient-reported outcomes OT - Real-world evidence OT - Type 2 diabetes COIS- Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose. The authors declare that there are no conflicts of interest related to the results of this study. EDAT- 2026/05/09 00:34 MHDA- 2026/06/12 00:39 CRDT- 2026/05/08 21:53 PHST- 2025/11/08 00:00 [received] PHST- 2026/02/21 00:00 [revised] PHST- 2026/03/13 00:00 [accepted] PHST- 2026/06/12 00:39 [medline] PHST- 2026/05/09 00:34 [pubmed] PHST- 2026/05/08 21:53 [entrez] AID - S0149-2918(26)00074-3 [pii] AID - 10.1016/j.clinthera.2026.03.012 [doi] PST - ppublish SO - Clin Ther. 2026 Jul;48(7):596-603. doi: 10.1016/j.clinthera.2026.03.012. Epub 2026 May 7. PMID- 42103200 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260729 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 272 DP - 2026 Aug 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Patients With Atherosclerotic Cardiovascular Disease and Obesity Without Diabetes. PG - 1-8 LID - S0002-9149(26)00335-8 [pii] LID - 10.1016/j.amjcard.2026.05.004 [doi] AB - The Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial demonstrated cardiovascular benefits of semaglutide in patients with obesity without diabetes; however, the real-world effect across multiple glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents in patients with established atherosclerotic cardiovascular disease (ASCVD) and overweight or obesity without diabetes mellitus remains unknown. We conducted a target trial emulation using data from the TriNetX US Collaborative Network (January 1, 2010, to December 1, 2025) in adults aged >/=45 years with established ASCVD (history of myocardial infarction, stroke, or coronary or peripheral revascularization), BMI >/=27 kg/m(2), and without type 2 diabetes. New initiation of any GLP-1 RA (liraglutide, semaglutide, dulaglutide, or exenatide) was compared with no GLP-1 RA use. The primary outcome was all-cause mortality; secondary outcomes were acute myocardial infarction, stroke, and heart failure hospitalization over 5 years, analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models to account for the competing risk of death. Among 14,844 propensity-matched patients without diabetes (7,422 per group; median age 63 [interquartile range 55 to 71] years; 64% women), GLP-1 RA use was associated with lower all-cause mortality (hazard ratio [HR] 0.68; 95% CI 0.53 to 0.88; p = 0.003), acute myocardial infarction (subdistribution HR [sHR] 0.63; 95% CI 0.41 to 0.98; p = 0.040), and heart failure hospitalization (sHR 0.61; 95% CI 0.39 to 0.95; p = 0.028); no significant association was observed for stroke (sHR 0.76; 95% CI 0.52 to 1.10; p = 0.146). Findings were consistent in landmark and age subgroup analyses; a sensitivity analysis including patients with diabetes (N = 31,910 matched pairs) showed similar associations. In conclusion, these real-world findings are broadly directionally consistent with the SELECT trial and provide complementary observational evidence across multiple GLP-1 RA agents in patients with established ASCVD and overweight or obesity without diabetes mellitus, though causal inference cannot be established from observational data alone. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Ali Akbar, Usman AU - Ali Akbar U AD - Department of Internal Medicine, WVU Camden Clark Medical Center, Parkersburg, West Virginia. FAU - Mondal, Avilash AU - Mondal A AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Vorla, Mounica AU - Vorla M AD - Department of Medicine, Carle Foundation Hospital, Urbana, Illinois. FAU - Alruwaili, Waleed AU - Alruwaili W AD - Department of Internal Medicine, West Virginia University, Morgantown, West Virginia. FAU - Lacoste, Jordan AU - Lacoste J AD - Department of Pharmacy, WVU Medicine, Morgantown, West Virginia. FAU - Thyagaturu, Harshith AU - Thyagaturu H AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Shafique, Nouman AU - Shafique N AD - Department of Medicine, AdventHealth Orlando, Orlando, Florida. FAU - Shakeel, Sana AU - Shakeel S AD - Gomal Medical College, Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. FAU - Taha, Amro AU - Taha A AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Balla, Sudarshan AU - Balla S AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. Electronic address: sudarshanballa@outlook.com. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260506 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Male MH - *Obesity/complications/drug therapy MH - *Atherosclerosis/drug therapy/complications MH - Middle Aged MH - Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Exenatide/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Myocardial Infarction/epidemiology MH - Recombinant Fusion Proteins/therapeutic use MH - Heart Failure/epidemiology MH - Stroke/epidemiology MH - United States/epidemiology MH - Cause of Death MH - Diabetes Mellitus, Type 2 OTO - NOTNLM OT - all-cause mortality OT - atherosclerotic cardiovascular disease OT - glucagon-like peptide-1 receptor agonists OT - heart failure OT - hospitalization OT - obesity OT - real-world evidence OT - secondary prevention OT - target trial emulation COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. All authors approved the final manuscript. EDAT- 2026/05/09 00:34 MHDA- 2026/07/10 16:10 CRDT- 2026/05/08 19:15 PHST- 2026/03/14 00:00 [received] PHST- 2026/04/17 00:00 [revised] PHST- 2026/05/03 00:00 [accepted] PHST- 2026/07/10 16:10 [medline] PHST- 2026/05/09 00:34 [pubmed] PHST- 2026/05/08 19:15 [entrez] AID - S0002-9149(26)00335-8 [pii] AID - 10.1016/j.amjcard.2026.05.004 [doi] PST - ppublish SO - Am J Cardiol. 2026 Aug 1;272:1-8. doi: 10.1016/j.amjcard.2026.05.004. Epub 2026 May 6. PMID- 42102896 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260616 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 299 DP - 2026 Sep TI - Serial assessment of NT-proBNP and high-sensitivity cardiac troponin with glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes: Insights from EXSCEL. PG - 107475 LID - S0002-8703(26)00137-7 [pii] LID - 10.1016/j.ahj.2026.107475 [doi] AB - BACKGROUND: In the EXSCEL trial, exenatide did not reduce major adverse cardiovascular events (MACE), but heterogeneity of benefit and the role of cardiac biomarkers remain uncertain. We evaluated the prognostic value of baseline and 1-year changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI), and whether baseline biomarker concentrations modified exenatide effects. METHODS: EXSCEL randomized 14,752 adults with type 2 diabetes to exenatide 2 mg weekly (EQW) or placebo. In a biomarker cohort, 4,292 participants had serial NT-proBNP or cTnI at baseline and 1 year. Biomarkers were log transformed and Cox models related baseline concentrations and 1-year change to MACE, all-cause mortality (ACM), cardiovascular (CV) death, hospitalization for heart failure (hHF), adjusting for clinical covariates and the alternate biomarker. Treatment interaction was tested with biomarker by treatment terms. RESULTS: Over median 1,480 days follow-up, 529 MACE, 310 all cause deaths, 193 CV deaths, and 157 hHF events occurred. Baseline NT-proBNP was strongly prognostic (adjusted HR per 1 integer unit 1.63 for MACE, 1.85 for ACM, 2.17 for CV death, and 2.17 for hHF; all P < .001). Baseline cTnI was also prognostic with a nonlinear pattern, with risk rising mainly above the median. Per SD rise in NT-proBNP over 1 year predicted later MACE (HR 1.85) and CV death (HR 2.81; both P < .001). Baseline NT-proBNP didn't modify treatment effects. Baseline cTnI didn't modify EQW treatment effect on MACE but lower rates of CV deaths and hHF with EQW were observed at higher cTnI concentrations. CONCLUSIONS: NT-proBNP and cTnI were strong prognostic markers of adverse outcomes in patients with type 2 diabetes and their 1-year increases signaled higher subsequent risk. Baseline cTnI may mark heterogeneity of EQW response, but mortality interactions are hypothesis generating and require confirmation. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Kittipibul, Veraprapas AU - Kittipibul V AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Division of Cardiology, Duke University School of Medicine, Durham, NC. Electronic address: veraprapas.kittipibul@duke.edu. FAU - Nguyen, Maggie AU - Nguyen M AD - Duke Molecular Physiology Institute, Duke University School of Medicine, Durham NC. FAU - Welsh, Paul AU - Welsh P AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC. FAU - Sourij, Harald AU - Sourij H AD - Division of Endocrinology and Diabetology, Cardiometabolic Trials Unit, Medical University of Graz, Graz, Austria. FAU - Hernandez, Adrian F AU - Hernandez AF AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Division of Cardiology, Duke University School of Medicine, Durham, NC. FAU - Holman, Rury R AU - Holman RR AD - Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. FAU - Shah, Svati H AU - Shah SH AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Division of Cardiology, Duke University School of Medicine, Durham, NC; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham NC. FAU - Mentz, Robert J AU - Mentz RJ AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Division of Cardiology, Duke University School of Medicine, Durham, NC. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20260506 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 0 (Biomarkers) RN - 0 (Troponin I) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - *Peptide Fragments/blood MH - *Natriuretic Peptide, Brain/blood MH - Biomarkers/blood MH - *Troponin I/blood MH - Female MH - Male MH - *Exenatide/therapeutic use/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Prognosis MH - *Cardiovascular Diseases/mortality/prevention & control/blood MH - Double-Blind Method MH - Heart Failure COIS- Conflict of interest PW reports grant income from Roche Diagnostics, AstraZeneca, Boehringer Ingelheim, and Novartis, and speaker fees from Novo Nordisk and Raisio Nutrition. JBB reports salary support from clinical trial contracts to his employer by Corcept, Dexcom, GentiBio, and Novo Nordisk; personal compensation for consulting from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand; stock/options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. HS is on the advisory board and speaker's bureau of Boehringer Ingelheim, Novo Nordisk, Sanofi-Aventis, Amgen, AstraZeneca, Bayer, Eli Lilly, Kapsch, MSD, and Daiichi Sankyo. AFH reports research support and/or honoraria from AstraZeneca, Boehringer Ingleheim, Boston Scientific Corporation, Bristol Myers Squibb, Eidos Therapeutics, Intellia, Intercept, Merck, Novartis, Novo Nordisk, Prolaio, TikkunLev Therapeutics, Inc. RRH reports personal fees from Lilly, Merck KGaA, MitoRx, Novartis and Owen Mumford Ltd. SHS reports researching funding from AstraZeneca. RJM reports research support and/or honoraria from Abbott, Alleviant Medical, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Cytokinetics, Daiichi Sankyo, Edwards, Eli Lilly, Endotronix, Lexicon, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Pharmacosmos, Reprieve Cardiovascular, Respicardia, Roche, Rocket Pharmaceuticals, Vifor, Windtree Therapeutics, and Zoll. All other authors report no relevant disclosures. EDAT- 2026/05/09 00:33 MHDA- 2026/06/11 18:36 CRDT- 2026/05/08 19:11 PHST- 2026/01/12 00:00 [received] PHST- 2026/05/05 00:00 [revised] PHST- 2026/05/05 00:00 [accepted] PHST- 2026/06/11 18:36 [medline] PHST- 2026/05/09 00:33 [pubmed] PHST- 2026/05/08 19:11 [entrez] AID - S0002-8703(26)00137-7 [pii] AID - 10.1016/j.ahj.2026.107475 [doi] PST - ppublish SO - Am Heart J. 2026 Sep;299:107475. doi: 10.1016/j.ahj.2026.107475. Epub 2026 May 6. PMID- 42101662 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260804 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 63 IP - 7 DP - 2026 Jul TI - The effect of GLP-1 receptor agonists on osteoarthritis risk in individuals with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized controlled trials. PG - 1247-1263 LID - 10.1007/s00592-026-02697-2 [doi] AB - OBJECTIVE: Current research has not yet drawn a definitive conclusion on the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). To supplement the evidence base in this field, the present study sought to systematically investigate the association between GLP-1RA administration and the risk of OA in adult T2DM patients through a meta-analysis of relevant randomized controlled trials (RCTs). METHODS: An exhaustive literature search was conducted across five major databases-PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Cochrane Library-covering the period from each database's inception up to May 6, 2025. The main objective of this literature search was to identify RCTs that enrolled adult patients with T2DM receiving GLP-1RAs and reported OA incidence. The Cochrane Risk of Bias 2.0 tool was employed to evaluate the risk of bias for all included studies, while the GRADE system was applied to assess the overall certainty of the evidence. Additionally, the node-splitting method was utilized to perform inconsistency testing between direct and indirect evidence. The occurrence of OA events was defined as the primary outcome of the study. A series of analyses were performed to evaluate the impact of each intervention on OA risk, including traditional meta-analysis, frequentist network meta-analysis (NMA), and sensitivity analysis. Summary estimates of effect size were presented as relative risk (RR) along with 95% confidence intervals (CI). RESULTS: The present study ultimately included 74 RCTs with a combined sample size of 105,415 individuals. Conventional pairwise meta-analysis revealed no statistically significant difference in OA risk between GLP-1RAs and placebo, insulin, or other oral antidiabetic drugs (OADs). Stratified subgroup analyses based on GLP-1RA formulation, treatment duration, and control group type also found no statistically significant differences in OA risk across all subgroups. Furthermore, NMA results indicated no notable variations in OA risk between GLP-1RAs and control interventions, and no such differences were observed among the different GLP-1RA formulations either. Sensitivity analyses verified the stability and reliability of the study outcomes. CONCLUSIONS: Among adult patients with T2DM, there was no significant difference in OA risk between GLP-1RA treatment and placebo, insulin, or OADs; this absence of statistical significance was also observed across different GLP-1RA formulations, varying treatment durations, and distinct control groups. PROSPERO REGISTRATION NUMBER: CRD420251034203. CI - (c) 2026. Associazione Medici Diabetologi / Association of Diabetologists (AMD), Societa Italiana di Diabetologia / Italian Society of Diabetology (SID). FAU - Zhou, Limin AU - Zhou L AD - Department of Pharmacy, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China. FAU - Wu, Peiyang AU - Wu P AD - Department of Pharmacy, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China. AD - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China. FAU - Xu, Yongxiang AU - Xu Y AD - Department of Pharmacy, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China. FAU - Xie, Baocheng AU - Xie B AUID- ORCID: 0000-0002-7109-402X AD - Department of Pharmacy, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, Guangdong, China. baochengxie@smu.edu.cn. LA - eng GR - 2022A1515140138, 2024A1515140131/Guangdong Basic and Applied Basic Research Foundation/ GR - A2024138, B2025580/Medical Scientific Research Foundation of Guangdong Province of China/ GR - 2025A01002/Guangdong Provincial Hospital Pharmacy Research Fund/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260508 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoarthritis/epidemiology/etiology/prevention & control MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP-1RA OT - Glucagon-like peptide-1 receptor agonists OT - Network meta-analysis OT - Osteoarthritis OT - Systematic review OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have reviewed and approved the manuscript for submission. EDAT- 2026/05/08 12:38 MHDA- 2026/07/23 12:37 CRDT- 2026/05/08 11:14 PHST- 2025/12/14 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/07/23 12:37 [medline] PHST- 2026/05/08 12:38 [pubmed] PHST- 2026/05/08 11:14 [entrez] AID - 10.1007/s00592-026-02697-2 [pii] AID - 10.1007/s00592-026-02697-2 [doi] PST - ppublish SO - Acta Diabetol. 2026 Jul;63(7):1247-1263. doi: 10.1007/s00592-026-02697-2. Epub 2026 May 8. PMID- 42098899 OWN - NLM STAT- MEDLINE DCOM- 20260608 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Beyond GLP-1 Monotherapy: Novel Multi-Agonists, Amylin Analogues, and Combination Strategies in Obesity and Type 2 Diabetes. PG - 5556-5589 LID - 10.1111/dom.70822 [doi] AB - AIMS: To provide a clinically oriented narrative review of recently reported human trial data on emerging pharmacotherapies for obesity and type 2 diabetes beyond glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy. MATERIALS AND METHODS: This narrative review summarizes recent clinical evidence on incretin-based and related therapeutic strategies, including dual and triple incretin- or glucagon-based agonists, long-acting amylin analogues, oral agents, and combination approaches targeting complementary satiety and metabolic pathways. The review focuses on human trial data and evaluates key outcomes including body weight reduction, glycemic control, body-composition effects, tolerability, and broader cardiometabolic changes. RESULTS: Incretin-based therapies have transformed the management of obesity and type 2 diabetes, with GLP-1RAs achieving levels of weight loss that begin to narrow the gap with metabolic surgery in selected populations. Recent developments have substantially expanded the field beyond GLP-1RA monotherapy. Emerging agents now include multi-agonists, amylin-based therapies, novel oral compounds, and combination strategies designed to improve not only the magnitude of weight loss, but also its quality, durability, and metabolic consequences. Across trials, these approaches have shown promising effects on body weight, glycemic control, and selected cardiometabolic parameters, although differences in tolerability, evidence maturity, and practical feasibility remain important. CONCLUSIONS: Current data indicate a rapid shift from single-pathway interventions toward multimodal therapeutic strategies in obesity and type 2 diabetes. Future positioning of these agents within treatment algorithms will depend not only on efficacy, but also on long-term safety, durability of effect, tolerability, adherence, access, and their impact on clinically meaningful outcomes beyond body weight alone. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Khachaturov, Mikhail AU - Khachaturov M AUID- ORCID: 0000-0001-7606-6565 AD - Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Goulis, Dimitrios G AU - Goulis DG AD - Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260507 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Islet Amyloid Polypeptide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use MH - *Islet Amyloid Polypeptide/therapeutic use/agonists MH - *Obesity/drug therapy/complications MH - Semaglutide/therapeutic use MH - Weight Loss/drug effects OTO - NOTNLM OT - GLP-1 OT - antiobesity drug OT - obesity therapy OT - semaglutide OT - type 2 diabetes OT - weight management EDAT- 2026/05/08 00:32 MHDA- 2026/06/09 00:34 CRDT- 2026/05/07 23:56 PHST- 2026/04/20 00:00 [revised] PHST- 2026/01/13 00:00 [received] PHST- 2026/04/20 00:00 [accepted] PHST- 2026/06/09 00:34 [medline] PHST- 2026/05/08 00:32 [pubmed] PHST- 2026/05/07 23:56 [entrez] AID - 10.1111/dom.70822 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5556-5589. doi: 10.1111/dom.70822. Epub 2026 May 7. PMID- 42091853 OWN - NLM STAT- MEDLINE DCOM- 20260629 LR - 20260813 IS - 2044-4052 (Electronic) IS - 2044-4052 (Linking) VI - 16 IP - 1 DP - 2026 May 6 TI - The molecular mechanisms of incretin resistance in Type 2 Diabetes Mellitus (T2DM). LID - 10.1038/s41387-026-00426-w [doi] LID - 19 AB - Incretin hormones, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), serve as crucial mediators of postprandial glucose homeostasis by primarily enhancing glucose-stimulated insulin secretion. Research indicates that the incretin effect accounts for approximately 50% of insulin secretion in individuals without diabetes, which is significantly reduced to 30% or less in those with Type 2 Diabetes Mellitus (T2DM). The mechanisms underlying this incretin resistance have emerged as critical causes of postprandial hyperglycemia. Incretin-based therapies, including GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors, have demonstrated efficacy in managing T2DM; however, intrinsic resistance mechanisms may limit their effectiveness. Understanding the processes by which T2DM affects incretin action, from hormone secretion to the modulation of signal transduction, is essential for optimizing current therapies and developing new interventions to enhance beta-cell responsiveness and improve glycemic control. The concept of incretin resistance has a well-established history in literature, dating back to at least the early 1990 s. It is used to describe a reduced insulinotropic responsiveness to incretin hormones in individuals diagnosed with T2DM. This review examines how hyperglycemia, chronic inflammation, and genetic susceptibility collectively inhibit incretin signaling through distinct yet interconnected molecular pathways. This impairment exacerbates postprandial hyperglycemia and accelerates beta-cell dysfunction. We propose novel hypotheses regarding selective beta-arrestin signaling, enhancers, epigenetic regulation, interactions between gut microbiota and incretins, inflammation-induced endoplasmic reticulum (ER) stress, and genotype-specific therapeutic responses. The hypotheses presented in this review serve as a framework for future research and therapeutic development to combat the phenomenon of incretin resistance and improve the clinical management of T2DM. CI - (c) 2026. The Author(s). FAU - Albaghlany, Rawayh Muslim AU - Albaghlany RM AUID- ORCID: 0000-0002-4940-1994 AD - Department of Medical Microbiology, College of Dentistry, University of Basrah, Basrah, Iraq. rawayh.albaghlany@uobasrah.edu.iq. AD - Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), University of Basrah, Basrah, Iraq. rawayh.albaghlany@uobasrah.edu.iq. FAU - Mansour, Abbas Ali AU - Mansour AA AD - Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), University of Basrah, Basrah, Iraq. LA - eng PT - Journal Article PT - Review DEP - 20260506 PL - England TA - Nutr Diabetes JT - Nutrition & diabetes JID - 101566341 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/genetics MH - *Incretins/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Gastric Inhibitory Polypeptide/metabolism MH - Insulin/metabolism MH - Signal Transduction MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor MH - *Drug Resistance PMC - PMC13315620 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/05/07 00:33 MHDA- 2026/06/30 00:31 PMCR- 2026/05/06 CRDT- 2026/05/06 23:24 PHST- 2025/05/05 00:00 [received] PHST- 2026/04/24 00:00 [accepted] PHST- 2026/04/15 00:00 [revised] PHST- 2026/06/30 00:31 [medline] PHST- 2026/05/07 00:33 [pubmed] PHST- 2026/05/06 23:24 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - 10.1038/s41387-026-00426-w [pii] AID - 426 [pii] AID - 10.1038/s41387-026-00426-w [doi] PST - epublish SO - Nutr Diabetes. 2026 May 6;16(1):19. doi: 10.1038/s41387-026-00426-w. PMID- 42089543 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260614 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 Suppl 1 DP - 2026 Jun TI - Semaglutide vs. Bariatric Surgery: Comparing Costs and Clinical Outcomes in Patients With Diabetes and Obesity. PG - 65-76 LID - 10.1002/oby.70209 [doi] AB - OBJECTIVE: We compared health care spending and utilization associated with semaglutide relative to bariatric surgery in patients with obesity and type 2 diabetes (T2D). METHODS: Using MarketScan insurance claims of patients with BMI >/= 35 and T2D from 2016 to 2021, we examined associations between choice of semaglutide, sleeve gastrectomy, or gastric bypass; 3-year health care spending (out-of-pocket [OOP] and total); and clinical outcomes (ED visits, hospital admissions, and major adverse cardiovascular events [MACE]). Analyses were adjusted using generalized linear models, inverse probability weighting, and instrumental variables. RESULTS: Among 6748 patients (2797 semaglutide, 2300 sleeve gastrectomy, 1651 gastric bypass), bariatric surgery patients had higher BMI and more comorbidities. In IPTW-adjusted analysis, semaglutide was associated with the highest 3-year OOP costs ($7752 vs. $5980 [sleeve gastrectomy] vs. $6591 [gastric bypass], p < 0.001), but total spending was not statistically different across the groups. Relative to semaglutide, the gastric bypass group showed higher observed ED visits (hazard ratio relative to semaglutide [95% CI]: 1.36 [1.28-1.45]) and inpatient admissions (1.25 [1.13-1.37]) and fewer MACE (0.71 [0.59-0.88]). Sleeve gastrectomy was associated with fewer long-term admissions (0.79 [0.72-0.86]) and MACE (0.79 [0.66-0.93]). CONCLUSIONS: For patients with T2D and obesity, compared with semaglutide, bariatric surgery is associated with lower OOP spending and similar total spending at 3 years, as well as lower long-term MACE rates. CI - (c) 2026 The Obesity Society. FAU - Chhabra, Karan R AU - Chhabra KR AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Gencerliler, Nihan AU - Gencerliler N AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. FAU - Orandi, Babak J AU - Orandi BJ AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Wang, Vivian Hsing-Chun AU - Wang VH AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. FAU - Kozato, Akio AU - Kozato A AUID- ORCID: 0000-0002-8965-9674 AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Surapaneni, Aditya AU - Surapaneni A AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Grams, Morgan AU - Grams M AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Mukhopadhyay, Amrita AU - Mukhopadhyay A AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Shin, Jung-Im AU - Shin JI AD - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Ren-Fielding, Christine AU - Ren-Fielding C AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Parikh, Manish AU - Parikh M AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Zhang, Donglan S AU - Zhang DS AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. LA - eng GR - L30DK144880/NH/NIH HHS/United States GR - R01DK115534/DK/NIDDK NIH HHS/United States GR - R01DK100446/DK/NIDDK NIH HHS/United States GR - R01DK124399/DK/NIDDK NIH HHS/United States GR - R01DK108803/DK/NIDDK NIH HHS/United States GR - K24HL115861/HL/NHLBI NIH HHS/United States GR - K23HL171636/HL/NHLBI NIH HHS/United States GR - National Kidney Foundation/ GR - AHA 23CDA1042602/American Heart Association/ GR - NYU Department of Medicine Chairman's Circle Research Award/ GR - Doucette Innovation Fund/ GR - L30DK144880/NH/NIH HHS/United States GR - R01DK115534/DK/NIDDK NIH HHS/United States GR - R01DK100446/DK/NIDDK NIH HHS/United States GR - R01DK124399/DK/NIDDK NIH HHS/United States GR - R01DK108803/DK/NIDDK NIH HHS/United States GR - K24HL115861/HL/NHLBI NIH HHS/United States GR - K23HL171636/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20260506 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/economics/methods MH - *Diabetes Mellitus, Type 2/economics/complications/drug therapy MH - Gastrectomy/economics MH - Gastric Bypass/economics MH - *Health Care Costs/statistics & numerical data MH - *Obesity/complications/drug therapy/economics/surgery MH - *Semaglutide/economics/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - bariatric surgery OT - health care costs OT - semaglutide EDAT- 2026/05/06 12:35 MHDA- 2026/06/11 06:36 CRDT- 2026/05/06 08:35 PHST- 2026/02/10 00:00 [revised] PHST- 2025/10/15 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/06/11 06:36 [medline] PHST- 2026/05/06 12:35 [pubmed] PHST- 2026/05/06 08:35 [entrez] AID - 10.1002/oby.70209 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jun;34 Suppl 1:65-76. doi: 10.1002/oby.70209. Epub 2026 May 6. PMID- 42087771 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 64 IP - 8 DP - 2026 Aug TI - Dulaglutide-associated body odor with dechallenge and rechallenge in a patient with type 2 diabetes. PG - 455-458 LID - 10.5414/CP204985 [doi] AB - OBJECTIVE: Although uncommon, medications may induce unpleasant body odor, potentially leading to psychosocial distress and reduced treatment adherence. To date, unpleasant body odor has not been recognized as an adverse effect of dulaglutide. We report a novel case of dulaglutide-associated body odor, confirmed by dechallenge and rechallenge. CASE REPORT: A 57-year-old man with a 6-year history of type 2 diabetes mellitus and hypertension was initiated on dulaglutide due to inadequate glycemic control and obesity. Two weeks after treatment initiation, an unpleasant body odor was noted by family members and colleagues. No changes in diet, hygiene practices, or concomitant medications were reported. Dermatological examination and extensive laboratory evaluation excluded infectious, metabolic, and endocrine causes. The odor resolved ~ 10 days after discontinuation of dulaglutide. Upon rechallenge, the odor recurred, confirming a causal relationship. Dulaglutide was permanently discontinued, and treatment was switched to semaglutide, after which the body odor did not recur and glycemic control improved. According to the Naranjo Adverse Drug Reaction Probability Scale, the association was classified as probable. CONCLUSION: This case highlights a rare and previously unreported adverse effect of dulaglutide. Although not medically serious, drug-induced body odor may substantially impair quality of life and treatment adherence. FAU - Marusic, Srecko AU - Marusic S FAU - Staresinic, Matea AU - Staresinic M FAU - Berkovic, Maja Cigrovski AU - Berkovic MC LA - eng PT - Case Reports PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis MH - *Glucagon-Like Peptides/analogs & derivatives/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Recombinant Fusion Proteins/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects MH - *Odorants MH - Semaglutide MH - Blood Glucose/drug effects/metabolism MH - Drug Substitution MH - Treatment Outcome EDAT- 2026/05/06 06:37 MHDA- 2026/07/13 06:33 CRDT- 2026/05/06 04:13 PHST- 2026/07/10 00:00 [accepted] PHST- 2026/07/13 06:33 [medline] PHST- 2026/05/06 06:37 [pubmed] PHST- 2026/05/06 04:13 [entrez] AID - 192905 [pii] AID - 10.5414/CP204985 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2026 Aug;64(8):455-458. doi: 10.5414/CP204985. PMID- 42087044 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260813 IS - 1496-8975 (Electronic) IS - 0832-610X (Print) IS - 0832-610X (Linking) VI - 73 IP - 4 DP - 2026 Apr TI - Glucagon-like peptide-1 receptor agonists and gastric emptying time: a systematic review and meta-analysis of prospective studies. PG - 345-356 LID - 10.1007/s12630-026-03114-6 [doi] AB - PURPOSE: Current management of type 2 diabetes mellitus and obesity increasingly includes treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). In this systematic review and meta-analysis, we sought to characterize the effect of GLP-1 RAs on gastric emptying half-time (T((1/2))). METHODS: We conducted a systematic review of prospective studies reporting T((1/2)) with and without GLP-1 RA treatment. Inclusion criteria were 1) patients aged >/= 18 yr taking a GLP-1 RA for diabetes mellitus and/or weight loss, 2) gastric emptying assessment reported as emptying T((1/2)), and 3) study design that was a randomized controlled trial or a prospective cohort study. We searched the following databases: MEDLINE, MEDLINE In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, American Psychological Association (APA) PsycInfo(R), and CINAHL. We assessed the quality of the studies with the risk of bias assessment tool for randomized controlled trials and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for nonrandomized trials. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification for assessment of the certainty of the evidence. We performed multilevel random effects meta-analysis to pool standardized mean differences. RESULTS: We included 10 studies (N = 300), one of which reported two independent samples; these were treated as two independent studies for the purpose of meta-analysis. Glucagon-like peptide-1 receptor agonists significantly increased gastric emptying T((1/2)), with a large effect size (standardized mean difference, 2.38; 95% confidence interval [CI], 1.05 to 3.71; P < 0.001) corresponding to a mean prolongation of 74 min (95% CI, 46 to 101). There was a trend towards a more pronounced effect with short-acting GLP-1 RAs, with a standardized mean difference of 3.86 (95% CI, 2.37 to 5.35) corresponding to a prolongation of 116 min (95% CI, 71 to 161) and early treatment phases (< 10 weeks) with a standardized mean difference of 2.72 (95% CI, 1.15 to 4.35) with a mean prolongation of 82 min (95% CI, 35 to 131). Nevertheless, the certainty of the effect size following the GRADE classification was "very low." CONCLUSIONS: In this systematic review and meta-analysis, we found that GLP-1 RAs significantly prolonged gastric emptying T((1/2)) by a mean of 74 min, which could have implications for perioperative care. There was a trend towards a more pronounced effect with short-acting (vs long-acting) drugs and in the early treatment phases (< 10 weeks). STUDY REGISTRATION: PROSPERO ( CRD42023461665 ); first submitted 8 September 2023. CI - (c) 2026. The Author(s). FAU - Chen, Alisia AU - Chen A AD - Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. FAU - Zhao, Karen AU - Zhao K AD - Department of Family Medicine, University of Toronto, Toronto, ON, Canada. FAU - Ceban, Felicia AU - Ceban F AD - Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada. FAU - Nabipoor, Majid AU - Nabipoor M AD - Biostatistics Department, University Health Network, Toronto, ON, Canada. FAU - Englesakis, Marina AU - Englesakis M AD - Library & Information Services, University Health Network, Toronto, ON, Canada. FAU - Chung, Frances AU - Chung F AD - Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. FAU - Perlas, Anahi AU - Perlas A AUID- ORCID: 0000-0002-8190-8314 AD - Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. Anahi.perlas@uhn.ca. AD - Department of Anesthesiology & Pain Medicine, University of Toronto, Toronto, ON, Canada. Anahi.perlas@uhn.ca. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review TT - Agonistes des recepteurs du peptide-1 de type glucagon et temps de vidange gastrique : revue systematique et meta-analyse d'etudes prospectives. DEP - 20260505 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Gastric Emptying/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Obesity/drug therapy/physiopathology MH - Prospective Studies MH - Randomized Controlled Trials as Topic MH - Time Factors PMC - PMC13249630 OTO - NOTNLM OT - GLP-1 RAs OT - gastric emptying OT - gastric emptying time OT - glucagon-like peptide-1 receptor agonists OT - meta-analysis COIS- Anahi Perlas performs consulting work for Fujifilm Sonosite and receives peer-reviewed funding from the SHS-UHN Innovation Fund Award and a Women's College Hospital Innovation Fund Award (both, Toronto, ON, Canada). Frances Chung reports research support from the Ontario Ministry of Health and Long-Term Care Innovation Grant, ResMed Foundation, University Health Network Foundation (Toronto, ON, Canada); being a consultant to Takeda Pharmaceuticals and Haisco Pharmaceutical Group; and STOP-Bang Questionnaire proprietary to University Health Network (Toronto, ON, Canada). EDAT- 2026/05/06 00:32 MHDA- 2026/06/15 11:33 PMCR- 2026/05/05 CRDT- 2026/05/05 23:35 PHST- 2024/12/31 00:00 [received] PHST- 2025/08/08 00:00 [accepted] PHST- 2025/07/29 00:00 [revised] PHST- 2026/06/15 11:33 [medline] PHST- 2026/05/06 00:32 [pubmed] PHST- 2026/05/05 23:35 [entrez] PHST- 2026/05/05 00:00 [pmc-release] AID - 10.1007/s12630-026-03114-6 [pii] AID - 3114 [pii] AID - 10.1007/s12630-026-03114-6 [doi] PST - ppublish SO - Can J Anaesth. 2026 Apr;73(4):345-356. doi: 10.1007/s12630-026-03114-6. Epub 2026 May 5. PMID- 42086986 OWN - NLM STAT- MEDLINE DCOM- 20260922 LR - 20260925 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 51 IP - 11 DP - 2026 Oct TI - Computational phenotyping of effort-based decision-making in type-2 diabetes on and off semaglutide. PG - 1924-1931 LID - 10.1038/s41386-026-02433-y [doi] AB - Motivation plays a fundamental role in human behaviour. Dopaminergic pathways have long been implicated in individual differences in motivation. Emerging evidence suggests such neural mechanisms interact with metabolic processes to coordinate energy expenditure with energy resources, thereby linking motivation with metabolic health. We ask whether a cognitive-computational index of motivation-reliably linked to neuropsychiatric symptoms-is altered in the context of type-2 diabetes and treatment with a GLP-1 agonist (semaglutide). In a pre-registered experiment, we quantified computational effort-based decision-making parameters in participants with diabetes on (N = 58) or off (N = 54) semaglutide treatment, compared to two groups of matched controls without diabetes (N = 58 each). Subjects with type-2 diabetes showed a blunted acceptance bias, a computational parameter describing the bias to accept effort for reward. This effect was not driven by neuropsychiatric comorbidity or antidepressant use. Across all participants, we found that increasing diabetes risk linearly predicted reduced acceptance bias. Participants with diabetes treated with semaglutide did not show restored motivation. Metabolic ill-health is associated with reduced acceptance bias during motivational decision-making. This blunting mirrors-but is largely independent of-neuropsychiatric motivational deficits. This suggests metabolic ill-health is accompanied by a cognitive shift towards energy conservation, potentially contributing to comorbidity between metabolic ill-health and mental illness. CI - (c) 2026. The Author(s). FAU - Mehrhof, Sara Z AU - Mehrhof SZ AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. sara.mehrhof@mrc-cbu.cam.ac.uk. FAU - Fleming, Hugo AU - Fleming H AUID- ORCID: 0000-0001-5421-8222 AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. FAU - Nord, Camilla L AU - Nord CL AUID- ORCID: 0000-0002-9281-3417 AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. AD - Department of Psychiatry, University of Cambridge, Cambridge, UK. LA - eng GR - MC_UU_00030/12/RCUK | Medical Research Council (MRC)/ GR - G102329/AXA Research Fund (Le Fonds AXA pour la Recherche)/ GR - 226490/Z/22/Z/Wellcome Trust (Wellcome)/ GR - WT_/Wellcome Trust/United Kingdom GR - BRC-1215-20014/DH | National Institute for Health Research (NIHR)/ PT - Journal Article DEP - 20260506 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Female MH - *Decision Making/drug effects/physiology MH - Male MH - *Motivation/drug effects/physiology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Phenotype MH - Aged MH - Reward PMC - PMC13597482 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/05/06 00:35 MHDA- 2026/09/23 05:34 PMCR- 2026/05/06 CRDT- 2026/05/05 23:34 PHST- 2025/12/23 00:00 [received] PHST- 2026/04/17 00:00 [accepted] PHST- 2026/03/30 00:00 [revised] PHST- 2026/09/23 05:34 [medline] PHST- 2026/05/06 00:35 [pubmed] PHST- 2026/05/05 23:34 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - 10.1038/s41386-026-02433-y [pii] AID - 2433 [pii] AID - 10.1038/s41386-026-02433-y [doi] PST - ppublish SO - Neuropsychopharmacology. 2026 Oct;51(11):1924-1931. doi: 10.1038/s41386-026-02433-y. Epub 2026 May 6. PMID- 42086460 OWN - NLM STAT- MEDLINE DCOM- 20260608 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Adherence and Persistence Among Individuals Living With Type 2 Diabetes and Using a Free Combination of Basal Insulin and an Injectable Glucagon-Like Peptide-1 Receptor Agonist Versus a Fixed-Ratio Combination Therapy: A Japanese Database Study. PG - 6291-6300 LID - 10.1111/dom.70812 [doi] AB - AIM: To investigate adherence to and persistence with free combination therapy (daily basal insulin plus an injectable glucagon-like peptide-1 receptor agonist [GLP-1 RA]) versus fixed-ratio combination (FRC) therapy (basal insulin plus a GLP-1 RA) among individuals with type 2 diabetes (T2D) in Japan. MATERIALS AND METHODS: This retrospective, observational cohort study used DeSC-IQVIA Integrated claims data from Japan to identify adults (aged >/= 18 years) with confirmed T2D and >/= 1 prescription for a GLP-1 RA (with predefined basal insulin persistence window) or an FRC during October 2019 to September 2023. Study index was date of first GLP-1 RA or FRC prescription; follow-up was 365 days. The primary objective was to evaluate adherence to and persistence with free combination therapy versus FRC therapy. RESULTS: Age (mean [standard deviation]) at index was statistically significantly higher in the free combination group (67.0 [13.85] years, n = 2063) than in the FRC group (65.7 [13.85] years, n = 2386) (p = 0.002). Odds of optimal adherence at end of follow-up were statistically significantly higher with FRC therapy than with free combination therapy (adjusted odds ratio [95% confidence interval]: 1.96 [1.73-2.23]; p < 0.001). Risk of discontinuation by end of follow-up was statistically significantly lower with FRC therapy than with free combination therapy (adjusted hazard ratio [95% confidence interval]: 0.66 [0.61-0.71]; p < 0.001). Adherence and persistence findings were similar in elderly individuals. CONCLUSIONS: In this real-world, adult population with T2D in Japan, FRC therapy was associated with improved adherence and persistence versus free combination therapy. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Miyatsuka, Takeshi AU - Miyatsuka T AUID- ORCID: 0000-0003-2618-3450 AD - Department of Diabetes, Endocrinology and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan. FAU - Brash, James AU - Brash J AD - IQVIA Inc, London, UK. FAU - Davies, Eleanor AU - Davies E AUID- ORCID: 0009-0002-2778-0353 AD - IQVIA Inc, London, UK. FAU - de Laguiche, Elisabeth AU - de Laguiche E AUID- ORCID: 0000-0003-2125-9006 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vistisen, Dorte AU - Vistisen D AUID- ORCID: 0000-0001-5045-5351 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Yin, Can AU - Yin C AUID- ORCID: 0009-0000-1115-4492 AD - IQVIA Inc, London, UK. FAU - Adam, Atif AU - Adam A AUID- ORCID: 0000-0003-0067-7110 AD - IQVIA Inc, London, UK. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Observational Study DEP - 20260505 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - 0 (Drug Combinations) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Japan/epidemiology MH - Retrospective Studies MH - Female MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Middle Aged MH - Male MH - Drug Therapy, Combination MH - *Drug Monitoring MH - Databases, Factual MH - *Insulin/administration & dosage/therapeutic use MH - Drug Combinations MH - East Asian People PMC - PMC13243944 OTO - NOTNLM OT - GLP-1 analogue OT - basal insulin OT - database research OT - fixed-ratio combination OT - type 2 diabetes COIS- Takeshi Miyatsuka declares no conflicts of interest related to this study. James Brash, Eleanor Davies, Can Yin and Atif Adam are employees of IQVIA. Elisabeth de Laguiche and Dorte Vistisen are employees and shareholders of Novo Nordisk. EDAT- 2026/05/06 00:34 MHDA- 2026/06/08 19:39 PMCR- 2026/06/08 CRDT- 2026/05/05 21:53 PHST- 2026/04/09 00:00 [revised] PHST- 2026/01/23 00:00 [received] PHST- 2026/04/16 00:00 [accepted] PHST- 2026/06/08 19:39 [medline] PHST- 2026/05/06 00:34 [pubmed] PHST- 2026/05/05 21:53 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70812 [pii] AID - 10.1111/dom.70812 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):6291-6300. doi: 10.1111/dom.70812. Epub 2026 May 5. PMID- 42084545 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 39 IP - 6 DP - 2026 Dec TI - Assessing the Impact of Glucagon-like Peptide-1 and Glucagon-like Peptide-1/glucose-dependent Insulinotropic Polypeptide Receptor Agonist Shortages on Glycemic Control: A Single Center Study. PG - 523-528 LID - 10.1177/08971900261449175 [doi] AB - Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) effectively manage type 2 diabetes mellitus (T2DM). Recent medication shortages have impacted patient access to treatment. The objectives of this study were to evaluate the effect of incretin therapy shortages on glycemic control and adverse patient outcomes. This retrospective cohort study evaluated the impact of interruptions in therapy on patients receiving maintenance doses of incretin therapy for at least three months. Patients were excluded if they were not on adequate maintenance doses, had missing hemoglobin A1c (HbA1c) levels, discontinued therapy due to side effects or cost, or had a history of chronic glucocorticoid use or organ transplant. The primary outcome was HbA1c levels before and after therapy interruption. Secondary outcomes were the incidence of gastrointestinal issues, hyperglycemia, and hypoglycemia-related hospital/clinic visits. A total of 71 patients were included. The median therapy duration was 9 months. Patients had a baseline HbA1c of 6.9%. Following interruption, 25.4% of patients had glucose-lowering therapy additions to their regimen, 35.2% dosage adjustments, and 39.4% no changes. HbA1c increased significantly to 7.2% at 12 months (P < 0.001). No significant differences were observed in adverse events or clinic/hospital visits (P = 0.571 and P = 1.00). Shortages of incretin therapy significantly increased patients' HbA1c levels up to 12 months post interruption. Long-term shortages or restrictions of these agents are likely to lead to adverse clinical outcomes. Further studies are needed to assess the outcomes of prolonged shortages or restrictions of these therapies. FAU - Dacon, Christian AU - Dacon C AD - Department of Pharmacy, Henry Ford St. John Hospital, Detroit, MI, USA. RINGGOLD: 738793 FAU - Kale-Pradhan, Pramodini AU - Kale-Pradhan P AUID- ORCID: 0000-0002-8729-7710 AD - Department of Pharmacy, Henry Ford St. John Hospital, Detroit, MI, USA. RINGGOLD: 738793 AD - Pharmacy practice, Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA. RINGGOLD: 15538 FAU - Lipari, Melissa AU - Lipari M AUID- ORCID: 0000-0003-2658-8247 AD - Department of Pharmacy, Henry Ford St. John Hospital, Detroit, MI, USA. RINGGOLD: 738793 AD - Pharmacy practice, Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA. RINGGOLD: 15538 LA - eng PT - Journal Article DEP - 20260505 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/supply & distribution/administration & dosage MH - Male MH - *Glycemic Control/methods MH - Glycated Hemoglobin/metabolism MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - Aged MH - *Incretins/therapeutic use/administration & dosage MH - *Glucagon-Like Peptide 1/agonists MH - *Receptors, Gastrointestinal Hormone/agonists MH - Cohort Studies OTO - NOTNLM OT - drug shortages OT - glucagon-like peptide-1 receptor agonist OT - glucose-dependent insulinotropic polypeptide receptor agonist OT - type 2 diabetes mellitus COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/05/05 12:37 MHDA- 2026/10/27 05:29 CRDT- 2026/05/05 10:13 PHST- 2026/10/27 05:29 [medline] PHST- 2026/05/05 12:37 [pubmed] PHST- 2026/05/05 10:13 [entrez] AID - 10.1177/08971900261449175 [doi] PST - ppublish SO - J Pharm Pract. 2026 Dec;39(6):523-528. doi: 10.1177/08971900261449175. Epub 2026 May 5. PMID- 42083728 OWN - NLM STAT- MEDLINE DCOM- 20261012 LR - 20261014 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 27 IP - 11 DP - 2026 Nov TI - Low Weight Loss Response to Incretin Analogs: A Systematic Review. PG - e70145 LID - 10.1111/obr.70145 [doi] LID - e70145 AB - The development of GLP-1 and GIP analogs has been a significant breakthrough in type 2 diabetes and obesity pharmacotherapy. However, individual responses to these medications can vary widely. This systematic review examines factors associated with low or no weight loss response to GLP-1 and GIP analogs. Key predictors of poor response include higher baseline body weight, BMI, HbA1c, and insulin resistance. Genetic factors, such as variants in the GLP1R gene, may also influence treatment outcomes. Metabolic health status, particularly glycemic control and insulin sensitivity, plays a crucial role in determining weight loss efficacy. Adherence to medication regimens is strongly associated with treatment success, with each additional month of treatment linked to greater weight loss. Lifestyle factors, including dietary habits and physical activity, can modulate responses to these medications. Emerging evidence suggests that gut microbiome composition may mediate weight loss outcomes. Demographic factors such as male sex and older age are associated with lower weight loss responses. Understanding these predictors is essential for optimizing treatment strategies, setting realistic expectations, and moving towards a precision medicine approach in obesity care. Further research is needed to validate these findings in diverse populations and develop practical tools for clinical decision-making. CI - (c) 2026 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Gaskin, Pamela S AU - Gaskin PS AUID- ORCID: 0000-0003-3185-6840 AD - Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados. FAU - Chami, Peter S AU - Chami PS AD - Faculty of Pure and Applied Sciences, University of the West Indies, Bridgetown, Barbados. AD - Faculty of Medical Sciences, The Warren Alpert Medical School, Bridgetown, Barbados. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260505 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Inhibitory Polypeptide/analogs & derivatives/therapeutic use MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - *Incretins/therapeutic use MH - *Obesity/drug therapy MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use PMC - PMC13655991 OTO - NOTNLM OT - GLP1 and GIP analogs OT - low weight loss response OT - obesity OT - weight loss COIS- The authors declare no conflicts of interest. EDAT- 2026/05/05 06:32 MHDA- 2026/10/12 11:41 PMCR- 2026/10/12 CRDT- 2026/05/05 03:43 PHST- 2025/04/02 00:00 [revised] PHST- 2024/08/02 00:00 [received] PHST- 2026/03/26 00:00 [accepted] PHST- 2026/10/12 11:41 [medline] PHST- 2026/05/05 06:32 [pubmed] PHST- 2026/05/05 03:43 [entrez] PHST- 2026/10/12 00:00 [pmc-release] AID - OBR70145 [pii] AID - 10.1111/obr.70145 [doi] PST - ppublish SO - Obes Rev. 2026 Nov;27(11):e70145. doi: 10.1111/obr.70145. Epub 2026 May 5. PMID- 42080079 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260813 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 23 IP - 5 DP - 2026 TI - Clinical effects of glucagon-like peptide-1 receptor agonist in type 2 diabetes with low body mass index: findings from large-scale emulated target trials. PG - 1748-1760 LID - 10.7150/ijms.130295 [doi] AB - AIMS: Chronic kidney disease (CKD) is a common and serious complication of type 2 diabetes, yet the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in non-obese or mildly overweight individuals remains uncertain. This study evaluated renal, cardiovascular, and systemic outcomes associated with GLP-1 RA therapy in adults with type 2 diabetes and body mass index (BMI) /=18 years) with overweight or obesity, antipsychotic exposure, and no prior T2DM diagnosis were identified. After propensity score matching, patients initiating GLP-1RA therapy were compared with those initiating metformin. The primary outcome was incident T2DM occurring between 1 and 5 years after treatment initiation. Secondary outcomes included all-cause mortality and BMI change. Among 9939 eligible patients, 3115 matched pairs were included. The incidence of T2DM was significantly lower in the GLP-1RA group compared with the metformin group (1.96% vs 7.26%; hazard ratio [HR]=0.34; 95% CI, 0.26-0.46; p < 0.001). All-cause mortality was also reduced in the GLP-1RA group (0.32% vs 1.96%; HR, 0.25; 95% CI, 0.13-0.49; p < 0.001). Regarding BMI change, patients receiving GLP-1RA experienced greater weight reduction than those receiving metformin. The mean (standard deviation) change in BMI was -2.66 (8.51) kg/m(2) in the GLP-1 group versus -1.36 (8.63) kg/m(2) in the metformin group (p < 0.001). In conclusion, in this large real-world cohort of antipsychotic-treated patients with overweight or obesity, GLP-1RA therapy was associated with significantly lower risks of T2DM and mortality, and greater BMI reduction compared with metformin. These findings suggest that GLP-1RAs may offer a more favorable profile against antipsychotic-induced glucose dysregulation. CI - Copyright (c) 2026 Elsevier B.V. and ECNP. All rights reserved. FAU - Liu, Ting-Hui AU - Liu TH AD - Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan. FAU - Lee, Chung-Han AU - Lee CH AD - Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Liu, Chia-Yu AU - Liu CY AD - Department of Audiology and Speech-Language Pathology, Asia University, Taichung, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Tsai, Ya-Wen AU - Tsai YW AD - Center for Integrative Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kao, Pei-Hsin AU - Kao PH AD - Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan; Department of Geriatric Psychiatry, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address: joek27@gmail.com. FAU - Lai, Chih-Cheng AU - Lai CC AD - Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: dtmed141@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260502 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 9100L32L2N (Metformin) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Antipsychotic Agents/adverse effects/therapeutic use MH - Female MH - *Diabetes Mellitus, Type 2/prevention & control/mortality/epidemiology MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Middle Aged MH - Adult MH - Body Mass Index MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy MH - Overweight/drug therapy MH - Treatment Outcome MH - Cohort Studies MH - Aged OTO - NOTNLM OT - Antipsychotic OT - Diabetes mellitus OT - GLP-1RA OT - Metformin COIS- Declaration of competing interest All authors declared there is no conflict of interest. EDAT- 2026/05/03 05:27 MHDA- 2026/07/10 18:44 CRDT- 2026/05/02 18:02 PHST- 2026/01/20 00:00 [received] PHST- 2026/04/08 00:00 [revised] PHST- 2026/04/12 00:00 [accepted] PHST- 2026/07/10 18:44 [medline] PHST- 2026/05/03 05:27 [pubmed] PHST- 2026/05/02 18:02 [entrez] AID - S0924-977X(26)00094-5 [pii] AID - 10.1016/j.euroneuro.2026.112853 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2026 Sep;110:112853. doi: 10.1016/j.euroneuro.2026.112853. Epub 2026 May 2. PMID- 42066004 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 18 IP - 20 DP - 2026 May 27 TI - An Ionic Liquid-Based Enteric Formulation for Enhanced Oral Delivery of Semaglutide in Type 2 Diabetes Mellitus. PG - 28368-28380 LID - 10.1021/acsami.5c24385 [doi] AB - Oral delivery of peptide therapeutics remains challenging due to gastrointestinal degradation, poor epithelial permeability, and extremely low bioavailability. To address these limitations, we developed an enteric solid formulation based on sorbic acid-choline ionic liquids (ILs) for the oral delivery of semaglutide (Sema), a glucagon-like peptide-1 (GLP-1) analogue. The IL-based enteric system was designed to enhance peptide stability, reduce gastric degradation, and promote intestinal absorption. In vitro studies demonstrated strong resistance to acidic conditions and pH-responsive release in simulated intestinal fluid. In vivo imaging further revealed prolonged intestinal retention of the IL-loaded enteric particles. Pharmacokinetic evaluation showed a 2.3-fold increase in maximum plasma concentration compared to the reference Rybelsus. In type 2 diabetes mellitus (T2DM) mice, the formulation achieved glucose-lowering efficacy comparable to subcutaneous Sema administration, with additional improvements in hepatic histology. Importantly, repeated-dose studies indicated favorable systemic and gastrointestinal tolerability under the tested conditions. Collectively, these results demonstrate that IL-based enteric formulation enhances oral peptide exposure while maintaining safety, offering a promising strategy for noninvasive T2DM management. FAU - Tao, Juan AU - Tao J AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. AD - School of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China. FAU - Lu, Xinrui AU - Lu X AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Wei, Yuning AU - Wei Y AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Feng, Jiayi AU - Feng J AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Yang, Jinlong AU - Yang J AUID- ORCID: 0000-0002-7358-3396 AD - Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China. FAU - Qi, Jianping AU - Qi J AUID- ORCID: 0000-0003-4833-1426 AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. LA - eng PT - Journal Article DEP - 20260501 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Ionic Liquids) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - Animals MH - *Glucagon-Like Peptides/chemistry/pharmacokinetics/pharmacology/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Administration, Oral MH - *Ionic Liquids/chemistry MH - Mice MH - Male MH - *Hypoglycemic Agents/chemistry/pharmacokinetics/therapeutic use/pharmacology/administration & dosage MH - *Diabetes Mellitus, Experimental/drug therapy MH - Humans OTO - NOTNLM OT - bioavailability OT - ionic liquid OT - oral peptide delivery OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2026/05/01 18:45 MHDA- 2026/05/27 12:35 CRDT- 2026/05/01 13:13 PHST- 2026/05/27 12:35 [medline] PHST- 2026/05/01 18:45 [pubmed] PHST- 2026/05/01 13:13 [entrez] AID - 10.1021/acsami.5c24385 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2026 May 27;18(20):28368-28380. doi: 10.1021/acsami.5c24385. Epub 2026 May 1. PMID- 42061677 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260902 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 29 IP - 9 DP - 2026 Sep TI - Assessment of Carbon Emission Impact of Semaglutide in Patients With Type 2 Diabetes in the United Kingdom Using an Innovative Modeling Approach. PG - 1626-1635 LID - S1098-3015(26)02397-1 [pii] LID - 10.1016/j.jval.2026.03.2249 [doi] AB - OBJECTIVES: To evaluate the carbon footprint and clinical outcomes of once-weekly subcutaneous semaglutide in patients with type 2 diabetes mellitus (T2DM) in the United Kingdom. METHODS: Using the IQVIA Core Diabetes Model, environmental and clinical impacts were projected over a lifetime horizon from the National Health Services perspective. Data from the SUSTAIN-2 (patients with T2DM) and SUSTAIN-6 (patients with T2DM and established cardiovascular [CV] risk) trials were used to compare semaglutide with sitagliptin and placebo, respectively. Outcomes included life expectancy measured in life-years (LYs) and quality-adjusted life expectancy measured in quality-adjusted life-years (QALYs) gained, incidence of diabetes-related complications and adverse events, carbon emissions, and incremental carbon footprint effectiveness ratios. RESULTS: In patients with T2DM, semaglutide dominates sitagliptin, with higher discounted LYs (0.096) and QALYs (0.095) gains, a 6.9% reduction in diabetes-related complications and adverse events, and reduced lifetime carbon emissions by 9.3% (13,899 kg carbon dioxide equivalent emissions [CO(2)e] versus 15,319 kg CO(2)e). Similarly, in patients with T2DM and established CV risk, semaglutide showed higher discounted LYs (0.206) and QALYs (0.164), with reductions in all complications except heart failure-related hospitalizations versus placebo. Lifetime carbon emissions were 5.2% lower with semaglutide (14,546 kg CO(2)e versus 15,341 kg CO(2)e), again with a dominant carbon footprint effectiveness ratio. The reduction in CO(2) was mainly driven by reduced complications and treatment needs. Sensitivity analyses supported the robustness of the results. CONCLUSION: Semaglutide offers environmental advantages over sitagliptin for patients with T2DM overall and over standard of care for those with established CV risk. CI - Copyright (c) 2026. Published by Elsevier Inc. FAU - Lund, Niels AU - Lund N AD - Novo Nordisk, Bagsvaerd, Denmark. Electronic address: nlnd@novonordisk.com. FAU - Rasche, Andreas AU - Rasche A AD - Copenhagen Business School, Frederiksberg, Denmark. FAU - Taylor, Matthew AU - Taylor M AD - York Health Economics Consortium, University of York, York, England, UK. FAU - Chubb, Barrie AU - Chubb B AD - Novo Nordisk Ltd, Gatwick, England, UK. FAU - Xu, Weiwei AU - Xu W AD - IQVIA, Amsterdam, Netherlands. FAU - Taneja, Loveleen AU - Taneja L AD - IQVIA, Gurugram, Haryana, India. FAU - Olivieri, Anamaria-Vera AU - Olivieri AV AD - IQVIA, Basel, Switzerland. FAU - Sharma, Yuvraj AU - Sharma Y AD - IQVIA Ltd, London, England, UK. LA - eng PT - Journal Article DEP - 20260428 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/economics/adverse effects MH - United Kingdom MH - *Hypoglycemic Agents/administration & dosage/adverse effects/economics/therapeutic use MH - Sitagliptin Phosphate/therapeutic use/administration & dosage/economics/adverse effects MH - *Carbon Footprint MH - Quality-Adjusted Life Years MH - Female MH - Male MH - Middle Aged MH - Cost-Benefit Analysis MH - Aged OTO - NOTNLM OT - ICFER OT - carbon emission OT - carbon footprint OT - incremental carbon footprint effectiveness ratio OT - semaglutide OT - type 2 diabetes COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2026/05/01 00:31 MHDA- 2026/09/03 01:19 CRDT- 2026/04/30 19:18 PHST- 2025/10/09 00:00 [received] PHST- 2026/03/23 00:00 [revised] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/09/03 01:19 [medline] PHST- 2026/05/01 00:31 [pubmed] PHST- 2026/04/30 19:18 [entrez] AID - S1098-3015(26)02397-1 [pii] AID - 10.1016/j.jval.2026.03.2249 [doi] PST - ppublish SO - Value Health. 2026 Sep;29(9):1626-1635. doi: 10.1016/j.jval.2026.03.2249. Epub 2026 Apr 28. PMID- 42061608 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260630 IS - 2254-8874 (Electronic) IS - 2254-8874 (Linking) VI - 226 IP - 6 DP - 2026 Jun-Jul TI - Real-world impact of oral semaglutide on inflammatory markers in patients at high cardiovascular risk. PG - 502562 LID - S2254-8874(26)00091-3 [pii] LID - 10.1016/j.rceng.2026.502562 [doi] AB - BACKGROUND AND OBJECTIVE: Inflammation plays a central role in the pathophysiology of atherosclerosis and contributes to residual cardiovascular risk (CVR). High-sensitivity C-reactive protein (hs-CRP) and fibrinogen are considered key biomarkers in this context. Although GLP-1 receptor agonists have demonstrated anti-inflammatory effects, real-world evidence on oral semaglutide is limited. The objective of this study was to evaluate the impact of oral semaglutide on inflammatory markers in patients with high cardiovascular risk (CVR) in routine clinical practice. MATERIALS AND METHODS: This was an observational study that included adult patients receiving treatment with oral semaglutide. The primary endpoint was the change in hs-CRP and fibrinogen levels. Secondary objectives included evaluating modifications in glycated hemoglobin (HbA1c), safety, and predictors of sustained anti-inflammatory response, defined as hs-CRP /= 5%) goals after semaglutide initiation. We compared baseline (1 year before initiation) with 1st-year and 2nd-year follow-up for cardiometabolic endpoints (3-point and 5-point major adverse cardiovascular events [MACE]), cardiometabolic risk factors, and renal outcomes. Sensitivity analysis was performed in an exploratory cohort of patients in the top tertile of Hb1Ac reduction and weight loss. RESULTS: We identified 413 patients in the primary cohort (mean age 59.6 years and balanced sex distribution). Significant reductions were observed in low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), total cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure and high-density lipoprotein cholesterol (HDL-C) increased at both 1 and 2 years after semaglutide initiation (all p < 0.001). Fewer than 1% of patients experienced a >/= 40% decline in estimated glomerular filtration rate (eGFR) during follow-up. Mean change in urine albumin-to-creatinine ratio (UACR) were - 20.13 mg/g in the 1st year (p < 0.001) and - 54.03 mg/g in the 2nd year (p < 0.001). The event rate of 3-point MACE decreased from 26.82 per 1000 person-years (PY) during baseline to 22.31 per 1000 PY in the 2nd year. The sensitivity analysis showed consistent results. CONCLUSION: In this real-world study, semaglutide users who achieved glycemic and weight goals exhibited marked improvements in cardiometabolic and renal outcomes over 2 years. CI - (c) 2026. The Author(s). FAU - Tan, Xi AU - Tan X AUID- ORCID: 0000-0002-2409-5927 AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. mxtz@novonordisk.com. FAU - Tsai, Wan-Lun AU - Tsai WL AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Swift, Caroline AU - Swift C AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Fang, Gang AU - Fang G AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, CT, USA. LA - eng PT - Journal Article PT - Observational Study DEP - 20260430 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects MH - Glycated Hemoglobin/metabolism MH - Aged MH - Cohort Studies MH - *Cardiovascular Diseases/prevention & control MH - Glycemic Control MH - Metabolic Syndrome MH - Blood Glucose PMC - PMC13290940 OTO - NOTNLM OT - Cardiovascular OT - Major adverse cardiovascular event OT - Renal OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Xi Tan, Yuanjie Liang, Caroline Swift, Gang Fang, and Chalak Muhammad are employees of Novo Nordisk Inc. Wan-Lun Tsai was a contractor for Novo Nordisk Inc. at the time of the study. Adam de Havenon reports research funding from NIH/NINDS and the AAN, consulting for Novo Nordisk Inc., royalites from UptoDate, and equity in TitinKM and Certus. Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki. This retrospective analysis used Optum(R) Market Clarity, a fully de-identified, HIPAA-compliant dataset; under US federal regulations (45 CFR 46), analyses of de-identified data do not constitute human subjects research and do not require review by an Institutional Review Board. No identifiable private information was accessed. This study analyzed secondary data from the de-identified Optum(R) Market Clarity without direct subject contact or intervention; per 45 CFR 46, analyses of secondary, de-identified data are not human subjects research and do not require consent. EDAT- 2026/04/30 12:35 MHDA- 2026/06/23 18:33 PMCR- 2026/04/30 CRDT- 2026/04/30 11:14 PHST- 2026/01/28 00:00 [received] PHST- 2026/04/13 00:00 [accepted] PHST- 2026/06/23 18:33 [medline] PHST- 2026/04/30 12:35 [pubmed] PHST- 2026/04/30 11:14 [entrez] PHST- 2026/04/30 00:00 [pmc-release] AID - 10.1007/s12325-026-03610-7 [pii] AID - 3610 [pii] AID - 10.1007/s12325-026-03610-7 [doi] PST - ppublish SO - Adv Ther. 2026 Jul;43(7):3088-3104. doi: 10.1007/s12325-026-03610-7. Epub 2026 Apr 30. PMID- 42056522 OWN - NLM STAT- MEDLINE DCOM- 20260521 LR - 20260922 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 653 IP - 8115 DP - 2026 May TI - GLP-1R-GIPR-PPARalpha/gamma/delta quintuple agonism corrects obesity and diabetes in mice. PG - 776-785 LID - 10.1038/s41586-026-10427-5 [doi] AB - There are increasing numbers of effective drugs to improve obesity-linked metabolic dysfunction; GLP-1R-GIPR co-agonism is effective in the management of obesity and type 2 diabetes(1,2), and lanifibranor-a nuclear-acting small-molecule triple agonist of PPARalpha, PPARgamma and PPARdelta-is in clinical phase 3 trials for the treatment of metabolic dysfunction-associated steatohepatitis(3). Here, seeking to further improve the metabolic efficacy of GLP-1R-GIPR co-agonism, we report the development of a unimolecular quintuple agonist that combines the body weight-reducing and blood glucose-lowering effects of GLP-1R-GIPR co-agonism with the insulin-sensitizing and anti-inflammatory effects of lanifibranor via its targeted delivery into GLP-1R- and GIPR-expressing cells. In vitro, GLP-1-GIP-lanifibranor is indistinguishable from GLP-1-GIP in relation to incretin receptor signalling and shows equal stimulation of insulin secretion in isolated mouse islets. In vivo, however, GLP-1-GIP-lanifibranor outperforms GLP-1R-GIPR co-agonism and semaglutide, further decreasing body weight, food intake and hyperglycaemia in obese and insulin-resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1-GIP-lanifibranor is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARdelta and is absent in DIO double incretin receptor-knockout mice, collectively suggesting that GLP-1-GIP-lanifibranor has substantial therapeutic value in the treatment of obesity and diabetes. CI - (c) 2026. The Author(s). FAU - Liskiewicz, Daniela AU - Liskiewicz D AUID- ORCID: 0000-0002-5859-6316 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Institute of Physiotherapy and Health Sciences, Academy of Physical Education, Katowice, Poland. FAU - Novikoff, Aaron AU - Novikoff A AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Khalil, Ahmed AU - Khalil A AUID- ORCID: 0009-0000-2204-8636 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Akindehin, Seun AU - Akindehin S AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Campbell, Jonathan E AU - Campbell JE AUID- ORCID: 0000-0003-4358-6331 AD - Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA. AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Candela, Pietra AU - Candela P AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Castelino, Russell L AU - Castelino RL AUID- ORCID: 0009-0008-7446-6299 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Coupland, Callum AU - Coupland C AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Culot, Maxime AU - Culot M AUID- ORCID: 0000-0001-7452-0867 AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Dodson, W Scott AU - Dodson WS AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. FAU - Douros, Jonathan D AU - Douros JD AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Embring, Hannes AU - Embring H AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Feuchtinger, Annette AU - Feuchtinger A AD - Core Facility Pathology and Tissue Analytics, Helmholtz, Munich, Germany. FAU - Finan, Brian AU - Finan B AUID- ORCID: 0000-0003-1178-8481 AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Garcia-Caceres, Cristina AU - Garcia-Caceres C AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Medizinische Klinik und Poliklinik IV, Klinikum der Universitat, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. FAU - Gao, Xiao-Bing AU - Gao XB AUID- ORCID: 0000-0002-2035-4936 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. FAU - Gosselet, Fabien AU - Gosselet F AUID- ORCID: 0000-0002-0481-5026 AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Grandl, Gerald AU - Grandl G AUID- ORCID: 0000-0003-4456-1988 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Gutgesell, Robert M AU - Gutgesell RM AUID- ORCID: 0000-0001-6137-0468 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Institute of Computational Biology, Helmholtz Munich, Munich, Germany. FAU - Haas, Daniel T AU - Haas DT AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Jastroch, Martin AU - Jastroch M AUID- ORCID: 0000-0003-0358-3865 AD - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. FAU - Karaoglu, Ezgi AU - Karaoglu E AUID- ORCID: 0009-0003-2639-6015 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Department of Pharmacology, Experimental Therapy and Toxicology, Institute for Experimental and Clinical Pharmacology and Pharmacogenomic, Eberhard Karls University, Interfaculty Center of Pharmacogenomic and Drug Research, Tubingen, Germany. FAU - Kakimoto, Pamela AU - Kakimoto P AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Kaltenbach, Anna Cristina AU - Kaltenbach AC AUID- ORCID: 0009-0006-3196-5288 AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. FAU - Keuper, Michaela AU - Keuper M AUID- ORCID: 0000-0003-0319-3509 AD - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. FAU - Kusminski, Christine M AU - Kusminski CM AUID- ORCID: 0000-0002-3671-0341 AD - Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Leander, Danielle C AU - Leander DC AUID- ORCID: 0009-0000-7507-001X AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Liskiewicz, Arkadiusz AU - Liskiewicz A AUID- ORCID: 0000-0002-4102-5373 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland. FAU - Liu, Xue AU - Liu X AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Maity-Kumar, Gandhari AU - Maity-Kumar G AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Martinez, Sara Martinez AU - Martinez SM AUID- ORCID: 0000-0002-7258-9083 AD - CIMUS, University of Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. FAU - Mowery, Stephanie A AU - Mowery SA AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Nogueiras, Ruben AU - Nogueiras R AUID- ORCID: 0000-0002-9976-9930 AD - CIMUS, University of Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. FAU - Paisley, Marshall AU - Paisley M AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Perez-Tilve, Diego AU - Perez-Tilve D AD - Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Petersen, Patricia S S AU - Petersen PSS AUID- ORCID: 0000-0003-2560-1446 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Pfluger, Paul T AU - Pfluger PT AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Research Unit Neurobiology of Diabetes, Helmholtz Munich, Neuherberg, Germany. AD - Division of NeuroBiology of Diabetes, TUM School of Medicine and Health, Technical University Munich, Munich, Germany. FAU - Prakash, Sneha AU - Prakash S AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Steffens, Sabine AU - Steffens S AUID- ORCID: 0000-0002-6892-9751 AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. AD - Institute for Diabetes and Cancer (IDC), Helmholtz Diabetes Center (HDC), Helmholtz Zentrum Munchen (Helmholtz Munich), Munich, Germany. AD - DZHK (German Centre for Cardiovascular Research) Partner Site, Munich Heart Alliance, Munich, Germany. FAU - Cebrian-Serrano, Alberto AU - Cebrian-Serrano A AUID- ORCID: 0000-0002-4737-0215 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Tost, Monica AU - Tost M AD - Core Facility Pathology and Tissue Analytics, Helmholtz, Munich, Germany. FAU - Wean, Jordan AU - Wean J AUID- ORCID: 0000-0002-9459-0093 AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Weber, Christian AU - Weber C AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. AD - DZHK (German Centre for Cardiovascular Research) Partner Site, Munich Heart Alliance, Munich, Germany. AD - Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. AD - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. FAU - Yoshida, Junichi AU - Yoshida J AUID- ORCID: 0000-0003-4175-4258 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. FAU - Gerhart-Hines, Zachary AU - Gerhart-Hines Z AUID- ORCID: 0000-0003-2981-4991 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Horvath, Tamas L AU - Horvath TL AUID- ORCID: 0000-0002-7522-4602 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. AD - Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary. FAU - Scherer, Philipp E AU - Scherer PE AUID- ORCID: 0000-0003-0680-3392 AD - Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Seeley, Randy J AU - Seeley RJ AUID- ORCID: 0000-0002-3721-5625 AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - DiMarchi, Richard D AU - DiMarchi RD AUID- ORCID: 0000-0003-0220-4085 AD - Department of Chemistry, Indiana University, Bloomington, IN, USA. FAU - Tschop, Matthias H AU - Tschop MH AD - Helmholtz Munich, Munich, Germany. AD - Ludwig-Maximilians-University (LMU) Munich, Munich, Germany. FAU - Krahmer, Natalie AU - Krahmer N AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Metabolic Cell Architecture, Department of Molecular Life Sciences, TUM School of Life Sciences, Technical University of Munich, Munich, Germany. FAU - Knerr, Patrick J AU - Knerr PJ AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Muller, Timo D AU - Muller TD AUID- ORCID: 0000-0002-0624-9339 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. timodirk.mueller@helmholtz-munich.de. AD - German Center for Diabetes Research (DZD), Munich, Germany. timodirk.mueller@helmholtz-munich.de. AD - Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany. timodirk.mueller@helmholtz-munich.de. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - R01 DK133140/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260429 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (PPAR delta) RN - 0 (PPAR alpha) RN - 0 (PPAR gamma) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Butyrates) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glp1r protein, mouse) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM EIN - Nature. 2026 Jun;654(8117):E11. doi: 10.1038/s41586-026-10619-z. PMID: 42151694 MH - Animals MH - Mice MH - *Obesity/drug therapy/metabolism MH - *PPAR delta/agonists/metabolism MH - Male MH - *PPAR alpha/agonists/metabolism MH - *PPAR gamma/agonists/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Insulin/metabolism MH - Humans MH - Blood Glucose/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Butyrates/pharmacology/therapeutic use MH - Female MH - Glucagon-Like Peptide 1/metabolism MH - Body Weight/drug effects MH - Weight Loss/drug effects MH - Mice, Inbred C57BL MH - Insulin Resistance MH - Receptors, Gastrointestinal Hormone PMC - PMC13190304 COIS- Competing interests: M.H.T. is a member of the scientific advisory board of ERX Pharmaceuticals, was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019, attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, in 2016, received funding for research projects from Novo Nordisk (2016-2020) and Sanofi-Aventis (2012-2019), and was a consultant for Bionorica SE (2013-2017), Menarini Ricerche S.p.A. (2016) and Bayer Pharma AG Berlin (2016). As former director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum Munchen (2011-2018), and since 2018, as CEO of Helmholtz Zentrum Munchen, M.H.T. has been responsible for collaborations with a multitude of companies and institutions worldwide. In this capacity, M.H.T. discussed potential projects with and has signed/signs contracts for his institute(s) and for the staff for research funding and/or collaborations with industry and academia worldwide, including but not limited to pharmaceutical corporations such as Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medigene, Arbormed, BioSyngen and others. In this role, M.H.T. was/is further responsible for commercial technology transfer activities of the institute(s), including diabetes related patent portfolios of Helmholtz Zentrum Munchen such as WO/2016/188932 A2 or WO/2017/194499 A1. M.H.T. confirms that to the best of his knowledge none of the above funding sources were involved in the preparation of this paper. T.D.M. holds stock from Eli Lilly and receives research funding from Novo Nordisk. T.D.M. has further received speaking fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Merck, AstraZeneca and Mercodia. J.E.C. received funding from Novo Nordisk, Eli Lilly, Merck, Structure Therapeutics and Prostasis. J.E.C. has served as an advisor/consultant in the past 12 months to Arrowhead Therapeutics, Boehringer Ingelheim, Neurocrine Biosciences, Prostasis, Protagonist and Structure Therapeutics. R.D.D. is a co-inventor on intellectual property owned by Indiana University and licensed to Novo Nordisk. R.D.D., B.F., J.D.D., S.A.M. and P.J.K. were previously employed by Novo Nordisk. J.D.D., S.A.M. and P.J.K. receive research funding from Eli Lilly and are co-founders and shareholders in Volari Therapeutics, both unrelated to this work. P.T.P. received speaker honoraria from Novo Nordisk. B.F. is a current employee of Eli Lilly. R.J.S. has received research support from Novo Nordisk, Fractyl, AstraZeneca, Congruence Therapeutics, Eli Lilly, Bullfrog AI, Glyscend Therapeutics and Amgen. R.J.S. has served as a paid consultant for Novo Nordisk, Eli Lilly, CinRx, Fractyl, Structure Therapeutics, Crinetics, Amgen, Congruence Therapeutics and Nuanced Health. R.J.S. has equity in Nuanced Health, Coro Bio. Fractyl and Rewind. The other authors declare no competing interests. EDAT- 2026/04/30 00:31 MHDA- 2026/05/21 06:32 PMCR- 2026/04/29 CRDT- 2026/04/29 23:30 PHST- 2025/04/19 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/05/21 06:32 [medline] PHST- 2026/04/30 00:31 [pubmed] PHST- 2026/04/29 23:30 [entrez] PHST- 2026/04/29 00:00 [pmc-release] AID - 10.1038/s41586-026-10427-5 [pii] AID - 10427 [pii] AID - 10.1038/s41586-026-10427-5 [doi] PST - ppublish SO - Nature. 2026 May;653(8115):776-785. doi: 10.1038/s41586-026-10427-5. Epub 2026 Apr 29. PMID- 42054048 OWN - NLM STAT- MEDLINE DCOM- 20260617 LR - 20260930 IS - 2168-6084 (Electronic) IS - 2168-6068 (Linking) VI - 162 IP - 6 DP - 2026 Jun 1 TI - The National Psoriasis Foundation Primer on GLP-1 Receptor Agonists in Psoriasis: A Review. PG - 619-630 LID - 10.1001/jamadermatol.2026.0859 [doi] AB - IMPORTANCE: Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis-conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1-based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment. OBSERVATIONS: GLP-1 RAs have been associated with reductions in Psoriasis Area and Severity Index (PASI) scores, particularly in patients with obesity or type 2 diabetes. Studies report relative PASI reductions ranging from approximately 40% to 80% with parallel quality-of-life gains, although most of these studies are small (7-48 patients), short term (/= 1 obesity-related comorbidity were included. Patients on semaglutide 2.4 mg for >/= 12 months were compared with non-users (including users of other obesity medications) using propensity score weighting with residual imbalances adjusted in regression model. Outcomes included time to onset of cardiometabolic comorbidities, change in cardiometabolic biomarkers and changes in 10-year ASCVD risk score at 12 months. RESULTS: 25 783 semaglutide 2.4 mg users and 8 948 913 non-users were identified. Semaglutide 2.4 mg was associated with significantly lower risks for incident prediabetes or type 2 diabetes, type 2 diabetes only, hypertension, ASCVD, heart failure and CVD (HRs 0.45-0.75; all p < 0.05), as well as greater improvements in BMI (-4.1 kg/m(2)), SBP (-6.2 mmHg), HbA1c (-0.4%), LDL cholesterol (-7.7 mg/dL), triglycerides (-28.6 mg/dL) and HDL cholesterol (+1.9 mg/dL; all p < 0.001). At 12 months, semaglutide 2.4 mg users (N = 161) demonstrated a greater reduction in ASCVD risk score (-0.7% vs. +0.3%; between-group difference -1.0%, p < 0.001), with a decrease in the proportion at intermediate-high ASCVD risk (14.9%-9.3% vs. 17.7%-18.7%; OR 0.3 [95% CI: 0.1, 0.6], p < 0.001). CONCLUSIONS: Semaglutide 2.4 mg was associated with lower risk of multiple cardiometabolic comorbidities, favourable changes in biomarkers, and lower estimated ASCVD risk in this population. CI - (c) 2026 Novo Nordisk Inc. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ruseva, Aleksandrina AU - Ruseva A AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Michalak, Wojciech AU - Michalak W AUID- ORCID: 0000-0002-3390-0182 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Bassan, Matthew AU - Bassan M AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Du, Ella Xiaoyan AU - Du EX AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Fabricatore, Anthony AU - Fabricatore A AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Hartaigh, Briain O AU - Hartaigh BO AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Man, Theo AU - Man T AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Ramasubramanian, Ramya AU - Ramasubramanian R AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Shen, Pangsibo AU - Shen P AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Lopez-Jimenez, Francisco AU - Lopez-Jimenez F AD - Mayo Clinic, Rochester, Minnesota, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article DEP - 20260427 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Comorbidity MH - *Diabetes Mellitus, Type 2/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Obesity/blood/drug therapy/epidemiology MH - Retrospective Studies MH - *Semaglutide MH - United States/epidemiology PMC - PMC13243985 OTO - NOTNLM OT - biomarkers OT - cardiometabolic comorbidities OT - cardiovascular risk OT - obesity OT - overweight OT - semaglutide COIS- Aleksandrina Ruseva, Zhenxiang Zhao, Anthony Fabricatore, Wojciech Michalak, Briain O. Hartaigh and Matthew Bassan are employees of Novo Nordisk Inc. and hold stock/options. Jinlin Song, Ella Xiaoyan Du, Ramya Ramasubramanian, Pangsibo Shen and Theo Man are employees of Analysis Group Inc., which has received consulting fees from Novo Nordisk Inc. for this study. Francisco Lopez-Jimenez has received consulting honoraria from Novo Nordisk Inc. EDAT- 2026/04/28 06:34 MHDA- 2026/06/12 06:38 PMCR- 2026/06/08 CRDT- 2026/04/28 00:23 PHST- 2026/03/27 00:00 [revised] PHST- 2025/12/22 00:00 [received] PHST- 2026/03/28 00:00 [accepted] PHST- 2026/06/12 06:38 [medline] PHST- 2026/04/28 06:34 [pubmed] PHST- 2026/04/28 00:23 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70746 [pii] AID - 10.1111/dom.70746 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):6121-6130. doi: 10.1111/dom.70746. Epub 2026 Apr 27. PMID- 42044422 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260716 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 32 IP - 4 DP - 2026 Apr TI - Medication use for patients with obesity: trends and characteristics for US employees. PG - 238-244 LID - 10.37765/ajmc.2026.89920 [doi] AB - OBJECTIVES: Obesity has a US prevalence of more than 40% and is associated with many comorbid conditions, posing a significant burden on employers. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recently available and effective weight loss agents. We examined characteristics and outcomes of employees with obesity and those using vs not using GLP-1 RAs. STUDY DESIGN: Retrospective analysis of employee patients in Workpartners Research Reference Database from 2016 to 2023. METHODS: Employees with obesity claims were identified and assigned to annual cohorts based on first year of obesity diagnosis (index). Study employees had at least 1 year of continuous data following their index diagnosis. Annual employee characteristics, comorbidities, absences, disability claims, and direct cost trends were explored for the year following diagnosis. Employees with obesity using and not using GLP-1 RAs were compared on the same metrics. Costs were inflation adjusted to December 2023 US$. RESULTS: We identified 127,408 employees with obesity. Obesity prevalence increased during the study. Employees with obesity and type 2 diabetes decreased slightly, and other comorbidities were relatively stable during the time frame. Overall, 5.8% of employees with obesity (n = 7359) used a GLP-1 RA. GLP-1 RA use increased annually (3.6% in 2016 to 18.3% in 2023) and accounted for approximately 30% of the cohort's 2023 pharmacy costs. During the 12-month study period, compared with non-GLP-1 RA users, those using GLP-1 RAs had higher Charlson Comorbidity Index scores (difference = 0.71), higher proportions with all study comorbidities, $11,360 higher direct all-category costs (total medical costs were $12,092 [19.4%] higher), and 0.86 more absence days. CONCLUSIONS: Prevalence of obesity is increasing, and use of GLP-1 RAs as the preferred antiobesity medication has increased as well. The long-term impact of this increased use warrants monitoring and management. FAU - Good, Chester B AU - Good CB AD - Insurance Services Division, UPMC Health Plan, Pittsburgh, PA. FAU - Beren, Ian A AU - Beren IA AD - Workpartners, LLC, Loveland, CO. FAU - Rosenberg, Eric M AU - Rosenberg EM AD - Workpartners, LLC, Pittsburgh, PA. FAU - Peasah, Samuel K AU - Peasah SK AD - Center for High-Value Health Care, UPMC Health Plan, Pittsburgh, PA. FAU - Brook, Richard A AU - Brook RA AD - Better Health Worldwide, Inc, 18 Hirth Dr, Newfoundland, NJ 07435-1710. Email: rich@bh-ww.com. LA - eng PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Obesity/drug therapy/epidemiology/economics MH - Female MH - Retrospective Studies MH - United States/epidemiology MH - Male MH - Middle Aged MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - Prevalence MH - *Anti-Obesity Agents/therapeutic use/economics MH - Comorbidity EDAT- 2026/04/27 18:34 MHDA- 2026/04/27 18:35 CRDT- 2026/04/27 15:54 PHST- 2026/04/27 18:35 [medline] PHST- 2026/04/27 18:34 [pubmed] PHST- 2026/04/27 15:54 [entrez] AID - 89920 [pii] AID - 10.37765/ajmc.2026.89920 [doi] PST - ppublish SO - Am J Manag Care. 2026 Apr;32(4):238-244. doi: 10.37765/ajmc.2026.89920. PMID- 42043919 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260921 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 5 DP - 2026 May TI - State-level variation in the use of glucagon-like peptide-1 receptor agonists for weight loss and diabetes: a real-world analysis. PG - 625-630 LID - 10.18553/jmcp.2026.32.5.625 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated clinical benefits beyond glycemic control, including weight loss and cardiovascular protection. Given the growing interest in the clinical value of GLP-1 RAs, greater understanding of geographic variation in utilization by disease prevalence and the influence of state-level coverage policies is desirable. OBJECTIVE: To assess (1) state-level utilization of GLP-1 RAs by indication for diabetes and obesity, (2) correlation of those rates to the state-level prevalence of diabetes and obesity, and (3) state-specific Medicaid formulary coverage of GLP-1 RAs for weight loss and diabetes. METHODS: We conducted a cross-sectional analysis of pharmacy claims from the Komodo Healthcare Map between January 1 and December 31, 2023. GLP-1 RA utilization was defined as the prevalence of members with GLP-1 RA claims for US Food and Drug Administration-approved indications for diabetes or obesity. State-level diabetes and obesity prevalence were obtained from the 2022-2023 Behavioral Risk Factor Surveillance System. Medicaid coverage for GLP-1 RAs was categorized as "not covered," "restricted," or "unrestricted." Pearson correlation coefficients were calculated to assess relationships between state-level disease prevalence and GLP-1 RA utilization. RESULTS: State-level utilization of GLP-1 RAs for diabetes was strongly correlated with diabetes prevalence in the commercially insured population, but correlation was moderate with those with Medicare and weak with the Medicaid population. For obesity, utilization showed only weak or negligible correlations with obesity prevalence. Medicaid coverage policies influenced access where utilization in states with "restricted" or "unrestricted" coverage was nominally higher than in states with "not covered" policies. CONCLUSIONS: GLP-1 RA utilization in the United States varies substantially by payer type, indication, and state-level coverage policies. FAU - Do, Steven AU - Do S AD - Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, PA. FAU - Christensen, Kathryn AU - Christensen K AD - Evernorth Research Institute, St. Louis, MO. FAU - Inneh, Angela AU - Inneh A AD - Evernorth Research Institute, St. Louis, MO. FAU - Peasah, Samuel AU - Peasah S AD - Center for Value-Based Pharmacy Initiatives, University of Pittsburgh Medical Center Health Plan, PA. FAU - Good, Chester AU - Good C AD - Center for Value-Based Pharmacy Initiatives, University of Pittsburgh Medical Center Health Plan, PA. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - United States/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cross-Sectional Studies MH - Medicaid/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use/economics MH - *Obesity/drug therapy/epidemiology MH - *Weight Loss/drug effects MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Prevalence MH - *Diabetes Mellitus/drug therapy/epidemiology MH - Middle Aged PMC - PMC13119483 EDAT- 2026/04/27 18:34 MHDA- 2026/04/27 18:35 PMCR- 2026/05/01 CRDT- 2026/04/27 12:33 PHST- 2026/04/27 18:35 [medline] PHST- 2026/04/27 18:34 [pubmed] PHST- 2026/04/27 12:33 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.5.625 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 May;32(5):625-630. doi: 10.18553/jmcp.2026.32.5.625. PMID- 42037563 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 2309-4990 (Electronic) IS - 1022-5536 (Linking) VI - 34 IP - 1 DP - 2026 Jan-Apr TI - Protective effects of SGLT2 inhibitors and GLP-1 receptor agonists on infection-related implant failure following ankle fracture ORIF: A global big data analysis. PG - 10225536261447739 LID - 10.1177/10225536261447739 [doi] AB - BackgroundPatients with type 2 diabetes (T2DM) undergoing ankle fracture open reduction and internal fixation (ORIF) face high risks of surgical site infection (SSI) and implant failure. This study evaluated whether preoperative use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improves these postoperative outcomes.MethodsUsing the TriNetX global database (2005-2025), we identified T2DM patients undergoing ankle fracture ORIF. Users of SGLT2is or GLP-1 RAs within 180 days before surgery were compared with non-users using 1:1 propensity score matching (PSM). The primary outcome was a 90-day composite of SSI or infection-related implant removal. Secondary outcomes included the 1-year composite and all-cause mortality.ResultsAfter PSM, 1289 users were compared with 1289 non-users. At 90 days, the composite infection-related outcome occurred in 1.45% of users versus 6.26% of non-users (HR 0.34, 95% CI 0.19-0.62; p < 0.001). At 1 year, the risk remained significantly lower in users (1.79% vs 11.92%; HR 0.42, 95% CI 0.25-0.72; p < 0.001). While 1-year mortality showed a downward trend in the primary cohort (HR 0.61, p = 0.1393), sensitivity analyses excluding dual-therapy users demonstrated a statistically significant survival advantage for single-agent users (HR 0.41, 95% CI 0.21-0.80; p = 0.007). Further analysis restricted to active users (30-day exposure) showed no observed instances of mortality or 1-year infection-related complications (both p < 0.001), although these findings should be interpreted cautiously given the small number of events.ConclusionsPreoperative use of SGLT2is or GLP-1 RAs was associated with a substantial reduction in infection-related implant failure and a lower risk of mortality, particularly when used as monotherapy or in closer proximity to surgery. These findings suggest that modern cardiometabolic agents may represent valuable components of preoperative optimization strategies in high-risk diabetic patients, although confirmation in prospective studies is warranted. FAU - Yang, Mao Yi AU - Yang MY AD - Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Hung, Li Wei AU - Hung LW AD - Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. LA - eng PT - Journal Article DEP - 20260427 PL - England TA - J Orthop Surg (Hong Kong) JT - Journal of orthopaedic surgery (Hong Kong) JID - 9440382 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Ankle Fractures/surgery/complications MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Fracture Fixation, Internal/adverse effects MH - Middle Aged MH - *Surgical Wound Infection/prevention & control/etiology MH - *Prosthesis Failure MH - Aged MH - Retrospective Studies MH - *Open Fracture Reduction MH - Adult OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - ankle fracture OT - open reduction internal fixation OT - surgical site infection OT - type 2 diabetes COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/04/27 12:34 MHDA- 2026/04/27 12:35 CRDT- 2026/04/27 06:12 PHST- 2026/04/27 12:35 [medline] PHST- 2026/04/27 12:34 [pubmed] PHST- 2026/04/27 06:12 [entrez] AID - 10.1177/10225536261447739 [doi] PST - ppublish SO - J Orthop Surg (Hong Kong). 2026 Jan-Apr;34(1):10225536261447739. doi: 10.1177/10225536261447739. Epub 2026 Apr 27. PMID- 42037117 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Dietary Strategies and Nutritional Management in Patients Receiving GLP-1 and Dual GIP/GLP-1 Receptor Agonists as Adjuncts to Lifestyle Interventions: A Systematic Review of Randomised Clinical Trials. PG - 5492-5507 LID - 10.1111/dom.70779 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 RAs are widely used to manage obesity, prediabetes and type 2 diabetes, typically in combination with lifestyle interventions. Their nutritional implications, however, remain unclear. This systematic review summarised evidence from randomised clinical trials investigating dietary strategies and nutritional management in individuals treated with these medications. METHODS: The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251181076). Searches were conducted in PubMed, Embase, Scopus and Web of Science. Eligible studies were randomised clinical trials evaluating adults receiving GLP-1 or dual GIP/GLP-1 agonists in conjunction with lifestyle or dietary guidance. Outcomes included gastrointestinal symptoms, muscle and bone health and nutritional adequacy. RESULTS: Sixteen trials involving 7096 participants were included. GLP-1 and dual agonists consistently increased gastrointestinal symptoms such as nausea, diarrhoea, constipation and vomiting. These effects were often dose-related and occurred despite background lifestyle or dietary interventions. Lean mass was generally preserved, with reductions proportional to overall weight loss. No study directly assessed bone health, and none reported clinically relevant nutritional deficiencies. Most trials presented a low risk of bias. CONCLUSION: GLP-1 and dual GIP/GLP-1 agonists frequently cause gastrointestinal discomfort but tend to preserve lean mass during weight loss when used alongside lifestyle interventions. Although dietary guidance is commonly provided, evidence on optimal nutritional approaches remains limited. Further trials are needed to clarify protein requirements, assess musculoskeletal outcomes and establish evidence-based dietary recommendations to support combined treatment strategies. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - de Paulo, Rayanne Santos AU - de Paulo RS AUID- ORCID: 0000-0002-0124-5179 AD - Department of Nutrition and Health, Universidade Federal de Vicosa, Vicosa, Brazil. FAU - Bonifacio, Dandara Baia AU - Bonifacio DB AD - Department of Nutrition and Health, Universidade Federal de Vicosa, Vicosa, Brazil. FAU - de Carvalho, Matheus Henrique Lana AU - de Carvalho MHL AD - Department of Nutrition and Health, Universidade Federal de Vicosa, Vicosa, Brazil. FAU - Bressan, Josefina AU - Bressan J AUID- ORCID: 0000-0002-4993-9436 AD - Department of Nutrition and Health, Universidade Federal de Vicosa, Vicosa, Brazil. LA - eng GR - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ PT - Journal Article PT - Systematic Review DEP - 20260427 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy/therapy MH - *Obesity/therapy/drug therapy/diet therapy MH - *Gastric Inhibitory Polypeptide/agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Life Style MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Prediabetic State/drug therapy/diet therapy MH - Glucagon-Like Peptide 1/agonists PMC - PMC13244000 OTO - NOTNLM OT - GIP/GLP-1 receptor agonists OT - diet OT - gastrointestinal symptoms OT - lean mass OT - nutrition OT - obesity OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/04/27 06:32 MHDA- 2026/06/12 06:38 PMCR- 2026/06/08 CRDT- 2026/04/27 03:23 PHST- 2026/03/30 00:00 [revised] PHST- 2026/02/01 00:00 [received] PHST- 2026/04/07 00:00 [accepted] PHST- 2026/06/12 06:38 [medline] PHST- 2026/04/27 06:32 [pubmed] PHST- 2026/04/27 03:23 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70779 [pii] AID - 10.1111/dom.70779 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5492-5507. doi: 10.1111/dom.70779. Epub 2026 Apr 27. PMID- 42036156 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1557-9859 (Electronic) IS - 0025-7125 (Linking) VI - 110 IP - 3 DP - 2026 May TI - Noninsulin Medications for Type 2 Diabetes. PG - 377-395 LID - S0025-7125(25)00194-4 [pii] LID - 10.1016/j.mcna.2025.12.006 [doi] AB - This article reviews the noninsulin medications to treat type 2 diabetes, including their mechanism of action, efficacy, safety, and clinical considerations. It highlights the shift in the treatment of diabetes from a glucose-centric to a patient-centered approach, with emphasis on the importance of choosing therapy based on the evidence to improve outcomes and prevent comorbidities. Major classes discussed include biguanides (metformin), insulin secretagogues (sulfonylureas, meglitinides), thiazolidinediones, alpha-glucosidase inhibitors, SGLT2 inhibitors, DPP4 inhibitors, GLP1 receptor agonists, dual GLP1/GIP receptor agonists, and amylin analogs. CI - Published by Elsevier Inc. FAU - Castro-Revoredo, Iris AU - Castro-Revoredo I AD - Division of General Medicine, Emory University School of Medicine, Faculty Office Building, Suite 486, 49 Jesse Hill Jr. Drive, Atlanta, GA 30303, USA. FAU - Webster, Sara C Markley AU - Webster SCM AD - Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, Atlanta, GA, USA; Endocrine Section, Joseph Maxwell Cleland Atlanta VA Healthcare System, 1670 Clairmont Rd, Decatur, GA 30030, USA. Electronic address: Sara.Markleywebster@va.gov. LA - eng PT - Journal Article PT - Review PL - United States TA - Med Clin North Am JT - The Medical clinics of North America JID - 2985236R RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Secretagogues) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biguanides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Insulin Secretagogues MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Metformin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Biguanides/therapeutic use OTO - NOTNLM OT - DPP4 inhibitor OT - GLP1 receptor agonist OT - Metformin OT - Non-insulin medications OT - SGLT2 inhibitor OT - Type 2 diabetes mellitus COIS- Disclosures The authors have nothing to disclose. EDAT- 2026/04/27 00:30 MHDA- 2026/04/27 00:31 CRDT- 2026/04/26 20:58 PHST- 2026/04/27 00:31 [medline] PHST- 2026/04/27 00:30 [pubmed] PHST- 2026/04/26 20:58 [entrez] AID - S0025-7125(25)00194-4 [pii] AID - 10.1016/j.mcna.2025.12.006 [doi] PST - ppublish SO - Med Clin North Am. 2026 May;110(3):377-395. doi: 10.1016/j.mcna.2025.12.006. PMID- 42035861 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20261004 IS - 1873-2402 (Electronic) IS - 0006-3223 (Linking) VI - 100 IP - 8 DP - 2026 Oct 15 TI - From the Discovery of GLP-1 to Today's Diabetes/Obesity Therapy and Beyond. PG - 805-813 LID - S0006-3223(26)01195-9 [pii] LID - 10.1016/j.biopsych.2026.04.010 [doi] AB - Glucagon-like peptide-1 (GLP-1) was discovered as an insulinotropic peptide from the gut during a search for candidates for the incretin effect. It was found to also inhibit glucagon secretion and is now considered an important regulator of glucose metabolism. In further investigations of its physiological effects, GLP-1 also inhibited gastrointestinal secretion and motility and inhibited appetite and food intake. Because of these effects, GLP-1 was eventually shown to be able to improve glucose control and beta cell function in patients with type 2 diabetes mellitus (T2DM) and was even associated with weight loss. Because of a very short half-life in the circulation due to renal clearance and enzymatic degradation, stable analogs were developed allowing long-term treatment. Analogs suitable for weekly administration proved highly effective in improving glycemic control in patients with T2DM, and the analogs showed efficacy with respect to weight loss. Moreover, in cardiovascular outcome trials, the agonists were protective against major cardiovascular events and showed renoprotection and neuroprotection. Several observational studies also indicated protection against psychiatric illnesses and dementia. Thus, GLP-1 receptor agonists seem to be an effective weapon against the obesity-associated cardiovascular-kidney-metabolic syndrome affecting millions of patients. CI - Copyright (c) 2026 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. FAU - Holst, Jens Juul AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260424 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/therapeutic use/metabolism/analogs & derivatives MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Appetite regulation OT - cardiovascular outcome trials OT - gut hormone OT - obesity OT - reward mechanisms OT - weight loss agents EDAT- 2026/04/27 00:30 MHDA- 2026/09/16 23:34 CRDT- 2026/04/26 19:12 PHST- 2026/01/20 00:00 [received] PHST- 2026/04/08 00:00 [revised] PHST- 2026/04/14 00:00 [accepted] PHST- 2026/09/16 23:34 [medline] PHST- 2026/04/27 00:30 [pubmed] PHST- 2026/04/26 19:12 [entrez] AID - S0006-3223(26)01195-9 [pii] AID - 10.1016/j.biopsych.2026.04.010 [doi] PST - ppublish SO - Biol Psychiatry. 2026 Oct 15;100(8):805-813. doi: 10.1016/j.biopsych.2026.04.010. Epub 2026 Apr 24. PMID- 42034831 OWN - NLM STAT- MEDLINE DCOM- 20260811 LR - 20260826 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 50 IP - 8 DP - 2026 Aug TI - GLP-1 agonists and changes in body mass and composition in adults with overweight or obesity with or without type 2 diabetes mellitus: a systematic review and meta-analysis. PG - 1603-1621 LID - 10.1038/s41366-026-02088-1 [doi] AB - BACKGROUND: The systematic review aimed to assess the effects of GLP-1 receptor agonists (GLP-1 RA) and dual GLP-1/GIP agonists on weight loss and body composition in individuals with overweight or obesity, with or without type 2 diabetes mellitus. METHODS: The study protocol was registered in PROSPERO (CRD420251002447). A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 2024 according to PRISMA guidelines. Following the predefined inclusion and exclusion criteria, 36 studies were included in this systematic review and underwent qualitative analysis. In addition, 24 studies met the criteria for quantitative synthesis (meta-analysis). Data were pooled using random-effects models with subgroup analyses by drug type and treatment duration (3, 6, and 12 months). RESULTS: GLP-1 RA treatment consistently reduced body weight, BMI, and waist circumference across all time points. At 3 months, mean body weight decreased by approximately 9%, accompanied by marked reductions in fat mass and visceral adipose tissue. At 6 months, weight reduction averaged 5%, with semaglutide, liraglutide, and exenatide showing comparable effects, while lean mass remained largely preserved. At 12 months, weight loss persisted at around 4%, with variability between agents, most notably liraglutide. Across studies, fat mass decline predominated, whereas reductions in lean body mass were modest. CONCLUSION: GLP-1 RAs provide clinically meaningful weight loss primarily through selective fat mass reduction, with relative preservation of lean tissue, supporting their role in achieving "quality" weight loss. Differences between agents highlight the importance of individualized treatment strategies, complemented by nutritional and exercise interventions to optimize long-term outcomes. CI - (c) 2026. The Author(s). FAU - Sawicka-Gutaj, Nadia AU - Sawicka-Gutaj N AUID- ORCID: 0000-0003-1510-4702 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Gruszczynski, Dawid AU - Gruszczynski D AUID- ORCID: 0000-0001-9519-4183 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. dawid.j.gruszczynski@gmail.com. AD - Doctoral School, Poznan University of Medical Sciences, Poznan, Poland. dawid.j.gruszczynski@gmail.com. FAU - Nijakowski, Kacper AU - Nijakowski K AUID- ORCID: 0000-0002-5042-5985 AD - Poznan University of Medical Sciences, Department of Conservative Dentistry, Poznan University of Medical Sciences, Poznan, Poland. FAU - Derwich-Rudowicz, Aleksandra AU - Derwich-Rudowicz A AUID- ORCID: 0000-0003-0413-2679 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Krenz, Michal AU - Krenz M AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Kumar, Anita AU - Kumar A AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Lu, Pei-Yin AU - Lu PY AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Ruchala, Marek AU - Ruchala M AUID- ORCID: 0000-0002-6296-7220 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260425 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy MH - *Body Composition/drug effects MH - Weight Loss/drug effects MH - Semaglutide MH - Liraglutide/therapeutic use MH - Body Mass Index MH - Hypoglycemic Agents/therapeutic use MH - Exenatide MH - Adult PMC - PMC13461353 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/04/26 05:13 MHDA- 2026/08/12 06:05 PMCR- 2026/04/25 CRDT- 2026/04/25 23:57 PHST- 2025/11/30 00:00 [received] PHST- 2026/04/04 00:00 [accepted] PHST- 2026/03/20 00:00 [revised] PHST- 2026/08/12 06:05 [medline] PHST- 2026/04/26 05:13 [pubmed] PHST- 2026/04/25 23:57 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - 10.1038/s41366-026-02088-1 [pii] AID - 2088 [pii] AID - 10.1038/s41366-026-02088-1 [doi] PST - ppublish SO - Int J Obes (Lond). 2026 Aug;50(8):1603-1621. doi: 10.1038/s41366-026-02088-1. Epub 2026 Apr 25. PMID- 42033296 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 1945-7243 (Electronic) IS - 0046-9580 (Print) IS - 0046-9580 (Linking) VI - 63 DP - 2026 Jan-Dec TI - Mapping Global Research on Adverse Effects of GLP-1 Receptor Agonists (2006-2025): A Scopus-Based Bibliometric and Thematic Analysis. PG - 469580261441498 LID - 10.1177/00469580261441498 [doi] LID - 00469580261441498 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for managing type 2 diabetes and obesity. As their clinical applications expand, interest in their safety and adverse effects has grown. This study provides a comprehensive bibliometric analysis of global research trends, collaboration patterns, and thematic evolution on GLP-1RA-related adverse effects from 2006 to 2025. This study is a bibliometric analysis. Data were extracted from the Scopus database and analyzed using Bibliometrix (R package) and VOS viewer. Indicators assessed included publication and citation metrics, institutional productivity, and keyword co-occurrence and mapping. Correlations were evaluated using Pearson and Spearman tests, and the Durbin-Watson statistic was applied to assess the independence of residuals. A total of 1075 articles published in 389 journals were identified, authored by 6068 researchers across 85 countries. The annual growth rate was 32.06%, with no single-author papers and 34.23% international co-authorship, indicating strong global collaboration. The United States (30.5%), the United Kingdom (10.6%), and Denmark (7.8%) led in publication output and total citations. Institutional analysis identified Novo Nordisk A/S (60 papers, 11 207 citations) and Eli Lilly & Co. (45 papers, 9948 citations) as the most influential contributors. Diabetes, Obesity and Metabolism published the most articles (n = 106), followed by Diabetes Care and The Lancet Diabetes & Endocrinology. Significant correlations were found between article count and h-index (r = .677, P < .001) and total citations (r = .779, P < .001). Keyword analysis revealed 2 main thematic clusters-one pharmacological (drug safety, efficacy, liraglutide, semaglutide) and 1 clinical (human, male, female, adult)-with an emerging focus on population-specific safety since 2021. Research on GLP-1RA-related adverse effects has expanded rapidly, shaped by strong international collaboration and industry-academic partnerships. Future efforts should prioritize balanced global participation, real-world safety data, and mechanistic insights to inform clinical practice and pharmacovigilance. FAU - Abdelrahman, Riad Mohammed AU - Abdelrahman RM AUID- ORCID: 0000-0002-1157-2739 AD - National University of Sudan, Khartoum, Sudan. AD - National Ribat University, Khartoum, Sudan. FAU - Musa, Taha Hussein AU - Musa TH AD - Libyan International Medical University, Benghazi, Libya. AD - Darfur University College, Nyala, Sudan. FAU - Arbab, Ismail Adam AU - Arbab IA AD - Libyan International Medical University, Benghazi, Libya. FAU - Ahmed, Eltieb Omer AU - Ahmed EO AD - International University of Africa, Khartoum, Sudan. FAU - Gasmallah, Sahar Ibrahim AU - Gasmallah SI AD - University of Bahri, Khartoum, Sudan. FAU - Jalal, Mohammed AU - Jalal M AD - Karary University, Khartoum, Sudan. FAU - Ahmed, Wafaa Ramadan AU - Ahmed WR AD - Libyan International Medical University, Benghazi, Libya. AD - Assiut University, Egypt. FAU - Fadul, Khalid Hamid AU - Fadul KH AD - International University of Africa, Khartoum, Sudan. AD - Sudan Medical Specialization Board, Khartoum, Sudan. LA - eng PT - Journal Article DEP - 20260425 PL - United States TA - Inquiry JT - Inquiry : a journal of medical care organization, provision and financing JID - 0171671 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Bibliometrics MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy PMC - PMC13129305 OTO - NOTNLM OT - GLP-1ras OT - adverse drug reactions OT - bibliometric analysis OT - citation network analysis OT - glucagon-like peptide-1 receptor agonists OT - pharmacovigilance OT - type 2 diabetes mellitus COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/04/26 05:10 MHDA- 2026/04/26 05:11 PMCR- 2026/04/25 CRDT- 2026/04/25 08:13 PHST- 2026/04/26 05:11 [medline] PHST- 2026/04/26 05:10 [pubmed] PHST- 2026/04/25 08:13 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - 10.1177_00469580261441498 [pii] AID - 10.1177/00469580261441498 [doi] PST - ppublish SO - Inquiry. 2026 Jan-Dec;63:469580261441498. doi: 10.1177/00469580261441498. Epub 2026 Apr 25. PMID- 42028610 OWN - NLM STAT- MEDLINE DCOM- 20260818 LR - 20260921 IS - 2574-8300 (Electronic) IS - 2574-8300 (Linking) VI - 19 IP - 4 DP - 2026 Aug TI - Long-Term Efficacy and Safety of GLP-1R Agonist and SGLT2 Inhibitor Therapy in the General Population: A Mendelian Randomization Study. PG - e005535 LID - 10.1161/CIRCGEN.125.005535 [doi] AB - BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors and GLP-1R (glucagon-like peptide-1 receptor) agonists reduce the risk of major adverse cardiovascular and kidney events in individuals with various cardiometabolic conditions. The long-term efficacy and safety of these therapies, especially in low- and moderate-risk populations, remain uncertain. METHODS: We conducted a biobank-scale analysis using genetic instruments derived from naturally occurring genetic variations in the genes encoding the targets of SGLT2 inhibitors (SLC5A2) and GLP-1R agonists (GLP1R) that are associated with glycated hemoglobin levels. This Mendelian randomization study utilized data from the All of Us Research Program, which includes whole genome sequencing and electronic health records of 633 547 participants. RESULTS: Higher SGLT2 inhibitor genetic instrument scores were associated with a lower risk of heart failure (odds ratio [OR], 0.97 [95% CI, 0.96-0.99]) and chronic kidney disease (OR, 0.98 [95% CI, 0.96-0.99]). Higher GLP-1R agonist genetic instrument scores were linked to reduced risks of heart failure (OR, 0.97 [95% CI, 0.96-0.99]), chronic kidney disease (OR, 0.96 [95% CI, 0.95-0.98]), and coronary artery disease (OR, 0.98 [95% CI, 0.96-0.99]). We did not detect associations between the GLP-1R agonist instrument and multiple endocrine neoplasia or medullary thyroid carcinoma. PheWAS (Phenome-Wide Association Study) identified associations between the SGLT2 inhibitor and GLP-1R agonist genetic instruments and a lower risk of diabetes, but no other phenotypes. CONCLUSIONS: This study demonstrates the utility of biobank-scale health data for pharmacology research and suggests that, if feasible to implement in routine practice, long-term, primary prevention with an SGLT2 inhibitor or GLP-1R agonist would safely lower the risk of major adverse cardiovascular and kidney events in low- to moderate-risk adults. FAU - Remala, Subbaramireddy AU - Remala S AUID- ORCID: 0009-0007-3942-1135 AD - Translational Cardiovascular Epidemiology Research Unit, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.R., A.M.S., L.F.B.). FAU - Liang, Liming AU - Liang L AUID- ORCID: 0000-0001-8261-3174 AD - Department of Epidemiology, TH Chan School of Public Health, Harvard University, Boston, MA (L.L.). FAU - Shah, Amil M AU - Shah AM AUID- ORCID: 0000-0003-1056-4451 AD - Translational Cardiovascular Epidemiology Research Unit, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.R., A.M.S., L.F.B.). FAU - Buckley, Leo F AU - Buckley LF AUID- ORCID: 0000-0003-1570-1486 AD - Translational Cardiovascular Epidemiology Research Unit, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.R., A.M.S., L.F.B.). LA - eng GR - K23 HL150311/HL/NHLBI NIH HHS/United States GR - K24 HL152008/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20260424 PL - United States TA - Circ Genom Precis Med JT - Circulation. Genomic and precision medicine JID - 101714113 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (SLC5A2 protein, human) RN - 0 (Sodium-Glucose Transporter 2) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mendelian Randomization Analysis MH - Glucagon-Like Peptide-1 Receptor/genetics MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - Male MH - Sodium-Glucose Transporter 2 PMC - PMC13120722 MID - NIHMS2164295 OTO - NOTNLM OT - glucagon-like peptide-1 receptor OT - heart failure OT - pharmacogenomic testing OT - primary prevention OT - sodium-glucose transporter 2 inhibitors COIS- Dr Buckley declares speakers fees from ASHP Advantage related to SGLT2 (sodium-glucose cotransporter-2) inhibitor use and consulting fees from scPharmaceuticals. The other authors report no conflicts. EDAT- 2026/04/24 06:33 MHDA- 2026/08/18 17:37 PMCR- 2026/04/28 CRDT- 2026/04/24 05:03 PHST- 2026/08/18 17:37 [medline] PHST- 2026/04/24 06:33 [pubmed] PHST- 2026/04/24 05:03 [entrez] PHST- 2026/04/28 00:00 [pmc-release] AID - 10.1161/CIRCGEN.125.005535 [doi] PST - ppublish SO - Circ Genom Precis Med. 2026 Aug;19(4):e005535. doi: 10.1161/CIRCGEN.125.005535. Epub 2026 Apr 24. PMID- 42025665 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260820 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 288 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients With Type 2 Diabetes and Diabetic Retinopathy. PG - 131-142 LID - S0002-9394(26)00219-9 [pii] LID - 10.1016/j.ajo.2026.04.021 [doi] AB - PURPOSE: To evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) use on macrovascular and microvascular outcomes in patients with type 2 diabetes (T2D) and diabetic retinopathy (DR)-a high-risk group often excluded from clinical trials. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Adults aged >/=18 years with T2D (with hemoglobin A1c of >/=6.5%) and a pre-existing diagnosis of DR from the TriNetX research network database between January 1, 2015, and December 31, 2022. METHODS: The study included 173,216 adults with T2D, all of whom had DR, adjusted for baseline characteristics through propensity score matching (PSM) based on whether the individuals received at least 2 prescriptions of a GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide, or lixisenatide) at least 6 months apart. MAIN OUTCOME MEASURES: Cox proportional hazard regression models were used to evaluate the association between GLP-1 RAs and the risk of incident macrovascular and microvascular complications over a 2-year follow-up period. RESULTS: After PSM, 30,613 individuals (mean [SD] age, 61.6 [11.4] years; 53.2% were females) were prescribed GLP-1 RAs. Patients on GLP-1 RAs had a decreased risk of myocardial infarctions (MIs; hazard ratio [HR], 0.65; 95% CI, 0.61-0.69), coronary artery revascularization procedures (HR, 0.75; 95% CI, 0.67-0.84), heart failure exacerbations (HR, 0.78; 95% CI, 0.76-0.81), ischemic strokes (HR, 0.78; 95% CI, 0.74-0.83), lower extremity amputations (HR, 0.78; 95% CI, 0.69-0.88), acute kidney injuries (AKI; HR, 0.68; 95% CI, 0.66-0.71), or the need for renal replacement therapy (RRT; HR, 0.40; 95% CI, 0.36-0.43). Fewer individuals also progressed to proliferative diabetic retinopathy (HR, 0.78; 95% CI, 0.71-0.86), experienced retinal vein occlusions (RVOs; HR, 0.70; 95% CI, 0.61-0.80), or developed neovascular glaucoma (HR, 0.65; 95% CI, 0.47-0.89); no association was observed for retinal artery occlusions (RAOs; HR, 0.85; 95% CI, 0.57-1.26) or cases of non-arteritic ischemic optic neuropathy (NAION; HR, 0.88; 95% CI, 0.54-1.44). CONCLUSIONS: In patients with T2D and pre-existing DR, the use of GLP-1 RAs was associated with a reduced risk of major macrovascular and microvascular complications, including those directly affecting the retina. Future studies are needed to assess the extent to which GLP-1 RAs benefit long-term outcomes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Shah, Jui AU - Shah J AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Makwana, Bhargav AU - Makwana B AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Panchal, Krisha AU - Panchal K AD - Division of Ophthalmology (K.P., D.J.R.), Department of Surgery, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Patel, Vahin AU - Patel V AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Patel, Tirth AU - Patel T AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Khadke, Sumanth AU - Khadke S AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Verma, Anushka AU - Verma A AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Vivekanandan, Suja AU - Vivekanandan S AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Kong, Yixin AU - Kong Y AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Upadhyay, Jagriti AU - Upadhyay J AD - Division of Endocrinology (J.U.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Dani, Sourbha S AU - Dani SS AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Ramsey, Kathryn Moynihan AU - Ramsey KM AD - Department of Medicine (K.M.R.), Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Ganatra, Sarju AU - Ganatra S AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Ramsey, David J AU - Ramsey DJ AD - Division of Ophthalmology (K.P., D.J.R.), Department of Surgery, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA; Department of Ophthalmology (D.J.R.), Tufts University School of Medicine, Boston, Massachusetts, USA. Electronic address: David.J.Ramsey@lahey.org. LA - eng PT - Journal Article DEP - 20260421 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 839I73S42A (Liraglutide) RN - 0 (hemoglobin A1c protein, human) RN - 74O62BB01U (lixisenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/drug therapy/diagnosis MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide/therapeutic use MH - Semaglutide MH - Glycated Hemoglobin/metabolism MH - Aged MH - Risk Factors MH - Exenatide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Blood Glucose/metabolism MH - Incidence MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Liraglutide/therapeutic use MH - Proportional Hazards Models MH - *Diabetic Angiopathies/epidemiology MH - Glucagon-Like Peptide 1/analogs & derivatives EDAT- 2026/04/24 00:32 MHDA- 2026/07/08 18:50 CRDT- 2026/04/23 22:42 PHST- 2025/08/11 00:00 [received] PHST- 2026/02/26 00:00 [revised] PHST- 2026/04/19 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2026/04/24 00:32 [pubmed] PHST- 2026/04/23 22:42 [entrez] AID - S0002-9394(26)00219-9 [pii] AID - 10.1016/j.ajo.2026.04.021 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Aug;288:131-142. doi: 10.1016/j.ajo.2026.04.021. Epub 2026 Apr 21. PMID- 42023428 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Efficacy, Safety and PK of Once-Daily Oral Semaglutide 25 mg for Obesity With and Without Type 2 Diabetes in Comparison With Subcutaneous Semaglutide 2.4 mg: A Model-Informed Drug Development Approach. PG - 5982-5991 LID - 10.1111/dom.70769 [doi] AB - AIMS: Semaglutide has previously been approved for weight management and cardiovascular disease as a subcutaneous formulation, and more recently also as an oral formulation. However, there is limited information across oral dose levels, and there are no studies for the 25 mg dose in people with obesity and type 2 diabetes (T2D). To fulfil health authority approval requirements, population pharmacokinetic and exposure-response analyses were used to extrapolate efficacy and safety data from subcutaneous to oral semaglutide. MATERIALS AND METHODS: Once-daily oral semaglutide 25 mg was approved for obesity treatment based on historical semaglutide data and the OASIS programme. Two studies were simulated: a modelled/virtual Phase 2 trial to establish efficacy across different oral semaglutide dose levels, and a modelled/virtual Phase 3 trial to assess efficacy in a population with overweight/obesity and T2D. RESULTS: Most participants (82.2%) treated with oral semaglutide 25 mg in OASIS 4 achieved exposure levels within the same range as participants treated with once-weekly subcutaneous semaglutide 2.4 mg in STEP 1. In the simulated studies, oral semaglutide 25 mg provided significantly greater weight reduction compared with placebo, for the trial product estimand and treatment policy estimand, respectively, in those with overweight/obesity and T2D (9.4% and 7.8%), and in those with overweight/obesity without T2D (16.3% and 14.7%). CONCLUSIONS: Estimated exposure levels and efficacy observed with oral semaglutide 25 mg were similar to those obtained with subcutaneous semaglutide 2.4 mg, supporting application of oral semaglutide 25 mg to treat individuals with overweight/obesity, with/without T2D. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Overgaard, Rune Viig AU - Overgaard RV AUID- ORCID: 0000-0001-7095-4270 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkhan, Oscar AU - Birkhan O AUID- ORCID: 0000-0002-7554-5035 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rathor, Naveen AU - Rathor N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sparso, Thomas AU - Sparso T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Strathe, Anders AU - Strathe A AUID- ORCID: 0000-0002-1598-2591 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - University of Toronto, York University, McMaster University, Wharton Weight Management Clinic, Burlington, Ontario, Canada. FAU - Rubino, Domenica AU - Rubino D AD - Washington Center for Weight Management and Research, Arlington, Virginia, USA. LA - eng GR - Novo Nordisk A/S/ PT - Comparative Study PT - Journal Article DEP - 20260423 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Anti-Obesity Agents/administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Administration Schedule MH - Drug Development MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/adverse effects MH - Injections, Subcutaneous MH - *Obesity/drug therapy/complications MH - *Semaglutide/administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects PMC - PMC13243942 OTO - NOTNLM OT - GLP-1 analogue OT - pharmacokinetics OT - semaglutide OT - type 2 diabetes OT - weight management COIS- Domenica Rubino has received grants/contracts from Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Tern Pharmaceuticals; has held consultancy roles at AbbVie, AstraZeneca, Boehringer Ingelheim, Cytoki Pharma, Eli Lilly, Neuraly, Neurocrine Biosciences, NodThera, Novo Nordisk, Pfizer, Regeneron Pharmaceuticals, Roche, Shionogi and Summit Clinical Trial Networks; and is a shareholder of AbbVie. Sean Wharton has participated in advisory boards for or received honoraria from AbbVie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Merck, Metsera, NGX, Novo Nordisk and Regeneron Pharmaceuticals; conducted clinical trials/research for Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Pfizer; has held academic or other roles at McMaster University, York University, University of Toronto and Obesity Canada. Rune Viig Overgaard, Oscar Birkhan, Naveen Rathor, Thomas Sparso and Anders Strathe are employees and shareholders at Novo Nordisk A/S. EDAT- 2026/04/23 06:31 MHDA- 2026/06/12 06:39 PMCR- 2026/06/08 CRDT- 2026/04/23 05:22 PHST- 2026/04/01 00:00 [revised] PHST- 2026/01/15 00:00 [received] PHST- 2026/04/03 00:00 [accepted] PHST- 2026/06/12 06:39 [medline] PHST- 2026/04/23 06:31 [pubmed] PHST- 2026/04/23 05:22 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70769 [pii] AID - 10.1111/dom.70769 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5982-5991. doi: 10.1111/dom.70769. Epub 2026 Apr 23. PMID- 42021007 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260806 IS - 1538-8662 (Electronic) IS - 0361-1817 (Linking) VI - 51 IP - 5 DP - 2026 May 1 TI - GLP-1 receptor agonists: The good, the bad, and the ugly-A comprehensive guide for NPs. PG - 22-30 LID - 10.1097/01.NPR.0000000000000430 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in primary care for diabetes, obesity, and other conditions, offering glycemic control, weight loss, and cardioprotection. This article explores the indications, benefits, risks, and prescribing considerations of GLP-1RAs for nurse practitioners (NPs). Although effective, GLP-1RAs present challenges, including gastrointestinal side effects, accessibility issues, and serious risks like pancreatitis. NPs play a key role in patient education, monitoring, and advocacy to ensure equitable access and safe prescribing. Emerging research suggests expanded indications for cardiovascular, hepatic, and neurocognitive benefits. This review provides a comprehensive guide for NPs to optimize GLP-1RA therapy in clinical practice. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Rodriguez, Megan E AU - Rodriguez ME FAU - Lavell, Julia AU - Lavell J FAU - Foreman, Ruth Madden AU - Foreman RM LA - eng PT - Journal Article PT - Review DEP - 20260423 PL - United States TA - Nurse Pract JT - The Nurse practitioner JID - 7603663 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/nursing MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Nurse Practitioners MH - Obesity/drug therapy MH - *Practice Guidelines as Topic OTO - NOTNLM OT - GLP-1 receptor agonists OT - accessibility OT - cardioprotection OT - chronic kidney disease OT - diabetes OT - obesity OT - obstructive sleep apnea EDAT- 2026/04/23 06:32 MHDA- 2026/04/23 06:33 CRDT- 2026/04/23 00:13 PHST- 2026/04/23 06:33 [medline] PHST- 2026/04/23 06:32 [pubmed] PHST- 2026/04/23 00:13 [entrez] AID - 00006205-202605000-00004 [pii] AID - 10.1097/01.NPR.0000000000000430 [doi] PST - ppublish SO - Nurse Pract. 2026 May 1;51(5):22-30. doi: 10.1097/01.NPR.0000000000000430. Epub 2026 Apr 23. PMID- 42020128 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 4 DP - 2026 Apr 22 TI - LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial. PG - e116911 LID - 10.1136/bmjopen-2026-116911 [doi] LID - e116911 AB - INTRODUCTION: Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy. METHODS AND ANALYSIS: This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers. ETHICS AND DISSEMINATION: The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT06885736. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Alawadhi, Ameenah A AU - Alawadhi AA AUID- ORCID: 0000-0003-4333-7319 AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alroudhan, Dherar AU - Alroudhan D AD - Education and Training Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alsaeed, Dalal J AU - Alsaeed DJ AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Almarshad, Bashayer W AU - Almarshad BW AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alshehabi, Dalal H AU - Alshehabi DH AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Allahou, Badreya A AU - Allahou BA AD - Nutrition Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Mashankar, Anant AU - Mashankar A AD - Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Al Ozairi, Ebaa AU - Al Ozairi E AD - Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait ebaa.alozairi@dasmaninstitute.org. FAU - Gray, Stuart AU - Gray S AUID- ORCID: 0000-0001-8969-9636 AD - Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. LA - eng SI - ClinicalTrials.gov/NCT06885736 PT - Clinical Trial Protocol PT - Journal Article DEP - 20260422 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Composition MH - Diabetes Mellitus, Type 2/complications MH - Kuwait MH - Muscle Strength MH - Muscle, Skeletal MH - *Obesity/therapy/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - *Resistance Training/methods MH - Sarcopenia/prevention & control MH - *Semaglutide/therapeutic use MH - *Tirzepatide/therapeutic use MH - Weight Loss PMC - PMC13110620 OTO - NOTNLM OT - DIABETES & ENDOCRINOLOGY OT - Exercise OT - NUTRITION & DIETETICS OT - Obesity OT - SPORTS MEDICINE COIS- Competing interests: None declared. EDAT- 2026/04/23 00:31 MHDA- 2026/04/23 00:32 PMCR- 2026/04/22 CRDT- 2026/04/22 21:13 PHST- 2026/04/23 00:32 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 21:13 [entrez] PHST- 2026/04/22 00:00 [pmc-release] AID - bmjopen-2026-116911 [pii] AID - 10.1136/bmjopen-2026-116911 [doi] PST - epublish SO - BMJ Open. 2026 Apr 22;16(4):e116911. doi: 10.1136/bmjopen-2026-116911. PMID- 42020116 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 14 IP - 2 DP - 2026 Apr 22 TI - Low uptake and disparities in therapeutic inertia of cardiorenal protective diabetes medications for patients with type 2 diabetes and above-target hemoglobin A1c. LID - 10.1136/bmjdrc-2025-005546 [doi] LID - e005546 AB - INTRODUCTION: Therapeutic inertia (failure to initiate or intensify therapy when therapeutic goals are unmet) contributes to poor glycemic control and diabetes-related complications. We assessed the extent of therapeutic inertia, defined as a lack of new prescription orders for sodium-glucose cotransporter-2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1RA), among patients with type 2 diabetes and above-target hemoglobin A1c who had clinical indications for use, were not currently using these medications, and had no contraindications. We also examined whether prescribing patterns differed by race and ethnicity. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort analysis of 2018-2022 electronic health record data. Log-link Poisson generalized estimating equation models estimated relative risks (RR) and assessed predictors of therapeutic inertia and trends over time. RESULTS: Among 10 345 eligible patients (30 740 encounters), 56% were White, 37% Black, 3% Hispanic, 2% Asian, and 2% other races and ethnicities. The rate of new prescribing increased over time but remained low (SGLT2i: 0.9%-4.3%; GLP-1RA: 1.2%-5.2%). After adjusting for sociodemographic, clinical, and service factors, Black patients were less likely than White patients to receive new SGLT2i (RR 0.59, 95% CI 0.42 to 0.82) and GLP-1RA (RR 0.62, 95% CI 0.49 to 0.79) prescriptions; Hispanic patients were less likely to receive new GLP-1RA prescriptions (RR 0.48, 95% CI 0.25 to 0.92). CONCLUSION: Despite compelling indications, initiation of SGLT2i and GLP-1RA remained low overall and was significantly lower among Black and Hispanic patients, underscoring therapeutic inertia as a modifiable barrier to optimal diabetes care. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - German, Jashalynn AU - German J AUID- ORCID: 0000-0002-8091-1941 AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA jashalynn.german@duke.edu. FAU - Huang, Wei Angel AU - Huang WA AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Brucker, Amanda AU - Brucker A AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Daniel, Khayla AU - Daniel K AD - Duke Health Integrated Practice, Duke Health, Durham, North Carolina, USA. FAU - Halpern, David AU - Halpern D AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. AD - Duke Primary Care, Duke University Medical Center, Durham, North Carolina, USA. FAU - Bhavsar, Nrupen AU - Bhavsar N AD - Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA. FAU - McPeek Hinz, Eugenia AU - McPeek Hinz E AD - Duke Health Technology Solutions, Duke University Health System Inc, Durham, North Carolina, USA. FAU - Shannon, Richard AU - Shannon R AD - Duke University Health System, Durham, North Carolina, USA. FAU - Pignone, Michael AU - Pignone M AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Crowley, Matthew J AU - Crowley MJ AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Batch, Bryan C AU - Batch BC AD - Medicine, Division of Endocrinology, Duke University, Durham, North Carolina, USA. FAU - Goldstein, Benjamin A AU - Goldstein BA AD - Duke University School of Medicine, Durham, North Carolina, USA. FAU - Spratt, Susan Elizabeth AU - Spratt SE AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. LA - eng PT - Journal Article DEP - 20260422 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Retrospective Studies MH - *Glycated Hemoglobin/analysis MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Middle Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Healthcare Disparities/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Follow-Up Studies MH - Undertreatment MH - Biomarkers/analysis MH - Prognosis PMC - PMC13110560 OTO - NOTNLM OT - Cardiovascular Agents OT - Diabetes Mellitus, Type 2 OT - Healthcare Disparities OT - Pharmacoepidemiology COIS- Competing interests: None declared. EDAT- 2026/04/23 00:31 MHDA- 2026/04/23 00:32 PMCR- 2026/04/22 CRDT- 2026/04/22 21:13 PHST- 2025/08/19 00:00 [received] PHST- 2026/04/04 00:00 [accepted] PHST- 2026/04/23 00:32 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 21:13 [entrez] PHST- 2026/04/22 00:00 [pmc-release] AID - 14/2/e005546 [pii] AID - bmjdrc-2025-005546 [pii] AID - 10.1136/bmjdrc-2025-005546 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2026 Apr 22;14(2):e005546. doi: 10.1136/bmjdrc-2025-005546. PMID- 42020100 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260617 IS - 1442-9071 (Electronic) IS - 1442-6404 (Linking) VI - 54 IP - 4 DP - 2026 May-Jun TI - Is There a Causal Link Between GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischaemic Optic Neuropathy? A Critique of the Clinical Evidence. PG - 554-564 LID - 10.1111/ceo.70096 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for managing Type 2 diabetes and obesity, with well-documented and significant cardiometabolic benefits. Recent observational reports and pharmacovigilance data have raised concerns about a possible association between GLP-1RAs-particularly semaglutide- and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare cause of sudden vision loss. While case reports and spontaneous reporting systems suggest a potential signal, these sources are subject to confounding and reporting bias. Observational studies offer mixed findings, with some Scandinavian registry studies reporting elevated risks while large electronic health record EHR) analyses from the U.S. and multi-national databases have reported null or weak associations. Meta-analyses of randomised controlled trials- the gold standard for causal inference- currently lack power to reliably assess this rare outcome but suggest, at most, a comparatively moderate increase in risk (e.g., odds ratio of 2-3). Overall while a causal link cannot be excluded, the numerous studies that assert an 'association' between GLP-1 RA exposure and NAION should motivate larger pooled analyses of RCTs with adjudicated ocular outcome to definitely assess risk. CI - (c) 2026 The Author(s). Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists. FAU - Danesh-Meyer, Helen V AU - Danesh-Meyer HV AD - Department of Ophthalmology, University of Auckland, Auckland, New Zealand. FAU - Rizzo, Joseph F 3rd AU - Rizzo JF 3rd AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article PT - Review DEP - 20260422 PL - Australia TA - Clin Exp Ophthalmol JT - Clinical & experimental ophthalmology JID - 100896531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - Risk Factors MH - Semaglutide EDAT- 2026/04/23 00:31 MHDA- 2026/06/10 11:44 CRDT- 2026/04/22 21:02 PHST- 2026/02/02 00:00 [revised] PHST- 2025/10/08 00:00 [received] PHST- 2026/02/06 00:00 [accepted] PHST- 2026/06/10 11:44 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 21:02 [entrez] AID - 10.1111/ceo.70096 [doi] PST - ppublish SO - Clin Exp Ophthalmol. 2026 May-Jun;54(4):554-564. doi: 10.1111/ceo.70096. Epub 2026 Apr 22. PMID- 42019817 OWN - NLM STAT- MEDLINE DCOM- 20261005 LR - 20261005 IS - 1916-7075 (Electronic) IS - 0828-282X (Linking) VI - 42 IP - 10 DP - 2026 Oct TI - Cardiovascular Outcomes With GLP-1 Receptor Agonists in Patients With Diabetes or Obesity Undergoing Transcatheter Aortic Valve Replacement. PG - 2299-2309 LID - S0828-282X(26)00358-2 [pii] LID - 10.1016/j.cjca.2026.04.003 [doi] AB - BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR) commonly have comorbid type 2 diabetes mellitus or obesity, both independently linked to adverse cardiovascular outcomes. Glucagon-like protein-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in these high-risk groups, but their utility in patients undergoing TAVR remains understudied. METHODS: We conducted a retrospective cohort study using the TriNetX database (2020-2025) to identify adults with type 2 diabetes mellitus or obesity undergoing TAVR. Patients were categorized as GLP-1 RA users or nonusers and matched using 1:1 propensity-score matching. The primary outcome was major adverse cardiovascular events (MACEs), defined as a composite of all-cause mortality, acute myocardial infarction, stroke, and heart failure exacerbation. Secondary outcomes included individual components and new-onset atrial fibrillation/flutter. RESULTS: After matching, 1708 patients were included in each cohort. GLP-1 RA users were associated with significantly lower risk of MACE (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.70, P < 0.001), all-cause mortality (HR 0.61, 95% CI 0.48-0.78, P < 0.001), acute myocardial infarction (HR 0.71, 95% CI 0.57-0.89, P = 0.002), stroke (HR 0.74, 95% CI 0.59-0.94, P = 0.011), heart failure exacerbation (HR 0.38, 95% CI 0.32-0.44, P < 0.001), and new-onset atrial fibrillation/flutter (HR 0.60, 95% CI 0.44-0.84, P = 0.002) compared with nonusers. Directionally consistent results were observed across subgroup analyses for the diabetes-only and obesity-only subgroups. CONCLUSIONS: Among adults with diabetes mellitus or obesity undergoing TAVR, GLP-1 RA use was associated with significantly lower risks of several outcomes. CI - Copyright (c) 2026 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. FAU - Goyal, Aman AU - Goyal A AD - Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Electronic address: http://x.com/AmanGoyalMD. FAU - Saeed, Humza AU - Saeed H AD - Department of Internal Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Jain, Hritvik AU - Jain H AD - Department of Cardiology, All India Institute of Medical Sciences, Jodhpur, India. FAU - Hurjkaliani, Sonia AU - Hurjkaliani S AD - Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Mahalwar, Gauranga AU - Mahalwar G AD - Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Jaiswal, Vikash AU - Jaiswal V AD - Section of Interventional Cardiology, Endeavor Health Cardiovascular Institute, University of Chicago Pritzker School of Medicine, Glenview, Illinois, USA. FAU - Ricciardi, Mark J AU - Ricciardi MJ AD - Section of Interventional Cardiology, Endeavor Health Cardiovascular Institute, University of Chicago Pritzker School of Medicine, Glenview, Illinois, USA. FAU - Kolte, Dhaval AU - Kolte D AD - Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Fonarow, Gregg C AU - Fonarow GC AD - Division of Cardiology, Ronald Reagan-UCLA Medical Center, Los Angeles, California, USA. FAU - Piazza, Gregory AU - Piazza G AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Kapadia, Samir AU - Kapadia S AD - Section of Invasive & Interventional Cardiology, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Qamar, Arman AU - Qamar A AD - Section of Interventional Cardiology, Endeavor Health Cardiovascular Institute, University of Chicago Pritzker School of Medicine, Glenview, Illinois, USA. Electronic address: aqamar@northshore.org. LA - eng PT - Journal Article DEP - 20260420 PL - England TA - Can J Cardiol JT - The Canadian journal of cardiology JID - 8510280 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Transcatheter Aortic Valve Replacement/methods MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Retrospective Studies MH - *Obesity/complications/epidemiology MH - *Aortic Valve Stenosis/surgery/complications MH - Aged, 80 and over MH - Aged MH - *Postoperative Complications/epidemiology/prevention & control MH - Stroke/epidemiology OTO - NOTNLM OT - glucagon-like protein-1 receptor agonist OT - mortality OT - outcomes OT - structural OT - transcatheter aortic valve replacement EDAT- 2026/04/23 00:31 MHDA- 2026/10/05 23:29 CRDT- 2026/04/22 19:16 PHST- 2025/12/24 00:00 [received] PHST- 2026/04/08 00:00 [revised] PHST- 2026/04/09 00:00 [accepted] PHST- 2026/10/05 23:29 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 19:16 [entrez] AID - S0828-282X(26)00358-2 [pii] AID - 10.1016/j.cjca.2026.04.003 [doi] PST - ppublish SO - Can J Cardiol. 2026 Oct;42(10):2299-2309. doi: 10.1016/j.cjca.2026.04.003. Epub 2026 Apr 20. PMID- 42017554 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 87 IP - 15 DP - 2026 Apr 21 TI - Balancing Clinical and Ethical Considerations Related to Placebo Use in Trials of Incretin-Based Therapies in Heart Failure. PG - 2034-2043 LID - S0735-1097(26)05517-8 [pii] LID - 10.1016/j.jacc.2026.02.5086 [doi] AB - Recent trials have shown that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dual gastric inhibitory polypeptide/GLP-1 RAs improve symptoms and functional capacity in patients with heart failure (HF) with preserved ejection fraction and obesity, with or without type 2 diabetes. These studies enrolled modest sample sizes and had few worsening HF events or cardiovascular (CV) deaths, limiting definitive conclusions regarding those endpoints. At the same time, the benefits of these drugs on major adverse CV and kidney outcomes in patients with obesity, diabetes, and chronic kidney disease raise questions about placebo-controlled designs in future HF trials. This article explores scientific, practical, and ethical considerations surrounding the design of future incretin-based therapy trials in HF. We highlight the current gaps in evidence and emphasize the need for event-driven outcome trials in HF. The use of placebo ensures methodologic rigor but may raise ethical concerns in the context of cardiometabolic benefit with GLP-1 RAs. Abandoning placebo, however, risks incomplete safety and efficacy data and premature therapeutic extrapolation. Such studies are essential to define the efficacy, durability, and safety of incretin-based therapy across the HF spectrum and to clarify whether improvements in patient-reported outcomes are bolstered by other benefits. To support balanced decision making, we introduce a structured framework outlining when placebo remains appropriate, when active comparison may be required, and how trial design features can address the ethical and operational challenges unique to incretin-based HF research. Ethically robust, clinically focused, and methodologically rigorous trials remain the only means to inform guideline recommendations and insurance coverage. The HF population is too large, too vulnerable, and too costly to remain without definitive evidence guiding the use of these therapies. CI - Copyright (c) 2026 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Fioretti, Francesco AU - Fioretti F AD - Baylor Scott & White Research Institute, Dallas, Texas, USA. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, United Kingdom. FAU - Dickert, Neal W AU - Dickert NW AD - Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA; Emory Health Services Research Center, Atlanta, Georgia, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott & White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. Electronic address: butlzih@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260421 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Placebos) SB - IM MH - Humans MH - *Heart Failure/drug therapy MH - *Incretins/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Clinical Trials as Topic/ethics/methods MH - Placebos OTO - NOTNLM OT - GLP-1 RAs OT - ethics OT - obesity OT - placebo OT - type 2 diabetes COIS- Funding Support and Author Disclosures Dr Petrie has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and has served as a consultant and on trial committees for Abbott, Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Corteria, Novartis, AstraZeneca, Novo Nordisk, Abbvie, Bayer, Horizon Therapeutics, Foundry, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, 3R Lifesciences, Reprieve, Corvia, and Regeneron. Dr Dickert has been a consultant for Abiomed; and has received research funding from Abiomed and Merck. Dr Butler is a consultant for Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Faraday, Idorsia, Impulse Dynamics, Imbria, Innolife, Intellia, Inventiva, Levator, Lexicon, Eli Lilly, Mankind, Medtronic, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, SC Pharma, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromic, Vera, and Zoll. Dr Fioretti has reported that he has no relationships relevant to the contents of this paper to disclose. EDAT- 2026/04/22 12:35 MHDA- 2026/04/22 18:32 CRDT- 2026/04/22 08:48 PHST- 2025/11/04 00:00 [received] PHST- 2026/01/27 00:00 [revised] PHST- 2026/02/10 00:00 [accepted] PHST- 2026/04/22 18:32 [medline] PHST- 2026/04/22 12:35 [pubmed] PHST- 2026/04/22 08:48 [entrez] AID - S0735-1097(26)05517-8 [pii] AID - 10.1016/j.jacc.2026.02.5086 [doi] PST - ppublish SO - J Am Coll Cardiol. 2026 Apr 21;87(15):2034-2043. doi: 10.1016/j.jacc.2026.02.5086. Epub 2026 Apr 21. PMID- 42013575 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 104 DP - 2026 Jan 1 TI - Cost-effectiveness of incretin therapies: a Canadian lens on diabetes, obesity, and emerging indications. PG - 1-7 LID - 10.1139/cjpp-2025-0248 [doi] AB - Incretin therapies have emerged as key interventions for glycemic control and weight reduction and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence on the cost-effectiveness of incretin-based therapies. These include glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., semaglutide) and dual agonists (e.g., tirzepatide) targeting both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, in patients with type 2 diabetes mellitus or for weight loss. We review data from clinical trials and recent Canadian and international economic models, identify emerging indications, and discuss limitations in current health-technology assessment frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations. FAU - Awadalla, Luke AU - Awadalla L AD - Western University, London, ON, Canada. RINGGOLD: 6221 FAU - Iskander, Siena AU - Iskander S AD - Queen's University, Kingston, ON, Canada. FAU - Chu, Cherry AU - Chu C AD - Women's College Hospital Research and Innovation Institute, Toronto, ON, Canada. RINGGOLD: 7938 FAU - Tadrous, Mina AU - Tadrous M AUID- ORCID: 0000-0003-1911-6129 AD - Women's College Hospital Research and Innovation Institute, Toronto, ON, Canada. RINGGOLD: 7938 AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada. RINGGOLD: 7985 LA - eng PT - Journal Article PT - Review PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/economics/therapeutic use MH - *Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Obesity/drug therapy/economics MH - Canada MH - *Hypoglycemic Agents/economics/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide MH - Animals MH - Cost-Effectiveness Analysis OTO - NOTNLM OT - incretin therapies OT - GLP-1RAs OT - cost-effectiveness OT - obesity OT - semaglutide OT - tirzepatide COIS- Mina Tadrous is supported by a Tier 2 Canada Research Chair in Pharmaceutical Policy and Real-world Evidence. He also reports receiving funding from the Ontario Ministry of Health and Canada's Drug Agency unrelated to this work. All other authors report no Conflicts of Interest. EDAT- 2026/04/22 00:37 MHDA- 2026/05/19 18:32 CRDT- 2026/04/21 18:03 PHST- 2026/05/19 18:32 [medline] PHST- 2026/04/22 00:37 [pubmed] PHST- 2026/04/21 18:03 [entrez] AID - 10.1139/cjpp-2025-0248 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2026 Jan 1;104:1-7. doi: 10.1139/cjpp-2025-0248. PMID- 42012433 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260608 IS - 1942-5546 (Electronic) IS - 0025-6196 (Linking) VI - 101 IP - 6 DP - 2026 Jun TI - Association of GLP-1 Receptor Agonist Use With Chronic Kidney Disease Risk in Type 2 Diabetes: Multicenter Emulated Target Trials. PG - 909-919 LID - S0025-6196(26)17385-6 [pii] LID - 10.1016/j.mayocp.2026.01.035 [doi] AB - OBJECTIVE: To determine whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) initiation is associated with reduction of incident renal outcomes compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes (T2D) without pre-existing chronic kidney disease (CKD). METHODS: This study identified 370,636 patients with T2D from the TriNetX Collaborative Network database between January 1, 2015, and June 30, 2023. An emulated target trial was constructed, comprising 24,510 propensity score-matched pairs of new users of GLP-1 RAs and DPP-4is. Composite CKD events (defined as a combination of CKD diagnosis, estimated glomerular filtration rate <60 mL/min per 1.73 m(2), dialysis, and kidney transplantation), acute kidney injury, major adverse cardiac events, and all-cause mortality were compared between two groups using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Participants were 57.6+/-12.0 years of age and 48.9% were male. Compared with DPP-4i users, GLP-1 RA users had significantly reduced risks of composite kidney outcomes (HR, 0.85; 95% CI, 0.82 to 0.87), incident CKD (HR, 0.85; 95% CI, 0.82 to 0.88), dialysis (HR, 0.53; 95% CI, 0.43 to 0.64), acute kidney injury (HR, 0.81; 95% CI, 0.76 to 0.86), major adverse cardiac events (HR, 0.84; 95% CI, 0.81 to 0.88), and all-cause mortality (HR, 0.55; 95% CI, 0.50 to 0.59). Kaplan-Meier analyses confirmed lower cumulative incidence of these outcomes in GLP-1 RA users. Subgroup analyses confirmed consistent benefits across various patient groups. CONCLUSION: In patients with T2D and no prior CKD, GLP-1 RA use was associated with lower risks of renal complications, incident CKD, cardiovascular events, and death compared with DPP-4is. CI - Copyright (c) 2026 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr Yen's Clinic, Taoyuan, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County; Department of Health Services Administration, China Medical University, Taichung; Department of Family Medicine, Min-Sheng General Hospital, Taoyuan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. FAU - Hung, Yao-Min AU - Hung YM AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung; College of Science and Engineering, National Taitung University, Taitung, Taiwan; Department of Internal Medicine, Taitung Hospital, Ministry of Health and Welfare, Taitung, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Beitou District; Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan. Electronic address: chhwu@vghtpe.gov.tw. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address: jccwei@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260421 PL - England TA - Mayo Clin Proc JT - Mayo Clinic proceedings JID - 0405543 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Renal Insufficiency, Chronic/epidemiology/etiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Aged EDAT- 2026/04/21 18:34 MHDA- 2026/06/05 18:36 CRDT- 2026/04/21 10:28 PHST- 2025/09/03 00:00 [received] PHST- 2026/01/12 00:00 [revised] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/06/05 18:36 [medline] PHST- 2026/04/21 18:34 [pubmed] PHST- 2026/04/21 10:28 [entrez] AID - S0025-6196(26)17385-6 [pii] AID - 10.1016/j.mayocp.2026.01.035 [doi] PST - ppublish SO - Mayo Clin Proc. 2026 Jun;101(6):909-919. doi: 10.1016/j.mayocp.2026.01.035. Epub 2026 Apr 21. PMID- 42010367 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Associations of Semaglutide With Skeletal Outcomes in People With Obesity, With and Without Type 2 Diabetes: A Target Trial Emulation. PG - 5834-5847 LID - 10.1111/dom.70786 [doi] AB - AIMS: To evaluate the associations between semaglutide initiation and long-term skeletal outcomes in people with obesity, stratified by type 2 diabetes (T2D) status, using target trial emulation. MATERIALS AND METHODS: This retrospective cohort study used the TriNetX federated electronic health record network. People with obesity initiating semaglutide were matched 1:1 via propensity score matching (215 covariates) to those initiating active comparators or usual care. The with-T2D cohort (n = 19 824-93 519 matched pairs per comparison) was followed for 3 years; the without-T2D cohort (n = 10 323-56 225 pairs) for 2 years. The primary outcome was major osteoporotic fracture (MOF). Secondary outcomes included osteoporosis diagnosis; exploratory outcomes included osteoarthritis and gout. RESULTS: In the with-T2D cohort, semaglutide initiation was associated with a lower risk of MOF compared with empagliflozin (HR 0.69; 95% CI 0.61-0.77), glipizide (HR 0.72; 0.63-0.83) and usual care (HR 0.84; 0.76-0.93). In the without-T2D cohort, no significant associations with MOF were observed across any comparison (all p > 0.05). Osteoporosis risk did not differ significantly in most comparisons in either cohort. Exploratory analyses of osteoarthritis and gout showed inconsistent patterns across comparators. CONCLUSIONS: Among people with obesity and T2D, semaglutide initiation was associated with a lower risk of MOF over 3 years compared with other glucose-lowering agents and usual care. This association was not observed in people with obesity without T2D. These findings support further investigation of the skeletal effects of GLP-1 receptor agonists. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Tsou, Min-Yu AU - Tsou MY AD - Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. FAU - Li, Pin-Hung AU - Li PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Jo-Ching AU - Chen JC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Shao-Chia AU - Chen SC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hsieh, Hao-I AU - Hsieh HI AUID- ORCID: 0009-0004-2637-6185 AD - School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Education, National Taiwan University Hospital, Taipei, Taiwan. FAU - Meyerowitz-Katz, Gideon AU - Meyerowitz-Katz G AD - School of Health and Society, University of Wollongong, Wollongong, Australia. FAU - Liu, Yen-Liang AU - Liu YL AD - Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. AD - Master Program for Biomedical Engineering, China Medical University, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2026-A-009/Chung Shan Medical University Hospital/ GR - CSH-2026-C-030/Chung Shan Medical University Hospital/ GR - CSH-2026-F-003/Chung Shan Medical University Hospital/ GR - NSTC 113-2314-B-040-026-MY2/National Science and Technology Council/ GR - NSTC 114-2622-B-04-001/National Science and Technology Council/ GR - NSTC 113-2124-M-039-002/National Science and Technology Council/ GR - NSTC 114-2124-M-039-001/National Science and Technology Council/ GR - NHRI-EX114-11206EC/National Health Research Institutes/ GR - NHRI-EX115-11206EC/National Health Research Institutes/ PT - Journal Article DEP - 20260420 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy/epidemiology MH - *Osteoporotic Fractures/epidemiology/prevention & control MH - Retrospective Studies MH - *Semaglutide/therapeutic use PMC - PMC13243989 OTO - NOTNLM OT - GLP-1 receptor agonists OT - major osteoporotic fractures OT - obesity OT - osteoporosis OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/21 13:11 MHDA- 2026/06/11 12:41 PMCR- 2026/06/08 CRDT- 2026/04/20 23:47 PHST- 2026/03/30 00:00 [revised] PHST- 2026/01/13 00:00 [received] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/06/11 12:41 [medline] PHST- 2026/04/21 13:11 [pubmed] PHST- 2026/04/20 23:47 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70786 [pii] AID - 10.1111/dom.70786 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5834-5847. doi: 10.1111/dom.70786. Epub 2026 Apr 20. PMID- 42009258 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260807 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 236 DP - 2026 Jun TI - GLP-1-based therapies and limb outcomes in PAD: a systematic review and meta-analysis of real-world studies. PG - 113271 LID - S0168-8227(26)00190-7 [pii] LID - 10.1016/j.diabres.2026.113271 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual incretin agonist tirzepatide have demonstrated cardiometabolic benefits in cardiovascular outcome trials, but their effects on limb outcomes in peripheral artery disease (PAD) remain unclear. This study evaluated whether GLP-1-based therapies reduce the risk of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality in real-world PAD populations. METHODS: A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD. RESULTS: Six studies including over 240,000 patients were analyzed. GLP-1-based therapies were associated with a significant reduction in MALE (HR 0.59, 95% CI 0.39-0.90), although heterogeneity was substantial. A significant reduction in MACE was also observed (HR 0.67, 95% CI 0.53-0.85), with greater consistency in diabetic populations. Stroke was significantly reduced (HR 0.75, 95% CI 0.63-0.89), demonstrating consistent effects across studies. Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude. CONCLUSION: In real-world PAD populations, GLP-1-based therapies are associated with meaningful reductions in both limb and cardiovascular outcomes. These findings support a vascular protective profile, particularly for stroke and MACE in more homogeneous populations such as patients with diabetes. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Boccatonda, Andrea AU - Boccatonda A AD - Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, via Massarenti n 9, 40138 Bologna, Italy. Electronic address: andrea.boccatonda2@unibo.it. FAU - D'Ardes, Damiano AU - D'Ardes D AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. FAU - Brighenti, Alice AU - Brighenti A AD - Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, via Massarenti n 9, 40138 Bologna, Italy. FAU - Cipollone, Alessia AU - Cipollone A AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. FAU - Simeone, Paola Giustina AU - Simeone PG AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. FAU - Guagnano, Maria Teresa AU - Guagnano MT AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. FAU - Serra, Carla AU - Serra C AD - Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, via Massarenti n 9, 40138 Bologna, Italy. FAU - Santilli, Francesca AU - Santilli F AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. FAU - Cipollone, Francesco AU - Cipollone F AD - Institute of "Clinica Medica", Department of Medicine and Aging Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260419 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide 1/therapeutic use/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Peripheral Arterial Disease/drug therapy MH - Tirzepatide MH - Treatment Outcome MH - Female OTO - NOTNLM OT - Atherosclerosis OT - Diabetes OT - GLP1-RA OT - PAD OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/04/21 13:11 MHDA- 2026/05/14 00:31 CRDT- 2026/04/20 19:14 PHST- 2026/03/07 00:00 [received] PHST- 2026/04/15 00:00 [revised] PHST- 2026/04/17 00:00 [accepted] PHST- 2026/05/14 00:31 [medline] PHST- 2026/04/21 13:11 [pubmed] PHST- 2026/04/20 19:14 [entrez] AID - S0168-8227(26)00190-7 [pii] AID - 10.1016/j.diabres.2026.113271 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jun;236:113271. doi: 10.1016/j.diabres.2026.113271. Epub 2026 Apr 19. PMID- 42009015 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261001 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 6 DP - 2026 Jun TI - Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. PG - 450-462 LID - S2213-8587(25)00402-4 [pii] LID - 10.1016/S2213-8587(25)00402-4 [doi] AB - BACKGROUND: The combination of cagrilintide and semaglutide has been shown in global studies to induce reductions in bodyweight. We assessed the efficacy and safety of a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg versus semaglutide 2.4 mg for weight management in an east Asian population. METHODS: This double-blind, parallel-group, phase 3a trial (REDEFINE 5) was conducted across 21 sites (community, hospital) in Japan and one site in Taiwan. We included participants aged at least 18 years with a BMI of at least 27 kg/m(2) and at least two obesity-related complications, or with a BMI of at least 35 kg/m(2) and at least one obesity-related complication (per the Japan Society for the Study of Obesity guidelines), with or without type 2 diabetes. Participants were randomly assigned (1:1) to once-weekly subcutaneous injections of cagrilintide-semaglutide or semaglutide (both escalated to 2.4 mg), plus lifestyle intervention, for 68 weeks. Randomisation was done centrally using an interactive web response system and stratified according to planned CT scan, BMI of at least 35 kg/m(2), and type 2 diabetes status. Participants, site staff, investigators, and study funder were all masked to active study treatments. The primary endpoint was relative change in bodyweight from baseline to week 68. Efficacy analyses were done in all participants who underwent randomisation, using the trial product estimand (ie, assuming the treatment was taken as intended, regardless of dose) as the primary estimand. Missing data at week 68 were imputed. Safety analyses were done in all participants who underwent randomisation and received at least one dose of trial product. This trial is registered with ClinicalTrials.gov (NCT05813925) and is complete. FINDINGS: Between April 3, 2023, and Sept 15, 2023, we screened 355 individuals; 331 were randomly assigned to cagrilintide-semaglutide (n=164) or semaglutide (n=167). 226 (68%) participants were male and 105 (32%) were female; 80 (24%) had type 2 diabetes. 17 (10%) participants discontinued cagrilintide-semaglutide and ten (6%) discontinued semaglutide. The estimated mean change in bodyweight from baseline to week 68 was -18.4% (SE 0.7) in the cagrilintide-semaglutide group versus -11.9% (0.7) in the semaglutide group (estimated treatment difference [ETD] -6.5 percentage points [95% CI -8.4 to -4.6]; p<0.0001). Adverse events were reported by 143 (87%) of 164 participants in the cagrilintide-semaglutide group and 141 (84%) of 167 in the semaglutide group, the most common of which were gastrointestinal disorders (87 [53%] of 164 participants in the cagrilintide-semaglutide group vs 85 [51%] of 167 in the semaglutide group). One death was reported in the semaglutide 2.4 mg group, which was not judged to be treatment related by the investigator. INTERPRETATION: These findings support the efficacy and safety of cagrilintide-semaglutide for weight management in individuals from east Asia with overweight or obesity, with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Japanese and Mandarin translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2026 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: tyamau@m.u-tokyo.ac.jp. FAU - Becker, Niels-Peter AU - Becker NP AD - Novo Nordisk, Soborg, Denmark. FAU - Hagemann, Christoffer Andersen AU - Hagemann CA AD - Novo Nordisk, Soborg, Denmark. FAU - Huang, Kuo-Chin AU - Huang KC AD - Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Kiyosue, Arihiro AU - Kiyosue A AD - Tokyo-Eki Center-building Clinic, Tokyo, Japan. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. FAU - Onishi, Yukiko AU - Onishi Y AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Tokyo, Japan. FAU - Kosuvaripalli, Ananda AU - Kosuvaripalli A AD - Novo Nordisk, Global Business Services, Bangalore, India. FAU - Takano, Tomoko AU - Takano T AD - Novo Nordisk Pharma, Tokyo, Japan. FAU - Ishigaki, Yasushi AU - Ishigaki Y AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan. CN - REDEFINE 5 study group LA - eng SI - ClinicalTrials.gov/NCT05813925 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260417 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Double-Blind Method MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Japan/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Semaglutide/administration & dosage/therapeutic use MH - Taiwan/epidemiology MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use COIS- Declaration of interests AKi received honoraria for lectures from Novo Nordisk. AKo, CAH, N-PB, and TT are employees of Novo Nordisk. SL received research grants from Merck Sharp & Dohme, Novo Nordisk, and LG Chem; and honoraria as a consultant or speaker for AstraZeneca, Boehringer Ingelheim, Abbott, LG Chem, Daewoong Pharmaceutical, Chong Kun Dang Pharmaceutical, and Novo Nordisk. TY received research grants from Novo Nordisk, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Ono Pharmaceutical, Sumitomo Pharma, Nipro, MED MIRAI, Boehringer Ingelheim Japan, Kowa Pharmaceuticals, Nitto Boseki, Asahi Mutual Life Insurance, and Sanwa Kagaku Kenkyusho; and received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott Japan, Daiichi Sankyo, Sanofi, Viatris, Medtronic Japan, Astellas Pharma, AstraZeneca, Terumo, Taisho Pharmaceutical, Amgen, ARKRAY Marketing, Bayer Yakuhin, Lindsay Advice, Kyowa Kirin, Sanwa Kagaku Kenkyusho, GSK, Ono Pharmaceutical, Merck Sharp & Dohme (Merck), Sumitomo Pharma, Teijin, Boehringer Ingelheim Japan, Novo Nordisk, Eli Lilly, Kowa Pharmaceuticals, Nipro, Mitsubishi Tanabe Pharma, Amgen, Dexcom Japan, Nitto Boseki, and ViewSend ICT. YI received honoraria for lectures from Novo Nordisk, Eli Lilly Japan, Sumitomo Pharma, and Kowa Pharmaceuticals; and received research grants from Novo Nordisk and Sanofi. YO received honoraria for lectures from: Novo Nordisk, Eli Lilly Japan, Sumitomo Pharma, AstraZeneca, and Mitsubishi Tanabe Pharma. K-CH declares no competing interests. EDAT- 2026/04/21 13:11 MHDA- 2026/05/13 00:29 CRDT- 2026/04/20 18:52 PHST- 2025/10/14 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/16 00:00 [accepted] PHST- 2026/05/13 00:29 [medline] PHST- 2026/04/21 13:11 [pubmed] PHST- 2026/04/20 18:52 [entrez] AID - S2213-8587(25)00402-4 [pii] AID - 10.1016/S2213-8587(25)00402-4 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Jun;14(6):450-462. doi: 10.1016/S2213-8587(25)00402-4. Epub 2026 Apr 17. PMID- 42002107 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 407 DP - 2026 Aug 15 TI - Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study. PG - 121802 LID - S0165-0327(26)00653-1 [pii] LID - 10.1016/j.jad.2026.121802 [doi] AB - INTRODUCTION: Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability. METHODS: We conducted a disproportionality analysis of the WHO VigiBase (2010-2024), including T2DM patients. Reports of depressed mood and suicidal thoughts associated with GLP-1RAs were compared with other glucose-lowering medications. Analyses incorporated age, sex, time-to-onset, dose, comorbid depression, and concomitant antidepressant use. Adjusted reporting odds ratios (RORs) and a Weibull time-to-event model were applied. Causality was explored using Bradford Hill criteria. RESULTS: A total of 1,183,817 adverse events related to GLP-1RA were identified. Depressed mood and suicidality signals were observed with semaglutide, liraglutide, and tirzepatide (adjusted ROR(0.25): 2.13, 1.52, 1.07) and (adjusted ROR(0.25): 6.76, 2.43, 3.39), respectively. No signal was identified for suicide attempts or completed suicide. Absolute reporting frequencies were low. Concomitant antidepressant use was 2.3-5 times more frequent, and comorbid depression 25%-120% higher, compared with other glucose-lowering medications. Median time-to-onset was 96 days. Survival analysis demonstrated an early increase in reporting followed by stabilization over time. Adjustment for antidepressant use modestly attenuated associations. CONCLUSION: GLP-1RAs were associated with increased reporting of depressed mood and suicidal thoughts, particularly in patients receiving concomitant antidepressants. These findings support a patient-centered model in which underlying affective vulnerability or reporting factors drive reported mood symptoms rather than a uniform drug-specific effect. GLP-1RAs remain clinically valuable, but psychiatric monitoring during early treatment in vulnerable patients is warranted. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Aboukaoud, Mohammed AU - Aboukaoud M AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. FAU - Hoch, Bosmat AU - Hoch B AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. FAU - Weiser, Mark AU - Weiser M AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. FAU - Amiaz, Revital AU - Amiaz R AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. LA - eng PT - Journal Article DEP - 20260417 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Tirzepatide/adverse effects MH - Semaglutide MH - *Suicidal Ideation MH - Male MH - *Depression/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Middle Aged MH - Aged MH - Liraglutide/adverse effects/therapeutic use OTO - NOTNLM OT - Completed suicide OT - Depressed mood OT - Depression OT - GLP-1RA OT - Suicidal attempt OT - Suicidal thoughts COIS- Declaration of competing interest The authors, Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser, and Revital Amiaz, have no conflicts of interest to declare and no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/04/20 13:10 MHDA- 2026/05/02 00:33 CRDT- 2026/04/19 19:22 PHST- 2026/01/20 00:00 [received] PHST- 2026/03/30 00:00 [revised] PHST- 2026/04/13 00:00 [accepted] PHST- 2026/05/02 00:33 [medline] PHST- 2026/04/20 13:10 [pubmed] PHST- 2026/04/19 19:22 [entrez] AID - S0165-0327(26)00653-1 [pii] AID - 10.1016/j.jad.2026.121802 [doi] PST - ppublish SO - J Affect Disord. 2026 Aug 15;407:121802. doi: 10.1016/j.jad.2026.121802. Epub 2026 Apr 17. PMID- 42000905 OWN - NLM STAT- MEDLINE DCOM- 20260806 LR - 20261028 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 31 IP - 9 DP - 2026 Sep TI - GLP-1 receptor agonists and risk of suicide or suicide attempts - A nationwide cohort and self-controlled case series study. PG - 5316-5322 LID - 10.1038/s41380-026-03619-y [doi] AB - The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have raised concerns about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicide or suicide attempts. We conducted two new-user, active comparator cohort studies. The GLP1-RAs vs sodium-glucose cotransporter-2 (SGLT-2) inhibitors cohort included new users of GLP-1 RAs (n = 83,464) or SGLT-2 inhibitors (n = 78,366), and the GLP1-RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors cohort included new users of GLP-1 RAs (n = 108,322) or DPP-4 inhibitors (n = 55,411). We also employed a self-controlled case series design to compare suicide, or suicide attempts before and after GLP-1 RA treatment initiation across three time periods. In the cohort analyses patients who initiated GLP-1 RAs did not differ in the hazard ratio (HR) for suicide or suicide attempts from SGLT-2 inhibitor users (HR: 0.93; 95% CI: 0.57-1.52), and GLP-1 RA users had a lower risk of suicide or suicide attempts compared with DPP-4 inhibitor users (HR: 0.58; 95% CI: 0.37-0.91). In the self-controlled case series design, use of GLP-1 RAs was associated with a lower incidence rate ratio (IRR) of suicide or suicide attempts one year after treatment initiation (IRR: 0.45; 95% CI: 0.10-0.50) and 13-24 months after treatment initiation compared with pretreatment. This study showed that use of GLP-1 RAs was not associated with increased incidence of suicide or suicide attempts in either the active comparator new-user design or in the self-controlled case series design. CI - (c) 2026. The Author(s). FAU - Stanislaus, Christoffer AU - Stanislaus C AUID- ORCID: 0009-0008-6716-118X AD - Section of Data, Biostatistics and Pharmacoepidemiology, Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. christoffer.stanislaus@regionh.dk. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. christoffer.stanislaus@regionh.dk. AD - The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Psychiatric Center, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark. christoffer.stanislaus@regionh.dk. FAU - Winther-Jensen, Matilde AU - Winther-Jensen M AD - Section of Data, Biostatistics and Pharmacoepidemiology, Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. FAU - Stanislaus, Sharleny AU - Stanislaus S AD - The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Psychiatric Center, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark. AD - Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Frederiksberg, Denmark. FAU - Osler, Merete AU - Osler M AUID- ORCID: 0000-0002-6921-220X AD - Section of Data, Biostatistics and Pharmacoepidemiology, Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. AD - Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Coello, Klara AU - Coello K AUID- ORCID: 0000-0003-1568-2991 AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Psychiatric Center, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark. FAU - Vinberg, Maj AU - Vinberg M AUID- ORCID: 0000-0002-5982-1335 AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Psychiatric Center, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260418 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Cohort Studies MH - Male MH - Middle Aged MH - *Suicide, Attempted/statistics & numerical data/psychology MH - *Suicide/statistics & numerical data/psychology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Adult MH - Sodium-Glucose Transporter 2 Inhibitors MH - Aged MH - Glucagon-Like Peptide 1 MH - Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Case-Control Studies PMC - PMC13441866 COIS- Competing interests: MV has within the last three years, served as consultant for Lundbeck, Eli Lilly and Johnson & Johnson. The remaining authors declare no conflicts of interests. Ethics: The Regional Data Protection Agency approved the study (p-2020-88). Informed consent was not required since the data only included register data. Data was stored at the research environment hosted by Statistics Denmark and accessed through a secure log-on process. Data is pseudonymized and microdata cannot be reported, thereby protecting the information of individuals. All methods were performed in accordance with the relevant guidelines and regulations. EDAT- 2026/04/19 07:10 MHDA- 2026/08/06 11:36 PMCR- 2026/04/18 CRDT- 2026/04/18 23:19 PHST- 2025/10/28 00:00 [received] PHST- 2026/04/09 00:00 [accepted] PHST- 2026/03/09 00:00 [revised] PHST- 2026/08/06 11:36 [medline] PHST- 2026/04/19 07:10 [pubmed] PHST- 2026/04/18 23:19 [entrez] PHST- 2026/04/18 00:00 [pmc-release] AID - 10.1038/s41380-026-03619-y [pii] AID - 3619 [pii] AID - 10.1038/s41380-026-03619-y [doi] PST - ppublish SO - Mol Psychiatry. 2026 Sep;31(9):5316-5322. doi: 10.1038/s41380-026-03619-y. Epub 2026 Apr 18. PMID- 41999297 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260903 IS - 1365-2060 (Electronic) IS - 0785-3890 (Print) IS - 0785-3890 (Linking) VI - 58 IP - 1 DP - 2026 Dec TI - GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers. PG - 2660386 LID - 10.1080/07853890.2026.2660386 [doi] LID - 2660386 AB - OBJECTIVES: To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. METHODS: A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. RESULTS: GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. CONCLUSION: GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management. FAU - Chikatimalla, Rahul AU - Chikatimalla R AUID- ORCID: 0000-0003-2967-1425 AD - Kamineni Institute of Medical Sciences, Narketpally, India. FAU - Shah, Ashka AU - Shah A AUID- ORCID: 0009-0004-6648-2396 AD - GMERS Medical College, Gotri, Vadodara, India. FAU - Shah, Twinkle AU - Shah T AUID- ORCID: 0009-0001-7143-2930 AD - GMERS Medical College, Valsad, India. FAU - Perry, Griffin AU - Perry G AUID- ORCID: 0009-0002-2716-6556 AD - Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. FAU - Banker, Himanshi AU - Banker H AUID- ORCID: 0009-0004-3824-1755 AD - Maulana Azad Medical College, New Delhi, India. FAU - Aggarwal, Kanishk AU - Aggarwal K AUID- ORCID: 0009-0005-7518-446X AD - Dayanand Medical College and Hospital, Ludhiana, Punjab, India. FAU - Jain, Rohit AU - Jain R AUID- ORCID: 0000-0002-9101-2351 AD - Division of Hospital Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260418 PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/pharmacology MH - *Stroke/prevention & control/etiology MH - Liraglutide/therapeutic use/pharmacology MH - Immunoglobulin Fc Fragments/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Recombinant Fusion Proteins PMC - PMC13094292 OAB - GLP-1 receptor agonist (GLP-1RA) therapy should be incorporated into a broad approach for risk reduction for stroke in patients with type 2 DM, especially in situations where prevention of ischaemic stroke is of high importance.Long-acting GLP-1 receptor agonists (e.g., semaglutide and dulaglutide) are preferred over shorter-acting preparations for their cerebrovascular protective effects, properties of which are more consistent and beneficial for the risk of ischaemia.GLP-1RA therapy could provide a special advantage to patients with multiple risk factors for cardiometabolic diseases such as obesity, hypertension, dyslipidemia and documented atherosclerotic cardiovascular disease.On the other hand, the neuroprotective properties of GLP-1RAs, which occur through anti-inflammatory, antioxidant, endothelial-stabilising or mitochondrial-protective actions, provide rationale for the use.Treatment should be individualised for renal function, tolerance, potential for compliance, cost and accessibility. This allows for maximal long-term cerebrovascular benefits. OABL- eng OTO - NOTNLM OT - Stroke OT - cerebrovascular circulation OT - glucagon-like peptide 1 receptor agonists OT - neuroprotection OT - type 2 diabetes mellitus COIS- No potential conflict of interest was reported by the authors. EDAT- 2026/04/19 04:18 MHDA- 2026/04/19 04:19 PMCR- 2026/04/18 CRDT- 2026/04/18 08:53 PHST- 2026/04/19 04:19 [medline] PHST- 2026/04/19 04:18 [pubmed] PHST- 2026/04/18 08:53 [entrez] PHST- 2026/04/18 00:00 [pmc-release] AID - 2660386 [pii] AID - 10.1080/07853890.2026.2660386 [doi] PST - ppublish SO - Ann Med. 2026 Dec;58(1):2660386. doi: 10.1080/07853890.2026.2660386. Epub 2026 Apr 18. PMID- 41997638 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1558-3171 (Electronic) IS - 0039-6109 (Linking) VI - 106 IP - 2 DP - 2026 Apr TI - Glucagon-like Peptide-1 Receptor Agonists: An Alternative for Dysglycemia in Hospitalized Patients? PG - 213-222 LID - S0039-6109(25)00140-9 [pii] LID - 10.1016/j.suc.2025.12.011 [doi] AB - In the outpatient management of type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are proven to benefit long-term glycemic control and reduce complications related to chronic inflammation. Emerging clinical data suggest that GLP-1 RAs may serve as an alternative or complement to insulin for glycemic management in hospitalized patients. Preclinical studies indicate that GLP-1 RAs influence the inflammatory response in models of acute inflammation, including ischemia-reperfusion injury, sepsis-induced vascular dysfunction, acute lung injury, and acute kidney injury. Although aspiration is a potential risk linked to GLP-1 RAs, it can be minimized by following established medical society guidelines. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Kligman, Mark AU - Kligman M AD - Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: mkligman@som.umaryland.edu. FAU - Holsten, Steven AU - Holsten S AD - Department of Surgery, R Adams Cowley Shock Trauma Center, Baltimore, MD, USA. LA - eng PT - Journal Article PT - Review DEP - 20260206 PL - United States TA - Surg Clin North Am JT - The Surgical clinics of North America JID - 0074243 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hospitalization MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Aspiration risk OT - Glucagon-like peptide-1 receptor agonists OT - Glycemic control OT - Inflammation OT - Inpatient use COIS- Disclosures The authors have no disclosures. EDAT- 2026/04/18 13:10 MHDA- 2026/04/18 13:11 CRDT- 2026/04/17 20:54 PHST- 2026/04/18 13:11 [medline] PHST- 2026/04/18 13:10 [pubmed] PHST- 2026/04/17 20:54 [entrez] AID - S0039-6109(25)00140-9 [pii] AID - 10.1016/j.suc.2025.12.011 [doi] PST - ppublish SO - Surg Clin North Am. 2026 Apr;106(2):213-222. doi: 10.1016/j.suc.2025.12.011. Epub 2026 Feb 6. PMID- 41995433 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 8 DP - 2026 Aug TI - The interplay of GLP-1 receptor agonist use, chronic kidney disease and fracture risk in obese pAtients: a retrospective cohort study. PG - 2788-2796 LID - 10.1002/bcp.70566 [doi] AB - AIMS: To evaluate the association between Glucagon-like peptide-1 receptor agonist (GLP-1RA) use and fracture risk in patients with or without chronic kidney disease (CKD). METHODS: A retrospective cohort study was conducted using TriNetX, including patients aged 18-50. Two primary cohorts were defined: obese patients with CKD on GLP-1RAs >/= 1 year (CKD+/GLP-1RA+) and obese patients with CKD not on GLP-1RAs (CKD+/GLP-1RA-). A subgroup analysis compared CKD+/GLP-1RA + patients to obese patients without CKD on GLP-1RAs (CKD-/GLP-1RA+). Primary outcomes were upper and lower limb fractures. Risk analysis and Kaplan-Meier survival analysis assessed fracture incidence over 5 years. RESULTS: After matching, 13 441 patients were included per cohort. CKD+/GLP-1RA + patients had fewer fractures than CKD+/GLP-1RA- patients (Risk Difference: -0.016, 95% CI: -0.018, -0.013; RR: 0.196, 95% CI: 0.145, 0.265; OR: 0.193, 95% CI: 0.143, 0.261), with higher fracture-free survival (99.31% vs. 95.47%; p < 0.001). Subgroup analysis (13 723 patients per cohort) showed CKD+/GLP-1RA + patients had a slightly higher fracture risk than CKD-/GLP-1RA + patients (Risk Difference: 0.003, 95% Cl: 0.001, 0.004; RR: 2.357, 95% Cl: 1.516, 3.665; OR: 2.364, 95% Cl: 1.518, 3.680), with lower fracture-free survival (98.87% vs. 99.19%; p < 0.001). CONCLUSION: These findings suggest a possible CKD-associated modification on the skeletal effects of GLP-1RAs, implicating that CKD patients' bone health should be monitored during GLP-1RA treatment. CI - (c) 2026 British Pharmacological Society. FAU - Eubanks, Amari AU - Eubanks A AUID- ORCID: 0009-0007-0797-4931 AD - Howard University College of Medicine, Washington, DC, USA. FAU - Allen, Kiana C AU - Allen KC AUID- ORCID: 0009-0009-1182-5749 AD - Howard University College of Medicine, Washington, DC, USA. FAU - Kearney, Dy' Quan AU - Kearney DQ AUID- ORCID: 0009-0001-0375-855X AD - Howard University College of Medicine, Washington, DC, USA. FAU - Bell, Brieanna AU - Bell B AUID- ORCID: 0009-0001-0599-6025 AD - Howard University College of Medicine, Washington, DC, USA. FAU - Albornoz, Anthony AU - Albornoz A AUID- ORCID: 0009-0007-1130-5239 AD - Howard University College of Medicine, Washington, DC, USA. FAU - Elkomi, Rawan AU - Elkomi R AD - Department of Internal Medicine, Howard University, Washington, DC, USA. FAU - Ross, Damon AU - Ross D AUID- ORCID: 0009-0004-1337-9168 AD - Howard University College of Medicine, Washington, DC, USA. FAU - Beyene, Elizabeth AU - Beyene E AD - Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Bisrat, Mekdem AU - Bisrat M AD - Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Gillani, Syed Fahad AU - Gillani SF AD - Department of Internal Medicine, Howard University, Washington, DC, USA. FAU - Michael, Miriam AU - Michael M AD - Department of Internal Medicine, Howard University, Washington, DC, USA. AD - Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. LA - eng PT - Journal Article DEP - 20260417 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/complications/epidemiology MH - Retrospective Studies MH - Female MH - *Obesity/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Male MH - *Fractures, Bone/epidemiology/etiology MH - Adult MH - Risk Factors MH - Young Adult MH - Incidence MH - *Hypoglycemic Agents/adverse effects MH - Kaplan-Meier Estimate MH - Adolescent MH - *Diabetes Mellitus, Type 2/drug therapy/complications PMC - PMC13421053 OTO - NOTNLM OT - GLP-1 receptor agonists OT - chronic kidney disease (CKD) OT - fracture risk OT - obesity COIS- All authors declare no conflicts of interest. EDAT- 2026/04/18 13:10 MHDA- 2026/07/30 00:38 PMCR- 2026/07/30 CRDT- 2026/04/17 09:33 PHST- 2026/03/11 00:00 [revised] PHST- 2025/12/23 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/07/30 00:38 [medline] PHST- 2026/04/18 13:10 [pubmed] PHST- 2026/04/17 09:33 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - BCP70566 [pii] AID - 10.1002/bcp.70566 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Aug;92(8):2788-2796. doi: 10.1002/bcp.70566. Epub 2026 Apr 17. PMID- 41994910 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study. PG - 5767-5778 LID - 10.1111/dom.70760 [doi] AB - AIMS: To investigate the association between use of GLP-1 receptor agonists and incident Parkinson's disease. MATERIAL AND METHODS: Cohort study using data from nationwide registers in Denmark, Norway and Sweden and an active-comparator, new-user design. We included 158 961 new users of GLP-1 receptor agonists and 188 065 new users of sulfonylureas, aged 45 years or older. Liraglutide accounted for 72.9% of GLP-1 receptor agonist follow-up time, followed by semaglutide (13.4%), exenatide (7.3%), dulaglutide (5.1%) and lixisenatide (1.3%). The primary outcome was incident Parkinson's disease, defined as a first-ever diagnosis of Parkinson's disease (ICD-10 G20) or Parkinson's disease dementia (ICD-10 F02.3) in national patient registers. Cox regression with propensity score weighting was used to estimate hazard ratios (HRs) and control for confounding. RESULTS: Mean age was 65 years and 43% were female. Incidence rates for Parkinson's disease were 5.2 and 8.0 per 10 000 person-years among GLP-1 receptor agonist and sulfonylurea users, respectively (adjusted HR 0.81 [95% CI 0.68-0.96]). Results were consistent in a 2-year lag-time analysis (HR 0.84 [95% CI 0.70-1.02]) after excluding or censoring users of DPP-4 inhibitors at cohort entry or during follow-up (HR 0.74 [95% CI 0.60-0.93]) and in subgroup analyses by sex and age. CONCLUSION: In this large observational cohort study, use of GLP-1 receptor agonists compared with sulfonylureas was associated with a lower risk of incident Parkinson's disease. These findings support a potential neuroprotective role of GLP-1 receptor agonists, though replication in additional studies is needed. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Engstrom, Arvid AU - Engstrom A AUID- ORCID: 0000-0001-7047-0217 AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Svanstrom, Henrik AU - Svanstrom H AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Hviid, Anders AU - Hviid A AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. AD - Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Pharmacovigilance Research Center, University of Copenhagen, Copenhagen, Denmark. FAU - Eliasson, Bjorn AU - Eliasson B AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. AD - The Swedish National Diabetes Register, Vastra Gotalandsregionen, Gothenburg, Sweden. FAU - Gudbjornsdottir, Soffia AU - Gudbjornsdottir S AD - The Swedish National Diabetes Register, Vastra Gotalandsregionen, Gothenburg, Sweden. AD - Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Wintzell, Viktor AU - Wintzell V AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Hveem, Kristian AU - Hveem K AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Faculty of Medicine, HUNT Research Center, NTNU-Norwegian University of Science and Technology, Levanger, Norway. FAU - Jonasson, Christian AU - Jonasson C AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Faculty of Medicine, HUNT Research Center, NTNU-Norwegian University of Science and Technology, Levanger, Norway. FAU - Melbye, Mads AU - Melbye M AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA. AD - Danish Cancer Institute, Copenhagen, Denmark. FAU - Ueda, Peter AU - Ueda P AUID- ORCID: 0000-0002-3275-8743 AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Pasternak, Bjorn AU - Pasternak B AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. LA - eng GR - Vetenskapsradet/ GR - Lundbeck Foundation/ GR - Region Stockholm/ GR - Novo Nordisk Fonden/ GR - Dr. Margaretha Nilsson's Foundation for Medical Research/ GR - Karolinska Institutet/ GR - Strategic Research Area Epidemiology programme/ GR - Independent Research Foundation Denmark/ GR - Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/ GR - Danish Cancer Society/ PT - Journal Article DEP - 20260417 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Insulin Secretagogues) RN - 839I73S42A (Liraglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sulfonylurea Compounds) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - Denmark/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use MH - Incidence MH - Insulin Secretagogues MH - Liraglutide/therapeutic use MH - Norway/epidemiology MH - *Parkinson Disease/epidemiology/prevention & control MH - Recombinant Fusion Proteins/therapeutic use MH - Registries MH - Semaglutide/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Sweden/epidemiology MH - Glucagon-Like Peptide 1/analogs & derivatives PMC - PMC13243990 OTO - NOTNLM OT - GLP-1 analogue OT - disease prevention OT - observational study OT - pharmaco-epidemiology COIS- The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and have the following declarations. Dr. Christian Jonasson is an employee of NordicRWE. Dr. Bjorn Eliasson reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, Novo Nordisk and Sanofi outside the submitted work. Dr. Henrik Svanstrom is a former employee of IQVIA. Prof. Anders Hviid is a scientific advisory board member of VAC4EU. The other authors declare no conflicts of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/06/15 11:33 PMCR- 2026/06/08 CRDT- 2026/04/17 06:03 PHST- 2026/03/26 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/27 00:00 [accepted] PHST- 2026/06/15 11:33 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/17 06:03 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70760 [pii] AID - 10.1111/dom.70760 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5767-5778. doi: 10.1111/dom.70760. Epub 2026 Apr 17. PMID- 41994903 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Semaglutide Treatment in Young Adults Living With Type 2 Diabetes: A Post Hoc Analysis From the SUSTAIN and PIONEER Clinical Trials. PG - 5787-5802 LID - 10.1111/dom.70770 [doi] AB - AIMS: Young adults (aged 40- 50 years). Selected safety outcomes were assessed, focusing on serious adverse events (SAEs) and gastrointestinal SAEs from the programmes. RESULTS: Findings indicate a reduction in HbA(1c) levels and BW in participants across all age subgroups that were treated with semaglutide, particularly in young adults versus other age subgroups. The proportion of participants experiencing SAEs was overall comparable between semaglutide treatment and comparators across age subgroups and administration route. CONCLUSIONS: Semaglutide shows notable and consistent efficacy in reducing HbA(1c) and BW across all age subgroups with T2D, including young adults. Effective glucose- and weight-lowering interventions in people living with T2D at an earlier stage in life may reduce the high risk of future health complications associated with developing T2D as a younger adult. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zaccardi, Francesco AU - Zaccardi F AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Arslan, Ecenur Guder AU - Arslan EG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bardtrum, Lars AU - Bardtrum L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Goldney, Jonathan AU - Goldney J AUID- ORCID: 0000-0001-8553-8296 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Ising, Erik AU - Ising E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Priyadarshini, Prachi AU - Priyadarshini P AD - Novo Nordisk GBS, Bengaluru, India. FAU - Slater, Tommy AU - Slater T AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. LA - eng GR - Novo Nordisk/ GR - NIHR201165/National Institute for Health and Care Research (NIHR)/ GR - NIHR Leicester Biomedical Research Centre/ GR - 223512/Z/21/Z/Wellcome Trust Leicestershire Healthcare Inequalities Improvement Doctoral Training Programme/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20260417 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Adult MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis MH - Male MH - Middle Aged MH - Young Adult MH - Treatment Outcome MH - Body Weight/drug effects MH - Blood Glucose/drug effects MH - Age Factors MH - Administration, Oral MH - Injections, Subcutaneous PMC - PMC13243996 OTO - NOTNLM OT - GLP-1 OT - cohort study OT - glycaemic control OT - meta-analysis OT - semaglutide OT - type 2 diabetes COIS- F.Z. acted as a consultant/advisor for Servier, Menarini, Daiichi Sankyo, and Adelphi Real World. M.J.D. has acted as a consultant/advisor and speaker for Eli Lilly, Novo Nordisk, and Sanofi, has attended advisory boards for Abbvie, Amgen, AstraZeneca, Biomea Fusion, Carmot/Roche, Sanofi, Zealand Pharma, Regeneron, GSK, and EktaH, and as a speaker for AstraZeneca and Boehringer Ingelheim. She has received grants from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. P.P., L.B., and E.I. are employees and shareholders of Novo Nordisk. E.G.A. was an employee of Novo Nordisk at the time of drafting this manuscript. V.R.A. has institutional contracts with Amgen, Applied Therapeutics, AstraZenaca, Biommea, Boehringer Ingelheim, Corcept, Eli Lilly, Fractyl, Novo Nordisk, Pfizer, Recordati, Rhythm, and Servier. V.R.A. has also served as a consultant for Baim Institute for Clinical Research, Mediflix, Roche, and Sanofi. EDAT- 2026/04/17 13:25 MHDA- 2026/06/13 00:38 PMCR- 2026/06/08 CRDT- 2026/04/17 06:03 PHST- 2026/04/01 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/04/06 00:00 [accepted] PHST- 2026/06/13 00:38 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/17 06:03 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70770 [pii] AID - 10.1111/dom.70770 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5787-5802. doi: 10.1111/dom.70770. Epub 2026 Apr 17. PMID- 41992023 OWN - NLM STAT- MEDLINE DCOM- 20260608 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis. PG - 5761-5766 LID - 10.1111/dom.70742 [doi] AB - AIMS: To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA). MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component. RESULTS: Nineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions >/= 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63). CONCLUSIONS: Higher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lu, Ying AU - Lu Y AD - Ividence Inc, Newark, Delaware, USA. FAU - Chen, Jiajie AU - Chen J AD - Ividence Inc, Newark, Delaware, USA. FAU - Guo, Yuqing AU - Guo Y AD - Ividence Inc, Newark, Delaware, USA. FAU - Ding, Hao AU - Ding H AD - Ividence Inc, Newark, Delaware, USA. FAU - Liu, Yu-Lun AU - Liu YL AD - UT Southwestern Medical Center, Peter O'Donnell Jr. School of Public Health, Dallas, Texas, USA. FAU - Van Name, Michelle A AU - Van Name MA AD - Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Sharifi, Mona AU - Sharifi M AD - Section of General Pediatrics, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260416 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Adult MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Injections, Subcutaneous MH - Liraglutide/administration & dosage MH - *Obesity/drug therapy/complications/metabolism MH - *Overweight/drug therapy/complications/metabolism MH - Randomized Controlled Trials as Topic MH - Semaglutide/administration & dosage MH - Weight Loss/drug effects MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13243969 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - network meta-analysis OT - weight management COIS- The authors declare no conflicts of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/06/08 19:42 PMCR- 2026/06/08 CRDT- 2026/04/16 23:36 PHST- 2026/03/11 00:00 [revised] PHST- 2026/02/02 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/06/08 19:42 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/16 23:36 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70742 [pii] AID - 10.1111/dom.70742 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5761-5766. doi: 10.1111/dom.70742. Epub 2026 Apr 16. PMID- 41991422 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1557-8194 (Electronic) IS - 0011-5029 (Linking) VI - 72 IP - 7 DP - 2026 Jul TI - Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review. PG - 102113 LID - S0011-5029(26)00051-9 [pii] LID - 10.1016/j.disamonth.2026.102113 [doi] AB - BACKGROUND: Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerability, and serious adverse events as the primary variables. METHODS: The systematic review, according to the PRISMA 2020 guidelines, analyzed the GLP-1-based anti-obesity pharmacotherapies. Five databases were utilized to extract information from research studies related to the demographic and procedural framework, weight loss, cardiometabolic efficacy, and safety. RESULTS: A total of 15 studies evaluated GLP-1-based and related anti-obesity therapies, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Participants were predominantly female (up to 79.3%), with mean age 22.4-59.8 years, BMI 29.3-43.0 kg/m(2), and common comorbidities including hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, metabolic syndrome, OSA, MASLD, insulin resistance, and PCOS. Weight loss was dose-dependent: semaglutide 2.4 mg/wk. -14.9% to -15.2%, tirzepatide 15-18.5%, liraglutide -8.8-11%, dulaglutide -1.3-2.0%, and dual GIP/GLP-1 therapy up to 21.5%. Glycemic and cardiometabolic improvements included HbA1c reductions up to -1.78%, SBP reductions -5.28 to -7.8 mmHg, and LDL-C decreases up to -11 mg/dL. Gastrointestinal adverse events were common (nausea 14.7-62%, vomiting 3-30.3%, diarrhoea 5-34.9%), while serious events, pancreatitis, and gallbladder complications were rare, with treatment discontinuation generally <15%. CONCLUSION: GLP-1-based and dual GIP/GLP-1 therapies provide substantial, dose-dependent weight loss with additional cardiometabolic benefits. They are generally well tolerated, with mostly mild gastrointestinal adverse events and rare serious complications, supporting their efficacy and safety in managing obesity. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Gunasekaran, Praveen AU - Gunasekaran P AD - Internal Medicine, Madras Medical College, Chennai, India. FAU - Inban, Pugazhendi AU - Inban P AD - Internal Medicine, St Mary's General Hospital and St Clare's Health, USA. Electronic address: ipugazhendi@primehealthcare.com. FAU - Agrawal, Ashita AU - Agrawal A AD - Internal Medicine, St Mary's General Hospital and St Clare's Health, USA. FAU - Thai, Andy AU - Thai A AD - Internal Medicine, Alameda Health System, Highland Hospital, Oakland, USA. FAU - Aravazhi, Prasanna Sakthi AU - Aravazhi PS AD - Internal Medicine, Madras Medical College, Chennai, India. FAU - Tariq, Halla AU - Tariq H AD - Internal Medicine, Mountain View Regional Medical Center, Las Cruces, New Mexico, USA. FAU - Prajjwal, Priyadarshi AU - Prajjwal P AD - Internal Medicine, Bharati Vidyapeeth University Medical College, Pune, India. FAU - John, Jobby AU - John J AD - Internal Medicine, Dr. Somervell Memorial CSI Medical College and Hospital, India. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260415 PL - United States TA - Dis Mon JT - Disease-a-month : DM JID - 0370657 RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Incretins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - Female MH - Incretins/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Diabetes Mellitus, Type 2 MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins OTO - NOTNLM OT - Anti-obesity agents OT - Drug toxicity OT - Gastrointestinal agents OT - Hypoglycemic agents OT - Incretins OT - Obesity OT - Weight loss COIS- Declaration of competing interest The Author(s) declare(s) that there is no conflict of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/05/28 00:29 CRDT- 2026/04/16 21:56 PHST- 2026/05/28 00:29 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/16 21:56 [entrez] AID - S0011-5029(26)00051-9 [pii] AID - 10.1016/j.disamonth.2026.102113 [doi] PST - ppublish SO - Dis Mon. 2026 Jul;72(7):102113. doi: 10.1016/j.disamonth.2026.102113. Epub 2026 Apr 15. PMID- 41991368 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260831 IS - 1424-3911 (Electronic) IS - 1424-3903 (Linking) VI - 26 IP - 6 DP - 2026 Sep TI - Glucagon-like Peptide-1 receptor agonists are not associated with increased risk of pancreatic cancer: A systematic review and meta-analysis. PG - 854-862 LID - S1424-3903(26)00147-X [pii] LID - 10.1016/j.pan.2026.04.005 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for glucose control and weight management. Concerns have arisen regarding a potential association with pancreatic ductal adenocarcinoma (PDAC), though evidence remains conflicting. We performed a systematic review and meta-analysis to evaluate PDAC risk in GLP-1 RA users. METHODS: We included studies with >/=24 weeks of follow-up assessing PDAC incidence in patients treated with GLP-1 RAs. Eligible studies included adults with type 2 diabetes or obesity. Pooled estimates were calculated using random-effects models. Heterogeneity was assessed with I(2), publication bias with Egger's test, and meta-regression explored potential effect modifiers. RESULTS: Sixty studies (49 randomized trials and 11 observational cohorts) including 4,932,290 patients (2,281,546 GLP-1 RA users; 2,650,744 non-users) were analyzed. GLP-1 RA use was not associated with an increased PDAC risk overall (OR 0.688, 95% CI 0.575-0.824; I(2) = 69.4%). An inverse association was observed mainly in observational cohorts, in overweight/obese patients with diabetes, and with prolonged exposure (>52 weeks) and follow-up (>60 weeks). Meta-regression confirmed treatment duration and indication as significant modifiers. Egger's test (p = 0.829) excluded publication bias. CONCLUSIONS: GLP-1 RA therapy was not associated with an increased risk of PDAC. Observational data suggest a possible inverse association, although further high-quality studies are warranted. CI - Copyright (c) 2026 IAP and EPC. Published by Elsevier B.V. All rights reserved. FAU - Lauri, Gaetano AU - Lauri G AD - Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. FAU - Arcidiacono, Paolo Giorgio AU - Arcidiacono PG AD - Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. FAU - Facciorusso, Antonio AU - Facciorusso A AD - Department of Experimental Medicine, Universita del Salento, Lecce, Italy. FAU - Capurso, Gabriele AU - Capurso G AD - Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. FAU - Tacelli, Matteo AU - Tacelli M AD - Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: tacelli.matteo@hsr.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260406 PL - Switzerland TA - Pancreatology JT - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JID - 100966936 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Pancreatic Neoplasms/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Carcinoma, Pancreatic Ductal/chemically induced/epidemiology MH - Risk Factors MH - Obesity/drug therapy/complications OTO - NOTNLM OT - Cancer risk OT - Diabetes OT - GLP-1 receptor agonists OT - Obesity OT - Pancreatic ductal adenocarcinoma EDAT- 2026/04/17 13:25 MHDA- 2026/08/25 23:33 CRDT- 2026/04/16 21:55 PHST- 2025/10/24 00:00 [received] PHST- 2026/02/09 00:00 [revised] PHST- 2026/04/03 00:00 [accepted] PHST- 2026/08/25 23:33 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/16 21:55 [entrez] AID - S1424-3903(26)00147-X [pii] AID - 10.1016/j.pan.2026.04.005 [doi] PST - ppublish SO - Pancreatology. 2026 Sep;26(6):854-862. doi: 10.1016/j.pan.2026.04.005. Epub 2026 Apr 6. PMID- 41987895 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Efficacy and safety of novel antidiabetic drugs in patients with type 2 diabetes and chronic kidney disease: a network meta-analysis. PG - 1750615 LID - 10.3389/fendo.2026.1750615 [doi] LID - 1750615 AB - BACKGROUND: A number of novel antidiabetic drugs have been developed. These drugs include sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). However, the optimal medication for individuals with type 2 diabetes mellitus (T2DM) and comorbid chronic kidney disease (CKD) has not been established. To this end, this study was conducted to compare specific novel antidiabetic drugs regarding efficacy and safety. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications dated as of July 9, 2025. Cochrane risk of bias tool version 2.0 (RoB 2.0) was applied to measure the quality of the publications, and R 4.2.2 and Stata 15.1 were used to execute a Bayesian network meta-analysis (NMA). Primary outcomes encompassed major adverse cardiovascular events (MACEs), composite renal outcomes, and all-cause mortality (ACM). Secondary outcomes comprised adverse events (AEs), hypoglycemia, and cardiovascular death. RESULTS: This NMA incorporated 30 studies, involving 39,844 participants with T2DM and comorbid CKD. The interventions were ranked by performance in various outcomes using the surface under the cumulative ranking curve (SUCRA) values. Sotagliflozin ranked first in reducing MACEs (SUCRA: 90.57%). Empagliflozin ranked first in improving composite renal outcomes (SUCRA: 89.76%) and reducing ACM (SUCRA: 72.38%). Canagliflozin ranked first in reducing AEs (SUCRA: 83.37%). Dapagliflozin + exenatide ranked first in reducing hypoglycemic events (SUCRA: 77.74%). Semaglutide ranked first in reducing cardiovascular mortality (SUCRA: 89.46%). CONCLUSION: Novel antidiabetic drugs offer benefits for patients with T2DM and comorbid CKD. However, the optimal intervention varies for different outcomes. Further clinical studies are anticipated to validate these findings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251146144. CI - Copyright (c) 2026 Zhu, Wang, Zhang, Yang, Zhao, Li, Shi, Zhao and Ma. FAU - Zhu, Xiaojian AU - Zhu X AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Wang, Xingjia AU - Wang X AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhang, Peiru AU - Zhang P AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Yang, Zhuoshi AU - Yang Z AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhao, Na AU - Zhao N AD - Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Li, Jiameng AU - Li J AD - The First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Shi, Yunze AU - Shi Y AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhao, Yichen AU - Zhao Y AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Ma, Jian AU - Ma J AD - Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260331 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Semaglutide MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Treatment Outcome PMC - PMC13076170 OTO - NOTNLM OT - antidiabetic drugs OT - cardiovascular outcomes OT - chronic kidney disease OT - meta-analysis OT - renal outcomes OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/16 13:09 MHDA- 2026/04/16 13:10 PMCR- 2026/03/31 CRDT- 2026/04/16 04:24 PHST- 2025/11/20 00:00 [received] PHST- 2026/03/13 00:00 [revised] PHST- 2026/03/16 00:00 [accepted] PHST- 2026/04/16 13:10 [medline] PHST- 2026/04/16 13:09 [pubmed] PHST- 2026/04/16 04:24 [entrez] PHST- 2026/03/31 00:00 [pmc-release] AID - 10.3389/fendo.2026.1750615 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 31;17:1750615. doi: 10.3389/fendo.2026.1750615. eCollection 2026. PMID- 41986942 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 3 DP - 2026 May TI - A Multicentre, Prospective, Non-Interventional Single-Arm Study Investigating the Impact of Once-Daily Oral Semaglutide in a Real-World Adult Population With Type 2 Diabetes in Mexico. PG - e70219 LID - 10.1002/edm2.70219 [doi] LID - e70219 AB - BACKGROUND: To investigate the oral semaglutide use among Mexican adults with type 2 diabetes. METHODS: PIONEER REAL was a multinational, open-label study evaluating oral semaglutide in patients without prior injectable glucose-lowering treatment. This analysis focuses on data from Mexico. RESULTS: Of 177 patients, 139 (78.5%) completed the study and 111 (62.7%) remained on treatment at the end. The mean (SD) age was 54.0 (10.96) years, 57.6% were women, 59.3% had obesity, and 44.6% had a medical history of cardiovascular disease. The average T2D duration was 5.7 years (SD 6.45), with mean HbA1c at 8.1% (SD 1.85). At week 38, mean HbA1c had decreased to 6.8% (estimated mean [SE] change in HbA1c, -1.3% [0.11]; p < 0.0001), and body weight had decreased from 87.8 kg (19.34) to 85.3 kg (estimated mean [SE] change in body weight, -4.3 kg [0.56]; p < 0.0001), as had waist circumference (estimated mean [SE] change, -3.7 cm [0.54]; p < 0.0001). Additionally, satisfaction with treatment increased over time. Only 6.2% of patients had adverse events leading to withdrawal of semaglutide. CONCLUSIONS: According to this real-world study, starting oral semaglutide treatment in Mexico is associated with notable decreases in both HbA1c levels and body weight among patients with type 2 diabetes. Satisfaction with treatment also improved significantly. Moreover, the safety profile is consistent with that of previous studies. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04601753. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Gonzalez-Galvez, Guillermo AU - Gonzalez-Galvez G AD - Instituto Jalisciense de Investigacion en Diabetes y Obesidad, Guadalajara, Mexico. FAU - Garnica-Cuellar, Juan C AU - Garnica-Cuellar JC AD - Endocrinology Division, Centro Medico Nacional 20 de Noviembre, Institute for Social Security and Services for State, Mexico City, Mexico. AD - Diabetes and Obesity Workgroup, Sociedad Mexicana de Nutricion y Endocrinologia, Mexico City, Mexico. FAU - Colin-Garcia, Miguel Angel AU - Colin-Garcia MA AD - Colegio Mexicano de Obesidad y Nutricion A.C. Jose Maria Rico, Mexico City, Mexico. AD - Hospital Angeles Santa Monica, Mexico City, Mexico. FAU - Ferreira-Hermosillo, Aldo AU - Ferreira-Hermosillo A AUID- ORCID: 0000-0002-5159-9856 AD - Unidad de Investigacion Medica en Enfermedades Endocrinas, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico. FAU - Jimenez-Ramos, Silvia A AU - Jimenez-Ramos SA AD - CICEJ Centro de Investigacion Clinica Endocrinologica de Jalisco, Guadalajara, Mexico. FAU - Contreras-Sandoval, Aleida Y AU - Contreras-Sandoval AY AD - Novo Nordisk Mexico, Mexico City, Mexico. FAU - Cruz-Puente, Patricia AU - Cruz-Puente P AD - Novo Nordisk Mexico, Mexico City, Mexico. FAU - Duarte-Vega, Manuel AU - Duarte-Vega M AD - Division de Medicina Interna, Hospital Civil Juan I. Menchaca, Guadalajara, Mexico. LA - eng SI - ClinicalTrials.gov/NCT04601753 GR - Novo Nordisk Pharma/ PT - Journal Article PT - Multicenter Study PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Mexico/epidemiology MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Prospective Studies MH - Administration, Oral MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - Adult MH - Aged MH - Treatment Outcome PMC - PMC13083220 OTO - NOTNLM OT - Mexico OT - diabetes treatment satisfaction OT - glycaemic control OT - oral semaglutide OT - real-world evidence OT - type 2 diabetes OT - weight loss COIS- Medical writing and editorial assistance were provided by Content Ed Net (Madrid, Spain). Editorial management was conducted by Reprints Unlimited Mexico. These services were funded by Novo Nordisk, in accordance with Good Publication Practice guidelines (www.ismpp.org/gpp-2022). Aleida Y. Contreras-Sandoval and Patricia Cruz-Puente are employees of Novo Nordisk. The rest of the authors declare not competing interests for this publication. EDAT- 2026/04/16 13:09 MHDA- 2026/04/16 13:10 PMCR- 2026/04/15 CRDT- 2026/04/16 00:13 PHST- 2026/03/13 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/04/16 13:10 [medline] PHST- 2026/04/16 13:09 [pubmed] PHST- 2026/04/16 00:13 [entrez] PHST- 2026/04/15 00:00 [pmc-release] AID - EDM270219 [pii] AID - 10.1002/edm2.70219 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 May;9(3):e70219. doi: 10.1002/edm2.70219. PMID- 41984352 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20261010 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 31 IP - 1 DP - 2026 Apr 15 TI - Tirzepatide versus dulaglutide in heart failure: another SURPASS attempt yielding a tie. LID - 57 [pii] LID - 10.1007/s10741-026-10627-1 [doi] AB - Heart failure (HF) is a major driver of morbidity in individuals with type 2 diabetes (T2D). While incretin-based therapies consistently reduce atherosclerotic cardiovascular (CV) events, their impact on HF outcomes remains uncertain. The SURPASS-CVOT (Comparison of tirzepatide and dulaglutide on major adverse CV events in participants with T2D and atherosclerotic disease), the first CV outcome trial directly comparing the dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists receptor agonist (GIP/GLP-1 RAs) tirzepatide with the selective GLP-1 RA dulaglutide, demonstrated noninferiority of tirzepatide for 3-point major adverse CV events (MACE), with greater metabolic and renal benefits. In the prespecified HF subgroup (20% of the trial population, defined according to investigator-reported medical history), tirzepatide reproduced the larger metabolic and renal benefits observed in the overall cohort, including greater weight loss, superior glycemic control, and a slower decline in renal function compared with dulaglutide, with similar effects in participants with and without HF. Tirzepatide was non inferior to dulaglutide for 3-point MACE irrespective of HF history. No differences were observed between treatment groups for composite HF endpoints (all-cause death or HF events; CV death or HF events) or HF events alone, both in participants with and without HF. However, as the trial was not powered for comparisons within the HF subgroup and HF endpoints were not included in the multiplicity-controlled testing hierarchy, these findings should be considered exploratory. This meeting report critically examines the SURPASS-CVOT HF subanalysis and place its results within the broader evidence on incretin-based therapies in patients with HF. FAU - Busti, Matteo AU - Busti M AD - CHRU de Nancy, Centre d'Investigation Clinique Plurithematique 1433, INSERM, Universite de Lorraine, INSERM U1116 - DCAC, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. AD - Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy. FAU - Canonico, Mario Enrico AU - Canonico ME AD - CPC Clinical Research, University of Colorado, Denver, CO, USA. FAU - Keramida, Kalliopi AU - Keramida K AD - Cardiology Department, General Anti-Cancer Oncological Hospital Agios Savvas, Athens, Greece. AD - Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens Medical School, Athens, Greece. FAU - Palazzuoli, Alberto AU - Palazzuoli A AD - Cardiovascular Diseases Unit Cardio Thoracic and Vascular Department Le Scotte Hospital Siena, University of Siena, Siena, Italy. FAU - Kato, Eri AU - Kato E AD - Department of Cardiovascular Medicine, Kyoto University Hospital, Kyoto, Japan. FAU - Sakata, Yasuhiko AU - Sakata Y AD - Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan. AD - Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan. FAU - Alexy, Tamas AU - Alexy T AD - University of Minnesota, Minnesota, MN, 55127, USA. FAU - Grupper, Avishay AU - Grupper A AD - Gray, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. FAU - Nodari, Savina AU - Nodari S AD - Department of Cardiology, University of Brescia, Brescia, Italy. FAU - Ojji, Dike B AU - Ojji DB AD - Department of Internal Medicine, University of Abuja, Abuja, Nigeria. FAU - Sverdlov, Aaron L AU - Sverdlov AL AD - College of Health Medicine and Wellbeing, University of Newcastle, Callaghan, Australia. AD - Cardiovascular Department, John Hunter Hospital, New Lambton Heights, Australia. FAU - Guimaraes, Patricia O AU - Guimaraes PO AD - Hospital Israelita Albert Einstein, Sao Paulo, Brazil. FAU - Musella, Francesca AU - Musella F AD - Department of Clinical Science and Education, Sodersjukhuset Karolinska Institute, Stockholm, Sweden. FAU - Ambrosy, Andrew P AU - Ambrosy AP AD - Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA. AD - Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, USA. FAU - Girerd, Nicolas AU - Girerd N AD - CHRU de Nancy, Centre d'Investigation Clinique Plurithematique 1433, INSERM, Universite de Lorraine, INSERM U1116 - DCAC, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. FAU - Monzo, Luca AU - Monzo L AD - CHRU de Nancy, Centre d'Investigation Clinique Plurithematique 1433, INSERM, Universite de Lorraine, INSERM U1116 - DCAC, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. l.monzo@tiscali.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260415 PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - OYN3CCI6QE (Tirzepatide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Heart Failure/drug therapy/complications MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Recombinant Fusion Proteins/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Heart failure OT - Incretins OT - Obesity OT - Type 2 diabetes COIS- Declarations. Competing interests: M.E.C. receives salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado. Y.S. reports lecture fees from AstraZeneca, Ono Pharmaceutical, Eli Lilly, and NovoNordisk. A.L.S. has received research grants from AstraZeneca, Glaxo Smith Kline, Novartis and RACE Oncology; and honoraria from Novartis, Eli Lilly, Bayer, AstraZeneca, Janssen, Cipla, Glaxo Smith Kline, Novo Nordisk and Boehringer Ingelheim. P.O.G. reports lecture fees from Libbs Pharmaceuticals. A.P.A. has received relevant research support through grants to his institution from the National Institutes of Health (R01HL173866 and R01AG091005), the Food and Drug Administration (U01FD008704), The American Heart Association, The Permanente Medical Group, Kaiser Permanente Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Abiomed, Amarin Pharma, Inc., Bayer Pharma AG, Boehringer Ingelheim, Cordio Medical, Edwards Lifesciences LLC, Esperion Therapeutics, Inc., Merck, and Novartis. Consulting for Bristol Meyer Squibb, Bayer Pharma AG, Corstasis, Merck, Novo Nordisk, Pharmacosmos A/S, Pfizer, scPharma, SQ Innovation, Reprieve Cardiovascular, and VisCardia. N.G. reports honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, NovoNordisk, Roche Diagnostics, NP Medical and Echosens. L.M. reports a travel grant from Boehringer Ingelheim. All conflicts of interest have been declared outside the present work. The other authors declare no conflicts of interest. EDAT- 2026/04/15 13:53 MHDA- 2026/06/28 06:36 CRDT- 2026/04/15 11:23 PHST- 2025/12/09 00:00 [received] PHST- 2026/04/06 00:00 [accepted] PHST- 2026/03/17 00:00 [revised] PHST- 2026/06/28 06:36 [medline] PHST- 2026/04/15 13:53 [pubmed] PHST- 2026/04/15 11:23 [entrez] AID - 10.1007/s10741-026-10627-1 [pii] AID - 10.1007/s10741-026-10627-1 [doi] PST - epublish SO - Heart Fail Rev. 2026 Apr 15;31(1):57. doi: 10.1007/s10741-026-10627-1. PMID- 41984016 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260922 IS - 1558-3597 (Electronic) IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 87 IP - 21 DP - 2026 Jun 2 TI - Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus. PG - 2963-2977 LID - S0735-1097(26)05724-4 [pii] LID - 10.1016/j.jacc.2026.02.5123 [doi] AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have established cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM), with similar class-level effectiveness found in previous studies. However, real-world comparative effectiveness assessments of individual agents remain limited. OBJECTIVES: The goal of this study was to compare the cardiovascular effectiveness of individual GLP-1RAs and SGLT2Is. METHODS: We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases. The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin). Empagliflozin (393,499; 31.6%), semaglutide (235,585; 18.9%), dapagliflozin (208,666; 16.8%), and dulaglutide (207,348; 16.8%) were most commonly used. A secondary subgroup analysis included 316,242 patients with established cardiovascular diseases (CVDs). Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure). Secondary outcomes included the individual components. HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding. Random-effects meta-analysis produced summary HR estimates across data sources that passed diagnostics. RESULTS: Across the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes. For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup. Study diagnostics confirmed adequate equipoise, covariate balance, and statistical power to detect similarity in HRs between 0.8 and 1.2 for commonly used agents. CONCLUSIONS: In this large-scale real-world study, individual GLP-1RAs and SGLT2Is exhibited largely comparable cardiovascular benefits, including in patients with established CVD. These findings align with network meta-analytic estimates from major cardiovascular outcome trials and broadly support current treatment guidelines. Clinical choices should be guided by relevant factors such as safety, adherence, tolerability, cost, and patient preference, where further work is needed. CI - Published by Elsevier Inc. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. FAU - Wu, Ruopeng AU - Wu R AD - Department of Mathematics, College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Observational Health Data Analytics, Janssen Research and Development, LLC, Titusville, New Jersey, USA. FAU - Aminorroaya, Arya AU - Aminorroaya A AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Chen, Hsin Yi AU - Chen HY AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Chai, Yi AU - Chai Y AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Shenzhen University Medical School, School of Public Health, Shenzhen University, Shenzhen, China. FAU - Dhingra, Lovedeep Singh AU - Dhingra LS AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Hsu, Jason C AU - Hsu JC AD - International PhD Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan. FAU - Kim, Chungsoo AU - Kim C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation (CORE), Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Lau, Wallis C Y AU - Lau WCY AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China; Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom. FAU - Man, Kenneth K C AU - Man KKC AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China; Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom. FAU - Minty, Evan AU - Minty E AD - Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada. FAU - Morales, Daniel R AU - Morales DR AD - Usher Institute, University of Edinburgh, Edinburgh, United Kingdom. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Thangraraj, Phyllis AU - Thangraraj P AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Van Zandt, Mui AU - Van Zandt M AD - Real World Solutions, IQVIA, Durham, North Carolina, USA. FAU - Yin, Can AU - Yin C AD - Real World Solutions, IQVIA, Shanghai, China. FAU - Khera, Rohan AU - Khera R AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation (CORE), Yale New Haven Hospital, New Haven, Connecticut, USA; Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA; Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA. FAU - Suchard, Marc A AU - Suchard MA AD - Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA; Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA; Department of Biomathematics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. Electronic address: msuchard@ucla.edu. LA - eng GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HG006139/HG/NHGRI NIH HHS/United States GR - R01 HL169171/HL/NHLBI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - K23 HL153775/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260415 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Semaglutide/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome PMC - PMC13191718 MID - NIHMS2170338 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - cardiovascular outcomes OT - comparative effectiveness OT - real-world evidence OT - type 2 diabetes mellitus COIS- Funding Support and Author Disclosures This study was partially funded through the National Institutes of Health grants K23 HL153775, R01 LM006910, R01 HG006139, R01HL69954, R01HL169171, R35GM160458, and T15LM00707934 and an Intergovernmental Personnel Act agreement with the U.S. Department of Veterans Affairs. The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Bu has received support from the U.S. Food and Drug Administration, Gates Foundation, and Patient-Centered Outcomes Research Institute outside of the scope of this work. Dr Ostropolets is an employee of Janssen Research and Development. Dr Lau received research funding from Diabetes UK outside the scope of this work. Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the scope of this work. Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship. Ms Van Zandt is an employee and shareholder of IQVIA. Ms Yin is employee of IQVIA. Dr Khera is an associate editor at JAMA; has received support from the Doris Duke Charitable Foundation, Bristol Myers Squibb, Novo Nordisk, and BridgeBio outside the scope of this work; and is a cofounder of Evidence2Health and Ensight-AI. Dr Hripcsak have received contracts and grants from the U.S. Food and Drug Administration, the U.S. National Institutes of Health, and Janssen Research & Development outside the scope of this work. Dr Suchard have received contracts and grants from the U.S. Food and Drug Administration, the U.S. National Institutes of Health, and Janssen Research & Development outside the scope of this work; and receives contracts from Gilead Sciences outside the scope of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2026/04/15 13:54 MHDA- 2026/06/11 05:39 PMCR- 2026/05/22 CRDT- 2026/04/15 10:30 PHST- 2025/08/27 00:00 [received] PHST- 2026/02/26 00:00 [revised] PHST- 2026/02/27 00:00 [accepted] PHST- 2026/06/11 05:39 [medline] PHST- 2026/04/15 13:54 [pubmed] PHST- 2026/04/15 10:30 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - S0735-1097(26)05724-4 [pii] AID - 10.1016/j.jacc.2026.02.5123 [doi] PST - ppublish SO - J Am Coll Cardiol. 2026 Jun 2;87(21):2963-2977. doi: 10.1016/j.jacc.2026.02.5123. Epub 2026 Apr 15. PMID- 41974347 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 52 IP - 3 DP - 2026 May TI - Comparative cardiovascular effectiveness of GLP-1RAs versus DPP-4is in dialysis patients with type 2 diabetes: a target trial emulation. PG - 101760 LID - S1262-3636(26)00039-X [pii] LID - 10.1016/j.diabet.2026.101760 [doi] AB - AIM: Patients with type 2 diabetes (T2D) receiving dialysis have a very high risk of cardiovascular events. Evidence for the cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this population remains limited. Here, we assessed this issue using a target trial emulation framework. METHODS: We conducted a cohort study using a Japanese administrative claims database. We included adults aged 20 years or older with T2D receiving maintenance dialysis who initiated a GLP-1RA or a DPP-4i between April 2015 and March 2023. The primary outcome was the 3-year risk of major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, stroke, and cardiovascular death. The observational analogue of the per-protocol effect was estimated using pooled logistic regression with inverse probability weighting to adjust for baseline and time-varying confounders. RESULTS: Among 4793 patients (557 GLP-1RA initiators and 4236 DPP-4i initiators), the estimated 3-year risk of MACE was 29.7% (95% CI, 22.3% to 38.3%) for GLP-1RA users and 37.6% (95% CI, 35.2% to 40.8%) for DPP-4i users, giving a risk difference of -8.0% (95% CI, -15.5% to 0.9%) and risk ratio of 0.79 (95% CI, 0.59 to 1.03). CONCLUSION: Compared with DPP-4is, sustained use of GLP-1RAs may reduce the risk of MACE among patients with T2D receiving maintenance dialysis. These findings suggest a potential cardiovascular benefit but require confirmation in randomized controlled trials before introduction into clinical practice. CI - Copyright (c) 2026 Elsevier Masson SAS. All rights reserved. FAU - Shimada, Hiroki AU - Shimada H AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. FAU - Fukasawa, Toshiki AU - Fukasawa T AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: fukasawa.toshiki.4a@kyoto-u.ac.jp. FAU - Mizuno, Kayoko AU - Mizuno K AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. FAU - Okazawa, Yuki AU - Okazawa Y AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. FAU - Yokogawa, Kasumi AU - Yokogawa K AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. FAU - Kawakami, Koji AU - Kawakami K AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyo-ku, Kyoto 606-8501, Japan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260412 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Middle Aged MH - *Renal Dialysis MH - Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Cohort Studies MH - Japan/epidemiology OTO - NOTNLM OT - Diabetes OT - Dipeptidyl peptidase-4 inhibitors OT - End-stage kidney disease OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse cardiovascular events OT - Target trial emulation COIS- Declaration of competing interest Toshiki Fukasawa was previously employed by the Department of Digital Health and Epidemiology at Kyoto University with support from Eisai Co., Ltd. and Kyowa Kirin Co., Ltd.; he has received research funding from AstraZeneca K.K. and the Pfizer Health Research Foundation, consulting fees from Asahi Kasei Pharma Corporation, JMDC Inc., MSD K.K., and Real World Data Co., Ltd., and honoraria from DeSC Healthcare, Inc., EPS Corporation, the Foundation for Biomedical Research and Innovation at Kobe, MeDiCU Inc., and the Research Institute of Healthcare Data Science; and his spouse is employed by MSD K.K. Kayoko Mizuno was previously employed by the Department of Digital Health and Epidemiology at Kyoto University with support from Eisai Co., Ltd. and Kyowa Kirin Co., Ltd. Koji Kawakami has received research funding from AstraZeneca K.K., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., OMRON Corporation, and Toppan Inc.; consulting fees from Advanced Medical Care Inc., JMDC Inc., LEBER Inc., Santen Pharmaceutical Co., Ltd., Shin Nippon Biomedical Laboratories Ltd., and Ubicom Holdings, Inc.; executive compensation from Cancer Intelligence Care Systems, Inc. and Mytreya Inc.; and honoraria from Kyoto University Original Co., Ltd., Pharma Business Academy Co., Ltd., SANSHO Co., Ltd., Shionogi & Co., Ltd., and Taisho Pharmaceutical Co., Ltd. The other authors have no conflict of interest. EDAT- 2026/04/14 00:31 MHDA- 2026/05/21 05:33 CRDT- 2026/04/13 19:37 PHST- 2026/03/04 00:00 [received] PHST- 2026/04/07 00:00 [revised] PHST- 2026/04/09 00:00 [accepted] PHST- 2026/05/21 05:33 [medline] PHST- 2026/04/14 00:31 [pubmed] PHST- 2026/04/13 19:37 [entrez] AID - S1262-3636(26)00039-X [pii] AID - 10.1016/j.diabet.2026.101760 [doi] PST - ppublish SO - Diabetes Metab. 2026 May;52(3):101760. doi: 10.1016/j.diabet.2026.101760. Epub 2026 Apr 12. PMID- 41974037 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 2471-254X (Electronic) IS - 2471-254X (Linking) VI - 10 IP - 5 DP - 2026 May 1 TI - GLP-1RA plus SGLT2i combination therapy and liver fibrosis progression in MASLD with type 2 diabetes. LID - 10.1097/HC9.0000000000000949 [doi] LID - e0949 AB - BACKGROUND AND AIM: The combined use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide synergistic benefits for liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). We evaluated the comparative effectiveness of GLP-1RA plus SGLT2i versus GLP-1RA monotherapy on liver fibrosis progression. METHODS: We conducted a retrospective cohort study using data from the Mass General Brigham healthcare network (2010-2024). Adults with MASLD and T2DM initiating GLP-1RA therapy were included if their baseline FIB-4 scores indicated low-risk (<1.3) or intermediate-risk (1.3-2.67) categories. Combination therapy was defined as concurrent SGLT2i use for >/=50% of the GLP-1RA treatment period. The primary outcome was fibrosis progression, defined as advancement to a high-risk FIB-4 category. The secondary outcome was hepatic complications (cirrhosis, hepatocellular carcinoma, liver transplantation, or decompensation). Propensity score matching (1:2) was performed to minimize confounding. RESULTS: After matching, 879 combination therapy users were compared with 1690 monotherapy users. Combination therapy was associated with a significantly lower risk of fibrosis progression (3.10 vs. 4.01/100 person-years; HR 0.76, 95% CI 0.61-0.95) and a numerically lower incidence of hepatic complications (1.05 vs. 1.34/100 person-years; HR 0.76, 95% CI 0.53-1.09). Subgroup analyses showed consistent protective associations, with a significant benefit observed among patients with a BMI /=90-day and >/=180-day landmark analyses. CONCLUSIONS: GLP-1RA plus SGLT2i therapy was associated with reduced fibrosis progression compared with GLP-1RA monotherapy in MASLD and T2DM. CI - Copyright (c) 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases. FAU - Choi, Jonggi AU - Choi J AUID- ORCID: 0000-0002-7470-5850 AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Mitchell, Gabby AU - Mitchell G AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Nguyen, Vy H AU - Nguyen VH AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Przybyszewski, Eric AU - Przybyszewski E AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Song, Jiunn AU - Song J AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Carroll, Allison AU - Carroll A AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Michta, Megan AU - Michta M AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Almazan, Erik AU - Almazan E AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Simon, Tracey G AU - Simon TG AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Chung, Raymond T AU - Chung RT AD - Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article DEP - 20260413 PL - United States TA - Hepatol Commun JT - Hepatology communications JID - 101695860 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Liver Cirrhosis/etiology/drug therapy MH - Female MH - Disease Progression MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13075898 OTO - NOTNLM OT - GLP-1RA OT - MASLD OT - liver fibrosis COIS- The authors have no conflicts to report. EDAT- 2026/04/13 18:31 MHDA- 2026/04/13 18:32 PMCR- 2026/04/13 CRDT- 2026/04/13 17:23 PHST- 2025/11/30 00:00 [received] PHST- 2026/02/06 00:00 [accepted] PHST- 2026/04/13 18:32 [medline] PHST- 2026/04/13 18:31 [pubmed] PHST- 2026/04/13 17:23 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - 02009842-202605010-00006 [pii] AID - HEP4-25-1611 [pii] AID - 10.1097/HC9.0000000000000949 [doi] PST - epublish SO - Hepatol Commun. 2026 Apr 13;10(5):e0949. doi: 10.1097/HC9.0000000000000949. eCollection 2026 May 1. PMID- 41974004 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260806 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 5_Supplement DP - 2026 May TI - Endocrinology: What You May Have Missed in 2025. PG - e2600925 LID - 10.7326/ANNALS-26-00925 [doi] AB - During 2025, endocrinology witnessed the expansion of pharmacotherapeutic options for type 2 diabetes (T2DM), obesity, and metabolic dysfunction-associated steatohepatitis (MASH); increasing complexity of treatment algorithms, including choices for intensification of therapy; and heightened concern about emerging side effects of commonly used medications. From the wealth of studies published in 2025, this article notes 9 studies that offer critical information for clinicians who manage or comanage patients with endocrine and metabolic disorders, including T2DM, obesity, and MASH. One of the 9 articles reviews the effectiveness of diabetes self-management education and support interventions, an important component of diabetes care, in improving hemoglobin A(1c) (HbA(1c)). Another is focused on comparing HbA(1c) lowering when escalating the dose of dulaglutide versus switching to tirzepatide in people with T2DM. Two of the 9 articles are focused on potential side effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs), including gastrointestinal side effects and nonarteritic anterior ischemic optic neuropathy. One article summarizes the risk for life-threatening pituitary immune-related adverse events caused by immune checkpoint inhibitors; another explores the use of GLP-1RAs in MASH. One additional study explores the risk for urogenital infections in patients with diabetes receiving sodium-glucose cotransporter-2 inhibitors (SGLT-2is) versus GLP-1RAs. Another study explores cardiovascular, kidney, and safety outcomes with canagliflozin (an SGLT-2i). The last article explores the efficacy and safety of finerenone in T2DM. The results of each study have a direct effect on clinical care for patients who often present to physicians who are not endocrinologists. FAU - Escudero, Carlos AU - Escudero C AD - McMaster University, Hamilton, Ontario, Canada (C.E.). FAU - Havranek, Kathryn AU - Havranek K AD - Duke University, Durham, North Carolina (K.H., M.M.C., B.B.). FAU - Martinez Cruz, Maria AU - Martinez Cruz M AD - Duke University, Durham, North Carolina (K.H., M.M.C., B.B.). FAU - Batch, Bryan AU - Batch B AUID- ORCID: 0000-0002-7138-2064 AD - Duke University, Durham, North Carolina (K.H., M.M.C., B.B.). LA - eng PT - Journal Article PT - Review DEP - 20260414 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Endocrinology/trends MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy/complications MH - Tirzepatide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/04/13 18:31 MHDA- 2026/05/18 18:32 CRDT- 2026/04/13 17:02 PHST- 2026/05/18 18:32 [medline] PHST- 2026/04/13 18:31 [pubmed] PHST- 2026/04/13 17:02 [entrez] AID - 10.7326/ANNALS-26-00925 [doi] PST - ppublish SO - Ann Intern Med. 2026 May;179(5_Supplement):e2600925. doi: 10.7326/ANNALS-26-00925. Epub 2026 Apr 14. PMID- 41973737 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260822 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 8 DP - 2026 Aug 1 TI - Clinical Potential of GIP in Type 2 Diabetes and Obesity. PG - 1308-1317 LID - 10.2337/dci25-0141 [doi] AB - Incretin-based pharmacology has revolutionized the medical treatment of type 2 diabetes and obesity. The most effective drug to date is tirzepatide, a dual incretin receptor agonist that engages both the glucagon-like peptide 1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). While the relative contributions of GIPR and GLP-1R actions to the clinical effects of tirzepatide have not been established, the potency of this agent has reignited interest in the clinical potential of GIPR agonism. Here, we discuss incretin biology as it relates to metabolic pharmacology and contextualize the mechanisms by which GIPR activity could contribute to the development of new and effective drugs. We explore current and future applications of GIPR agonists and antagonists, to underscore the potential that this signaling system could add to treatment of type 2 diabetes and obesity. CI - (c) 2026 by the American Diabetes Association. FAU - Nauck, Michael AU - Nauck M AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum, Sankt Josef-Hospital, Ruhr-University, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Gribble, Fiona AU - Gribble F AUID- ORCID: 0000-0002-4232-2898 AD - Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K. FAU - Reimann, Frank AU - Reimann F AD - Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K. FAU - D'Alessio, David A AU - D'Alessio DA AD - Duke Molecular Physiology Institute, Durham, NC. AD - Division of Endocrinology, Department of Medicine, Duke University, Durham, NC. FAU - Campbell, Jonathan E AU - Campbell JE AUID- ORCID: 0000-0003-4358-6331 AD - Duke Molecular Physiology Institute, Durham, NC. AD - Division of Endocrinology, Department of Medicine, Duke University, Durham, NC. AD - Department of Pharmacology and Cancer Biology, Duke University, Durham, NC. LA - eng GR - DK141090/DK/NIDDK NIH HHS/United States GR - P30-K124723/DK/NIDDK NIH HHS/United States GR - DK132324/DK/NIDDK NIH HHS/United States GR - R01 DK125353/DK/NIDDK NIH HHS/United States GR - R01 DK143978/DK/NIDDK NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - R01 DK141090/DK/NIDDK NIH HHS/United States GR - DK143978/DK/NIDDK NIH HHS/United States GR - R01 DK046492/DK/NIDDK NIH HHS/United States GR - DK046492/DK/NIDDK NIH HHS/United States GR - R37 DK046492/DK/NIDDK NIH HHS/United States GR - R01 DK123075/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Incretins) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Obesity/drug therapy/metabolism MH - *Gastric Inhibitory Polypeptide/therapeutic use/metabolism MH - Receptors, Gastrointestinal Hormone/agonists/metabolism/antagonists & inhibitors MH - Incretins/therapeutic use MH - Tirzepatide MH - Animals MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13385947 COIS- Duality of Interest. M.N. has been a member of advisory boards of or has consulted with Eli Lilly & Co., Pfizer, Regor, Sun Pharma, and Structure Therapeutics (Gasherbrum). He has also served on the speakers' bureau of Eli Lilly & Co., Medscape, Medical Learning Institute, and Novo Nordisk and is a member on a data monitoring and safety board for a clinical trial with Inventiva. F.G. and F.R. have received research funding from Eli Lilly and AstraZeneca and sponsorship for hosting the 5th European Incretin Study Group Meeting in Cambridge, U.K. (April 2024), from AstraZeneca, Eli Lilly, Mercodia, and Sun Pharma. F.G. has consulted for Kallyope, Roche, and Antag Therapeutics. D.D. has consulted for Eli Lilly and Co., Sun Pharma, Structure Therapeutics, MBX Biosciences, Fractyl Health, Proteostasis Therapeutics, Arrowhead Pharmaceuticals, and Vertex Pharmaceuticals. The Campbell group receives funding for basic science from Novo Nordisk, Eli Lilly and Co., Merck, Structure Therapeutics, and Prostasis. J.E.C. has served as an advisor/consultant in the past 12 months to Arrowhead Pharmaceuticals, Boehringer Ingelheim, Neurocrine Biosciences, Prostasis, Protagonist Therapeutics, and Structure Therapeutics. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/04/13 18:32 MHDA- 2026/07/20 18:35 PMCR- 2026/04/13 CRDT- 2026/04/13 13:43 PHST- 2025/12/02 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/07/20 18:35 [medline] PHST- 2026/04/13 18:32 [pubmed] PHST- 2026/04/13 13:43 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - 164707 [pii] AID - i250141 [pii] AID - 10.2337/dci25-0141 [doi] PST - ppublish SO - Diabetes Care. 2026 Aug 1;49(8):1308-1317. doi: 10.2337/dci25-0141. PMID- 41973192 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261010 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Apr 13 TI - Pharmacologic Treatment of Obesity in the Context of Type 2 Diabetes. LID - 11 [pii] LID - 10.1007/s11892-026-01626-5 [doi] AB - PURPOSE OF REVIEW: To examine the role of pharmacologic obesity treatment in people with type 2 diabetes (T2D), with a focus on efficacy, safety, and clinical positioning in the context of T2D-specific metabolic and therapeutic challenges. RECENT FINDINGS: Contemporary incretin receptor agonists enable clinically meaningful weight loss in people with T2D while improving glycemic control and cardio-renal, hepatic, and functional outcomes, including improvements in physical performance and symptoms in heart failure with preserved ejection fraction (HFpEF). However, weight loss is consistently attenuated compared with obesity without diabetes, reflecting reduced metabolic flexibility (impaired ability to appropriately adjust fuel utilization), background therapies, and social determinants of health rather than treatment failure. Obesity pharmacotherapy should be considered a disease-modifying component of T2D care. Treatment success should be defined by improvements in adiposity-related complications, organ protection, and patient-centered outcomes, not by fixed weight-loss thresholds. A complication-focused, individualized approach is essential to optimize long-term benefit in T2D. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Conte, Caterina AU - Conte C AUID- ORCID: 0000-0001-7066-5292 AD - San Raffaele Roma University, Via di Val Cannuta 247, Rome, 00166, Italy. caterina.conte@uniroma5.it. AD - IRCCS MultiMedica, Milan, Italy. caterina.conte@uniroma5.it. FAU - Amaro, Anastassia AU - Amaro A AUID- ORCID: 0000-0002-3132-5778 AD - University of Pennsylvania, Philadelphia, PA, USA. LA - eng GR - Ricerca Corrente IRCCS MultiMedica/Italian Ministry of Health/ PT - Journal Article PT - Review DEP - 20260413 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Incretins) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Obesity/drug therapy/complications MH - Weight Loss/drug effects MH - Incretins/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Diabesity OTO - NOTNLM OT - Cardiometabolic risk OT - GLP‑1 agonists OT - Incretin therapy OT - Sarcopenic diabetes OT - Semaglutide OT - Tirzepatide COIS- Declarations. Competing Interests: CC has received consultancy and speaker's fees from Novo Nordisk and Eli Lilly. AA has received research grant from Novo Nordisk, Fractyl Laboratories, Eli Lilly; consultancy fees from Novo Nordisk, AbbVie, CVS Caremark. EDAT- 2026/04/13 12:37 MHDA- 2026/04/13 12:38 CRDT- 2026/04/13 11:08 PHST- 2026/02/11 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/04/13 12:38 [medline] PHST- 2026/04/13 12:37 [pubmed] PHST- 2026/04/13 11:08 [entrez] AID - 10.1007/s11892-026-01626-5 [pii] AID - 10.1007/s11892-026-01626-5 [doi] PST - epublish SO - Curr Diab Rep. 2026 Apr 13;26(1):11. doi: 10.1007/s11892-026-01626-5. PMID- 41970978 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Real-world use of semaglutide in patients with type 2 diabetes and end-stage renal disease: a multicenter retrospective cohort study. PG - 1805015 LID - 10.3389/fendo.2026.1805015 [doi] LID - 1805015 AB - BACKGROUND: Semaglutide and other Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus (T2DM); however, individuals with end-stage renal disease (ESRD) have been systematically excluded from landmark outcome trials. Consequently, real-world data evaluating the safety and effectiveness of GLP-1 RAs in this high-risk population remain limited. METHODS: This multicenter retrospective cohort study evaluated adult patients with T2DM and ESRD, including those receiving maintenance hemodialysis, who were prescribed injectable semaglutide between January 2016 and July 2025 at tertiary care centers in Saudi Arabia. The primary efficacy outcomes were changes in glycemic control and insulin requirements following initiation of injectable semaglutide. Secondary outcomes included changes in body weight. Safety outcomes comprised acute kidney injury (AKI), severe hypoglycemia, treatment discontinuation due to adverse events, expanded major adverse cardiovascular events (MACE), and all-cause mortality. RESULTS: Seventeen patients were included, with a median follow-up of 1,187 days (IQR 602-1,442); 58.8% were receiving hemodialysis. Mean HbA1c decreased from 9.06 +/- 1.69% to 8.75 +/- 2.48% (-0.31 +/- 2.57%; p = 0.630), with insulin dose reductions observed among the subset of patients with available documentation. Among 16 patients with paired weight measurements, mean body weight decreased by -12.63 +/- 24.03 kg (p = 0.074). No cardiovascular deaths, nonfatal myocardial infarctions, or nonfatal strokes were observed. Three expanded MACE events, all hospitalizations for heart failure, occurred during follow-up. AKI occurred in 57.1% of non-dialysis patients, and severe hypoglycemia was reported in two patients (11.8%). CONCLUSIONS: In real-world practice, injectable semaglutide was associated with descriptive changes in metabolic parameters in patients with ESRD, including those on hemodialysis. Larger prospective studies are needed to better define the role of GLP-1 RAs in this underrepresented population. CI - Copyright (c) 2026 Alkhezi, Alfehaid, Alanezi, Alotaibi and Alshaya. FAU - Alkhezi, Omar AU - Alkhezi O AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Al-Qassim Buraydah, Qassim, Saudi Arabia. FAU - Alfehaid, Lama AU - Alfehaid L AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia. FAU - Alanezi, Amal AU - Alanezi A AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. FAU - Alotaibi, Monirah AU - Alotaibi M AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. FAU - Alshaya, Omar AU - Alshaya O AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260326 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Retrospective Studies MH - *Kidney Failure, Chronic/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Blood Glucose MH - Renal Dialysis MH - Glycated Hemoglobin/analysis MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13061728 OTO - NOTNLM OT - cardiovascular outcomes OT - chronic kidney disease OT - end-stage renal disease OT - glucagon-like peptide-1 receptor agonists OT - hemodialysis OT - real-world evidence OT - semaglutide OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/13 18:17 MHDA- 2026/04/13 18:18 PMCR- 2026/03/26 CRDT- 2026/04/13 06:37 PHST- 2026/02/05 00:00 [received] PHST- 2026/03/06 00:00 [revised] PHST- 2026/03/12 00:00 [accepted] PHST- 2026/04/13 18:18 [medline] PHST- 2026/04/13 18:17 [pubmed] PHST- 2026/04/13 06:37 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - 10.3389/fendo.2026.1805015 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 26;17:1805015. doi: 10.3389/fendo.2026.1805015. eCollection 2026. PMID- 41969210 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - SemaGBA: A System Dynamics Model of the Semaglutide-Responsive Gut-Brain Axis A Model of How the Brain and Semaglutide Regulate Appetite and Weight. PG - 5184-5194 LID - 10.1111/dom.70722 [doi] AB - AIMS: Semaglutide is a GLP-1 receptor agonist for the treatment of type 2 diabetes and obesity. Its clinical effects are well established, but the underlying mechanisms remain unclear. This study aims to use computational modelling to generate hypotheses about semaglutide's long-term metabolic (body weight, net energy intake, blood glucose, insulin, insulin sensitivity, glucotoxicity, leptin, leptin sensitivity, lipotoxicity, GLP-1 and betacell function) and neural (AgRP, POMC, and dopamine neural activity) effects. MATERIALS AND METHODS: The SemaGBA computational model was developed in Julia using a system dynamics approach, integrating 14 metabolic and neural variables. First, a version without neural variables was constructed and validated against clinical data for blood glucose and weight loss. Subsequently, the model was extended with neural variables. To represent distinct population groups, baseline variable profiles were defined, capturing the typical physiological characteristics for people with type 2 diabetes, obesity, and a healthy condition. Simulations were performed for semaglutide treatment in groups with prediabetes induced by chronic overeating, type 2 diabetes, and obesity over periods ranging from 30 weeks to 5 years. RESULTS: The reduced model accurately reproduced clinical outcomes. It predicts glucose reductions of 38.0 mg/dL (data: 41.0 mg/dL) and weight loss of 3.2 kg (data: 3.8 kg) for diabetes (0.5 mg semaglutide), and 15.1% weight loss (data: 14.9%-17.1%) for obesity (2.4 mg semaglutide). Simulations showed semaglutide's interconnected mechanisms, including reduced lipotoxicity and glucotoxicity, enhanced beta-cell function, and glucose-dependent insulin secretion. Intervention during prediabetes prevented progression to diabetes by preserving beta-cell function and maintaining glucose in the pre-diabetic range. Neural variables illustrated the potential contribution of AgRP, POMC, and dopamine neuron activity to reduced net energy intake. CONCLUSION: The SemaGBA model demonstrates how semaglutide achieves glucose control and weight loss through integrated metabolic and neural pathways. Validation is limited by data availability, but the framework provides hypotheses for future research into semaglutide's neural effects. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kennis, Vivan C W AU - Kennis VCW AUID- ORCID: 0009-0006-1340-8058 AD - Eindhoven University of Technology, Department of Biomedical Engineering, Computational Biology, Eindhoven, the Netherlands. FAU - van Riel, Natal A W AU - van Riel NAW AD - Eindhoven University of Technology, Department of Biomedical Engineering, Computational Biology, Eindhoven, the Netherlands. AD - Amsterdam UMC Location AMC-Vascular Medicine, Amsterdam, the Netherlands. LA - eng GR - Dutch Research Council (NWO)/ PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications/physiopathology MH - *Brain/drug effects/metabolism MH - Obesity/drug therapy/metabolism MH - Weight Loss/drug effects MH - *Body Weight/drug effects MH - *Appetite/drug effects MH - Computer Simulation MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - *Appetite Regulation/drug effects MH - *Gastrointestinal Tract/drug effects MH - Insulin/metabolism MH - Models, Biological MH - Prediabetic State/drug therapy/metabolism PMC - PMC13146202 OTO - NOTNLM OT - GLP-1 analogue OT - appetite control OT - drug mechanism OT - obesity therapy OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 12:38 MHDA- 2026/05/06 06:38 PMCR- 2026/05/06 CRDT- 2026/04/13 06:03 PHST- 2026/03/19 00:00 [revised] PHST- 2026/01/15 00:00 [received] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/04/13 12:38 [pubmed] PHST- 2026/04/13 06:03 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70722 [pii] AID - 10.1111/dom.70722 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5184-5194. doi: 10.1111/dom.70722. Epub 2026 Apr 13. PMID- 41969200 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Association of Semaglutide Treatment With Liver Cirrhosis and Hepatocellular Carcinoma in Type 2 Diabetes: A Population-Based Cohort Study. PG - 5704-5714 LID - 10.1111/dom.70763 [doi] AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease is common among individuals with type 2 diabetes mellitus and substantially increases the risk of liver cirrhosis and hepatocellular carcinoma. Effective therapies that improve metabolic control while preventing advanced liver outcomes are limited. AIMS: To evaluate the association between semaglutide treatment and the risk of liver cirrhosis and hepatocellular carcinoma in adults with type 2 diabetes mellitus. METHODS: We performed a retrospective population-based cohort study using electronic health records from a large integrated healthcare organization. Adults with type 2 diabetes mellitus and no prior diagnosis of liver cirrhosis or hepatocellular carcinoma were included. Exposure was defined as treatment with semaglutide for at least four consecutive months compared with matched control patients. Cox proportional hazards models estimated adjusted hazard ratios with 95% confidence intervals, accounting for demographic factors, body mass index, smoking status, glycaemic control, other antidiabetic treatments and baseline liver fibrosis risk. RESULTS: Among 71 612 individuals, 35 806 received semaglutide and 35 806 were matched controls. Over a median follow-up of 4628 days for liver cirrhosis and 4090 days for HCC, 245 patients developed liver cirrhosis and 21 developed hepatocellular carcinomas. In the Cox model, there was no association between semaglutide treatment and the diagnosis of liver cirrhosis (HR 1.3, 95% CI 0.98-1.77) or hepatocellular carcinoma (HR 0.6, 95% CI 0.21-1.51). CONCLUSIONS: In this real-world study, semaglutide treatment was not associated with a reduced risk of liver cirrhosis or hepatocellular carcinoma among adults with type 2 diabetes mellitus. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Issachar, Assaf AU - Issachar A AUID- ORCID: 0000-0002-7004-7897 AD - Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. AD - Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Razi, Talish AU - Razi T AUID- ORCID: 0009-0006-2172-1044 AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - School of Industrial and Intelligent System Engineering, Tel Aviv University, Tel Aviv, Israel. FAU - Borochov, Ilya AU - Borochov I AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. FAU - Duskin Bitan, Hadar AU - Duskin Bitan H AUID- ORCID: 0000-0002-1721-1360 AD - Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - Institute of Endocrinology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. FAU - Arbel, Ronen AU - Arbel R AUID- ORCID: 0000-0002-6058-8665 AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - Maximizing Health Outcomes Research Lab, Sapir College, Sderot, Israel. LA - eng PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Carcinoma, Hepatocellular/chemically induced/epidemiology/prevention & control MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liver Cirrhosis/epidemiology/prevention & control/chemically induced MH - *Liver Neoplasms/epidemiology/prevention & control MH - Retrospective Studies MH - *Semaglutide/adverse effects/therapeutic use PMC - PMC13243961 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - hepatocellular carcinoma OT - liver cirrhosis OT - metabolic liver disease OT - real-world data OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 06:32 MHDA- 2026/06/11 12:38 PMCR- 2026/06/08 CRDT- 2026/04/13 05:43 PHST- 2026/04/06 00:00 [revised] PHST- 2026/01/01 00:00 [received] PHST- 2026/04/07 00:00 [accepted] PHST- 2026/06/11 12:38 [medline] PHST- 2026/04/13 06:32 [pubmed] PHST- 2026/04/13 05:43 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70763 [pii] AID - 10.1111/dom.70763 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5704-5714. doi: 10.1111/dom.70763. Epub 2026 Apr 13. PMID- 41969188 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Differential Impact of Metabolic Bariatric Surgery Versus Semaglutide on Adverse Hepatic and Extrahepatic Outcomes in Individuals With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes. PG - 5684-5695 LID - 10.1111/dom.70757 [doi] AB - AIM: We compared the impact of metabolic bariatric surgery (MBS) versus semaglutide on clinical outcomes in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). METHODS: Patients with MASLD and T2D who had MBS or semaglutide in 2018-2023 were identified (TriNetX database). The primary outcome was a composite of major adverse liver outcomes (MALO): decompensation events or liver transplant. Secondary outcomes included a composite of major adverse cardiovascular events (MACE), first diagnosis of cirrhosis, heart failure, or obesity-associated cancer (OAC), and all-cause mortality (ACM). Subgroup analyses were performed for Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). RESULTS: MBS, compared with semaglutide, was associated with a higher hazard rate (HR) of MALO (HR 1.63; 95% CI 1.12-2.37); this was driven by RYGB (2.01; 1.26-3.20) but not by SG (0.97; 0.52-1.78). However, after excluding patients with pre-existing cirrhosis, MBS was associated with a reduced HR of new cirrhosis (0.46; 0.29-0.73). For extrahepatic events, MBS was associated with a reduced HR of MACE (0.51; 0.38-0.67), heart failure (0.41; 0.27-0.62), and OAC (0.56; 0.34-0.92). There was no difference in ACM between MBS and semaglutide, but in subgroup analysis, RYGB was associated with increased ACM compared to semaglutide (1.64; 1.01-2.67). CONCLUSION: In patients with MASLD and T2D, MBS, and specifically RYGB, as compared to semaglutide, may drive a relatively increased risk of MALO despite protection against MACE, the first diagnosis of cirrhosis, heart failure, and OAC. Liver evaluation in individuals with T2D referred for MBS may help optimize their treatment. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Stupalkowska, Weronika AU - Stupalkowska W AUID- ORCID: 0000-0003-1230-7651 AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Laboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Henney, Alex E AU - Henney AE AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Sheu, Eric G AU - Sheu EG AUID- ORCID: 0000-0003-2707-1768 AD - Laboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Boston, Massachusetts, USA. AD - Division of General and GI Surgery, Mass General Brigham, Boston, Massachusetts, USA. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/adverse effects/methods MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Non-alcoholic Fatty Liver Disease/complications MH - *Semaglutide/therapeutic use MH - Treatment Outcome PMC - PMC13243962 OTO - NOTNLM OT - bariatric surgery OT - cohort study OT - database research OT - fatty liver disease OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 06:32 MHDA- 2026/06/11 12:38 PMCR- 2026/06/08 CRDT- 2026/04/13 05:43 PHST- 2026/03/16 00:00 [revised] PHST- 2026/01/19 00:00 [received] PHST- 2026/04/02 00:00 [accepted] PHST- 2026/06/11 12:38 [medline] PHST- 2026/04/13 06:32 [pubmed] PHST- 2026/04/13 05:43 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70757 [pii] AID - 10.1111/dom.70757 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5684-5695. doi: 10.1111/dom.70757. Epub 2026 Apr 13. PMID- 41969171 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Estimated Glomerular Filtration Rate Change and Heart Failure Events With GLP-1 Receptor Agonists: A Meta-Analysis and Meta-Regression of Randomised Controlled Trials. PG - 5649-5657 LID - 10.1111/dom.70749 [doi] AB - AIMS: To examine whether on-treatment changes in kidney function and cardiometabolic markers are associated with the magnitude of heart failure (HF) risk reduction across large-scale trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs). MATERIALS AND METHODS: We searched PubMed and Embase from inception to 29 January 2026 for randomised, placebo-controlled GLP-1RA trials enrolling >/= 1000 adults with type 2 diabetes and/or overweight or obesity and a follow-up of at least one year. The primary outcome was clinical HF events (hospitalisation for HF, with or without urgent HF visits). We pooled hazard ratios (HRs) using random-effects meta-analysis and performed mixed-effects meta-regression to test whether between-group changes in annualised estimated glomerular filtration rate (eGFR) improvement, body weight, systolic blood pressure (SBP), and heart rate were associated with the treatment effect on clinical HF events. RESULTS: Eleven trials were included (90 867 participants; 2863 clinical HF events). GLP-1RAs reduced the risk of clinical HF events (HR 0.86, 95% CI 0.80 to 0.93, p < 0.001, I (2) = 2.1%). In meta-regression, annualised eGFR improvement was significantly associated with greater HF risk reduction (p = 0.009); at the trial level, each 1 mL/min/1.73 m(2)/year greater improvement in eGFR corresponded to a 21% lower hazard of clinical HF events (95% CI 7% to 32%). In contrast, changes in body weight, SBP, and heart rate were not associated with HF risk reduction. CONCLUSIONS: Across large-scale GLP-1RA trials, greater annualised eGFR improvement was associated with larger reductions in clinical HF events. Annualised eGFR change may serve as a useful marker of HF benefit with GLP-1RAs. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hasebe, Masashi AU - Hasebe M AUID- ORCID: 0000-0001-7031-2446 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Kamido, Hisashi AU - Kamido H AUID- ORCID: 0009-0007-3971-1327 AD - Nephrology Center, Toranomon Hospital Kajigaya, Kawasaki, Kanagawa, Japan. FAU - Su, Chen-Yang AU - Su CY AUID- ORCID: 0000-0001-6071-4660 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Quantitative Life Sciences Program, McGill University, Montreal, Quebec, Canada. FAU - Keidai, Yamato AU - Keidai Y AUID- ORCID: 0000-0001-6271-9609 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Yoshiji, Satoshi AU - Yoshiji S AUID- ORCID: 0000-0001-8863-2413 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Quantitative Life Sciences Program, McGill University, Montreal, Quebec, Canada. LA - eng GR - 183596/CIHR/Canada GR - Canada Research Chairs Program/ GR - DNA to RNA (D2R) Foundational Program/ GR - Japan Society for the Promotion of Science/ GR - McGill University/ GR - 183596/CIHR/Canada PT - Journal Article PT - Meta-Analysis DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - *Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Heart Failure/epidemiology/prevention & control/etiology MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC13243948 OTO - NOTNLM OT - GLP-1 receptor agonists OT - estimated glomerular filtration rate OT - heart failure OT - meta-analysis OT - meta-regression COIS- Daisuke Yabe received clinically commissioned or joint research grants from Novo Nordisk, Ono Pharmaceutical, Taisho Pharmaceutical, Terumo, and Arklay. Daisuke Yabe also received consulting or speaker fees from Sumitomo Dainippon Pharma, Boehringer Ingelheim, Astellas Pharma, MSD, Novo Nordisk, Ono Pharmaceutical, Eli Lilly, and Takeda Pharmaceutical. Satoshi Yoshiji serves as a consultant to the Broad Institute of MIT and Harvard through Precision Global Consulting and to PriveBio Inc., unrelated to this project. The other authors declare no conflicts of interest. EDAT- 2026/04/13 06:32 MHDA- 2026/06/15 11:35 PMCR- 2026/06/08 CRDT- 2026/04/13 05:33 PHST- 2026/03/19 00:00 [revised] PHST- 2026/02/08 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/06/15 11:35 [medline] PHST- 2026/04/13 06:32 [pubmed] PHST- 2026/04/13 05:33 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70749 [pii] AID - 10.1111/dom.70749 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5649-5657. doi: 10.1111/dom.70749. Epub 2026 Apr 13. PMID- 41968307 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20260813 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 26 IP - 1 DP - 2026 Apr 12 TI - Real-world prescribing patterns and early weight and blood pressure outcomes of GLP-1-based therapies: a retrospective observational study in the United Arab Emirates. LID - 10.1186/s12902-026-02273-3 [doi] LID - 149 AB - PURPOSE: The use of glucagon-like peptide-1 (GLP-1) receptor agonists (RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA tirzepatide has increased rapidly for the management of type 2 diabetes mellitus and obesity. This study aimed to describe real-world prescribing patterns, patient characteristics, and observational short-term changes in weight and blood pressure among adults receiving GLP-1 RA and dual GIP/GLP-1 RA in a tertiary academic healthcare setting in the United Arab Emirates. METHODS: This retrospective observational study included adult patients prescribed GLP-1 RA or tirzepatide (dual GIP/GLP-1 RA) between January 2022 and December 2024. Electronic health records and pharmacy dispensing databases were reviewed. Prescription trends were standardized using monthly treatment units. Baseline demographic and clinical characteristics were described, and short-term changes in body weight and blood pressure were assessed where follow-up data were available. The mean treatment duration among patients with follow-up data was 6.99 months. An exploratory multivariable logistic regression adjusted for age group, sex, BMI category, treatment group, and HbA1c category was performed to evaluate factors associated with achieving clinically meaningful weight loss (>/= 5%). RESULTS: A total of 238 patient records and 1,744 dispensing records were analyzed. Utilization of GLP-1-based therapies increased by 371.7% over the study period, with a marked shift toward tirzepatide as the predominant agent. Most patients had obesity (83.6%), type 2 diabetes mellitus (89.0%), and multiple cardiometabolic comorbidities. Among patients with paired follow-up data, the mean percentage weight reduction was 3.91% (SD 7.32; 95% CI 2.70 to 5.12), and the mean treatment duration was 6.99 months (SD 3.69). Weight responses were heterogeneous, reflecting substantial interindividual variability in patient weight outcomes, with 35.6% achieving >/= 5% weight loss and 25.1% experiencing weight gain. After adjustment for age group, sex, BMI category, treatment group, and HbA1c category, no independent association was observed between treatment group and achieving >/= 5% weight loss. CONCLUSION: In this tertiary care setting, prescribing of GLP-1-based therapies expanded rapidly, accompanied by heterogeneous short-term changes in weight and blood pressure observed in routine clinical practice. These findings highlight the need for longer-term, multicentre studies to evaluate the real-world effectiveness, safety, and population-level impact of GLP-1 RA and dual GIP/GLP-1 RA. CLINICAL TRIAL NUMBER: Not applicable. FAU - Almemari, Salma AU - Almemari S AD - College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. FAU - Almulla, Nour AU - Almulla N AD - College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. FAU - Alsarraf, Yasmin AU - Alsarraf Y AD - College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. FAU - Badri, Ghada AU - Badri G AD - Thumbay University Hospital, Ajman, United Arab Emirates. FAU - Khan, Nelofar Sami AU - Khan NS AD - College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. neloferkhan@gmu.ac.ae. LA - eng PT - Journal Article PT - Observational Study DEP - 20260412 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - United Arab Emirates/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Tirzepatide/therapeutic use MH - Middle Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Blood Pressure/drug effects MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy MH - Follow-Up Studies MH - *Body Weight/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - Weight Loss/drug effects MH - Prognosis PMC - PMC13181871 OTO - NOTNLM OT - GLP-1 receptor agonists OT - GLP-1-based therapies OT - Obesity OT - Prescribing patterns OT - Real-world evidence OT - Tirzepatide OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Gulf Medical University (Ref. no. IRB-COM-STD-60-Jan-2025). As this was a retrospective study using anonymized electronic health records, the requirement for informed consent was waived. Consent for publication: Consent to publish was not applicable, as this study involved retrospective analysis of anonymized electronic health records with no identifiable patient information. Competing interests: The authors declare no competing interests. EDAT- 2026/04/13 00:31 MHDA- 2026/06/28 06:35 PMCR- 2026/04/12 CRDT- 2026/04/12 23:43 PHST- 2026/02/12 00:00 [received] PHST- 2026/04/08 00:00 [accepted] PHST- 2026/06/28 06:35 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 23:43 [entrez] PHST- 2026/04/12 00:00 [pmc-release] AID - 10.1186/s12902-026-02273-3 [pii] AID - 2273 [pii] AID - 10.1186/s12902-026-02273-3 [doi] PST - epublish SO - BMC Endocr Disord. 2026 Apr 12;26(1):149. doi: 10.1186/s12902-026-02273-3. PMID- 41967915 OWN - NLM STAT- MEDLINE DCOM- 20261004 LR - 20261006 IS - 1460-2156 (Electronic) IS - 0006-8950 (Linking) VI - 149 IP - 10 DP - 2026 Oct 5 TI - GLP1R expression and Parkinson's disease and related disorders in GLP-1 receptor agonist-treated type 2 diabetes. PG - 3431-3439 LID - 10.1093/brain/awag130 [doi] AB - Preclinical and epidemiologic data suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce the risk of Parkinson's disease and related disorders (PDRD), yet clinical trial findings have been mixed, raising the possibility of biologically meaningful heterogeneity. We tested whether interindividual differences in systemic GLP1R expression are associated with PDRD risk among adults with type 2 diabetes initiating GLP-1RAs. We conducted an electronic health record-based new-user cohort study in the National Institutes of Health All of Us Research Program, focusing on adults with type 2 diabetes aged 50 years or older who initiated a GLP-1RA between 2005 and 2023 and had no prior PDRD or Alzheimer's disease and related dementias (ADRD). Systemic GLP1R expression was genetically proxied by a 15-variant cis-expression quantitative trait locus (cis-eQTL) genetic risk score dichotomized at the cohort median. Follow-up ended at the earliest of incident PDRD, death or 1 October 2023. Hazard ratios (HR) were estimated using multivariable Cox proportional hazards models adjusting for baseline covariates, and incidence rates and rate differences per 1000 person-years were estimated using Poisson models. Prespecified sensitivity analyses excluded early outcome events and short drug exposure; an exploratory analysis evaluated incident ADRD. The cohort included 7039 initiators (3520 high versus 3519 low genetic score; mean age 61.7 +/- 8.4 years; 59.8% female; mean follow-up 3.8 +/- 3.1 years). Compared with the low-score group, the high-score group had a lower hazard of incident PDRD [HR 0.78; 95% confidence interval (CI) 0.62 to 0.98] and a lower incidence rate (rate difference -1.36 per 1000 person-years; 95% CI -2.51 to -0.20). Associations were consistent across sensitivity analyses. No association was observed for incident ADRD (HR 1.02; 95% CI 0.81 to 1.28). These findings link a mechanism-anchored genetic proxy for higher systemic GLP1R expression to a lower risk of incident PDRD among GLP-1RA-treated adults with type 2 diabetes. Systemic GLP1R-mediated pathways may be relevant to interindividual differences in observed PDRD risk, and genetic instruments for GLP1R expression may inform hypotheses for future PDRD trial design. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Woo, Kyung Ah AU - Woo KA AUID- ORCID: 0000-0001-5457-7348 AD - Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. AD - Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. FAU - Jang, Yoonhyuk AU - Jang Y AUID- ORCID: 0009-0004-5991-7822 AD - Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. AD - Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. FAU - Kim, Han-Joon AU - Kim HJ AUID- ORCID: 0000-0001-8219-9663 AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. FAU - Park, Peter J AU - Park PJ AUID- ORCID: 0000-0001-9378-960X AD - Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. LA - eng GR - Korea Health Industry Development Institute/ GR - RS-2024-00403047/Ministry of Health & Welfare/ PT - Journal Article PL - England TA - Brain JT - Brain : a journal of neurology JID - 0372537 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/complications MH - Female MH - *Glucagon-Like Peptide-1 Receptor/genetics/biosynthesis/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Parkinson Disease/genetics/epidemiology MH - Male MH - Middle Aged MH - Aged MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP1R OT - Parkinson's disease OT - genetics OT - glucagon-like peptide-1 receptor agonist OT - type 2 diabetes EDAT- 2026/04/13 00:31 MHDA- 2026/10/04 23:29 CRDT- 2026/04/12 21:14 PHST- 2025/12/23 00:00 [received] PHST- 2026/03/11 00:00 [revised] PHST- 2026/03/21 00:00 [accepted] PHST- 2026/10/04 23:29 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 21:14 [entrez] AID - 8651260 [pii] AID - 10.1093/brain/awag130 [doi] PST - ppublish SO - Brain. 2026 Oct 5;149(10):3431-3439. doi: 10.1093/brain/awag130. PMID- 41967797 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260929 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 50 IP - 6 DP - 2026 Aug TI - Preferred Glucagon-like Peptide-1 Receptor Agonists in Adults With Type 2 Diabetes and Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-analysis of Randomized Trials. PG - 429-439.e26 LID - S1499-2671(26)00065-1 [pii] LID - 10.1016/j.jcjd.2026.04.001 [doi] AB - The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain. PubMed, Embase, Web of Science, Scopus, and CENTRAL were searched from inception to December 20, 2025, for randomized controlled trials. We conducted a frequentist random-effects network meta-analysis and reported risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores. Regimens were analyzed as individual agents, including albiglutide, dulaglutide, efpeglenatide, exenatide extended release, ITCA 650, liraglutide, lixisenatide, subcutaneous semaglutide, oral semaglutide, tirzepatide, and placebo. Eleven trials (n=83,215) were included. In the 3-point major adverse CV events (MACE) network (11 trials, 11 regimens), heterogeneity and inconsistency were absent (I(2)=0%, tau(2)=0). MACE rate was reduced with subcutaneous semaglutide (RR 0.74, 95% CI 0.58 to 0.94), efpeglenatide (RR 0.76, 95% CI 0.61 to 0.94), and albiglutide (RR 0.79, 95% CI 0.69 to 0.91); tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo. Top ranked were subcutaneous semaglutide (P-score 0.87), efpeglenatide (0.84), and albiglutide (0.80). No regimen significantly reduced all-cause or CV death compared with placebo. Stroke was reduced with tirzepatide (RR 0.71, 95% CI 0.54 to 0.93) and dulaglutide (RR 0.77, 95% CI 0.63 to 0.95) vs placebo. Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650. Several GLP-1-based therapies reduced MACE vs placebo, with 3-point MACE emerging as the most consistent efficacy signal. Overall, these findings support guideline-based use of GLP-1 RAs in high-risk T2D while highlighting the need for individualized treatment selection. CI - Copyright (c) 2026 Diabetes Canada. All rights reserved. FAU - Abomohsen, Mustafa AU - Abomohsen M AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. FAU - Rifai, Mohamed AU - Rifai M AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. Electronic address: mohamed.ali181@med.menofia.edu.eg. FAU - Gadelmawla, Ahmed Farid AU - Gadelmawla AF AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. FAU - Alghzawi, Hamzah M AU - Alghzawi HM AD - School of Nursing, Tennessee State University, Nashville, Tennessee, United States. FAU - Elgendy, Mohamed S AU - Elgendy MS AD - Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Bakr, Hager Mohamed AU - Bakr HM AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. FAU - Friedman, Adam AU - Friedman A AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. FAU - Idries, Iyad Y AU - Idries IY AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20260410 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Adult MH - Humans MH - *Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - GLP-1 receptor agonist OT - agoniste des recepteurs du GLP-1 OT - cardiovascular outcomes OT - diabete de type 2 OT - essais controles randomises OT - major adverse cardiovascular event OT - meta-analyse en reseau OT - network meta-analysis OT - randomized controlled trial OT - resultats cardiovasculaires OT - tirzepatide OT - tirzepatide OT - type 2 diabetes OT - evenements cardiovasculaires indesirables majeurs EDAT- 2026/04/13 00:31 MHDA- 2026/09/25 23:47 CRDT- 2026/04/12 19:37 PHST- 2026/01/13 00:00 [received] PHST- 2026/03/07 00:00 [revised] PHST- 2026/04/04 00:00 [accepted] PHST- 2026/09/25 23:47 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 19:37 [entrez] AID - S1499-2671(26)00065-1 [pii] AID - 10.1016/j.jcjd.2026.04.001 [doi] PST - ppublish SO - Can J Diabetes. 2026 Aug;50(6):429-439.e26. doi: 10.1016/j.jcjd.2026.04.001. Epub 2026 Apr 10. PMID- 41967795 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260925 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 50 IP - 6 DP - 2026 Aug TI - Oral Health Considerations and Dental Management Guidelines for Semaglutide Medications. PG - 440-447 LID - S1499-2671(26)00066-3 [pii] LID - 10.1016/j.jcjd.2026.03.008 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically meaningful weight-loss effects in individuals with type 2 diabetes and high body mass index, and dental practitioners and physicians often encounter patients who take these medications. Semaglutide is known to be associated with several systemic side effects, including delayed gastric emptying, belching, reflux and nausea, nutritional changes, and gastrointestinal discomfort. Systemic effects secondarily manifest in the oral cavity and, as a result, individuals taking semaglutide may present with xerostomia (dry mouth), halitosis (bad breath), enamel erosion tied to vomiting, and altered taste, among other oral signs and symptoms. It is important for dental professionals and physicians to become informed of possible symptoms and corresponding management strategies, given the multiple potential indirect effects on the oral cavity and relevance to dental treatment planning. In this article, we review the pharmacodynamics of semaglutide and present the current evidence on oral manifestations of the drug family and implications for dental and oral health. Practical management recommendations for dentists and the broader interdisciplinary health-care team are outlined. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Kofman, Karina AU - Kofman K AD - Faculty of Dentistry, Dental Surgery Program, University of Toronto, Toronto, Ontario, Canada. FAU - Ouanounou, Aviv AU - Ouanounou A AD - Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: avivouanounou@dentistry.utoronto.ca. LA - eng PT - Journal Article PT - Review DEP - 20260410 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Oral Health/standards MH - *Practice Guidelines as Topic/standards MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - adaptations des soins dentaires OT - dental modification OT - diabetes OT - diabete OT - oral health OT - sante bucco-dentaire EDAT- 2026/04/13 00:31 MHDA- 2026/09/25 23:47 CRDT- 2026/04/12 19:37 PHST- 2025/12/28 00:00 [received] PHST- 2026/02/27 00:00 [revised] PHST- 2026/03/27 00:00 [accepted] PHST- 2026/09/25 23:47 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 19:37 [entrez] AID - S1499-2671(26)00066-3 [pii] AID - 10.1016/j.jcjd.2026.03.008 [doi] PST - ppublish SO - Can J Diabetes. 2026 Aug;50(6):440-447. doi: 10.1016/j.jcjd.2026.03.008. Epub 2026 Apr 10. PMID- 41966038 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 2639-9636 (Print) IS - 2639-9636 (Linking) VI - 41 IP - 3 DP - 2026 Apr 1 TI - Geriatric Pharmacotherapy Case Series: GLP-1 RA for Weight Management in Older Adults. PG - 78-87 LID - 10.4140/TCP.n.2026.78 [doi] AB - Background: This case study reviews the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for weight management in older adults. A 69-year-old male patient discusses weight loss goals with his health care provider and seeks pharmacotherapy options in addition to lifestyle modifications. His medical history includes type 2 diabetes mellitus (T2D), coronary artery disease (CAD), prior coronary artery bypass graft, heart failure with reduced ejection fraction (HFrEF), hypertension, hyperlipidemia, and allergic rhinitis. He initiated weight loss efforts following a myocardial infarction; however, dietary and physical activity changes alone have not resulted in substantial weight reduction. Assessment: This patient is an appropriate candidate for GLP-1 RA therapy given his T2D, obesity, CAD, and a recent elevation in serum creatinine (SCr). The patient will initiate semaglutide, a medication approved for weight management with demonstrated cardiovascular benefit. The dose will be titrated to a maintenance dose of 2 mg once weekly, with ongoing monitoring of tolerability and weight loss.Given his age, there is concern for sarcopenia associated with excessive weight loss. The patient will be advised to maintain a balanced diet with an emphasis on protein intake and to engage in regular physical activity to minimize loss of muscle mass. Outcome: The patient experiences weight reduction within the first few weeks of therapy and tolerates treatment well. He has incorporated additional strength training into his exercise routine and increased his intake of vegetables and protein. The patient has insurance coverage for semaglutide due to his comorbid T2D; therefore, medication cost is not a barrier to treatment. Conclusion: When evaluating the use of GLP-1 RA agents in older adults, these agents demonstrate benefits beyond glycemic control and weight loss, including cardiovascular and renal outcomes. However, GLP-1 RA-associated weight loss may contribute to muscle loss, which is of particular concern in older adults who are at risk for frailty or falls. Patients receiving GLP-1 RA therapy should be encouraged to maintain adequate protein intake and engage in regular physical activity, particularly resistance training, to preserve muscle mass. Additionally, the high cost of GLP-1 RA agents may limit access for patients without insurance. FAU - Toma, Lauren AU - Toma L FAU - Buckley, Kelsey AU - Buckley K FAU - Early, Nicole AU - Early N LA - eng PT - Case Reports PT - Journal Article PL - United States TA - Sr Care Pharm JT - The Senior care pharmacist JID - 101737969 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Male MH - Aged MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Obesity/drug therapy EDAT- 2026/04/12 06:38 MHDA- 2026/04/12 06:39 CRDT- 2026/04/12 00:32 PHST- 2026/04/12 06:39 [medline] PHST- 2026/04/12 06:38 [pubmed] PHST- 2026/04/12 00:32 [entrez] AID - 10.4140/TCP.n.2026.78 [doi] PST - ppublish SO - Sr Care Pharm. 2026 Apr 1;41(3):78-87. doi: 10.4140/TCP.n.2026.78. PMID- 41964153 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2026 IP - 1 DP - 2026 TI - Tirzepatide in Metabolically Dysfunctional-Associated Steatohepatitis (MASH): A Bibliometric and Evidence-Based Review. PG - e1853763 LID - 10.1155/jdr/1853763 [doi] LID - 1853763 AB - PURPOSE: Metabolically-dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) and is strongly linked to obesity and type 2 diabetes mellitus (T2D). Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a promising therapeutic option due to its profound metabolic effects and potential hepatic benefits. This study integrates bibliometric mapping with current clinical evidence to evaluate tirzepatide's role in MASLD/MASH. METHODS: A bibliometric search was conducted in the Web of Science Core Collection (2018-2025) using predefined keywords related to tirzepatide and metabolic liver disease. Twenty-five full-text publications-including randomized controlled trials, post hoc analyses, meta-analyses, mechanistic reviews, and international guidelines-were systematically reviewed. Co-occurrence networks were generated using VOSviewer. RESULTS: Scientific output on tirzepatide and MASLD/MASH has increased rapidly since 2020, with thematic clusters centered on metabolic regulation, hepatic inflammation, and fibrosis. Clinical evidence shows that tirzepatide induces substantial weight loss, improves glycaemic control, and reduces hepatic biomarkers such as ALT, AST, K 18, and Pro C3. The SYNERGY-nonalcoholic steatohepatitis (NASH) trial demonstrated high rates of MASH resolution without fibrosis worsening and meaningful fibrosis regression at 52 weeks. Network meta-analyses position tirzepatide among the most effective therapies currently available. Recent EASL-EASD-EASO guidelines recommend tirzepatide for MASLD patients with obesity, T2D, or cardiometabolic risk. CONCLUSIONS: Tirzepatide combines potent metabolic effects with significant hepatic improvements, positioning it as a promising therapy for MASLD/MASH. Although long-term and phase III data are still needed, current evidence supports tirzepatide as a key component of modern metabolic liver disease management. CI - Copyright (c) 2026 Ileana Pantea and Angela Repanovici. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Pantea, Ileana AU - Pantea I AUID- ORCID: 0009-0006-2540-7781 AD - Transilvania University of Brasov, Brasov, Romania, unitbv.ro. FAU - Repanovici, Angela AU - Repanovici A AUID- ORCID: 0000-0002-8748-5332 AD - Transilvania University of Brasov, Brasov, Romania, unitbv.ro. LA - eng PT - Journal Article PT - Review PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Tirzepatide/therapeutic use MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity MH - Evidence-Based Medicine PMC - PMC13068985 OTO - NOTNLM OT - GIP/GLP-1 agonists OT - MASH OT - MASLD OT - fibrosis OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/11 06:32 MHDA- 2026/04/11 06:33 PMCR- 2026/04/10 CRDT- 2026/04/11 00:52 PHST- 2026/03/14 00:00 [revised] PHST- 2026/01/05 00:00 [received] PHST- 2026/03/21 00:00 [accepted] PHST- 2026/04/11 06:33 [medline] PHST- 2026/04/11 06:32 [pubmed] PHST- 2026/04/11 00:52 [entrez] PHST- 2026/04/10 00:00 [pmc-release] AID - JDR1853763 [pii] AID - 10.1155/jdr/1853763 [doi] PST - ppublish SO - J Diabetes Res. 2026;2026(1):e1853763. doi: 10.1155/jdr/1853763. PMID- 41963153 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 20 IP - 3 DP - 2026 Jun TI - Impact of automatic e-consults on use of SGLT2i and GLP-1 RA in rural veterans with type 2 diabetes and chronic kidney disease. PG - 401-403 LID - S1751-9918(26)00076-8 [pii] LID - 10.1016/j.pcd.2026.04.004 [doi] AB - In this pilot study, we identified rural veterans with chronic kidney disease and type 2 diabetes who have an indication for SGLT2i or GLP-1 RA but not yet on either of these agents. Nearly a third of providers changed their practice based on automatic e-consult; however, there were still 69% of cases where providers did not. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Sarwal, Amara AU - Sarwal A AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: amara.sarwal@hsc.utah.edu. FAU - Throolin, Michael AU - Throolin M AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Wei, Guo AU - Wei G AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Nevers, McKenna AU - Nevers M AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Informatics, Decision-Enhancement, and Analytic Sciences (IDEAS) Center of Innovation, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA. FAU - Hartsell, Sydney E AU - Hartsell SE AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Shen, Jincheng AU - Shen J AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA. FAU - Boucher, Robert E AU - Boucher RE AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Beddhu, Srinivasan AU - Beddhu S AD - Cardiovascular, Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA. LA - eng GR - NGO/US Non-government Organization/United States PT - Journal Article DEP - 20260410 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology MH - *Renal Insufficiency, Chronic/diagnosis/drug therapy/epidemiology MH - Pilot Projects MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - *Veterans MH - Digital Health MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Chronic kidney disease OT - Guideline-directed medical therapy OT - Primary care OT - Rural Health OT - Type 2 Diabetes EDAT- 2026/04/11 00:32 MHDA- 2026/05/20 00:35 CRDT- 2026/04/10 21:54 PHST- 2026/01/30 00:00 [received] PHST- 2026/04/02 00:00 [revised] PHST- 2026/04/05 00:00 [accepted] PHST- 2026/05/20 00:35 [medline] PHST- 2026/04/11 00:32 [pubmed] PHST- 2026/04/10 21:54 [entrez] AID - S1751-9918(26)00076-8 [pii] AID - 10.1016/j.pcd.2026.04.004 [doi] PST - ppublish SO - Prim Care Diabetes. 2026 Jun;20(3):401-403. doi: 10.1016/j.pcd.2026.04.004. Epub 2026 Apr 10. PMID- 41962156 OWN - NLM STAT- MEDLINE DCOM- 20260801 LR - 20260801 IS - 1933-0693 (Electronic) IS - 0022-3085 (Linking) VI - 145 IP - 2 DP - 2026 Aug 1 TI - Glucagon-like peptide-1 receptor agonists in patients with moyamoya disease and type 2 diabetes mellitus. PG - 390-396 LID - 10.3171/2025.12.JNS251072 [doi] AB - OBJECTIVE: Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease that is commonly associated with comorbidities such as type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1) receptor agonists are antihyperglycemic agents that have demonstrated the ability to reduce stroke. The aim of this study was to analyze the role of GLP-1 receptor agonists in the treatment of patients with MMD and T2DM by comparing those with and without GLP-1 agonist therapy. METHODS: Patients with MMD and T2DM were retrospectively identified from the TriNetX research network and subsequently dichotomized into those who were prescribed GLP-1 receptor agonists and those who were not. Propensity score matching (PSM) was performed to estimate the effect of GLP-1 treatment. Kaplan-Meier survival curves were used to analyze outcomes of interest, which were stroke, intracerebral hemorrhage (ICH), and death. RESULTS: Of 2770 patients, 476 (17.2%) had a history of GLP-1 receptor agonist usage. Of 2294 (82.8%) who did not have a history of GLP-1 receptor agonist usage, 2272 were included. PSM resulted in 413 patients in each group. Patients with MMD and T2DM who received GLP-1 receptor agonists had 33% lower risk of stroke (HR 0.67, 95% CI 0.55-0.81; p < 0.001), 71% lower risk of ICH (HR 0.29, 95% CI 0.15-0.58; p < 0.001), and 66% lower risk of death (HR 0.34, 95% CI 0.21-0.56; p < 0.001) compared with patients with MMD and T2DM who did not receive GLP-1 agonists. CONCLUSIONS: In this study, patients with MMD and T2DM who were prescribed a GLP-1 receptor agonist had lower risk of stroke, ICH, and death. Prospective studies and randomized controlled trials are needed to clarify the role of GLP-1 receptor agonists in the management of MMD. FAU - Roy, Joanna M AU - Roy JM AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Musmar, Basel AU - Musmar B AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Hafer, Ramsay AU - Hafer R AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Papadopoulos, Eleni AU - Papadopoulos E AD - 2Rowan-Virtua School of Osteopathic Medicine, Stratford, New Jersey. FAU - Kata, Rithvik AU - Kata R AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Patel, Shray AU - Patel S AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Karadimas, Spyridon AU - Karadimas S AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Koduri, Sravanthi AU - Koduri S AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Tjoumakaris, Stavropoula I AU - Tjoumakaris SI AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Gooch, M Reid AU - Gooch MR AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Rosenwasser, Robert H AU - Rosenwasser RH AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. FAU - Jabbour, Pascal M AU - Jabbour PM AD - 1Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania; and. LA - eng PT - Journal Article DEP - 20260410 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Moyamoya Disease/drug therapy/complications MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Stroke/prevention & control/epidemiology MH - Aged MH - Treatment Outcome OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - medical management OT - moyamoya disease OT - stroke OT - vascular disorders EDAT- 2026/04/10 18:33 MHDA- 2026/08/02 00:50 CRDT- 2026/04/10 17:52 PHST- 2025/04/18 00:00 [received] PHST- 2025/12/03 00:00 [accepted] PHST- 2026/08/02 00:50 [medline] PHST- 2026/04/10 18:33 [pubmed] PHST- 2026/04/10 17:52 [entrez] AID - 10.3171/2025.12.JNS251072 [doi] PST - epublish SO - J Neurosurg. 2026 Apr 10;145(2):390-396. doi: 10.3171/2025.12.JNS251072. Print 2026 Aug 1. PMID- 41957308 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261027 IS - 1179-1888 (Electronic) IS - 1175-0561 (Print) IS - 1175-0561 (Linking) VI - 27 IP - 3 DP - 2026 May TI - The Impact of GLP-1 Receptor Agonists on Hair: Beneficial Effects or Adverse Outcomes? PG - 579-586 LID - 10.1007/s40257-026-01021-6 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the treatment of type II diabetes and obesity. Since their introduction, studies continue to reveal their beneficial effects in a range of other conditions. However, hair loss associated with GLP-1RAs is still a controversial topic. This narrative review explores the current evidence linking GLP-1RAs to hair-related conditions because, while some studies have reported hair regrowth in patients with androgenetic alopecia and a decrease in inflammatory infiltrate in patients with cicatricial alopecia, many more have suggested association with telogen effluvium. Given the heterogeneity of current reports, careful clinical evaluation, monitoring weight trends, and assessing relevant laboratory parameters is recommended. Prospective, controlled studies, including immunohistochemical or molecular profiling of GLP-1 receptor expression in human hair follicles, are necessary to better clarify the potential role of GLP-1RAs in hair biology, to inform safe prescribing practices and to avoid discontinuation of a beneficial treatment. CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Seyed Jafari, S Morteza AU - Seyed Jafari SM AUID- ORCID: 0000-0002-6466-2199 AD - Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. morteza.jafari@insel.ch. FAU - Caro, Gemma AU - Caro G AD - Department of Dermatology, Ente Ospedaliero Cantonale, Bellinzona, Switzerland. FAU - Lipner, Shari R AU - Lipner SR AD - Department of Dermatology, Weill Cornell Medicine, New York, NY, USA. FAU - Iorizzo, Matilde AU - Iorizzo M AD - Private Dermatology Practice, Lugano/Bellinzona, Switzerland. LA - eng PT - Journal Article PT - Review DEP - 20260409 PL - New Zealand TA - Am J Clin Dermatol JT - American journal of clinical dermatology JID - 100895290 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Alopecia/drug therapy/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hair/drug effects/growth & development MH - Hair Follicle/drug effects/growth & development MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/adverse effects/therapeutic use/pharmacology MH - Obesity/drug therapy MH - Semaglutide MH - Treatment Outcome PMC - PMC13695661 COIS- Declarations. Conflicts of Interest: None. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Code Availability: Not applicable. Authors Contributions: Conceptualization-M.I., S.M.S.J.; investigation-all authors; project administration/supervision-M.I., S.R.L.; writing-original draft-M.I., G.C., S.M.S.J.; writing-review and editing-all authors. All authors read and approved the final manuscript. EDAT- 2026/04/10 00:33 MHDA- 2026/05/13 12:31 PMCR- 2026/04/09 CRDT- 2026/04/09 23:29 PHST- 2025/09/08 00:00 [received] PHST- 2026/02/25 00:00 [accepted] PHST- 2026/05/13 12:31 [medline] PHST- 2026/04/10 00:33 [pubmed] PHST- 2026/04/09 23:29 [entrez] PHST- 2026/04/09 00:00 [pmc-release] AID - 10.1007/s40257-026-01021-6 [pii] AID - 1021 [pii] AID - 10.1007/s40257-026-01021-6 [doi] PST - ppublish SO - Am J Clin Dermatol. 2026 May;27(3):579-586. doi: 10.1007/s40257-026-01021-6. Epub 2026 Apr 9. PMID- 41955563 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260828 IS - 2561-326X (Electronic) IS - 2561-326X (Linking) VI - 10 DP - 2026 Apr 9 TI - A Text Messaging-Based Program to Transition From Basal Insulin to Glucagon-Like Peptide-1 Receptor Agonists in Safety-Net Diabetes Care: Pilot Quality Improvement Intervention Study. PG - e76993 LID - 10.2196/76993 [doi] LID - e76993 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin both lower blood sugar, but while insulin puts people at risk of hypoglycemia and weight gain, GLP-1 RAs do not. In addition, GLP-1 RAs have added cardiometabolic and renal benefits. For these reasons, when possible, many primary care providers prefer their patients with well-controlled type 2 diabetes to be transitioned from basal insulin to a GLP-1 RA. This transition process can be labor intensive, requiring multiple dosing adjustments and a watchful eye for hypoglycemia and hyperglycemia. The Mobile Insulin Titration Intervention (MITI)-GLP1 program uses SMS text messaging-based technology to support a streamlined and supervised transition process from basal insulin to a GLP-1 RA. This program takes place at a multilingual safety-net clinic. OBJECTIVE: Our objectives were to assess program feasibility and acceptability to determine whether the intervention was doable, practical, and worthy of further investigation via a larger controlled trial. Preliminary clinical outcomes are also discussed in this paper. METHODS: Patients were enrolled on a secure web platform that sent them a daily SMS text message asking the following: "What was your fasting blood sugar this morning?" Each weekday, texted responses containing patients' fasting blood sugar levels were checked for alarm values, and once weekly, patients were called and advised on whether and how to lower their basal insulin and increase their GLP-1 RA dose. The program was co-run by general internal medicine physicians and nurses and continued until the patient had their insulin stopped completely and/or their GLP-1 RA dose reached the maximum, or 16 weeks elapsed. All enrolled patients were included in the analyses. RESULTS: A total of 72 patients completed the pilot program. Feasibility and acceptability were high. Of 3671 SMS text messages sent by the program, 3520 (95.89%) received a response from patients. Of 719 cumulative weeks in which Thursday titration phone calls were attempted, successful connections with patients were made in 649 (90.26%) instances. Preliminary clinical outcomes were promising. Insulin doses were meaningfully reduced (55/72, 76.39% had their basal insulin reduced by at least 50%; 45/72, 62.5% had their insulin stopped completely). GLP-1 RA doses were meaningfully increased (64/72, 88.89% had their GLP-1 RA dose increased by >/=1 level; 45/72, 62.5% were discharged on the maximum dose of their GLP-1 RA). There was minimal hypoglycemia (5/3520, 0.14% of the SMS text messages reported a value of <80 mg/dL) and hyperglycemia (1/3520, 0.03% of the SMS text messages reported a value of >400 mg/dL). CONCLUSIONS: A general internal medicine-run MITI-GLP1 pilot program using SMS text messaging and interdisciplinary teamwork between internists and nurses is a feasible and acceptable intervention for safely and effectively transitioning people with well-controlled type 2 diabetes away from basal insulin and toward a GLP-1 RA. CI - (c) Natalie Levy, Katie Nerlino, Sherlane Bongalos, Alex Dasilva, Chinye Uzor, Ying Jie Liang, Olubunmi Sonubi. Originally published in JMIR Formative Research (https://formative.jmir.org). FAU - Levy, Natalie AU - Levy N AUID- ORCID: 0000-0003-2956-5876 AD - Division of General Internal Medicine and Clinical Innovation, NYU Grossman School of Medicine, OBV - A620, 462 First Avenue, New York, NY, 10016, United States. AD - Department of Medicine, NYC Health + Hospital/Bellevue, New York, NY, United States. FAU - Nerlino, Katie AU - Nerlino K AUID- ORCID: 0009-0002-4141-2215 AD - Division of General Internal Medicine and Clinical Innovation, NYU Grossman School of Medicine, OBV - A620, 462 First Avenue, New York, NY, 10016, United States. AD - Department of Medicine, NYC Health + Hospital/Bellevue, New York, NY, United States. FAU - Bongalos, Sherlane AU - Bongalos S AUID- ORCID: 0009-0005-3103-4419 AD - Department of Nursing, NYC Health + Hospitals/Bellevue, New York, NY, United States. FAU - Dasilva, Alex AU - Dasilva A AUID- ORCID: 0009-0007-7146-9198 AD - Department of Nursing, NYC Health + Hospitals/Bellevue, New York, NY, United States. FAU - Uzor, Chinye AU - Uzor C AUID- ORCID: 0009-0003-8117-6357 AD - Department of Nursing, NYC Health + Hospitals/Bellevue, New York, NY, United States. FAU - Liang, Ying Jie AU - Liang YJ AUID- ORCID: 0009-0009-7337-1025 AD - Department of Nursing, NYC Health + Hospitals/Bellevue, New York, NY, United States. FAU - Sonubi, Olubunmi AU - Sonubi O AUID- ORCID: 0009-0003-2452-2372 AD - Department of Nursing, NYC Health + Hospitals/Bellevue, New York, NY, United States. LA - eng PT - Journal Article DEP - 20260409 PL - Canada TA - JMIR Form Res JT - JMIR formative research JID - 101726394 RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Text Messaging/statistics & numerical data/instrumentation/standards MH - Pilot Projects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Insulin/therapeutic use/administration & dosage MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Quality Improvement MH - Hypoglycemic Agents/therapeutic use MH - Safety-net Providers MH - Adult MH - Adherence Interventions PMC - PMC13065235 OTO - NOTNLM OT - GLP-1 receptor agonist dosing OT - GLP-1 receptor agonists OT - SMS text messaging OT - basal insulin OT - basal insulin dosing OT - delivery of health care OT - eHealth OT - glucagon-like peptide-1 receptor agonist dosing OT - glucagon-like peptide-1 receptor agonists OT - health care disparities OT - mHealth OT - mobile health OT - primary health care OT - safety net OT - social drivers of health OT - telemedicine OT - type 2 diabetes COIS- Conflicts of Interest: None declared. EDAT- 2026/04/09 18:31 MHDA- 2026/04/09 18:32 PMCR- 2026/04/09 CRDT- 2026/04/09 16:12 PHST- 2025/05/05 00:00 [received] PHST- 2026/03/12 00:00 [revised] PHST- 2026/03/12 00:00 [accepted] PHST- 2026/04/09 18:32 [medline] PHST- 2026/04/09 18:31 [pubmed] PHST- 2026/04/09 16:12 [entrez] PHST- 2026/04/09 00:00 [pmc-release] AID - v10i1e76993 [pii] AID - 76993 [pii] AID - 10.2196/76993 [doi] PST - epublish SO - JMIR Form Res. 2026 Apr 9;10:e76993. doi: 10.2196/76993. PMID- 41955540 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260626 IS - 1537-7385 (Electronic) IS - 0894-9115 (Linking) VI - 105 IP - 7 DP - 2026 Jul 1 TI - "Ozempic Limb": Understanding the Impact of Semaglutide on Prosthesis Use and Residual Limb Care in Individuals With Lower Limb Amputation. PG - 657-660 LID - 10.1097/PHM.0000000000002989 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are well-known medications commonly prescribed for type 2 diabetes management and pharmacologic management of obesity. While GLP-1 RAs have many positive effects on glycemic control and cardiovascular health, the secondary effect of weight loss can present a challenge in maintaining optimal prosthesis fitting and functionality among individuals with prosthetic limbs. More specifically, weight loss can lead to decreased muscle mass and volume of the residual limb, resulting in loosening of the prosthesis. In turn, individuals often require more frequent prosthetic adjustments to ensure their safety and comfort while using the prosthetic device. Herein, we describe 3 cases of semaglutide use in patients with prosthetic limbs who subsequently presented with a variety of complications, including skin breakdown, disproportionate residual limb volume loss, decreased prosthetic use, and increased residual limb pain. Such "Ozempic limbs" have not yet been reported in the literature. These observations suggest that further research in GLP-1 RA selection is required for persons with amputation, as well as increased patient education regarding the unique complications. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Bykowski, Janelle AU - Bykowski J AUID- ORCID: 0000-0002-7542-2713 AD - Department of Medicine, Schulich School of Medicine and Dentistry, Western University, Windsor Campus, Ontario, Canada. FAU - Loewen, Garrick AU - Loewen G AD - Loewen Prosthetic Services Ltd, Ontario, Canada. FAU - Loewen, Brock AU - Loewen B AD - Loewen Prosthetic Services Ltd, Ontario, Canada. FAU - Seslija, Dana AU - Seslija D AD - Department of Medicine, Schulich School of Medicine and Dentistry, Western University, Windsor Campus, Ontario, Canada. AD - Department of Physical Medicine and Rehabilitation, Hotel-Dieu Grace Healthcare, Ontario, Canada. LA - eng PT - Case Reports PT - Journal Article DEP - 20260326 PL - United States TA - Am J Phys Med Rehabil JT - American journal of physical medicine & rehabilitation JID - 8803677 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Amputation, Surgical MH - Female MH - Male MH - *Artificial Limbs MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Amputation Stumps MH - Prosthesis Fitting OTO - NOTNLM OT - Case Report OT - Lower Limb Amputation OT - Ozempic Limb OT - Prosthetics COIS- Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. EDAT- 2026/04/09 18:30 MHDA- 2026/06/26 00:42 CRDT- 2026/04/09 16:02 PHST- 2025/11/10 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/06/26 00:42 [medline] PHST- 2026/04/09 18:30 [pubmed] PHST- 2026/04/09 16:02 [entrez] AID - 00002060-202607000-00014 [pii] AID - 10.1097/PHM.0000000000002989 [doi] PST - ppublish SO - Am J Phys Med Rehabil. 2026 Jul 1;105(7):657-660. doi: 10.1097/PHM.0000000000002989. Epub 2026 Mar 26. PMID- 41954719 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261010 IS - 1708-0428 (Electronic) IS - 0960-8923 (Linking) VI - 36 IP - 5 DP - 2026 May TI - Glucagon-Like Peptide-1 Receptor Agonists vs. Bariatric Endoscopy: A Systematic Review and Meta Analysis of Efficacy, Safety, and Metabolic Outcomes. PG - 2553-2562 LID - 10.1007/s11695-026-08588-3 [doi] AB - BACKGROUND: Metabolic bariatric surgery (MBS) is currently regarded as the most established intervention for achieving durable weight loss and metabolic improvement in patients with obesity and Type 2 diabetes mellitus (T2DM). This review aims to compare the efficacy of GLP-1 receptor agonists and bariatric endoscopic interventions in adults with obesity or T2DM by assessing key clinical outcomes including change in body mass index (BMI), glycated hemoglobin (HbA1c), weight loss, and T2DM remission. METHODS: We searched Scopus, Web of Science, PubMed and Embase from inception to July 3 2025 using a pre-defined search strategy. We enrolled full-text published manuscripts of randomized clinical trials (RCTs) and observational studies using a predefined framework. RESULTS: Eight studies (7 retrospective cohorts and 1 randomized controlled trial) including 637 participants were analyzed. Follow-up ranged from 4 to 12 months. Pooled analysis showed no statistically significant difference between GLP-1-based therapies and EBT in weight loss (MD 2.43; 95% CI - 2.89 to 7.75; I(2) = 96%), BMI change (MD 0.32; 95% CI - 0.77 to 1.42; I(2) = 97%), HbA1c reduction (MD 0.43; 95% CI - 0.44 to 1.31; I(2) = 88%), or T2DM remission (RR 1.22; 95% CI 0.72-2.08; I(2) = 0%). Substantial heterogeneity was observed for weight loss and BMI outcomes. Safety profiles differed, with gastrointestinal adverse events predominating in GLP-1 therapies and device-related intolerance reported in EBT. CONCLUSION: Within short-term follow-up, pooled analyses did not demonstrate statistically significant differences between GLP-1-based pharmacotherapy and endoscopic bariatric interventions for weight loss or glycemic outcomes. However, high heterogeneity and predominance of retrospective data limit definitive comparative conclusions. Larger, well-designed randomized trials with longer follow-up are required to clarify relative efficacy and durability. FAU - Khan, Sariya AU - Khan S AD - Batterjee Medical College, Jeddah, Saudi Arabia. sariyak2003@gmail.com. FAU - Khan, Saleha Shafi AU - Khan SS AD - Batterjee Medical College, Jeddah, Saudi Arabia. FAU - Mouazen, Saaid Mounzer AU - Mouazen SM AD - Batterjee Medical College, Jeddah, Saudi Arabia. FAU - Ramadan, Ziad Mumtaz AU - Ramadan ZM AD - Batterjee Medical College, Jeddah, Saudi Arabia. FAU - Khan, Shady Saud AU - Khan SS AD - Batterjee Medical College, Jeddah, Saudi Arabia. FAU - Aldawood, Yara Osama AU - Aldawood YO AD - Batterjee Medical College, Jeddah, Saudi Arabia. FAU - Neto, Manoel Galvao AU - Neto MG AD - Orlando Health Weight Loss and Bariatric Surgery Institute, Orlando, FL, USA. manoel.galvaoneto@orlandohealth.com. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260409 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy/therapy MH - Weight Loss MH - *Bariatric Surgery/methods MH - Treatment Outcome MH - Glycated Hemoglobin/metabolism MH - *Obesity/surgery MH - *Endoscopy, Gastrointestinal MH - Body Mass Index OTO - NOTNLM OT - Bariatric endoscopy OT - EndoBarrier OT - GLP-1 agonists OT - Obesity COIS- Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Competing Interests: The authors declare no competing interests. EDAT- 2026/04/09 12:45 MHDA- 2026/06/28 00:37 CRDT- 2026/04/09 11:06 PHST- 2025/10/14 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/02/20 00:00 [revised] PHST- 2026/06/28 00:37 [medline] PHST- 2026/04/09 12:45 [pubmed] PHST- 2026/04/09 11:06 [entrez] AID - 10.1007/s11695-026-08588-3 [pii] AID - 10.1007/s11695-026-08588-3 [doi] PST - ppublish SO - Obes Surg. 2026 May;36(5):2553-2562. doi: 10.1007/s11695-026-08588-3. Epub 2026 Apr 9. PMID- 41953701 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Real-world glycemic control, exploratory cardiorenal indicators, and safety of polyethylene glycol loxenatide versus semaglutide in type 2 diabetes patients: a Chinese two-center retrospective cohort study. PG - 1756581 LID - 10.3389/fendo.2026.1756581 [doi] LID - 1756581 AB - OBJECTIVE: To compare the real-world efficacy and safety of high dose once-weekly glucagon-like peptide-1 receptor agonists polyethylene glycol loxenatide (PEG-Loxe) and subcutaneous (s.c.) semaglutide in patients with suboptimally controlled type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort China two-center study. Patients newly initiated on once-weekly PEG-Loxe 200 mug or s.c. semaglutide 1.0 mg between January 2021 and October 2022 were matched 1:1 using propensity score matching. The primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 months. Secondary endpoints included changes in HbA1c, body weight (BW), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and estimated glomerular filtration rate (eGFR) from baseline to 3, 6, 12, and 24 months. Records of adverse drug reactions were collected and extracted from the institutional medical record system. RESULTS: A total of 510 matched patient pairs demonstrated balanced baseline characteristics. No statistically significant between-group difference was observed in HbA1c changes from baseline across all follow-up assessments (p > 0.05). At month 24, HbA1c was reduced by least-squares mean 2.02% with PEG-Loxe and 2.23% with s.c. semaglutide (estimated treatment difference [ETD] -0.21%, 95% CI: -0.52, -0.10, p = 0.260). Semaglutide was consistently and significantly superior to PEG-Loxe in improving BW (ETD at 24 months: -3.55 kg, 95% CI: -5.22, -1.88, p < 0.001), BMI (ETD -0.82 kg/m(2), 95%CI: -1.33, -0.32, p = 0.001), LDL-C (ETD -0.51 mmol/L, 95% CI: -0.68, -0.34, p < 0.001), SBP (ETD -2.08 mmHg, 95% CI: -9.33, -0.11, p < 0.001), eGFR [ETD 0.75 mL/(min.1.73m(2)), 95% CI: -2.53, 4.039, p < 0.001]. Gastrointestinal symptoms were the most common safety concern, occurring more frequently in the semaglutide group during the first 3 months (p < 0.05). CONCLUSIONS: In real-world clinical practice, at the same high dose, PEG-Loxe provided equivalent glycemic control to s.c. semaglutide with a potential lower incidence of gastrointestinal side effects. Conversely, semaglutide offered more substantial improvement of cardiorenal parameters. These findings highlight the clinical utility of both agents in personalized T2DM management. CI - Copyright (c) 2026 Yu, Fu, Xu, Lin, Yin, Cai, Jiang, Ling, Chen and Zhuo. FAU - Yu, Zelin AU - Yu Z AD - Department of Clinical Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Fu, Duoyi AU - Fu D AD - Department of Biology, School of Science, Shantou University, Shantou, China. FAU - Xu, Jing AU - Xu J AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Lin, Chujia AU - Lin C AD - Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Yin, Guoshu AU - Yin G AD - Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Cai, De AU - Cai D AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Jiang, Hongyan AU - Jiang H AD - Department of Pharmacology, Shantou University Medical College, Shantou, China. FAU - Ling, Kai AU - Ling K AD - Department of Pharmacology, Shantou University Medical College, Shantou, China. FAU - Chen, Jianqin AU - Chen J AD - Department of Geriatric Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Zhuo, Yeye AU - Zhuo Y AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260324 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects MH - China/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glomerular Filtration Rate MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Polyethylene Glycols/therapeutic use/administration & dosage/adverse effects MH - Retrospective Studies MH - Semaglutide PMC - PMC13053266 OTO - NOTNLM OT - HbA1c OT - adverse drug events OT - body weight OT - estimated glomerular filtration rate OT - lipid profiles OT - polyethylene glycol loxenatide OT - s.c. semaglutide OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/09 06:30 MHDA- 2026/04/09 06:31 PMCR- 2026/03/24 CRDT- 2026/04/09 04:45 PHST- 2025/11/28 00:00 [received] PHST- 2026/03/08 00:00 [revised] PHST- 2026/03/09 00:00 [accepted] PHST- 2026/04/09 06:31 [medline] PHST- 2026/04/09 06:30 [pubmed] PHST- 2026/04/09 04:45 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 10.3389/fendo.2026.1756581 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 24;17:1756581. doi: 10.3389/fendo.2026.1756581. eCollection 2026. PMID- 41951127 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260819 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 236 DP - 2026 Jun TI - Oral semaglutide reduces diabetes-related distress in adults with type 2 diabetes mellitus switching from DPP-4 inhibitors. The DOORS prospective real-world Italian study. PG - 113244 LID - S0168-8227(26)00163-4 [pii] LID - 10.1016/j.diabres.2026.113244 [doi] AB - AIMS: To evaluate glycemic control, weight management, and patient-reported outcomes (PROs) in adults with type 2 diabetes mellitus who transitioned to oral semaglutide (OS) after inadequate glycemic control on dipeptidyl peptidase-4 inhibitors (DPP-4i). METHODS: This 40-week, observational, prospective study included three visits: baseline (V1, OS initiation), intermediate visits (V2.X), and final visit (V3, week 40 +/- 4). The primary endpoint was change in glycated haemoglobin (HbA1c) from V1 to V3. Secondary endpoints included changes in body weight (BW), PROs - assessed by the Diabetes Distress Scale (DDS) and the Dutch Eating Behaviour Questionnaire (DEBQ) - and anthropometric/clinical parameters. RESULTS: 281 patients were enrolled (mean age 67.5 +/- 12.0 years; 55.9% male). In the in-study set (all patients initiating OS, regardless of discontinuation), mean HbA1c decreased by - 0.7 +/- 0.05% (p < 0.0001), and mean BW decreased by - 3.6 +/- 0.22 kg (p < 0.0001) from V1 to V3. Scores on the DDS domains and the DEBQ (emotional and external eating domains) decreased, indicating reduced diabetes-related distress and improved eating behaviours. Adverse events were reported by 23.1% of patients, with no hypoglycaemic episodes observed. CONCLUSIONS: OS was safe and effective in improving glycemic control, reducing BW, and alleviating diabetes-related distress and unhealthy eating behaviors in patients with type 2 diabetes mellitus switched from DPP-4i. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Giaccari, Andrea AU - Giaccari A AD - Universita Cattolica del Sacro Cuore and Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: andrea.giaccari@unicatt.it. FAU - Borroni, Francesca AU - Borroni F AD - Ospedale Generale Provinciale di Macerata, Macerata, Italy. FAU - Dauriz, Marco AU - Dauriz M AD - Section of Endocrinology and Diabetes, Department of Internal Medicine, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Via Lorenz Bohler 5, 39100 Bolzano, Italy. FAU - Gioia, Daniela AU - Gioia D AD - Casa di cure Triolo Zancla, Palermo, Italy. FAU - Baptiste, Paris AU - Baptiste P AD - Novo Nordisk LTD, Gatwich, UK. FAU - Bisio, Alessandro AU - Bisio A AD - Novo Nordisk s.p.a., Rome, Italy. FAU - Lastoria, Giusi AU - Lastoria G AD - Novo Nordisk s.p.a., Rome, Italy. FAU - Udupa, Keerthana AU - Udupa K AD - Novo Nordisk A/S, Bangalore, India. FAU - Barbagallo, Mario AU - Barbagallo M AD - A.O.U. Policlinico Giaccone, Palermo, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20260406 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/blood MH - Female MH - Male MH - Aged MH - Prospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Italy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Blood Glucose/drug effects MH - Glycemic Control MH - Drug Substitution OTO - NOTNLM OT - Diabetes-related distress OT - Glycemic control OT - Oral semaglutide OT - Patient-reported outcomes (PROs) OT - Real world evidence OT - Type 2 diabetes mellitus OT - Weight management COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.Giaccari has received speaker honoraria from Abbott, AstraZeneca, Lilly, Novo Nordisk, and Sanofi. F.Borroni, M.Dauriz, D.Gioia, M.Barbagallo have no competing interests to declare that are relevant to the content of this article. P.Baptiste, G.Lastoria, K.Udupa work at Novo Nordisk, and A.Bisio worked at Novo Nordisk at the time of study conduct and manuscript development. EDAT- 2026/04/09 00:34 MHDA- 2026/05/14 00:31 CRDT- 2026/04/08 19:13 PHST- 2025/12/12 00:00 [received] PHST- 2026/03/20 00:00 [revised] PHST- 2026/04/05 00:00 [accepted] PHST- 2026/05/14 00:31 [medline] PHST- 2026/04/09 00:34 [pubmed] PHST- 2026/04/08 19:13 [entrez] AID - S0168-8227(26)00163-4 [pii] AID - 10.1016/j.diabres.2026.113244 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jun;236:113244. doi: 10.1016/j.diabres.2026.113244. Epub 2026 Apr 6. PMID- 41947610 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260803 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 46 IP - 5 DP - 2026 May TI - Beyond Monotherapy: The Superior Efficacy of Combined GLP-1 Receptor Agonist and SGLT2 Inhibitors on Renal Biomarkers: A Systematic Review and Meta-Analysis. PG - e70142 LID - 10.1002/phar.70142 [doi] AB - Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage renal diseases. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer renoprotection; however, emerging evidence suggests that combination therapy has synergistic benefits. This meta-analysis evaluated dual versus monotherapy, focusing on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Scopus, Embase, CINAHL, Medline, and Web of Science were searched until August 2025 for RCTs comparing GLP-1RA plus SGLT2i versus monotherapy or placebo in adults with T2D. The primary outcome was the change in UACR, and the secondary outcome was eGFR. Pooled standardized mean differences (SMD) were estimated using random-effects models, including subgroup and sensitivity analyses. Eight RCTs (n = 1974; sample size, 41-4000; follow-up, 16 weeks-3.4 years) were included. Combination therapy was well tolerated and significantly reduced UACR compared with monotherapy (SMD -0.25, 95% confidence interval (CI) -0.38, -0.13; I(2) = 0%). The benefits remained significant against SGLT2i alone (SMD, -0.28) but not for GLP-1RA alone. For eGFR, dual therapy provided a modest benefit versus SGLT2i (SMD 0.12, 95% CI 0.00-0.23) but not for GLP-1RA. The effects were consistent in patients with DKD and in larger trials. Early SGLT2is and GLP-1RA combination therapy is safe and provides superior renoprotection compared to monotherapy in patients with type 2 diabetes, albuminuria, and high cardiorenal risk. Broader adoption of combination therapy could improve outcomes, although cost and access barriers remain an issue. CI - (c) 2026 ACCP Foundation, Ltd. FAU - AbdelMagid, Aya M AU - AbdelMagid AM AUID- ORCID: 0000-0001-6175-1690 AD - Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. FAU - Kamel, Ahmed M AU - Kamel AM AUID- ORCID: 0000-0002-3791-5998 AD - Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. FAU - Farid, Samar F AU - Farid SF AUID- ORCID: 0000-0002-6048-847X AD - Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Nephropathies/drug therapy/prevention & control MH - Glomerular Filtration Rate/drug effects MH - Biomarkers MH - Randomized Controlled Trials as Topic MH - Hypoglycemic Agents/administration & dosage OTO - NOTNLM OT - GLP-1RA OT - SGLT2i OT - combination therapy OT - diabetic kidney disease OT - renoprotection OT - type 2 diabetes mellitus EDAT- 2026/04/08 06:33 MHDA- 2026/04/08 06:34 CRDT- 2026/04/08 03:03 PHST- 2026/02/04 00:00 [revised] PHST- 2025/09/19 00:00 [received] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/04/08 06:34 [medline] PHST- 2026/04/08 06:33 [pubmed] PHST- 2026/04/08 03:03 [entrez] AID - 10.1002/phar.70142 [doi] PST - ppublish SO - Pharmacotherapy. 2026 May;46(5):e70142. doi: 10.1002/phar.70142. PMID- 41944572 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260804 IS - 1557-8518 (Electronic) IS - 1540-4196 (Linking) VI - 24 IP - 3 DP - 2026 Apr TI - Semaglutide-Induced Weight Loss Is the Main Determinant for the Improvement of Hepatic Biochemistry and Elastographic Repeated Measurements with FibroScan(R) in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease. PG - 121-128 LID - 10.1177/15578518251409025 [doi] AB - BACKGROUND: Semaglutide is currently being investigated for its effectiveness in metabolic dysfunction-associated steatotic liver disease (MASLD), irrespective of type 2 diabetes mellitus (T2DM) presence, even though its action on hepatic fibrosis is still debated. The aim of this study was to examine the effect of semaglutide on hepatic parameters in patients with both T2DM and MASLD in real-world clinical practice, and to further assess the significance of weight loss during treatment. METHODS: In consecutive patients with T2DM and MASLD, hepatic biochemistry and Fibrosis-4 (FIB-4) score were recorded. In participants with high FIB-4, elastographic liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) were acquired with FibroScan(R) before and after treatment with semaglutide. For within-group comparisons, Wilcoxon signed ranked test for related samples was performed, while the role of weight loss was further investigated. RESULTS: A total of 111 patients were included: 31 males (27.9%), with a mean age 56.4 +/- 9.7 years old, body mass index 32.7 +/- 6.3 kg/m(2), and median glycated hemoglobin (HbA1c) 5.8% (interquartile range [IQR]: 5.6-6.2). Semaglutide (0.5-2.4 mg/week) was administered subcutaneously for a median of 12 months (IQR: 6.6-17). Thirty-three patients (29.7%) had aspartate aminotransferase and/or alanine aminotransferase above normal, and 35 (31.5%) high FIB-4 score. Apart from an overall drop in HbA1c of 5.6% (IQR: 1.6-8.6) and weight loss of 10% (IQR: 3.2-19.6), statistically significant reductions were recorded in all liver enzymes and elastographic parameters (p < 0.001). In multiple regression analysis, weight loss was found to independently predict improvements in aminotransferases and measured CAP (p < 0.001), irrespective of treatment duration and baseline FIB-4. CONCLUSION: In this cohort of T2DM/MASLD patients with baseline optimal glycemic control, semaglutide-induced weight loss led to significant improvements of all hepatic parameters (biochemistry, liver stiffness, and steatosis assessed with CAP), even in MASLD patients with baseline liver enzymes within normal. This study supports the advantages of semaglutide administration in concomitant T2DM and MASLD. FAU - Savvidou, Savvoula AU - Savvidou S AUID- ORCID: 0000-0002-4226-6400 AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Augousti-Varela, Elektra AU - Augousti-Varela E AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Damianakou, Aikaterini AU - Damianakou A AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Chalkias, Miltiadis AU - Chalkias M AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Stergiou, Ioannis AU - Stergiou I AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Observational Study DEP - 20251220 PL - United States TA - Metab Syndr Relat Disord JT - Metabolic syndrome and related disorders JID - 101150318 RN - 53AXN4NNHX (Semaglutide) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Semaglutide/pharmacology MH - *Weight Loss/drug effects MH - Liver/diagnostic imaging/drug effects/metabolism MH - Elasticity Imaging Techniques MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy/physiopathology MH - Liver Function Tests MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged MH - Aspartate Aminotransferases/blood/drug effects MH - Alanine Transaminase/blood/drug effects MH - Treatment Outcome MH - Glycated Hemoglobin/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology OTO - NOTNLM OT - FibroScan(R) OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide OT - type 2 diabetes mellitus COIS- Author Disclosure StatementAuthors declare no conflict of interest. EDAT- 2026/04/07 12:33 MHDA- 2026/04/07 12:34 CRDT- 2026/04/07 08:43 PHST- 2026/04/07 12:34 [medline] PHST- 2026/04/07 12:33 [pubmed] PHST- 2026/04/07 08:43 [entrez] AID - 10.1177/15578518251409025 [doi] PST - ppublish SO - Metab Syndr Relat Disord. 2026 Apr;24(3):121-128. doi: 10.1177/15578518251409025. Epub 2025 Dec 20. PMID- 41940793 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20261001 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 10 DP - 2026 Oct 1 TI - Estimating the True MACE Benefits From Tirzepatide in SURPASS-CVOT Using an Imputed Placebo Analysis of REWIND. PG - 1771-1778 LID - 10.2337/dc26-0298 [doi] AB - OBJECTIVE: In prespecified analyses, the treatment effect for major adverse cardiovascular event (MACE) of tirzepatide compared with imputed placebo was estimated using SURPASS-Cardiovascular Outcomes Trial (SURPASS-CVOT) and Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial data. RESEARCH DESIGN AND METHODS: The indirect comparison with placebo was conducted for primary (MACE-3) and secondary outcomes of SURPASS-CVOT. The analysis included data from REWIND participants who would have been eligible for SURPASS-CVOT and all participants from SURPASS-CVOT. Propensity score estimation was used to adjust for differences in participant characteristics between studies. The indirect analysis of the treatment effect was derived by multiplying the hazard ratio (HR) for MACE-3 between tirzepatide and dulaglutide in SURPASS-CVOT by the HR for dulaglutide versus placebo in REWIND. Sensitivity analyses were performed using unadjusted analyses, including both the selected REWIND and the entire REWIND populations, and adjusted analysis in the entire REWIND population. Post hoc sensitivity analyses used data from a recent glucagon-like peptide 1 receptor agonist (GLP-1RA) meta-analysis that included REWIND. RESULTS: Analyses included 2,055 of 9,901 participants from REWIND and all 13,165 participants from SURPASS-CVOT. In indirect treatment effect comparisons, tirzepatide versus placebo was associated with lower MACE-3 (HR 0.72; 95% CI 0.55, 0.94), death from CV cause or heart failure events (HR 0.70; 95% CI 0.51, 0.96), and all-cause death (HR 0.61; 95% CI 0.45, 0.82). Sensitivity analyses, including nonadjusted or the entire REWIND cohort data or meta-analysis data for GLP-1RAs, were generally consistent. CONCLUSIONS: In this indirect prespecified exploratory comparison, tirzepatide compared with imputed placebo was associated with reduced CV outcomes and all-cause mortality in participants with type 2 diabetes and established atherosclerotic CV disease. CI - (c) 2026 by the American Diabetes Association. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular Medicine and Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Gerstein, Hertzel C AU - Gerstein HC AUID- ORCID: 0000-0001-8072-2836 AD - Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. FAU - D'Alessio, David AU - D'Alessio D AD - Duke University Medical Center, Durham, NC. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY. FAU - Buse, John B AU - Buse JB AD - University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Kahn, Steven E AU - Kahn SE AD - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, TX. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology and Metabolism Section, Department of Medicine, St. Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University of Bochum, Bochum, Germany. FAU - Nissen, Steven E AU - Nissen SE AD - Cleveland Clinic Coordinating Center for Clinical Research and Department of Medicine, Cleveland Clinic, Cleveland, OH. FAU - Zinman, Bernard AU - Zinman B AUID- ORCID: 0000-0002-0041-1876 AD - University of Toronto, Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital, Toronto, Ontario, Canada. FAU - Zoungas, Sophia AU - Zoungas S AUID- ORCID: 0000-0003-2672-0949 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. FAU - Bartee, Amy AU - Bartee A AD - Eli Lilly and Company, Indianapolis, IN. FAU - Miller, Debra AU - Miller D AD - Eli Lilly and Company, Indianapolis, IN. FAU - Nishiyama, Hiroshi AU - Nishiyama H AD - Eli Lilly and Company, Indianapolis, IN. FAU - Qu, Yongming AU - Qu Y AD - Eli Lilly and Company, Indianapolis, IN. FAU - Weerakkody, Govinda AU - Weerakkody G AD - Eli Lilly and Company, Indianapolis, IN. FAU - Wiese, Russell J AU - Wiese RJ AUID- ORCID: 0009-0007-6705-7545 AD - Eli Lilly and Company, Indianapolis, IN. FAU - Pavo, Imre AU - Pavo I AD - Eli Lilly and Company, Indianapolis, IN. FAU - Nicholls, Stephen J AU - Nicholls SJ AUID- ORCID: 0000-0002-9668-4368 AD - Victorian Heart Institute, Monash University, Melbourne, Australia. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Diabetes Care. 2026 Oct 1;49(10):1765-1767. doi: 10.2337/dci26-0047. PMID: 42766767 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Tirzepatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use PMC - PMC13594787 COIS- Duality of Interest. N.S. has consulted for and/or received speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly and Company, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Kailera, Mass Medicines, Menarini-Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly and Company, Novo Nordisk, and Hanmi; continuing education grants from Eli Lilly and Company, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly and Company, Novo Nordisk, Zuellig, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly and Company, Novo Nordisk, and Sanofi. He holds a patent for the use of GDF15 as a biomarker for metformin intake. D.D. has consulted for Eli Lilly and Company, Sun Pharmaceuticals, Structure Therapeutics, MBX, Fractyl, Proteostasis, Arrowhead, and Vertex. D.L.B. discloses the following relationships: advisory board participation for Angiowave, Antlia Bioscience, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, NirvaMed, Novo Nordisk, Repair Biotechnologies, Stasys, and Tourmaline Bio; board of directors participation for the American Heart Association New York City, Angiowave (stock options), Bristol-Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultation with Alnylam, Altimmune, Broadview Ventures, Corcept Therapeutics, Corsera, GlaxoSmithKline, Hims, SERB, SFJ, Summa Therapeutics, and Worldwide Clinical Trials; data monitoring committee participation for Acesion Pharma, Assistance Publique-Hopitaux de Paris, Baim Institute for Clinical Research, Boston Scientific (chair, Pulmonary Embolish International Thrombolysis High Risk [PEITHO] trial), Cleveland Clinic, Contego Medical (chair, Protection Against Emboli During Carotid Artery Stenting [PERFORMANCE 2] trial), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ABILITY-Diabetes Mellitus [ABILITY-DM] trial, funded by Concept Medical, and for the Safety and Efficacy of the Alleviant System for No-Implant Interatrial Shunt Creation in Patients With Chronic Heart Failure [ALLAY-HF], funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded Myocardial Ischemia and Transfusion [MINT] Trial); honoraria from the American College of Cardiology (ACC) (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (ApoA-I Event Reducing in Ischemic Syndromes II [AEGIS-II] executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Duke Clinical Research Institute, Engage Health Media, HMP Global (editor in chief, Journal of Invasive Cardiology), Medtelligence/ReachMD (continuing medical education [CME] steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Philips (Becker's Webinar on artificial intelligence), Population Health Research Institute, WebMD (CME steering committees), and Wiley (steering committee); other for Clinical Cardiology (deputy editor) and Progress in Cardiovascular Diseases (deputy editor); named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon, for which neither he nor Brigham and Women's Hospital receive any income); research funding from Abbott, Acesion Pharma, Afimmune, Alnylam, Amarin, Amgen, AstraZeneca, Atricure, Bayer, Boehringer Ingelheim, Boston Scientific, CellProthera, Cereno Scientific, Chiesi, Cleerly, CSL Behring, Faraday Pharmaceuticals, Fractyl, Idorsia, Janssen, Javelin, Lexicon, Eli Lilly and Company, Medtronic, Merck, MiRUS, Moderna, Novartis, Novo Nordisk, Pfizer, PhaseBio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, 89Bio; royalties from Elsevier (editor, Braunwald's Heart Disease); and site coinvestigator for Cleerly. J.B.B. has received salary support from clinical trial contracts to his employer by Corcept, Dexcom, GentiBio, and Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly and Company, Embecta, GentiBio, Insulet, Metsera, MiniMed, Novo Nordisk, Tandem, Recordati, Sparrow Pharmaceuticals, Vertex, vTv Therapeutics, and Zealand; and has stock/stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. S.D.P. has served as an advisor for Abbott, Applied Therapeutics, Biomea Fusion, Eli Lilly and Company, Menarini International, Novo Nordisk, Roche, and Sun Pharmaceuticals; has received fees for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Laboratori Guidotti, Menarini International, and Novo Nordisk; has served as past-president of the European Association for the Study of Diabetes; and is currently president of the European Diabetes Forum and of the Menarini Foundation. S.E.K., during the course of the study, has received grant support from Corcept Therapeutics and consulted or served on advisory boards for Amgen, AltPep, Anji Pharmaceuticals, Biomea Fusion, Boehringer Ingelheim, Casma Therapeutics, Congruence Therapeutics, Intarcia, Eli Lilly and Company, Merck, Neurochem, Novo Nordisk, Oramed, Pfizer, and Third Rock Ventures. A.M.L. has received honoraria for consultancy from Novo Nordisk, Eli Lilly and Company, Alnylam, Amgen, Ardelyx, Brainstorm Cell, Capricor, Cadrenal, Johnson & Johnson, Medtronic, Neovasc, ReCor, TD Cowen, and V-Wave and has received research funding paid to his institution from AbbVie, AstraZeneca, CSL Behring, Eli Lilly and Company, Esperion, and Novartis. D.K.M. has received honoraria for clinical trial leadership from Novo Nordisk, Eli Lilly and Company USA, Pfizer, Boehringer Ingelheim, NewAmsterdam, Amgen, and Lexicon and for consultancy from Eli Lilly and Company USA, Boehringer Ingelheim, Novo Nordisk, Lexicon, Amgen, Neurotronic, Kailera, Metsera, Alveus, Zealand, CSL Behring and has stock option equity interest in Kailera. M.A.N. has been a member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Regor, Sun Pharmaceuticals, and Structure Therapeutics (ShouTi, Gasherbrum); has received grant support from Merck Sharp & Dohme; served on the speakers' bureaus of Eli Lilly and Company, Merck Sharp & Dohme, Medscape, Medical Learning Institute, and Novo Nordisk; and is on a data monitoring and safety board for Inventiva. S.E.N. reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Amgen, Arrowhead, Bristol-Myers Squibb, Kardigan, CRISPR Therapeutics, Eli Lilly and Company, Esperion, Medtronic, MyoKardia, NewAmsterdam, Novartis, Pfizer, and Silence Therapeutics. He is involved in conducting these clinical trials but receives no personal remuneration for his participation, and he consults for these pharmaceutical companies but does not accept compensation. B.Z. reports being a consultant for Eli Lilly and Company. S.Z. reports previous payments to her institution (Monash University) from AstraZeneca, Boehringer Ingelheim, CSL Seqirus, Eli Lilly and Company Australia, GlaxoSmithKline, Moderna, Sanofi, and Novo Nordisk for her participation on advisory boards, on steering committees, and in educational meetings. S.J.N. received grant/research support from AstraZeneca, NewAmsterdam, Amgen, Anthera, Cyclarity, Eli Lilly and Company, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience and was a consultant for Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly and Company, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo, Scribe, Silence Therapeutics, CSL Seqirus, and Vaxxinity. A.B., D.M., H.N., Y.Q., G.W., R.J.W., and I.P. are current employees and shareholders of Eli Lilly and Company. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/04/06 12:35 MHDA- 2026/09/21 17:47 PMCR- 2026/04/06 CRDT- 2026/04/06 10:23 PHST- 2026/02/06 00:00 [received] PHST- 2026/03/06 00:00 [accepted] PHST- 2026/09/21 17:47 [medline] PHST- 2026/04/06 12:35 [pubmed] PHST- 2026/04/06 10:23 [entrez] PHST- 2026/04/06 00:00 [pmc-release] AID - 164674 [pii] AID - 260298 [pii] AID - 10.2337/dc26-0298 [doi] PST - ppublish SO - Diabetes Care. 2026 Oct 1;49(10):1771-1778. doi: 10.2337/dc26-0298. PMID- 41938526 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 23 IP - 4 DP - 2026 TI - Risk of peripheral vestibular disorders and hearing impairment among users of glucagon-like peptide-1 receptor agonists. PG - 1577-1587 LID - 10.7150/ijms.131397 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used antidiabetic agents with established glycemic efficacy. Peripheral vestibular disorders and hearing impairment are inner ear conditions that may be influenced by metabolic and glycemic status. This study aimed to investigate the association between GLP-1 RA use and the development of peripheral vestibular disorders, dizziness, and hearing impairment. This retrospective cohort study identified patients who received GLP-1 RA treatment and matched them with non-GLP-1 RA users. After propensity score matching, a total of 684,092 participants were included, with 342,046 in the GLP-1 RA group and 342,046 in the non-GLP-1 RA groups. The primary outcomes were newly diagnosed peripheral vestibular disorders, dizziness, and hearing impairment. Cox proportional hazards regression models were applied to compare outcome incidences between groups. During the follow-up period, 4,407 cases of peripheral vestibular disorders occurred in the GLP-1 RA group compared with 3,946 cases in the non-GLP-1 RA group, indicating a significantly higher incidence among GLP-1 RA users (P < 0.001). Dizziness was diagnosed in 32,545 GLP-1 RA users and 29,931 nonusers, while hearing impairment occurred in 9,522 and 7,898 participants, respectively; both outcomes were significantly more frequent in the GLP-1 RA group (P < 0.001). Cumulative incidence analyses showed significantly higher risks for all three outcomes in the GLP-1 RA group. In conclusion, GLP-1 RA use may presented be with higher incidences of peripheral vestibular disorders, dizziness, and hearing impairment in white population. CI - (c) The author(s). FAU - Huang, Jing-Yang AU - Huang JY AD - Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Lu, Yen-Ting AU - Lu YT AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Department of Otolaryngology, St. Martin De Porres Hospital, Chiayi, Taiwan. FAU - Hsin, Chung-Han AU - Hsin CH AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Lo, Tun-Shin AU - Lo TS AD - Department of Speech Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Lee, Chia-Yi AU - Lee CY AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Yang, Shun-Fa AU - Yang SF AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Liao, Miao-Yu AU - Liao MY AD - Department of Family Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20260317 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Vestibular Diseases/epidemiology/chemically induced MH - *Hearing Loss/epidemiology/chemically induced MH - Male MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - *Hypoglycemic Agents/adverse effects MH - *Dizziness/epidemiology/chemically induced MH - Incidence MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13048892 OTO - NOTNLM OT - epidemiology OT - glucagon-like peptide-1 receptor agonists OT - hearing impairment OT - peripheral vestibular disorder OT - type 2 diabetes mellitus COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2026/04/06 12:36 MHDA- 2026/04/06 12:37 PMCR- 2026/03/17 CRDT- 2026/04/06 06:10 PHST- 2026/01/13 00:00 [received] PHST- 2026/03/13 00:00 [accepted] PHST- 2026/04/06 12:37 [medline] PHST- 2026/04/06 12:36 [pubmed] PHST- 2026/04/06 06:10 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - ijmsv23p1577 [pii] AID - 10.7150/ijms.131397 [doi] PST - epublish SO - Int J Med Sci. 2026 Mar 17;23(4):1577-1587. doi: 10.7150/ijms.131397. eCollection 2026. PMID- 41938505 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 23 IP - 4 DP - 2026 TI - Association of Glucagon-like Peptide-1 Receptor Agonists with Mortality and Aspiration Pneumonia in Patients with Type 2 Diabetes After Gastrostomy: A Target Trial Emulation Study. PG - 1444-1455 LID - 10.7150/ijms.128956 [doi] AB - BACKGROUND: This study aimed to compare the safety and effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes following gastrostomy. METHODS: We conducted a target trial emulation using real-world data. From January 1, 2015, to December 31, 2024, we identified 728 patients who initiated either GLP-1 RA or DPP-4i after gastrostomy. After 1:1 propensity score matching to balance baseline covariates, 364 patients were included in each group. The primary analysis followed an intention-to-treat principle, and follow-up continued until June 30, 2025. Several sensitivity analyses, including landmark analysis and E-value calculation, were performed to assess the robustness of the findings. RESULTS: Compared with DPP-4i initiation, GLP-1 RA initiation was associated with lower all-cause mortality (adjusted hazard ratio [aHR], 0.71; 95% confidence interval [CI], 0.54-0.93) and aspiration pneumonia (aHR, 0.64; 95% CI, 0.44-0.93). CONCLUSIONS: Our findings indicate that initiation of GLP-1 RA, compared with initiation of DPP-4i, was associated with lower all-cause mortality and a lower risk of aspiration pneumonia in patients with type 2 diabetes following gastrostomy. Further prospective studies are warranted to confirm these findings in this vulnerable population. CI - (c) The author(s). FAU - Tseng, Yuan-Tsung AU - Tseng YT AD - Department of Public Health, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan. AD - Department of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), No. 670, Chongde Road, East District, Tainan City 701, Taiwan. FAU - Chen, Chung-Hung AU - Chen CH AD - Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Road, Lugang Township, Changhua County 505, Taiwan. AD - Nursing Department, Nursing College, Hung Kuang University, No. 1018, Section 6, Taiwan Boulevard, Shalu District, Taichung City 433304, Taiwan. FAU - Chou, Li-Ping AU - Chou LP AD - Division of Cardiology, Department of Medicine, Tainan Sin-Lau Hospital, No. 57, Section 1, Dongmen Road, East District, Tainan City 701001, Taiwan. AD - Department of Health Care Administration, Chang Jung Christian University, No. 1, Changda Road, Gueiren District, Tainan City 711301, Taiwan. FAU - Chen, Shu-Ying AU - Chen SY AD - Nursing Department, Nursing College, Hung Kuang University, No. 1018, Section 6, Taiwan Boulevard, Shalu District, Taichung City 433304, Taiwan. FAU - Huang, Huai-Yi AU - Huang HY AD - Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Road, Lugang Township, Changhua County 505, Taiwan. AD - Department of Nursing, Jenteh Junior College of Medicine, Nursing and Management, No. 79-9, Sha-Luen Hu, Xi-Zhou Li, Houlong Township, Miaoli County 356, Taiwan. FAU - Wang, Jyun-Wei AU - Wang JW AD - Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Road, Lugang Township, Changhua County 505, Taiwan. FAU - Li, Chung-Yi AU - Li CY AD - Department of Public Health, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan. AD - Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan. LA - eng PT - Journal Article DEP - 20260317 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/mortality/drug therapy/complications MH - *Gastrostomy/adverse effects MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Pneumonia, Aspiration/etiology/epidemiology/prevention & control/mortality MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - *Postoperative Complications/etiology/prevention & control/mortality PMC - PMC13048897 OTO - NOTNLM OT - all-cause mortality OT - gastrostomy OT - glucagon-like peptide-1 receptor agonists OT - target trial emulation COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2026/04/06 12:36 MHDA- 2026/04/06 12:37 PMCR- 2026/03/17 CRDT- 2026/04/06 06:10 PHST- 2025/11/25 00:00 [received] PHST- 2026/03/04 00:00 [accepted] PHST- 2026/04/06 12:37 [medline] PHST- 2026/04/06 12:36 [pubmed] PHST- 2026/04/06 06:10 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - ijmsv23p1444 [pii] AID - 10.7150/ijms.128956 [doi] PST - epublish SO - Int J Med Sci. 2026 Mar 17;23(4):1444-1455. doi: 10.7150/ijms.128956. eCollection 2026. PMID- 41937314 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 3 DP - 2026 May TI - Comparative Efficacy and Safety of Ecnoglutide in Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - e70217 LID - 10.1002/edm2.70217 [doi] LID - e70217 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) affects over 500 million people worldwide, with traditional therapies often failing to maintain long-term glycaemic control. Ecnoglutide, a novel long-acting GLP-1 receptor agonist, has emerged as a promising therapeutic option. This systematic review and meta-analysis evaluated the efficacy and safety of ecnoglutide in adults with T2DM. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, ScienceDirect, ClinicalTrials.gov, and Google Scholar through September 2025. Randomized controlled trials comparing ecnoglutide with placebo or active comparators in adults with T2DM were included. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included fasting plasma glucose, insulin resistance markers, lipid profile, liver enzymes, and adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analysis was performed using random-effects models, with mean differences and risk ratios calculated at 95% confidence intervals. RESULTS: Four RCTs comprising 1643 participants (1162 receiving ecnoglutide, 444 controls) were included. Ecnoglutide significantly reduced HbA1c (MD = -0.44, 95% CI -0.55 to -0.33, p < 0.00001), body weight (MD = -5.63, 95% CI -7.90 to -3.35, p < 0.01), and fasting plasma glucose (MD = -0.81, 95% CI -1.03 to -0.59, p < 0.00001). Improvements were observed in insulin sensitivity, lipid profile, and liver enzymes. Adverse events occurred more frequently with ecnoglutide (RR = 1.09, p < 0.01), although predominantly gastrointestinal and mild-to-moderate, with no significant differences in serious adverse events. CONCLUSIONS: Ecnoglutide demonstrates robust efficacy in glycaemic control, weight reduction, and cardiometabolic parameters with an acceptable safety profile in adults with T2DM, supporting its therapeutic potential as a next-generation GLP-1 receptor agonist. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Kumar, Mukesh AU - Kumar M AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Kumar, Sumet AU - Kumar S AUID- ORCID: 0009-0004-2215-311X AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Ali, Sheikh Muhammad Ebtehaj AU - Ali SME AUID- ORCID: 0009-0008-2223-4488 AD - Department of Medicine, Abbasi Shaheed Hospital, Karachi, Pakistan. FAU - Qazi, Hadia AU - Qazi H AUID- ORCID: 0009-0002-9406-3776 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Janjua, Arshia Arif AU - Janjua AA AUID- ORCID: 0009-0002-6779-483X AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Ahmed, Hanzlah AU - Ahmed H AUID- ORCID: 0009-0009-0336-1446 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Babar, Rayan AU - Babar R AUID- ORCID: 0009-0000-3641-1651 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Sheikh, Rumaisa Imtiaz AU - Sheikh RI AUID- ORCID: 0009-0000-0488-7938 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Kumar, Laksh AU - Kumar L AUID- ORCID: 0009-0002-6978-5080 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Ali, Sana Mohammad AU - Ali SM AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Hanif, Fatima AU - Hanif F AUID- ORCID: 0009-0006-7995-5169 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Gul, Khizra AU - Gul K AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Ali, Ayesha Sarwar AU - Ali AS AUID- ORCID: 0009-0005-5322-1709 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Bukhari, Shehzadi Umme Rubab AU - Bukhari SUR AUID- ORCID: 0009-0000-3123-3497 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Raja, Adarsh AU - Raja A AUID- ORCID: 0009-0003-2964-9452 AD - Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. FAU - Chaulagain, Aayush AU - Chaulagain A AUID- ORCID: 0009-0001-9259-0612 AD - Department of Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Blood Glucose/drug effects MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13052322 OTO - NOTNLM OT - Ecnoglutide OT - GLP-1 receptor agonist OT - glycaemic control OT - meta-analysis OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/04/06 06:31 MHDA- 2026/04/06 06:32 PMCR- 2026/04/05 CRDT- 2026/04/06 01:03 PHST- 2026/02/24 00:00 [revised] PHST- 2025/12/07 00:00 [received] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/04/06 06:32 [medline] PHST- 2026/04/06 06:31 [pubmed] PHST- 2026/04/06 01:03 [entrez] PHST- 2026/04/05 00:00 [pmc-release] AID - EDM270217 [pii] AID - 10.1002/edm2.70217 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 May;9(3):e70217. doi: 10.1002/edm2.70217. PMID- 41935054 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260823 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Apr 4 TI - Real-world evidence for comparative safety of second-line antihyperglycemic agents in older adults with type 2 diabetes. LID - 10.1038/s41467-026-71307-0 [doi] LID - 7195 AB - As prescribing of newer antihyperglycemic agents expands, there remains limited comparative safety data for older adults-a population particularly vulnerable to adverse drug events and underrepresented in clinical trials. We conduct a multinational cohort study using nine databases from the U.S. and Europe. Among adults aged >/=65, we compare eighteen safety outcomes across four classes of second-line antihyperglycemic agents. We use propensity score adjustment, empirical calibration, and prespecified diagnostics and estimated hazard ratios. In a cohort of 1.8 million, both GLP-1 receptor agonists and SGLT2 inhibitors are linked to significantly lower risks of hypoglycemia and hyperkalemia than sulfonylureas. GLP-1 receptor agonists show lower risks of peripheral edema than DPP-4 inhibitors. However, SGLT2 inhibitors are associated with a higher risk of diabetic ketoacidosis compared to GLP-1 receptor agonists and sulfonylureas. These results support informed, safety-conscious prescribing in the older adults underrepresented in clinical trials yet highly susceptible to adverse events. CI - (c) 2026. The Author(s). FAU - Kim, Chungsoo AU - Kim C AUID- ORCID: 0000-0003-1802-1777 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. AD - Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, USA. FAU - Blacketer, Clair AU - Blacketer C AUID- ORCID: 0000-0003-2570-2124 AD - Johnson and Johnson, New Brunswick, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Johnson and Johnson, New Brunswick, USA. FAU - Duarte-Salles, Talita AU - Duarte-Salles T AUID- ORCID: 0000-0002-8274-0357 AD - Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina, Barcelona, Spain. AD - Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands. FAU - Viernes, Benjamin AU - Viernes B AD - VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USA. FAU - Falconer, Thomas AU - Falconer T AUID- ORCID: 0000-0001-6904-1394 AD - Department of Biomedical Informatics, Columbia University, New York, USA. FAU - Pistillo, Andrea AU - Pistillo A AUID- ORCID: 0000-0002-4467-0220 AD - Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Li, Jing AU - Li J AD - Real World Solutions, IQVIA, Shanghai, China. FAU - Yin, Can AU - Yin C AD - Real World Solutions, IQVIA, Shanghai, China. FAU - Van Zandt, Mui AU - Van Zandt M AUID- ORCID: 0000-0002-5426-8657 AD - Real World Solutions, IQVIA, Durham, USA. FAU - Nagy, Paul AU - Nagy P AD - Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, USA. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA. FAU - Minty, Evan AU - Minty E AD - O'Brien Institute for Public Health, University of Calgary, Calgary, Canada. FAU - You, Seng Chan AU - You SC AUID- ORCID: 0000-0002-5052-6399 AD - Department of Biomedicine Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Sawano, Mitsuaki AU - Sawano M AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. FAU - Sawano, Shoko AU - Sawano S AUID- ORCID: 0009-0000-6568-1781 AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. FAU - Jeon, Ja Young AU - Jeon JY AD - Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Aminorroaya, Arya AU - Aminorroaya A AUID- ORCID: 0000-0003-3197-2657 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. FAU - Dhingra, Lovedeep S AU - Dhingra LS AUID- ORCID: 0000-0002-5664-4126 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. FAU - Pedroso, Aline F AU - Pedroso AF AUID- ORCID: 0000-0002-1876-8304 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. FAU - Thangaraj, Phyllis AU - Thangaraj P AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. FAU - Dorr, David A AU - Dorr DA AD - Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, USA. FAU - Pratt, Nicole AU - Pratt N AD - Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia. FAU - Man, Kenneth K C AU - Man KKC AUID- ORCID: 0000-0001-8645-1942 AD - Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom. FAU - Lau, Wallis C Y AU - Lau WCY AD - Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom. FAU - Morales, Daniel R AU - Morales DR AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, USA. FAU - Khera, Rohan AU - Khera R AUID- ORCID: 0000-0001-9467-6199 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. FAU - Schuemie, Martijn J AU - Schuemie MJ AUID- ORCID: 0000-0002-0817-5361 AD - Johnson and Johnson, New Brunswick, USA. FAU - Ryan, Patrick B AU - Ryan PB AD - Johnson and Johnson, New Brunswick, USA. AD - Department of Biomedical Informatics, Columbia University, New York, USA. FAU - Hripcsak, George AU - Hripcsak G AD - VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USA. AD - Department of Biomedical Informatics, Columbia University, New York, USA. FAU - Krumholz, Harlan M AU - Krumholz HM AUID- ORCID: 0000-0003-2046-127X AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. FAU - Suchard, Marc A AU - Suchard MA AUID- ORCID: 0000-0001-9818-479X AD - VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USA. msuchard@ucla.edu. AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, USA. msuchard@ucla.edu. FAU - Lu, Yuan AU - Lu Y AUID- ORCID: 0000-0001-5264-2169 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. y.lu@yale.edu. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. y.lu@yale.edu. LA - eng GR - R01HL169954/U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HG006139/HG/NHGRI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - K23 HL153775/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20260404 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin Secretagogues) SB - IM UOF - medRxiv. 2025 May 09:2025.05.08.25327248. doi: 10.1101/2025.05.08.25327248. PMID: 40385382 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Sulfonylurea Compounds/adverse effects/therapeutic use MH - Hypoglycemia/chemically induced MH - Female MH - Male MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hyperkalemia/chemically induced MH - Aged, 80 and over MH - United States MH - Diabetic Ketoacidosis/chemically induced MH - Europe MH - Insulin Secretagogues MH - Cohort Studies PMC - PMC13396638 COIS- Competing interests: Dr. Sawano has received partial research funding through Yale University from PolyBio, Pfizer, and Norvatis. He has also received lecture honoraria from Boehringer Ingelheim and Abbott and receives compensation for his role as Execute Associate Editor for JACC, all outside the scope of this work. Dr. Nishimura received support from the National Institute of General Medical Sciences of the National Institute of Health. Dr. Khera is an associate editor at JAMA; and has received support from the National Institutes of Health (awards R01 AG089981, R01 HL167858 and K23 HL153775) and the Doris Duke Charitable Foundation (award 2022060); has received research support, through Yale University, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. provisional patent applications WO2023230345A1, US20220336048A1, 63/177,117, 63/346,610, 63/428,569, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, unrelated to the present work; and is a cofounder of Evidence2Health and Ensight-AI, precision health platforms to improve evidence-based cardiovascular care and cardiovascular diagnostics. Dr. Thangaraj is a coinventor on provisional patent 63/606,203, unrelated to the present work, and is funded by grant 5T32 HL155000-03. Ms. Blacketer, Dr. Ostropolets, Dr. Schuemie, and Dr. Ryan are employees of Johnson & Johnson and shareholders of Johnson & Johnson. Ms. Li and Ms. Yin are employees of IQVIA. Ms. Zandt is an employee of IQVIA and a shareholder of IQVIA. Dr. Lau received research funding from Diabetes UK outside the scope of this work. Dr. Minty discloses a consulting relationship with Orpyx Medical Technologies, equity ownership in Orpyx Medical Technologies, and status as co-inventor on 2 patent applications (US 20250000440, US 20250000440), all of which are outside the scope of this work. Dr. You reports being a chief executive officer of PHI Digital Healthcare and grants from Daiichi Sankyo. He is a co-inventor of granted Korea Patent DP-2023-1223 and DP-2023-0920, and pending Patent Applications DP-2024-0909, DP-2024-0908, DP-2022-1658, DP-2022-1478, and DP-2022-1365, unrelated to current work. Dr. Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government, outside the submitted work). Dr. Hripcsak received a grant from Johnson & Johnson for methods work unrelated to this study. Dr. Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, HugoHealth, and Ensight-AI; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and, through Yale University, from Johnson & Johnson. Dr. Suchard receives additional contracts and grants from the US Food & Drug Administration, the US National Institutes of Health, Janssen Research & Development and Gliead Sciences outside the scope of this work. Dr. Lu received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under awards R01HL69954 and R01HL169171), the Patient-Centered Outcomes Research Institute (under award HM-2022C2-28354), Sentara Research Foundation, and Novartis through Yale University. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2026/04/05 04:22 MHDA- 2026/07/24 00:37 PMCR- 2026/04/04 CRDT- 2026/04/04 23:13 PHST- 2025/07/01 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/07/24 00:37 [medline] PHST- 2026/04/05 04:22 [pubmed] PHST- 2026/04/04 23:13 [entrez] PHST- 2026/04/04 00:00 [pmc-release] AID - 10.1038/s41467-026-71307-0 [pii] AID - 71307 [pii] AID - 10.1038/s41467-026-71307-0 [doi] PST - epublish SO - Nat Commun. 2026 Apr 4;17(1):7195. doi: 10.1038/s41467-026-71307-0. PMID- 41931929 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260803 IS - 1873-3360 (Electronic) IS - 0306-4530 (Linking) VI - 188 DP - 2026 Jun TI - The effect of GLP-1 receptor agonists on anxiety: A systematic review. PG - 107844 LID - S0306-4530(26)00104-6 [pii] LID - 10.1016/j.psyneuen.2026.107844 [doi] AB - Anxiety-like behaviors are highly prevalent and frequently co-occur with metabolic conditions such as type 2 diabetes and obesity, suggesting the potential for shared biological mechanisms. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and weight management, emerging evidence indicates that they may also influence neuroinflammation, neuroplasticity, and affective regulation. However, findings across preclinical and clinical studies remain fragmented, and no systematic synthesis has directly evaluated their effects on anxiety-like behaviors. This review addresses this gap by examining whether GLP-1 RA administration reduces anxiety-like behaviors or clinically coded anxiety outcomes. Following PRISMA guidelines, preclinical and clinical studies were systematically identified, screened using PICOS-defined criteria, and evaluated with validated quality assessment tools. Across animal studies, GLP-1 RAs consistently reduced anxiety-like behaviors and improved neurobiological markers related to stress resilience, while clinical cohorts demonstrated mixed but suggestive evidence of reduced anxiety incidence and lower suicidal ideation risk. These findings highlight the potential for GLP-1 RAs to modulate both metabolic and psychiatric pathways, underscoring the need for randomized controlled trials to clarify causal effects and inform their role in metabolic psychiatry. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Yi, Yu Tian AU - Yi YT AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, ON, Canada. Electronic address: parthenia.yu@mail.utoronto.ca. FAU - Zheng, Yang Jing AU - Zheng YJ AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address: yangjing.zheng@mail.utoronto.ca. FAU - Bargiota, Stavroula I AU - Bargiota SI AD - Department of Psychiatry, University of Thessaly, Larissa, Greece. Electronic address: stbargiota@uth.gr. FAU - Dri, Christine E AU - Dri CE AD - Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: christine.dri@alumni.utoronto.ca. FAU - Teopiz, Kayla M AU - Teopiz KM AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address: kayla.teopiz@alumni.utoronto.ca. FAU - Wong, Sabrina AU - Wong S AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, ON, Canada. Electronic address: sabrinal.wong@mail.utoronto.ca. FAU - Han Le, Gia AU - Han Le G AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address: hanny.le@mail.utoronto.ca. FAU - Kwan, Angela T H AU - Kwan ATH AD - Brain and Cognition Discovery Foundation, Toronto, Canada; Faculty of Medicine, University of Ottawa, Ottawa, Canada. Electronic address: angela.kwan@alumni.utoronto.ca. FAU - Cao, Bing AU - Cao B AD - Faculty of Psychology, Southwest University, Chongqing 400715, PR China. Electronic address: bingcao@swu.edu.cn. FAU - Ho, Roger AU - Ho R AD - Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Division of Life Science (LIFS), Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Hong Kong. Electronic address: rogercmho@ust.hk. FAU - Balanag, Earl Marvin P AU - Balanag EMP AD - Department of Psychiatry and Behavioral Medicine, University of the Philippines - Philippine General Hospital, Manila, Philippines. Electronic address: epbalanag@up.edu.ph. FAU - McIntyre, Roger S AU - McIntyre RS AD - Department of Psychiatry, Univeristy of Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, ON, Canada. Electronic address: roger.mcintyre@bcdf.org. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260321 PL - England TA - Psychoneuroendocrinology JT - Psychoneuroendocrinology JID - 7612148 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Humans MH - *Anxiety/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Anxiety OT - Depression OT - GLP-1 OT - Generalized anxiety OT - Glucagon-like peptide-1 receptor agonist OT - Metabolic psychiatry COIS- Declaration of Competing Interest Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Bristol Myers Squibb (BMS) and Atai Life Sciences. Yu Tian Yi, Yang Jing Zheng, Stavroula I. Bargiota, Christine E. Dri, Kayla M. Teopiz, Sabrina Wong, Gia Han Le, Angela T.H. Kwan, Bing Cao, Roger Ho, Earl Marvin P. Balanag, Roger S. McIntyre have no conflicts of interest to disclose. EDAT- 2026/04/04 00:35 MHDA- 2026/05/13 00:28 CRDT- 2026/04/03 18:02 PHST- 2025/12/06 00:00 [received] PHST- 2026/03/17 00:00 [revised] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/05/13 00:28 [medline] PHST- 2026/04/04 00:35 [pubmed] PHST- 2026/04/03 18:02 [entrez] AID - S0306-4530(26)00104-6 [pii] AID - 10.1016/j.psyneuen.2026.107844 [doi] PST - ppublish SO - Psychoneuroendocrinology. 2026 Jun;188:107844. doi: 10.1016/j.psyneuen.2026.107844. Epub 2026 Mar 21. PMID- 41931049 OWN - NLM STAT- MEDLINE DCOM- 20260403 LR - 20260406 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 394 IP - 13 DP - 2026 Apr 2 TI - GLP-1 Receptor Agonists. PG - 1313-1324 LID - 10.1056/NEJMra2500106 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are incretin analogues that promote glucose-mediated insulin release and are used to treat type 2 diabetes mellitus and obesity. GLP-1 receptor agonists and GLP-1 and glucose-dependent insulinotropic peptide agonists have several mechanisms of action, including reduction of gastric emptying, inhibition of glucagon secretion, beneficial changes in the intestinal microbiome, and direct effects on hypothalamic nuclei to enhance satiety (which promotes weight loss). Beyond the impressive effects of GLP-1 receptor agonists on blood glucose levels and body weight, large-scale randomized, controlled trials have shown that GLP-1 receptor agonists reduce cardiovascular risk and slow progression to renal failure in persons at high risk and those with type 2 diabetes. Adverse side effects from GLP-1 receptor agonists are mostly gastrointestinal but may also include loss of muscle and bone mass. Questions remain about long-term adherence, weight regain after discontinuation of treatment, and the functional implications of the loss of muscle and bone mass. Recent and ongoing targeted studies suggest the possibility of additional uses for GLP-1 receptor agonists. CI - Copyright (c) 2026 Massachusetts Medical Society. FAU - Rosen, Clifford J AU - Rosen CJ AD - Tufts University School of Medicine, Boston. AD - Maine Medical Center Institute for Research, Scarborough. FAU - Ingelfinger, Julie R AU - Ingelfinger JR LA - eng PT - Journal Article PT - Review PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Anti-Obesity Agents) RN - 9007-92-5 (Glucagon) SB - IM MH - Humans MH - *Cardiovascular Diseases/etiology/metabolism/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - Glucagon-Like Peptide 1/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/pharmacology/therapeutic use MH - Hypoglycemic Agents/adverse effects/pharmacology/therapeutic use MH - Incretins/metabolism MH - *Obesity/complications/drug therapy/metabolism MH - *Renal Insufficiency/etiology/metabolism/prevention & control MH - Anti-Obesity Agents/adverse effects/pharmacology/therapeutic use MH - Disease Progression MH - Gastric Emptying/drug effects MH - Glucagon/metabolism MH - Gastrointestinal Microbiome/drug effects MH - Satiety Response/drug effects MH - Randomized Controlled Trials as Topic MH - Medication Adherence EDAT- 2026/04/03 13:47 MHDA- 2026/04/03 13:48 CRDT- 2026/04/03 10:13 PHST- 2026/04/03 13:48 [medline] PHST- 2026/04/03 13:47 [pubmed] PHST- 2026/04/03 10:13 [entrez] AID - 10.1056/NEJMra2500106 [doi] PST - ppublish SO - N Engl J Med. 2026 Apr 2;394(13):1313-1324. doi: 10.1056/NEJMra2500106. PMID- 41925713 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 3 DP - 2026 Sep TI - Impact of hypoglycemic agents on glycemic control and cognitive decline in older adults with type 2 diabetes: real-world evidence on glucagon like peptide 1 receptor agonists. PG - 257-265 LID - 10.23736/S2724-6507.26.04501-X [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is frequently associated with cognitive decline in the older population. Although optimal glycemic control is known to be essential for disease management, the impact of hypoglycemic agents on cognitive function remains poorly investigated. METHODS: This retrospective study included 93 geriatric outpatients with T2DM. Hypoglycemic treatments consisted of metformin, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors, and insulin. Patient evaluations included glycated hemoglobin (HbA1c) measurements, Standardized Mini-Mental State Examination (MMSE), and Mini Nutritional Assessment (MNA). RESULTS: After one year of treatment, patients exhibited a significant reduction in HbA1c levels (from 8.06% [+/-1.19] to 7.19% [+/-0.84], P<0.001), improvement of MMSE scores (from 25.87 [+/-3.09] to 27.47 [+/-2.9], P<0.001). Regression analysis identified GLP-1RAs as the most effective agent in improving glycemic control (P<0.001) and cognitive function (P=0.016). Treatment with GLP-1RAs was associated with a reduction in MNA scores (P<0.001), though these remained above the malnutrition threshold. CONCLUSIONS: Our findings suggest that improved glycemic control may help slow cognitive decline in older patients with T2DM. Among the drug classes examined, GLP-1RAs showed the largest reductions in HbA1c and were linked to greater MMSE score gains. FAU - DI Marzio, Benedetta AU - DI Marzio B AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. AD - PhD Program in Translation Specialistic Medicine, "G.B. Morgagni" Curriculum "Endocrine and Metabolic Sciences", University of Padua, Padua, Italy. FAU - Gasparini, Giulia AU - Gasparini G AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Ambrosio, Andrea AU - Ambrosio A AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy - andrea.ambrosio@studenti.unipd.it. FAU - Coin, Alessandra AU - Coin A AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Filipponi, Luca AU - Filipponi L AD - Department of General Psychology (DPG), University of Padua, Padua, Italy. FAU - Sartore, Giovanni AU - Sartore G AD - Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Ferra, Elisabetta AU - Ferra E AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Papa, Mario V AU - Papa MV AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Ravelli, Adele AU - Ravelli A AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Ceolin, Chiara AU - Ceolin C AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. AD - Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Aging Research Center, University of Stockholm, Stockholm, Sweden. FAU - DE Rui, Marina AU - DE Rui M AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Zanforlini, Bruno M AU - Zanforlini BM AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Curreri, Chiara AU - Curreri C AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Bertocco, Anna AU - Bertocco A AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. FAU - Devita, Maria AU - Devita M AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. AD - Department of General Psychology (DPG), University of Padua, Padua, Italy. FAU - Sergi, Giuseppe AU - Sergi G AD - Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy. LA - eng PT - Journal Article DEP - 20260402 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications/psychology MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Glycemic Control/methods MH - *Cognitive Dysfunction/etiology/prevention & control MH - Glycated Hemoglobin/analysis MH - Aged, 80 and over MH - Blood Glucose/drug effects MH - Cognition/drug effects EDAT- 2026/04/02 12:36 MHDA- 2026/09/07 11:37 CRDT- 2026/04/02 10:45 PHST- 2026/09/07 11:37 [medline] PHST- 2026/04/02 12:36 [pubmed] PHST- 2026/04/02 10:45 [entrez] AID - S2724-6507.26.04501-X [pii] AID - 10.23736/S2724-6507.26.04501-X [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Sep;51(3):257-265. doi: 10.23736/S2724-6507.26.04501-X. Epub 2026 Apr 2. PMID- 41922811 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20261010 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Apr 2 TI - The Role of GLP1 Receptor Agonists and Multi-agonist Incretin Therapies for Specific Obesity-related Health Conditions: Evidence and Rationale for Prioritisation. LID - 29 [pii] LID - 10.1007/s13679-026-00707-6 [doi] AB - PURPOSE OF REVIEW: This review evaluates the strength and scope of clinical evidence for GLP-1RAs-liraglutide, semaglutide, and tirzepatide-across obesity and associated complications, providing a structured rationale for prioritisation in clinical practice and policy. RECENT FINDINGS: GLP-1RAs demonstrate significant and reproducible weight loss-approximately 15% with semaglutide and 20% with tirzepatide at one year. Their efficacy in obesity-related health conditions has been best demonstrated through large clinical trials in cardiovascular disease, type 2 diabetes, obstructive sleep apnoea and metabolic dysfunction-associated steatotic liver disease. There is emerging evidence in the form of clinical trials and large retrospective studies for a number of other health conditions including chronic kidney disease, polycystic ovary syndrome, osteoarthritis, and other inflammatory conditions. Finally, GLP-1RAs may be a safe and effective treatment in time-critical contexts requiring rapid weight reduction for access to interventions such as organ transplantation, oncology surgery, sight-threatening idiopathic intracranial hypertension, and assisted conception. While all individuals meeting NICE eligibility criteria should ultimately access GLP-1RA therapy, current capacity constraints necessitate a phased approach prioritising high-evidence or time-sensitive conditions. This framework provides a scientifically grounded and evidence-based model to support clinical decision-making and service development in obesity management. Continued research is warranted to expand the evidence base, optimise cost-effectiveness, and ensure equitable implementation of obesity pharmacotherapy within public health services. FAU - Albor, Christo AU - Albor C AUID- ORCID: 0000-0002-4037-5734 AD - King's College Hospital NHS Foundation Trust, London, UK. c.albor@nhs.net. AD - Royal Free London NHS Foundation Trust, London, UK. c.albor@nhs.net. FAU - Anyiam, Oluwaseun AU - Anyiam O AUID- ORCID: 0000-0003-2425-2299 AD - University Hospitals of Derby & Burton NHS Foundation Trust, Derby, UK. FAU - Boyle, Luke D AU - Boyle LD AUID- ORCID: 0000-0003-4739-9170 AD - Department of Endocrinology, Centre for Obesity, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT2, UK. AD - Barts Health NHS Trust, West Smithfield, London, EC1A 7BE, UK. FAU - Makaronidis, Janine AU - Makaronidis J AD - Department of Diabetes and Metabolism, Royal London Hospital, Barts Health NHS Trust, London, UK. AD - National Institute of Health Research, UCLH Biomedical Research Centre, London, UK. AD - Centre for Obesity Research, Department of Medicine, Rayne Institute, University College London, London, UK. FAU - Tan, Rachael AU - Tan R AUID- ORCID: 0000-0003-4013-6810 AD - King's College Hospital NHS Foundation Trust, London, UK. FAU - Iftikhar, Sahar AU - Iftikhar S AD - Royal Surrey Hospital NHS Trust, Guildford, UK. FAU - Burzic, Amna AU - Burzic A AUID- ORCID: 0009-0009-1099-820X AD - Division of Medicine, University of Nottingham, Nottingham, NG5 1PB, UK. FAU - Lajeunesse Trempe, Fannie AU - Lajeunesse Trempe F AD - Institut Universitaire de Cardiologie Et de Pneumologie de Quebec, Quebec, QC, Canada. AD - Faculty of Pharmacy, Laval University, Quebec, QC, Canada. FAU - Stanley, Moira AU - Stanley M AD - Helier Hospital, Sutton, UK. FAU - Bhatti, Aniqah AU - Bhatti A AUID- ORCID: 0000-0001-7778-2272 AD - Nottingham University Hospitals, University of Nottingham, Nottingham, UK. FAU - Scragg, Jadine AU - Scragg J AUID- ORCID: 0000-0003-1424-712X AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Badawy, Layla AU - Badawy L AUID- ORCID: 0000-0002-4104-9404 AD - Royal Free London NHS Foundation Trust, London, UK. FAU - Moqeem, Komal AU - Moqeem K AD - Kings College Hospital, London, UK. FAU - Idris, Iskandar AU - Idris I AUID- ORCID: 0000-0002-7548-8288 AD - University of Nottingham, Nottingham, UK. AD - University Hospitals of Derby & Burton FT, Derby, UK. FAU - Andrews, Rob C AU - Andrews RC AUID- ORCID: 0000-0003-4939-1738 AD - University of Exeter Medical School, Exeter, UK. FAU - Sen Gupta, Piya AU - Sen Gupta P AUID- ORCID: 0000-0002-2800-7365 AD - Guy's and St Thomas's Hospitals NHS Trust, King's College London, London, UK. FAU - Hughes, David AU - Hughes D AD - University Hospitals of Derby & Burton FT, Derby, UK. FAU - McCullough, Katherine AU - McCullough K AD - Royal Surrey Hospital NHS Trust, Guildford, UK. AD - Ashford and St Peter's Hospital NHS Trust, Surrey, UK. AD - Royal College of Physicians, London, UK. AD - NHS England, London, UK. FAU - Tan, Tricia AU - Tan T AD - Department of Metabolism, Digestion and Reproduction, Imperial College London, London, W12 0HS, UK. FAU - McGowan, Barbara AU - McGowan B AD - Guy's and St Thomas's Hospitals NHS Trust, King's College London, London, UK. LA - eng PT - Journal Article PT - Review DEP - 20260402 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Incretins/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - Weight Loss/drug effects MH - Female MH - Cardiovascular Diseases/drug therapy MH - Renal Insufficiency, Chronic/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Polycystic Ovary Syndrome/drug therapy OTO - NOTNLM OT - Asthma OT - CKD OT - Cancer OT - Cancer survival OT - Cardiovascular disease OT - Chronic kidney disease OT - Evidence review OT - GLP-1RA OT - Genetic obesity OT - Glucagon-like peptide-1 receptor agonist OT - Hidradenitis suppurativa OT - IIH OT - IVF OT - Idiopathic intracranial hypertension OT - In-vitro fertilisation OT - Liraglutide OT - MASH OT - MASLD OT - Metabolic dysfunction-associated steatotic liver disease OT - Metabolic-associated steatohepatitis OT - Mounjaro OT - OA OT - OSA OT - Obesity OT - Obesity pharmacotherapy OT - Obstructive sleep apnoea OT - Osteoarthritis OT - Overweight OT - PCOS OT - Polycystic ovary syndrome OT - Precancerous conditions OT - Psoriasis OT - Rare monogenic obesity OT - Saxenda OT - Semaglutide OT - Subfertility OT - T2DM OT - Tirzepatide OT - Transplant surgery OT - Type 2 diabetes OT - Wegovy COIS- Compliance with Ethical Standards. Competing Interest: Conflicts of interest/Competing interests Funding: JM has received research funding from the NIHR and the Society for Endocrinology. JM has received institutional funding form NovoNordisk and Rhythm Pharmaceuticals. JS is supported by the NIHR Oxford Biomedical Research Centre (NIHR203311) and is an investigator in a trial funded by the Novo Nordisk Foundation (NNF22SA0080921). IS has received research grants or Speaker fees from: Eli Lilly, Novo Nordisk, Abbott, Boehringer, Sanofi. PSG has received speaker & course director fees from Novo Nordisk, advisory/speaker fees from Eli Lilly, and research support from Recordari. BM has received educational and/or advisory fees Lilly, Novonordisk, Boheringer ingelheim, Astra Zeneca. BM has received a research grant from Novo Nordisk. CA has received reimbursement for attending conferences from Novo Nordisk. Financial interests: TT declares she is a former shareholder in, and consultant for Zihipp Ltd., as well as advisory board consultancies for Amylyx Inc. Non-financial interests: JM has a voluntary role with the Asociation for the Study of Obesity (ASO) as sponsorship lead. BM is a shareholder of Reset Health. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. EDAT- 2026/04/02 00:29 MHDA- 2026/06/28 13:04 CRDT- 2026/04/01 23:32 PHST- 2025/10/26 00:00 [received] PHST- 2026/03/23 00:00 [accepted] PHST- 2026/06/28 13:04 [medline] PHST- 2026/04/02 00:29 [pubmed] PHST- 2026/04/01 23:32 [entrez] AID - 10.1007/s13679-026-00707-6 [pii] AID - 10.1007/s13679-026-00707-6 [doi] PST - epublish SO - Curr Obes Rep. 2026 Apr 2;15(1):29. doi: 10.1007/s13679-026-00707-6. PMID- 41915565 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 2325-6621 (Electronic) IS - 2325-6621 (Linking) VI - 23 IP - 4 DP - 2026 Apr 1 TI - Impact of GLP-1 and dual agonists on the incidence of new cases of physician-reported sleep apnea: a real-world study. PG - 607-613 LID - 10.1093/annalsats/aaoaf071 [doi] AB - RATIONALE: Previous studies have shown that glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists (tirzepatide) reduced severity of sleep apnea. However, whether these medications impact incidence of new cases of physician-reported sleep apnea (PRSA) is unknown. OBJECTIVE: To determine the potential impact of GLP-1 and dual agonists on the incidence of sleep apnea reports and to explore potential treatment consequences for this sleep-disordered breathing. METHODS: We conducted a retrospective cohort study using the TriNetX Global Health Research Network through anonymized electronic medical records. We identified adult patients with obesity and/or type 2 diabetes mellitus never prescribed GLP-1 or dual agonist therapy (reference arm) and those new initiators of these medications. The index event (June 2022) was chosen to coincide with the launching of tirzepatide in the market. We excluded patients with type 1 diabetes; previous diagnosis of PRSA; previous use of GLP-1/dual agonists, orlistat, phentermine/topiramate, or bupropion/naltrexone; or previous bariatric surgery. Initiators were matched to the reference cohort using propensity score matching in a 1:1 ratio for age, sex, ethnicity, body mass index, and menopause. We used a validated algorithm to identify PRSA using International Classification of Diseases, 10th Revision codes. RESULTS: The follow-up time was 1044 days. After propensity score matching, a total of 1 253 188 patients were included in the reference arm and GLP-1/dual agonist comparison. Overall, GLP-1/dual agonists were associated with a 54% lower incidence of PRSA (HR, 0.46 [95% CI, 0.45-0.49]). Individually, all drugs were able to reach this outcome as compared to the reference arm: liraglutide (HR, 0.64 [95% CI, 0.51-0.80]), dulaglutide (HR, 0.32 [95% CI, 0.28-0.36]), semaglutide (HR, 0.57 [95% CI, 0.54-0.61]), and tirzepatide (HR, 0.74 [95% CI, 0.67-0.92]). Exploratory analysis revealed a 79% lower incidence of positive airway pressure reports in the GLP-1/dual agonist group as compared to controls. CONCLUSIONS: GLP-1/dual agonists reduced the incidence of new cases of PRSA in patients with obesity and/or type 2 diabetes. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Prado, Beatriz S AU - Prado BS AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Mazzotti, Diego R AU - Mazzotti DR AUID- ORCID: 0000-0003-3924-9199 AD - Division of Medical Informatics, Division of Pulmonary Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, MO, United States. FAU - Franci, Andre AU - Franci A AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Baracioli, Luciano M AU - Baracioli LM AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Barbado, Karoline Razimavicius AU - Barbado KR AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Saretta, Roberta AU - Saretta R AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Kalil-Filho, Roberto AU - Kalil-Filho R AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Drager, Luciano F AU - Drager LF AUID- ORCID: 0000-0002-2081-6846 AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. LA - eng GR - Hospital Sirio Libanes/ PT - Journal Article PL - England TA - Ann Am Thorac Soc JT - Annals of the American Thoracic Society JID - 101600811 RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Sleep Apnea Syndromes/epidemiology MH - Male MH - Retrospective Studies MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic peptide OT - incidence OT - obesity OT - sleep apnea EDAT- 2026/03/31 18:49 MHDA- 2026/03/31 18:50 CRDT- 2026/03/31 12:53 PHST- 2025/08/24 00:00 [received] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/03/31 18:50 [medline] PHST- 2026/03/31 18:49 [pubmed] PHST- 2026/03/31 12:53 [entrez] AID - 8471057 [pii] AID - 10.1093/annalsats/aaoaf071 [doi] PST - ppublish SO - Ann Am Thorac Soc. 2026 Apr 1;23(4):607-613. doi: 10.1093/annalsats/aaoaf071. PMID- 41915388 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 3 DP - 2026 Mar 2 TI - GLP-1 Receptor Agonists and Noncardiometabolic Outcomes: An Umbrella Review of Meta-Analyses. PG - e264722 LID - 10.1001/jamanetworkopen.2026.4722 [doi] LID - e264722 AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are foundational therapies for type 2 diabetes and obesity. Beyond established cardiometabolic benefits, GLP-1 RAs' associations with noncardiometabolic outcomes remain uncertain. OBJECTIVE: To evaluate the associations between GLP-1 RAs and noncardiometabolic outcomes, and to appraise the certainty and credibility of the supporting evidence. DATA SOURCES: A systematic search of PubMed, Web of Science, Embase, Scopus, and the Cochrane Database of Systematic Reviews was conducted from database inception to January 15, 2026. STUDY SELECTION: Eligible studies were systematic reviews with meta-analyses of randomized clinical trials evaluating GLP-1 RAs and outcomes beyond glycemic control, weight management, and major cardiorenal end points. DATA EXTRACTION AND SYNTHESIS: This umbrella review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. For each eligible meta-analysis, relevant data were extracted by 2 independent reviewers at both the meta-analysis level and individual study level. Data were reanalyzed using random-effects models to estimate odds ratios (ORs) and 95% CIs. MAIN OUTCOMES AND MEASURES: The primary outcomes were noncardiometabolic outcomes across gastrointestinal, adverse event (AE), cancer, fracture, respiratory, neurologic, psychiatric, hepatic, and endocrine domains. Methodological quality was appraised via AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews). Evidence certainty was categorized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework and prespecified credibility criteria. RESULTS: A total of 60 meta-analyses representing 116 unique adverse health outcomes were included, comprising 1751 randomized clinical trials and 3 580 616 participants. The study populations primarily involved people with type 2 diabetes (43 [71.7%]) and obesity (20 [33.3%]), with follow-up durations ranging from 3 months to 5.4 years or longer. The most consistent signals were for gastrointestinal AEs, with higher odds of nausea (OR, 2.47 [95% CI, 1.84-3.34]; GRADE: high quality of evidence), vomiting (OR, 2.78 [95% CI, 1.91-4.06]; GRADE: moderate quality of evidence), and diarrhea (OR, 1.94 [95% CI, 1.52-2.49]; GRADE: high quality of evidence), although between-study heterogeneity and 95% prediction intervals suggested residual uncertainty. Infection-related outcomes suggested possible protective associations, particularly for serious infections (OR, 0.89 [95% CI, 0.87-0.92]; GRADE: high quality of evidence), and a suggestive association was observed for incident respiratory disease (OR, 0.85 [95% CI, 0.80-0.92]). Other outcomes, including gastrointestinal disease and biliary events (eg, gallbladder or biliary disease: OR, 1.34 [95% CI, 1.16-1.55]), did not meet stringent credibility thresholds and should be considered exploratory. CONCLUSIONS AND RELEVANCE: In this umbrella review of meta-analyses, evidence for most noncardiometabolic outcomes associated with GLP-1 RAs was of lower certainty. Potential safety signals were observed for gastrointestinal AEs, while suggested protective associations with respiratory diseases and serious infections require further confirmation. FAU - Yang, Kaijie AU - Yang K AD - Department of Endocrinology and Metabolism and the Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China. FAU - Liu, Changyuan AU - Liu C AD - Department of Endocrinology and Metabolism and the Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China. FAU - Guo, Qiqiang AU - Guo Q AD - The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, China. FAU - Li, Yongze AU - Li Y AD - Department of Endocrinology and Metabolism and the Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260302 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Meta-Analysis as Topic MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy PMC - PMC13040404 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2026/03/31 12:33 MHDA- 2026/03/31 12:34 PMCR- 2026/03/31 CRDT- 2026/03/31 11:33 PHST- 2026/03/31 12:34 [medline] PHST- 2026/03/31 12:33 [pubmed] PHST- 2026/03/31 11:33 [entrez] PHST- 2026/03/31 00:00 [pmc-release] AID - 2847134 [pii] AID - zoi260170 [pii] AID - 10.1001/jamanetworkopen.2026.4722 [doi] PST - epublish SO - JAMA Netw Open. 2026 Mar 2;9(3):e264722. doi: 10.1001/jamanetworkopen.2026.4722. PMID- 41913544 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260811 IS - 1527-330X (Electronic) IS - 1090-820X (Linking) VI - 46 IP - 7 DP - 2026 Jun 16 TI - Beyond Weight Loss: Metabolic and Immunologic Power of GLP-1 Agonists in Plastic Surgery. PG - 753-758 LID - 10.1093/asj/sjag064 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and weight management in patients with type 2 diabetes and obesity, and their use has become increasingly common among candidates for elective plastic surgery. As a result, plastic surgeons are frequently encountering patients receiving GLP-1 RA therapy in the setting of metabolic and inflammatory comorbidities that may influence perioperative risk. This focused review examines the existing literature on GLP-1 RAs and contextualizes their biologic effects with considerations relevant to elective plastic surgery. A review of studies identified through PubMed, MEDLINE, and ClinicalKey was performed, with emphasis on the effects of GLP-1 RAs on chronic inflammation, immune signaling, endothelial function, and tissue biology in populations with metabolic or inflammatory disease. Across preclinical and clinical studies, GLP-1 RAs have been associated with attenuation of chronic inflammatory signaling, including reductions in circulating inflammatory markers and modulation of immune cell activity. Clinical benefits have been reported in conditions frequently encountered in plastic surgery practice, such as metabolic syndrome, polycystic ovary syndrome, and inflammatory skin diseases; however, direct evidence evaluating postoperative outcomes in surgical populations remains limited. Rather than acting on the acute postoperative healing response, GLP-1 RAs primarily influence chronic metabolic and inflammatory disease states that contribute to surgical risk. Understanding these effects may assist plastic surgeons in the perioperative setting, as GLP-1 RA therapy becomes increasingly prevalent in elective practice. Level of Evidence: 3 (Therapeutic). CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Patel, Niki K AU - Patel NK AUID- ORCID: 0009-0000-0722-972X FAU - Henriksson, Tatiana AU - Henriksson T FAU - Sidhu, Anna AU - Sidhu A FAU - Carruthers, Katherine H AU - Carruthers KH FAU - Woodberry, Kerri AU - Woodberry K LA - eng PT - Journal Article PT - Review PL - England TA - Aesthet Surg J JT - Aesthetic surgery journal JID - 9707469 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy/immunology MH - *Plastic Surgery Procedures/adverse effects MH - Weight Loss/drug effects MH - Inflammation/immunology/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals EDAT- 2026/03/31 07:00 MHDA- 2026/06/16 06:35 CRDT- 2026/03/31 02:23 PHST- 2026/03/12 00:00 [accepted] PHST- 2026/06/16 06:35 [medline] PHST- 2026/03/31 07:00 [pubmed] PHST- 2026/03/31 02:23 [entrez] AID - 8565883 [pii] AID - 10.1093/asj/sjag064 [doi] PST - ppublish SO - Aesthet Surg J. 2026 Jun 16;46(7):753-758. doi: 10.1093/asj/sjag064. PMID- 41913529 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Downstream Treatment Burden and Health-Care Utilization Following Initiation of GLP-1 Receptor Agonists or SGLT2 Inhibitors in Type 2 Diabetes. PG - 5163-5173 LID - 10.1111/dom.70718 [doi] AB - AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used for the treatment of type 2 diabetes, yet their downstream consequences in routine clinical practice remain incompletely characterized. We compared downstream treatment burden following initiation of GLP-1 receptor agonists versus SGLT2 inhibitors among adults with type 2 diabetes. MATERIALS AND METHODS: We conducted a retrospective, propensity score-matched cohort study using a multi-centre electronic health record network. Adults with type 2 diabetes who newly initiated a GLP-1 receptor agonist or an SGLT2 inhibitor between 1 January 2017 and 1 June 2025 were included. After 1:1 matching, approximately 164 000 patients were retained in each treatment group. Outcome-specific baseline-free cohorts with uniform washout periods were constructed, yielding sample sizes of approximately 124 000-164 000 per outcome. Primary outcomes were initiation of seven downstream medication classes. Secondary outcomes included gastrointestinal and nutritional diagnoses and health-care utilization. RESULTS: Across all seven medication classes, downstream pharmacotherapy initiation occurred more frequently among GLP-1 initiators. The largest differences were observed for symptom-driven medications, including antidepressant, an absolute risk difference of 3.38% (95% CI -3.61 to -3.15) and a hazard ratio (HR) of 0.78 (95% CI 0.76-0.80), antiemetic, sedatives/hypnotics. Proton pump inhibitors, laxatives, histamine-2 receptor antagonists and antidiarrheal were also more frequently initiated, though differences were modest. Differences in secondary diagnoses were smaller. Gastroesophageal reflux disease and esophagitis were more common after GLP-1 initiation, whereas peptic ulcer disease and endoscopic procedures occurred more frequently among SGLT2 initiators. Nutrient deficiency and unspecified anaemia were more frequent following GLP-1 therapy. Overall health-care utilization was similar, except for inpatient acute care, which was more frequent among SGLT2 initiators. CONCLUSIONS: Initiation of GLP-1 receptor agonists is associated with a downstream pharmacologic cascade characterized by increased use of symptom-driven medication without corresponding increases in health-care utilization. Medication initiation may provide a more sensitive measure of treatment burden than diagnostic codes or utilization metrics in routine diabetes care. To our knowledge, this study represents the largest multicentre real-world evaluation of downstream pharmacologic cascades following initiation of GLP-1 receptor agonists and SGLT2 inhibitors. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Alhamdan, Yazan AU - Alhamdan Y AUID- ORCID: 0009-0001-9540-6403 AD - Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia. AD - Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, St Leonards, Australia. FAU - Hsu, Jason C AU - Hsu JC AUID- ORCID: 0000-0003-2997-2404 AD - International Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan. AD - Clinical Data Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan. AD - Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei, Taiwan. AD - Research Center of Data Science on Health Care Industry, College of Management, Taipei Medical University, Taipei, Taiwan. FAU - Lu, Christine Y AU - Lu CY AUID- ORCID: 0000-0002-7550-6837 AD - Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia. AD - Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, St Leonards, Australia. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260330 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - *Patient Acceptance of Health Care/statistics & numerical data PMC - PMC13146132 OTO - NOTNLM OT - GLP-1 OT - SGLT2 inhibitor OT - antidiabetic drug OT - real-world evidence COIS- The authors declare no conflicts of interest. EDAT- 2026/03/31 06:59 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/31 02:14 PHST- 2026/03/13 00:00 [revised] PHST- 2026/02/03 00:00 [received] PHST- 2026/03/15 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/31 06:59 [pubmed] PHST- 2026/03/31 02:14 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70718 [pii] AID - 10.1111/dom.70718 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5163-5173. doi: 10.1111/dom.70718. Epub 2026 Mar 30. PMID- 41913157 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20260930 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Mar 30 TI - Inpatient safety, effectiveness of SGLT2 inhibitors and GLP-1 RAs in type 2 diabetes: ENDOCARE, a pragmatic prospective cohort study. LID - 10.1186/s12933-026-03156-6 [doi] LID - 131 AB - BACKGROUND: Current guidelines recommend baseline insulin as the standard treatment for most people hospitalised with type 2 diabetes (PWT2D). However, they generally discourage the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists due to safety concerns and a lack of randomised evidence. We aim to assess primarily safety, and secondarily, effectiveness of non-insulin glucose-lowering therapy for inpatients, as implemented within a structured start-stop clinical practice guideline. METHODS: We conducted a 9-month pragmatic prospective cohort study including PWT2D adults who were admitted to the medical and surgical wards of a tertiary hospital. Participants were managed either on oral antidiabetic drugs (with or without insulin) under a start-stop protocol (Group A) or with insulin-only therapy (Group B). The primary outcome was safety, defined as severe adverse events (level 2-3 hypoglycaemia or diabetic ketoacidosis). Secondary outcomes included median daily capillary glucose and glycaemic variability. Hospital stay, intensive care unit admission and mortality were exploratory outcomes. Multivariable logistic regression and propensity score matching were employed to adjust for confounding factors. RESULTS: A total of 979 participants were included in the study: 582 in the Group A and 397 in the Group B. Seventy-three severe adverse events occurred, primarily hypoglycaemia. Non-insulin therapy was independently associated with a lower risk of severe adverse events (aOR 0.53 [95%CI 0.29-0.97]), and these results remained consistent after propensity score matching (OR 0.31 [95%CI 0.15-0.61]). The Group A had a lower median daily glucose level (153 mg/dL vs. 179 mg/dL; p < 0.001), lower glycaemic variability and a shorter hospital stay (5 days vs. 7 days; p < 0.001). No differences were observed in intensive care unit admission or mortality. CONCLUSIONS: In real hospital settings, the use of non-insulin therapies, predominantly SGLT2 inhibitors and GLP-1 RAs guided by a start-stop CPG, was associated with a safe and effective glycemic management profile. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. omorenoperez@hotmail.es. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. omorenoperez@hotmail.es. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - University Centre for Health Sciences - HM Hospitals (CUHMED), Camilo Jose Cela University, Madrid, Spain. FAU - Leiva-Mora, Nuria AU - Leiva-Mora N AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Santacruz, Elisa AU - Santacruz E AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Sanchez-Ortiga, Ruth AU - Sanchez-Ortiga R AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Arrarte, Vicente AU - Arrarte V AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. AD - Department of Cardiology, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Climent-Grana, Eduardo AU - Climent-Grana E AD - Department of Pharmacy, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Sandin, Miriam AU - Sandin M AD - Department of Cardiology, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Riera, Geronima AU - Riera G AD - Department of Pharmacy, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Lopez-Mondejar, Pedro AU - Lopez-Mondejar P AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Lopez-Munoz, Beatriz AU - Lopez-Munoz B AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Navarro, Clara AU - Navarro C AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Roldan-Sanchez, Ada AU - Roldan-Sanchez A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Sanchez-Pacheco, Myriam AU - Sanchez-Pacheco M AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Abad-Gonzalez, Angel Luis AU - Abad-Gonzalez AL AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Llorens, Pere AU - Llorens P AD - Emergency Department, Short Stay Unit and Hospitalization at Home Unit, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. AD - Medicine Area, University of Alicante, Alicante, Spain. FAU - Pico-Alfonso, Antonio AU - Pico-Alfonso A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. AD - Center for Biomedical Research On Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain. FAU - Serrano-Gotarredona, Joaquin AU - Serrano-Gotarredona J AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. LA - eng PT - Journal Article PT - Pragmatic Clinical Trial PT - Research Support, Non-U.S. Gov't DEP - 20260330 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Biomarkers) RN - 0 (GLP1R protein, human) RN - 0 (Insulin) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/mortality MH - Female MH - Prospective Studies MH - Middle Aged MH - Treatment Outcome MH - Male MH - *Blood Glucose/drug effects/metabolism MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage MH - Time Factors MH - Risk Factors MH - Biomarkers/blood MH - Hypoglycemia/chemically induced/blood MH - *Insulin/adverse effects/administration & dosage MH - *Glycemic Control/adverse effects/mortality MH - *Incretins/adverse effects/administration & dosage MH - Risk Assessment MH - *Inpatients MH - Diabetic Ketoacidosis/chemically induced MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Drug Therapy, Combination MH - Patient Admission MH - Administration, Oral PMC - PMC13126886 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Guideline OT - Hospital OT - Inpatients OT - Oral semaglutide OT - Prospective study OT - Real world evidence OT - SGLT2 inhibitors OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the principles of the Declaration of Helsinki and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. The protocol was reviewed and approved by the Ethics Committee of the Dr Balmis General University Hospital (ref. 2022-054). Given the pragmatic observational design and the use of routinely collected anonymised clinical data, the requirement for written informed consent was waived by the Ethics Committee. Competing interests: The authors declare no competing interests. EDAT- 2026/03/31 06:58 MHDA- 2026/06/28 06:35 PMCR- 2026/03/30 CRDT- 2026/03/31 00:08 PHST- 2026/02/13 00:00 [received] PHST- 2026/03/15 00:00 [accepted] PHST- 2026/06/28 06:35 [medline] PHST- 2026/03/31 06:58 [pubmed] PHST- 2026/03/31 00:08 [entrez] PHST- 2026/03/30 00:00 [pmc-release] AID - 10.1186/s12933-026-03156-6 [pii] AID - 3156 [pii] AID - 10.1186/s12933-026-03156-6 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Mar 30;25(1):131. doi: 10.1186/s12933-026-03156-6. PMID- 41908934 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - A Comprehensive Review on the Cardioprotective and Nephroprotective Effects of Semaglutide, and Its Therapeutic Efficacy and Mechanisms in Cardiorenal Syndrome. PG - 581491 LID - 10.2147/DDDT.S581491 [doi] LID - 581491 AB - Semaglutide (SEM), a GLP-1 receptor agonist (GLP-1RA), is commonly used to manage blood glucose and weight in type 2 diabetes mellituspatients (T2DM). Research indicates that SEM protects the kidneys and heart by slowing estimated glomerular filtration rate (eGFR) decline, reducing proteinuria, enhancing cardiac outcomes, and lowering cardiovascular risk. These benefits are linked to various mechanisms, including reduced oxidative stress and inflammation, anti-fibrotic effects, modulation of metabolism, inhibition of apoptosis, suppression of ferroptosis, and improved mitochondrial function for energy regulation. However, some studies have also found that SEM may potentially lead to renal impairment or even promote the progression of cardiorenal syndrome (CRS). Due to conflicting results, more animal studies and large-scale clinical trials are needed to understand SEM's effects on CRS and its side effects, aiding in personalized treatment strategies. This review summarizes the functions and mechanisms of SEM in CRS, and highlights current research limitations and proposed directions for future studies. CI - (c) 2026 Ye et al. FAU - Ye, Lu AU - Ye L AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Tang, Pusong AU - Tang P AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Wan, Haixu AU - Wan H AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Zhong, Xing AU - Zhong X AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Chen, Xin AU - Chen X AUID- ORCID: 0000-0003-2180-5564 AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Liu, Changzhao AU - Liu C AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Huang, Rui AU - Huang R AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. LA - eng PT - Journal Article PT - Review DEP - 20260324 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Cardiotonic Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Cardio-Renal Syndrome/drug therapy/metabolism MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Animals MH - *Cardiotonic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/pharmacology MH - Kidney/drug effects PMC - PMC13032732 OTO - NOTNLM OT - GLP-1RA OT - cardiorenal syndrome OT - cardiovascular outcomes OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/30 12:49 MHDA- 2026/03/30 12:50 PMCR- 2026/03/24 CRDT- 2026/03/30 06:31 PHST- 2025/11/14 00:00 [received] PHST- 2026/02/28 00:00 [accepted] PHST- 2026/03/30 12:50 [medline] PHST- 2026/03/30 12:49 [pubmed] PHST- 2026/03/30 06:31 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 581491 [pii] AID - 10.2147/DDDT.S581491 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Mar 24;20:581491. doi: 10.2147/DDDT.S581491. eCollection 2026. PMID- 41906117 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20260813 IS - 1756-994X (Electronic) IS - 1756-994X (Linking) VI - 18 IP - 1 DP - 2026 Mar 29 TI - Type 2 diabetes risk alleles in peptidyl-glycine alpha-amidating monooxygenase influence GLP-1 levels and response to GLP-1 receptor agonists. LID - 10.1186/s13073-026-01630-0 [doi] LID - 40 AB - BACKGROUND: Type 2 diabetes (T2D) is a leading cause of morbidity and mortality worldwide. Despite the availability of multiple glucose-lowering agents, only half of individuals with T2D achieve the recommended HbA1c target of < 7.0%. Precision medicine approaches that leverage patient-specific markers offer a promising strategy to improve therapeutic outcomes. The PAM gene encodes the sole enzyme responsible for amidating bioactive hormones, including GLP-1, and harbors two hypomorphic T2D-risk alleles (p.D563G and p.S539W); however, whether PAM regulates GLP-1, a key amidated incretin hormone, and whether this influences response to GLP-1 receptor agonist (GLP-1RA) therapy, remains unknown. METHODS: PAM amidation activity, postprandial GLP-1 levels, and the incretin effect were measured in carriers of PAM T2D-risk alleles and matched non-carriers from the Oxford Biobank in a prospective observational study and in Danish cohorts. Inducible whole-body Pam knockout mice were generated; gastric emptying was assessed by paracetamol absorption assay with and without exendin-4. Glycemic response to GLP-1RAs was evaluated in a meta-analysis of 1,119 participants across three cohorts (IMI-DIRECT, GoDARTS, PRIBA), with comparative assessment of sulphonylurea, metformin, and DPP-4 inhibitor response. RESULTS: Carriers of p.S539W and p.D563G alleles demonstrated 52% and 20% reductions in serum PAM amidation activity, respectively. Both human carriers and Pam knockout mice exhibited elevated circulating GLP-1 levels; however, p.S539W carriers showed an 18% reduction in endogenous GLP-1 sensitivity. PamKO mice displayed accelerated gastric emptying that was refractory to exendin-4, alongside impaired cAMP signaling downstream of the GLP-1 receptor in the pylorus. In the clinical meta-analysis, p.S539W carriers showed a significantly attenuated HbA1c reduction following GLP-1RA therapy (- 0.69% vs. - 1.24% in non-carriers; p = 0.025), representing a 44% relative loss of glycemic benefit; only 11.5% of carriers achieved HbA1c < 7% compared with 25.3% of non-carriers. No differences in response to sulphonylureas, metformin, or DPP-4 inhibitors were observed. CONCLUSIONS: Hypomorphic PAM T2D-risk alleles reduce amidating enzyme activity, elevate circulating GLP-1 levels, and impair GLP-1 post-receptor signaling, culminating in a selective and clinically meaningful reduction in GLP-1RA efficacy. These findings establish PAM genotype as a novel pharmacogenomic determinant of GLP-1RA response, supporting its incorporation into precision medicine frameworks to optimize drug selection in T2D management. TRIAL REGISTRATION: NCT02723110, NCT02465515 and NCT01144338. FAU - Umapathysivam, Mahesh M AU - Umapathysivam MM AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Department of Endocrinology, Queen Elizabeth Hospital, SA Health, Woodville South, Australia. AD - Southern Adelaide and Diabetes and Endocrinology Service, Bedford Park, Australia. AD - Centre of Research Excellence: Translating Nutritional Science to Good Health, Adelaide University, Adelaide, South Australia, Australia. FAU - Araldi, Elisa AU - Araldi E AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. AD - Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. AD - Department of Medicine and Surgery, University of Parma, Parma, Italy. FAU - Hastoy, Benoit AU - Hastoy B AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. FAU - Dawed, Adem Y AU - Dawed AY AD - Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK. AD - Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK. FAU - Vatandaslar, Hasan AU - Vatandaslar H AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Mayrhofer, Johanna E AU - Mayrhofer JE AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Lindquist, Peter AU - Lindquist P AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University, Copenhagen, Denmark. FAU - Silva, Pamuditha N AU - Silva PN AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Goga, Algera AU - Goga A AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Trullinger, Geraldine O AU - Trullinger GO AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Godbersen, Svenja AU - Godbersen S AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Sengupta, Shahana AU - Sengupta S AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. FAU - Kaufmann, Adrian AU - Kaufmann A AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Thomsen, Soren Krogsgaard AU - Thomsen SK AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University, Copenhagen, Denmark. FAU - Chen, Yi-Chun AU - Chen YC AD - Departments of Surgery and Pathology and Laboratory Medicine, Centre for Molecular Medicine and Therapeutics, Faculty of Medicine, University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, BC, Canada. FAU - Jonsson, Anna E AU - Jonsson AE AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. FAU - Kabakci, Hasan AU - Kabakci H AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. FAU - Thaman, Swaraj AU - Thaman S AD - Division of Endocrinology, Department of Pediatrics, Stanford School of Medicine, Stanford, USA. FAU - Grarup, Niels AU - Grarup N AD - Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Center for Clinical Metabolic Research, Gentofte University Hospital, Copenhagen, Denmark. FAU - Have, Christian T AU - Have CT AD - Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Pallo, Lindsay P AU - Pallo LP AD - Departments of Surgery and Pathology and Laboratory Medicine, Centre for Molecular Medicine and Therapeutics, Faculty of Medicine, University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, BC, Canada. FAU - Faerch, Kristine AU - Faerch K AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University, Copenhagen, Denmark. AD - Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Gjesing, Anette P AU - Gjesing AP AD - Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Nawaz, Sameena AU - Nawaz S AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. FAU - Cheeseman, Jane AU - Cheeseman J AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. FAU - Neville, Matthew J AU - Neville MJ AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. FAU - Pedersen, Oluf AU - Pedersen O AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. AD - Center for Clinical Metabolic Research, Gentofte University Hospital, Copenhagen, Denmark. FAU - Walker, Mark AU - Walker M AD - Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. FAU - Sun, Han AU - Sun H AD - Division of Endocrinology, Department of Pediatrics, Stanford School of Medicine, Stanford, USA. FAU - Jennison, Christopher AU - Jennison C AD - Department of Mathematics, University of Bath, Bath, UK. FAU - Hattersley, Andrew T AU - Hattersley AT AD - University of Exeter College of Medicine & Health, Exeter, UK. FAU - Rehfeld, Jens F AU - Rehfeld JF AD - Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Holman, Rury R AU - Holman RR AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. FAU - Verchere, Bruce C AU - Verchere BC AD - Departments of Surgery and Pathology and Laboratory Medicine, Centre for Molecular Medicine and Therapeutics, Faculty of Medicine, University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, BC, Canada. FAU - Hansen, Torben AU - Hansen T AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. FAU - Karpe, Fredrik AU - Karpe F AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. FAU - Rosenkilde, Mette M AU - Rosenkilde MM AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University, Copenhagen, Denmark. FAU - Jones, Angus G AU - Jones AG AD - University of Exeter College of Medicine & Health, Exeter, UK. FAU - Ristow, Michael AU - Ristow M AD - Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. FAU - McCarthy, Mark I AU - McCarthy MI AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. AD - Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. AD - Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA. FAU - Pearson, Ewan R AU - Pearson ER AD - Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK. FAU - Stoffel, Markus AU - Stoffel M AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland. AD - Medical Faculty, University of Zurich, Zurich, Switzerland. FAU - Gloyn, Anna L AU - Gloyn AL AD - Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. agloyn@stanford.edu. AD - Division of Endocrinology, Department of Pediatrics, Stanford School of Medicine, Stanford, USA. agloyn@stanford.edu. AD - Oxford Biomedical Research Centre, National Institute of Health Research, Churchill Hospital, Headington, Oxford, UK. agloyn@stanford.edu. AD - Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. agloyn@stanford.edu. AD - Stanford Diabetes Research Centre, Stanford, USA. agloyn@stanford.edu. AD - Department of Pediatrics, Division of Endocrinology & Diabetes, Stanford School of Medicine, Centre for Academic Medicine, 453 Quarry Road, Palo Alto, CA, 94304, USA. agloyn@stanford.edu. LA - eng SI - ClinicalTrials.gov/NCT02723110 SI - ClinicalTrials.gov/NCT02465515 SI - ClinicalTrials.gov/NCT01144338 GR - UM1 DK126185/DK/NIDDK NIH HHS/United States GR - 095101/WT_/Wellcome Trust/United Kingdom GR - 200837/WT_/Wellcome Trust/United Kingdom GR - 098381/WT_/Wellcome Trust/United Kingdom GR - 106130/WT_/Wellcome Trust/United Kingdom GR - 203141/WT_/Wellcome Trust/United Kingdom GR - MR/L020149/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20260329 PL - England TA - Genome Med JT - Genome medicine JID - 101475844 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - EC 1.- (Mixed Function Oxygenases) RN - 9100L32L2N (Metformin) RN - 0 (Insulin Secretagogues) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM UOF - medRxiv. 2023 Apr 12:2023.04.07.23288197. doi: 10.1101/2023.04.07.23288197. PMID: 37090505 MH - *Diabetes Mellitus, Type 2/genetics/drug therapy/blood/metabolism MH - Humans MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Alleles MH - Mice MH - *Glucagon-Like Peptide 1/blood/metabolism MH - Female MH - Mice, Knockout MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Mixed Function Oxygenases/genetics/metabolism MH - Male MH - Middle Aged MH - Metformin MH - Insulin Secretagogues MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13072570 COIS- Declarations. Ethics approval and consent to participate: A prospective observational study was conducted. All volunteers provided written informed consent. The protocol was approved by Oxford B NRES Research Ethics Committee (15/SC/0072) and registered via clincaltrial.gov (NCT02723110). All research presented conformed with the principles of the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: MMU has received an honorarium from Boehringer Ingelheim and has received a project grant from AstraZeneca. ERP has received honoraria from Lilly, Sanofi and Illumina. MIM holds stock options in Roche. ALG's spouse is an employee of Genentech and holds stock options in Roche. M.M.R is co-founder and minority shareholder of Antag Therapeutics ApS. M.M.R. is co-founder and minority shareholders of Bainan Biotech ApS. M.M.R. is chairman of the board of directors (Bainan Biotech ApS). C.B.V. is co-founder, advisor, and holds founder's shares in Integrated Nanotherapeutics. R.R.H. reports personal fees from AstraZeneca, Lilly and Novartis. KF is currently employed by and holds shares in Novo Nordisk A/S. The remaining authors declare that they do not have any competing interests. All animal experiments were in accordance with institutional guidelines and approved by the kantonale Veterinaramt Zurich (ZH186/2020, ZH228/2020, ZH251/2019, ZH043/2019). EDAT- 2026/03/30 00:29 MHDA- 2026/06/28 06:36 PMCR- 2026/03/29 CRDT- 2026/03/29 23:14 PHST- 2025/10/10 00:00 [received] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/06/28 06:36 [medline] PHST- 2026/03/30 00:29 [pubmed] PHST- 2026/03/29 23:14 [entrez] PHST- 2026/03/29 00:00 [pmc-release] AID - 10.1186/s13073-026-01630-0 [pii] AID - 1630 [pii] AID - 10.1186/s13073-026-01630-0 [doi] PST - epublish SO - Genome Med. 2026 Mar 29;18(1):40. doi: 10.1186/s13073-026-01630-0. PMID- 41905685 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260921 IS - 1544-3450 (Electronic) IS - 1544-3191 (Print) IS - 1086-5802 (Linking) VI - 66 IP - 4 DP - 2026 Jul-Aug TI - A cross-sectional study of prescribing rates for SGLT2 inhibitors and GLP-1 receptor agonists among primary care clinics with and without embedded pharmacists. PG - 103106 LID - S1544-3191(26)00091-9 [pii] LID - 10.1016/j.japh.2026.103106 [doi] AB - BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are cardio- and kidney-protective, yet their uptake in clinical practice has been suboptimal. The association between pharmacists embedded in primary care clinics and prescribing rates of SGLT2i and GLP-1RA is unknown. OBJECTIVE: To compare the prescribing rates of SGLT2i and GLP-1 RA among primary care clinics with and without embedded pharmacists. METHODS: A cross-sectional study using electronic health record data from Bon Secours Mercy Health outpatient clinics across Virginia (2019, 2020, and 2021) included patients >/=18 year old with type 2 diabetes and either cardiovascular disease (CVD), including atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), or chronic kidney disease (CKD), and >/=1 outpatient visit. Adults with type 1 diabetes, CKD stage 4/5, end-stage kidney disease, on dialysis, pregnant, or on hospice or palliative care were excluded. Overall and condition-specific prescribing rates were compared between the 8 clinics with embedded pharmacists vs. 5 matched clinics without pharmacists using generalized linear mixed modeling with a random practice-level effect. RESULTS: The 6377 included patients had a mean age of 68.6 years, 49.8% were female, 36.8% were Black, and 73.2% were Medicare beneficiaries. The overall raw prescribing rate was higher at clinics with embedded pharmacists (16.2%) vs. those without (13.8%), and for patients with ASCVD or CKD, but not HF, though this difference did not reach statistical significance when adjusting only for the pharmacist group (P = 0.76) or after adjusting for age, sex, race, and insurance coverage (P = 0.49). Factors associated with higher prescribing rates included being older, male, or commercially insured. CONCLUSION: Prescribing rates for SGLT2i and GLP-1 RA were numerically higher in primary care clinics with embedded pharmacists than those without; however, the difference was not statistically significant. CI - Copyright (c) 2026 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Dixon, Dave L AU - Dixon DL FAU - Salgado, Teresa M AU - Salgado TM FAU - Robinson, Amanda AU - Robinson A FAU - Carbone, Salvatore AU - Carbone S FAU - Wagner, Tyler D AU - Wagner TD FAU - Hyder, Haroon AU - Hyder H FAU - Kirschner, Bryan AU - Kirschner B FAU - Musselman, Kerri T AU - Musselman KT FAU - Buffington, Tonya M AU - Buffington TM FAU - Sabo, Roy T AU - Sabo RT LA - eng GR - UM1 TR004360/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20260327 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cross-Sectional Studies MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Primary Health Care/statistics & numerical data/organization & administration MH - *Pharmacists/organization & administration/statistics & numerical data MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Virginia MH - Hypoglycemic Agents/administration & dosage MH - Adult MH - Non-Medical Prescribing MH - Cardiovascular Diseases/drug therapy PMC - PMC13137380 MID - NIHMS2164600 COIS- Disclosure This was a collaborative research study where Boehringer Ingelheim was involved in the design, analysis, or interpretation of the results but was not the regulatory sponsor. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to Boehringer Ingelheim substances, as well as intellectual property considerations. EDAT- 2026/03/30 00:29 MHDA- 2026/08/13 21:17 PMCR- 2026/05/05 CRDT- 2026/03/29 20:30 PHST- 2025/10/29 00:00 [received] PHST- 2026/03/20 00:00 [revised] PHST- 2026/03/20 00:00 [accepted] PHST- 2026/08/13 21:17 [medline] PHST- 2026/03/30 00:29 [pubmed] PHST- 2026/03/29 20:30 [entrez] PHST- 2026/05/05 00:00 [pmc-release] AID - S1544-3191(26)00091-9 [pii] AID - 10.1016/j.japh.2026.103106 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2026 Jul-Aug;66(4):103106. doi: 10.1016/j.japh.2026.103106. Epub 2026 Mar 27. PMID- 41905447 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 1021 DP - 2026 Apr 15 TI - Genetic variations in GLP-1R: Impact on diabetes and obesity therapeutics. PG - 178805 LID - S0014-2999(26)00287-6 [pii] LID - 10.1016/j.ejphar.2026.178805 [doi] AB - The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that is essential for glucose homeostasis, energy balance and appetite. GLP-1R is a key therapeutic target for the treatment of type 2 diabetes and obesity, owing to its central role in insulin secretion, glucagon suppression, and body weight regulation. Increasing evidence suggests that genetic polymorphisms in GLP-1R can influence the expression of the receptor, ligand binding, and downstream signalling processes, thereby affecting individual responses to GLP-1R agonists. Understanding these variants is essential for advancing precision medicine, as inter-individual genetic differences can influence both therapeutic efficacy and susceptibility to adverse events. This review highlights the current knowledge on GLP-1R polymorphisms, with particular focus on their structural and functional consequences and their potential clinical implications. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Al-Zaid, Bashaier AU - Al-Zaid B AD - Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait. FAU - Abubaker, Jehad AU - Abubaker J AD - Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait. FAU - Mohammad, Anwar AU - Mohammad A AD - Translational Research Department, Dasman Diabetes Institute, Kuwait. FAU - Abufarha, Mohamed AU - Abufarha M AD - Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait; Translational Research Department, Dasman Diabetes Institute, Kuwait. FAU - Al-Mulla, Fahd AU - Al-Mulla F AD - Translational Research Department, Dasman Diabetes Institute, Kuwait. Electronic address: fahd.almulla@dasmaninstitute.org. FAU - Al-Sabah, Suleiman AU - Al-Sabah S AD - Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait. Electronic address: Sulaiman.alsabah@ku.edu.kw. LA - eng PT - Journal Article PT - Review DEP - 20260327 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism/chemistry MH - *Obesity/genetics/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/genetics/drug therapy/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Genetic Variation MH - Polymorphism, Single Nucleotide OTO - NOTNLM OT - G protein-coupled receptors OT - Glucagon-like peptide-1 receptor OT - Obesity OT - Single nucleotide polymorphism OT - Type 2 diabetes COIS- Declaration of competing interest We can confirm that the contents of this manuscript have not been published previously and are not under consideration for publication elsewhere. The authors of this manuscript have no conflict of interest to declare. EDAT- 2026/03/30 00:29 MHDA- 2026/04/13 00:31 CRDT- 2026/03/29 20:27 PHST- 2025/10/16 00:00 [received] PHST- 2026/02/22 00:00 [revised] PHST- 2026/03/26 00:00 [accepted] PHST- 2026/04/13 00:31 [medline] PHST- 2026/03/30 00:29 [pubmed] PHST- 2026/03/29 20:27 [entrez] AID - S0014-2999(26)00287-6 [pii] AID - 10.1016/j.ejphar.2026.178805 [doi] PST - ppublish SO - Eur J Pharmacol. 2026 Apr 15;1021:178805. doi: 10.1016/j.ejphar.2026.178805. Epub 2026 Mar 27. PMID- 41904481 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1750-1172 (Electronic) IS - 1750-1172 (Linking) VI - 21 IP - 1 DP - 2026 Mar 28 TI - Outcomes of GLP-1 receptor agonist therapy in adults with sickle cell disease and type 2 diabetes: a real-world cohort analysis. LID - 10.1186/s13023-026-04322-5 [doi] LID - 126 AB - PURPOSE: Outcomes of patients with sickle cell disease (SCD) and type 2 diabetes mellitus (T2DM) treated with glucagon-like peptide-1 (GLP1-RA) remain poorly understood. This study evaluated the impact of GLP-1 on adults with SCD and T2DM beyond glycemic control. METHODS: We conducted a retrospective study within the TriNetX Network, identifying adults with SCD and T2DM. GLP-1 users and non-GLP-1 users were matched using Propensity score matching. The index date was defined as the first GLP-1 prescription, and outcomes were assessed over 12 months. Outcomes were major adverse cardiovascular events (MACE), chronic kidney disease (CKD), vaso-occlusive crises (VOC), and hypoglycemia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We included 1,391 patients in each cohort, with similar age (48.5 vs. 48.8), and most participants were Black (84.5% vs. 83.8%). GLP-1 therapy was associated with lower risk of MACE (HR 0.61, 95% CI 0.49-0.76; P < 0.00001) and a reduced risk of stroke (HR 0.47, 95% CI 0.23-0.97; P = 0.036). Additionally, GLP-1 use was linked to a 36% lower risk of VOC (HR 0.64, 95% CI 0.45-0.91; P = 0.013). There was no difference in risk of hypoglycemia (HR 1.10, 95% CI 0.60-1.76; P = 0.688) or progression to CKD between the two groups (HR 1.26, 95% CI 0.82-1.95; P = 0.294). CONCLUSIONS: GLP-1 therapies demonstrate favorable cardioprotective, vaso stabilizing, and safety benefits in adults with SCD and T2DM, supporting their use in this high-risk population. CLINICAL TRIAL NUMBER: Not applicable. CI - (c) 2026. The Author(s). FAU - Nguefang, Guy Loic AU - Nguefang GL AUID- ORCID: 0009-0009-0418-3864 AD - Texas Tech University Health Sciences Center, Odessa, TX, USA. FAU - Boateng, Sarpong AU - Boateng S AD - Yale New Haven Health, Bridgeport Hospital, New Haven, Connecticut, USA. FAU - Gyabaah, Solomon AU - Gyabaah S AD - Komfo Anokye Teaching Hospital, Kumasi, Ghana. FAU - Issaka, Yussif AU - Issaka Y AD - Yale New Haven Health, Bridgeport Hospital, New Haven, Connecticut, USA. FAU - Konlack, Joel Gabin AU - Konlack JG AD - New York City Health and Hospitals South Brooklyn Health, Brooklyn, NY, USA. FAU - Landa, Edgar Luna AU - Landa EL AD - Texas Tech University Health Sciences Center, Odessa, TX, USA. FAU - Eze, Elvis AU - Eze E AD - Yale University, New Haven, Connecticut, USA. FAU - Njei, Basile AU - Njei B AUID- ORCID: 0000-0003-0714-4368 AD - Yale University, New Haven, Connecticut, USA. basilenjei@gmail.com. AD - Engelhardt School of Global Health and Bioethics, Euclid University, Bangui, Central African Republic. basilenjei@gmail.com. AD - Artificial Intelligence Program, University of Cumbria, Carlisle, UK. basilenjei@gmail.com. AD - Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA. basilenjei@gmail.com. AD - Yale Liver Center, Yale New Haven Health, New Haven, Connecticut, USA. basilenjei@gmail.com. AD - Yale International Medicine Program, Yale University, New Haven, Connecticut, USA. basilenjei@gmail.com. LA - eng PT - Journal Article DEP - 20260328 PL - England TA - Orphanet J Rare Dis JT - Orphanet journal of rare diseases JID - 101266602 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Anemia, Sickle Cell/drug therapy MH - Female MH - Male MH - Retrospective Studies MH - Middle Aged MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Vaso-Occlusive Crises MH - Glucagon-Like Peptide 1/therapeutic use PMC - PMC13047803 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist (GLP-1) OT - Major adverse cardiovascular events (MACE) OT - Sickle cell disease OT - Type 2 diabetes mellitus OT - Vaso-occlusive crises COIS- Declarations. Ethical approval: For this type of study formal consent is not required. Assistance with the study: No external assistance was sought or received for the design, execution, analysis, or reporting of this study. Presentation: This work has not been previously presented elsewhere. Conflict of interest: The authors declare that they have no conflicts of interest, financial or otherwise, relevant to the content of this article. EDAT- 2026/03/29 07:35 MHDA- 2026/04/03 06:31 PMCR- 2026/03/28 CRDT- 2026/03/28 23:25 PHST- 2026/02/02 00:00 [received] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/04/03 06:31 [medline] PHST- 2026/03/29 07:35 [pubmed] PHST- 2026/03/28 23:25 [entrez] PHST- 2026/03/28 00:00 [pmc-release] AID - 10.1186/s13023-026-04322-5 [pii] AID - 4322 [pii] AID - 10.1186/s13023-026-04322-5 [doi] PST - epublish SO - Orphanet J Rare Dis. 2026 Mar 28;21(1):126. doi: 10.1186/s13023-026-04322-5. PMID- 41903539 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 189 IP - 9 DP - 2026 Apr 30 TI - Advancing precision health discovery in a genetically diverse health system. PG - 2533-2555.e31 LID - S0092-8674(26)00274-6 [pii] LID - 10.1016/j.cell.2026.03.007 [doi] AB - Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. We analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. We discovered numerous unreported gene-phenotype associations, including FN3K with intestinal disaccharidase deficiency in Europeans and admixed Americans. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, we reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations, including ANKZF1 and peripheral vascular disease in African Americans. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes, and is modulated by genetic variation in PTPRU. These findings illustrate how ancestrally diverse biobanks from a single health system yield robust disease associations and pharmacogenomic insights. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Haas, Roni AU - Haas R AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rhaas@mednet.ucla.edu. FAU - Margolis, Michael P AU - Margolis MP AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Wei, Angela AU - Wei A AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Interdepartmental Bioinformatics Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Yamaguchi, Takafumi N AU - Yamaguchi TN AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Feng, Jeffrey AU - Feng J AD - Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tran, Thai AU - Tran T AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tozzo, Veronica AU - Tozzo V AD - Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Queen, Katelyn J AU - Queen KJ AD - Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Mootor, Mohammed Faizal Eeman AU - Mootor MFE AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Patil, Vishakha AU - Patil V AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Broudy, Michael E AU - Broudy ME AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tung, Paul AU - Tung P AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Alam, Shafiul AU - Alam S AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Martinez, Danielle B AU - Martinez DB AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Patel, Yash AU - Patel Y AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Caggiano, Christa AU - Caggiano C AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA. FAU - Zeltser, Nicole AU - Zeltser N AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Hugh-White, Rupert AU - Hugh-White R AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Arbet, Jaron AU - Arbet J AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Shemirani, Ruhollah AU - Shemirani R AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA. FAU - Tian, Mao AU - Tian M AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Thapaliya, Prapti AU - Thapaliya P AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Eloyan, Lora AU - Eloyan L AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Chen, Lawrence O AU - Chen LO AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Lapinska, Sandra AU - Lapinska S AD - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Ariannejad, Maryam AU - Ariannejad M AD - Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Lajonchere, Clara AU - Lajonchere C AD - Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. CN - UCLA Precision Health Data Discovery Repository Working Group CN - UCLA Precision Health ATLAS Working Group CN - UCLA Health IT HPC Team CN - Regeneron Genetics Center FAU - Kenny, Eimear E AU - Kenny EE AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA; Center for Translational Genomics, Icahn School of Medicine, New York, NY 10027, USA; Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine, New York, NY 10027, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York, NY 10027, USA. FAU - Pasaniuc, Bogdan AU - Pasaniuc B AD - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Bui, Alex A T AU - Bui AAT AD - Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Arboleda, Valerie A AU - Arboleda VA AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Chang, Timothy S AU - Chang TS AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Zaitlen, Noah AU - Zaitlen N AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Spellman, Paul T AU - Spellman PT AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: pspellman@mednet.ucla.edu. FAU - Boutros, Paul C AU - Boutros PC AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: pboutros@sbpdiscovery.org. FAU - Geschwind, Daniel H AU - Geschwind DH AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu. LA - eng GR - U54 NS123746/NS/NINDS NIH HHS/United States GR - F30 MH135712/MH/NIMH NIH HHS/United States GR - T15 LM013976/LM/NLM NIH HHS/United States GR - T32 HG002536/HG/NHGRI NIH HHS/United States GR - R01 AG085518/AG/NIA NIH HHS/United States GR - R01 HG011345/HG/NHGRI NIH HHS/United States GR - K08 AG065519/AG/NIA NIH HHS/United States GR - T32 EB016640/EB/NIBIB NIH HHS/United States GR - F31 HG013462/HG/NHGRI NIH HHS/United States GR - F31 CA281168/CA/NCI NIH HHS/United States GR - T32 GM008042/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20260327 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 53AXN4NNHX (Semaglutide) SB - IM UOF - medRxiv. 2025 Jun 12:2025.06.11.25329386. doi: 10.1101/2025.06.11.25329386. PMID: 40585105 MH - Humans MH - *Precision Medicine/methods MH - Genetic Risk Score MH - Diabetes Mellitus, Type 2/genetics/drug therapy MH - Semaglutide MH - European People MH - Electronic Health Records MH - Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Multifactorial Inheritance/genetics MH - Genetic Variation MH - White People/genetics MH - Black or African American/genetics MH - Female PMC - PMC13353064 MID - NIHMS2161011 OTO - NOTNLM OT - GLP-1 receptor agonists OT - ancestry OT - electronic health records OT - exome-wide association study OT - genetic association OT - genomic medicine OT - health-system biobank OT - phenome-wide association study OT - polygenic scores OT - semaglutide COIS- Declaration of interests E.E.K. has received personal fees from Regeneron Pharmaceuticals, 23&Me, Allelica, and Illumina; has received research funding from Allelica; and serves on the advisory boards for Encompass Biosciences, Overtone, and Galateo Bio. P.T.S. is a consultant for 10x Genomics, Illumina, Foresight Diagnostics, Natera, and Twinstrand. P.C.B. sits on the scientific advisory board of Intersect Diagnostics Inc. and previously sat on those of Sage Bionetworks and BioSymetrics Inc. EDAT- 2026/03/29 07:35 MHDA- 2026/05/02 00:33 PMCR- 2026/07/10 CRDT- 2026/03/28 19:41 PHST- 2025/07/14 00:00 [received] PHST- 2025/11/21 00:00 [revised] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/05/02 00:33 [medline] PHST- 2026/03/29 07:35 [pubmed] PHST- 2026/03/28 19:41 [entrez] PHST- 2026/07/10 00:00 [pmc-release] AID - S0092-8674(26)00274-6 [pii] AID - 10.1016/j.cell.2026.03.007 [doi] PST - ppublish SO - Cell. 2026 Apr 30;189(9):2533-2555.e31. doi: 10.1016/j.cell.2026.03.007. Epub 2026 Mar 27. PMID- 41902614 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260613 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 Suppl 1 DP - 2026 Jun TI - Real-World Weight-Loss Outcomes in Weight-Reduced Patients Treated With Tirzepatide. PG - 97-101 LID - 10.1002/oby.70179 [doi] AB - OBJECTIVE: This study compared weight-loss outcomes in patients prescribed tirzepatide by weight-loss status and assessed results among patients transitioning from semaglutide. METHODS: This retrospective cohort study analyzed 6-month weight-loss outcomes in adults treated with tirzepatide between May 2022 and January 2023. Patients were classified as weight-reduced if they had lost >/= 10% total body weight (TBW) before starting tirzepatide. Among those who switched from therapeutic semaglutide (>/= 1.7 mg weekly for >/= 1 month), reasons for switching were categorized as non-response (< 5% weight loss after >/= 3 months), plateau (>/= 5% loss followed by weight stabilization), or other. RESULTS: Of 941 charts, 293 (31.1%) met inclusion criteria (65% female; mean age 52 years; mean BMI 36.15 kg/m(2)). Weight-reduced patients (n = 133) lost 7.2% TBW versus 10.3% in non-weight-reduced patients (n = 160; p < 0.001). When analyses were stratified by type 2 diabetes (T2D) status, this difference remained significant among patients without T2D. Sixty-one patients switched from semaglutide due to non-response or plateau and lost 5.3% TBW. Those switching at a plateau (n = 28) lost 8.1% versus 2.9% for non-responders (n = 33; p < 0.001). CONCLUSIONS: Tirzepatide produced meaningful weight loss across groups but outcomes varied based on weight-reduction status, T2D status, and prior response to semaglutide. CI - (c) 2026 The Obesity Society. FAU - Barenbaum, Sarah R AU - Barenbaum SR AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, New York, USA. AD - Weill Cornell Medical College, New York, New York, USA. FAU - Gonzalez, Ariel AU - Gonzalez A AD - Weill Cornell Medical College, New York, New York, USA. FAU - Verzani, Zoe AU - Verzani Z AD - Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA. FAU - Zhao, Alice S AU - Zhao AS AD - Department of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. FAU - Shukla, Alpana P AU - Shukla AP AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, New York, USA. AD - Weill Cornell Medical College, New York, New York, USA. LA - eng GR - UL1TR002384/Clinical and Translational Science Center, Weill Cornell Medical College/ PT - Journal Article DEP - 20260328 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - Semaglutide MH - Retrospective Studies MH - Male MH - Treatment Outcome MH - Adult MH - *Obesity/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Aged MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy EDAT- 2026/03/29 07:29 MHDA- 2026/06/15 11:32 CRDT- 2026/03/28 06:02 PHST- 2026/01/23 00:00 [revised] PHST- 2025/11/21 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/06/15 11:32 [medline] PHST- 2026/03/29 07:29 [pubmed] PHST- 2026/03/28 06:02 [entrez] AID - 10.1002/oby.70179 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jun;34 Suppl 1:97-101. doi: 10.1002/oby.70179. Epub 2026 Mar 28. PMID- 41902399 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260814 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 111 IP - 9 DP - 2026 Aug 13 TI - Patterns of TSH test after GLP-1 RAs initiation in patients on levothyroxine: a trial emulation study. PG - 2536-2547 LID - 10.1210/clinem/dgag131 [doi] AB - CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity and can lead to substantial weight loss. In patients taking levothyroxine, weight loss can reduce thyroid hormone requirements and potentially associated adverse effects. Thyroid-stimulating hormone (TSH) monitoring is essential but unclear whether thyroid function is routinely reassessed after GLP-1 RAs initiation. OBJECTIVE: Examine the changes in the timing of TSH testing after GLP-1 RAs. DESIGN: Retrospective cohort study emulating a target trial using Medicare from January 1, 2011, to December 31, 2020. The primary analysis followed an intention-to-treat approach. Patients were matched 1:1 using propensity scores. Logistic regression models and informed by least absolute shrinkage operator variable selection were used. SETTING: The 15% sample of U.S. Medicare fee-for-service claims data. PATIENTS OR OTHER PARTICIPANTS: Adults aged >/=65 years with type 2 diabetes on a stable levothyroxine dose at baseline. INTERVENTION(S): Initiation of GLP-1 RAs vs initiation/ongoing use of sodium-glucose cotransporter-2 inhibitors (SGLT-2is). MAIN OUTCOME MEASURE(S): TSH testing during follow-up. RESULTS: Among 5370 matched patients, the mean age was 73.2 years. 71.6% were women, and 87.1% were White. Approximately 83.0% of patients in both treatment groups receive a TSH testing within a 1-year follow-up. The mean time to TSH testing was approximately 130.5 days for both groups. CONCLUSION: TSH testing patterns did not differ between GLP-1 RAs and SGLT-2is, despite the greater likelihood of requiring levothyroxine dose adjustment associated with weight loss seen with GLP-1 RA therapy. Given levothyroxine's widespread use, this gap suggests missed opportunities for timely and weight-responsive thyroid monitoring. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Chen, Yishan AU - Chen Y AUID- ORCID: 0009-0001-5474-5900 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA. FAU - Du, Fanxing AU - Du F AUID- ORCID: 0009-0003-0487-9171 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA. FAU - Singh Ospina, Naykky M AU - Singh Ospina NM AUID- ORCID: 0000-0001-7229-5061 AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA. FAU - Brito, Juan P AU - Brito JP AUID- ORCID: 0000-0003-1840-1745 AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. AD - Care and AI Lab, Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55902, USA. FAU - Shao, Hui AU - Shao H AUID- ORCID: 0000-0002-4088-546X AD - Emory Global Diabetes Research Center of Woodruff Health Sciences Center, Rollin School of Public Health, Emory University, Atlanta, GA 30322, USA. AD - Hubert Department of Global Health, Rollin School of Public Health, Emory University, Atlanta, GA 30322, USA. FAU - Liu, Qing AU - Liu Q AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA. FAU - McCoy, Rozalina G AU - McCoy RG AUID- ORCID: 0000-0002-2289-3183 AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. AD - University of Maryland Institute for Health Computing, North Bethesda, MD 20852, USA. FAU - Jiao, Tianze AU - Jiao T AUID- ORCID: 0000-0002-2608-616X AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA. AD - Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. LA - eng GR - CA/NCI NIH HHS/United States GR - K08CA248972/NH/NIH HHS/United States PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 9002-71-5 (Thyrotropin) RN - Q51BO43MG4 (Thyroxine) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Male MH - *Thyrotropin/blood MH - *Thyroxine/therapeutic use/administration & dosage MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Thyroid Function Tests/statistics & numerical data MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged, 80 and over MH - Follow-Up Studies PMC - PMC13466952 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists (GLP-1 RAs) OT - hypothyroidism OT - sodium-glucose cotransporter-2 inhibitors (SGLT-2is) OT - target trial emulation OT - thyroid-stimulating hormone (TSH) OT - type 2 diabetes (T2D) EDAT- 2026/03/28 06:39 MHDA- 2026/08/13 04:18 PMCR- 2027/03/27 CRDT- 2026/03/28 02:33 PHST- 2025/12/04 00:00 [received] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/08/13 04:18 [medline] PHST- 2026/03/28 06:39 [pubmed] PHST- 2026/03/28 02:33 [entrez] PHST- 2027/03/27 00:00 [pmc-release] AID - 8552549 [pii] AID - dgag131 [pii] AID - 10.1210/clinem/dgag131 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 Aug 13;111(9):2536-2547. doi: 10.1210/clinem/dgag131. PMID- 41898712 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 6 DP - 2026 Mar 21 TI - GLP-1 Receptor Agonists at the Crossroads of Circadian Biology, Sleep, and Metabolic Disease. LID - 10.3390/ijms27062853 [doi] LID - 2853 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes and obesity, yet their actions extend beyond glycemic control and weight loss. This narrative review synthesizes current preclinical and clinical evidence examining the bidirectional relationship between glucagon-like peptide-1 (GLP-1) receptor agonists and circadian biology. A structured literature search was conducted in PubMed using combinations of the terms 'GLP-1,' 'circadian,' 'chronobiology,' 'sleep,' 'obesity,' and 'type 2 diabetes' through January 2026. Accumulating evidence indicates that GLP-1 physiology is closely coupled to circadian timing systems and sleep-wake regulation. In this narrative review, we synthesize emerging data that reframe GLP-1RAs as chronometabolic modulators, acting at the intersection of metabolism, circadian biology, and sleep. We review circadian control of GLP-1 secretion by intestinal L-cells, emphasizing the role of core clock genes and the vulnerability of incretin rhythms to circadian misalignment from shift work, nocturnal light exposure, and sleep loss. We then examine GLP-1 receptor signaling within central and peripheral clock networks, including feedback effects on hypothalamic and hepatic circadian regulation. Emerging data suggest that GLP-1 signaling is under circadian regulation and may, in turn, influence central and peripheral clock systems. Comparative discussion of semaglutide, liraglutide, and tirzepatide highlights agent-specific pharmacokinetics and emerging clinical data linking GLP-1RA therapy to sleep outcomes, particularly obstructive sleep apnea. Finally, we outline translational opportunities for chronotherapy and precision medicine, positioning GLP-1RAs as integrative tools for metabolic and sleep-related disease rather than purely weight-centric therapies. We propose that GLP-1 receptor agonists may function as chronometabolic modulators, with potential implications for personalized chronopharmacological strategies in metabolic disease. FAU - Gandhi, Ayush AU - Gandhi A AUID- ORCID: 0009-0008-8508-152X AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Phyu, Ei Moe AU - Phyu EM AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Koom-Dadzie, Kwame AU - Koom-Dadzie K AUID- ORCID: 0000-0002-6365-9203 AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Dickson, Kodwo Bosomefi AU - Dickson KB AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Halm, Josiah AU - Halm J AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. LA - eng PT - Journal Article PT - Review DEP - 20260321 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Circadian Rhythm/drug effects MH - Animals MH - *Metabolic Diseases/drug therapy/metabolism MH - *Sleep/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Semaglutide MH - Obesity/drug therapy/metabolism MH - Tirzepatide MH - Hypoglycemic Agents/pharmacology/therapeutic use PMC - PMC13026677 OTO - NOTNLM OT - GLP-1 receptor agonists OT - chronopharmacology OT - chronotherapy OT - circadian rhythms OT - clock genes OT - incretin hormones OT - metabolic disease OT - obstructive sleep apnea OT - sleep disorder OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/03/28 06:39 MHDA- 2026/03/28 06:40 PMCR- 2026/03/21 CRDT- 2026/03/28 01:23 PHST- 2026/02/15 00:00 [received] PHST- 2026/03/16 00:00 [revised] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/03/28 06:40 [medline] PHST- 2026/03/28 06:39 [pubmed] PHST- 2026/03/28 01:23 [entrez] PHST- 2026/03/21 00:00 [pmc-release] AID - ijms27062853 [pii] AID - ijms-27-02853 [pii] AID - 10.3390/ijms27062853 [doi] PST - epublish SO - Int J Mol Sci. 2026 Mar 21;27(6):2853. doi: 10.3390/ijms27062853. PMID- 41898482 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 6 DP - 2026 Mar 13 TI - Gastric Neoplasm Risk with DPP-4 Inhibitors, GLP-1 Receptor Agonists, and SGLT2 Inhibitors: Network Meta-Analysis of Randomized Trials. LID - 10.3390/ijms27062619 [doi] LID - 2619 AB - Whether the risk of gastric neoplasm is modified by newer glucose-lowering therapies-dipeptidyl peptidase-4 inhibitors (DPP4is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2is)-remains uncertain. Given their global uptake and long-term use in populations already predisposed to malignancy, decision-grade comparative safety evidence is needed. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults without baseline gastric neoplasms. PubMed, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, ClinicalKey, ProQuest, and ScienceDirect were searched from inception to 10 January 2026, without language restrictions. The primary outcome was incident gastric neoplasms (benign or malignant). Random-effects frequentist NMA estimated risk ratios (RRs) with 95% confidence intervals (CIs); Bayesian NMA served as sensitivity analysis. Certainty of evidence was assessed using GRADE adapted for NMA (PROSPERO CRD420261282728). Fifty-two RCTs (171,165 participants; mean age 63.6 years; 36.9% women; mean follow-up 141.8 weeks) were included. At the class level, GLP1RAs were associated with lower gastric neoplasm risk versus controls (RR = 0.51, 95% CI = 0.28-0.92), whereas DPP4is were associated with higher risk (RR = 1.77, 95% CI = 1.09-2.85). These signals persisted in prespecified subgroup analyses among participants with diabetes mellitus, in trials with duration >/=52 weeks (GLP1RA: RR = 0.52, 95% CI = 0.28-0.95; DPP4i: RR = 2.05, 95% CI = 1.19-3.55), and in older populations (age >/=60 years; DPP4i: RR = 2.08, 95% CI = 1.15-3.77). No class showed a significant association in younger participants (<60 years) or shorter trials (<52 weeks). Across available RCT evidence, GLP1RA prescription generally had a relatively lower gastric neoplasm risk than controls. In contrast, among patients with diabetes mellitus receiving longer-term therapy, GLP1RAs may be the preferable option from the perspective of gastric neoplasm risk, while DPP4is warrant heightened vigilance and mechanistic clarification. These findings support improved neoplasms ascertainment in future trials rather than immediate prescribing changes. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AUID- ORCID: 0000-0002-8650-4060 AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. FAU - Zeng, Bing-Syuan AU - Zeng BS AD - Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Suen, Mein-Woei AU - Suen MW AUID- ORCID: 0000-0002-3991-0322 AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan. AD - Gender Equality Education and Research Center, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, Asia University Hospital, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 406, Taiwan. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 807, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3216, Australia. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK. AD - Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, 1090 Vienna, Austria. AD - Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AUID- ORCID: 0000-0001-8462-1311 AD - Department of Psychiatry, Tri-Service General Hospital, Taipei 114, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei 114, Taiwan. FAU - Hsu, Shih-Pin AU - Hsu SP AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan. AD - Department of Neurology, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Wang, Hung-Yu AU - Wang HY AD - Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung 802, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical University, Taipei 114, Taiwan. AD - Department of Psychiatry, National Defense Medical University, Taipei 114, Taiwan. FAU - Tu, Yu-Kang AU - Tu YK AUID- ORCID: 0000-0002-2461-474X AD - Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, No. 17, Xuzhou Road, Taipei 100, Taiwan. AD - Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan. FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, No. 70 Lienhai Rd., Kaohsiung 804, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260313 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Stomach Neoplasms/epidemiology/chemically induced/etiology MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Female MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors PMC - PMC13026302 OTO - NOTNLM OT - DPP-4 inhibitor OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - diabetes mellitus OT - gastric neoplasms OT - semaglutide COIS- The authors declare no conflict of interest. The authors of this work were supported by the following grants: Brendon Stubbs is supported by an NIHR Advanced Fellowship. Brendon Stubbs is partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. EDAT- 2026/03/28 06:39 MHDA- 2026/03/28 06:40 PMCR- 2026/03/13 CRDT- 2026/03/28 01:22 PHST- 2026/01/15 00:00 [received] PHST- 2026/02/10 00:00 [revised] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/03/28 06:40 [medline] PHST- 2026/03/28 06:39 [pubmed] PHST- 2026/03/28 01:22 [entrez] PHST- 2026/03/13 00:00 [pmc-release] AID - ijms27062619 [pii] AID - ijms-27-02619 [pii] AID - 10.3390/ijms27062619 [doi] PST - epublish SO - Int J Mol Sci. 2026 Mar 13;27(6):2619. doi: 10.3390/ijms27062619. PMID- 41895521 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260807 IS - 1878-8769 (Electronic) IS - 1878-8750 (Linking) VI - 210 DP - 2026 Jun TI - GLP-1 Receptor Agonists and Long-Term Survival after Spontaneous Intracerebral Hemorrhage in Type 2 Diabetes. PG - 124932 LID - S1878-8750(26)00148-8 [pii] LID - 10.1016/j.wneu.2026.124932 [doi] AB - BACKGROUND: Survivors of spontaneous intracerebral hemorrhage (sICH) experience substantial long-term mortality, particularly among those with type 2 diabetes mellitus (T2DM). Evidence to guide post-sICH metabolic management remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiometabolic risk profiles and reduce major adverse cardiovascular events in patients with T2DM; however, their association with long-term outcomes after sICH has not been well characterized. METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with T2DM who experienced sICH between 2018 and 2024 were identified. Patients who received a GLP-1 RA within 6 months after sICH were compared with matched controls without GLP-1 RA exposure. Propensity score matching (1:1) was performed using demographic, clinical and pharmacologic variables. The primary outcome was all-cause mortality at 2 and 5 years. Hazard ratios (HRs) were estimated using Cox proportional hazards models. RESULTS: After propensity score matching, 2710 patients were included in each cohort with balanced baseline characteristics. At 2 years, all-cause mortality was lower among GLP-1 RA users than controls (6.5% vs. 7.6%; 0.77 (0.63-0.95)). This association persisted at 5 years (11.2% vs. 13.1%; 0.77 (0.66-0.90)). The study did not assess recurrent intracerebral hemorrhage or cause-specific mortality. CONCLUSIONS: In this large real-world cohort of sICH survivors with T2DM, post-hemorrhage GLP-1 RA use was associated with lower long-term all-cause mortality. Given the observational design, causality cannot be inferred. These findings provide hypothesis-generating evidence supporting further prospective studies to clarify the role of GLP-1 RAs in post-sICH secondary prevention. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Chen, Chien-Min AU - Chen CM AD - Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; Department of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan. FAU - Lyu, Xiajie AU - Lyu X AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. FAU - Chang, Yu AU - Chang Y AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: yuchang1112359@gmail.com. FAU - Lin, Hong-Min AU - Lin HM AD - Department of Family Medicine, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address: hongml2828@gmail.com. LA - eng PT - Journal Article DEP - 20260325 PL - United States TA - World Neurosurg JT - World neurosurgery JID - 101528275 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - World Neurosurg. 2026 Sep;213:125199. doi: 10.1016/j.wneu.2026.125199. PMID: 42567099 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Cerebral Hemorrhage/mortality/drug therapy/complications MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - Cohort Studies OTO - NOTNLM OT - GLP-1 receptor agonist OT - Intracerebral hemorrhage OT - Mortality OT - Propensity score matching OT - Real-world study OT - Survival OT - Type 2 diabetes EDAT- 2026/03/28 00:42 MHDA- 2026/06/11 05:39 CRDT- 2026/03/27 20:17 PHST- 2026/03/07 00:00 [received] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/06/11 05:39 [medline] PHST- 2026/03/28 00:42 [pubmed] PHST- 2026/03/27 20:17 [entrez] AID - S1878-8750(26)00148-8 [pii] AID - 10.1016/j.wneu.2026.124932 [doi] PST - ppublish SO - World Neurosurg. 2026 Jun;210:124932. doi: 10.1016/j.wneu.2026.124932. Epub 2026 Mar 25. PMID- 41893299 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260823 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 6 DP - 2026 Jun 1 TI - Safety of Semaglutide After Dialysis Initiation: An Individual-Level Pooled Analysis. PG - 999-1005 LID - 10.2337/dc26-0112 [doi] AB - OBJECTIVE: People receiving dialysis are at high risk of cardiovascular and all-cause mortality. Semaglutide reduces major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and those without T2D with obesity and high cardiovascular risk. Data to establish safety and efficacy in dialysis-dependent kidney failure are scarce. We aimed to assess the safety of semaglutide in people who initiate dialysis. RESEARCH DESIGN AND METHODS: In this post hoc analysis of four randomized, placebo-controlled trials (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT], Evaluate Renal Function With Semaglutide Once Weekly [FLOW], and Semaglutide Cardiovascular Outcomes [SOUL]), we evaluated systematically collected adverse events (AEs) from participants who initiated dialysis during study follow-up. We compared the proportion and event rates of systematically collected serious AEs (SAEs), including adjudicated MACE, and AEs leading to permanent treatment discontinuation in participants originally randomized to semaglutide or placebo who remained on treatment after dialysis initiation. RESULTS: Among 34,064 participants randomized across the trials, 307 initiated dialysis, of whom 165 participants randomized to semaglutide (n = 71) or placebo (n = 94) remained on treatment. After dialysis initiation, SAEs were reported in 32 of 71 (45%) and 54 of 94 (57%) participants, and the proportion of participants who permanently discontinued trial medication was 8.5% and 10.6% in the semaglutide and placebo groups, respectively. The MACE event rates were 9.7 and 16.1 events per 100 person-years, and all-cause mortality event rates were 13.8 and 18.1 events per 100 person-years, in the semaglutide and placebo groups, respectively. CONCLUSIONS: Although more evidence is needed, continuation of semaglutide after dialysis initiation appears safe and warrants efficacy testing regarding reduction in MACE and death. CI - (c) 2026 by the American Diabetes Association. FAU - Klein, Klara R AU - Klein KR AUID- ORCID: 0000-0002-5894-9054 AD - Division of Endocrinology and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Menacher, Anna AU - Menacher A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Mann, Johannes F E AU - Mann JFE AD - University Hospital Erlangen, Erlangen, Germany. AD - KfH Kidney Centre, Munich, Germany. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Division of Nephrology, University of Washington, Seattle, WA. FAU - Kvist, Kajsa AU - Kvist K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Andersen, Margit R AU - Andersen MR AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mayrdorfer, Manuel AU - Mayrdorfer M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX. LA - eng GR - R01 DK125831/DK/NIDDK NIH HHS/United States GR - R44 DK096803/DK/NIDDK NIH HHS/United States GR - UC4 DK108612/DK/NIDDK NIH HHS/United States GR - U01 DK100846/DK/NIDDK NIH HHS/United States GR - R01 DK119913/DK/NIDDK NIH HHS/United States GR - R01 DK112939/DK/NIDDK NIH HHS/United States GR - OT2 OD032581/OD/NIH HHS/United States GR - U54 DK118612/DK/NIDDK NIH HHS/United States GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - R01 MD014712/MD/NIMHD NIH HHS/United States GR - UM1 TR004406/TR/NCATS NIH HHS/United States GR - P30 DK127984/DK/NIDDK NIH HHS/United States GR - R01 DK127365/DK/NIDDK NIH HHS/United States GR - R33 HL142680/HL/NHLBI NIH HHS/United States GR - U2C DK114886/DK/NIDDK NIH HHS/United States GR - OT2 HL161847/HL/NHLBI NIH HHS/United States GR - U01 DK098246/DK/NIDDK NIH HHS/United States GR - U54 DK083912/DK/NIDDK NIH HHS/United States GR - UL1 TR002489/TR/NCATS NIH HHS/United States GR - UL1 TR002319/TR/NCATS NIH HHS/United States GR - K12 TR004416/TR/NCATS NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Renal Dialysis MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cardiovascular Diseases/prevention & control PMC - PMC13191398 COIS- Duality of Interest. K.R.K. has received advisory/consulting fees and/or other support from Antag Therapeutics, Metsera, Novo Nordisk, and Roche Pharmaceuticals. Additionally, K.R.K. has received research-related contracts (paid to the institution) from Bayer, Boehringer-Ingelheim, Carmot, Diasome, Eli Lilly, Gentibio, Novo Nordisk, Rhythm Pharmaceuticals, Roche Pharmaceuticals, and vTv Therapeutics. J.B.B. has received salary support from clinical trial contracts to his employer by Corcept Therapeutics, Dexcom, GentiBio, Novo Nordisk, and Sparrow Pharmaceuticals; has received salary support from consulting contracts to his employer by Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Kayothera, Metsera, MiniMed, Recordati, Sparrow Pharmaceuticals, Vertex Pharmaceuticals, vTv Therapeutics, and Zealand Pharma; and has stock/options in Aardvark Therapeutics, Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. J.F.E.M. reports grants from Novo Nordisk; honoraria from AstraZeneca, Bayer, Cytel, ICON plc, IQVIA, Hexal, Novo Nordisk, Sanofi, UpToDate, and WCG; and a leadership role in the Kidney Disease: Improving Global Outcomes (KDIGO) group. K.R.T. has received investigator-initiated grant support from Travere Therapeutics Inc., Bayer, and Benaroya Research Institute. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bayer, ProKidney, and Alnylam Pharmaceuticals, as well as speaker fees from Novo Nordisk, Bayer, Boehringer Ingelheim, and AstraZeneca. Additionally, she reports being chair of data safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Disease, and George Clinical Institute, and a member of the data safety monitoring board for AstraZeneca. She reports leadership roles as chair for the Diabetic Kidney Disease Collaborative and chair for Kidney Week 2025 Program Committee, both for the American Society of Nephrology. A.M., K.K., M.R.A., and M.M. are employees of Novo Nordisk. K.K. and M.M. are also shareholders of Novo Nordisk. I.L. has received research funding (paid to the institution) from Novo Nordisk, Sanofi, Boehringer Ingelheim, and Roche; research-related consulting fees (paid to the institution) from Novo Nordisk; and advisory/consulting fees and/or other support from Abbvie, Altimmune, AstraZeneca, Bayer, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Mediflix, Merck, Metsera, Novo Nordisk, PharmaVentures, Pfizer, Regeneron, Sanofi, Shionogi, Structure Therapeutics, TARGET RWE, TERNS Pharmaceuticals, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/03/27 17:38 MHDA- 2026/05/20 18:33 PMCR- 2026/03/27 CRDT- 2026/03/27 11:25 PHST- 2026/01/15 00:00 [received] PHST- 2026/03/02 00:00 [accepted] PHST- 2026/05/20 18:33 [medline] PHST- 2026/03/27 17:38 [pubmed] PHST- 2026/03/27 11:25 [entrez] PHST- 2026/03/27 00:00 [pmc-release] AID - 164644 [pii] AID - 260112 [pii] AID - 10.2337/dc26-0112 [doi] PST - ppublish SO - Diabetes Care. 2026 Jun 1;49(6):999-1005. doi: 10.2337/dc26-0112. PMID- 41891915 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 2325-8179 (Electronic) IS - 2325-8160 (Linking) VI - 57 IP - 4 DP - 2026 Apr TI - GLP-1 Receptor Agonists: Clinical Considerations and Risk Management for Patients Undergoing Ophthalmic Surgery. PG - 263-267 LID - 10.3928/23258160-20260310-01 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity due to their benefits in glycemic control, weight loss, and cardiovascular risk reduction. However, their pharmacologic effect of delayed gastric emptying raises perioperative concerns. Even though ophthalmic procedures are often performed under local or topical anesthesia, there still remains the concern that GLP-1 RA-induced gastroparesis can increase the risk of aspiration. Additionally, adjunctive sedation, conversion to deeper sedation, or general anesthesia is sometimes necessary for ophthalmic surgery. This review outlines the perioperative implications of GLP-1 RA use in ophthalmic surgery, emphasizing the importance of preoperative screening, interdisciplinary coordination, and familiarity with the evolving anesthesia guidelines. FAU - Baumal, Caroline R AU - Baumal CR AD - New England Eye Center. FAU - Choi, Stephanie AU - Choi S AD - New England Eye Center. FAU - Balonov, Konstantin AU - Balonov K AD - Department of Anesthesiology. FAU - Do, Diana V AU - Do DV AD - Tufts Medical Center, Boston, Massachusetts; and Byers Eye Institute, Stanford University, Palo Alto, California. LA - eng PT - Journal Article PT - Review DEP - 20260327 PL - United States TA - Ophthalmic Surg Lasers Imaging Retina JT - Ophthalmic surgery, lasers & imaging retina JID - 101599215 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Ophthalmologic Surgical Procedures MH - *Risk Management/methods MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects COIS- Disclosure: CRB is the Chief Medical Officer at Apellis. DVD has received contracts from Regeneron, Regenxbio, Ocular Therapeutix, Belite Bio, and Malinkrodt; is a consultant for Regeneron, Ocular Therapeutix, Regenxbio, Kodiak Sciences, Apellis, Astellas, Belite Bio, and Bayer; and holds stock or stock options in Kodiak Sciences. The remaining authors have disclosed no potential conflicts of interest, financial or otherwise. EDAT- 2026/03/27 17:38 MHDA- 2026/04/19 17:47 CRDT- 2026/03/27 10:33 PHST- 2026/04/19 17:47 [medline] PHST- 2026/03/27 17:38 [pubmed] PHST- 2026/03/27 10:33 [entrez] AID - 10.3928/23258160-20260310-01 [doi] PST - ppublish SO - Ophthalmic Surg Lasers Imaging Retina. 2026 Apr;57(4):263-267. doi: 10.3928/23258160-20260310-01. Epub 2026 Mar 27. PMID- 41889157 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Lower Risk of Cardiovascular Events in Patients With Clinical Atherosclerotic Cardiovascular Disease Who Initiated Semaglutide 2.4 mg in the Real-World: Results From the SCORE-Clinical ASCVD Study. PG - 4975-4990 LID - 10.1111/dom.70686 [doi] AB - AIMS: To evaluate the association between semaglutide 2.4 mg and major adverse cardiovascular events (MACE) among adults with clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes in real-world clinical practice. MATERIALS AND METHODS: Adults aged >/= 45 years with overweight/obesity and clinical ASCVD were identified from a United States database (2016-2024). Patients initiating semaglutide 2.4 mg were matched 1:2 with individuals not treated with semaglutide 2.4 mg through a propensity score model including > 70 demographic and clinical covariates. Primary outcomes were revised 3-point MACE (rMACE-3: myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, heart failure [HF] hospitalisation, coronary revascularization). Secondary outcomes included 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular-related mortality) and HF composite outcomes; exploratory outcomes were incident type 2 diabetes (T2D), major adverse kidney events (MAKE) and major obesity-related adverse events (MORAE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: The final sample comprised 38 308 patients with semaglutide 2.4 mg use propensity-score matched to 76 615 patients without. Over a mean follow-up of 8.6 months, semaglutide 2.4 mg significantly reduced the risk of rMACE-3 (HR: 0.55; 95% CI: 0.47-0.65), rMACE-5 (0.63; 0.56-0.71), MACE-3 (0.66; 0.56-0.78) and MACE-5 (0.69; 0.62-0.77). Semaglutide 2.4 mg also significantly reduced the risk of HF composite outcomes, T2D, MAKE and MORAE. CONCLUSIONS: Semaglutide 2.4 mg was associated with a significantly reduced risk of MACE and other obesity-related outcomes, extending prior evidence of benefits to a broader clinical ASCVD population. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Mena-Hurtado, Carlos AU - Mena-Hurtado C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Divino, Victoria AU - Divino V AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Chen, Yan AU - Chen Y AUID- ORCID: 0000-0002-5317-1909 AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Boland, Joanna AU - Boland J AUID- ORCID: 0000-0001-7858-979X AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Traina, Andrea AU - Traina A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Ozer, Kerem AU - Ozer K AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Knop, Filip K AU - Knop FK AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Smolderen, Kim G AU - Smolderen KG AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Section of Psychology, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA. LA - eng GR - Novo Nordisk, Inc./ PT - Journal Article DEP - 20260326 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Middle Aged MH - *Atherosclerosis/epidemiology/complications/drug therapy MH - Obesity/complications/drug therapy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Diabetes Mellitus, Type 2/epidemiology MH - Overweight/complications/drug therapy MH - Propensity Score MH - United States/epidemiology MH - Risk Factors PMC - PMC13146205 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - cohort study OT - observational study OT - real-world evidence OT - semaglutide COIS- Zhenxiang Zhao, Victoria Divino, Andrea Traina, Kerem Ozer, and Filip K. Knop are employees of Novo Nordisk and hold stock/options. Jinlin Song, Yan Chen and Joanna Boland are employees of Analysis Group Inc., which has received consulting fees from Novo Nordisk Inc. for this work. Kim G. Smolderen receives research grants from Johnson & Johnson, Merck, and Abbott. She is a consultant for Dario Health, Terumo, Novo Nordisk and Merck. She is the owner of BoboDream LLC. She receives funding from the National Institutes of Health (R01HL163640-03S1; R01HL163640-02S1; R21AT012430-01). Carlos Mena-Hurtado is a consultant for Terumo, Novo Nordisk, HMP Global and Cook. He receives research grants from Merck, Shockwave, and the National Institutes of Health. Michael G. Nanna: Dr. Nanna reports current research support from the American College of Cardiology Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging (K76AG088428). Dr. Nanna also reports being a consultant for Novo Nordisk, Heartflow, Novartis and Merck. EDAT- 2026/03/27 07:15 MHDA- 2026/05/06 06:38 PMCR- 2026/05/06 CRDT- 2026/03/27 02:32 PHST- 2026/03/10 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/11 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/03/27 07:15 [pubmed] PHST- 2026/03/27 02:32 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70686 [pii] AID - 10.1111/dom.70686 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4975-4990. doi: 10.1111/dom.70686. Epub 2026 Mar 26. PMID- 41889156 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Clinical Management of Weight Regain and Cardiometabolic Consequences After Discontinuation of GLP-1 Receptor Agonists. PG - 4546-4558 LID - 10.1111/dom.70713 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin therapies produce substantial weight loss and cardiometabolic improvement, yet treatment discontinuation is common and associated with adverse metabolic consequences. AIMS: This review aims to synthesize current mechanistic and clinical evidence on metabolic trajectories following GLP-1RA discontinuation, identify predictors of relapse, and propose a multidisciplinary framework for post-treatment management. MATERIALS AND METHODS: We conducted a narrative review of evidence from randomized withdrawal trials (including STEP-1 extension, STEP-4, and SURMOUNT-4), systematic reviews, meta-analyses, and large real-world observational cohorts encompassing over 289,000 patients. RESULTS: Discontinuation is associated with substantial weight regain (60%-90% within one year) and parallel reversal of cardiometabolic benefits. Modelling studies suggest that glycaemic, blood pressure, and lipid parameters return to baseline within approximately 12 months, while HbA1c normalizes within 12-18 months. Early discontinuation (< 1 year) is associated with increased risks of coronary artery disease and heart failure compared with continued therapy. DISCUSSION: Weight recurrence reflects biological adaptations to weight loss, including reactivation of orexigenic pathways and adaptive thermogenesis. In the absence of validated tapering strategies, structured multidisciplinary transition approaches combining pharmacological, behavioral, and psychological interventions may mitigate post-discontinuation relapse. CONCLUSION: GLP-1RA discontinuation should be considered a high-risk clinical transition rather than a treatment endpoint. Structured follow-up and multidisciplinary management are essential to preserve long-term cardiometabolic benefits. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Shah, Ermeena AU - Shah E AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - AlShiab, Rama AU - AlShiab R AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Abdo, Anas AU - Abdo A AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Ozbek, Lasin AU - Ozbek L AD - Department of Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Covic, Adrian AU - Covic A AD - Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University, Iasi, Romania. FAU - Kanbay, Mehmet AU - Kanbay M AUID- ORCID: 0000-0002-1297-0675 AD - Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey. LA - eng PT - Journal Article PT - Review DEP - 20260326 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Weight Gain/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Interruption MH - Weight Loss/drug effects MH - Incretins/therapeutic use OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonists OT - tirzepatide OT - weight gain EDAT- 2026/03/27 07:15 MHDA- 2026/05/06 06:37 CRDT- 2026/03/27 02:32 PHST- 2026/03/09 00:00 [revised] PHST- 2026/02/13 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/05/06 06:37 [medline] PHST- 2026/03/27 07:15 [pubmed] PHST- 2026/03/27 02:32 [entrez] AID - 10.1111/dom.70713 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4546-4558. doi: 10.1111/dom.70713. Epub 2026 Mar 26. PMID- 41886296 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 42 IP - 4 DP - 2026 May TI - Not All GLP-1 Receptor Agonists Are Alike: Real-World Evidence of Differential Endocrine and Dermatologic Safety. PG - e70163 LID - 10.1002/dmrr.70163 [doi] LID - e70163 AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database. MATERIALS AND METHODS: This study analysed the U.S. FDA Adverse Event Reporting System (FAERS) data (Q2 2022-Q2 2025) for six GLP-1 Ras (exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide) to identify alopecia- and reproductive or endocrine-related a AEs. Disproportionality analyses were conducted using crude and adjusted reporting odds ratios (cROR and aROR) from logistic regression controlling for potential confounding factors. Sensitivity analyses with positive and negative controls were used to validate the signal robustness. RESULTS: A total of 1276 alopecia-related and 759 reproductive or endocrine-related cases were identified. Semaglutide showed significant positive associations with alopecia (aROR 1.23 [1.11-1.35]) and reproductive/hormonal disorders, including polycystic ovary syndrome (aROR 6.59 [3.73-11.64]) and menstrual abnormalities. In contrast, dulaglutide and tirzepatide demonstrated negative associations for several reproductive outcomes (e.g., dysmenorrhoea, amenorrhoea, heavy menstrual bleeding), indicating lower reporting odds in this dataset. Sensitivity analyses using control drugs confirmed the consistency and specificity of these findings. CONCLUSION: This real-world pharmacovigilance study identified agent-specific differences in the endocrine and dermatologic safety profiles of GLP-1 RAs. While semaglutide exhibited disproportionate reporting for alopecia and hormonal imbalance, dulaglutide and tirzepatide showed lower or non-significant disproportionality signals for these events. These results highlight the need for personalised agent selection and continued pharmacovigilance to optimise long-term patient safety. CI - (c) 2026 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Lee, Nai AU - Lee N AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. FAU - Kim, Yun AU - Kim Y AUID- ORCID: 0000-0002-9809-7351 AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. AD - Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. LA - eng GR - Catholic University of Daegu/ GR - 2025-RISE-15-107/Gyeongsangbuk-do RISE Project/ PT - Journal Article PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Alopecia/chemically induced/epidemiology MH - Female MH - Tirzepatide MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Pharmacovigilance MH - *Hypoglycemic Agents/adverse effects MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Male MH - Exenatide/adverse effects MH - Liraglutide/adverse effects MH - Follow-Up Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13020769 OTO - NOTNLM OT - FDA adverse event reporting system OT - GLP-1 receptor agonists OT - alopecia OT - reproductive or endocrine-related adverse events COIS- The authors declare no conflicts of interest. EDAT- 2026/03/26 18:49 MHDA- 2026/03/26 18:50 PMCR- 2026/03/26 CRDT- 2026/03/26 12:53 PHST- 2026/02/21 00:00 [revised] PHST- 2025/12/18 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/03/26 18:50 [medline] PHST- 2026/03/26 18:49 [pubmed] PHST- 2026/03/26 12:53 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - DMRR70163 [pii] AID - 10.1002/dmrr.70163 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 May;42(4):e70163. doi: 10.1002/dmrr.70163. PMID- 41885954 OWN - NLM STAT- MEDLINE DCOM- 20260614 LR - 20260813 IS - 1555-905X (Electronic) IS - 1555-9041 (Print) IS - 1555-9041 (Linking) VI - 21 IP - 6 DP - 2026 Jun 1 TI - Target Trial Emulation: Glucagon-Like Peptide-1 Receptor Agonist, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors for Kidney Outcome Prevention. PG - 997-1009 LID - 10.2215/CJN.0000001033 [doi] AB - KEY POINTS: Unknown if addition of newer diabetes medications is associated with kidney disease among older patients who were under recruited in clinical trials. In this target trial emulation, we report a protective association for kidney events and death for both glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor, compared with dipeptidyl peptidase-4 inhibitor. The association of glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor on kidney disease extended across multiple subgroups including short duration of use and in the older population. BACKGROUND: A trial emulation approach evaluated kidney outcomes for addition of three diabetes medications among Veterans, including older Veterans underrepresented in trials. METHODS: A retrospective cohort of Veterans with diabetes who were new users adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), or dipeptidyl peptidase-4 inhibitors (DPP4is). Each group was followed until a composite of death or kidney event defined as a 50% decline in eGFR, kidney failure (transplant or dialysis) or censored for nonpersistence of drug class, loss of follow-up, and study end. The primary analysis used propensity score weights to compare the hazard of the composite outcome. The secondary analysis considered cause-specific hazard of kidney events with death as censoring. An Aalen-Johansen plot displayed individual outcomes of kidney event or death as a competing risk. Subgroup analyses evaluated Veterans by duration of use, age, eGFR, and urine protein. RESULTS: After propensity score weighting, the cohort included 42,684 GLP-1 RA, 44,198 SGLT2i, and 44,213 DPP4i episodes. The median age was 69 years, diabetes duration was 10.6 years (6.8-15.2), and eGFR was 75 ml/min per 1.73 m 2 (58-92). Event rates per 1000 person-years were 34.6 (33.3-36.0) versus 29.0 (27.8-30.3) versus 47.4 (46.0-48.9) for GLP-1 RA, SGLT2i, and DPP4i, respectively. There was a protective association for composite of kidney event and death for GLP-1 RA, hazard ratio (HR) 0.70 (0.67 to 0.74), and SGLT2i users (HR, 0.65 [0.61 to 0.68]) versus DPP4i. The results were similar for the cause-specific hazard of kidney event alone GLP-1 RA (HR, 0.72 [0.65 to 0.80]) and SGLT2i (HR, 0.48 [0.43 to 0.55]) and for subgroups. CONCLUSIONS: GLP-1 RA and SGLT2i as add-on diabetes treatment were associated with lower composite and individual outcomes of kidney event and death. The association was similar across subgroups highlighting the value in primary prevention among older populations. CI - Copyright (c) 2026 by the American Society of Nephrology. FAU - Hung, Adriana AU - Hung A AUID- ORCID: 0000-0002-3203-1608 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Beck, Cole AU - Beck C AUID- ORCID: 0000-0002-6849-6255 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Greevy, Robert A AU - Greevy RA AUID- ORCID: 0000-0002-1821-3544 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Hackstadt, Amber J AU - Hackstadt AJ AUID- ORCID: 0000-0002-0164-6589 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Elasy, Tom A AU - Elasy TA AUID- ORCID: 0000-0002-1651-8387 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Roumie, Christianne L AU - Roumie CL AUID- ORCID: 0000-0002-6555-2055 AD - Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC), Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. LA - eng GR - CX000570-13/Clinical Science Research and Development/ GR - CIN 24-128/Office of Research and Development/ GR - P30DK092986/Division of Diabetes, Endocrinology, and Metabolic Diseases/ PT - Journal Article DEP - 20260326 PL - United States TA - Clin J Am Soc Nephrol JT - Clinical journal of the American Society of Nephrology : CJASN JID - 101271570 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Aged MH - *Diabetic Nephropathies/prevention & control/mortality MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glomerular Filtration Rate PMC - PMC13268379 OTO - NOTNLM OT - clinical epidemiology OT - diabetes COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/CJN/C689. EDAT- 2026/03/26 13:31 MHDA- 2026/06/15 11:36 PMCR- 2026/06/01 CRDT- 2026/03/26 12:03 PHST- 2025/05/30 00:00 [received] PHST- 2026/03/23 00:00 [accepted] PHST- 2026/06/15 11:36 [medline] PHST- 2026/03/26 13:31 [pubmed] PHST- 2026/03/26 12:03 [entrez] PHST- 2026/06/01 00:00 [pmc-release] AID - 01277230-202606000-00011 [pii] AID - CJASN-2025-000899 [pii] AID - 10.2215/CJN.0000001033 [doi] PST - ppublish SO - Clin J Am Soc Nephrol. 2026 Jun 1;21(6):997-1009. doi: 10.2215/CJN.0000001033. Epub 2026 Mar 26. PMID- 41885293 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 1473-6500 (Electronic) IS - 0952-7907 (Linking) VI - 39 IP - 3 DP - 2026 Jun 1 TI - Perioperative anesthesia care for patients with diabetes mellitus: a review of current literature with focus on oral antidiabetic medication. PG - 381-389 LID - 10.1097/ACO.0000000000001644 [doi] AB - PURPOSE OF REVIEW: Every fifth surgical patient presents with diabetes mellitus and the use of modern oral antidiabetic agents is rapidly expanding. Therefore, comprehensive and current knowledge of benefits and risks is essential for anesthesiologists. RECENT FINDINGS: The 2025 international guidelines for perioperative management of patients with type 2 diabetes mellitus recommend continuation of glucagon-like peptide-1 receptor agonists in patients without an elevated risk of aspiration, temporary discontinuation of sodium-glucose-co-transporter-2 inhibitors one to four days before surgery, and do not provide specific recommendations for dipeptidyl peptidase-4 inhibitors. Emerging evidence focuses on two principal areas: the additive metabolic and cardiovascular benefits of combination therapy, and the real-world perioperative safety of these agents. Large cohort studies now demonstrate exceedingly low incidences of pulmonary aspiration and euglycemic ketoacidosis, with adverse events previously documented predominantly in case reports. SUMMARY: Detailed pathophysiological understanding of the mechanisms, benefits, and potential risks associated with oral antidiabetic agents remains indispensable and should foster individualized, risk-based perioperative management strategies for patients with diabetes mellitus. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Riesemann, Sophia AU - Riesemann S AD - Department of Anesthesiology and Operative Intensive Care, University of Augsburg, Augsburg. AD - Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. FAU - Tenge, Theresa AU - Tenge T AD - Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. FAU - Roth, Sebastian AU - Roth S AD - Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. LA - eng PT - Journal Article PT - Review DEP - 20260319 PL - United States TA - Curr Opin Anaesthesiol JT - Current opinion in anaesthesiology JID - 8813436 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Perioperative Care/methods/standards MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Administration, Oral MH - *Anesthesia/methods/adverse effects/standards MH - Practice Guidelines as Topic MH - Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - aspiration OT - dipeptidyl peptidase-4 OT - glucagon-like peptide-1 OT - ketoacidosis OT - sodium-glucose-co-transporter-2 inhibitors EDAT- 2026/03/26 13:31 MHDA- 2026/04/29 12:42 CRDT- 2026/03/26 08:13 PHST- 2026/04/29 12:42 [medline] PHST- 2026/03/26 13:31 [pubmed] PHST- 2026/03/26 08:13 [entrez] AID - 00001503-990000000-00411 [pii] AID - 10.1097/ACO.0000000000001644 [doi] PST - ppublish SO - Curr Opin Anaesthesiol. 2026 Jun 1;39(3):381-389. doi: 10.1097/ACO.0000000000001644. Epub 2026 Mar 19. PMID- 41883191 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 13 IP - 2 DP - 2026 Mar 3 TI - Glucagon-like peptide-1 receptor agonists for prevention of heart failure events in type 2 diabetes and/or obesity. LID - 10.1093/eschf/xvag091 [doi] LID - xvag091 AB - INTRODUCTION: Heart failure (HF) is a common sequela of diabetes and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists may prevent HF events. This meta-analysis estimates absolute risk reduction (ARR) and number needed to treat (NNT) for GLP-1 receptor agonists to prevent one HF event in patients with type 2 diabetes and/or obesity, including those without baseline HF. METHODS: The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint. Random effects meta-analysis using the Mantel-Haenszel Method was performed to synthesize risk ratios (RR), ARRs, and NNTs with 95% confidence intervals (CI). RESULTS: Twelve placebo-controlled RCTs involving 95 023 patients were included. GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82-0.95; ARR 0.42%, 95% CI 0.17%-0.62%; NNT 238, 95% CI 161-588), and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72-0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113-313). Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74-0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100-526), and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55-0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55-208). CONCLUSION: GLP-1 receptor agonists have limited absolute benefit for preventing HF events in patients with type 2 diabetes and/or obesity, including in those without baseline HF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD420251074882. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Raveendra, Keerthenan AU - Raveendra K AUID- ORCID: 0000-0001-8766-9433 AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Joseph, Tobin AU - Joseph T AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Kang, Jing AU - Kang J AD - Centre for Clinical Translational Science, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK. FAU - Hurdus, Ben AU - Hurdus B AUID- ORCID: 0000-0001-8149-3449 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Cutting, Uther AU - Cutting U AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Haris, Mohammad AU - Haris M AUID- ORCID: 0009-0007-3859-7809 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Younsi, Tanina AU - Younsi T AUID- ORCID: 0009-0000-3680-4180 AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. FAU - Aslam, Amaan AU - Aslam A AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Petrie, Mark AU - Petrie M AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. FAU - Metra, Marco AU - Metra M AD - Institute of Cardiology, ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. FAU - Ajjan, Ramzi A AU - Ajjan RA AUID- ORCID: 0000-0002-1636-3725 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Wu, Jianhua AU - Wu J AUID- ORCID: 0000-0001-6093-599X AD - Wolfson Institute of Population Health, Queen Mary University of London, London, UK. FAU - Gale, Chris P AU - Gale CP AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. AD - Leeds Institute of Data Analytics, University of Leeds, Leeds LS2 9NL, UK. FAU - Nadarajah, Ramesh AU - Nadarajah R AUID- ORCID: 0000-0001-9895-9356 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. AD - Leeds Institute of Data Analytics, University of Leeds, Leeds LS2 9NL, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Randomized Controlled Trials as Topic PMC - PMC13064920 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Heart failure OT - Meta-analysis OT - Obesity OT - Type 2 diabetes EDAT- 2026/03/26 07:08 MHDA- 2026/04/09 18:30 PMCR- 2026/03/25 CRDT- 2026/03/26 03:53 PHST- 2026/02/21 00:00 [received] PHST- 2026/03/15 00:00 [revised] PHST- 2026/03/22 00:00 [accepted] PHST- 2026/04/09 18:30 [medline] PHST- 2026/03/26 07:08 [pubmed] PHST- 2026/03/26 03:53 [entrez] PHST- 2026/03/25 00:00 [pmc-release] AID - 8540500 [pii] AID - xvag091 [pii] AID - 10.1093/eschf/xvag091 [doi] PST - ppublish SO - ESC Heart Fail. 2026 Mar 3;13(2):xvag091. doi: 10.1093/eschf/xvag091. PMID- 41881006 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1439-3646 (Electronic) IS - 0947-7349 (Print) IS - 0947-7349 (Linking) VI - 134 IP - 3 DP - 2026 Mar TI - GLP-1 receptor agonists or SGLT2-inhibitors? Evaluation of a personalized treatment algorithm for individuals with type 2 diabetes: a registry-based cohort study. PG - 79-87 LID - 10.1055/a-2798-6496 [doi] AB - Guidelines recommend GLP-1 receptor agonists (GLP-1-RA) and SGLT2-inhibitors (SGLT2i) for individuals with type 2 diabetes (T2D) at high risk of atherosclerotic cardiovascular disease (ASCVD). In the context of precision medicine, we evaluated a personalized treatment algorithm to guide the initial decision between these therapies.Using data from the observational Diabetes Prospective Follow-up registry (Germany/Austria) we studied individuals with T2D who initiated GLP-1-RA (n=1433) or SGLT2i (n=2547) in a multicenter, real-world setting. Baseline characteristics included age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), HbA1c, diabetes duration, and history of ASCVD. Non-fatal ASCVD events (myocardial infarction, angina, revascularization, stroke, transient ischemic attack, and peripheral artery disease) were analyzed using dynamic weighted survival modeling to predict the optimal treatment for each individual.The algorithm predicted 48% of individuals to have better ASCVD outcomes with GLP-1-RA and 52% with SGLT2i. GLP-1-RA-optimal individuals had on average a higher BMI (37 vs 31 kg/m(2)), lower eGFR (71 vs 93 ml/min per 1.73 m(2)) and less history of ASCVD (9 vs 18%) compared to SGLT2i-optimal individuals. However, an internal model validation showed that the predicted optimal treatment did not statistically significantly prolong the average time to a non-fatal ASCVD event compared to the suboptimal treatment (AFT parameter: 1.13; 95% CI: 0.83-1.56; HR: 0.88; 95% CI: 0.64-1.21).The personalized treatment algorithm for GLP-1-RA and SGLT2i did not result in clear individual ASCVD benefits on either drug, a finding consistent with the clinical equipoise reflected in current T2D treatment guidelines. CI - The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). FAU - Mori, Tim AU - Mori T AUID- ORCID: 0009-0000-8363-7434 AD - German Diabetes Center Institute for Biometrics and Epidemiology, Dusseldorf, Germany. AD - German Center for Diabetes Research, Neuherberg, Germany. FAU - Kuss, Oliver AU - Kuss O AUID- ORCID: 0000-0003-3301-5869 AD - German Diabetes Center Institute for Biometrics and Epidemiology, Dusseldorf, Germany. AD - German Center for Diabetes Research, Neuherberg, Germany. AD - Centre for Health and Society, Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Mader, Julia K AU - Mader JK AUID- ORCID: 0000-0001-7854-4233 AD - Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Naudorf, Michael AU - Naudorf M AD - Diabetes Center Lindlar, Lindlar, Germany. FAU - Seufert, Jochen AU - Seufert J AUID- ORCID: 0000-0001-5654-7310 AD - Department of Medicine II, Medical Center - University of Freiburg, Freiburg, Germany. FAU - Holl, Reinhard W AU - Holl RW AUID- ORCID: 0000-0003-1395-4842 AD - Ulm University Institute of Epidemiology & Medical Biometry, Ulm, Germany. AD - German Center for Diabetes Research, Neuherberg, Germany. FAU - Lanzinger, Stefanie AU - Lanzinger S AUID- ORCID: 0000-0002-3789-6459 AD - Ulm University Institute of Epidemiology & Medical Biometry, Ulm, Germany. AD - German Center for Diabetes Research, Neuherberg, Germany. FAU - Grimsmann, Julia M AU - Grimsmann JM AUID- ORCID: 0000-0003-3627-1163 AD - Ulm University Institute of Epidemiology & Medical Biometry, Ulm, Germany. AD - German Center for Diabetes Research, Neuherberg, Germany. LA - eng GR - German Diabetes Center (DDZ)/Bundesministerium fur Gesundheit/ GR - Early career mentorship program (Tim Mori)/European Association for the Study of Diabetes/ GR - 82DZD14H03/Deutsches Zentrum fur Diabetesforschung/ GR - German Diabetes Center (DDZ)/Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen/ GR - 101095556/HORIZON EUROPE European Innovation Council/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260325 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Registries MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/administration & dosage MH - *Algorithms MH - Middle Aged MH - *Precision Medicine MH - Aged MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - Cohort Studies MH - Germany MH - Austria MH - *Atherosclerosis/prevention & control/epidemiology PMC - PMC13016828 COIS- JMG, RWH, OK, TM and SL report no conflicts of interest. JKM is a member of advisory boards of Abbott Diabetes Care, Becton-Dickinson, Biomea Fusion, Dexcom, Eli Lilly, Embecta, Insulet, Medtronic, myLife, Novo Nordisk A/S, Pharmasens, Roche Diabetes Care, Sanofi-Aventis, Tandem, Viatris and received speaker honoraria from A. Menarini Diagnostics, Abbott Diabetes Care, Dexcom, Eli Lilly, Medtrust, MSD, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Viatris and Ypsomed. She is a shareholder of decide Clinical Software GmbH and elyte Diagnostics and serves as CMO of elyte Diagnostics. J. S. reports honoraria for talks and/or consultancy and/or research funding from Abbott Diabetes Care, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, LifeScan, MedScape, MSD, Novartis, Novo Nordisk, Sanofi, and Ypsomed. EDAT- 2026/03/26 01:03 MHDA- 2026/03/26 01:04 PMCR- 2026/03/01 CRDT- 2026/03/25 19:33 PHST- 2026/03/26 01:04 [medline] PHST- 2026/03/26 01:03 [pubmed] PHST- 2026/03/25 19:33 [entrez] PHST- 2026/03/01 00:00 [pmc-release] AID - ECED-12-2025-0341-Diabetes-Art [pii] AID - 10.1055/a-2798-6496 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2026 Mar;134(3):79-87. doi: 10.1055/a-2798-6496. Epub 2026 Mar 25. PMID- 41880122 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20261009 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Mar 25 TI - GLP-1 Receptor Agonists and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes. LID - 42 [pii] LID - 10.1007/s11886-026-02356-6 [doi] AB - PURPOSE OF REVIEW: Whether body mass index (BMI) influences cardiovascular and kidney outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2 diabetes (T2DM) and to understand how metabolic phenotype may influence treatment response. RECENT FINDINGS: Across randomized trials, GLP-1 RAs consistently reduced cardiovascular events in diverse populations, with no statistically significant heterogeneity by BMI. Observational analyses suggest that individuals with overweight or obesity may experience greater absolute cardiovascular risk reduction, potentially reflecting improvements in visceral adiposity, inflammation, and insulin resistance. In contrast, renal benefits such as slower decline in kidney function, reduced albuminuria, and delayed kidney failure were uniform across BMI categories. This BMI-independent nephroprotection aligns with mechanisms involving natriuresis, reduced oxidative and inflammatory injury, and attenuation of fibrotic pathways. GLP-1 RAs provide clinically meaningful cardiovascular and kidney protection across the BMI spectrum. Cardiovascular benefits may be accentuated in individuals with elevated BMI, whereas renal benefits remain consistent regardless of adiposity. These findings support broad use of GLP-1 RAs for cardiorenal risk reduction and highlight the potential value of incorporating body-composition metrics beyond BMI in future treatment algorithms. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ramadurgum, Prerana AU - Ramadurgum P AD - Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 75505, USA. prerana.ramadurgum@gmail.com. FAU - Sharma, Kunal AU - Sharma K AD - Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 75505, USA. FAU - Pinon, Alec AU - Pinon A AD - Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 75505, USA. FAU - Kattamuri, Lakshmi AU - Kattamuri L AD - Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 75505, USA. FAU - Botros, Monica AU - Botros M AD - Department of Cardiovascular Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 75505, USA. LA - eng PT - Journal Article PT - Review DEP - 20260325 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Body Mass Index MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/complications MH - *Diabetic Nephropathies/prevention & control OTO - NOTNLM OT - Body mass index OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1 receptor agonists OT - Type 2 diabetes COIS- Declarations. Human and Animal Rights and Informed Consent: All studies with human or animal subjects are published and followed ethical standards. Competing interests: The authors declare no competing interests. EDAT- 2026/03/25 19:36 MHDA- 2026/03/25 19:37 CRDT- 2026/03/25 12:18 PHST- 2026/03/05 00:00 [received] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/03/25 19:37 [medline] PHST- 2026/03/25 19:36 [pubmed] PHST- 2026/03/25 12:18 [entrez] AID - 10.1007/s11886-026-02356-6 [pii] AID - 10.1007/s11886-026-02356-6 [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Mar 25;28(1):42. doi: 10.1007/s11886-026-02356-6. PMID- 41879791 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260918 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 11 IP - 5 DP - 2026 May 1 TI - Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes: A Post Hoc Secondary Analysis of the SOUL Randomized Clinical Trial. PG - 427-437 LID - 10.1001/jamacardio.2026.0245 [doi] AB - IMPORTANCE: Individuals with type 2 diabetes (T2D) are at high risk of atherosclerotic cardiovascular disease (ASCVD). In the SOUL randomized clinical trial, once-daily oral semaglutide reduced risk of major adverse cardiovascular (CV) events by 14% vs placebo in people with T2D and ASCVD and/or chronic kidney disease (CKD) receiving standard of care (SoC); however, whether oral semaglutide modifies recognized CV risk factors in the long term is unclear. OBJECTIVE: To investigate whether treatment with oral semaglutide was associated with changes in ASCVD risk factors vs placebo. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC. Participants underwent randomization from June 2019 to March 2021, with a mean (SD) of 47.5 (10.9) months of follow-up, and data were analyzed from February to December 2025. INTERVENTION(S): Participants were treated with either once-daily oral semaglutide (maximum dose, 14 mg) or placebo, in addition to standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was the association of oral semaglutide vs placebo with glycated hemoglobin (HbA1c), body weight, and blood pressure (BP) using estimated treatment differences (ETDs) and with high-sensitivity C-reactive protein (hsCRP) and lipid plasma levels using estimated treatment ratios (ETRs). RESULTS: Of 9650 randomized participants (mean [SD] age, 66.1 (7.6) years; 2790 female participants [28.9%]), 9495 participants (98.4%) completed the trial. Early (13 weeks) improvements in HbA1c (-0.87 percentage points), body weight (-2.54%), systolic BP (SBP, -3.84 mm Hg), pulse pressure (-3.81 mm Hg), hsCRP (-18.08%), total cholesterol (TC, -7.00%), non-high-density lipoprotein cholesterol (non-HDL-C, -8.02%), HDL-C (-4.49%), and triglycerides (-8.15%) were observed with oral semaglutide vs placebo and sustained over the trial duration. Body weight reductions were gradual across both groups. At week 156, in favor of oral semaglutide were ETDs for HbA1c (-0.47 percentage points; 95% CI, -0.52 to -0.42), body weight (-3.26 percentage points; 95% CI, -3.55 to -2.98), SBP (-1.83 mm Hg; 95% CI, -2.47 to -1.18), and pulse pressure (-2.17 mm Hg; 95% CI, -2.72 to -1.61) and ETRs for hsCRP (0.77; 95% CI, 0.74-0.81), TC (0.99; 95% CI, 0.98-1.00), non-HDL-C (0.98; 95% CI, 0.97-0.99), HDL-C (1.01; 95% CI, 1.01-1.02), and triglycerides (0.94; 95% CI, 0.93-0.96). No significant treatment differences were observed for low-density lipoprotein cholesterol or diastolic BP. CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with early and sustained improvements vs placebo in multiple ASCVD risk factors in high-risk participants with T2D and ASCVD and/or CKD, incremental to SoC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03914326. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London, United Kingdom. FAU - Deanfield, John E AU - Deanfield JE AD - Institute for Cardiovascular Sciences, University College London, London, United Kingdom. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle. FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mandavya, Kabirdev AU - Mandavya K AD - Novo Nordisk Service Centre India Pvt Ltd, Bangalore, India. FAU - Davicevic-Elez, Zaklina AU - Davicevic-Elez Z AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lorenzatti, Alberto AU - Lorenzatti A AD - Instituto Medico Docencia Asistencia Medica e Investigacion Clinica (DAMIC), Cordoba, Argentina. FAU - Oguz, Aytekin AU - Oguz A AD - Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkiye. FAU - Mankovsky, Boris AU - Mankovsky B AD - Institute of Gerontology, Kiev, Ukraine. FAU - Deerochanawong, Chaicharn AU - Deerochanawong C AD - Diabetes and Endocrinology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand. FAU - Gorgojo-Martinez, Juan J AU - Gorgojo-Martinez JJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Fundacion Alcorcon, Madrid, Spain. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology, Peking University People's Hospital, Beijing, China. FAU - Bain, Stephen C AU - Bain SC AD - School of Medicine, Swansea University, Swansea, United Kingdom. FAU - McGuire, Darren K AU - McGuire DK AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas. AD - Parkland Health System, Dallas, Texas. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM CIN - JAMA Cardiol. 2026 May 1;11(5):437-438. doi: 10.1001/jamacardio.2026.0261. PMID: 41879748 MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Heart Disease Risk Factors MH - Double-Blind Method MH - Aged MH - *Cardiovascular Diseases/prevention & control MH - Glycated Hemoglobin/metabolism MH - Blood Pressure PMC - PMC13019341 COIS- Conflict of Interest Disclosures: Dr Mulvagh reported personal fees from Novo Nordisk during the conduct of the study and personal fees from Merck outside the submitted work. Dr Inzucchi reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Corcept Therapeutics outside the submitted work. Dr Marx reported steering committee fees from Novo Nordisk during the conduct of the study and grants paid to university hospital from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk, and Sanofi-Aventis outside the submitted work. Dr Poulter reported speaker fees from Novo Nordisk, Servier, and Takeda; advisory board activities for AstraZeneca and Novo Nordisk; and research grants for his research group relating to type 2 diabetes from the British Heart Foundation, Diabetes UK, Julius Clinical, and the UK National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation program. Dr Deanfield reported receiving continuing medical education honoraria and/or consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; grants from Aegerion, Alzheimer's Research UK, the British Heart Foundation, Colgate, the Medical Research Council (UK), MSD, NIHR, Pfizer, Public Health England, and Roche; and advisory agreements with Caristo Diagnostics, eMed Healthcare, Floe Oral Care Ltd, Friede-Springer Cardiovascular Prevention Center, iOWNA, PMI Harm Reduction Group, and Smarter Cardiovascular Outcomes By Research And Education Ltd (SCORE) outside the submitted work. Dr Pop-Busui reported personal fees from Novo Nordisk during the conduct of the study; grants from Bayer, Lexicon Pharma, and Novo Nordisk; and personal fees from Averitas Pharma, Bayer, Biogen, Lexicon Pharma, Nevro, Roche Diagnostic, Vertex, and Viatris outside the submitted work. Dr Emerson reported steering committee fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Novartis, Roche, Sanofi, and Vertex outside the submitted work. Dr Mann reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Bayer, Icon, IQVIA, Sanofi, and WCG outside the submitted work. Drs Engelmann, Hovingh, and Davicevic-Elez and Mr Jeppesen reported being employees of and shareholders in Novo Nordisk A/S during the conduct of the study. Dr Lorenzatti reported grants from Amgen, Arrowhead, Ionis, MSD, and Novartis outside the submitted work. Dr Oguz reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Lilly, and Novo Nordisk outside the submitted work. Dr Mankovsky reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Sanofi, and Servier outside the submitted work. Dr Deerochanawong reported grants from Novo Nordisk during the conduct of the study and personal fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, and Roche outside the submitted work. Dr Gorgojo-Martinez reported research fees from Novo Nordisk during the conduct of the study; grants from Mundipharma; and personal fees from AstraZeneca, Boehringer Ingelheim, Menarini, and Novo Nordisk outside the submitted work. Dr Bain reported payments for clinical activity in the SOUL trial from Novo Nordisk during the conduct of the study. Dr McGuire reported executive committee fees from Novo Nordisk during the conduct of the study and personal fees from Alveus, Amgen, AstraZeneca, Boehringer Ingelheim, Kailera, Lexicon, Lilly, Metsera, Neurotronic, New Amsterdam, Novartis, Novo Nordisk, Regor, Roche Genentech, and Zealand outside the submitted work. Dr Buse reported grants from Novo Nordisk during the conduct of the study; personal fees from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, AstraZeneca, Aqua Medical, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand; grants from Corcept Therapeutics , Dexcom, GentiBio, and Novo Nordisk; and holding stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health outside the submitted work. No other disclosures were reported. EDAT- 2026/03/25 12:48 MHDA- 2026/05/13 12:32 PMCR- 2026/03/25 CRDT- 2026/03/25 11:33 PHST- 2026/05/13 12:32 [medline] PHST- 2026/03/25 12:48 [pubmed] PHST- 2026/03/25 11:33 [entrez] PHST- 2026/03/25 00:00 [pmc-release] AID - 2847041 [pii] AID - hoi260005 [pii] AID - 10.1001/jamacardio.2026.0245 [doi] PST - ppublish SO - JAMA Cardiol. 2026 May 1;11(5):427-437. doi: 10.1001/jamacardio.2026.0245. PMID- 41879623 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 1532-5520 (Electronic) IS - 0009-9201 (Linking) VI - 69 IP - 2 DP - 2026 Jun 1 TI - Type 2 Diabetes in Pregnancy: Management and Novel Therapies. PG - 203-209 LID - 10.1097/GRF.0000000000001008 [doi] AB - Type 2 diabetes mellitus (T2DM) is estimated to affect 2% of all pregnancies, and it is associated with numerous adverse perinatal outcomes. Glycemic monitoring and strict glycemic control are required to improve overall outcomes. Insulin is the mainstay of treatment, with limited data regarding newer medications like glucagon-like peptide 1 receptors agonists (GLP-1 RAs), dual incretin agonists like tirzepatide, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i). This chapter will provide a review of the current available literature regarding T2DM management in pregnancy. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Wilkie, Gianna AU - Wilkie G AUID- ORCID: 0000-0002-1712-0514 AD - Department of Obstetrics and Gynecology, UMass Chan School of Medicine, Worcester, Massachusetts. LA - eng PT - Journal Article PT - Review DEP - 20260325 PL - United States TA - Clin Obstet Gynecol JT - Clinical obstetrics and gynecology JID - 0070014 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9100L32L2N (Metformin) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Pregnancy MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Pregnancy in Diabetics/drug therapy MH - Insulin/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Metformin/therapeutic use MH - Tirzepatide OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonists OT - glycemic monitoring OT - insulin OT - metformin OT - perinatal outcomes OT - type 2 diabetes mellitus EDAT- 2026/03/25 12:48 MHDA- 2026/05/05 18:32 CRDT- 2026/03/25 10:14 PHST- 2026/05/05 18:32 [medline] PHST- 2026/03/25 12:48 [pubmed] PHST- 2026/03/25 10:14 [entrez] AID - 00003081-990000000-00272 [pii] AID - 10.1097/GRF.0000000000001008 [doi] PST - ppublish SO - Clin Obstet Gynecol. 2026 Jun 1;69(2):203-209. doi: 10.1097/GRF.0000000000001008. Epub 2026 Mar 25. PMID- 41877352 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Use of Oral Semaglutide and Associated Clinical Outcomes in Thai Patients With Type 2 Diabetes: Real-World Evidence From the REALISED Study. PG - 5058-5067 LID - 10.1111/dom.70701 [doi] AB - AIMS: The REALISED study assessed the clinical outcomes associated with oral semaglutide use in Thai patients with type 2 diabetes (T2D) in real-world clinical settings. MATERIALS AND METHODS: This retrospective, multi-centre cohort study included 195 patients with T2D initiating oral semaglutide between April 2022 and December 2023. Eligible participants had no prior injectable therapy and completed at least 26 weeks of treatment. The primary endpoint was the change in HbA1c from baseline to the end-of-study (EoS, Week 26); Week 52 outcomes were exploratory. Secondary endpoints included changes in body weight and the proportion achieving HbA1c < 7%. Severe hypoglycaemia was the safety endpoint. A post hoc composite endpoint combined HbA1c < 7% with >/= 3% weight loss. Analyses used a mixed model for repeated measures and descriptive statistics. RESULTS: Oral semaglutide was predominantly used as add-on therapy (190/195 [97.4%]). Mean HbA1c decreased by -0.7% (95% CI: -0.9 to -0.5; p < 0.0001), and the mean body weight decreased by -4.3 kg (95% CI: -5.5 to -3.2; p < 0.0001). At the EoS, 75.9% (117/154) achieved an HbA1c < 7%, and 57.7% (71/123) met the composite endpoint. No severe hypoglycaemia occurred. Dose escalation from 3 mg to 14 mg was observed in 53.2% by Week 26 and 70.4% by Week 52. CONCLUSIONS: The REALISED study provides the first real-world evidence of the use of oral semaglutide in Thai patients with T2D, demonstrating significant improvements in glycaemic control and weight reduction across routine care settings. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wannachalee, Taweesak AU - Wannachalee T AD - Division of Endocrinology and Metabolism, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - Anthanont, Pimjai AU - Anthanont P AD - Endocrinology and Metabolism Unit, Department of Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand. FAU - Sirisreetreerux, Supamas AU - Sirisreetreerux S AD - Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand. FAU - Nayak, Gurudutt AU - Nayak G AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Chumchujan, Woralak AU - Chumchujan W AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Iamsudjai, Yodying AU - Iamsudjai Y AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Buranapin, Supawan AU - Buranapin S AUID- ORCID: 0000-0003-2205-8900 AD - Section of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. LA - eng GR - Novo Nordisk/ GR - Chiang Mai University/ PT - Journal Article PT - Multicenter Study DEP - 20260324 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - Thailand/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Treatment Outcome MH - Aged MH - Hypoglycemia/chemically induced MH - Blood Glucose/drug effects MH - Weight Loss/drug effects PMC - PMC13146152 OTO - NOTNLM OT - GLP-1 OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes OT - weight control COIS- G.N., W.C., and Y.I. are employees of Novo Nordisk. S.B. received a research grant from Novo Nordisk. T.W. and P.A. declare no conflicts of interest. EDAT- 2026/03/25 07:09 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/25 01:03 PHST- 2026/03/04 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/12 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/25 07:09 [pubmed] PHST- 2026/03/25 01:03 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70701 [pii] AID - 10.1111/dom.70701 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5058-5067. doi: 10.1111/dom.70701. Epub 2026 Mar 24. PMID- 41876542 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260818 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Mar 24 TI - Bispecific GLP-1/GLP-2 agonism in advanced type 2 diabetes: preclinical characterization and a randomized, double-blind, placebo-controlled phase I trial. LID - 10.1038/s41467-026-71080-0 [doi] LID - 4477 AB - PG-102 is a potency-optimized bispecific Fc fusion protein targeting GLP-1 and GLP-2 receptors. In db/db mouse models of advanced diabetes characterized by uncontrolled hyperglycemia and catabolic weight loss, PG-102 achieved superior and sustained glycemic control compared with semaglutide or tirzepatide while preserving body weight, uncoupling glycemic control from catabolic weight loss. Mechanistic studies indicated that these effects were not driven by acute insulinotropic activity, but by beta-cell preservation and enhanced glucose uptake. These benefits required dual GLP-1R/GLP-2R engagement, as PG-102 outperformed monospecific Fc fusion agonists or their combination and promoted coordinated receptor trafficking with delayed internalization. We conducted a randomized, double-blind, placebo-controlled multiple ascending dose phase 1 study at a single center in the Republic of Korea in adults with overweight (BMI 25-30 kg/m(2)). Twenty-four participants were randomized within three weekly dose cohorts (15 mg, 30 mg, and 30/60 mg; n = 6 per cohort) in a 6:2 ratio to receive PG-102 (n = 18) or placebo (n = 6). All randomized participants (PG-102 n = 18; placebo n = 6) received at least one dose and were included in the safety analysis. Safety and tolerability were predefined as the primary endpoint and assessed by treatment-emergent adverse events (TEAEs). TEAEs occurred in 5/6 (83.3%) participants in each PG-102 cohort and 4/6 (66.7%) in placebo; treatment-related AEs occurred in 5/6 (83.3%) and 3/6 (50.0%), respectively. No serious adverse events or discontinuations due to adverse events occurred. Gastrointestinal events were mild to moderate. These findings support bispecific GLP-1/GLP-2 agonism as a mechanistically distinct incretin strategy in advanced T2D. ClinicalTrials.gov identifier: NCT06309667. CI - (c) 2026. The Author(s). FAU - Yang, Sang-In AU - Yang SI AUID- ORCID: 0000-0001-5225-6508 AD - ProGen Co. Ltd., Seoul, Republic of Korea. AD - SL BiGen Inc., Incheon, Republic of Korea. FAU - Kim, Sae Won AU - Kim SW AUID- ORCID: 0000-0003-0395-2026 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Son, Kyung-Hwa AU - Son KH AUID- ORCID: 0009-0006-4778-9610 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Lee, Seung-Ah AU - Lee SA AUID- ORCID: 0000-0002-9192-2849 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Kim, Jong-Gyun AU - Kim JG AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Roh, Jae-Il AU - Roh JI AD - ProGen Co. Ltd., Seoul, Republic of Korea. AD - SL BiGen Inc., Incheon, Republic of Korea. FAU - Sung, Young Chul AU - Sung YC AUID- ORCID: 0000-0003-2726-907X AD - SL BiGen Inc., Incheon, Republic of Korea. ycsung@postech.ac.kr. AD - Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. ycsung@postech.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT06309667 GR - RS-2024-00335179/Korea Drug Development Fund (KDDF)/ PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial DEP - 20260324 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 53AXN4NNHX (Semaglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide 2) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Double-Blind Method MH - Female MH - Male MH - Middle Aged MH - Semaglutide MH - Animals MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Tirzepatide MH - Blood Glucose/drug effects/metabolism MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 2/agonists MH - *Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Mice MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide-2 Receptor/metabolism MH - Aged PMC - PMC13187202 COIS- Competing interests: Y.C.S. and S.Y. are inventors on patents related to this work (PCT/KR2021/003127 & PCT/KR2021/003128). Y.C.S. is a current employee of SL BiGen, Inc. S.I. is a former employee of SL BiGen, Inc. and now a current employee of ProGen Co., Ltd. J.R. is a former employee of both SL BiGen, Inc. and ProGen Co., Ltd. S.W.K., K.S., S.L., and J.K. are current employees of ProGen Co., Ltd. EDAT- 2026/03/25 07:09 MHDA- 2026/05/20 06:31 PMCR- 2026/03/24 CRDT- 2026/03/25 00:17 PHST- 2025/05/13 00:00 [received] PHST- 2026/03/03 00:00 [accepted] PHST- 2026/05/20 06:31 [medline] PHST- 2026/03/25 07:09 [pubmed] PHST- 2026/03/25 00:17 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 10.1038/s41467-026-71080-0 [pii] AID - 71080 [pii] AID - 10.1038/s41467-026-71080-0 [doi] PST - epublish SO - Nat Commun. 2026 Mar 24;17(1):4477. doi: 10.1038/s41467-026-71080-0. PMID- 41875502 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 198 DP - 2026 May TI - Injectable thermosensitive hydrogel-based sustained delivery system for anti-diabetic peptides in type 2 diabetes mellitus therapy: A review. PG - 119249 LID - S0753-3322(26)00282-9 [pii] LID - 10.1016/j.biopha.2026.119249 [doi] AB - Injectable thermosensitive hydrogels have emerged as a promising class of biomaterials for the sustained delivery of drug. These smart systems undergo a sol-gel phase transition in response to physiological temperature, enabling minimally invasive injection and the formation of an in situ drug depot capable of controlled and sustained drug release. In recent years, thermosensitive hydrogels have drawn increasing attention in type 2 diabetes mellitus (T2DM) therapy, offering enhanced patient adherence, stable glycemic control, and reduced injection frequency compared with conventional formulations. Importantly, beyond glucose lowering, several hydrogel-based incretin therapies-particularly GLP-1 receptor agonists and dual GIP/GLP-1 agonists-have demonstrated clinically significant body-weight reduction and improved metabolic outcomes, addressing both hyperglycemia and obesity, two core components of T2DM pathophysiology. This review summarizes the classification, polymer composition, and drug release mechanisms of thermosensitive hydrogels. Special emphasis is placed on their use in the sustained delivery of insulin, GLP-1 receptor agonists and dual GIP/GLP-1 agonists. These hydrogel-based depots have demonstrated prolonged pharmacological efficacy, while preserving drug bioactivity, minimizing burst release, and achieving superior improvements in glycemic control and providing superior body-weight management with GLP-1 receptor agonists-loaded thermosensitive hydrogels, as compared with conventional injectable regimens. Finally, the challenges and future prospects of thermosensitive hydrogel systems are discussed, including the need for improved formulation stability, scalable manufacturing, and regulatory translation. With continued interdisciplinary advancements, injectable thermosensitive hydrogels hold strong potential as next-generation, long-acting, and patient-friendly delivery platforms for comprehensive diabetes management, encompassing both glycemic control and body-weight reduction in T2DM patients. CI - Copyright (c) 2026 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Vu, Lam Quoc AU - Vu LQ AD - School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Falcuty of Pharmacy, Thai Nguyen University of Medicine and Pharmacy, 284 Luong Ngoc Quyen Str., Thai Nguyen 250000, Viet Nam. Electronic address: vuquoclam@tump.edu.vn. FAU - Chiu, I-Hui AU - Chiu IH AD - School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: u113830006@kmu.edu.tw. FAU - Hoang, Cuong Thai Hoa AU - Hoang CTH AD - Falcuty of Pharmacy, Thai Nguyen University of Medicine and Pharmacy, 284 Luong Ngoc Quyen Str., Thai Nguyen 250000, Viet Nam. Electronic address: hoangthaihoacuong@tump.edu.vn. FAU - Bui, Nhung Thi Quynh AU - Bui NTQ AD - Falcuty of Pharmacy, Thai Nguyen University of Medicine and Pharmacy, 284 Luong Ngoc Quyen Str., Thai Nguyen 250000, Viet Nam. Electronic address: buithiquynhnhung@tump.edu.vn. FAU - Suhail, Muhammad AU - Suhail M AD - Institute of Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China. Electronic address: u108830004@kmu.edu.tw. FAU - Wu, Pao-Chu AU - Wu PC AD - School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Department of Pharmacy, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 81267, Taiwan. Electronic address: pachwu@kmu.edu.tw. LA - eng PT - Journal Article PT - Review DEP - 20260323 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Hypoglycemic Agents) RN - 0 (Delayed-Action Preparations) RN - 0 (Hydrogels) RN - 0 (Peptides) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/chemistry MH - Delayed-Action Preparations/administration & dosage MH - *Hydrogels/chemistry/administration & dosage MH - Animals MH - Injections MH - *Drug Delivery Systems/methods MH - *Peptides/administration & dosage MH - Temperature MH - Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Insulin/administration & dosage OTO - NOTNLM OT - Body-weight reduction OT - Glycemic control OT - Injectable thermosensitive hydrogel OT - Sustained release OT - Type 2 diabetes mellitus therapy COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/03/25 01:05 MHDA- 2026/05/04 06:32 CRDT- 2026/03/24 19:00 PHST- 2025/12/23 00:00 [received] PHST- 2026/03/01 00:00 [revised] PHST- 2026/03/16 00:00 [accepted] PHST- 2026/05/04 06:32 [medline] PHST- 2026/03/25 01:05 [pubmed] PHST- 2026/03/24 19:00 [entrez] AID - S0753-3322(26)00282-9 [pii] AID - 10.1016/j.biopha.2026.119249 [doi] PST - ppublish SO - Biomed Pharmacother. 2026 May;198:119249. doi: 10.1016/j.biopha.2026.119249. Epub 2026 Mar 23. PMID- 41874854 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 5 DP - 2026 May TI - Evidence-Based Positioning of Sodium-Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Receptor Agonists in the Management of Chronic Kidney Disease with Type 2 Diabetes and Overweight or Obesity: A Systematic Literature Review. PG - 1983-2000 LID - 10.1007/s12325-026-03559-7 [doi] AB - INTRODUCTION: Both sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have demonstrated kidney benefits in adults with chronic kidney disease (CKD) with type 2 diabetes (T2D) and overweight/obesity. However, questions remain regarding the optimal positioning, combination and sequencing of the two drug classes. This systematic literature review (SLR) identified evidence on comparisons, combinations or sequencing of SGLT2is and GLP-1 RAs in this population. METHODS: Databases were searched in May 2025. Relevant congresses between 2023 and 2025, SLR bibliographies and ClinicalTrials.gov were hand-searched. Articles were screened by two independent reviewers. Kidney and composite kidney outcomes were prioritised as the most clinically relevant for a population with CKD; additional safety, cardiovascular, HbA1c and weight endpoints were also extracted. RESULTS: Electronic databases identified 922 records, with an additional 117 records from hand searches. In total, 48 publications were included reporting on 38 unique studies; comprising 11 meta-analyses (MAs) and 27 primary publications. Findings from MAs consistently favoured SGLT2is over GLP-1 RAs for composite kidney outcomes. Primary research studies showed no clear direction of benefit for change in estimated glomerular filtration rate (eGFR) or albuminuria from baseline, or eGFR decline. However, progression of kidney disease, where reported, was consistently reduced with SGLT2is versus GLP-1 RAs. CONCLUSION: In the absence of head-to-head trials, the evidence identified supports the use of SGLT2is as a foundational therapy in adults with CKD and T2D, offering kidney protection, metabolic and cardiovascular benefits, with GLP-1 RAs positioned as a complementary adjunct. PROSPERO ID: CRD420251053598. CI - (c) 2026. The Author(s). FAU - Handelsman, Yehuda AU - Handelsman Y AD - Metabolic Institute of America, Los Angeles, CA, USA. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - University of Toronto, Toronto, Canada. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Kushner, Pam AU - Kushner P AD - University of California Irvine Medical Center, Orange, CA, USA. FAU - Bonnet, Fabrice AU - Bonnet F AD - University of Rennes, Rennes, France. FAU - Fioretto, Paola AU - Fioretto P AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. FAU - Kanumilli, Naresh AU - Kanumilli N AD - Northenden Group Practice, Wythenshawe, UK. FAU - Cos, Xavier AU - Cos X AD - IDIAP Jordi Gol, Institut Catala de la Salut, CIBERDEM, Barcelona, Spain. FAU - Frese, Thomas AU - Frese T AD - Institute of General Practice and Family Medicine, Interdisciplinary Center of Health Sciences, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle / Saale, Germany. FAU - Ji, Linong AU - Ji L AD - Peking University People's Hospital, Beijing, China. FAU - Murton, Molly AU - Murton M AD - Costello Medical, Cambridge, UK. FAU - Foulcer, Simon AU - Foulcer S AD - AstraZeneca, Cambridge, UK. FAU - Pentakota, Surendra AU - Pentakota S AD - AstraZeneca, Cambridge, UK. FAU - Rossing, Peter AU - Rossing P AD - University of Copenhagen, Copenhagen, Denmark. Peter.Rossing@RegionH.dk. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260324 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications MH - *Overweight/complications MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13156165 OTO - NOTNLM OT - Chronic kidney disease OT - Glucagon-like peptide 1 receptor agonist OT - Obesity OT - Sodium-glucose co-transporter 2 inhibitor OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Yehuda Handelsman: Received research grants, consultant & speaker honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Eli Lilly, Ionis, Merck, Novo Nordisk, Regeneron, Sanofi, Verdiva Bio; Alice Cheng: Received consulting and speaking honoraria from Abbott, Astellas, Aspen, AstraZeneca, Amgen, Bausch, Bayer, Biomea Fusion, Boehringer Ingelheim, Dexcom, Eisai, Eli Lilly, GSK, HLS Therapeutics, Insulet, Medtronic, Merck, MSD, Novo Nordisk, Pfizer, Sandoz, Sanofi, and Vertex; Gian Paolo Fadini: Received grants, honoraria or lecture fees from AstraZeneca, Boehringer, Eli Lilly, Guidotti, Mundipharma, Novartis, Novo Nordisk, Servier, and Sanofi; Pam Kushner: Received honoraria for consulting or advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and VERDIVA; Fabrice Bonnett: No competing interests; Paola Fioretti: Received fees as consultant and speaker for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Novo Nordisk; Takashi Kadowaki: Received research grants from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd.; receiving consulting fees from Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Novo Nordisk Pharma Ltd.; receiving honoraria for lectures from Nippon Boehringer Ingelheim Co., Ltd., Sumitomo Pharma Co., Ltd., Teijin Pharma Ltd., MSD Corporation, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co., Ltd. and Novo Nordisk Pharma Ltd.; Naresh Kanumilli: No competing interests; Xavier Cos: No competing interests; Thomas Frese: Received payments from Astra Zeneca and Boehringer Ingelheim; Linong Ji: No competing interests; Molly Murton: Employee of Costello Medical; Simon Foulcer: Employee of AstraZeneca and hold associated stock options; Surendra Pentakota: Employee of AstraZeneca and held associated stock options at time of project; Peter Rossing: Received consultancy and/or speaker fees (to his institution) from Abbott, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk and Roche; research grants from AstraZeneca, Bayer and Novo Nordisk; study drugs from AstraZeneca, Bayer Lexicon and Novo Nordisk. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2026/03/24 18:47 MHDA- 2026/05/08 12:38 PMCR- 2026/03/24 CRDT- 2026/03/24 12:21 PHST- 2025/12/18 00:00 [received] PHST- 2026/03/03 00:00 [accepted] PHST- 2026/05/08 12:38 [medline] PHST- 2026/03/24 18:47 [pubmed] PHST- 2026/03/24 12:21 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 10.1007/s12325-026-03559-7 [pii] AID - 3559 [pii] AID - 10.1007/s12325-026-03559-7 [doi] PST - ppublish SO - Adv Ther. 2026 May;43(5):1983-2000. doi: 10.1007/s12325-026-03559-7. Epub 2026 Mar 24. PMID- 41872986 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - GLP-1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta-Analysis of RCTs. PG - 5043-5057 LID - 10.1111/dom.70698 [doi] AB - AIM: This study used a network meta-analysis (NMA) as the primary approach to compare the efficacy and tolerability of GLP-1 receptor agonists and dual agonists in overweight or obese adults with and without Type 2 diabetes. MATERIALS AND METHODS: PubMed, Embase, Scopus, CENTRAL, and trial registries were searched through April 30, 2025. Randomized clinical trials (RCTs) of GLP-1 receptor agonists in adults with and without Type 2 diabetes were included. Data were extracted according to PRISMA 2020. Pairwise and using random-effects models were performed, with treatment rankings derived using SUCRA. Outcomes included >/= 5% and >/= 10% weight loss, weight change (absolute and percentage weight loss) at 24-52 weeks, and adverse events. RESULTS: A total of 127 RCTs (58 976) Participants; (39 520 with and 19 456 without T2DM) assessed seven GLP-1RAs. Compared to placebo, NMA indicated that tirzepatide, subcutaneous semaglutide (Semaglutide_SC), and oral semaglutide (Semaglutide_oral) increased >/= 5% weight loss (RR 7.17 [95% CI 4.38-11.73], 4.74 [3.17-7.08], 2.85 [1.78-4.58]) in T2DM. Only tirzepatide and Semaglutide_SC were effective (2.99 [1.20-7.44], 2.75 [1.14-6.61]) in non-T2DM. For >/= 10% loss, tirzepatide was most effective (14.34 [5.98-34.35]), followed by Semaglutide_oral (6.86 [2.63-17.90]) and Semaglutide_SC (6.12 [2.97-12.59]) in T2DM. In non-T2DM, Semaglutide_SC (10.72 [3.29-34.90]) and tirzepatide (4.70 [1.02-21.73]) were effective when compared to placebo. Mixed treatment effects (direct head to head and indirect comparisons) showed that tirzepatide reduced weight more than Semaglutide_oral (MD -6.75% [-8.34 to -5.17]) and Semaglutide_SC (-4.94% [-6.35 to -3.52]) in T2DM and was the only effective agent in non-T2DM (-16.48% [-21.70 to -11.27]) when compared to placebo. Higher doses enhanced weight loss; nausea/vomiting were more common with tirzepatide (RR 3.64 [2.40-5.52]). CONCLUSIONS: Tirzepatide and Semaglutide_SC are most effective for clinically meaningful weight loss. Optimal dosing and adherence remain essential in practice. TRAIL REGISTRATION: PROSPERO (CRD42024539634). CI - (c) 2026 John Wiley & Sons Ltd. FAU - Vienghirun, Jirawan AU - Vienghirun J AUID- ORCID: 0009-0003-3069-5747 AD - Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Sawangjit, Ratree AU - Sawangjit R AUID- ORCID: 0000-0002-6868-4336 AD - Clinical Trials and Evidence-Based Syntheses Research Unit (CTEBs RU), Mahasarakham University, Maha Sarakham, Thailand. AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Suttiruksa, Saithip AU - Suttiruksa S AD - Clinical Trials and Evidence-Based Syntheses Research Unit (CTEBs RU), Mahasarakham University, Maha Sarakham, Thailand. AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Chaiyakunapruk, Nathorn AU - Chaiyakunapruk N AUID- ORCID: 0000-0003-4572-8794 AD - College of Pharmacy, University of Utah, Salt Lake City, Utah, USA. FAU - Jinathongthai, Peerawat AU - Jinathongthai P AD - Pharmacy Practice Division, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand. AD - UPCOR: UBU Pharmacy Clinical Outcome Research Group, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Lee, Shaun Wen Huey AU - Lee SWH AUID- ORCID: 0000-0001-7361-6576 AD - School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia. LA - eng GR - Grant Number: 6811075/2568/Mahasarakham University/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260323 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Anti-Obesity Agents/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor/dual agonists (GLP-1RAs) OT - non-T2DM OT - obesity OT - semaglutide OT - tirzepatide OT - weight loss EDAT- 2026/03/24 07:41 MHDA- 2026/05/06 06:38 CRDT- 2026/03/24 01:06 PHST- 2026/03/07 00:00 [revised] PHST- 2025/09/25 00:00 [received] PHST- 2026/03/11 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/03/24 07:41 [pubmed] PHST- 2026/03/24 01:06 [entrez] AID - 10.1111/dom.70698 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5043-5057. doi: 10.1111/dom.70698. Epub 2026 Mar 23. PMID- 41870800 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1534-3170 (Electronic) IS - 1523-3782 (Print) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Mar 23 TI - Oral Glucagon-Like Peptide-1 Receptor Agonists for Preventing Cardiorenal Complications. LID - 10.1007/s11886-026-02357-5 [doi] LID - 38 AB - PURPOSE OF REVIEW: This article reviews the evidence for cardiovascular and renal risk reduction with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2 diabetes mellitus (T2DM), based on randomized controlled trials, including emerging oral agents. RECENT FINDINGS: Injectable GLP-1 RAs have consistently demonstrated reductions in major adverse cardiovascular events (MACE) and clinically relevant kidney outcomes, establishing their role in cardiorenal risk reduction. Oral semaglutide, the first approved oral GLP-1 RA, met criteria for cardiovascular non-inferiority in PIONEER 6 among patients with T2DM at high cardiovascular risk. The SOUL trial (oral semaglutide) subsequently demonstrated superiority for MACE reduction versus placebo in patients with established cardiovascular disease or multiple risk factors, with benefit driven largely by fewer nonfatal myocardial infarctions. However, oral semaglutide did not significantly reduce major kidney outcomes. Orforglipron, an investigational non-peptide oral GLP-1 RA with once-daily, food-independent dosing, has shown robust glycemic and weight-loss efficacy in phase 3 trials, though cardiovascular and renal outcome data are pending. Oral semaglutide has demonstrated cardiovascular benefit, but evidence supporting prevention of renal outcomes with oral GLP-1 RAs remains limited. Injectable GLP-1 RAs currently have the strongest evidence base for cardiorenal risk reduction, and ongoing outcome trials will clarify whether newer oral agents can close this gap. FAU - Odeleye, Victoria AU - Odeleye V AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Singh, Nikita AU - Singh N AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Gautam, Swotantra AU - Gautam S AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Shannon, Elizabeth AU - Shannon E AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Bibb, William Matthew AU - Bibb WM AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - McClure, Mary AU - McClure M AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Paul, Timir K AU - Paul TK AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. timirpaul@gmail.com. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. timirpaul@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260323 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Administration, Oral MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetic Nephropathies/prevention & control MH - Randomized Controlled Trials as Topic PMC - PMC13009101 OTO - NOTNLM OT - Cardiovascular outcomes OT - Oral GLP-1 receptor agonists OT - Oral semaglutide OT - Orforglipron OT - Renal outcomes OT - Type 2 diabetes mellitus COIS- Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing interests: The authors declare no competing interests. EDAT- 2026/03/23 19:54 MHDA- 2026/06/28 04:09 PMCR- 2026/03/23 CRDT- 2026/03/23 12:21 PHST- 2026/03/05 00:00 [received] PHST- 2026/03/06 00:00 [accepted] PHST- 2026/06/28 04:09 [medline] PHST- 2026/03/23 19:54 [pubmed] PHST- 2026/03/23 12:21 [entrez] PHST- 2026/03/23 00:00 [pmc-release] AID - 10.1007/s11886-026-02357-5 [pii] AID - 2357 [pii] AID - 10.1007/s11886-026-02357-5 [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Mar 23;28(1):38. doi: 10.1007/s11886-026-02357-5. PMID- 41870668 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20261009 IS - 1432-1068 (Electronic) IS - 1633-8065 (Linking) VI - 36 IP - 1 DP - 2026 Mar 23 TI - Association of GLP-1 receptor agonist use with outcomes after surgical fixation of femoral neck fracture in patients with type 2 diabetes: a propensity score-matched analysis. LID - 145 [pii] LID - 10.1007/s00590-026-04720-2 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve glycemic control and support weight management in type 2 diabetics, but their safety during the perioperative period in fracture surgery remains unclear. We hypothesized that preoperative use of GLP-1RA would not increase postoperative complications after surgical fixation of femoral neck fractures. METHODS: We conducted a retrospective propensity score-matched cohort study within an integrated United States health system. Adults with type 2 diabetes undergoing open reduction and internal fixation or closed reduction and percutaneous pinning for AO OTA 31B femoral neck fractures from 2016 to 2023 were included. Exposure was active GLP-1RA use at admission. Matching was 1:2 on age, sex, body mass index, smoking status, and Elixhauser Comorbidity Index. Primary outcomes were aspiration pneumonitis and composite medical complications at 30, 90, and 365 days. Secondary outcomes were implant failure, nonunion, malunion, revision surgery, and mortality. RESULTS: We matched 112 GLP-1RA users to 224 patients not using a GLP-1RA. Aspiration pneumonitis was not significantly different (1.8% vs. 2.2%, P = .790). There were no significant differences in length of stay (P = .256), time to surgery (P = .965), ACE (30/90/365-day P > .80), composite medical complications at 30, 90, or 365 days (all P >/= .363), or mortality/discharge to hospice through 365 days (P = .120). Revision surgery within 365 days occurred in 0% of GLP-1RA users vs. 4.5% in nonusers (P = .063). DISCUSSION: Preoperative GLP-1RA use was not associated with higher perioperative morbidity or mortality after femoral neck fracture fixation and may be linked to fewer reoperations. Larger multicenter studies are warranted. LEVEL OF EVIDENCE: III, retrospective cohort. FAU - Box, McKenna AU - Box M AD - Department of Orthopaedic Surgery, Medical City Denton, Denton, TX, USA. mckenna.box.med@gmail.com. FAU - Puga, Troy AU - Puga T AD - Department of Orthopaedic Surgery, Medical City Denton, Denton, TX, USA. troypugaorthopaedics@gmail.com. FAU - Poffenbarger, Mason AU - Poffenbarger M AD - Department of Orthopaedic Surgery, Medical City Denton, Denton, TX, USA. FAU - Liu, Yingxian AU - Liu Y AD - Physician Services Group Statistician, Graduate Medical Education, HCA Healthcare (United States), Brentwood, TN, USA. FAU - Riehl, John AU - Riehl J AD - Department of Orthopaedic Surgery, Medical City Denton, Denton, TX, USA. LA - eng PT - Journal Article DEP - 20260323 PL - France TA - Eur J Orthop Surg Traumatol JT - European journal of orthopaedic surgery & traumatology : orthopedie traumatologie JID - 9518037 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Femoral Neck Fractures/surgery/complications MH - Retrospective Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Propensity Score MH - *Postoperative Complications/epidemiology/etiology MH - *Fracture Fixation, Internal/adverse effects/methods MH - Middle Aged MH - Aged, 80 and over MH - Pneumonia, Aspiration/epidemiology/etiology MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Open Fracture Reduction OTO - NOTNLM OT - Aspiration pneumonitis OT - Femoral neck fracture OT - Glucagon-like peptide-1 receptor agonist OT - Hip fracture OT - Internal fixation OT - Perioperative complications OT - Revision surgery OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interests: JT Riehl or an immediate family member serves as a paid consultant to Arthrex Inc. and has received royalties from Arthrex Inc. None of the remaining authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article. This research was supported (in whole or in part) by HCA Healthcare and/ or an HCA Healthcare-affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any affiliated entities. EDAT- 2026/03/23 19:53 MHDA- 2026/06/28 13:04 CRDT- 2026/03/23 12:17 PHST- 2025/11/27 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/06/28 13:04 [medline] PHST- 2026/03/23 19:53 [pubmed] PHST- 2026/03/23 12:17 [entrez] AID - 10.1007/s00590-026-04720-2 [pii] AID - 10.1007/s00590-026-04720-2 [doi] PST - epublish SO - Eur J Orthop Surg Traumatol. 2026 Mar 23;36(1):145. doi: 10.1007/s00590-026-04720-2. PMID- 41864758 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260715 IS - 1878-3562 (Electronic) IS - 1590-8658 (Linking) VI - 58 IP - 5 DP - 2026 May TI - AISF practice guidance on pharmacological treatment of metabolic-dysfunction associated steatotic liver disease and steatohepatitis (MASLD/MASH): A 2026 Update. PG - 599-607 LID - S1590-8658(26)00292-6 [pii] LID - 10.1016/j.dld.2026.02.014 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly emerged as the leading cause of chronic liver disease worldwide, gradually replacing viral hepatitis in clinical and epidemiological relevance. Italian data mirror global trends, with prevalence escalating in general and high-risk populations, particularly among individuals with type 2 diabetes (T2D), obesity, and metabolic syndrome (MetS). Disease progression from steatosis to steatohepatitis (MASH) and advanced fibrosis markedly increases the risk of cirrhosis, hepatocellular carcinoma (HCC), and cardiovascular mortality. Recent regulatory frameworks from FDA and EMA have accelerated therapeutic development, with Resmetirom and Semaglutide representing the first agents to achieve histological efficacy in Phase 3 trials for patients with MASH and F2-F3 fibrosis. Building upon these advances, the AISF STEPS-MASH framework provides a structured approach for the identification, selection, and monitoring of patients eligible for therapy. This position paper outlines evidence-based recommendations for the integration of emerging pharmacological strategies into clinical practice in Italy, emphasizing both high-risk and broader metabolic populations. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. CN - Associazione Italiana per lo Studio del Fegato (AISF) LA - eng PT - Journal Article PT - Review DEP - 20260320 PL - Netherlands TA - Dig Liver Dis JT - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JID - 100958385 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 2J3H5C81A5 (elifibranor) RN - 0 (Propionates) RN - 0 (Chalcones) SB - IM MH - Humans MH - Semaglutide MH - *Metabolic Syndrome/complications MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - *Fatty Liver/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Disease Progression MH - Italy MH - Hypoglycemic Agents/therapeutic use MH - Practice Guidelines as Topic MH - Obesity/complications MH - Propionates MH - Chalcones OTO - NOTNLM OT - Metabolic-dysfunction associated steatohepatitis (MASH) OT - Metabolic-dysfunction associated steatotic liver disease (MASLD) OT - Resmetirom OT - Semaglutide OT - Steatosis OT - Tirzepatide COIS- Declaration of competing interest AAg: speaking and/or advisory board for Gilead, Ipsen, BMS, Novo Nordisk, Madrigal, AbbVie. AAr: speaking for Novonordisk, Sanofi, Echosense. EB: speaking and/or advisory board for AstraZeneca, Boheringer, Eli Lilly, Inventiva, MSD, Novo Nordisk. GC: speaking and/or advisory board for Eisai, Ipsen, AstraZeneca, MSD, Roche, Gilead. MC: consultant/speaker bureau for Advanz, Alentis, Albireo, Alfasigma, Amgen, Calliditas, Echosense, Genetic spa, GSK, Ipsen, Intercept, Kowa, Mayloly, Mirun, Perspectum, Zydus; scientific board advisor for Advanz/Intercept, Falk, Gilead, GSK, Ipsen, Kowa, Mirum, Cymabay, Moderna. RD: speaking, teaching and advisory board for Gilead Science and AbbVie; consultant and advisory board for Madrigal. AD speaking and/or advisory board for Astrazeneca, Eisai, MSD, Novonordisk and Roche. SDC: speaking and/or advisory board for AbbVie, Alfasigma. AG: consultant and advisory borad for for Roche, Ipsen, Novonordisk, MSD, BMS, AstraZeneca, Alfasigma, Actial, Wellmicro. GG: speaking, consulting fee fees and/or travel fees for Chiesi, Alfasigma, Ipsen, Biotest, Novartis. SG: speaking and/or advisory board for Gilead. MI: consultant for Roche, Roche Diagnostic, Eisai, MSD, AstraZeneca; speaking for Roche, AstraZeneca, Ipsen, Eisai, MSD, Gilead; Travel fees from Roche; research funding by Gilead, Astrazeneca, Roche Diagnostic. FM: consultant and/or speaking and/or advisory board and/or travel grant for Aofasigma, AstraZeneca, Biomarin, Boehringer Ingelheim, Gilead, Gore, Ipsen, Madrigal, MSD/Eisai, Novo Nordisk, Roche. GM: speaking for MSD-Eisai, Chiesi, Kedrion, Ipsen, Alfasigma. MM: speaking and/or advisory board for Gilead, Ipsen, Novo Nordisk, Alfasigma, AbbVie, Mirum. LM: speaking and advisory board for Alexion, Boheringer-Ingelheim, Echosens, GSK, Madrigal, MSD, Mirum, Novonordisk, Reslis Pharma, Siemens Healthineers. GP: speaking and/or advisory board and/or consultant for Novo Nordisk, Echosense, Advanz Pharma, Madrigal. SP: speaking and/or advisory board for Boeringher, Echosens, Madrigal, Novonordisk, Resalis. FRP: speaking and/or consultant and/or travel grant from AstraZeneca, Ipsen, Roche, AbbVie, Gilead, Alfasigma, Mirum. FR: research support by Boheringer Ingelheim, Ely Lilly; travel grant by Novo Nordisk; speaking for Novo Nordisk, Eli Lilly, Echosense. FPR: speaking, travel grant and advisory board for Gilead, Biotest, Grifols, AbbVie, GSK, Novonordisk. FT: consultant for Astrazeneca, Roche, Eisai, BMS, Ipsen; LV: speaking for Viatris, Novo Nordisk, GSK; consulting for Novo Nordisk, Pfizer, Boehringer Ingelheim, Resalis, GSK, Almac, AIRNA; travelling by Novo Nordisk. UVG: speaking and/or advisory board and/or funding for research by Advanz, Gilead, Ipsen, Mirum, Novo Nordisk, Madrigal, Astra Zeneca. MV: speaking and teaching for Gilead, Ipse, AbbVie, Novo Nordisk, Eli Lilly, Kedrion. FIR - Aghemo, Alessio IR - Aghemo A IRAD- Department of Biochemical Science, Humanitas University, Rozzano (MI), Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy. FIR - Armandi, Angelo IR - Armandi A IRAD- Department of Medical Sciences, Department of Gastroenterology, A.O.U. Citta della Salute e della Scienza di Torino, University of Turin, Milan, Italy. FIR - Bugianesi, Elisabetta IR - Bugianesi E IRAD- Department of Medical Sciences, Department of Gastroenterology, A.O.U. Citta della Salute e della Scienza di Torino, University of Turin, Milan, Italy. FIR - Cabibbo, Giuseppe IR - Cabibbo G IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Carbone, Marco IR - Carbone M IRAD- Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. FIR - D'Ambrosio, Roberta IR - D'Ambrosio R IRAD- Gastroenterology and Hepatology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy. FIR - Dalbeni, Andrea IR - Dalbeni A IRAD- General Medicina C - Unit and Liver Unit - Department of Medicine. AOUI Verona, University of Verona, Verona, Italy. FIR - Di Cola, Simone IR - Di Cola S IRAD- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. FIR - Gasbarrini, Antonio IR - Gasbarrini A IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Germani, Giacomo IR - Germani G IRAD- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale, Universita di Padova, Padua, Italy. FIR - Gitto, Stefano IR - Gitto S IRAD- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. FIR - Iavarone, Massimo IR - Iavarone M IRAD- Gastroenterology and Hepatology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A.M. e A. Migliavacca Center for Liver Disease", Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FIR - Marra, Fabio IR - Marra F IRAD- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. FIR - Masarone, Mario IR - Masarone M IRAD- Internal Medicine and Hepatology, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy. FIR - Marrone, Giuseppe IR - Marrone G IRAD- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Miele, Luca IR - Miele L IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Pennisi, Grazia IR - Pennisi G IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Petta, Salvatore IR - Petta S IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Ponziani, Francesca Romana IR - Ponziani FR IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Ravaioli, Federico IR - Ravaioli F IRAD- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, University of Bologna, Bologna, Italy. FIR - Russo, Francesco Paolo IR - Russo FP IRAD- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale, Universita di Padova, Padua, Italy. FIR - Tovoli, Francesco IR - Tovoli F IRAD- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, University of Bologna, Bologna, Italy. FIR - Valenti, Luca IR - Valenti L IRAD- Precision Medicine Lab, Biological Resource Center and Trasfusion Medicine, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FIR - Vespasiani-Gentilucci, Umberto IR - Vespasiani-Gentilucci U IRAD- Research Unit of Clinical Medicine and Hepatology, Universita Campus Bio-medico di Roma, Rome, Italy. FIR - Vigano, Mauro IR - Vigano M IRAD- Gastroenterology, Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo, Italy. EDAT- 2026/03/22 06:07 MHDA- 2026/04/19 17:46 CRDT- 2026/03/21 22:52 PHST- 2025/12/07 00:00 [received] PHST- 2026/02/11 00:00 [revised] PHST- 2026/02/15 00:00 [accepted] PHST- 2026/04/19 17:46 [medline] PHST- 2026/03/22 06:07 [pubmed] PHST- 2026/03/21 22:52 [entrez] AID - S1590-8658(26)00292-6 [pii] AID - 10.1016/j.dld.2026.02.014 [doi] PST - ppublish SO - Dig Liver Dis. 2026 May;58(5):599-607. doi: 10.1016/j.dld.2026.02.014. Epub 2026 Mar 20. PMID- 41862354 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260730 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 48 IP - 4 DP - 2026 Apr TI - Effect of Glucagon-Like-Peptide-1 Receptor Agonists (GLP-1 RA) on Neuropsychiatric Outcomes: A Systematic Review and Meta-Analysis. PG - 347-384 LID - S0149-2918(26)00044-5 [pii] LID - 10.1016/j.clinthera.2026.02.010 [doi] AB - PURPOSE: Type 2 diabetes mellitus (T2D) is associated with an increased burden of neuropsychiatric disorders, including cognitive decline, affective disorders, and substance use disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control and weight reduction, have been hypothesized to confer neuroprotective and psychotropic benefits via central and peripheral mechanisms. However, evidence across individual studies remains inconsistent. METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD420251025534) of randomized controlled trials (RCTs) and observational studies assessing the effect of GLP-1 RAs on neuropsychiatric outcomes. Searches were performed in MEDLINE, SCOPUS, CENTRAL, and Web of Science up to 30(th) October 2025. Eligible comparators included placebo, standard care, or alternative glucose-lowering agents. Data were synthesized using random-effects models, and risk of bias was assessed using RoB2 and ROBINS-I. Evidence certainty was graded using GRADE methodology. FINDINGS: From 10,037 records, 82 studies were included. GLP-1 RAs were associated with a reduced risk of idiopathic Parkinson's disease (PD) (pooled HR 0.70, 95% CI: 0.53-0.92, I(2) = 38%) but no improvements in motor symptoms in established PD (MDS-UPDRS Part III off-medication: mean difference -3.29, 95% CI: -7.84, 1.26, I(2) = 80%). No consistent improvements in non-motor symptoms, quality of life, or dyskinesia scores were seen. GLP-1 RAs were associated with a reduced risk of cannabis use disorder (pooled HR 0.55, 95% CI: 0.39-0.77, I(2) = 71%) but showed no significant effect on opioid use disorder (pooled HR 0.61, 95% CI: 0.24-1.52, I(2) = 91%). Liraglutide reduced binge frequency in binge eating disorder (mean difference -1.28, 95% CI: -1.67, -0.89, I(2) = 53%) compared to placebo. In observational studies versus non-user controls, GLP-1 RA use was associated with a lower reported risk of suicidality (pooled OR 0.34, 95% CI: 0.18-0.63, I(2) = 99%), but no such association was seen with Semaglutide alone (pooled OR 0.71, 95% CI: 0.29-1.73, I(2) = 99%), active-comparator studies (pooled HR 0.96, 95% CI: 0.81-1.15, I(2)=0%) or RCTs (pooled RR 1.13, 95% CI: 0.53-2.41, I(2)=0%). No associations were observed for depression or anxiety. For dementia, findings were mixed: no benefit versus SGLT2 inhibitors (pooled RR 1.07, 95% CI: 0.73-1.56, I(2) = 78%), but there was a reduced risk of Alzheimer's disease when compared to unmatched or non-exposed controls (pooled RR 0.37, 95% CI: 0.14-0.96, I(2) = 98%). Certainty of evidence ranged from moderate to very low. IMPLICATIONS: Current evidence, largely of low to very low certainty, suggests potential selective neuropsychiatric associations of GLP-1 RAs, particularly in Parkinson's disease risk reduction and binge eating disorder. Benefits for dementia risk reduction were observed primarily in comparisons with non-exposed or DPP4i, whereas no advantage was seen versus other active comparators, such as SGLT2 inhibitors. Our findings should be interpreted as hypothesis-generating due to significant heterogeneity and wide confidence intervals, indicating imprecision. Longer-term studies with neuropsychiatric outcomes as the primary endpoint are required. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Choudhury, Ishraq AU - Choudhury I AD - Salford Royal Hospital, Northern Care Alliance, Salford, UK. FAU - Ward, John Headly AU - Ward JH AD - Department of Psychiatry, University of Cambridge, Cambridge, UK. FAU - Mahesh, Sahana AU - Mahesh S AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK. FAU - Azmi, Shazli AU - Azmi S AD - Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. FAU - Anson, Matthew AU - Anson M AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Electronic address: manson1@liverpool.ac.uk. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260319 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Mental Disorders/prevention & control MH - Randomized Controlled Trials as Topic MH - Parkinson Disease/prevention & control OTO - NOTNLM OT - Addiction OT - GLP-1 OT - Glucagon-like-peptide-1 OT - Neurology OT - Psychiatiry OT - Type 2 diabetes COIS- Declaration of competing interest MA receives a fellowship from the Novo Nordisk UK research foundation and Breakthrough T1D. UA has received honoraria from Eli Lilly, Theras, Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Sanofi and Diiachi Sankyo. UA has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. EDAT- 2026/03/21 00:34 MHDA- 2026/04/21 17:43 CRDT- 2026/03/20 22:54 PHST- 2025/12/06 00:00 [received] PHST- 2026/02/10 00:00 [revised] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/04/21 17:43 [medline] PHST- 2026/03/21 00:34 [pubmed] PHST- 2026/03/20 22:54 [entrez] AID - S0149-2918(26)00044-5 [pii] AID - 10.1016/j.clinthera.2026.02.010 [doi] PST - ppublish SO - Clin Ther. 2026 Apr;48(4):347-384. doi: 10.1016/j.clinthera.2026.02.010. Epub 2026 Mar 19. PMID- 41862258 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260711 IS - 2215-0374 (Electronic) IS - 2215-0366 (Linking) VI - 13 IP - 4 DP - 2026 Apr TI - Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study. PG - 327-335 LID - S2215-0366(26)00014-3 [pii] LID - 10.1016/S2215-0366(26)00014-3 [doi] AB - BACKGROUND: People with diabetes have an elevated risk of developing depression, anxiety, and suicide. GLP-1 receptor agonists are licensed to treat diabetes and obesity, but data on whether these medications alleviate or exacerbate anxiety, depression, and self-harm are mixed. We studied the risk of worsening mental illness in people already diagnosed with depression, anxiety, or both who were prescribed antidiabetic medications including GLP-1 receptor agonists. METHODS: The study cohort, identified from national Swedish electronic health registers, included people with a diagnosis of depression or anxiety disorder who used any antidiabetic medication between the years 2009 and 2022. GLP-1 receptor agonists, individually and as a group, were compared with non-use of GLP-1 receptor agonists and directly with other second-line antidiabetic medications. A within-individual design was used for all comparisons to reduce confounding, comparing periods of use versus periods of non-use of a medication in the same individual. The primary outcome was worsening of mental illness, defined as a composite of psychiatric hospitalisation; sick leave from work for more than 14 days for psychiatric reasons; hospitalisation due to self-harm; or death by suicide. Secondary outcomes were worsening of depression or anxiety, analysed separately, worsening of substance use disorder, and self-harm. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% CIs were used. A person with related lived experience was involved in the design and write-up of this study. FINDINGS: The cohort included 95 490 people (56 976 [59.7%] female and 38 514 [40.3%] male) with a mean age of 50.6 years (SD 12.3). Ethnicity data were not available. GLP-1 receptor agonists were used by 22 480 individuals during the follow-up period. Compared with non-use of GLP-1 receptor agonists, semaglutide (aHR 0.58 [95% CI 0.51-0.65]) and liraglutide (0.82 [0.76-0.89]) were associated with lower risk of worsening mental illness, whereas exenatide (1.01 [0.69-1.46]) and dulaglutide (1.01 [0.85-1.20]) were not. Semaglutide was associated with a decreased risk of worsening depression (0.56 [0.44-0.71]), of worsening anxiety (0.62 [0.52-0.73]), and of worsening substance use disorder (0.53 [0.35-0.80]). Liraglutide was associated only with lower risk of worsening depression (0.74 [0.64-0.87]). GLP-1 receptor agonists as a group were associated with a reduced risk of self-harm (0.56 [0.34-0.92]). INTERPRETATION: For anxiety and depression that co-occur with diabetes and obesity, semaglutide and, to a lesser extent, liraglutide might be useful dually effective therapeutic options. Randomised controlled trials evaluating these findings are warranted. FUNDING: Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, and Finnish Ministry of Social Affairs and Health. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Taipale, Heidi AU - Taipale H AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; School of Pharmacy, University of Eastern Finland, Kuopio, Finland. FAU - Taylor, Mark AU - Taylor M AD - School of Medicine and Dentistry, Griffith University, Gold Coast, QLD Australia; The Edinburgh Practice, Edinburgh, UK. Electronic address: andrewmarktaylor55@gmail.com. FAU - Lahteenvuo, Markku AU - Lahteenvuo M AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. FAU - Mittendorfer-Rutz, Ellenor AU - Mittendorfer-Rutz E AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tanskanen, Antti AU - Tanskanen A AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tiihonen, Jari AU - Tiihonen J AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. LA - eng PT - Journal Article PL - England TA - Lancet Psychiatry JT - The lancet. Psychiatry JID - 101638123 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Sweden/epidemiology MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Cohort Studies MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - *Anxiety Disorders/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hospitalization/statistics & numerical data MH - *Depression/epidemiology MH - Registries MH - *Depressive Disorder/epidemiology COIS- Declaration of interests HT, EM-R, and JT have participated in research projects funded by grants from Janssen to their employing institution. HT reports personal fees from Gedeon Richter, Janssen, Lundbeck and Otsuka; and has been a consultant or advisor to or has received honoraria from Healthcare Global Village, HLS Therapeutics, Janssen-Cilag, Lundbeck, Orion, Otsuka, Teva, and WebMD Global. ML has received honoraria from Lundbeck, Otsuka Pharma, Janssen, Johnson & Johnson, Orion Pharma, and Recordati. MT declares no competing interests. EDAT- 2026/03/21 00:34 MHDA- 2026/03/21 00:35 CRDT- 2026/03/20 21:56 PHST- 2025/10/06 00:00 [received] PHST- 2026/01/07 00:00 [revised] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/03/21 00:35 [medline] PHST- 2026/03/21 00:34 [pubmed] PHST- 2026/03/20 21:56 [entrez] AID - S2215-0366(26)00014-3 [pii] AID - 10.1016/S2215-0366(26)00014-3 [doi] PST - ppublish SO - Lancet Psychiatry. 2026 Apr;13(4):327-335. doi: 10.1016/S2215-0366(26)00014-3. PMID- 41861108 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2026 IP - 1 DP - 2026 TI - Safety Assessment of Glucagon-Like Peptide 1 Receptor Agonists Based on the FAERS Database: Focus on Tumorigenic Risk in Subpopulations. PG - e8893769 LID - 10.1155/jdr/8893769 [doi] LID - 8893769 AB - GLP-1 receptor agonists (GLP-1RAs) are extensively used in treating Type 2 diabetes due to their therapeutic benefits. However, clinical reports have highlighted adverse events, particularly the underexplored association with tumor development. This study investigates GLP-1RA-related adverse events, focusing on tumorigenic risks, using data from the FDA Adverse Event Reporting System (FAERS). FAERS data from Q1 2005 to Q4 2023 were analyzed using the proportional reporting ratio (PRR) method to identify GLP-1RA-associated adverse events. Detailed analyses examined event distribution across genders, ages, and body weights, with an emphasis on tumor-related risks in vulnerable subpopulations. A total of 195,250 GLP-1RA-related adverse event reports were identified, spanning 25 system organ classes (SOCs). The most reported SOCs were gastrointestinal disorders (n = 110,451, PRR 2.44), investigative findings (n = 80,126, PRR 2.46), and metabolism and nutrition disorders (n = 25,236, PRR 2.21). Notably, 7457 cases involved benign, malignant, and unspecified tumors (PRR 0.5). Further analysis revealed that the risk of GLP-1RA-associated tumorigenesis varied by age, sex, and weight, suggesting that tumorigenesis risk differed in specific subpopulations. These findings underscore the need for vigilance regarding GLP-1RA-related adverse events, particularly tumor risks in specific subgroups. Clinicians should consider patient-specific factors, such as age, gender, and body weight, to ensure safe and effective GLP-1RAs therapy. CI - Copyright (c) 2026 Zhenhan Li et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Li, Zhenhan AU - Li Z AUID- ORCID: 0000-0002-1989-0539 AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Huang, Jun AU - Huang J AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Zhou, Sha AU - Zhou S AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Luan, Yongan AU - Luan Y AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Xie, Huang AU - Xie H AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, China, cqmu.edu.cn. FAU - Chen, Zhongpei AU - Chen Z AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Xu, Juan AU - Xu J AUID- ORCID: 0000-0001-9347-0375 AD - Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Qian, Jun AU - Qian J AUID- ORCID: 0000-0002-0020-0286 AD - Department of Cardiology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China, tongji.edu.cn. LA - eng GR - CSTB2025TIAD-KPX0096/Key Project of Chongqing Municipal Technological Innovation and Application Development Special Fund/ GR - YXQN202441/Chongqing Medical Youth Top Talent Project/ GR - 2023QNXM002/Chongqing Municipal Science and Health Joint Medical Research Project/ GR - 4th Young Talent Project of Chongqing Traditional Chinese Medicine Hospital/ GR - ITJ(QN)2203/Clinical Research Project of Tongji Hospital of Tongji University/ GR - CQBX202212/Chongqing Postdoctoral Innovative Talents Support Program Fund/ PT - Journal Article PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Middle Aged MH - United States/epidemiology MH - Adult MH - Databases, Factual MH - *Neoplasms/chemically induced/epidemiology MH - Aged MH - Risk Assessment MH - Adolescent MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor MH - Young Adult MH - *Carcinogenesis/drug effects MH - United States Food and Drug Administration MH - Child PMC - PMC13140801 OTO - NOTNLM OT - FAERS OT - adverse drug events OT - glucagon-like peptide 1 receptor agonists OT - real-world data analysis OT - tumor-related risks COIS- The authors declare no conflicts of interest. EDAT- 2026/03/20 18:37 MHDA- 2026/03/20 18:38 PMCR- 2026/03/20 CRDT- 2026/03/20 14:53 PHST- 2025/11/21 00:00 [revised] PHST- 2024/12/19 00:00 [received] PHST- 2025/12/19 00:00 [accepted] PHST- 2026/03/20 18:38 [medline] PHST- 2026/03/20 18:37 [pubmed] PHST- 2026/03/20 14:53 [entrez] PHST- 2026/03/20 00:00 [pmc-release] AID - JDR8893769 [pii] AID - 10.1155/jdr/8893769 [doi] PST - ppublish SO - J Diabetes Res. 2026;2026(1):e8893769. doi: 10.1155/jdr/8893769. PMID- 41857480 OWN - NLM STAT- MEDLINE DCOM- 20260619 LR - 20260813 IS - 1728-7731 (Electronic) IS - 1726-4901 (Print) IS - 1726-4901 (Linking) VI - 89 IP - 6 DP - 2026 Jun 1 TI - Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and clinical recommendations. PG - 407-414 LID - 10.1097/JCMA.0000000000001370 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-central to type 2 diabetes mellitus (T2DM) management owing to their comprehensive benefits (glycemic control, weight reduction, cardiovascular benefits, and renal protection)-exhibit a concerning ocular safety profile. Clinical trial data, notably from SUSTAIN-6, revealed a higher incidence of diabetic retinopathy (DR) complications with semaglutide, particularly in patients with preexisting DR and rapid HbA1c reduction, reflecting early worsening. Conversely, the REWIND and LEADER trials reported no significant increase in DR risk, suggesting variability among agents and the potential influence of glycemic trajectory. Observational studies and meta-analyses provide mixed findings: some suggest increased DR progression risk in vulnerable populations, while others indicate a lower risk than insulin therapy. Beyond DR, recent pharmacoepidemiologic studies and pharmacovigilance reports have implicated GLP-1 RAs-especially semaglutide-in nonarteritic anterior ischemic optic neuropathy (NAION), leading the European Medicines Agency to classify NAION as a very rare adverse effect and prompting regulatory scrutiny. Conversely, real-world data suggest possible protective associations with other retinal disorders, including reduced incidence of neovascular age-related macular degeneration and diabetic macular edema, although findings remain inconsistent. The mechanistic pathways involve rapid metabolic shifts, vascular dysregulation, and potentially direct effects on retinal or optic nerve tissue. While GLP-1 RAs confer substantial systemic benefits, their ocular risks appear concentrated in high-risk subgroups. Individualized prescribing, baseline ophthalmic assessment, and interdisciplinary monitoring are essential until ongoing prospective trials clarify their long-term ocular impact. CI - Copyright (c) 2026, the Chinese Medical Association. FAU - Wu, Tzu-En AU - Wu TE AD - Department of Ophthalmology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. FAU - Chen, Harn-Shen AU - Chen HS AUID- ORCID: 0000-0001-8748-229 AD - Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Review DEP - 20260317 PL - Netherlands TA - J Chin Med Assoc JT - Journal of the Chinese Medical Association : JCMA JID - 101174817 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Retinopathy/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - *Semaglutide/adverse effects PMC - PMC13286313 OTO - NOTNLM OT - Diabetic retinopathy OT - Glucagon-like peptide-1 receptor agonists OT - Neovascular age-related macular degeneration OT - Nonarteritic anterior ischemic optic neuropathy COIS- Conflicts of interest: Dr. Harn-Shen Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. EDAT- 2026/03/20 07:10 MHDA- 2026/06/19 12:36 PMCR- 2026/03/17 CRDT- 2026/03/20 00:30 PHST- 2026/06/19 12:36 [medline] PHST- 2026/03/20 07:10 [pubmed] PHST- 2026/03/20 00:30 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - 02118582-990000000-00641 [pii] AID - JCMA-D-25-00577 [pii] AID - 10.1097/JCMA.0000000000001370 [doi] PST - ppublish SO - J Chin Med Assoc. 2026 Jun 1;89(6):407-414. doi: 10.1097/JCMA.0000000000001370. Epub 2026 Mar 17. PMID- 41855048 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 3 DP - 2026 Sep TI - A review of survodutide: a new dual acting agonist. PG - 306-321 LID - 10.23736/S2724-6507.26.04406-4 [doi] AB - Survodutide represents an innovative approach to obesity management and metabolic-associated fatty liver disease (MAFLD). These conditions, often closely linked with type 2 diabetes (T2DM) and cardiovascular diseases, demand effective treatment strategies. Survodutide acts by targeting both GLP-1 and glucagon receptors. This new dual agonist offers potential transformative benefits, with early clinical trials showcasing significant weight loss and improvements in metabolic markers. Survodutide's mechanism of action includes appetite regulation, enhanced glucose metabolism, and increased energy expenditure, making it a promising option for those struggling with obesity and related health issues. This review assesses Survodutide's pharmacology, efficacy, and safety in MASH and obesity, while also outlining its broader metabolic and cardiovascular benefits. It compares Survodutide's dual-agonist mechanism and clinical performance with single-target incretin therapies to clarify its potential role in the evolving treatment landscape. While the initial results are promising, the review emphasizes the importance of continued research to fully understand Survodutide's long-term safety and effectiveness. Ongoing trials will provide critical insights into its overall impact, side effects, patient response, and cost considerations. This article highlights Survodutide's potential in the treatment of obesity and metabolic disordersand evaluates its place in therapy for seeking improved outcomes. FAU - Yathindra, Meenakshi R AU - Yathindra MR AD - Department of Internal Medicine, Kasturba Medical College, Mangalore, India. FAU - Bhattacharjee, Ayush AU - Bhattacharjee A AD - Department of Internal Medicine, Vinayaka Missions Medical College and Hospital, Karaikal, India. FAU - Pundir, Nikhil AU - Pundir N AD - Department of Internal Medicine, American University of Barbados, Bridgetown, Barbados - nickhillthakur16@gmail.com. FAU - Patel, Pooja AU - Patel P AD - Department of Internal Medicine, GMERS Medical College and Hospital, Gujarat, India. FAU - Jacob, Nidhi E AU - Jacob NE AD - Department of General Medicine, Government Medical College, Mahasamund, India. FAU - Jossy, Preeti E AU - Jossy PE AD - Department of Internal Medicine, Government Medical College Trivandrum, Thiruvananthapuram, India. FAU - Seetharaman, Rajmohan AU - Seetharaman R AD - Department of Internal Medicine, MGM Medical College and Hospital, Nerul, MGM Institute of Health Sciences, Navi Mumbai, India. LA - eng PT - Journal Article PT - Review DEP - 20260319 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 51110-01-1 (Somatostatin) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Glucagon) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Somatostatin/analogs & derivatives/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Receptors, Glucagon/agonists MH - Animals EDAT- 2026/03/19 21:43 MHDA- 2026/09/07 11:37 CRDT- 2026/03/19 12:33 PHST- 2026/09/07 11:37 [medline] PHST- 2026/03/19 21:43 [pubmed] PHST- 2026/03/19 12:33 [entrez] AID - S2724-6507.26.04406-4 [pii] AID - 10.23736/S2724-6507.26.04406-4 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Sep;51(3):306-321. doi: 10.23736/S2724-6507.26.04406-4. Epub 2026 Mar 19. PMID- 41855031 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260729 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 22 IP - 954 DP - 2026 Mar 18 TI - [GLP-1 agonists : indications and pancreatic and endoscopic safety considerations]. PG - 520-524 LID - 10.53738/REVMED.2026.22.954.48466 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have transformed the management of type 2 diabetes and obesity, and they are increasingly being used in metabolic dysfunction-associated steatotic liver disease. However, their rapid uptake has raised safety concerns, particularly regarding the risk of acute pancreatitis and periprocedural management in endoscopy, given the delayed gastric emptying and risk of aspiration under sedation or anesthesia. This article summarizes the current indications for GLP-1 RAs in Switzerland, the available clinical evidence on the risk of pancreatitis, and practical strategies for risk mitigation and periprocedural management in endoscopy. FAU - Cuenoud, Sophie AU - Cuenoud S AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Sanga, Morgane AU - Sanga M AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Santini, Sara AU - Santini S AUID- ORCID: 0000-0003-2422-4896 AD - Adobes, Ch du Centenaire 5, 1008 Prilly. AD - Centre de l'obesite, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Godat, Sebastien AU - Godat S AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Moradpour, Darius AU - Moradpour D AUID- ORCID: 0000-0003-1977-6792 AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Marx, Mariola AU - Marx M AUID- ORCID: 0000-0001-6058-2178 AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. FAU - Vieira Barbosa, Joana AU - Vieira Barbosa J AUID- ORCID: 0000-0002-4495-6974 AD - Service de gastroenterologie et d'hepatologie, Centre hospitalier universitaire vaudois, Universite de Lausanne, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Agonistes du GLP-1 : indications et enjeux de securite pancreatique et endoscopique. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Pancreatitis/chemically induced/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Switzerland COIS- les auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2026/03/19 21:43 MHDA- 2026/03/19 21:44 CRDT- 2026/03/19 12:22 PHST- 2026/03/19 21:44 [medline] PHST- 2026/03/19 21:43 [pubmed] PHST- 2026/03/19 12:22 [entrez] AID - RMS0954-003 [pii] AID - 10.53738/REVMED.2026.22.954.48466 [doi] PST - ppublish SO - Rev Med Suisse. 2026 Mar 18;22(954):520-524. doi: 10.53738/REVMED.2026.22.954.48466. PMID- 41852334 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Challenging the Consensus Statement: Is It Time to Recognise Pharmacological Remission of Type 2 Diabetes? PG - 4474-4487 LID - 10.1111/dom.70674 [doi] AB - Plasma glucose and HbA(1c) concentrations below the diagnostic threshold for diabetes have been achieved in people with type 2 diabetes (T2DM) in three clinical settings: with intensive weight-management programs that induce > 10-15 kg bodyweight loss, following bariatric surgery, and during treatment with highly effective glucose- and weight-lowering medications. The current consensus definition of T2DM remission excludes a status of absence of diabetes achieved with concomitant use of glucose- and weight-lowering medications. However, since these treatments can safely achieve HbA(1c) and plasma glucose concentrations lower than the ones currently used to define remission, we propose to consider a separate category of diabetes remission mainly achieved and maintained with pharmacological treatment. Our arguments are based on: (1) the similar endocrine mechanisms associated with bariatric surgery and use of GLP-1 receptor agonists or GIP/GLP-1 dual receptor agonists, (2) the lack of evidence that the effects of near-normoglycemic states achieved with lifestyle, surgery or glucose- and weight-lowering medications on long-term complications differ and (3) the frequent use of these medications in conjunction with both lifestyle interventions and following bariatric surgery. With this proposal, we aim to invite further discussion towards expanding the current narrow definition of T2D remission to include remission during treatment with newer highly effective glucose- and weight-lowering medications. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Bianchi, Cristina AU - Bianchi C AUID- ORCID: 0000-0003-2799-2380 AD - Endocrine-Metabolic and Transplant Medicine and Surgery Department, University Hospital of Pisa, Pisa, Italy. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center 'Health Science', Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Rothberg, Amy E AU - Rothberg AE AD - Division of Metabolism, Endocrinology & Diabetes, Michigan Medicine, Ann Arbor, Michigan, USA. AD - Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism, Section Medical Department I St. Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr-University-Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. LA - eng PT - Consensus Statement PT - Journal Article PT - Review DEP - 20260319 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/therapy MH - *Hypoglycemic Agents/therapeutic use MH - Bariatric Surgery MH - Remission Induction MH - Glycated Hemoglobin/metabolism/analysis MH - Blood Glucose/metabolism MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incretins/therapeutic use OTO - NOTNLM OT - GLP-1 analogue OT - incretin therapy OT - type 2 diabetes OT - weight management EDAT- 2026/03/19 07:10 MHDA- 2026/05/06 06:38 CRDT- 2026/03/19 04:53 PHST- 2026/02/27 00:00 [revised] PHST- 2025/12/04 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/03/19 07:10 [pubmed] PHST- 2026/03/19 04:53 [entrez] AID - 10.1111/dom.70674 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4474-4487. doi: 10.1111/dom.70674. Epub 2026 Mar 19. PMID- 41852258 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Psychiatric Disorders: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. PG - 5011-5019 LID - 10.1111/dom.70692 [doi] AB - AIM: To explore the association of GLP-1 receptor agonists (GLP-1 RAs) with the risk of psychiatric disorders. METHODS: A systematic search was performed in PubMed, EMBASE, Cochrane Library and Web of Science (inception to June 13, 2025). Randomised clinical trials (RCTs) that compared the use of GLP-1 RAs with either placebo or other non-GLP-1 RAs treatments were included. Psychiatric disorders were collected based on reported treatment-emergent adverse events. Following PRISMA guidelines, two reviewers independently extracted data and evaluated the quality of each study using the Cochrane tool. Evidence quality was assessed using the GRADE framework. RESULTS: A total of 133 378 participants were included across 86 RCTs. No significant statistical difference was found in the incidence of psychiatric disorders between the GLP-1 RAs group and the control group (RR, 0.96; 95% CI, 0.85-1.08; I(2) = 0%; ARD, -9 per 10 000 persons/year). GLP-1 RAs treatment was not associated with depression (RR, 0.88; 95% CI, 0.70-1.10), suicide (RR, 0.90; 95% CI, 0.59-1.38), anxiety (RR, 0.92; 95% CI, 0.72-1.19), sleep disorder (RR, 0.98; 95% CI, 0.70-1.37), bipolar disorder (RR, 1.19; 95% CI, 0.56-2.55), delirium (RR, 1.11; 95% CI, 0.74-1.66), addictive disorder (RR, 0.89; 95% CI, 0.45-1.77) or schizophrenia (RR, 1.45; 95% CI, 0.61-3.47). No statistically significant associations were observed for drug type, indication, dose, treatment duration, comparator type, baseline BMI, trial designation, age, inclusion of baseline psychiatric disorders or reporting category. Meta-regression analyses revealed no significant effect of changes in fasting blood glucose, haemoglobin A1c, weight or BMI on the risk of psychiatric disorders. CONCLUSION: GLP-1 RAs use was not associated with the risk of psychiatric disorders, including depression, suicide or anxiety. TRIAL REGISTRATION: PROSPERO Identifier: CRD42024546896. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Han, Shumeng AU - Han S AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Yang, Yucheng AU - Yang Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Liu, Zijun AU - Liu Z AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Liu, Yiwen AU - Liu Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Xing, Baodi AU - Xing B AUID- ORCID: 0000-0002-8735-2505 AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Wang, Xuechen AU - Wang X AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Yu, Jie AU - Yu J AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Ping, Fan AU - Ping F AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Li, Wei AU - Li W AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Xu, Lingling AU - Xu L AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Li, Yuxiu AU - Li Y AUID- ORCID: 0000-0001-7500-0855 AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhang, Huabing AU - Zhang H AUID- ORCID: 0000-0001-6259-7584 AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. AD - Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China. LA - eng GR - 82470934/National Natural Science Foundation of China/ GR - 2023-I2M-C&T-B-043;2021-I2M-1-002/CAMS Innovation Fund for Medical Sciences/ GR - 2022-PUMCH-B-015/National High Level Hospital Clinical Research Funding/ GR - M22014/Beijing Municipal Natural Science Foundation/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260319 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - *Mental Disorders/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - GLP-1 RAs OT - anxiety OT - depression OT - drug safety OT - psychiatric disorders OT - suicide EDAT- 2026/03/19 07:10 MHDA- 2026/05/06 06:40 CRDT- 2026/03/19 04:23 PHST- 2026/03/02 00:00 [revised] PHST- 2025/12/13 00:00 [received] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/05/06 06:40 [medline] PHST- 2026/03/19 07:10 [pubmed] PHST- 2026/03/19 04:23 [entrez] AID - 10.1111/dom.70692 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5011-5019. doi: 10.1111/dom.70692. Epub 2026 Mar 19. PMID- 41851446 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261016 IS - 1433-2965 (Electronic) IS - 0937-941X (Print) IS - 0937-941X (Linking) VI - 37 IP - 6 DP - 2026 Jun TI - The association between GLP-1 receptor agonists and fractures: a nationwide Danish nested case-control study. PG - 1611-1620 LID - 10.1007/s00198-026-07950-6 [doi] AB - To examine whether GLP1-RA is associated with increased fracture risk, we compared 337,648 people with fractures to 675,296 people without fractures. Our adjusted analysis found that people with fractures tended to use GLP1-RA less often than people without fractures. This suggests that GLP1-RA may reduce fracture risk. BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists were introduced as a treatment for type 2 diabetes mellitus with weight loss as a beneficial side effect. Since then, the medications have been approved as weight-loss medication. However, rapid and substantial weight loss can lead to bone loss and increased fracture risk. METHODS: We identified persons aged 30-90 years with a fracture between 2017 and 2021 and matched them 1:2 with fracture-free controls by sex and year of birth. Conditional logistic regression models were used to estimate odds ratios (ORs) for any fracture and major osteoporotic fracture (MOF) associated with GLP-1 receptor agonist use. Analyses were adjusted for relevant risk factors. RESULTS: A total of 337,648 fracture cases and 675,296 fracture-free controls were included. In the unadjusted analyses, GLP-1 receptor agonist use did not differ between cases and controls (any fracture OR [confidence intervals (CI)], 1.00 [0.97-1.04]; MOF OR [CI], 0.96 [0.90-1.02]). In the adjusted analyses, GLP-1 receptor agonists were used less frequently in the group that sustained any fracture (OR [CI], 0.94 [0.90-0.97]) or MOF (OR [CI], 0.88 [0.83-0.94]) compared to the controls. CONCLUSION: GLP-1 receptor agonists may reduce fracture risk, suggesting a potential protective effect on bone health. CI - (c) 2026. The Author(s). FAU - Kvist, Annika Vestergaard AU - Kvist AV AUID- ORCID: 0000-0002-4291-544X AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. annika.k@rn.dk. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. annika.k@rn.dk. FAU - Andersen, Sally Sogaard AU - Andersen SS AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Vestergaard, Peter AU - Vestergaard P AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. AD - Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. FAU - Viggers, Rikke AU - Viggers R AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. AD - Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. LA - eng PT - Journal Article DEP - 20260318 PL - England TA - Osteoporos Int JT - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JID - 9100105 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Female MH - *Osteoporotic Fractures/epidemiology/prevention & control/chemically induced MH - Male MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Denmark/epidemiology MH - Case-Control Studies MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Aged, 80 and over MH - Middle Aged MH - Adult MH - Risk Assessment/methods MH - Drug Utilization/statistics & numerical data PMC - PMC13661666 OTO - NOTNLM OT - Fractures OT - Glucagon-like peptide-1 OT - Incretins OT - Osteoporosis OT - Type 2 diabetes COIS- Declarations. Conflicts of interest: PV is head of research at the Steno Diabetes Center North Denmark, funded by an unrestricted grant from the Novo Nordisk Foundation. AVK reports a relationship with Novo Nordisk that includes equity or stocks. RV reports financial support was provided by Amgen Inc, a relationship with Novo Nordisk that includes equity or stocks, a relationship with Amgen Inc. that includes equity or stocks, a relationship with Eli Lilly that includes equity or stocks. SSA declares that she has no conflict of interest. EDAT- 2026/03/19 07:10 MHDA- 2026/10/13 23:35 PMCR- 2026/03/18 CRDT- 2026/03/19 00:29 PHST- 2025/10/17 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/10/13 23:35 [medline] PHST- 2026/03/19 07:10 [pubmed] PHST- 2026/03/19 00:29 [entrez] PHST- 2026/03/18 00:00 [pmc-release] AID - 10.1007/s00198-026-07950-6 [pii] AID - 7950 [pii] AID - 10.1007/s00198-026-07950-6 [doi] PST - ppublish SO - Osteoporos Int. 2026 Jun;37(6):1611-1620. doi: 10.1007/s00198-026-07950-6. Epub 2026 Mar 18. PMID- 41850932 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260918 IS - 1878-3562 (Electronic) IS - 1590-8658 (Linking) VI - 58 IP - 6 DP - 2026 Jun TI - Practical management of glucagon-like peptide-1 receptor agonists in gastroenterology: a position paper by the Italian Society of Gastroenterology (SIGE). PG - 737-746 LID - S1590-8658(26)00296-3 [pii] LID - 10.1016/j.dld.2026.02.018 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut-pancreas-liver axis have raised both therapeutic interest and safety concerns, particularly regarding hepatic outcomes, gastrointestinal cancers, peri-endoscopic management, and gastrointestinal adverse events. This position paper, endorsed by the Italian Society of Gastroenterology (SIGE), was developed according to the GRADE framework and provides evidence-based recommendations for the safe and effective management of GLP-1RAs in gastroenterology, highlighting their favorable benefit-risk profile while identifying key knowledge gaps requiring future prospective studies. GLP-1RAs may be safely used in patients with diabetes or obesity and metabolic dysfunction-associated steatotic liver disease. In cirrhotic patients with diabetes or obesity, GLP-1RAs appear safe and are associated with reduced hepatic decompensation. Available evidence does not support an increased risk of esophageal, gastric, colorectal, or pancreatic cancer, while a potential reduction in hepatocellular carcinoma incidence is suggested. Routine discontinuation of GLP-1RAs before upper gastrointestinal endoscopy is not recommended. GLP-1RAs increase the risk of mild, transient gastrointestinal adverse events and cholelithiasis but are not associated with severe gastrointestinal complications or acute pancreatitis. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Facciorusso, Antonio AU - Facciorusso A AD - Gastroenterology Unit, Department of Experimental Medicine, University of Salento, Lecce, 73100, Italy. Electronic address: antonio.facciorusso@unisalento.it. FAU - Giannini, Edoardo G AU - Giannini EG AD - Gastroenterology Unit, Department of Internal Medicine, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - Tacelli, Matteo AU - Tacelli M AD - Division of Biliopancreatic Endoscopy and Endoscopic Ultrasonography Unit, IRCCS San Raffaele Hospital, Milan, Italy. FAU - Zanetto, Alberto AU - Zanetto A AD - Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy. FAU - Spada, Cristiano AU - Spada C AD - Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Boskoski, Ivo AU - Boskoski I AD - Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Furnari, Manuele AU - Furnari M AD - Gastroenterology Unit, Department of Internal Medicine, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - Pennisi, Grazia AU - Pennisi G AD - Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Italy. FAU - Capurso, Gabriele AU - Capurso G AD - Division of Biliopancreatic Endoscopy and Endoscopic Ultrasonography Unit, IRCCS San Raffaele Hospital, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. FAU - Vitello, Alessandro AU - Vitello A AD - Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy. FAU - Marasco, Giovanni AU - Marasco G AD - IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. FAU - Sarnelli, Giovanni AU - Sarnelli G AD - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. FAU - Frulloni, Luca AU - Frulloni L AD - Gastroenterology Unit, Department of Medicine University of Verona, Verona, Italy. FAU - Maida, Marcello AU - Maida M AD - Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy. CN - Italian Society of Gastroenterology (SIGE) LA - eng PT - Consensus Statement PT - Journal Article DEP - 20260318 PL - Netherlands TA - Dig Liver Dis JT - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JID - 100958385 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastroenterology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Italy MH - *Obesity/drug therapy MH - Societies, Medical OTO - NOTNLM OT - Endoscopy OT - GLP-1 receptor agonists OT - Gastrointestinal adverse events OT - MASLD COIS- Declaration of competing interest All the other authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript. EDAT- 2026/03/19 01:32 MHDA- 2026/05/17 06:29 CRDT- 2026/03/18 22:53 PHST- 2026/01/19 00:00 [received] PHST- 2026/02/10 00:00 [revised] PHST- 2026/02/25 00:00 [accepted] PHST- 2026/05/17 06:29 [medline] PHST- 2026/03/19 01:32 [pubmed] PHST- 2026/03/18 22:53 [entrez] AID - S1590-8658(26)00296-3 [pii] AID - 10.1016/j.dld.2026.02.018 [doi] PST - ppublish SO - Dig Liver Dis. 2026 Jun;58(6):737-746. doi: 10.1016/j.dld.2026.02.018. Epub 2026 Mar 18. PMID- 41850718 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 14 IP - 2 DP - 2026 Mar 18 TI - Association of GLP-1 receptor agonists with intentional self-harm in patients with type 2 diabetes: a Sentinel Distributed Database study. LID - 10.1136/bmjdrc-2025-005840 [doi] LID - e005840 AB - INTRODUCTION: The U.S. Food and Drug Administration (FDA) investigated the potential risk of suicidal ideation and behaviors for glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on learning of post-marketing reports of suicidal ideation and behaviors in patients taking GLP-1 RAs. This study assessed a potential association with intentional self-harm comparing GLP-1 RAs to other antidiabetic products. RESEARCH DESIGN AND METHODS: We conducted an active-comparator, new-user cohort study-using FDA's Sentinel System-with data from October 1, 2015, to September 30, 2023. The study included health plan members >/=18 years old diagnosed with type 2 diabetes, newly initiated GLP-1 RAs (n=1 161 983), sodium-glucose cotransporter-2 inhibitors (SGLT-2is, n=1 081 155), or dipeptidyl peptidase-4 inhibitors (DPP-4is, n=1 396 382), and continuously enrolled in a health plan with medical and drug coverage for >/=183 days. The main outcome was intentional self-harm. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for intentional self-harm events and used inverse probability of treatment weighting of propensity scores to control for confounding. RESULTS: The comparator groups had a mean age that was slightly above 60 years and similar percentages of males and females. Adjusted incidence rates of intentional self-harm per 1000 person-years were 1.13 for GLP-1 RAs, 1.22 for SGLT-2is, and 1.37 for DPP-4is. Adjusted HRs indicated no increased risk of intentional self-harm comparing GLP-1 RAs to SGLT-2is (HR 0.93; 95% CI 0.81 to 1.08) or DPP-4is (HR 0.94; 95% CI 0.82 to 1.07). Subgroup analyses by comorbid obesity and diabetes, psychiatric history, prior intentional self-harm, age, and sex yielded similar results. CONCLUSIONS: The use of GLP-1 RAs did not show increased risk of intentional self-harm compared with SGLT-2is or DPP-4is, which provides some reassurance regarding the safety of GLP-1 RA use in patients with type 2 diabetes. CI - I am a US Federal Government officer or employee creating the Work as part of my official duties. FAU - Kuzucan, Aida AU - Kuzucan A AD - Formerly at U.S. Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Tran, Van AU - Tran V AD - U.S. Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Jones, Jamal T AU - Jones JT AUID- ORCID: 0000-0002-2709-0806 AD - U.S. Food and Drug Administration, Silver Spring, Maryland, USA Jamal.Jones@fda.hhs.gov. FAU - Dutcher, Sarah K AU - Dutcher SK AD - U.S. Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Her, Meg AU - Her M AD - Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA. FAU - Kempner, Maria E AU - Kempner ME AD - Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA. FAU - Lee, Joo-Yeon AU - Lee JY AD - U.S. Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Mosholder, Andrew AU - Mosholder A AUID- ORCID: 0000-0001-7821-8067 AD - Formerly at U.S. Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Round, Katherine E AU - Round KE AD - Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA. FAU - Toh, Sengwee AU - Toh S AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Lyons, Jennifer G AU - Lyons JG AD - Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article DEP - 20260318 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Self-Injurious Behavior/epidemiology/chemically induced/psychology MH - United States/epidemiology MH - Databases, Factual MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Follow-Up Studies MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Adult MH - Prognosis MH - Aged PMC - PMC13007165 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Epidemiology OT - Glucagon-Like Peptide 1 OT - Pharmacoepidemiology COIS- Competing interests: None declared. EDAT- 2026/03/19 01:32 MHDA- 2026/03/19 01:33 PMCR- 2026/03/18 CRDT- 2026/03/18 21:12 PHST- 2025/12/15 00:00 [received] PHST- 2026/02/24 00:00 [accepted] PHST- 2026/03/19 01:33 [medline] PHST- 2026/03/19 01:32 [pubmed] PHST- 2026/03/18 21:12 [entrez] PHST- 2026/03/18 00:00 [pmc-release] AID - 14/2/e005840 [pii] AID - bmjdrc-2025-005840 [pii] AID - 10.1136/bmjdrc-2025-005840 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2026 Mar 18;14(2):e005840. doi: 10.1136/bmjdrc-2025-005840. PMID- 41850681 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260610 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 66 IP - 3 DP - 2026 May-Jun TI - Medication adherence and persistence of newly initiated medications in older adults with diabetes. PG - 103075 LID - S1544-3191(26)00060-9 [pii] LID - 10.1016/j.japh.2026.103075 [doi] AB - BACKGROUND: Older adults with type 2 diabetes (T2D) face increased complications compared with younger counterparts and the challenge of multimorbidity, which may result in complex medication burden, high-cost regimens, polypharmacy, and nonadherence. OBJECTIVES: This study sought to evaluate primary and secondary medication adherence and persistence patterns of newly initiated glucose-lowering medications in older adults with T2D. METHODS: This retrospective cohort study included adults aged 65 years and older with T2D newly prescribed a dipeptidyl peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), or sulfonylurea (SU) across 6 health care systems between 2014 and 2021. Medication order and dispensing data were used to quantify primary and secondary adherence and early- and late-stage persistence, during 365 days of follow-up. Multivariable logistic regression models determined associations between medication class and adherence, adjusting for site, demographics, and clinical characteristics. RESULTS: Among 109,118 older adults with T2D prescribed study medications, 1-year adherence was 42% for GLP-1 RA, 46% for DPP4i, 52% for SU, and 60% for SGLT2i. Primary adherence was 94% with little variation among classes. Secondary adherence and late-stage persistence among those who filled the first prescription were lowest for GLP-1 RA (60% and 61%) and highest for SGLT2i (81% and 84%). SGLT2i was associated with a higher adjusted odds of primary (odds ratio [OR] 1.14 [95% CI 1.00-1.30]) and secondary adherence (OR 2.41 [95% CI 2.24-2.59]) compared with GLP-1 RA. Select demographic and baseline clinical characteristics were associated with differences in adherence and persistence. CONCLUSIONS: Adherence to glucose-lowering medications in older adults with T2D varies by medication class, clinical characteristics, and demographics. To effectively address individual adherence and persistence, it is important to consider factors beyond the branded status of a drug when designing targeted interventions. CI - Copyright (c) 2026 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Dombrowski, Sarah Krahe AU - Dombrowski SK FAU - An, Jaejin AU - An J FAU - Huang, Xuan AU - Huang X FAU - Lewis, Meredith AU - Lewis M FAU - Hayduk, Vanessa A AU - Hayduk VA FAU - Neugebauer, Romain AU - Neugebauer R FAU - O'Connor, Patrick J AU - O'Connor PJ FAU - Schmittdiel, Julie AU - Schmittdiel J FAU - Hooker, Stephanie A AU - Hooker SA FAU - Karter, Andrew J AU - Karter AJ FAU - Oshiro, Caryn E S AU - Oshiro CES FAU - Cassidy-Bushrow, Andrea E AU - Cassidy-Bushrow AE FAU - Nance, Nerissa AU - Nance N FAU - Nolan, Margaret B AU - Nolan MB FAU - Gilliam, Lisa K AU - Gilliam LK FAU - Graham, Jove AU - Graham J FAU - Wright, Eric A AU - Wright EA LA - eng PT - Journal Article DEP - 20260316 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Drug Monitoring MH - Male MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage MH - Aged, 80 and over MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sulfonylurea Compounds/therapeutic use/administration & dosage MH - Cohort Studies COIS- Disclosures During the drafting of this manuscript, N.N. began a position at Novo Nordisk A/S, a pharmaceutical company that produces diabetes drugs. The other authors declare no relevant conflicts of interest or financial relationships. EDAT- 2026/03/19 01:32 MHDA- 2026/06/11 05:42 CRDT- 2026/03/18 20:18 PHST- 2025/12/03 00:00 [received] PHST- 2026/03/02 00:00 [revised] PHST- 2026/03/03 00:00 [accepted] PHST- 2026/06/11 05:42 [medline] PHST- 2026/03/19 01:32 [pubmed] PHST- 2026/03/18 20:18 [entrez] AID - S1544-3191(26)00060-9 [pii] AID - 10.1016/j.japh.2026.103075 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2026 May-Jun;66(3):103075. doi: 10.1016/j.japh.2026.103075. Epub 2026 Mar 16. PMID- 41850241 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 7 IP - 3 DP - 2026 Mar 17 TI - Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials. PG - 102614 LID - S2666-3791(26)00031-5 [pii] LID - 10.1016/j.xcrm.2026.102614 [doi] LID - 102614 AB - Semaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve >/=5% or >/=10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving >/=10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132). CI - Copyright (c) 2026. Published by Elsevier Inc. FAU - Ko, Donghyun AU - Ko D AD - Department of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, CT, USA. Electronic address: donghyun.ko@bpthosp.org. FAU - Kim, Do Han AU - Kim DH AD - Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Tan, Faith Xin Ning AU - Tan FXN AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Ho, Glenn Jun Kit AU - Ho GJK AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chandra, Rubhan AU - Chandra R AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Xuan, Zhang Zi AU - Xuan ZZ AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Jun, Ethan Tham Kai AU - Jun ETK AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Tang, Nicole Shu Ying AU - Tang NSY AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Yang, Hee Seung AU - Yang HS AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. FAU - Koh, Jeffery Wei Heng AU - Koh JWH AD - Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore. FAU - Danpanichkul, Pojsakorn AU - Danpanichkul P AD - Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. FAU - Dalakoti, Mayank AU - Dalakoti M AD - Department of Cardiology, National University Heart Centre, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. FAU - Syn, Nicholas L AU - Syn NL AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Wijarnpreecha, Karn AU - Wijarnpreecha K AD - Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, AZ, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, AZ, USA; BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA. FAU - Takahashi, Hirokazu AU - Takahashi H AD - Liver Center, Saga University Hospital, Saga, Japan. FAU - Zheng, Ming-Hua AU - Zheng MH AD - MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Key Laboratory of Hepatology, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease, Wenzhou, Zhejiang, China. FAU - Nakajima, Atsushi AU - Nakajima A AD - Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Noureddin, Mazen AU - Noureddin M AD - Houston Methodist Hospital and Houston Research Institute, Houston, TX, USA. FAU - Muthiah, Mark AU - Muthiah M AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore. FAU - Le Roux, Carel W AU - Le Roux CW AD - University College Dublin, Diabetes Complications Research Centre, Dublin, Ireland. FAU - Siddiqui, Mohammad Shadab AU - Siddiqui MS AD - Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, USA. Electronic address: mohammad.siddiqui@vcuhealth.org. FAU - Ng, Cheng Han AU - Ng CH AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; Houston Methodist Hospital and Houston Research Institute, Houston, TX, USA; Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: chenghanng@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Female PMC - PMC13006432 OTO - NOTNLM OT - longitudinal OT - randomized clinical trials OT - reduction OT - semaglutide COIS- Declaration of interests C.H.N. serves as the CEO of LiverGENIX Pte Ltd. M.M. has served as a consultant to Roche, Estella, and Gilead. He has been an advisor for LernaBio. M.M. has received payment for speaking at Boston Scientific, Olympus Medical, Roche, and Astellas. He also serves as the CMO of LiverGENIX Pte Ltd. M.M. is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd., under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF), under the NMRC Open Fund - Large Collaborative Grant (MOH-001325), administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. N.L.S. serves as the CTO of LiverGENIX Pte Ltd. M.N. consults and received grants from Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda, and Terns. He consults, advises, and owns stock in Cytodyn. He consults and advises 89 Bio, Altimmune, Boehringer Ingelheim, Merck, and Perspectum. He has received grants and owns stock in Viking. He advises Blade, CohBar, EchoSens, Fractyl, Intercept, NorthSea, Pfizer, Siemens, and Roche Diagnostics. He has received grants from Allergan, Bristol Myers Squibb, Conatus, Corcept, Enanta, Galmed, Galectin, Genfit, Madrigal, Novartis, Pfizer, Shire, and Zydus. He owns stock in Anaetos, ChronWell, Cima, and Rivus Pharma. H.T. has received research grants from Astellas Pharma, AbbVie GK, and Sysmex. M.-h.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. M.-h.Z. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition and Liver International. A.N. has served as a medical advisor to EA Pharma Co., Ltd. M.S.S. has received consulting fees from Sagimet, 89 Bio, and AMRA and grant support from Novo Nordisk. EDAT- 2026/03/19 01:32 MHDA- 2026/03/19 01:33 PMCR- 2026/03/17 CRDT- 2026/03/18 19:22 PHST- 2025/06/20 00:00 [received] PHST- 2025/11/28 00:00 [revised] PHST- 2026/01/13 00:00 [accepted] PHST- 2026/03/19 01:33 [medline] PHST- 2026/03/19 01:32 [pubmed] PHST- 2026/03/18 19:22 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - S2666-3791(26)00031-5 [pii] AID - 102614 [pii] AID - 10.1016/j.xcrm.2026.102614 [doi] PST - ppublish SO - Cell Rep Med. 2026 Mar 17;7(3):102614. doi: 10.1016/j.xcrm.2026.102614. PMID- 41847743 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Association of GLP-1 Receptor Agonists With Hepatic Decompensation in the All of Us Research Program. PG - 4837-4846 LID - 10.1111/dom.70668 [doi] AB - AIMS: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) initiation and the risk of hepatic decompensation compared with dipeptidyl peptidase 4 inhibitors (DPP4is) in a racially and ethnically diverse cohort of adults with Type 2 diabetes. MATERIALS AND METHODS: This retrospective active-comparator new-user cohort study utilised data from the National Institutes of Health's All of Us Research Program. Adult participants with Type 2 diabetes initiating GLP-1RAs or DPP4is without prior hepatic decompensation or competing causes of chronic liver disease were identified. Stratified propensity score matching (1:1) was employed to balance baseline covariates. The primary outcome was a composite of hepatic decompensation events (oesophageal varices with bleeding, ascites, hepatic encephalopathy, hepatic failure, or liver transplantation). Hazard ratios (HRs) were estimated using Cox proportional hazards regression. RESULTS: The matched cohort included 7854 participants (mean age 57.3 years; 58.8% female; 24.8% Black or African American). GLP-1RA use was associated with a significantly reduced risk of hepatic decompensation compared with DPP4i use (HR 0.67; 95% CI 0.47-0.95; p = 0.026), corresponding to an absolute rate difference of -1.66 events per 1000 person-years. Estimates were directionally similar in prespecified sensitivity analyses. CONCLUSIONS: In this diverse nationwide cohort, initiation of GLP-1RAs was associated with a significantly reduced risk of hepatic decompensation compared with DPP4is. These findings extend prior evidence by demonstrating this association in a cohort enriched for populations historically underrepresented in biomedical research. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hwang, Inyoung AU - Hwang I AUID- ORCID: 0000-0003-4953-759X AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, Republic of Korea. FAU - Kim, Yun AU - Kim Y AUID- ORCID: 0000-0002-9809-7351 AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Republic of Korea. AD - Convergence Research Institute for Biomedical Sciences at Daegu Catholic University, Gyeongsan, Gyeongbuk, South Korea. FAU - Lee, Sang Won AU - Lee SW AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, Republic of Korea. AD - Department of Pharmacology, Hanyang University College of Medicine, Seoul, Republic of Korea. LA - eng GR - 2025-RISE-15-107/Gyeongsangbuk-do RISE (Regional Innovation System & Education) project/ PT - Journal Article DEP - 20260318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Retrospective Studies MH - Middle Aged MH - United States/epidemiology MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liver Failure/epidemiology/chemically induced MH - Aged PMC - PMC13146207 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - pharmaco-epidemiology OT - real-world evidence COIS- The authors declare no conflicts of interest. EDAT- 2026/03/18 07:25 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/18 04:52 PHST- 2026/03/06 00:00 [revised] PHST- 2026/01/05 00:00 [received] PHST- 2026/03/06 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/18 07:25 [pubmed] PHST- 2026/03/18 04:52 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70668 [pii] AID - 10.1111/dom.70668 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4837-4846. doi: 10.1111/dom.70668. Epub 2026 Mar 18. PMID- 41841288 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260711 IS - 0301-0430 (Print) IS - 0301-0430 (Linking) VI - 105 IP - 5 DP - 2026 May TI - Real world, retrospective experience of glucagon-like peptide-1 receptor agonists in kidney transplant recipients: A single-center case series. PG - 318-324 LID - 10.5414/CN111893 [doi] AB - We conducted a retrospective chart review of adult kidney transplant recipients (KTxR) with type 2 diabetes treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA). A total of 211, 207, 161, and 92 KTxR were followed for 6, 12, 36, and 60 months, respectively. Over 5 years, we observed statistically significant reductions in the primary endpoints of weight, HbA1c, and major adverse cardiovascular events (MACE). The mean weight reduction was as follows: 1.17 kg at 6 months (p < 0.006), 1.2 kg at 12 months (p < 0.03), 3.7 kg at 36 months (p < 0.0001), and 4.1 kg at 60 months (p = 0.001) compared to baseline. The HbA1c levels showed reductions of 0.6 mmol/mol at 6 months (p < 0.0001), 0.5 mmol/mol at 12 months (p = 0.0004), 0.3 mmol/mol at 36 months (p = 0.04), and 0.35 mmol/mol at 60 months (p = 0.35). MACE rates fell from 45.5% at GLP-1RA initiation to 18.9% during follow-up (OR 3.6 (2.3 - 5.6), p < 0.0001). Insulin requirements decreased from 50 to 27 units over 5 years. Kidney function reduces over time in KTx, likely secondary to hemodynamic or vascular-mediated risk factors, chronic immunosuppressive agents, treatment for rejections, and solitary transplanted kidney. In our study, estimated glomerular filtration rate (eGFR) not only stayed stable but also showed a trend towards improvement (eGFR improved from 50 to 53 mL/min/1.73m(2)). Further prospective randomized trials are needed to assess GLP-1RA efficacy and safety in KTxR. FAU - Singh, Priyamvada AU - Singh P FAU - McGowan, Melissa AU - McGowan M FAU - Von Stein, Lauren AU - Von Stein L FAU - Papanikolla, Johanna AU - Papanikolla J FAU - Nolan, Annelise AU - Nolan A FAU - Lingren, Hannah AU - Lingren H FAU - Jagielski, Noah AU - Jagielski N FAU - Singh, Navdeep AU - Singh N FAU - Meng, Shumei AU - Meng S FAU - Pesavento, Todd AU - Pesavento T LA - eng PT - Journal Article PL - Germany TA - Clin Nephrol JT - Clinical nephrology JID - 0364441 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 9P1872D4OL (Exenatide) RN - 0 (Peptides) RN - 0 (Venoms) SB - IM MH - Humans MH - *Kidney Transplantation/adverse effects MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/complications MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - Glycated Hemoglobin/metabolism MH - Male MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor MH - Time Factors MH - Aged MH - Cardiovascular Diseases MH - Exenatide MH - Adult MH - Peptides/therapeutic use MH - Venoms/therapeutic use EDAT- 2026/03/17 06:48 MHDA- 2026/04/21 18:33 CRDT- 2026/03/17 05:23 PHST- 2026/04/16 00:00 [accepted] PHST- 2026/04/21 18:33 [medline] PHST- 2026/03/17 06:48 [pubmed] PHST- 2026/03/17 05:23 [entrez] AID - 192795 [pii] AID - 10.5414/CN111893 [doi] PST - ppublish SO - Clin Nephrol. 2026 May;105(5):318-324. doi: 10.5414/CN111893. PMID- 41840391 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20261004 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Mar 16 TI - Is there still room for pioglitazone in contemporary type 2 diabetes management? LID - 10.1186/s12933-026-03093-4 [doi] LID - 87 AB - Recent real-world evidence comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) with pioglitazone indicates broadly comparable cardiovascular and hepatic outcomes in individuals with type 2 diabetes, with a lower risk of heart failure among GLP-1RA users. These findings must be interpreted in the context of contemporary guidelines, which increasingly prioritize therapies with cardiometabolic benefits while restricting the role of pioglitazone to selected settings. Despite recognized adverse effects, pioglitazone retains clinical relevance due to its glycaemic efficacy, potential cardio-hepatic benefits, and low cost, particularly in health-care systems with limited access to newer agents. Rather than being interchangeable, pioglitazone and GLP-1RA occupy complementary positions within the current therapeutic landscape, underscoring the importance of individualized treatment selection. CI - (c) 2026. The Author(s). FAU - Caruso, Irene AU - Caruso I AD - Endocrinology Unit, University Hospital "Consorziale Policlinico", Bari, Italy. ireneca91@gmail.com. LA - eng PT - Letter DEP - 20260316 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Humans MH - Biomarkers/blood MH - *Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/epidemiology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycemic Control/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - *Pioglitazone/therapeutic use/adverse effects MH - Treatment Outcome PMC - PMC12990594 COIS- Declarations. Competing interests: Speaker fees from Eli Lilly, Novo Nordisk, Boeringher Inghelheim.Travel support from Abbott, Guidotti SpA. EDAT- 2026/03/17 06:48 MHDA- 2026/03/17 06:49 PMCR- 2026/03/16 CRDT- 2026/03/17 00:43 PHST- 2025/12/19 00:00 [received] PHST- 2026/01/18 00:00 [accepted] PHST- 2026/03/17 06:49 [medline] PHST- 2026/03/17 06:48 [pubmed] PHST- 2026/03/17 00:43 [entrez] PHST- 2026/03/16 00:00 [pmc-release] AID - 10.1186/s12933-026-03093-4 [pii] AID - 3093 [pii] AID - 10.1186/s12933-026-03093-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Mar 16;25(1):87. doi: 10.1186/s12933-026-03093-4. PMID- 41838277 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20261010 IS - 1437-7799 (Electronic) IS - 1342-1751 (Linking) VI - 30 IP - 5 DP - 2026 May TI - Comparison of renal outcomes between sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist in Japanese patients with type 2 diabetes and obesity. PG - 747-756 LID - 10.1007/s10157-026-02845-6 [doi] AB - INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1Ra) have shown renoprotective effects in type 2 diabetes (T2D). Our previous findings suggested superior renal outcomes with SGLT2i compared to GLP-1Ra, particularly due to greater reductions in blood pressure (BP). However, whether this benefit extends to obese patients remains unclear. This study compared renal outcomes between SGLT2i and GLP-1Ra in obese Japanese patients with T2D. METHODS: This retrospective study included patients with T2D and body mass index >/= 25 kg/m(2) treated with either SGLT2i (n = 439) or GLP-1Ra (n = 174) for over one year. Patients receiving both drugs were excluded. The renal composite outcome was defined as an annual decline in estimated glomerular filtration rate (eGFR) > 30%, progression of albuminuria category, or both. Propensity score matching was applied to balance baseline characteristics. RESULTS: After matching (n = 89 per group), the incidence of renal events did not differ significantly between the two groups. The annual decline in eGFR tended to be smaller with SGLT2i than with GLP-1Ra (- 1.6 +/- 3.5 vs. - 2.8 +/- 5.8 mL/min/1.73 m(2)/year, p = 0.13). SGLT2i-treated patients also showed greater reductions in systolic BP and body weight (BW) (- 5.0 +/- 19.7 vs. - 1.1 +/- 18.0 mmHg, p = 0.19; - 3.3 +/- 4.6 vs. - 1.9 +/- 4.9 kg, p = 0.05, respectively). CONCLUSION: Among this population, the annual eGFR decline appeared numerically smaller with SGLT2i-tretament, without statistical significance. Greater BP and BW reductions were observed, though their impact on renal outcomes remains uncertain. CI - (c) 2026. The Author(s), under exclusive licence to Japanese Society of Nephrology. FAU - Wada, Yukihiro AU - Wada Y AUID- ORCID: 0000-0001-5996-8735 AD - Department of Nephrology, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-Ku, Sagamihara, Kanagawa, 224-0474, Japan. wada-y@kitasato-u.ac.jp. FAU - Toyoda, Masao AU - Toyoda M AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Tokai University, Isehara, Japan. FAU - Kobayashi, Kazuo AU - Kobayashi K AD - Committee of Hypertension and Kidney Disease, Kanagawa Physicians Association, Yokohama, Japan. AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Aoyama, Togo AU - Aoyama T AD - Department of Health Management Center, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. FAU - Kanamori, Akira AU - Kanamori A AD - Committee of Hypertension and Kidney Disease, Kanagawa Physicians Association, Yokohama, Japan. FAU - Takeuchi, Yasuo AU - Takeuchi Y AD - Department of Nephrology, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-Ku, Sagamihara, Kanagawa, 224-0474, Japan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260316 PL - Japan TA - Clin Exp Nephrol JT - Clinical and experimental nephrology JID - 9709923 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/diagnosis MH - Female MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glomerular Filtration Rate/drug effects MH - Middle Aged MH - Japan/epidemiology MH - *Obesity/complications MH - Aged MH - Albuminuria/physiopathology MH - *Diabetic Nephropathies/prevention & control/physiopathology/diagnosis/etiology/epidemiology MH - Treatment Outcome MH - *Kidney/physiopathology/drug effects MH - Blood Pressure/drug effects MH - Disease Progression MH - East Asian People OTO - NOTNLM OT - GLP-1Ra OT - Obesity OT - Renal outcome OT - SGLT2i COIS- Declarations. Conflict of interest: Yukihiro Wada reports payment or honoraria from DAIICHI SANKYO and Nippon Boehringer Ingelheim Co., Ltd. Masao Toyoda reports grants or contracts from LifeScan Japan, Mitsubishi Tanabe, DAIICHI SANKYO, Novo Nordisk, Sanofi, Takeda, Eli Lilly, MSD, Roche, and Dexcom, and payment or honoraria from Taisho, Kissei, Medtronic, Terumo, Abbott, MSD, Eli Lilly, Novartis, Takeda, Sumitomo, Sanofi, Novo Nordisk, Daiich Sankyo, Mitsubishi Tanabe, Ono, Boehringer Ingelheim, AstraZeneca, Astellas, Kyowa Kirin, Kowa. Kazuo Kobayashi reports payment or honoraria from Novartis Pharmacy and Otsuka Pharmacy. Togo Aoyama reports payment or honoraria from Nippon Boehringer Ingelheim Co., Ltd. The other authors have declared no conflicts of interest. Ethics approval: This study was reviewed and approved by the Special Ethics Committee of the Kanagawa Medical Association, Japan. Approval for the SGLT2i survey was obtained on March 6, 2018 (approval no. Krec304401), and approval for the GLP-1Ra survey and the present comparison study was granted on March 23, 2020 (approval no. Krec202005). Human and animal rights: No animals were involved in this research so a statement on their welfare does not apply. EDAT- 2026/03/16 21:57 MHDA- 2026/04/19 17:46 CRDT- 2026/03/16 12:22 PHST- 2026/01/14 00:00 [received] PHST- 2026/03/07 00:00 [accepted] PHST- 2026/04/19 17:46 [medline] PHST- 2026/03/16 21:57 [pubmed] PHST- 2026/03/16 12:22 [entrez] AID - 10.1007/s10157-026-02845-6 [pii] AID - 10.1007/s10157-026-02845-6 [doi] PST - ppublish SO - Clin Exp Nephrol. 2026 May;30(5):747-756. doi: 10.1007/s10157-026-02845-6. Epub 2026 Mar 16. PMID- 41838266 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20261001 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 10 DP - 2026 Aug TI - Association of Social Determinants of Health with Utilization of SGLT2 Inhibitors and GLP1 Receptor Agonists: A Systematic Review and Meta-Analysis. PG - 2859-2872 LID - 10.1007/s11606-026-10178-z [doi] AB - BACKGROUND: SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) reduce cardiovascular and metabolic risks in type-2 diabetes, cardiovascular disease, and obesity, yet social determinants of health (SDOH) may influence access to these therapies. We conducted a systematic review and meta-analysis to assess whether SDOH-socioeconomic status (SES), insurance status, education, geography, neighborhood deprivation-and demographic characteristics-race and sex-are associated with differential utilization of SGLT2i or GLP-1RA. METHODS: Six databases (Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar) were searched through February 2025. Retrospective and cross-sectional studies reporting association between at least one SDOH and prescription of SGLT2i and/or GLP-1RA were included. The primary outcome was the adjusted odds of utilization of SGLT2i, GLP-1RA, or both drugs by SDOH categories. Meta-analyses were conducted separately for SGLT2i and GLP-1RA using random-effects models. Risk of bias was assessed using ROBINS-I. RESULTS: Twenty-six studies (> 14.6 million patients) were included. Low-SES patients had reduced odds of utilization (aOR 0.73; 95% CI 0.61-0.76). Medicaid (aOR 0.70; 95% CI 0.55-0.89), Medicare (0.68; 0.60-0.78), and Medicare Advantage (aOR 0.41; 95% CI 0.30-0.57) patients had lower odds than privately insured patients. Lower educational attainment (aOR 0.70; 95% CI 0.53-0.93) and rurality (aOR 0.91; 95% CI 0.87-0.95) were associated with reduced utilization. Patients in high-deprivation neighborhoods (aOR 0.80; 95% CI 0.69-0.93) had lower odds of GLP-1RA utilization. Women had lower odds of SGLT2i utilization (aOR 0.89; 95% CI 0.82-0.95), but greater odds of GLP-1RA (aOR 1.33, 1.23-1.43). Black (aOR 0.80; 95% CI 0.79-0.82) patients had reduced utilization of both drugs, while Hispanic (aOR 0.81; 95% CI 0.69-0.96), and Asian (aOR 0.49; 95% CI 0.41-0.58) patients had reduced odds of GLP-1RA. DISCUSSION: Disparities in SGLT2i and GLP-1RA utilization span SES, insurance, education, geography, neighborhood deprivation, race, and sex, potentially limiting population-level benefits and warranting interventions to improve access. CI - (c) 2026. The Author(s), under exclusive licence to Society of General Internal Medicine. FAU - Shah, Nisarg AU - Shah N AD - Yale School of Medicine, New Haven, CT, USA. nisarg.shah@yale.edu. FAU - Edjimbi, Johann Alexandre Chafa AU - Edjimbi JAC AD - Sinai Hospital, Baltimore, MD, USA. FAU - Daou, Melissa AU - Daou M AD - Yale School of Medicine, New Haven, CT, USA. FAU - Grimshaw, Alyssa A AU - Grimshaw AA AD - Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA. FAU - Gunderson, Craig AU - Gunderson C AD - Yale School of Medicine, New Haven, CT, USA. FAU - Gupta, Shaili AU - Gupta S AD - Yale School of Medicine, New Haven, CT, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260316 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Social Determinants of Health MH - *Diabetes Mellitus, Type 2/drug therapy MH - Socioeconomic Disparities in Health MH - Low Socioeconomic Status MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13421548 COIS- Declarations. Human Ethics and Consent to Participate: Not applicable. Clinical Trial Number: Not applicable. Conflict of interest: None reported. EDAT- 2026/03/16 21:56 MHDA- 2026/07/30 00:38 PMCR- 2027/08/01 CRDT- 2026/03/16 12:22 PHST- 2025/08/09 00:00 [received] PHST- 2025/12/31 00:00 [accepted] PHST- 2026/07/30 00:38 [medline] PHST- 2026/03/16 21:56 [pubmed] PHST- 2026/03/16 12:22 [entrez] PHST- 2027/08/01 00:00 [pmc-release] AID - 10.1007/s11606-026-10178-z [pii] AID - 10178 [pii] AID - 10.1007/s11606-026-10178-z [doi] PST - ppublish SO - J Gen Intern Med. 2026 Aug;41(10):2859-2872. doi: 10.1007/s11606-026-10178-z. Epub 2026 Mar 16. PMID- 41832437 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260926 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 26 IP - 1 DP - 2026 Mar 14 TI - Comparative effectiveness of semaglutide and dulaglutide combined with hypocaloric diet in newly diagnosed type 2 diabetes: a retrospective real-world study. LID - 10.1186/s12902-026-02232-y [doi] LID - 86 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in early T2D management due to their glycemic and weight-reducing effects. However, real-world comparative data in newly diagnosed treatment-naive individuals remain limited. METHODS: This retrospective real-world study evaluated 106 adults aged 18-75 years with newly diagnosed T2D who initiated semaglutide (1.0 mg) or dulaglutide (1.5 mg) between December 2023 and December 2024. All patients received concurrent hypocaloric dietary intervention (1,200-1,400 kcal/day). Clinical and biochemical parameters were assessed at baseline and 6 months, with additional weight assessments at 3 months. Multivariable analyses were performed to adjust for baseline differences. RESULTS: Both treatment groups demonstrated significant reductions in HbA1c, fasting blood glucose, liver enzymes, and lipid parameters at 6 months. After adjustment for baseline covariates, semaglutide was associated with greater weight reduction and LDL cholesterol improvement, whereas HbA1c reduction was comparable between groups. Mild increases in pancreatic enzyme levels were observed in both groups, with higher elevations in the dulaglutide group. Gastrointestinal adverse events were common but generally mild. CONCLUSIONS: In this retrospective real-world cohort receiving structured dietary intervention, both semaglutide and dulaglutide improved glycemic control and metabolic parameters in newly diagnosed T2D. Semaglutide demonstrated superior weight reduction, while glycemic effects were similar. Baseline differences and the retrospective design should be considered when interpreting these findings. CLINICAL TRIAL NUMBER: Not applicable. FAU - Cetiner, Serap AU - Cetiner S AUID- ORCID: 0000-0002-0846-5908 AD - Department of Internal Medicine, Centermed Plus Medical Center, Nisantasi, Istanbul, 34365, Turkey. dr.serapboscetiner@gmail.com. AD - Department of Internal Medicine, Uskudar University, NP Health Campus, Umraniye, Istanbul, 34768, Turkey. dr.serapboscetiner@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260314 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy/therapy MH - Female MH - Retrospective Studies MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Middle Aged MH - Male MH - *Recombinant Fusion Proteins/therapeutic use MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Diet, Reducing/methods MH - Blood Glucose/analysis MH - Young Adult MH - Adolescent MH - Glycated Hemoglobin/analysis MH - Weight Loss MH - Prognosis MH - Follow-Up Studies MH - Treatment Outcome MH - Biomarkers/analysis PMC - PMC13020155 OTO - NOTNLM OT - Dulaglutide OT - Semaglutide OT - Type 2 diabetes OT - Weight loss COIS- Declarations. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey (Approval number: 2024/374; Date: 25 December 2024) Consent to publish: Not applicable. Informed consent: Informed consent forms were obtained from all patients. Competing interests: The authors declare no competing interests. EDAT- 2026/03/15 06:48 MHDA- 2026/06/28 00:35 PMCR- 2026/03/14 CRDT- 2026/03/15 00:23 PHST- 2025/12/30 00:00 [received] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/06/28 00:35 [medline] PHST- 2026/03/15 06:48 [pubmed] PHST- 2026/03/15 00:23 [entrez] PHST- 2026/03/14 00:00 [pmc-release] AID - 10.1186/s12902-026-02232-y [pii] AID - 2232 [pii] AID - 10.1186/s12902-026-02232-y [doi] PST - epublish SO - BMC Endocr Disord. 2026 Mar 14;26(1):86. doi: 10.1186/s12902-026-02232-y. PMID- 41831086 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1539-0829 (Electronic) IS - 1534-4827 (Print) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Mar 14 TI - Pharmacologic Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Context of Type 2 Diabetes. LID - 10.1007/s11892-026-01621-w [doi] LID - 6 AB - PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among individuals with type 2 diabetes (T2D). This review summarizes current evidence on the pharmacologic treatment of MASLD, with emphasis on agents currently approved for the management of T2D. RECENT FINDINGS: Among glucose-lowering therapies, GLP-1 RAs, dual GIP/GLP-1 RAs, pioglitazone, and SGLT2 inhibitors demonstrate meaningful benefits in steatohepatitis. Semaglutide provides the most robust evidence for fibrosis benefit, while data suggest potential antifibrotic effects of tirzepatide and dapagliflozin. Resmetirom and semaglutide are the only agents specifically approved for MASLD. An expanding pipeline of dual glucagon/GLP-1 and triple GIP/GLP-1/glucagon agonists such as retatrutide has shown marked reductions in liver fat and signals of MASH benefit. Additional therapies, including pan-PPAR agonists, and FGF21 analogues are advancing through phase 3 development. The therapeutic landscape is rapidly evolving toward integrated metabolic, hepatic, and cardiovascular risk reduction in T2D and MASLD. FAU - Malandris, Konstantinos AU - Malandris K AD - Clinical research and evidence-based medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Charalampidis, Konstantinos AU - Charalampidis K AD - Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, Altman Clinical and Translational Research Institute, La Jolla, San Diego, CA, USA. FAU - Sinakos, Emmanouil AU - Sinakos E AD - Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece. esinakos@auth.gr. AD - Medicine and Hepatology, Aristotle University of Thessaloniki, Hippokratio Hospital, 49, Konstantinoupoleos Str, Thessaloniki, 54642, Greece. esinakos@auth.gr. LA - eng PT - Journal Article PT - Review DEP - 20260314 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (PPAR-gamma Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Fatty Liver/drug therapy/etiology MH - Semaglutide MH - Tirzepatide MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - PPAR-gamma Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC12989002 OTO - NOTNLM OT - MASH OT - MASLD OT - Pharmacological management OT - T2D COIS- Declarations. Conflict of Interest Disclosure Statement: KM and KC declare no conflicts of interest. ES participates in clinical trials for NovoNordisk, GlaxoSmithKline and Boehringer Ingelheim; Stockholder in Akero Therapeutics and 89bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. RL has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Competing interests: KM and KC declare no conflicts of interest. ES participates in clinical trials for NovoNordisk, GlaxoSmithKline and Boehringer Ingelheim; Stockholder in Akero Therapeutics and 89bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. RL has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. RL receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK121378, P30DK120515), NHLBI (P01HL147835), and John C Martin Foundation (RP124). EDAT- 2026/03/15 05:36 MHDA- 2026/06/28 00:36 PMCR- 2026/03/14 CRDT- 2026/03/14 12:16 PHST- 2026/01/29 00:00 [received] PHST- 2026/03/02 00:00 [accepted] PHST- 2026/06/28 00:36 [medline] PHST- 2026/03/15 05:36 [pubmed] PHST- 2026/03/14 12:16 [entrez] PHST- 2026/03/14 00:00 [pmc-release] AID - 10.1007/s11892-026-01621-w [pii] AID - 1621 [pii] AID - 10.1007/s11892-026-01621-w [doi] PST - epublish SO - Curr Diab Rep. 2026 Mar 14;26(1):6. doi: 10.1007/s11892-026-01621-w. PMID- 41830481 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260711 IS - 1557-8518 (Electronic) IS - 1540-4196 (Linking) VI - 24 IP - 5 DP - 2026 Jun TI - Allostatic Load in Patients with Type 2 Diabetes Treated with GLP-1 Receptor Agonists. PG - 228-234 LID - 10.1177/15578518261431688 [doi] AB - BACKGROUND: In patients with type 2 diabetes (T2DM), glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control and have been shown to enhance stress regulation, potentially attenuating the cumulative impact of chronic stress. Despite these links, few studies have examined allostatic load in patients with T2DM treated with GLP-1s. OBJECTIVES: To compare allostatic load among patients with T2DM treated with GLP-1s and three comparison groups: individuals without T2DM, individuals with T2DM not receiving medication treatment, and individuals with T2DM treated with non-GLP-1 medications. METHODS: We analyzed data from 16,830 adults in the 2007-2018 National Health and Nutrition Examination Survey. Medication status was based on self-reported prescription use within the past month. Allostatic load was calculated primarily using a 13 biomarker index spanning metabolic, autonomic, and immune function and secondarily using a modified score that excluded HbA1c and insulin resistance. General linear regression was used to assess associations, adjusting for sociodemographics, comorbidities, and health behaviors. RESULTS: Participants with T2DM treated with GLP-1s had higher allostatic load than those without T2DM (beta = 1.57, 95% CI: 0.88, 2.25) but did not differ from participants with T2DM who were untreated or treated with non-GLP-1s. After excluding HbA1c and insulin resistance from the score, allostatic load in the GLP-1s-treated group was comparable across all comparison groups. CONCLUSIONS: GLP-1 treatment was not associated with lower allostatic load compared with other treatment regimens in patients with T2DM. Longitudinal studies with neuroendocrine measures are needed to better characterize its effects on stress regulation. FAU - Yu, Yang AU - Yu Y AUID- ORCID: 0000-0003-3635-1139 AD - School of Nursing, University of Rochester, Rochester, NY, USA. FAU - Groth, Susan AU - Groth S AD - School of Nursing, University of Rochester, Rochester, NY, USA. LA - eng PT - Journal Article DEP - 20260314 PL - United States TA - Metab Syndr Relat Disord JT - Metabolic syndrome and related disorders JID - 101150318 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology/psychology MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Allostasis/drug effects/physiology MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Adult MH - Nutrition Surveys MH - Biomarkers/blood MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Blood Glucose/metabolism/drug effects OTO - NOTNLM OT - GLP-1 receptor agonists OT - allostatic load OT - stress regulation OT - type 2 diabetes COIS- Author Disclosure StatementNo conflicting financial interests exist. EDAT- 2026/03/15 05:33 MHDA- 2026/05/12 12:35 CRDT- 2026/03/14 06:23 PHST- 2026/05/12 12:35 [medline] PHST- 2026/03/15 05:33 [pubmed] PHST- 2026/03/14 06:23 [entrez] AID - 10.1177/15578518261431688 [doi] PST - ppublish SO - Metab Syndr Relat Disord. 2026 Jun;24(5):228-234. doi: 10.1177/15578518261431688. Epub 2026 Mar 14. PMID- 41830068 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260803 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 2 DP - 2026 Apr TI - Comparison of Semaglutide and Lifestyle Counselling for Weight Loss Using Multi-Site Electronic Health Records. PG - e70076 LID - 10.1111/cob.70076 [doi] AB - To evaluate the effectiveness of semaglutide compared with lifestyle counselling alone for weight loss in diabetic and non-diabetic patients with obesity. This multi-site, retrospective, observational study uses data from electronic health records which are part of the Greater Plains Collaborative (GPC) in a time-to-event analysis for comparative effectiveness. Participants were adults with obesity receiving semaglutide for a minimum of 16 weeks or lifestyle counselling with at least three sessions within the first 16 weeks. The primary outcome is incidence of 10% or greater reduction in weight from baseline. Of 3927 eligible participants, 615 were prescribed semaglutide and 3312 received lifestyle counselling. Following propensity score matching, each group (diabetic and non-diabetic) consisted of 120 and 495 participants, respectively. Hazard ratios for 10% weight loss were significantly higher from semaglutide for non-diabetic (1.63 [95% CI: 1.32, 2.01; p < 0.001]) and diabetic (2.45 [95% CI: 1.47, 4.09; p < 0.001]) populations. These data from our study suggest that semaglutide therapy compared with lifestyle counselling alone is more effective in achieving at least 10% weight loss. This information may be used to inform clinical practice guidelines and stimulate future research on the long-term effectiveness of various weight loss options for individuals with obesity. CI - (c) 2026 World Obesity Federation. FAU - Powell, William J B AU - Powell WJB AUID- ORCID: 0009-0001-1966-657X AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Mazzotti, Diego R AU - Mazzotti DR AD - Division of Medical Informatics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Herrmann, Stephen D AU - Herrmann SD AD - Kansas Center for Metabolism and Obesity Research, The University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Davis, Ann M AU - Davis AM AD - Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA. AD - Center for Children's Healthy Lifestyles & Nutrition, Kansas City, Missouri, USA. FAU - Mittendorfer, Bettina AU - Mittendorfer B AUID- ORCID: 0000-0003-0049-2677 AD - Departments of Medicine and Nutrition & Exercise Physiology, University of Missouri, School of Medicine, Columbia, Missouri, USA. FAU - Bruce, Jared AU - Bruce J AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Song, Xing AU - Song X AUID- ORCID: 0000-0002-3712-2904 AD - Department of Biomedical Informatics, Biostatistics, and Medical Epidemiology, University of Missouri School of Medicine, Columbia, Missouri, USA. FAU - Waitman, Lemuel R AU - Waitman LR AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. AD - Department of Biomedical Informatics, Biostatistics, and Medical Epidemiology, University of Missouri School of Medicine, Columbia, Missouri, USA. LA - eng GR - RI-MISSOURI-01-PS1/PCORI/Patient-Centered Outcomes Research Institute/United States GR - University of Missouri/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Counseling/methods MH - Diabetes Mellitus, Type 2 MH - Electronic Health Records MH - *Life Style MH - *Obesity/therapy/drug therapy MH - Retrospective Studies MH - *Semaglutide/therapeutic use MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - databases OT - glucagon-like peptide 1 (GLP-1) OT - lifestyle modifications EDAT- 2026/03/14 06:32 MHDA- 2026/03/14 06:33 CRDT- 2026/03/14 01:42 PHST- 2026/01/20 00:00 [revised] PHST- 2025/02/03 00:00 [received] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/03/14 06:33 [medline] PHST- 2026/03/14 06:32 [pubmed] PHST- 2026/03/14 01:42 [entrez] AID - 10.1111/cob.70076 [doi] PST - ppublish SO - Clin Obes. 2026 Apr;16(2):e70076. doi: 10.1111/cob.70076. PMID- 41829912 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 5 DP - 2026 Feb 26 TI - Nutritional Counseling Is Independently Associated with Greater Knowledge of Drug-Food Interactions in Patients with Type 2 Diabetes. LID - 10.3390/nu18050742 [doi] LID - 742 AB - Background: Type 2 diabetes mellitus (T2DM) is commonly managed with complex pharmacotherapy combined with dietary modification, which increases the risk of clinically relevant drug-food interactions (DFIs). Despite their potential impact on treatment efficacy and safety, patient knowledge of DFIs-particularly in the context of modern therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-remains insufficiently explored. Methods: This cross-sectional study assessed knowledge of DFIs among 103 adults with T2DM using a self-administered, expert-validated questionnaire. Data on sociodemographic characteristics, clinical variables, anti-diabetic therapy (including GLP-1 RAs), sources of education, and attendance at dietary consultations were collected. Knowledge scores were calculated based on correct responses and categorized into tertiles (low, moderate, high). Associations were analyzed using non-parametric tests. Multivariable logistic regression was performed to identify independent predictors of moderate-to-high DFI knowledge. Results: Substantial gaps in DFI knowledge were identified, particularly regarding interactions involving dietary fiber, dairy products, grapefruit juice, and nutrient deficiencies associated with long-term pharmacotherapy. Knowledge level was not significantly associated with age, educational attainment, diabetes duration, or GLP-1 RA use. Female sex was associated with higher knowledge in univariate analysis (p = 0.026); however, this association did not remain significant in the multivariable regression model. Attendance at at least one dietary consultation in the previous year was significantly associated with higher knowledge levels (p = 0.041) and remained an independent predictor in multivariable analysis (OR = 2.31; 95% CI: 1.04-5.15; p = 0.039). Most participants reported not receiving prior education on DFIs, while expressing a strong need for more frequent counseling. Conclusions: Patients with T2DM demonstrate insufficient knowledge of clinically relevant DFIs, including selected issues related to GLP-1 RA therapy. Attendance at structured dietary consultations was independently associated with higher levels of DFI knowledge; however, the directionality and causality of this relationship cannot be established. Given the cross-sectional design and the assessment of knowledge rather than behavioral or clinical outcomes, these findings should be interpreted as hypothesis-generating. Further longitudinal and interventional studies are required to determine whether improved DFI knowledge translates into meaningful changes in dietary behavior, treatment adherence, or metabolic outcomes. FAU - Korbela, Joanna AU - Korbela J AD - School of Health and Medical Sciences, VIZJA University, Okopowa 59, 01-043 Warsaw, Poland. FAU - Bialek, Agnieszka AU - Bialek A AUID- ORCID: 0000-0002-7879-300X AD - School of Health and Medical Sciences, VIZJA University, Okopowa 59, 01-043 Warsaw, Poland. AD - The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jablonna, Poland. LA - eng PT - Journal Article DEP - 20260226 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - Female MH - Male MH - Middle Aged MH - *Health Knowledge, Attitudes, Practice MH - Cross-Sectional Studies MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Food-Drug Interactions MH - *Counseling MH - Aged MH - Surveys and Questionnaires MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Patient Education as Topic PMC - PMC12987031 OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes education OT - drug-food interactions (DFIs) OT - nutritional support OT - patient knowledge OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/03/14 06:33 MHDA- 2026/03/14 06:34 PMCR- 2026/02/26 CRDT- 2026/03/14 01:10 PHST- 2025/12/22 00:00 [received] PHST- 2026/02/13 00:00 [revised] PHST- 2026/02/24 00:00 [accepted] PHST- 2026/03/14 06:34 [medline] PHST- 2026/03/14 06:33 [pubmed] PHST- 2026/03/14 01:10 [entrez] PHST- 2026/02/26 00:00 [pmc-release] AID - nu18050742 [pii] AID - nutrients-18-00742 [pii] AID - 10.3390/nu18050742 [doi] PST - epublish SO - Nutrients. 2026 Feb 26;18(5):742. doi: 10.3390/nu18050742. PMID- 41828377 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 5 DP - 2026 Feb 25 TI - Hypothesis: Nutrient Off-Loading and Ectopic Fat Reduction Reverse Insulin Resistance and Improve Cardiovascular Outcomes in Type 2 Diabetes-A Narrative Review. LID - 10.3390/ijms27052150 [doi] LID - 2150 AB - Insulin resistance in type 2 diabetes is associated with cardiovascular disease. Nutritional overload, hyperinsulinemia, and physical inactivity are the major etiological factors driving the development of insulin resistance. In an obesogenic environment, insulin resistance has been proposed to protect the body against toxic fuel overload, hyperinsulinemia-induced injury, and metabolic stress. Insulin resistance has been further hypothesized to defend the heart and blood vessels against fuel overload when an individual is chronically overeating. Recent landmark cardiovascular outcome trials in type 2 diabetes show major improvements in cardiovascular disease outcomes after treatment with GLP-1 receptor agonists or SGLT2 inhibitors. Bariatric surgery achieves even greater improvements in cardiovascular disease outcomes than treatments with these newer pharmacological agents. It had been previously predicted that glucose-lowering approaches that normalize whole-body energy balance have the greatest potential to improve cardiovascular outcomes in type 2 diabetes. This review hypothesizes that treatment with bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors lowers glucose and nutritional off-loading, normalizes whole-body energy balance, and reduces ectopic fat depositions. This plays a central role in the dramatic reduction in cardiovascular disease and the reversal of insulin resistance in type 2 diabetes, which are observed after these three treatments. FAU - Janssen, Joseph A M J L AU - Janssen JAMJL AUID- ORCID: 0000-0002-9363-6408 AD - Department of Internal Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. LA - eng PT - Journal Article PT - Review DEP - 20260225 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/metabolism/complications/therapy/drug therapy MH - *Insulin Resistance MH - Bariatric Surgery MH - *Cardiovascular Diseases/metabolism/etiology MH - Animals MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12984968 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - Western diet OT - bariatric surgery OT - blood glucose control OT - cardiovascular disease OT - ectopic fat OT - hyperinsulinemia OT - insulin resistance OT - metabolic stress OT - nutrient off-loading OT - nutritional overload OT - physical inactivity OT - superoxide OT - toxic fuel overload OT - type 2 diabetes COIS- The author declares no conflicts of interest. EDAT- 2026/03/14 06:34 MHDA- 2026/03/14 06:35 PMCR- 2026/02/25 CRDT- 2026/03/14 01:05 PHST- 2025/12/14 00:00 [received] PHST- 2026/02/19 00:00 [revised] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/03/14 06:35 [medline] PHST- 2026/03/14 06:34 [pubmed] PHST- 2026/03/14 01:05 [entrez] PHST- 2026/02/25 00:00 [pmc-release] AID - ijms27052150 [pii] AID - ijms-27-02150 [pii] AID - 10.3390/ijms27052150 [doi] PST - epublish SO - Int J Mol Sci. 2026 Feb 25;27(5):2150. doi: 10.3390/ijms27052150. PMID- 41825483 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 13 IP - 2 DP - 2026 Mar 3 TI - Genetic evidence for GLP1R agonists in non-ischaemic heart failure. LID - 10.1093/eschf/xvag077 [doi] LID - xvag077 AB - BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists reduce cardiovascular events in patients with obesity and diabetes, and recent trials demonstrate symptomatic and functional benefits in heart failure with preserved ejection fraction (HFpEF). Whether these benefits reflect glycaemic control, weight reduction, or additional mechanisms remains uncertain. METHODS: We performed drug-target Mendelian randomization (MR) using genetic variants in the GLP1R-locus to proxy GLP1R activation. MR estimates for GLP1R agonism were scaled to per 0.1 log-odds lower liability to type 2 diabetes (T2DM) and compared with general type 2 diabetes (T2DM) or body mass index (BMI) lowering effects. Summary statistics were obtained from the largest available GWAS of HF, non-ischaemic HF (ni-HF), ni-HFpEF, ni-HFrEF, and atrial fibrillation (AF). Primary inverse-variance weighted analysis was adjusted for multiple testing and validated via weighted median and MR-Egger sensitivity analyses. RESULTS: Genetically proxied GLP1R activation was associated with lower risk of overall HF [OR 0.96 (95% CI 0.95-0.98), P & .0002], ni-HF [0.94 (0.91-0.96), P & .0001], and ni-HFpEF [0.82 (0.74-0.90), P & .0001] per 0.1 log-odds lower T2DM liability. The GLP1R-proxied effects were greater than those expected from glycaemic lowering alone and were of comparable magnitude to those from BMI reduction. Associations for ni-HFrEF were directionally adverse but not significant. AF showed a nominal, exploratory association consistent with BMI lowering and driven by a single cis-BMI variant. CONCLUSIONS: This study provides genetic support for a protective association between GLP1R activation and HF, particularly ni-HFpEF, with effects beyond glycaemia. The magnitude and subtype specificity are consistent with contemporary trial evidence and support further evaluation of GLP1R agonism in cardio-metabolic HFpEF. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Le, Nhu Ngoc AU - Le NN AUID- ORCID: 0000-0002-9373-8404 AD - BHF Cardiovascular Research Centre, School of Cardiovascular & Metabolic Health, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. FAU - Gill, Dipender AU - Gill D AUID- ORCID: 0000-0001-7312-7078 AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK. FAU - Padmanabhan, Sandosh AU - Padmanabhan S AUID- ORCID: 0000-0003-3869-5808 AD - BHF Cardiovascular Research Centre, School of Cardiovascular & Metabolic Health, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. LA - eng GR - RE/18/6/34217/British Heart Foundation Centre of Excellence/ GR - SIPF00007/1/United Kingdom Research and Innovation Strength in Places Fund/ GR - Pontecorvo Chair of Pharmacogenomics endowment/ PT - Journal Article PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 9007-49-2 (DNA) SB - IM MH - Humans MH - *Heart Failure/genetics/drug therapy/physiopathology/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - *Stroke Volume/physiology MH - Mendelian Randomization Analysis MH - Diabetes Mellitus, Type 2/genetics/drug therapy/complications MH - *DNA/genetics MH - Genome-Wide Association Study PMC - PMC13043000 OTO - NOTNLM OT - BMI OT - Drug-target Mendelian randomization OT - GLP1RA OT - Glycemia OT - HFpEF OT - Non-ischaemic heart failure EDAT- 2026/03/14 00:31 MHDA- 2026/04/01 18:30 PMCR- 2026/03/14 CRDT- 2026/03/13 20:02 PHST- 2025/11/10 00:00 [received] PHST- 2026/01/28 00:00 [revised] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/04/01 18:30 [medline] PHST- 2026/03/14 00:31 [pubmed] PHST- 2026/03/13 20:02 [entrez] PHST- 2026/03/14 00:00 [pmc-release] AID - 8519583 [pii] AID - xvag077 [pii] AID - 10.1093/eschf/xvag077 [doi] PST - ppublish SO - ESC Heart Fail. 2026 Mar 3;13(2):xvag077. doi: 10.1093/eschf/xvag077. PMID- 41825212 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260831 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 5 DP - 2026 May TI - Tirzepatide versus semaglutide for the prevention of mild cognitive impairment, dementia, and Alzheimer's disease in type 2 diabetes: A real-world, retrospective cohort study. PG - 109306 LID - S1056-8727(26)00051-6 [pii] LID - 10.1016/j.jdiacomp.2026.109306 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in managing type 2 diabetes mellitus (T2DM) and provide metabolic and cardiovascular benefits. Their associations with neurocognitive outcomes in clinical populations remain uncertain. METHODS: We conducted a retrospective, population-based cohort study using de-identified electronic health records from the global TriNetX research network, predominantly comprising U.S.-based healthcare organizations. Adults with T2DM who initiated tirzepatide or semaglutide were included. Propensity score matching (1:1) was applied to balance baseline characteristics, including age, sex, race, and cardiometabolic and psychiatric comorbidities. Incident diagnoses of mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD) occurring at least 12 months after treatment initiation were assessed using risk ratios (RRs) and time-to-event analyses with Kaplan-Meier estimators. FINDINGS: A total of 290,606 patients initiated semaglutide and 44,471 initiated tirzepatide. After propensity score matching, each group included 44,470 patients. Compared with semaglutide, initiation of tirzepatide was associated with a lower risk of MCI (RR 0.12; 95% CI 0.06-0.22), dementia (RR 0.15; 95% CI 0.09-0.26), and AD (RR 0.48; 95% CI 0.22-1.01). Absolute risks were low for all outcomes, and separation of survival curves was more consistent for MCI than for dementia or AD. INTERPRETATION: In this real-world observational analysis of adults with T2DM, initiation of tirzepatide was associated with a lower incidence of MCI compared with semaglutide, whereas associations for dementia and AD were less consistent. These findings should be interpreted descriptively and as hypothesis-generating. Prospective randomized trials with longer follow-up and systematic neurocognitive assessment are needed to clarify whether, and under which conditions, incretin-based therapies influence neurocognitive outcomes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - da Silva, Anderson Matheus Pereira AU - da Silva AMP AD - Division of Biostatistics and Clinical Epidemiology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. Electronic address: anderson.mhps@icloud.com. FAU - Januario Campos Cardoso, Leonardo AU - Januario Campos Cardoso L AD - Department of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. FAU - Batista, Savio AU - Batista S AD - Department of Neurology, Grady Memorial Hospital, Emory University, Atlanta, GA, USA. FAU - Goncalves, Ocilio Ribeiro AU - Goncalves OR AD - Department of Medicine, Federal University of Piaui, Teresina, PI, Brazil. FAU - Paranhos, Thiago AU - Paranhos T AD - Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Teixeira, Ivan Petterson Santana AU - Teixeira IPS AD - Department of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. FAU - Guimaraes, Pedro Duarte AU - Guimaraes PD AD - Faculty of Medicine, Faculdade de Ciencias Medicas de Santos, Santos, Sao Paulo, SP, Brazil. FAU - Espinosa Franco, Beatriz AU - Espinosa Franco B AD - Department of Endocrinology, Hospital Alemao Oswaldo Cruz, Sao Paulo, SP, Brazil; Department of Endocrinology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil. FAU - Cal, Henrique AU - Cal H AD - Division of Neurology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. FAU - Salles, Joao Eduardo Nunes AU - Salles JEN AD - Division of Endocrinology, Department of Internal Medicina of Santa Casa of Sao Paulo Scholl of Medical Science, Sao Paulo, SP, Brazil. FAU - Perry, George AU - Perry G AD - Department of Neurosciences, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX, USA. FAU - Hoilund-Carlsen, Poul F AU - Hoilund-Carlsen PF AD - Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Santos, Diogo Haddad AU - Santos DH AD - Department of Neurology, Hospital Alemao Oswaldo Cruz, Sao Paulo, SP, Brazil; Division of Neurology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. Electronic address: dhaddadsantos@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260225 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Alzheimer Disease/prevention & control/epidemiology MH - Female MH - Retrospective Studies MH - *Cognitive Dysfunction/prevention & control/epidemiology/etiology MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Aged MH - *Dementia/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - Dementia OT - Mild cognitive impairment OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no financial or personal relationships with individuals or organizations that could inappropriately influence, or be perceived to influence, the work reported in this manuscript. EDAT- 2026/03/14 00:31 MHDA- 2026/04/12 04:37 CRDT- 2026/03/13 19:08 PHST- 2025/11/18 00:00 [received] PHST- 2026/01/06 00:00 [revised] PHST- 2026/02/22 00:00 [accepted] PHST- 2026/04/12 04:37 [medline] PHST- 2026/03/14 00:31 [pubmed] PHST- 2026/03/13 19:08 [entrez] AID - S1056-8727(26)00051-6 [pii] AID - 10.1016/j.jdiacomp.2026.109306 [doi] PST - ppublish SO - J Diabetes Complications. 2026 May;40(5):109306. doi: 10.1016/j.jdiacomp.2026.109306. Epub 2026 Feb 25. PMID- 41823026 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260812 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 46 IP - 4 DP - 2026 Apr TI - Early Adoption and Prescribing Patterns of Resmetirom: A Multi-Institutional National Analysis. PG - e70580 LID - 10.1111/liv.70580 [doi] AB - Resmetirom received FDA approval in March 2024 as the first therapy for noncirrhotic MASH with moderate-to-advanced fibrosis. This retrospective cohort study used the TriNetX Research Network to assess early prescribing patterns among 3712 patients across 44 healthcare organisations. The mean age was 57.6 years, 57% were female, and the mean BMI was 33.9 kg/m(2). The cohort was predominantly White (73.8%), with representation from Hispanic/Latino (11.7%) and Asian (8.1%) populations. MASLD and MASH diagnoses were documented in 72% and 56% of patients, while 15% carried cirrhosis codes. Common comorbidities included dyslipidaemia (55%), hypertension (52%) and type 2 diabetes (41%). GLP-1 receptor agonists were commonly prescribed, with semaglutide (n = 1124), tirzepatide (n = 842), dulaglutide (n = 391) and liraglutide (n = 203) representing the most frequently used agents. Among 19 643 treatment-eligible patients (1057 treated and 18 586 untreated), 5.4% received resmetirom. Treated patients were more frequently Asian or Hispanic and more likely to be prescribed GLP-1 receptor agonists, statins, metformin or ARBs (all p < 0.01). Early prescribing demonstrates preferential use among individuals with higher metabolic burden but reveals potential miscoding or off-label use and significant underutilization among eligible populations. CI - (c) 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Solpari, Kate AU - Solpari K AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Gouda, Zane AU - Gouda Z AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Saggese, Allysa AU - Saggese A AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Buckholz, Adam AU - Buckholz A AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Sharaiha, Reem Z AU - Sharaiha RZ AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Kumar, Sonal AU - Kumar S AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Kushner, Tatyana AU - Kushner T AUID- ORCID: 0000-0001-6663-6253 AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. AD - Division of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA. LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Retrospective Studies MH - Semaglutide MH - Tirzepatide/therapeutic use MH - United States MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins EDAT- 2026/03/13 06:52 MHDA- 2026/03/13 12:40 CRDT- 2026/03/13 05:43 PHST- 2026/02/05 00:00 [revised] PHST- 2025/09/18 00:00 [received] PHST- 2026/02/19 00:00 [accepted] PHST- 2026/03/13 12:40 [medline] PHST- 2026/03/13 06:52 [pubmed] PHST- 2026/03/13 05:43 [entrez] AID - 10.1111/liv.70580 [doi] PST - ppublish SO - Liver Int. 2026 Apr;46(4):e70580. doi: 10.1111/liv.70580. PMID- 41820778 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 5 DP - 2026 May TI - Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials. PG - 2090-2105 LID - 10.1007/s12325-026-03523-5 [doi] AB - INTRODUCTION: Recent pharmacological options for weight management include the glucagon-like peptide 1 (GLP-1) receptor agonists semaglutide and liraglutide, and the glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide, but head-to-head comparisons of all three of these interventions are lacking. METHODS: Based on a systematic literature review (SLR) and Bayesian network meta-analysis (NMA), the efficacy and safety of semaglutide 2.4 mg, liraglutide 3 mg and tirzepatide 5, 10 and 15 mg were compared in adults without type 2 diabetes, and with either obesity (body mass index [BMI] >/= 30 kg/m(2)) or overweight (BMI >/= 27 kg/m(2)) with >/= 1 obesity-related complication. RESULTS: Following a stringent heterogeneity assessment, six of 42 randomised controlled trials identified in the SLR were included in the NMA. Efficacy estimand results showed all tirzepatide doses were associated with statistically greater improvements in weight reduction outcomes versus liraglutide, and for tirzepatide 10 and 15 mg versus semaglutide: including percentage weight reduction (- 12.86% for tirzepatide 10 mg and - 13.95% for tirzepatide 15 mg versus liraglutide; - 4.85% and - 6.26% versus semaglutide) and waist circumference (- 11.79 cm and - 12.30 cm versus liraglutide; - 4.81 cm and - 5.32 cm versus semaglutide). All tirzepatide doses were associated with statistically greater improvements in triglycerides and diastolic blood pressure versus liraglutide, and generally comparable improvements in other glycaemic, lipid and blood pressure parameters versus liraglutide and semaglutide. All interventions had a comparable safety profile. CONCLUSION: In this NMA, tirzepatide 10 and 15 mg were associated with improved efficacy versus liraglutide, improved or comparable efficacy versus semaglutide, and all interventions had a generally comparable safety profile for achieving weight reduction and reducing cardiometabolic risk factors among patients with obesity or overweight. CI - (c) 2026. The Author(s). FAU - Ciudin, Andreea AU - Ciudin A AUID- ORCID: 0000-0001-5622-0203 AD - Endocrinology and Nutrition, Vall d'Hebron University Hospital, Pg. de la Vall d'Hebron, 119, 08035, Barcelona, Spain. FAU - Sapin, Helene AU - Sapin H AUID- ORCID: 0000-0003-2602-8450 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Fan, Ludi AU - Fan L AUID- ORCID: 0000-0001-9298-8025 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AUID- ORCID: 0000-0002-6662-804X AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Zimner-Rapuch, Sarah AU - Zimner-Rapuch S AUID- ORCID: 0009-0008-6687-1921 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Curteis, Tristan AU - Curteis T AD - Costello Medical, 1 New York St, Manchester, M1 4HD, UK. FAU - Clark, Laura J AU - Clark LJ AUID- ORCID: 0000-0003-4378-2420 AD - Costello Medical, 1 New York St, Manchester, M1 4HD, UK. FAU - Rubinstein, Manon AU - Rubinstein M AD - Costello Medical, 8 Emerson Street, London, SE1 9DU, UK. FAU - Johansson, Erin AU - Johansson E AUID- ORCID: 0009-0006-3178-1622 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. johansson_erin@lilly.com. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260312 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Tirzepatide MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - *Liraglutide/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - Bayes Theorem MH - Diabetes Mellitus, Type 2 MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Anti-Obesity Agents/therapeutic use PMC - PMC13156185 OAB - Obesity management is crucial for reducing the health risks associated with obesity, and comprises of behavioural interventions, psychological support, dietary changes and physical activity programs. Medications may also be prescribed, or surgical options may also be considered. Three such medications for weight management are injectable weekly treatments tirzepatide and semaglutide, or daily liraglutide, which help to control appetite by prolonging patients' feeling of fullness. Because there are no clinical trials directly comparing tirzepatide and liraglutide, and no trials comparing all three medications, this study aimed to indirectly compare the effectiveness and safety of tirzepatide, semaglutide and liraglutide for weight management in patients without type 2 diabetes, who also have obesity or overweight. A systematic review of literature identified all published clinical trials reporting on tirzepatide, semaglutide and liraglutide. Following strict eligibility criteria, six suitable randomised controlled trials were chosen for analysis. These studies had similar designs and patients, making it possible to compare their results meaningfully. Tirzepatide demonstrated improved results across various outcomes, including weight loss and cardiometabolic health factors compared with liraglutide. Compared with semaglutide, the higher doses of tirzepatide demonstrated consistent improvements in weight reduction and cardiometabolic health factors, whilst the lower dose was broadly comparable with semaglutide. The safety profile of tirzepatide was generally similar to both liraglutide and semaglutide. Overall, the analysis supports the clinical effectiveness and safety of tirzepatide compared with liraglutide and semaglutide in weight reduction and other clinical outcomes associated with weight management in patients with obesity or overweight. OABL- eng OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Network meta-analysis OT - Obesity OT - Overweight OT - Tirzepatide OT - Weight reduction COIS- Declarations. Conflict of Interest: Andreea Ciudin: Honoraria from AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk; Member of the DMC of Boehringer Ingelheim clinical trials-SYNCRONIZE program; Helene Sapin, Ludi Fan, Georgios K. Dimitriadis, Sarah Zimner-Rapuch, Erin Johansson: Employees and shareholders of Eli Lilly and Company; Tristan Curteis, Laura J. Clark, Manon Rubinstein: Employees of Costello Medical, which received payment from Eli Lilly and Company for analytical services for this study. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2026/03/13 06:52 MHDA- 2026/05/08 12:38 PMCR- 2026/03/12 CRDT- 2026/03/13 00:46 PHST- 2025/10/23 00:00 [received] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/05/08 12:38 [medline] PHST- 2026/03/13 06:52 [pubmed] PHST- 2026/03/13 00:46 [entrez] PHST- 2026/03/12 00:00 [pmc-release] AID - 10.1007/s12325-026-03523-5 [pii] AID - 3523 [pii] AID - 10.1007/s12325-026-03523-5 [doi] PST - ppublish SO - Adv Ther. 2026 May;43(5):2090-2105. doi: 10.1007/s12325-026-03523-5. Epub 2026 Mar 12. PMID- 41820018 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1744-7674 (Electronic) IS - 1354-3776 (Linking) VI - 36 IP - 5 DP - 2026 May TI - Patent landscape and therapeutic evolution of mazdutide: a dual GLP-1/Glucagon receptor agonist for obesity and type 2 diabetes. PG - 459-469 LID - 10.1080/13543776.2026.2645812 [doi] AB - INTRODUCTION: Mazdutide is a dual glucagon-like peptide-1 receptor (GLP-1 R) and glucagon receptor (GCGR) agonist representing a new generation of incretin-based therapeutics for obesity and type 2 diabetes. While its clinical efficacy is increasingly recognized, the intellectual property framework that underpins its development and long-term positioning has not been systematically examined. AREAS COVERED: This review presents a comprehensive patent landscape analysis of mazdutide and related oxyntomodulin analogs. Patent documents were identified using the Patentscope database, covering filings between 2015 and 2025. Twelve patent families were analyzed, encompassing composition-of-matter, process chemistry, formulation technologies, dosing regimens, and therapeutic applications. The analysis traces the evolution of innovation from early peptide design by Eli Lilly to later formulation, clinical, and indication-expansion strategies led by Innovent Biologics, including obesity, type 2 diabetes, hyperuricemia, and adolescent obesity. EXPERT OPINION: Mazdutide illustrates how layered patent strategies integrating molecular design, manufacturability, formulation stability, and clinical use claims can secure durable exclusivity. This approach provides a strategic model for future dual and multi-receptor peptide therapeutics. FAU - Abdul Fasi, Mohammed AU - Abdul Fasi M AD - Research Administrative Operations, Innovation and Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260329 PL - England TA - Expert Opin Ther Pat JT - Expert opinion on therapeutic patents JID - 9516419 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Glucagon) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) SB - IM MH - Humans MH - Patents as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/physiopathology MH - Animals MH - Receptors, Glucagon/agonists MH - Drug Design MH - Anti-Obesity Agents/pharmacology/administration & dosage MH - Hypoglycemic Agents/pharmacology/administration & dosage MH - Drug Development MH - Peptides OTO - NOTNLM OT - Mazdutide OT - dual GLP-1/glucagon receptor agonist OT - oxyntomodulin analog OT - patent landscape OT - peptide therapeutics EDAT- 2026/03/13 00:50 MHDA- 2026/05/04 12:33 CRDT- 2026/03/12 22:32 PHST- 2026/05/04 12:33 [medline] PHST- 2026/03/13 00:50 [pubmed] PHST- 2026/03/12 22:32 [entrez] AID - 10.1080/13543776.2026.2645812 [doi] PST - ppublish SO - Expert Opin Ther Pat. 2026 May;36(5):459-469. doi: 10.1080/13543776.2026.2645812. Epub 2026 Mar 29. PMID- 41819195 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260713 IS - 1873-2763 (Electronic) IS - 1873-2763 (Linking) VI - 207 DP - 2026 Jun TI - Association between glucagon-like peptide-1 receptor agonists and femur fracture risk in type 2 diabetes: A large-scale target trial emulation. PG - 117851 LID - S8756-3282(26)00077-3 [pii] LID - 10.1016/j.bone.2026.117851 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) paradoxically increases fracture risk despite normal or elevated bone mineral density. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise in bone health, evidence remains controversial. This large-scale real-world study evaluated the primary outcome of femur fracture risk associated with GLP-1 RAs versus dipeptidyl peptidase-4 inhibitors (DPP-4is) in T2DM patients using a rigorous target trial emulation approach. METHODS: This retrospective cohort study adopted a large-scale target trial emulation framework with a new-user, active-comparator design using data from the TriNetX US Collaborative Network. Adults (>/=18 years) with T2DM identified between 2018 and 2022 (n = 3,620,983) were classified as GLP-1 RA (n = 491,936) or DPP-4i (n = 345,484) users at treatment initiation. Propensity score matching (PSM) was performed to emulate random assignment and balance baseline characteristics. Cox proportional-hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for bone fractures during a maximum 5-year follow-up. RESULTS: After 1:1 PSM, each cohort included 172,381 patients (mean age 59 years; 51% male) with a mean follow-up of 40 months. GLP-1 RA users demonstrated significantly lower femoral fracture risk compared to DPP-4i users (HR 0.91, 95% CI 0.85-0.98), with consistent protective effects across all sensitivity analyses. Similar associations were observed when comparing GLP-1 RAs with most other antidiabetic medications. CONCLUSIONS: GLP-1 RA use was associated with a modest reduction in femur fracture risk. However, given the observational design, possible residual confounding, and multiple testing, these findings are exploratory and require prospective confirmation before clinical application. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Chang, Yao-Jen AU - Chang YJ AD - Department of Plastic Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan. FAU - Fuh, Chiou-Shann AU - Fuh CS AD - Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan. FAU - Chang, Jie-Fan AU - Chang JF AD - Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan. FAU - Chen, Meng-Ting AU - Chen MT AD - Data Analytics Team, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AD - Data Analytics Team, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Electronic address: chaosmyth.tw@gmail.com.tw. LA - eng PT - Journal Article DEP - 20260310 PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Femoral Fractures/epidemiology/etiology MH - Aged MH - Retrospective Studies MH - Risk Factors MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Bone fracture OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Real-world data OT - Target trial emulation OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/03/13 00:50 MHDA- 2026/04/09 00:34 CRDT- 2026/03/12 20:11 PHST- 2026/01/05 00:00 [received] PHST- 2026/02/25 00:00 [revised] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/04/09 00:34 [medline] PHST- 2026/03/13 00:50 [pubmed] PHST- 2026/03/12 20:11 [entrez] AID - S8756-3282(26)00077-3 [pii] AID - 10.1016/j.bone.2026.117851 [doi] PST - ppublish SO - Bone. 2026 Jun;207:117851. doi: 10.1016/j.bone.2026.117851. Epub 2026 Mar 10. PMID- 41818791 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 104 DP - 2026 Jan 1 TI - The potential for complex interplay between GLP-1 receptor agonists, gut microbiome, and obesity management. PG - 1-8 LID - 10.1139/cjpp-2025-0219 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications used to treat and manage type 2 diabetes mellitus (T2DM) and obesity. The present narrative review explores potential interactions between the gut microbiome and GLP-1 RAs. Limited research has been conducted at the intersection of the gut microbiome and GLP-1 RA therapy. Therefore, this review focuses on potential relationships among GLP-1 RA, the microbiome, body weight, dietary changes, and gastrointestinal symptoms. The review of the current literature reveals significant gaps, particularly concerning the role of diet in mediating or confounding any impact of GLP-1 RA medications on the gut microbiome. Therefore, the body of the review is structured as a series of proposed directional and causal relationships. The limited available evidence suggests changes in behavior, diet, and weight loss resulting from GLP-1 RA treatment are the primary drivers of microbiome changes observed after GLP-1 RA treatment. The review concludes by proposing directions for future studies to clarify the complex interplay between GLP-1 RAs, the gut microbiome, diet, and obesity management. FAU - Johnson, Abigail J AU - Johnson A AUID- ORCID: 0000-0002-5998-4724 AD - Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. RINGGOLD: 5635 AD - Riddet Institute, Massey University, Palmerston North, New Zealand. FAU - O'Sullivan, Erin N AU - O'Sullivan E AD - Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN, USA. FAU - Valyasevi, Peerada AU - Valyasevi P AD - Faculty of Medicine, Thammasat University, Bangkok, Thailand. FAU - Metras, Breanna AU - Metras B AD - Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. RINGGOLD: 5635 FAU - Jang, Subin AU - Jang S AD - Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. RINGGOLD: 5635 FAU - Shields-Cutler, Robin AU - Shields-Cutler R AD - Department of Biology, Macalester College, St. Paul, MN, USA. AD - Division of Surgical Outcomes and Precision Medicine, Department of Surgery, University of Minnesota, Minneapolis, MN, USA. FAU - Hendel, Katherine R AU - Hendel K AD - Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. RINGGOLD: 5635 FAU - Harindhanavudhi, Tasma AU - Harindhanavudhi T AD - Division of Diabetes, Endocrinology, and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Teigen, Levi AU - Teigen L AD - Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN, USA. LA - eng PT - Journal Article PT - Review PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastrointestinal Microbiome/drug effects MH - *Obesity/drug therapy/microbiology/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/microbiology MH - *Obesity Management/methods MH - *Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - GLP-1 receptor agonists OT - incretins OT - microbiome COIS- The authors declare there are no competing interests. EDAT- 2026/03/12 18:53 MHDA- 2026/04/06 12:36 CRDT- 2026/03/12 17:43 PHST- 2026/04/06 12:36 [medline] PHST- 2026/03/12 18:53 [pubmed] PHST- 2026/03/12 17:43 [entrez] AID - 10.1139/cjpp-2025-0219 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2026 Jan 1;104:1-8. doi: 10.1139/cjpp-2025-0219. PMID- 41818107 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 3 DP - 2026 Mar TI - Semaglutide Hype or Hope: Evidence-based Review in Diabesity. PG - 103-107 LID - 10.59556/japi.74.1439 [doi] AB - India is struggling with the twin epidemics of diabetes and weight issues, holding the second position globally in the former and third in the latter. Despite multiple advancements with therapies that offer glycemic control and weight benefits, there has remained a gap for a comprehensive drug for the management of "diabesity." Semaglutide, since its global approval in 2017, has become a blockbuster, owing to the popularity of "Ozempic." While Ozempic has been traditionally approved for glycemic control in type 2 diabetes mellitus (T2DM), it does offer significant other benefits powerful weight loss, cardiovascular benefits, renal protection benefits, and functional improvement in peripheral arterial disease. The drug is approved in India for first-line use in adults with T2DM as an adjunct to diet and exercise. The long use of semaglutide globally and in India has ensured adequate data on efficacy and safety, ensuring confidence and trust. Gastrointestinal side effects are the most common adverse events seen with the molecule, as with other GLP-1 drugs. This review highlights the global clinical data and practicalities of the use of Ozempic in diabesity in the Indian context. CI - (c) Journal of The Association of Physicians of India 2026. FAU - Gupta, Sunil AU - Gupta S AD - Managing Director, Department of Diabetology, Nagpur, Maharashtra, India, Corresponding Author. FAU - Makkar, Brij Mohan AU - Makkar BM AD - Senior Physician, Diabetologist and Obesity Specialist, Dr Makkar's Diabetes and Obesity Centre, Delhi, India. FAU - Kesavadev, Jothydev AU - Kesavadev J AD - Chairman and Managing Director, Jothydev's Diabetes Research Center, Trivandrum, Kerala, India. FAU - Kumar, Ajay AU - Kumar A AD - Senior Diabetologist, Diabetes Care and Research Centre, Patna, Bihar, India. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - India MH - *Obesity/drug therapy EDAT- 2026/03/12 18:52 MHDA- 2026/03/12 18:53 CRDT- 2026/03/12 12:57 PHST- 2026/03/12 18:53 [medline] PHST- 2026/03/12 18:52 [pubmed] PHST- 2026/03/12 12:57 [entrez] AID - 10.59556/japi.74.1439 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Mar;74(3):103-107. doi: 10.59556/japi.74.1439. PMID- 41817629 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20261023 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 37 IP - 9 DP - 2026 Sep 1 TI - Cardiovascular Outcomes among New Users of GLP-1 Receptor Agonists Compared with DPP-4 Inhibitors and Sulfonylureas in Kidney Failure. PG - 1992-2003 LID - 10.1681/ASN.0000001061 [doi] AB - KEY POINTS: Glucagon-like peptide-1 receptor agonists are increasingly used in patients with kidney failure despite trial exclusion. Initiation was associated with a 13% lower risk of cardiovascular events and 17% lower mortality versus dipeptidyl peptidase-4 inhibitors. Initiation was associated with a 10% lower risk of heart failure hospitalization versus dipeptidyl peptidase-4 inhibitors. BACKGROUND: Few therapies improve cardiovascular outcomes for people with kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular risk in patients with non-dialysis-dependent CKD, but the cardiovascular benefits in patients with kidney failure remain uncertain. The objective of this study was to compare cardiovascular outcomes among patients with kidney failure and type 2 diabetes newly initiated on GLP-1 RA versus other antiglycemic agents. METHODS: We analyzed electronic health records, Medicare claims, and Part D data from the United States Renal Data System (2011-2021) to identify new users of GLP-1 RA ( n =3629), dipeptidyl peptidase-4 inhibitors (DPP4i; n =21,369), and sulfonylureas ( n =32,296) among patients with type 2 diabetes receiving maintenance dialysis. For the primary analysis, we performed 1:1 propensity score matching of GLP-1 RA to DPP4i initiators using 61 covariates. A prespecified secondary analysis compared propensity score-matched initiators of GLP-1 RA and sulfonylureas. The primary outcome was a modified major adverse cardiovascular event (MACE) composite of myocardial infarction, stroke, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome and hospitalizations for heart failure. Cause-specific Cox models were used to estimate hazard ratios (HRs). RESULTS: Among 3284 matched pairs of GLP-1 RA and DPP4i initiators, GLP-1 RA use was associated with lower risks of MACE (HR, 0.87; 95% confidence interval [CI], 0.78 to 0.97), all-cause mortality (HR, 0.83; 95% CI, 0.74 to 0.94), and heart failure hospitalization (HR, 0.90; 95% CI, 0.83 to 0.99) over up to 2 years of follow-up. Among 2792 matched pairs, GLP-1 RA and sulfonylurea initiators, GLP-1 RA was associated with lower risks of MACE (HR, 0.83; 95% CI, 0.74 to 0.93) and all-cause mortality (HR, 0.80; 95% CI, 0.69 to 0.91). CONCLUSIONS: Among patients with type 2 diabetes receiving maintenance dialysis, GLP-1 RA initiation was associated with lower risk of cardiovascular events and all-cause mortality compared with other commonly prescribed antiglycemic agents. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2026_06_12_ASN0000001061.mp3. CI - Copyright (c) 2026 by the American Society of Nephrology. FAU - Catanese, Benjamin AU - Catanese B AUID- ORCID: 0009-0000-7734-6550 AD - Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. FAU - Miller, Cameron AU - Miller C AUID- ORCID: 0000-0001-5744-3038 AD - Department of Medicine, Duke University School of Medicine, Durham, North Carolina. FAU - Wolf, Myles AU - Wolf M AUID- ORCID: 0000-0002-1127-1442 AD - Weill Department of Medicine, Weill Cornell Medicine, New York, New York. FAU - Edmonston, Daniel AU - Edmonston D AUID- ORCID: 0000-0003-2589-6993 AD - Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. LA - eng GR - TL1 DK139567/DK/NIDDK NIH HHS/United States GR - U2C DK133491/DK/NIDDK NIH HHS/United States GR - School of Medicine, Duke University/ PT - Comparative Study PT - Journal Article DEP - 20260312 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sulfonylurea Compounds/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology/mortality MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Renal Insufficiency/complications MH - Heart Failure MH - Aged, 80 and over MH - United States/epidemiology MH - *Kidney Failure, Chronic/complications MH - Hospitalization/statistics & numerical data PMC - PMC13240616 MID - NIHMS2176563 OTO - NOTNLM OT - ESKD OT - GLP-1 receptor agonists OT - cardiovascular disease OT - cardiovascular events OT - diabetes mellitus OT - heart failure COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F753. EDAT- 2026/03/12 18:53 MHDA- 2026/09/01 17:39 PMCR- 2026/09/01 CRDT- 2026/03/12 12:05 PHST- 2025/11/03 00:00 [received] PHST- 2026/03/09 00:00 [accepted] PHST- 2026/09/01 17:39 [medline] PHST- 2026/03/12 18:53 [pubmed] PHST- 2026/03/12 12:05 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - 00001751-202609000-00015 [pii] AID - JASN-2025-001479 [pii] AID - 10.1681/ASN.0000001061 [doi] PST - ppublish SO - J Am Soc Nephrol. 2026 Sep 1;37(9):1992-2003. doi: 10.1681/ASN.0000001061. Epub 2026 Mar 12. PMID- 41817564 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 1998-3689 (Electronic) IS - 0301-4738 (Print) IS - 0301-4738 (Linking) VI - 74 IP - 7 DP - 2026 Jul 1 TI - Ocular complications associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) - Clinical evidence and insights. PG - 974-981 LID - 10.4103/IJO.IJO_2659_25 [doi] AB - Type 2 diabetes mellitus (T2DM) and obesity are commonly treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, there have been growing concerns over the possibility that these medications may result in ocular adverse events, such as nonarteritic anterior ischemic optic neuropathy (NAION). Standard clinical care can overlook these potentially fatal adverse effects. The purpose of this review was to compile the most recent data on ocular side effects associated with GLP-1 RA therapy, assess their clinical relevance, and highlight necessary preventative and monitoring measures. A thorough search of the literature was conducted using Medline/PubMed/PMC, Google Scholar, Scopus, Web of Science, and ScienceDirect. Relevant literature, including observational studies, randomized trials, case reports, and pharmacovigilance data, was selected for its discussion of GLP-1 RAs and associated eye-related adverse events. Semaglutide, a GLP-1 RA, has been associated in a number of studies and safety assessments with an increased risk of NAION and the progression of diabetic retinopathy, especially in patients with underlying eye disorders. Findings, however, were mixed because no statistically significant link was found in a number of cohort studies and meta-analyses. The necessity for additional research was supported by data from adverse event reporting systems that showed disproportionality signals. Clinicians should be mindful of the potential ocular hazards associated with GLP-1 RAs, even though these medications remain useful in treating T2DM and obesity. Closer ophthalmologic monitoring may be beneficial for patients with known diabetic eye problems. Further prospective research with well-defined ocular outcomes is required to elucidate these correlations and guarantee the secure administration of GLP-1 RAs. CI - Copyright (c) 2026 Indian Journal of Ophthalmology. FAU - Maideen, Naina Mohamed Pakkir AU - Maideen NMP AD - Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE. FAU - Al Rashid, Sulthan AU - Al Rashid S AD - Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Department of Pharmacology, Chennai, Tamil Nadu, India. FAU - Balasubramanian, Rajkapoor AU - Balasubramanian R AD - Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India. FAU - Amirthalingam, Palanisamy AU - Amirthalingam P AD - Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260312 PL - India TA - Indian J Ophthalmol JT - Indian journal of ophthalmology JID - 0405376 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Semaglutide MH - Diabetic Retinopathy/chemically induced MH - *Optic Neuropathy, Ischemic/chemically induced MH - Glucagon-Like Peptides/adverse effects PMC - PMC13422913 OTO - NOTNLM OT - Diabetic retinopathy progression OT - GLP-1 receptor agonists OT - glucagon-like peptide-1 OT - ischemic optic neuropathy OT - macular edema OT - nonarteritic anterior ischemic optic neuropathy OT - ocular complications OT - semaglutide OT - tirzepatide COIS- There are no conflicts of interest. EDAT- 2026/03/12 13:55 MHDA- 2026/06/30 18:42 PMCR- 2026/07/01 CRDT- 2026/03/12 11:43 PHST- 2024/10/18 00:00 [received] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/06/30 18:42 [medline] PHST- 2026/03/12 13:55 [pubmed] PHST- 2026/03/12 11:43 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 02223307-990000000-00446 [pii] AID - IJO-74-974 [pii] AID - 10.4103/IJO.IJO_2659_25 [doi] PST - ppublish SO - Indian J Ophthalmol. 2026 Jul 1;74(7):974-981. doi: 10.4103/IJO.IJO_2659_25. Epub 2026 Mar 12. PMID- 41816857 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide. PG - 4795-4805 LID - 10.1111/dom.70660 [doi] AB - AIMS: To describe obesity treatments in real-world settings after discontinuation of semaglutide or tirzepatide and variability in weight change post-discontinuation. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2021, to 30 June 2025, in a large health system in Ohio and Florida. Adults with overweight or obesity who initiated injectable semaglutide or tirzepatide for obesity or T2D between 2021 and 2023 and discontinued the medication within 3-12 months were included. Main outcomes were reinitiation of the index medication or receipt of an alternative treatment, body weight changes from baseline to index medication discontinuation and from discontinuation to 1-year post discontinuation. RESULTS: A total of 7938 patients (mean [SD] age, 55.7 [13.4] years; 5061 [63.8%] female) were identified. During 1-year post-discontinuation, 19.6% restarted the index medication and 35.2% received an alternative obesity treatment, including starting another medication (27.4%), lifestyle modification visit (13.7%) and metabolic and bariatric surgery (0.6%). Mean percentage weight change from baseline to discontinuation was -8.4% [95% CI, -8.7%, -8.1%] when treating obesity and -4.4% [95% CI, -4.7%, -4.2%] when treating T2D. Mean percentage weight change from discontinuation to 1 year later was 0.5% [95% CI, 0.0%, 1.0%] when treating obesity and -1.3% [95% CI, -1.6%, -1.0%] when treating T2D; however, there was considerable individual-level variability. CONCLUSION: In this large sample of patients who discontinued semaglutide or tirzepatide, reinitiation of the original medication or receipt of alternative obesity treatment was common. The average weight change 1-year post-discontinuation was relatively small; however, there was considerable individual-level variability. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Boyer, Christopher B AU - Boyer CB AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. FAU - Aminian, Ali AU - Aminian A AUID- ORCID: 0000-0001-5756-9917 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Griebeler, Marcio L AU - Griebeler ML AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Department, Medical Specialty Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Burguera, Bartolome AU - Burguera B AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Department, Medical Specialty Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. LA - eng GR - MAG0030/Cleveland Clinic - Jack, Joseph and Morton Mandel Accelerator Grants/ PT - Journal Article DEP - 20260312 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - Female MH - *Obesity/drug therapy/therapy MH - Retrospective Studies MH - Middle Aged MH - Male MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Aged MH - Adult MH - Florida MH - Ohio MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13146129 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - lifestyle modification OT - long-term weight outcomes OT - metabolic and bariatric surgery OT - obesity pharmacotherapy OT - treatment discontinuation COIS- Dr. Hamlet Gasoyan reported receiving grant funding from the National Cancer Institute outside the submitted work. Dr. Christopher B. Boyer reports consulting fees from Janssen Pharmaceuticals outside the submitted work. Dr. W. Scott Butsch is currently employed by Novo Nordisk A/S; he also reported advisory board fees from Eli Lilly, Boehringer Ingelheim and Abbott and research funding from Eli Lilly and Co outside the submitted work. Dr. Ali Aminian reported receiving research grants from Amgen, Ethicon and Medtronic outside the submitted work. He serves as a consultant for Amylyx, Eli Lilly, Ethicon and Medtronic. Dr. Marcio L. Griebeler reported research funding from Novo Nordisk A/S outside the submitted work. Dr. Michael B. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. The other authors declare no conflicts of interest. EDAT- 2026/03/12 07:03 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/12 05:43 PHST- 2026/03/03 00:00 [revised] PHST- 2026/01/29 00:00 [received] PHST- 2026/03/04 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/12 07:03 [pubmed] PHST- 2026/03/12 05:43 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70660 [pii] AID - 10.1111/dom.70660 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4795-4805. doi: 10.1111/dom.70660. Epub 2026 Mar 12. PMID- 41815966 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 14 DP - 2026 TI - Quality and reliability of semaglutide content on different Chinese short video platforms: a study focusing on side effects. PG - 1750738 LID - 10.3389/fpubh.2026.1750738 [doi] LID - 1750738 AB - OBJECTIVE: This study aims to evaluate the quality, reliability, and content characteristics of semaglutide-related short videos on three major Chinese short-video platforms (Bilibili, TikTok, and Rednote), with a focus on exploring differences in the presentation of side effects across different platforms and uploader types. Rather than examining specific clinical indications or dosing regimens, this study focuses on how semaglutide-related information is presented to the general public in real-world short-video contexts. It seeks to clarify the impact of platform ecology and creator identity on drug information dissemination, thereby providing a basis for optimizing the quality of online health information and conducting targeted public health communication. METHODS: A cross-sectional content analysis was adopted. Semaglutide-related videos were retrieved from three major Chinese short-video platforms using the Chinese keyword "" (the standard Mandarin term for "semaglutide"). This exact search term was used to simulate real-world user behavior and ensure reproducibility across platforms. Because most videos did not specify approved indications (type 2 diabetes vs. obesity) or dosage levels, analyses were conducted without stratification by clinical dose or indication. After rigorous screening, eligible videos were assessed for quality and reliability using the modified DISCERN scale and Global Quality Score (GQS). Video content was categorized into five thematic dimensions, and mentions of nine predefined side effects were systematically recorded. A dual-perspective analytical approach-comparing the full sample and a side effect-focused subsample-was employed to examine platform-based differences in adverse event portrayal. RESULTS: A total of 607 semaglutide-related videos were included (Bilibili: 309, TikTok: 153, Rednote: 145). The results showed significant differences in content quality (M-DISCERN and GQS scores), video duration, and user engagement metrics across platforms (p < 0.05). There were statistically significant differences in content distribution among platforms (p < 0.05): Bilibili focused on Policy News and Events, Personal Experience Sharing, and Commercial Promotion; Rednote centered on Medication Education and Medical Advice/Medication Guidance; TikTok mainly focused on Policy News and Events. Regarding side effects, the distribution of gastrointestinal and hepatobiliary side effects among the three platforms was statistically significant (p < 0.05), with TikTok having the highest mention rate. These side effect narratives were typically presented without reference to specific dosing levels or approved indications. The dual-perspective analysis further revealed systematic differences in side effect portrayal, with TikTok conferring greater visibility for adverse-event narratives. In terms of content quality, the three platforms showed a gradient difference of "Rednote > TikTok > Bilibili" (p < 0.001). CONCLUSION: The quality and reliability of semaglutide-related short videos are significantly influenced by platform ecology. Publicly accessible drug information on short-video platforms often lacks clear differentiation between approved indications and dosage regimens, contributing to generalized interpretations of drug risks. The drug information accessible to the public exhibits structural biases, with side effect narratives demonstrating a clear "platformization" pattern. The dual-perspective analysis revealed that inter-platform differences in the portrayal of specific adverse events (e.g., gastrointestinal and hepatobiliary effects) were more discernible in the side effect-focused subsample. Future interventions should be tailored to platform-specific features to enhance the completeness and scientific rigor of online pharmaceutical information. CI - Copyright (c) 2026 Song, He, Cui, Sun, Liu, Yu, Li and Jin. FAU - Song, Jiayuan AU - Song J AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - He, Xingchen AU - He X AD - The Affiliated Guangzhou Hospital of TCM of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Cui, Zhenhai AU - Cui Z AD - Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China. FAU - Sun, Ye AU - Sun Y AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Liu, Yanlin AU - Liu Y AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Yu, Han AU - Yu H AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Li, Aimin AU - Li A AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Jin, Meiying AU - Jin M AD - Department of Endocrine Metabolism and Spleen and Stomach, The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China. LA - eng PT - Journal Article DEP - 20260224 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - China MH - Cross-Sectional Studies MH - Diabetes Mellitus, Type 2/drug therapy MH - Digital Media MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Information Dissemination/methods MH - Reproducibility of Results MH - Semaglutide MH - *Video Recording PMC - PMC12971943 OTO - NOTNLM OT - content characteristics OT - creator identity OT - information quality OT - semaglutide OT - short-video platforms OT - side effects COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/12 07:03 MHDA- 2026/03/12 13:56 PMCR- 2026/02/24 CRDT- 2026/03/12 05:13 PHST- 2025/11/20 00:00 [received] PHST- 2026/02/01 00:00 [revised] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/03/12 13:56 [medline] PHST- 2026/03/12 07:03 [pubmed] PHST- 2026/03/12 05:13 [entrez] PHST- 2026/02/24 00:00 [pmc-release] AID - 10.3389/fpubh.2026.1750738 [doi] PST - epublish SO - Front Public Health. 2026 Feb 24;14:1750738. doi: 10.3389/fpubh.2026.1750738. eCollection 2026. PMID- 41815032 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260730 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 81 IP - 3 DP - 2026 Mar TI - [SURPASS CVOT : cardiovascular benefits with tirzepatide versus dulaglutide in type 2 diabetes]. PG - 187-193 AB - Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their ability to reduce major adverse cardiovascular events (MACEs) among at-risk patients living with type 2 diabetes (T2D). Tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrated a better control of hyperglycaemia, body weight and several cardiovascular risk factors than pure GLP-1RAs (including semaglutide) in dedicated studies of the SURPASS programme. SURPASS CVOT has the primary objective to demonstrate, in a population with T2D and atheromatous cardiovascular disease, the non-inferiority of tirzepatide regarding both efficacy and safety compared with dulaglutide, a selective GLP-RA that has already proven a significant reduction in MACEs versus placebo in the REWIND trial. Non-inferiority was met in SURPASS CVOT (p = 0.003), but not superiority of tirzepatide compared to dulaglutide (hazard ratio [HR] 0.92; 95 % confidence interval [IC] 0.83 to 1.01; P = 0.09) regarding the primary end point (reduction in MACEs). Several secondary end points tended to favour tirzepatide versus dulaglutide, among which a reduction in the incidence of all-cause deaths after four years of median follow-up (HR 0.84 ; 95 % CI 0.75 to 0.94; exploratory analysis). SURPASS CVOT, the first and unique study that used an active comparator rather than a placebo, confirms the efficacy and safety of the dual agonist tirzepatide in patients with T2D and atheromatous cardiovascular disease. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), ULiege, Belgique. FAU - Lancellotti, Patrizio AU - Lancellotti P AD - Service de Cardiologie, CHU Liege, Belgique. AD - GIGA Cardiovasculaire, Uliege, Belgique. LA - fre PT - English Abstract PT - Equivalence Trial PT - Journal Article TT - L'etude clinique du mois. SURPASS CVOT : benefices cardiovasculaires avec le tirzepatide versus le dulaglutide dans le diabete de type 2. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Tirzepatide/therapeutic use OTO - NOTNLM OT - Cardiovascular protection OT - Dulaglutide OT - GIP/GLP-1 dual agonist OT - GLP-1 receptor agonist OT - Tirzepatide OT - Type 2 diabetes EDAT- 2026/03/12 07:04 MHDA- 2026/03/12 13:57 CRDT- 2026/03/12 04:34 PHST- 2026/03/12 13:57 [medline] PHST- 2026/03/12 07:04 [pubmed] PHST- 2026/03/12 04:34 [entrez] PST - ppublish SO - Rev Med Liege. 2026 Mar;81(3):187-193. PMID- 41813606 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 63 IP - 11 DP - 2026 Jun TI - Real-World Alcohol Use Disorder Outcomes in Patients With Concurrent Metabolic Dysfunction: GLP-1 Receptor Agonists Versus FDA-Approved AUD Medications. PG - 1507-1516 LID - 10.1111/apt.70596 [doi] AB - BACKGROUND: Metabolic dysfunction (MetD) and alcohol use disorder (AUD) frequently coexist as synergistic risk factors for steatotic liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established therapies for MetD, including type 2 diabetes mellitus (T2DM) and obesity. Recent studies suggested potential beneficial effects of GLP-1RA to decrease addictive behaviours in AUD. We evaluated the outcomes of GLP-1RA therapy compared with FDA-approved pharmacotherapies for AUD, including naltrexone, acamprosate, and disulfiram, in patients with dual risk factors of MetD and AUD. METHODS: We conducted a retrospective cohort study of patients at Stanford Health Care (2017-2025). Eligible patients had a concurrent diagnosis of alcohol-related complications meeting criteria for AUD and MetD, including obesity (BMI > 25) and/or a history of T2DM with HbA1c > 5.7. Those with advanced liver disease within 1 year of diagnosis were excluded. Exposure groups included >/= 6 months of GLP-1RA therapy (semaglutide or tirzepatide) in comparison with FDA-approved pharmacotherapies for AUD. Propensity score matching was employed to reduce the effects of confounding factors. RESULTS: In total, 1946 patients were diagnosed concurrently with AUD and MetD. Of them, 274 patients were exposed to GLP-1RA, 1272 to naltrexone, 232 to acamprosate, and 168 to disulfiram. Patients were followed for an average of 1341 days. Patients exposed to GLP-1RA had higher BMI (35.5 vs. 30.1) and more T2DM (66% vs. 14%). GLP-1RA therapy was associated with lower 1-year AUD relapse [IRR 0.55, 95% CI 0.42-0.73; p < 0.01], greater BMI reduction (-1.3 vs. -0.3; p = 0.004), and HbA1c improvement (-1.0 vs. +0.1; p = 0.02). The incidence of decompensated cirrhosis trended lower but was not statistically significant [HR 0.52, p = 0.09]. Mortality was similar. CONCLUSIONS: GLP-1RAs are a promising option for patients with concurrent MetD and AUD, improving relapse rates and metabolic outcomes compared with currently FDA-approved pharmacotherapies for AUD. Trends toward better liver outcomes support further prospective evaluation. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Gougol, Amir AU - Gougol A AUID- ORCID: 0009-0001-7346-2121 AD - Department of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA. FAU - Kwo, Paul AU - Kwo P AD - Department of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA. FAU - Pike, William AU - Pike W AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Farokhnia, Mehdi AU - Farokhnia M AUID- ORCID: 0000-0003-0902-4212 AD - National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and, Bethesda, MD, USA. FAU - Hui, Gavin AU - Hui G AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Gombar, Saurabh AU - Gombar S AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Mirminachi, Babak AU - Mirminachi B AD - University of Pittsburgh Medical Center, Pittsburgh, PA, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260311 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Alcohol Deterrents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - N4K14YGM3J (Acamprosate) RN - 5S6W795CQM (Naltrexone) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Retrospective Studies MH - *Alcoholism/drug therapy/complications MH - *Alcohol Deterrents/therapeutic use MH - Treatment Outcome MH - Tirzepatide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Metabolic Diseases/drug therapy/complications MH - Adult MH - Acamprosate/therapeutic use MH - United States MH - Aged MH - Obesity MH - Risk Factors MH - Naltrexone/therapeutic use OTO - NOTNLM OT - GLP-1RA; AUD; fatty liver disease OT - alcohol-associated liver disease OT - major liver-related outcome OT - metabolic dysfunction EDAT- 2026/03/12 01:09 MHDA- 2026/05/13 12:33 CRDT- 2026/03/11 23:43 PHST- 2026/02/08 00:00 [revised] PHST- 2025/12/11 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/05/13 12:33 [medline] PHST- 2026/03/12 01:09 [pubmed] PHST- 2026/03/11 23:43 [entrez] AID - 10.1111/apt.70596 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2026 Jun;63(11):1507-1516. doi: 10.1111/apt.70596. Epub 2026 Mar 11. PMID- 41812723 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 139 IP - 6 DP - 2026 Jun TI - Glucagon-like peptide-1 receptor agonist and lupus nephritis in systemic lupus erythematosus with type 2 diabetes. PG - 769-781.e8 LID - S0002-9343(26)00146-4 [pii] LID - 10.1016/j.amjmed.2026.02.016 [doi] AB - BACKGROUND: Systemic lupus erythematosus and type 2 diabetes mellitus are chronic inflammatory diseases that impact kidney function. Glucagon-like peptide-1 receptor agonist (GLP-1 RA), have shown benefits in several inflammatory diseases. However, their role in systemic lupus erythematosus, particularly in lupus nephritis, and disease flare are not well understood. We explored the hypothesized association between exposure to GLP-1 RA and renal and inflammatory outcomes in patients with systemic lupus erythematosus and type 2 diabetes mellitus. METHODS: This retrospective cohort study utilized a global database of electronic health records from approximately 141 million patients. After propensity score matching, the study included 9,386 systemic lupus erythematosus patients with type 2 diabetes mellitus, stratified by GLP-1 RA exposure. RESULTS: Among 9,386 systemic lupus erythematosus patients with type 2 diabetes mellitus, the average age in the GLP-1 RA-exposed group was 61.6 years. The relative risk of lupus nephritis was comparable (RR 0.57, 95% CI: 0.26-1.25, P = 0.15) at one-month follow-up; however, GLP-1 RA exposure was associated with a lower risk of lupus nephritis at one year (RR 0.59, 95% CI: 0.40-0.86, P < 0.01) compared to the control group. Secondary outcomes, including systemic lupus erythematosus flare, all-cause mortality, acute myocardial infarction, and hospitalization rate were observed less frequently in the GLP-1 RA group at one-year follow-up. The ischemic stroke risk was similar between the two groups at one month, however, GLP-1 RA exposure was associated with a lower risk of ischemic stroke at one year CONCLUSION: GLP-1 RA exposure in systemic lupus erythematosus patients with type 2 diabetes mellitus is associated with reduced risks of lupus nephritis, and systemic lupus erythematosus flares. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Hanif, Muhammad AU - Hanif M AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. FAU - Nagarajan, Jai S AU - Nagarajan JS AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. FAU - Murphy, Ryan AU - Murphy R AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. FAU - Sah, Shiva P AU - Sah SP AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. FAU - Ye, Shuang AU - Ye S AD - Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Perl, Andras AU - Perl A AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. FAU - Taub, Cynthia C AU - Taub CC AD - Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. Electronic address: taubc@upstate.edu. LA - eng PT - Journal Article DEP - 20260309 PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Lupus Nephritis/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - *Lupus Erythematosus, Systemic/complications/drug therapy/epidemiology MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Male MH - Aged OTO - NOTNLM OT - Glucagon-like receptor-I receptor agonist OT - Ischemic stroke OT - Lupus nephritis OT - Systemic lupus erythematosus OT - Systemic lupus erythematosus flare COIS- Declaration of competing interest Muhamad Hanif, Jai S. Nagarajan, Ryan Murphy, Shiva P. Sah, Shuang Ye, Andras Perl, and Cynthia C. Taub have no conflict of interest to declare. EDAT- 2026/03/12 01:09 MHDA- 2026/05/07 00:32 CRDT- 2026/03/11 20:13 PHST- 2025/10/08 00:00 [received] PHST- 2026/02/13 00:00 [revised] PHST- 2026/02/20 00:00 [accepted] PHST- 2026/05/07 00:32 [medline] PHST- 2026/03/12 01:09 [pubmed] PHST- 2026/03/11 20:13 [entrez] AID - S0002-9343(26)00146-4 [pii] AID - 10.1016/j.amjmed.2026.02.016 [doi] PST - ppublish SO - Am J Med. 2026 Jun;139(6):769-781.e8. doi: 10.1016/j.amjmed.2026.02.016. Epub 2026 Mar 9. PMID- 41811375 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 82 IP - 4 DP - 2026 Mar 11 TI - Economic evaluation of sodium-glucose transporter 2 inhibitors compared with glucagon-like peptide 1 receptor agonist for the treatment of type 2 diabetes: a systematic review. LID - 94 [pii] LID - 10.1007/s00228-026-04015-9 [doi] AB - PURPOSE: A systematic review was performed to assess the economic evaluation of sodium glucose transporters 2 (SGLT2) inhibitors vs GLP-1 receptor agonists (GLP-1RA) in treating type 2 diabetes. METHODS: The relevant studies were searched in PubMed, Web of Science, Scopus, Embase, and Cochrane from the inception date to February 20, 2025. The titles, abstracts, and full texts were independently evaluated and screened by two authors. Additionally, the economic evaluation studies were assessed independently by two authors. RESULTS: 18 studies were included, evaluating oral semaglutide vs empagliflozin (n = 7), both oral semaglutide vs empagliflozin and subcutaneous semaglutide vs canagliflozin (n = 1), subcutaneous semaglutide vs empagliflozin (n = 4), liraglutide vs empagliflozin (n = 4), liraglutide vs dapagliflozin (n = 1), and subcutaneous semaglutide vs canagliflozin (n = 1). CONCLUSION: The results showed that when patients were assumed to receive initial therapies until HbA1c exceeded the target level and then treatment was intensified to basal insulin, GLP-1RA was cost-effective compared to SGLT2 inhibitors (semaglutide vs empagliflozin and liraglutide vs dapagliflozin). Empagliflozin demonstrated cost-effectiveness when the treatment with either empagliflozin or semaglutide would have continued indefinitely. Compared with empagliflozin, liraglutide may not be a cost-effective treatment option for patients with T2D who were not well-controlled with metformin. FAU - Wang, Lu AU - Wang L AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. wanglu784940819@163.com. FAU - Wang, Yinglin AU - Wang Y AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. FAU - Zhao, Quan AU - Zhao Q AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. zhaoquan_1419@163.com. LA - eng PT - Comparative Study PT - Journal Article PT - Systematic Review DEP - 20260311 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0SAC974Z85 (Canagliflozin) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Cost-Benefit Analysis MH - Benzhydryl Compounds/economics/therapeutic use MH - Glucosides/economics/therapeutic use MH - Glucagon-Like Peptides/economics/therapeutic use MH - Canagliflozin/economics/therapeutic use MH - Cost-Effectiveness Analysis MH - Glycated Hemoglobin MH - Liraglutide/economics/therapeutic use OTO - NOTNLM OT - Cost-effectiveness OT - GLP-1 Receptor Agonists OT - Sodium-Glucose Transporter 2 Inhibitors OT - Systematic Review OT - Type 2 Diabetes COIS- Declarations. Institutional review board statement: Not applicable. Informed consent statement: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/03/11 19:00 MHDA- 2026/06/28 00:37 CRDT- 2026/03/11 12:03 PHST- 2025/11/27 00:00 [received] PHST- 2026/02/21 00:00 [accepted] PHST- 2026/06/28 00:37 [medline] PHST- 2026/03/11 19:00 [pubmed] PHST- 2026/03/11 12:03 [entrez] AID - 10.1007/s00228-026-04015-9 [pii] AID - 10.1007/s00228-026-04015-9 [doi] PST - epublish SO - Eur J Clin Pharmacol. 2026 Mar 11;82(4):94. doi: 10.1007/s00228-026-04015-9. PMID- 41806782 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260807 IS - 1879-1379 (Electronic) IS - 0022-3956 (Linking) VI - 197 DP - 2026 Jun TI - The dual role of GLP-1 receptor agonists in weight management and eating disorders: Potential benefits and risks. PG - 243-249 LID - S0022-3956(26)00156-1 [pii] LID - 10.1016/j.jpsychires.2026.03.008 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective therapies for type 2 diabetes mellitus (T2DM) and obesity, as they improve glycaemic control, promote weight loss and modulate metabolic processes. However, their potent appetite-suppressing effects pose a complex challenge in patients with or at risk of eating disorders (EDs). This narrative review examines the dual role of GLP-1RAs in weight management and in the development or exacerbation of EDs, such as binge eating disorder (BED) and bulimia nervosa (BN). GLP-1RAs have been reported to reduce binge-eating episodes in some trials, but evidence is limited and often inconsistent due to small sample sizes. Conversely, psychiatric adverse effects - including anxiety, depression and disordered eating behaviours - have been observed, raising concerns about the use of these medications in individuals susceptible to EDs. There are case reports of extreme appetite suppression, pathological dietary restriction and psychiatric complications with GLP-1RA therapy, sometimes necessitating discontinuation. Moreover, GLP-1RAs influence brain reward pathways, which may further complicate their impact on eating behaviours. Although these drugs hold promise for mitigating certain ED symptoms, this review highlights the need for caution when prescribing GLP-1RAs to patients with disordered eating and calls for further research to delineate their benefits and risks in this population. CI - Copyright (c) 2026. Published by Elsevier Ltd. FAU - Leziak, Aleksandra AU - Leziak A AD - Students' Scientific Association, Department of Pathophysiology, Poland. FAU - Kochman, Klaudia AU - Kochman K AD - Students' Scientific Association, Department of Pathophysiology, Poland. FAU - Kocelak, Piotr AU - Kocelak P AD - Department of Pathophysiology, Medical University of Silesia, Medykow Street 18, 40-752 Katowice, Poland. Electronic address: pkocelak@sum.edu.pl. LA - eng PT - Journal Article PT - Review DEP - 20260307 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Feeding and Eating Disorders/drug therapy/chemically induced MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Binge-Eating Disorder/drug therapy OTO - NOTNLM OT - Appetite regulation OT - Binge eating disorder OT - Bulimia nervosa OT - Diabetes OT - Eating disorders OT - GLP-1 receptor agonists OT - Obesity COIS- Declaration of competing interest I have nothing to declare. EDAT- 2026/03/11 01:11 MHDA- 2026/03/28 00:42 CRDT- 2026/03/10 19:10 PHST- 2025/11/15 00:00 [received] PHST- 2026/02/26 00:00 [revised] PHST- 2026/03/06 00:00 [accepted] PHST- 2026/03/28 00:42 [medline] PHST- 2026/03/11 01:11 [pubmed] PHST- 2026/03/10 19:10 [entrez] AID - S0022-3956(26)00156-1 [pii] AID - 10.1016/j.jpsychires.2026.03.008 [doi] PST - ppublish SO - J Psychiatr Res. 2026 Jun;197:243-249. doi: 10.1016/j.jpsychires.2026.03.008. Epub 2026 Mar 7. PMID- 41806022 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Mar 10 TI - Glucagon-Like Peptide-1 and Dual Incretin Agonists in Type 2 Diabetes with Peripheral Artery Disease: A Systematic Review and Meta-Analysis of Vascular, Cardiovascular, Metabolic, and Mortality Outcomes : Incretin Therapy in T2DM and PAD. LID - 5 [pii] LID - 10.1007/s11892-026-01619-4 [doi] AB - PURPOSE OF REVIEW: Peripheral artery disease (PAD) is a serious complication in type 2 diabetes, increasing vascular morbidity and mortality. While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists show cardiovascular benefits in diabetes, their effects on PAD-related outcomes are unclear. This meta-analysis assessed the impact of these therapies on vascular outcomes in type 2 diabetes with PAD. RECENT FINDINGS: A systematic review and meta-analysis were conducted per PRISMA guidelines (PROSPERO CRD420251083622). PubMed, Embase, and Cochrane Central were searched. A random-effects model pooled data. Primary outcomes were major adverse limb events, peripheral revascularization, and amputation. Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction, stroke, HbA1c, and weight changes. Six studies (four RCTs, two propensity score-matched cohorts) with 25,866 patients were included. Incretin-based therapies significantly reduced all-cause mortality (RR 0.52 [0.28-0.95], p = 0.032) and HbA1c (MD - 0.73% [-1.32 to - 0.15], p = 0.013) compared to placebo or standard care. No significant differences were found for major adverse limb events, revascularization, amputation, MACE, myocardial infarction, or stroke. Heterogeneity and low evidence certainty were noted. FAU - Araujo de Lucena, Larissa AU - Araujo de Lucena L AUID- ORCID: 0000-0002-6482-5920 AD - Federal University of Rio Grande do Norte, Natal, RN, Brazil. FAU - Cavalcante, Deivyd V S AU - Cavalcante DVS AD - University of North Texas Health Science Center, Fort Worth, TX, USA. FAU - Montenegro, Marcela V AU - Montenegro MV AD - University of Pernambuco, Recife, PE, Brazil. FAU - Hespanhol, Larissa C AU - Hespanhol LC AD - Federal University of Campina Grande, Cajazeiras, PB, Brazil. FAU - de Oliveira, William S AU - de Oliveira WS AD - Federal University of Rio Grande do Norte, Natal, RN, Brazil. FAU - Muniz, Juliana Q AU - Muniz JQ AD - Schmieder Klinik Heidelberg, Heidelberg, Germany. FAU - Prathivadhi-Bhayankaram, Sruti AU - Prathivadhi-Bhayankaram S AD - University of Illinois, Chicago, IL, USA. FAU - Kaplinsky, Edgardo AU - Kaplinsky E AD - Hospital Municipal de Badalona, Barcelona, Spain. FAU - Barbagelata, Alejandro AU - Barbagelata A AD - Universidad Catolica Argentina, Buenos Aires, Argentina. AD - Duke University, Durham, NC, USA. FAU - Giorgi, Juliana AU - Giorgi J AUID- ORCID: 0009-0007-7271-4845 AD - Sirio-Libanes Hospital, Sao Paulo, SP, Brazil. julianagiorgi@hotmail.com. AD - Albert Einstein Hospital, Sao Paulo, Sao Paulo, Brazil. julianagiorgi@hotmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260310 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Curr Diab Rep. 2026 Apr 10;26(1):9. doi: 10.1007/s11892-026-01622-9. PMID: 41961366 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality/metabolism MH - *Incretins/therapeutic use MH - *Peripheral Arterial Disease/drug therapy/mortality/complications/metabolism MH - *Glucagon-Like Peptide 1/agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes Mellitus OT - Glucagon-Like Peptide 1 OT - Glucose-Dependent Insulinotropic Polypeptide OT - Peripheral Arterial Disease COIS- Declarations. Ethics Approval: This systematic review and meta-analysis utilized data from previously published studies and did not involve primary data collection from human or animal subjects. Consequently, ethical approval was not required. Data were extracted from publicly available sources in accordance with ethical guidelines for secondary data analysis. Human Studies Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of Interest: The authors declare no competing interests. Competing Interests: The authors declare no competing interests. EDAT- 2026/03/10 18:36 MHDA- 2026/06/27 12:37 CRDT- 2026/03/10 17:25 PHST- 2025/08/12 00:00 [received] PHST- 2026/02/19 00:00 [accepted] PHST- 2026/06/27 12:37 [medline] PHST- 2026/03/10 18:36 [pubmed] PHST- 2026/03/10 17:25 [entrez] AID - 10.1007/s11892-026-01619-4 [pii] AID - 10.1007/s11892-026-01619-4 [doi] PST - epublish SO - Curr Diab Rep. 2026 Mar 10;26(1):5. doi: 10.1007/s11892-026-01619-4. PMID- 41805656 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260918 IS - 1940-5480 (Electronic) IS - 1067-151X (Linking) VI - 34 IP - 19 DP - 2026 Oct 1 TI - Impact of GLP-1 Receptor Agonist Use on Total Knee Arthroplasty Outcomes in Metformin-Treated Diabetic Patients With and Without Comorbid Obesity: A Propensity-Matched Analysis. PG - e2795-e2805 LID - 10.5435/JAAOS-D-25-00982 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been linked to improved outcomes following total knee arthroplasty (TKA). However, it remains unclear whether the observed benefits are attributable to weight loss, glycemic control, or first-line type 2 diabetes mellitus (T2DM) medications such as metformin. This study aimed to evaluate the impact of perioperative GLP-1RA use on TKA outcomes in T2DM patients stratified by obesity status. METHODS: The TriNetX Global Collaborative Network was queried using relevant Current Procedural Terminology and ICD-10 codes for metformin-treated T2DM patients aged 18 years or older undergoing primary TKA. Patients were divided into two groups based on obesity status and further stratified based on GLP-1RA use within three months of surgery. The groups were propensity matched (1:1) based on age, sex, body mass index (BMI), HbA1c, and comorbidities. Surgical outcomes, medical complications, and resource utilization were assessed at 90 days and 1 year. Surgical outcomes and revision rates were also assessed at two years. RESULTS: In obese patients (n = 8,170), GLP-1RA use was associated with notable reductions in postoperative anemia (odds ratio [OR] 0.714; P = 0.001), acute kidney injury (OR 0.755; P = 0.021), 90-day readmission (OR 0.776; P = 0.001), emergency department (ED) visits (OR 0.836; P = 0.008), and aseptic loosening at two years (OR 0.498; P = 0.037). These patients also demonstrated greater postoperative reductions in BMI and HbA1c. In nonobese patients (n = 1,328), GLP-1RA use was similarly associated with lower rates of 90-day readmission (OR 0.514; P = 0.004) and ED visits (OR 0.649; P = 0.024), although no notable differences in other outcomes were observed. CONCLUSION: Among metformin-treated T2DM patients undergoing TKA, GLP-1RA use was associated with reduced resource utilization irrespective of obesity. However, additional reductions in medical complications and aseptic loosening were observed in the obese group, suggesting a potential synergistic effect between weight loss and glycemic control. These findings highlight the effectiveness of GLP-1RAs in optimizing high-risk candidates undergoing TKA. CI - Copyright (c) 2026 by the American Academy of Orthopaedic Surgeons. FAU - Lee, Seungjun AU - Lee S AD - From the Boston University Chobanian and Avedisian School of Medicine, Boston, MA (Lee), the Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA (Sellig), and the Department of Orthopaedic Surgery, Boston University Medical Center, Boston, MA (Kim, Jayne, Seo, and Goh). FAU - Sellig, Mason T AU - Sellig MT FAU - Kim, Matthew T AU - Kim MT FAU - Jayne, Christopher AU - Jayne C FAU - Seo, Henry H AU - Seo HH FAU - Goh, Graham S AU - Goh GS AUID- ORCID: 0000-0002-7337-3321 LA - eng PT - Journal Article DEP - 20260310 PL - United States TA - J Am Acad Orthop Surg JT - The Journal of the American Academy of Orthopaedic Surgeons JID - 9417468 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Knee MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Metformin/therapeutic use MH - Male MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Treatment Outcome MH - Postoperative Complications/epidemiology MH - Propensity Score MH - Comorbidity EDAT- 2026/03/10 18:36 MHDA- 2026/09/18 23:36 CRDT- 2026/03/10 17:13 PHST- 2025/08/05 00:00 [received] PHST- 2026/01/18 00:00 [accepted] PHST- 2026/09/18 23:36 [medline] PHST- 2026/03/10 18:36 [pubmed] PHST- 2026/03/10 17:13 [entrez] AID - 00124635-990000000-01615 [pii] AID - 10.5435/JAAOS-D-25-00982 [doi] PST - ppublish SO - J Am Acad Orthop Surg. 2026 Oct 1;34(19):e2795-e2805. doi: 10.5435/JAAOS-D-25-00982. Epub 2026 Mar 10. PMID- 41804851 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Relative Efficacy of Next-Generation Incretin Therapies for Cardio-Renal Protection in Type 2 Diabetes: Evidence From a Network Meta-Analysis. PG - 4630-4652 LID - 10.1111/dom.70635 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) management has shifted towards integrated cardiometabolic and renal risk reduction. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual agonists show promising benefits, comparative evidence across agents and outcomes remains limited. OBJECTIVES: To compare the cardiovascular and renal effects of modern GLP-1RAs (dulaglutide, semaglutide, lixisenatide), tirzepatide and cotadutide in high-risk T2D populations, and to explore multivariate relationships among clinical outcomes. METHODS: A systematic review and network meta-analysis was conducted following PRISMA and Cochrane guidance (PROSPERO: CRD42024592825). Randomised controlled trials published between 2014 and 2025 with >/= 6 months follow-up were included. Outcomes were cardiovascular death, myocardial infarction (MI), stroke, total major adverse cardiovascular events (MACE), eGFR and UACR. Random- and common-effects models were applied using netmeta (R). Treatment rankings were estimated using p-scores. Inconsistency, heterogeneity and small-study effects were evaluated. Correlation networks and principal component analysis (PCA) were performed to characterise interrelationships among clinical variables. RESULTS: Thirty-four trials were included, predominantly multinational CVOTs and CKD-focused studies. Semaglutide regimens showed the most consistent reduction in MACE and MI versus placebo, with the strongest effect observed for semaglutide combined with SGLT2 inhibition. Dulaglutide 1.5 mg and tirzepatide 15 mg significantly reduced stroke risk. Cardiovascular death estimates were largely imprecise with evidence of small-study effects. Renal effects differed by endpoint: eGFR changes were generally modest, whereas UACR showed marked reductions, particularly with dulaglutide plus dapagliflozin, DPP-4 inhibitors and semaglutide 1 mg. PCA confirmed strong cardiometabolic-renal interdependence. CONCLUSIONS: Cardiovascular and renal benefits of GLP-1-based therapies are outcome-specific. Semaglutide favoured MACE/MI reduction, dulaglutide and tirzepatide supported stroke prevention, and albuminuria outcomes were more responsive than eGFR. Further long-term head-to-head trials are needed. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Pham, Thi-Phuong-Thao AU - Pham TP AD - Pharmacy Department, School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Vo, Thi-Minh-Nhat AU - Vo TM AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Nguyen, The-Anh AU - Nguyen TA AD - Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan. AD - Department of Acupuncture, Vietnam University of Traditional Medicine, Hanoi, Vietnam. FAU - Dao, Tien-Phat AU - Dao TP AD - International Public Health Department, China Medical University, Taichung, Taiwan. FAU - Ngo, Ngoc-Phuoc AU - Ngo NP AD - Pharmacy Department, School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Le, Thi-Thuy-Duong AU - Le TT AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Tran, Thanh-Thien AU - Tran TT AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Pham, Thanh-Huong AU - Pham TH AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Huynh, Dang-Mai-Linh AU - Huynh DM AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Ha, Hai-Anh AU - Ha HA AUID- ORCID: 0000-0002-4252-2128 AD - Faculty of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260310 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 74O62BB01U (lixisenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Incretins/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Myocardial Infarction/prevention & control MH - Glucagon-Like Peptide 1/analogs & derivatives OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - dual-pathway incretin therapies OT - network meta-analysis OT - renal outcomes OT - type 2 diabetes EDAT- 2026/03/10 12:55 MHDA- 2026/05/06 06:40 CRDT- 2026/03/10 06:23 PHST- 2026/02/14 00:00 [revised] PHST- 2025/11/04 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/05/06 06:40 [medline] PHST- 2026/03/10 12:55 [pubmed] PHST- 2026/03/10 06:23 [entrez] AID - 10.1111/dom.70635 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4630-4652. doi: 10.1111/dom.70635. Epub 2026 Mar 10. PMID- 41804217 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Identifying Predictors of Early Treatment Intensification in Individuals With Type 2 Diabetes Treated With GLP-1 Receptor Agonists: A Machine Learning-Based Analysis of a Large Real World Cohort. PG - 4718-4727 LID - 10.1111/dom.70648 [doi] AB - AIMS: Despite the proven efficacy of GLP-1 receptor agonists (GLP-1 RAs), many patients with type 2 diabetes (T2DM) are not able to achieve glycaemic targets with these agents and they require additional therapies. Timely identification of individuals at higher risk of early intensification may improve outcomes and reduce therapeutic inertia. MATERIALS AND METHODS: In this retrospective cohort study, we analysed data from 69 194 individuals with T2DM initiating GLP-1 RA. We applied logic learning machine (LLM), an explainable machine-learning algorithm, to identify-at the time of GLP-1 RA prescription-predictors of early intensification ( 5 years of GLP-1 RA treatment). RESULTS: Both models identified the same clinical phenotype, characterised by longer diabetes duration, unstable glycaemic control, prior insulin use, and cardio-renal complications. Model 1 showed limited discriminative ability (AUC 0.65) with many false positives, suggesting therapeutic inertia in real-world practice. Model 2, while selecting same predictors of Model 1, achieved better performance (AUC 0.78), suggesting clearer differentiation between patient cohorts. CONCLUSIONS: Explainable AI identified a reproducible phenotype of patients associated with early intensification after GLP-1 RA initiation. These models may support earlier, more personalised treatment decisions in routine diabetes care. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Falcetta, Pierpaolo AU - Falcetta P AUID- ORCID: 0000-0002-3182-0453 AD - Diabetes Unit, Azienda USL Toscana Centro, Empoli, Italy. FAU - Zilich, Rita AU - Zilich R AD - Mix-X Partner, Milan, Italy. FAU - Baccetti, Fabio AU - Baccetti F AD - Diabetes Unit, ASL Toscana Nord-Ovest, Massa-Carrara, Italy. FAU - Baronti, Walter AU - Baronti W AD - Diabetes Unit, ASL Toscana Sud-Est, Grosseto, Italy. FAU - Morviducci, Lelio AU - Morviducci L AD - UOC Diabetologia e Dietologia, Ospedale S. Spirito - ASL Roma 1, Rome, Italy. FAU - Musacchio, Nicoletta AU - Musacchio N AD - UOS Integrating Primary and Specialist Care, ASST Nord Milano, Milan, Italy. FAU - Muselli, Marco AU - Muselli M AD - Rulex Innovation Labs, Rulex Inc, Genoa, Italy. FAU - Ozzello, Alessandro AU - Ozzello A AD - AI-AMD National Group, Bruino, Italy. FAU - Pisani, Federico AU - Pisani F AD - Mix-X Partner, Milan, Italy. FAU - Rossi, Antonio AU - Rossi A AD - I.R.C.C.S. Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy. AD - Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. FAU - Salomone, Enrica AU - Salomone E AD - Diabetes Unit, Rome, Italy. FAU - Verda, Damiano AU - Verda D AD - Rulex Innovation Labs, Rulex Inc, Genoa, Italy. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy. FAU - Ponzani, Paola AU - Ponzani P AD - Metabolism and Diabetes Unit, ASL 4, Chiavari, Italy. LA - eng GR - Sanofi/ PT - Journal Article DEP - 20260309 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Male MH - *Machine Learning MH - Middle Aged MH - Predictive Learning Models MH - Aged MH - Blood Glucose/metabolism MH - Glycated Hemoglobin/analysis MH - Prediction Algorithms MH - Data Analytics OTO - NOTNLM OT - diabetes mellitus type 2 OT - glucagon-like peptide-1 receptor agonists OT - insulin OT - machine learning OT - therapeutic inertia OT - therapy intensification EDAT- 2026/03/10 07:00 MHDA- 2026/05/06 06:37 CRDT- 2026/03/10 03:03 PHST- 2026/02/26 00:00 [revised] PHST- 2025/12/30 00:00 [received] PHST- 2026/02/27 00:00 [accepted] PHST- 2026/05/06 06:37 [medline] PHST- 2026/03/10 07:00 [pubmed] PHST- 2026/03/10 03:03 [entrez] AID - 10.1111/dom.70648 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4718-4727. doi: 10.1111/dom.70648. Epub 2026 Mar 9. PMID- 41804113 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 16 IP - 2 DP - 2026 Apr TI - GLP-1 Receptor Agonists Versus Bariatric Surgery: Effects of Weight Loss and BMI on Subsequent General Surgical Procedures. PG - e70075 LID - 10.1111/cob.70075 [doi] LID - e70075 AB - Obesity and T2DM substantially increase postoperative risk, with higher surgical site infections in obesity and up to a 65% increase in overall complications in T2DM. This study assesses the impact of weight loss interventions-metabolic bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonists (GLP-1RA)-on BMI reduction and how that translates to postoperative outcomes in general surgery patients. Patients undergoing general surgery (2016-2024) were identified in the Epic Cosmos database. GLP-1RA or MBS exposure occurred 1-3 years preoperatively (GLP-1RA coverage >/= 80%). Entropy balancing produced weighted cohorts with similar baseline profiles, followed by multivariable regression models assessing the association between weight loss intervention and BMI change, and the impact of BMI on postoperative outcomes. Overall 9470 individuals underwent a general surgery procedure. Median patient age was 64, with mostly females (60.6%). More patients received GLP-1RA (n = 7823, 82.3%) than MBS (n = 1647, 17.4%). MBS patients had higher initial BMIs (>/= 40: 60.8% vs. 24.5%, p < 0.001). MBS led to greater BMI reduction than GLP-1RA (Mean difference: -9.89, 95% CI: -9.64, -10.34). Higher BMI at time of a general surgical procedure correlated with increased postoperative complications (OR: 1.01, 95% CI: 1.00-1.01) and extended LOS (OR: 1.01, 95% CI: 1.00-1.01). MBS was associated with lower complication odds (OR: 0.87, 95% CI: 0.78-0.98). MBS improved surgical outcomes in patients with obesity and T2DM through greater BMI reduction compared with GLP-1RAs. These findings support the role of preoperative weight loss to mitigate surgical risk; however, evaluating outcomes relative to no intervention remains an important future direction. CI - (c) 2026 The Author(s). Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Zindani, Shahzaib AU - Zindani S AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Woldesenbet, Selamawit AU - Woldesenbet S AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Altaf, Abdullah AU - Altaf A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Khalil, Mujtaba AU - Khalil M AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Rashid, Zayed AU - Rashid Z AUID- ORCID: 0009-0000-0500-8325 AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Kawashima, Jun AU - Kawashima J AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Mevawalla, Areesh AU - Mevawalla A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Sarfraz, Azza AU - Sarfraz A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Noria, Sabrena AU - Noria S AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Needleman, Bradley AU - Needleman B AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. FAU - Pawlik, Timothy M AU - Pawlik TM AUID- ORCID: 0000-0002-7994-9870 AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA. LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - *Bariatric Surgery MH - *Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Body Mass Index MH - Middle Aged MH - Male MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Obesity/surgery MH - Aged MH - Postoperative Complications MH - Treatment Outcome MH - Adult PMC - PMC12972600 OTO - NOTNLM OT - GLP-1 receptor agonists OT - bariatric surgery OT - obesity OT - surgical outcomes OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/03/10 07:00 MHDA- 2026/03/10 07:01 PMCR- 2026/03/10 CRDT- 2026/03/10 02:03 PHST- 2025/12/20 00:00 [revised] PHST- 2025/08/10 00:00 [received] PHST- 2025/12/23 00:00 [accepted] PHST- 2026/03/10 07:01 [medline] PHST- 2026/03/10 07:00 [pubmed] PHST- 2026/03/10 02:03 [entrez] PHST- 2026/03/10 00:00 [pmc-release] AID - COB70075 [pii] AID - 10.1111/cob.70075 [doi] PST - ppublish SO - Clin Obes. 2026 Apr;16(2):e70075. doi: 10.1111/cob.70075. PMID- 41803464 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20261010 IS - 1759-4782 (Electronic) IS - 1759-4774 (Linking) VI - 23 IP - 6 DP - 2026 Jun TI - Glucagon-like peptide 1 receptor agonists and cancer risk: the good, the bad and the unknown. PG - 459-470 LID - 10.1038/s41571-026-01135-0 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP1RAs) are widely used for the treatment of type 2 diabetes mellitus (T2DM) and, at higher doses, obesity. Both T2DM and obesity are associated with a higher risk of cancer, which can be reduced by intentional weight loss, whereas effects of a reduction in hyperglycaemia are uncertain. GLP1RAs might have further direct effects, either beneficial or detrimental, on the development of specific malignancies. Evidence from preclinical and clinical studies suggests heterogeneous effects of GLP1RAs on cancer risk: the incidence of hepatocellular, oesophageal, endometrial, ovarian and prostate cancers might be reduced, whereas safety concerns persist with respect to thyroid (both medullary and non-medullary) carcinomas. Conversely, initial concerns on the risk of pancreatic cancer have not been confirmed. Nonetheless, the interpretation of current data is limited by detection and prescription biases in observational studies as well as insufficient follow-up and number of events in randomized trials. In this Review, we summarize current preclinical and clinical evidence, showing that the risk-benefit profile of GLP1RAs remains favourable in individuals with T2DM and obesity, although caution is warranted in those with a low cardiometabolic risk, for whom the potential risks of cancer might outweigh any expected benefits; conversely, the potential use of GLP1RAs as adjuvant therapies for certain forms of cancer needs to be further investigated. CI - (c) 2026. Springer Nature Limited. FAU - Mannucci, Edoardo AU - Mannucci E AUID- ORCID: 0000-0001-9759-9408 AD - Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. edoardo.mannucci@unifi.it. FAU - Dicembrini, Ilaria AU - Dicembrini I AD - Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260309 PL - England TA - Nat Rev Clin Oncol JT - Nature reviews. Clinical oncology JID - 101500077 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Neoplasms/chemically induced/epidemiology/prevention & control MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors MH - Animals COIS- Competing interests: E.M. has acted as a consultant of Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk and Sanofi and received speaking fees from Eli Lilly, Novo Nordisk and Sanofi. I.D. has acted as a consultant of Medtronic, Novo Nordisk and Sanofi and received speaking fees from Abbott, Eli Lilly, Medtronic, MOVI, Novo Nordisk and Sanofi. EDAT- 2026/03/10 07:00 MHDA- 2026/05/28 00:29 CRDT- 2026/03/10 00:31 PHST- 2026/02/12 00:00 [accepted] PHST- 2026/05/28 00:29 [medline] PHST- 2026/03/10 07:00 [pubmed] PHST- 2026/03/10 00:31 [entrez] AID - 10.1038/s41571-026-01135-0 [pii] AID - 10.1038/s41571-026-01135-0 [doi] PST - ppublish SO - Nat Rev Clin Oncol. 2026 Jun;23(6):459-470. doi: 10.1038/s41571-026-01135-0. Epub 2026 Mar 9. PMID- 41803337 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Mar 10 TI - Efficacy and safety of GLP-1 receptor agonists in the treatment of type 2 diabetes and/or obesity in patients with Cushing's syndrome: a multicenter retrospective study. LID - 108 [pii] LID - 10.1007/s12020-026-04587-7 [doi] AB - BACKGROUND: Cushing's syndrome (CS) is characterized by profound metabolic derangements, including obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown potent metabolic benefits in type 2 diabetes (T2D) and obesity, but their efficacy and safety in CS remain unexplored. OBJECTIVE: To assess the metabolic efficacy and safety of GLP-1RAs in patients with CS and concurrent T2D and/or obesity. METHODS: This retrospective multicenter study included 20 adults with biochemically confirmed CS treated with GLP-1RAs (liraglutide, semaglutide, tirzepatide, or dulaglutide) for >/= 3 months. Anthropometric, hemodynamic, metabolic, hepatic, and hormonal parameters were compared before and after therapy using paired statistical tests. RESULTS: After a median follow-up of 13 months, significant reductions were observed in body weight (- 10.3 +/- 8.8 kg; p < 0.001) and BMI (- 4.2 +/- 2.8 kg/m(2); p < 0.001). Fasting glucose (- 12.1 +/- 35.3 mg/dL; p = 0.015) and HbA1c (- 0.5 +/- 0.9%; p = 0.011) decreased significantly. No significant changes occurred in blood pressure or lipid parameters. Liver enzymes improved, with decreases in ALT (- 3.9 +/- 21.4 U/L; p = 0.005) and GGT (- 25.9 +/- 57.3 U/L; p = 0.012), while the slight reduction in AST (- 5.2 +/- 9.2 U/L; p = 0.046) was statistically significant but not clinically relevant. Hormonal parameters, including ACTH and cortisol levels, remained stable. GLP-1RAs were generally well tolerated, with only mild gastrointestinal side effects in 26.3% of patients. CONCLUSIONS: GLP-1RA therapy in patients with CS and associated metabolic disorders led to significant improvements in weight, BMI, and glycemic control without worsening cortisol dynamics or liver function. Although limited by its retrospective design and small sample size, this study supports the safety and potential metabolic efficacy of GLP-1RAs in patients with CS, suggesting that these agents may constitute a useful adjunct for managing obesity and diabetes in this population. FAU - Iglesias, Pedro AU - Iglesias P AD - Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. piglo65@gmail.com. FAU - Nobre, Ema L AU - Nobre EL AD - Endocrinology Department, ULS Santa Maria, Lisbon, Portugal. FAU - Hanzu, Felicia AU - Hanzu F AD - Department of Endocrinology and Nutrition, Hospital Clinic, CIBERDEM, Barcelona, Universidad Barcelona, Barcelona, Spain. FAU - Schweizer, Junia R O L AU - Schweizer JROL AD - Department of Medicine IV, LMU University Hospital, LMU Munich, Germany. FAU - Manzano Valero, Lucia AU - Manzano Valero L AD - Department of Endocrinology and Nutrition, Hospital General Universitario de Toledo, Toledo, Spain. FAU - Araujo-Castro, Marta AU - Araujo-Castro M AD - Department of Endocrinology, Hospital Universitario Ramony Cajal, Madrid, Spain. FAU - Castro Luna, Ana AU - Castro Luna A AD - Department of Endocrinology and Nutrition, Hospital General Universitario de Toledo, Toledo, Spain. FAU - Albacete, Francisco Javier AU - Albacete FJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. FAU - Villar-Taibo, Rocio AU - Villar-Taibo R AD - Department of Endocrinology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. FAU - Reinke, Martin AU - Reinke M AD - Department of Medicine IV, LMU University Hospital, LMU Munich, Germany. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260310 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Male MH - Middle Aged MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - Adult MH - *Cushing Syndrome/complications/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Treatment Outcome MH - Liraglutide/therapeutic use/adverse effects MH - Blood Glucose MH - Aged OTO - NOTNLM OT - Cushing's syndrome OT - Diabetes mellitus OT - Liraglutide OT - Obesity OT - Semaglutide OT - Tirzepatide COIS- Declarations. Conflict of interests: The authors declare no competing interests. EDAT- 2026/03/10 07:00 MHDA- 2026/06/27 16:09 CRDT- 2026/03/10 00:26 PHST- 2025/11/12 00:00 [received] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/06/27 16:09 [medline] PHST- 2026/03/10 07:00 [pubmed] PHST- 2026/03/10 00:26 [entrez] AID - 10.1007/s12020-026-04587-7 [pii] AID - 10.1007/s12020-026-04587-7 [doi] PST - epublish SO - Endocrine. 2026 Mar 10;91(1):108. doi: 10.1007/s12020-026-04587-7. PMID- 41802676 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 235 DP - 2026 May TI - Cardiovascular outcomes of GLP-1RA vs SGLT2i in MASLD and type 2 diabetes: real-world evidence. PG - 113206 LID - S0168-8227(26)00125-7 [pii] LID - 10.1016/j.diabres.2026.113206 [doi] AB - BACKGROUND: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) are at high cardiovascular risk. Whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide cardiovascular protection comparable to sodium-glucose cotransporter-2 inhibitors (SGLT2is) remain uncertain. METHODS: Using the TriNetX global health research network, we conducted a retrospective cohort study of adults with MASLD and T2D initiating GLP-1 RAs or SGLT2is between 2017 and 2025. Propensity score matching balanced demographics, comorbidities, medications, and laboratory variables. Outcomes were analyzed using Cox proportional-hazards models, Kaplan-Meier curves, landmark analyses, negative control outcomes, and E-value estimation. Target-trial emulation principles were applied to reduce immortal-time and confounding bias. RESULTS: After matching, 52,094 patients were included (mean age 58.5 years; 49.7% women) with a median follow-up of 3.0 years. GLP-1 RA use was associated with a lower risk of major adverse cardiovascular and cerebrovascular events compared with SGLT2is (HR 0.86, 95% CI 0.80-0.92; p < 0.001). Risks of heart failure, myocardial infarction, stroke, and all-cause mortality were also significantly reduced. Results were consistent across sensitivity analyses. CONCLUSIONS: Among patients with MASLD and T2D, GLP-1 RA therapy was associated with a lower risk of cardiovascular events than SGLT2is, providing real-world comparative evidence in this population. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Yang, Chun-Chi AU - Yang CC AD - Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine and Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Cheng, Ya-Yun AU - Cheng YY AD - School of Medicine and Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; The Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan; Aerosol Science Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Chang, Hsuan-Yuan AU - Chang HY AD - Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Wang, Su-Hung AU - Wang SH AD - Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Feng, I-Che AU - Feng IC AD - Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Hsing-Tao AU - Kuo HT AD - Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Yu, Ming-Lung AU - Yu ML AD - School of Medicine and Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; The Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: d780178@kmu.edu.tw. FAU - Chang, Wei-Ting AU - Chang WT AD - School of Medicine and Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; The Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan; Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: weiting9901@mail.nsysu.edu.tw. LA - eng PT - Journal Article DEP - 20260307 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Middle Aged MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP-1RAs OT - MASLD OT - Real-world evidence OT - SGLT2is OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/03/10 01:06 MHDA- 2026/04/12 04:37 CRDT- 2026/03/09 20:17 PHST- 2026/01/19 00:00 [received] PHST- 2026/02/23 00:00 [revised] PHST- 2026/03/04 00:00 [accepted] PHST- 2026/04/12 04:37 [medline] PHST- 2026/03/10 01:06 [pubmed] PHST- 2026/03/09 20:17 [entrez] AID - S0168-8227(26)00125-7 [pii] AID - 10.1016/j.diabres.2026.113206 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 May;235:113206. doi: 10.1016/j.diabres.2026.113206. Epub 2026 Mar 7. PMID- 41801847 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 46 IP - 4 DP - 2026 Apr TI - Real-World Cardiovascular Outcomes of GLP-1 Receptor Agonists in Women With Type 2 Diabetes and Breast Cancer. PG - e70130 LID - 10.1002/phar.70130 [doi] AB - INTRODUCTION: The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D). OBJECTIVES: The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications. METHODS: This retrospective study included women with T2D, diagnosed with breast cancer at >/= 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome. RESULTS: After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001). CONCLUSIONS: This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings. CI - (c) 2026 ACCP Foundation, Ltd. FAU - Cornelio, Cyrille K AU - Cornelio CK AUID- ORCID: 0000-0003-0499-675X AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Cowart, Kevin AU - Cowart K AUID- ORCID: 0000-0002-6880-1600 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Perkins, Janelle AU - Perkins J AUID- ORCID: 0000-0002-5681-9061 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Alomar, Mohammed E AU - Alomar ME AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA. FAU - Gayoso, Ricardo Pineda AU - Gayoso RP AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA. FAU - Miranda, Aimon C AU - Miranda AC AUID- ORCID: 0000-0003-1683-3982 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Phan, Anh T AU - Phan AT AD - Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - White, Raechel T AU - White RT AUID- ORCID: 0000-0002-5929-5590 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. LA - eng PT - Journal Article PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Breast Neoplasms/complications/epidemiology/drug therapy MH - Middle Aged MH - Retrospective Studies MH - *Cardiovascular Diseases/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - Incidence MH - Semaglutide MH - Adult OTO - NOTNLM OT - breast cancer OT - cancer survivorship OT - cardiovascular risk reduction OT - glucagon-like-peptide-1 receptor agonists EDAT- 2026/03/09 19:00 MHDA- 2026/03/09 19:01 CRDT- 2026/03/09 13:24 PHST- 2026/01/14 00:00 [revised] PHST- 2025/09/30 00:00 [received] PHST- 2026/01/15 00:00 [accepted] PHST- 2026/03/09 19:01 [medline] PHST- 2026/03/09 19:00 [pubmed] PHST- 2026/03/09 13:24 [entrez] AID - 10.1002/phar.70130 [doi] PST - ppublish SO - Pharmacotherapy. 2026 Apr;46(4):e70130. doi: 10.1002/phar.70130. PMID- 41801203 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 3 DP - 2026 Mar 2 TI - Digital Microsteps as Scalable Adjuncts for Adults Using GLP-1 Receptor Agonists: A Randomized Clinical Trial. PG - e260577 LID - 10.1001/jamanetworkopen.2026.0577 [doi] LID - e260577 AB - IMPORTANCE: With the rapid global uptake of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), scalable behavioral adjuncts are urgently needed to support lifestyle change alongside pharmacotherapy. Microsteps, small behavior change prompts, could be one route to introduce lifestyle change. OBJECTIVE: To evaluate whether digitally delivered microsteps, augmented with short video boosters, increases behavioral expectation to adopt lifestyle behaviors among adults using GLP-1 RAs. DESIGN, SETTING, AND PARTICIPANTS: This 3-arm online randomized clinical trial was conducted between June 19 and July 1, 2025, with baseline data collection, immediate postexposure, and a 2-week follow-up. Participants were English-speaking adults using GLP-1 RAs in the US, the UK, and other countries and were recruited online through Prolific Academic. Data were collected via the Stanford Medicine Qualtrics platform. INTERVENTIONS: Participants received a single exposure to either written microsteps plus a short (approximately 2-minute) storytelling video (arm A) or written microsteps plus a short didactic video (arm B) compared with a do-nothing control condition (arm C). Behavioral nudges focused on small dietary improvements, physical activity, stress management strategies, and sleep hygiene. MAIN OUTCOMES AND MEASURES: The primary outcome was behavioral expectation to adopt health nudges, immediately after exposure and 2 weeks later. The effect on the main outcome of the microsteps intervention vs the control condition was compared; the effect of the intervention with a storytelling vs didactic video was also compared. Secondary outcomes were postexposure hope and happiness, as well as changes (over 2 weeks) in 3 key self-reported diet and exercise behaviors. RESULTS: Data from 5054 adults using GLP-1 RAs (mean [SD] age, 38.8 [12.6] years; 3361 females [66.5%]) were analyzed. Of these, 3437 (68%) lived in the US and the UK and 1617 (32%) lived in other countries. Immediately after exposure to the interventions, compared with control, standardized effects in SD units across the 8 microsteps expectation outcomes ranged from 0.30 (95% CI, 0.25-0.35) to 0.72 (95% CI, 0.68-0.77) in arm A and from 0.26 (95% CI, 0.21-0.32) to 0.77 (95% CI, 0.72-0.81) in arm B, with smaller effects 2 weeks later. The storytelling video was more effective across 7 of the 8 microsteps (breathe when stressed: arm A, 0.57 [95% CI, 0.52-0.62] vs arm B, 0.50 [95% CI, 0.44-0.55] and go outside for 5 minutes: arm A, 0.53 [95% CI, 0.49-0.58] vs arm B, 0.48 [95% CI, 0.43-0.52]). Immediate increases in hope (arm A, 0.31 [95% CI, 0.27-0.34]; arm B, 0.25 [95% CI, 0.22-0.28]) and happiness (arm A, 0.26 [95% CI, 0.23-0.30]; arm B, 0.22 [95% CI, 0.19-0.25]) were observed but dissipated by 2 weeks. At follow-up, the storytelling video group also reported reduced sugar-sweetened beverage consumption compared with the control group (-0.10 [95% CI, -0.16 to -0.03]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a low-cost digital intervention increased expectation to adopt health behaviors among adults using GLP-1 RAs, with effects persisting for 2 weeks. These findings suggest a potential role for the written microsteps intervention plus short video boosters as adjuncts to pharmacotherapy. Longer trials are warranted to determine whether the behavioral expectations stimulated by such interventions may lead to sustained behavior change. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06967337. FAU - Adam, Maya AU - Adam M AD - Department of Pediatrics, Stanford University School of Medicine, Stanford, California. AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Heidelberg Institute of Global Health, Medical Faculty and University Hospital, Heidelberg University, Heidelberg, Germany. FAU - Freget, Louis AU - Freget L AD - Universite Paris Dauphine-Paris Sciences et Lettres (PSL), Paris, France. AD - Centre pour la recherche economique et ses applications (CEPREMAP), Paris, France. FAU - Barnighausen, Till AU - Barnighausen T AD - Heidelberg Institute of Global Health, Medical Faculty and University Hospital, Heidelberg University, Heidelberg, Germany. AD - Harvard T.H. Chan School of Public Health, Boston, Massachusetts. AD - Africa Health Research Institute, Somkhele, South Africa. FAU - Rodriguez, Fatima AU - Rodriguez F AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California. FAU - Amsalem, Doron AU - Amsalem D AD - Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical School, New York, New York. FAU - Linos, Eleni AU - Linos E AD - Stanford Center for Digital Health, Department of Medicine, Stanford University, Stanford, California. AD - Department of Medicine, Stanford University School of Medicine, Stanford, California. AD - Department of Dermatology, Stanford University School of Medicine, Stanford, California. LA - eng SI - ClinicalTrials.gov/NCT06967337 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260302 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Digital Media PMC - PMC12973101 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2026/03/09 13:42 MHDA- 2026/03/09 13:43 PMCR- 2026/03/09 CRDT- 2026/03/09 11:33 PHST- 2026/03/09 13:43 [medline] PHST- 2026/03/09 13:42 [pubmed] PHST- 2026/03/09 11:33 [entrez] PHST- 2026/03/09 00:00 [pmc-release] AID - 2846023 [pii] AID - zoi260038 [pii] AID - 10.1001/jamanetworkopen.2026.0577 [doi] PST - epublish SO - JAMA Netw Open. 2026 Mar 2;9(3):e260577. doi: 10.1001/jamanetworkopen.2026.0577. PMID- 41800749 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 46 IP - 4 DP - 2026 Apr TI - Impact of Glucagon-Like Peptide-1 Receptor Agonists on Proteinuria in Kidney Transplant Recipients. PG - e70123 LID - 10.1002/phar.70123 [doi] AB - INTRODUCTION: Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown significant cardiorenal benefits in chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the impact of GLP-1 RAs on cardiorenal outcomes in kidney transplant recipients (KTRs) remains unclear. This study aims to assess the effect of GLP-1 RA therapy on proteinuria and metabolic parameters in KTRs, with and without T2DM, 12 months following GLP-1 RA initiation. METHODS: A single-center, retrospective study was conducted to evaluate the safety and efficacy of GLP-1 RAs in adult KTRs from June 1, 2022 to December 31, 2023. Primary outcomes were changes in urine protein-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) at 1, 3, 6, and 12 months after initiation of GLP-1 RAs. Secondary outcomes assessed changes in estimated glomerular filtration (eGFR), body mass index (BMI), and hemoglobin A1c (A1C). Safety outcomes included cardiovascular hospitalizations, acute kidney injury, pancreatitis, and biopsy-proven rejection within 12 months. RESULTS: Forty KTRs received GLP-1 RA therapy with a mean time to initiation of 4.3 months post-transplant, and the majority of patients had T2DM (87.5%). Baseline UPCR and UACR were 0.86 and 669 mg/g, respectively. UPCR at 1, 3, and 6 months post-initiation was 0.38 g/g, 0.37 g/g, and 0.30 g/g, respectively. UACR at 1, 3, and 6 months post-initiation was 313 mg/g, 285 mg/g, and 234 mg/g, respectively. A 55% decrease from baseline in UPCR and UACR was observed at 1 month (p = 0.070) and a 50% decrease from baseline was observed at 12 months (p = 0.058), achieving UPCR of 0.43 g/g and UACR of 320 mg/g. A1C, eGFR, and BMI remained stable. Minimal safety events occurred. CONCLUSION: GLP-1 RAs demonstrated clinically significant improvements in proteinuria as early as 1 month post-initiation in KTRs. Proteinuria significantly improved from severely increased to moderately increased at 6 months following GLP-1 RAs, with good tolerability. GLP-1 RAs may offer renal benefits in KTRs with T2DM without compromising allograft function. Future studies should include closer monitoring of KTRs on immunosuppression with high gastrointestinal adverse effect profiles, and larger studies are needed to assess the long-term impact of GLP-1 RAs in KTRs irrespective of T2DM. CI - (c) 2026 ACCP Foundation, Ltd. FAU - Shabanowitz, Stephanie AU - Shabanowitz S AUID- ORCID: 0009-0004-2180-3037 AD - UNC Medical Center, Chapel Hill, North Carolina, USA. FAU - Clark, Ryan AU - Clark R AUID- ORCID: 0009-0007-9367-7983 AD - UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA. FAU - Allen, Rachel Bassett AU - Allen RB AUID- ORCID: 0009-0003-9020-1307 AD - UNC Medical Center, Chapel Hill, North Carolina, USA. FAU - Chandran, Mary AU - Chandran M AUID- ORCID: 0000-0003-4309-7896 AD - UNC Medical Center, Chapel Hill, North Carolina, USA. FAU - Yang, Anita AU - Yang A AUID- ORCID: 0000-0002-7362-205X AD - UNC Medical Center, Chapel Hill, North Carolina, USA. LA - eng PT - Journal Article PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Kidney Transplantation MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Proteinuria/drug therapy MH - Middle Aged MH - Glomerular Filtration Rate/drug effects MH - Glycated Hemoglobin MH - Adult MH - Transplant Recipients OTO - NOTNLM OT - albuminuria OT - glucagon-like peptide-1 receptor agonists OT - kidney transplant EDAT- 2026/03/09 13:42 MHDA- 2026/03/09 13:43 CRDT- 2026/03/09 07:53 PHST- 2026/01/06 00:00 [revised] PHST- 2025/08/13 00:00 [received] PHST- 2026/01/13 00:00 [accepted] PHST- 2026/03/09 13:43 [medline] PHST- 2026/03/09 13:42 [pubmed] PHST- 2026/03/09 07:53 [entrez] AID - 10.1002/phar.70123 [doi] PST - ppublish SO - Pharmacotherapy. 2026 Apr;46(4):e70123. doi: 10.1002/phar.70123. PMID- 41798193 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Glucagon-like peptide-1 agonists in children with obesity and type 2 diabetes. an umbrella review. PG - 1777907 LID - 10.3389/fendo.2026.1777907 [doi] LID - 1777907 AB - INTRODUCTION: Obesity and type 2 diabetes mellitus (Type 2 DM) are rising at an alarming rate among children and adolescents. This population often exhibits suboptimal glycemic control and diabetes-related complications. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) have emerged as a promising therapeutic option for pediatric patients due to their beneficial effects on weight reduction and glycemic regulation. Literature on this important issue is scarce. We aimed to assess the effects of GLP-1 agonists on body weight, HbA1c, body mass index z (BMI z), and systolic blood pressure (SBP). Additionally, we discussed adverse events and hypoglycemia. METHODS: We searched PubMed/MEDLINE, Web of Science, and the Cochrane Library from October to November 2025 using the following terms: GLP-1 agonists, semaglutide, tirzepatide, liraglutide, exenatide, children, obesity, adolescents, blood pressure, BMI z, hypoglycemia, body weight, and HbA1c. We retrieved 1600 articles. Out of the 44 reviews found, only 11 meta-analyses were included in the final results. RESULTS: GLP-1 agonists were more effective than control in reducing body weight, HbA1c, BMI z, and blood pressure, MD = 0.11, 95% CI 0.05-0.25, MD = 0.65, 95% CI 0.53-0.80, MD = 0.85, 95% CI 0.81-0.90, and MD = 0.19, 95% CI 0.04-83, respectively. The total adverse events and hypoglycemia were not different, log ratios=1.29, 95% CI 0.80-2.09, and log ratios=1.26, 95% CI 0.59-2.70, respectively. DISCUSSION: GLP-1 agonists are a promising and effective therapy for lowering weight, HbA1c, BMI z, and SBP in adolescents with obesity or youth with type 2 DM. Moreover, GLP-1 agonists were well tolerated, and the total adverse events and hypoglycemia were comparable to those of controls. CI - Copyright (c) 2026 Mirghani, Albishi and Alblewi. FAU - Mirghani, Hyder AU - Mirghani H AD - Internal Medicine Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Albishi, Laila AU - Albishi L AD - Pediatrics Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alblewi, Sawsan Mohmmad AU - Alblewi SM AD - Pediatrics Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260219 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Child MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Pediatric Obesity/drug therapy/complications MH - Semaglutide MH - Adolescent MH - Tirzepatide MH - Liraglutide/therapeutic use MH - Glycated Hemoglobin PMC - PMC12960479 OTO - NOTNLM OT - GLP-1 agonists OT - HbA1c OT - adolescents OT - blood pressure OT - children OT - hypoglycemia OT - obesity OT - side effects COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/09 17:37 MHDA- 2026/03/09 17:38 PMCR- 2026/02/19 CRDT- 2026/03/09 06:08 PHST- 2025/12/30 00:00 [received] PHST- 2026/01/30 00:00 [revised] PHST- 2026/02/02 00:00 [accepted] PHST- 2026/03/09 17:38 [medline] PHST- 2026/03/09 17:37 [pubmed] PHST- 2026/03/09 06:08 [entrez] PHST- 2026/02/19 00:00 [pmc-release] AID - 10.3389/fendo.2026.1777907 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Feb 19;17:1777907. doi: 10.3389/fendo.2026.1777907. eCollection 2026. PMID- 41797511 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260904 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 Suppl 2 IP - Suppl 2 DP - 2026 Sep TI - Evaluating the Evolving Real-World Adverse Events of GLP-1RAs Using FDA Adverse Event Reporting System (FAERS). PG - 101-108 LID - 10.1002/oby.70176 [doi] AB - OBJECTIVE: This study aimed to assess the spectrum and frequency of adverse events (AEs) linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) using the US FDA Adverse Event Reporting System (FAERS). Emphasis was placed on emerging safety concerns in context-specific use. METHODS: A retrospective analysis of FAERS reports between 2012 and 2025 was conducted. Five commonly prescribed FDA-approved GLP-1RAs were included. Disproportionality analyses were applied to detect AE signals. Subgroup analyses evaluated associations by indication, GLP-1RAs compared to other drugs, and AEs specific to individual GLP-1RAs. RESULTS: From over 18 million FAERS reports, 137,451 involved GLP-1RAs. The most frequent AEs were gastrointestinal, nutritional and metabolic, and psychiatric disorders, occurring at higher rates compared to other drugs. In diabetes use, GLP-1RAs were associated with retinopathy, hearing loss, and cataracts. In contrast, when prescribed for weight management/obesity, nutritional, metabolic, and psychiatric AEs predominated. We also developed an open-access portal for AE exploration, available at http://glp1.tanlab.org. CONCLUSIONS: GLP-1RAs are linked to a broad range of AEs across indications. These findings stress the need for careful clinical monitoring and long-term safety evaluation. This study also illustrates how real-world evidence can inform safety communications, as well as hypothesis generation for research on next-generation GLP-1RAs. CI - (c) 2026 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Stone, David AU - Stone D AD - Departments of Oncological Sciences and Biomedical Informatics, University of Utah, Salt Lake City, Utah, USA. AD - Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. FAU - Playdon, Mary AU - Playdon M AD - Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. AD - Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, USA. FAU - Hursting, Stephen D AU - Hursting SD AD - Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. AD - Nutrition Research Institute, University of Carolina at Chapel Hill, Kannapolis, North Carolina, USA. AD - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. FAU - Tan, Aik Choon AU - Tan AC AD - Departments of Oncological Sciences and Biomedical Informatics, University of Utah, Salt Lake City, Utah, USA. AD - Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. LA - eng GR - Huntsman Cancer Institute, University of Utah/ PT - Journal Article DEP - 20260309 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - United States Food and Drug Administration MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide PMC - PMC13535732 COIS- The authors declare no conflicts of interest. EDAT- 2026/03/09 07:41 MHDA- 2026/09/02 05:36 PMCR- 2026/09/02 CRDT- 2026/03/09 03:43 PHST- 2026/01/15 00:00 [revised] PHST- 2025/09/02 00:00 [received] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/09/02 05:36 [medline] PHST- 2026/03/09 07:41 [pubmed] PHST- 2026/03/09 03:43 [entrez] PHST- 2026/09/02 00:00 [pmc-release] AID - OBY70176 [pii] AID - 10.1002/oby.70176 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Sep;34 Suppl 2(Suppl 2):101-108. doi: 10.1002/oby.70176. Epub 2026 Mar 9. PMID- 41796736 OWN - NLM STAT- MEDLINE DCOM- 20260703 LR - 20260703 IS - 2173-5794 (Electronic) IS - 2173-5794 (Linking) VI - 101 IP - 7 DP - 2026 Jul TI - Simultaneous bilateral NAION following initiation of high-dose semaglutide: a case report. PG - 502490 LID - S2173-5794(26)00058-7 [pii] LID - 10.1016/j.oftale.2026.502490 [doi] AB - We report a case of simultaneous bilateral non-arteritic anterior ischemic optic neuropathy (NAION) in a 68-year-old man with poorly controlled type 2 diabetes mellitus and significant hyperopia (+5 diopters). Visual loss began 14 days after initiating semaglutide at a relatively high dose (0.5mg/week), progressing to functional blindness within four weeks. Ophthalmologic examination revealed bilateral optic disc edema with hemorrhages, exudates, and subretinal fluid. Infectious and autoimmune causes were ruled out, and cerebrospinal fluid analysis was normal. Following the high dose of semaglutide, glycated hemoglobin decreased, although the magnitude and speed of this decline should be interpreted with caution, and the association between the drug and the optic nerve event must be considered purely temporal, with no evidence of direct causality. Despite drug discontinuation and corticosteroid treatment, visual loss persisted. The simultaneous bilateral presentation, rapid progression, and predisposing anatomical factors-crowded optic discs and possible scleral rigidity-highlight extreme vulnerability. This case illustrates a possible temporal association, representing one of the few such cases reported to date, and underscores the importance of baseline ophthalmic evaluation, close monitoring, and careful consideration of initial dosing in patients treated with GLP-1 receptor agonists. CI - Copyright (c) 2026 Sociedad Espanola de Oftalmologia. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Asensio-Sanchez, V M AU - Asensio-Sanchez VM AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. Electronic address: vmasensio@yahoo.es. FAU - Rodriguez-Espinosa, J AU - Rodriguez-Espinosa J AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Silva-Schultz, S AU - Silva-Schultz S AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Gonzalez-Fernandez, G AU - Gonzalez-Fernandez G AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Lallana-Serrano, S AU - Lallana-Serrano S AD - Servicio de Neurologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. LA - eng PT - Case Reports PT - Journal Article DEP - 20260306 PL - Spain TA - Arch Soc Esp Oftalmol (Engl Ed) JT - Archivos de la Sociedad Espanola de Oftalmologia JID - 101715860 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Optic Neuropathy, Ischemic/chemically induced MH - Glycated Hemoglobin/analysis MH - Blindness/chemically induced OTO - NOTNLM OT - Adverse effect OT - Agonista GLP-1 OT - Bilateral OT - Efecto adverso OT - GLP-1 receptor agonist OT - Neuropatia optica isquemica anterior no arteritica OT - Non-arteritic anterior ischemic optic neuropathy OT - Semaglutida OT - Semaglutide COIS- Declaration of competing interest None declared. EDAT- 2026/03/09 07:41 MHDA- 2026/07/04 00:33 CRDT- 2026/03/09 00:45 PHST- 2025/09/22 00:00 [received] PHST- 2025/11/16 00:00 [revised] PHST- 2025/11/30 00:00 [accepted] PHST- 2026/07/04 00:33 [medline] PHST- 2026/03/09 07:41 [pubmed] PHST- 2026/03/09 00:45 [entrez] AID - S2173-5794(26)00058-7 [pii] AID - 10.1016/j.oftale.2026.502490 [doi] PST - ppublish SO - Arch Soc Esp Oftalmol (Engl Ed). 2026 Jul;101(7):502490. doi: 10.1016/j.oftale.2026.502490. Epub 2026 Mar 6. PMID- 41796096 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - GLP-1 Receptor Agonists in Brazil: Landscape of Consumption, Safety and Regulation. PG - 4185-4193 LID - 10.1111/dom.70609 [doi] AB - BACKGROUND: The escalating use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is reshaping pharmaceutical consumption patterns and posing unprecedented challenges to healthcare systems worldwide. This study analyzes the landscape of GLP-1 RA consumption, safety monitoring and regulatory oversight in Brazil. METHODS: A retrospective regulatory surveillance study was carried out triangulating data from three official sources: (1) national sales covering 2020-2024, classifying according to Anatomical Therapeutic Chemical (ATC) system; (2) adverse event reports submitted to Vigimed, the national pharmacovigilance platform integrated with global VigiBase; and (3) official alerts of falsified products. Sales data were sourced from industrial reports and the National System for the Management of Controlled Products (SNGPC). RESULTS: Semaglutide emerged as the predominant GLP-1 RA in the Brazilian market. Consumption was markedly concentrated in regions with higher Gross Domestic Product (GDP), revealing a disconnect between medication use and regional diabetes prevalence. Pharmacovigilance analysis uncovered a significant proportion of reports involving off-label use, pointing to potential clinical and regulatory gaps. Furthermore, documented cases of counterfeit products underscore critical supply chain vulnerabilities. CONCLUSION: The convergence of escalating demand, widespread off-label use and product falsification requires a coordinated and agile regulatory response. The observed trends suggest significant access disparities driven by economic factors rather than epidemiological need. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hurtado, Renato Lopes AU - Hurtado RL AUID- ORCID: 0009-0008-0556-5015 AD - Agencia Nacional de Vigilancia Sanitaria (Anvisa), Brasilia, Brazil. AD - University of Brasilia, Brasilia, Brazil. FAU - Amato, Angelica Amorim AU - Amato AA AUID- ORCID: 0000-0002-8454-5504 AD - University of Brasilia, Brasilia, Brazil. FAU - de Luca Correa, Hugo AU - de Luca Correa H AD - Catholic University of Brasilia, Brasilia, Brazil. FAU - Silveira, Damaris AU - Silveira D AD - University of Brasilia, Brasilia, Brazil. LA - eng PT - Journal Article DEP - 20260308 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Brazil/epidemiology MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Pharmacovigilance MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use/adverse effects PMC - PMC13071213 OTO - NOTNLM OT - GLP-1 analogue OT - pharmaco-epidemiology OT - population study OT - real-world evidence COIS- The authors declare no conflicts of interest. EDAT- 2026/03/09 00:36 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/03/08 23:43 PHST- 2026/02/15 00:00 [revised] PHST- 2026/01/12 00:00 [received] PHST- 2026/02/17 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/03/09 00:36 [pubmed] PHST- 2026/03/08 23:43 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70609 [pii] AID - 10.1111/dom.70609 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):4185-4193. doi: 10.1111/dom.70609. Epub 2026 Mar 8. PMID- 41794178 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260623 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 66 IP - 3 DP - 2026 May-Jun TI - Semaglutide use in a patient with a long-term ileostomy: A case report highlighting clinical risks and evidence gaps. PG - 103069 LID - S1544-3191(26)00054-3 [pii] LID - 10.1016/j.japh.2026.103069 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, dulaglutide, liraglutide, and exenatide, are increasingly used to treat type 2 diabetes and support weight loss. These agents function by enhancing glucose-dependent insulin secretion, suppressing inappropriate glucagon secretion, slowing gastric emptying, and regulating appetite through central nervous system pathways. Since semaglutide's approval in 2017 and U.S. market availability in 2018, its use has expanded significantly. However, there remains limited literature evaluating its safety and efficacy in patients with altered gastrointestinal anatomy, particularly those with ostomies. CASE SUMMARY: A 56-year-old Hispanic male with type 2 diabetes, body mass index (BMI) of 54.3, and an ileostomy placed in 2012 was prescribed semaglutide for glycemic control and weight loss by an endocrinology clinic. He continued intermittent use over an 18-month period without complications. Initially, semaglutide was associated with reduced appetite and weight loss of 19 pounds (from 278 lbs., BMI 54.3, to 259 lbs., BMI 50.6) over 5 months. He paused the medication 1 week prior to a scheduled colonoscopy and resumed 1 week after. Within 2 weeks of restarting, he experienced progressive slowing of gastrointestinal motility, including hard stools and bowel movements every other day. These symptoms culminated in fecal impaction requiring hospitalization later that month. He permanently discontinued semaglutide and has not resumed since. PRACTICE IMPLICATIONS: To date, no clinical trials or guidelines address the safety of GLP-1 RAs in patients with ileostomies or significant gastrointestinal alterations. This case emphasizes a critical gap in literature. While GLP-1 RAs offer metabolic benefits in type 2 diabetes and weight management, they may pose underrecognized risks in patients with altered bowel anatomy. Until further evidence is available, clinicians should exercise caution, perform individualized risk-benefit assessments, and consider close collaboration with gastroenterology. Further research is needed to evaluate the safety, tolerability, and pharmacokinetics of GLP-1 RAs in patients with ostomies. CI - Copyright (c) 2026 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Gaytan, Gabriela AU - Gaytan G FAU - Pabon, Andrea AU - Pabon A FAU - Rosario, Natalie AU - Rosario N LA - eng PT - Case Reports PT - Journal Article DEP - 20260305 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Ileostomy MH - *Semaglutide/administration & dosage/adverse effects MH - Weight Loss/drug effects MH - *Postoperative Complications/chemically induced EDAT- 2026/03/08 01:38 MHDA- 2026/06/12 13:04 CRDT- 2026/03/07 19:12 PHST- 2025/10/21 00:00 [received] PHST- 2026/02/14 00:00 [revised] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/06/12 13:04 [medline] PHST- 2026/03/08 01:38 [pubmed] PHST- 2026/03/07 19:12 [entrez] AID - S1544-3191(26)00054-3 [pii] AID - 10.1016/j.japh.2026.103069 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2026 May-Jun;66(3):103069. doi: 10.1016/j.japh.2026.103069. Epub 2026 Mar 5. PMID- 41793524 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260718 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 31 IP - 3 DP - 2026 Mar 7 TI - Semaglutide attenuates diabetic vascular calcification by enhancing autophagy and lysosomal function via targeting CPNE1. LID - 93 [pii] LID - 10.1007/s10495-026-02269-3 [doi] AB - Patients with diabetes exhibit an increased susceptibility to vascular calcification, which is associated with significantly elevated risks of mortality and disability. As a new Glucagon-like peptide-1 receptor agonist, Semaglutide is primarily indicated for type 2 diabetes mellitus and obesity, while also demonstrating definitive cardiovascular protective effects. However, the effect of semaglutide on diabetic vascular calcification remains unknown. Our results demonstrated a dose-dependent reduction in calcium deposition with Semaglutide treatment, which was accompanied by downregulation of RUNX2 and BMP2 protein expression in aortic tissues. Additionally, Semaglutide also conferred protective effects in AGE-BSA stimulated mouse aortic smooth muscle cells (MOVAS). Autophagy, a lysosomal degradation pathway, is intimately involved in the pathological process of diabetic vascular calcification. During stimulation with AGEs-BSA, impaired lysosomal function and blocked autophagic flux were observed, as evidenced by increased protein levels of LC3-II and P62, alongside decreased expression of CTSD, CTSB, LAMP1 and LAMP2. These changes were accompanied by a decline in lysosomal pH, activity, and degradative capacity. Treatment with Semaglutide mitigated these abnormalities, restoring autophagic flux and lysosomal function, and consequently attenuating AGEs-BSA-induced calcification in MOVAS. Combined bioinformatics and Western blot analysis confirmed the significant downregulation of CPNE1 by Semaglutide in AGEs-BSA stimulated MOVAS. Copine-1 (CPNE1), a member of the copine protein family, is characterized as a calcium-dependent phospholipid-binding protein that primarily resides in the cytoplasm. These findings indicate that the attenuation of diabetic vascular calcification (DVC) by Semaglutide is associated with the inhibition of CPNE1-mediated autophagy, suggesting a potential novel therapeutic strategy for managing DVC. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Xiao, Shengjue AU - Xiao S AD - The Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China. FAU - Li, Wei AU - Li W AD - Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu Province, China. AD - Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China. FAU - Liu, Naifeng AU - Liu N AD - Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China. liunf@seu.edu.cn. LA - eng GR - 82170478/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260307 PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Runx2 protein, mouse) RN - 0 (Bmp2 protein, mouse) SB - IM MH - Semaglutide MH - Animals MH - *Autophagy/drug effects MH - *Vascular Calcification/drug therapy/metabolism/pathology/genetics MH - Mice MH - *Lysosomes/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology MH - Myocytes, Smooth Muscle/drug effects/metabolism/pathology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Core Binding Factor Alpha 1 Subunit/metabolism/genetics MH - Muscle, Smooth, Vascular/drug effects/metabolism MH - Bone Morphogenetic Protein 2/metabolism/genetics MH - Aorta/drug effects/pathology/metabolism MH - Male OTO - NOTNLM OT - Autophagy OT - CPNE1 OT - Diabetic vascular calcification OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All animal experiments were performed in accordance with the protocols approved by the Animal Care and Use Committee of Southeast University (Approval number: 20240217004 and 20240217005). Consent for publication: Not applicable. EDAT- 2026/03/07 16:09 MHDA- 2026/03/08 01:38 CRDT- 2026/03/07 11:16 PHST- 2025/10/10 00:00 [received] PHST- 2026/01/03 00:00 [accepted] PHST- 2026/03/08 01:38 [medline] PHST- 2026/03/07 16:09 [pubmed] PHST- 2026/03/07 11:16 [entrez] AID - 10.1007/s10495-026-02269-3 [pii] AID - 10.1007/s10495-026-02269-3 [doi] PST - epublish SO - Apoptosis. 2026 Mar 7;31(3):93. doi: 10.1007/s10495-026-02269-3. PMID- 41793207 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 17 IP - 5 DP - 2026 May TI - Association of glucagon-like peptide-1 receptor agonist use with clinical outcomes in patients with rheumatoid arthritis and type 2 diabetes. PG - 766-780 LID - 10.1111/jdi.70281 [doi] AB - OBJECTIVES: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with improved survival and renal outcomes in patients with rheumatoid arthritis and type 2 diabetes, a population at high cardiometabolic risk. MATERIALS AND METHODS: We conducted a retrospective cohort study using an active-comparator, new-user design within the TriNetX US Collaborative Network. Adults with rheumatoid arthritis and type 2 diabetes initiating GLP-1 RAs or dipeptidyl peptidase-4 inhibitors (DPP-4is) between 2016 and 2023 were included. The primary outcome was all-cause mortality; secondary outcomes were major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), and all-cause hospitalization. Hazard ratios (HRs) were estimated using Cox regression after 1:1 propensity score matching. RESULTS: A total of 4,607 patients per group were followed for up to 4 years. GLP-1 RA use was associated with lower all-cause mortality (HR 0.68; 95% confidence intervals (CI), 0.58-0.80), reduced MAKE (HR 0.89; 95% CI, 0.82-0.97), and fewer hospitalizations (HR 0.92; 95% CI, 0.86-0.98), compared with DPP-4is. No significant difference was observed for MACE (HR 0.96; 95% CI, 0.89-1.04). Results were consistent across prespecified subgroups and sensitivity analyses. CONCLUSIONS: In patients with rheumatoid arthritis and type 2 diabetes, GLP-1 RA therapy was associated with 32% lower mortality, 11% fewer kidney events, and 8% fewer hospitalizations vs DPP-4is. These findings support GLP-1 RAs as a promising therapeutic option for this high-risk population. CI - (c) 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yu, Yu-Ting AU - Yu YT AD - Division of Family Medicine, Department of Community Medicine, Landseed International Hospital, Taoyuan, Taiwan. FAU - Lee, Ying Chun AU - Lee YC AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Hsieh, Wen-Hui AU - Hsieh WH AD - Data Analysis Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AUID- ORCID: 0000-0003-3561-4689 AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. AD - Data Analysis Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. LA - eng GR - 2024SKHADR010/Shin Kong Wu Ho-Su Memorial Hospital/ PT - Journal Article DEP - 20260307 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Arthritis, Rheumatoid/drug therapy/complications/mortality MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Treatment Outcome MH - Follow-Up Studies PMC - PMC13137280 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Rheumatoid arthritis OT - Type 2 diabetes mellitus COIS- The authors declare no conflict of interest. Approval of the research protocol: This study was approved by the Institutional Review Board of Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (approval no.: 20250104R). Informed consent: Not applicable. This study used de-identified data from the TriNetX research network. Registry and registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2026/03/07 06:40 MHDA- 2026/05/04 12:34 PMCR- 2026/03/07 CRDT- 2026/03/07 05:53 PHST- 2026/01/17 00:00 [revised] PHST- 2025/10/24 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/05/04 12:34 [medline] PHST- 2026/03/07 06:40 [pubmed] PHST- 2026/03/07 05:53 [entrez] PHST- 2026/03/07 00:00 [pmc-release] AID - JDI70281 [pii] AID - 10.1111/jdi.70281 [doi] PST - ppublish SO - J Diabetes Investig. 2026 May;17(5):766-780. doi: 10.1111/jdi.70281. Epub 2026 Mar 7. PMID- 41790761 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 23 IP - 3 DP - 2026 Mar TI - SGLT2 inhibitors, GLP-1 RAs, and DPP4 inhibitors and the risk of hypomagnesemia in type 2 diabetes: A target trial emulation. PG - e1004968 LID - 10.1371/journal.pmed.1004968 [doi] LID - e1004968 AB - BACKGROUND: Recent studies have suggested potential effects on magnesium homeostasis associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We sought to determine whether these effects lead to a reduced risk of hypomagnesemia among adults with type 2 diabetes in clinical practice. METHODS AND FINDINGS: We conducted a target trial emulation study using the multi-institutional cohort data from the TriNetX Global Collaborative Network. We compared 1:1 propensity score-matched patients with type 2 diabetes newly initiating SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors (n = 718,798), GLP-1 RAs versus DPP4 inhibitors (n = 623,390), and SGLT2 inhibitors versus GLP-1 RAs (n = 702,808) from 2016 to 2024. Propensity scores were estimated using logistic regression models that included baseline covariates such as age, sex, race, comorbidities, and medication and laboratory data. In each comparison, patients receiving DPP4 inhibitors were considered the active-comparator group. The primary outcome was incident hypomagnesemia, defined by clinical diagnosis or serum magnesium <1.80 mg/dL. Patients were followed until the occurrence of an outcome of interest, last clinical visit, death, or the end of database period (March 31, 2025), whichever came first. We found that initiation of SGLT2 inhibitors was associated with a significantly lower risk of hypomagnesemia, compared with both DPP4 inhibitors (Hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.79, 0.82; p < 0.05) and GLP-1 RAs (HR: 0.92; 95% CI: 0.91, 0.93; p < 0.05). Similarly, GLP-1 RA use was associated with a lower risk of hypomagnesemia, compared with DPP4 inhibitors (HR: 0.89; 95% CI: 0.88, 0.91; p < 0.05). These associations were consistent across individual agents within each drug class. The main limitation of our study is that residual confounding inherent to retrospective observational research cannot be completely ruled out. CONCLUSIONS: Treatment with SGLT2 inhibitors and GLP-1 RAs was associated with a lower risk of hypomagnesemia, compared with DPP4 inhibitors. These findings suggest that SGLT2 inhibitors and GLP-1 RAs may be preferable options for patients at risk of hypomagnesemia. CI - Copyright: (c) 2026 Shao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Shao, Shih-Chieh AU - Shao SC AUID- ORCID: 0000-0003-4867-6686 AD - Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Tsai, Daniel Hsiang-Te AU - Tsai DH AUID- ORCID: 0000-0003-2841-0338 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Chuang, Albert Tzu-Ming AU - Chuang AT AUID- ORCID: 0009-0000-1738-9671 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Liu, Kuan-Hung AU - Liu KH AUID- ORCID: 0000-0001-5988-6123 AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AUID- ORCID: 0000-0002-5852-7652 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260306 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - I38ZP9992A (Magnesium) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Magnesium/blood MH - Risk Factors MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects PMC - PMC12987583 COIS- The authors have declared that no competing interests exist. EDAT- 2026/03/06 19:43 MHDA- 2026/03/13 19:31 PMCR- 2026/03/06 CRDT- 2026/03/06 13:43 PHST- 2025/08/08 00:00 [received] PHST- 2026/02/17 00:00 [accepted] PHST- 2026/03/13 00:00 [revised] PHST- 2026/03/13 19:31 [medline] PHST- 2026/03/06 19:43 [pubmed] PHST- 2026/03/06 13:43 [entrez] PHST- 2026/03/06 00:00 [pmc-release] AID - PMEDICINE-D-25-02820 [pii] AID - 10.1371/journal.pmed.1004968 [doi] PST - epublish SO - PLoS Med. 2026 Mar 6;23(3):e1004968. doi: 10.1371/journal.pmed.1004968. eCollection 2026 Mar. PMID- 41787737 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 2 DP - 2026 Mar TI - Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled Trials. PG - e70187 LID - 10.1002/edm2.70187 [doi] LID - e70187 AB - INTRODUCTION: Glucagon receptor agonists (GRAs) are an emerging class of therapies for obesity and type 2 diabetes, demonstrating encouraging metabolic and weight-reducing effects. Several investigational GRA-based agents, including retatrutide, cotadutide, mazdutide, and survodutide, have reported promising results across early and mid-phase clinical trials. This comprehensive meta-analysis evaluates the efficacy and safety of these agents in individuals with type 2 diabetes, overweight, or obesity. METHODS: PubMed, Cochrane, Embase, and Scopus databases were systematically searched. Fourteen randomised controlled trials meeting the inclusion criteria were analysed using frequentist network meta-analysis. Random-effects models were applied to assess mean differences (MD) in weight change, both absolute and percent changes, HbA1c, adverse events, and discontinuation due to adverse events. Heterogeneity was quantified using the I(2) statistic. RESULTS: Retatrutide demonstrated the greatest weight reduction versus placebo (MD -13.44 kg; 95% CI [-18.38, -8.51]), followed by survodutide (MD -10.74 kg; 95% CI [-15.68, -5.80]) and mazdutide (MD -6.47 kg; 95% CI [-10.71, -2.24]). Cotadutide showed the smallest and nonsignificant effect (MD -3.41 kg; 95% CI [-11.63, 4.81]). Regarding HbA1c reduction, retatrutide showed the largest effect, followed by survodutide, mazdutide, and cotadutide; however, only the effect of retatrutide reached statistical significance. In terms of safety, mazdutide demonstrated the most favourable tolerability profile, whereas retatrutide and cotadutide were associated with comparatively lower tolerability. CONCLUSIONS: Retatrutide and survodutide exhibit the most favourable efficacy profiles for obesity and T2DM, with acceptable safety. These findings support their potential clinical use and highlight the need for future head-to-head trials. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Abulehia, Ayah AU - Abulehia A AUID- ORCID: 0009-0003-4670-5065 AD - Faculty of Medicine, Al-Quds University, Jerusalem, Palestine. FAU - Ayesh, Hazem AU - Ayesh H AUID- ORCID: 0000-0001-8231-705X AD - Deaconess Health System, Evansville, Indiana, USA. AD - Indiana University, School of Medicine, Indianapolis, Indiana, USA. FAU - Ayesh, Omar AU - Ayesh O AD - Department of Medical Laboratory Sciences, Al-Aqsa University, Gaza, Palestine. FAU - Jaber, Doha AU - Jaber D AUID- ORCID: 0009-0007-8047-5768 AD - Faculty of Medicine, Al-Quds University, Jerusalem, Palestine. FAU - Asad, Thekrayat AU - Asad T AD - Faculty of Medicine, Al-Quds University, Jerusalem, Palestine. AD - Department of Internal Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York, USA. FAU - Itbaisha, Adham AU - Itbaisha A AD - Faculty of Medicine, Al-Quds University, Jerusalem, Palestine. FAU - Abugharbieh, Hamzeh AU - Abugharbieh H AD - Department of Internal Medicine, University of Toledo, Toledo, Ohio, USA. FAU - Gharbia, Raged AU - Gharbia R AD - Department of Internal Medicine, University Hospitals Geauge Medical Center, Chardon, Ohio, USA. FAU - Abu-Hilal, Lila H AU - Abu-Hilal LH AD - Faculty of Medicine, Al-Quds University, Jerusalem, Palestine. FAU - Leon, Barbara Gisella Carranza AU - Leon BGC AD - Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Randomized Controlled Trials as Topic MH - *Obesity/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - Receptors, Glucagon/agonists MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin PMC - PMC12963462 OTO - NOTNLM OT - HbA1c OT - body weight OT - diabetes OT - glucagon receptor agonists OT - metabolism OT - obesity COIS- The authors declare no conflicts of interest. EDAT- 2026/03/06 09:08 MHDA- 2026/03/08 01:38 PMCR- 2026/03/05 CRDT- 2026/03/06 01:03 PHST- 2026/02/10 00:00 [revised] PHST- 2025/10/24 00:00 [received] PHST- 2026/02/13 00:00 [accepted] PHST- 2026/03/08 01:38 [medline] PHST- 2026/03/06 09:08 [pubmed] PHST- 2026/03/06 01:03 [entrez] PHST- 2026/03/05 00:00 [pmc-release] AID - EDM270187 [pii] AID - 10.1002/edm2.70187 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Mar;9(2):e70187. doi: 10.1002/edm2.70187. PMID- 41785010 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 19 IP - 4 DP - 2026 Apr TI - Retatrutide in type 2 diabetes mellitus and obesity: an overview. PG - 313-339 LID - 10.1080/17512433.2026.2642415 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for T2DM and obesity. AREAS COVERED: An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Retatrutide (LY3437943) is a novel triple agonist targeting glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1 R). In subjects with type 2 diabetes mellitus (T2DM), decreased glycated hemoglobin (HbA(1c)) by up to 2.16% and decreased fasting glucose by up to 69.1 mg/dL have been seen. Weight loss up to 16.94% was observed in subjects with T2DM. Subjects with overweight or obesity experienced a greater weight loss by up to 26.56% (24.15 kg). Reductions in body-mass index and waist circumference were achieved. In subjects with T2DM and overweight or obesity, decreased systolic blood pressure was found. Finally, relative liver fat count in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) was reduced by up to 86%. Increased frequency of mild-to-moderate gastrointestinal adverse events (mainly nausea, vomiting, constipation, and diarrhea) was reported in participants on the highest retatrutide doses, likely due to rapid dose escalation and higher starting dose. EXPERT OPINION: These promising effects on glycemic control, weight loss, and emerging pleiotropic actions merit further investigation. FAU - Panou, Theodoros AU - Panou T AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Gouveri, Evanthia AU - Gouveri E AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Novi Sad, Serbia. AD - Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260310 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glycated Hemoglobin) RN - 0 (retatrutide) RN - 0 (Fatty Acids) RN - 0 (Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Obesity/drug therapy/physiopathology MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/pharmacology/adverse effects/administration & dosage/therapeutic use MH - Animals MH - Blood Glucose/drug effects MH - Receptors, Gastrointestinal Hormone/agonists MH - Glycated Hemoglobin/metabolism MH - Body Mass Index MH - Fatty Acids MH - Peptides OTO - NOTNLM OT - LY3437943 OT - Retatrutide OT - glucagon-like peptide-1 receptor agonists OT - metabolic dysfunction-associated steatotic liver disease OT - obesity OT - type 2 diabetes mellitus EDAT- 2026/03/05 12:48 MHDA- 2026/04/12 04:35 CRDT- 2026/03/05 11:52 PHST- 2026/04/12 04:35 [medline] PHST- 2026/03/05 12:48 [pubmed] PHST- 2026/03/05 11:52 [entrez] AID - 10.1080/17512433.2026.2642415 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2026 Apr;19(4):313-339. doi: 10.1080/17512433.2026.2642415. Epub 2026 Mar 10. PMID- 41784517 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1661-8157 (Print) IS - 1661-8157 (Linking) VI - 115 IP - 2 DP - 2026 Feb TI - [Modern treatment of type 2 diabetes: 3 medications and 3 targets]. PG - 43-44 LID - 10.23785/PRAXIS.2026.02.004 [doi] AB - Modern treatment of type 2 diabetes considers the use of three medications in all patients regardless of HbA1c (metformin, SGLT-2i, and GLP-1(+)-RA) as well as achieving three target values (HbA1c, blood pressure, and LDL cholesterol). These three target values are set individually. Ideally, most patients with type 2 diabetes should have HbA1c 6.5 %, blood pressure 130/80 mmHg, and LDL cholesterol 1.8 mmol/l. In patients with established cardiovascular disease should have LDL cholesterol 1.4 mmol/l. CI - (c) 2026 Aerzteverlag medinfo AG. FAU - Wiesli, Peter AU - Wiesli P AD - Medizinische Klinik, Kantonsspital Frauenfeld, Frauenfeld. AD - peter.wiesli@stgag.ch. LA - ger PT - English Abstract PT - Journal Article PT - Review TT - Moderne Therapie des Diabetes Typ 2: 3 Medikamente und 3 Ziele. PL - Switzerland TA - Praxis (Bern 1994) JT - Praxis JID - 101468093 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cholesterol, LDL) RN - 9100L32L2N (Metformin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - *Sodium-Glucose Transporter 2 Inhibitors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Cholesterol, LDL/blood MH - *Metformin/therapeutic use/adverse effects MH - Drug Therapy, Combination MH - Blood Pressure/drug effects MH - Hypertension/drug therapy/blood OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - Type 2 diabetes OT - dyslipidemia OT - hypertension EDAT- 2026/03/05 12:48 MHDA- 2026/03/07 01:37 CRDT- 2026/03/05 10:03 PHST- 2026/03/07 01:37 [medline] PHST- 2026/03/05 12:48 [pubmed] PHST- 2026/03/05 10:03 [entrez] AID - 10.23785/PRAXIS.2026.02.004 [doi] PST - ppublish SO - Praxis (Bern 1994). 2026 Feb;115(2):43-44. doi: 10.23785/PRAXIS.2026.02.004. PMID- 41784422 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1473-5687 (Electronic) IS - 0954-691X (Linking) VI - 38 IP - 6 DP - 2026 Jun 1 TI - Glucagon-like peptide-1 receptor agonist reduces risk of alcohol-associated cirrhosis in type 2 diabetes and alcohol use disorder patients. PG - 747-754 LID - 10.1097/MEG.0000000000003162 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can reduce alcohol consumption and craving; however, it is unclear whether GLP-1 RAs can prevent the development of alcohol-associated cirrhosis. We analyzed the incidence of cirrhosis and hepatic decompensation in individuals with type 2 diabetes and alcohol use disorder (AUD) who received GLP-1 RAs compared with other antidiabetic medications. METHODS: Using the TriNetX database, we identified adult patients with AUD and type 2 diabetes between 2010 and 2022 and compared outcomes among patients who received either a GLP-1 RA or other antidiabetic medications. Primary outcomes were alcohol-associated cirrhosis and its complications, and a propensity score model was built adjusting for demographics, comorbidities, AUD treatment, BMI, hemoglobin A1c, and alanine aminotransferase. RESULTS: After matching, sample sizes ranged from 2543 patients each in the GLP-1 RA versus thiazolidinedione group to 6776 patients each in the GLP-1 RA versus sulfonylurea group. The hazard ratio of GLP-1 RA versus dipeptidyl peptidase 4 inhibitor on any cirrhosis or decompensation event was 0.684 [95% confidence interval (CI): 0.615-0.762], while the hazard ratio of GLP-1 RA versus metformin was 0.87 (95% CI: 0.752-1.006). In patients with obesity, GLP-1 RA exhibited a lower risk of any cirrhosis or decompensation event than insulin group (hazard ratio: 0.327, 95% CI: 0.263-0.406) and sodium-glucose co-transporter 2 inhibitor group (hazard ratio: 0.81, 95% CI: 0.674-0.973), whereas in nonobese patients, GLP-1 RA showed a lower risk of any cirrhosis or decompensation event compared with the insulin group (hazard ratio: 0.222, 95% CI: 0.133-0.373) and dipeptidyl peptidase 4 inhibitor group (hazard ratio: 0.732, 95% CI: 0.574-0.933). CONCLUSION: GLP-1 RAs were associated with lower odds of the development of advanced alcohol-associated liver disease, including cirrhosis or hepatic decompensation. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Hwang, Soo Young AU - Hwang SY AD - Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. AD - University of Maryland Medical Center, Midtown Campus, Baltimore, Maryland. FAU - Hsieh, Pinghsin AU - Hsieh P AD - University of Maryland Medical Center, Midtown Campus, Baltimore, Maryland. FAU - Diaz, Luis Antonio AU - Diaz LA AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA. AD - Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Goodman, Russell P AU - Goodman RP AD - Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. AD - Harvard Medical School. FAU - Schaefer, Esperance A AU - Schaefer EA AD - Harvard Medical School. AD - Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Wong, Robert J AU - Wong RJ AD - Division of Gastroenterology and Hepatology, VA Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California, USA. FAU - Luther, Jay AU - Luther J AD - Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. AD - Harvard Medical School. FAU - Zhang, Wei AU - Zhang W AD - Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. AD - Harvard Medical School. LA - eng PT - Journal Article DEP - 20260219 PL - England TA - Eur J Gastroenterol Hepatol JT - European journal of gastroenterology & hepatology JID - 9000874 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Thiazolidinediones) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Liver Cirrhosis, Alcoholic/prevention & control/epidemiology MH - *Alcoholism/complications/drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged MH - Risk Factors MH - Thiazolidinediones/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Databases, Factual MH - Adult MH - Incidence OTO - NOTNLM OT - 1 receptor agonists OT - GLP- OT - alcohol- OT - associated cirrhosis OT - associated liver disease OT - decompensation EDAT- 2026/03/05 12:47 MHDA- 2026/05/01 18:45 CRDT- 2026/03/05 09:23 PHST- 2025/11/17 00:00 [received] PHST- 2026/01/21 00:00 [accepted] PHST- 2026/05/01 18:45 [medline] PHST- 2026/03/05 12:47 [pubmed] PHST- 2026/03/05 09:23 [entrez] AID - 00042737-990000000-00663 [pii] AID - 10.1097/MEG.0000000000003162 [doi] PST - ppublish SO - Eur J Gastroenterol Hepatol. 2026 Jun 1;38(6):747-754. doi: 10.1097/MEG.0000000000003162. Epub 2026 Feb 19. PMID- 41781102 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1932-2275 (Print) IS - 1932-2275 (Linking) VI - 44 IP - 1 DP - 2026 Mar TI - Airway Management in the Age of GLP-1 Receptor Agonists: New Challenges and Solutions. PG - 125-137 LID - S1932-2275(25)00104-1 [pii] LID - 10.1016/j.anclin.2025.10.010 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have rapidly become commonplace in clinical practice as treatment for type II diabetes and obesity. Their mechanism of action results in an increased risk of residual gastric content, despite adequate preprocedural fasting, which may increase the risk of regurgitation and aspiration. This is particularly relevant for patients with preexisting comorbidities such as gastroparesis or who are undergoing procedures without definitive airway protection. This article summarizes the current evidence around GLP-1 RAs including a review of the various international consensus guidelines and gives structured recommendations for perioperative management and risk stratification. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Valkeniers, Karolien AU - Valkeniers K AD - Department of Anaesthesia, UZ Leuven, Leuven, Belgium. FAU - Wallyn, An AU - Wallyn A AD - Department of Anaesthesiology, Imeldaziekenhuis, Bonheiden, Belgium. FAU - Van de Putte, Peter AU - Van de Putte P AD - Department of Anaesthesiology, Imeldaziekenhuis, Bonheiden, Belgium. FAU - Hogg, Rosemary M G AU - Hogg RMG AD - Department of Anaesthesia, Belfast Health and Social Care Trust, Belfast, UK. Electronic address: rosemary.hogg@belfasttrust.hscni.net. LA - eng PT - Journal Article PT - Review DEP - 20251209 PL - United States TA - Anesthesiol Clin JT - Anesthesiology clinics JID - 101273663 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Airway Management/methods MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Airway management OT - Delayed gastric emptying OT - GLP-1 receptor agonists OT - Gastric ultrasound OT - Point of care ultrasound OT - Pulmonary aspiration OT - Residual gastric content OT - Risk COIS- Disclosure All authors have no disclosures other than those quoted in the declaration of interest. EDAT- 2026/03/05 00:39 MHDA- 2026/03/07 01:37 CRDT- 2026/03/04 20:54 PHST- 2026/03/07 01:37 [medline] PHST- 2026/03/05 00:39 [pubmed] PHST- 2026/03/04 20:54 [entrez] AID - S1932-2275(25)00104-1 [pii] AID - 10.1016/j.anclin.2025.10.010 [doi] PST - ppublish SO - Anesthesiol Clin. 2026 Mar;44(1):125-137. doi: 10.1016/j.anclin.2025.10.010. Epub 2025 Dec 9. PMID- 41781010 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 392 DP - 2026 Mar 4 TI - Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study. PG - e086886 LID - 10.1136/bmj-2025-086886 [doi] LID - e086886 AB - OBJECTIVES: To investigate whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD related adverse clinical outcomes among people with a pre-existing SUD (protocol 2). DESIGN: Emulation of eight parallel, new user, active comparator target trials using electronic health records: seven trials for each incident SUD outcome (protocol 1) and one trial for adverse outcomes in people with pre-existing SUD (protocol 2). SETTING: US Department of Veterans Affairs. PARTICIPANTS: From a base population of 606 434 US veterans with type 2 diabetes, participants were assigned to one of the two protocols and followed for up to three years. Trial 1 (primary trial) of protocol 1 included 524 817 initiators of GLP-1 receptor agonists (n=124 001) or sodium-glucose cotransporter-2 (SGLT-2) inhibitors (n=400 816). Protocol 2 included 81 617 initiators of GLP-1 receptor agonists (n=16 768) and SGLT-2 inhibitors (n=64 849). MAIN OUTCOME MEASURES: Incident outcomes were alcohol, cannabis, cocaine, nicotine, opioid, other SUDs, and a composite of these outcomes. Adverse outcomes among participants with pre-existing SUDs included SUD related emergency department visits, SUD related hospital admissions, and SUD related mortality, and drug overdose and suicidal ideation or attempt. Hazard ratios and net three year risk difference (NRD) per 1000 people were reported based on inverse probability weighted (standardised mortality ratio weighted) cause specific Cox survival models. RESULTS: Compared with initiation of SGLT-2 inhibitors, initiation of GLP-1 receptor agonists was associated with reduced risk of disorders related to alcohol use (hazard ratio 0.82 (95% confidence interval (CI) 0.78 to 0.85); NRD per 1000 people -5.57 (-6.61 to -4.53)), cannabis use (0.86 (0.81 to 0.90), NRD -2.25 (-3.00 to -1.50)), cocaine use (0.80 (0.72 to 0.88), NRD -0.97 (-1.37 to -0.57)), nicotine use (0.80 (0.74 to 0.87), NRD -1.64 (-2.19 to -1.09)), and opioid use (0.75 (0.67 to 0.85), NRD -0.86 (-1.19 to -0.52)), and other SUDs (0.87 (0.81 to 0.94), NRD -1.12 (-1.68 to -0.55)) and composite outcome of all incident SUDs (0.86 (0.83 to 0.88), NRD -6.61 (-7.95 to -5.26)). Among people with pre-existing SUDs, initiation of GLP-1 receptor agonists was associated with reduced risk of SUD related emergency department visits (0.69 (0.61 to 0.78), NRD -8.92 (-11.59 to -6.25)), SUD related hospital admissions (0.74 (0.65 to 0.85), NRD -6.23 (-8.73 to -3.74)), and SUD related mortality (0.50 (0.32 to 0.79), NRD -1.52 (-2.32 to -0.72)), and drug overdose (0.61 (0.42 to 0.88), NRD -1.49 (-2.43 to -0.55)) and suicidal ideation or attempt (0.75 (0.67 to 0.83), NRD -9.95 (-13.14 to -6.77)). Analyses of treatment adherence showed directionally consistent results with analyses of treatment initiation for both incident SUDs and adverse outcomes among participants with pre-existing SUDs. CONCLUSIONS: Use of GLP-1 receptor agonists was consistently associated with reduced risks of developing various incident SUDs, suggesting a broad preventive effect across multiple substance types. Use was also associated with reduced risks of adverse clinical outcomes in people with pre-existing SUDs. These observational data suggest a potential role for GLP-1 receptor agonists in both the prevention and the treatment of various SUDs, warranting further evaluation. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Cai, Miao AU - Cai M AUID- ORCID: 0000-0003-0170-6905 AD - Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Veterans Research and Education Foundation of Saint Louis, Saint Louis, MO, USA. FAU - Choi, Taeyoung AU - Choi T AUID- ORCID: 0009-0002-1484-9227 AD - Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Veterans Research and Education Foundation of Saint Louis, Saint Louis, MO, USA. AD - Division of Pharmacoepidemiology, Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. FAU - Xie, Yan AU - Xie Y AUID- ORCID: 0000-0002-2457-9382 AD - Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Veterans Research and Education Foundation of Saint Louis, Saint Louis, MO, USA. AD - Division of Pharmacoepidemiology, Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Al-Aly, Ziyad AU - Al-Aly Z AUID- ORCID: 0000-0002-2600-0434 AD - Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Veterans Research and Education Foundation of Saint Louis, Saint Louis, MO, USA. AD - Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. AD - Nephrology Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, MO, USA. AD - Institute for Public Health, Washington University in Saint Louis, Saint Louis, MO, USA. LA - eng PT - Journal Article DEP - 20260304 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Veterans/statistics & numerical data MH - United States/epidemiology MH - *Substance-Related Disorders/epidemiology/prevention & control MH - Male MH - Middle Aged MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies MH - Semaglutide PMC - PMC12958796 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare. YX reports consulting (uncompensated) for Pfizer; ZAA reports funding from the US Department of Veterans Affairs; no financial relationships with any organisations that may have a financial interest in the submitted work in the previous three years; and no relationships or activities that could have influenced the submitted work. EDAT- 2026/03/05 00:39 MHDA- 2026/03/06 19:43 PMCR- 2026/03/04 CRDT- 2026/03/04 20:42 PHST- 2026/03/06 19:43 [medline] PHST- 2026/03/05 00:39 [pubmed] PHST- 2026/03/04 20:42 [entrez] PHST- 2026/03/04 00:00 [pmc-release] AID - bmj-2025-086886.R2 [pii] AID - caim086886 [pii] AID - 10.1136/bmj-2025-086886 [doi] PST - epublish SO - BMJ. 2026 Mar 4;392:e086886. doi: 10.1136/bmj-2025-086886. PMID- 41778928 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260823 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 5 DP - 2026 May 1 TI - Comparative Effectiveness of Tirzepatide Versus Dulaglutide or Semaglutide on Major Cardiovascular Events in Type 2 Diabetes and Cardiovascular Disease: Insights From Two Target-Trial Emulations. PG - 808-817 LID - 10.2337/dc25-3063 [doi] AB - OBJECTIVE: To evaluate the comparative effectiveness of dulaglutide or semaglutide versus tirzepatide on cardiovascular outcomes in adults with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: Two target trial emulations included commercially insured adults (June 2022-December 2024) with T2D and ASCVD who initiated subcutaneous tirzepatide, dulaglutide, or semaglutide. The primary outcome was modified major adverse cardiovascular events (MACE), defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. First, new users of tirzepatide and dulaglutide were propensity score (PS) matched one to one. Second, new users of tirzepatide and semaglutide were PS matched one to one. Incidence rates (IRs) per 1,000 person-years and hazard ratios (HRs) were estimated. RESULTS: After PS matching, 9,233 pairs of tirzepatide or dulaglutide initiators and 25,266 pairs of tirzepatide or semaglutide initiators were identified. Tirzepatide initiators experienced a lower rate of modified MACE versus dulaglutide initiators (IR 31.3 vs. 39.4, respectively; HR 0.80 [95% CI 0.65-0.99]), which seemed to be driven by lower all-cause mortality among tirzepatide versus dulaglutide initiators (HR 0.60 [95% CI 0.43-0.83]). In post hoc analyses, tirzepatide was associated with lower rates of pneumonia-related hospitalization when compared with dulaglutide. Rates of modified MACE were similar among tirzepatide and semaglutide initiators (IR 23.7 vs. 23.2, respectively; HR 1.03 [95% CI 0.90-1.17]). CONCLUSIONS: Among adults with T2D and ASCVD in routine care, tirzepatide was associated with a lower risk of modified MACE when compared with dulaglutide, driven by reduction in all-cause mortality. Risks of modified MACE seemed similar with tirzepatide and semaglutide. CI - (c) 2026 by the American Diabetes Association. FAU - Ostrominski, John W AU - Ostrominski JW AUID- ORCID: 0000-0002-2866-9414 AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Ortega-Montiel, Janinne AU - Ortega-Montiel J AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Everett, Brendan M AU - Everett BM AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Cromer, Sara J AU - Cromer SJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Byrne, Caroline F AU - Byrne CF AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA. FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. LA - eng GR - L30 HL175757/HL/NHLBI NIH HHS/United States GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Female MH - *Cardiovascular Diseases/drug therapy MH - Male MH - Middle Aged MH - *Recombinant Fusion Proteins/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged PMC - PMC13241951 COIS- Duality of Interest. J.W.O. has served on advisory boards or had speaker engagements with Corcept Therapeutics and Bayer AG. S.J.C. reports having a spouse employed by Depuy Synthes. B.M.E. reports grants (site coinvestigator) and personal fees (end point adjudication) from Novo Nordisk, a grant to Brigham and Women's Hospital (principal investigator), and personal fees from Kowa not clearly relevant to the work; personal fees from Ipsen Pharmaceuticals for consulting and from NIDDK outside the submitted work; and consulting fees (editorial board member) from American Heart Association journal Circulation and royalties for peer review of UptoDate articles. R.J.G. reports grants from Amarin, Kowa, and Novartis (to employer) outside the submitted work. D.J.W. has served on data monitoring committees for Amgen. E.P. reports research grants to Brigham and Women's Hospital (principal investigator) from Boehringer Ingelheim, AstraZeneca, and Bayer unrelated to the submitted work and receives royalties from UpToDate. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/03/04 15:49 MHDA- 2026/04/21 17:51 PMCR- 2026/03/04 CRDT- 2026/03/04 10:23 PHST- 2025/12/18 00:00 [received] PHST- 2026/02/01 00:00 [accepted] PHST- 2026/04/21 17:51 [medline] PHST- 2026/03/04 15:49 [pubmed] PHST- 2026/03/04 10:23 [entrez] PHST- 2026/03/04 00:00 [pmc-release] AID - 164532 [pii] AID - 253063 [pii] AID - 10.2337/dc25-3063 [doi] PST - ppublish SO - Diabetes Care. 2026 May 1;49(5):808-817. doi: 10.2337/dc25-3063. PMID- 41773040 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20260901 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 25 IP - 9 DP - 2026 Sep TI - GLP-1 receptor agonists in older people with type 2 diabetes: safety evidence from the real world. PG - 1623-1627 LID - 10.1080/14740338.2026.2640982 [doi] AB - INTRODUCTION: GLP-1 receptor agonists (GLP-1RA) are glucose- and body weight-lowering therapies provided with cardio-renal benefits. Use of GLP-1RA in older adults with type 2 diabetes mellitus (T2DM) is increasing but concerns remain about their safety in this age group, particularly in light of multimorbidity, frailty, and polypharmacy, as well as age-related vulnerability to adverse events (AEs). AREAS COVERED: We discuss the opportunities and challenges of GLP-1RA in older people with T2DM, focusing on real-world (RW) safety evidence. Available RW studies confirm the established GLP-1RA safety profile, with AEs in 10-30% of older users, predominantly gastrointestinal and mild-to-moderate in severity. Age-stratified analyses provide mixed results on AE susceptibility, but discontinuation due to intolerance appears more frequent in older adults. Weight loss is preserved across age groups, with no consistent evidence of harmful unintended reductions. However, the effects on muscle mass and sarcopenia risk remain largely unexplored. EXPERT OPINION: Current RW evidence supports GLP-1RA as a safe therapeutic option for older individuals with T2DM, without age-specific safety signals. Clinical phenotype-driven selection is essential to balance benefits and risks, particularly regarding nutritional status and frailty. Prospective, phenotype-stratified studies with body composition assessment are needed to guide optimal, individualized use in aging populations. FAU - Marassi, Marella AU - Marassi M AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy. AD - Laboratory of Experimental Diabetology, Veneto Institute of Molecular Medicine, Padua, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260304 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/pharmacology/administration & dosage/therapeutic use MH - Aged MH - Age Factors MH - Weight Loss/drug effects MH - Polypharmacy MH - Animals MH - Sarcopenia OTO - NOTNLM OT - Diabetes OT - incretin OT - older OT - sarcopenia OT - weight EDAT- 2026/03/03 06:30 MHDA- 2026/09/01 11:40 CRDT- 2026/03/03 03:33 PHST- 2026/09/01 11:40 [medline] PHST- 2026/03/03 06:30 [pubmed] PHST- 2026/03/03 03:33 [entrez] AID - 10.1080/14740338.2026.2640982 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2026 Sep;25(9):1623-1627. doi: 10.1080/14740338.2026.2640982. Epub 2026 Mar 4. PMID- 41772229 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20261010 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 40 IP - 4 DP - 2026 Apr TI - A single-center retrospective review of food retention during upper endoscopy following GLP-1 receptor agonist usage and introduction of the Tampa Intraluminal Gastric Residue (TiGR) grading scale. PG - 3454-3460 LID - 10.1007/s00464-026-12640-9 [doi] AB - INTRODUCTION: Our study has two objectives: (1) to evaluate the incidence and severity of food retention observed during esophagogastroduodenoscopies (EGDs) in patients with and without history of glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and (2) to create a grading scale to standardize the language regarding food retention. GLP-1 RAs have gained attention for treating obesity and type 2 diabetes (T2DM), largely due to their ability to reduce gastric motility. We aim to evaluate if this reduction leads to increased gastric food retention, raising the risk of aspiration. METHODS & PROCEDURES: A retrospective cross-sectional study was performed on patients who underwent an EGD from 2022 to 2024. The chi-square test was used to evaluate associations between categorical variables, including sex, gastroparesis diagnosis, T2DM diagnosis, and the presence of retained gastric contents (categorized by grade). Fisher's exact test was employed in cases where expected cell counts were less than five. RESULTS: The study consisted of 150 patients, with 73 GLP-1 RA users in the experimental group and 77 non-users in the control group. Most patients in both groups had no significant gastric retention at the time of EGD. When retention grades were grouped into a binary classification (None/A vs. B/C/D), there was no significant association between GLP-1 RA use and gastric retention (p = 0.67). Patients in the experimental group were significantly more likely to have a documented diagnosis of gastroparesis (p < 0.001) and T2DM (p < 0.001) as compared to the control group. CONCLUSIONS: Our initial data suggest that GLP-1 RA use does not lead to substantial gastric food retention as observed in EGDs. We propose using this study's grading scale as the standard for quantifying gastric food retention. By defining stages from no residue to severe obstruction, it enhances study comparisons and procedure planning while promoting a shared understanding among providers. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Patel, Yash AU - Patel Y AUID- ORCID: 0009-0002-8995-0530 AD - USF Health Morsani College of Medicine, Tampa, FL, USA. ypatel7@usf.edu. FAU - McDonald, Alice AU - McDonald A AD - Division of General Surgery, USF Health Department of Surgery, Tampa, FL, USA. FAU - Taylor, George Malcolm AU - Taylor GM AD - Division of General Surgery, Baptist Health, Birmingham, AL, USA. FAU - Sher, Theo AU - Sher T AD - University of California Los Angeles Medical Center, Los Angeles, CA, USA. FAU - DuCoin, Christopher AU - DuCoin C AD - Division of General Surgery, USF Health Department of Surgery, Tampa, FL, USA. FAU - Sujka, Joseph AU - Sujka J AD - Division of General Surgery, USF Health Department of Surgery, Tampa, FL, USA. FAU - Docimo, Salvatore AU - Docimo S AD - Division of General Surgery, USF Health Department of Surgery, Tampa, FL, USA. LA - eng PT - Journal Article DEP - 20260302 PL - Germany TA - Surg Endosc JT - Surgical endoscopy JID - 8806653 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Cross-Sectional Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Gastroparesis/diagnosis MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - *Endoscopy, Digestive System/adverse effects MH - Aged MH - Severity of Illness Index MH - *Gastrointestinal Contents OTO - NOTNLM OT - Diabetes OT - Endoscopy OT - GLP-1 OT - Gastroparesis EDAT- 2026/03/03 00:30 MHDA- 2026/06/30 16:10 CRDT- 2026/03/02 23:29 PHST- 2025/10/07 00:00 [received] PHST- 2026/02/05 00:00 [accepted] PHST- 2026/06/30 16:10 [medline] PHST- 2026/03/03 00:30 [pubmed] PHST- 2026/03/02 23:29 [entrez] AID - 10.1007/s00464-026-12640-9 [pii] AID - 10.1007/s00464-026-12640-9 [doi] PST - ppublish SO - Surg Endosc. 2026 Apr;40(4):3454-3460. doi: 10.1007/s00464-026-12640-9. Epub 2026 Mar 2. PMID- 41771166 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 29 IP - 1 DP - 2026 Dec TI - Annual pharmacy cost per patient achieving composite treatment endpoints: a cost to target analysis of tirzepatide versus subcutaneous semaglutide 1 mg in patients with type 2 diabetes in the UK. PG - 698-711 LID - 10.1080/13696998.2026.2631920 [doi] AB - INTRODUCTION: Tirzepatide is a treatment for type 2 diabetes associated with improvements in glycemic control and weight loss, and a low risk of hypoglycemia when not used in combination with insulin or insulin secretagogues. A cost to target analysis of tirzepatide 5, 10 and 15 mg versus subcutaneous semaglutide 1 mg in the UK setting was performed, calculating the annual pharmacy cost per patient treated to six composite endpoints combining glycemic control (glycated hemoglobin [HbA1c] /=5%, >/=10%, >/=15%) and avoidance of hypoglycemia. The costing analysis was based on the tirzepatide costs appraised by NICE as part of TA924. METHODS: The proportions of patients achieving composite treatment targets with tirzepatide and semaglutide (both in combination with metformin) were taken from a post-hoc analysis of the SURPASS-2 clinical trial (N = 1,845). Costs per patient treated to target were calculated by dividing the annual treatment costs associated with each intervention by the proportion of patients achieving the treatment target with each intervention. RESULTS: Tirzepatide 5, 10 and 15 mg were associated with a lower pharmacy cost per patient achieving treatment target than semaglutide 1 mg for the majority of endpoints evaluated. Differences became greater at more strict treatment targets. For example, the cost per patient achieving HbA1c /=15%, and no hypoglycemia was GBP 5,650, GBP 8,665 and GBP 9,462 lower with tirzepatide 5, 10 and 15 mg, respectively, compared with semaglutide 1 mg over a 1-year time horizon. The only endpoint where semaglutide 1 mg was associated with a lower cost per patient achieving target was HbA1c <7.0%, weight loss >/=5%, and no hypoglycemia. CONCLUSIONS: Compared to semaglutide, tirzepatide was associated with a lower annual pharmacy cost per patient with diabetes achieving treatment target in the UK for the majority of endpoints, with greater differences at more strict treatment targets. FAU - Kanumilli, Naresh AU - Kanumilli N AUID- ORCID: 0000-0003-3080-7713 AD - Northenden Group Practice, Manchester, UK. FAU - Osumili, Beatrice AU - Osumili B AUID- ORCID: 0000-0002-5862-9325 AD - Eli Lilly and Company Limited, Bracknell, UK. FAU - Evans, Jerome AU - Evans J AUID- ORCID: 0009-0005-8492-0625 AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Webb, Joanne AU - Webb J AUID- ORCID: 0000-0001-5883-9077 AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Buckingham, Mike AU - Buckingham M AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Debackere, Nele AU - Debackere N AD - S.A. Eli Lilly Benelux N.V, Brussels, Belgium. FAU - Nowakowski, Piotr AU - Nowakowski P AD - Eli Lilly Polska Sp. z o. o, Warsaw, Poland. FAU - Cattin, Juliette AU - Cattin J AUID- ORCID: 0009-0001-2528-4359 AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. LA - eng PT - Journal Article DEP - 20260302 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - United Kingdom MH - Glycated Hemoglobin MH - Female MH - Male MH - Weight Loss/drug effects MH - Middle Aged MH - Injections, Subcutaneous MH - Drug Therapy, Combination MH - Hypoglycemia/chemically induced MH - Aged MH - Blood Glucose MH - Metformin/therapeutic use/economics OTO - NOTNLM OT - Cost per patient treated to target OT - I10 OT - I19 OT - glycemic control OT - hypoglycemia OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight loss EDAT- 2026/03/02 18:57 MHDA- 2026/03/06 13:45 CRDT- 2026/03/02 17:43 PHST- 2026/03/06 13:45 [medline] PHST- 2026/03/02 18:57 [pubmed] PHST- 2026/03/02 17:43 [entrez] AID - 10.1080/13696998.2026.2631920 [doi] PST - ppublish SO - J Med Econ. 2026 Dec;29(1):698-711. doi: 10.1080/13696998.2026.2631920. Epub 2026 Mar 2. PMID- 41767554 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260927 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2026 DP - 2026 TI - Identifying Provider Prescribing Practices for GLP-1RAs and SGLT-2is in Patients With Type 2 Diabetes to Address Pharmacoinequity. PG - 7439681 LID - 10.1155/jdr/7439681 [doi] LID - 7439681 AB - BACKGROUND AND AIMS: Evidence-based treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with Type 2 diabetes (T2DM) focuses on glycemic control and lifestyle modification to achieve weight loss, which slows the progression of liver disease and reduces the risk of liver-related complications. We aimed to qualitatively explore provider-level determinants in glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium/glucose cotransporter 2 inhibitors (SGLT-2is) prescription. METHODS: We identified a cohort of 189 outpatient adult primary care providers who cared for at least 50 annual T2DM patients in a tertiary academic health system in the United States in 2021. GLP-1RA and SGLT-2i prescribing rates were calculated with a median rate of 0.494 (IQR 0.393-0.594). Guided by the Consolidate Framework for Implementation Research, we conducted 1:1 interviews with high-prescribing and low-prescribing providers. All providers interviewed were either MDs or DOs. RESULTS: Nine providers from the high-prescribing quartile (prescribing rate 59.5%-78.6%) and eight from the low-prescribing quartile (prescribing rate 4.8%-39.3%) were interviewed. High-prescribing providers reported more patient-facing hours and exposure to GLP-1RAs and SGLT-2is in residency. All providers cited task-sharing, patient-provider relationship longevity, and medication effectiveness as facilitators of GLP-1RA and SGLT-2i prescription. Barriers to prescribing included medication costs, prior authorization processes, and prescription inertia. Using the Expert Recommendations for Implementing Change, we mapped barriers and facilitators to implementation strategies. CONCLUSIONS: This interview series identified key barriers and facilitators of GLP-1RA and SGTL-2i prescription. Implementation strategies may help improve prescribing highly effective, newer treatments in patients with T2DM, including those with metabolic comorbidities. CI - Copyright (c) 2026 Parnnate Wongsirisakul et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Wongsirisakul, Parnnate AU - Wongsirisakul P AUID- ORCID: 0009-0009-6711-1761 AD - Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA, umich.edu. FAU - Chen, Vincent L AU - Chen VL AUID- ORCID: 0000-0002-0157-6066 AD - Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA, umich.edu. FAU - Perumalswami, Ponni V AU - Perumalswami PV AUID- ORCID: 0000-0003-3070-3906 AD - Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA, umich.edu. LA - eng GR - P30 DK092926/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260226 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Female MH - Middle Aged MH - United States PMC - PMC12943470 OTO - NOTNLM OT - GLP-1RA OT - SGLT-2i OT - Type 2 diabetes OT - liver disease OT - pharmacoequity OT - provider interview COIS- The authors declare no conflicts of interest. EDAT- 2026/03/02 13:17 MHDA- 2026/03/06 09:11 PMCR- 2026/02/26 CRDT- 2026/03/02 06:32 PHST- 2025/11/05 00:00 [received] PHST- 2026/01/07 00:00 [revised] PHST- 2026/01/13 00:00 [accepted] PHST- 2026/03/06 09:11 [medline] PHST- 2026/03/02 13:17 [pubmed] PHST- 2026/03/02 06:32 [entrez] PHST- 2026/02/26 00:00 [pmc-release] AID - JDR7439681 [pii] AID - 10.1155/jdr/7439681 [doi] PST - epublish SO - J Diabetes Res. 2026 Feb 26;2026:7439681. doi: 10.1155/jdr/7439681. eCollection 2026. PMID- 41765256 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 266 DP - 2026 May 1 TI - Association of GLP-1 Receptor Agonist and SGLT2 Inhibitor With Cardiovascular Outcomes After Transcatheter Aortic Valve Replacement. PG - 99-103 LID - S0002-9149(26)00087-1 [pii] LID - 10.1016/j.amjcard.2026.02.043 [doi] AB - Aortic valve disease is the most common valvular disease and is often seen in the elderly population. Transcatheter aortic valve replacement (TAVR) is a favorable and rapidly evolving intervention. Despite highly effective procedural outcomes, the TAVR population remains at high risk for heart failure and death, and medical therapy after TAVR is understudied. Diabetic medications including GLP-1 receptor agonists (GLP-1 RA) and SGLT2 inhibitors (SGLT2i) have had emerging data suggesting cardioprotective effects. In this study, we aim to evaluate cardiovascular outcomes in post-TAVR patients who are treated with GLP-1 RA, SGLT2i, or both compared to those who are not treated. Using TriNetX, we identified a cohort of patients who underwent a TAVR procedure and then classified them as treated with GLP-1 RA, SGLT2i, both, or none. After propensity matching for demographics, comorbidities, and medications, patient outcomes for all-cause mortality (ACM) and cardiovascular disorders were evaluated using a Kaplan-Meier analysis. Our results showed a decrease in ACM in those who were on GLP-1 RA after TAVR compared to those who were not. There was also a statistically significant decrease in arrhythmia in patients on SGLT2i after TAVR compared to those who were not. When GLP-1 RA and SGLT2i were combined, there was a decrease in ACM, myocardial infarction, acute heart failure, and arrhythmia after TAVR compared to those who were not. In conclusion, these findings further suggest cardioprotective effects of these drugs in patients treated with TAVR. Future trials should further investigate the role of these medications in patients with aortic valve stenosis. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Fahoury, Alan M AU - Fahoury AM AD - Department of Internal Medicine, University of Toledo College of Medicine, Toledo, Ohio. Electronic address: Alan.Fahoury@rockets.utoledo.edu. FAU - Kamel-Abusalha, Louie AU - Kamel-Abusalha L AD - Department of Internal Medicine, University of Toledo College of Medicine, Toledo, Ohio. FAU - Didier, Alexander J AU - Didier AJ AD - Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Wunderly, Kevin AU - Wunderly K AD - Department of Internal Medicine, University of Toledo College of Medicine, Toledo, Ohio. FAU - Sarrouj, Sami AU - Sarrouj S AD - Department of Internal Medicine, University of Toledo College of Medicine, Toledo, Ohio. FAU - Issa, Rochell AU - Issa R AD - Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio. FAU - Afifi, Ahmed AU - Afifi A AD - Department of Emergency Medicine, University of Toledo College of Medicine, Toledo, Ohio. FAU - Gupta, Rajesh AU - Gupta R AD - Division of Cardiovascular Medicine, University of Toledo College of Medicine, Toledo, Ohio. LA - eng PT - Journal Article DEP - 20260227 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Transcatheter Aortic Valve Replacement MH - Female MH - *Aortic Valve Stenosis/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Aged, 80 and over MH - Retrospective Studies MH - Aged MH - Treatment Outcome MH - *Postoperative Complications/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cause of Death/trends OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - aortic stenosis OT - transcatheter aortic valve replacement COIS- Declaration of competing interest The authors have no competing interests to declare. EDAT- 2026/03/02 00:38 MHDA- 2026/04/11 00:32 CRDT- 2026/03/01 19:14 PHST- 2025/09/12 00:00 [received] PHST- 2026/01/15 00:00 [revised] PHST- 2026/02/05 00:00 [accepted] PHST- 2026/04/11 00:32 [medline] PHST- 2026/03/02 00:38 [pubmed] PHST- 2026/03/01 19:14 [entrez] AID - S0002-9149(26)00087-1 [pii] AID - 10.1016/j.amjcard.2026.02.043 [doi] PST - ppublish SO - Am J Cardiol. 2026 May 1;266:99-103. doi: 10.1016/j.amjcard.2026.02.043. Epub 2026 Feb 27. PMID- 41765029 OWN - NLM STAT- MEDLINE DCOM- 20260321 LR - 20260924 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10534 DP - 2026 Mar 21 TI - Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. PG - 1147-1160 LID - S0140-6736(26)00202-3 [pii] LID - 10.1016/S0140-6736(26)00202-3 [doi] AB - BACKGROUND: Orforglipron is a novel non-peptide (GLP-1) receptor agonist designed for daily oral administration without food or water restrictions. This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin. METHODS: In this 52-week, randomised, open-label, active-controlled, multicentre, multinational, phase 3 study, we enrolled adults (>/=18 years) with type 2 diabetes inadequately controlled with metformin (>/=1500 mg per day), glycated haemoglobin (HbA(1c)) between 7.0% and 10.5% (53-91 mmol/mol), and BMI at least 25 kg/m(2) from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico, and the USA. Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day. The primary objective of the study was to assess non-inferiority of orforglipron 36 mg versus semaglutide 14 mg and orforglipron 12 mg versus semaglutide 7 mg for mean change at week 52 from baseline in HbA(1c) (with a non-inferiority margin of 0.3%) in the intention-to-treat population. Hierarchical analysis for superiority was prespecified after attainment of non-inferiority. The treatment regimen estimand, based on data from all randomly assigned participants regardless of intercurrent events, was the primary estimand; the efficacy estimand was considered supportive. The safety endpoints used data from all participants who received at least one dose of the study drug. This trial was registered on ClinicalTrials.gov (NCT06045221) and is completed. FINDINGS: From Sept 22, 2023, to Aug 22, 2025, 1698 participants were recruited and randomly assigned to orforglipron (n=424 on 12 mg and n=423 on 36 mg) or semaglutide (n=426 on 7 mg and n=425 on 14 mg). For the treatment regimen estimand, mean changes at week 52 from a baseline HbA(1c) of 8.3% were -1.71% (SE 0.07) with orforglipron 12 mg, -1.91% (0.08) with orforglipron 36 mg, -1.23% (0.05) with semaglutide 7 mg, and -1.47% (0.06) with semaglutide 14 mg. Estimated treatment differences were -0.48% (95% CI -0.65 to -0.31; p<0.0001) for orforglipron 12 mg versus semaglutide 7 mg; -0.44% (-0.62 to -0.26; p<0.0001) for orforglipron 36 mg versus semaglutide 14 mg; -0.24% (95% CI -0.41 to -0.072; p=0.0050) for orforglipron 12 mg versus semaglutide 14 mg; and -0.68% (-0.85 to -0.50; p<0.0001) for orforglipron 36 mg versus semaglutide 7 mg. The primary objective of non-inferiority was met and both orforglipron doses showed superiority to both semaglutide doses, including orforglipron 12 mg versus semaglutide 14 mg. The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity. More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg), and mean increase in pulse rate was greater in the orforglipron groups (12 mg 3.7 bpm; 36 mg 4.7 bpm) than in the semaglutide groups (7 mg 1.0 bpm; 14 mg 1.5 bpm). Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group. INTERPRETATION: In individuals with type 2 diabetes inadequately controlled with metformin, orforglipron 12 mg and 36 mg was non-inferior and superior to semaglutide 7 mg and 14 mg with respect to the mean change in HbA(1c) from baseline to 52 weeks. Although the safety profiles of both orforglipron and semaglutide were generally consistent with the GLP-1 receptor agonist class, the incidence of gastrointestinal events, discontinuations due to adverse events, and mean increase in pulse rate were higher with orforglipron than oral semaglutide. FUNDING: Eli Lilly. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Rosenstock, Julio AU - Rosenstock J AD - Division of Endocrinology, University of Texas, Southwestern Medical Center, Dallas, TX, USA. Electronic address: juliorosenstock@dallasdiabetes.com. FAU - Yabe, Daisuke AU - Yabe D AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan; Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Studies, Gifu, Japan. FAU - Cox, David AU - Cox D AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Li, Jianghao AU - Li J AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Denning, Max AU - Denning M AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Wu, Wen-Shuo AU - Wu WS AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Liu, Rong AU - Liu R AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Zhao, Youna AU - Zhao Y AD - Eli Lilly and Company, Indianapolis, IN, USA. CN - ACHIEVE-3 Investigators LA - eng SI - ClinicalTrials.gov/NCT06045221 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260226 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (orforglipron) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Fluorine Compounds) RN - 0 (Oxadiazoles) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Fluorine Compounds/administration & dosage/adverse effects/therapeutic use MH - Oxadiazoles/administration & dosage/adverse effects/therapeutic use MH - Semaglutide/administration & dosage/therapeutic use COIS- Declaration of interests JL, MD, W-SW, RL, DC, and YZ are current employees and shareholders of Eli Lilly. JR has served on scientific advisory boards and received honoraria or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Corcept, Eccogene, Eli Lilly, Novo Nordisk, Oramed Pharmaceuticals, Regeneron, Regor, Sanofi, Scholar Rock, Structure Therapeutics, and Terns Pharmaceuticals and has received grants and research support from Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Corcept, Eli Lilly, Hanmi Pharmaceutical, Merck, Novo Nordisk, Oramed Pharmaceuticals, Pfizer, Regeneron, Regor, Sanofi, Structure Therapeutics, and Terns Pharmaceuticals. DY reports support from Eli Lilly for the present manuscript; grants or contracts from Boehringer Ingelheim, Taisho Pharmaceutical, Novo Nordisk, and Arkray; consulting fees from Kansai Medical Net, Eli Lilly, Novo Nordisk, Sanofi, and Boehringer Ingelheim; payments or honoraria from Mitsubishi Tanabe, Ono Pharmaceutical, Boehringer Ingelheim, Kowa, Sumitomo Pharmaceutical, Eli Lilly, Novo Nordisk, Sanofi, and Taisho Pharmaceutical; roles in International Diabetes Federation Western Pacific Region (Executive Board), The European Association for the Study of Diabetes (Global Council), The Japan Association for Diabetes Care and Education (Executive Board), The Japan Society of Clinical Nutrition and Metabolism (Executive Board), The Japan Society of Diabetes Complication (Executive Board), The Asian Association for the Study of Diabetes (Executive Board), The Japan Diabetes Society (Auditor), The Japan Endocrine Society (Executive Board), The Japan Society of Constitutional Medicine (Executive Board), and The Japan Society of Informatics for Diabetes Mellitus (Vice President). FIR - Manghi, Federico Perez IR - Manghi FP FIR - Abalos, Franklin IR - Abalos F FIR - Costanzo, Pablo IR - Costanzo P FIR - Chiesa, Ana IR - Chiesa A FIR - Maldonado, Natacha IR - Maldonado N FIR - Salzberg, Susana IR - Salzberg S FIR - Goycoa, Claudia IR - Goycoa C FIR - Sessa, Horacio IR - Sessa H FIR - Aizenberg, Diego IR - Aizenberg D FIR - Vico, Marisa IR - Vico M FIR - Guerlloy, Fernando IR - Guerlloy F FIR - Schiavoni, Maria IR - Schiavoni M FIR - Chahin, Mariano IR - Chahin M FIR - Villarino, Adriana IR - Villarino A FIR - Bartolacci, Ines IR - Bartolacci I FIR - Hernandez Gauna, Adrian IR - Hernandez Gauna A FIR - Mayer, Marcos IR - Mayer M FIR - Li, Shunbin IR - Li S FIR - An, Zhenmei IR - An Z FIR - Ma, Jianhua IR - Ma J FIR - Li, Shu IR - Li S FIR - Zhou, Jian IR - Zhou J FIR - Yuan, Guoyue IR - Yuan G FIR - Lu, Yibing IR - Lu Y FIR - Wang, Hongman IR - Wang H FIR - Li, Qingju IR - Li Q FIR - Li, Xinyu IR - Li X FIR - Wu, Tian Feng IR - Wu TF FIR - Jiang, Xiaozhen IR - Jiang X FIR - Zhang, Yawei IR - Zhang Y FIR - Li, Yufeng IR - Li Y FIR - Zhu, Hong IR - Zhu H FIR - Wang, Yihua IR - Wang Y FIR - Jiang, Hongwei IR - Jiang H FIR - Shen, Jie IR - Shen J FIR - Dong, Xiaolin IR - Dong X FIR - Cheng, ZhiFeng IR - Cheng Z FIR - Niiya, Tetsuji IR - Niiya T FIR - Nakamoto, Shinya IR - Nakamoto S FIR - Sato, Nobuyuki IR - Sato N FIR - Takai, Masahiko IR - Takai M FIR - Kato, Takehiro IR - Kato T FIR - Shiraiwa, Toshihiko IR - Shiraiwa T FIR - Bando, Hidenori IR - Bando H FIR - Ohishi, Akira IR - Ohishi A FIR - Osonoi, Takeshi IR - Osonoi T FIR - Salazar, Melchor Alpizar IR - Salazar MA FIR - Hernandez, Pedro Garcia IR - Hernandez PG FIR - Cantu, Elias Alberto Garcia IR - Cantu EAG FIR - Ibarra, Manuel de Los Rios IR - Ibarra MLR FIR - Orozco, Emilia Pelayo IR - Orozco EP FIR - Granell, Maria Arechavaleta IR - Granell MA FIR - Soto, Jose Lazcano IR - Soto JL FIR - Carrillo, Luis Virgen IR - Carrillo LV FIR - Castrezana, Laura Castro IR - Castrezana LC FIR - Ramos, Silvia Jimenez IR - Ramos SJ FIR - Gonzalez, Arnulfo IR - Gonzalez A FIR - de Alba, Carlos Alejandro Stobschinski IR - de Alba CAS FIR - Elizondo, Ramiro Banda IR - Elizondo RB FIR - Reza, Raymundo Garcia IR - Reza RG FIR - Galvez, Guillermo Gonzalez IR - Galvez GG FIR - Gonzalez, Jose Gerardo Gonzalez IR - Gonzalez JGG FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Sarwar, Jawad IR - Sarwar J FIR - Gangi, Sumana IR - Gangi S FIR - Wieskopf, Bram IR - Wieskopf B FIR - Gaufin, Thaidra IR - Gaufin T FIR - Anderson, Rachel IR - Anderson R FIR - Garcia-Torres, Eric IR - Garcia-Torres E FIR - Luna, Eduardo IR - Luna E FIR - Philander, Peter IR - Philander P FIR - Chow, Christopher IR - Chow C FIR - Guduri, Sridhar IR - Guduri S FIR - Gonzalez-Bossolo, Alex IR - Gonzalez-Bossolo A FIR - McConnehey, Brock IR - McConnehey B FIR - Usdan, Lisa IR - Usdan L FIR - Brautigam, Donald IR - Brautigam D FIR - Gomez-Cuellar, Martha IR - Gomez-Cuellar M FIR - Adams, Michael IR - Adams M FIR - Schneider, Alison IR - Schneider A FIR - Tsang, Dennis IR - Tsang D FIR - Mattar, Peter IR - Mattar P FIR - Powell, Talessa IR - Powell T FIR - Mansilla-Letelier, Paola IR - Mansilla-Letelier P FIR - Connery, Lisa IR - Connery L FIR - Lopez, Reynaldo IR - Lopez R FIR - Buynak, Robert IR - Buynak R FIR - Vega, Damaris IR - Vega D FIR - Loy, Juan IR - Loy J FIR - Conaway, Herbert IR - Conaway H FIR - Schultz, James IR - Schultz J FIR - Kim, John IR - Kim J FIR - Finley, Jon IR - Finley J FIR - Beach, James IR - Beach J FIR - Hutchins, Bob IR - Hutchins B FIR - Brian, Susan IR - Brian S FIR - Lynn, Lon IR - Lynn L FIR - Tan, Anjanette IR - Tan A FIR - Vazquez-Tanus, Jose IR - Vazquez-Tanus J FIR - Moran, Joseph IR - Moran J FIR - Crystal, Chad IR - Crystal C FIR - Pant, Nicole IR - Pant N FIR - Palchick, Bryce IR - Palchick B FIR - Packer, Flint IR - Packer F FIR - Broyles, Frances IR - Broyles F FIR - Alleman, Brandon IR - Alleman B FIR - Mandry, Jose IR - Mandry J FIR - Audish, Hanid IR - Audish H FIR - Davidson, Evelyne IR - Davidson E FIR - Ard, Jamy IR - Ard J FIR - Horowitz, Barry IR - Horowitz B FIR - Lucas, Kathryn IR - Lucas K FIR - Puente, Orlando IR - Puente O FIR - Rosenstock, Julio IR - Rosenstock J FIR - Serje, Jorge IR - Serje J FIR - Dennis, Patrick IR - Dennis P FIR - Washington, Tonita IR - Washington T FIR - Murray, Alexander IR - Murray A FIR - Oliver, Michael IR - Oliver M FIR - Busch, Robert IR - Busch R FIR - Ross, Samuel Harrison IR - Ross SH FIR - London, Jeffrey IR - London J FIR - Montano, Charles IR - Montano C FIR - Zimmerman, Michael IR - Zimmerman M FIR - Saad, Abdulhassan IR - Saad A FIR - Al-Karadsheh, Amer IR - Al-Karadsheh A FIR - Dunn, Leonard IR - Dunn L FIR - Hopson, Shannon IR - Hopson S FIR - Freilich, Bradley IR - Freilich B EDAT- 2026/03/02 00:38 MHDA- 2026/03/22 06:07 CRDT- 2026/03/01 18:53 PHST- 2025/12/22 00:00 [received] PHST- 2026/01/28 00:00 [revised] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/03/22 06:07 [medline] PHST- 2026/03/02 00:38 [pubmed] PHST- 2026/03/01 18:53 [entrez] AID - S0140-6736(26)00202-3 [pii] AID - 10.1016/S0140-6736(26)00202-3 [doi] PST - ppublish SO - Lancet. 2026 Mar 21;407(10534):1147-1160. doi: 10.1016/S0140-6736(26)00202-3. Epub 2026 Feb 26. PMID- 41763234 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20261001 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 4 DP - 2026 Apr TI - Combined associations of GLP-1 receptor agonists and a healthy lifestyle with cardiovascular outcomes among individuals with type 2 diabetes: a prospective cohort study. PG - 317-326 LID - S2213-8587(25)00395-X [pii] LID - 10.1016/S2213-8587(25)00395-X [doi] AB - BACKGROUND: The long-term combined effects of lifestyle habits and GLP-1 receptor agonists on cardiovascular outcomes are unknown. We aimed to examine the combined association of GLP-1 receptor agonist use and adherence to eight lifestyle habits with cardiovascular outcomes. METHODS: We did a prospective cohort study of individuals with type 2 diabetes enrolled within the US Veterans Affairs' Million Veteran Program between Jan 10, 2011, and Sept 30, 2023. Participants had no previous history of myocardial infarction, stroke, or advanced chronic kidney disease. The eight low-risk lifestyle habits assessed were a higher quality diet, being physically active, not smoking, restful sleep, no heavy alcohol intake, good stress management, social connection and support, and no opioid use disorder. We assessed the risk of major adverse cardiovascular events (MACE), defined as non-fatal stroke or myocardial infarction, or cardiovascular death, according to GLP-1 receptor agonist use and low-risk lifestyle habits using Cox proportional hazard regression models. FINDINGS: Of the 963 753 veterans enrolled, a total of 98 261 participants were included in the study with 632 543 person-years of follow-up, during which 10 443 people developed MACE. Multivariable-adjusted hazard ratio (HR) of MACE was 0.40 (95% CI 0.30-0.54) when comparing participants adhering to all eight low-risk lifestyle habits to those adopting one habit or less. Multivariable-adjusted HR of MACE was 0.84 (0.76-0.92) when comparing users of GLP-1 receptor agonists with non-users. Participants using GLP-1 receptor agonists and adhering to six to eight low-risk lifestyle factors had a 43% lower risk of MACE than did those with three or fewer low-risk lifestyle factors and no GLP-1 receptor agonist use (0.57; 0.46-0.71). INTERPRETATION: Adherence to low-risk lifestyle habits combined with GLP-1 receptor agonist use was associated with a greater reduction in MACE risk than either approach alone, underscoring the importance of integrating lifestyle modification with pharmacotherapy in type 2 diabetes management. FUNDING: Department of Veterans Affairs. CI - Copyright (c) 2026 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Nguyen, Xuan-Mai T AU - Nguyen XT AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. FAU - Li, Yanping AU - Li Y AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA. FAU - Czernichow, Sebastien AU - Czernichow S AD - Department of Nutrition, George Pompidou European Hospital, AP-HP, Paris, France; Universite Paris Cite, Centre for Research in Epidemiology and Statistics (CRESS), Paris, France. FAU - Rassy, Nathalie AU - Rassy N AD - Department of Nutrition, George Pompidou European Hospital, AP-HP, Paris, France. FAU - Houghton, Serena C AU - Houghton SC AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA. FAU - Lu, Bing AU - Lu B AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Department of Public Health, University of Connecticut Health Center, Farmington, CT, USA. FAU - Ho, Yuk-Lam AU - Ho YL AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA. FAU - Charest, Brian R AU - Charest BR AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA. FAU - Wang, Dong D AU - Wang DD AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA; The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Gagnon, David R AU - Gagnon DR AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Boston University School of Public Health, Boston, MA, USA. FAU - Gaziano, John Michael AU - Gaziano JM AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Division of Aging, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Willett, Walter C AU - Willett WC AD - Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA; The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Wilson, Peter W F AU - Wilson PWF AD - Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Atlanta VA Health Care System, Decatur, GA, USA; Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA. FAU - Cho, Kelly AU - Cho K AD - Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, Boston, MA, USA; Division of Aging, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Hu, Frank B AU - Hu FB AD - Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: fhu@hsph.harvard.edu. CN - VA Million Veteran Program LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260225 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Lancet Diabetes Endocrinol. 2026 Apr;14(4):e7. doi: 10.1016/S2213-8587(26)00038-0. PMID: 41771284 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Prospective Studies MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Middle Aged MH - *Healthy Lifestyle MH - United States/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use COIS- Declaration of interests SC received consulting fees from Novo Nordisk, Boehringer, AstraZeneca, MSD, Roche, Amgen, Pfizer, and Fresenius; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novo Nordisk, Janssen-Cilag, J&J, and Novartis; support for attending meetings or travel from Novo Nordisk and Lilly; participated in an advisory board for Novo Nordisk and Lilly; and has stock or stock options for Alifert and Jellynov. FBH received a research grant from Analysis Group. All other authors declare no competing interests. EDAT- 2026/03/01 00:35 MHDA- 2026/03/20 00:59 CRDT- 2026/02/28 18:52 PHST- 2025/09/19 00:00 [received] PHST- 2025/12/07 00:00 [revised] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2026/03/01 00:35 [pubmed] PHST- 2026/02/28 18:52 [entrez] AID - S2213-8587(25)00395-X [pii] AID - 10.1016/S2213-8587(25)00395-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Apr;14(4):317-326. doi: 10.1016/S2213-8587(25)00395-X. Epub 2026 Feb 25. PMID- 41761267 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20261004 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Feb 27 TI - Comparative efficacy of tirzepatide and glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes: a systematic review and network meta-analysis. LID - 10.1186/s12933-026-03113-3 [doi] LID - 115 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used therapies for cardiovascular risk reduction in type 2 diabetes (T2D). With the emergence of the SURPASS-CVOT trial, tirzepatide (a dual GIP/GLP-1 receptor agonist) has entered the therapeutic landscape; however, its comparative effect on cardiovascular outcomes compared to placebo and individual GLP-1RAs remains undefined. METHODS: We conducted a systematic review and frequentist network meta-analysis (NMA) of RCTs enrolling adults with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular (CV) risk. Eligible RCTs evaluated tirzepatide or GLP-1RAs and reported major adverse cardiovascular events (MACE), CV mortality, all-cause mortality, non-fatal myocardial infarction (MI) or non-fatal stroke. A class-level NMA was conducted to estimate the incremental benefit of tirzepatide and GLP-1RAs over placebo, and an agent-level NMA was conducted to explore differences between tirzepatide and individual GLP-1RA agents. Subgroup analyses, including established cardiovascular disease populations, and leave-one-out sensitivity analyses were performed. RESULTS: Eleven trials met inclusion criteria (10 GLP-1RA trials and 1 tirzepatide trial [SURPASS-CVOT]). In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo. Formal statistical comparisons between tirzepatide and the GLP-1RA class could not be performed within the constraints of the NMA; however, point estimates across outcomes numerically favored tirzepatide compared with placebo. In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97). Subgroup and sensitivity analyses did not substantially change point estimates. CONCLUSION: Among adults with T2D and established ASCVD or high CV risk, class-level analysis demonstrated that tirzepatide significantly reduced the risk of cardiovascular events compared to placebo; at the agent-level, tirzepatide demonstrated comparable efficacy to individual GLP-1RAs. These findings suggest that tirzepatide provides cardiovascular benefit at least comparable to established GLP-1RAs, supporting its emerging role in cardiovascular risk reduction in T2D. CI - (c) 2026. The Author(s). FAU - Shokravi, Arveen AU - Shokravi A AD - Department of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada. shokravi@student.ubc.ca. AD - Department of Medicine, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N4N1, Canada. shokravi@student.ubc.ca. FAU - Seth, Jayant AU - Seth J AD - Department of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada. FAU - Mancini, G B John AU - Mancini GBJ AD - Department of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada. AD - Centre for Cardiovascular Innovation, Dilwari Cardiovascular Institute, Division of Cardiology, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260227 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Biomarkers) SB - IM MH - *Tirzepatide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/blood MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Risk Assessment MH - Randomized Controlled Trials as Topic MH - Biomarkers/blood MH - Heart Disease Risk Factors PMC - PMC13049956 OTO - NOTNLM OT - cardiovascular outcomes OT - glucagon-like peptide-1 receptor agonists OT - meta-analysis OT - tirzepatide OT - type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. This study is a meta-analysis and did not involve direct recruitment of human participants. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this manuscript, the authors used ChatGPT to assist with proofreading and improving the readability of the text. The authors subsequently reviewed and edited the content as needed and take full responsibility for the final version of the manuscript. EDAT- 2026/02/28 00:41 MHDA- 2026/04/04 06:35 PMCR- 2026/02/27 CRDT- 2026/02/27 23:41 PHST- 2025/10/12 00:00 [received] PHST- 2026/02/08 00:00 [accepted] PHST- 2026/04/04 06:35 [medline] PHST- 2026/02/28 00:41 [pubmed] PHST- 2026/02/27 23:41 [entrez] PHST- 2026/02/27 00:00 [pmc-release] AID - 10.1186/s12933-026-03113-3 [pii] AID - 3113 [pii] AID - 10.1186/s12933-026-03113-3 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Feb 27;25(1):115. doi: 10.1186/s12933-026-03113-3. PMID- 41757397 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Dose-Escalation Regimens for Incretin Mimetics in Type 2 Diabetes Are Associated With Tolerance for Nausea and Vomiting. PG - 4232-4242 LID - 10.1111/dom.70613 [doi] AB - AIMS/HYPOTHESIS: Initial dose-escalation has been shown to mitigate gastrointestinal adverse events in people treated with incretin-based medications. We aimed to analyse dose-response relationships for the proportion of study participants reporting nausea and vomiting among those exposed to incretin mimetics approved for Type 2 diabetes (GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide) in Phase 1 (no or short dose escalation) and Phase 3 (with dose escalation) trials. METHODS: Non-linear regression analysis (curve fitting) was used to estimate the dose that would elicit nausea or vomiting in 50% of exposed subjects (ED(50)). We used the ratio of ED(50)ies determined for Phase 1 and Phase 3 trials as an indicator of developing tolerance. RESULTS: The development of tolerance for nausea and vomiting (indicated by a ratio of ED(50)ies Phase 3/Phase 1) for semaglutide (both s.c. and oral) and for tirzepatide was significantly higher than 1. Comparing all approved incretin-based medications, a higher ratio, indicating the development of more tolerance, was associated with (a) a longer drug escalation period and (b) a greater number of dose-escalation steps. This ED(50) ratio (Phase 3/Phase 1) was also significantly associated with effect sizes for intended therapeutic actions of incretin mimetics (reductions in HbA(1c) and body weight). CONCLUSIONS/INTERPRETATION: Taken together, optimised dose-escalation regimens may lead to greater tolerance for nausea and vomiting, which allows to use of higher doses, which are associated with greater therapeutic effectiveness. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Punov, Viktoria AU - Punov V AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - Division of Endocrinology, Diabetes and Hypertension and TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - Drug Tolerance MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects/administration & dosage/analogs & derivatives MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - *Incretins/administration & dosage/adverse effects MH - *Nausea/chemically induced MH - Semaglutide MH - Tirzepatide MH - *Vomiting/chemically induced MH - Clinical Trials, Phase I as Topic MH - Clinical Trials, Phase III as Topic MH - Clinical Trials, Phase IV as Topic PMC - PMC13071187 OTO - NOTNLM OT - GLP-1 analogue OT - pharmaco-epidemiology OT - type 2 diabetes OT - weight control COIS- M.A.N. has been a member on advisory boards or has consulted with Eli Lilly & Co., Pfizer, Regor, Sun Pharma and Structure Therapeutics (Gasherbrum). He has also served on the speakers' bureau of Eli Lilly & Co., Medscape, Medical Learning Institute and NovoNordisk. V.P. and Y.M.K. declare no conflicts of interest. S.L. received research grants from Merck Sharp & Dohme, Novo Nordisk and LG Chem; and honoraria as a consultant or speaker for AstraZeneca, Boehringer Ingelheim, Abbott, LG Chem, Daewoong Pharmaceutical, Chong Kun Dang Pharmaceutical and Novo Nordisk. EDAT- 2026/02/27 06:32 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/02/27 05:09 PHST- 2026/02/15 00:00 [revised] PHST- 2026/01/09 00:00 [received] PHST- 2026/02/15 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/27 06:32 [pubmed] PHST- 2026/02/27 05:09 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70613 [pii] AID - 10.1111/dom.70613 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):4232-4242. doi: 10.1111/dom.70613. Epub 2026 Feb 27. PMID- 41755685 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 17 IP - 5 DP - 2026 May TI - Impact of renal function on antidiabetic drug selection in Japan: A real-world analysis using the J-DREAMS database. PG - 801-809 LID - 10.1111/jdi.70280 [doi] AB - AIMS: To describe renal function-specific prescribing patterns of antidiabetic drugs in Japanese patients with type 2 diabetes using real-world data and to identify selection trends up to the second therapy. MATERIALS AND METHODS: We retrospectively analyzed data from the J-DREAMS registry (2015-2023) to evaluate the proportions of first and second drug classes stratified by renal function (eGFR >/=60 vs <60 mL/min/1.73 m(2)) and to examine temporal changes across registration periods. Prescription proportions by renal function were also compared using propensity score matching. RESULTS: Among 24,868 patients, 36.1% had an eGFR <60 mL/min/1.73 m(2). DPP-4 inhibitors were the most common first agents regardless of renal function, followed commonly by metformin and insulin. The use of SGLT2 inhibitors and GLP-1 receptor agonists increased as second-line therapies; in more recent periods, SGLT2 inhibitors were most frequently selected in the normal renal function group (25.6%), while GLP-1 receptor agonists ranked third in the reduced renal function group (15.9%). After matching, prescription proportions of SGLT2 inhibitors were similar between groups, whereas sulfonylureas (SUs), metformin, and thiazolidinediones were less frequent in the reduced renal function group. CONCLUSIONS: Prescribing patterns in Japan have shifted toward earlier use of SGLT2 inhibitors and GLP-1 receptor agonists, with medications appropriately tailored to renal function. CI - (c) 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Kubota, Masashi AU - Kubota M AUID- ORCID: 0009-0003-4106-8132 AD - Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan. FAU - Ohsugi, Mitsuru AU - Ohsugi M AD - Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan. AD - Diabetes and Metabolism Information Center, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan. FAU - Ueki, Kohjiro AU - Ueki K AUID- ORCID: 0000-0003-1523-8102 AD - Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan. AD - Diabetes Research Center, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan. LA - eng GR - Dainippon Sumitomo Pharma/ PT - Journal Article DEP - 20260227 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Japan/epidemiology MH - Retrospective Studies MH - Female MH - Male MH - Aged MH - Glomerular Filtration Rate MH - Middle Aged MH - Registries MH - Databases, Factual MH - *Kidney/physiopathology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians'/statistics & numerical data PMC - PMC13137285 OTO - NOTNLM OT - Chronic renal insufficiency OT - Drug prescriptions OT - Type 2 diabetes mellitus EDAT- 2026/02/27 06:31 MHDA- 2026/05/04 12:35 PMCR- 2026/02/27 CRDT- 2026/02/27 03:53 PHST- 2026/01/31 00:00 [revised] PHST- 2026/01/08 00:00 [received] PHST- 2026/02/02 00:00 [accepted] PHST- 2026/05/04 12:35 [medline] PHST- 2026/02/27 06:31 [pubmed] PHST- 2026/02/27 03:53 [entrez] PHST- 2026/02/27 00:00 [pmc-release] AID - JDI70280 [pii] AID - 10.1111/jdi.70280 [doi] PST - ppublish SO - J Diabetes Investig. 2026 May;17(5):801-809. doi: 10.1111/jdi.70280. Epub 2026 Feb 27. PMID- 41752784 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 2 DP - 2026 Feb 16 TI - Preliminary Real-World Experience with Semaglutide in Obese Patients with Type 2 Diabetes on Chronic Hemodialysis: A Multicenter Pilot Study. LID - 10.3390/medicina62020386 [doi] LID - 386 AB - Background and Objectives: Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has demonstrated metabolic and weight benefits in diabetic and obese patients with chronic kidney disease (CKD) who are not on dialysis; however, evidence in the hemodialysis (HD) population is scarce. Weight control and body composition optimization are particularly challenging in HD because of fluid shifts and the risk of protein-energy wasting. Materials and Methods: This prospective, multicenter, real-world, uncontrolled observational pilot study explored the short-term safety and changes in anthropometric and body-composition parameters after semaglutide initiation in obese adults with type 2 diabetes mellitus (T2DM) undergoing chronic HD. Patients were assessed at baseline and at 3 and 6 months. The primary endpoint was the change in body mass index (BMI), dry weight, and fat mass assessed by bioimpedance spectroscopy (BIS). Results: Thirteen patients were included (10 male, 77%), with a median age of 61.9 years (IQR 55-69). Semaglutide was started at 0.25 mg/week and titrated up to 1 mg/week according to tolerance. Three patients (23.1%) experienced transient nausea that was resolved over time or after dose adjustment, without discontinuation. From baseline to month +6, BMI decreased by a median of 1.5 kg/m(2) and dry weight by 5.0 kg, mainly driven by a median reduction in fat mass of 9 kg; lean tissue mass and serum albumin did not change significantly. Conclusions: In this small, uncontrolled exploratory study, semaglutide was generally well tolerated and was associated with short-term reductions in body weight and fat mass in obese patients with T2DM on HD. These findings are hypothesis-generating and require confirmation in larger controlled prospective studies to define safety and clinical benefit in this population. FAU - Yugueros, Alejandra AU - Yugueros A AUID- ORCID: 0000-0002-8020-7276 AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - D'Marco, Luis AU - D'Marco L AUID- ORCID: 0000-0003-0148-891X AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - Valero, Alejandro AU - Valero A AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Vivo, Elena AU - Vivo E AD - Servicio de Nefrologia, Hospital de la Ribera, 46600 Alzira, Spain. FAU - Martinez-Mas, Amparo AU - Martinez-Mas A AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Calve, Manuel AU - Calve M AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Alonso, Juan Carlos AU - Alonso JC AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Vizcaino, Belen AU - Vizcaino B AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Gonzalez-Moya, Mercedes AU - Gonzalez-Moya M AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Checa-Ros, Ana AU - Checa-Ros A AUID- ORCID: 0000-0001-8958-6711 AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - Sancho, Asuncion AU - Sancho A AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Molina, Pablo AU - Molina P AUID- ORCID: 0000-0002-8311-6214 AD - Servicio de Nefrologia, Hospital Universitari i Politecnic La Fe, 46026 Valencia, Spain. AD - Departament de Medicina, Facultat de Medicina i Odontlogia, Universitat de Valencia, 46010 Valencia, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260216 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Pilot Projects MH - Middle Aged MH - Female MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Prospective Studies MH - *Obesity/drug therapy/complications MH - Aged MH - Renal Dialysis/methods MH - Hypoglycemic Agents/therapeutic use MH - Body Mass Index PMC - PMC12942463 OTO - NOTNLM OT - GLP1-RA OT - chronic kidney disease OT - diabetes OT - hemodialysis OT - obesity OT - semaglutide COIS- The author declares no conflicts of interest. EDAT- 2026/02/27 06:31 MHDA- 2026/03/06 09:09 PMCR- 2026/02/16 CRDT- 2026/02/27 01:12 PHST- 2025/12/26 00:00 [received] PHST- 2026/02/02 00:00 [revised] PHST- 2026/02/09 00:00 [accepted] PHST- 2026/03/06 09:09 [medline] PHST- 2026/02/27 06:31 [pubmed] PHST- 2026/02/27 01:12 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - medicina62020386 [pii] AID - medicina-62-00386 [pii] AID - 10.3390/medicina62020386 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Feb 16;62(2):386. doi: 10.3390/medicina62020386. PMID- 41752654 OWN - NLM STAT- MEDLINE DCOM- 20260909 LR - 20260909 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 2 DP - 2026 Jan 25 TI - Vascular and Myocardial Function in Patients with Type 2 Diabetes and Ischemic Stroke Treated with Dulaglutide or Empagliflozin. LID - 10.3390/medicina62020254 [doi] LID - 254 AB - Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (-11.8% vs. -4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (-14% vs. -10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness. FAU - Pavlidis, George AU - Pavlidis G AUID- ORCID: 0000-0003-3220-3446 AD - 4th Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Prentza, Vasiliki AU - Prentza V AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Ikonomidis, Ignatios AU - Ikonomidis I AUID- ORCID: 0000-0001-8241-7886 AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Katogiannis, Konstantinos AU - Katogiannis K AUID- ORCID: 0000-0003-1631-5210 AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Kountouri, Aikaterini AU - Kountouri A AUID- ORCID: 0000-0001-5829-7327 AD - 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Thymis, John AU - Thymis J AUID- ORCID: 0000-0002-3916-5350 AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Michalopoulou, Eleni AU - Michalopoulou E AD - 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Pliouta, Loukia AU - Pliouta L AUID- ORCID: 0009-0007-8693-4443 AD - 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Korakas, Emmanouil AU - Korakas E AUID- ORCID: 0000-0002-7813-5488 AD - 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Stefanou, Maria-Ioanna AU - Stefanou MI AUID- ORCID: 0000-0002-2305-6627 AD - 2nd Department of Neurology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Palaiodimou, Lina AU - Palaiodimou L AUID- ORCID: 0000-0001-7757-609X AD - 2nd Department of Neurology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Tsivgoulis, Georgios AU - Tsivgoulis G AUID- ORCID: 0000-0002-0640-3797 AD - 2nd Department of Neurology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. LA - eng PT - Journal Article PT - Observational Study DEP - 20260125 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - WTT295HSY5 (dulaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - *Ischemic Stroke/complications/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology/therapeutic use/analogs & derivatives MH - Immunoglobulin Fc Fragments/pharmacology/therapeutic use MH - Recombinant Fusion Proteins/pharmacology/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Benzhydryl Compounds/pharmacology/therapeutic use MH - Glucosides/pharmacology/therapeutic use MH - Vascular Stiffness/drug effects/physiology MH - Glycocalyx/drug effects/physiology MH - Global Longitudinal Strain/drug effects/physiology MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged MH - Treatment Outcome PMC - PMC12941497 OTO - NOTNLM OT - arterial stiffness OT - endothelial glycocalyx OT - glucagon-like peptide-1 receptor agonists OT - ischemic stroke OT - left ventricular myocardial strain OT - sodium-glucose cotransporter 2 inhibitors OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/02/27 06:32 MHDA- 2026/03/06 09:03 PMCR- 2026/01/25 CRDT- 2026/02/27 01:12 PHST- 2025/12/27 00:00 [received] PHST- 2026/01/18 00:00 [revised] PHST- 2026/01/22 00:00 [accepted] PHST- 2026/03/06 09:03 [medline] PHST- 2026/02/27 06:32 [pubmed] PHST- 2026/02/27 01:12 [entrez] PHST- 2026/01/25 00:00 [pmc-release] AID - medicina62020254 [pii] AID - medicina-62-00254 [pii] AID - 10.3390/medicina62020254 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Jan 25;62(2):254. doi: 10.3390/medicina62020254. PMID- 41752021 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 4 DP - 2026 Feb 15 TI - The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases. LID - 10.3390/ijms27041886 [doi] LID - 1886 AB - The aim of this article is to present the current state of knowledge regarding the use of GLP-1 agonists in the treatment of type 2 diabetes, obesity, and other potential clinical indications, including neurodegenerative conditions. The article describes the characteristics of the diseases discussed, with particular emphasis on the pathophysiological mechanisms and the impact of metabolic disorders on the course of the diseases. In addition, the specific role of GLP-1 receptor agonists and their mechanisms of action leading to improved clinical outcomes were discussed, including their impact on molecular pathways involved in glucose metabolism regulation, inflammatory processes, carcinogenesis, and neuroprotection. Based on meta-analyses of available clinical trials, the evidence supporting the effectiveness of GLP-1 agonist therapy in glycemic control, weight loss, and improvement of metabolic parameters was synthesized. Additionally, potential benefits beyond the metabolic system are discussed, including neuroprotective effects and impact on patients' cardiovascular profiles, as well as risks and adverse effects associated with the use of GLP-1 agonists. The collected data indicate the growing role of GLP-1 agonists as an innovative and effective therapeutic strategy, while emphasizing the need for further research in the context of new clinical indications. FAU - Kowalska, Malgorzata Katarzyna AU - Kowalska MK AUID- ORCID: 0000-0001-8947-2861 AD - Department of Applied Chemistry, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. FAU - El-Mallul, Ahmed AU - El-Mallul A AD - Department of Health Sciences and Physical Culture, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. FAU - Hudecka, Weronika AU - Hudecka W AD - Department of Health Sciences and Physical Culture, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. FAU - Lubojanska, Joanna Elzbieta AU - Lubojanska JE AD - Department of Health Sciences and Physical Culture, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. FAU - Lubojanski, Piotr Jan AU - Lubojanski PJ AD - Specialist Hospital Named Dr. Tytus Chalubinski, 1 Adolfa Tochtermana Street, 26-600 Radom, Poland. FAU - Orlowska, Sara Malgorzata AU - Orlowska SM AUID- ORCID: 0009-0008-2785-4985 AD - Department of Health Sciences and Physical Culture, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. FAU - Bednarczyk, Lukasz AU - Bednarczyk L AUID- ORCID: 0009-0002-9211-6264 AD - Department of Health Sciences and Physical Culture, Casimir Pulaski Radom University, Street Chrobrego 27, 26-600 Radom, Poland. LA - eng PT - Journal Article PT - Review DEP - 20260215 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Neurodegenerative Diseases/metabolism/drug therapy MH - *Signal Transduction MH - *Glucagon-Like Peptide 1/metabolism/agonists MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Metabolic Diseases/metabolism/drug therapy MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/metabolism/drug therapy PMC - PMC12941302 OTO - NOTNLM OT - GLP-1 OT - GLP-1 receptor agonists OT - appetite regulation OT - cardiometabolic risk OT - mesolimbic reward pathway OT - molecular pathways OT - obesity OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/02/27 06:31 MHDA- 2026/03/06 19:44 PMCR- 2026/02/15 CRDT- 2026/02/27 01:10 PHST- 2025/12/21 00:00 [received] PHST- 2026/02/07 00:00 [revised] PHST- 2026/02/13 00:00 [accepted] PHST- 2026/03/06 19:44 [medline] PHST- 2026/02/27 06:31 [pubmed] PHST- 2026/02/27 01:10 [entrez] PHST- 2026/02/15 00:00 [pmc-release] AID - ijms27041886 [pii] AID - ijms-27-01886 [pii] AID - 10.3390/ijms27041886 [doi] PST - epublish SO - Int J Mol Sci. 2026 Feb 15;27(4):1886. doi: 10.3390/ijms27041886. PMID- 41749007 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20261001 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 7 DP - 2026 May TI - Cancer Incidence Among Users of Glucagon-Like Peptide-1 Receptor Agonists. PG - 1771-1779 LID - 10.1007/s11606-026-10300-1 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel antidiabetic agents that may influence cancer risk. While some studies suggest protective effects, others raise concerns about potential oncogenic associations. OBJECTIVE: To investigate the risk of common cancers with GLP-1RA initiation. DESIGN: Retrospective cohort study. PARTICIPANTS AND MAIN MEASURES: Patients diagnosed with type 2 diabetes between 2013-2021 were identified using IBM-MarketScan database and were categorized into exposure (i.e., GLP-1RA) and comparison (i.e., insulin) groups. Overlap Propensity Score Weighting (OPSW), followed by Cox proportional hazards models, was used to assess cancer risk. KEY RESULTS: Among 106,088 patients, most were male (n = 44,059, 51.3%), and the mean age was 51 (SD: +/- 9.8) years; 50.8% (n = 53,924) of patients had GLP-1RA initiation. Overall, 1.9% (n = 1,594) of the individuals developed cancer (thyroid: n = 110, 0.1%; lung: n = 127, 0.1%; breast: n = 369, 0.4%; esophagus: n = 20, 0.02%; gastric: n = 34, 0.03%; liver: n = 116, 0.1%; biliary: n = 20, 0.02%; pancreatic: n = 87, 0.1%; small intestine: n = 23, 0.02%; renal: n = 128, 0.1%; bladder: n = 66, 0.1%; colorectal: n = 175, 0.2%; prostate: n = 322, 0.4%; ovarian: n = 51, 0.1%; endometrial: n = 130, 0.2%; neuroendocrine: n = 60, 0.1%). Compared to insulin, GLP-1RA medications were associated with a significantly lower risk of liver cancer (HR: 0.47, 95% CI: 0.27-0.82) and pancreatic cancer (HR: 0.23, 95% CI: 0.11-0.51). Risk of all other cancers remained comparable between the two groups (all p > 0.05). CONCLUSIONS: GLP-1RA use was associated with a lower incidence of liver and pancreatic cancer, with no increased risk observed for other major cancers. As these medications become more widely used, further research is warranted to better define their long-term cancer-related safety profile. CI - (c) 2026. The Author(s). FAU - Rashid, Zayed AU - Rashid Z AD - Department of Internal Medicine, Conemaugh Memorial Medical Center, Johnstown, PA, USA. FAU - Woldesenbet, Selamawit AU - Woldesenbet S AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Khalil, Mujtaba AU - Khalil M AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Altaf, Abdullah AU - Altaf A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Zindani, Shahzaib AU - Zindani S AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Mevawalla, Areesh AU - Mevawalla A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Sarfraz, Azza AU - Sarfraz A AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. FAU - Mumtaz, Khalid AU - Mumtaz K AD - Department of Internal Medicine, Division of Gastroenterology, Hepatology & Nutrition, College of Medicine, The Ohio State University, Columbus, OH, USA. FAU - Pawlik, Timothy M AU - Pawlik TM AUID- ORCID: 0000-0002-7994-9870 AD - Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. tim.pawlik@osumc.edu. LA - eng PT - Journal Article DEP - 20260226 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Middle Aged MH - Incidence MH - *Neoplasms/epidemiology/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Adult MH - Cohort Studies PMC - PMC13176436 OTO - NOTNLM OT - GLP-1RA medications OT - diabetes OT - hepatocellular carcinoma OT - obesity OT - pancreas cancer OT - thyroid cancer COIS- Declarations. Human Ethics and Consent to Participate: Not applicable. Conflicts of interest: Nothing to report. The authors declare no conflict of interest. Disclaimer: None. Disclosures: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. EDAT- 2026/02/27 00:33 MHDA- 2026/05/14 18:36 PMCR- 2026/02/26 CRDT- 2026/02/26 23:29 PHST- 2025/10/29 00:00 [received] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/05/14 18:36 [medline] PHST- 2026/02/27 00:33 [pubmed] PHST- 2026/02/26 23:29 [entrez] PHST- 2026/02/26 00:00 [pmc-release] AID - 10.1007/s11606-026-10300-1 [pii] AID - 10300 [pii] AID - 10.1007/s11606-026-10300-1 [doi] PST - ppublish SO - J Gen Intern Med. 2026 May;41(7):1771-1779. doi: 10.1007/s11606-026-10300-1. Epub 2026 Feb 26. PMID- 41748946 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 399 IP - 8 DP - 2026 May TI - Musculoskeletal adverse events with incretin-based diabetes drugs: a FAERS pharmacovigilance study. PG - 11975-11991 LID - 10.1007/s00210-026-05113-2 [doi] AB - Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and the dual GIP/GLP-1 RA tirzepatide, are widely prescribed for type 2 diabetes mellitus (T2DM). Their musculoskeletal adverse events (AEs) remain underexplored. We analyzed FAERS reports (Q1 2004-Q2 2024) for musculoskeletal and connective tissue disorders. After de-duplication, 15,052 reports were subjected to disproportionality analyses using reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and information component (IC). Differences between serious and non-serious events were assessed, and time to onset was examined by cumulative curves and Weibull models. No signals were detected at the SOC level. At the PT level, GLP-1 RAs were linked to back pain, myalgia, and neck mass, while tirzepatide was associated with muscle atrophy and neck mass. Among DPP-4is, sitagliptin, linagliptin, and alogliptin showed signals for osteoarthritis, rhabdomyolysis, and arthritis. Sex-, age-, and weight-related differences were noted for dulaglutide, liraglutide, semaglutide, sitagliptin, linagliptin, alogliptin, and saxagliptin. Median onset was shorter for GLP-1 RAs and tirzepatide (/=35 kg/m(2). RESULTS: We included 29 780 GLP-1RA initiators, with 62.2% (n = 18 517) initiating pre-2018 and 37.8% (n = 11 263) post-2018. Consistent over calendar time, most GLP-1RA initiators (63.5%) received their first GLP-1RA as fourth-line (35.4%) or later-line therapy (28.1%), with fewer initiating GLP-1RAs as first- (0.8%), second- (10.5%), or third-line (25.2%) treatments. After 2018, 50.8% of individuals initiating GLP-1RA therapy used SGLT-2is concomitantly, regardless of CVD status (47.8% with established CVD vs. 51.5% without). Individuals with BMI >/=35 kg/m(2) initiated GLP-1RA therapy earlier compared to those with BMI <35 kg/m(2) (46.3% vs. 29.1% as first-, second-, or third-line treatment). CONCLUSIONS: GLP-1RAs were predominantly initiated following >/=3 glucose-lowering agents, consistent with contemporary UK guidance (NG28). Post-2018, most GLP-1RA initiators received SGLT-2is concomitantly. However, CVD history did not influence prescribing patterns, underscoring missed opportunities to optimise the prevention of cardiovascular events and slow the progression of CVD. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ulrich, Franziska S AU - Ulrich FS AUID- ORCID: 0009-0005-2278-7400 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. FAU - Frost Nielsen, Morten AU - Frost Nielsen M AUID- ORCID: 0000-0002-5608-1589 AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark. FAU - Napoli, Nicola AU - Napoli N AUID- ORCID: 0000-0002-3091-8205 AD - Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy. AD - Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico University of Rome, Rome, Italy. AD - Division of Bone and Mineral Diseases, Washington University, St Louis, Missouri, USA. FAU - Burden, Andrea M AU - Burden AM AUID- ORCID: 0000-0001-7082-8530 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. AD - Division of Clinical Immunology and Rheumatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng GR - 24B110/Novartis Foundation for Medical-Biological Research/ PT - Journal Article DEP - 20260225 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United Kingdom/epidemiology MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - Practice Guidelines as Topic MH - *Guideline Adherence/statistics & numerical data MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Cardiovascular Diseases/epidemiology MH - Cohort Studies MH - Primary Health Care PMC - PMC13071226 OTO - NOTNLM OT - GLP-1 receptor agonist OT - United Kingdom OT - cardiovascular disease OT - clinical guidance OT - drug utilisation OT - glucose-lowering therapy OT - obesity OT - primary care OT - real-world evidence OT - type 2 diabetes COIS- All authors declare no conflicts of interest and acknowledge support from the funder for the submitted work. EDAT- 2026/02/26 15:20 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/02/25 23:26 PHST- 2026/01/19 00:00 [revised] PHST- 2025/11/14 00:00 [received] PHST- 2026/01/28 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/26 15:20 [pubmed] PHST- 2026/02/25 23:26 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70548 [pii] AID - 10.1111/dom.70548 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3692-3702. doi: 10.1111/dom.70548. Epub 2026 Feb 25. PMID- 41740927 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260709 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 234 DP - 2026 Apr TI - Cost-effectiveness analysis of oral semaglutide versus subcutaneous dulaglutide in patients with type 2 diabetes mellitus: A Markov model study. PG - 113186 LID - S0168-8227(26)00105-1 [pii] LID - 10.1016/j.diabres.2026.113186 [doi] AB - AIM: This study assessed the cost-effectiveness of oral semaglutide versus subcutaneous dulaglutide for type 2 diabetes mellitus (T2DM) from the perspective of the Taiwanese healthcare payer, considering the self-paid status of oral semaglutide and the reimbursed but injectable route of dulaglutide under the National Health Insurance (NHI). METHODS: A Markov decision-analytic model simulated clinical and economic outcomes over a 10-year horizon. Transition probabilities, utilities, and treatment costs were derived from clinical trials, national databases, and expert consensus. Costs and health outcomes were discounted at 3% annually. The willingness-to-pay (WTP) threshold was set at US$33,983, reflecting per capita gross domestic product in Taiwan. Probabilistic and one-way sensitivity analyses evaluated model robustness. RESULTS: Oral semaglutide was dominant, yielding an incremental gain of 0.33 quality-adjusted life years (QALYs) and reducing costs by US$1,137 compared with dulaglutide, with an incremental cost-utility ratio of -US$3,478.66/QALYs. Sensitivity analyses confirmed the robustness, with a 96.5% probability of cost-effectiveness across all WTP thresholds. Cost differences were most sensitive to drug price, particularly in patients without cardiovascular disease. CONCLUSION: Oral semaglutide demonstrated higher clinical effectiveness and strong economic favorability relative to dulaglutide, supporting its potential inclusion in Taiwan NHI formulary to optimize the allocation of healthcare resources in T2DM. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Hsu, Hsiao-Yuan AU - Hsu HY AD - Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Kaohsiung, Taiwan; Department of Healthcare Administration and Medical Informatics, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Shi, Hon-Yi AU - Shi HY AD - Department of Healthcare Administration and Medical Informatics, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Business Management, College of Management, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. Electronic address: hshi@kmu.edu.tw. LA - eng PT - Journal Article DEP - 20260223 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/economics/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Recombinant Fusion Proteins/economics/administration & dosage/therapeutic use MH - Semaglutide MH - Cost-Benefit Analysis MH - *Immunoglobulin Fc Fragments/economics/administration & dosage/therapeutic use MH - Cost-Effectiveness Analysis MH - Markov Chains MH - *Hypoglycemic Agents/administration & dosage/economics/therapeutic use MH - Administration, Oral MH - Injections, Subcutaneous MH - Taiwan MH - Quality-Adjusted Life Years MH - Female MH - Middle Aged OTO - NOTNLM OT - Cost-effectiveness analysis OT - Dulaglutide OT - Markov model OT - Oral semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/02/26 15:20 MHDA- 2026/03/12 07:04 CRDT- 2026/02/25 19:34 PHST- 2025/08/31 00:00 [received] PHST- 2025/12/22 00:00 [revised] PHST- 2026/02/22 00:00 [accepted] PHST- 2026/03/12 07:04 [medline] PHST- 2026/02/26 15:20 [pubmed] PHST- 2026/02/25 19:34 [entrez] AID - S0168-8227(26)00105-1 [pii] AID - 10.1016/j.diabres.2026.113186 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Apr;234:113186. doi: 10.1016/j.diabres.2026.113186. Epub 2026 Feb 23. PMID- 41735212 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1875-5607 (Electronic) IS - 1389-5575 (Linking) VI - 26 IP - 5 DP - 2026 TI - Efficacy of Dual Glucagon and GLP-1 Agonists as New Treatments for Type II Diabetes. PG - 371-387 LID - 10.2174/0113895575419389251118100027 [doi] AB - Globally, conditions like type 2 diabetes mellitus (T2DM) are on the rise. This situation is brought on by an increase in insulin volume and a decrease in insulin manifestation. Currently available medications are designed to either improve insulin activity or promote insulin resilience. The prevalence of type 2 diabetes mellitus in the US exceeds 26 million individuals. Long-term glycaemic control in T2D patients is still difficult to achieve despite the abundance of available therapeutic choices. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide a therapeutic option that enhances glycaemic regulation and facilitates weight loss, while presenting a little risk of hypoglycemia. A novel approach to enhancing glycaemic control and addressing the complex ecology of type 2 diabetes is to reduce dependence on glucagon and glucagon-like peptide 1 (GLP- 1). Therapeutic interventions focused on glucagon-like peptide 1 (GLP-1) offer a promising initial approach to managing type 2 diabetes mellitus (T2DM), as they effectively reduce body fat percentage and have a significant impact on cardiovascular health. The scientists involved have discovered that individuals with type 2 diabetes have inadequate responses to supraphysiological infusions of glucose-dependent insulinotropic polypeptide (GIP), resulting in its initial dismissal as an inefficient hypoglycaemic agent. The simultaneous administration of GLP-1 and GIP, as opposed to their separate administration, resulted in an altered insulin and glucagon static response, as demonstrated in a more recent study. This article provides a concise overview of the latest findings on dual glucagon and GLP-1 agonists, including a description of their mechanisms of action, clinical outcomes, advantages and disadvantages, and challenges to their development. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Vats, Jatin AU - Vats J AD - Department of Pharmacy, Hindu College of Pharmacy, Sonipat, Haryana, India. FAU - Chauhan, Ajesh AU - Chauhan A AD - Department of Pharmacy, Hindu College of Pharmacy, Sonipat, Haryana, India. AD - Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India. FAU - Rajput, Shivam AU - Rajput S AD - Department of Pharmacy, Hindu College of Pharmacy, Sonipat, Haryana, India. AD - Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India. FAU - Sridhar, Sathvik Belagodu AU - Sridhar SB AD - RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Vashist, Chetan AU - Vashist C AD - Department of Pharmacy, Hindu College of Pharmacy, Sonipat, Haryana, India. FAU - Mittal, Arun AU - Mittal A AD - Department of Pharmacy, Hindu College of Pharmacy, Sonipat, Haryana, India. FAU - Malviya, Rishabha AU - Malviya R AUID- ORCID: 0000-0003-2874-6149 AD - Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India. LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Mini Rev Med Chem JT - Mini reviews in medicinal chemistry JID - 101094212 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9007-92-5 (Glucagon) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology/chemistry MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon/agonists/metabolism MH - *Glucagon-Like Peptide 1/agonists/metabolism MH - Animals OTO - NOTNLM OT - Insulin OT - cardiovascular health OT - clinical outcomes OT - diabetes mellitus OT - glucagon-like peptide OT - glucose-dependent insulinotropic polypeptide EDAT- 2026/02/25 00:30 MHDA- 2026/07/15 12:35 CRDT- 2026/02/24 22:43 PHST- 2025/06/01 00:00 [received] PHST- 2025/09/17 00:00 [revised] PHST- 2025/09/17 00:00 [accepted] PHST- 2026/07/15 12:35 [medline] PHST- 2026/02/25 00:30 [pubmed] PHST- 2026/02/24 22:43 [entrez] AID - MRMC-EPUB-153087 [pii] AID - 10.2174/0113895575419389251118100027 [doi] PST - ppublish SO - Mini Rev Med Chem. 2026;26(5):371-387. doi: 10.2174/0113895575419389251118100027. PMID- 41735082 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260722 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 148 DP - 2026 Jun TI - Assessing the proportion of patients with type 2 diabetes in tertiary care eligible for combination therapy with GLP-1 receptor agonist and SGLT2 inhibitors. PG - 106787 LID - S0953-6205(26)00092-0 [pii] LID - 10.1016/j.ejim.2026.106787 [doi] AB - BACKGROUND: Combination of GLP-1 receptor agonist (GLP-1 RA) and SGLT2 inhibitor (SGLT2i) is a recommended treatment in national and international diabetes guidelines, and the implementation is restricted by Swiss reimbursement standards. The implications for quality of care is partly dependent on the magnitude of patients affected. The aim was therefore to estimate the proportion of outpatients with type 2 diabetes in tertiary care that would be eligible for the combination therapy based on national treatment recommendations. METHODS: Cross-sectional analysis of patients enrolled in SwissDiab at Kantonsspital St. Gallen with a visit in 2021 or later. Patients with a BMI >/=28 kg/m(2) and thus eligible for GLP-1 RA were identified, including patients prescribed GLP-1 RA with a BMI >/=28 kg/m(2) at treatment initiation. Of these, patients with heart failure, chronic kidney disease and/or insufficient glycaemic control were considered eligible for the addition of SGLT2i. FINDINGS: Of 401 identified patients, 73.1% were eligible for GLP-1 RA. Of these, 61.1% had heart failure, chronic kidney disease and/or insufficient glycaemic control. The prevalence of heart failure was 25.7%, chronic kidney disease 77.7%, and insufficient glycaemic control 37.4%. Overall, 44.6% of the patients would stand to benefit from combination therapy. INTERPRETATION: That almost half of the patients with type 2 diabetes in tertiary care were eligible for combination therapy with GLP-1 RA and SGLT2i highlight the potential negative impact of restricting access to evidence-based care central for the prevention of cardiorenal outcomes and premature death. FUNDING: The current study received unrestricted support from AstraZeneca. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Jensen, Anders B AU - Jensen AB AD - Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, St. Gallen, Switzerland; Department of Endocrinology, Spital Bulach, Bulach, Switzerland. Electronic address: anders.jensen@spitalbuelach.ch. FAU - Renstrom, Frida AU - Renstrom F AD - Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, St. Gallen, Switzerland. FAU - Brandle, Michael AU - Brandle M AD - Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, St. Gallen, Switzerland; Division of General Internal, Family, and Emergency Medicine, HOCH Health Ostschweiz, St. Gallen, Switzerland. LA - eng PT - Journal Article DEP - 20260223 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Cross-Sectional Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Male MH - Middle Aged MH - Switzerland MH - Renal Insufficiency, Chronic/epidemiology MH - Heart Failure/epidemiology OTO - NOTNLM OT - Combination therapy OT - Glucagon-like peptide-1 receptor agonist OT - Reimbursement OT - Sodium-glucose cotransporter 2 inhibitor OT - Type 2 diabetes mellitus COIS- Declaration of competing interest A.J. has received honoraria for presentations and support for attending meetings from Novo Nordisk. F.R. reports no conflict of interest. M.B. has received unrestricted financial support for this study from AstraZeneca, which did not have any influence on the study design, data collection, analysis or interpretation, writing, or the decision to submit the manuscript for publication, beyond any interest in the overall topic of the study. Honoraria for lectures and presentations from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk. Participation on advisory board meetings for Eli Lilly, Novo Nordisk. EDAT- 2026/02/25 00:30 MHDA- 2026/06/06 00:35 CRDT- 2026/02/24 21:56 PHST- 2025/12/11 00:00 [received] PHST- 2026/02/16 00:00 [revised] PHST- 2026/02/17 00:00 [accepted] PHST- 2026/06/06 00:35 [medline] PHST- 2026/02/25 00:30 [pubmed] PHST- 2026/02/24 21:56 [entrez] AID - S0953-6205(26)00092-0 [pii] AID - 10.1016/j.ejim.2026.106787 [doi] PST - ppublish SO - Eur J Intern Med. 2026 Jun;148:106787. doi: 10.1016/j.ejim.2026.106787. Epub 2026 Feb 23. PMID- 41732861 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 153 IP - 15 DP - 2026 Apr 14 TI - Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation. PG - 1086-1100 LID - 10.1161/CIRCULATIONAHA.125.075157 [doi] AB - BACKGROUND: Novel treatments are needed for the primary and secondary prevention of heart failure in patients with type 2 diabetes, including individuals with and those without a history of heart failure. Conflicting trial evidence exists on whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of hospitalization for heart failure (HHF) in this broad population and whether this is a class effect or varies by specific agent. Furthermore, their comparative effectiveness against sodium-glucose cotransporter-2 inhibitors (SGLT-2is) is unknown. METHODS: We emulated 2 target trials using population-based health care data from Stockholm, Sweden (2010-2021). Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i. The primary outcome was HHF. Cox regression was used to estimate intention-to-treat hazard ratios, with inverse probability of treatment weighting used to balance 72 confounders. Major adverse cardiovascular events were used as the positive control outcome. Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide. RESULTS: Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female. Starting a GLP-1RA was associated with a lower 3-year absolute risk of HHF than starting a DPP-4i (3.4% versus 4.3%), corresponding to a weighted hazard ratio of 0.77 (95% CI, 0.66-0.91). Absolute 3-year risks for GLP-1RA compared with SGLT-2i on HHF were 3.6% and 3.3% with a weighted hazard ratio of 1.02 (95% CI, 0.85-1.18). The absolute risk difference was largest for patients with higher predicted risk of heart failure at baseline. Results were consistent for single agents, in per-protocol analyses, and in the majority of subgroups. In positive control outcome analyses, GLP-1RA use was associated with a lower rate of major adverse cardiovascular events than DPP-4i use (weighted hazard ratio, 0.85 [95% CI, 0.74-0.99]), consistent with trial findings. CONCLUSIONS: GLP-1RA use is associated with a lower risk of HHF compared with DPP-4i and similar risks compared with SGLT-2i in routine clinical care for patients with type 2 diabetes. FAU - Xu, Yang AU - Xu Y AUID- ORCID: 0000-0002-1074-608X AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China (Y.X., T.H., Y.Z., D.J.). AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Y.X., J.-J.C., E.L.F.). FAU - Huang, Tao AU - Huang T AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China (Y.X., T.H., Y.Z., D.J.). FAU - Zhang, Yue AU - Zhang Y AUID- ORCID: 0009-0000-5619-2898 AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China (Y.X., T.H., Y.Z., D.J.). FAU - Ji, Dongze AU - Ji D AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China (Y.X., T.H., Y.Z., D.J.). FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA (K.R.T.). AD - Department of Medicine and Kidney Research Institute and Institute of Translational Health Sciences, University of Washington, Seattle (K.R.T.). FAU - Carrero, Juan-Jesus AU - Carrero JJ AUID- ORCID: 0000-0003-4763-2024 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Y.X., J.-J.C., E.L.F.). AD - Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden (J.-J.C.). FAU - Fu, Edouard L AU - Fu EL AUID- ORCID: 0000-0002-9698-6825 AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Y.X., J.-J.C., E.L.F.). AD - Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands (E.L.F.). LA - eng PT - Comparative Study PT - Journal Article DEP - 20260224 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/diagnosis MH - Female MH - *Heart Failure/epidemiology/diagnosis MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - *Hospitalization MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sweden/epidemiology MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - cardiovascular diseases OT - clinical trial OT - hypoglycemic agents OT - metabolic diseases COIS- Dr Tuttle has received investigator-initiated grant support from Travere Therapeutics Inc, Bayer, Benaroya Research Institute, and the Doris Duke Charitable Foundation. She reports consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Travere, and ProKidney, as well as speaker fees from Novo Nordisk. In addition, she reports being chair of data safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Disease and George Clinical Institute and a member of the data safety monitoring board for AstraZeneca. She reports leadership roles as chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology, chair for Kidney Week 2025 Program Committee, and a member of the American Heart Association/American College of Cardiology Cardiovascular-Kidney-Metabolic Guideline Committee. The other authors report no conflicts. EDAT- 2026/02/24 06:32 MHDA- 2026/04/13 18:32 CRDT- 2026/02/24 05:03 PHST- 2026/04/13 18:32 [medline] PHST- 2026/02/24 06:32 [pubmed] PHST- 2026/02/24 05:03 [entrez] AID - 10.1161/CIRCULATIONAHA.125.075157 [doi] PST - ppublish SO - Circulation. 2026 Apr 14;153(15):1086-1100. doi: 10.1161/CIRCULATIONAHA.125.075157. Epub 2026 Feb 24. PMID- 41730540 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1488-2329 (Electronic) IS - 0820-3946 (Print) IS - 0820-3946 (Linking) VI - 198 IP - 7 DP - 2026 Feb 22 TI - Cost-effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists for patients with high cardiovascular risk and type 2 diabetes in Canada. PG - E249-E259 LID - 10.1503/cmaj.250591 [doi] AB - BACKGROUND: Diabetes Canada and the Canadian Cardiovascular Society recommend that patients with type 2 diabetes and cardiovascular disease, renal disease, or multiple cardiovascular risk factors begin glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter 2 inhibitors (SGLT2i). We assessed cost-effectiveness in patients meeting these criteria in Canada. METHODS: Our patient-level simulation estimated lifetime costs, clinical events, and quality-adjusted life-years (QALYs) for patients initiating SGLT2i or GLP-1 RA or remaining on "baseline treatment"; i.e., other standard-of-care medications. We based initial laboratory values and characteristics on 216 patients from a Quebec clinic focused on initiating guideline-directed diabetes therapies from 2022 to 2025. We calibrated risk equations and treatment effects to end points from placebo-controlled cardiovascular outcome trials. We estimated cost-effectiveness over a patient lifetime horizon from a Canadian health care payer perspective using a 1.5% annual discount rate. We performed probabilistic sensitivity analysis. RESULTS: Compared with baseline treatment, SGLT2i and GLP-1 RA reduced lifetime rates of cardiovascular and renal events and produced higher net present QALYs (+0.24 SGLT2i; +0.23 GLP-1 RA ), but at a higher net present cost (+$5000 SGLT2i; +$27 000 GLP-1 RA [2023 Canadian $]). Sodium-glucose cotransporter 2 inhibitors cost $21 400 per QALY gained and were consistently cost-effective in sensitivity analyses. In 62% of probabilistic sensitivity analysis iterations, GLP-1 RA were dominated, producing fewer QALYs at a higher cost than SGLT2i. INTERPRETATION: Sodium-glucose cotransporter 2 inhibitors provided more QALYs at a lower price than GLP-1 RA and were cost-effective at current prices. Glucagon-like peptide-1 RA cost-effectiveness may improve if outcomes beyond typical diabetes complications are considered and if generic GLP-1 RA become available. CI - (c) 2026 CMA Impact Inc. or its licensors. FAU - McNally, Ethan S AU - McNally ES AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Marques, Pedro AU - Marques P AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Possik, Elite AU - Possik E AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Pandya, Ankur AU - Pandya A AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Tsoukas, Michael A AU - Tsoukas MA AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Mavrakanas, Thomas A AU - Mavrakanas TA AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Dasgupta, Kaberi AU - Dasgupta K AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Gupta, Nisha AU - Gupta N AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. FAU - Sharma, Abhinav AU - Sharma A AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. abhinav.sharma@mcgill.ca. FAU - Russell, W Alton AU - Russell WA AD - Department of Economics (McNally), and School of Population and Global Health (McNally, Russell), McGill University; DREAM-CV Lab (Marques, Possik, Sharma), Research Institute of the McGill University Health Centre (MUHC), Montreal, Que.; Department of Surgery and Physiology (Marques), Faculty of Medicine of the University of Porto, Cardiovascular Research and Development Center, Porto, Portugal; Department of Health Policy and Management (Pandya), Harvard T.H. Chan School of Public Health, Boston, Mass.; Centre for Outcome Research & Evaluation (Tsoukas, Mavrakanas, Dasgupta, Gupta, Sharma, Russell), Division of Endocrinology (Tsoukas), and Division of Nephrology (Mavrakanas), Department of Medicine, MUHC; Department of Medicine (Dasgupta, Gupta), Faculty of Medicine and Health Sciences, McGill University, Montreal, Que. LA - eng PT - Journal Article DEP - 20260222 PL - Canada TA - CMAJ JT - CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne JID - 9711805 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics/complications MH - Cost-Benefit Analysis MH - Cost-Effectiveness Analysis MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - *Cardiovascular Diseases/prevention & control/economics MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Canada MH - Quality-Adjusted Life Years MH - Middle Aged MH - *Hypoglycemic Agents/economics/therapeutic use MH - Heart Disease Risk Factors MH - Aged PMC - PMC12959951 COIS- Competing interests:: Pedro Marques reports receiving honoraria from Novartis, Bial, Recordati, and Daiichi-Sankyo, and support for attending meetings from Bial, Daiichi-Sankyo, and Servier. Ankur Pandya reports serving as President-Elect, Society for Medical Decision-Making (unpaid). Abhinav Sharma reports receiving support for the present manuscript from Mitacs and the McGill University Health Centre Foundation. Outside the submitted work, Dr. Sharma reports receiving grants from Astra-Zeneca, Boehringer-Ingelheim, Medtronic, Merck, Novartis, Novo Nordisk, Takeda Development Center Americas, Roche Diagnostics, Janssen, and Eli-Lilly; consulting fees from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Servier, Novo Nordisk, Novartis, Viatris, Vifor Pharma, and Bayer Inc.; and honoraria from AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, and Novartis. Dr. Sharma reports holding patents in AeroCardia, Perc-Assist, and AREA19; stock in AREA19; and equity in AREA19, AeroCardia, and Perc-Assist. Michael Tsoukas reports receiving speaker honoraria from Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Janssen, Sanofi, and Abbott. Thomas Mavrakanas reports receiving salary support from a clinician research scholar J2 award from the Fonds de Recherche de Sante-Quebec (in support of the current manuscript), and has received research grants from AstraZeneca, the Canadian Institute of Health Research, and the Heart & Stroke Foundation of Canada, as well as fellowship grants from Pfizer, Janssen, and Bayer (outside the submitted work, payment to institution). Dr. Mavrakanas has also received speaker honoraria from Bayer, Janssen, AstraZeneca, Novo Nordisk, and Boehringer-Ingelheim, and has served on advisory boards for Boehringer-Ingelheim, Servier, GSK, Novo Nordisk, and Bayer. No other competing interests were declared. EDAT- 2026/02/24 00:29 MHDA- 2026/02/24 00:30 PMCR- 2026/02/23 CRDT- 2026/02/23 20:32 PHST- 2025/12/12 00:00 [accepted] PHST- 2026/02/24 00:30 [medline] PHST- 2026/02/24 00:29 [pubmed] PHST- 2026/02/23 20:32 [entrez] PHST- 2026/02/23 00:00 [pmc-release] AID - 198/7/E249 [pii] AID - 198e249 [pii] AID - 10.1503/cmaj.250591 [doi] PST - epublish SO - CMAJ. 2026 Feb 22;198(7):E249-E259. doi: 10.1503/cmaj.250591. PMID- 41730476 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1541-6100 (Electronic) IS - 0022-3166 (Linking) VI - 156 IP - 4 DP - 2026 Apr TI - Fiber Supplementation during and after Glucagon-Like Peptide-1 Receptor Agonists Treatment: A Perspective on Clinical Benefits. PG - 101436 LID - S0022-3166(26)00085-4 [pii] LID - 10.1016/j.tjnut.2026.101436 [doi] AB - BACKGROUND: Pharmaceutical advancements with glucagon-like peptide-1 receptor agonists (GLP-1RA) treatment have dramatically shifted medical treatment for obesity and diabetes. The mechanism of GLP-1RA can lead to unwanted side effects, with nearly half of patients discontinuing treatment within 1 year. There is currently limited evidence on weight maintenance after treatment, but available data suggest that sustained benefits require continued use of GLP-1RA. A comprehensive position article encourages fiber intake during and after GLP-1RA treatment, but consuming high-fiber diets can be challenging. In the United States, only 5% of individuals meet the adequate intake for dietary fiber. Fiber supplementation could be advantageous for filling those gaps and providing targeted benefits both during and after GLP-1RA treatment. Therefore, complementary care plans are needed both during and after GLP-1RA treatment. METHODS: A review of existing evidence was conducted to assess the potential complementary role of dietary fiber supplementation during and after GLP-1RA. Meta-analyses from prior studies involving populations with obesity and diabetes using fiber supplement interventions were evaluated. RESULTS: During GLP-1RA treatment, patients may experience gastrointestinal side effects such as constipation and diarrhea. Several human clinical trials have found that fiber supplementation improves bowel function and stool consistency, offering a potential solution for patients experiencing side effects from GLP-1RA. After treatment, patients may experience greater difficulty maintaining weight loss and stable blood glucose. In multiple meta-analyses, fiber supplementation has improved appetite, fasting insulin and glucose levels, and body weight. Fiber supplements have also shown benefits for general digestive health, obesity indices, lipid profiles, and blood pressure. CONCLUSIONS: Although research on optimal nutrition therapy protocols during and after GLP-1RA treatment is still emerging, existing research provides evidence-based guidance to inform patient care. This perspective argues that fiber supplements could be a low-cost, effective nutritional intervention during and after GLP-1RA treatment. Dietary fiber supplementation may help reduce side effects during GLP-1RA and support appetites, glycemic control, and healthy body weight after GLP-1RA. CI - Copyright (c) 2026 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. FAU - Johnson, Brittany Vb AU - Johnson BV AD - Department of Research, Education, and Innovation, The B Fueled Foundation, Dallas, TX, United States. Electronic address: Brittany.johnson@futureceuticals.com. LA - eng PT - Journal Article PT - Review DEP - 20260221 PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Dietary Fiber) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Dietary Fiber/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dietary Supplements MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - dietary supplements OT - fiber supplement OT - nutritional strategies OT - obesity management OT - weight loss COIS- Conflict of Interest BVBJ is employed full-time in the dietary supplement industry. The author's current affiliation is VDF Future Ceuticals, Inc. EDAT- 2026/02/24 00:30 MHDA- 2026/04/06 00:30 CRDT- 2026/02/23 19:26 PHST- 2025/12/10 00:00 [received] PHST- 2026/01/22 00:00 [revised] PHST- 2026/02/19 00:00 [accepted] PHST- 2026/04/06 00:30 [medline] PHST- 2026/02/24 00:30 [pubmed] PHST- 2026/02/23 19:26 [entrez] AID - S0022-3166(26)00085-4 [pii] AID - 10.1016/j.tjnut.2026.101436 [doi] PST - ppublish SO - J Nutr. 2026 Apr;156(4):101436. doi: 10.1016/j.tjnut.2026.101436. Epub 2026 Feb 21. PMID- 41728915 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260911 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 9 DP - 2026 Aug 27 TI - Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial. PG - 1696-1708 LID - 10.1093/ndt/gfag036 [doi] AB - BACKGROUND: In the FLOW trial (Evaluate Renal Function with Semaglutide Once-Weekly; ClinicalTrials.gov, NCT03819153), once-weekly subcutaneous semaglutide 1.0 mg versus placebo reduced the risk of major kidney, cardiovascular (CV) and mortality outcomes in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD). This pre-specified analysis assesses the impact of semaglutide on risks of serious infections and coronavirus disease 2019 (COVID-19) in the FLOW trial. METHODS: The main outcome was a three-component composite [time from randomization to first infection serious adverse event (SAE), first hospitalization due to infection, or all-cause death]. Other outcomes included all infection SAEs, COVID-19 adverse events, COVID-19 SAEs, death due to infection and death concurrent with a COVID-19 SAE. RESULTS: Semaglutide reduced the risk of the main outcome versus placebo [hazard ratio (HR) (95% confidence interval) 0.79 (0.69-0.89); P = .0002]. This risk reduction was greater in subgroups with baseline hemoglobin A1c >8% [HR 0.63 (0.52-0.76)] versus /=2000 mg/g [HR 0.53 (0.39-0.72)] versus UACR <100 mg/g [HR 0.90 (0.58-1.39); Pinteraction = .0367]. The semaglutide group had a lower rate of infection SAEs (17.9% versus 21.3%; P = .0070), COVID-19 SAEs (6.7% versus 8.8%; P = .0155), COVID-19 adverse events (20.3% versus 22.9%; P = .0190) and hospitalization due to infection (17.5% versus 20.4%; P = .015). CONCLUSIONS: Semaglutide reduced risks of infection SAEs, hospitalization due to infection, and all-cause death with greater benefit among those with poorer glycemic control and greater baseline albuminuria. These findings support potential clinical benefits of semaglutide beyond kidney, CV and metabolic outcomes in high-risk patients with T2D and CKD. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. FAU - Rayner, Brian AU - Rayner B AD - Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Department of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munchen, Germany. AD - University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tran, Minh Chau AU - Tran MC AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chernin, Gil AU - Chernin G AUID- ORCID: 0000-0001-7514-156X AD - Kaplan Medical Center, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 GR - Novo Nordisk/ PT - Journal Article PT - Randomized Controlled Trial PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *COVID-19/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Pandemics MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - SARS-CoV-2 MH - Semaglutide PMC - PMC13518088 OTO - NOTNLM OT - CKD OT - clinical trial OT - diabetic kidney disease OT - pneumonia OT - type 2 diabetes COIS- B.R. reports receiving honoraria for CME presentations from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim and Novartis; and has served on advisory boards for Astellas, AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk. K.W.M. reports receiving grants from AHA, Apple, Bayer, California Institute Regenerative Medicine (CIRM), CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior and Sanifit; consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel and Theravance; and equity in Human, Medeloop, Precordior and Regencor. J.F.E.M. reports receiving grants from Bayer and Novo Nordisk; consulting fees from Bayer and Novo Nordisk; honoraria from AstraZeneca, Bayer, Novartis, UpToDate Inc. and Novo Nordisk; and has participated on a data safety monitoring board for Cytel, Icon, Iqvia, Parexel, WCG and Sanofi; as well as having a leadership role in the KDIGO (Kidney Disease: Improving Global Outcomes) group. R.E.P. reports receiving speaker fees from Eli Lilly, Lilly USA and Novo Nordisk; consulting fees from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Eli Lilly, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA), Intas Pharmaceuticals, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompe, Eli Lilly, Endogenex, Fractyl, Novo Nordisk and Sanofi. All grants are directed to R.E.P.'s institution. Through 31 December 2023, payment for R.E.P.'s consultant and speaker services was made directly to his employer, AdventHealth, a nonprofit entity; as of 1 January 2024, payment is directed to R.E.P. personally. P.R. reports receiving grants from AstraZeneca, Bayer and Novo Nordisk; honoraria to the Steno Diabetes Centre Copenhagen from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Merck, Mundipharma, Novo Nordisk and Sanofi; and consulting fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma and Sanofi. G.C. reports receiving speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk and Sanofi. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568 and OT2OD032581, and CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Bayer, the Doris Duke Foundation and Travere, and outside of the submitted work. She reports consultancy fees from Boehringer Ingelheim, Eli Lilly and Novo Nordisk; and speaker fees from Novo Nordisk. N.B., O.K.J. and M.C.T. are employees of and shareholders in Novo Nordisk. H.B.-T. was an employee of Novo Nordisk until July 2025, and is a current shareholder of Novo Nordisk. EDAT- 2026/02/23 13:05 MHDA- 2026/08/27 05:35 PMCR- 2026/02/23 CRDT- 2026/02/23 08:42 PHST- 2025/11/06 00:00 [received] PHST- 2026/02/04 00:00 [accepted] PHST- 2026/08/27 05:35 [medline] PHST- 2026/02/23 13:05 [pubmed] PHST- 2026/02/23 08:42 [entrez] PHST- 2026/02/23 00:00 [pmc-release] AID - 8494850 [pii] AID - gfag036 [pii] AID - 10.1093/ndt/gfag036 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Aug 27;41(9):1696-1708. doi: 10.1093/ndt/gfag036. PMID- 41725422 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Flexible dose of semaglutide reduces early discontinuation while maintaining comparable outcomes in obese patients: FLEX-SEMA 2.4 mg, an Italian real-world study. PG - 3623-3631 LID - 10.1111/dom.70538 [doi] AB - AIMS: To evaluate real-world clinical use of semaglutide in obese patients, focusing on titration, tolerability and short-term efficacy. MATERIALS AND METHODS: This retrospective study included obese patients treated with the weekly injectable semaglutide. Data on body weight, waist circumference, lipid profile, doses, reasons for maintenance, adverse events, and discontinuations were collected at 3 and 6 months. RESULTS: A total of 111 patients were included (80% women; mean age 51.12; median body mass index (BMI) 35.56 kg/m(2); median body weight 97.00 kg). About 81.1% of patients initiated therapy at 0.25 mg, while 72.1% increased to 1 mg after 3 months. By 6 months, 2% remained on 0.5 mg, 40% on 1 mg, and 26% on 2.4 mg. The main reasons for maintaining the dose were satisfaction with the outcomes, followed by cost and adverse events. Significant reductions in weight, BMI, waist circumference and waist-to-height ratio were observed at both time points, with greater improvements seen in patients with a baseline BMI of >/=35. Weight loss of >/=5%, >/=10%, >/=15% and >/=20% was achieved by 23.5%, 34.6%, 30.8% and 11.1% of patients, respectively. There were no differences by sex, previous treatment or final dose. Adverse events occurred in 56.8% of patients at 3 months, leading to discontinuation in three patients. This percentage halved by 6 months (a 32.6% rate), with two cases leading to discontinuation. The rate of early discontinuation was 6.3% at 3 months, rising to 10.5% at 6 months due to cost, adverse events, or inefficacy. CONCLUSION: This real-world analysis provides valuable insights into the use of semaglutide in routine clinical practice, confirming a favourable efficacy profile with flexible dosing patterns. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Pampanelli, Simone AU - Pampanelli S AUID- ORCID: 0000-0003-0255-4210 AD - SS Clinical Nutrition and Dietetics Hospital Santa Maria Novella, Perugia, Italy. FAU - Terzoni, Stefano AU - Terzoni S AD - Department of Biomedical Sciences for Health, University of Study of Milano, Milan, Italy. FAU - Pantanetti, Paola AU - Pantanetti P AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Di Loreto, Chiara AU - Di Loreto C AD - USL Umbria 1, Perugia, Italy. FAU - Mazzieri, Alessio AU - Mazzieri A AD - USL Umbria 1, Perugia, Italy. FAU - Cangelosi, Giovanni AU - Cangelosi G AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Alberti, Sara AU - Alberti S AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Badiali, Cristina AU - Badiali C AD - UOSD Hospital Clinical Nutrition San Donato, Arezzo, Italy. FAU - Grandone, Ilenia AU - Grandone I AD - SC University Department of Andrology and Endocrinology Metabolic Diseases, Terni, Italy. FAU - Migliarelli, Sara AU - Migliarelli S AD - Unveristy of Perugia, Perugia, Italy. FAU - Castagna, Maria Grazia AU - Castagna MG AD - UOC Endocrinology, Siena Hospital, Siena, Italy. FAU - Cerrai Ceroni, Mariaclaudia AU - Cerrai Ceroni M AD - UOC Endocrinology, Siena Hospital, Siena, Italy. FAU - Benenati, Nicoletta AU - Benenati N AD - UOC Endocrinology, Siena Hospital, Siena, Italy. LA - eng PT - Journal Article DEP - 20260223 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Obesity/drug therapy MH - Retrospective Studies MH - Middle Aged MH - Italy/epidemiology MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects MH - Body Mass Index MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Drug Administration Schedule MH - Waist Circumference/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications PMC - PMC13071210 OTO - NOTNLM OT - obesity care OT - real-world evidence OT - semaglutide OT - weight management COIS- The authors have no conflicts of interest to declare. EDAT- 2026/02/23 06:27 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/02/23 04:03 PHST- 2026/01/22 00:00 [revised] PHST- 2025/12/02 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/23 06:27 [pubmed] PHST- 2026/02/23 04:03 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70538 [pii] AID - 10.1111/dom.70538 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3623-3631. doi: 10.1111/dom.70538. Epub 2026 Feb 23. PMID- 41725345 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Comparative effectiveness of combination therapy with SGLT-2 inhibitors and GLP-1 RAs compared with SGLT-2 inhibitors in individuals with type 2 diabetes: A prevalent new-user cohort study. PG - 3273-3284 LID - 10.1111/dom.70523 [doi] AB - AIMS: To evaluate the effectiveness of combination therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared with continued SGLT-2 inhibitor therapy in routine practice among individuals with type 2 diabetes. MATERIALS AND METHODS: We used nationwide BARMER health claims data and implemented a prevalent new-user design. Individuals initiating a GLP-1 RA, either simultaneously with SGLT-2 inhibitors or during ongoing SGLT-2 inhibitor exposure, were matched to SGLT-2 inhibitor continuers using hybrid exposure sets and time-conditional propensity scores. The study cohort included individuals enrolled between 2013 and 2023, with possible follow-up including 2024. The primary outcome was all-cause mortality. Secondary outcomes included a modified cardiovascular composite (all-cause mortality, myocardial infarction, stroke), heart failure, nephropathy, and renal failure. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 21 664 matched pairs with a median follow-up of 1.3 years, combination therapy was associated with a 29% lower hazard of all-cause mortality (HR 0.71, 95% CI 0.63-0.80), consistent across subgroups and sensitivity analyses. Hazard reductions were also observed for the modified cardiovascular composite (HR 0.81, 95% CI 0.74-0.88) and heart failure (HR 0.78, 95% CI 0.68-0.89). CONCLUSIONS: In this large real-world cohort, combination therapy with SGLT-2 inhibitors and GLP-1 RAs was associated with a lower hazard of all-cause mortality, while most secondary cardiorenal outcomes showed generally favourable but imprecise estimates. These findings suggest that sustained concurrent use of both drug classes may offer meaningful clinical benefits in routine practice, although residual confounding cannot be fully excluded. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Maier, Gregor A AU - Maier GA AUID- ORCID: 0009-0000-4528-9475 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Hennig, Beata AU - Hennig B AD - Department of Medicine and Health Services Research, BARMER Health Insurance, Wuppertal, Germany. FAU - Rathmann, Wolfgang AU - Rathmann W AUID- ORCID: 0000-0001-7804-1740 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. FAU - Kuss, Oliver AU - Kuss O AUID- ORCID: 0000-0003-3301-5869 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. AD - German Center for Diabetes Research, Munchen-Neuherberg, Germany. AD - Centre for Health and Society, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University, Dusseldorf, Germany. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260222 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - Drug Therapy, Combination MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies MH - Treatment Outcome PMC - PMC12992157 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - observational study OT - pharmacoepidemiology OT - real-world evidence OT - type 2 diabetes COIS- W.R. reports the receipt of consulting fees for attending educational sessions by Novo Nordisk outside of the topic of the current work. O.K. received honoraria for biostatistical education from Berlin-Chemie. G.M. and B.H. have nothing to disclose. EDAT- 2026/02/23 06:27 MHDA- 2026/03/17 06:48 PMCR- 2026/03/17 CRDT- 2026/02/23 03:02 PHST- 2026/01/21 00:00 [revised] PHST- 2025/11/25 00:00 [received] PHST- 2026/01/22 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/02/23 06:27 [pubmed] PHST- 2026/02/23 03:02 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70523 [pii] AID - 10.1111/dom.70523 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3273-3284. doi: 10.1111/dom.70523. Epub 2026 Feb 22. PMID- 41722869 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260730 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 234 DP - 2026 Apr TI - Glucagon-like peptide-1 receptor agonists and the risk of obesity-related cancers: a systematic review and meta-analysis. PG - 113158 LID - S0168-8227(26)00077-X [pii] LID - 10.1016/j.diabres.2026.113158 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are increasing and are established risk factors for malignancy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for T2DM and obesity, but their association with cancer risk remains uncertain. We assessed the association between GLP-1RA use and obesity-related cancers. METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 20 November 2025. Observational studies and randomized controlled trials of adults (>/=18 years) with T2DM and/or obesity reporting cancer risk after GLP-1RA or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor co-agonist use were included. Obesity-related cancers comprised uterine, esophageal, thyroid, gastric, colorectal, liver, gallbladder, pancreatic, breast, ovarian, kidney cancers, cholangiocarcinoma, meningioma, and multiple myeloma. FINDINGS: Twenty-four studies involving 3,960,974 patients were included. GLP-1RA use was associated with a significantly lower overall risk of obesity-related cancers within ten years (RR 0.70, 95% CI 0.54-0.89). Reduced risks were observed for hepatocellular carcinoma, colorectal, pancreatic, endometrial, esophageal, gallbladder, ovarian cancers, and multiple myeloma, with no significant association for thyroid cancer. INTERPRETATION: GLP-1RA use is associated with a lower risk of several obesity-related cancers. Prospective studies are required to validate these findings and clarify underlying mechanisms. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Ateiwi, Yousef A AU - Ateiwi YA AD - School of Medicine, University of Jordan, Amman, Jordan. FAU - Mahmood, Rahil AU - Mahmood R AD - School of Medicine, Trinity College Dublin, Dublin, Ireland. FAU - Wong, Hon Jen AU - Wong HJ AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Low, Chen Ee AU - Low CE AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Yau, Chun En AU - Yau CE AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Lee, Ainsley Ryan Yan Bin AU - Lee ARYB AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Hospital, Singapore. FAU - Eng, Pei Chia AU - Eng PC AD - Division of Endocrinology, Department of Medicine, National University Hospital, Singapore. FAU - Lee, Matilda AU - Lee M AD - Department of Haematology-Oncology, National University Cancer Institute (NCIS), Singapore. FAU - Chan, Mark Y AU - Chan MY AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore. FAU - Sia, Ching-Hui AU - Sia CH AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, Singapore. Electronic address: ching_hui_sia@nuhs.edu.sg. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260219 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications/drug therapy MH - *Neoplasms/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Cancer risk OT - Glucagon-like peptide-1 receptor agonists OT - Hepatocellular carcinoma OT - Obesity-related cancers OT - Pancreatic cancer OT - Thyroid cancer OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Ching Hui Sia has received speaker fees from Amgen, Novartis, Bristol Myers Squibb, and Pfizer; consulting fees from Boehringer Ingelheim; and travel grants from Amgen and Pfizer. All other authors declare that they have no competing interests]. EDAT- 2026/02/22 05:35 MHDA- 2026/03/12 07:04 CRDT- 2026/02/21 19:31 PHST- 2025/12/18 00:00 [received] PHST- 2026/02/11 00:00 [revised] PHST- 2026/02/11 00:00 [accepted] PHST- 2026/03/12 07:04 [medline] PHST- 2026/02/22 05:35 [pubmed] PHST- 2026/02/21 19:31 [entrez] AID - S0168-8227(26)00077-X [pii] AID - 10.1016/j.diabres.2026.113158 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Apr;234:113158. doi: 10.1016/j.diabres.2026.113158. Epub 2026 Feb 19. PMID- 41722857 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260807 IS - 1916-7075 (Electronic) IS - 0828-282X (Print) IS - 0828-282X (Linking) VI - 42 IP - 8 DP - 2026 Aug TI - Clinical Knowns and Mechanistic Unknowns: Cardioprotection and Inflammation Modulation of GLP-1 Receptor Agonists and SGLT2 Inhibitors. PG - 1766-1780 LID - S0828-282X(26)00141-8 [pii] LID - 10.1016/j.cjca.2026.02.024 [doi] AB - Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. In recent years, clinical trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated positive results for several cardiovascular endpoints. In addition to the positive clinical endpoint-focused trials, several mechanistic and clinical studies have outlined the inflammation-modulating properties of SGLT2 inhibitors and GLP-1RAs. While inflammation play a key role in development of cardiovascular disease and ultimate end-organ damages, there are limited data on the precise ways in which these therapies alter immune responses. In this review we summarize the known and putative immune/inflammatory-modulating effects of SGLT2 inhibitors and GLP-1RAs, as well as the evidence for cardiovascular benefit from outcomes trials currently available. CI - Copyright (c) 2026 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. FAU - Kim, Ellis Y AU - Kim EY AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Feinstein, Matthew J AU - Feinstein MJ AD - Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. Electronic address: mfeinst@iu.edu. LA - eng GR - R01 HL175893/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Review DEP - 20260219 PL - England TA - Can J Cardiol JT - The Canadian journal of cardiology JID - 8510280 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Inflammation MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications PMC - PMC12971158 MID - NIHMS2150450 OTO - NOTNLM OT - GLP-1RAs OT - SGLT2 inhibitors OT - heart failure OT - inflammation COIS- Disclosures / Declarations of Interest: M.J.F: Gilead (Consultant / advisory board), Novo Nordisk (Consultant / advisory board) EDAT- 2026/02/22 05:35 MHDA- 2026/08/08 00:37 PMCR- 2027/02/19 CRDT- 2026/02/21 19:31 PHST- 2025/12/01 00:00 [received] PHST- 2026/02/05 00:00 [revised] PHST- 2026/02/13 00:00 [accepted] PHST- 2026/08/08 00:37 [medline] PHST- 2026/02/22 05:35 [pubmed] PHST- 2026/02/21 19:31 [entrez] PHST- 2027/02/19 00:00 [pmc-release] AID - S0828-282X(26)00141-8 [pii] AID - 10.1016/j.cjca.2026.02.024 [doi] PST - ppublish SO - Can J Cardiol. 2026 Aug;42(8):1766-1780. doi: 10.1016/j.cjca.2026.02.024. Epub 2026 Feb 19. PMID- 41718943 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 43 IP - 4 DP - 2026 Apr TI - Flash Glucose Monitoring System Enhances Glycemic Control and Metabolic Health in People with Type 2 Diabetes on GLP-1RA-Based Therapy: Real-World Evidence. PG - 1671-1688 LID - 10.1007/s12325-026-03495-6 [doi] AB - INTRODUCTION: To evaluate the effect of adding flash glucose monitoring (Flash GM) to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy on glycemic and metabolic outcomes in people with type 2 diabetes (PwT2D) who failed to achieve target HbA1c levels. METHODS: A prospective cohort study enrolled 264 PwT2D who were on stable GLP-1RA therapy and had failed to reach an HbA1c target of /=1-year, were identified using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, A Cegedim Database. The absolute 1-year risk of discontinuation was estimated using the Aalen-Johansen estimator, while multivariable cause-specific Cox models assessed associations with patient characteristics. Dosing trajectories were characterised across individual prescriptions during the first therapy year. RESULTS: Among 8200 GLP-1RA initiators (46.5% dulaglutide, 38.7% semaglutide), the 1-year discontinuation risk was 41.1% (95% CI 40.1-42.2), higher among those without obesity (BMI <30 kg/m(2): 49.2%, 46.5-52.0) versus with BMI >/=30 kg/m(2) (BMI 30-<35/>/=35 kg/m(2): 40.4%/37.2%, 38.4-42.4/35.4-39.1). Discontinuation was lower with dulaglutide (36.9%, 35.4-38.4) than with subcutaneous/oral semaglutide (46.4%/55.8%, 44.4-48.4/52.3-59.4). Only 58% of subcutaneous/oral semaglutide initiators reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses. At prescription 10, most common doses were 0.5/1 mg subcutaneous semaglutide (44.0%/48.6%), 7/14 mg oral semaglutide (50.2%/36.6%), and 0.75/1.5/3 mg dulaglutide (20.4%/71.5%/6.7%). Faster dose escalation occurred with higher BMI and subcutaneous semaglutide (1 mg at prescription 5: 20.8%/25.9%/33.2% with BMI <30/30-<35/>/=35 kg/m(2)). Additional analyses (e.g., by CVD history) revealed no further heterogeneity. CONCLUSIONS: In UK primary care, GLP-1RA persistence was suboptimal and dose escalation was frequently delayed across all patient stratifications, including individuals with established CVD. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ulrich, Franziska S AU - Ulrich FS AUID- ORCID: 0009-0005-2278-7400 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. FAU - Napoli, Nicola AU - Napoli N AUID- ORCID: 0000-0002-3091-8205 AD - Unit of Endocrinology and Diabetes, Campus, Bio-Medico University of Rome, Rome, Italy. AD - Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus, Bio-Medico University of Rome, Rome, Italy. AD - Division of Bone and Mineral Diseases, Washington University, St Louis, Missouri, USA. FAU - Nielsen, Morten Frost AU - Nielsen MF AUID- ORCID: 0000-0002-5608-1589 AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark. FAU - Burden, Andrea M AU - Burden AM AUID- ORCID: 0000-0001-7082-8530 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. AD - Division of Clinical Immunology and Rheumatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng GR - 24B110/Novartis Foundation for Medical-Biological Research/ PT - Journal Article DEP - 20260217 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United Kingdom/epidemiology MH - Semaglutide MH - *Obesity/complications/epidemiology MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/complications MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments/administration & dosage/therapeutic use MH - *Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Cohort Studies MH - Adult MH - Dose-Response Relationship, Drug PMC - PMC12992168 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - United Kingdom OT - cardiovascular disease OT - dose titration OT - drug utilisation OT - glucose-lowering therapy OT - obesity OT - primary care OT - real-world evidence OT - treatment discontinuation COIS- The authors declare no conflicts of interest. EDAT- 2026/02/18 10:06 MHDA- 2026/03/17 06:47 PMCR- 2026/03/17 CRDT- 2026/02/18 00:53 PHST- 2026/01/22 00:00 [revised] PHST- 2025/11/24 00:00 [received] PHST- 2026/01/24 00:00 [accepted] PHST- 2026/03/17 06:47 [medline] PHST- 2026/02/18 10:06 [pubmed] PHST- 2026/02/18 00:53 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70535 [pii] AID - 10.1111/dom.70535 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3386-3395. doi: 10.1111/dom.70535. Epub 2026 Feb 17. PMID- 41703411 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260727 IS - 1558-2035 (Electronic) IS - 1558-2027 (Linking) VI - 27 IP - 2 DP - 2026 Feb 1 TI - Use of semaglutide after acute coronary syndrome: an exploratory retrospective study. PG - 144-150 LID - 10.2459/JCM.0000000000001837 [doi] AB - AIMS: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated cardiovascular benefit in patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic disease. Its role in the immediate postacute coronary syndrome (ACS) setting, however, remains unexplored. This study evaluated the early real-world use of semaglutide prescribed at hospital discharge after ACS. METHODS: We conducted a retrospective, multicenter observational study of adults with T2DM hospitalized for ACS between January 2022 and December 2024 and discharged with a prescription for semaglutide. Baseline demographics, therapies, and ACS features were collected together with follow-up data on treatment persistence, reasons for discontinuation, adverse events, metabolic parameters, and cardiovascular outcomes. RESULTS: A total of 60 patients (mean age 61.1 +/- 10.8 years, 73% male) were included. At discharge, all received semaglutide (83.3% injectable, 16.7% oral) at the lowest dose. At the first follow-up (108 +/- 39 days), 81% remained on therapy; discontinuations occurred mainly for gastrointestinal intolerance (15%). Body weight decreased by 4.7 +/- 1.6 kg, BMI decreased by 1.7 +/- 0.6 kg/m2, and HbA1c improved from 64.3 +/- 18.2 to 49.6 +/- 10.4 mmol/mol. At the second follow-up (278 +/- 60 days, n = 39), 97.4% were still on semaglutide. Additional weight loss (-2.6 +/- 3.8 kg) and further HbA1c reduction (40.5 +/- 18.6 mmol/mol) were observed. No cardiovascular events, renal decline, or pancreatic events were reported. CONCLUSIONS: In this exploratory real-world cohort, initiating semaglutide at hospital discharge after ACS was feasible, well tolerated, and associated with high persistence and early cardiometabolic improvements. CI - Copyright (c) 2026 Italian Federation of Cardiology - I.F.C. All rights reserved. FAU - Biasin, Marco AU - Biasin M AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Stratinaki, Maria AU - Stratinaki M AD - Venizeleio General Hospital, Heraklion, Greece. FAU - Cordioli, Nicolo AU - Cordioli N AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Armani, Ilaria AU - Armani I AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - De Giovanni, Sara AU - De Giovanni S AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Aletras, George AU - Aletras G AD - Venizeleio General Hospital, Heraklion, Greece. FAU - Betta, Davide AU - Betta D AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Callegarin, Luca AU - Callegarin L AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Gambaro, Alessia AU - Gambaro A AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Morani, Giovanni AU - Morani G AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260119 PL - United States TA - J Cardiovasc Med (Hagerstown) JT - Journal of cardiovascular medicine (Hagerstown, Md.) JID - 101259752 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Acute Coronary Syndrome/drug therapy/diagnosis MH - Retrospective Studies MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Aged MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - Blood Glucose/drug effects/metabolism OTO - NOTNLM OT - acute coronary syndrome OT - cardiometabolic risk OT - glucagon-like peptide-1 receptor agonists OT - secondary prevention OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2026/02/18 00:49 MHDA- 2026/02/18 00:50 CRDT- 2026/02/17 23:36 PHST- 2025/09/21 00:00 [received] PHST- 2025/12/19 00:00 [accepted] PHST- 2026/02/18 00:50 [medline] PHST- 2026/02/18 00:49 [pubmed] PHST- 2026/02/17 23:36 [entrez] AID - 01244665-202602000-00009 [pii] AID - 10.2459/JCM.0000000000001837 [doi] PST - ppublish SO - J Cardiovasc Med (Hagerstown). 2026 Feb 1;27(2):144-150. doi: 10.2459/JCM.0000000000001837. Epub 2026 Jan 19. PMID- 41701611 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 49 IP - 5 DP - 2026 May 1 TI - Glucagon-Like Peptide 1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients With Type 2 Diabetes. PG - 763-771 LID - 10.2337/dc25-2577 [doi] AB - OBJECTIVE: To estimate the effect of initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase 4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) among adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: This active-comparator, new-user cohort emulated a pragmatic target trial using the U.K. Clinical Practice Research Datalink. Patients aged >/=18 years with a physician diagnosis of type 2 diabetes who newly initiated a GLP-1 RA or a DPP-4 inhibitor were included. DPP-4 inhibitors were selected as the comparator because they may be used as second-line treatment, like GLP-1 RAs, and have no established association with NAION. We estimated risks, risk differences (RDs), and risk ratios (RRs) of incident NAION, adjusted using propensity-score fine-stratification weighting. RESULTS: At 1 year, there were 14 NAION events among 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 among 416,369 DPP-4 inhibitor initiators (7.2 per 100,000). GLP-1 RAs were associated with an increased risk of NAION compared with DPP-4 inhibitors (RR 2.56; 95% CI 1.44-4.86; RD 11.3 per 100,000). The risk of NAION was higher during the first 6 months of use, diminishing with longer duration of use, and was higher in patients aged <50 years, men, ever-smokers, and those with >/=1% hemoglobin A1c reduction. CONCLUSIONS: GLP-1 RAs were associated with an increased 1-year risk of NAION compared with DPP-4 inhibitors among adults with type 2 diabetes, particularly in younger patients, men, ever-smokers, and patients with a marked hemoglobin A1c reduction. CI - (c) 2026 by the American Diabetes Association. FAU - Noh, Yunha AU - Noh Y AD - College of Pharmacy, Chonnam National University, Gwangju, South Korea. FAU - Yin, Hui AU - Yin H AD - Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. FAU - Ben Ghezala, Ines AU - Ben Ghezala I AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Department of Ophthalmology, Dijon University Hospital, Dijon, France. AD - Clinical Investigation Center 1432, Clinical Epidemiology/Clinical Trials Unit, INSERM, Dijon University Hospital, Dijon, France. FAU - Yu, Oriana H Y AU - Yu OHY AD - Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, Canada. FAU - Suissa, Samy AU - Suissa S AD - Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. FAU - Azoulay, Laurent AU - Azoulay L AUID- ORCID: 0000-0001-5162-3556 AD - Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada. LA - eng GR - CIHR/Canada GR - Canadian Foundation for Innovation/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/etiology MH - Female MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Adult MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor EDAT- 2026/02/17 18:52 MHDA- 2026/04/21 17:51 CRDT- 2026/02/17 12:52 PHST- 2025/10/21 00:00 [received] PHST- 2026/01/26 00:00 [accepted] PHST- 2026/04/21 17:51 [medline] PHST- 2026/02/17 18:52 [pubmed] PHST- 2026/02/17 12:52 [entrez] AID - 164499 [pii] AID - 10.2337/dc25-2577 [doi] PST - ppublish SO - Diabetes Care. 2026 May 1;49(5):763-771. doi: 10.2337/dc25-2577. PMID- 41699622 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 27 IP - 1 DP - 2026 Feb 16 TI - GLP-1RAs: antidiabetic drug crossover-new hope for chronic inflammatory airway diseases. LID - 10.1186/s12931-026-03569-7 [doi] LID - 144 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent a novel class of antidiabetic agents recognized not only for their efficacy in glycemic control and weight management but also for their distinctive cardiovascular benefits. Type 2 diabetes mellitus, a prevalent chronic metabolic disorder worldwide, frequently coexists with chronic inflammatory airway diseases (CIADs), including chronic obstructive pulmonary disease (COPD), asthma, and obstructive sleep apnea (OSA). In recent years, growing attention has been directed toward the potential role of GLP-1RAs in the context of CIADs. This review examines the mechanistic underpinnings of GLP-1RAs in CIADs and evaluates their therapeutic potential in COPD, asthma, and OSA. Clinical evidence indicates that GLP-1RAs can reduce the risk of acute exacerbations in COPD, attenuate obesity-associated asthma exacerbations, and improve respiratory outcomes in patients with OSA. Although certain findings remain inconsistent and prospective clinical studies are still limited, the therapeutic promise of GLP-1RAs in CIADs has been preliminarily supported. Further large-scale randomized controlled trials are warranted to clarify their precise effects in chronic inflammatory airway diseases and to assess long-term efficacy and safety. CI - (c) 2026. The Author(s). FAU - Chen, Yinan AU - Chen Y AD - Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China. FAU - Shen, Yili AU - Shen Y AD - Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China. shenxisa@126.com. AD - Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang, Chinese Medical University, Huzhou, Zhejiang, China. shenxisa@126.com. FAU - Shen, Hui AU - Shen H AD - Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China. 37696833@qq.com. AD - Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang, Chinese Medical University, Huzhou, Zhejiang, China. 37696833@qq.com. FAU - Liu, Zhicong AU - Liu Z AD - Department of Respiratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China. liuzhicongcong@163.com. AD - Department of Respiratory Medicine, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang, Chinese Medical University, Huzhou, Zhejiang, China. liuzhicongcong@163.com. LA - eng GR - 2023GY15;/Yili Shen/ PT - Journal Article PT - Review DEP - 20260216 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism/epidemiology MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/metabolism MH - *Sleep Apnea, Obstructive/drug therapy/epidemiology/metabolism MH - *Asthma/drug therapy/metabolism/epidemiology PMC - PMC13014972 OTO - NOTNLM OT - Asthma OT - Chronic inflammatory airway diseases OT - Chronic obstructive pulmonary disease OT - Glucagon-like peptide receptor agonists OT - Mechanism of action OT - Obstructive sleep apnea COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/02/17 06:31 MHDA- 2026/03/26 07:09 PMCR- 2026/02/16 CRDT- 2026/02/17 00:13 PHST- 2025/07/08 00:00 [received] PHST- 2026/02/05 00:00 [accepted] PHST- 2026/03/26 07:09 [medline] PHST- 2026/02/17 06:31 [pubmed] PHST- 2026/02/17 00:13 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - 10.1186/s12931-026-03569-7 [pii] AID - 3569 [pii] AID - 10.1186/s12931-026-03569-7 [doi] PST - epublish SO - Respir Res. 2026 Feb 16;27(1):144. doi: 10.1186/s12931-026-03569-7. PMID- 41698477 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260722 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 52 IP - 2 DP - 2026 Mar TI - Reassessing the role of GLP-1 receptor agonists in colorectal cancer Care. PG - 101742 LID - S1262-3636(26)00021-2 [pii] LID - 10.1016/j.diabet.2026.101742 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in type 2 diabetes, yet their management after colorectal cancer diagnosis remains uncertain. A recent population-based cohort study reported lower mortality and fewer metastatic events among GLP-1 RA users than among patients receiving other glucose-lowering therapies. However, causal inference is limited by potential immortal time bias from the exposure definition, incomplete reporting of key prognostic and treatment factors (stage, surgery, systemic therapy, performance status), and unclear cohort entry and follow-up windows. In addition, reliance on routine administrative codes may misclassify outcomes. Time-varying exposure models, active-comparator new-user or landmark designs, and registry linkage/validation would strengthen the evidence. CI - Copyright (c) 2026. Published by Elsevier Masson SAS. FAU - Wang, Baodong AU - Wang B AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China. FAU - Huang, Jiayuan AU - Huang J AD - Hangzhou Integrative Medicine Hospital Affiliated to Zhejiang Chinese Medical University (Hangzhou Red Cross Hospital), Hangzhou, Zhejiang, China. FAU - Chen, Zhiyun AU - Chen Z AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China. Electronic address: jcyjzxchen@163.com. LA - eng PT - Letter DEP - 20260214 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Colorectal Neoplasms/drug therapy/complications/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - colorectal cancer OT - immortal time bias OT - residual confounding OT - type 2 diabetes COIS- Declaration of competing interest All authors have contributed substantially to its conception and drafting and have approved the final version. There are no conflicts of interest or financial disclosures related to this submission. EDAT- 2026/02/17 00:53 MHDA- 2026/03/23 06:31 CRDT- 2026/02/16 19:25 PHST- 2026/02/06 00:00 [received] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/03/23 06:31 [medline] PHST- 2026/02/17 00:53 [pubmed] PHST- 2026/02/16 19:25 [entrez] AID - S1262-3636(26)00021-2 [pii] AID - 10.1016/j.diabet.2026.101742 [doi] PST - ppublish SO - Diabetes Metab. 2026 Mar;52(2):101742. doi: 10.1016/j.diabet.2026.101742. Epub 2026 Feb 14. PMID- 41697744 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 136 IP - 4 DP - 2026 Feb 16 TI - GLP-1 and the cardiovascular system. LID - 10.1172/JCI194748 [doi] LID - e194748 AB - The incretin hormone glucagon-like peptide-1 (GLP-1) exerts potent effects on glucose metabolism, prompting the development of therapeutic strategies that enhance activity of the GLP-1 receptor (GLP-1R) pathway. Inhibitors of dipeptidyl peptidase 4 (DPP-4) prolong the half-life of endogenous GLP-1 and typically achieve reductions in HbA1c of 0.5%-0.8%. However, large-scale cardiovascular (CV) outcomes trials (CVOTs) with DPP-4 inhibitors demonstrated CV safety but did not show a reduction in CV events. A second incretin-based therapeutic approach was the development of GLP-1R agonists (GLP-1RAs). Various GLP-1RAs, including liraglutide, semaglutide, and dulaglutide, demonstrated a reduction in CV outcomes in large CVOTs. Initially, these medications were only available as injectable agents for subcutaneous administration, but recent technological advancements have enabled the development of orally available GLP-1RAs. A third incretin-based approach is tirzepatide, a dual agonist of GLP-1R and glucose-dependent insulinotropic polypeptide receptor (GIPR), which achieves greater HbA1c reduction and weight loss compared with GLP-1RAs alone. Ongoing large-scale CVOTs will determine its effects on hard cardiovascular endpoints. This Review summarizes the effects of GLP-1 and GLP-1RAs in the CV system as well as clinical data of GLP-1RAs in individuals with CV disease or high CV risk. FAU - Kahles, Florian AU - Kahles F AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Aachen, Germany. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Department of Internal Medicine IV, Diabetology, Endocrinology and Nephrology, Eberhard-Karls University Tubingen, Tubingen, Germany. AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, Tubingen, Germany. AD - School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine, Kings College London, London, United Kingdom. FAU - Marx, Nikolaus AU - Marx N AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Aachen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20260216 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (GLP1R protein, human) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/metabolism MH - *Cardiovascular Diseases/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Tirzepatide MH - *Cardiovascular System/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC12904707 COIS- Conflict of interest: NM has given lectures for Bayer, Boehringer Ingelheim, Sanofi- EDAT- 2026/02/16 12:32 MHDA- 2026/02/16 18:34 PMCR- 2026/02/16 CRDT- 2026/02/16 11:52 PHST- 2026/02/16 18:34 [medline] PHST- 2026/02/16 12:32 [pubmed] PHST- 2026/02/16 11:52 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - 194748 [pii] AID - 10.1172/JCI194748 [doi] PST - epublish SO - J Clin Invest. 2026 Feb 16;136(4):e194748. doi: 10.1172/JCI194748. eCollection 2026 Feb 16. PMID- 41697736 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 136 IP - 4 DP - 2026 Feb 16 TI - The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications. LID - 10.1172/JCI194740 [doi] LID - e194740 AB - GLP-1 receptor agonist (GLP-1RA) medications have transformed the treatment of type 2 diabetes (T2D) and obesity, with robust evidence for cardiovascular and renal benefits. Nevertheless, GLP-1RA therapy is associated with a pattern of adverse events affecting their safety and tolerability. Here, we delineate mechanisms potentially leading to adverse responses to GLP-1RAs, describe the impact of side effects on treatment persistence, discuss potential mitigation strategies, and identify areas requiring further studies. Concerns that GLP-1RAs raise the risk for acute pancreatitis and pancreatic cancer have been dispelled by long-term clinical trials. However, GLP-1RAs may confer an increased risk for thyroid cancer. Sight-threatening eye complications resulting from rapid reductions in glycemia may be avoided by retinal screening and ophthalmologic treatment before GLP-1RA initiation. The slowing of gastric emptying with GLP-1RA treatment increases the propensity for retained gastric contents, which could increase the risk of aspiration during upper gastrointestinal endoscopy or general anesthesia. These risks may, however, be elevated in individuals with long-standing T2D even in the absence of GLP-1RA treatment. Improved pharmacovigilance and a more standardized, quantitative assessment of adverse events in clinical trials, particularly in the assessment of gastrointestinal symptoms, would facilitate definition of the benefit-risk relationship for individual medications and indications. FAU - Jalleh, Ryan J AU - Jalleh RJ AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. FAU - Talley, Nicholas J AU - Talley NJ AD - School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia. FAU - Horowitz, Michael AU - Horowitz M AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. LA - eng PT - Journal Article PT - Review DEP - 20260216 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Pancreatitis/chemically induced MH - Glucagon-Like Peptide-1 Receptor MH - Animals MH - Pancreatic Neoplasms/chemically induced MH - Gastric Emptying/drug effects PMC - PMC12904723 COIS- Conflict of interest: RJJ has received grant support from the Royal Australasian College of Physicians and Australian Diabetes Society. NJT has consulted with Brown University and Agency for Health Care Research and Quality (fiber and laxation), outside the submitted work. In addition, NJT reports the license Nepean Dyspepsia Index (NDI) 1998 (MAPI), Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo Clinic/Talley, and patents "Performance of a biomarker panel for irritable bowel syndrome" (Patent WO2012158831A1), "Diagnostic marker for functional gastrointestinal disorders" Australian Provisional (Patent Application 2021901692), "Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis" (US Patent Application No. 63/537,725), and "Compositions and methods for the treatment of oesophageal disorders" (Australian Provisional Patent ID 2025902002). EDAT- 2026/02/16 12:31 MHDA- 2026/02/16 18:34 PMCR- 2026/02/16 CRDT- 2026/02/16 11:52 PHST- 2026/02/16 18:34 [medline] PHST- 2026/02/16 12:31 [pubmed] PHST- 2026/02/16 11:52 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - 194740 [pii] AID - 10.1172/JCI194740 [doi] PST - epublish SO - J Clin Invest. 2026 Feb 16;136(4):e194740. doi: 10.1172/JCI194740. eCollection 2026 Feb 16. PMID- 41697578 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1708-0428 (Electronic) IS - 0960-8923 (Print) IS - 0960-8923 (Linking) VI - 36 IP - 3 DP - 2026 Mar TI - Efficacy of Metabolic and Bariatric Surgery Compared with GLP-1 Receptor Agonist Treatment in Preventing Mortality and Major Adverse Cardiac Events Among Individuals with Obesity and Type 2 Diabetes: A Systematic Review and Meta-analysis. PG - 1377-1388 LID - 10.1007/s11695-026-08508-5 [doi] AB - INTRODUCTION: Obesity and type 2 diabetes mellitus (T2DM) significantly increase cardiovascular morbidity and mortality worldwide. Metabolic and bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective interventions for T2DM and obesity, but comparative evidence on their long-term impact on major adverse cardiovascular events (MACE) and all-cause mortality is lacking. This systematic review and meta-analysis evaluated the efficacy of MBS versus GLP-1 RAs therapy in reducing these outcomes. METHODS: The review was registered in PROSPERO beforehand and carried out following the PRISMA framework. A comprehensive literature search identified randomized controlled trials (RCTs) and observational studies comparing MBS with GLP-1 RAs regimens in adults with obesity and T2DM. The primary outcomes were all-cause mortality and MACE. We used the Cochrane Risk of Bias 2.0 (ROB 2) tool and Newcastle-Ottawa Scale (NOS) to assess the quality of the study. Meta-analytic techniques were used to synthesize effect estimates. RESULTS: Pooled analysis of eligible studies suggested that MBS offered greater reductions in both MACE and all-cause mortality than GLP-1 RAs therapy. The relative risk reduction for MACE was approximately 52% in favor of MBS. Despite notable heterogeneity, sensitivity analyses confirmed result robustness. The overall certainty of evidence was moderate, reflecting variations in populations, interventions, and study designs. CONCLUSION: MBS offers significantly greater cardiovascular protection than GLP-1 RAs therapy in individual with obesity and T2DM, reducing MACE and all-cause mortality. GLP-1 RAs remains an important option, particularly for patients contraindicated for surgery or preferring pharmacotherapy. Further long-term comparative and cost effectiveness studies are needed to inform the clinical decisions. FAU - Chadwick, Joshua AU - Chadwick J AD - ICMR-National Institute of Epidemiology, Chennai, India. joshuachadwick89@gmail.com. FAU - Sivamani, Chandru AU - Sivamani C AD - ICMR-National Institute of Epidemiology, Chennai, India. FAU - Lakshmi, Suchitra AU - Lakshmi S AD - ICMR-National Institute of Epidemiology, Chennai, India. FAU - Baskaran, Vishali AU - Baskaran V AD - SRM Institute of Science and Technology, Chennai, India. FAU - N L, Swathi AU - N L S AD - Manipal College of Nursing, Manipal Academy of Higher Education, Manipal, Karnataka, India. FAU - Ayyasamy, Lavanya AU - Ayyasamy L AD - SRM Medical College Hospital and Research Centre, Chennai, India. FAU - Parasuraman, Ganeshkumar AU - Parasuraman G AD - ICMR-National Institute of Epidemiology, Chennai, India. FAU - Bagepally, Bhavani Shankara AU - Bagepally BS AD - ICMR-National Institute of Epidemiology, Chennai, India. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260216 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Bariatric Surgery MH - *Cardiovascular Diseases/prevention & control/mortality MH - *Diabetes Mellitus, Type 2/complications/drug therapy/therapy/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/surgery/therapy/mortality MH - Treatment Outcome PMC - PMC13038674 OTO - NOTNLM OT - All-cause mortality OT - Long-term CVD outcomes OT - MACE OT - Obesity OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/02/16 12:30 MHDA- 2026/06/28 00:36 PMCR- 2026/02/16 CRDT- 2026/02/16 11:31 PHST- 2025/08/28 00:00 [received] PHST- 2026/01/22 00:00 [accepted] PHST- 2025/12/29 00:00 [revised] PHST- 2026/06/28 00:36 [medline] PHST- 2026/02/16 12:30 [pubmed] PHST- 2026/02/16 11:31 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - 10.1007/s11695-026-08508-5 [pii] AID - 8508 [pii] AID - 10.1007/s11695-026-08508-5 [doi] PST - ppublish SO - Obes Surg. 2026 Mar;36(3):1377-1388. doi: 10.1007/s11695-026-08508-5. Epub 2026 Feb 16. PMID- 41697144 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260827 IS - 1460-2385 (Electronic) IS - 0931-0509 (Linking) VI - 41 IP - 9 DP - 2026 Aug 27 TI - GLP-1 receptor agonists reduce dementia and Alzheimer disease risk in diabetic patients with CKD. PG - 1673-1685 LID - 10.1093/ndt/gfag032 [doi] AB - BACKGROUND: Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia and Alzheimer's disease due to vascular dysfunction, insulin resistance and chronic inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown neuroprotective properties; however, their impact on dementia risk in diabetic patients with CKD remains uncertain. This study evaluated the association between GLP-1RA use and dementia risk in patients with CKD stage 3 or later, compared with dipeptidyl peptidase-4 inhibitors (DPP4is). METHODS: This retrospective cohort study analyzed data from the TriNetX global research network, comprising electronic medical records from 67 healthcare organizations in the US Collaborative Network. We identified patients with CKD stage 3 or later and T2DM who were newly prescribed GLP-1RAs or DPP4is between 1 January 2015 and 31 December 2020. Patients with prior GLP-1RAs or DPP4i use, a dementia diagnosis within 12 months before the index date or recent hospitalization were excluded. The primary outcome was the incidence of dementia, Alzheimer's disease, vascular dementia, frontotemporal dementia, Parkinson's disease, extrapyramidal and movement disorders, and dementia with Lewy bodies, assessed over a follow-up period ranging from 90 days to 5 years. Statistical analyses included Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: GLP-1RA use was associated with a significantly lower risk of dementia [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71-0.91, P = .001] and Alzheimer's disease (HR 0.76, 95% CI 0.59-0.98, P = .033) compared with DPP4i use. However, no significant differences were observed in vascular dementia, frontotemporal dementia, Parkinson's disease, extrapyramidal and movement disorders, or dementia with Lewy bodies. CONCLUSIONS: GLP-1RA therapy may reduce the risk of dementia and Alzheimer's disease in patients with CKD stage 3 or later, offering potential neuroprotective benefits beyond glycemic control. Research is needed to confirm these findings and optimize treatment strategies for this vulnerable population. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Lee, Wen-Teng AU - Lee WT AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. FAU - Wang, Jing-Tong AU - Wang JT AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. FAU - Tsai, Ming-Hsien AU - Tsai MH AUID- ORCID: 0000-0003-3561-4689 AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. AD - Department of Medicine, Fu-Jen Catholic University School of Medicine, Taipei, Taiwan, ROC. FAU - Fang, Yu-Wei AU - Fang YW AUID- ORCID: 0000-0002-1302-1885 AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. AD - Department of Medicine, Fu-Jen Catholic University School of Medicine, Taipei, Taiwan, ROC. LA - eng GR - 2025SKHADR009/Shin-Kong Wu Ho-Su Memorial Hospital/ PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Female MH - Male MH - *Alzheimer Disease/prevention & control/etiology/epidemiology MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - *Renal Insufficiency, Chronic/complications MH - *Dementia/prevention & control/etiology/epidemiology MH - Follow-Up Studies MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Prognosis MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Middle Aged MH - Aged, 80 and over OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonists OT - chronic kidney disease OT - dementia OT - type 2 diabetes EDAT- 2026/02/16 12:32 MHDA- 2026/08/27 05:35 CRDT- 2026/02/16 10:13 PHST- 2025/08/12 00:00 [received] PHST- 2026/01/26 00:00 [accepted] PHST- 2026/08/27 05:35 [medline] PHST- 2026/02/16 12:32 [pubmed] PHST- 2026/02/16 10:13 [entrez] AID - 8487645 [pii] AID - 10.1093/ndt/gfag032 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Aug 27;41(9):1673-1685. doi: 10.1093/ndt/gfag032. PMID- 41692115 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260730 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 133 IP - 6 DP - 2026 Jun TI - Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis. PG - 799-810 LID - S0161-6420(26)00082-5 [pii] LID - 10.1016/j.ophtha.2026.02.013 [doi] AB - TOPIC: This systematic review and meta-analysis evaluates whether semaglutide use, compared with non-glucagon-like peptide-1 receptor agonist (GLP-1 RA) receptor agonist therapies, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). CLINICAL RELEVANCE: Nonarteritic anterior ischemic optic neuropathy is a rare, vision-threatening optic neuropathy whose major risk factors overlap with populations prescribed semaglutide, making clarification of any associated risk clinically important for treatment decisions and patient counseling. METHODS: This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered (PROSPERO CRD420251107346). Seven databases and Google Scholar were searched from inception to August 20, 2025. Eligible studies enrolled adults, compared semaglutide with non-GLP-1 RA users, and reported NAION as a distinct outcome with extractable odds ratios (ORs) or adjusted hazard ratios (aHRs). Two reviewers independently performed study selection, data extraction, and Newcastle-Ottawa risk of bias assessment. Random-effects models pooled ORs and aHRs. Prespecified subgroup analyses examined treatment indication. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Six observational studies (n = 4 831 654) met inclusion. In pooled OR analyses, semaglutide was not associated with a statistically significant increase in NAION compared with non-GLP-1 RA comparators (OR = 2.44; 95% confidence interval [CI], 0.59-10.15; I(2) = 99.34%; very low certainty). Time-stratified ORs at 1 to 3 years were likewise nonsignificant (very low certainty). Compared with SGLT2 inhibitors, the pooled OR was 0.72 (95% CI, 0.38-1.35; I(2) = 81.59%; very low certainty). In adjusted time-to-event analyses, the pooled aHR was 1.63 (95% CI, 0.88-2.39; I(2) = 67.15%; low certainty). Exclusion of 1 influential study shifted the estimate (aHR = 1.92; 95% CI, 1.03-2.81; low certainty), indicating fragility. By indication, pooled aHRs were 1.70 (95% CI, 1.10-2.64; low certainty) for type 2 diabetes and 0.47 (95% CI, 0.19-1.13; moderate certainty) for obesity/overweight. Time-stratified aHRs were insufficient for meta-analysis. CONCLUSION: Across observational studies comparing semaglutide with non-GLP-1 RA therapies, pooled adjusted evidence does not demonstrate a consistent overall increase in NAION risk. However, estimates are limited by substantial heterogeneity, residual confounding, outcome misclassification, and fragility, resulting in low to very low certainty. Apparent indication-based differences should be interpreted cautiously and may reflect underlying disease-related risk rather than a drug-specific effect. Causality cannot be established, and further well-designed studies with standardized NAION ascertainment are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Abdelaal, Abdelaziz AU - Abdelaal A AD - Clinical Research Scholar, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Abu Serhan, Hashem AU - Abu Serhan H AD - Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar. FAU - Alsaadi, Mustafa AU - Alsaadi M AD - Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Kufa, Iraq. FAU - Yaldo, Luke AU - Yaldo L AD - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. FAU - Gaier, Eric D AU - Gaier ED AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Picower Institute of Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts. FAU - Elhusseiny, Abdelrahman M AU - Elhusseiny AM AD - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address: amelhusseiny@uams.edu. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260213 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - NAION OT - Nonarteritic OT - Optic neuropathy OT - Semaglutide EDAT- 2026/02/16 00:31 MHDA- 2026/05/22 00:33 CRDT- 2026/02/15 19:30 PHST- 2025/08/29 00:00 [received] PHST- 2026/02/04 00:00 [revised] PHST- 2026/02/05 00:00 [accepted] PHST- 2026/05/22 00:33 [medline] PHST- 2026/02/16 00:31 [pubmed] PHST- 2026/02/15 19:30 [entrez] AID - S0161-6420(26)00082-5 [pii] AID - 10.1016/j.ophtha.2026.02.013 [doi] PST - ppublish SO - Ophthalmology. 2026 Jun;133(6):799-810. doi: 10.1016/j.ophtha.2026.02.013. Epub 2026 Feb 13. PMID- 41690504 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260711 IS - 1542-2224 (Electronic) IS - 1067-2516 (Linking) VI - 65 IP - 4 DP - 2026 Jul-Aug TI - Association of GLP-1 receptor agonists with post-operative outcomes after achilles tendon repair in obese patients. PG - 124.e1-124.e4 LID - S1067-2516(26)00043-8 [pii] LID - 10.1053/j.jfas.2026.02.007 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming increasingly popular for managing type 2 diabetes and obesity. Beyond their metabolic effects, they have shown anti-inflammatory properties, which may impact post-surgical recovery. However, their role in orthopedic procedures is not yet well defined. This study investigates whether GLP-1 RA use affects post-operative complications, including wound infection, venous thromboembolism, hospital readmission, and reintervention for Achilles tendon repair patients. METHODS: A retrospective cohort study was conducted on 337 patients who underwent Achilles tendon repair. Among them, 11.6% were GLP-1 RA users. Post-operative complications, including wound infection, Deep Vein Thrombosis and Pulmonary Embolism (DVT/PE), readmission, and reintervention, were analyzed. Logistic regression models and correlation analysis were used to estimate odds ratios (OR) for complications while controlling for potential confounders. Variance inflation factor (VIF) analysis was conducted to evaluate collinearity between independent variables. RESULTS: GLP-1 RA users had a lower risk of wound infection compared to non-users (OR: 0.19, 95% CI: 0.04-0.88, p = 0.03). Additionally, GLP-1 RA users had lower rates of Venous Thromboembolism (VTE) (2.6% vs. 6.4%, p = 0.5), readmission (2.6% vs. 7.7%, p = 0.12), and reintervention (0.0% vs. 6.7%, p = 1.00); however, these differences were not statistically significant. Diabetes showed the strongest positive correlation with wound infection (r = 0.29, p < 0.01). CONCLUSION: This study suggests that GLP-1 RA use is associated with a lower risk of wound infection following Achilles tendon repair. These findings suggest a potential protective role of GLP-1 RAs in surgical outcomes. CI - Published by Elsevier Inc. FAU - Rai, Carl AU - Rai C AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA. Electronic address: chrai@mgh.harvard.edu. FAU - Woodrow, Jackson AU - Woodrow J AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA; University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA. FAU - O'Neill, Colin AU - O'Neill C AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA. FAU - Lee, Ivy AU - Lee I AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA. FAU - Ashkani-Esfahani, Soheil AU - Ashkani-Esfahani S AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA. FAU - Waryasz, Gregory AU - Waryasz G AD - Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Mass General Brigham, Harvard Medical School, 158 Boston Post Rd, Boston, MA, USA. LA - eng PT - Journal Article DEP - 20260212 PL - United States TA - J Foot Ankle Surg JT - The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons JID - 9308427 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - *Achilles Tendon/surgery/injuries MH - Retrospective Studies MH - *Obesity/complications/drug therapy MH - *Postoperative Complications/epidemiology/prevention & control MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Patient Readmission/statistics & numerical data MH - Surgical Wound Infection MH - Aged MH - Treatment Outcome OTO - NOTNLM OT - Achilles rupture OT - Diabetes OT - Glucagon-like peptide-1 OT - Obesity OT - Perioperative management OT - Readmission OT - Reintervention OT - Tendon repair outcomes OT - VTE OT - Wound infection COIS- Declaration of competing interest The authors declare no conflicts of interest related to this work. EDAT- 2026/02/15 00:31 MHDA- 2026/07/12 00:56 CRDT- 2026/02/14 19:13 PHST- 2025/09/30 00:00 [received] PHST- 2026/01/24 00:00 [revised] PHST- 2026/02/10 00:00 [accepted] PHST- 2026/07/12 00:56 [medline] PHST- 2026/02/15 00:31 [pubmed] PHST- 2026/02/14 19:13 [entrez] AID - S1067-2516(26)00043-8 [pii] AID - 10.1053/j.jfas.2026.02.007 [doi] PST - ppublish SO - J Foot Ankle Surg. 2026 Jul-Aug;65(4):124.e1-124.e4. doi: 10.1053/j.jfas.2026.02.007. Epub 2026 Feb 12. PMID- 41687959 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 52 IP - 2 DP - 2026 Mar TI - Glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischemic optic neuropathy: Evidence from a global real-world cohort. PG - 101740 LID - S1262-3636(26)00019-4 [pii] LID - 10.1016/j.diabet.2026.101740 [doi] AB - AIMS: To evaluate whether GLP-1 RA therapy is associated with an increased risk of NAION in a large, diverse real-world population. METHODS: This retrospective cohort study utilized the TriNetX U.S. Collaborative Network from 2015 to 2024. Adults (>/=18 years) with type 2 diabetes mellitus (T2DM) were identified and grouped as GLP-1 RA users versus other antidiabetic users and GLP-1 RA users versus sodium-glucose cotransporter-2 inhibitors (SGLT-2 i) users. Patients with preexisting optic neuropathy or severe ocular disease were excluded. Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was incident NAION, defined by ICD-10 codes. Cox proportional hazards models and Kaplan-Meier analyses were used to estimate hazard ratios (HRs) and cumulative probabilities. RESULTS: After matching, 799 036 GLP-1 RA users were compared with 799 036 other antidiabetic users, and 429 985 GLP-1 RA users were compared with 429 985 SGLT-2i users. Over 9 years, GLP-1 RA users showed higher cumulative NAION incidence vs other agents (0.21% vs 0.17%; HR 1.38; 95% CI, 1.23-1.55) and vs SGLT-2i users (0.20% vs 0.20%; HR 1.30; 95% CI, 1.11-1.52). Kaplan-Meier curves demonstrated consistent early separation favoring higher risk among GLP-1 RA users. Sensitivity analyses yielded similar patterns. CONCLUSIONS: GLP-1 RA therapy was associated with a modest but statistically significant increased risk of NAION. While the absolute risk remains low, clinicians should consider ophthalmic risk assessment-particularly in patients with anatomical susceptibility or vascular risk factors-as GLP-1 RA use expands for diabetes and obesity management. Further mechanistic and prospective research is warranted. CI - Copyright (c) 2026. Published by Elsevier Masson SAS. FAU - Chen, Jun-Wei AU - Chen JW AD - Department of Medical Education, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan. FAU - Yu, Frederick Tzu-En AU - Yu FT AD - School of Medicine, Chang Gung University, Taoyuan, Taoyuan City, Taiwan. FAU - Chen, Hsin-An AU - Chen HA AD - Department of Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan. FAU - Huang, Tzu-Fu AU - Huang TF AD - Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan. FAU - Chen, Harn-Shen AU - Chen HS AD - Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan. Electronic address: chenhs@vghtpe.gov.tw. FAU - Wu, Tzu-En AU - Wu TE AD - Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan. Electronic address: wu001055@gmail.com. LA - eng PT - Journal Article DEP - 20260211 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Risk Factors MH - Adult MH - Cohort Studies OTO - NOTNLM OT - GLP-1 agonists OT - Nonarteritic anterior ischemic optic neuropathy OT - TriNetX OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare no conflicts of interest. EDAT- 2026/02/14 05:30 MHDA- 2026/03/23 06:31 CRDT- 2026/02/13 19:14 PHST- 2025/12/23 00:00 [received] PHST- 2026/02/03 00:00 [revised] PHST- 2026/02/06 00:00 [accepted] PHST- 2026/03/23 06:31 [medline] PHST- 2026/02/14 05:30 [pubmed] PHST- 2026/02/13 19:14 [entrez] AID - S1262-3636(26)00019-4 [pii] AID - 10.1016/j.diabet.2026.101740 [doi] PST - ppublish SO - Diabetes Metab. 2026 Mar;52(2):101740. doi: 10.1016/j.diabet.2026.101740. Epub 2026 Feb 11. PMID- 41687055 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260722 IS - 1536-3708 (Electronic) IS - 0148-7043 (Linking) VI - 96 IP - Suppl 5 DP - 2026 May 1 TI - Active GLP-1 RA Use Is Associated With Lower Rates of Surgical Complications Across Diabetic BMI Cohorts: A Retrospective Analysis of 72,578 Surgical Encounters. PG - S192-S197 LID - 10.1097/SAP.0000000000004657 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly expanding for diabetes and weight loss. However, limited research exists regarding its effect on postoperative surgical outcomes, particularly in higher-risk patients with comorbidities such as diabetes and obesity. We sought to analyze the effect of GLP-1 RA use on postoperative complications in diabetic patients stratified by BMI. METHODS: A retrospective, observational cohort analysis was conducted in all patients diagnosed with type 1 or type 2 diabetes mellitus undergoing a surgical procedure between February 2020 to July 2023 at a multicenter quaternary-care health care system. Patients with and without an active GLP-1 RA prescription were compared in each of 4 cohorts: normal weight (BMI 18.5-24.9 kg/m 2 ), overweight (25-29.9), obese (30-40), and morbidly obese (>40). Outcomes examined were dehiscence, infection, hematoma, and bleeding within 180 days after surgery, and 30-day readmission. RESULTS: From 72,578 procedures in 21,544 diabetic patients, 23% of patients were classified as normal weight, 34% overweight, 35% obese, and 8% morbidly obese, with active GLP-1 RA use in 15.4%, 24.4%, 33.8%, and 46.5%, respectively. Mean A1C of GLP-1 RA users was significantly higher than nonusers in all cohorts. Active GLP-1 RA cohorts demonstrated a significantly reduced relative risk of postoperative wound dehiscence in normal-weight (0.59), overweight (0.60), obese (0.67), and morbidly obese (0.40) cohorts; a significantly reduced risk of readmission in all cohorts (0.74, 0.82, 0.62, 0.55, respectively); and a significantly reduced risk of postoperative hematoma in obese patients (0.19). CONCLUSION: Active perioperative GLP-1 RA use was associated with significant reductions in readmission and wound dehiscence in diabetic patients across weight categories, despite higher A1C levels, with the greatest reductions in morbidly obese patients. These findings suggest a potential wound healing benefit, with promising implications for diabetic and obese/overweight patients. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Salingaros, Sophia AU - Salingaros S AUID- ORCID: 0009-0004-0760-7427 AD - Division of Plastic and Reconstructive Surgery, Weill Cornell Medicine, New York, NY. FAU - Zhang, Ashley AU - Zhang A AD - Division of Plastic and Reconstructive Surgery, Weill Cornell Medicine, New York, NY. FAU - Rohde, Christine H AU - Rohde CH AD - Division of Plastic and Reconstructive Surgery, Columbia University Irving Medical Center, New York, NY. FAU - Spector, Jason A AU - Spector JA AD - Division of Plastic and Reconstructive Surgery, Weill Cornell Medicine, New York, NY. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260213 PL - United States TA - Ann Plast Surg JT - Annals of plastic surgery JID - 7805336 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - *Postoperative Complications/epidemiology/prevention & control MH - Middle Aged MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Diabetes Mellitus, Type 1/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Patient Readmission/statistics & numerical data MH - Adult MH - Obesity/complications OTO - NOTNLM OT - BMI OT - GLP-1 RA OT - diabetes OT - obesity OT - surgical complication COIS- Conflicts of interest and sources of funding: The authors report no conflicts of interest or sources of funding in support of this work. EDAT- 2026/02/13 19:07 MHDA- 2026/05/14 14:50 CRDT- 2026/02/13 16:12 PHST- 2026/05/14 14:50 [medline] PHST- 2026/02/13 19:07 [pubmed] PHST- 2026/02/13 16:12 [entrez] AID - 00000637-202605001-00006 [pii] AID - 10.1097/SAP.0000000000004657 [doi] PST - ppublish SO - Ann Plast Surg. 2026 May 1;96(Suppl 5):S192-S197. doi: 10.1097/SAP.0000000000004657. Epub 2026 Feb 13. PMID- 41683853 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 3 DP - 2026 Jan 31 TI - Glucagon-like Peptide-1 Receptor Agonists and Ocular Disease: Mechanisms, Evidence and Therapeutic Perspectives. LID - 10.3390/ijms27031432 [doi] LID - 1432 AB - Ocular diseases, including glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), remain major global causes of irreversible vision loss. Despite advances in clinical management, current therapies insufficiently address the shared metabolic, inflammatory, vascular, and neurodegenerative mechanisms underlying these conditions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Preclinical studies consistently demonstrate that GLP-1RAs preserve blood-retina barrier integrity, suppress pathological angiogenesis, mitigate oxidative and inflammatory stress, and protect retinal neurons from degeneration. Complementary clinical and real-world evidence shows a robust and reproducible reduction in glaucoma risk among GLP-1RA users across diabetic and non-diabetic populations. By contrast, findings for DR and AMD are more heterogeneous and appear context-dependent, with potential benefits most evident in early or non-exudative disease stages. Emerging safety considerations-including reports of nonarteritic anterior ischemic optic neuropathy and early DR worsening in the setting of rapid glycemic improvement-highlight the need for careful interpretation, individualized risk assessment, and appropriate ophthalmic monitoring. This review synthesizes molecular mechanisms, experimental data, clinical and pharmacoepidemiologic evidence, and safety signals to critically evaluate the therapeutic potential of GLP-1RAs in ocular disease. We also outline key translational challenges, including the need for ocular-targeted delivery strategies, prospective ophthalmology-specific trials, and precision-medicine approaches to determine when and how GLP-1RAs can be safely advanced as disease-modifying treatments in ophthalmology. FAU - Gong, Xiaoming AU - Gong X AUID- ORCID: 0009-0009-8687-0763 AD - Vision Center, Akron Children's Hospital, Akron, OH 44308, USA. AD - Rebecca D. Considine Research Institute, Akron Children's Hospital, Akron, OH 44308, USA. FAU - Orge, Faruk H AU - Orge FH AD - Vision Center, Akron Children's Hospital, Akron, OH 44308, USA. AD - Rebecca D. Considine Research Institute, Akron Children's Hospital, Akron, OH 44308, USA. LA - eng PT - Journal Article PT - Review DEP - 20260131 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Eye Diseases/drug therapy/metabolism MH - Diabetic Retinopathy/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC12897703 OTO - NOTNLM OT - age-related macular degeneration OT - diabetic retinopathy OT - glaucoma OT - glucagon-like peptide-1 receptor agonists OT - nonarteritic anterior ischemic optic neuropathy COIS- The authors declare no conflicts of interest. EDAT- 2026/02/13 06:32 MHDA- 2026/02/13 06:33 PMCR- 2026/01/31 CRDT- 2026/02/13 01:10 PHST- 2026/01/08 00:00 [received] PHST- 2026/01/28 00:00 [revised] PHST- 2026/01/30 00:00 [accepted] PHST- 2026/02/13 06:33 [medline] PHST- 2026/02/13 06:32 [pubmed] PHST- 2026/02/13 01:10 [entrez] PHST- 2026/01/31 00:00 [pmc-release] AID - ijms27031432 [pii] AID - ijms-27-01432 [pii] AID - 10.3390/ijms27031432 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jan 31;27(3):1432. doi: 10.3390/ijms27031432. PMID- 41683830 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 3 DP - 2026 Jan 30 TI - Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes. LID - 10.3390/ijms27031409 [doi] LID - 1409 AB - Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) designed to replicate the efficacy of injectable GLP-1 RAs for glycemic control and weight reduction while improving convenience and adherence. Preclinical studies have demonstrated potent receptor engagement, favorable pharmacokinetics, and central nervous system activity. Phase 1-3 clinical trials have shown significant reductions in glycated hemoglobin (HbA1c), fasting and postprandial glucose, body weight, and cardiovascular risk biomarkers, with an acceptable safety profile. This comprehensive review integrates pharmacological, clinical, and mechanistic evidence, critically evaluates the data, identifies knowledge gaps, and outlines future directions for orforglipron in the treatment of type 2 diabetes and obesity. FAU - Kansakar, Urna AU - Kansakar U AD - School of Medicine, City University of New York, Manhattan, NY 10031, USA. FAU - Jankauskas, Stanislovas S AU - Jankauskas SS AD - School of Medicine, City University of New York, Manhattan, NY 10031, USA. FAU - Pande, Shivangi AU - Pande S AD - School of Medicine, City University of New York, Manhattan, NY 10031, USA. FAU - Mone, Pasquale AU - Mone P AD - Casa di Cura "Clinica Montevergine", 83013 Mercogliano, Italy. FAU - Varzideh, Fahimeh AU - Varzideh F AD - School of Medicine, City University of New York, Manhattan, NY 10031, USA. FAU - Santulli, Gaetano AU - Santulli G AUID- ORCID: 0000-0001-7231-375X AD - School of Medicine, City University of New York, Manhattan, NY 10031, USA. LA - eng PT - Journal Article PT - Review DEP - 20260130 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 7ZW40D021M (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Obesity/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/pharmacology MH - Administration, Oral MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC12898445 OTO - NOTNLM OT - GLP-1 OT - cardiology OT - diabetes mellitus OT - metabolism OT - obesity OT - orforglipron COIS- The authors declare no conflicts of interest. EDAT- 2026/02/13 06:33 MHDA- 2026/02/13 06:34 PMCR- 2026/01/30 CRDT- 2026/02/13 01:10 PHST- 2025/12/31 00:00 [received] PHST- 2026/01/17 00:00 [revised] PHST- 2026/01/21 00:00 [accepted] PHST- 2026/02/13 06:34 [medline] PHST- 2026/02/13 06:33 [pubmed] PHST- 2026/02/13 01:10 [entrez] PHST- 2026/01/30 00:00 [pmc-release] AID - ijms27031409 [pii] AID - ijms-27-01409 [pii] AID - 10.3390/ijms27031409 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jan 30;27(3):1409. doi: 10.3390/ijms27031409. PMID- 41683613 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 3 DP - 2026 Jan 24 TI - Semaglutide-Mediated Remodeling of Adipose Tissue in Type 2 Diabetes: Molecular Mechanisms Beyond Glycemic Control. LID - 10.3390/ijms27031186 [doi] LID - 1186 AB - Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. FAU - Abel, Tatjana AU - Abel T AD - Department of Dietetics and Nutritional Sciences, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary. FAU - Csobod Csajbokne, Eva AU - Csobod Csajbokne E AD - Department of Dietetics and Nutritional Sciences, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary. LA - eng PT - Journal Article PT - Review DEP - 20260124 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy/pathology MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/metabolism MH - *Adipose Tissue/metabolism/drug effects/pathology MH - Animals MH - Glycemic Control MH - Lipid Metabolism/drug effects MH - Insulin Resistance PMC - PMC12898281 OTO - NOTNLM OT - GLP-1 receptor agonist OT - adipose tissue remodeling OT - beige adipocytes OT - extracellular matrix remodeling OT - immunometabolism OT - mitochondrial biogenesis OT - semaglutide OT - type 2 diabetes mellitus OT - visceral adiposity COIS- The authors declare no conflicts of interest. EDAT- 2026/02/13 06:32 MHDA- 2026/02/13 06:33 PMCR- 2026/01/24 CRDT- 2026/02/13 01:09 PHST- 2025/12/18 00:00 [received] PHST- 2026/01/19 00:00 [revised] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/02/13 06:33 [medline] PHST- 2026/02/13 06:32 [pubmed] PHST- 2026/02/13 01:09 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - ijms27031186 [pii] AID - ijms-27-01186 [pii] AID - 10.3390/ijms27031186 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jan 24;27(3):1186. doi: 10.3390/ijms27031186. PMID- 41678180 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260910 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 144 IP - 3 DP - 2026 Mar 1 TI - New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes. PG - 259-264 LID - 10.1001/jamaophthalmol.2025.6262 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered safe, effective medications for type 2 diabetes (T2D) and weight loss, used by millions worldwide. While their cardiometabolic benefits are well established, emerging observations suggest a potential association between GLP-1RA use and new-onset nonarteritic anterior ischemic optic neuropathy (NAION). OBJECTIVE: To emulate a target trial evaluating the risk of NAION associated with initiation of semaglutide (GLP-1RA), compared with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) as second-line therapy for T2D in a nationwide cohort of US veterans. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted nationwide using data from the Veterans Health Administration health care system between March 1, 2018, and March 1, 2025. This active-comparator, new-user, target trial emulation used cause-specific hazard ratios (HRs) that were estimated using overlap weighting to account for confounding. Participants included US veterans with T2D, current metformin use, and no prior GLP-1RA or SGLT2i use. Data analysis was conducted from July 2025 through September 2025. EXPOSURE: Initiation of semaglutide or any SGLT2i. MAIN OUTCOME AND MEASURE: Incident NAION, identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and Systematized Nomenclature of Medicine codes. RESULTS: A total of 102 361 US veterans met inclusion criteria, including 11 478 initiators of semaglutide and 90 883 initiators of an SGLT2i. Baseline characteristics were well balanced between treatment groups after overlap weighting (mean [SD] age, 60.1 [11.7] years; body mass index, 37.8 [6.7]; hemoglobin A1c, 7.0% [1.4]; 85.5% male and 14.5% female; 20.7% Black, 8.1% Hispanic, and 61.9% non-Hispanic White). Over a maximum follow-up of 7.5 years, 173 total incident NAION events occurred. The incidence rate of NAION was 123 per 100 000 person-years among semaglutide initiators and 67 per 100 000 person-years among SGLT2i. In 2.1 years of median follow-up, semaglutide initiators had a 2.33-fold higher risk than SGLT2i initiators (hazard ratio, 2.33; 95% CI, 1.54-3.54; P < .001). The overlap weighted incidence rate of NAION was 0.29% for semaglutide initiators and 0.13% for SGLT2i initiators, with a corresponding average treatment effect of 0.16 percentage points. CONCLUSIONS AND RELEVANCE: In this nationwide cohort of US veterans with T2D, semaglutide initiators had a 2-fold NAION risk than SGLT2i initiators, while the absolute risk was low. Clinicians and patients should be counseled on the rare but evident increased risk of NAION after semaglutide initiation. FAU - Heberer, Kent AU - Heberer K AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Bress, Adam P AU - Bress AP AD - VA Salt Lake City Healthcare System, Salt Lake City, Utah. AD - Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City. FAU - Cogill, Steven AU - Cogill S AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Maldonado, Ana I AU - Maldonado AI AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Kim, Sun H AU - Kim SH AD - Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, California. FAU - Nallamshetty, Shriram AU - Nallamshetty S AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - Division of Cardiovascular Medicine, Stanford School of Medicine, Stanford, California. FAU - Chen, Ying Q AU - Chen YQ AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California. FAU - Shih, Mei-Chiung AU - Shih MC AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California. FAU - Lynch, Julie A AU - Lynch JA AD - VA Salt Lake City Healthcare System, Salt Lake City, Utah. AD - Division of Epidemiology, School of Medicine, University of Utah, Salt Lake City. FAU - Lee, Jennifer S AU - Lee JS AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, California. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM EIN - JAMA Ophthalmol. 2026 Jun 1;144(6):571. doi: 10.1001/jamaophthalmol.2026.1060. PMID: 41954895 MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Female MH - United States/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Veterans/statistics & numerical data MH - Aged MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Incidence MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects PMC - PMC12902922 COIS- Conflict of Interest Disclosures: Dr Kim reported personal fees from TeCure Consulting outside the submitted work. Dr Nallamshetty reported grants from Novartis outside the submitted work. Dr Lynch reported grants from the US Department of Veterans Affairs during the conduct of the study and grants from Alnylam, AstraZeneca, Biodesix, Celgene, Janssen, and Novartis through the University of Utah or Western Institute for Veteran Research outside the submitted work. No other disclosures were reported. EDAT- 2026/02/12 12:49 MHDA- 2026/03/19 15:13 PMCR- 2026/02/12 CRDT- 2026/02/12 11:33 PHST- 2026/03/19 15:13 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 11:33 [entrez] PHST- 2026/02/12 00:00 [pmc-release] AID - 2844873 [pii] AID - ebr250010 [pii] AID - 10.1001/jamaophthalmol.2025.6262 [doi] PST - ppublish SO - JAMA Ophthalmol. 2026 Mar 1;144(3):259-264. doi: 10.1001/jamaophthalmol.2025.6262. PMID- 41678136 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 4 DP - 2026 Apr TI - Psychometric Validation of the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) for Type 2 Diabetes. PG - 1521-1535 LID - 10.1007/s12325-025-03448-5 [doi] AB - INTRODUCTION: Over the past 2 decades, treatment for type 2 diabetes (T2D) has evolved with the introduction of medications that offer greater simplicity. The Simplicity of Diabetes Treatment Questionnaire (Sim-Q) was developed to assess the simplicity or complexity of treatment for T2D. This study assessed the psychometric properties of the Sim-Q. METHODS: Eight clinical sites in the USA recruited participants treated for T2D with a variety of medications, including oral medications, insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, and a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist. Psychometric analysis of the Sim-Q focused on item performance, item selection, exploratory factor analysis (EFA), reliability (internal consistency and test-retest), and validity (construct and known-groups). RESULTS: The study included 250 participants (mean age 59.7 years; 54.4% female). On the basis of item performance and EFA, eight items were retained for the Simplicity of Diabetes Management Subscale assessing simplicity of treatment attributes. Two global items assessing simplicity of medication for diabetes and simplicity of overall diabetes management were scored separately. The Simplicity of Diabetes Management Subscale had good internal consistency reliability (Cronbach's alpha 0.90). The Simplicity of Diabetes Management Subscale and two global items had acceptable test-retest reliability (intraclass correlation coefficients 0.80, 0.72, and 0.73). Convergent validity was supported by significant correlations (P < 0.0001) with related measures. The Sim-Q distinguished between groups of participants who differed in their satisfaction with the ease and convenience of their treatment. For example, the two global items differentiated between groups receiving different treatments (tirzepatide and injectable semaglutide). CONCLUSION: The Sim-Q demonstrated good reliability and validity in this psychometric study. This measure may be useful for assessing individuals' perceptions of treatment simplicity in clinical trials and clinical practice. CI - (c) 2026. The Author(s). FAU - Boye, Kristina S AU - Boye KS AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. Boye_Kristina_Secnik@lilly.com. FAU - Cutts, Katelyn N AU - Cutts KN AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. FAU - Coyne, Karin S AU - Coyne KS AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. FAU - Matza, Louis S AU - Matza LS AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. LA - eng PT - Journal Article PT - Multicenter Study PT - Validation Study DEP - 20260212 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Psychometrics MH - Middle Aged MH - Reproducibility of Results MH - Male MH - Surveys and Questionnaires/standards MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Factor Analysis, Statistical MH - Insulin/therapeutic use PMC - PMC13065586 OTO - NOTNLM OT - Diabetes OT - Ease of use OT - Patient experience OT - Patient-reported outcomes OT - Psychometric validation OT - Sim-Q OT - Simplicity of Diabetes Treatment Questionnaire OT - Treatment simplicity OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Kristina Boye is employed by and owns shares in Eli Lilly and Company. Louis Matza, Katelyn Cutts, and Karin Coyne are employed by Thermo Fisher Scientific, which received funding from Lilly for the time spent conducting this research. Ethical Approval: All study methods and materials, as well as all eight clinical sites participating in the study, were approved by an independent review board (Salus Institutional Review Board study number 23069). The study was performed according to the Helsinki Declaration of 1964 and its later amendments. Participants provided informed consent before completing any study measures and were remunerated for their time. The consent form informed participants that their data may be published, but they would not be personally identified in any publications. EDAT- 2026/02/12 12:49 MHDA- 2026/04/09 12:45 PMCR- 2026/02/12 CRDT- 2026/02/12 11:22 PHST- 2025/09/01 00:00 [received] PHST- 2025/11/20 00:00 [accepted] PHST- 2026/04/09 12:45 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 11:22 [entrez] PHST- 2026/02/12 00:00 [pmc-release] AID - 10.1007/s12325-025-03448-5 [pii] AID - 3448 [pii] AID - 10.1007/s12325-025-03448-5 [doi] PST - ppublish SO - Adv Ther. 2026 Apr;43(4):1521-1535. doi: 10.1007/s12325-025-03448-5. Epub 2026 Feb 12. PMID- 41677473 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 2767-9764 (Electronic) IS - 2767-9764 (Linking) VI - 6 IP - 3 DP - 2026 Mar 1 TI - Weight Loss Patterns and Clinical Outcomes of GLP1 Receptor Agonists in Breast Cancer Survivors. PG - 447-455 LID - 10.1158/2767-9764.CRC-25-0554 [doi] AB - The use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer survivors remain unclear. This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in breast cancer survivors receiving GLP1-RA at an academic institution. We evaluated patients with nonmetastatic [ductal carcinoma in situ (DCIS), stage 1-3] breast cancer who received GLP1-RA (2005-2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free survival (DFS) and overall survival (OS) between GLP1-RA users versus nonusers in the subgroup with invasive disease. We identified 1,022 patients; 79% had type 2 diabetes mellitus. The median weight and body mass index at GLP1-RA initiation were 86.8 kg (47.2-175 kg) and 33.5 kg/m2 (18.9-61.8 kg/m2). In semaglutide or tirzepatide users (442, 43.2%), the median weight change at 3, 6, and 12 months after GLP1-RA initiation was -1.9% (-13.2% to 14.9%), -3.1% (-20.2% to 19%), and -2.6% (-27.8% to 11.5%), respectively. Endocrine therapy and metformin use were associated with weight gain and loss, respectively; invasive disease stage was linked to greater weight loss. GLP1-RA was not associated with DFS, but OS significantly differed between GLP1-RA users (n = 810) and nonusers (n = 1,620; hazard ratio, 0.37; 95% confidence interval, 0.27-0.53; P < 0.0001). In conclusion, in this real-world study in breast cancer survivors, GLP1-RA was associated with modest weight loss and improved all-cause survival. Clinical trials are warranted to study GLP1-RA in this population. SIGNIFICANCE: This is the largest study describing real-world patterns of GLP1 receptor agonists in breast cancer survivors. Clinical trials should evaluate these agents for weight management as an adjunct to lifestyle interventions and the potential role in cancer control in breast cancer survivors. CI - (c)2026 The Authors; Published by the American Association for Cancer Research. FAU - Sukumar, Jasmine S AU - Sukumar JS AUID- ORCID: 0000-0001-6994-8527 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Raghavendra, Akshara S AU - Raghavendra AS AUID- ORCID: 0000-0002-6425-4400 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Pasyar, Sarah AU - Pasyar S AUID- ORCID: 0000-0003-4914-0728 AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Bassett, Roland L AU - Bassett RL AUID- ORCID: 0000-0002-4534-2042 AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Tripathy, Debu AU - Tripathy D AUID- ORCID: 0000-0002-5711-2404 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Barcenas, Carlos H AU - Barcenas CH AUID- ORCID: 0000-0001-5377-9167 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Basen-Engquist, Karen M AU - Basen-Engquist KM AUID- ORCID: 0000-0001-7299-0646 AD - Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Arun, Banu K AU - Arun BK AUID- ORCID: 0000-0002-5475-8509 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. LA - eng GR - K12 AR084228/AR/NIAMS NIH HHS/United States GR - University Cancer Foundation via the Institutional Research Grant at MD Anderson Cancer Center/ GR - NIH/NCI P30 CA016672/University of Texas MD Anderson Cancer Center (MD Anderson)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res Commun JT - Cancer research communications JID - 9918281580506676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/drug therapy/mortality/pathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Middle Aged MH - *Cancer Survivors/statistics & numerical data MH - Semaglutide MH - Aged MH - Tirzepatide MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Adult PMC - PMC13043164 COIS- No disclosures were reported. EDAT- 2026/02/12 12:49 MHDA- 2026/03/07 06:38 PMCR- 2026/03/02 CRDT- 2026/02/12 10:23 PHST- 2025/10/27 00:00 [received] PHST- 2025/12/08 00:00 [revised] PHST- 2026/02/10 00:00 [accepted] PHST- 2026/03/07 06:38 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 10:23 [entrez] PHST- 2026/03/02 00:00 [pmc-release] AID - 774517 [pii] AID - CRC-25-0554 [pii] AID - 10.1158/2767-9764.CRC-25-0554 [doi] PST - ppublish SO - Cancer Res Commun. 2026 Mar 1;6(3):447-455. doi: 10.1158/2767-9764.CRC-25-0554. PMID- 41671787 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260723 IS - 1532-2653 (Electronic) IS - 0967-5868 (Linking) VI - 147 DP - 2026 May TI - GLP-1 receptor agonists and aneurysm rupture risk in type 2 diabetes: a multicenter retrospective study. PG - 111905 LID - S0967-5868(26)00056-1 [pii] LID - 10.1016/j.jocn.2026.111905 [doi] AB - BACKGROUND AND OBJECTIVES: Intracranial aneurysms (IAs) occur in up to 3% of the population, with rupture leading to substantial morbidity and mortality. Preclinical evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide vascular protection. Their role in IA rupture prevention has not been readily assessed in large human cohorts. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network to identify adults with type 2 diabetes mellitus (T2DM) and unruptured IAs between 2008 and 2025. Patients were classified as GLP-1RA users or non-users. Propensity score matching (PSM) was applied to balance demographics, comorbidities, laboratory values, and medication use. The primary outcome was nontraumatic subarachnoid hemorrhage (SAH) at 3- and 5-year follow-up. RESULTS: A total of 24,776 T2DM patients with unruptured IA(s) were identified: 3119 of those with GLP-1RA prescriptions and 8063 without GLP-1RA prescriptions. After 1:1 PSM, 2651 patients remained in each cohort. GLP-1RA prescriptions were associated with significantly lower risk of SAH diagnoses at 3 years (HR 0.62, 95% CI 0.44-0.88) with a decreased effect at 5 years (HR 0.65, 95% CI 0.47-0.92). Follow-up laboratory values showed no significant differences between groups. CONCLUSIONS: GLP-1RA prescriptions in patients with T2DM and unruptured IAs were associated with reduced risk of aneurysmal rupture. These results suggest a possible stabilizing effect of GLP-1RAs on IAs, although future prospective, imaging-based studies will be required to further investigate this association. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved. FAU - Li, Sean Y AU - Li SY AD - Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Sonti, Anisha AU - Sonti A AD - Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Departments of Internal Medicine, Pediatrics, and Population and Quantitative Health Sciences, Case Western Reserve University, USA; The Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Ben-Israel, David AU - Ben-Israel D AD - Department of Neurological Surgery, MetroHealth System, Cleveland, OH, USA. FAU - Bowles, Alfred Jr AU - Bowles A Jr AD - Department of Neurological Surgery, MetroHealth System, Cleveland, OH, USA. FAU - Reddy, Deven AU - Reddy D AD - Department of Neurological Surgery, MetroHealth System, Cleveland, OH, USA. FAU - Kelly, Michael L AU - Kelly ML AD - Department of Neurological Surgery, MetroHealth System, Cleveland, OH, USA. Electronic address: mkelly4@metrohealth.org. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260210 PL - Scotland TA - J Clin Neurosci JT - Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia JID - 9433352 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Retrospective Studies MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Intracranial Aneurysm/epidemiology/complications MH - *Aneurysm, Ruptured/epidemiology/prevention & control MH - Aged MH - *Subarachnoid Hemorrhage/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Adult OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Intracranial aneurysm OT - Subarachnoid hemorrhage COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/02/12 00:47 MHDA- 2026/03/07 18:37 CRDT- 2026/02/11 18:06 PHST- 2026/01/08 00:00 [received] PHST- 2026/01/24 00:00 [revised] PHST- 2026/02/01 00:00 [accepted] PHST- 2026/03/07 18:37 [medline] PHST- 2026/02/12 00:47 [pubmed] PHST- 2026/02/11 18:06 [entrez] AID - S0967-5868(26)00056-1 [pii] AID - 10.1016/j.jocn.2026.111905 [doi] PST - ppublish SO - J Clin Neurosci. 2026 May;147:111905. doi: 10.1016/j.jocn.2026.111905. Epub 2026 Feb 10. PMID- 41670332 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1532-6535 (Electronic) IS - 0009-9236 (Print) IS - 0009-9236 (Linking) VI - 119 IP - 5 DP - 2026 May TI - Maternal-to-Infant Transfer of Medications for Type 2 Diabetes Mellitus Via Breastmilk: A Systematic Review of Available Evidence and Clinical Guidelines. PG - 1223-1234 LID - 10.1002/cpt.70211 [doi] AB - This review evaluates the available pharmacokinetic data on the plasma-to-breastmilk transfer of first- and second-line T2DM drugs against available clinical guideline recommendations. A list of drug therapies for treating T2DM was generated from national and international clinical guidelines. A systematic search of research articles reporting human plasma and breastmilk drug concentrations was conducted in Scopus, PubMed, Google Scholar, and LactMed(R) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating breastmilk drug transfer in T2DM, with fully accessible abstract and main text reported in English, were included. Study quality was evaluated using the ClinPK checklist. Authors evaluated clinical guideline recommendations on the use of T2DM drugs in lactation and the basis upon which such recommendations were made. Only 5 out of 20 drugs (metformin, glyburide, glipizide, tolbutamide, and semaglutide) have clinical data on plasma-to-breastmilk transfer. Metformin and tolbutamide were detectable in maternal plasma and breastmilk. Half (51.7%) of guideline recommendations provide explicit guidance. Only 4.4% of recommendations were based on clinical evidence. Over half (57.8%) of recommendations were accessible online, and most guideline recommendations (78%) were against the use of antiglycemic agents while breastfeeding. The scarce clinical evidence to guide T2DM drug therapy during breastfeeding available has several design and methodological limitations. Published recommendations remain largely inconsistent, thus perpetuating uncertainty in the use of T2DM drug therapies in lactation. Addressing knowledge gaps is critical in developing clinical consensus to optimize T2DM drug therapy among breastfeeding mothers. CI - (c) 2026 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Richardson, Katherine AU - Richardson K AUID- ORCID: 0009-0007-3491-1514 AD - School of Medicine, University of Liverpool, Liverpool, UK. FAU - Kiptoo, Joshua AU - Kiptoo J AUID- ORCID: 0000-0001-8077-6666 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Pharmacy, Faculty of Medicine, Mbarara University of Science & Technology, Mbarara, Uganda. FAU - Mpora Odongkara, Beatrice AU - Mpora Odongkara B AUID- ORCID: 0000-0002-6283-9114 AD - Department of Pediatrics & Child Health, Faculty of Medicine, Gulu University, Gulu, Uganda. FAU - Ojara, Francis Williams AU - Ojara FW AUID- ORCID: 0000-0002-6425-6828 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Pharmacology and Therapeutics, Faculty of Medicine, Gulu University, Gulu, Uganda. FAU - Waitt, Catriona AU - Waitt C AUID- ORCID: 0000-0003-0134-5855 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Women's and Children's Health, School of Medicine, University of Liverpool, Liverpool, UK. LA - eng GR - 222075/Z/20/Z/Wellcome Clinical Research Career Development Fellowship/ GR - NIHR304266/NIHR Global Health Research Professorship/ GR - INV052005/GATES/Gates Foundation/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260211 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Milk, Human/metabolism/chemistry MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Female MH - *Hypoglycemic Agents/pharmacokinetics/therapeutic use MH - Practice Guidelines as Topic MH - Lactation/metabolism MH - Pregnancy MH - Breast Feeding MH - Infant, Newborn PMC - PMC13083373 COIS- The authors declare no conflicts of interest. EDAT- 2026/02/11 13:08 MHDA- 2026/04/17 04:10 PMCR- 2026/02/11 CRDT- 2026/02/11 08:53 PHST- 2025/07/25 00:00 [received] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/04/17 04:10 [medline] PHST- 2026/02/11 13:08 [pubmed] PHST- 2026/02/11 08:53 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - CPT70211 [pii] AID - 10.1002/cpt.70211 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 May;119(5):1223-1234. doi: 10.1002/cpt.70211. Epub 2026 Feb 11. PMID- 41668679 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 Suppl 2 IP - Suppl 2 DP - 2026 Apr TI - Providing holistic care for patients with metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis: Key aspects of clinical assessment and how to develop individualised care plans for surveillance and interventions. PG - 46-62 LID - 10.1111/dom.70545 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic steatosis and metabolic dysfunction (i.e., obesity, type 2 diabetes, dyslipidaemia, and hypertension), is affecting over 30% of the adult population worldwide. It can progress to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, cirrhosis and even hepatocellular carcinoma. However, most patients with non-cirrhotic MASLD die from extrahepatic causes, particularly cardiovascular disease and non-hepatic cancers, underscoring the need for a holistic approach to surveillance and treatment. Emerging research on MASLD has revealed a substantial heterogeneity in the MASLD population, driven by sex-specific factors, genetic susceptibility, cardiometabolic risk profile, lifestyle and socio-economic determinants, highlighting the necessity of individualised and holistic management of MASLD patients. Although lifestyle intervention remains the cornerstone of MASLD, the pharmacotherapeutic landscape is rapidly evolving, with resmetirom and semaglutide now approved for non-cirrhotic MASH with moderate-to-advanced fibrosis. In addition, metabolic/bariatric surgery has proven to be a highly effective option for patients with MASH. Given its close association with cardiometabolic and malignant comorbidities, MASLD requires individualised, holistic management integrating hepatic and extrahepatic risks. Multiprofessional care, involving among others behavioural therapists, dieticians and physiotherapists, may improve outcomes of lifestyle interventions, particularly in high-risk settings. A stepwise and integrated care model combining early case-finding, risk stratification, and tailored lifestyle and pharmacological interventions is essential to address both hepatic and extrahepatic complications. This review summarises the current understanding of MASLD heterogeneity, clinical assessment, and therapeutic advances, and outlines principles for individualised and coordinated care. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chen, Lanlan AU - Chen L AUID- ORCID: 0000-0002-1075-5592 AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. AD - Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, the First Hospital of Jilin University, Changchun, China. FAU - Horn, Paul AU - Horn P AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. AD - BIH Biomedical Innovation Academy, BIH Charite Digital Clinician Scientist Program, Berlin Institute of Health at Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Tacke, Frank AU - Tacke F AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. LA - eng GR - DFGCRC/TRR412(Project-ID535081457)/Deutsche Forschungsgemeinschaft/ GR - SFB1382(Project-ID403224013)/Deutsche Forschungsgemeinschaft/ GR - EXC3118/1(projectnumber533770413)/Germany's Excellence Strategy/ PT - Journal Article PT - Review DEP - 20260211 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/therapy/diagnosis MH - *Holistic Health MH - *Fatty Liver/therapy/diagnosis MH - Precision Medicine/methods MH - Diabetes Mellitus, Type 2/complications/therapy MH - Patient Care Planning MH - Bariatric Surgery MH - Obesity/therapy/complications MH - *Metabolic Diseases/therapy/complications MH - Life Style PMC - PMC13094696 OAB - Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most common liver diseases worldwide, affecting over 30% of the adult population. It is characterised by excessive lipid accumulation in the liver along with cardiometabolic risk factors such as obesity, type 2 diabetes, abnormal serum glucose, abnormal serum lipids, or high blood pressure. If left untreated, MASLD can progress to liver inflammation, fibrosis, cirrhosis, and liver cancer. Yet, most people with early MASLD do not die from liver-related events, but from cardiovascular diseases or cancers outside the liver, showing that MASLD affects the whole body rather than just the liver. MASLD develops differently from person to person, and many factors (e.g., sex, genetics, lifestyle, socio-economic conditions) play important roles as they impact on the liver, heart, kidney, and other organs. This means that healthcare in individuals with MASLD should be holistic, considering liver disease and extrahepatic risk factors alike. A simple stepwise case-finding algorithm helps to identify patients at risk in primary care, and appropriate risk stratification can pave the way for individualised management. Healthy lifestyle modification remains the foundation of treatment. Weight loss, regular exercise, improved diet, and objective assessment of alcohol intake are essential. New medications such as resmetirom and semaglutide now offer options for patients with advanced fibrosis. For some individuals with severe MASLD, bariatric surgery can also be effective. This review provides guidance on early detection, risk stratification, and personalised, holistic care to improve long-term health outcomes in MASLD. OABL- eng OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - diabetes complications OT - fatty liver disease OT - obesity care OT - weight management COIS- Frank Tacke's lab has received research grants (funding to the institution) from AstraZeneca, MSD, Gilead, Agomab. Frank Tacke has received honoraria for consulting or lectures from Gilead, Abbvie, Falk, AstraZeneca, Boehringer, Madrigal, MSD, GSK, Ipsen, Pfizer, Novartis, Novo Nordisk, Sanofi. Paul Horn reports research grants from MSD and Novo Nordisk (to the institution), honoraria for lectures from Falk and Orphalan, and travel support from Falk and Ipsen. Lanlan Chen reports no potential conflict of interest. EDAT- 2026/02/11 06:30 MHDA- 2026/04/21 18:34 PMCR- 2026/04/20 CRDT- 2026/02/11 04:23 PHST- 2026/01/24 00:00 [revised] PHST- 2025/12/15 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/04/21 18:34 [medline] PHST- 2026/02/11 06:30 [pubmed] PHST- 2026/02/11 04:23 [entrez] PHST- 2026/04/20 00:00 [pmc-release] AID - DOM70545 [pii] AID - 10.1111/dom.70545 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28 Suppl 2(Suppl 2):46-62. doi: 10.1111/dom.70545. Epub 2026 Feb 11. PMID- 41668634 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260710 IS - 1520-7560 (Electronic) IS - 1520-7552 (Linking) VI - 42 IP - 2 DP - 2026 Feb TI - Association Between GLP-1 Receptor Agonists and the Risk of Colon Cancer in Adults With Type 2 Diabetes or Obesity: A Systematic Review and Network Meta-Analysis. PG - e70134 LID - 10.1002/dmrr.70134 [doi] AB - BACKGROUND AND OBJECTIVE: To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and intestinal cancers and to explore the risk factors for these associations. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched through 13 June 2024, to identify randomised clinical trials (RCTs) assessing the relationship between GLP-1 RA use and colorectal, colon, rectal, and intestinal cancers. Pooled relative risks (RRs) and 95% confidence intervals (CIs) for each outcome were calculated. RESULTS: In 17 RCTs comprising 36,415 patients, GLP-1 RAs was associated with a significantly reduced risk of colon cancer (RR, 0.34; 95% CI, 0.17-0.68; I(2) = 0.0%), and showed a neutral effect on the risk of colorectal carcinoma, rectal, and intestinal cancer, with RRs of 1.13 (95% CI, 0.92-1.39; I(2) = 0.0%), 3.64 (95% CI, 0.76-17.40; I(2) = 0.0%), and 0.76 (95% CI, 0.31-1.84; I(2) = 23.3%), respectively. In the network meta-analysis and subgroup analysis, a potential association was observed between albiglutide and subcutaneous semaglutide and a lower incidence of colon cancer among adults treated for a longer duration and with lower baseline HbA1c levels, regardless of baseline body mass index, age, or type of control group. CONCLUSIONS: GLP-1 RAs may be associated with a lower risk of colon cancer in adults with type 2 diabetes mellitus, warranting further validation in trials among high-risk populations. TRIAL REGISTRATION: The study protocol was pre-registered and published on PROSPERO (CRD: 42024548010; https://www.crd.york.ac.uk/prospero/#recordDetails). CI - (c) 2026 John Wiley & Sons Ltd. FAU - Guo, Man AU - Guo M AUID- ORCID: 0000-0001-7646-669X AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Liu, Yong AU - Liu Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. AD - Department of Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Intensive Care Unit, Wangcang People's Hospital, Guangyuan, China. FAU - Zeng, Yan AU - Zeng Y AUID- ORCID: 0000-0002-4083-0127 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Chen, Jiao AU - Chen J AUID- ORCID: 0000-0003-3414-1170 AD - Department of Endocrinology, Sichuan Mental Health Center, The Third Hospital of Mianyang, Mianyang, China. FAU - Zeng, Chen AU - Zeng C AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Huang, Lin-Lin AU - Huang LL AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Wang, Ji-Ying AU - Wang JY AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Wu, Yang-Hao-Tian AU - Wu YH AD - School of Public Health, Chongqing Medical University, Chongqing, China. FAU - Wu, Qi AU - Wu Q AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, and Luzhou Key Laboratory of Precision Pathology Diagnosis for Serious Diseases, Luzhou, China. AD - State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China. FAU - Teng, Fang-Yuan AU - Teng FY AUID- ORCID: 0000-0002-9564-0961 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Xu, Yong AU - Xu Y AUID- ORCID: 0000-0002-9534-6252 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. AD - State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China. LA - eng GR - 82300911/Natural Science Foundation of China/ GR - U22A20286/Natural Science Foundation of China/ GR - 82470854/Natural Science Foundation of China/ GR - 32201056/Natural Science Foundation of China/ GR - 2025ZNSFSC1622/Sichuan Province Science and Technology Support Program/ GR - 2025JYJ054/Luzhou Science and Technology Program/ GR - 2025LCYXZX42/Scientific Research Projects of Southwest Medical University/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Colonic Neoplasms/epidemiology/prevention & control/etiology MH - *Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Semaglutide OTO - NOTNLM OT - colon cancer OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - meta-analysis OT - obesity OT - semaglutide EDAT- 2026/02/11 06:30 MHDA- 2026/02/11 06:31 CRDT- 2026/02/11 04:03 PHST- 2026/01/19 00:00 [revised] PHST- 2025/10/12 00:00 [received] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/02/11 06:31 [medline] PHST- 2026/02/11 06:30 [pubmed] PHST- 2026/02/11 04:03 [entrez] AID - 10.1002/dmrr.70134 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 Feb;42(2):e70134. doi: 10.1002/dmrr.70134. PMID- 41667347 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260723 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 35 IP - 4 DP - 2026 Apr TI - Initiators of Semaglutide in General Practice in New South Wales, 2020-2023: A Retrospective Cohort Study. PG - 554-562 LID - S1443-9506(25)01690-7 [pii] LID - 10.1016/j.hlc.2025.09.012 [doi] AB - AIM: We aimed to analyse trends and demographic and clinical profiles in initial prescriptions of semaglutide ("Ozempic") by general practitioners in New South Wales between 2020 and 2023. METHOD: This retrospective cohort study used electronic medical records from the New South Wales Health Lumos program, covering 680 general practices from January 2020 to November 2023. Individuals aged >/=18 years with a first general practice prescription for semaglutide ("initiators") were included. Counts and proportions of semaglutide initiators by year, sex, age, socioeconomic status, body mass index, and type 2 diabetes mellitus (T2DM) status were compared over time. RESULTS: Between 2020 and 2023, 59,009 individuals had a first general practice prescription for semaglutide, increasing from 448 in 2020 to 36,814 in 2023. Women comprised 63.6% of total initiators. The proportion of initiators with T2DM decreased from 92.2% in 2020 to 65.9% in 2023. Initiators with T2DM had a higher median age (women 53 years, men 59 years) compared to non-T2DM initiators (45 years for both sexes) and were more likely to live in socioeconomically disadvantaged areas. Greater proportions of non-T2DM initiators were aged <40 years, were female, and resided in less disadvantaged areas. Non-T2DM female initiators were less likely to be obese than those with T2DM (75.7% vs 79.3%), but the converse was true for men (91.0% vs 77.3%). Almost 30% of male initiators and 20% of female initiators without T2DM had a body mass index of >40 kg/m(2). CONCLUSIONS: The use of semaglutide in Australia is expanding rapidly, particularly among individuals without T2DM. Patterns in general practice prescribing of semaglutide differ by sex, T2DM status, and socioeconomic factors, raising important questions about equitable access. These trends underscore the need for coordinated policy responses to support fair and sustainable use as demand continues to grow. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Kuo, Nicholas I-Hsien AU - Kuo NI AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. FAU - Hill, Flynn AU - Hill F AD - New South Wales Ministry of Health, Sydney, NSW, Australia. FAU - Arnott, Clare AU - Arnott C AD - The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. FAU - Douglas, Kirsty AU - Douglas K AD - College of Health and Medicine, Australian National University, Canberra, ACT, Australia. FAU - Barbieri, Sebastiano AU - Barbieri S AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia; Queensland Digital Health Centre, University of Queensland, Brisbane, Qld, Australia. FAU - Ferdousi, Shahana AU - Ferdousi S AD - Western Sydney Primary Health Network, Westmead, NSW, Australia. FAU - Gandomkar, Ziba AU - Gandomkar Z AD - Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. FAU - Gallego-Luxan, Blanca AU - Gallego-Luxan B AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. FAU - Woodward, Mark AU - Woodward M AD - The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; The George Institute for Global Health, School of Public Health, Imperial College London, London, UK. FAU - Jorm, Louisa AU - Jorm L AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. Electronic address: l.jorm@unsw.edu.au. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260209 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Middle Aged MH - New South Wales/epidemiology MH - *General Practice MH - Hypoglycemic Agents/therapeutic use MH - Adult MH - Follow-Up Studies OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Ozempic OT - Population health OT - Primary care OT - Semaglutide OT - Socioeconomic disparities OT - Type 2 diabetes COIS- Declaration of Competing Interests There are no conflicts of interest to disclose. EDAT- 2026/02/11 00:39 MHDA- 2026/04/05 04:22 CRDT- 2026/02/10 21:53 PHST- 2025/06/18 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/06 00:00 [accepted] PHST- 2026/04/05 04:22 [medline] PHST- 2026/02/11 00:39 [pubmed] PHST- 2026/02/10 21:53 [entrez] AID - S1443-9506(25)01690-7 [pii] AID - 10.1016/j.hlc.2025.09.012 [doi] PST - ppublish SO - Heart Lung Circ. 2026 Apr;35(4):554-562. doi: 10.1016/j.hlc.2025.09.012. Epub 2026 Feb 9. PMID- 41665888 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260616 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 7 DP - 2026 Jun 17 TI - GLP-1 receptor agonists and the risk of fragility fractures in older adults with type 2 diabetes. PG - 1949-1958 LID - 10.1210/clinem/dgag056 [doi] AB - CONTEXT: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly prescribed to older adults with type 2 diabetes for their metabolic and cardiovascular benefits, but their effects on bone health in this high-risk population are not well established. OBJECTIVE: The aim of this study was to assess the risk of fragility fractures associated with GLP-1RA therapy compared to sodium-glucose cotransporter-2 inhibitors or dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes. METHODS: We conducted a population-based retrospective new-user cohort study using the nationwide Clalit Health Services database. Participants included people with type 2 diabetes aged 65 years or older who initiated GLP-1RA therapy or comparator drugs during 2018 to 2022. The primary outcome was first fragility fracture. Follow-up continued until fracture occurrence, death, or March 31, 2024. An intention-to-treat approach was used. Baseline characteristics were balanced using inverse probability of treatment weighting based on propensity scores. Hazard ratios (HRs) were estimated using multivariate survival analysis accounting for the competing risk of death. RESULTS: The study included 46 177 participants: 11 257 GLP-1RA users and 34 920 comparator drug users. During a median follow-up of 34.7 months, 4086 (8.8%) individuals experienced a fragility fracture and 4595 (10.0%) died. In the propensity score-weighted model adjusted for baseline characteristics and competing risk of death, new users of GLP-1RAs had an 11% increased fracture risk compared to the comparator group (HR 1.11; 95% CI, 1.01-1.21). CONCLUSION: Initiating GLP-1RA therapy was associated with a modestly increased risk of fragility fractures in older adults with type 2 diabetes. These findings may inform clinical decisions by balancing clinical benefits against potential skeletal risks in this vulnerable population. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Kasher Meron, Michal AU - Kasher Meron M AUID- ORCID: 0000-0001-8149-8514 AD - Department of Endocrinology, Meir Medical Center, Kfar Saba 4428164, Israel. AD - School of Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel. AD - The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan 5266202, Israel. FAU - Hornik-Lurie, Tzipi AU - Hornik-Lurie T AUID- ORCID: 0000-0002-2122-5116 AD - Research Department, Meir Medical Center, Kfar Saba 4428164, Israel. FAU - Twig, Gilad AU - Twig G AUID- ORCID: 0000-0003-2829-3645 AD - The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan 5266202, Israel. AD - The Institute of Endocrinology Diabetes and Metabolism, Sheba Medical Center, Ramat Gan 5266202, Israel. AD - Department of Preventive Medicine and Epidemiology, School of Public Health, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel. AD - Incumbent of the Hella Gertner Chair for Research in Hypertension, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel. FAU - Rotman-Pikielny, Pnina AU - Rotman-Pikielny P AUID- ORCID: 0000-0002-6029-7593 AD - Department of Endocrinology, Meir Medical Center, Kfar Saba 4428164, Israel. AD - School of Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel. LA - eng PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Aged MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged, 80 and over MH - Follow-Up Studies MH - *Osteoporotic Fractures/epidemiology/chemically induced MH - *Fractures, Bone/epidemiology MH - Risk Factors MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects OTO - NOTNLM OT - GLP-1 receptor agonists OT - aged OT - bone OT - cohort studies OT - fractures OT - type 2 diabetes mellitus EDAT- 2026/02/10 19:00 MHDA- 2026/06/17 00:36 CRDT- 2026/02/10 12:15 PHST- 2025/12/14 00:00 [received] PHST- 2026/02/04 00:00 [accepted] PHST- 2026/06/17 00:36 [medline] PHST- 2026/02/10 19:00 [pubmed] PHST- 2026/02/10 12:15 [entrez] AID - 8471581 [pii] AID - 10.1210/clinem/dgag056 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 Jun 17;111(7):1949-1958. doi: 10.1210/clinem/dgag056. PMID- 41665869 OWN - NLM STAT- MEDLINE DCOM- 20260731 LR - 20260731 IS - 1460-2385 (Electronic) IS - 0931-0509 (Linking) VI - 41 IP - 8 DP - 2026 Jul 31 TI - Renal and urothelial cancer risks with SGLT2 inhibitors vs GLP-1 receptor agonists in type 2 diabetes: a target trial emulation. PG - 1543-1553 LID - 10.1093/ndt/gfag028 [doi] AB - BACKGROUND: The cardiovascular and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are well established among patients with type 2 diabetes (T2D). However, comparative evidence regarding cancer risk remains limited. METHODS: We compared the risk of renal cell carcinoma (RCC) and urothelial cell carcinoma (UCC), two malignancies with rising incidence and poor prognosis, in patients with T2D initiating SGLT2i vs GLP-1 RA. A new-user comparative cohort study with a target trial emulation framework was conducted using the TriNetX database from 1 June 2014, to 31 May 2024. We included adults with T2D who initiated SGLT2i and those who initiated GLP-1 RA. Patients were matched 1:1 using propensity scores based on age, sex, race, socioeconomic status, lifestyle factors, medical utilization, comorbidities, medications and laboratory measurements. Outcomes were incident RCC and UCC, analyzed with Kaplan-Meier plots and Cox regression. RESULTS: There were 294 664 patients in each group after matching, with 278 760 female individuals (47.3%), a mean age of 59.3 years, 377 312 White individuals (64.0%), 117 542 African American or Black individuals (20.0%), and 29 750 Asian individuals (5.1%). Over a mean follow-up of 44.2 months, SGLT2i use was associated with a lower incidence of RCC [1.07 vs 1.26 per 1000 patient-years; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.79-0.92] and UCC (0.89 vs 1.05 per 1000 patient-years; HR 0.85; 95% CI 0.78-0.92) than GLP-1 RA use. Subgroup analyses stratified by demographics and comorbidities showed consistent results. CONCLUSION: Based on the established cardiorenal benefits of both agents, our findings provide comparative safety and cancer risk data warranting further investigation. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Huang, Chien-Wei AU - Huang CW AUID- ORCID: 0000-0001-5753-9654 AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AUID- ORCID: 0000-0001-7935-0991 AD - Primary Aldosteronism Center, National Taiwan University Hospital, Taipei, Taiwan. FAU - Hsieh, Miyuki Hsing-Chun AU - Hsieh MH AUID- ORCID: 0000-0002-7995-7408 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Li, Chia-Jung AU - Li CJ AD - Department of Obstetrics and Gynaecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. AD - Institute of Biopharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Chang, Renin AU - Chang R AUID- ORCID: 0000-0003-1016-2233 AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. FAU - Chen, Jin-Shuen AU - Chen JS AD - Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. FAU - Tsai, Yau-Sheng AU - Tsai YS AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Sung, Junne-Ming AU - Sung JM AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. LA - eng GR - KSVGH115-D01-3/Kaohsiung Veterans General Hospital/ PT - Comparative Study PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Middle Aged MH - *Kidney Neoplasms/epidemiology/chemically induced/etiology/pathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Aged MH - Prognosis MH - *Carcinoma, Renal Cell/epidemiology/chemically induced/etiology MH - Risk Factors MH - Incidence MH - Follow-Up Studies MH - *Carcinoma, Transitional Cell/epidemiology/etiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonist OT - renal cell carcinoma OT - sodium-glucose cotransporter-2 inhibitor OT - type 2 diabetes OT - urothelial cell carcinoma EDAT- 2026/02/10 19:00 MHDA- 2026/07/31 06:36 CRDT- 2026/02/10 12:11 PHST- 2025/09/09 00:00 [received] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/07/31 06:36 [medline] PHST- 2026/02/10 19:00 [pubmed] PHST- 2026/02/10 12:11 [entrez] AID - 8471556 [pii] AID - 10.1093/ndt/gfag028 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Jul 31;41(8):1543-1553. doi: 10.1093/ndt/gfag028. PMID- 41660088 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260925 IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 14 DP - 2026 TI - The effects of GLP-1 receptor agonists on metabolic inflammatory markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. PG - e20710 LID - 10.7717/peerj.20710 [doi] LID - e20710 AB - OBJECTIVE: This study aimed to evaluate the impact of GLP-1 receptor agonists (GLP-1 RAs) on metabolic inflammatory markers in patients with type 2 diabetes mellitus (T2DM), providing evidence-based insights for their potential application in anti-inflammatory therapy. METHODS: Research questions were developed using the PICOS framework, and the study strictly adhered to PRISMA guidelines. Comprehensive literature searches were conducted across PubMed, EBSCO, Embase, Web of Science, and the Cochrane Library. Data synthesis and subgroup analyses (focusing on GLP-1 RA subtypes, treatment duration, and administration frequency) were performed using RevMan 5.4 software. RESULTS: Out of 1,347 articles retrieved, 25 studies were ultimately included, comprising a total sample of 1,878 participants (879 in the experimental groups and 999 in the control groups). Quality assessment indicated that most studies exhibited a low risk of bias, with only one study rated as high risk and three studies showing some concerns. Meta-analysis results demonstrated that 18 studies reported a significant reduction in CRP levels in T2DM patients treated with GLP-1 RAs (SMD = -0.39, 95% CI [-0.72 to -0.06], P = 0.02, I(2) = 88%). Although the results from 13 studies indicated a decreasing trend in IL-6 levels (SMD = -0.52), this change was not statistically significant (95% CI [-1.34 to 0.29], P = 0.21, I(2) = 96%). Additionally, 14 studies showed that GLP-1 RAs significantly reduced TNF-alpha levels (SMD = -0.51, 95% CI [-0.81 to -0.20], P = 0.001, I(2) = 81%). Subgroup analyses revealed that both the type of GLP-1 RA and a longer treatment duration (>/=36 weeks) were associated with more pronounced improvements in inflammatory markers. CONCLUSION: GLP-1 RAs exhibit a certain degree of anti-inflammatory effect in patients with T2DM, effectively reducing CRP and TNF-alpha levels. The anti-inflammatory efficacy appears to be influenced by both the type of drug used and the duration of treatment, with more pronounced effects observed for specific drug classes and with longer treatment periods. These findings provide further evidence supporting the use of GLP-1 RAs in the anti-inflammatory management of T2DM. CI - (c)2026 Zhao et al. FAU - Zhao, Fang AU - Zhao F AD - Department of Sports Teaching and Research, Lanzhou University, Lanzhou, GanSu, China. FAU - Wang, Haoshu AU - Wang H AD - School of Physical Education, Southwest Medical University, Luzhou, Sichuan, China. FAU - Li, Shenguang AU - Li S AD - School of Physical Education, Huzhou University, Huzhou, Zhejiang, China. FAU - Yun, Hezhang AU - Yun H AD - Faculty of Health Sciences and Sports, Macao Polytechnic University, Macao, China. AD - School of Physical Education, Zhejiang Guangsha Vocational and Technical University of Construction, Dongyang, Zhejiang, China. FAU - Su, Wenbo AU - Su W AD - Department of Sports Teaching and Research, Lanzhou University, Lanzhou, GanSu, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260203 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Biomarkers/blood MH - *Hypoglycemic Agents/therapeutic use MH - *Inflammation/drug therapy MH - C-Reactive Protein/metabolism/analysis MH - Interleukin-6/blood MH - Tumor Necrosis Factor-alpha/blood PMC - PMC12880101 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Inflammatory markers OT - Meta-analysis OT - Metabolic inflammation OT - Systematic review OT - Type 2 diabetes mellitus COIS- The authors declare there are no competing interests. EDAT- 2026/02/09 12:53 MHDA- 2026/02/09 12:54 PMCR- 2026/02/03 CRDT- 2026/02/09 06:58 PHST- 2025/06/18 00:00 [received] PHST- 2025/12/10 00:00 [accepted] PHST- 2026/02/09 12:54 [medline] PHST- 2026/02/09 12:53 [pubmed] PHST- 2026/02/09 06:58 [entrez] PHST- 2026/02/03 00:00 [pmc-release] AID - 20710 [pii] AID - 10.7717/peerj.20710 [doi] PST - epublish SO - PeerJ. 2026 Feb 3;14:e20710. doi: 10.7717/peerj.20710. eCollection 2026. PMID- 41655841 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1097-6787 (Electronic) IS - 0190-9622 (Linking) VI - 94 IP - 6 DP - 2026 Jun TI - Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with psoriasis and comorbid type 2 diabetes: A population-based target trial emulation. PG - 1686-1696 LID - S0190-9622(26)00171-4 [pii] LID - 10.1016/j.jaad.2026.02.008 [doi] AB - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) offer cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: To evaluate safety and effectiveness of SGLT2i in improving clinical outcomes in patients with psoriasis and comorbid T2DM, compared with dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 receptor agonists (GLP1RA). METHODS: This emulated target trial included adults with psoriasis and T2DM initiating SGLT2i, DPP4i, or GLP1RA between 2013 and 2025. SGLT2i initiators were propensity score-matched to DPP4i initiators and GLP1RA initiators, respectively. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the outcomes. RESULTS: A total of 8799 SGLT2i initiators and 8799 matched DPP4i initiators with psoriasis and comorbid T2DM, and 11,550 SGLT2i initiators and 11,550 matched GLP1RA initiators, were included. Compared with DPP4i, treatment with SGLT2i was associated with significantly lower all-cause mortality (HR = 0.633, 95% CI = 0.564-0.711) and reduced risks of emergency visits (HR = 0.915, 95% CI = 0.871-0.961), acute kidney injury (HR = 0.834, 95% CI = 0.759-0.916), chronic kidney disease (HR = 0.866, CI = 0.791-0.949), end-stage renal disease (HR = 0.555, 95% CI = 0.438-0.703), and severe sepsis (HR = 0.689, CI = 0.594-0.799). Compared with GLP1RA, treatment with SGLT2i was associated with reduced risks of asthma (HR = 0.822, 95% CI = 0.713-0.946), depression (HR = 0.887, CI = 0.801-0.983), sleep disorders (HR = 0.856, CI = 0.783-0.936), and malignancies (HR = 0.852, 95% CI = 0.764-0.951). LIMITATIONS: Retrospective design. CONCLUSION: Treatment with SGLT2i was associated with favorable clinical outcomes in patients with psoriasis and comorbid T2DM. These findings support investigation of SGLT2i as an adjunct therapy in this population. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Cheng, Debby AU - Cheng D AD - Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Ji, Helen AU - Ji H AD - Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Theodosakis, Nicholas AU - Theodosakis N AD - Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Noe, Megan H AU - Noe MH AD - Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Chen, Steven T AU - Chen ST AD - Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. FAU - Ma, Kevin Sheng-Kai AU - Ma KS AD - Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts; Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: kevinskma1@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260206 PL - United States TA - J Am Acad Dermatol JT - Journal of the American Academy of Dermatology JID - 7907132 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Psoriasis/drug therapy/epidemiology/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Comorbidity OTO - NOTNLM OT - anti-inflammatory therapy OT - comorbidity management OT - diabetes OT - general dermatology OT - medical dermatology OT - psoriasis OT - sodium-glucose cotransporter-2 inhibitors COIS- Conflicts of interest Dr Megan Noe was affiliated with Brigham and Women's Hospital at the time the work was conducted. She is currently an employee of Sanofi and receives a salary. Dr Noe previously received research grants from Boehringer Ingelheim and Bristol Myers Squibb, served as a consultant for Boehringer Ingelheim, Argenx and Takeda, and received honoraria from these entities. Dr Steven Chen has received honoraria from Pfizer for advisory board work. EDAT- 2026/02/09 00:29 MHDA- 2026/05/22 06:37 CRDT- 2026/02/08 19:15 PHST- 2025/04/06 00:00 [received] PHST- 2026/02/02 00:00 [revised] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/05/22 06:37 [medline] PHST- 2026/02/09 00:29 [pubmed] PHST- 2026/02/08 19:15 [entrez] AID - S0190-9622(26)00171-4 [pii] AID - 10.1016/j.jaad.2026.02.008 [doi] PST - ppublish SO - J Am Acad Dermatol. 2026 Jun;94(6):1686-1696. doi: 10.1016/j.jaad.2026.02.008. Epub 2026 Feb 6. PMID- 41655764 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260620 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 10 IP - 6 DP - 2026 Jun TI - Ocular Outcomes with Tirzepatide versus Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes. PG - 625-632 LID - S2468-6530(26)00046-1 [pii] LID - 10.1016/j.oret.2026.02.002 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown both protective and adverse effects on ocular outcomes. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, achieves greater glycemic and cardiometabolic improvements than non-GIP agonistic GLP-1 RAs, yet its ocular safety profile remains poorly characterized. PURPOSE: To compare the risk of retinal complications in patients with type 2 diabetes (T2D) treated with tirzepatide versus non-GIP GLP-1 RAs. DESIGN: A retrospective cohort study analyzed a nationwide electronic health records network from June 2022 to June 2025. PARTICIPANTS: Adults with T2D initiating tirzepatide or a non-GIP GLP-1 RA, with no prior use of either drug class. Individuals who initiated any other second-line glucose-lowering therapies within 6 months before or during the study period were excluded to isolate the effect of the medication. METHODS: A cohort of patients initiating therapy with tirzepatide was compared with another cohort initiating a non-GIP GLP-1 RA. Hazard ratios (HRs) for several ocular outcomes over a 36-month follow-up period were calculated, using propensity score-matched cohorts (1:1) to address confounding from demographics, comorbidities, and medication use. Similar analyses were performed among subpopulations of metformin or insulin users at cohort entry and among those who initiated additional antihyperglycemic therapy after index prescription. MAIN OUTCOME MEASURES: Risk of diabetic retinopathy (DR), diabetic macular edema (DME), vitreous hemorrhage (VH)/retinal detachment (RD), need for vision-saving interventions (intravitreal injections, panretinal photocoagulation, or pars plana vitrectomy), and nonarteritic anterior ischemic optic neuropathy (NAION). RESULTS: After matching, each cohort included 102 590 patients. Tirzepatide use was associated with decreased risk of DR (HR, 0.79; 95% confidence interval [CI], 0.72-0.87), DME (HR, 0.82; 95% CI, 0.68-0.96), VH/RD (HR, 066; 95% CI, 0.45-0.95), DR-related vision-saving interventions (HR, 0.65; 95% CI, 0.49-0.88), and NAION (HR, 0.45; 95% CI, 0.27-0.86) compared with non-GIP GLP-1 RA use. Associations were consistent among metformin and insulin users and in those who initiated additional antihyperglycemic therapy during follow-up. CONCLUSIONS: Among patients with T2D taking a GLP-1 RA, tirzepatide was associated with lower risks of retinal complications, need for vision-saving interventions, and NAION compared with GLP-1 RAs without GIP activity. These findings support a favorable ocular safety profile for tirzepatide, though confirmation in prospective studies is warranted. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - Hong, Alexander T AU - Hong AT AD - Keck School of Medicine of University of Southern California, Los Angeles, California. FAU - Lin, Forest AU - Lin F AD - University of South Florida Health Morsani College of Medicine, Tampa, Florida. FAU - Keenan, Jeremy D AU - Keenan JD AD - Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California. FAU - Stewart, Jay M AU - Stewart JM AD - Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California. Electronic address: jay.stewart@ucsf.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260206 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Blood Glucose) SB - IM MH - *Tirzepatide/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Female MH - Male MH - Hypoglycemic Agents/therapeutic use MH - *Diabetic Retinopathy/etiology/prevention & control MH - Middle Aged MH - Aged MH - Incretins/therapeutic use MH - Blood Glucose/metabolism OTO - NOTNLM OT - Diabetic retinopathy OT - GLP-1 receptor agonists OT - Nonarteritic anterior ischemic optic neuropathy OT - Retinal complications OT - Tirzepatide EDAT- 2026/02/09 00:29 MHDA- 2026/06/11 06:35 CRDT- 2026/02/08 19:13 PHST- 2025/09/24 00:00 [received] PHST- 2026/01/16 00:00 [revised] PHST- 2026/02/02 00:00 [accepted] PHST- 2026/06/11 06:35 [medline] PHST- 2026/02/09 00:29 [pubmed] PHST- 2026/02/08 19:13 [entrez] AID - S2468-6530(26)00046-1 [pii] AID - 10.1016/j.oret.2026.02.002 [doi] PST - ppublish SO - Ophthalmol Retina. 2026 Jun;10(6):625-632. doi: 10.1016/j.oret.2026.02.002. Epub 2026 Feb 6. PMID- 41655226 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260616 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 7 DP - 2026 Jun 17 TI - Skeletal effect of semaglutide and tirzepatide in patients with increased risk of fractures. PG - 1959-1966 LID - 10.1210/clinem/dgag052 [doi] AB - CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP1-RA) have potent glucose-lowering and weight loss benefits, but their effects on bone remain unclear. OBJECTIVE: To investigate changes in bone mineral density (BMD) in patients using semaglutide (SEM) and tirzepatide (TIR), a dual agonist of GLP-1/glucose dependent insulinotropic polypeptide. METHODS: Single-center retrospective study. Adult patients using SEM/TIR for >/=6 months with DXA scans before initiation and at least 6 months after were matched by age, sex, BMI, and diabetes mellitus (DM) to nonusers with at least 2 DXA scans over the same period. The primary outcome was the percentage change in total hip (TH) BMD. RESULTS: We included 255 patients using SEM or TIR in the GLP-1 RA group (92% female, mean age 64 +/- 9 years, BMI 31.0 +/- 5.6 kg/m(2)) and 255 controls. After a median follow-up of 17 months, the GLP-1 RA group achieved a median 5% weight loss. Both groups had significant declines in BMD at TH and FN, with a similar magnitude between groups. In the GLP-1RA group, weight loss was directly associated with bone loss at the TH and FN (r = 0.32 for TH, r = 0.17 for FN, both P < .01). Among patients without DM, greater TH bone loss was noted in the GLP-1 RA group compared to controls (-1% vs -0.6%, P = .04), whereas TH bone loss was similar between groups among patients with DM. CONCLUSION: SEM/TIR use was associated with greater annualized TH bone loss in patients without DM, whereas TH bone loss was comparable between GLP-1 RA and controls in patients with DM. These findings suggest GLP-1 RA's effects on bone may differ by DM status, with weight loss driving bone loss in patients without DM. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Liu, Yi AU - Liu Y AUID- ORCID: 0009-0003-5448-3626 AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Walzer, Dalia AU - Walzer D AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Schmitz, Sarah AU - Schmitz S AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Shukla, Alpana P AU - Shukla AP AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Ma, Xiaoyue AU - Ma X AD - Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Chirko, Dawn AU - Chirko D AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Pipia, Ilissa AU - Pipia I AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Sathi, Swetha AU - Sathi S AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Shukairy, Uthman AU - Shukairy U AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Greenberg, Michael AU - Greenberg M AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Kashyap, Sangeeta R AU - Kashyap SR AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Stein, Emily M AU - Stein EM AD - Division of Endocrinology, Hospital for Special Surgery, New York, NY 10021, USA. LA - eng PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Tirzepatide MH - Semaglutide MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - Retrospective Studies MH - *Bone Density/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - *Fractures, Bone/prevention & control/epidemiology MH - Follow-Up Studies OTO - NOTNLM OT - bone loss OT - diabetes OT - obesity OT - osteoporosis OT - semaglutide OT - tirzepatide EDAT- 2026/02/08 18:28 MHDA- 2026/06/17 00:36 CRDT- 2026/02/08 13:12 PHST- 2025/11/13 00:00 [received] PHST- 2026/02/04 00:00 [accepted] PHST- 2026/06/17 00:36 [medline] PHST- 2026/02/08 18:28 [pubmed] PHST- 2026/02/08 13:12 [entrez] AID - 8467122 [pii] AID - 10.1210/clinem/dgag052 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 Jun 17;111(7):1959-1966. doi: 10.1210/clinem/dgag052. PMID- 41653035 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 56 IP - 2 DP - 2026 Feb TI - Beyond glycemic control: How incretins are changing the cardiovascular trajectories of diabetes and obesity. PG - e70184 LID - 10.1111/eci.70184 [doi] AB - BACKGROUND: Diabetes mellitus is a leading global health concern. The parallel rise in obesity has exacerbated this burden, with projections suggesting over half of the adult population will be overweight or obese by 2050. Incretin-based therapies have emerged as cornerstone treatments for type 2 diabetes (T2DM), offering glycemic control alongside promising cardiovascular and renal benefits. RESULTS: This review consolidates current evidence regarding the cardiovascular effects of incretin-based medications. GLP-1 receptor agonists (GLP-1RAs) have demonstrated protective effects in preclinical models. Clinical trials show modest but consistent reductions in major adverse cardiovascular events (MACE), with additional renal benefits. Conversely, DPP-4 inhibitors display cardiovascular neutrality. Real-world studies largely support the superiority of GLP-1RAs over other glucose-lowering agents (e.g. DPP-4 inhibitors, insulin) in reducing MACE, though their benefits in heart failure (HF) with reduced ejection fraction remain limited. Recent trials in patients with obesity-related HFpEF demonstrate that GLP-1RAs and dual GIP/GLP-1 agonists significantly improve symptoms, functional status, and reduce HF events. CONCLUSIONS: While incretin therapies represent a transformative advancement in cardiometabolic care, challenges remain-including gastrointestinal side effects, adherence issues, lean mass loss and cost. As next-generation agents (e.g. triple agonists) advance, lifestyle interventions remain essential for durable, management of diabetes, obesity and associated cardiovascular conditions. CI - (c) 2026 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - School of Medicine, University of Padova, Padova, Italy. LA - eng PT - Journal Article PT - Review PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Incretins/therapeutic use MH - *Obesity/complications/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Heart Failure/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control MH - Glycemic Control MH - Gastric Inhibitory Polypeptide/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcome trials OT - diabetes OT - heart failure EDAT- 2026/02/07 12:44 MHDA- 2026/02/07 12:45 CRDT- 2026/02/07 06:12 PHST- 2025/12/12 00:00 [received] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/02/07 12:45 [medline] PHST- 2026/02/07 12:44 [pubmed] PHST- 2026/02/07 06:12 [entrez] AID - 10.1111/eci.70184 [doi] PST - ppublish SO - Eur J Clin Invest. 2026 Feb;56(2):e70184. doi: 10.1111/eci.70184. PMID- 41651756 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260727 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) VI - 73 IP - 3 DP - 2026 Mar TI - Impact of oral semaglutide on quality of life and metabolic parameters in patients with type 2 diabetes mellitus: A multicenter observational study. PG - 501713 LID - S2530-0180(26)00013-2 [pii] LID - 10.1016/j.endien.2026.501713 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) significantly impacts the patients' quality of life due to chronic complications and associated comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated benefits in glycemic control. This study evaluates the effect of oral semaglutide on quality of life, metabolic parameters, and treatment adherence of T2DM patients. PATIENTS AND METHODS: We conducted a multicenter prospective observational study Galicia (Spain). A total of 43 adult T2DM patients on oral semaglutide were evaluated at baseline and 3-6 months later using validated questionnaires (DTSQ and EuroQol), anthropometric measures, and metabolic parameters. Changes in quality of life, HbA1c, weight, lipid profile, and insulin dose were analyzed. RESULTS: Oral semaglutide significantly improved quality of life according to the visual analog scale (from 62.8 to 72.6 points; p < 0.001) and DTSQ questionnaire (from 28.2 to 33.0 points; p < 0.001). Significant reductions were observed in HbA1c (8.3% to 7.2%; p < 0.001) and body weight (-4.9%; p = 0.018). The most common adverse effects were nausea and vomiting, reported by 39.5% of patients, with no impact on the overall quality of life. CONCLUSION: Oral semaglutide significantly improves quality of life and metabolic parameters in T2DM patients, with good tolerance and low discontinuation rates. These findings support its utility in the comprehensive management of T2DM. CI - Copyright (c) 2025 SEEN and SED. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Lago Garma, Javier AU - Lago Garma J AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Gil Mouce, Cristina AU - Gil Mouce C AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Lucus Augusti, Lugo, Spain. FAU - Rodriguez Novo, Nazareth AU - Rodriguez Novo N AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Lucus Augusti, Lugo, Spain. FAU - Diaz Trastoy, Olaia AU - Diaz Trastoy O AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruna, Spain; Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Santamaria Nieto, Alicia AU - Santamaria Nieto A AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ferrol, Ferrol, A Coruna, Spain. FAU - Perez Castro, Patricia AU - Perez Castro P AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Diaz Ortega, Carmen AU - Diaz Ortega C AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Fernandez Rodriguez, Eva AU - Fernandez Rodriguez E AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Palmeiro Carballeira, Regina AU - Palmeiro Carballeira R AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Pinal Osorio, Iria AU - Pinal Osorio I AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Prieto Tenreiro, Alma AU - Prieto Tenreiro A AD - Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Sanchez Sobrino, Paula AU - Sanchez Sobrino P AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. FAU - Tejera Perez, Cristina AU - Tejera Perez C AD - Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Pita Gutierrez, Francisco AU - Pita Gutierrez F AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain. Electronic address: franciscopitagutierrez@gmail.com. FAU - Villar Taibo, Rocio AU - Villar Taibo R AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruna, Spain. FAU - Vidal Casariego, Alfonso AU - Vidal Casariego A AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260205 PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Lipids) SB - IM MH - Semaglutide MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood/psychology MH - *Quality of Life MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects/pharmacology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Administration, Oral MH - Prospective Studies MH - Glycated Hemoglobin/analysis MH - Aged MH - Insulin/administration & dosage/therapeutic use MH - Body Weight/drug effects MH - Blood Glucose/analysis MH - Lipids/blood OTO - NOTNLM OT - Calidad de vida OT - Diabetes mellitus tipo 2 OT - Farmacos hipoglucemiantes OT - Hypoglycemic agents OT - Patient satisfaction OT - Quality of life OT - Satisfaccion del paciente OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest None declared. EDAT- 2026/02/07 00:31 MHDA- 2026/03/10 01:06 CRDT- 2026/02/06 21:54 PHST- 2025/05/26 00:00 [received] PHST- 2025/07/19 00:00 [revised] PHST- 2025/08/28 00:00 [accepted] PHST- 2026/03/10 01:06 [medline] PHST- 2026/02/07 00:31 [pubmed] PHST- 2026/02/06 21:54 [entrez] AID - S2530-0180(26)00013-2 [pii] AID - 10.1016/j.endien.2026.501713 [doi] PST - ppublish SO - Endocrinol Diabetes Nutr (Engl Ed). 2026 Mar;73(3):501713. doi: 10.1016/j.endien.2026.501713. Epub 2026 Feb 5. PMID- 41644273 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260730 IS - 1525-6049 (Electronic) IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 48 IP - 1 DP - 2026 Dec TI - Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis. PG - 2620155 LID - 10.1080/0886022X.2026.2620155 [doi] LID - 2620155 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in patients with chronic kidney disease (CKD), but existing evidence regarding their efficacy and safety remains inconsistent. To evaluate the cardiorenal outcomes and adverse effects of GLP-1 RAs in this population, we conducted a systematic review and meta-analysis of randomized controlled trials from PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to December 2024. Nine trials involving 21,717 patients, the vast majority of whom had T2DM, were included. GLP-1RAs treatment for CKD was associated with decreasing the incidence of major adverse kidney events (MAKE; RR, 0.84; 95% CI, 0.76-0.94) and major adverse cardiac and cerebrovascular events (MACE; RR, 0.84; 95% CI, 0.72-0.97), reducing all-cause mortality (RR, 0.83; 95% CI, 0.76-0.90) and albuminuria level (SMD, -1.22; 95% CI, -1.53 - 0.90). Gastrointestinal events associated with GLP-1 RA treatments including nausea (RR, 4.14; 95% CI, 2.70-6.33), vomiting (RR, 3.05; 95% CI, 1.88-4.97), diarrhea (RR, 2.65; 95% CI, 1.76-3.98), and dyspepsia (RR, 3.79; 95% CI, 1.02-14.12) have garnered significant attention. In conclusion, administration of GLP-1RAs treatment demonstrates excellent cardiorenal protective effects in CKD, primarily in patients with co-existing T2DM, though with notable gastrointestinal concerns. FAU - Wang, Yuqi AU - Wang Y AUID- ORCID: 0009-0003-9580-6145 AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Feng, Luda AU - Feng L AUID- ORCID: 0000-0002-7259-4421 AD - Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Wang, Yajing AU - Wang Y AD - Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China. FAU - Li, Boyang AU - Li B AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Liang, Ning AU - Liang N AD - Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Song, Xuan AU - Song X AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Qin, Jianguo AU - Qin J AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhang, Mianzhi AU - Zhang M AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Yu AU - Li Y AUID- ORCID: 0000-0002-2970-3522 AD - Beijing University of Chinese Medicine, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260205 PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC12879500 OTO - NOTNLM OT - CKD outcomes OT - GLP-1 receptor agonists OT - Semaglutide OT - liraglutide OT - meta-analysis COIS- The authors declare that they have no competing interests. EDAT- 2026/02/06 00:30 MHDA- 2026/02/06 00:31 PMCR- 2026/02/05 CRDT- 2026/02/05 21:02 PHST- 2026/02/06 00:31 [medline] PHST- 2026/02/06 00:30 [pubmed] PHST- 2026/02/05 21:02 [entrez] PHST- 2026/02/05 00:00 [pmc-release] AID - 2620155 [pii] AID - 10.1080/0886022X.2026.2620155 [doi] PST - ppublish SO - Ren Fail. 2026 Dec;48(1):2620155. doi: 10.1080/0886022X.2026.2620155. Epub 2026 Feb 5. PMID- 41643685 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 58 IP - 3 DP - 2026 Mar TI - Exploring the Therapeutic Potential of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis in Patients with Type 2 Diabetes: A Narrative Review. PG - 81-89 LID - 10.1055/a-2787-1205 [doi] AB - Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are increasingly concerning health issues, especially in people with type 2 diabetes mellitus, where metabolic problems drive liver disease progression. While lifestyle changes remain essential, new drug strategies-particularly sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists-have gained growing interest for their potential to protect the liver. This review examines how sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists might help treat metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, focusing on their mechanisms of action, study evidence, and results from meta-analyses. A thorough search of the literature found studies on how these drugs affect insulin sensitivity, liver fat, and inflammation. Preclinical models show that they can lower liver fat, reduce oxidative stress, and decrease fibrosis markers. Clinical trials and meta-analyses support their potential to improve liver enzyme levels, decrease liver fat, and slow fibrosis growth. Overall, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists appear promising in the management of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, especially in type 2 diabetes mellitus patients. Still, more long-term research studies are needed to confirm how well they work, how safe they are, and the best way to use them, either alone or in combination with other treatments. These drugs may represent important advances in the treatment of liver diseases linked to metabolic problems. CI - Thieme. All rights reserved. FAU - Al Rashid, Sulthan AU - Al Rashid S AD - Pharmacology, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, India. FAU - Suriyan, Arun AU - Suriyan A AD - Medical Gastroenterology, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, India. FAU - Bilal Azam, Mohamed AU - Bilal Azam M AD - Medical Gastroenterology, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, India. FAU - Balasubramanian, Rajkapoor AU - Balasubramanian R AUID- ORCID: 0000-0002-1125-7800 AD - Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, India. FAU - Pakkir Maideen, Naina Mohamed AU - Pakkir Maideen NM AD - Clinical Pharmacology, Pharmacy practice, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates. FAU - Chidambaram, Kumarappan AU - Chidambaram K AD - Pharmacology, College of Pharmacy King Khalid University, Abha 62223, Saudi Arabia. FAU - Amirthalingam, Palanisamy AU - Amirthalingam P AD - Pharmacy practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260205 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM EIN - Horm Metab Res. 2026 Feb 17. doi: 10.1055/a-2811-1672. PMID: 41702547 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Fatty Liver/drug therapy/metabolism/etiology MH - Animals MH - *Non-alcoholic Fatty Liver Disease/drug therapy COIS- The authors declare that they have no conflict of interest. EDAT- 2026/02/06 00:30 MHDA- 2026/03/18 01:43 CRDT- 2026/02/05 18:44 PHST- 2026/03/18 01:43 [medline] PHST- 2026/02/06 00:30 [pubmed] PHST- 2026/02/05 18:44 [entrez] AID - 10.1055/a-2787-1205 [doi] PST - ppublish SO - Horm Metab Res. 2026 Mar;58(3):81-89. doi: 10.1055/a-2787-1205. Epub 2026 Feb 5. PMID- 41640144 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260813 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 71 IP - 5 DP - 2025 Dec 2 TI - [A personalized, evidence-based approach to obesity therapy using clinical algorithms: semaglutide or tirzepatide]. PG - 19-30 LID - 10.14341/probl13677 [doi] AB - On June 26, 2025, a meeting of the expert working group was held in Moscow. The discussion focused on the personalized approach of tirzepatide (<>) and semaglutide (<>) in patients with excess body weight, obesity, and type 2 diabetes. Following the meeting, the objective was set to develop a consensus-based algorithm for prescribing these drugs to ensure their effective use in Russian clinical practice. FAU - Troshina, E A AU - Troshina EA AD - Endocrinology Research Centre. FAU - Antsiferov, M B AU - Antsiferov MB AD - Endocrinological Dispensary. FAU - Ametov, A S AU - Ametov AS AD - Russian Medical Academy of Continuing Professional Education. FAU - Galstyan, G R AU - Galstyan GR AD - Endocrinology Research Centre. FAU - Markova, T N AU - Markova TN AD - Russian University of Medicine. FAU - Romantsova, T I AU - Romantsova TI AD - Russian Medical Academy of Continuing Professional Education. FAU - Mazurina, N V AU - Mazurina NV AD - Endocrinology Research Centre. FAU - Koteshkova, O M AU - Koteshkova OM AD - Endocrinological Dispensary. LA - rus PT - English Abstract PT - Journal Article DEP - 20251202 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy MH - *Algorithms MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Precision Medicine/methods MH - Hypoglycemic Agents/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Evidence-Based Medicine PMC - PMC12954439 COIS- The authors declare that there are no conflicts of interest present. EDAT- 2026/02/05 06:31 MHDA- 2026/02/05 06:32 PMCR- 2025/12/02 CRDT- 2026/02/05 02:03 PHST- 2025/10/21 00:00 [received] PHST- 2025/10/21 00:00 [accepted] PHST- 2026/02/05 06:32 [medline] PHST- 2026/02/05 06:31 [pubmed] PHST- 2026/02/05 02:03 [entrez] PHST- 2025/12/02 00:00 [pmc-release] AID - 10.14341/probl13677 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2025 Dec 2;71(5):19-30. doi: 10.14341/probl13677. PMID- 41640110 OWN - NLM STAT- MEDLINE DCOM- 20260801 LR - 20260819 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Efficacy and Safety of Oral GLP-1 RA Orforglipron on Weight and Glycemic Control According to Diabetes Status: A Systematic Review and Meta-Analysis. PG - 881-886 LID - 10.1177/15209156261420404 [doi] AB - Excess body weight and poor metabolic control remain major contributors to cardiometabolic disease, highlighting the need for effective therapeutic options. This meta-analysis aimed to evaluate the efficacy and safety of once-daily oral orforglipron in obese adults with and without diabetes. Searches were conducted across four databases through November 2025. Five randomized controlled trials (n = 6140) were included. Orforglipron produced consistent, dose-dependent reductions in body weight, ranging from modest losses at 3 mg to more than 6 kg at 36 mg in patients with diabetes. Individuals without diabetes experienced greater weight reductions, approaching 12 kg at the highest dose. Significant improvements in body mass index, waist circumference, and glycated hemoglobin (HbA1c; -1.29%) were also observed. Gastrointestinal adverse events increased with higher dose, and no significant difference in the incidence of acute pancreatitis was identified. Overall, orforglipron demonstrated clinically meaningful metabolic benefits with an acceptable safety profile. FAU - Hammad, Noha AU - Hammad N AUID- ORCID: 0009-0003-3088-517X AD - Faculty of Medicine, Port-Said University, Port-Said, Egypt. FAU - Ramadan, Aya M AU - Ramadan AM AD - Faculty of Medicine, Menoufia University, Menoufia, Egypt. FAU - Nazmy, Ahmed AU - Nazmy A AD - Faculty of Medicine, Kafr-Elsheikh University, Kafr-Elsheikh, Egypt. FAU - Elazab, Ahmed AU - Elazab A AD - Faculty of Medicine, South Valley University, Qena, Egypt. FAU - Abdelaziz, Ahmed AU - Abdelaziz A AD - Division of Cardiology, Montefiore Health System/Albert Einstein College of Medicine, Bronx, New York, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260204 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 7ZW40D021M (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Glycemic Control MH - *Obesity/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Administration, Oral MH - Blood Glucose/drug effects MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - Glycated Hemoglobin/analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Body Weight/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Oxadiazoles MH - Fluorine Compounds OTO - NOTNLM OT - GLP-1 RA OT - diabetes mellitus OT - meta-analysis OT - obesity OT - orforglipron COIS- Author Disclosure StatementThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/02/05 06:31 MHDA- 2026/08/01 06:35 CRDT- 2026/02/05 01:45 PHST- 2026/08/01 06:35 [medline] PHST- 2026/02/05 06:31 [pubmed] PHST- 2026/02/05 01:45 [entrez] AID - 10.1177/15209156261420404 [doi] PST - ppublish SO - Diabetes Technol Ther. 2026 Aug;28(8):881-886. doi: 10.1177/15209156261420404. Epub 2026 Feb 4. PMID- 41640092 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260918 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 Suppl 2 IP - Suppl 2 DP - 2026 Sep TI - Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Use in Elderly People With Obesity-A Meta-Analysis. PG - 25-35 LID - 10.1002/oby.70098 [doi] AB - OBJECTIVE: This meta-analysis evaluates the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for the treatment of older adults with obesity compared to younger individuals. METHODS: A systematic review was conducted following PRISMA guidelines (PROSPERO CRD420251074381). PubMed, Embase, and Scopus were searched until May 17, 2025, for randomized controlled trials and observational studies assessing GLP-1 RA in adults >/= 65 years with obesity with or without type 2 diabetes. Random effects meta-analyses calculated the log odds ratios (LOR) for dichotomous outcomes and the mean differences (MD) for continuous outcomes, with equivalence testing via two one-sided tests (TOST) and meta-regression for baseline adjustments. RESULTS: Five studies involving 1229 participants were included. No significant difference in serious adverse events was found between older and younger adults (pooled LOR: 0.06, p = 0.9). Older adults had a trend toward lower frequency of nausea (LOR: -0.44, p = 0.06) but higher incidence of constipation (LOR: 0.72, p = 0.02) and hypoglycemia (LOR: 0.97, p < 0.001). Efficacy in metabolic and weight control was comparable. Additionally, one study suggested that liraglutide could reduce fat mass without worsening sarcopenia. CONCLUSIONS: GLP-1 RA therapy seems to be safe and effective in older adults with obesity, achieving similar effects on weight loss and glycemic control as in younger individuals. CI - (c) 2026 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Rego de Figueiredo, Ines AU - Rego de Figueiredo I AUID- ORCID: 0000-0002-6492-7185 AD - Multidisciplinary Unit of Bariatric and Metabolic Surgery, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. AD - Egas Moniz School of Health and Science, Almada, Portugal. AD - NOVA Medical School/Faculdade de Ciencias Medicas, New University of Lisbon, Lisbon, Portugal. FAU - Simas, Filipa Sofia AU - Simas FS AD - Multidisciplinary Unit of Bariatric and Metabolic Surgery, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. AD - Department of Nutrition, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. FAU - Ghiletchi, Angela AU - Ghiletchi A AD - Department of Internal Medicine, Hospital Garcia de Orta, Unidade Local de Saude Almada-Seixal, Almada, Portugal. FAU - Oliveira Torres, Joao AU - Oliveira Torres J AD - Multidisciplinary Unit of Bariatric and Metabolic Surgery, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. AD - NOVA Medical School/Faculdade de Ciencias Medicas, New University of Lisbon, Lisbon, Portugal. AD - Department of Endocrinology, Diabetes, and Metabolism, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. AD - Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. FAU - Silva-Nunes, Jose AU - Silva-Nunes J AD - Multidisciplinary Unit of Bariatric and Metabolic Surgery, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. AD - NOVA Medical School/Faculdade de Ciencias Medicas, New University of Lisbon, Lisbon, Portugal. AD - Department of Endocrinology, Diabetes, and Metabolism, Curry Cabral Hospital, Unidade Local de Saude Sao Jose, Centro Clinico Academico de Lisboa, Lisbon, Portugal. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260204 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Liraglutide/therapeutic use MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Female MH - Glucagon-Like Peptide-1 Receptor MH - Weight Loss/drug effects MH - Constipation/chemically induced MH - Nausea/chemically induced PMC - PMC13535706 OTO - NOTNLM OT - efficacy OT - elderly with obesity OT - glucagon-like peptide-1 receptor agonists OT - safety COIS- The authors declare no conflicts of interest. EDAT- 2026/02/05 06:32 MHDA- 2026/09/02 05:36 PMCR- 2026/09/02 CRDT- 2026/02/05 01:33 PHST- 2025/10/14 00:00 [revised] PHST- 2025/07/30 00:00 [received] PHST- 2025/10/14 00:00 [accepted] PHST- 2026/09/02 05:36 [medline] PHST- 2026/02/05 06:32 [pubmed] PHST- 2026/02/05 01:33 [entrez] PHST- 2026/09/02 00:00 [pmc-release] AID - OBY70098 [pii] AID - 10.1002/oby.70098 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Sep;34 Suppl 2(Suppl 2):25-35. doi: 10.1002/oby.70098. Epub 2026 Feb 4. PMID- 41640042 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260708 IS - 1744-8409 (Electronic) IS - 1744-666X (Linking) VI - 22 IP - 1 DP - 2026 Jan TI - The role of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in chronic obstructive pulmonary disease. PG - 31-41 LID - 10.1080/1744666X.2026.2625967 [doi] AB - INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide, with type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease being common co-morbidities associated with worse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, which were originally developed for treatment of T2DM and/or obesity, have recently been shown to reduce exacerbations in observational studies of patients with COPD, suggesting that repurposing GLP-1RAs and SGLT2 inhibitors could improve clinical outcomes in COPD. AREAS COVERED: COPD, diabetes, and obesity share several common inflammatory pathways, including macrophage dysfunction, inflammasome activation, and metabolic dysregulation. Here we review the pharmacology, pre-clinical, and emerging clinical data which could support repurposing of GLP-1RAs and SGLT2 inhibitors for use in COPD through a search of articles in PubMed and Medline from 01/1950 to 08/2025. EXPERT OPINION: Reevaluating metabolic therapeutic targets has the potential to redefine treatment strategies for patients with COPD and metabolic comorbidities. Potential mechanisms of action could be via modulation of the NLRP3 inflammasome and macrophage polarization or better control of co-morbid conditions. However, randomized controlled trials and mechanistic studies are needed to confirm these observational findings and elucidate underlying mechanisms. FAU - Mah, Jordina S Y AU - Mah JSY AD - National Heart and Lung Institute, Imperial College London, London, UK. FAU - Eng, Pei Chia AU - Eng PC AD - Endocrinology Department, National University Hospital, Singapore, Singapore. FAU - Izzi-Engbeaya, Chioma AU - Izzi-Engbeaya C AD - Department of Metabolism and Digestion, Imperial College London, London, UK. AD - Department of Medicine, Imperial College Healthcare NHS Trust, London, UK. FAU - Finney, Lydia J AU - Finney LJ AD - National Heart and Lung Institute, Imperial College London, London, UK. AD - Department of Medicine, Imperial College Healthcare NHS Trust, London, UK. LA - eng PT - Journal Article PT - Review DEP - 20260210 PL - England TA - Expert Rev Clin Immunol JT - Expert review of clinical immunology JID - 101271248 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Pulmonary Disease, Chronic Obstructive/drug therapy/immunology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism OTO - NOTNLM OT - Chronic obstructive pulmonary disease (COPD) OT - exacerbations OT - glucagon-like peptide-1 (GLP-1) receptor agonist OT - inflammation OT - obesity OT - sodium-glucose cotransporter-2 (SGLT2) inhibitor OT - type 2 diabetes EDAT- 2026/02/05 06:32 MHDA- 2026/02/19 07:03 CRDT- 2026/02/05 01:03 PHST- 2026/02/19 07:03 [medline] PHST- 2026/02/05 06:32 [pubmed] PHST- 2026/02/05 01:03 [entrez] AID - 10.1080/1744666X.2026.2625967 [doi] PST - ppublish SO - Expert Rev Clin Immunol. 2026 Jan;22(1):31-41. doi: 10.1080/1744666X.2026.2625967. Epub 2026 Feb 10. PMID- 41638310 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260625 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 6 DP - 2026 Jun TI - Lower Extremity Complications in Adults With Type 2 Diabetes Treated With Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas: An Emulated Target Trial. PG - 916-926 LID - S1530-891X(26)00029-7 [pii] LID - 10.1016/j.eprac.2026.01.012 [doi] AB - OBJECTIVE: Lower extremity complications significantly impact morbidity and health care costs among people with type 2 diabetes (T2D). Evidence regarding the impact of different glucose-lowering medications on these outcomes remains inconclusive. METHODS: We emulated a target trial using 2 linked national claims databases (Optum Labs Data Warehouse, Medicare fee-for-service). We included adults with T2D at moderate cardiovascular risk who initiated glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), or sulfonylurea between 2014 and 2021, and used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the incidence rates of the primary composite outcome of incident foot ulcer/abscess, osteomyelitis, Charcot arthropathy, or amputation across the 4 medication classes under the intention-to-treat framework. RESULTS: The weighted study cohort included 81,998 DPP-4i initiators, 43,734 GLP-1RA initiators, 57,399 SGLT2i initiators, and 206,374 sulfonylurea initiators; they were well balanced on all examined baseline characteristics. Sulfonylurea use was associated with a higher risk of the composite lower extremity complications outcome compared with DPP-4i (hazard ratio [HR] 1.15; 95% CI 1.11-1.19), GLP-1RA (HR 1.20; 95% CI 1.13-1.28), and SGLT2i (HR 1.08; 95% CI 1.02-1.14). SGLT2i use was also associated with a higher risk compared with GLP-1RA (HR 1.11; 95% CI 1.03-1.21). Amputation events were rare in all treatment groups. CONCLUSION: We observed greater relative risks of lower extremity complications with sulfonylurea use compared with DPP-4i, GLP-1RA, and SGLT2i use, and with SGLT2i use compared with GLP-1RA use. Reassuringly, the absolute event rate differences between the medication classes were <1%. Diabetes management teams may consider these medication-associated risks when selecting glucose-lowering therapies for individuals without high cardiovascular risk, especially those predisposed to lower extremity morbidity. CI - Copyright (c) 2026 AACE. Published by Elsevier Inc. All rights reserved. FAU - McCoy, Rozalina G AU - McCoy RG AD - Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; University of Maryland Institute for Health Computing, North Bethesda, MD; OptumLabs, Eden Prairie, MN. Electronic address: Rozalina.McCoy@som.umaryland.edu. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - OptumLabs, Eden Prairie, MN; Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, IL. FAU - Deng, Yihong AU - Deng Y AD - OptumLabs, Eden Prairie, MN; Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN. FAU - Chawla, Sagar AU - Chawla S AD - Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, Spokane, WA; Providence Medical Research Center, Spokane, WA. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, Yale School of Medicine, New Haven, CT; Department of Health Policy and Management, Yale School of Public Health, New Haven, CT. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT. LA - eng PT - Journal Article DEP - 20260202 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Secretagogues) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Insulin Secretagogues MH - *Lower Extremity/pathology MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - *Sulfonylurea Compounds/adverse effects OTO - NOTNLM OT - SGLT2 inhibitor OT - amputation OT - comparative effectiveness OT - lower extremity complications OT - trial emulation OT - type 2 diabetes COIS- Disclosure In the last 36 months, Dr McCoy has received support from the NIH and the American Diabetes Association for projects unrelated to this work; has served as a consultant to EmmiEducate(R) (Wolters Kluwer) and the Yale-New Haven Health System; and received speaking honoraria and travel support from the American Diabetes Association. Dr Neumiller receives research funding from the NIH and the American College of Clinical Pharmacy; reports serving as a consultant to Bayer, Eli Lilly, Boehringer Ingelheim, and Proteomics International; and reports receiving other support from the American Diabetes Association for projects unrelated to this work. Dr Galindo receives research funding from the NIH, Novo Nordisk, Boehringer, Eli Lilly, and Dexcom; and reports consulting/advisory feeds from Abbott Diabetes, Aztra-Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, Novo Nordisk, and Medtronic. Dr Umpierrez is supported by research grants from the NIH and has received research support (to Emory University) from Abbott, Dexcom, Corcept, and Bayer, and served as a member of advisory boards for Dexcom, Glucotrack, Corcept, and GlyCare. Dr Ross currently receives research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, the US Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), AHRQ, and Arnold Ventures; he formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST); and was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled September 2022. Dr Herrin currently receives support from the Centers for Medicare and Medicaid Services to develop measures of quality and equity; the NIH, Agency for Healthcare Research and Quality (AHRQ), PCORI, and the American Heart Association (AHA) for multiple research projects. All other authors have no conflicts of interest to disclose. EDAT- 2026/02/05 00:30 MHDA- 2026/06/13 00:38 CRDT- 2026/02/04 19:11 PHST- 2025/10/14 00:00 [received] PHST- 2025/12/12 00:00 [revised] PHST- 2026/01/23 00:00 [accepted] PHST- 2026/06/13 00:38 [medline] PHST- 2026/02/05 00:30 [pubmed] PHST- 2026/02/04 19:11 [entrez] AID - S1530-891X(26)00029-7 [pii] AID - 10.1016/j.eprac.2026.01.012 [doi] PST - ppublish SO - Endocr Pract. 2026 Jun;32(6):916-926. doi: 10.1016/j.eprac.2026.01.012. Epub 2026 Feb 2. PMID- 41637494 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260902 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 12 IP - 6 DP - 2026 Feb 6 TI - In vivo functional profiling and structural characterization of the human GLP1R A316T variant. PG - eadw0899 LID - 10.1126/sciadv.adw0899 [doi] LID - eadw0899 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human GLP1R A316T mouse model. Human GLP1R(A316T/A316T) mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in beta cell models demonstrated that human GLP1R A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R-targeting therapies. FAU - El Eid, Liliane AU - El Eid L AUID- ORCID: 0000-0002-6511-6210 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Manchanda, Yusman AU - Manchanda Y AUID- ORCID: 0000-0002-2874-5608 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Austin, Gregory AU - Austin G AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Deane-Alder, Kieran AU - Deane-Alder K AUID- ORCID: 0000-0003-2762-2240 AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Rujan, Roxana-Maria AU - Rujan RM AUID- ORCID: 0000-0002-4335-3338 AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. FAU - Mariam, Zamara AU - Mariam Z AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. FAU - Oqua, Affiong I AU - Oqua AI AUID- ORCID: 0000-0002-0584-120X AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Belousoff, Matthew J AU - Belousoff MJ AUID- ORCID: 0000-0002-3229-474X AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - de la Serna, Jorge Bernardino AU - de la Serna JB AUID- ORCID: 0000-0002-1396-3338 AD - National Heart and Lung Institute, Imperial College London, London, UK. FAU - Sloop, Kyle W AU - Sloop KW AUID- ORCID: 0000-0001-6748-9929 AD - Diabetes, Obesity and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. FAU - Rutter, Guy A AU - Rutter GA AUID- ORCID: 0000-0001-6360-0343 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. AD - CHUM Research Centre, Faculty of Medicine, University of Montreal, Montreal, QC, Canada. AD - Research Institute of the McGill University Health Centre, Montreal, QC, Canada. AD - LKC School of Medicine, Nanyang Technological University, Singapore. FAU - Montoya, Alex AU - Montoya A AUID- ORCID: 0000-0002-6501-883X AD - MRC Laboratory of Medical Sciences, London, UK. FAU - Withers, Dominic J AU - Withers DJ AUID- ORCID: 0000-0002-8009-7521 AD - MRC Laboratory of Medical Sciences, London, UK. AD - Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. FAU - Millership, Steven J AU - Millership SJ AUID- ORCID: 0000-0001-6947-7059 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Bouzakri, Karim AU - Bouzakri K AUID- ORCID: 0000-0002-0703-5105 AD - Centre Europeen d'Etude du Diabete, Strasbourg, France. FAU - Jones, Ben AU - Jones B AUID- ORCID: 0000-0003-0461-2584 AD - Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Reynolds, Christopher A AU - Reynolds CA AUID- ORCID: 0000-0001-9267-5141 AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. AD - School of Life Sciences, University of Essex, Colchester, UK. FAU - Sexton, Patrick M AU - Sexton PM AUID- ORCID: 0000-0001-8902-2473 AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Wootten, Denise AU - Wootten D AUID- ORCID: 0000-0003-4563-1642 AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Deganutti, Giuseppe AU - Deganutti G AUID- ORCID: 0000-0001-8780-2986 AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. FAU - Tomas, Alejandra AU - Tomas A AUID- ORCID: 0000-0002-2290-8453 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. LA - eng PT - Journal Article DEP - 20260204 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM UOF - bioRxiv. 2025 Jan 26:2024.10.19.619191. doi: 10.1101/2024.10.19.619191. PMID: 39484598 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Animals MH - Mice MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Molecular Dynamics Simulation MH - Insulin-Secreting Cells/metabolism MH - Protein Conformation MH - Blood Glucose/metabolism MH - Mutation, Missense MH - Disease Models, Animal MH - Homeostasis/physiology PMC - PMC13267291 COIS- P.M.S. is a cofounder and stockholder of Septerna Inc. and Dacra Therapeutics. D.W. is a Scientific Advisor and shareholder of Septerna Inc. and a cofounder of Dacra Therapeutics. K.W.S. is an employee of Eli Lilly and Company. A.T. has received funding from Eli Lilly and Company and Sun Pharmaceutical Industries. G.A.R. has received funding from Sun Pharmaceutical Industries. B.J. has received funding from Eli Lilly and Company and Metsera Inc. and acted as a consultant for Metsera Inc. All other authors declare that they have no competing interests. EDAT- 2026/02/04 19:36 MHDA- 2026/02/04 19:37 PMCR- 2026/02/04 CRDT- 2026/02/04 14:03 PHST- 2026/02/04 19:37 [medline] PHST- 2026/02/04 19:36 [pubmed] PHST- 2026/02/04 14:03 [entrez] PHST- 2026/02/04 00:00 [pmc-release] AID - adw0899 [pii] AID - 10.1126/sciadv.adw0899 [doi] PST - ppublish SO - Sci Adv. 2026 Feb 6;12(6):eadw0899. doi: 10.1126/sciadv.adw0899. Epub 2026 Feb 4. PMID- 41636679 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 2 DP - 2026 Feb TI - Beyond glycemic control: Sex differences shaping glucagon-like peptide-1 receptor agonist utilization in the United States. PG - 166-175 LID - 10.18553/jmcp.2026.32.2.166 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a modern class of medications initially approved for type 2 diabetes mellitus (T2DM) but now also widely used for obesity. Although these drugs offer significant benefits for glycemic control, weight loss, and cardiorenal health, studies consistently show a pronounced sex difference in their use. However, there is a scarcity of studies addressing the factors responsible for these sex differences in GLP-1RA utilization in the United States. OBJECTIVE: To examine time- and sex-specific factors associated with GLP-1RA utilization among US adults before and after the landmark approval of semaglutide for chronic weight management. METHODS: We analyzed data from the 2019-2022 Medical Expenditure Panel Survey, a nationally representative survey of US adults (aged >/=18 years). GLP-1RA use was identified via prescription drug files. Descriptive statistics and chi-square tests compared characteristics of GLP-1RA users by time and sex. Multivariable logistic regression models estimated associations between individual characteristics and GLP-1RA use, both overall and among time- and sex-stratified cohorts. Subgroup analysis was conducted in adults with T2DM. RESULTS: The weighted prevalence of GLP-1RA use increased significantly from 6,158,326 (0.47%) in 2019-2020 to 10,410,021 (0.79%) in 2021-2022 (P < 0.0001). The rate of use was 0.48% and 0.46% in women and men, respectively, in 2019-2020 (P = 0.837) and increased to 0.82% in women and 0.76% in men in 2020-2022 (P = 0.964). T2DM was the strongest predictor of GLP-1RA use (odds ratio [OR] = 56.1 [2019-2020] and OR = 32.7 [2021-2022]), but the proportion of users with T2DM slightly decreased over time (92.8% in 2019-2020 to 90.2% in 2021-2022 [P = 0.239]). This decrease was especially pronounced in women during the 2021-2022 period, with men exhibiting a notably higher proportion of T2DM patients (94.4%) compared with women (86.2%) (P = 0.002). The proportion of users with obesity increased significantly (5.3% to 9.2%, P = 0.024), nearly doubling among female users (4.9% to 10.6%). The association with obesity strengthened over time (OR = 1.85 to 5.59), especially among women (OR: 6.43 vs 2.04 in men). Among women, depression was linked to greater use. In patients with T2DM, the use of insulin and oral antidiabetic medications was associated with higher GLP-1RA utilization. CONCLUSIONS: This study confirms the increasing utilization of GLP-1RAs in the United States, particularly among women. Although type 2 diabetes remains the primary predictor of GLP-1RA use, obesity has emerged as a key associated factor, especially among women. The stronger associations observed in women with obesity and depression highlight the role of clinical and psychosocial factors, which underscores the need for sex-sensitive approaches in obesity and diabetes management. FAU - Ofili, Samuel C AU - Ofili SC AD - Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, TX. FAU - Chen, Hua AU - Chen H AD - Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, TX. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - United States MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Sex Factors MH - Middle Aged MH - Adult MH - *Glycemic Control/methods MH - Glucagon-Like Peptides/therapeutic use MH - Aged MH - Obesity/drug therapy MH - Young Adult MH - Blood Glucose/drug effects PMC - PMC12871523 EDAT- 2026/02/04 15:12 MHDA- 2026/02/04 15:13 PMCR- 2026/02/01 CRDT- 2026/02/04 10:33 PHST- 2026/02/04 15:13 [medline] PHST- 2026/02/04 15:12 [pubmed] PHST- 2026/02/04 10:33 [entrez] PHST- 2026/02/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.2.166 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Feb;32(2):166-175. doi: 10.18553/jmcp.2026.32.2.166. PMID- 41635458 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 1844-3117 (Electronic) IS - 1844-122X (Print) IS - 1844-122X (Linking) VI - 18 IP - 12 DP - 2025 Dec TI - Modulation of metabolic syndrome components by oral semaglutide in hypothyroid-T2DM patients: a retrospective analysis. PG - 1094-1099 LID - 10.25122/jml-2025-0144 [doi] AB - Metabolic syndrome (MetS) represents the concurrent manifestation of multiple cardiometabolic risk factors, including visceral obesity, hyperglycemia, hypertension, hypertriglyceridemia, and low HDL-cholesterol, cumulatively predisposing to accelerated atherosclerosis and type 2 diabetes mellitus (T2DM). Hypothyroidism frequently coexists with T2DM and further exacerbates insulin resistance (IR), lipid abnormalities, and systemic inflammation, increasing the prevalence and severity of MetS in this population. Oral semaglutide is a glucagon-like peptide-1 receptor agonist approved for T2DM management; however, its impact on MetS parameters in patients with coexisting hypothyroidism remains insufficiently explored. This study aimed to evaluate the effects of oral semaglutide on key MetS components in this high-risk subgroup. We conducted a single-center retrospective cohort study involving 51 adult patients with confirmed hypothyroidism and T2DM, on oral semaglutide (final dose = 14 mg daily) and monitored for 6 months. Clinical and biochemical parameters were analyzed, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, and lipid profile. At 6 months, mean HbA1c decreased by 6.7% (P < 0.001), BMI was reduced by 4.04% (P < 0.001), triglycerides decreased by 6.7% (P < 0.001), and HDL-C increased by 9% (P = 0.002). In this observational study, treatment with oral semaglutide was associated with improvements in several components of MetS among patients with coexisting hypothyroidism and T2DM. While these findings suggest a potential therapeutic role for semaglutide in complex metabolic profiles, they should be interpreted with caution due to the study's design limitations. Further prospective studies are warranted to confirm these observations and to explore the interaction between semaglutide and levothyroxine. CI - (c) 2025 The Author(s). FAU - Tilici, Dana-Mihaela AU - Tilici DM AD - Doctoral School, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Costinescu, Ruxandra-Mihaela AU - Costinescu RM AD - University Emergency Hospital of Bucharest, Bucharest, Romania. FAU - Paun, Diana-Loreta AU - Paun DL AD - Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Paun, Sorin Constantin AU - Paun SC AD - Bucharest Emergency Clinical Hospital, Bucharest, Romania. FAU - Guja, Cristian AU - Guja C AD - Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. LA - eng PT - Journal Article PL - Romania TA - J Med Life JT - Journal of medicine and life JID - 101477617 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Metabolic Syndrome/drug therapy/complications MH - Retrospective Studies MH - Female MH - Male MH - *Hypothyroidism/complications/drug therapy MH - Middle Aged MH - Administration, Oral MH - Glycated Hemoglobin/metabolism MH - Adult MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage PMC - PMC12863099 OTO - NOTNLM OT - BMI, body mass index OT - GLP-1 receptor agonist OT - GLP-1, glucagon-like peptide-1 OT - HDL, high-density lipoprotein OT - HbA1c, glycated hemoglobin OT - IR, insulin resistance OT - LDL, low-density lipoprotein OT - MetS, metabolic syndrome OT - SAH, systemic arterial hypertension OT - SCH, subclinical hypothyroidism OT - T2DM, type 2 diabetes mellitus OT - TSH, thyroid-stimulating hormone OT - dyslipidemia OT - hypothyroidism OT - insulin resistance OT - metabolic syndrome OT - oral semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/02/04 11:32 MHDA- 2026/02/04 11:33 PMCR- 2025/12/01 CRDT- 2026/02/04 04:06 PHST- 2025/09/18 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2026/02/04 11:33 [medline] PHST- 2026/02/04 11:32 [pubmed] PHST- 2026/02/04 04:06 [entrez] PHST- 2025/12/01 00:00 [pmc-release] AID - JMedLife-18-1094 [pii] AID - 10.25122/jml-2025-0144 [doi] PST - ppublish SO - J Med Life. 2025 Dec;18(12):1094-1099. doi: 10.25122/jml-2025-0144. PMID- 41635113 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20261016 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Prevalence and predictors of residual gastric content in patients with type 2 diabetes on GLP-1 receptor agonists: A prospective observational study. PG - 3612-3622 LID - 10.1111/dom.70537 [doi] AB - AIMS: To assess the prevalence and risk factors of increased residual gastric content (RGC) under fasting conditions in patients with type 2 diabetes mellitus (T2DM) treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), providing evidence for peri-procedural medication management. MATERIALS AND METHODS: This single-centre prospective cohort study enrolled inpatients with T2DM at the Endocrinology Department of Ningbo No.2 Hospital between April and December 2024. Patients aged 18-80 years with BMI <40 kg/m(2) were categorized as GLP-1 RA users or non-users. Those with conditions known to affect gastric motility were excluded. After a standard overnight fast, bedside gastric ultrasonography was performed. The primary outcome was the prevalence of increased RGC, defined as solid content or clear fluid volume >1.5 mL/kg. Secondary analyses explored associated risk factors. RESULTS: Of 390 patients included (237 [60.8%] male), 224 (57.4%) were GLP-1 RA users. After propensity score matching, the prevalence of increased RGC remained significantly higher in GLP-1 RA users compared with non-users (53.3% vs. 32.1%; p < 0.001). In multivariate logistic regression adjusted by inverse probability of treatment weighting (IPTW), GLP-1 RA use was robustly associated with increased RGC (OR 2.52; 95% CI 1.84-3.45). Notably, diabetic retinopathy (OR 1.84; 95% CI 1.14-2.99) and diabetic kidney disease (OR 1.67; 95% CI 1.17-2.39) emerged as independent risk factors, identifying a high-risk microvascular phenotype. Furthermore, among GLP-1 RA users, each additional day since the last GLP-1 RA dose reduced the odds of increased RGC by 23% (adjusted OR 0.77; 95% CI 0.65-0.90). CONCLUSIONS: GLP-1 RA therapy is a potent, independent driver of significant gastric retention in patients with T2DM, persisting despite standard fasting. Crucially, the presence of diabetic retinopathy or nephropathy identifies a "double-hit" high-risk phenotype, where pharmacological delay interacts with microvascular burden. These findings suggest that current fasting protocols may be insufficient for these patients, necessitating individualized preoperative assessment based on microvascular status and dosing timing. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Li, Xiao-Yu AU - Li XY AD - Department of Anesthesiology, Ningbo No.2 Hospital, Ningbo, China. FAU - Jin, Yun AU - Jin Y AD - Department of Anesthesiology, Fenghua District People's Hospital, Ningbo, China. FAU - Feng, Xiu-Ye AU - Feng XY AD - Department of Anesthesiology, Zhenhai Hospital of Traditional Chinese Medicine, Ningbo, China. FAU - Wang, Rui-Chun AU - Wang RC AD - Department of Anesthesiology, Ningbo No.2 Hospital, Ningbo, China. FAU - Zeng, Fan-Fu AU - Zeng FF AD - Center for Disease Control and Prevention of Zhenhai District, Ningbo, China. FAU - Qin, Jin-Ling AU - Qin JL AD - Department of Anesthesiology, Ningbo No.2 Hospital, Ningbo, China. FAU - Li, Jian-Hui AU - Li JH AD - Department of Endocrinology, Ningbo No.2 Hospital, Ningbo, China. FAU - Xia, Jin-Ying AU - Xia JY AD - Department of Endocrinology, Ningbo No.2 Hospital, Ningbo, China. FAU - Mo, Ye-Ping AU - Mo YP AD - Department of Anesthesiology, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China. FAU - Zhai, Xiao-Jie AU - Zhai XJ AD - Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo, China. FAU - Chen, Jun-Ping AU - Chen JP AD - Department of Anesthesiology, Ningbo No.2 Hospital, Ningbo, China. FAU - Lu, Bo AU - Lu B AUID- ORCID: 0000-0003-1815-6778 AD - Department of Anesthesiology, Ningbo No.2 Hospital, Ningbo, China. LA - eng GR - 2023KY272/Medical Scientific Research Foundation of Zhejiang Province, China/ GR - 2025KY259/Medical Scientific Research Foundation of Zhejiang Province, China/ GR - LGF22H090012/Zhejiang Provincial Public Service and Application Research Foundation/ GR - PPXK2024-05/Ningbo Medical and Health Brand Discipline/ GR - 202402225/Second Batch Agricultural and Technology Plan Projects in Fenghua District for the Year 2024/ GR - 202312/Medical Science and Technology Program Project of Zhenhai District Health Bureau/ PT - Journal Article PT - Observational Study DEP - 20260203 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - Prospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prevalence MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Risk Factors MH - Aged, 80 and over MH - Ultrasonography MH - Stomach/diagnostic imaging OTO - NOTNLM OT - diabetes mellitus OT - gastric ultrasound OT - glucagon-like peptide 1 receptor agonists OT - perioperative care OT - residual gastric content EDAT- 2026/02/04 11:33 MHDA- 2026/04/13 06:32 CRDT- 2026/02/04 01:54 PHST- 2026/01/27 00:00 [revised] PHST- 2025/12/15 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/04 11:33 [pubmed] PHST- 2026/02/04 01:54 [entrez] AID - 10.1111/dom.70537 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3612-3622. doi: 10.1111/dom.70537. Epub 2026 Feb 3. PMID- 41634285 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1937-6995 (Electronic) IS - 1556-9039 (Print) IS - 1556-9039 (Linking) VI - 22 IP - 2 DP - 2026 Apr TI - National Poison Center Trends in GLP-1 Receptor Agonist Exposures Following FDA Approval for Weight Loss. PG - 275-285 LID - 10.1007/s13181-026-01121-z [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are therapies for type 2 diabetes whose use expanded sharply after semaglutide's 2021 approval for obesity. Although gastrointestinal effects are well described, national patterns of acute GLP-1 RA exposures are poorly characterized. This study evaluated trends in GLP-1 RA exposures reported to U.S. poison centers, focusing on demographic shifts, exposure circumstances, and clinical outcomes before and after the 2021 FDA approval. METHODS: We analyzed human GLP-1 RA exposures reported to the National Poison Data System from 2012 to 2023, using July 1, 2021, to define pre- and post-approval periods. Demographics, exposure characteristics, therapies, and medical outcomes were compared using standardized statistical tests. Quarterly call counts were modeled with segmented Poisson regression to assess changes in reporting trajectory. RESULTS: A total of 10,033 exposures were identified (3,113 pre-approval; 6,920 post-approval). Semaglutide predominated post-approval (64.2%). The exposed population shifted younger and more female. Most cases were unintentional therapeutic errors with mild gastrointestinal symptoms. The proportion managed in or referred to a health care facility increased from 23.0% to 33.5% (RR = 1.46, [95% CI: 1.36, 1.57], p < 0.001). Segmented Poisson modeling demonstrated a significant inflection in call volume, with semaglutide exposures increasing an additional 9.9% per quarter after approval. CONCLUSIONS: GLP-1 RA exposures rose sharply following semaglutide's weight-loss approval, accompanied by increased health care utilization despite generally mild clinical effects. Although multiple factors likely contributed to these trends, improved patient counseling and clearer poison center guidance may help reduce preventable therapeutic errors and unnecessary emergency evaluation. CI - (c) 2026. The Author(s). FAU - Miller, Jordan AU - Miller J AD - College of AI, Cyber and Computing, UT San Antonio, San Antonio, TX, USA. FAU - Miller, Robert AU - Miller R AUID- ORCID: 0009-0000-8647-7552 AD - South Texas Poison Center, Department of Emergency Medicine, Long School of Medicine, UT San Antonio, San Antonio, TX, USA. MillerRS@uthscsa.edu. FAU - Varney, Shawn M AU - Varney SM AD - South Texas Poison Center, Department of Emergency Medicine, Long School of Medicine, UT San Antonio, San Antonio, TX, USA. FAU - Han, David AU - Han D AD - College of AI, Cyber and Computing, UT San Antonio, San Antonio, TX, USA. LA - eng PT - Journal Article DEP - 20260203 PL - United States TA - J Med Toxicol JT - Journal of medical toxicology : official journal of the American College of Medical Toxicology JID - 101284598 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Poison Control Centers/trends/statistics & numerical data MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States/epidemiology MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - Adult MH - *Weight Loss/drug effects MH - Aged MH - Adolescent MH - Drug Approval MH - Young Adult MH - Child MH - Child, Preschool MH - United States Food and Drug Administration MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13076849 OTO - NOTNLM OT - Glucagon-like peptide receptor agonists OT - Pharmacovigilance OT - Poison centers OT - Semaglutide COIS- Declarations. Ethics Approval: This study was determined to be exempt from human subjects review by our Institutional Review Board. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflict of Interest: All authors declare that they have no conflict of interest. Previous Presentation: Data in this manuscript were previously presented at the American College of Medical Toxicology's (ACMT) Annual Scientific Meeting, Vancouver, BC, 2025. EDAT- 2026/02/04 05:06 MHDA- 2026/04/13 12:38 PMCR- 2026/02/03 CRDT- 2026/02/03 23:30 PHST- 2025/10/10 00:00 [received] PHST- 2026/01/20 00:00 [accepted] PHST- 2025/12/21 00:00 [revised] PHST- 2026/04/13 12:38 [medline] PHST- 2026/02/04 05:06 [pubmed] PHST- 2026/02/03 23:30 [entrez] PHST- 2026/02/03 00:00 [pmc-release] AID - 10.1007/s13181-026-01121-z [pii] AID - 1121 [pii] AID - 10.1007/s13181-026-01121-z [doi] PST - ppublish SO - J Med Toxicol. 2026 Apr;22(2):275-285. doi: 10.1007/s13181-026-01121-z. Epub 2026 Feb 3. PMID- 41628920 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260716 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 2 DP - 2026 Feb 2 TI - Use of SGLT2 inhibitors and GLP-1 receptor agonists in patients with ischaemic heart disease and type 2 diabetes in Swedish primary care: a cross-sectional analysis of regional primary care registry data (QregPV). PG - e110395 LID - 10.1136/bmjopen-2025-110395 [doi] LID - e110395 AB - OBJECTIVES: To assess the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) among patients with coexisting ischaemic heart disease (IHD) and type 2 diabetes (T2D) in primary care, in relation to European guidelines. DESIGN: Cross-sectional observational study. SETTING: 209 primary healthcare centres in Region Vastra Gotaland, Sweden (population 1.8 million in 2023). PARTICIPANTS: 14 414 patients with registered prevalent diagnoses of coexisting IHD and T2D, September 2023, in QregPV, the regional primary care quality of care register in Region Vastra Gotaland. Data on dispensed drugs were retrieved from the regional prescribed drug register, Digitalis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of patients with dispensed SGLT2i or GLP-1 RA in relation to sex, age and primary healthcare centres (including private vs public ownership). The secondary outcome was estimated additional prescription costs. RESULTS: SGLT2i was dispensed to 37.2%, less often to women (adjusted OR (aOR) 0.64 (95% CI 0.59 to 0.70)). GLP-1 RA was dispensed to 10.0%, with no sex difference (aOR 1.04 (95% CI 0.92 to 1.18)). Use of SGLT2i and GLP-1 RA declined with age (p<0.001). Use across primary healthcare centres (95% central range) varied from 17.1% to 56.4% for SGLT2i and 0.0% to 23.4% for GLP-1 RA, without differences between private versus public primary healthcare centres (SGLT2i: aOR 0.95 (95% CI 0.85 to 1.06); GLP-1 RA: aOR 1.06 (95% CI 0.89 to 1.26)). Variation across primary healthcare centres was substantial (SGLT2i: adjusted median OR (aMOR) 1.29 (95% CI 1.23 to 1.36); GLP-1 RA: aMOR 1.48 (95% CI 1.37 to 1.62)). Treating all patients would increase the annual prescription costs, euro3.9 million for SGLT2i and euro10.4 million for GLP-1 RA. CONCLUSION: SGLT2i and GLP-1 RA were underutilised in patients with coexisting IHD and T2D. The sex disparity in SGLT2i use warrants attention, as does the substantial variation between primary healthcare centres and the challenges of implementing costly cardioprotective therapies. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. FAU - Andersson, Tobias AU - Andersson T AUID- ORCID: 0000-0003-1419-8460 AD - General Practice/Family Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden tobias.andersson@gu.se. AD - Regionhalsan R&D Centre, Skaraborg Primary Care, Skovde, Sweden. FAU - Bager, Johan-Emil AU - Bager JE AUID- ORCID: 0000-0002-7771-7216 AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. AD - Department of Emergency Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Hellgren, Margareta AU - Hellgren M AD - General Practice/Family Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Aberg, Maria AU - Aberg M AD - General Practice/Family Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. AD - Regionhalsan, Region Vastra Gotaland, Gothenburg, Sweden. FAU - Mourtzinis, Georgios AU - Mourtzinis G AUID- ORCID: 0000-0003-0147-8746 AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. AD - Department of Medicine, Geriatrics and Emergency Care Molndal, Sahlgrenska University Hospital, Gothenburg, Sweden. LA - eng PT - Journal Article PT - Observational Study DEP - 20260202 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Cross-Sectional Studies MH - Female MH - *Myocardial Ischemia/drug therapy/complications/epidemiology MH - Male MH - Sweden/epidemiology MH - Primary Health Care/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Middle Aged MH - Aged MH - Registries MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12878446 OTO - NOTNLM OT - Coronary heart disease OT - Diabetes Mellitus, Type 2 OT - Drug Therapy OT - Guideline Adherence OT - Primary Health Care COIS- Competing interests: J-EB has received financial compensation for advisory board participation from Servier and speaker honouraria from AstraZeneca, unrelated to the present work. MH has received lecture honouraria, unrelated to the present work. All other authors declare no competing interests. EDAT- 2026/02/03 00:27 MHDA- 2026/02/03 00:28 PMCR- 2026/02/02 CRDT- 2026/02/02 20:32 PHST- 2026/02/03 00:28 [medline] PHST- 2026/02/03 00:27 [pubmed] PHST- 2026/02/02 20:32 [entrez] PHST- 2026/02/02 00:00 [pmc-release] AID - bmjopen-2025-110395 [pii] AID - 10.1136/bmjopen-2025-110395 [doi] PST - epublish SO - BMJ Open. 2026 Feb 2;16(2):e110395. doi: 10.1136/bmjopen-2025-110395. PMID- 41627802 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260823 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 186 IP - 4 DP - 2026 Apr 1 TI - Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial. PG - 426-436 LID - 10.1001/jamainternmed.2025.7774 [doi] AB - IMPORTANCE: Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown. OBJECTIVE: To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analyzed from December 2024 to August 2025. INTERVENTION: Once-daily oral semaglutide or placebo in addition to standard of care. MAIN OUTCOMES AND MEASURES: Prespecified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death). RESULTS: Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomized, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 646 [6.7%] with unknown subtype). For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline (P for interaction = .06). Among participants with HF, the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction and 0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction. There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77). Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]). CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SOUL randomized clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03914326. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland. AD - Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London, England, United Kingdom. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, RWTH Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, School of Public Health, University of Washington, Seattle. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Faculty of Medicine, Imperial College London, London, England, United Kingdom. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bayer Tanggaard, Katrine AU - Bayer Tanggaard K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Tubingen, Germany. AD - Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich, Eberhard Karls University of Tubingen, Tubingen, Germany. AD - German Center for Diabetes Research (DZD), Tubingen, Germany. FAU - Connelly, Kim A AU - Connelly KA AD - Keenan Research Centre for Biomedical Science, Departments of Medicine and Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czechia. FAU - Cavender, Matthew A AU - Cavender MA AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Kellerer, Monika AU - Kellerer M AD - Department of Diabetology and Endocrinology, Clinic for Internal Medicine, Marienhospital Stuttgart, Stuttgart, Germany. FAU - Jhund, Pardeep S AU - Jhund PS AD - British Heart Foundation Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, United Kingdom. FAU - Gregersen, Soren AU - Gregersen S AD - Steno Diabetes Center Aarhus, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Nielsen, Olav Wendelboe AU - Nielsen OW AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lam, Carolyn S P AU - Lam CSP AD - National Heart Centre Singapore, Outram, Singapore. AD - Duke-National University of Singapore, Outram, Singapore. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Parkland Health System, Dallas. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - *Heart Failure/etiology/prevention & control/drug therapy MH - Male MH - Double-Blind Method MH - Administration, Oral MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use PMC - PMC12865694 COIS- Conflict of Interest Disclosures: Dr Pop-Busui reported personal fees from Novo Nordisk during the conduct of the study, as well as grants from the National Institute of Diabetes and Digestive and Kidney Diseases, Breakthrough T1D, Bayer, and Novo Nordisk, and personal fees from Lexicon, Roche Diagnostic, and Vertex outside the submitted work. Dr Rasmussen reported employment with and holding stocks in Novo Nordisk. Prof Deanfield reported honoraria and/or consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; grants from Alzheimer's Research UK, British Heart Foundation, Medical Research Council (UK), National Institute for Health and Care Research, Public Health England, MSD, Pfizer, Aegerion, Colgate, and Roche; personal fees from Caristo Diagnostics, eMed Healthcare, Floe Oral Care, Friede-Springer Cardiovascular Prevention Center, iOWNA, Philip Morris International Harm Reduction Group, and Smarter Cardiovascular Outcomes by Research and Education (SCORE); and serving as a member of study steering committees for Novo Nordisk (SOUL and SELECT) outside the submitted work. Dr Buse reported grants from Novo Nordisk during the conduct of the study, as well as grants from Corcept, Dexcom, GentiBio, and Novo Nordisk; personal fees from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Lilly, Embecta, General Medicines, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand; and stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health outside the submitted work. Prof Marx reported serving as a member of a steering committee for Novo Nordisk during the conduct of the study and other support paid to University Hospital from Boehringer Ingelheim, Bayer, MSD, AstraZeneca, Sanofi, Lilly, and Novo Nordisk outside the submitted work. Dr Mulvagh reported personal fees from Novo Nordisk for serving as a steering committee member during the conduct of the study, as well as personal fees from Merck outside the submitted work. Dr Inzucchi reported personal fees from Novo Nordisk during the conduct of the study, as well as personal fees from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Bayer, and Corcept outside the submitted work. Dr Mann reported personal fees from Novo Nordisk, Bayer, AstraZeneca, Cytel, Icon, IQVIA, and WCG during the conduct of the study. Dr Emerson reported personal fees from Novo Nordisk during the conduct of the study, as well as personal fees from Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GSK, Lilly, Novartis, Bristol Myers Squibb, and Sanofi outside the submitted work. Dr Poulter reported personal fees from Servier and Novo Nordisk outside the submitted work. Dr Engelmann reported employment with and shares in Novo Nordisk outside the submitted work. Dr Hovingh reported employment with and shares in Novo Nordisk during the conduct of the study. Dr Bayer Tanggaard reported employment with Novo Nordisk during the conduct of the study. Prof Birkenfeld reported departmental research support from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, and Lilly. Dr Connelly reported grants from Novo Nordisk and Lilly during the conduct of the study; personal fees from Abbott, Janssen, Novartis, Sanofi, and GSK, as well as grants from AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, and Servier outside the submitted work; and a patent for medical use of a dipeptidyl peptidase-4 inhibitor (Boehringer Ingelheim). Dr Haluzik reported personal fees from Novo Nordisk, Sanofi, Lilly, Berlin Chemie, GSK, and ProMed outside the submitted work. Dr Cavender reported personal fees from Novo Nordisk during the conduct of the study, as well as grants from Cleerly, Janssen, Silence Therapeutics, MGH, Amgen, and Boehringer Ingelheim, and personal fees from AbbVie, AOP Pharma, Corcept, Faraday, and New Amsterdam, outside the submitted work. Dr Kellerer reported trial participation funded by Novo Nordisk during the conduct of the study, as well as personal fees from Abbott Diabetes Care, AstraZeneca, Bayer AG, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, and SCIARC, and trial participation funded by AstraZeneca, Lilly, GSK, and Novo Nordisk outside the submitted work. Dr Jhund reported fees for trial work paid to employer from Novo Nordisk during the conduct of the study; grants and clinical trial fees paid to employer from AstraZeneca and Bayer, as well as grants from Roche and Analog Devices outside the submitted work; and serving as director for GCTP. Prof Nielsen reported employment with and stock in Novo Nordisk. Prof Lam reported grants from the National Medical Research Council of Singapore, Novo Nordisk, and Roche Diagnostics; advisory, consulting, and trial leadership roles with Alnylam Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Corteria, CPC Clinical Research, Cytokinetics, Lilly, Impulse Dynamics, Intellia Therapeutics, Janssen Research & Development, Medscape/WebMD Global, Merck, Novartis, Novo Nordisk, Pfizer, Quidel Corporation, Radcliffe Group, Roche, and Us2.ai; serving as cofounder and nonexecutive director of Us2.ai; and a patent for PCT/SG2016/050217 pending and US Patent Nos. 10,631,828 B1; US 10,702,247 B2; US 11,301,996 B2; US 11,446,009 B2; US 11,931,207 B2; US 12,001,939; and US 12,400,762 B2 issued. Prof McGuire reported personal fees from Novo Nordisk, Lilly, Boehringer Ingelheim, Lexicon, Amgen, Neurotronic, Kailera, Alveus, Regor, F. Hoffmann-La Roche, New Amsterdam, Metsera, and Novartis during the conduct of the study. No other disclosures were reported. FIR - Schelde, Peter B IR - Schelde PB FIR - Amod, Aslam IR - Amod A FIR - Mankovsky, Borys IR - Mankovsky B FIR - Desouza, Cyrus V IR - Desouza CV FIR - Gorgojo-Martinez, Juan J IR - Gorgojo-Martinez JJ FIR - Arechavaleta, Rosario IR - Arechavaleta R FIR - Tu, Shih-Te IR - Tu ST FIR - Francisco, Jose IR - Francisco J FIR - Sanchez Garcia, Robinson IR - Sanchez Garcia R FIR - Chun Chung Chow, Francis IR - Chun Chung Chow F FIR - Watada, Hirotaka IR - Watada H FIR - Yoon, Kun Ho IR - Yoon KH FIR - Perez Manghi, Federico IR - Perez Manghi F FIR - Pozzi, Jose M IR - Pozzi JM FIR - Lorenzatti, Alberto J IR - Lorenzatti AJ FIR - Visco, Virginia E IR - Visco VE FIR - Piskorz, Daniel IR - Piskorz D FIR - Nardone, Lucrecia IR - Nardone L FIR - Chahin, Mariano I IR - Chahin MI FIR - Bustamante Labarta, Miguel IR - Bustamante Labarta M FIR - Luquez, Cecilia IR - Luquez C FIR - MacKinnon, Ignacio J IR - MacKinnon IJ FIR - Pieber, Thomas IR - Pieber T FIR - Prager, Rudolf IR - Prager R FIR - Fliesser-Gorzer, Evelyn IR - Fliesser-Gorzer E FIR - Ebenbichler, Christoph IR - Ebenbichler C FIR - Fasching, Peter IR - Fasching P FIR - Mathieu, Chantal IR - Mathieu C FIR - De Block, Christophe IR - De Block C FIR - Duyck, Francis IR - Duyck F FIR - Heyns, Ellen IR - Heyns E FIR - Lapauw, Bruno IR - Lapauw B FIR - Turatti, Luiz A A IR - Turatti LAA FIR - Franco, Denise R IR - Franco DR FIR - Rea, Rosangela R IR - Rea RR FIR - Kurtz Lisboa, Hugo R IR - Kurtz Lisboa HR FIR - Salles, Joao E IR - Salles JE FIR - Saraiva, Jose F K IR - Saraiva JFK FIR - Fonseca, Alberto G T IR - Fonseca AGT FIR - Vidotti, Maria H IR - Vidotti MH FIR - Leite, Silmara O IR - Leite SO FIR - Aggarwal, Naresh IR - Aggarwal N FIR - Bajaj, Harpreet IR - Bajaj H FIR - Schlosser, Robert IR - Schlosser R FIR - Noronha, Luis IR - Noronha L FIR - Pedersen, Sue IR - Pedersen S FIR - Tellier, Guy IR - Tellier G FIR - Weisnagel, John IR - Weisnagel J FIR - Beca, Sorin IR - Beca S FIR - Alasaad, Hani IR - Alasaad H FIR - Punthakee, Zubin IR - Punthakee Z FIR - Mancini, John G B IR - Mancini JGB FIR - Tytus, Richard IR - Tytus R FIR - Ransom, Thomas P P IR - Ransom TPP FIR - Husain, Mansoor IR - Husain M FIR - Tsoukas, Michael IR - Tsoukas M FIR - Ji, Linong IR - Ji L FIR - Liu, Jun IR - Liu J FIR - Yuan, Guoyue IR - Yuan G FIR - Ye, Xinhua IR - Ye X FIR - Dong, Xiaolin IR - Dong X FIR - Bian, Fang IR - Bian F FIR - Angelo Cadena Bonfanti, A IR - Angelo Cadena Bonfanti A FIR - Hernandez Erazo, Ivan D IR - Hernandez Erazo ID FIR - Hernandez Ruiz, Eder A IR - Hernandez Ruiz EA FIR - Gomez Mesa, Juan E IR - Gomez Mesa JE FIR - Canecki-Varzic, Silvija IR - Canecki-Varzic S FIR - Vucak Loncar, Jelena IR - Vucak Loncar J FIR - Simegi-Djekic, Vesna IR - Simegi-Djekic V FIR - Ticinovic Kurir, Tina IR - Ticinovic Kurir T FIR - Tusek, Srecko IR - Tusek S FIR - Rahelic, Dario IR - Rahelic D FIR - Marusic, Srecko IR - Marusic S FIR - Kruljac, Ivan IR - Kruljac I FIR - Fabris Vitkovic, Daniela IR - Fabris Vitkovic D FIR - Oznerova, Martina IR - Oznerova M FIR - 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Rose, Ludger IR - Rose L FIR - Schaum, Thomas IR - Schaum T FIR - Schulze, Jorg IR - Schulze J FIR - Staudenmeyer, Andreas IR - Staudenmeyer A FIR - Wenzl-Bauer, Veronika IR - Wenzl-Bauer V FIR - Ma, Ronald C W IR - Ma RCW FIR - Thomas, Nihal IR - Thomas N FIR - Mohan, V IR - Mohan V FIR - Reddy, Vijay Sekhar IR - Reddy VS FIR - Rao, Paturi V IR - Rao PV FIR - Sahay, Rakesh IR - Sahay R FIR - Singh, Jasminder IR - Singh J FIR - Prakash, Anupam IR - Prakash A FIR - Tandon, Nikhil IR - Tandon N FIR - Marwah, Tiven IR - Marwah T FIR - Chaudhury, Tirthankar IR - Chaudhury T FIR - Ghosh, Sujoy IR - Ghosh S FIR - Kanungo, Alok K IR - Kanungo AK FIR - Mittal, Naveen IR - Mittal N FIR - Jacob, Jubbin J IR - Jacob JJ FIR - Chadha, Manoj IR - Chadha M FIR - Bhagwat, Nikhil M IR - Bhagwat NM FIR - Jain, Sunil M IR - Jain SM FIR - Thulaseedharan, N K IR - Thulaseedharan NK FIR - Girithara, Gopalakrishnan IR - Girithara G FIR - Desai, A IR - Desai A FIR - Sharma, S K IR - Sharma SK FIR - Murthy, Sreenivasa IR - Murthy S FIR - Sethi, Bipin K IR - Sethi BK FIR - Kadam, Yogesh IR - Kadam Y FIR - Kesavadev, Jothydev IR - Kesavadev J FIR - Daxini, Bipin IR - Daxini B FIR - Chawla, Rajeev IR - Chawla R FIR - Gopalakrishnan, Unnikrishnan A IR - Gopalakrishnan UA FIR - Baruah, Manash P IR - Baruah MP FIR - Reddy, Sudhakar P IR - Reddy SP FIR - Suryanarayana, K M IR - Suryanarayana KM FIR - Singh, Kiran P IR - Singh KP FIR - Saboo, Banshi IR - Saboo B FIR - Aharon-Hananel, Genya IR - Aharon-Hananel G FIR - Hochberg, Irit IR - Hochberg I FIR - Sofer, Yael IR - Sofer Y FIR - Tirosh, Amir IR - Tirosh A FIR - Shimon, Ilan IR - Shimon I FIR - Vishlitzky, Victor IR - Vishlitzky V FIR - Bashkin, Amir IR - Bashkin A FIR - Tsur, Anat IR - Tsur A FIR - Shechter, Michael IR - Shechter M FIR - Andreozzi, Francesco IR - Andreozzi F FIR - Setola, Emanuela IR - Setola E FIR - Consoli, Agostino IR - Consoli A FIR - Lupoli, Roberta IR - Lupoli R FIR - Genovese, Stefano IR - Genovese S FIR - Maranghi, Marianna IR - Maranghi M FIR - Lauro, Davide IR - Lauro D FIR - Citarrella, Roberto IR - Citarrella R FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Murdolo, Giuseppe IR - Murdolo G FIR - Di Carlo, Alberto IR - Di Carlo A FIR - Giorgino, Francesco IR - Giorgino F FIR - Buscemi, Silvio IR - Buscemi S FIR - Hanaoka, Keiichi IR - Hanaoka K FIR - Osonoi, Takeshi IR - Osonoi T FIR - Ohashi, Hiroshi IR - Ohashi H FIR - Ezaki, Hirotaka IR - Ezaki H FIR - Yuki, Haruhito IR - Yuki H FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Hata, Yoshiki IR - Hata Y FIR - Sugawara, Masahiro IR - Sugawara M FIR - Domae, Hiroshi IR - Domae H FIR - Iwata, Hiroshi IR - Iwata H FIR - Nishida, Yuya IR - Nishida Y FIR - Igarashi, Masaki IR - Igarashi M FIR - Fujino, Susumu IR - Fujino S FIR - Oiwa, Ako IR - Oiwa A FIR - Oh, Fumiki IR - Oh F FIR - Sueyoshi, Atsushi IR - Sueyoshi A FIR - Murakami, Takaaki IR - Murakami T FIR - Tanaka, Muhei IR - Tanaka M FIR - Idogaki, Akira IR - Idogaki A FIR - Onaka, Haruhiko IR - Onaka H FIR - Mizote, Isamu IR - Mizote I FIR - Doi, Masayuki IR - Doi M FIR - Ebisui, Osamu IR - Ebisui O FIR - Tanabe, Makito IR - Tanabe M FIR - Natsuaki, Masahiro IR - Natsuaki M FIR - Jinnouchi, Hideaki IR - Jinnouchi H FIR - Nakamura, Shuji IR - Nakamura S FIR - Wan Mohamed, Wan Mohd Izani IR - Wan Mohamed WMI FIR - Yahaya, Norhayati IR - Yahaya N FIR - Ratnasingam, Jeyakantha IR - Ratnasingam J FIR - Ong, Tiong Kiam IR - Ong TK FIR - Mohamad, Masni IR - Mohamad M FIR - Yusoff Azmi Merican, Nor Shaffinaz IR - Yusoff Azmi Merican NS FIR - Abdul Ghani, Rohana IR - Abdul Ghani R FIR - Adam, Noor Lita IR - Adam NL FIR - Fam, Tem Lom IR - Fam TL FIR - Tan, Florence H S IR - Tan FHS FIR - Morales Villegas, Enrique C IR - Morales Villegas EC FIR - Gonzalez-Galvez, Guillermo IR - Gonzalez-Galvez G FIR - Espinoza Peralta, Diego IR - Espinoza Peralta D FIR - Medina Pech, Carlos E IR - Medina Pech CE FIR - Garcia Ulloa, Ana C IR - Garcia Ulloa AC FIR - Laviada Molina, Hugo A IR - Laviada Molina HA FIR - Banda Elizondo, Ramiro G IR - Banda Elizondo RG FIR - Garza Ruiz, Jose A IR - Garza Ruiz JA FIR - Garcia Cantu, Elias A IR - Garcia Cantu EA FIR - van Bemmel, Thomas IR - van Bemmel T FIR - de Valk, Harold W IR - de Valk HW FIR - Kooy, Adriaan IR - Kooy A FIR - Lieverse, Louis IR - Lieverse L FIR - Landewe-Cleuren, S A N T IR - Landewe-Cleuren SANT FIR - Hoogenberg, Klaas IR - Hoogenberg K FIR - van Raalte, Daniel IR - van Raalte D FIR - Jebbink, Max IR - Jebbink M FIR - Oldenburg-Ligtenberg, Christine IR - Oldenburg-Ligtenberg C FIR - Abbink-Zandbergen, Evertine IR - Abbink-Zandbergen E FIR - Mihai, Bogdan IR - Mihai B FIR - Crisan, Carmen IR - Crisan C FIR - Filip, Iuliana IR - Filip I FIR - Busegeanu, Mihaela M IR - Busegeanu MM FIR - Roman, Gabriela IR - Roman G FIR - Mot, Alina C IR - Mot AC FIR - Nicoara, Anca IR - Nicoara A FIR - Anghel, Veronica IR - Anghel V FIR - Pletea, Noemi N IR - Pletea NN FIR - Suciu, Mirela IR - Suciu M FIR - Strajer, Daniela IR - Strajer D FIR - Cernea, Simona IR - Cernea S FIR - Zilov, Alexei IR - Zilov A FIR - Kobalava, Zhanna IR - Kobalava Z FIR - Ruyatkina, Ludmila A IR - Ruyatkina LA FIR - Suplotova, Lyudmila A IR - Suplotova LA FIR - Sergeeva-Kondrachenko, Marina Y IR - Sergeeva-Kondrachenko MY FIR - Yanovskaya, Maria E IR - Yanovskaya ME FIR - Kargina, Lubov IR - Kargina L FIR - Ignatyeva, Anna IR - Ignatyeva A FIR - Astamirova, Khavra IR - Astamirova K FIR - Zalevskaya, Alsu IR - Zalevskaya A FIR - Zagrebelnaya, Olga IR - Zagrebelnaya O FIR - Frolova, Elena V IR - Frolova EV FIR - Peskov, Andrey B IR - Peskov AB FIR - Mishchenko Golinskaya, Olga IR - Mishchenko Golinskaya O FIR - Otroshchenko, Olga IR - Otroshchenko O FIR - Gaysina, Leylya IR - Gaysina L FIR - Shabelnikova, Olesya Y IR - Shabelnikova OY FIR - Saprina, Tatiana V IR - Saprina TV FIR - Lysenko, Tatyana A IR - Lysenko TA FIR - Kunitsyna, Marina IR - Kunitsyna M FIR - Zyangirova, Svetlana T IR - Zyangirova ST FIR - Lalic, Nebojsa IR - Lalic N FIR - Lalic, Katarina IR - Lalic K FIR - Beljic Zivkovic, Teodora IR - Beljic Zivkovic T FIR - Kikovic, Sasa IR - Kikovic S FIR - Djukic, Aleksandar IR - Djukic A FIR - Pesic, Milica IR - Pesic M FIR - Dimic, Dragan IR - Dimic D FIR - Stokic, Edita IR - Stokic E FIR - Mitrovic, Milena IR - Mitrovic M FIR - Polovina, Snezana IR - Polovina S FIR - Djordjevic, Miodrag IR - Djordjevic M FIR - Sosovec, Dalibor IR - Sosovec D FIR - Pella, Daniel IR - Pella D FIR - Donicova, Viera IR - Donicova V FIR - Hanackova Prasekova, Sandra IR - Hanackova Prasekova S FIR - Koleny, Daniel IR - Koleny D FIR - Culak, Jan IR - Culak J FIR - Cerna, Katarina IR - Cerna K FIR - Hundza, Viktor IR - Hundza V FIR - Gmitrov, Juraj IR - Gmitrov J FIR - Lacka, Jozef IR - Lacka J FIR - Plasil, Radovan IR - Plasil R FIR - Bacus, Hajira B IR - Bacus HB FIR - Bhorat, Qasim E IR - Bhorat QE FIR - Joshi, Pankaj IR - Joshi P FIR - Lakha, Deepak R IR - Lakha DR FIR - Makan, Vikash IR - Makan V FIR - Ntusi, Ntobeko IR - Ntusi N FIR - Padayachee, Trevenesan IR - Padayachee T FIR - Seeber, Mary E IR - Seeber ME FIR - Pillay, Deenadayalan IR - Pillay D FIR - Joshi, Mukesh IR - Joshi M FIR - Mayet, Leila IR - Mayet L FIR - Lee, Joonyub IR - Lee J FIR - Kim, Sin Gon IR - Kim SG FIR - Min, KyungWan IR - Min K FIR - Kang, Eun Seok IR - Kang ES FIR - Lee, Woo Je IR - Lee WJ FIR - Choi, Sung Hee IR - Choi SH FIR - Lee, Chang Beom IR - Lee CB FIR - Lopez Suarez, Alejandro IR - Lopez Suarez A FIR - Garcia Ordonez, Miguel Angel IR - Garcia Ordonez MA FIR - Garcia Quintana, Antonio IR - Garcia Quintana A FIR - Mazon Ramos, Pilar IR - Mazon Ramos P FIR - Cigarran, Secundino IR - Cigarran S FIR - Barrios, Clara IR - Barrios C FIR - Soto Gonzalez, Alfonso IR - Soto Gonzalez A FIR - Jodar, Esteban IR - Jodar E FIR - Delgado Lista, Javier IR - Delgado Lista J FIR - Morales Portillo, Cristobal IR - Morales Portillo C FIR - Montalban Carrasco, Coral IR - Montalban Carrasco C FIR - Tinahones, Francisco IR - Tinahones F FIR - Huang, Chien-Ning IR - Huang CN FIR - Chen, Szu-Tah IR - Chen ST FIR - Buranasupkajorn, Patinut IR - Buranasupkajorn P FIR - Sriwijitkamol, Apiradee IR - Sriwijitkamol A FIR - Buranapin, Supawan IR - Buranapin S FIR - Suwanagool, Arisara IR - Suwanagool A FIR - Tantiwong, Puntip IR - Tantiwong P FIR - Boonyavarakul, Apussanee IR - Boonyavarakul A FIR - Benjachareonwong, Sunun IR - Benjachareonwong S FIR - Leelawattana, Rattana IR - Leelawattana R FIR - Vathesatogkit, Prin IR - Vathesatogkit P FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Sonmez, Yusuf A IR - Sonmez YA FIR - Oguz, Aytekin IR - Oguz A FIR - Tabak, Omur IR - Tabak O FIR - Kocak, Mustafa IR - Kocak M FIR - Sariakcali, Baris IR - Sariakcali B FIR - Bayram, Fahri IR - Bayram F FIR - Guclu, Metin IR - Guclu M FIR - Gurkan, Eren IR - Gurkan E FIR - Kebapci, Nur IR - Kebapci N FIR - Comlekci, Abdurrahman IR - Comlekci A FIR - Acibucu, Fettah IR - Acibucu F FIR - Ahbab, Suleyman IR - Ahbab S FIR - Bilen, Habib IR - Bilen H FIR - Urbanovych, Alina IR - Urbanovych A FIR - Kuskalo, Petro IR - Kuskalo P FIR - Bondarets, Iryna IR - Bondarets I FIR - Petrosyan, Olena IR - Petrosyan O FIR - Pashkovska, Nataliia IR - Pashkovska N FIR - Oleksyk, Olga IR - Oleksyk O FIR - Kaydashev, Igor IR - Kaydashev I FIR - Maliar, Kateryna IR - Maliar K FIR - Myshanych, Galyna IR - Myshanych G FIR - Bain, Stephen C IR - Bain SC FIR - Black, Duncan IR - Black D FIR - Johnston, Philip IR - Johnston P FIR - Dang, Cuong IR - Dang C FIR - Dhatariya, Ketan IR - Dhatariya K FIR - English, Patrick IR - English P FIR - Field, Ben IR - Field B FIR - Grimmer, Philip IR - Grimmer P FIR - Gunstone, Anthony IR - Gunstone A FIR - Ray, Sutapa IR - Ray S FIR - Tatovic, Danijela IR - Tatovic D FIR - Kernohan, Andrew IR - Kernohan A FIR - Lindsay, Robert IR - Lindsay R FIR - Mcknight, John A IR - Mcknight JA FIR - Park, Adrian IR - Park A FIR - Patel, Dipesh IR - Patel D FIR - Philip, Sam IR - Philip S FIR - Randeva, Harpal IR - Randeva H FIR - Sathyapalan, Thozhukat IR - Sathyapalan T FIR - Turner, Wayne IR - Turner W FIR - Wyatt, Nell IR - Wyatt N FIR - Allison, Dale C IR - Allison DC FIR - Awasty, Vivex IR - Awasty V FIR - Ayele, Etsegenet IR - Ayele E FIR - Bajaj, Chris IR - Bajaj C FIR - Budoff, Matthew J IR - Budoff MJ FIR - Busch, Robert IR - Busch R FIR - Casaubon, Luis IR - Casaubon L FIR - Chaidarun, Sushela S IR - Chaidarun SS FIR - Chochinov, Ronald H IR - Chochinov RH FIR - Chu, James W IR - Chu JW FIR - Daboul, Nizar Y IR - Daboul NY FIR - Dang, Andy H IR - Dang AH FIR - Everhart, Brian G IR - Everhart BG FIR - Arambasick, Justin IR - Arambasick J FIR - Fink, Raymond I IR - Fink RI FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Fogarty, Charles M IR - Fogarty CM FIR - Gilbert, Matthew P IR - Gilbert MP FIR - Johnson, David M IR - Johnson DM FIR - Krishnasamy, Sathya S IR - Krishnasamy SS FIR - Lane, Wendy S IR - Lane WS FIR - Nakhle, Samer N IR - Nakhle SN FIR - Levenson, David IR - Levenson D FIR - O'Donnell, Philip IR - O'Donnell P FIR - Weiss, Daniel IR - Weiss D FIR - Risser, Joseph A IR - Risser JA FIR - Wierum, Craig IR - Wierum C FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Gupta, Dinesh IR - Gupta D FIR - Philis-Tsimikas, Athena IR - Philis-Tsimikas A FIR - Pratley, Richard E IR - Pratley RE FIR - Mirza, Lubna IR - Mirza L FIR - Snyder, Brian IR - Snyder B FIR - Rasouli, Neda IR - Rasouli N FIR - Porter, John IR - Porter J FIR - Ledesma, Gilbert N IR - Ledesma GN FIR - Powell, Talessa IR - Powell T FIR - Tandron, Ileana J IR - Tandron IJ FIR - Lingvay, Ildiko IR - Lingvay I FIR - Reed, John C H 3rd IR - Reed JCH 3rd FIR - Patel, Minesh B IR - Patel MB FIR - Lovre, Dragana IR - Lovre D FIR - Chaicha-Brom, Tira IR - Chaicha-Brom T FIR - Jantzi, Curtis IR - Jantzi C FIR - Brautigam, Donald IR - Brautigam D FIR - Bao, Shichun IR - Bao S FIR - Mbogua, Caroline N IR - Mbogua CN FIR - Zemel, Leonard R IR - Zemel LR FIR - Hasan, Syed IR - Hasan S FIR - Rosenstock, Julio IR - Rosenstock J FIR - Tran, Hien IR - Tran H FIR - Poremba, John IR - Poremba J FIR - Baker, Claire IR - Baker C FIR - Prier, Kevin IR - Prier K FIR - Chilka, Sapna IR - Chilka S FIR - Agaiby, John M IR - Agaiby JM FIR - Condit, Jonathan IR - Condit J FIR - Eagerton, Donald C IR - Eagerton DC FIR - Huffman, David IR - Huffman D FIR - Cornett, George M IR - Cornett GM FIR - Traylor, Henry IR - Traylor H FIR - Brinson, Cynthia IR - Brinson C FIR - Bays, Harold E IR - Bays HE FIR - Jerkins, Terri IR - Jerkins T FIR - Nicol, Philip R IR - Nicol PR FIR - Siddiqui, Imran A IR - Siddiqui IA FIR - Hewitt, Mitzie IR - Hewitt M FIR - Odugbesan, Adeniyi O IR - Odugbesan AO FIR - Lillestol, Michael J IR - Lillestol MJ FIR - Thrasher, James R IR - Thrasher JR FIR - Gandy, Winston H Jr IR - Gandy WH Jr FIR - Pant, Nicole IR - Pant N FIR - Nagelberg, Steven IR - Nagelberg S FIR - Cannon, Kevin IR - Cannon K FIR - Anderson, Marshall W IR - Anderson MW FIR - Bhargava, Anuj IR - Bhargava A FIR - Doshi, Ankur IR - Doshi A FIR - Jardula, Michael F IR - Jardula MF FIR - Montero, Manuel IR - Montero M FIR - Purighalla, Raman S IR - Purighalla RS FIR - Warren, Mark L IR - Warren ML FIR - Harris, Kathleen IR - Harris K FIR - Jackson, Richard A IR - Jackson RA FIR - Khaira, Ajit S IR - Khaira AS FIR - Gonzalez-Orozco, Luis IR - Gonzalez-Orozco L FIR - Gagianas, Peter J IR - Gagianas PJ FIR - Pantalone, Kevin IR - Pantalone K FIR - Murray, Alexander V IR - Murray AV EDAT- 2026/02/03 00:06 MHDA- 2026/04/06 12:36 PMCR- 2026/02/02 CRDT- 2026/02/02 11:33 PHST- 2026/04/06 12:36 [medline] PHST- 2026/02/03 00:06 [pubmed] PHST- 2026/02/02 11:33 [entrez] PHST- 2026/02/02 00:00 [pmc-release] AID - 2844096 [pii] AID - ioi250094 [pii] AID - 10.1001/jamainternmed.2025.7774 [doi] PST - ppublish SO - JAMA Intern Med. 2026 Apr 1;186(4):426-436. doi: 10.1001/jamainternmed.2025.7774. PMID- 41627917 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260813 IS - 2641-7650 (Electronic) IS - 2641-7650 (Linking) VI - 7 IP - 6 DP - 2026 Jun 1 TI - Diabetic Ketoacidosis Risk in Sodium-Glucose Cotransporter 2 Inhibitors versus Glucagon-Like Peptide-1 Receptor Agonists Initiators with CKD Stages 3-4 and Type 2 Diabetes. PG - 1285-1295 LID - 10.34067/KID.0000001144 [doi] AB - KEY POINTS: The risk of diabetic ketoacidosis associated with sodium-glucose cotransporter 2 inhibitors among patients with CKD stages 3-4 and type 2 diabetes is not well established. We found that the overall incidence of hospitalization with diabetic ketoacidosis remained low among sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists initiators with CKD stages 3-4 and type 2 diabetes. sodium-glucose cotransporter 2 inhibitors was associated with a 40% higher risk of hospitalization with diabetic ketoacidosis compared with glucagon-like peptide-1 receptor agonists initiation. BACKGROUND: sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective in managing CKD and type 2 diabetes (T2D). However, there are concerns about an increased risk of diabetic ketoacidosis (DKA) associated with the use of SGLT2i, particularly in patients with CKD. METHODS: The is a population-based, new-user, active comparator cohort study comparing SGLT2i versus GLP-1 RA initiators using three US health care databases: Optum's deidentified Clinformatics Data Mart (2014-2024), Merative MarketScan (2014-2022), and Medicare Fee-for-Service (2014-2020). The exposure is initiation of either SGLT2i or GLP-1 RA, defined as a new prescription without prior use in 365 days. The primary outcome was hospitalization with DKA identified using inpatient International Classification of Diseases, Ninth/Tenth Revision codes. Incidence rates, rate differences, and hazard ratios were calculated. RESULTS: After 1:1 propensity score matching, the study population included 143,858 patients, 71,929 in the SGLT2i arm, and 71,929 in the GLP-1 RA arm. The mean age (SD) was 71.28 (8.16) years, and 48.8% were female. Patients initiating SGLT2i had higher risk of hospitalization with DKA compared with GLP-1 RA initiators (incidence rate 4.37 versus 3.13 events per 1000 person-years; rate differences 1.23 [95% confidence interval, 0.54 to 1.92]; hazard ratios 1.40 [95% confidence interval, 1.16 to 1.68]). The number needed to harm was 813 per 1000 person-years for SGLT2i compared with GLP-1 RA initiation. Results remained consistent in subgroup analyses stratified by age (younger than 70 versus 70 years or older), sex, body mass index (<30 versus >/=30 kg/m 2 ), frailty status, baseline cardiovascular disease, diabetic retinopathy, hyperglycemia, metformin use, and insulin use. CONCLUSIONS: The incidence rate of DKA among SGLT2i and GLP-1 RA initiators remained low overall. However, SGLT2i use was associated with a 40% increased risk of hospitalization with DKA compared with GLP-1 RA use among patients with CKD stages 3-4 and T2D. Clinicians should remain vigilant when monitoring patients with CKD and T2D treated with SGLT2i. CI - Copyright (c) 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology. FAU - Hansrivijit, Panupong AU - Hansrivijit P AUID- ORCID: 0000-0002-5041-4290 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Tesfaye, Helen AU - Tesfaye H AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Wexler, Deborah J AU - Wexler DJ AUID- ORCID: 0000-0001-6979-402 AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Paik, Julie M AU - Paik JM AUID- ORCID: 0000-0002-1315-5445 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts. LA - eng GR - R01DK135706/DK/NIDDK NIH HHS/United States GR - R01AR075117/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - 5U01FD007213/U.S. Food and Drug Administration/ GR - DB-2020C2-20326/PCORI/Patient-Centered Outcomes Research Institute/United States GR - R01DK135706/DK/NIDDK NIH HHS/United States GR - R01AR075117/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - 5U01FD007213/U.S. Food and Drug Administration/ GR - DB-2020C2-20326/PCORI/Patient-Centered Outcomes Research Institute/United States PT - Comparative Study PT - Journal Article DEP - 20260202 PL - United States TA - Kidney360 JT - Kidney360 JID - 101766381 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - *Diabetic Ketoacidosis/epidemiology/chemically induced MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Hospitalization/statistics & numerical data MH - Incidence MH - Aged MH - Middle Aged MH - Risk Factors MH - Hypoglycemic Agents/adverse effects PMC - PMC13337201 OTO - NOTNLM OT - CKD OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - acidosis OT - diabetes COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/B523. EDAT- 2026/02/02 19:41 MHDA- 2026/06/26 04:10 PMCR- 2026/02/02 CRDT- 2026/02/02 12:03 PHST- 2025/11/14 00:00 [received] PHST- 2026/01/16 00:00 [accepted] PHST- 2026/06/26 04:10 [medline] PHST- 2026/02/02 19:41 [pubmed] PHST- 2026/02/02 12:03 [entrez] PHST- 2026/02/02 00:00 [pmc-release] AID - 02200512-202606000-00011 [pii] AID - K360-2025-001369 [pii] AID - 10.34067/KID.0000001144 [doi] PST - ppublish SO - Kidney360. 2026 Jun 1;7(6):1285-1295. doi: 10.34067/KID.0000001144. Epub 2026 Feb 2. PMID- 41625236 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260708 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis. PG - 1734549 LID - 10.3389/fendo.2025.1734549 [doi] LID - 1734549 AB - BACKGROUND: Type 2 diabetes (T2D) is strongly linked to chronic inflammation and oxidative stress, which drive cardiovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate cardioprotective benefits that may extend beyond glycemic control, but their effects on key inflammatory and oxidative stress biomarkers compared to other glucose-lowering medications remain inconsistently reported across individual studies. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Databases were searched for RCTs comparing GLP-1 RAs against other antidiabetic drugs or placebo in adults with T2D, reporting changes in inflammatory biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha]) or the oxidative stress marker malondialdehyde (MDA). Data were pooled using a random-effects model, and outcomes were stratified by comparator type (placebo, insulin, other oral antidiabetic drugs [OADs]). RESULTS: Forty RCTs (n=6029 participants) were included. GLP-1 RA therapy significantly reduced CRP levels compared to placebo (SMD = -0.59; 95% CI: -0.84 to -0.34) and other OADs (SMD = -1.06; 95% CI: -1.64 to -0.47). A significant reduction in TNF-alpha was observed versus placebo (SMD = -0.61; 95% CI: -0.89 to -0.32) and oral antidiabetic drugs add on (SMD = -1.62; 95% CI: -2.86 to -0.38). Data for MDA were limited and showed a non-significant trend toward reduction. GLP-1 RAs also significantly reduced IL-6 versus insulin (SMD = -0.24; 95% CI: -0.46 to -0.02). While significant heterogeneity was noted across the analyses, sensitivity analyses confirmed a consistent direction of effect, reinforcing the class-wide anti-inflammatory properties of GLP-1 RAs. CONCLUSION: GLP-1 RAs significantly improve key biomarkers of systemic inflammation (CRP, TNF-alpha) in patients with T2D compared to various active comparators and placebo. These pleiotropic effects provide a mechanistic rationale for their cardiovascular benefits and support their use as a multifaceted therapeutic strategy in T2D management. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251157476, identifier CRD420251157476. CI - Copyright (c) 2026 Alrasheed, Mostafa, Madkhali and Khairy. FAU - Alrasheed, Tariq AU - Alrasheed T AD - Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Mostafa, Mohamed E A AU - Mostafa MEA AD - Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Madkhali, Mohammed A AU - Madkhali MA AD - Department of Internal Medicine, Division of Endocrinology, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia. FAU - Khairy, Hesham A AU - Khairy HA AD - Department of Anatomy and Physiology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260115 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Biomarkers) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Humans MH - Biomarkers/blood/metabolism MH - C-Reactive Protein/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Inflammation/drug therapy/metabolism/blood MH - Oxidative Stress/drug effects MH - Randomized Controlled Trials as Topic MH - Tumor Necrosis Factor-alpha PMC - PMC12852008 OTO - NOTNLM OT - GLP-1 RA OT - IL-6 OT - MDA OT - T2D OT - TNF-alpha OT - crp OT - inflammatory biomarker COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/02/02 18:13 MHDA- 2026/02/02 18:14 PMCR- 2026/01/15 CRDT- 2026/02/02 06:51 PHST- 2025/10/28 00:00 [received] PHST- 2025/12/15 00:00 [revised] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/02/02 18:14 [medline] PHST- 2026/02/02 18:13 [pubmed] PHST- 2026/02/02 06:51 [entrez] PHST- 2026/01/15 00:00 [pmc-release] AID - 10.3389/fendo.2025.1734549 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jan 15;16:1734549. doi: 10.3389/fendo.2025.1734549. eCollection 2025. PMID- 41622983 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study. PG - 3229-3237 LID - 10.1111/dom.70515 [doi] AB - AIM: Coronary artery calcium (CAC) scoring is observed to improve risk stratification for major adverse cardiovascular events (MACE). Semaglutide, a recently introduced anti-obesity drug, is very effective, but wider use is limited due to high costs. Hence, this study investigated the cost-effectiveness (CEA) of semaglutide across CAC groups. MATERIALS AND METHODS: CAC scores for 38 058 CLARIFY registry participants meeting SELECT criteria were included. They were stratified into four CAC groups: 0, 1-99, 100-399, >/=400. To determine MACE (composite of myocardial infarction, heart failure, stroke or all-cause mortality) risk across CAC groups, hazard ratios (HR) were estimated from multi-variable adjusted Cox proportional hazard models. Next, lifetime-horizon Markov models were created to simulate semaglutide therapy and the potential clinical benefit (reported as number needed to treat [NNT]) and CEA (estimated with incremental cost-effectiveness ratio [ICER]) were examined for CAC groups. Multiple scenarios to mimic real-world experience were fitted for robust sensitivity analyses. RESULTS: Compared to CAC = 0, MACE risk was higher for CAC >/=400 (HR: 1.97 [95% CI: 1.66-2.35]), heart failure (HR: 1.76 [95% CI: 1.36-2.28]), mortality (HR: 1.62 [95% CI: 1.21-2.17]). Modelling 3.3 years of semaglutide use resulted in potential MACE NNT values of 151 (95% CI: 108-302) and 34 (95% CI: 25-69) for CAC = 0 and CAC >/=400. Markov modelled ICER for semaglutide use reduced across CAC groups ($625 863/QALY [CAC = 0] vs. $168 666/QALY [CAC >/=400]). CONCLUSIONS: CAC scores have potential use as a tool to estimate potential clinical benefit and cost for lifetime semaglutide therapy among obese individuals. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ponnana, Sai Rahul AU - Ponnana SR AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Zhang, Tong AU - Zhang T AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Sirasapalli, Santosh Kumar AU - Sirasapalli SK AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Chen, Zhuo AU - Chen Z AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Dazard, Jean-Eudes AU - Dazard JE AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Surya, Niketh AU - Surya N AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Elhussain, Shamsa AU - Elhussain S AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Sivanantham, Kanimozhi AU - Sivanantham K AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Okyere, Robert AU - Okyere R AD - Department of Internal Medicine, University Hospitals, Cleveland, Ohio, USA. FAU - Neeland, Ian J AU - Neeland IJ AD - Department of Internal Medicine, University Hospitals, Cleveland, Ohio, USA. FAU - Rajagopalan, Sanjay AU - Rajagopalan S AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Deo, Salil V AU - Deo SV AUID- ORCID: 0000-0002-4729-1461 AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. AD - Surgical Services, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA. AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. LA - eng PT - Journal Article DEP - 20260202 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - SY7Q814VUP (Calcium) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - Humans MH - Cost-Benefit Analysis MH - Cost-Effectiveness Analysis MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Female MH - Male MH - Middle Aged MH - Risk Assessment MH - Aged MH - *Coronary Artery Disease/economics/epidemiology MH - *Coronary Vessels MH - *Vascular Calcification/epidemiology/economics MH - Calcium/metabolism/analysis MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/economics PMC - PMC12992155 OTO - NOTNLM OT - antiobesity drug OT - cohort study OT - database research OT - risk prediction OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/02/02 06:28 MHDA- 2026/03/17 06:47 PMCR- 2026/03/17 CRDT- 2026/02/02 04:34 PHST- 2026/01/09 00:00 [revised] PHST- 2025/11/16 00:00 [received] PHST- 2026/01/18 00:00 [accepted] PHST- 2026/03/17 06:47 [medline] PHST- 2026/02/02 06:28 [pubmed] PHST- 2026/02/02 04:34 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70515 [pii] AID - 10.1111/dom.70515 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3229-3237. doi: 10.1111/dom.70515. Epub 2026 Feb 2. PMID- 41621451 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260730 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 402 DP - 2026 Jun 1 TI - The effect of glucagon-like peptide 1 (GLP-1) receptor agonists on cognition: A systematic review of systematic reviews and meta-analyses. PG - 121310 LID - S0165-0327(26)00161-8 [pii] LID - 10.1016/j.jad.2026.121310 [doi] AB - BACKGROUND: Results from extant studies indicate that type 2 diabetes mellitus (T2DM) is associated with decreased cognitive function and increased risk for dementia, notably Alzheimer's Disease (AD). Herein, we aimed to evaluate the effect of glucacon-like peptide-1 receptor agonists (GLP-1 RAs) on cognitive measures in persons with cognitive impairment and T2DM from available systematic reviews and meta-analyses. METHODS: A literature search was conducted using Web of Science and MEDLINE from inception to July 15, 2025. Article screening and data extraction were conducted by three reviewers (H.B., C.D., S.L.). Primary research studies examining race, sex, children, animals and neurodegenerative diseases other than AD were excluded. RESULTS: Nine systematic reviews and meta-analyses examining the effect of GLP-1 RAs on cognitive function in adults with T2DM were included. Evidence suggests that GLP-1 RAs are associated with a reduction in overall cognitive decline in adults with T2DM and dementia/AD. Replicated findings from meta-analyses indicated that GLP-1 RAs improved performance on cognitive assessments (total learning; p = 0.039; p < 0.00001). Some meta-analyses observed a change in cognitive measures but lacked sufficient statistical significance (p > 0.05). CONCLUSIONS: GLP-1 RAs positively affect cognitive function in AD patients with T2DM. However, their efficacy on disparate cognitive domains requires further replication in larger scale controlled clinical trials. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Ballum, Hana AU - Ballum H AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: hana.ballum@mail.utoronto.ca. FAU - Dri, Christine AU - Dri C AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: christine.dri@mail.utoronto.ca. FAU - Liao, Sonya AU - Liao S AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: sonya.liao@mail.utoronto.ca. FAU - Yu, Minyi AU - Yu M AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: mindy.yu@mail.utoronto.ca. FAU - Le, Gia Han AU - Le GH AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: hanny.le@mail.utoronto.ca. FAU - Wong, Sabrina AU - Wong S AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: sabrinal.wong@mail.utoronto.ca. FAU - Teopiz, Kayla M AU - Teopiz KM AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: kayla.teopiz@mail.utoronto.ca. FAU - Kwan, Angela T H AU - Kwan ATH AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: angela.kwan@mail.utoronto.ca. FAU - Ho, Roger AU - Ho R AD - Department of Psychological Medicine, Yong Loo Lin School of Medicine, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Division of Life Science (LIFS), Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Hong Kong. Electronic address: rogercmho@ust.hk. FAU - Choi, Hayun AU - Choi H AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Veteran Health Service Medical Center, Seoul, Republic of Korea. Electronic address: hayun.choi@utoronto.ca. FAU - Rosenblat, Joshua D AU - Rosenblat JD AD - Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: joshua.rosenblat@uhn.ca. FAU - Vinberg, Maj AU - Vinberg M AD - The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk. FAU - K Y Lo, Heidi AU - K Y Lo H AD - Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong. Electronic address: lokaying@hku.hk. FAU - McIntyre, Roger S AU - McIntyre RS AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: roger.mcintyre@bcdf.org. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260130 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cognition/drug effects MH - *Cognitive Dysfunction/drug therapy MH - Alzheimer Disease MH - *Hypoglycemic Agents/therapeutic use MH - Cognitive Enhancement MH - Meta-Analysis as Topic OTO - NOTNLM OT - Alzheimer's Disease OT - Cognitive function OT - Dementia OT - Glucagon-like peptide 1 receptor agonist OT - Major neurocognitive disorders OT - Metabolic OT - Type 2 diabetes mellitus (T2DM) COIS- Declaration of competing interest Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Kayla M. Teopiz has received fees from Braxia Scientific Corp. Roger Ho received funding from the Institute for Health Innovation & Technology (iHeathtech) at the National University of Singapore (NUS, Other Operating Expenses: A-0001415-09-00). Maj Vinberg has received consultation fees from Lundbeck Pharma and Janssen Cilag. H.B., C.D., S.L., M.Y., G.H.L. and S.W. have no conflicts of interest to declare. EDAT- 2026/02/02 00:29 MHDA- 2026/02/24 00:29 CRDT- 2026/02/01 19:11 PHST- 2024/11/08 00:00 [received] PHST- 2026/01/26 00:00 [revised] PHST- 2026/01/28 00:00 [accepted] PHST- 2026/02/24 00:29 [medline] PHST- 2026/02/02 00:29 [pubmed] PHST- 2026/02/01 19:11 [entrez] AID - S0165-0327(26)00161-8 [pii] AID - 10.1016/j.jad.2026.121310 [doi] PST - ppublish SO - J Affect Disord. 2026 Jun 1;402:121310. doi: 10.1016/j.jad.2026.121310. Epub 2026 Jan 30. PMID- 41620207 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260729 IS - 1715-3360 (Electronic) IS - 0008-4182 (Linking) VI - 61 IP - 3 DP - 2026 Jun TI - Association between semaglutide use and thyroid eye disease-related outcomes in autoimmune thyroiditis with type II diabetes. PG - 665-669 LID - S0008-4182(26)00011-6 [pii] LID - 10.1016/j.jcjo.2026.01.010 [doi] AB - OBJECTIVE: To evaluate whether semaglutide use is associated with thyroid eye disease (TED)-related outcomes among patients with autoimmune thyroiditis and type II diabetes mellitus (T2DM). METHODS: Adults with thyrotoxicosis (International Classification of Diseases [ICD-10]: E05) and T2DM were identified from the TriNetX US Collaborative Network. T2DM was defined by ICD-10 (E11) or laboratory criteria. The exposed cohort included individuals prescribed semaglutide on or after its Foood and Drug Administration approval (December 5, 2017). The control cohort included patients treated with non-glucogon-like peptide-1 receptor agonist antihyperglycemic agents without prior glucagon-like peptide-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographics, comorbidities, medications, and health care utilization variables. Five-year outcomes included: (1) TED-related diagnoses; (2) systemic corticosteroid use; (3) TED-related surgical interventions; (4) radiation treatment; and (5) teprotumumab use. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: After matching, 23,279 patients were included per group (mean age: 60.1 years; 75% female). At 5-year, semaglutide users had lower rates of TED-related diagnoses (2.16% vs 2.82%; RR: 0.76; 95% CI: 0.68-0.86), systemic corticosteroid use (22.71% vs 26.39%; RR: 0.86; 95% CI: 0.82-0.90), TED-related surgical interventions (0.30% vs 0.42%; RR: 0.70; 95% CI: 0.51-0.96), and radiation treatment (1.17% vs 2.05%; RR: 0.57; 95% CI: 0.49-0.67). Teprotumumab use was rare and similar between groups (0.08% vs 0.08%; RR: 1.00; 95% CI: 0.52-1.92). CONCLUSIONS: Semaglutide use was associated with fewer TED-related diagnoses and treatments over 5 years, supporting a potential protective role. Further studies are warranted to confirm these associations and clarify underlying mechanisms. CI - Copyright (c) 2026 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. FAU - Shlomov, Tehila AU - Shlomov T AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Nitzan, Itay AU - Nitzan I AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Pollack, Rena AU - Pollack R AD - Department of Endocrinology and Metabolism, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Zloto, Ofira AU - Zloto O AD - Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel; Faculty of Medicine and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Gur, Zvi AU - Gur Z AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address: Zvigur90@gmail.com. LA - eng PT - Journal Article PL - England TA - Can J Ophthalmol JT - Canadian journal of ophthalmology. Journal canadien d'ophtalmologie JID - 0045312 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Thyroiditis, Autoimmune/drug therapy/complications MH - *Graves Ophthalmopathy/diagnosis/drug therapy/etiology MH - Aged MH - Retrospective Studies MH - Adult EDAT- 2026/02/01 00:43 MHDA- 2026/05/22 00:33 CRDT- 2026/01/31 19:20 PHST- 2025/06/15 00:00 [received] PHST- 2025/11/22 00:00 [revised] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/05/22 00:33 [medline] PHST- 2026/02/01 00:43 [pubmed] PHST- 2026/01/31 19:20 [entrez] AID - S0008-4182(26)00011-6 [pii] AID - 10.1016/j.jcjo.2026.01.010 [doi] PST - ppublish SO - Can J Ophthalmol. 2026 Jun;61(3):665-669. doi: 10.1016/j.jcjo.2026.01.010. PMID- 41619919 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260730 IS - 1532-6500 (Electronic) IS - 1058-2746 (Linking) VI - 35 IP - 6 DP - 2026 Jun TI - GLP-1 receptor agonist therapy is not associated with adverse events following shoulder surgery: a systematic review and meta-analysis. PG - 1560-1569 LID - S1058-2746(26)00026-1 [pii] LID - 10.1016/j.jse.2025.12.005 [doi] AB - BACKGROUND: Glucagon-like peptide-1 agonists (GLP-1s) are increasingly prescribed for type 2 diabetes mellitus (T2DM) and obesity, with over 12% of the United States population reported to being using this medication. While GLP-1s have been associated with reduced complication rates in total hip and knee arthroplasty populations, their association with outcomes after shoulder surgery remains unclear. The purpose of the current study was to perform a systematic review and meta-analysis of studies comparing adverse events between GLP-1 users and non-users following shoulder surgery. METHODS: A PRISMA-compliant literature search of PubMed, Embase, and Scopus was performed in August 2025. Comparative studies (Level of Evidence I-III) assessing postoperative adverse events in GLP-1 and non-GLP-1 users undergoing total shoulder arthroplasty (TSA) or shoulder arthroscopic procedures were included. Data pertaining to 90-day and 2-year complication rates were extracted. Random effects meta-analyses were conducted independently for TSA studies and pooled odds ratios with confidence estimates were quantified. Outcomes of studies examining arthroscopic procedures were described narratively given limited data. RESULTS: Six studies encompassing outcomes of 43,415 patients were included. Four (66.7%) studies evaluated TSA, while one evaluated arthroscopic RCR and one manipulation under anesthesia/capsular release for adhesive capsulitis (AC). The overall pooled 90-day complication rate following TSA was 18.1% for GLP-1 users and 15.9% for non-users (OR = 0.86, 95% CI: 0.36-2.07, P = .74). The overall pooled 2-year complication rate following TSA was 3.8% in the GLP-1 group and 3.7% in the non-GLP-1 group (OR = 1.24, 95% CI: 0.73-2.00, P = .42). The RCR and AC studies reported significantly lower 90-day complication rates for GLP-1 users (11.0% vs. 27.4%) and (2.5% vs. 4.8%), respectively. A lower re-tear rate was observed in GLP-1 users compared with non-users by 2-years postoperatively (12.5% vs. 18.3%). CONCLUSION: GLP-1 agonist use is not significantly associated with 90-day or 2-year adverse events following TSA. Based on this data, GLP-1 agonist use should not be a contraindication for proceeding with TSA. Lower complication rates were observed in both studies concerning arthroscopic intervention for non-arthritic shoulder conditions. CI - Copyright (c) 2026 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved. FAU - Moews, Logan D AU - Moews LD AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Kunze, Kyle N AU - Kunze KN AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Thamrongskulsiri, Napatpong AU - Thamrongskulsiri N AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Vega, Tomas F AU - Vega TF AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Morgan, Jacob T AU - Morgan JT AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Nishioka, Tanner AU - Nishioka T AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA. FAU - Chahla, Jorge AU - Chahla J AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA; Rush Medical College, Chicago, IL, USA. FAU - Verma, Nikhil N AU - Verma NN AD - Midwest Orthopaedics at Rush: Division of Sports Medicine, Chicago, IL, USA; Rush Medical College, Chicago, IL, USA. Electronic address: Nikhil.verma@rushortho.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260129 PL - United States TA - J Shoulder Elbow Surg JT - Journal of shoulder and elbow surgery JID - 9206499 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Postoperative Complications/epidemiology MH - *Arthroplasty, Replacement, Shoulder/adverse effects MH - *Arthroscopy/adverse effects MH - *Shoulder Joint/surgery MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - GLP-1 OT - adverse events OT - complications OT - shoulder surgery EDAT- 2026/02/01 00:44 MHDA- 2026/05/11 00:30 CRDT- 2026/01/31 19:12 PHST- 2025/08/25 00:00 [received] PHST- 2025/11/26 00:00 [revised] PHST- 2025/12/06 00:00 [accepted] PHST- 2026/05/11 00:30 [medline] PHST- 2026/02/01 00:44 [pubmed] PHST- 2026/01/31 19:12 [entrez] AID - S1058-2746(26)00026-1 [pii] AID - 10.1016/j.jse.2025.12.005 [doi] PST - ppublish SO - J Shoulder Elbow Surg. 2026 Jun;35(6):1560-1569. doi: 10.1016/j.jse.2025.12.005. Epub 2026 Jan 29. PMID- 41619807 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 2468-1210 (Electronic) IS - 2468-1210 (Linking) VI - 45 IP - 2 DP - 2026 Apr TI - Relationship between glucagon-like peptide-1 receptor agonist use and incidence of trigger finger in patients with type 2 diabetes. PG - 102589 LID - S2468-1229(26)00024-1 [pii] LID - 10.1016/j.hansur.2026.102589 [doi] AB - PURPOSE: The relationship between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and trigger finger (TF) remains unknown. This study aims to compare rates of TF, TF release, and complications of TF release between diabetic patients with and without a history of GLP-1 RA use. METHODS: This study utilized the TriNetX database to identify adult patients with Type II diabetes mellitus. The primary analysis included patients with and without a history of GLP-1 RA use. The secondary analysis included patients with a history of TF separated by the presence or absence of GLP-1 RA use, respectively. The tertiary analysis included patients with and without a history of GLP-1 RA use within the 6 months prior to TF release. Cohorts were propensity-matched 1:1 based on demographic characteristics and medical comorbidities. The primary outcome was the incidence of TF; the secondary outcome was the incidence of TF release. Tertiary outcomes included postoperative complications within 90 days of surgery. RESULTS: GLP-1 RA use was associated with a significant reduction in the prevalence of trigger finger. In contrast, GLP-1 RA users demonstrated a higher prevalence of TF release and similar rates of surgical site infection, joint stiffness, wound dehiscence, and abscess irrigation and debridement following operative release. CONCLUSIONS: Glucagon-like peptide-1 receptor agonist use in patients with type 2 diabetes mellitus is associated with a reduction in the prevalence of trigger finger without an elevation in complication risk following surgical release. Interestingly, we also observed increased prevalence of trigger finger release among glucagon-like peptide-1 receptor agonist users. CI - Copyright (c) 2026 SFCM. Published by Elsevier Masson SAS. All rights reserved. FAU - Stump, Kyle AU - Stump K AD - Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America. Electronic address: tus57436@temple.edu. FAU - Morar, Henry AU - Morar H AD - Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America. FAU - Talsania, Alec AU - Talsania A AD - Temple University Hospital, Department of Orthopaedics, 3509 N. Broad Street, Boyer Pavillion, 5th Floor, Philadelphia, PA 19140, United States of America. FAU - Centeno, Dianly AU - Centeno D AD - Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, United States of America. FAU - Sethi, Lasya AU - Sethi L AD - Temple University Hospital, Department of Orthopaedics, 3509 N. Broad Street, Boyer Pavillion, 5th Floor, Philadelphia, PA 19140, United States of America. FAU - Wiekrykas, Bradley AU - Wiekrykas B AD - Temple University Hospital, Department of Orthopaedics, 3509 N. Broad Street, Boyer Pavillion, 5th Floor, Philadelphia, PA 19140, United States of America. LA - eng PT - Journal Article DEP - 20260129 PL - France TA - Hand Surg Rehabil JT - Hand surgery & rehabilitation JID - 101681801 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Trigger Finger Disorder/epidemiology/surgery MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Middle Aged MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Postoperative Complications/epidemiology OTO - NOTNLM OT - Glucagon-like peptide-1 agonist OT - Stenosing tenosynovitis OT - Trigger finger OT - Trigger finger release COIS- Declaration of competing interest The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper. EDAT- 2026/02/01 00:44 MHDA- 2026/04/13 00:31 CRDT- 2026/01/31 19:11 PHST- 2025/12/19 00:00 [received] PHST- 2026/01/24 00:00 [revised] PHST- 2026/01/26 00:00 [accepted] PHST- 2026/04/13 00:31 [medline] PHST- 2026/02/01 00:44 [pubmed] PHST- 2026/01/31 19:11 [entrez] AID - S2468-1229(26)00024-1 [pii] AID - 10.1016/j.hansur.2026.102589 [doi] PST - ppublish SO - Hand Surg Rehabil. 2026 Apr;45(2):102589. doi: 10.1016/j.hansur.2026.102589. Epub 2026 Jan 29. PMID- 41619622 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260831 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 3 DP - 2026 Mar TI - Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis. PG - 109271 LID - S1056-8727(26)00016-4 [pii] LID - 10.1016/j.jdiacomp.2026.109271 [doi] AB - BACKGROUND AND AIMS: Vascular dementia (VaD) is strongly associated with type 2 diabetes (T2DM), overweight, and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk and exhibit neuroprotective properties, yet their effects in incident VaD remain uncertain. This study evaluated whether GLP-1 RAs have preventive potential for VaD in adults with T2DM, overweight, or obesity. METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was conducted to estimate the risk of incident VaD among patients with T2DM or overweight/obesity treated with GLP-1 RAs versus placebo. Data were pooled using a random-effects model, with outcomes expressed as risk ratios (RRs) and 95% confidence intervals (CIs). Subgroup analysis was performed after stratification by population type (T2DM vs. overweight/obesity), and meta-regression assessed the association between RCT duration and effect size. RESULTS: Seven RCTs (six in T2DM, one in overweight/obesity) comprising 61,610 participants were included. GLP-1 RA treatment was not associated with a statistically significant difference in VaD incidence (RR: 0.50; 95% CI: 0.19-1.32; I(2) = 0%). Subgroup analysis revealed no significant between-group differences (p for subgroups = 0.612), although numerically lower VaD rates were observed in the T2DM subgroup (RR: 0.38; 95% CI: 0.13-1.11). Meta-regression did not demonstrate a significant association between follow-up duration and treatment effect (beta = -0.291; SE = 0.212; 95% CI: -0.843 to 0.262; p = 0.229). CONCLUSIONS: The pooled evidence did not confirm a statistically significant reduction in VaD risk with GLP-1 RA therapy. Numerically lower VaD incidence in T2DM populations warrants further investigation in adequately powered and systematically adjudicated trials. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Stefanou, Maria-Ioanna AU - Stefanou MI AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Department of Neurology & Stroke, Eberhard-Karls University of Tubingen, Tubingen, Germany. FAU - Tentolouris, Anastasios AU - Tentolouris A AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Panagiotopoulos, Evangelos AU - Panagiotopoulos E AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Theodorou, Aikaterini AU - Theodorou A AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Mengel, Annerose AU - Mengel A AD - Department of Neurology & Stroke, Eberhard-Karls University of Tubingen, Tubingen, Germany; Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tubingen, Tubingen, Germany. FAU - Athanasaki, Athanasia AU - Athanasaki A AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - Second Department of Internal Medicine, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Peppa, Melpomeni AU - Peppa M AD - Second Department of Internal Medicine, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Papadopoulou, Marianna AU - Papadopoulou M AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Paraskevas, Georgios P AU - Paraskevas GP AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Giannopoulos, Sotirios AU - Giannopoulos S AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Siasos, Gerasimos AU - Siasos G AD - Third Department of Cardiology, Sotiria Thoracic Diseases General Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Sharma, Vijay K AU - Sharma VK AD - Division of Neurology, Department of Medicine, National University Hospital, Singapore; School of Medicine, National University of Singapore, Singapore. FAU - Ziemann, Ulf AU - Ziemann U AD - Department of Neurology & Stroke, Eberhard-Karls University of Tubingen, Tubingen, Germany; Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tubingen, Tubingen, Germany. FAU - Tsivgoulis, Georgios AU - Tsivgoulis G AD - Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: tsivgoulisgiorg@yahoo.gr. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260126 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Dementia, Vascular/prevention & control/epidemiology/etiology MH - Obesity/complications/epidemiology/drug therapy MH - Randomized Controlled Trials as Topic MH - Overweight/complications MH - *Hypoglycemic Agents/therapeutic use MH - Incidence OTO - NOTNLM OT - Diabetes OT - GLP-1 OT - MACE OT - Obesity OT - Overweight OT - Vascular dementia COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/02/01 00:44 MHDA- 2026/02/14 05:30 CRDT- 2026/01/31 18:07 PHST- 2025/10/10 00:00 [received] PHST- 2025/12/08 00:00 [revised] PHST- 2026/01/24 00:00 [accepted] PHST- 2026/02/14 05:30 [medline] PHST- 2026/02/01 00:44 [pubmed] PHST- 2026/01/31 18:07 [entrez] AID - S1056-8727(26)00016-4 [pii] AID - 10.1016/j.jdiacomp.2026.109271 [doi] PST - ppublish SO - J Diabetes Complications. 2026 Mar;40(3):109271. doi: 10.1016/j.jdiacomp.2026.109271. Epub 2026 Jan 26. PMID- 41616750 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260806 IS - 1879-1379 (Electronic) IS - 0022-3956 (Linking) VI - 195 DP - 2026 Apr TI - Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage. PG - 92-96 LID - S0022-3956(26)00053-1 [pii] LID - 10.1016/j.jpsychires.2026.01.042 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Beyond metabolic effects, GLP-1 signaling influences central pathways involved in mood, reward, and stress regulation, raising interest in possible psychiatric implications. METHODS: We conducted a retrospective chart review of adults (>/=18 years) prescribed GLP-1 RAs at a private university hospital between January 2021 and April 2024. Demographic, medication, and psychiatric data were extracted from electronic health records. Primary outcomes included stability, improvement, worsening, or new onset of psychiatric disorders during treatment. RESULTS: Among 226 patients (mean age 53.5 years; 66.8 % female; mean BMI 33.6 kg/m(2)), semaglutide was most frequently prescribed (73 %). The mean treatment duration was 20.2 months, with an average 6.7 % weight loss. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were most prevalent (68.6 % and 65.9 % of patients, respectively). Most remained stable (MDD: 73.6 %; GAD: 78.5 %). New-onset MDD occurred in 9.0 % and GAD in 8.7 % of affected patients, with mean latencies of 15.8 and 16.8 months, respectively. Adjustment disorder, ADHD, and insomnia also emerged in a subset, with ADHD showing the shortest latency to onset (7.8 months). Rare new-onset alcohol use disorder, trichotillomania, and opioid use disorder were observed. CONCLUSIONS: GLP-1 RAs appear psychiatrically well-tolerated for most patients, though new-onset or worsening symptoms occur in a minority, underscoring the need for monitoring, particularly in high-risk populations. Prospective studies are warranted to clarify causality, mechanisms, and potential therapeutic roles in psychiatric care. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved. FAU - Sa, Brianna AU - Sa B AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: bcs103@miami.edu. FAU - Maristany, Anthony AU - Maristany A AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Subramaniam, Ashwin AU - Subramaniam A AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Kumbkarni, Nayha AU - Kumbkarni N AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Lange, Rachel AU - Lange R AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Oldak, Sean AU - Oldak S AD - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. FAU - Buciuc, Adela-Georgiana AU - Buciuc AG AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Padilla, Vanessa AU - Padilla V AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. LA - eng PT - Journal Article DEP - 20260128 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - Middle Aged MH - Male MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Generalized Anxiety Disorder MH - *Major Depressive Disorder/epidemiology/chemically induced MH - *Glucagon-Like Peptides/adverse effects/pharmacology MH - Aged MH - *Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy MH - *Mental Disorders/chemically induced OTO - NOTNLM OT - Anxiety disorders OT - GLP-1 receptor agonists OT - Mood disorders OT - Neuropsychiatric effects OT - Psychiatric manifestations OT - Retrospective chart review OT - Semaglutide COIS- Declaration of competing interest All authors report no competing interests. EDAT- 2026/01/31 00:29 MHDA- 2026/02/19 01:35 CRDT- 2026/01/30 18:10 PHST- 2025/08/13 00:00 [received] PHST- 2025/12/18 00:00 [revised] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/02/19 01:35 [medline] PHST- 2026/01/31 00:29 [pubmed] PHST- 2026/01/30 18:10 [entrez] AID - S0022-3956(26)00053-1 [pii] AID - 10.1016/j.jpsychires.2026.01.042 [doi] PST - ppublish SO - J Psychiatr Res. 2026 Apr;195:92-96. doi: 10.1016/j.jpsychires.2026.01.042. Epub 2026 Jan 28. PMID- 41611096 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 233 DP - 2026 Mar TI - Comparative risk of infections with GLP-1 receptor agonists versus SGLT2 inhibitors in patients with advanced chronic kidney disease and type 2 diabetes. PG - 113115 LID - S0168-8227(26)00034-3 [pii] LID - 10.1016/j.diabres.2026.113115 [doi] AB - AIMS: To compare the risk of infections between GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and advanced chronic kidney disease (CKD). METHODS: Using the TriNetX U.S. Collaborative Network, we conducted a retrospective cohort study of adults with T2DM and eGFR /=1 stage histological fibrosis improvement) was pooled using a risk ratio (RR) and random-effects model. FINDINGS: Eight out of 3,751 identified records, describing three placebo-controlled RCTs with histological endpoints (2,086 noncirrhotic MASH patients, 62% with T2DM, trial duration range 52-72 weeks) were included. In MASH patients with T2DM, semaglutide did not improve fibrosis stage (RR = 1.21, 95% CI 0.94-1.56, p = 0.13; I(2) = 0%, N comparisons = 4, 646 participants), while resmetirom significantly improved fibrosis vs. placebo (RR = 1.99, 95% CI 1.35-2.93, p = 0.0005, 647 participants). In MASH patients without T2DM, semaglutide improved fibrosis stage (RR = 1.72, 95% CI 1.21-2.44, p = 0.002, N comparisons = 4, I(2) = 3%, 474 participants), while resmetirom did not (RR = 1.37, 95% CI 0.83-2.25, p = 0.21, 319 participants). Resmetirom treatment was associated with significant fibrosis reduction regardless of background treatment with glucagon-like peptide-1 receptor agonists. CONCLUSIONS: T2DM modifies fibrosis response to semaglutide and resmetirom in noncirrhotic MASH. FUNDING: This study received no funding. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Musso, Giovanni AU - Musso G AD - MECAU Department San Luigi Gonzaga Hospital, Orbassano, Turin, Italy. Electronic address: giovanni_musso@yahoo.it. FAU - Pinach, Silvia AU - Pinach S AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Cassader, Maurizio AU - Cassader M AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Mariano, Filippo AU - Mariano F AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Gambino, Roberto AU - Gambino R AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260128 PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Liver Cirrhosis/drug therapy/pathology/etiology MH - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology OTO - NOTNLM OT - GLP-1 RAs OT - MASH OT - NAFLD OT - NASH OT - incretin OT - thyroid receptor agonists OT - translation to patients OT - weight loss COIS- Declaration of interests The authors declare no competing interests. EDAT- 2026/01/30 00:54 MHDA- 2026/02/15 00:31 CRDT- 2026/01/29 18:41 PHST- 2025/08/13 00:00 [received] PHST- 2025/10/17 00:00 [revised] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2026/01/30 00:54 [pubmed] PHST- 2026/01/29 18:41 [entrez] AID - S2666-6340(25)00386-1 [pii] AID - 10.1016/j.medj.2025.100959 [doi] PST - ppublish SO - Med. 2026 Feb 13;7(2):100959. doi: 10.1016/j.medj.2025.100959. Epub 2026 Jan 28. PMID- 41609518 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 47 IP - 19 DP - 2026 May 18 TI - GLP-1R agonists and heart failure: novel beneficial effects suggested by Mendelian randomization. PG - 2308-2322 LID - 10.1093/eurheartj/ehaf1066 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists reduce heart failure (HF) risk in patients with diabetes or obesity. However, the extent to which this reduced risk is dependent on, or extends beyond, glucose control and weight reduction remains unclear. METHODS: Two-sample cis-Mendelian randomization (MR) was used to assess causal effects of GLP-1R activation on HF risk, using glycated haemoglobin (HbA1c) reduction as a surrogate biomarker. The HF outcome was derived from a genome-wide association meta-analysis that included seven original studies and 1 665 481 participants. Primary analyses used inverse variance-weighted (IVW) and MR-robust adjusted profile score (MR-RAPS) methods. Mendelian randomization Bayesian model averaging was used to identify key mediators of the observed effects, while multivariable cis-MR with principal component generalized method of moments and network cis-MR were used to minimize the impact of confounders. RESULTS: Genetically proxied GLP-1R activation was associated with reduced HF risk IVW: odds ratio [OR] [95% confidence interval (CI)] .502 [.339, .743]; MR-RAPS: OR [95% CI] .492 [.320, .756]. Mendelian randomization Bayesian model averaging identified body mass index (BMI) (marginal inclusion probability 67.2%) and Type 2 diabetes (T2D) (45.0%) as primary mediators. In multivariable cis-MR with principal component generalized method of moments, genetically predicted HbA1c levels from the GLP-1R locus remained significantly associated with HF risk after BMI adjustment, even in instances where BMI effects were non-significant [OR (95% CI) 1.663 (1.087, 2.544) at 99% variance threshold]. Network cis-MR confirmed persistent protection after adjusting for BMI [IVW: OR (95% CI) .587 (.394, .877); MR-RAPS: OR (95% CI) .577 (.375, .887)] or T2D [IVW: OR (95% CI) .508 (.343, .754); MR-RAPS: OR (95% CI) .499 (.327, .762)]. CONCLUSIONS: Glucagon-like peptide-1 receptor agonist-associated HF risk reduction is primarily mediated by BMI reduction rather than glucose control, but not fully explained by either. Residual effects after BMI and T2D adjustment suggest direct cardioprotective actions, supporting trials in non-obese, non-diabetic HF patients. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Hu, Yiqing AU - Hu Y AUID- ORCID: 0000-0002-1813-9778 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Zhao, Yongchao AU - Zhao Y AUID- ORCID: 0000-0002-2145-7187 AD - Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China. FAU - Dai, Neng AU - Dai N AUID- ORCID: 0000-0003-3620-0699 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Zhou, You AU - Zhou Y AUID- ORCID: 0000-0001-9250-0982 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - Department of Cardiology, Shanghai Geriatric Medical Center, Shanghai 201100, China. FAU - Yao, Yunqian AU - Yao Y AUID- ORCID: 0000-0003-4353-4398 AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University Shanghai 200031, China. AD - State Key Laboratory of Molecular Development Biology, Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Beijing 100101, China. FAU - Li, Ziang AU - Li Z AUID- ORCID: 0000-0002-3744-7602 AD - State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100037, China. FAU - Cai, Wufeng AU - Cai W AUID- ORCID: 0000-0002-9043-0295 AD - Department of Orthopaedic, Orthopaedic Research Institute, West China Hospital, Chengdu, Sichuan 610041, China. AD - Department of Engineering, University of Exeter, Exeter EX4 4QJ, UK. FAU - Xiong, Weidong AU - Xiong W AUID- ORCID: 0009-0000-4244-3713 AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. FAU - Song, Shuai AU - Song S AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Deng, Xin AU - Deng X AUID- ORCID: 0000-0003-4593-9700 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Yin, Jiasheng AU - Yin J AUID- ORCID: 0000-0002-8088-6053 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Zhao, Xin AU - Zhao X AUID- ORCID: 0000-0002-4796-0899 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Weng, Xinyu AU - Weng X AUID- ORCID: 0000-0002-7620-0813 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Li, Chenguang AU - Li C AUID- ORCID: 0000-0002-5287-5269 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Sun, Aijun AU - Sun A AUID- ORCID: 0000-0003-1488-0937 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Qian, Juying AU - Qian J AUID- ORCID: 0000-0002-7512-3692 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Lu, Hao AU - Lu H AUID- ORCID: 0000-0002-0322-4400 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. FAU - Ge, Junbo AU - Ge J AUID- ORCID: 0000-0002-9360-7332 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - National Clinical Research Center for Interventional Medicine, #1609 Xietu Road, Xuhui District, Shanghai 200032, China. AD - Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China. LA - eng GR - Medical Science Data Center of Fudan University/ GR - T2288101/Project of Basic Science Center of the National Natural Science Foundation of China/ GR - 82370261/National Natural Science Foundation of China/ GR - 82470405/National Natural Science Foundation of China/ GR - 82200290/National Natural Science Foundation of China/ GR - 82370513/National Natural Science Foundation of China/ GR - 823B2020/National Natural Science Foundation of China/ GR - Student Scientific Research Program of Shanghai Medical College/ GR - FQXZ202301A/Fudan University/ GR - Innovation Program of Shanghai Municipal Education Commission, China/ GR - shslczdzk01701/Shanghai Municipal Key Clinical Specialty, China/ GR - 19MC1910300/Shanghai Clinical Research Center/ GR - Guizhou Provincial Department of Science and Technology Outstanding Young Talents Support Program, China/ GR - Guizhou Provincial Department of Education Young Scientific and Technological Elite Talent Program, China/ GR - Guizhou Provincial Basic Research Program/ GR - Qiankehe Foundation-ZK/ GR - General/ GR - GASTYESS202416/Young Elite Scientist Sponsorship Program of GAST, China/ PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Heart Failure/prevention & control/genetics MH - Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications/genetics MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptide-1 Receptor/genetics MH - Obesity/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Genome-Wide Association Study MH - Bayes Theorem OTO - NOTNLM OT - cis-Mendelian randomization OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure EDAT- 2026/01/29 14:02 MHDA- 2026/05/18 18:32 CRDT- 2026/01/29 10:23 PHST- 2024/10/15 00:00 [received] PHST- 2025/04/29 00:00 [revised] PHST- 2025/12/12 00:00 [accepted] PHST- 2026/05/18 18:32 [medline] PHST- 2026/01/29 14:02 [pubmed] PHST- 2026/01/29 10:23 [entrez] AID - 8444645 [pii] AID - 10.1093/eurheartj/ehaf1066 [doi] PST - ppublish SO - Eur Heart J. 2026 May 18;47(19):2308-2322. doi: 10.1093/eurheartj/ehaf1066. PMID- 41605684 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260813 IS - 1348-4540 (Electronic) IS - 0918-8959 (Print) IS - 0918-8959 (Linking) VI - 73 IP - 5 DP - 2026 May 8 TI - Effects of semaglutide, a GLP-1 receptor agonist, on food preferences in Japanese subjects with type 2 diabetes and visceral fat accumulation. PG - 607-619 LID - 10.1507/endocrj.EJ25-0402 [doi] AB - Obesity and type 2 diabetes mellitus (T2DM) are growing global health burdens, with dietary patterns, particularly high intake of carbohydrate- and fat-rich foods, contributing to disease progression. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is effective for both lowering blood glucose and reducing weight; however, its effects on food preferences for specific macronutrients remain unclear. In this retrospective observational study, we enrolled 32 obese subjects with T2DM who were hospitalized for glycemic control, including 20 who started semaglutide treatment (the Sema group) and 12 who did not receive GLP-1RA therapy. Eating behaviors were assessed using the Dietary Behavior Questionnaire from the Japan Society for the Study of Obesity (JASSO-DBQ), and food preferences for carbohydrates, fat, protein, and dietary fiber were quantitatively evaluated using the Japan Food Preference Questionnaire (JFPQ). Thirteen subjects in the Sema group and eight in the Non-GLP-1 group completed 6-months of follow-up. The Sema group showed significant decreases in HbA1c levels (-1.1%) and body weight (-5.7 kg), with fat loss exceeding skeletal muscle loss. Significant decreases were observed in eating behavior scores for "Eating Motives," "Way of Eating," and "Dietary Content." Notably, semaglutide significantly reduced preferences for sweet and non-sweet carbohydrates and non-sweet fats, without changing protein or dietary fiber preferences. In particular, significant reductions were observed in preferences for Japanese staple foods (e.g., white rice and udon/soba) and high-fat snacks. The Non-GLP-1 group showed no significant changes in food preferences for any of the nutrient categories. In summary, semaglutide treatment in obese subjects with T2DM facilitated weight loss, in part by altering food preferences, which potentially contributed to its metabolic benefits. FAU - Hara, Tomoyuki AU - Hara T AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fujishima, Yuya AU - Fujishima Y AUID- ORCID: 0000-0003-0028-1757 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Kimura, Yu AU - Kimura Y AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fujii, Kohei AU - Fujii K AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Kawachi, Yusuke AU - Kawachi Y AD - Department of Diabetes Endocrinology, Rinku General Medical Center, Osaka 598-0048, Japan. FAU - Nagao, Hirofumi AU - Nagao H AUID- ORCID: 0009-0001-1261-4160 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Department of Metabolism and Atherosclerosis, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Obata, Yoshinari AU - Obata Y AUID- ORCID: 0000-0002-3443-3635 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fukuda, Shiro AU - Fukuda S AUID- ORCID: 0000-0003-0712-7154 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Nagai, Naoko AU - Nagai N AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Division of Nutrition Management, The University of Osaka Hospital, Osaka 565-0871, Japan. FAU - Nishizawa, Hitoshi AU - Nishizawa H AUID- ORCID: 0000-0002-7845-9693 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Department of Metabolism and Atherosclerosis, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Shimomura, Iichiro AU - Shimomura I AUID- ORCID: 0000-0002-0851-9603 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20260129 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Japanese people SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Feeding Behavior/drug effects MH - *Food Preferences/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use MH - Japan MH - *Obesity/complications/drug therapy MH - Retrospective Studies MH - *Semaglutide/pharmacology/therapeutic use MH - Weight Loss/drug effects MH - East Asian People PMC - PMC13195457 OTO - NOTNLM OT - Eating behavior OT - Food preference OT - GLP-1 receptor agonist OT - Obesity OT - Type 2 diabetes mellitus COIS- None of the authors has any potential conflicts of interest associated with this research. EDAT- 2026/01/29 01:49 MHDA- 2026/05/11 00:30 PMCR- 2026/01/29 CRDT- 2026/01/28 21:43 PHST- 2026/05/11 00:30 [medline] PHST- 2026/01/29 01:49 [pubmed] PHST- 2026/01/28 21:43 [entrez] PHST- 2026/01/29 00:00 [pmc-release] AID - 10.1507/endocrj.EJ25-0402 [doi] PST - ppublish SO - Endocr J. 2026 May 8;73(5):607-619. doi: 10.1507/endocrj.EJ25-0402. Epub 2026 Jan 29. PMID- 41605300 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260830 IS - 1872-8227 (Electronic) IS - 0168-8227 (Print) IS - 0168-8227 (Linking) VI - 233 DP - 2026 Mar TI - GLP-1 RA initiation versus metformin and risk of cardiomyopathy in patients with cancer and diabetes treated with chemotherapy, radiation, or immunotherapy: a target trial emulation. PG - 113119 LID - S0168-8227(26)00038-0 [pii] LID - 10.1016/j.diabres.2026.113119 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have demonstrated cardioprotective effects; however, their association with cardiomyopathy remains unclear among patients with cancer and type 2 diabetes mellitus (T2D) treated with chemotherapy, radiation, or immunotherapy. We evaluated whether GLP-1 RA initiation reduces cardiomyopathy risk compared with metformin. METHODS: We conducted a retrospective cohort study using a target trial emulation framework within a large global electronic health record database. Adults aged 18-75 years with cancer and T2D, and prior exposure to chemotherapy, radiation, or immunotherapy were included. Treatment strategies were initiation of GLP-1 RA or metformin between January 2006 and July 2024. The primary outcome was incident cardiomyopathy. A 1:1 propensity score-matched cohort was created, and risk differences (RD) and hazard ratios (HR) were estimated. RESULTS: Among 10,382 matched patients, cardiomyopathy risk at 18.5 years was lower among GLP-1 RA initiators than metformin initiators (0.31% vs 0.94%; RD - 0.64%, 95% CI - 0.90 to - 0.30; HR 0.43, 95% CI 0.24-0.76). Results were consistent across high-risk subgroups. CONCLUSIONS: GLP-1 RA initiation was associated with a lower risk of cardiomyopathy compared with metformin among patients with cancer and T2D, supporting a potential role for GLP-1 RA in cardio-oncology prevention strategies. CI - Published by Elsevier B.V. FAU - Hernandez-Perez, Jesus Gibran AU - Hernandez-Perez JG AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Population Health Research, National Institute of Public Health, Cuernavaca, Morelos 62100, Mexico. FAU - Abdelgadir, Omer AU - Abdelgadir O AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: omer.abdelgadir@utsouthwestern.edu. FAU - Hussain, Maryam R AU - Hussain MR AD - Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; School of Public and Population Health, University of Texas Medical Branch, Galveston, TX 77555, USA. FAU - Almandoz, Jaime P AU - Almandoz JP AD - Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. FAU - Barcenas, Carlos H AU - Barcenas CH AD - Department of Breast Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Shah, Amil AU - Shah A AD - Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. FAU - Cowell, Lindsay G AU - Cowell LG AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. FAU - Messiah, Sarah E AU - Messiah SE AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. FAU - Lopez, David S AU - Lopez DS AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. LA - eng GR - P30 AG059301/AG/NIA NIH HHS/United States GR - P30 CA142543/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20260126 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Middle Aged MH - Male MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - *Neoplasms/therapy/complications/drug therapy MH - *Cardiomyopathies/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Immunotherapy MH - Young Adult MH - Adolescent PMC - PMC13525917 MID - NIHMS2199533 OTO - NOTNLM OT - Cancer OT - Cardio-oncology OT - Cardiomyopathy OT - Glucagon-like peptide-1 receptor agonists OT - Metformin OT - Type 2 diabetes COIS- Declaration of Competing Interest Dr. Lopez reported receiving grants for the National Institute of Health (NIH) and Cancer Prevention and Research Institute of Texas (CPRIT) during the conduct of the study. No other disclosures were reported. EDAT- 2026/01/29 01:47 MHDA- 2026/03/06 09:03 PMCR- 2026/08/29 CRDT- 2026/01/28 19:10 PHST- 2025/12/12 00:00 [received] PHST- 2026/01/16 00:00 [revised] PHST- 2026/01/24 00:00 [accepted] PHST- 2026/03/06 09:03 [medline] PHST- 2026/01/29 01:47 [pubmed] PHST- 2026/01/28 19:10 [entrez] PHST- 2026/08/29 00:00 [pmc-release] AID - S0168-8227(26)00038-0 [pii] AID - 10.1016/j.diabres.2026.113119 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Mar;233:113119. doi: 10.1016/j.diabres.2026.113119. Epub 2026 Jan 26. PMID- 41604151 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260730 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 1 DP - 2026 Jan 2 TI - Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes. PG - e2555952 LID - 10.1001/jamanetworkopen.2025.55952 [doi] LID - e2555952 AB - IMPORTANCE: Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited. OBJECTIVE: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation. EXPOSURES: Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed. RESULTS: Among 17 288 patients (mean [SD] age, 70.7 [12.0] years; 10 010 male [57.9%]), 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70). CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population. FAU - Hsiao, Fu-Chih AU - Hsiao FC AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hsu, Tzyy-Jer AU - Hsu TJ AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Hsieh, Yu-Jui AU - Hsieh YJ AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Tung, Ying-Chang AU - Tung YC AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Chen, Dong-Yi AU - Chen DY AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Lin, Chia-Pin AU - Lin CP AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Chen, Shao-Wei AU - Chen SW AD - Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan. AD - Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Chu, Pao-Hsien AU - Chu PH AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260102 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - Taiwan/epidemiology MH - Middle Aged MH - Female MH - Amputation, Surgical/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Cardiovascular Diseases/epidemiology/prevention & control PMC - PMC12853205 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2026/01/28 13:12 MHDA- 2026/01/28 19:34 PMCR- 2026/01/28 CRDT- 2026/01/28 11:33 PHST- 2026/01/28 19:34 [medline] PHST- 2026/01/28 13:12 [pubmed] PHST- 2026/01/28 11:33 [entrez] PHST- 2026/01/28 00:00 [pmc-release] AID - 2844425 [pii] AID - zoi251490 [pii] AID - 10.1001/jamanetworkopen.2025.55952 [doi] PST - epublish SO - JAMA Netw Open. 2026 Jan 2;9(1):e2555952. doi: 10.1001/jamanetworkopen.2025.55952. PMID- 41596262 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260131 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 2 DP - 2026 Jan 7 TI - Agent- and Dose-Specific Intestinal Obstruction Safety of GLP-1 Receptor Agonists and SGLT2 Inhibitors: A Network Meta-Analysis of Randomized Trials. LID - 10.3390/ijms27020608 [doi] LID - 608 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01-6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08-10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24-0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AUID- ORCID: 0000-0002-8650-4060 AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan. FAU - Suen, Mein-Woei AU - Suen MW AUID- ORCID: 0000-0002-3991-0322 AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan. AD - Gender Equality Education and Research Center, Asia University, Taichung 41354, Taiwan. AD - Department of Medical Research, Asia University Hospital, Asia University, Taichung 41354, Taiwan. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan. FAU - Wang, Hung-Yu AU - Wang HY AD - Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung 80276, Taiwan. FAU - Yang, Wei-Chieh AU - Yang WC AD - Department of Pediatrics, Ping An Medical Clinic, Tainan 708, Taiwan. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. AD - Department of Sport, University of Vienna, 1010 Vienna, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AUID- ORCID: 0000-0001-8462-1311 AD - Department of Psychiatry, Tri-Service General Hospital, Taipei 114202, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei 114202, Taiwan. FAU - Lei, Wei-Te AU - Lei WT AD - Division of Pediatric Allergy, Immunology, and Rheumatology, Department of Pediatrics, Hsinchu Municipal MacKay Children's Hospital, Hsinchu 30068, Taiwan. AD - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3220, Australia. FAU - Hsu, Shih-Pin AU - Hsu SP AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan. AD - Department of Neurology, E-Da hospital, I-Shou University, Kaohsiung 82445, Taiwan. FAU - Shiue, Yow-Ling AU - Shiue YL AUID- ORCID: 0000-0003-0798-5028 AD - Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. AD - Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 82445, Taiwan. FAU - Li, Cheng-Ta AU - Li CT AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112201, Taiwan. AD - Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan. AD - Institute of Brain Science and Brain Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan. FAU - Su, Kuan-Pin AU - Su KP AUID- ORCID: 0000-0002-4501-2502 AD - Mind-Body Interface Research Center (MBI Lab & Care), China Medical University Hospital, Taichung 40447, Taiwan. AD - Office of Research and Development, Asia University, Taichung 413305, Taiwan. AD - College of Medicine, China Medical University, Taichung 404328, Taiwan. AD - An-Nan Hospital, China Medical University, Tainan 709, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical University, Taipei 114202, Taiwan. AD - Department of Psychiatry, National Defense Medical University, Taipei 114202, Taiwan. FAU - Zeng, Bing-Syuan AU - Zeng BS AD - Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan. FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. AD - Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20260107 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Intestinal Obstruction/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use PMC - PMC12841245 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - adverse effect OT - ileus OT - intestine obstruction OT - network meta-analysis COIS- The authors report no financial interests or potential conflicts of interest. EDAT- 2026/01/28 07:48 MHDA- 2026/01/28 19:20 PMCR- 2026/01/07 CRDT- 2026/01/28 01:09 PHST- 2025/12/17 00:00 [received] PHST- 2025/12/31 00:00 [revised] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/01/28 19:20 [medline] PHST- 2026/01/28 07:48 [pubmed] PHST- 2026/01/28 01:09 [entrez] PHST- 2026/01/07 00:00 [pmc-release] AID - ijms27020608 [pii] AID - ijms-27-00608 [pii] AID - 10.3390/ijms27020608 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jan 7;27(2):608. doi: 10.3390/ijms27020608. PMID- 41592697 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 233 DP - 2026 Mar TI - Association of glucagon-like peptide-1 receptor agonist use with anxiety disorders, depression, self-harm, and suicidality: a large cohort study. PG - 113104 LID - S0168-8227(26)00023-9 [pii] LID - 10.1016/j.diabres.2026.113104 [doi] AB - AIMS: This study examines the incidence of anxiety disorders, depression, self-harm, and suicidality after treatment initiation with antihyperglycemic medications in patients with type 2 diabetes (T2D) who take metformin as first-line treatment. METHODS: A large cohort study was conducted using TriNetX electronic health records andincluded adults (>/=18 years) with T2D who used metformin and initiated GLP-1 RAs, SGLT2i, DPP4i, or SU between 1 April 2013 and 31 December 2019. RESULTS: The final three propensity-matched cohorts were 1) GLP-1 RA vs DPP4i (n = 28,536), 2) GLP-1 RA vs SU (n = 23,486), and 3) GLP-1 RA vs SGLT2i (n = 24,052). In a median follow-up of 5.5 years, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i (HR 1.19, 95% CI 1.11-1.28), and DPP4i (HR 1.06, 95% CI 1.00-1.13) but not SU. Anxiety disorder risk was also higher for GLP-1 RAs versus SGLT2i (HR 1.09, 95% CI 1.02- 1.16) and DPP4i (HR 1.07, 95% CI 1.02-1.13) but not SU. On the contrary, GLP-1 RAs were associated with a lower risk for suicidal ideation in comparison with SU (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: GLP-1 RAs were associated with a higher risk of anxiety disorders and depression, but no difference in suicidality or self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU. CI - Copyright (c) 2026. Published by Elsevier B.V. FAU - Anagnostakis, Filippos AU - Anagnostakis F AD - Centre for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA; Department of Medical and Surgical Sciences, Alma Mater University of Bologna, Bologna, Italy. FAU - Kokkorakis, Michail AU - Kokkorakis M AD - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Anastasiou, Georgia AU - Anastasiou G AD - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece. FAU - Nagarajan, Shrihari AU - Nagarajan S AD - Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA. FAU - Mantzoros, Christos S AU - Mantzoros CS AD - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA. Electronic address: cmantzor@bidmc.harvard.edu. LA - eng PT - Journal Article DEP - 20260125 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Self-Injurious Behavior/epidemiology/chemically induced MH - *Anxiety Disorders/epidemiology/chemically induced MH - *Depression/epidemiology/chemically induced MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Adult MH - Cohort Studies MH - Metformin/therapeutic use MH - *Suicide/statistics & numerical data OTO - NOTNLM OT - Antihyperglycemic medications OT - Anxiety disorders OT - Depression OT - GLP-1RAs OT - Psychiatric outcomes OT - Self-harm OT - Suicidality OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [FA, GA, and SN have no competing interests. MK received funding support from an MD-PhD grant from the University Medical Center Groningen. Over the past three years, CSM reports grants through his institution from Merck, Massachusetts Life Sciences Center, and Boehringer Ingelheim; he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Nestle, Amgen, Corcept, Aligos, Intercept, 89 Bio, Madrigal, Novo Nordisk, and Regeneron, reports travel support and fees from TMIOA, Elsevier, and the Cardio Metabolic Health Conference. No consulting activity above is related to the work presented herein]. EDAT- 2026/01/28 01:35 MHDA- 2026/03/06 19:43 CRDT- 2026/01/27 19:11 PHST- 2025/08/19 00:00 [received] PHST- 2025/11/07 00:00 [revised] PHST- 2026/01/11 00:00 [accepted] PHST- 2026/03/06 19:43 [medline] PHST- 2026/01/28 01:35 [pubmed] PHST- 2026/01/27 19:11 [entrez] AID - S0168-8227(26)00023-9 [pii] AID - 10.1016/j.diabres.2026.113104 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Mar;233:113104. doi: 10.1016/j.diabres.2026.113104. Epub 2026 Jan 25. PMID- 41589628 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 0332-3102 (Print) IS - 0332-3102 (Linking) VI - 119 IP - 1 DP - 2026 Jan 22 TI - Non-Arteritic Ischaemic Optic Neuropathy Associated with Semaglutide Use. PG - 13 AB - PRESENTATION: A 50-year-old obese male with non-insulin dependent diabetes mellitus (NIDDM) taking Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) presented with sudden, painless vision-loss from his right eye. DIAGNOSIS: Right eye visual acuity was 6/24. There was Frisen grade IV optic nerve head (ONH) oedema. This was confirmed at imaging with ocular coherence tomography (OCT). The patient was diagnosed with non-arteritic anterior ischaemic optic neuropathy. TREATMENT: Semaglutide was ceased. DISCUSSION: GLP-1RAs such as Semaglutide are being increasingly recognised as a potential risk factor for NAION. A case such as this has not yet been reported in Ireland. FAU - Kelly, A AU - Kelly A FAU - Hasif, A AU - Hasif A FAU - McAnena, L AU - McAnena L FAU - O'Brien, C AU - O'Brien C LA - eng PT - Case Reports PT - Journal Article DEP - 20260122 PL - Ireland TA - Ir Med J JT - Irish medical journal JID - 0430275 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Middle Aged MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Glucagon-Like Peptides/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Tomography, Optical Coherence COIS- None declared. EDAT- 2026/01/27 12:59 MHDA- 2026/01/27 13:00 CRDT- 2026/01/27 07:30 PHST- 2026/01/27 13:00 [medline] PHST- 2026/01/27 12:59 [pubmed] PHST- 2026/01/27 07:30 [entrez] PST - epublish SO - Ir Med J. 2026 Jan 22;119(1):13. PMID- 41588354 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 26 IP - 1 DP - 2026 Jan 26 TI - Recurrent bilateral brachial plexus neuritis following rapid semaglutide-induced weight loss: a case report. PG - 123 LID - 10.1186/s12883-026-04664-4 [doi] LID - 123 AB - BACKGROUND: Brachial plexus neuritis, or Parsonage-Turner syndrome, is an uncommon neuropathy marked by acute pain followed by weakness, often triggered by infection, vaccination, trauma, or metabolic stress but the exact cause of this disease remained unknown. Semaglutide is widely used for the treatment of type 2 diabetes and obesity. With its increasing use, there have been reports suggesting a possible association with neuropathies. Currently, there is no information suggesting a possible association between the use of semaglutide and brachial plexus neuritis. CASE PRESENTATION: A 39-year-old man with a prior episode of unilateral brachial neuritis developed recurrent bilateral upper limb weakness after an eight-month, 70-pound semaglutide-associated weight loss. He presented with bilateral radial sensory loss, finger extensor paralysis, right triceps weakness and decreased grip strength on the left side. Corticosteroids provided pain relief, but motor and sensory deficits persisted despite physiotherapy. CONCLUSION: This case highlights a temporal association between rapid pharmacologic weight loss and recurrent idiopathic brachial plexus neuritis, emphasizing the importance of gradual, nutritionally supported weight reduction and vigilance for neuromuscular complications during GLP-1 receptor agonist therapy. FAU - Lesinszki, Lukacs S AU - Lesinszki LS AD - Department of Physiology, Semmelweis University School of Medicine, Tuzolto utca 37-47, Budapest, 1094, Hungary. lesinszki.lukacs.sandor@semmelweis.hu. FAU - Khalili, Radmanesh AU - Khalili R AD - Department of Neurology, Karl Landsteiner University of Health Sciences, Vienna, Austria. FAU - Jiang, Haiyang AU - Jiang H AD - Tongji Medical College of Huazhong, University of Science and Technology, Wuhan, China. FAU - Jha, Shivangi AU - Jha S AD - Albert Szent-Gyorgyi Medical School, University of Szeged, Szeged, Hungary. FAU - Bernad, Peter G AU - Bernad PG AD - Department of Neurology and Rehabilitation Medicine, George Washington University, Washington D.C, United States of America. LA - eng PT - Case Reports PT - Journal Article DEP - 20260126 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Adult MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/adverse effects MH - *Brachial Plexus Neuritis/chemically induced/etiology MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Recurrence PMC - PMC12918017 OTO - NOTNLM OT - Brachial plexus neuritis OT - Case report OT - GLP-1 agonists OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The patient gave written informed consent for their clinical details along with any identifying images to be published in this study. Competing interests: The authors declare no competing interests. EDAT- 2026/01/27 00:52 MHDA- 2026/06/27 06:46 PMCR- 2026/01/26 CRDT- 2026/01/26 23:32 PHST- 2025/10/23 00:00 [received] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/06/27 06:46 [medline] PHST- 2026/01/27 00:52 [pubmed] PHST- 2026/01/26 23:32 [entrez] PHST- 2026/01/26 00:00 [pmc-release] AID - 10.1186/s12883-026-04664-4 [pii] AID - 4664 [pii] AID - 10.1186/s12883-026-04664-4 [doi] PST - epublish SO - BMC Neurol. 2026 Jan 26;26(1):123. doi: 10.1186/s12883-026-04664-4. PMID- 41587701 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 1879-260X (Electronic) IS - 0925-4439 (Linking) VI - 1872 IP - 4 DP - 2026 Apr TI - Mitigating loss of lean muscle in GLP-1 and dual GLP-1/GIP agonists: Pipeline opportunities and limitations. PG - 168172 LID - S0925-4439(26)00020-7 [pii] LID - 10.1016/j.bbadis.2026.168172 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists drive significant transformation in the landscape for type 2 diabetes and obesity management, yet 15-40% of weight loss in trials like STEP and SURMOUNT stems from lean muscle mass. This catabolic loss impairs glucose disposal, muscle strength, and physical function; elevating risks for the loss of force generating capacity in the skeletal muscles leading to sarcopenia, particularly in elderly patients. Unfortunately, current FDA guidelines emphasize total weight reduction over body composition, featuring an unmet critical need for elucidating strategies to preserve loss of lean muscle. This review will feature the emerging therapeutics to mitigate loss of lean muscle, including selective androgen receptor modulators, myostatin-targeting TGF-beta inhibitors, and gene-silencing siRNA therapies. Despite promising preclinical and early clinical data, limitations persist, including reliance on parenteral biologics, limited mechanistic diversity, short trial durations, and sparse functional outcome data. Future research must prioritize precise muscle assessments, body composition, long-term trials, and accessible interventions integrating pharmacotherapy. These advances could redefine weight loss paradigms, ensuring therapeutic efficacy aligns with optimal body composition and patient outcomes. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Hierholzer, Justin AU - Hierholzer J AD - Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. FAU - Benson, Harrison AU - Benson H AD - Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. FAU - Ewida, Heba A AU - Ewida HA AD - Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA; Department of Biochemistry, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt. FAU - Ahmed, Mahmoud Salama AU - Ahmed MS AD - Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA; Brain Drug Discovery Center, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. Electronic address: mahmoudsalama.ahmed@ttuhsc.edu. LA - eng PT - Journal Article PT - Review DEP - 20260124 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Myostatin) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Muscle, Skeletal/metabolism/drug effects/pathology MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/agonists/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/pathology MH - *Gastric Inhibitory Polypeptide/agonists/metabolism MH - *Sarcopenia/metabolism/pathology/drug therapy MH - Myostatin/antagonists & inhibitors/metabolism MH - *Obesity/metabolism/drug therapy/pathology MH - *Receptors, Gastrointestinal Hormone/agonists/metabolism MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism COIS- Declaration of competing interest The authors declare no conflicts of interests. EDAT- 2026/01/27 00:52 MHDA- 2026/03/07 06:39 CRDT- 2026/01/26 19:13 PHST- 2025/09/22 00:00 [received] PHST- 2026/01/13 00:00 [revised] PHST- 2026/01/23 00:00 [accepted] PHST- 2026/03/07 06:39 [medline] PHST- 2026/01/27 00:52 [pubmed] PHST- 2026/01/26 19:13 [entrez] AID - S0925-4439(26)00020-7 [pii] AID - 10.1016/j.bbadis.2026.168172 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2026 Apr;1872(4):168172. doi: 10.1016/j.bbadis.2026.168172. Epub 2026 Jan 24. PMID- 41587563 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260707 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 49 IP - 3 DP - 2026 Mar 1 TI - GLP-1 Receptor Agonists and Risk of Optic Nerve or Vision-Threatening Events in Patients With Type 2 Diabetes or Cardiometabolic Diseases: A Meta-analysis of Randomized Controlled Trials. PG - 526-535 LID - 10.2337/dc25-1929 [doi] AB - BACKGROUND: Data concerning glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on risk of ischemic optic neuropathy (ION) are conflicting. PURPOSE: We synthesize current evidence of GLP-1 RAs on risk of optic nerve or vision-threatening events from randomized controlled trials (RCTs) in patients with type 2 diabetes or cardiometabolic diseases. DATA SOURCE: A total of 83,288 participants with type 2 diabetes/cardiometabolic diseases from 20 published RCTs were analyzed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). STUDY SELECTION: RCTs investigating GLP-1 RAs for type 2 diabetes/cardiometabolic disease populations and reported optic nerve or vision-related adverse events were assessed. DATA EXTRACTION: Primary outcome was a composite of optic nerve and/or vision-threatening serious adverse events, including ION, ocular ischemic syndrome, papilledema, blindness, blurred vision, visual impairment, and reduced visual acuity. Odds ratios (ORs) were derived. DATA SYNTHESIS: Type 2 diabetes occurred in 76.4% of participants. Over mean follow-up duration of 2.97 years (estimated cumulative exposure of 240,334 patient-years), GLP-1 RA use was not associated with increased risk of primary end point (OR 1.20, 95% CI 0.73-1.97, I2 = 0%). Prespecified individual adverse events, including ION (OR 1.50, 95% CI 0.49-4.63), and vision loss/disturbance events (OR 1.08, 95% CI 0.60-1.94) were not significantly associated with GLP-1 RA use. LIMITATIONS: RCTs reported vision-threatening events as adverse events rather than as prespecified outcomes. CONCLUSIONS: Based on a large number of patients who contributed to a meta-analysis of RCTs involving participants with type 2 diabetes and cardiometabolic disease, GLP-1 RAs were not associated with an increased risk of optic nerve/vision-threatening events. CI - (c) 2026 by the American Diabetes Association. FAU - Li, Hoi-Ying AU - Li HY AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Chan, Tsz-Kwan AU - Chan TK AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Co Shih, Kendrick AU - Co Shih K AD - Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China. FAU - Cheung, Bernard M Y AU - Cheung BMY AUID- ORCID: 0000-0001-9106-7363 AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Yiu, Kai-Hang AU - Yiu KH AUID- ORCID: 0000-0003-2145-3108 AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine, Shenzhen Hong Kong University Hospital, Shenzhen, China. AD - Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Tse, Hung-Fat AU - Tse HF AUID- ORCID: 0000-0003-4665-7887 AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Department of Medicine, Shenzhen Hong Kong University Hospital, Shenzhen, China. FAU - Chan, Yap-Hang AU - Chan YH AUID- ORCID: 0000-0001-5384-8468 AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, U.K. LA - eng GR - 2024/25/Doris Zimmern HKU-Cambridge Hughes Hall Fellowship/ GR - 2022/Li Shu Pui Medical Foundation Fellowship/ GR - 2024/25/Hong Kong Research Grants Council Clinical Research Fellowship/ GR - 104006735, 109000417, 109001395/Seed Funding for Basic Research/ Translational and Applied Research/ GR - GRF 17110122 and 17108523/Hong Kong Research Grants Council General Research Fund/ PT - Journal Article PT - Meta-Analysis PT - Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Cardiovascular Diseases/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Optic Nerve/drug effects MH - *Vision Disorders EDAT- 2026/01/27 00:52 MHDA- 2026/02/20 21:28 CRDT- 2026/01/26 19:03 PHST- 2025/08/06 00:00 [received] PHST- 2025/12/12 00:00 [accepted] PHST- 2026/02/20 21:28 [medline] PHST- 2026/01/27 00:52 [pubmed] PHST- 2026/01/26 19:03 [entrez] AID - 164303 [pii] AID - 10.2337/dc25-1929 [doi] PST - ppublish SO - Diabetes Care. 2026 Mar 1;49(3):526-535. doi: 10.2337/dc25-1929. PMID- 41582696 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - GLP-1RAs versus metformin and Parkinson's risk in type 2 diabetes. PG - 2815-2826 LID - 10.1111/dom.70459 [doi] AB - BACKGROUND: Parkinson's disease (PD) is an increasingly prevalent neurodegenerative condition, particularly among individuals with type 2 diabetes mellitus (T2DM). While prior studies have suggested that GLP-1 receptor agonists (GLP-1RAs) and metformin may confer neuroprotective effects, most were limited by small sample sizes, short follow-up, uncontrolled designs, or lacked direct comparisons between therapies-making their findings inconclusive for clinical decision-making. METHODS: Using the TriNetX Global Collaborative Network, we identified 92 485 patients with T2DM initiating GLP-1RA therapy and matched them 1:1 to new metformin users using propensity score matching. Patients with prior antidiabetic therapy, PD, or dementia were excluded. Incident PD was the primary outcome; all-cause mortality served as a secondary endpoint. Adjusted hazard ratios (aHRs) were estimated using Cox models. Competing risk and time-stratified (10 years) analyses were conducted. Positive and negative outcome/exposure controls were employed to validate internal consistency. RESULTS: The overall PD risk was comparable between GLP-1RA and metformin groups (aHR, 0.91; 95% CI, 0.79-1.05). However, between years 5 and 10, GLP-1RA use was associated with a significantly lower PD risk (aHR, 0.56; 95% CI, 0.34-0.93). Mortality risk did not differ significantly. Validation analyses confirmed the specificity of the findings. CONCLUSIONS: By addressing key limitations of earlier studies through a large-scale, active-comparator, new-user design, this study provides novel evidence of a delayed neuroprotective effect of GLP-1RAs. These findings support incorporating neurologic outcomes into long-term diabetes management and may inform therapy selection in high-risk populations. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Sun, Mingyang AU - Sun M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Wang, Xiaoling AU - Wang X AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. AD - Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China. FAU - Lu, Zhongyuan AU - Lu Z AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. AD - Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China. FAU - Yang, Yitian AU - Yang Y AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Lv, Shuang AU - Lv S AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Miao, Mengrong AU - Miao M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. FAU - Wu, Szu-Yuan AU - Wu SY AUID- ORCID: 0000-0001-5637-558X AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. AD - Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Taiwan. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. AD - Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Taiwan. AD - Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Zhang, Jiaqiang AU - Zhang J AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. LA - eng GR - 2023YFC25069003/National Key Research and Development Program of China/ GR - 11403/Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital/ GR - 11404/Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital/ PT - Comparative Study PT - Journal Article DEP - 20260126 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Metformin/therapeutic use MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Parkinson Disease/epidemiology/prevention & control MH - Middle Aged OTO - NOTNLM OT - GLP-1 receptor agonists OT - Parkinson's disease OT - comparative effectiveness research OT - metformin OT - type 2 diabetes mellitus EDAT- 2026/01/26 06:27 MHDA- 2026/03/17 06:48 CRDT- 2026/01/26 03:33 PHST- 2025/12/25 00:00 [revised] PHST- 2025/11/28 00:00 [received] PHST- 2026/01/01 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/26 06:27 [pubmed] PHST- 2026/01/26 03:33 [entrez] AID - 10.1111/dom.70459 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2815-2826. doi: 10.1111/dom.70459. Epub 2026 Jan 26. PMID- 41582648 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 64 IP - 5 DP - 2026 May TI - Hemoglobin A1c levels in patients with type 2 diabetes mellitus receiving oral semaglutide with versus without proton pump inhibitors: An exploratory study. PG - 250-258 LID - 10.5414/CP204899 [doi] AB - OBJECTIVE: Oral semaglutide contains salcaprozate sodium, which promotes the opening of epithelial tight junctions and increases gastric pH to prevent its degradation; these actions together improve absorption. Proton pump inhibitors (PPIs) increase gastric pH. However, it is unclear whether PPIs affect the absorption of semaglutide and may therefore enhance the blood glucose lowering effect of semaglutide or affect the reduction of hemoglobin A1c (HbA1c). Therefore, this study investigated differences in HbA1c changes and adverse events between those with and without PPI co-administration. MATERIALS AND METHODS: This single-center retrospective study included patients with type 2 diabetes who received oral semaglutide. Patients were categorized into two groups: those on treatment with PPI (w/PPI) and those not on treatment with PPI (without PPI (w/o PPI)). The primary outcome was the change in HbA1c levels at 52 weeks, while the secondary outcomes included changes at 26 weeks and the incidence of adverse events. RESULTS: A total of 66 patients were included. HbA1c reduction at 52 weeks was significantly greater in the w/PPI group (-1.56 +/- 0.37%) than in the w/o PPI group (-1.08 +/- 0.76%, p = 0.024). The incidences of adverse events were 24.0% and 31.7% in the w/PPI and w/o PPI groups, respectively (p = 0.502). CONCLUSION: HbA1c reduction at 52 weeks was significantly greater in the PPI co-administration group than in the group without PPI. Future research should include larger sample sizes and pharmacokinetic studies to clarify the clinical implications and interactions between oral semaglutide and PPIs. FAU - Matsunuma, Satoru AU - Matsunuma S FAU - Hirota, Yusuke AU - Hirota Y FAU - Yoshimoto, Koichi AU - Yoshimoto K LA - eng PT - Comparative Study PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Proton Pump Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis MH - *Glycated Hemoglobin/metabolism MH - Female MH - *Proton Pump Inhibitors/administration & dosage/adverse effects/therapeutic use MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use/pharmacokinetics MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Administration, Oral MH - Aged MH - Drug Therapy, Combination MH - Blood Glucose/drug effects/metabolism MH - Drug Interactions MH - Treatment Outcome EDAT- 2026/01/26 06:27 MHDA- 2026/04/21 18:07 CRDT- 2026/01/26 03:03 PHST- 2026/04/16 00:00 [accepted] PHST- 2026/04/21 18:07 [medline] PHST- 2026/01/26 06:27 [pubmed] PHST- 2026/01/26 03:03 [entrez] AID - 192692 [pii] AID - 10.5414/CP204899 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2026 May;64(5):250-258. doi: 10.5414/CP204899. PMID- 41582388 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20260915 IS - 2212-3873 (Electronic) IS - 1871-5303 (Linking) VI - 26 DP - 2026 TI - Prevalence, Glycemic Efficacy, and Safety of Four Non-Insulin Antidiabetic Drug Combinations in Patients with Type 2 Diabetes. PG - e18715303402479 LID - 10.2174/0118715303402479251129144029 [doi] AB - INTRODUCTION: Only a few studies have investigated the prevalence and safety of oral quadruple regimens for treating type 2 diabetes (T2D), and evidence regarding combinations that include glucagon-like peptide-1 receptor (GLP-1R) agonists remains limited. METHODS: A descriptive, retrospective, cross-sectional study was conducted to collect information on the use of four non-insulin drug combinations in patients with T2D over a 12-month period. RESULTS: A total of 1,463 patients with T2D were evaluated during the study period, of whom 13.7% met the inclusion criteria and were enrolled. The mean duration of quadruple therapy was 37.0 +/- 23.3 months. Sodium-glucose co-transporter-2 (SGLT2) inhibitors were the most common add-on therapy to a prior triple-drug regimen (32.3%), followed by pioglitazone (30.4%), sulfonylureas (21.9%), and GLP-1R agonists (12.9%). The mean reduction in glycated hemoglobin A1c (A1C) during quadruple therapy was 0.98 +/- 0.88% compared to baseline values (p < 0.001), with no significant adverse effects or safety concerns reported. Notably, the addition of GLP-1R agonists as the fourth drug resulted in greater weight loss than any other oral antidiabetic medication. DISCUSSION: Despite the limitations inherent to a retrospective design, this study demonstrates that quadruple regimens can achieve significant reductions in A1C levels while maintaining a favorable safety profile. CONCLUSION: In this study, 13.7% of patients with T2D received quadruple non-insulin drug combinations. Larger randomized controlled trials are needed to further evaluate their safety, efficacy, limitations, and potential role in T2D management. FAU - Papaetis, Georgios S AU - Papaetis GS AUID- ORCID: 0000-0002-8143-7145 AD - K.M.P. Therapis Paphos Medical Center, Internal Medicine and Diabetes Clinic, 14 Vasileos Georgiou B Street, Office 201, 8010, Paphos, Cyprus. AD - CDA College, 73 Democratias Avenue, Paphos, Cyprus. FAU - Christophi, Costas A AU - Christophi CA AUID- ORCID: 0000-0003-0503-1538 AD - Cyprus International Institute for Environmental & Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Till, Andriana M AU - Till AM AUID- ORCID: 0009-0004-2609-4719 AD - Cyprus International Institute for Environmental & Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Papapostolou, Anastasia AU - Papapostolou A AUID- ORCID: 0000-0002-6157-2761 AD - Alithias Endocrinology Centre, 9A Alithias Street, 2324, Lakatamia, Nicosia, Cyprus. AD - Department of Endocrinology, European University of Cyprus, Nicosia, Cyprus. FAU - Picolos, Michalis K AU - Picolos MK AUID- ORCID: 0000-0003-3562-8810 AD - Alithias Endocrinology Centre, 9A Alithias Street, 2324, Lakatamia, Nicosia, Cyprus. AD - Department of Endocrinology, European University of Cyprus, Nicosia, Cyprus. LA - eng PT - Journal Article PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Retrospective Studies MH - Female MH - Cross-Sectional Studies MH - Male MH - Drug Therapy, Combination MH - *Blood Glucose/drug effects/metabolism MH - Middle Aged MH - Aged MH - Prevalence MH - Treatment Outcome MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects MH - Sulfonylurea Compounds/administration & dosage/adverse effects MH - Glycemic Control MH - Pioglitazone/administration & dosage/adverse effects OTO - NOTNLM OT - GLP-1R agonists OT - SGLT2 inhibitors OT - Type 2 diabetes OT - glycemic efficacy OT - non-insulin drug OT - quadruple therapy EDAT- 2026/01/26 06:26 MHDA- 2026/09/15 11:37 CRDT- 2026/01/26 00:13 PHST- 2025/04/20 00:00 [received] PHST- 2025/07/27 00:00 [revised] PHST- 2025/08/05 00:00 [accepted] PHST- 2026/09/15 11:37 [medline] PHST- 2026/01/26 06:26 [pubmed] PHST- 2026/01/26 00:13 [entrez] AID - EMIDDT-EPUB-152660 [pii] AID - 10.2174/0118715303402479251129144029 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2026;26:e18715303402479. doi: 10.2174/0118715303402479251129144029. PMID- 41581971 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 1558-1357 (Electronic) IS - 0029-6465 (Linking) VI - 61 IP - 1 DP - 2026 Mar TI - Glucagon-like-peptide-1 and Mental Health: The Unexpected Outcomes. PG - 91-100 LID - S0029-6465(25)00073-8 [pii] LID - 10.1016/j.cnur.2025.09.005 [doi] AB - The potential benefits of glucagon-like-peptide-1 receptor agonists (GLP1-RAs) have continued to mount exponentially in recent years, with suggested roles in combating chronic disease and mental illness (Drucker, 2024; Hendershot and colleagues, 2025; Jerlhag, 2023). Evolved from the discovery of the naturally occurring incretin hormone, glucose-dependent insulinotropic polypeptide in the 1970s, GLP1-RAs were initially developed to treat type II diabetes. Their profound effect on second and third-order comorbidities such as obesity, depression, anxiety, and substance use disorders has garnered enormous interest in the mental health community (Drucker, 2024). CI - Published by Elsevier Inc. FAU - O'Connor, Melody A AU - O'Connor MA AD - 2D Medical Battalion, PSC Box 20129, Camp Lejeune, NC 28542-0129, USA. Electronic address: melody.a.oconnor.mil@usmc.mil. FAU - Peters, Angela AU - Peters A AD - Doctor of Nursing Practice, Psychiatric Mental Health Nurse Practitioner Program, College of Nursing, Rosalind Franklin University of Medicine & Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. FAU - Reddin, Christopher J AU - Reddin CJ AD - Doctor of Nursing Practice, Psychiatric Mental Health Nurse Practitioner Program, College of Nursing, Rosalind Franklin University of Medicine & Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. LA - eng PT - Journal Article PT - Review DEP - 20251030 PL - United States TA - Nurs Clin North Am JT - The Nursing clinics of North America JID - 0042033 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Mental Disorders/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Mental Health MH - Obesity/drug therapy OTO - NOTNLM OT - GLP OT - GLP1 OT - GLP1 receptor agonists OT - MAT weight loss COIS- Disclosures The authors have nothing to disclose. EDAT- 2026/01/26 00:33 MHDA- 2026/01/26 00:34 CRDT- 2026/01/25 20:55 PHST- 2026/01/26 00:34 [medline] PHST- 2026/01/26 00:33 [pubmed] PHST- 2026/01/25 20:55 [entrez] AID - S0029-6465(25)00073-8 [pii] AID - 10.1016/j.cnur.2025.09.005 [doi] PST - ppublish SO - Nurs Clin North Am. 2026 Mar;61(1):91-100. doi: 10.1016/j.cnur.2025.09.005. Epub 2025 Oct 30. PMID- 41580697 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260813 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Jan 24 TI - Progression to type 2 diabetes among post-myocardial infarction patients with overweight or obesity: a real-world cohort study. PG - 56 LID - 10.1186/s12933-026-03085-4 [doi] LID - 56 AB - BACKGROUND: Semaglutide has demonstrated the ability to reduce the risk of progression to type 2 diabetes in patients with myocardial infarction and overweight or obesity without diabetes. However, implementation of semaglutide treatment in daily clinical care is challenging due to costs and limited supply. Thus, it is essential to identify patients who are most likely to benefit from this treatment. Therefore, we aimed to investigate the 5-year risk of progression to type 2 diabetes in SELECT-eligible patients with a recent myocardial infarction and overweight or obesity without diabetes, and to assess the estimated preventive potential of semaglutide in a real-world cohort. METHODS: We included patients registered in the Western Denmark Heart Registry with first-time myocardial infarction and body mass index (BMI) >/= 27 kg/m(2) without diabetes, thus meeting the eligibility criteria of the SELECT trial. The cohort was grouped by glycemic status at baseline: HbA1c 6.0-6.4% (prediabetes(6.0-6.4%)), 5.7-6.4% (prediabetes(5.7-6.4%)), or < 5.7% (normoglycemia). A Cox proportional hazards regression model was used to calculate cause-specific hazard ratios (HR), adjusted for sex, age, hypertension, and smoking. The main endpoint was progression to type 2 diabetes. The 5-year number-needed-to-treat (NNT(5)) with semaglutide was estimated based on the SELECT trial. RESULTS: The cohort comprised 7398 patients with median follow-up of 4.7 (Q1-Q3 2.8-5.0) years. At baseline, 1385 (19%) patients had prediabetes(6.0-6.4%), 3751 (51%) had prediabetes(5.7-6.4%), and 3647 (49%) had normoglycemia. The median BMI was similar across the groups: 30 kg/m(2) (Q1-Q3 28-33), 30 kg/m(2) (Q1-Q3 28-32), and 29 kg/m(2) (Q1-Q3 28-31). The 5-year risks of progression to type 2 diabetes were 54%, 30%, and 5%, respectively. Compared with normoglycemia, those with prediabetes(6.0-6.4%) were associated with an 18-fold increased risk of progression to type 2 diabetes (HR 18.3, 95% CI 15.2-22.1) and the estimated NNT(5) with semaglutide to prevent one case of type 2 diabetes was 2.7 in this subgroup. CONCLUSIONS: In real-world patients with recent myocardial infarction and overweight or obesity, prediabetes was much stronger associated with progression to type 2 diabetes than previously reported in the SELECT trial. Further, we estimated that treatment with semaglutide might be able to substantially reduce progression to type 2 diabetes. CI - (c) 2026. The Author(s). FAU - Tonnesen, Pernille Tilma AU - Tonnesen PT AUID- ORCID: 0000-0001-8285-2087 AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. pernille.tilma@clin.au.dk. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. pernille.tilma@clin.au.dk. FAU - Olesen, Kevin Kris Warnakula AU - Olesen KKW AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Gyldenkerne, Christine AU - Gyldenkerne C AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Hansen, Malene Kaerslund AU - Hansen MK AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Stodkilde-Jorgensen, Nina AU - Stodkilde-Jorgensen N AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Thrane, Pernille Gro AU - Thrane PG AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Andersen, Malene Hojgaard AU - Andersen MH AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Thomsen, Reimar Wernich AU - Thomsen RW AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland. FAU - Sorensen, Henrik Toft AU - Sorensen HT AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark. FAU - Maeng, Michael AU - Maeng M AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. LA - eng GR - NNF22OC0074083/Novo Nordisk Fonden/ PT - Journal Article PT - Observational Study DEP - 20260124 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/diagnosis/epidemiology/prevention & control/blood MH - Female MH - Disease Progression MH - Male MH - *Myocardial Infarction/diagnosis/epidemiology MH - Aged MH - Middle Aged MH - Risk Factors MH - *Obesity/diagnosis/epidemiology/drug therapy MH - Time Factors MH - Biomarkers/blood MH - Denmark/epidemiology MH - Registries MH - Risk Assessment MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Overweight/diagnosis/epidemiology PMC - PMC12911086 OTO - NOTNLM OT - Coronary artery disease OT - Myocardial infarction OT - Prediabetes OT - SELECT-eligible OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was reported to the Danish Data Protection Agency (record no. 1-16-02-193-18). Patient consent requirements were waived by regional data protection authorities (record no. 14-45-70-24-22). Consent for publication: Not applicable. Competing interests: MHA is a minor shareholder in Novo Nordisk and is supported by the Danish Cardiovascular Academy (grant number PhD2023001-HF), which is funded by the Novo Nordisk Foundation, grant number NNF20SA0067242, and the Danish Heart Foundation. KKWO is supported by a research grant from the Danish Cardiovascular Academy funded by the Danish Heart Association and Novo Nordisk.RWT has given single lectures on medical research for pharmaceutical companies (with and without compensation), including AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi.NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novartis, Novo Nordisk, Pfizer, and Roche; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. HTS is head of the Department of Clinical Epidemiology, Aarhus University, which receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. The Department of Clinical Epidemiology confirms that none of these studies have any relation to the present study. MM is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083), has received lecture and/or advisory board fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received research grants from Philips, Bayer and Novo Nordisk, has received a travel grant from Novo Nordisk, has ongoing institutional research contracts with Janssen, Novo Nordisk and Philips, and has equity interests in Novo Nordisk, Eli Lilly & Company, and Verve Therapeutics. The remaining authors did not report any competing interests. EDAT- 2026/01/25 00:37 MHDA- 2026/02/18 10:06 PMCR- 2026/01/24 CRDT- 2026/01/24 23:25 PHST- 2025/11/11 00:00 [received] PHST- 2026/01/07 00:00 [accepted] PHST- 2026/02/18 10:06 [medline] PHST- 2026/01/25 00:37 [pubmed] PHST- 2026/01/24 23:25 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - 10.1186/s12933-026-03085-4 [pii] AID - 3085 [pii] AID - 10.1186/s12933-026-03085-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Jan 24;25(1):56. doi: 10.1186/s12933-026-03085-4. PMID- 41580554 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 16 IP - 1 DP - 2026 Jan 24 TI - Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake. PG - 6126 LID - 10.1038/s41598-026-36318-3 [doi] LID - 6126 AB - The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. Considering this, we investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyze whether the pre-treatment gut microbiome can predict the treatment efficacy. In the study, patients with type 2 diabetes donated gut microbiome fecal samples at four timepoints (Baseline, Month 1, Month 3, Month 12) that were studied using 16S ribosomal RNA gene sequencing and analysis. Subjects additionally donated plasma and urine samples for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12. Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome. Pearson correlation was used to identify microbial features associated with the change in clinical parameters. First, semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, but changes in microbial diversity were not detected. Moreover, the baseline gut microbiome predicted changes in glycohemoglobin for semaglutide and empagliflozin users. Based on the results, our findings suggest that semaglutide and empagliflozin impact the gut microbial community during treatment. In addition, the baseline gut microbiome can predict semaglutide treatment effects. CI - (c) 2026. The Author(s). FAU - Klemets, Annabel AU - Klemets A AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Reppo, Ingrid AU - Reppo I AD - Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. AD - Internal Medicine Clinic of Tartu University Hospital, Tartu, Estonia. FAU - Krigul, Kertu Liis AU - Krigul KL AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Volke, Vallo AU - Volke V AD - Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. AD - Internal Medicine Clinic of Tartu University Hospital, Tartu, Estonia. FAU - Aasmets, Oliver AU - Aasmets O AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Org, Elin AU - Org E AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. elin.org@ut.ee. LA - eng GR - IUT2041/Eesti Teadusagentuur/ GR - PRG1414/Eesti Teadusagentuur/ GR - No. 3573/European Molecular Biology Organization/ PT - Journal Article DEP - 20260124 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (RNA, Ribosomal, 16S) SB - IM MH - Humans MH - Semaglutide MH - *Benzhydryl Compounds/therapeutic use/pharmacology MH - *Glucosides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Feces/microbiology MH - Male MH - *Gastrointestinal Microbiome/drug effects MH - Female MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Middle Aged MH - Treatment Outcome MH - RNA, Ribosomal, 16S/genetics MH - Aged PMC - PMC12902008 OTO - NOTNLM OT - Empagliflozin OT - Gut microbiome OT - Jardiance OT - Ozempic OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/01/25 00:37 MHDA- 2026/02/13 01:27 PMCR- 2026/01/24 CRDT- 2026/01/24 23:17 PHST- 2024/12/21 00:00 [received] PHST- 2026/01/12 00:00 [accepted] PHST- 2026/02/13 01:27 [medline] PHST- 2026/01/25 00:37 [pubmed] PHST- 2026/01/24 23:17 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - 10.1038/s41598-026-36318-3 [pii] AID - 36318 [pii] AID - 10.1038/s41598-026-36318-3 [doi] PST - epublish SO - Sci Rep. 2026 Jan 24;16(1):6126. doi: 10.1038/s41598-026-36318-3. PMID- 41579346 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260903 IS - 1522-1539 (Electronic) IS - 0363-6135 (Linking) VI - 330 IP - 2 DP - 2026 Feb 1 TI - GLP-1 receptor agonists, SGLT-2 inhibitors, and their combination: effects on carotid atherosclerosis regression, oxidative stress, and amyloid-beta1-40 in diabetes. PG - H610-H619 LID - 10.1152/ajpheart.00996.2025 [doi] AB - Carotid intima-media thickness (cIMT), amyloid-beta1-40 (Abeta1-40), and oxidative stress are markers of vascular aging and cardiovascular risk. We compared the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on the aforementioned markers in type 2 diabetes (T2DM). We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin. Six-segment cIMT and plaque-equivalent lesions (cIMT >/= 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Abeta1-40 and malondialdehyde (MDA) were measured. All regimens were associated with reductions in cIMT and Abeta1-40 at 12 mo (P < 0.05). MDA decreased overall with the largest reduction in GLP-1RA-based regimens. Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P < 0.05) and in Abeta1-40 (-52.1, -40.3, and -50.7% vs. -30.7%, P < 0.05). Patients achieving cIMT < 1.5 mm at 12 mo was the highest with combination therapy (75%), followed by liraglutide (67%) and empagliflozin (54%) versus insulin (40%; P < 0.05). Patients who regressed <1.5 mm showed greater reduction in Abeta1-40 than those with >/=1.5 mm (-56.2% vs. -25.1%, P = 0.028). Liraglutide, empagliflozin, and their combination induced greater reduction of cIMT (-8.2, -5.6, and -10.7% vs. -1.7%) and Abeta1-40 (-52.1, -40.3, and -50.7% vs. -30.7%; P < 0.05) compared with insulin. cIMT regression was associated with Abeta1-40 and MDA reductions (P < 0.05). In T2DM patients, GLP-1RA and SGLT-2i-particularly in combination-were associated with improvements in carotid atherosclerotic burden, amyloid-related vascular injury, and oxidative stress.NEW & NOTEWORTHY We investigated the effect of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on carotid intima-media thickness (cIMT) and amyloid-beta1-40 (Abeta1-40) in diabetes. Twelve-month treatment with GLP-1RA, SGLT-2i, and their combination confers significant reductions in cIMT and Abeta1-40 compared with insulin. cIMT regression was associated with Abeta1-40 and malondialdehyde reductions. Our findings support that newer antidiabetic agents can favorably modify structural and biochemical markers of atherosclerosis. CI - Copyright (c) 2026 The Authors. FAU - Ikonomidis, Ignatios AU - Ikonomidis I AUID- ORCID: 0000-0001-8241-7886 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Papageorgiou, Anastasios AU - Papageorgiou A AUID- ORCID: 0009-0007-5852-6370 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Pavlidis, George AU - Pavlidis G AUID- ORCID: 0000-0003-3220-3446 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Georgiopoulos, Georgios AU - Georgiopoulos G AUID- ORCID: 0000-0001-7661-5253 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Katogiannis, Konstantinos AU - Katogiannis K AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Maratou, Eirini AU - Maratou E AD - Laboratory of Clinical Biochemistry, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Thymis, John AU - Thymis J AUID- ORCID: 0000-0002-3916-5350 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Pliouta, Loukia AU - Pliouta L AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Kountouri, Aikaterini AU - Kountouri A AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Korakas, Emmanouil AU - Korakas E AUID- ORCID: 0000-0002-7813-5488 AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Kostelli, Gabriella AU - Kostelli G AUID- ORCID: 0000-0002-1732-2255 AD - 2nd Department of Cardiology, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Parissis, John AU - Parissis J AD - University Department of Emergency Medicine, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Nikolaou, Panagiota Efstathia AU - Nikolaou PE AUID- ORCID: 0000-0002-7777-6726 AD - Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece. FAU - Andreadou, Ioanna AU - Andreadou I AD - Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, University General Hospital "Attikon," School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260124 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Benzhydryl Compounds) RN - 0 (Amyloid beta-Peptides) RN - 0 (Peptide Fragments) RN - 839I73S42A (Liraglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Insulin) RN - 0 (amyloid beta-protein (1-40)) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucosides) RN - 0 (Biomarkers) RN - 0 (Incretins) RN - 4Y8F71G49Q (Malondialdehyde) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Carotid Artery Diseases/drug therapy/blood/diagnostic imaging MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/complications MH - *Oxidative Stress/drug effects MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Benzhydryl Compounds/therapeutic use/adverse effects MH - Carotid Intima-Media Thickness MH - *Amyloid beta-Peptides/blood MH - Female MH - *Peptide Fragments/blood MH - *Liraglutide/therapeutic use MH - Male MH - Drug Therapy, Combination MH - Insulin/therapeutic use MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucosides/therapeutic use/adverse effects MH - Aged MH - Biomarkers/blood MH - *Incretins/therapeutic use/adverse effects MH - Prospective Studies MH - Malondialdehyde/blood MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Metformin/therapeutic use MH - Time Factors OTO - NOTNLM OT - amyloid-beta OT - carotid intima-media thickness OT - glucagon-like peptide-1 receptor agonists OT - sodium-glucose cotransporter-2 inhibitors OT - type 2 diabetes mellitus EDAT- 2026/01/24 22:33 MHDA- 2026/02/05 17:34 CRDT- 2026/01/24 12:02 PHST- 2026/02/05 17:34 [medline] PHST- 2026/01/24 22:33 [pubmed] PHST- 2026/01/24 12:02 [entrez] AID - 10.1152/ajpheart.00996.2025 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2026 Feb 1;330(2):H610-H619. doi: 10.1152/ajpheart.00996.2025. Epub 2026 Jan 24. PMID- 41578841 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 1 DP - 2026 Jan TI - A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes. PG - e70165 LID - 10.1002/edm2.70165 [doi] LID - e70165 AB - AIMS: Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality. METHODS: A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity. RESULTS: The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53-0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64-1.01) and 1.17 (0.87-1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups. CONCLUSIONS: New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Hastrup, Sidsel AU - Hastrup S AUID- ORCID: 0000-0002-5232-8409 AD - Department of Neurology, Danish Stroke Center, Aarhus University Hospital, Aarhus, Denmark. FAU - Hedegaard, Jakob N AU - Hedegaard JN AD - Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark. FAU - Andersen, Grethe AU - Andersen G AD - Department of Neurology, Danish Stroke Center, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, University of Aarhus, Aarhus, Denmark. FAU - Osler, Merete AU - Osler M AD - Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark. AD - Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Rungby, Jorgen AU - Rungby J AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Johnsen, Soren Paaske AU - Johnsen SP AD - Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark. LA - eng GR - Novo Nordisk/ PT - Comparative Study PT - Journal Article PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Myocardial Infarction/epidemiology/mortality/prevention & control MH - Female MH - Denmark/epidemiology MH - Male MH - *Stroke/epidemiology/mortality/prevention & control/etiology MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies MH - Comparative Effectiveness Research MH - Risk Factors MH - Incidence PMC - PMC12831120 OTO - NOTNLM OT - DPP-4i OT - GLP-1 RA OT - SGLT2i OT - stroke OT - type 2 diabetes COIS- The authors declared the funding as a potential conflicts of interest. However, Novo Nordisk A/S, Denmark had no influence on data collection, no data access and no influence on the interpretation of the results. EDAT- 2026/01/24 06:35 MHDA- 2026/01/24 06:36 PMCR- 2026/01/24 CRDT- 2026/01/24 04:52 PHST- 2025/12/29 00:00 [revised] PHST- 2025/09/23 00:00 [received] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/01/24 06:36 [medline] PHST- 2026/01/24 06:35 [pubmed] PHST- 2026/01/24 04:52 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - EDM270165 [pii] AID - 10.1002/edm2.70165 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Jan;9(1):e70165. doi: 10.1002/edm2.70165. PMID- 41575133 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260630 IS - 2101-017X (Electronic) IS - 0035-2640 (Linking) VI - 75 IP - 9 DP - 2025 Nov TI - [Pharmacological management of non-insulin-treated type 2 diabetes: practical implementation of HAS guidelines]. PG - s6-s9 AB - PHARMACOLOGICAL MANAGEMENT OF NON-INSULIN-TREATED TYPE 2 DIABETES: PRACTICAL IMPLEMENTATION OF HAS GUIDELINES. French health authorities' guidelines for type 2 diabetes were updated in May 2024. These guidelines provide a framework for the appropriate positioning of various therapeutic options in the management of type 2 diabetes. Lifestyle modifications and metformin remain the first-line treatment. A paradigm shift introduced by these new recommendations emphasizes the need to prioritize cardiovascular and renal status over glycemic control when initiating therapy. Consequently, these guidelines recommend early use of SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors) or GLP-1 receptor agonists in patients requiring secondary cardiovascular prevention. In cases of chronic kidney disease or heart failure, SGLT2 inhibitors are preferred, followed by GLP-1 receptor agonists. FAU - Hadjadj, Hadjadj AU - Hadjadj H AD - Nantes Universite, CHU de Nantes, CNRS, Inserm, Institut du thorax, Nantes, France. LA - fre PT - English Abstract PT - Journal Article TT - Strategie medicamenteuse du patient DT2 non insuline : mise en oeuvre pratique des recommandations HAS. PL - France TA - Rev Prat JT - La Revue du praticien JID - 0404334 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Practice Guidelines as Topic MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Metformin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular Diseases OT - Diabetes Mellitus OT - Hypoglycemic Agents OT - Insulin OT - Renal Insufficiency, Chronic COIS- L'auteur declare les liens d'interets suivants : consultant AstraZeneca/Valbiotis ; honoraires : AstraZeneca, Abbott, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier ; soutien a la recherche : Abbott, Asten Sante, AstraZeneca, Dinno Sante, Homeperf, Isis Diabete, Nestle Home Care, VitalAire. EDAT- 2026/01/23 13:04 MHDA- 2026/01/23 13:05 CRDT- 2026/01/23 08:39 PHST- 2026/01/23 13:05 [medline] PHST- 2026/01/23 13:04 [pubmed] PHST- 2026/01/23 08:39 [entrez] PST - ppublish SO - Rev Prat. 2025 Nov;75(9):s6-s9. PMID- 41574970 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Efficacy and safety of once-weekly insulins in type 2 diabetes: A systematic review and meta-analysis. PG - 3491-3501 LID - 10.1111/dom.70497 [doi] AB - AIMS: Once-weekly (OW) insulins represent a promising strategy to reduce injection burden and improve adherence in type 2 diabetes management. This meta-analysis aimed to quantify pooled effect sizes for key biological and clinical outcomes, integrating new findings from the five large trials published in 2025. MATERIALS AND METHODS: We systematically searched PubMed, WoS, ClinicalTrials.gov and EU Clinical Trials databases up to June 2025 for randomized controlled trials (RCTs) evaluating OW insulins in type 2 diabetes. Primary outcomes included efficacy (HbA1c, fasting plasma glucose (FPG), time-in-range (TIR), time-above-range) and safety outcomes (body weight, hypoglycaemia, time-below-range). Data were analysed using both frequentist and Bayesian approaches. RESULTS: Among 435 screened records, 16 RCTs were included. OW insulins achieved a greater reduction in HbA1c compared to once-daily insulin or semaglutide (pooled mean difference: -0.12%, 95% CI: -0.19 to -0.04, p = 0.007). TIR was significantly longer in the OW insulin group (+2.41% of total time, 95% CI: 1.13 to 3.69, p = 0.002), while FPG changes were comparable (-3.37 mg/dL, 95% CI: -7.95 to 1.21 mg/dL, p = 0.14). Body weight changes were generally similar, but excluding trials using IcoSema revealed a modest weight gain (+0.33 kg, 95% CI: 0.04 to 0.62, p = 0.030). The incidence of clinically significant or severe hypoglycaemia did not differ between groups (pooled incidence rate ratio: 1.04, 95% CI: 0.79 to 1.28, p = 0.75). Meta-regression confirmed consistent effect sizes across OW insulin types, treatment durations and prior insulin regimens. CONCLUSIONS: OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bourron, Olivier AU - Bourron O AUID- ORCID: 0000-0001-7348-7161 AD - Sorbonne Universite, UMRS 1166, AP-HP, Hopital Pitie-Salpetriere, Service de Diabetologie, INSERM, IHU ICAN, Paris, France. FAU - Denimal, Damien AU - Denimal D AUID- ORCID: 0000-0001-5454-954X AD - Universite Bourgogne Europe, CHU Dijon Bourgogne, Service Biochimie, INSERM, U1231, PADYS Team, Dijon, France. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260123 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis MH - *Insulin/administration & dosage/adverse effects MH - Blood Glucose/drug effects MH - Hypoglycemia/chemically induced MH - Semaglutide MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC13071184 OTO - NOTNLM OT - insulin analogues OT - insulin therapy OT - meta-analysis OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/01/23 13:05 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/01/23 08:13 PHST- 2026/01/04 00:00 [revised] PHST- 2025/10/09 00:00 [received] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/01/23 13:05 [pubmed] PHST- 2026/01/23 08:13 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70497 [pii] AID - 10.1111/dom.70497 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3491-3501. doi: 10.1111/dom.70497. Epub 2026 Jan 23. PMID- 41572751 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260630 IS - 1875-6417 (Electronic) IS - 1573-3998 (Linking) VI - 22 IP - 8 DP - 2026 TI - The Beneficial Effects of Combination Therapy With SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus. PG - e15733998419380 LID - 10.2174/0115733998419380251126073540 [doi] AB - Type 2 diabetes mellitus is a chronic metabolic disorder associated with microvascular and macrovascular complications. Hyperglycemia and insulin resistance are core pathophysiological components of diabetes, linked to subclinical inflammation and persistent oxidative stress, which result in endothelial dysfunction and subsequent atherogenesis. Nowadays, several arrows in the diabetologist's quiver are available for the management of diabetes, providing flexibility and the ability to adopt a personalized approach tailored to each patient's needs. Two of the most commonly prescribed antidiabetic drugs are sodium-glucose cotransporter 2 inhibitors and glucagon- like peptide-1 receptor agonists. Both agents are associated with beneficial metabolic, cardioand nephro-protective effects independent of their antidiabetic properties; thus, their indications have and are continuously expanding over and beyond the treatment of diabetes. Given that these two drug classes have different mechanisms of action, the use of their combination achieves a synergistic interaction and confers additional benefits. The aim of this review is to provide a summary of current knowledge regarding the use of these two drug classes, shed light on the available evidence on their combination, and discuss future perspectives on optimal therapeutic decisions in clinical practice. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in combination therapy are a promising therapeutic duo and are expected to influence future guidelines and decision-making in everyday clinical practice. FAU - Kalogeris, Aimilianos AU - Kalogeris A AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Ikonomidis, Ignatios AU - Ikonomidis I AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Kyriakoulis, Konstantinos G AU - Kyriakoulis KG AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Pavlidis, George AU - Pavlidis G AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Thymis, John AU - Thymis J AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Katogiannis, Konstantinos AU - Katogiannis K AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Kountouri, Aikaterini AU - Kountouri A AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Pliouta, Loukia AU - Pliouta L AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Pililis, Sotirios AU - Pililis S AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Korakas, Emmanouil AU - Korakas E AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - National and Kapodistrian University of Athens, School of Health Sciences, Department of Medicine, Athens, Greece. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Cardiovascular disease OT - GLP-1 receptor agonist OT - SGLT-2 inhibitors OT - combination therapy OT - glycemic control OT - type 2 diabetes mellitus EDAT- 2026/01/23 06:30 MHDA- 2026/06/30 06:31 CRDT- 2026/01/23 02:06 PHST- 2025/06/01 00:00 [received] PHST- 2025/08/19 00:00 [revised] PHST- 2025/09/11 00:00 [accepted] PHST- 2026/06/30 06:31 [medline] PHST- 2026/01/23 06:30 [pubmed] PHST- 2026/01/23 02:06 [entrez] AID - CDR-EPUB-152543 [pii] AID - 10.2174/0115733998419380251126073540 [doi] PST - ppublish SO - Curr Diabetes Rev. 2026;22(8):e15733998419380. doi: 10.2174/0115733998419380251126073540. PMID- 41567800 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20261020 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Implementation of guideline-recommended organ-protective therapy in people with type 2 diabetes and cardiovascular disease, heart failure, or kidney disease: real-world evidence from a German University Hospital. PG - 1736984 LID - 10.3389/fendo.2025.1736984 [doi] LID - 1736984 AB - BACKGROUND: Organ-protective therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) is recommended for people with type 2 diabetes (PwT2D) and cardiorenal comorbidities, yet real-world uptake remains uncertain. METHODS: Using the University Hospital Essen FHIR data lake (2019-2024), we identified PwT2D and cardiorenal comorbidities qualifying for organ-protective therapy [atherosclerotic cardiovascular disease (ASCVD/high ASCVD risk), heart failure (HF), chronic kidney disease (CKD)] by International Classification of Diseases (ICD-10) diagnoses, German surgery procedure codes (OPS), and clinical data. Guideline adherence and treatment trends were assessed by Anatomical Therapeutic Chemical (ATC) medication data for SGLT2i and GLP1RA. Group differences and factors associated with guideline adherent therapy were analyzed using X(2)-test and multivariable modeling. RESULTS: The total cohort comprised 19,684 individuals (age: 70.3 +/- 11.2 years, female sex: 36.8%, mean HbA1c 7.2 +/- 1.5%, BMI 29.7 +/- 6.4 kg/m(2)). In group analysis, female sex was the most prominent difference with lower rates of women among those treated with SGLT2i and/or GLP1RA with small to moderate effect size (standardized mean difference 0.48). Guideline adherent therapy with SGLT2i and/GLP1RA increased steadily from 10.2% to 48.7% in PwT2D eligible for organ-protective therapy. Treatment rates varied by comorbidity and drug class, with the lowest overall uptake observed in people with T2D and CKD (32.5%) and the highest in those with all three cardiorenal comorbidities (63.9%). Among drug classes, SGLT2i use was 44.7%, GLP1RA use was 9.5%, and combination therapy remained low at 5.5%. Female sex (OR 0.76, 95% CI 0.66-0.89, p<0.001), and higher age (OR 0.98, 95% CI 0.99-0.97, p<0.0001) reduced the likelihood, while higher number of comorbidities (OR 1.26, 95% CI 1.18-1.34, p<0.0001) and higher number of medication (OR 1.98, 95% CI 1.88-2.08, p<0.0001) increased the likelihood of guideline adherent therapy. CONCLUSIONS: Guideline recommendations for organ protection in PwT2D and cardiorenal comorbidities are increasingly reflected in clinical practice, yet a substantial care gap persists, with the majority of individuals remaining untreated. Certain subpopulations - particularly women - are underrepresented among those receiving guideline adherent therapy. Further research into the causes of undertreatment and development of targeted implementation strategies is needed to close remaining evidence-practice gaps. CI - Copyright (c) 2026 Suliman, Lee-Barkey, Brehmer, Stratmann, Klose, Lenfers, Kleesiek, Reger-Tan and Keyl. FAU - Suliman, Karzan AU - Suliman K AD - Department of Diabetes and Endocrinology, Heart and Diabetes Center NRW, University Hospital of Ruhr-University Bochum, Bochum, Germany. FAU - Lee-Barkey, Young Hee AU - Lee-Barkey YH AD - Department of Diabetes and Endocrinology, Heart and Diabetes Center NRW, University Hospital of Ruhr-University Bochum, Bochum, Germany. FAU - Brehmer, Alexander AU - Brehmer A AD - Institute for Artificial Intelligence in Medicine (IKIM), University Hospital Essen, Essen, Germany. FAU - Stratmann, Bernd AU - Stratmann B AD - Department of Diabetes and Endocrinology, Heart and Diabetes Center NRW, University Hospital of Ruhr-University Bochum, Bochum, Germany. FAU - Klose, Jasmin M AU - Klose JM AD - Department of Diabetes and Endocrinology, Heart and Diabetes Center NRW, University Hospital of Ruhr-University Bochum, Bochum, Germany. FAU - Lenfers, Tim AU - Lenfers T AD - Institute for Artificial Intelligence in Medicine (IKIM), University Hospital Essen, Essen, Germany. FAU - Kleesiek, Jens AU - Kleesiek J AD - Institute for Artificial Intelligence in Medicine (IKIM), University Hospital Essen, Essen, Germany. FAU - Reger-Tan, Susanne AU - Reger-Tan S AD - Department of Diabetes and Endocrinology, Heart and Diabetes Center NRW, University Hospital of Ruhr-University Bochum, Bochum, Germany. FAU - Keyl, Julius AU - Keyl J AD - Institute for Artificial Intelligence in Medicine (IKIM), University Hospital Essen, Essen, Germany. AD - Institute of Pathology, University Hospital Essen, Essen, Germany. LA - eng PT - Journal Article DEP - 20260106 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Front Endocrinol (Lausanne). 2026 Oct 05;17:1954561. doi: 10.3389/fendo.2026.1954561. PMID: 42898842 MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - *Heart Failure/drug therapy/epidemiology MH - Germany/epidemiology MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Cardiovascular Diseases/drug therapy/epidemiology/prevention & control MH - Hospitals, University MH - *Guideline Adherence MH - Practice Guidelines as Topic MH - Middle Aged MH - *Kidney Diseases/drug therapy/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use PMC - PMC12816769 OTO - NOTNLM OT - GLP1RA OT - SGLT2i OT - atherosclerotic cardiovascular disease OT - chronic kidney disease OT - guidelines OT - heart failure OT - organ protection OT - type 2 diabetes COIS- ST reports honoraria for lectures from Abbott, Bayer, Berlin-Chemie, Boehringer-Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Sanofi Aventis and SinoCare, for consulting and advisory from Abbott, Boehringer-Ingelheim, Dexcom, Insulet, Novo Nordisk, Sanofi Aventis, SinoCare and funded research from Abbott, Amgen, Apo Science, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Hoffmann-La Roche, Medtronic, NeoplasMed, Novartis, Novo Nordisk. BS honoraria for invited speeches from NeoplasMed and research funding from Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Novartis, Novo Nordisk, Roche Pharma, Vertex Pharmaceuticals. YL-B has received honoraria for speaking/consulting activities from Allergan, Amgen, Applied Therapeutics, Astra Zeneca, Bayer, BDI, Boehringer-Ingelheim, BristolMyers Squibb, Chiesi, Hoffmann-La Roche, Eli Lilly, Pfizer, Novartis, NovoNordisk, Sanofi Aventis, Santis and Servier. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/01/22 11:57 MHDA- 2026/01/22 11:58 PMCR- 2026/01/06 CRDT- 2026/01/22 04:41 PHST- 2025/10/31 00:00 [received] PHST- 2025/12/06 00:00 [revised] PHST- 2025/12/11 00:00 [accepted] PHST- 2026/01/22 11:58 [medline] PHST- 2026/01/22 11:57 [pubmed] PHST- 2026/01/22 04:41 [entrez] PHST- 2026/01/06 00:00 [pmc-release] AID - 10.3389/fendo.2025.1736984 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jan 6;16:1736984. doi: 10.3389/fendo.2025.1736984. eCollection 2025. PMID- 41565576 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - GLP-1 receptor agonists and cardiovascular outcomes in Asian, Black or African American, and White populations: An updated meta-analysis including the SOUL trial. PG - 2806-2814 LID - 10.1111/dom.70458 [doi] AB - AIMS: To evaluate the cardiovascular efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in Asian, Black or African American, and White populations, and to assess whether the magnitude of cardiovascular risk reduction differs across these populations. MATERIALS AND METHODS: PubMed and EMBASE were searched to 11 November 2025 for randomized placebo-controlled GLP-1RA trials in adults with type 2 diabetes or overweight/obesity that reported race-stratified major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Hazard ratios (HRs) for MACE were extracted for Asian, Black or African American, and White populations. Random-effects meta-analyses were used to obtain pooled HRs and ratios of HRs (RHRs) comparing treatment effects between populations. RESULTS: Nine trials, including the recent SOUL trial, were included, comprising 8164 Asian, 4036 Black or African American, and 62 503 White participants. GLP-1RAs reduced MACE risk in Asian (HR 0.73; 95% CI 0.63-0.85; p < 0.001) and White populations (HR 0.86; 95% CI 0.81-0.91; p < 0.001). In Black or African American populations, the effect was similar to that in White populations (HR 0.88; 95% CI 0.67-1.15; p = 0.34) but did not reach statistical significance. The pooled RHR for Asian versus White populations was 0.84 (95% CI 0.71-0.98; p = 0.027), indicating a significantly greater risk reduction in Asian populations. The RHR for Asian versus Black or African American populations was 0.81 (95% CI 0.57-1.16; p = 0.25), with point estimates favouring Asian populations. CONCLUSIONS: GLP-1RAs reduced MACE risk across populations, with greater relative risk reduction in Asian populations and broadly similar benefits in Black or African American and White populations. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hasebe, Masashi AU - Hasebe M AUID- ORCID: 0000-0001-7031-2446 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Su, Chen-Yang AU - Su CY AUID- ORCID: 0000-0001-6071-4660 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Quantitative Life Sciences Program, McGill University, Montreal, Quebec, Canada. FAU - Kamido, Hisashi AU - Kamido H AUID- ORCID: 0009-0007-3971-1327 AD - Nephrology Center, Toranomon Hospital Kajigaya, Kawasaki, Kanagawa, Japan. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Yoshiji, Satoshi AU - Yoshiji S AUID- ORCID: 0000-0001-8863-2413 AD - Canada Excellence Research Chair Program in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Quantitative Life Sciences Program, McGill University, Montreal, Quebec, Canada. LA - eng GR - CRC-2025-00097/the Canada Research Chairs Program/ GR - 183596/the Canadian Institutes of Health Research/ GR - DNA to RNA (D2R) Foundational Program, Japan Society for the Promotion of Science/ GR - McGill University/ PT - Journal Article PT - Meta-Analysis DEP - 20260121 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Black or African American/statistics & numerical data MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - White People/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Asian People/statistics & numerical data MH - Asian/statistics & numerical data PMC - PMC12992182 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular disease OT - meta-analysis OT - race COIS- Daisuke Yabe received clinically commissioned or joint research grants from Novo Nordisk, Ono Pharmaceutical, Taisho Pharmaceutical, Terumo, and Arklay. Daisuke Yabe also received consulting or speaker fees from Sumitomo Dainippon Pharma, Boehringer Ingelheim, Astellas Pharma, MSD, Novo Nordisk, Ono Pharmaceutical, Eli Lilly, and Takeda Pharmaceutical. Satoshi Yoshiji serves as a consultant to the Broad Institute of MIT and Harvard through Precision Global Consulting and to PriveBio, Inc., unrelated to this project. All other authors declare no conflicts of interest. EDAT- 2026/01/22 01:09 MHDA- 2026/03/17 06:48 PMCR- 2026/03/17 CRDT- 2026/01/21 22:02 PHST- 2025/12/25 00:00 [revised] PHST- 2025/11/17 00:00 [received] PHST- 2026/01/02 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/22 01:09 [pubmed] PHST- 2026/01/21 22:02 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70458 [pii] AID - 10.1111/dom.70458 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2806-2814. doi: 10.1111/dom.70458. Epub 2026 Jan 21. PMID- 41565568 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260702 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 20 IP - 2 DP - 2026 Apr TI - Semaglutide and tirzepatide in prediabetes: Evidence for diabetes prevention and cardiovascular protection. PG - 178-184 LID - S1751-9918(26)00002-1 [pii] LID - 10.1016/j.pcd.2026.01.003 [doi] AB - BACKGROUND: Prediabetes represents an intermediate stage in the dysglycemia continuum, associated with increased cardiometabolic risk but also substantial opportunity for prevention. The aim of this review was to summarize and critically evaluate the available evidence on the effects of semaglutide and tirzepatide in individuals with prediabetes, focusing on diabetes prevention and cardiovascular (CV) outcomes. METHODS: A narrative synthesis of data from randomized controlled trials, meta-analyses, and real-world studies assessing semaglutide and tirzepatide in people with prediabetes. RESULTS: Across the STEP 1, STEP 5, and SELECT trials, semaglutide 2.4 mg significantly increased regression to normoglycemia (up to 84 %) and reduced the risk of progression to diabetes compared with placebo. In the SURMOUNT-1 trial, tirzepatide reduced the incidence of diabetes by nearly 90 % (Hazard Ratio: 0.07; p < 0.001), an effect largely mediated by substantial weight loss. Regarding CV outcomes, the SELECT trial, of which 66.4 % of participants had prediabetes, demonstrated a significant reduction in the primary composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke with semaglutide versus placebo (hazard ratio 0.80; 95 % CI: 0.72-0.90). A prespecified analysis showed that CV risk reduction was independent of baseline HbA1c, supporting CV benefit in people with prediabetes. The ongoing SURMOUNT-MMO trial will further clarify the CV effects of tirzepatide in individuals with obesity without diabetes. CONCLUSION: Semaglutide and tirzepatide markedly increase regression to normoglycemia and reduce progression to diabetes in people with obesity and prediabetes. Semaglutide has also demonstrated CV benefit in SELECT, including among participants with prediabetes. Ongoing outcome data, particularly from SURMOUNT-MMO, will further define the cardioprotective potential of GLP-1-based medicines across the dysglycemia spectrum. CI - Copyright (c) 2026 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. FAU - Tentolouris, Anastasios AU - Tentolouris A AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. Electronic address: antentol@med.uoa.gr. FAU - Siafarikas, Christos AU - Siafarikas C AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Ntanasis-Stathopoulos, Ioannis AU - Ntanasis-Stathopoulos I AD - Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece. FAU - Anastasiou, Ioanna A AU - Anastasiou IA AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Kalara, Eirini AU - Kalara E AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Briasoulis, Alexandros AU - Briasoulis A AD - Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260120 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Incretins) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use/adverse effects MH - *Prediabetic State/drug therapy/diagnosis/blood/epidemiology MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology MH - Treatment Outcome MH - *Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Biomarkers/blood MH - *Diabetes Mellitus, Type 2/prevention & control/diagnosis/epidemiology/blood MH - *Incretins/therapeutic use/adverse effects MH - Risk Factors OTO - NOTNLM OT - Cardiovascular Disease OT - Diabetes Prevention OT - GLP-1-Based Therapies OT - Prediabetes OT - Semaglutide OT - Tirzepatide COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/01/22 01:09 MHDA- 2026/03/20 00:59 CRDT- 2026/01/21 21:54 PHST- 2025/11/10 00:00 [received] PHST- 2025/12/09 00:00 [revised] PHST- 2026/01/04 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2026/01/22 01:09 [pubmed] PHST- 2026/01/21 21:54 [entrez] AID - S1751-9918(26)00002-1 [pii] AID - 10.1016/j.pcd.2026.01.003 [doi] PST - ppublish SO - Prim Care Diabetes. 2026 Apr;20(2):178-184. doi: 10.1016/j.pcd.2026.01.003. Epub 2026 Jan 20. PMID- 41565054 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260630 IS - 1542-2224 (Electronic) IS - 1067-2516 (Linking) VI - 65 IP - 3 DP - 2026 May-Jun TI - The association of GLP-1 receptor agonists and outcomes following midfoot arthrodesis. PG - 102.e1-102.e6 LID - S1067-2516(26)00012-8 [pii] LID - 10.1053/j.jfas.2026.01.011 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly utilized in managing type 2 diabetes mellitus (T2DM) and obesity. Emerging evidence suggests their role in enhancing bone metabolism, with potential implications for orthopedic outcomes. PURPOSE: To evaluate the impact of perioperative GLP-1RA use on outcomes following midfoot arthrodesis. STUDY DESIGN: This retrospective cohort study used the TriNetX U.S. Collaborative Network to evaluate outcomes following midfoot fusion in patients with versus without perioperative GLP-1RA use. METHODS: Patients were propensity score matched (1:1) for key demographic and clinical variables. Primary outcomes included 90-day and 1-year surgical complications, nonunion, and mechanical issues. Logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Among 1504 matched patients (752 per cohort), GLP-1RA use was associated with significantly reduced odds of nonunion at 1 year (OR = 0.712; 95% CI = 0.52-0.958). However, GLP-1RA users had higher 90-day rates of wound complications (OR = 1.713, 95% CI = 1.141-2.57), irrigation and debridement (OR = 1.873; 95% CI = 1.223-2.869), and elevated 1-year mechanical complications rates (OR = 2.446; 95% CI = 1.552-3.857). No significant differences were observed in infection rates or overall hospital admissions. CONCLUSION: There is an observed association with perioperative GLP-1RA use and lower nonunion rates following midfoot arthrodesis, indicating a potential benefit for bone healing. However, increased mechanical and wound-related complications warrant further investigation into their surgical safety profile in foot and ankle procedures. CI - Copyright (c) 2026 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved. FAU - Bank, Nicholas C AU - Bank NC AD - University of North Carolina Hospitals and Clinics, United States. Electronic address: Nicholas.Bank@unchealth.unc.edu. FAU - Lauck, Bradley J AU - Lauck BJ AD - University of North Carolina Hospitals and Clinics, United States. FAU - Dalola, Joseph AU - Dalola J AD - University of North Carolina Hospitals and Clinics, United States. FAU - Duggan, Sam AU - Duggan S AD - Sidney Kimmel Medical College at Thomas Jefferson University, United States. FAU - Dyke, William B AU - Dyke WB AD - University of North Carolina Hospitals and Clinics, United States. FAU - Lalli, Trapper A AU - Lalli TA AD - University of North Carolina Hospitals and Clinics, United States. LA - eng PT - Journal Article DEP - 20260119 PL - United States TA - J Foot Ankle Surg JT - The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons JID - 9308427 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Arthrodesis/methods MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Treatment Outcome MH - Aged MH - Postoperative Complications MH - Propensity Score OTO - NOTNLM OT - Diabetes OT - GLP-1 OT - GLP-1RA OT - Midfoot arthrodesis OT - Midfoot fusion OT - Nonunion EDAT- 2026/01/22 01:09 MHDA- 2026/05/23 05:39 CRDT- 2026/01/21 19:12 PHST- 2025/09/11 00:00 [received] PHST- 2025/10/31 00:00 [revised] PHST- 2026/01/17 00:00 [accepted] PHST- 2026/05/23 05:39 [medline] PHST- 2026/01/22 01:09 [pubmed] PHST- 2026/01/21 19:12 [entrez] AID - S1067-2516(26)00012-8 [pii] AID - 10.1053/j.jfas.2026.01.011 [doi] PST - ppublish SO - J Foot Ankle Surg. 2026 May-Jun;65(3):102.e1-102.e6. doi: 10.1053/j.jfas.2026.01.011. Epub 2026 Jan 19. PMID- 41563358 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260826 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 37 IP - 8 DP - 2026 Aug 1 TI - Comparative Effectiveness of SGLT2 Inhibitor and GLP-1 Receptor Agonist on Kidney and Cardiovascular Outcomes by Kidney Failure Risk. PG - 1733-1747 LID - 10.1681/ASN.0000001016 [doi] AB - KEY POINTS: In veterans with type 2 diabetes and low kidney failure risk, sodium-glucose cotransporter 2 inhibitors (SGLT2is) were more kidney protective while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were more cardioprotective. For cardiovascular-kidney-metabolic outcomes, GLP-1 RAs were more protective at moderate kidney failure risk and SGLT2is were more protective at high kidney failure risk. The kidney failure risk equation might be a clinically useful tool to guide therapy in type 2 diabetes. BACKGROUND: Head-to-head comparisons of non-exendin glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on kidney failure or cardiovascular-kidney-metabolic (CKM) composite end points are lacking. Whether kidney failure risk modifies the comparative effectiveness of GLP-1 RA versus SGLT2i is clinically relevant. METHODS: We defined a national veterans cohort with type 2 diabetes who initiated an SGLT2i, non-exendin GLP-1 RA, or insulin glargine between January 1, 2018, and December 31, 2021. After applying inverse probability of treatment weighting to balance baseline characteristics, outcomes were compared across new-user groups through March 31, 2023. Outcomes included kidney failure (stage 5 CKD or long-term KRT), major adverse cardiovascular events (MACEs: heart failure, myocardial infarction, or stroke), CKM composite (kidney failure or MACE), all-cause death, and composites of outcomes with death. We tested for effect modification by the kidney failure risk equation (KFRE) score on comparative pairwise drug effectiveness. RESULTS: Out of 160,428 veterans, 53%, 14%, and 34% were new users of SGLT2i, GLP-1 RA, and insulin glargine, respectively. Relative to GLP-1 RA new-users, SGLT2i new-users had similar mortality risk, a trend toward lower kidney failure risk (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.74 to 1.06), but higher risk of MACE (HR, 1.14; 95% CI, 1.09 to 1.20) and CKM composite (HR, 1.13; 95% CI, 1.08 to 1.19). The effect of SGLT2i versus GLP-1 RA differed significantly between moderate-risk (2%-6%) and high-risk (>/=6%) KFRE subgroups for all outcomes except all-cause death. In those with moderate-risk KFRE, GLP-1 RA seemed more protective for kidney failure, MACE, and CKM composite, while SGLT2i appeared more protective in those with high-risk KFRE. CONCLUSIONS: Compared with GLP-1 RA, SGLT2i had comparable risks of mortality, perhaps a lower risk of kidney failure, but modestly higher risk of cardiovascular events in the entire cohort. However, GLP-1 RA were more beneficial in those with moderate kidney failure risk and SGLT2i more beneficial in those with high kidney failure risk. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_07_29_KTS_July2026.mp3. CI - Copyright (c) 2026 by the American Society of Nephrology. FAU - Hartsell, Sydney E AU - Hartsell SE AUID- ORCID: 0000-0001-7328-3732 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research and Training Institute, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Wei, Guo AU - Wei G AUID- ORCID: 0000-0002-4971-8430 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. FAU - Singh, Ravinder AU - Singh R AUID- ORCID: 0000-0002-7221-8557 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. AD - Division of Biostatistics, Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Throolin, Michael AU - Throolin M AUID- ORCID: 0009-0001-4773-2781 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. AD - Division of Biostatistics, Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Nevers, McKenna R AU - Nevers MR AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. AD - Informatics Decision Enhancement and Surveillance (IDEAS) Center, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Sarwal, Amara AU - Sarwal A AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Derington, Catherine G AU - Derington CG AUID- ORCID: 0000-0001-7382-4607 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Cardiology, Department of Medicine, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado. AD - Adult and Child Center for Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Curtis, Christa AU - Curtis C AUID- ORCID: 0009-0008-2864-7988 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Epidemiology, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Boucher, Robert E AU - Boucher RE AUID- ORCID: 0000-0002-5455-002 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Shen, Jincheng AU - Shen J AUID- ORCID: 0000-0002-6551-3558 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Epidemiology, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Drakos, Stavros AU - Drakos S AUID- ORCID: 0000-0002-1223-327 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research and Training Institute, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Greene, Tom AU - Greene T AUID- ORCID: 0000-0002-3706-7570 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Biostatistics, Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Epidemiology, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. FAU - Beddhu, Srinivasan AU - Beddhu S AUID- ORCID: 0000-0002-3312-315 AD - Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah. AD - George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. LA - eng GR - REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology/National Kidney Foundation/ GR - UM1TR004409/TR/NCATS NIH HHS/United States GR - UM1 TR004409/TR/NCATS NIH HHS/United States GR - UL1 TR002538/TR/NCATS NIH HHS/United States GR - UL1TR002538/TR/NCATS NIH HHS/United States GR - R01 DK128640/DK/NIDDK NIH HHS/United States GR - REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology/Bayer/ GR - R01 AG074592/AG/NIA NIH HHS/United States GR - T32 HL007576/HL/NHLBI NIH HHS/United States GR - T35 DK103596/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20260113 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - doi: 10.1681/ASN.0000001178 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - *Cardiovascular Diseases/prevention & control/etiology/epidemiology MH - Female MH - Middle Aged MH - Aged MH - *Renal Insufficiency/etiology/prevention & control/epidemiology PMC - PMC12924663 MID - NIHMS2139451 OTO - NOTNLM OT - CKD OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - clinical nephrology OT - diabetes OT - heart disease OT - heart failure OT - kidney failure OT - mortality risk OT - progression of renal failure COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F653. EDAT- 2026/01/21 12:59 MHDA- 2026/08/03 18:37 PMCR- 2026/08/01 CRDT- 2026/01/21 10:53 PHST- 2025/06/30 00:00 [received] PHST- 2026/01/08 00:00 [accepted] PHST- 2026/08/03 18:37 [medline] PHST- 2026/01/21 12:59 [pubmed] PHST- 2026/01/21 10:53 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - 00001751-202608000-00013 [pii] AID - JASN-2025-000850 [pii] AID - 10.1681/ASN.0000001016 [doi] PST - ppublish SO - J Am Soc Nephrol. 2026 Aug 1;37(8):1733-1747. doi: 10.1681/ASN.0000001016. Epub 2026 Jan 13. PMID- 41562647 OWN - NLM STAT- MEDLINE DCOM- 20260121 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 29 IP - 1 DP - 2026 Dec TI - Calculating cost per event avoided using a composite number needed to treat. PG - 242-248 LID - 10.1080/13696998.2026.2615606 [doi] AB - OBJECTIVE: Number needed to treat (NNT) and cost per event avoided (CPEA) are measures used to represent the clinical and economic value of chronic treatments and are commonly calculated based on primary endpoints from trials. This approach, although widely used, does not reflect the complete value of a treatment, as it does not consider outcomes beyond the primary endpoints. This research aims to overcome this limitation by developing multiple composite NNTs to derive the CPEA to estimate a total value of semaglutide and dulaglutide in people with established cardiovascular disease. METHODS: Two cardiovascular outcomes trials were selected, SELECT (NCT03574597, semaglutide 2.4 mg) and REWIND (NCT01394952, dulaglutide 1.5 mg). NNT was calculated as NNT = 1/ARR where ARR = control event rate - experimental event rate. NNT was estimated for 3-point major adverse cardiovascular events (MACE-3; primary endpoint of the trials), 5-point MACE (MACE-5), and cardiovascular-kidney-metabolic events (CKM). CPEA of MACE-3, MACE-5, and CKM was calculated as NNT*duration of mean follow-up (semaglutide) or duration of median follow-up (dulaglutide)*estimated net price. RESULTS: The NNT decreased as the number of outcomes in the composite endpoint increased, where NNT(MACE-3), NNT(MACE-5), and NNT(CKM) were 67, 49, and 8 for semaglutide, and 72, 64, and 23 for dulaglutide, respectively. Similarly, the CPEA decreased as the number of outcomes in the composite endpoint increased, where the CPEA for MACE-3, MACE-5 and CKM calculations were $1,662,001, $1,232,417, and $190,387 for semaglutide and $1,884,013, $1,670,366, and $607,886 for dulaglutide. CONCLUSIONS: This research illustrates the limitations of using a NNT focused only on the primary endpoint, as it does not capture the total benefit of the treatment. When considering the value of treatments through NNT or CPEA analyses, a composite endpoint capturing broader benefit should be utilized. FAU - Toliver, Joshua AU - Toliver J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Wang, Julia AU - Wang J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Bhavsar, Jigish AU - Bhavsar J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Sullivan, Sean D AU - Sullivan SD AD - Curta, Inc, Seattle, Washington, USA. AD - CHOICE Institute, School of Pharmacy, University of Washington, Seattle, Washington, USA. LA - eng PT - Journal Article DEP - 20260121 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/economics/therapeutic use MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Immunoglobulin Fc Fragments/economics/therapeutic use MH - *Recombinant Fusion Proteins/economics/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - Clinical Trials, Phase III as Topic OAB - This study demonstrates how to assess the clinical and economic value of different drugs and how to assist decision-makers and payers for informed decision-making. This is substantial in diabetes and obesity, due to the surging costs of treating these diseases, both preventive and curative as well. We use data (from clinical trials) for semaglutide and dulaglutide in people with cardiovascular disease as an example. We calculated the number of people that need to be treated to avoid one major adverse cardiovascular event (MACE) and how much it would cost. We show that it is important to include several types of outcomes (here we look at different types of cardiovascular, kidney and metabolic outcomes), beyond the primary endpoint of a trial, to capture the full value of treatment. OABL- eng OTO - NOTNLM OT - Pharmacoeconomics OT - cardiovascular disease OT - disease management OT - health economics OT - number needed to treat EDAT- 2026/01/21 13:00 MHDA- 2026/01/21 13:01 CRDT- 2026/01/21 09:13 PHST- 2026/01/21 13:01 [medline] PHST- 2026/01/21 13:00 [pubmed] PHST- 2026/01/21 09:13 [entrez] AID - 10.1080/13696998.2026.2615606 [doi] PST - ppublish SO - J Med Econ. 2026 Dec;29(1):242-248. doi: 10.1080/13696998.2026.2615606. Epub 2026 Jan 21. PMID- 41560595 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Comparative effectiveness of GLP-1 receptor agonists, SGLT2 inhibitors and DPP-4 inhibitors on liver outcomes in metabolic dysfunction-associated steatotic liver disease: A retrospective cohort study. PG - 3155-3164 LID - 10.1111/dom.70505 [doi] AB - AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with type 2 diabetes mellitus (T2DM). MASLD carries a substantial risk of progression to cirrhosis or hepatocellular carcinoma (HCC). Whether the metabolic benefits of antidiabetic therapy may alter this progression remains under-investigated. We aimed to evaluate the incidence of cirrhosis or HCC across the commonly used second-line antidiabetic agent classes in patients with coexisting MASLD and T2DM. MATERIALS AND METHODS: We conducted a retrospective cohort study using healthcare claims databases in the United States. Patients with MASLD and T2DM initiating one of the three antidiabetic agent classes, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) were included. Propensity score (PS) matching was applied to control for baseline differences between treatment groups. Cumulative incidence of cirrhosis or HCC over 2 years was estimated with Kaplan-Meier method, and risks between treatment groups were compared using Cox regression. RESULTS: The analysis included three PS-matched cohorts: 4538 GLP-1RA versus DPP-4i pairs, 4754 SGLT2i versus GLP-1RA pairs, and 4333 SGLT2i versus DPP-4i pairs. In the intention-to-treat analysis, no statistically significant differences in the risk of cirrhosis or HCC were observed at 2 years across treatment comparisons (GLP-1RA vs. DPP-4i: hazard ratios [HR] 0.80, 95% confidence intervals [CI] 0.58-1.09; GLP-1RA vs. SGLT2i: HR 0.76, 95% CI 0.55-1.04; SGLT2i vs. DPP-4i: HR 0.78, 95% CI 0.58-1.05). CONCLUSIONS: In this large real-world study, we found no clear or consistent differences in liver-related outcomes across GLP-1RA, SGLT2i, and DPP-4i users over a 2-year period. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Sarker, Jyotirmoy AU - Sarker J AUID- ORCID: 0000-0002-2528-5458 AD - Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Okpara, Ebere AU - Okpara E AUID- ORCID: 0000-0003-0766-3993 AD - Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - De Los Santos, Bertha AU - De Los Santos B AD - Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Kim, Michael AU - Kim M AUID- ORCID: 0009-0002-8944-8823 AD - Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA. FAU - Kim, Kibum AU - Kim K AUID- ORCID: 0000-0002-8676-7434 AD - Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260121 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Liver Neoplasms/epidemiology MH - Liver Cirrhosis/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Carcinoma, Hepatocellular/epidemiology MH - United States/epidemiology MH - Incidence MH - *Fatty Liver/complications/epidemiology/drug therapy MH - Treatment Outcome MH - Disease Progression OTO - NOTNLM OT - GLP-1RA OT - MASLD OT - cirrhosis OT - hepatocellular carcinoma EDAT- 2026/01/21 06:31 MHDA- 2026/03/17 06:48 CRDT- 2026/01/21 04:03 PHST- 2026/01/05 00:00 [revised] PHST- 2025/09/29 00:00 [received] PHST- 2026/01/13 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/21 06:31 [pubmed] PHST- 2026/01/21 04:03 [entrez] AID - 10.1111/dom.70505 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3155-3164. doi: 10.1111/dom.70505. Epub 2026 Jan 21. PMID- 41557360 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260823 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 186 IP - 3 DP - 2026 Mar 1 TI - SGLT2 Inhibitors vs GLP-1 Receptor Agonists for Kidney Outcomes in Individuals With Type 2 Diabetes. PG - 353-361 LID - 10.1001/jamainternmed.2025.7409 [doi] AB - IMPORTANCE: No randomized clinical trial has directly compared the effectiveness of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment in reducing acute and chronic kidney outcomes. OBJECTIVE: To examine the comparative effectiveness of SGLT2i and GLP-1RA treatment for acute and chronic kidney outcomes in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study with a target trial emulation design used nationwide, population-based data from Denmark. Participants were individuals with metformin-treated type 2 diabetes who initiated SGLT2i or GLP-1RA treatment from January 2014 to November 2020, with follow-up through October 2024. EXPOSURE: Initiation of an SGLT2i or a GLP-1RA. MAIN OUTCOMES AND MEASURES: The 2 coprimary outcomes were chronic kidney disease (CKD; 40% reduction in estimated glomerular filtration rate [eGFR], severe albuminuria, or kidney failure) and acute kidney injury (AKI). Secondary outcomes included the individual components of CKD, albuminuria, and death. Intention-to-treat effects were estimated using inverse probability of treatment weights, comparing risks for CKD assessed by the Aalen-Johansen estimator, and AKI burden by mean cumulative counts (MCCs; mean number of events per individual as multiple AKI events were possible). Subgroup analyses included stratification by preexisting cardiovascular or kidney disease. RESULTS: The study included 36 279 individuals who initiated an SGLT2i and 18 782 who initiated a GLP-1RA (median [IQR] age, 63 [55-71] years vs 61 [52-70] years), with comparable diabetes duration, eGFR, and urine albumin-creatinine ratios. The weighted 5-year risk of CKD was 6.7% (95% CI, 6.4%-7.0%) for SGLT2i initiators and 8.2% (95% CI, 7.8%-8.6%) for GLP-1RA initiators (risk ratio: 0.81 [95% CI, 0.76-0.87]; risk difference: -1.5% [95% CI, -2.0% to -1.0%]). The 5-year MCC of AKI per 100 individuals was 25.2 (95% CI, 24.4-26.1) for SGLT2i initiators and 28.7 (95% CI, 27.4-30.0) for GLP-1RA initiators (MCC ratio: 0.88 [95% CI, 0.83-0.93]; MCC difference: -3.5 [95% CI, -5.0 to -2.0]). In contrast, the secondary outcomes of albuminuria and mortality were slightly reduced in GLP-1RA initiators. Results were consistent across subgroups, with the most pronounced CKD and AKI reductions with SGLT2i observed among individuals without preexisting kidney disease. CONCLUSIONS AND RELEVANCE: This comparative effectiveness study found that initiation of SGLT2i vs GLP-1RA treatment in individuals with type 2 diabetes was associated with a lower 5-year risk of CKD and a lower 5-year count of AKI. These findings underscore the potential of SGLT2i treatment for primary prevention of kidney disease in individuals with type 2 diabetes. FAU - Jensen, Simon K AU - Jensen SK AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. AD - Department of Anesthesiology and Intensive Care, Regional Hospital Viborg, Viborg, Denmark. FAU - Heide-Jorgensen, Uffe AU - Heide-Jorgensen U AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. FAU - Andersen, Ina T AU - Andersen IT AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. FAU - Bonnesen, Kasper AU - Bonnesen K AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. AD - Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark. AD - Department of Cardiology, Regional Hospital Godstrup, Denmark. FAU - Fu, Edouard L AU - Fu EL AD - Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Stockholm, Sweden. FAU - Thomsen, Reimar W AU - Thomsen RW AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. FAU - Christiansen, Christian F AU - Christiansen CF AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Renal Insufficiency, Chronic/epidemiology/prevention & control/etiology MH - Denmark/epidemiology MH - Aged MH - Glomerular Filtration Rate MH - *Acute Kidney Injury/epidemiology/prevention & control MH - Albuminuria MH - Hypoglycemic Agents/therapeutic use MH - Diabetic Nephropathies PMC - PMC12820778 COIS- Conflict of Interest Disclosures: Drs Heide-Jorgensen and Andersen reported being involved, through the Department of Clinical Epidemiology, in studies with funding from various companies as research grants to (and administered by) Aarhus University; none of these studies are related to the current study. Dr Thomsen reported giving occasional presentations and lectures on medical epidemiological research (with or without financial compensation) for companies during the last 15 years, including AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. No other disclosures were reported. EDAT- 2026/01/20 14:03 MHDA- 2026/03/06 13:44 PMCR- 2027/01/20 CRDT- 2026/01/20 11:33 PHST- 2026/03/06 13:44 [medline] PHST- 2026/01/20 14:03 [pubmed] PHST- 2026/01/20 11:33 [entrez] PHST- 2027/01/20 00:00 [pmc-release] AID - 2843983 [pii] AID - ioi250091 [pii] AID - 10.1001/jamainternmed.2025.7409 [doi] PST - ppublish SO - JAMA Intern Med. 2026 Mar 1;186(3):353-361. doi: 10.1001/jamainternmed.2025.7409. PMID- 41555812 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 17 IP - 3 DP - 2026 Mar TI - Retrospective comparison of the clinical effects of oral semaglutide and SGLT2 inhibitors treatment in patients with type 2 diabetes. PG - 432-438 LID - 10.1111/jdi.70240 [doi] AB - INTRODUCTION: Recent studies have demonstrated that both oral semaglutide and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects on glycemic and weight management as well as providing renal and cardiovascular protection. However, direct comparisons of the effects of these two drugs in clinical practice remain limited. MATERIALS AND METHODS: This study is a single-center, retrospective, observational study. Patients with type 2 diabetes who were initiated on oral semaglutide or SGLT2is and continued treatment for 6 months or more were retrospectively analyzed and compared. RESULTS: The semaglutide group (84 patients) and the SGLT2is group (231 patients) showed similar, significant reductions in glycated hemoglobin (HbA1c) (semaglutide: -0.88 +/- 0.14%; P < 0.01, and SGLT2is: -0.86 +/- 0.06%; P < 0.01, at 6 months), body weight (semaglutide: -2.58 +/- 0.37 kg; P < 0.01, and SGLT2is: -2.30 +/- 0.18 kg; P < 0.01, at 6 months), and fat mass (semaglutide: -2.20 +/- 0.50 kg; P < 0.01, and SGLT2is: -1.93 +/- 0.44 kg; P < 0.01, at 6 months), being decreased similarly and significantly in both groups. On the other hand, there was a significant reduction in skeletal muscle mass only in the SGLT2is group (semaglutide: -0.10 +/- 0.30 kg; P = 0.74, and SGLT2is: -0.40 +/- 0.14 kg; P < 0.01 at 6 months). CONCLUSIONS: While both drugs elicited comparable effects on glycemic management and body weight reduction in patients with type 2 diabetes, caution is needed when using SGLT2is in patients at potential risk for sarcopenia, as they may lead to less favorable changes in skeletal muscle mass compared to oral semaglutide. CI - (c) 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Omori, Yasuhiro AU - Omori Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Usui, Ryota AU - Usui R AUID- ORCID: 0000-0002-4641-0158 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Yamazaki, Yuji AU - Yamazaki Y AUID- ORCID: 0009-0007-5876-8695 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Kuwata, Hitoshi AU - Kuwata H AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Seino, Yutaka AU - Seino Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260120 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Retrospective Studies MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Middle Aged MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Aged MH - Blood Glucose/analysis MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Biomarkers/analysis MH - Follow-Up Studies MH - Prognosis PMC - PMC12950920 OTO - NOTNLM OT - Oral semaglutide OT - SGLT2 inhibitors OT - Skeletal muscle mass COIS- YH received grants from Sumitomo Pharma Co. and Nippon Boehringer Ingelheim Co. Ltd.; and honoraria for lectures from Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Company, Tanabe Pharma Corporation, Taisho Pharmaceutical Co., MSD K.K., and Sumitomo Pharma Co. YY received honoraria for lectures from Sumitomo Pharma Co. and Tanabe Pharma Corporation. HK received grants from Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., and Novo Nordisk Pharma Ltd.; and honoraria for lectures from Sanofi K.K. and Taisho Pharmaceutical Co. YuiY has received honoraria for lectures from Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Novo Nordisk Pharma Ltd., and Teijin Pharma Limited. YS has received grants from Nippon Boehringer Ingelheim Co., Ltd., ARKRAY Marketing, Inc., Taisho Pharmaceutical Co., Novo Nordisk Pharma Ltd., Terumo Corporation, and Sumitomo Pharma Co.; and honoraria for lectures from Taisho Pharmaceutical Co., Nippon Becton Dickinson Company, Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co., Ono Pharmaceutical Co., Ltd., and Kyowa Kirin Co., Ltd. The other authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: Opt-out method. Approval date of Registry and the Registration No. of the study/trial: 22-98. Animal Studies: N/A. EDAT- 2026/01/20 07:44 MHDA- 2026/03/06 19:43 PMCR- 2026/01/20 CRDT- 2026/01/20 03:22 PHST- 2025/12/23 00:00 [revised] PHST- 2025/09/12 00:00 [received] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/03/06 19:43 [medline] PHST- 2026/01/20 07:44 [pubmed] PHST- 2026/01/20 03:22 [entrez] PHST- 2026/01/20 00:00 [pmc-release] AID - JDI70240 [pii] AID - 10.1111/jdi.70240 [doi] PST - ppublish SO - J Diabetes Investig. 2026 Mar;17(3):432-438. doi: 10.1111/jdi.70240. Epub 2026 Jan 20. PMID- 41555588 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Preferences for basal insulin treatments in adults with type 2 diabetes: A discrete choice experiment in France and Spain. PG - 2277-2285 LID - 10.1111/dom.70422 [doi] AB - AIM: To quantify the relative importance of frequency of administration in basal insulin treatment preferences of people living with type 2 diabetes (T2D) in France and Spain, using a discrete choice experiment (DCE). MATERIALS AND METHODS: A targeted literature review and qualitative patient interviews informed an attributes and levels grid consisting of six attributes (2-3 levels each). Pilot interviews were conducted to test the DCE. A quantitative DCE survey was administered to adults with T2D in France and Spain. Hierarchical Bayesian estimation was used to identify the relative importance of each attribute. RESULTS: The survey was completed by N = 239 participants from France (n = 166) and Spain (n = 73) across three treatment experience categories: basal insulin and injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) naive (n = 86), basal insulin naive but injectable GLP-1 RA experienced (n = 85), and basal insulin experienced (n = 68). Frequency of administration had a relative importance of 39%, nearly double that of the attribute with the next highest relative importance 'risk of severe hypoglycemic event (insulin experienced rates)' (21%). A preference for once weekly (OW) administration was observed relative to once daily (OD) or twice daily (BD). Reduction in the frequency of missing doses and taking doses at the prescribed time were considered the most positive impacts of OW administration. Findings were consistent across treatment experience groups. CONCLUSION: This study highlights the importance of administration frequency in basal insulin treatment decisions when glycemic control is held constant. Participants indicated a preference for OW injection frequency, suggesting fewer injections may reduce the burden of insulin administration. These insights support clinical consideration of less frequent injections when making T2D treatment decisions. CI - (c) 2026 Novo Nordisk. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jones, Amy M AU - Jones AM AUID- ORCID: 0000-0003-3645-746X AD - Adelphi Values Ltd., Patient-Centered Outcomes, Cheshire, UK. FAU - Hallworth, Pam AU - Hallworth P AUID- ORCID: 0000-0001-5828-9722 AD - Adelphi Research, Cheshire, UK. FAU - Kendal, Helen AU - Kendal H AD - Adelphi Values Ltd., Patient-Centered Outcomes, Cheshire, UK. FAU - Mottershead, Claire AU - Mottershead C AD - Adelphi Research, Cheshire, UK. FAU - Ormerod, Lewis AU - Ormerod L AD - Adelphi Research, Cheshire, UK. FAU - Pascual, Virginia AU - Pascual V AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Antier, Clemence AU - Antier C AD - Novo Nordisk, Puteaux, France. FAU - Belbute, Diogo AU - Belbute D AD - Novo Nordisk A/S, Soborg, Denmark. FAU - de Laguiche, Elisabeth AU - de Laguiche E AUID- ORCID: 0000-0003-2125-9006 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bellido, Virginia AU - Bellido V AUID- ORCID: 0000-0002-8384-043X AD - Unidad de Gestion Clinica de Endocrinologia y Nutricion, Hospital Universitario Virgen del Rocio, Sevilla, Spain. AD - Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain. LA - eng GR - Novo Nordisk Denmark/ PT - Journal Article DEP - 20260119 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/blood MH - Female MH - Male MH - Spain/epidemiology MH - Middle Aged MH - France/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Patient Preference/statistics & numerical data/psychology MH - Choice Behavior MH - Aged MH - *Insulin/administration & dosage MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Administration Schedule MH - Surveys and Questionnaires MH - Hypoglycemia/chemically induced PMC - PMC12890752 OTO - NOTNLM OT - attitudes OT - barriers OT - basal insulin OT - perceptions OT - type 2 diabetes COIS- AMJ, PH, HK, CM, and LO are employees of Adelphi Values and Adelphi Research, which received consulting fees from Novo Nordisk A/S. DB and EL are employees and shareholders of Novo Nordisk A/S who provided funding for this study. VB has served as a consultant for or received research support, lecture fees, or travel reimbursement from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esteve, Merck, Novo Nordisk, and Sanofi. EDAT- 2026/01/20 07:44 MHDA- 2026/02/11 00:40 PMCR- 2026/02/11 CRDT- 2026/01/20 01:03 PHST- 2025/12/10 00:00 [revised] PHST- 2025/10/09 00:00 [received] PHST- 2025/12/19 00:00 [accepted] PHST- 2026/02/11 00:40 [medline] PHST- 2026/01/20 07:44 [pubmed] PHST- 2026/01/20 01:03 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - DOM70422 [pii] AID - 10.1111/dom.70422 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2277-2285. doi: 10.1111/dom.70422. Epub 2026 Jan 19. PMID- 41549912 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 1 DP - 2026 Feb TI - Micronutrient and Nutritional Deficiencies Associated With GLP-1 Receptor Agonist Therapy: A Narrative Review. PG - e70070 LID - 10.1111/cob.70070 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RA) such as semaglutide, liraglutide and tirzepatide are effective for obesity and type 2 diabetes mellitus (T2DM) but may predispose users to micronutrient deficiencies through appetite suppression, delayed gastric emptying and altered absorption. Given the rapid rise in GLP-1RA use, clarifying their nutritional impact is clinically important. We conducted a structured search of PubMed and the Cochrane Database (January 2019-May 2025) for adult studies evaluating nutritional or micronutrient outcomes during GLP-1RA therapy. Paediatric studies, those lacking nutrient endpoints, and review articles were excluded. Methods followed SANRA and PRISMA-ScR guidance, and data were synthesised descriptively. Six studies met the inclusion criteria, encompassing 480 825 adults. Vitamin D deficiency was the most common abnormality, occurring in 7.5% at 6 months and 13.6% at 12 months. Iron depletion was frequent, with GLP-1RA users demonstrating 26%-30% lower ferritin levels than SGLT2 inhibitor comparators. More than 60% of users consumed below estimated requirements for calcium and iron, and vitamin D intake averaged 20% of recommendations. Protein and calcium insufficiency contributed to lean mass loss, while thiamine and cobalamin deficits increased over time. GLP-1RA therapy is associated with meaningful nutritional deficiencies. Targeted nutritional assessment and individualised laboratory evaluation may be appropriate for patients at increased risk of malnutrition. Findings are mainly derived from observational datasets, and causality between GLP-1RA therapy and nutritional deficiencies cannot be definitively established. CI - (c) 2026 World Obesity Federation. FAU - Urbina, Jorge AU - Urbina J AUID- ORCID: 0009-0008-6287-6354 AD - Universidad Autonoma de Guadalajara, Guadalajara, Jalisco, Mexico. FAU - Salinas-Ruiz, Luis Eduardo AU - Salinas-Ruiz LE AD - Instituto Tecnologico de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo Leon, Mexico. FAU - Valenciano, Cesar AU - Valenciano C AD - Universidad Autonoma de Guadalajara, Guadalajara, Jalisco, Mexico. FAU - Clapp, Benjamin AU - Clapp B AUID- ORCID: 0000-0002-9892-4708 AD - Department of Surgery, Texas Tech University Health Sciences Center, El Paso, Texas, USA. LA - eng PT - Journal Article PT - Review PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Micronutrients) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Micronutrients/deficiency MH - Obesity/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Vitamin D Deficiency MH - Tirzepatide OTO - NOTNLM OT - GLP-1 receptor agonists OT - iron and vitamin D deficiency OT - micronutrient deficiency OT - sarcopenia OT - semaglutide EDAT- 2026/01/19 06:28 MHDA- 2026/01/19 06:29 CRDT- 2026/01/19 04:53 PHST- 2025/12/24 00:00 [revised] PHST- 2025/12/01 00:00 [received] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/01/19 06:29 [medline] PHST- 2026/01/19 06:28 [pubmed] PHST- 2026/01/19 04:53 [entrez] AID - 10.1111/cob.70070 [doi] PST - ppublish SO - Clin Obes. 2026 Feb;16(1):e70070. doi: 10.1111/cob.70070. PMID- 41547635 OWN - NLM STAT- MEDLINE DCOM- 20260606 LR - 20260702 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 20 IP - 2 DP - 2026 Apr TI - SGLT-2 inhibitors and GLP-1 receptor agonists in primary care pharmacotherapy of type 2 diabetes in people living with HIV versus HIV-negative controls: Findings from a multicenter study in Germany. PG - 211-216 LID - S1751-9918(26)00005-7 [pii] LID - 10.1016/j.pcd.2026.01.005 [doi] AB - AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycemic control and reduce cardiovascular (CV) mortality. However, evidence regarding their real-world utilization in people living with HIV (PLWH) receiving primary care remains limited. METHODS: The present study evaluates the real-world diabetes management, prescription patterns and outcomes in PLWH with type 2 diabetes (T2D) compared to HIV-negative controls in primary care, using retrospective and prospective data from multiple outpatient healthcare facilities from urban outpatient clinics in Germany. RESULTS: No significant difference was found for treatment with either SGLT-2i or GLP-1 RA (PLWH [30.0 %] vs. controls [28.3 %], p = 0.86) or the combined therapy (p = 0.34). Among participants with established CV disease, only a third received an SGLT-2i and/or a GLP-1 RA (p = 0.63). Regarding quality of life, PLWH had more difficulties with self-care (p = 0.038) and there was a trend towards a greater burden of anxiety and depression (p = 0.051). CONCLUSIONS: PLWH and T2D in primary care received similar evidence-based therapies as controls, however, prescription rates in participants with CV disease were relatively low. Future studies with a larger sample size and longitudinal follow-up are needed to confirm the present findings. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Hilgefort, L AU - Hilgefort L AD - WIR - Walk In Ruhr, Center for Sexual Health and Medicine, Interdisciplinary Immunological Outpatient Clinic, Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Grosse Beckstr. 12, Bochum 44787, Germany. FAU - Potthoff, A AU - Potthoff A AD - WIR - Walk In Ruhr, Center for Sexual Health and Medicine, Interdisciplinary Immunological Outpatient Clinic, Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Grosse Beckstr. 12, Bochum 44787, Germany. FAU - Nambiar, S AU - Nambiar S AD - WIR - Walk In Ruhr, Center for Sexual Health and Medicine, Interdisciplinary Immunological Outpatient Clinic, Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Grosse Beckstr. 12, Bochum 44787, Germany. FAU - Schlottmann, R AU - Schlottmann R AD - Department of Internal Medicine, St. Josef-Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, Bochum 44791, Germany. FAU - Kaup, B AU - Kaup B AD - Department of Internal Medicine, St. Josef-Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, Bochum 44791, Germany. FAU - Ebigbo, A AU - Ebigbo A AD - Department of Internal Medicine, St. Josef-Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, Bochum 44791, Germany. FAU - Schmidt, W E AU - Schmidt WE AD - Department of Internal Medicine, St. Josef-Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, Bochum 44791, Germany. FAU - Nonseid-Jansen, H AU - Nonseid-Jansen H AD - General Medical Practice of Dr. med. Hilde Nonseid-Jansen, Dr. med. Susanne Gehendges and Wilhelm Jansen, Hattinger Str. 848, Bochum 44879, Germany. FAU - Jansen, W A AU - Jansen WA AD - General Medical Practice of Dr. med. Hilde Nonseid-Jansen, Dr. med. Susanne Gehendges and Wilhelm Jansen, Hattinger Str. 848, Bochum 44879, Germany. FAU - Skaletz-Rorowski, A AU - Skaletz-Rorowski A AD - WIR - Walk In Ruhr, Center for Sexual Health and Medicine, Interdisciplinary Immunological Outpatient Clinic, Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Grosse Beckstr. 12, Bochum 44787, Germany. FAU - Quast, D R AU - Quast DR AD - Department of Internal Medicine, St. Josef-Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, Bochum 44791, Germany. Electronic address: daniel.quast@klinikum-bochum.de. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260116 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology MH - Germany/epidemiology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/metabolism MH - Glycemic Control/adverse effects MH - *HIV Infections/diagnosis/epidemiology/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Practice Patterns, Physicians'/trends MH - Primary Health Care MH - Prospective Studies MH - Quality of Life MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Time Factors MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor agonist OT - HIV OT - SGLT-2 inhibitor OT - Type 2 diabetes COIS- Declaration of Competing Interest DRQ has received honoraria for lectures, presentations, and educational events by Eli Lilly & Co. and Novo Nordisk and has received support for attending meetings and/or travel from Novo Nordisk, Eli Lilly & Co. and Cook Medical. AP has participated in advisory boards by ViiV and received support for attending meetings and/or travel compensation or honoraria for lectures by ViiV, Gilead and Abbvie. ASR has received honoraria for lectures, presentations, and educational events by Abbvie, MSD and Gilead. LH has no potentially competing interests to report. EDAT- 2026/01/18 00:37 MHDA- 2026/03/20 00:59 CRDT- 2026/01/17 21:52 PHST- 2025/11/02 00:00 [received] PHST- 2026/01/09 00:00 [revised] PHST- 2026/01/10 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2026/01/18 00:37 [pubmed] PHST- 2026/01/17 21:52 [entrez] AID - S1751-9918(26)00005-7 [pii] AID - 10.1016/j.pcd.2026.01.005 [doi] PST - ppublish SO - Prim Care Diabetes. 2026 Apr;20(2):211-216. doi: 10.1016/j.pcd.2026.01.005. Epub 2026 Jan 16. PMID- 41547436 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 52 IP - 2 DP - 2026 Mar TI - Association between glucagon-like peptide-1 receptor agonists and colorectal cancer survival: A population-based cohort study. PG - 101734 LID - S1262-3636(26)00013-3 [pii] LID - 10.1016/j.diabet.2026.101734 [doi] AB - OBJECTIVES: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP1-RA) use and all-cause mortality in patients with type 2 diabetes treated for colorectal cancer, using a real-world health database. METHODS: This retrospective cohort study was conducted using the TriNetX global health records network. Adult patients with type 2 diabetes diagnosed with colorectal cancer between 2010 and 2025 were included. Patients were divided into two cohorts based on GLP1-RA exposure versus other oral antidiabetic drugs. Propensity score matching was applied to balance covariates. Overall survival (primary outcome) and metastasis-free survival (secondary outcome) were analysed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: After propensity score matching, each cohort included 751 patients. Median follow-up period was 731 days in the GLP1-RA cohort and 779 days in the non-GLP1-RA cohort. GLP1-RA users had a significantly reduced all-cause mortality rate (11.5%) compared with non-users a (20.4%), with a hazard ratio of 0.58 (95%CI: 0.45-0.76; P < 0.001). Metastasis-free survival rate were 5.3% in the GLP1-RA cohort versus 8.9% in the matched non-user cohort, with a hazard ratio of 0.60 (95%CI: 0.40-0.87; P = 0.01). The incidence of major adverse cardiovascular events (MACE) did not differ significantly between cohorts, with a hazard ratio of 0.84 (95%CI: 0.66-1.06; P = 0.16). CONCLUSIONS: In this real-world cohort of diabetic patients treated for colorectal cancer, GLP1-RA therapy was associated with a significant improvement in overall survival. These findings support the continued use of GLP1-RA agents in this population and may provide reassurance to clinicians and patients regarding the safety and potential benefit of these agents following a colorectal cancer diagnosis. CI - Copyright (c) 2026 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Dosda, Arnaud AU - Dosda A AD - Department of Endocrinology, Diabetology, and Nutrition, Centre Hospitalier Universitaire de Tours, Universite de Tours 37000, Tours, France; INRAE UMR85 Physiologie de la Reproduction et des Comportements 37520, Nouzilly, France. Electronic address: a.dosda@chu-tours.fr. FAU - Fauchier, Gregoire AU - Fauchier G AD - Department of Endocrinology, Diabetology, and Nutrition, Centre Hospitalier Universitaire d'Orleans, Universite de Tours, 37000, Tours, France. FAU - Sabbah, Nadia AU - Sabbah N AD - Department of Endocrinology, Diabetology, and Nutrition, Centre Hospitalier Universitaire d'Orleans, Universite de Tours, 37000, Tours, France. FAU - Fauchier, Laurent AU - Fauchier L AD - Cardiology Department, Centre Hospitalier Universitaire de Tours, Universite de Tours 37000, Tours, France. FAU - Lecomte, Thierry AU - Lecomte T AD - Department of hepatogastroenterology and digestive oncology, CHU de Tours, Tours, France; INSERM UMR 1069, N2COx "Niche, Nutrition, Cancer and Oxidative Metabolism", Universite de Tours, Tours, France. FAU - Ducluzeau, Pierre Henri AU - Ducluzeau PH AD - Department of Endocrinology, Diabetology, and Nutrition, Centre Hospitalier Universitaire de Tours, Universite de Tours 37000, Tours, France; INRAE UMR85 Physiologie de la Reproduction et des Comportements 37520, Nouzilly, France. LA - eng PT - Journal Article DEP - 20260116 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Colorectal Neoplasms/mortality/complications/drug therapy MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies OTO - NOTNLM OT - Colorectal cancer OT - Glucagon-like peptide-1 receptor agonists OT - Type 2 diabetes COIS- Declaration of competing interest PHD: consultant or speaker fees of small amounts for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi; outside of this work. LF: consultant or speaker fees of small amounts for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Boston Scientific, Medtronic, Novo Nordisk, and Zoll outside of this work. TL: consultant or speaker fees of small amounts for Servier, Pierre Fabre, Merck Serono, BMS, Astra Zeneca, AAA, Sanofi, IPSEN, Novartis, CHUGAI and research funding from Pierre Fabre and Leo Pharma outside of this work. All remaining authors: no conflicts of interest. EDAT- 2026/01/18 00:37 MHDA- 2026/03/23 06:32 CRDT- 2026/01/17 19:14 PHST- 2025/11/26 00:00 [received] PHST- 2026/01/12 00:00 [revised] PHST- 2026/01/14 00:00 [accepted] PHST- 2026/03/23 06:32 [medline] PHST- 2026/01/18 00:37 [pubmed] PHST- 2026/01/17 19:14 [entrez] AID - S1262-3636(26)00013-3 [pii] AID - 10.1016/j.diabet.2026.101734 [doi] PST - ppublish SO - Diabetes Metab. 2026 Mar;52(2):101734. doi: 10.1016/j.diabet.2026.101734. Epub 2026 Jan 16. PMID- 41547366 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260924 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10531 DP - 2026 Feb 28 TI - Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits. PG - 892-908 LID - S0140-6736(25)02105-1 [pii] LID - 10.1016/S0140-6736(25)02105-1 [doi] AB - GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes, Endocrinology, Metabolism Section, Medical Department 1, St Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University Bochum, Bochum, Germany; Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address: michael.nauck@rub.de. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Inland Northwest Health, Division of Nephrology and Kidney Research Institute, University of Washington School of Medicine, Spokane, WA, USA. FAU - Tschop, Matthias H AU - Tschop MH AD - Division of Metabolic Diseases, Technische Universitat Munchen, Helmholtz Diabetes Center, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Bluher, Matthias AU - Bluher M AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen, University of Leipzig and University Hospital Leipzig, Leipzig, Germany. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20260114 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Lancet. 2026 Mar 14;407(10533):1058. doi: 10.1016/S0140-6736(26)00467-8. PMID: 41831846 MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Incretins/therapeutic use MH - Liraglutide/therapeutic use MH - Obesity/drug therapy MH - Tirzepatide/therapeutic use MH - Semaglutide/therapeutic use COIS- Declaration of interests MAN has been member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co, Medtronic, Merck, Sharp & Dohme, NovoNordisk, Pfizer, Regor, Sun Pharma, and Structure Therapeutics (Gasherbrum); has received grant support from Merck and Sharp & Dohme; has served on the speakers bureau of Eli Lilly & Co, Merck, Sharp & Dohme, Medscape, Medical Learning Institute, and NovoNordisk; and is on a Data Monitoring and Safety Board for Inventiva. KRT has received investigator-initiated grant support from Travere, Bayer, Benaroya Research Institute, the Doris Duke Charitable Foundation, and Breakthrough-T1D; reports consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, AstraZeneca, Alnylam, Bayer, and ProKidney; and reports speaker fees from Novo Nordisk, Bayer, and Boehringer Ingelheim. She reports US National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581, and US Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She reports being chair of Data Safety Monitoring boards for the US National Institutes of Health National Institute of Diabetes and Digestive and Kidney Disease, and the George Clinical Institute, and reports being a member of the Data Safety Monitoring Board for AstraZeneca. She reports leadership roles as chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology, chair for Kidney Week 2025 Program Committee, member of the American Heart Association publication committee, and a member of the American Heart Association-American College of Cardiology Cardiovascular Kidney Metabolic Guideline Committee. MHT has delivered scientific lectures for Boehringer Ingelheim (2024), KG (2024), AstraZeneca (2024), Lilly Deutschland (2024), and Novo Nordisk (2024). He is co-founder of the biotech startup Bluewater Biotech (founded in 2024). As CEO and CSO of Helmholtz Munich, he is co-responsible for countless collaborations of the employees with a multitude of companies and institutions, worldwide. In this capacity, he discusses potential projects with and has signed/signs contracts for the centre's institute(s) related to research collaborations worldwide, including but not limited to pharmaceutical corporations such as Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics, Arbormed, Eli Lilly, SCG Cell Therapy, and others. As the CEO of Helmholtz Munich, he was/is further overall responsible for commercial technology transfer activities. He confirms that, to the best of his knowledge, none of the above funding sources or collaborations were involved in or had an influence on the preparation of this manuscript. MB received honoraria as a consultant and speaker from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, MSD, Novo Nordisk, Novartis, Pfizer, and Sanofi; and reports chairing a Clinical Trial Data Safety Monitoring Board for Boehringer Ingelheim. EDAT- 2026/01/18 00:37 MHDA- 2026/03/06 08:57 CRDT- 2026/01/17 18:52 PHST- 2025/04/02 00:00 [received] PHST- 2025/10/13 00:00 [revised] PHST- 2025/10/13 00:00 [accepted] PHST- 2026/03/06 08:57 [medline] PHST- 2026/01/18 00:37 [pubmed] PHST- 2026/01/17 18:52 [entrez] AID - S0140-6736(25)02105-1 [pii] AID - 10.1016/S0140-6736(25)02105-1 [doi] PST - ppublish SO - Lancet. 2026 Feb 28;407(10531):892-908. doi: 10.1016/S0140-6736(25)02105-1. Epub 2026 Jan 14. PMID- 41545715 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 2662-1347 (Electronic) IS - 2662-1347 (Linking) VI - 7 IP - 2 DP - 2026 Feb TI - Glucagon-like peptide-1 medicines and cancer. PG - 260-271 LID - 10.1038/s43018-025-01110-1 [doi] AB - Glucagon-like peptide-1 (GLP-1) medicines reduce food intake, body weight, insulin resistance and inflammation, thus improving outcomes for people with type 2 diabetes and obesity and potentially contributing to decreased cancer incidence. GLP-1 medicines acting through weight loss-dependent and weight loss-independent mechanisms hold potential for suppression of tumorigenesis and reduction of rates of obesity-associated cancer. In this Perspective, we summarize data on cancer incidence from trials and registries in individuals with type 2 diabetes, describe the actions of GLP-1 medicines on preclinical cancer models and highlight possible direct and indirect mechanisms linking GLP-1R signaling to cancer development and progression. CI - (c) 2026. Springer Nature America, Inc. FAU - Yabut, Julian M AU - Yabut JM AUID- ORCID: 0009-0001-3318-2854 AD - Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. drucker@lunenfeld.ca. LA - eng PT - Journal Article PT - Review DEP - 20260116 PL - England TA - Nat Cancer JT - Nature cancer JID - 101761119 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/therapeutic use/metabolism MH - *Neoplasms/prevention & control/epidemiology/drug therapy/etiology MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Signal Transduction/drug effects MH - Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Competing interests: J.M.Y. has no competing interests or conflict of interest. D.J.D. has served as a consultant or speaker within the past 12 months to Alnylam, Amgen, AstraZeneca, Crinetics, Eli Lilly, General Medicines Inc., Kallyope, Metsera, Novo Nordisk, Pfizer Protagonist Therapeutivs Inc and Sanofi. Neither D.J.D. nor his family members hold issued stock directly or indirectly in any of these companies. D.J.D. holds nonexercised options in Kallyope. Mt. Sinai Hospital receives grant support from Amgen, Eli Lilly and Zealand Pharma for preclinical studies in the laboratory of D.J.D. EDAT- 2026/01/17 00:36 MHDA- 2026/03/07 01:37 CRDT- 2026/01/16 23:23 PHST- 2025/01/21 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/03/07 01:37 [medline] PHST- 2026/01/17 00:36 [pubmed] PHST- 2026/01/16 23:23 [entrez] AID - 10.1038/s43018-025-01110-1 [pii] AID - 10.1038/s43018-025-01110-1 [doi] PST - ppublish SO - Nat Cancer. 2026 Feb;7(2):260-271. doi: 10.1038/s43018-025-01110-1. Epub 2026 Jan 16. PMID- 41544899 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 235 DP - 2026 May TI - Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study. PG - 113083 LID - S0168-8227(26)00002-1 [pii] LID - 10.1016/j.diabres.2026.113083 [doi] AB - AIMS: Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists may reduce the onset/progression of dementia. The effect of the dual GLP1/GIP receptor agonist tirzepatide on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i in relation to incident dementia in patients with type 2 diabetes. METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes without dementia at baseline were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching. RESULTS: After matching, TTE1 included 14,462 patients; TTE2, 57,959; TTE3 12,246. Tirzepatide was associated with a lower risk of dementia versus semaglutide (HR 0.69, 95% CI 0.48-0.99, p = 0.04) and SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02), and lower mortality (HR 0.72, 95% CI 0.58-0.90, p < 0.01; HR 0.29, 95% CI 0.23-0.37, p < 0.01). Tirzepatide and semaglutide reduced MACE vs SGLT2-i. CONCLUSIONS: Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-i in type 2 diabetes. Our findings are hypothesis generating, requiring confirmation in randomised controlled trials. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Younis, Alhena AU - Younis A AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. FAU - Henney, Alex E AU - Henney AE AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Zhao, Sizheng S AU - Zhao SS AD - Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. FAU - Ibarburu, Gema H AU - Ibarburu GH AD - TriNetX LLC, Cambridge, MA, USA. FAU - Malik, Rayaz A AU - Malik RA AD - Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar. FAU - Su, Li AU - Su L AD - Sheffield Institute of Translational Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK; Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Lip, Gregory Y H AU - Lip GYH AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Cardiology, Lipidology and Internal Medicine with Intensive Coronary Care Unit, Medical University of Bialystok, Bialystok, Poland. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. Electronic address: Uazman.alam@liverpool.ac.uk. LA - eng PT - Journal Article DEP - 20260114 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Aged MH - Retrospective Studies MH - *Dementia/epidemiology/prevention & control/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Aged, 80 and over OTO - NOTNLM OT - Dementia OT - Diabetes OT - GLP1-RA OT - Tirzepatide COIS- Declaration of competing interest SSZ has received: (1) support for conference attendance from Novartis, UCB, AlfaSigma, Eli Lilly; (2) consultancy/speaker fees from Novartis, UCB, AlfaSigma, AbbVie, Jassen. GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos (No fees are received personally). He is co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation programme. DJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. UA has received honoraria from Procter & Gamble, Viatris, Grunenthal, Daiichi Sankyo, Eli Lilly, Theras and Sanofi for educational meetings and funding for attendance to an educational meeting from Sanofi and Daiichi Sankyo. UA has also received investigator-led funding by Procter & Gamble, consultancy fees from Axonis therapeutics and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. EDAT- 2026/01/17 00:36 MHDA- 2026/04/12 04:37 CRDT- 2026/01/16 19:14 PHST- 2025/11/19 00:00 [received] PHST- 2025/12/28 00:00 [revised] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/04/12 04:37 [medline] PHST- 2026/01/17 00:36 [pubmed] PHST- 2026/01/16 19:14 [entrez] AID - S0168-8227(26)00002-1 [pii] AID - 10.1016/j.diabres.2026.113083 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 May;235:113083. doi: 10.1016/j.diabres.2026.113083. Epub 2026 Jan 14. PMID- 41543478 OWN - NLM STAT- MEDLINE DCOM- 20260116 LR - 20261017 IS - 2471-254X (Electronic) IS - 2471-254X (Linking) VI - 10 IP - 2 DP - 2026 Feb 1 TI - Effect of glucagon-like peptide-1 receptor agonists on histologic MASH: A meta-analysis of randomized controlled trials. LID - 10.1097/HC9.0000000000000871 [doi] LID - e0871 AB - BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is the most common chronic liver disease worldwide, with a particularly high incidence among individuals with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective weight loss agents, with growing evidence suggesting potential benefits in MASH. This study aimed to evaluate the efficacy and safety of GLP-1RAs in improving the histologic features of MASH. METHODS: This study is a meta-analysis of randomized controlled trials evaluating the effect of FDA-approved GLP-1RAs in patients with biopsy-confirmed MASH, up to May 2025. The primary outcomes were resolution of MASH without worsening of fibrosis and a >/=1 improvement in fibrosis stage without worsening of MASH at 12-18 months. Secondary outcomes included >/=1-point improvements in the nonalcoholic fatty liver disease activity score, changes in liver histologic features, and the incidence of serious adverse events. RESULTS: A total of 6 randomized controlled trials with 1555 patients (1082 GLP-1RA and 473 placebo) with MASH were included. At 18 months, a significantly greater proportion of patients in the GLP-1RA group achieved MASH resolution without worsening fibrosis compared with the placebo group (OR: 4.16, 95% CI: 2.33-7.42, p<0.001). A subgroup analysis excluding studies with patients with cirrhosis showed a significant benefit on fibrosis regression (OR: 2.02, 95% CI: 1.56-2.62, p=0.01). GLP-1RAs significantly improved nonalcoholic fatty liver disease activity scores and liver histologic features, including balloon degeneration, lobular inflammation, and steatosis, compared with placebo. The pooled serious adverse event rate for GLP-1RAs was comparable to placebo. CONCLUSIONS: In patients with noncirrhotic MASH, GLP-1RAs appear to be associated with both MASH resolution without fibrosis worsening and >/=1-stage fibrosis regression without MASH worsening. CI - Copyright (c) 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases. FAU - Siranart, Noppachai AU - Siranart N AUID- ORCID: 0000-0003-3315-6020 AD - Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, USA. FAU - Thompson, Christopher C AU - Thompson CC AUID- ORCID: 0000-0002-6105-5270 AD - Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Jirapinyo, Pichamol AU - Jirapinyo P AUID- ORCID: 0000-0001-5273-6851 AD - Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260116 PL - United States TA - Hepatol Commun JT - Hepatology communications JID - 101695860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology MH - Liver/pathology MH - Diabetes Mellitus, Type 2/complications MH - Treatment Outcome MH - *Fatty Liver/drug therapy/pathology MH - Liver Cirrhosis PMC - PMC13671594 OTO - NOTNLM OT - GLP-1 OT - MASH OT - liver biopsy OT - pathology COIS- Christopher C. Thompson has served as a consultant for Apollo Endosurgery, Boston Scientific, Enterasense, EnVision Endoscopy, Fractyl, USGI Medical, Medtronic/Covidien, Olympus/Spiration, and GI Dynamics, has served as an advisory board member for USGI Medical and Fractyl, has received research grant and support from USGI Medical, Apollo Endosurgery, Boston Scientific, ERBE, FujiFilm, Lumendi Olympus/Spiration, Aspire Bariatrics, and GI Dynamics, has served as a general partners for Blueframe Healthcare, has served as a founder for Enterasense, EnVision Endoscopy, and GI Windows, and holds stock and royalties for GI Windows. Pichamol Jirapinyo has received research support from Apollo Endosurgery, Boston Scientific, Fractyl, GI Dynamics, and USGI Medical, has served as a consultant to Apollo Endosurgery, ERBE, GI Dynamics, and Spatz Medical, and has received royalties from Endosim. The remaining author has no conflicts to report. EDAT- 2026/01/16 15:04 MHDA- 2026/01/16 15:05 PMCR- 2026/01/16 CRDT- 2026/01/16 10:33 PHST- 2025/07/06 00:00 [received] PHST- 2025/10/08 00:00 [accepted] PHST- 2026/01/16 15:05 [medline] PHST- 2026/01/16 15:04 [pubmed] PHST- 2026/01/16 10:33 [entrez] PHST- 2026/01/16 00:00 [pmc-release] AID - 02009842-202602010-00005 [pii] AID - HEP4-25-0898 [pii] AID - 10.1097/HC9.0000000000000871 [doi] PST - epublish SO - Hepatol Commun. 2026 Jan 16;10(2):e0871. doi: 10.1097/HC9.0000000000000871. eCollection 2026 Feb 1. PMID- 41542765 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260926 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 136 IP - 2 DP - 2026 Jan 16 TI - GLP-1RA precision medicine in people with type 2 diabetes: current insights and future prospects. LID - 10.1172/JCI194742 [doi] LID - e194742 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an essential drug class for treating type 2 diabetes, offering proven benefits in glycemic control, weight reduction, and cardiovascular and renal protection. However, growing evidence of heterogeneity in GLP-1RA treatment effects highlights the potential for developing precision medicine approaches to more accurately allocate GLP-1RAs to maximize patient benefit. In this Review, we explore the evidence for treatment effect heterogeneity with GLP-1RAs, focusing on clinical and genetic factors that robustly influence established therapeutic outcomes. We also highlight the potential of recent predictive models that integrate routine clinical data with personalize treatment decisions, comparing GLP-1RA to other major type 2 diabetes drug classes. While such models have shown considerable promise in identifying optimal type 2 diabetes treatment based on glycemic response, their utility for informing treatment choice for other clinical outcomes remains largely unexplored. FAU - Cardoso, Pedro AU - Cardoso P AD - Clinical and Biomedical Sciences, Royal Devon & Exeter Hospital, University of Exeter Medical School, Exeter, United Kingdom. FAU - Dennis, John M AU - Dennis JM AD - Clinical and Biomedical Sciences, Royal Devon & Exeter Hospital, University of Exeter Medical School, Exeter, United Kingdom. FAU - Pearson, Ewan R AU - Pearson ER AD - Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom. LA - eng PT - Journal Article PT - Review DEP - 20260116 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism MH - *Precision Medicine MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Effect Heterogeneity PMC - PMC12807466 COIS- Conflict of interest: ERP has received honoraria for speaking from Lilly and Novo Nordisk in the past 36 months. EDAT- 2026/01/16 15:04 MHDA- 2026/01/16 15:05 PMCR- 2026/01/16 CRDT- 2026/01/16 06:04 PHST- 2026/01/16 15:05 [medline] PHST- 2026/01/16 15:04 [pubmed] PHST- 2026/01/16 06:04 [entrez] PHST- 2026/01/16 00:00 [pmc-release] AID - 194742 [pii] AID - 10.1172/JCI194742 [doi] PST - epublish SO - J Clin Invest. 2026 Jan 16;136(2):e194742. doi: 10.1172/JCI194742. eCollection 2026 Jan 16. PMID- 41540866 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 22 IP - 945 DP - 2026 Jan 14 TI - [Nephrology : what's new in 2025]. PG - 49-52 LID - 10.53738/REVMED.2026.22.945.47996 [doi] AB - Complement inhibitors are expanding their indications in nephrology. In patients with type 2 diabetes, semaglutide prevents chronic kidney disease (CKD), while retatrutide reduces albuminuria in patients with diabetes and established CKD. Obinutuzumab improves the renal response in patients with lupus nephropathy. A double dose of icodextrin did not reduce mortality, peritonitis, or hospitalization rates compared to standard peritoneal dialysis treatment, though it increased ultrafiltration. In patients on hemodialysis, using a dialysate with an intermediate potassium concentration combined with a potassium chelator appears to stabilize serum potassium levels and reduce the occurrence of arrhythmias. Xenotransplantation and ex vivo perfusion techniques are being perfected in the search for a solution to organ shortage. FAU - Nanchen, Giliane AU - Nanchen G AUID- ORCID: 0000-0002-8522-7524 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Lamine, Faiza AU - Lamine F AUID- ORCID: 0000-0001-6299-714X AD - Unite d'endocrinologie-diabetologie, Service de medecine interne, Centre hospitalier de Rennaz, 1847 Rennaz. AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Golshayan, Dela AU - Golshayan D AUID- ORCID: 0000-0001-5631-6096 AD - Centre de transplantation d'organes, Departement de medecine, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Fakhouri, Fadi AU - Fakhouri F AUID- ORCID: 0000-0001-5390-8002 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Nephrologie : ce qui a change en 2025. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Complement Inactivating Agents) SB - IM MH - Humans MH - *Nephrology/trends MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Renal Insufficiency, Chronic/therapy MH - Complement Inactivating Agents/therapeutic use MH - Renal Dialysis/methods COIS- M. Pruijm a participe a des conferences pour Astellas, Vifor, B. Braun, Theramed, Vantive, Boehringer Ingelheim et Astra Zeneca, et il a exerce une fonction d'expert pour Novo Nordisk et Nephrospec. F. Fakhouri a recu des honoraires de consultant de Roche, AstraZeneca, Alexion, Sobi, Novartis. Les autres auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2026/01/16 17:21 MHDA- 2026/01/16 17:22 CRDT- 2026/01/16 03:35 PHST- 2026/01/16 17:22 [medline] PHST- 2026/01/16 17:21 [pubmed] PHST- 2026/01/16 03:35 [entrez] AID - RMS0945-010 [pii] AID - 10.53738/REVMED.2026.22.945.47996 [doi] PST - ppublish SO - Rev Med Suisse. 2026 Jan 14;22(945):49-52. doi: 10.53738/REVMED.2026.22.945.47996. PMID- 41534460 OWN - NLM STAT- MEDLINE DCOM- 20260204 LR - 20260626 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 57 DP - 2026 Feb TI - Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review. PG - 106571 LID - S0261-5614(25)00351-6 [pii] LID - 10.1016/j.clnu.2025.106571 [doi] AB - BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes mellitus and obesity in recent years. While gastrointestinal adverse events are common, their association with nutritional deficiencies, including thiamine, has not been comprehensively investigated. This study aimed to evaluate whether treatment with GLP-1 RAs is associated with the occurrence of Wernicke encephalopathy (WE). METHODS: We conducted a pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) and a narrative literature review. Disproportionality analysis assessed WE reporting following GLP-1 RA treatment using the reporting odds ratio (ROR) and the lower bound of the information component (IC) 95 % credibility interval. RESULTS: We identified 15 cases of GLP-1 RA-associated WE: 13 from FAERS, 1 from published literature, and 1 from our medical center. Most cases occurred with semaglutide (n = 8/15) or tirzepatide (6/15), and were reported in 2023-2024 (14/15). Most patients (13/15) reported gastrointestinal manifestations of either weight loss, vomiting, loss of appetite, or malnutrition. Classic WE symptoms were reported in 11 patients, and the full clinical triad in 2 patients. Long-term neurological sequelae were noted in 7 of 11 patients with follow-up data. Disproportionality analysis showed increased reporting of WE with GLP-1 RAs compared with other medications (ROR = 2.35 [95%CI, 1.38-4.01]; IC(025) = 0.29). CONCLUSIONS: WE is a potentially rare but severe adverse event of GLP-1 RA treatment, mainly with semaglutide or tirzepatide. As early detection may prevent neurological sequelae, increased clinical awareness is warranted, especially in individuals experiencing severe gastrointestinal symptoms. CI - Copyright (c) 2026. Published by Elsevier Ltd. FAU - Lev, Dana AU - Lev D AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel. FAU - Leibowitz, Avshalom AU - Leibowitz A AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Lang, Alon AU - Lang A AD - Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel. FAU - Shlomai, Gadi AU - Shlomai G AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. FAU - Twig, Gilad AU - Twig G AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat-Gan, Israel. FAU - Eden-Friedman, Yehudit AU - Eden-Friedman Y AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. FAU - Engel, Tal AU - Engel T AD - Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Dankner, Rachel AU - Dankner R AD - Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat-Gan, Israel. FAU - Gerstein, Hertzel C AU - Gerstein HC AD - Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. FAU - Goldman, Adam AU - Goldman A AD - Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: Adam.Goldman@sheba.health.gov.il. LA - eng PT - Journal Article PT - Review DEP - 20260102 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Wernicke Encephalopathy/chemically induced/epidemiology MH - Tirzepatide MH - *Pharmacovigilance MH - Male MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - *Glucagon-Like Peptides/adverse effects MH - Adverse Drug Reaction Reporting Systems MH - United States OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide OT - Thiamine deficiency OT - Tirzepatide OT - Wernicke encephalopathy COIS- Conflict of interest The authors declare no conflicts of interest. EDAT- 2026/01/15 16:13 MHDA- 2026/02/05 00:30 CRDT- 2026/01/14 18:09 PHST- 2025/07/04 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/25 00:00 [accepted] PHST- 2026/02/05 00:30 [medline] PHST- 2026/01/15 16:13 [pubmed] PHST- 2026/01/14 18:09 [entrez] AID - S0261-5614(25)00351-6 [pii] AID - 10.1016/j.clnu.2025.106571 [doi] PST - ppublish SO - Clin Nutr. 2026 Feb;57:106571. doi: 10.1016/j.clnu.2025.106571. Epub 2026 Jan 2. PMID- 41534440 OWN - NLM STAT- MEDLINE DCOM- 20260202 LR - 20260710 IS - 1878-5883 (Electronic) IS - 0022-510X (Linking) VI - 481 DP - 2026 Feb 15 TI - Diabetic lumbosacral radiculoplexus neuropathy after glucagon-like peptide 1 receptor agonist use: A case series. PG - 125755 LID - S0022-510X(26)00036-5 [pii] LID - 10.1016/j.jns.2026.125755 [doi] AB - BACKGROUND: Diabetic Lumbosacral Radiculoplexus Neuropathy (DLRPN) is a rare form of debilitating neuropathy, usually preceded by rapid glycemic control. METHODS: We describe a case series of patients with DLRPN who had been exposed to GLP-1 Receptor Agonists (GLP-1 RA) prior to symptom onset. RESULTS: Six patients (3 men; aged 53-73) with type 2 diabetes developed sudden-onset, asymmetric lower limb pain followed by weakness-bilateral in 5/6. Most had substantial weight loss (35-52 lbs) and rapid HbA1c decline (>5) in months preceding symptoms. Four patients had electrophysiologic evidence of lumbosacral plexopathy; imaging was supportive in 2. One patient received intravenous steroids with improvement; others were managed supportively, with 3 showing stabilization or mild recovery. DISCUSSION: This series highlights a potential association between rapid glycemic and weight changes from GLP-1 RA use and DLRPN. Clinicians should be alert to subacute neuropathy with muscle weakness in patients undergoing aggressive glycemic control. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Chandrashekhar, Swathy AU - Chandrashekhar S AD - Neuromuscular Division, Department of Neurology, University of California San Francisco, USA. FAU - Davalos, Long AU - Davalos L AD - Neuromuscular Division, Department of Neurology, University of Kansas Medical Center, USA. FAU - Pradhan, Richeek AU - Pradhan R AD - Centre for Medicine Use and Safety, Monash University, Australia. FAU - Paul, Pritikanta AU - Paul P AD - Neuromuscular Division, Department of Neurology, University of California San Francisco, USA. Electronic address: pritikanta.paul@gmail.com. LA - eng PT - Case Reports PT - Journal Article DEP - 20260109 PL - Netherlands TA - J Neurol Sci JT - Journal of the neurological sciences JID - 0375403 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Diabetic Neuropathies/chemically induced/diagnostic imaging MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Lumbosacral Plexus/diagnostic imaging MH - *Radiculopathy/chemically induced OTO - NOTNLM OT - Diabetic amyotrophy OT - Diabetic radiculoplexus neuropathy OT - GLP-1 receptor agonist OT - Treatment induced neuropathy of diabetes COIS- Declaration of competing interest Swathy Chandrashekhar: Nothing to disclose. Long Davalos Loo: Nothing to disclose. Richeek Pradhan: Nothing to disclose. Pritikanta Paul: The institution of Dr. Paul has received research support from ZS Associates. EDAT- 2026/01/15 16:13 MHDA- 2026/02/03 00:27 CRDT- 2026/01/14 18:08 PHST- 2025/09/18 00:00 [received] PHST- 2025/12/18 00:00 [revised] PHST- 2026/01/08 00:00 [accepted] PHST- 2026/02/03 00:27 [medline] PHST- 2026/01/15 16:13 [pubmed] PHST- 2026/01/14 18:08 [entrez] AID - S0022-510X(26)00036-5 [pii] AID - 10.1016/j.jns.2026.125755 [doi] PST - ppublish SO - J Neurol Sci. 2026 Feb 15;481:125755. doi: 10.1016/j.jns.2026.125755. Epub 2026 Jan 9. PMID- 41528611 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20261009 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Jan 13 TI - Pharmacological Management of Diabesity: Current and Emerging Therapies. PG - 5 LID - 10.1007/s13679-025-00681-5 [doi] AB - PURPOSE OF REVIEW: This review aims to provide a comprehensive synthesis of current clinical evidence on the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists on body mass index (BMI), body composition, and glucose metabolism in patients with obesity and type 2 diabetes mellitus (T2DM), a condition often referred to as "diabesity." RECENT FINDINGS: The coexistence of obesity and T2DM represents a major clinical and public health challenge due to their synergistic effects on metabolic dysfunction and the increased risk of cardiovascular and renal complications. Traditional approaches focused solely on glycemic control have proven insufficient to address the intertwined pathophysiology of excess adiposity and impaired glucose metabolism. Recently, novel pharmacological agents, including SGLT2 inhibitors, GLP-1 RAs, and dual GIP/GLP-1 receptor agonists, have demonstrated dual benefits in improving glycemic control and reducing body weight. These drugs act through distinct but complementary mechanisms-such as promoting glycosuria, enhancing satiety, delaying gastric emptying, and modulating energy homeostasis-resulting in significant reductions in BMI and visceral fat. Among these agents, tirzepatide has shown superior efficacy in improving metabolic parameters and body composition compared with single receptor agonists. Understanding the multifaceted metabolic benefits of these pharmacotherapies is essential for optimizing individualized therapeutic strategies for patients with diabesity. Integrating these agents into comprehensive diabetes care allows clinicians to more effectively target the complex pathophysiology of diabesity, ultimately improving long-term metabolic and clinical outcomes in this growing patient population. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Galasso, Martina AU - Galasso M AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. FAU - Caporusso, Mariangela AU - Caporusso M AD - Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy. FAU - Volatile, Alessandra AU - Volatile A AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Verde, Ludovica AU - Verde L AD - Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Unit of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, 70124, IT, Italy. FAU - Perrini, Sebastio AU - Perrini S AD - Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy. AD - Section of Endocrinology, Department of Medicine and Surgery, Libera Universita Mediterranea (LUM), Casamassima, Bari, IT, 70010, Italy. FAU - Colao, Annamaria AU - Colao A AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. AD - Dipartimento Di Medicina Clinica E Chirurgia, Unita Di Endocrinologia, Universita Degli Studi Di Napoli Federico II, Naples, 80131, Italy. AD - Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy. FAU - Barrea, Luigi AU - Barrea L AD - Dipartimento Di Psicologia e Scienze Della Salute, Universita Telematica Pegaso, Centro Direzionale, Via Porzio, Isola F2, Naples, 80143, Italy. FAU - Muscogiuri, Giovanna AU - Muscogiuri G AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - Dipartimento Di Medicina Clinica E Chirurgia, Unita Di Endocrinologia, Universita Degli Studi Di Napoli Federico II, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - University of Naples Federico II, Via Sergio Pansini 5, Naples, 80031, Italy. giovanna.muscogiuri@unina.it. CN - Obesity Programs of nutrition, Education, Research and Assessment (OPERA) Group LA - eng PT - Journal Article PT - Review DEP - 20260113 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Diabesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Body Mass Index MH - Body Composition/drug effects OTO - NOTNLM OT - Body composition OT - Diabesity OT - Glycemic control OT - SGLT2 inhibitors OT - Semaglutide OT - Tirzepatide COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/01/13 13:16 MHDA- 2026/01/13 13:17 CRDT- 2026/01/13 11:20 PHST- 2025/11/01 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/01/13 13:17 [medline] PHST- 2026/01/13 13:16 [pubmed] PHST- 2026/01/13 11:20 [entrez] AID - 10.1007/s13679-025-00681-5 [pii] AID - 10.1007/s13679-025-00681-5 [doi] PST - epublish SO - Curr Obes Rep. 2026 Jan 13;15(1):5. doi: 10.1007/s13679-025-00681-5. PMID- 41528550 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260916 IS - 1539-0829 (Electronic) IS - 1534-4827 (Print) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Jan 13 TI - SGLT-2 Inhibitors and GLP-1 Receptor Agonists as Combination Therapy in Type 2 Diabetes. PG - 1 LID - 10.1007/s11892-025-01616-z [doi] LID - 1 AB - PURPOSE OF REVIEW: The pharmacologic management of type 2 diabetes prioritises sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists for their demonstrated cardiovascular benefits in individuals with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors, chronic kidney disease, and heart failure. However, while current guidelines recommend these drug classes alone, combination therapy is not explicitly advocated. Herein we summarise the rationale and available evidence in support for combination therapy. RECENT FINDINGS: Evidence suggests that combining SGLT-2 inhibitors and GLP-1 receptor agonists improves metabolic outcomes, including HbA(1c), body weight, and blood pressure. More importantly, combination therapy can offer potential advantages for addressing residual cardiovascular risk, particularly in high-risk populations. Data from cardiovascular outcomes trials and real-world studies demonstrate consistent benefits of combination therapy across diverse subpopulations, including those with established atherosclerotic cardiovascular disease or chronic kidney disease. However, robust evidence remains limited for individuals at low cardiovascular risk, where therapy should primarily focus on metabolic goals. Of note, combination therapy faces significant barriers, including safety concerns in older or frail individuals, underutilisation in disadvantaged populations, while economic challenges may further hinder the accessibility of these therapies. Upfront combination therapy with both SGLT-2 inhibitors and GLP-1 receptor agonists could further reduce cardiovascular risk in people with type 2 diabetes, although it is crucial to pare down cost and disparities to access to maximise widespread benefits at population level. CI - (c) 2026. The Author(s). FAU - Liakos, Aris AU - Liakos A AUID- ORCID: 0000-0003-3261-2979 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. arliakos@auth.gr. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. arliakos@auth.gr. FAU - Karagiannis, Thomas AU - Karagiannis T AUID- ORCID: 0000-0001-5242-0574 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Avgerinos, Ioannis AU - Avgerinos I AUID- ORCID: 0000-0003-2232-1342 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Bekiari, Eleni AU - Bekiari E AUID- ORCID: 0000-0001-9975-3835 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260113 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Cardiovascular Diseases/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - *Hypoglycemic Agents/administration & dosage MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage PMC - PMC12799618 OTO - NOTNLM OT - Combination therapy OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - Type 2 diabetes COIS- Declarations. Ethical Approval: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing interests: AL has received research support from Novo Nordisk, speaker honoraria from Astra Zeneca, Elpen. Novo Nordisk, Menarini Phasmaserve-Lilly and Sanofi and support for attending meetings and travel from Novo Nordisk, Menarini, Sanofi and Vianex, outside the submitted work. AL is the section editor for the Pharmacologic Treatment of Type 2 Diabetes section in Current Diabetes Reports. TK declares no relationships or activities that might bias, or be perceived to bias, this work. IA has received research support from Novo Nordisk, outside the submitted work. EB has received research support from Novo Nordisk and speaker honoraria from Menarini and Sanofi, outside the submitted work. EDAT- 2026/01/13 13:15 MHDA- 2026/01/13 13:16 PMCR- 2026/01/13 CRDT- 2026/01/13 11:18 PHST- 2025/12/17 00:00 [accepted] PHST- 2026/01/13 13:16 [medline] PHST- 2026/01/13 13:15 [pubmed] PHST- 2026/01/13 11:18 [entrez] PHST- 2026/01/13 00:00 [pmc-release] AID - 10.1007/s11892-025-01616-z [pii] AID - 1616 [pii] AID - 10.1007/s11892-025-01616-z [doi] PST - epublish SO - Curr Diab Rep. 2026 Jan 13;26(1):1. doi: 10.1007/s11892-025-01616-z. PMID- 41527269 OWN - NLM STAT- MEDLINE DCOM- 20260326 LR - 20260626 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 63 IP - 8 DP - 2026 Apr TI - Clinical Trial: Semaglutide Versus Placebo in NIT-Assessed MASH-A Multicenter Randomised Placebo-Controlled Trial (SAMARA). PG - 1080-1088 LID - 10.1111/apt.70516 [doi] AB - BACKGROUND/AIMS: Non-invasive test (NIT)-based assessment of eligibility and treatment response with semaglutide is needed to inform clinical practice guidance. Therefore, utilising a randomised, placebo-controlled study design, we evaluated the utility of NITs to assess eligibility and treatment response in patients with suspected at-risk MASH randomised to semaglutide versus placebo. METHODS: In this multicentre, randomised, double-blind placebo-controlled 52-week trial, patients meeting AASLD criteria for MASLD with BMI >/= 27 kg/m(2), or BMI >/= 25 kg/m(2) and prediabetes or type 2 diabetes with liver stiffness by VCTE >/= 8 kPa and a FAST score >/= 0.5 were randomised to either semaglutide 2.4 mg subcutaneously weekly or placebo. The primary outcome was change in the FAST score at end of treatment from baseline. Other endpoints included changes in body weight, MRI-PDFF, ALT and HbA1c. RESULTS: Fifty-five participants were randomised (55% women, 20% with diabetes). Mean (SD) age, BMI, and FAST at baseline were 48.8 (14) years, 40.2 (15) kg/m(2), 0.62 (0.12), respectively. The semaglutide group had a significantly greater reduction in FAST compared with placebo (-0.28 vs. -0.12; p = 0.002). More semaglutide recipients achieved >/= 5% weight loss (64% vs. 8.3%; p < 0.001) and >/= 30% reduction in MRI-PDFF (60% vs. 17%; p = 0.047). Semaglutide led to a significantly greater reduction in ALT, AST, GGT, HbA1c and LDL cholesterol (p < 0.05). Gastrointestinal-related adverse events were common but not significantly different between the two groups (p = 0.59). CONCLUSIONS: A NIT-based approach to identify at-risk MASH patients for semaglutide treatment is feasible and effective. This study provides RCT data showing that FAST, ALT, AST and MRI-PDFF can be used to monitor treatment response. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Ajmera, Veeral AU - Ajmera V AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. FAU - Vuppalanchi, Raj AU - Vuppalanchi R AD - Division of Gastroenterology, Indiana University, Bloomington, Indiana, USA. FAU - Khalili, Mandana AU - Khalili M AUID- ORCID: 0000-0001-9178-9139 AD - Department of Medicine, University of California San Francisco, San Francisco, California, USA. AD - Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA. FAU - Sheikh, Muhammad Y AU - Sheikh MY AD - Fresno Clinical Research Center, Fresno, California, USA. FAU - Risser, Joseph AU - Risser J AD - Herbert Wertheim School of Public Health, University of California at San Diego, San Diego, California, USA. FAU - Klein, Samuel AU - Klein S AD - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Tincopa, Monica AU - Tincopa M AUID- ORCID: 0000-0002-9954-8548 AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. FAU - Madamba, Egbert AU - Madamba E AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Singh, Seema AU - Singh S AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Siddiqi, Harris AU - Siddiqi H AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Cortez-Moreno, Diana AU - Cortez-Moreno D AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Contrano, Darryl AU - Contrano D AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Hofflich, Heather AU - Hofflich H AD - Division of Endocrinology, University of California, San Diego, California, USA. FAU - Abeles, Ruth AU - Abeles R AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Lunde, Ottar AU - Lunde O AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Grunvald, Eduardo AU - Grunvald E AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Bettencourt, Ricki AU - Bettencourt R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - He, Feng AU - He F AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA. FAU - Jain, Sonia AU - Jain S AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA. FAU - Richards, Lisa AU - Richards L AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Loomba, Rohit AU - Loomba R AUID- ORCID: 0000-0002-4845-9991 AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. LA - eng GR - 5UL1TR001442/TR/NCATS NIH HHS/United States GR - P01HL147835/HL/NHLBI NIH HHS/United States GR - P30DK120515/DK/NIDDK NIH HHS/United States GR - R01DK106419/DK/NIDDK NIH HHS/United States GR - R01DK121378/DK/NIDDK NIH HHS/United States GR - R01DK124318/DK/NIDDK NIH HHS/United States GR - U01DK061734/DK/NIDDK NIH HHS/United States GR - U01DK130190/DK/NIDDK NIH HHS/United States GR - Novo Nordisk Foundation/ GR - John C Martin Foundation/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260112 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - Middle Aged MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult MH - Treatment Outcome MH - Glycated Hemoglobin/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy OTO - NOTNLM OT - VCTE OT - glucagon-like peptide 1 receptor agonists OT - metabolic dysfunction OT - noninvasive tests OT - steatotic liver disease EDAT- 2026/01/13 07:42 MHDA- 2026/03/27 01:10 CRDT- 2026/01/13 01:03 PHST- 2025/11/27 00:00 [revised] PHST- 2025/11/03 00:00 [received] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/03/27 01:10 [medline] PHST- 2026/01/13 07:42 [pubmed] PHST- 2026/01/13 01:03 [entrez] AID - 10.1111/apt.70516 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2026 Apr;63(8):1080-1088. doi: 10.1111/apt.70516. Epub 2026 Jan 12. PMID- 41520798 OWN - NLM STAT- MEDLINE DCOM- 20260519 LR - 20260625 IS - 1879-3304 (Electronic) IS - 0039-6257 (Linking) VI - 71 IP - 4 DP - 2026 Jul-Aug TI - Too much of a good thing. PG - 1236-1245 LID - S0039-6257(26)00001-9 [pii] LID - 10.1016/j.survophthal.2026.01.001 [doi] AB - A 38-year-old man with poorly controlled type 2 diabetes mellitus and arterial hypertension on semaglutide presented with acute, painless, vision loss in the left eye. Ophthalmic examination revealed optic disc edema (ODE) in the left eye and optic disc pallor (ODP) in the right eye, accompanied by severe nonproliferative diabetic retinopathy and cystoid macular edema in both eyes. The combination of ODE in one eye and ODP in the fellow eye raised concern for the Foster Kennedy syndrome secondary to an intracranial mass; however, neuroimaging and systemic evaluation were unremarkable. Ultimately, it was decided the ODP was due to a prior unrecognized non-arteritic anterior ischemic optic neuropathy (NAION) event, and the ODE was the result of an acute NAION in the symptomatic fellow eye (i.e. pseudo-Foster Kennedy syndrome). CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Varghese, Danny AU - Varghese D AD - Texas A&M College of Medicine, Bryan, TX, USA. FAU - Abdelsalam, Dina AU - Abdelsalam D AD - Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. FAU - Ibrahim, Safa AU - Ibrahim S AD - Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. FAU - Lee, Andrew G AU - Lee AG AD - Texas A&M College of Medicine, Bryan, TX, USA; Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. Electronic address: aglee@houstonmethodist.org. FAU - Bhatti, M Tariq AU - Bhatti MT AD - The Permanente Medical Group. Department of Ophthalmology, Kaiser Permanente, Northern California, Roseville, California, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20260109 PL - United States TA - Surv Ophthalmol JT - Survey of ophthalmology JID - 0404551 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Papilledema/diagnosis/etiology MH - *Optic Neuropathy, Ischemic/diagnosis/complications MH - Male MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Semaglutide MH - Adult MH - *Diabetic Retinopathy/diagnosis MH - Visual Acuity MH - Tomography, Optical Coherence MH - *Optic Disk/pathology MH - Glucagon-Like Peptides/therapeutic use OTO - NOTNLM OT - Autoregulatory failure OT - Bilateral sequential OT - Glucagon-like peptide-1 receptor agonist OT - Non-arteritic anterior ischemic optic neuropathy OT - Optic disc edema OT - Pseudo-Foster Kennedy syndrome OT - Semaglutide COIS- Declaration of Competing Interest Andrew G. Lee, MD has served as a consultant for the National Aeronautics and Space Administration (NASA), the National Football League (NFL), US Department of Justice, and is a consultant for Amgen, AstraZeneca, Argenx, Bristol-Myers Squibb, Alexion, Celgene, Stoke, Ethyreal, Catalyst, Dompe, and Viridian. Dr. Lee is also on the editorial board of Frontiers in Ophthalmology, JNO, CJO, JJO, and JAMA Ophthalmology. M. Tariq Bhatti, MD: none. EDAT- 2026/01/12 00:37 MHDA- 2026/05/20 00:32 CRDT- 2026/01/11 19:13 PHST- 2025/12/20 00:00 [received] PHST- 2026/01/05 00:00 [revised] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/05/20 00:32 [medline] PHST- 2026/01/12 00:37 [pubmed] PHST- 2026/01/11 19:13 [entrez] AID - S0039-6257(26)00001-9 [pii] AID - 10.1016/j.survophthal.2026.01.001 [doi] PST - ppublish SO - Surv Ophthalmol. 2026 Jul-Aug;71(4):1236-1245. doi: 10.1016/j.survophthal.2026.01.001. Epub 2026 Jan 9. PMID- 41520703 OWN - NLM STAT- MEDLINE DCOM- 20260206 LR - 20260630 IS - 2254-8874 (Electronic) IS - 2254-8874 (Linking) VI - 226 IP - 2 DP - 2026 Feb TI - Patients after acute myocardial infarction: potential of semaglutide in prognosis for reducing events and mortality. PG - 502455 LID - S2254-8874(26)00010-X [pii] LID - 10.1016/j.rceng.2026.502455 [doi] AB - INTRODUCTION: GLP-1 receptor agonists, such as semaglutide, have demonstrated cardiovascular benefits in trials such as SELECT and SOUL. This study assesses the proportion of post-myocardial infarction patients who meet eligibility criteria to benefit from semaglutide. METHODS: A retrospective, single-centre observational study was conducted including 100 consecutive patients following myocardial infarction. Clinical, demographic, and laboratory data were analysed. Eligibility was assessed using the criteria from the SELECT trial (body mass index >/=27kg/m(2), no diabetes, established atherosclerotic disease) and the SOUL trial (type 2 diabetes mellitus and atherosclerotic cardiovascular disease). RESULTS: SELECT criteria were met by 42 patients, SOUL criteria by 34, and both by 76. This combined group was characterised by older age, greater comorbidity burden (hypertension, dyslipidaemia, type 2 diabetes mellitus), higher body mass index, and a more atherogenic lipid profile. DISCUSSION: The high proportion of eligible patients suggests that these trials truly represent real-world clinical practice. The SELECT+SOUL group exhibited features consistent with metabolic syndrome, potentially explaining their elevated cardiovascular risk and the likely benefit from semaglutide. CONCLUSIONS: Semaglutide shows high potential for prescription in specialties managing patients with cardiovascular events, identifying a target group with characteristics typical of metabolic syndrome. CI - Copyright (c) 2026 Elsevier Espana, S.L.U. and Sociedad Espanola de Medicina Interna (SEMI). All rights reserved. FAU - Velasco, A AU - Velasco A AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain. FAU - Pascual Ramos, I AU - Pascual Ramos I AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Rodriguez Alonso, P AU - Rodriguez Alonso P AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Denche Sanz, C AU - Denche Sanz C AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Tello, R AU - Tello R AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERCV, Madrid, Spain. FAU - Solis, J AU - Solis J AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERCV, Madrid, Spain. Electronic address: jsolismartin@yahoo.es. LA - eng PT - Case Reports PT - Journal Article PT - Observational Study DEP - 20260109 PL - Spain TA - Rev Clin Esp (Barc) JT - Revista clinica espanola JID - 101632437 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Retrospective Studies MH - Male MH - Aged MH - *Myocardial Infarction/mortality/drug therapy/complications MH - Middle Aged MH - Prognosis MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/complications/drug therapy OTO - NOTNLM OT - Metabolic syndrome OT - Prevencion secundaria OT - Secondary prevention OT - Semaglutida OT - Semaglutide OT - Sindrome metabolico EDAT- 2026/01/12 00:37 MHDA- 2026/02/07 00:30 CRDT- 2026/01/11 19:11 PHST- 2025/05/04 00:00 [received] PHST- 2025/10/07 00:00 [accepted] PHST- 2026/02/07 00:30 [medline] PHST- 2026/01/12 00:37 [pubmed] PHST- 2026/01/11 19:11 [entrez] AID - S2254-8874(26)00010-X [pii] AID - 10.1016/j.rceng.2026.502455 [doi] PST - ppublish SO - Rev Clin Esp (Barc). 2026 Feb;226(2):502455. doi: 10.1016/j.rceng.2026.502455. Epub 2026 Jan 9. PMID- 41518129 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 1099-1387 (Electronic) IS - 1075-2617 (Linking) VI - 32 IP - 2 DP - 2026 Feb TI - Emerging Therapies in Metabolic Health: A Comprehensive Review of GLP-1, GIP, and Glucagon Agonists. PG - e70083 LID - 10.1002/psc.70083 [doi] AB - Incretin-based therapies have become central to type 2 diabetes (T2D) management, offering benefits beyond glycemic control, including weight reduction, cardiovascular protection, and emerging roles in renal and neurological health. This review addresses the question: What are the recent advances in GLP-1, GIP, and glucagon receptor agonists, and how do formulation strategies overcome biopharmaceutical challenges? We systematically analyzed late-stage clinical trials and formulation approaches for peptide-based therapies. The review focuses on therapeutic efficacy, structural and physicochemical properties influencing absorption, distribution, and metabolic stability, and strategies to mitigate degradation pathways such as enzymatic hydrolysis and peptide aggregation. Additionally, innovative delivery systems such as oral peptide formulations and long-acting injectables demonstrate promise in addressing inherent challenges of peptide drug delivery. By integrating clinical outcomes with mechanistic and formulation insights, this review highlights the evolving landscape of incretin-based therapies and underscores innovative solutions for peptide stabilization and delivery. These findings provide a forward-looking perspective for clinicians, researchers, and pharmaceutical scientists engaged in T2D management and drug development. CI - (c) 2026 European Peptide Society and John Wiley & Sons Ltd. FAU - Khan, Mohammed Shareef AU - Khan MS AD - Biopharmaceutics Group, Global Clinical Management, Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. FAU - Bhutani, Utkarsh AU - Bhutani U AD - Product Selection and Ideation Group (BRaIN), Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. FAU - Venugopal, Hariharan AU - Venugopal H AD - Product Selection and Ideation Group (BRaIN), Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. FAU - Saini, Anuj Kumar AU - Saini AK AD - Biopharmaceutics Group, Global Clinical Management, Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. FAU - Naidu, Venkat Ramana AU - Naidu VR AD - Product Selection and Ideation Group (BRaIN), Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. FAU - Kollipara, Sivacharan AU - Kollipara S AUID- ORCID: 0000-0002-7332-9021 AD - Biopharmaceutics Group, Global Clinical Management, Dr. Reddy's Laboratories Ltd., Integrated Product Development Organization (IPDO), Hyderabad, Telangana, India. LA - eng GR - Dr. Reddy's Laboratories Ltd/ PT - Journal Article PT - Review PL - England TA - J Pept Sci JT - Journal of peptide science : an official publication of the European Peptide Society JID - 9506309 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 9007-92-5 (Glucagon) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Glucagon) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Gastric Inhibitory Polypeptide/agonists/metabolism MH - *Glucagon-Like Peptide 1/agonists/metabolism MH - *Hypoglycemic Agents/therapeutic use/chemistry MH - *Glucagon/agonists MH - Peptides/chemistry/therapeutic use MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Receptors, Glucagon/agonists MH - Drug Delivery Systems OTO - NOTNLM OT - clinical trials OT - drug delivery OT - emerging technologies OT - metabolic disease OT - peptide stability EDAT- 2026/01/10 22:40 MHDA- 2026/01/10 22:41 CRDT- 2026/01/10 06:52 PHST- 2025/12/14 00:00 [revised] PHST- 2025/11/07 00:00 [received] PHST- 2025/12/17 00:00 [accepted] PHST- 2026/01/10 22:41 [medline] PHST- 2026/01/10 22:40 [pubmed] PHST- 2026/01/10 06:52 [entrez] AID - 10.1002/psc.70083 [doi] PST - ppublish SO - J Pept Sci. 2026 Feb;32(2):e70083. doi: 10.1002/psc.70083. PMID- 41516231 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 1 DP - 2025 Dec 29 TI - Cardiovascular Disease and Diabetes: A New Challenge in the Treatment and Management. LID - 10.3390/ijms27010354 [doi] LID - 354 AB - Cardiovascular diseases (CVDs) represent one of the leading causes of morbidity and mortality in patients with diabetes. However, a correct and effective glycaemic control obtained by pharmacologic interventions, such as the use the novel glucose-lowering agents, demonstrated efficacy in reducing the risk of both cardiovascular events and mortality. The latest classes of glucose-lowering drugs introduced in the clinical practice are DPP4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin), GLP-1 receptor agonists (semaglutide, liraglutide, albiglutide, dulaglutide, exenatide, and lixenatide), and SGLT-2 inhibitors (empaglifozin, canaglifozin, and dapaglifozin). Multiple lines of evidence show that all these new drugs associated with the treatment of diabetic disease have the same effectiveness as the traditional antidiabetic drugs, and excellent cardiovascular safety, highlighting their potential in significantly reducing major cardiovascular events and mortality. The aim of our review is to summarise the clinical efficacy of these recently introduced drugs to optimise treatment strategies, especially in the early phase of diabetic disease. FAU - Riccioni, Graziano AU - Riccioni G AD - Cardiology Care Unit, "San Camillo de Lellis" Hospital, 71043 Foggia, Italy. FAU - Notarangelo, Chiara AU - Notarangelo C AUID- ORCID: 0009-0006-2085-9017 AD - Department of Cardiovascular Disease, University of Firenze, 50134 Florence, Italy. FAU - Riccioni, Mario AU - Riccioni M AD - Faculty of Medicine, University of Torino, 10126 Turin, Italy. FAU - D'Orazio, Nicolantonio AU - D'Orazio N AD - Department of Biomedical Sciences, University of Pescara-Chieti, 66100 Chieti, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251229 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Animals PMC - PMC12785618 OTO - NOTNLM OT - DDP-4 inhibitors OT - GLP-1 receptor antagonists OT - SGLT2 inhibitors OT - cardiovascular disease OT - diabetes OT - metformin OT - prevention COIS- The authors declare no conflict of interest. EDAT- 2026/01/10 06:32 MHDA- 2026/01/10 06:33 PMCR- 2025/12/29 CRDT- 2026/01/10 01:10 PHST- 2025/08/03 00:00 [received] PHST- 2025/12/09 00:00 [revised] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/01/10 06:33 [medline] PHST- 2026/01/10 06:32 [pubmed] PHST- 2026/01/10 01:10 [entrez] PHST- 2025/12/29 00:00 [pmc-release] AID - ijms27010354 [pii] AID - ijms-27-00354 [pii] AID - 10.3390/ijms27010354 [doi] PST - epublish SO - Int J Mol Sci. 2025 Dec 29;27(1):354. doi: 10.3390/ijms27010354. PMID- 41515907 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 1 DP - 2025 Dec 19 TI - The Roles of Incretin Hormones GIP and GLP-1 in Metabolic and Cardiovascular Health: A Comprehensive Review. LID - 10.3390/ijms27010027 [doi] LID - 27 AB - The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) play central roles in metabolic and cardiovascular regulation. GLP-1 receptor agonists (GLP-1RAs) are established therapies for type 2 diabetes mellitus (T2DM) and obesity because of their insulinotropic effects, weight reduction, and proven cardiovascular benefit in trial level. In contrast, GIP was historically overlooked due to reduced beta-cell responsiveness in T2DM. The development of dual GIP/GLP-1 receptor agonists has reshaped this view. Tirzepatide, the first-in-class co-agonist, an antidiabetic medication to treat type 2 diabetes and for weight loss, provides superior glycemic control and weight loss compared with selective GLP-1RAs in clinical trials, demonstrating synergistic actions between the two incretin pathways. This review summarizes key physiology, pathophysiology, and therapeutic evidence in incretin biology. We describe secretion patterns, receptor distributions, and distinct actions of GIP and GLP-1, as well as alterations in incretin signaling in T2DM and obesity. Cardiovascular protective mechanisms are outlined, including improvements in lipid metabolism, reductions in blood pressure, enhanced endothelial nitric oxide activity, suppression of macrophage inflammation, decreased foam-cell formation, and stabilization of atherosclerotic plaques. At the therapeutic level, emerging directions-such as dual and triple agonists-and unresolved questions regarding long-term vascular effects of GIP and the potential for genotype-guided incretin therapy are also discussed. Collectively, these findings highlight an emerging shift toward integrated incretin-axis modulation as a therapeutic strategy for metabolic and cardiovascular disease. FAU - Yamanouchi, Dai AU - Yamanouchi D AUID- ORCID: 0000-0002-5720-3939 AD - Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. AD - Department of Vascular Surgery, Fujita Health University, Toyoake 470-1192, Japan. LA - eng PT - Journal Article PT - Review DEP - 20251219 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/metabolism MH - Animals MH - *Incretins/metabolism MH - *Glucagon-Like Peptide 1/metabolism MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - *Cardiovascular Diseases/metabolism MH - Tirzepatide MH - Obesity/metabolism/drug therapy MH - *Cardiovascular System/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12785922 OTO - NOTNLM OT - GIP signaling OT - GLP-1 receptor agonists OT - atherosclerosis OT - cardiovascular protection OT - dual agonists OT - incretin hormones OT - insulin secretion OT - metabolic disease OT - obesity treatment OT - tirzepatide COIS- The author declares no conflicts of interest. EDAT- 2026/01/10 06:32 MHDA- 2026/01/10 06:33 PMCR- 2025/12/19 CRDT- 2026/01/10 01:08 PHST- 2025/11/18 00:00 [received] PHST- 2025/12/17 00:00 [revised] PHST- 2025/12/18 00:00 [accepted] PHST- 2026/01/10 06:33 [medline] PHST- 2026/01/10 06:32 [pubmed] PHST- 2026/01/10 01:08 [entrez] PHST- 2025/12/19 00:00 [pmc-release] AID - ijms27010027 [pii] AID - ijms-27-00027 [pii] AID - 10.3390/ijms27010027 [doi] PST - epublish SO - Int J Mol Sci. 2025 Dec 19;27(1):27. doi: 10.3390/ijms27010027. PMID- 41513440 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1755-5248 (Electronic) IS - 0012-6543 (Linking) VI - 64 IP - 2 DP - 2026 Jan 28 TI - Navigating the benefits and harms of GLP-1 and GLP-1/GIP agonists in obesity. PG - 19-23 LID - 10.1136/dtb.2025.000039 [doi] AB - Obesity is becoming increasingly common worldwide. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) type drugs have the potential to help patients achieve considerable weight loss. Several benefits have been described in the short term, especially relating to diseases associated with obesity, where rapid weight loss results in undoubted improvements. These conditions include type 2 diabetes mellitus, cardiovascular disease and metabolic dysfunction-associated steatotic liver disease. Known adverse effects include gastrointestinal (nausea, vomiting, acute pancreatitis, dehydration and malnutrition), reduced efficacy of oral contraceptives and allergic reactions. Rarer adverse effects include thyroid cell tumours and non-arteritic anterior ischaemic optic neuropathy. Up to 33% of the weight lost is lean tissue mass (muscle and bone). Discontinuation rates can be up to 80% after 2 years. Subsequent weight regain can be up to two-thirds of prior weight loss. There is a risk of much of this regain being fatty tissue. To avoid this and associated malnutrition, GLP-1 RAs should only be initiated along with a supervised exercise programme and individualised dietetic advice. Subsequent patient monitoring to detect cessation, malnutrition and inappropriate fatty tissue weight gain is recommended. CI - (c) Author(s) (or their employer(s)) 2026. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - O'Connor, Raymond AU - O'Connor R AUID- ORCID: 0000-0003-0042-675X AD - Department of General Practice, University of Limerick School of Medicine, Limerick, Ireland Raymond.oconnor@ul.ie. AD - General Practitioner, Meelick, County Clare, Ireland. LA - eng PT - Journal Article PT - Review DEP - 20260128 PL - England TA - Drug Ther Bull JT - Drug and therapeutics bulletin JID - 0112037 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Anti-Obesity Agents) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/agonists MH - Weight Loss/drug effects MH - *Anti-Obesity Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Receptors, Gastrointestinal Hormone/agonists OTO - NOTNLM OT - Diet food and nutrition OT - Drug-Related Side Effects and Adverse Reactions OT - Metabolic Diseases OT - Obesity COIS- Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s). EDAT- 2026/01/10 00:34 MHDA- 2026/01/29 01:47 CRDT- 2026/01/09 21:22 PHST- 2026/01/29 01:47 [medline] PHST- 2026/01/10 00:34 [pubmed] PHST- 2026/01/09 21:22 [entrez] AID - dtb.2025.000039 [pii] AID - 10.1136/dtb.2025.000039 [doi] PST - epublish SO - Drug Ther Bull. 2026 Jan 28;64(2):19-23. doi: 10.1136/dtb.2025.000039. PMID- 41513044 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 232 DP - 2026 Feb TI - Glucagon-like peptide-1 receptor agonists and risk of osteoarthritis among individuals with type 2 diabetes: A population-based cohort study. PG - 113091 LID - S0168-8227(26)00010-0 [pii] LID - 10.1016/j.diabres.2026.113091 [doi] AB - AIMS: To compare the risk of osteoarthritis among patients with type 2 diabetes mellitus (T2DM) initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP4Is). METHODS: We conducted a nationwide cohort study applying a target trial emulation framework. From the National Health Insurance Service data of South Korea (2010-2022), eligible patients included adult patients with T2DM initiated GLP-1RAs or DPP4Is. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs of incident osteoarthritis, and were weighted using propensity score fine stratification. RESULTS: Among 2,056,824 eligible patients, 9,866 started GLP-1RAs (mean age 45 years; 55% male; 67% dulaglutide) and 2,047,158 started DPP4Is (mean age 56 years; 70% male). After weighting, all covariates were well balanced, with patients having a mean age of 45 years and 55% being male. The incidence rates per 100 person-years for osteoarthritis were 3.99 (95% CI, 3.54-4.48) and 4.36 (4.34-4.38) among GLP-1RAs and DPP4Is users, respectively. Compared to DPP4Is, GLP-1RAs were not associated with a lower risk of osteoarthritis (HR 0.93, 95% CI, 0.83-1.05). CONCLUSIONS: The use of GLP-1RAs, primarily dulaglutide, was not associated with lower risk of osteoarthritis compared with DPP4Is use among patients with T2DM. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Jeon, Minjeong AU - Jeon M AD - School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea. Electronic address: mjeon18@g.skku.edu. FAU - Hong, Bin AU - Hong B AD - School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea. Electronic address: hongbin@g.skku.edu. FAU - Ko, Hwa Yeon AU - Ko HY AD - School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea. Electronic address: hy12@g.skku.edu. FAU - Song, Hong Ji AU - Song HJ AD - Department of Family Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea. Electronic address: hongji@hallym.ac.kr. FAU - Kwak, Soo Heon AU - Kwak SH AD - Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, South Korea. Electronic address: shkwak@snu.ac.kr. FAU - Kim, Ju Hwan AU - Kim JH AD - School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea. Electronic address: jukim928@skku.edu. FAU - Shin, Ju-Young AU - Shin JY AD - School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea; Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea; Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea. Electronic address: shin.jy@skku.edu. LA - eng PT - Journal Article DEP - 20260107 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - *Osteoarthritis/epidemiology/chemically induced MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Republic of Korea/epidemiology MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Adult MH - Immunoglobulin Fc Fragments/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Incidence MH - Aged MH - Recombinant Fusion Proteins/therapeutic use MH - Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - Osteoarthritis OT - Pharmacoepidemiology OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ju-Young Shin reports financial support was provided by Ministry of Food and Drug Safety. Ju-Young Shin reports a relationship with Ministry of Health & Welfare that includes: funding grants. Ju-Young Shin reports a relationship with National Research Foundation of Korea that includes: funding grants. Ju-Young Shin reports a relationship with Pfizer that includes: funding grants. Ju-Young Shin reports a relationship with Celltrion that includes: funding grants. Ju-Young Shin reports a relationship with SK Bioscience that includes: funding grants. Ju-Young Shin reports a relationship with LG Chemical that includes: funding grants. Ju-Young Shin reports a relationship with Union Chimique Belge that includes: funding grants. Ju-Young Shin reports a relationship with GlaxoSmithKline that includes: funding grants. Ju Hwan Kim reports financial support was provided by the Ministry of Health & Welfare. Ju Hwan Kim reports a relationship with the Ministry of Health & Welfare that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/01/10 00:34 MHDA- 2026/02/03 00:27 CRDT- 2026/01/09 19:12 PHST- 2025/11/18 00:00 [received] PHST- 2026/01/06 00:00 [revised] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/02/03 00:27 [medline] PHST- 2026/01/10 00:34 [pubmed] PHST- 2026/01/09 19:12 [entrez] AID - S0168-8227(26)00010-0 [pii] AID - 10.1016/j.diabres.2026.113091 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Feb;232:113091. doi: 10.1016/j.diabres.2026.113091. Epub 2026 Jan 7. PMID- 41512269 OWN - NLM STAT- MEDLINE DCOM- 20260109 LR - 20260115 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - Spec. No. 15 DP - 2025 Dec TI - GLP-1 receptor agonists: trend, necessity, or blessing? PG - SP1084-SP1085 LID - 10.37765/ajmc.2025.89854 [doi] AB - The recent endorsement of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Wegovy), by the American College of Cardiology as first-line therapy for weight management marks a paradigm shift in cardiometabolic care. Semaglutide offers significant benefits, including improved glycemic control and substantial weight loss, with emerging data demonstrating its impact even in individuals without diabetes. However, GLP-1 receptor agonists' growing popularity raises important concerns regarding long-term safety, access equity, and health care priorities. Although common adverse effects are gastrointestinal, less frequent but serious risks such as gallbladder disease, pancreatitis, and anesthesia-related complications deserve attention. Obesity, a global epidemic, has traditionally been managed through lifestyle interventions. The increasing reliance on pharmacologic options must not overshadow the foundational role of diet, physical activity, and education. Although GLP-1 receptor agonists represent a powerful advancement in obesity and cardiovascular risk management, its widespread adoption demands a balanced, evidence-based approach that integrates it into a broader, patient-centered strategy. There is a pressing need for comprehensive care models that address both the physiological and behavioral aspects of obesity. As health care systems navigate this therapeutic shift, they must ensure ethical use, cost-effectiveness, and long-term safety. GLP-1 receptor agonists may indeed be a blessing, but only if applied judiciously within the context of holistic obesity management. FAU - Shoaib, Navaira AU - Shoaib N FAU - Azhar, Naveen AU - Azhar N AD - Dow Medical College, House No. A-137, Block 1 FB Area, Karachi, Pakistan. Email: naveen.azhar40@gmail.com. FAU - Shoaib, Maria AU - Shoaib M LA - eng PT - Editorial PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Weight Loss/drug effects EDAT- 2026/01/09 18:30 MHDA- 2026/01/09 18:31 CRDT- 2026/01/09 16:33 PHST- 2026/01/09 18:31 [medline] PHST- 2026/01/09 18:30 [pubmed] PHST- 2026/01/09 16:33 [entrez] AID - 89854 [pii] AID - 10.37765/ajmc.2025.89854 [doi] PST - ppublish SO - Am J Manag Care. 2025 Dec;31(Spec. No. 15):SP1084-SP1085. doi: 10.37765/ajmc.2025.89854. PMID- 41508745 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - GLP1-1RAs improve walking distance and reduce amputation in people with type 2 diabetes and peripheral artery disease: A systematic review and meta-analysis of randomised controlled trials and cohort studies. PG - 2775-2783 LID - 10.1111/dom.70454 [doi] AB - AIMS: The aim of this systematic review and meta-analysis was to evaluate the effect of GLP-1RAs on functional walking distance and the risk of major adverse limb events (MALE) or lower extremity amputation (LEA) in people with type 2 diabetes and peripheral artery disease (PAD). MATERIALS AND METHODS: We searched many electronic databases up to 10 October 2025 for randomised controlled trials (RCTs) and cohort studies. We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs. The primary outcomes were walking distance, MALE, or LEA. Data were pooled using a random-effects model, with hazard ratios (HR) or risk ratios (RR). Risk of bias was assessed using RoB2 for RCTs and ROBINS-I for cohort studies; evidence certainty was evaluated using the GRADE approach. RESULTS: We included seven studies (3 RCTs, 4 cohorts) enrolling 107 092 participants. The meta-analysis of two RCTs with 847 participants demonstrated a significant improvement in walking distance with liraglutide or semaglutide (HR = 1.10, 95% CI 1.05-1.15, p < 0.001), with no heterogeneity (I(2) = 0.0%) and moderate certainty of evidence. In the additional meta-analysis of two RCTs with 3592 participants, the incidence of MALE or LEA did not differ significantly between patients receiving exenatide or semaglutide and those receiving placebo. The meta-analysis of four cohort studies with 104 292 participants showed that GLP-1RAs reduced the risk of LEA (RR = 0.53, 95% CI 0.39-0.73, p < 0.001), with high heterogeneity (I(2) = 85.96%), totally related to one study, and very low certainty of evidence. Subgroup analyses showed a significant difference (p < 0.001) between GLP-1RA therapies, with the strongest associations with LEA reduction for tirzepatide and semaglutide (55% and 54% risk reduction, respectively); there was no difference in the LEA outcome excluding from the analysis patients with type 2 diabetes and diabetic foot ulcers at baseline. CONCLUSIONS: This meta-analysis suggests that GLP-1RAs are associated with a significant improvement in functional walking distance and a reduction in the risk of LEA in people with type 2 and PAD. Further dedicated RCTs are needed to confirm these limb-specific benefits of GLP-1RAs. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Longo, Miriam AU - Longo M AUID- ORCID: 0000-0002-6459-5854 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy. FAU - Di Martino, Nicole AU - Di Martino N AUID- ORCID: 0009-0001-8062-3958 AD - PhD Program of Translational Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AUID- ORCID: 0009-0007-7628-2226 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Caruso, Paola AU - Caruso P AUID- ORCID: 0000-0002-4756-2022 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AUID- ORCID: 0000-0002-4748-321X AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - PhD Program of Translational Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Peripheral Arterial Disease/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *Amputation, Surgical/statistics & numerical data MH - *Walking/physiology MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies MH - Diabetic Angiopathies MH - Tirzepatide OTO - NOTNLM OT - GLP-1RA OT - cohort studies OT - meta-analysis OT - peripheral artery disease OT - randomised controlled trials OT - systematic review OT - type 2 diabetes EDAT- 2026/01/09 07:06 MHDA- 2026/03/17 06:48 CRDT- 2026/01/09 02:24 PHST- 2025/12/17 00:00 [revised] PHST- 2025/10/30 00:00 [received] PHST- 2025/12/29 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/09 07:06 [pubmed] PHST- 2026/01/09 02:24 [entrez] AID - 10.1111/dom.70454 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2775-2783. doi: 10.1111/dom.70454. Epub 2026 Jan 8. PMID- 41508706 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Comparison of cardiovascular outcomes between once-weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States. PG - 2661-2671 LID - 10.1111/dom.70440 [doi] AB - AIMS: This study aims to compare the risk of major adverse cardiovascular events (MACE) among United States individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) treated with once-weekly semaglutide vs. dulaglutide. MATERIALS AND METHODS: This was a retrospective cohort study using Optum's de-identified Clinformatics Data Mart (Optum CDM) from 1 January 2007 through 30 September 2024. New initiators of semaglutide or dulaglutide >/=18 years with both T2D and ASCVD were included. The index date was the first date of a prescription claim for semaglutide or dulaglutide within the index medication identification period (1 January 2018 through 31 March 2024). The primary outcome was 3-point MACE (stroke, myocardial infarction [MI], cardiovascular [CV]-related death). Entropy balancing was applied to balance baseline characteristics. Weighted incidence rates per 1000 person-years and doubly robust Cox proportional hazard ratios were reported. RESULTS: There were 75 243 enrolees included (semaglutide, 42 007; dulaglutide, 33 236). The mean age was 68.2 and 69.3 years (unweighted) in the semaglutide and dulaglutide cohorts, respectively. After balancing, standardized mean differences were <0.1 for all variables. The incidence rates of the primary outcome, 3-point MACE, were 25.7 and 33.0 in the semaglutide and dulaglutide cohorts, respectively. Compared with the dulaglutide cohort, the semaglutide cohort had a 22% lower risk of 3-point MACE (hazard ratio, 0.78 [95% CI, 0.70-0.87]; p < 0.001). CONCLUSIONS: Among United States Medicare Optum CDM enrolees with T2D and ASCVD, semaglutide was associated with reduced risks of CV outcomes compared with dulaglutide. These results help to address an important evidence gap in selecting glucagon-like peptide-1 receptor agonists for this high-risk population. CI - (c) 2026 Novo Nordisk, Genesis Research, LLC and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tan, Xi AU - Tan X AUID- ORCID: 0000-0002-2409-5927 AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, Connecticut, USA. LA - eng GR - Novo Nordisk/ PT - Comparative Study PT - Journal Article DEP - 20260108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects MH - Female MH - Male MH - United States/epidemiology MH - Retrospective Studies MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Aged MH - Middle Aged MH - *Atherosclerosis/epidemiology/complications/drug therapy MH - *Cardiovascular Diseases/epidemiology MH - Drug Administration Schedule PMC - PMC12992163 OTO - NOTNLM OT - cardiovascular disease OT - cohort study OT - dulaglutide OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- XT, YL, LX, CM, and CS are employees of Novo Nordisk Inc. JH and CG are employees of Genesis Research Group (Hoboken, NJ), which was contracted by Novo Nordisk Inc. to perform the analyses. AdH receives research funding from the American Academy of Neurology and National Institutes of Health (UG3NS133209, UH3NS130228, R01NS130189, R21NS138995), consultant fees from Novo Nordisk, royalty fees from UpToDate, and has equity in TitinKM and Certus. EDAT- 2026/01/09 07:06 MHDA- 2026/03/17 06:48 PMCR- 2026/03/17 CRDT- 2026/01/09 02:23 PHST- 2025/12/19 00:00 [revised] PHST- 2025/10/17 00:00 [received] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/09 07:06 [pubmed] PHST- 2026/01/09 02:23 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70440 [pii] AID - 10.1111/dom.70440 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2661-2671. doi: 10.1111/dom.70440. Epub 2026 Jan 8. PMID- 41507425 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20261009 IS - 1759-507X (Electronic) IS - 1759-5061 (Linking) VI - 22 IP - 4 DP - 2026 Apr TI - GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease. PG - 265-282 LID - 10.1038/s41581-025-01036-y [doi] AB - Chronic kidney disease (CKD) remains a major public health problem, with type 2 diabetes and obesity representing key risk factors worldwide. The complex pathophysiology and the metabolic risk factors shared between type 2 diabetes, obesity, CKD and cardiovascular disease have led to the concept of a cardiovascular-kidney-metabolic (CKM) syndrome. The treatment landscape for CKM changed dramatically when agents from several medication classes, originally developed as glucose-lowering therapies, were recognized to reduce the risk of multiple components of CKM syndrome. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic-GLP-1RAs, have evolved from metabolic therapies to agents with either proven or potential protective effects on the kidney and heart. In addition to their potent metabolic actions that reduce hyperglycaemia and body weight, GLP-1RAs also lower the risk of major kidney, cardiovascular and mortality outcomes across broad populations with cardiovascular disease or CKD, with and without diabetes or obesity. GLP-1RAs have been combined with glucose-dependent insulinotropic agonism, as well as glucagon agonism or amylin analogues to further enhance their metabolic benefits. However, kidney and heart protection are not fully explainable by the metabolic actions of these agents. Rather, a growing body of evidence suggests that the systemic and local actions of incretins and metabolic hormones modulate multiple pathways that can promote inflammatory and fibrotic injury. CI - (c) 2026. Springer Nature Limited. FAU - Alicic, Radica Z AU - Alicic RZ AUID- ORCID: 0000-0002-5437-5700 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. AD - Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. FAU - Neumiller, Joshua J AU - Neumiller JJ AUID- ORCID: 0000-0002-4734-7402 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. AD - Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. katherine.tuttle@providence.org. AD - Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. katherine.tuttle@providence.org. AD - Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle, WA, USA. katherine.tuttle@providence.org. LA - eng PT - Journal Article PT - Review DEP - 20260108 PL - England TA - Nat Rev Nephrol JT - Nature reviews. Nephrology JID - 101500081 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy/metabolism/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Incretins/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Cardiovascular Diseases MH - Metabolic Syndrome/drug therapy COIS- Competing interests: R.Z.A. is supported by NIH research grants OT2HL161847, OT2OD032581, U24TR001608 and CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264; and reports other support from Travere Therapeutics Inc, the Doris Duke Charitable Foundation, Bayer AG, AstraZeneca, Novo Nordisk, The George Institute for Global Health, CareDx and KBP BioSciences, and personal fees from Boehringer Ingelheim, Bayer Pharmaceuticals and Eli Lilly. J.J.N. is supported by NIH research grant OT2OD032581 and a research grant from the American College of Clinical Pharmacy, reports consulting fees from Bayer AG, Sanofi, Boehringer Ingelheim, Eli Lilly and Proteomics International, reports payments for lectures from Dexcom and Med Learning Group and serves on the Board of Directors for the American Diabetes Association. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581 and CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Travere Therapeutics Inc, Bayer, the Doris Duke Charitable Foundation and Breakthrough T1D. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Bayer, Eli Lilly, Novo Nordisk, Travere Therapeutics Inc, ProKidney and Alnylam; and speaker fees from Novo Nordisk Boehringer Ingelheim and Bayer. EDAT- 2026/01/09 00:26 MHDA- 2026/03/24 07:41 CRDT- 2026/01/08 23:28 PHST- 2025/11/13 00:00 [accepted] PHST- 2026/03/24 07:41 [medline] PHST- 2026/01/09 00:26 [pubmed] PHST- 2026/01/08 23:28 [entrez] AID - 10.1038/s41581-025-01036-y [pii] AID - 10.1038/s41581-025-01036-y [doi] PST - ppublish SO - Nat Rev Nephrol. 2026 Apr;22(4):265-282. doi: 10.1038/s41581-025-01036-y. Epub 2026 Jan 8. PMID- 41504921 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260627 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 63 IP - 4 DP - 2026 Apr TI - Decoupling weight loss from organoprotective benefits in GLP-1RA, dual agonists, and SGLT2I therapy: A narrative review. PG - 727-735 LID - 10.1007/s00592-025-02636-7 [doi] AB - Over the past decade, incretin-based therapies and SGLT2 inhibitors have redefined management of type 2 diabetes (T2D) and obesity. While their glucose-lowering and weight-reducing properties are well established, growing evidence highlights benefits that extend beyond these metabolic endpoints. Large cardiovascular outcome trials, renal protection programs, and liver disease studies demonstrate that reductions in cardiovascular events, kidney failure, and steatohepatitis are only partly explained by changes in body weight or glycated hemoglobin. Instead, these agents may exert direct disease-modifying actions through anti-inflammatory, antifibrotic, hemodynamic, and endothelial pathways. This narrative review synthesizes evidence from major randomized trials and large prospective cohorts published between 2010 and 2025, prioritized based on hard clinical endpoints and relevance to organ-protection outcomes. Trials such as SURPASS-CVOT, SOUL, SELECT, SUSTAIN-6, LEADER, REWIND, EMPA-REG OUTCOME, DAPA-CKD, EMPA-KIDNEY, and ESSENCE collectively illustrate protection across cardiovascular, renal, and hepatic systems. Importantly, trials conducted predominantly in individuals with higher baseline body weight demonstrated more pronounced weight loss, whereas other pivotal trials involving participants with lower baseline weight showed comparable organoprotective benefits despite far smaller weight changes-highlighting that these effects extend beyond the advantages conferred by weight reduction alone. Emerging data also suggest possible benefits in neurological and respiratory domains. Recognition of these broader effects has important implications for chronic disease management and the development of future therapeutic paradigms. FAU - Bhaduri, Gaurab AU - Bhaduri G AUID- ORCID: 0009-0007-4000-9287 AD - Parkview Super Specialty Hospital, Kolkata, West Bengal, India. FAU - Bhattacharyya, Supratik AU - Bhattacharyya S AUID- ORCID: 0000-0002-2351-7470 AD - SKN Diabetes and Endocrine Centre, Naihati, West Bengal, India. FAU - Mukherjee, Shatavisa AU - Mukherjee S AUID- ORCID: 0000-0001-9524-1525 AD - Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India. shatavisa100@gmail.com. FAU - Gokalani, Rutul AU - Gokalani R AUID- ORCID: 0000-0001-8546-002X AD - AHC Diabetes Centre, Ahmedabad, Gujarat, India. LA - eng PT - Journal Article PT - Review DEP - 20260108 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy OTO - NOTNLM OT - Dual agonists OT - Glucagon like peptide - 1 receptor agonists OT - Organ protection OT - SGLT2 inhibitors OT - Weight reduction COIS- Declarations. Conflict of interest: None. Ethical approval: Not Applicable. EDAT- 2026/01/08 17:52 MHDA- 2026/06/27 06:44 CRDT- 2026/01/08 11:13 PHST- 2025/10/23 00:00 [received] PHST- 2025/12/11 00:00 [accepted] PHST- 2026/06/27 06:44 [medline] PHST- 2026/01/08 17:52 [pubmed] PHST- 2026/01/08 11:13 [entrez] AID - 10.1007/s00592-025-02636-7 [pii] AID - 10.1007/s00592-025-02636-7 [doi] PST - ppublish SO - Acta Diabetol. 2026 Apr;63(4):727-735. doi: 10.1007/s00592-025-02636-7. Epub 2026 Jan 8. PMID- 41504379 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Sex differences in trial representation and the cardiovascular effectiveness of newer glucose-lowering agents in patients with and without type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. PG - 2183-2202 LID - 10.1111/dom.70411 [doi] AB - AIMS: The extent to which the cardiovascular benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by sex remains unclear. This systematic meta-analysis aimed to investigate sex differences in trial representation and the cardiovascular and kidney efficacy of SGLT-2is and GLP-1RAs in patients with and without type 2 diabetes (T2D). MATERIALS AND METHODS: Cardiovascular outcome trials (CVOTs) were identified through searches in MEDLINE, Embase, and CENTRAL, and manual search of ClinicalTrials.gov up to August 2025. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sex-differential treatment effects were assessed using the ratio of HRs and meta-regression. RESULTS: Across 47 articles from 25 unique CVOTs (n > 185 000) published between 2015 and 2025, women were less represented (approximately one-third of trial participants). SGLT-2is and GLP-1RAs significantly reduced cardio-kidney outcomes in both men and women. In individuals with T2D, SGLT-2is significantly reduced risks of major adverse cardiovascular events (MACE) 0.87 (0.80-0.95) and composite cardiovascular death or hospitalization for heart failure 0.73 (0.64-0.83) in men, with broadly similar results for women and also for both sexes in individuals without T2D. In individuals with T2D, GLP-1RAs reduced MACE risk in men 0.89 (0.82-0.96) and women 0.83 (0.77-0.91). Pooled ratio of HRs showed no significant sex differences, though some cardiovascular benefits appeared slightly greater in women; formal interactions were not statistically significant. CONCLUSIONS: SGLT-2is and GLP-1RAs provide broadly comparable cardio-kidney benefits across sexes in patients with and without T2D. The lower representation of women in CVOTs warrants attention. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zawadka, Magdaline AU - Zawadka M AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Taguiam, Erwin AU - Taguiam E AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. AD - Cardiovascular Real-World Evidence (CARDIO-RWE) Research Group, Section of Cardiology, I.H. Asper Institute, St. Boniface Hospital, Winnipeg, Manitoba, Canada. FAU - Le, Me-Linh AU - Le ML AD - Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Sanjanwala, Rohan AU - Sanjanwala R AD - Department of Internal Medicine, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Liu, Shuangbo AU - Liu S AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Shah, Ashish H AU - Shah AH AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. AD - Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Kunutsor, Setor K AU - Kunutsor SK AUID- ORCID: 0000-0002-2625-0273 AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. AD - Cardiovascular Real-World Evidence (CARDIO-RWE) Research Group, Section of Cardiology, I.H. Asper Institute, St. Boniface Hospital, Winnipeg, Manitoba, Canada. AD - Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. LA - eng GR - University Research Grants Program (URGP) of the University of Manitoba/ GR - Cardiology Research Development Fund of the Section of Cardiology, University of Manitoba/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sex Factors MH - Treatment Outcome MH - Clinical Trials as Topic/statistics & numerical data PMC - PMC12890774 OTO - NOTNLM OT - GLP-1RA OT - SGLT-2i OT - cardiovascular disease OT - kidney events OT - randomized controlled trial OT - sex OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/01/08 17:52 MHDA- 2026/02/11 00:40 PMCR- 2026/02/11 CRDT- 2026/01/08 08:33 PHST- 2025/12/02 00:00 [revised] PHST- 2025/11/02 00:00 [received] PHST- 2025/12/16 00:00 [accepted] PHST- 2026/02/11 00:40 [medline] PHST- 2026/01/08 17:52 [pubmed] PHST- 2026/01/08 08:33 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - DOM70411 [pii] AID - 10.1111/dom.70411 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2183-2202. doi: 10.1111/dom.70411. Epub 2026 Jan 8. PMID- 41502515 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 1555-3906 (Electronic) IS - 0965-0407 (Print) IS - 0965-0407 (Linking) VI - 34 IP - 1 DP - 2025 TI - Early GLP-1 Agonist Use and Cancer Risk in Type 2 Diabetes: A Real-World Data Cohort Study. PG - 12 LID - 10.32604/or.2025.072875 [doi] LID - 12 AB - BACKGROUND: To determine whether initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA) within 3 months of type 2 diabetes (T2DM) diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index (BMI). METHODS: This retrospective cohort study used electronic health records from the TriNetX U.S. research network. Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis. Following 1:1 propensity score matching, both the GLP-1 RA user and non-user groups included 183,264 patients. The study outcome was defined as a diagnosis of malignant neoplasms. Hazard ratios (HRs) for overall and site-specific cancer risk were estimated using Cox proportional hazards models. Kaplan-Meier analysis and stratified analysis by BMI were performed. RESULTS: Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk (HR 0.93; 95% CI: 0.90-0.96). Reduced risks were noted for cancers of the digestive (HR 0.81), respiratory (HR 0.66), and female genital (HR 0.87) systems. In stratified analysis, benefits were more pronounced in patients with BMI >/= 30, particularly for pancreatic and colorectal cancers. CONCLUSION: Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk, particularly among individuals with obesity. These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy. CI - (c) 2026 The Authors. FAU - Chuang, Cheng-Hsun AU - Chuang CH AD - Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. AD - Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. AD - Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan. FAU - Tsai, Ping-Kun AU - Tsai PK AD - Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan. AD - Department of Internal Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, 813, Taiwan. AD - Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan. AD - Graduate Institute of Aerospace and Undersea Medicine, College of Biomedical Sciences, National Defense Medical University, Taipei, 114, Taiwan. FAU - Kao, Shih-Wen AU - Kao SW AD - Department of Orthopedic Surgery, Chung Shan Medical University Hospital, Taichung, 402, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. FAU - Wang, Yu-Hsun AU - Wang YH AD - School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 402, Taiwan. FAU - Yeh, Chao-Bin AU - Yeh CB AD - Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. AD - Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan. AD - Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan. LA - eng PT - Journal Article DEP - 20251230 PL - United States TA - Oncol Res JT - Oncology research JID - 9208097 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/epidemiology/etiology/prevention & control MH - Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Body Mass Index MH - Risk Factors PMC - PMC12774574 OTO - NOTNLM OT - Glucagon-like peptide-1 (GLP-1) receptor agonists OT - cancer risk OT - cohort study OT - obesity OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest to report regarding the present study. EDAT- 2026/01/08 07:13 MHDA- 2026/01/08 07:14 PMCR- 2025/12/30 CRDT- 2026/01/08 04:35 PHST- 2025/09/05 00:00 [received] PHST- 2025/10/29 00:00 [accepted] PHST- 2026/01/08 07:14 [medline] PHST- 2026/01/08 07:13 [pubmed] PHST- 2026/01/08 04:35 [entrez] PHST- 2025/12/30 00:00 [pmc-release] AID - 72875 [pii] AID - 10.32604/or.2025.072875 [doi] PST - epublish SO - Oncol Res. 2025 Dec 30;34(1):12. doi: 10.32604/or.2025.072875. eCollection 2025. PMID- 41501776 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260921 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 24 IP - 1 DP - 2026 Jan 8 TI - Prevalence of use and interest in using glucagon-like peptide-1 receptor agonists for weight loss: a population study in Great Britain. PG - 1 LID - 10.1186/s12916-025-04528-7 [doi] LID - 1 AB - BACKGROUND: This study aimed to assess the prevalence of glucagon-like peptide-1 (GLP-1) receptor agonist use and interest in using medications for weight loss among adults (>/= 18 years) in Great Britain. METHODS: Nationally representative household survey, January-March 2025 (n = 5893). Participants were asked whether they had used medication in the past year to manage type 2 diabetes (excluding insulin), reduce the risk of heart disease, or support weight loss and, if so, whether they had used any of five specific GLP-1 or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Those who had not used medication to support weight loss in the past year were asked how likely they would be to consider doing so in the next year. Estimates were reported stratified by participant characteristics and extrapolated to the national population. RESULTS: Overall, 2.9% [2.4-3.4%]- approximately 1.6 million adults-reported using a GLP-1 or GLP-1/GIP medication to support weight loss in the past year, with 1.7% [1.4-2.1%] (~ 910,000 adults) using them exclusively for this purpose. Of those who used them exclusively for weight loss, the majority (91.4% [85.6-97.2%]) reported using medications licensed for this purpose in Great Britain, most commonly Mounjaro (tirzepatide; 80.2% [71.9-88.6%]). Of those who had not used weight-loss medication in the past year, 6.5% [5.7-7.3%] (~ 3.3 million adults) expressed an interest in doing so in the next year. Use and interest were more prevalent among women, people in mid-life, and those reporting past-month psychological distress. Interest was also higher among people facing greater socioeconomic disadvantage. CONCLUSIONS: In the first quarter of 2025, an estimated 4.9 million adults in Great Britain-nearly one in ten-either had recently used a GLP-1 or GLP-1/GIP medication to support weight loss or were interested in doing so in the near future. A substantial minority reported using a type of GLP-1 medication that was not licensed for weight management, suggesting off-label use. Interest was particularly high among less advantaged socioeconomic groups, while use was similar across groups, highlighting the importance of addressing equity in access. These findings underscore the need to monitor who is accessing these medications and to ensure their safe, appropriate, and equitable provision. CI - (c) 2025. The Author(s). FAU - Jackson, Sarah E AU - Jackson SE AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. s.e.jackson@ucl.ac.uk. FAU - Brown, Jamie AU - Brown J AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. FAU - Llewellyn, Clare AU - Llewellyn C AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. FAU - Mytton, Oliver AU - Mytton O AD - Institute for Child Health, University College London, London, UK. FAU - Shahab, Lion AU - Shahab L AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. LA - eng GR - PRCRPG-Nov21\100002/CRUK_/Cancer Research UK/United Kingdom GR - ES/Y001044/1/Economic and Social Research Council/ PT - Journal Article DEP - 20260108 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - United Kingdom/epidemiology MH - Female MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Middle Aged MH - Male MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Prevalence MH - Young Adult MH - Adolescent MH - Tirzepatide PMC - PMC12781702 OTO - NOTNLM OT - Liraglutide OT - Mounjaro OT - Ozempic OT - Saxenda OT - Semaglutide OT - Tirzepatide OT - Wegovy COIS- Declarations. Ethics approval and consent to participate: Ethical approval for the STS was granted originally by the UCL Ethics Committee (ID 0498/001). All participants provided verbal consent which was recorded on computers by trained interviewers. All methods are carried out in accordance with relevant regulations. The data are not collected by UCL and are anonymised when received by UCL. Consent for publication: Not applicable. Competing interests: LS has acted as paid reviewer for grant awarding bodies and as a paid consultant for health care companies. EDAT- 2026/01/08 07:13 MHDA- 2026/01/08 07:14 PMCR- 2026/01/08 CRDT- 2026/01/08 00:02 PHST- 2025/06/20 00:00 [received] PHST- 2025/11/13 00:00 [accepted] PHST- 2026/01/08 07:14 [medline] PHST- 2026/01/08 07:13 [pubmed] PHST- 2026/01/08 00:02 [entrez] PHST- 2026/01/08 00:00 [pmc-release] AID - 10.1186/s12916-025-04528-7 [pii] AID - 4528 [pii] AID - 10.1186/s12916-025-04528-7 [doi] PST - epublish SO - BMC Med. 2026 Jan 8;24(1):1. doi: 10.1186/s12916-025-04528-7. PMID- 41501059 OWN - NLM STAT- MEDLINE DCOM- 20260127 LR - 20260131 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Jan 7 TI - Comprehensive evaluation of GLP-1 receptor agonists: an umbrella review of clinical outcomes across multiple diseases. PG - 972 LID - 10.1038/s41467-025-67701-9 [doi] LID - 972 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were initially approved for type 2 diabetes mellitus. Recent evidence suggests their therapeutic potential in various diseases, though their efficacy and safety remain incompletely understood. Here, we conduct an umbrella review including 123 meta-analyses covering 464 outcomes from 5617 articles to comprehensively assess the effectiveness and adverse events (AEs) of GLP-1 RAs across diverse outcomes. GLP-1 RAs showed trends toward improvements in endocrine and metabolic, cardiovascular, renal, and respiratory outcomes, cognitive function, with a potential reduction in fracture risk and all-cause mortality in certain populations. However, increased risks of certain AEs, including diabetic retinopathy, ketoacidosis, gastrointestinal events, and treatment discontinuation, were also observed. AMSTAR 2 assessments indicate that the existing evidence is limited by methodological shortcomings, including incomplete reporting of excluded studies, suboptimal literature search strategies, and insufficient evaluation of how bias in primary studies may influence meta-analytic estimates. Some outcomes did not reach statistical significance in all populations, highlighting the need for further high-quality clinical research. Careful consideration of potential benefits and risks is essential for optimizing treatment outcomes and ensuring patient safety when using GLP-1 RAs in clinical practice. CI - (c) 2026. The Author(s). FAU - Kong, Fanjing AU - Kong F AUID- ORCID: 0009-0004-1453-8562 AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Zhao, Yanru AU - Zhao Y AD - School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Zhang, Weiming AU - Zhang W AD - School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Wang, Xinyi AU - Wang X AD - School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Wu, Tianyu AU - Wu T AUID- ORCID: 0009-0003-0206-3101 AD - School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Zhou, Ziyi AU - Zhou Z AD - School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Xu, Ying AU - Xu Y AUID- ORCID: 0000-0003-1445-4997 AD - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. xuying.doctor@gmail.com. FAU - Xia, Lina AU - Xia L AUID- ORCID: 0000-0001-5338-9126 AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China. xialina@cdutcm.edu.cn. FAU - Sun, Tao AU - Sun T AUID- ORCID: 0000-0003-2773-9174 AD - School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. suntao513@gmail.com. AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. suntao513@gmail.com. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260107 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Meta-Analysis as Topic MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12847739 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/01/08 00:26 MHDA- 2026/01/28 19:20 PMCR- 2026/01/07 CRDT- 2026/01/07 23:17 PHST- 2025/01/07 00:00 [received] PHST- 2025/12/05 00:00 [accepted] PHST- 2026/01/28 19:20 [medline] PHST- 2026/01/08 00:26 [pubmed] PHST- 2026/01/07 23:17 [entrez] PHST- 2026/01/07 00:00 [pmc-release] AID - 10.1038/s41467-025-67701-9 [pii] AID - 67701 [pii] AID - 10.1038/s41467-025-67701-9 [doi] PST - epublish SO - Nat Commun. 2026 Jan 7;17(1):972. doi: 10.1038/s41467-025-67701-9. PMID- 41500509 OWN - NLM STAT- MEDLINE DCOM- 20260504 LR - 20260813 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 27 IP - 6 DP - 2026 Jun TI - Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence. PG - e70079 LID - 10.1111/obr.70079 [doi] LID - e70079 AB - Next-generation incretin therapies, including semaglutide and tirzepatide, have transformed obesity and Type 2 diabetes management. However, evidence-based nutritional strategies to support safe and effective use of these agents remain limited. To address this gap, we conducted a systematic scoping review across five databases of studies published between January 2015 and April 2025 to map and appraise clinical trials incorporating nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes. Eligible studies included adults receiving semaglutide or tirzepatide with either an active dietary intervention or measured nutrition-related outcomes. Study quality was assessed using established tools. Twelve studies were included: 10 randomized controlled trials, one non-randomized comparative study, and one cross-sectional observational study. Interventions ranged from structured very-low-energy or ketogenic diets to general lifestyle counseling and observational dietary assessments. Across studies, energy intake decreased by 24% to 39%, but lean tissue loss accounted for up to 40% of total weight reduction. Only three studies involved nutrition professionals, and systematic assessment of protein or micronutrient intake was rare. One observational study found widespread nutrient inadequacies and limited access to dietetic support. Despite the effectiveness of semaglutide and tirzepatide for weight loss, evidence on optimal dietary strategies is sparse. Early dietitian involvement, high-protein, nutrient-dense diets, and routine nutritional monitoring should be prioritized. Robust trials are needed to define best practice for integrating dietary care alongside pharmacotherapy. CI - (c) 2026 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Spreckley, Marie AU - Spreckley M AUID- ORCID: 0000-0002-8346-2408 AD - MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. FAU - Ruggiero, Cara F AU - Ruggiero CF AUID- ORCID: 0000-0001-6498-991X AD - MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. FAU - Brown, Adrian AU - Brown A AUID- ORCID: 0000-0003-1818-6192 AD - Centre for Obesity Research, University College London, Longdon, UK. AD - Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital NHS Foundation Trust, London, UK. AD - National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, London, UK. LA - eng GR - 303041/National Institute for Health and Care Research/ PT - Journal Article PT - Scoping Review DEP - 20260107 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - *Obesity/drug therapy/diet therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Weight Loss PMC - PMC13136787 OTO - NOTNLM OT - GLP-1 receptor agonists OT - nutrition OT - semaglutide OT - tirzepatide COIS- M.S. and C.F.R. declare no competing interests. A.B. declares researcher-led grants from the National Institute for Health Research, Rosetrees Trust, MRC, INNOVATE UK, British Dietetic Association, British Association of Parenteral and Enteral Nutrition, BBSRC, the Office of Health Improvement and Disparities and NovoNordisk. A.B. reports honoraria from Novo Nordisk and Eli Lilly outside the submitted work and is on the Medical Advisory Board and a shareholder of Reset Health Clinics Ltd. EDAT- 2026/01/08 00:27 MHDA- 2026/05/04 12:34 PMCR- 2026/05/04 CRDT- 2026/01/07 19:20 PHST- 2025/09/22 00:00 [revised] PHST- 2025/06/13 00:00 [received] PHST- 2025/12/10 00:00 [accepted] PHST- 2026/05/04 12:34 [medline] PHST- 2026/01/08 00:27 [pubmed] PHST- 2026/01/07 19:20 [entrez] PHST- 2026/05/04 00:00 [pmc-release] AID - OBR70079 [pii] AID - 10.1111/obr.70079 [doi] PST - ppublish SO - Obes Rev. 2026 Jun;27(6):e70079. doi: 10.1111/obr.70079. Epub 2026 Jan 7. PMID- 41493256 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260127 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 25 IP - 1 DP - 2026 Jan 1 TI - Cutaneous Adverse Events Associated With GLP-1 Receptor Agonists: A FAERS Database Analysis From 2018-2024. PG - 11-16 LID - 10.36849/JDD.9448 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for conditions beyond type 2 diabetes, including psoriasis and hidradenitis suppurativa. Despite this, little is known about their dermatologic safety profiles. METHODS: We analyzed FDA Adverse Event Reporting System (FAERS) data from 2018 to 2024 for semaglutide, liraglutide, exenatide, and dulaglutide. Cutaneous adverse events (AEs) were identified using MedDRA-coded terms: "rash," "pruritus," "urticaria," "alopecia," and "angioedema". Frequency and proportional reporting ratios (PRRs) were calculated using dipeptidyl peptidase-4 (DPP-4) inhibitors as a comparator. Logistic regression assessed predictors of cutaneous AEs, with dulaglutide as a reference and sex, age, and GLP-1 RA type as independent variables. RESULTS: Cutaneous AEs were reported in up to 8.16% of GLP-1 RA cases, more often in females, with a mean patient age of 60. Semaglutide was associated with the highest rate, and dulaglutide the lowest. PRR analysis (0.27; 95% CI: 0.257-0.284) showed these AEs were proportionally less common relative to DPP-4 inhibitor users. Exenatide was associated with increased odds (OR = 5.01, 95% CI: 4.69–5.35), while liraglutide and semaglutide showed decreased odds. DISCUSSION: Possibly influenced by dosage, immune modulation, and patient perception of efficacy, cutaneous GLP-1RA adverse effects were less frequent than DPP-4 inhibitors, but still warrant clinician awareness. These reactions might impact patient adherence, which highlights the need for further investigation into their mechanisms. CONCLUSION: Cutaneous AEs are infrequent but vary by GLP-1 RA. Greater awareness may improve patient counseling as indications expand.  . FAU - Fat, Marisa N AU - Fat MN FAU - Johnson, Hayden C AU - Johnson HC FAU - Farberg, Aaron S AU - Farberg AS LA - eng PT - Journal Article PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives/administration & dosage MH - Middle Aged MH - Exenatide/adverse effects/administration & dosage MH - Liraglutide/adverse effects/administration & dosage MH - Aged MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Adult MH - Databases, Factual/statistics & numerical data MH - Recombinant Fusion Proteins/adverse effects/administration & dosage MH - United States/epidemiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Drug Eruptions/etiology/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - Young Adult MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2026/01/06 19:17 MHDA- 2026/01/06 19:18 CRDT- 2026/01/06 12:42 PHST- 2026/01/06 19:18 [medline] PHST- 2026/01/06 19:17 [pubmed] PHST- 2026/01/06 12:42 [entrez] AID - S1545961626P9448X [pii] AID - 10.36849/JDD.9448 [doi] PST - ppublish SO - J Drugs Dermatol. 2026 Jan 1;25(1):11-16. doi: 10.36849/JDD.9448. PMID- 41492776 OWN - NLM STAT- MEDLINE DCOM- 20260223 LR - 20260223 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 57 IP - 3 DP - 2026 Mar TI - Glucagon-Like Peptide-1 Receptor Agonists and Decreased Subarachnoid Hemorrhage Risk in Patients With Intracranial Aneurysm. PG - 802-807 LID - 10.1161/STROKEAHA.125.053599 [doi] AB - BACKGROUND: The potential protective effect of GLP‑1RAs against nontraumatic subarachnoid hemorrhage (SAH) in individuals with intracranial aneurysms (IAs) remains unclear. Since GLP-1RAs (glucagon-like peptide-1 receptor agonists) have known anti-inflammatory and antihypertensive properties, we proposed to evaluate whether they reduce the risk of nontraumatic SAH in patients with IA with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the global TriNetX database, which spans over 90 health care organizations across North America, South America, Europe, and Asia, with the majority of data contributed by the United States. Analysis included data from January 2010 to January 2025. Patients with unruptured IAs and type 2 diabetes who received GLP‑1RAs (n=2517) were compared with those who did not (n=23 431). Propensity score matching (1:1) was performed on 95 demographic and clinical variables, including smoking and hypertension. A subgroup and matched analysis excluded patients who had a history of IA treatment. The primary outcomes were nontraumatic SAH and all‑cause mortality over a 5‑year follow‑up period. Hazard ratios (HRs) and 95% CIs were calculated, and a falsification analysis was performed to evaluate whether patients taking GLP-1RAs were receiving more medical care. RESULTS: After matching, each cohort comprised 2275 patients. GLP‑1RA use was associated with a significantly lower rate of nontraumatic SAH (HR, 0.66 [95% CI, 0.50-0.87]) and all‑cause mortality (HR, 0.63 [95% CI, 0.52-0.76]). In the matched subgroup analysis of untreated patients, GLP‑1RA use was similarly associated with reduced risk of nontraumatic SAH (HR, 0.68 [95% CI, 0.47-0.98]) and all‑cause mortality (HR, 0.64 [95% CI, 0.53-0.77]). Falsification analysis confirmed the absence of confounding by indication and health care access bias. CONCLUSIONS: GLP‑1RAs have a potential role in mitigating nontraumatic SAH and improving survival among patients with IA with type 2 diabetes. Prospective trials are warranted to confirm these findings. FAU - Feghali, James AU - Feghali J AUID- ORCID: 0000-0001-7168-4751 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Ruchika, Fnu AU - Ruchika F AUID- ORCID: 0000-0003-0027-3175 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Horowitz, Melanie A AU - Horowitz MA AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Xu, Risheng AU - Xu R AUID- ORCID: 0000-0003-4288-1232 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Jackson, Christopher M AU - Jackson CM AUID- ORCID: 0000-0002-5958-2004 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Caplan, Justin M AU - Caplan JM AUID- ORCID: 0000-0002-0289-3661 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Huang, Judy AU - Huang J AUID- ORCID: 0000-0002-0675-1935 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Tamargo, Rafael J AU - Tamargo RJ AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Gonzalez, L Fernando AU - Gonzalez LF AUID- ORCID: 0000-0003-4121-1755 AD - Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD. LA - eng PT - Journal Article DEP - 20260106 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Subarachnoid Hemorrhage/prevention & control/epidemiology MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Intracranial Aneurysm/complications/drug therapy/epidemiology MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - cerebral hemorrhage OT - diabetes OT - ischemic stroke OT - neuroprotection OT - smoking COIS- Dr Jackson is a consultant for Egret Therapeutics with equity interests in the company. He receives research support from Biohaven Pharmaceuticals Inc and Grifols Biologicals Inc. Dr Huang reports compensation from Longeviti Neuro Solutions LLC for other services; service as Director for the American Board of Neurological Surgery; and intellectual property for the textbook Fundamentals of Operative Neurosurgery. The other authors report no conflicts. EDAT- 2026/01/06 19:17 MHDA- 2026/02/23 18:52 CRDT- 2026/01/06 12:04 PHST- 2026/02/23 18:52 [medline] PHST- 2026/01/06 19:17 [pubmed] PHST- 2026/01/06 12:04 [entrez] AID - 10.1161/STROKEAHA.125.053599 [doi] PST - ppublish SO - Stroke. 2026 Mar;57(3):802-807. doi: 10.1161/STROKEAHA.125.053599. Epub 2026 Jan 6. PMID- 41492180 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Oral semaglutide and survival in heart failure with preserved ejection fraction and type 2 diabetes. PG - 2374-2382 LID - 10.1111/dom.70433 [doi] AB - AIMS: Heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D) commonly coexist and are associated with poor outcomes. Although injectable semaglutide has demonstrated benefits in HFpEF, the effectiveness of oral semaglutide in this setting remains uncertain. This study compared all-cause death and hospitalisation between oral semaglutide and sitagliptin in patients with HFpEF and T2D. MATERIALS AND METHODS: Using a global healthcare data and analytics platform, the TriNetX research network, we conducted a retrospective multi-centre observational study. We identified patients aged >/=18 years with HFpEF diagnosed before December 31, 2023 (N = 1 731 548), of whom 812 259 had concomitant T2D. Among them, 3470 initiated oral semaglutide and 22 840 initiated sitagliptin between October 1, 2019, and December 31, 2023. After propensity score matching, each group included 3452 patients. The primary outcome was all-cause death; the secondary outcome was hospitalisation. RESULTS: Over 1 year, the risk for all-cause death in patients who received oral semaglutide relative to those who received sitagliptin was significantly lower (4.3% [145/3452] vs. 7.0% [229/3452]; log-rank p < 0.001; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50 to 0.75). Similarly, patients who received oral semaglutide experienced fewer hospitalisations than those who received sitagliptin (37.1% vs. 42.4%; log-rank p < 0.001; HR, 0.83; 95% CI, 0.77 to 0.90). CONCLUSIONS: Oral semaglutide appeared to be associated with a lower 1-year risk of all-cause death compared with sitagliptin in patients with HFpEF and T2D. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Shimada, Takenobu AU - Shimada T AD - Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260105 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - *Heart Failure/mortality/drug therapy/complications/physiopathology MH - Aged MH - Retrospective Studies MH - Stroke Volume/drug effects MH - Middle Aged MH - Sitagliptin Phosphate/therapeutic use/administration & dosage MH - Administration, Oral MH - Hospitalization/statistics & numerical data MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged, 80 and over MH - Cause of Death OTO - NOTNLM OT - all-cause death OT - heart failure with preserved ejection fraction OT - hospitalisation OT - oral semaglutide OT - type 2 diabetes EDAT- 2026/01/06 13:06 MHDA- 2026/02/11 00:39 CRDT- 2026/01/06 11:47 PHST- 2025/12/16 00:00 [revised] PHST- 2025/10/14 00:00 [received] PHST- 2025/12/26 00:00 [accepted] PHST- 2026/02/11 00:39 [medline] PHST- 2026/01/06 13:06 [pubmed] PHST- 2026/01/06 11:47 [entrez] AID - 10.1111/dom.70433 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2374-2382. doi: 10.1111/dom.70433. Epub 2026 Jan 5. PMID- 41490610 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260106 IS - 1099-1557 (Electronic) IS - 1053-8569 (Linking) VI - 35 IP - 1 DP - 2026 Jan TI - The Risk of Hypothyroidism With the Use of GLP-1 Receptor Agonists in Saudi Arabia. PG - e70315 LID - 10.1002/pds.70315 [doi] AB - AIM: Preclinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may induce thyroid gland hyperplasia, raising concerns about potential thyroid-related risks. Given their increasing use and the limited evidence on thyroid safety, this study assessed the association between GLP-1RA use and the incidence of hypothyroidism using real-world data. METHODS: We conducted an active-comparator, new-user cohort study using the Real-World Evidence Research Network (SRWEN) (2016-2023). Adults (>/= 18 years) initiating GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP-4is) were followed from first prescription until hypothyroidism, treatment discontinuation, switching, death, or study end. Hypothyroidism was identified through ICD-10 codes or levothyroxine prescriptions. Inverse probability of treatment weighting was applied to adjust for confounding, and weighted Cox proportional hazards models were used to estimate hazard ratios (HRs). RStudio 4.4.0 was used for analyses. RESULTS: A total of 47 017 patients were included (6800 GLP-1RA users; 40 217 DPP-4i users). GLP-1RA users were younger (mean age 50 vs. 58 years) and more often female. The incidence rate of hypothyroidism was 128 per 10 000 person-years in GLP-1RA users compared to 150 per 10 000 person-years in DPP-4i users. GLP-1RA use was not associated with a statistically significant risk of hypothyroidism (adjusted HR 1.04, 95% CI 0.69-1.57). Sensitivity analyses extending follow-up by 30 and 60 days yielded consistent findings. CONCLUSION: In this real-world analysis, GLP-1RA use was not associated with an increased incidence of hypothyroidism compared to DPP-4is. Findings were consistent across sensitivity and subgroup analyses. Although findings do not suggest a short-term risk, longer-term studies are warranted to further evaluate thyroid safety. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Alfakhri, Almaha AU - Alfakhri A AUID- ORCID: 0009-0003-5284-1805 AD - Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Almadani, Ohoud AU - Almadani O AD - Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Alroba, Raseel AU - Alroba R AD - Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Alrwisan, Adel AU - Alrwisan A AUID- ORCID: 0000-0002-9422-7390 AD - Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Alshaya, Omar AU - Alshaya O AD - King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. FAU - Albogami, Yasser AU - Albogami Y AUID- ORCID: 0000-0002-2816-6526 AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Hypothyroidism/epidemiology/chemically induced MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Incidence MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/administration & dosage MH - Saudi Arabia/epidemiology MH - Cohort Studies MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - drug safety OT - hypothyroidism OT - pharmacovigilance OT - real-world data OT - real-world evidence OT - thyroid disorders EDAT- 2026/01/06 13:06 MHDA- 2026/01/06 13:07 CRDT- 2026/01/06 10:45 PHST- 2025/12/01 00:00 [revised] PHST- 2025/10/08 00:00 [received] PHST- 2025/12/15 00:00 [accepted] PHST- 2026/01/06 13:07 [medline] PHST- 2026/01/06 13:06 [pubmed] PHST- 2026/01/06 10:45 [entrez] AID - 10.1002/pds.70315 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2026 Jan;35(1):e70315. doi: 10.1002/pds.70315. PMID- 41490509 OWN - NLM STAT- MEDLINE DCOM- 20260316 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 3 DP - 2026 Mar TI - Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists on Diabetic Foot Disease : An Emulated Target Trial. PG - 340-352 LID - 10.7326/ANNALS-25-01262 [doi] AB - BACKGROUND: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2is) on diabetic foot disease have been mixed in prior trials of SGLT-2is compared with placebo. The comparative risk for diabetic foot disease with SGLT-2is compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs) is unknown. OBJECTIVE: To compare risks for foot disease in new users of SGLT-2is and GLP-1RAs. DESIGN: Cohort study using target trial emulation. SETTING: Danish population-based study. PARTICIPANTS: Patients with type 2 diabetes initiating SGLT-2i or GLP-1RA treatment, identified using national health care registry data from 2013 to 2023, and a convenience sample enrolled in a research cohort study with additional behavioral and clinical assessments. MEASUREMENTS: Incident diagnosis of foot disease outcomes (peripheral neuropathy, peripheral artery disease, foot ulcers, or lower-limb amputation) as defined by the International Working Group on the Diabetic Foot. Inverse probability of treatment-weighted risk ratios (RRs) were estimated, with adjustment for 45 demographic, clinical, and other factors. RESULTS: The registry cohort included 53 769 new users of SGLT-2is and 30 380 of GLP-1RAs. During 6 years of follow-up, any foot disease occurred in 10.8% of SGLT-2i users and 12.0% of GLP-1RA users, corresponding to an RR of 0.90 (95% CI, 0.84 to 0.97) in an intention-to-treat analysis; differences did not emerge until after year 3, when 40% of SGLT-2i users and 32% of GLP-1RA users had discontinued initial treatment. The modest reduction in risk among SGLT-2i users was driven by lower risk for neuropathy (RR, 0.78 [CI, 0.68 to 0.87]). Users of SGLT-2is and GLP-1RAs had similar risks for peripheral artery disease, foot ulcers, amputations, and all-cause mortality. LIMITATION: Residual confounding; exposure and outcome misclassification. CONCLUSION: New SGLT-2i users had a modestly lower risk for foot disease largely driven by a lower risk for neuropathy than GLP-1RA users. PRIMARY FUNDING SOURCE: Aarhus University and Center for Population Medicine. FAU - Kristensen, Frederik P B AU - Kristensen FPB AUID- ORCID: 0000-0001-5311-8924 AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark (F.P.B.K., H.T.S., R.W.T.). FAU - Christensen, Diana H AU - Christensen DH AUID- ORCID: 0000-0002-2693-5651 AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (D.H.C.). FAU - Callaghan, Brian C AU - Callaghan BC AUID- ORCID: 0000-0002-8885-6748 AD - Department of Neurology, University of Michigan, Ann Arbor, Michigan (B.C.C.). FAU - Nielsen, Jens S AU - Nielsen JS AUID- ORCID: 0000-0003-3179-1186 AD - Steno Diabetes Center Odense, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark (J.S.N.). FAU - Andersen, Henning AU - Andersen H AD - Department of Neurology, Aarhus University Hospital, Aarhus, Denmark (H.A.). FAU - Sorensen, Henrik T AU - Sorensen HT AUID- ORCID: 0000-0003-4299-7040 AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark (F.P.B.K., H.T.S., R.W.T.). FAU - Thomsen, Reimar W AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark (F.P.B.K., H.T.S., R.W.T.). LA - eng PT - Comparative Study PT - Journal Article DEP - 20260106 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Foot/prevention & control/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Denmark/epidemiology MH - Amputation, Surgical/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/01/06 13:06 MHDA- 2026/03/16 21:57 CRDT- 2026/01/06 10:42 PHST- 2026/03/16 21:57 [medline] PHST- 2026/01/06 13:06 [pubmed] PHST- 2026/01/06 10:42 [entrez] AID - 10.7326/ANNALS-25-01262 [doi] PST - ppublish SO - Ann Intern Med. 2026 Mar;179(3):340-352. doi: 10.7326/ANNALS-25-01262. Epub 2026 Jan 6. PMID- 41489846 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20261009 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Jan 5 TI - Exploring the rates of Gastrointestinal adverse effects among five GLP-1 receptor agonists: A systematic review and Meta-Analysis of randomized controlled trials. PG - 23 LID - 10.1007/s12020-025-04494-3 [doi] AB - PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective and commonly used agents in treating type 2 diabetes and obesity. Due to their success in weight loss, usage of this class of medications is becoming more common. Yet any use of GLP-1 RAs does not come without disadvantages. This meta-analysis aimed to analyze the gastrointestinal (GI)-related adverse effects (AEs) of GLP-1 RAs use. METHODS: A systematic review search following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed in three databases for studies reporting GI AEs after GLP-1 RA usage. A pair-wise meta-analysis evaluating the six most common GI AEs (nausea, vomiting, diarrhea, constipation, decreased appetite, and pancreatitis) among GLP-1 RAs was performed, along with a network meta-analysis comparing semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide to one another in the context of GI AEs. RESULTS: 101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies). All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and pancreatitis (2.24; 1.07%). Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea while semaglutide carries the highest risk ratios for vomiting and constipation. CONCLUSIONS: Regardless of the GLP-1 RAs used, it is apparent that GI AEs are significant and highly prevalent. Thus, it is crucial that patients and providers alike are aware of these AEs when considering their use. FAU - Joy, Bethany AU - Joy B AUID- ORCID: 0009-0002-5707-146X AD - California Northstate University College of Medicine, California, USA. Bethany.Joy7985@cnsu.edu. FAU - Ramsamooj, Anya AU - Ramsamooj A AD - California Northstate University College of Medicine, California, USA. FAU - Ibrahim, Steven AU - Ibrahim S AD - California Northstate University College of Medicine, California, USA. FAU - Wen, Jimmy AU - Wen J AD - California Northstate University College of Medicine, California, USA. FAU - Hsu, Neil AU - Hsu N AD - California Northstate University College of Medicine, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - California Northstate University College of Medicine, California, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Network Meta-Analysis PT - Systematic Review DEP - 20260105 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Randomized Controlled Trials as Topic MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Exenatide/adverse effects MH - Liraglutide/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Pancreatitis/chemically induced MH - Vomiting/chemically induced MH - Diarrhea/chemically induced MH - Nausea/chemically induced MH - Diabetes Mellitus, Type 2/drug therapy MH - Recombinant Fusion Proteins OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - Meta-analysis OT - Systematic review OT - Weight management COIS- Declarations. Conflict of interests: The authors declare no competing interests. Consent to participate: This study did not involve the use of human subjects. Consent to publish: This study did not involve the use of human subjects. EDAT- 2026/01/05 12:47 MHDA- 2026/06/27 00:51 CRDT- 2026/01/05 11:56 PHST- 2025/07/25 00:00 [received] PHST- 2025/11/20 00:00 [accepted] PHST- 2026/06/27 00:51 [medline] PHST- 2026/01/05 12:47 [pubmed] PHST- 2026/01/05 11:56 [entrez] AID - 10.1007/s12020-025-04494-3 [pii] AID - 10.1007/s12020-025-04494-3 [doi] PST - epublish SO - Endocrine. 2026 Jan 5;91(1):23. doi: 10.1007/s12020-025-04494-3. PMID- 41484761 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260813 IS - 1708-0428 (Electronic) IS - 0960-8923 (Print) IS - 0960-8923 (Linking) VI - 36 IP - 2 DP - 2026 Feb TI - Roux-en-Y Gastric Bypass Compared to Glucagon-Like Peptide-1 Receptor Agonists is Associated with Lower Out-of-Pocket Costs in Insured Patients with Type 2 Diabetes and Obesity: A Matched Analysis Over Two Years. PG - 376-385 LID - 10.1007/s11695-025-08467-3 [doi] AB - OBJECTIVE: To evaluate two-year costs to insured patients treated with Roux-en-Y gastric bypass (RYGB) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes (T2D) and obesity. METHODS: Using the 2017 to 2023 Merative claims database, we identified adult patients with severe obesity and T2D who were treated with a RYGB or GLP-1 RAs. Patients with RYGB had no treatment with GLP-1 RAs, and those who received GLP-1 RAs therapy with tirzepatide or semaglutide for >/= 2 years had no metabolic and bariatric surgery (MBS) procedures. The study cohorts were matched on demographics including obesity, associated medical problems, and baseline direct or out-of-pocket (OOP) costs to patients in the year prior to treatment initiation. Direct costs included those from outpatient services, inpatient admissions, and outpatient prescription filled that were paid directly by patients. We compared this cost up to two years after treatment initiation using paired t-tests. RESULTS: 1012 matched RYGB and GLP-1 RAs patients were analyzed, including 35% male. At 1-year after treatment initiation, healthcare costs paid directly by patients were similar for the RYGB ($2,301) and GLP-1 RAs ($2,179) (delta = $122, p = 0.15) cohorts. From one to two years after index treatment date, OOP costs were significantly lower in the RYGB treatment group ($1,277 vs. $2,104, p < 0.01). Two years after treatment initiation, RYGB patients spent $704 less in OOP costs than similar patients treated with GLP-1 RAs medications (p < 0.01). CONCLUSIONS: Direct OOP healthcare costs were lower for RYGB compared to treatment with GLP-1 RAs two years after treatment initiation. CI - (c) 2026. The Author(s). FAU - Thiyagarajan, Sibi AU - Thiyagarajan S AD - Division of Advanced GI and Bariatric Surgery, Mayo Clinic, Jacksonville, FL, USA. FAU - Wall-Wieler, Elizabeth AU - Wall-Wieler E AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. FAU - Liu, Yuki AU - Liu Y AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. FAU - Zheng, Feibi AU - Zheng F AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. AD - DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. FAU - Edwards, Michael AU - Edwards M AD - Division of Advanced GI and Bariatric Surgery, Mayo Clinic, Jacksonville, FL, USA. maeedw@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260103 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/economics/drug therapy/complications MH - *Gastric Bypass/economics MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Health Expenditures/statistics & numerical data MH - *Obesity, Morbid/economics/surgery/complications MH - *Hypoglycemic Agents/therapeutic use/economics MH - Retrospective Studies PMC - PMC12957123 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Obesity OT - Out-of-Pocket Costs OT - Roux-en-Y gastric bypass OT - Type-2 Diabetes COIS- Declarations. Competing interests: Intuitive Surgical Inc. funded access to the Merative MarketScan Research Databases used for this study. Three co-authors are employed by Intuitive Surgical, Inc. (EW, YL, FZ) and were involved in the design, analysis, or preparation of this manuscript. Author MAE is a recipient of an Intuitive Foundation Research Grant Award for another research project. EDAT- 2026/01/04 06:35 MHDA- 2026/03/08 01:38 PMCR- 2026/01/03 CRDT- 2026/01/04 01:55 PHST- 2025/09/15 00:00 [received] PHST- 2025/12/21 00:00 [accepted] PHST- 2025/12/07 00:00 [revised] PHST- 2026/03/08 01:38 [medline] PHST- 2026/01/04 06:35 [pubmed] PHST- 2026/01/04 01:55 [entrez] PHST- 2026/01/03 00:00 [pmc-release] AID - 10.1007/s11695-025-08467-3 [pii] AID - 8467 [pii] AID - 10.1007/s11695-025-08467-3 [doi] PST - ppublish SO - Obes Surg. 2026 Feb;36(2):376-385. doi: 10.1007/s11695-025-08467-3. Epub 2026 Jan 3. PMID- 41484025 OWN - NLM STAT- MEDLINE DCOM- 20260311 LR - 20260311 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 36 IP - 4 DP - 2026 Apr TI - Combined SGLT2i and GLP1ra therapy reduces all-cause mortality in people with diabetes, with greater benefit in women. PG - 104483 LID - S0939-4753(25)00638-6 [pii] LID - 10.1016/j.numecd.2025.104483 [doi] AB - BACKGROUND AND AIMS: Combined therapy, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce all-cause mortality in patients with diabetes. We aimed to analyse the differential behaviour of combined therapy between women and men regarding all-cause mortality. METHODS AND RESULTS: This is a retrospective observational cohort study. Using "Big data" according to electronic medical records in the Santiago-Barbanza health area, which covers 450,000 patients. Out of 15,118 patients, 41 % were women. The median follow-up was 33 months. Women were older (71 [62-78] vs. 67 [59-75], p: <0.001) and with a higher incidence of obesity (53 % vs. 41 %, p: <0.001), meanwhile, men presented more coronary artery disease (CAD) (19 % vs. 9 %, p: <0.001). The multinomial propensity score and multivariate Cox regression were used for statistical analysis. All-cause mortality was compared between combined vs. monotherapy in women or men. Men had a higher risk of all-cause mortality than women in this population (HR [95 % CI] 1.50 [1.28-1.75]). Combined regarding monotherapy (GLP1ra (HR [95 % CI] 0.19 [0.14-0.27]), or SGLT2i (HR [95 % CI] 0.30 [0.23-0.40]), and treatment duration (HR [95 % CI] 0.95 [0.94-0.96] were associated with lower risk of all-cause mortality; with higher benefit in women (GLP1ra (HR [95 % CI] 0.14 [0.08-0.27]), or SGLT2i (HR [95 % CI] 0.18 [0.11-0.30]) regarding men (HR [95 % CI] 0.25 [0.16-0.40] for GLP1ra, and HR [95 % CI] 0.41 [0.29-0.58] for SGLT2i). CONCLUSIONS: Combined therapy vs. monotherapy was associated with a lower risk of all-cause mortality in patients regardless of sex. Nevertheless, a higher benefit was observed in women regarding men. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Garcia-Vega, David AU - Garcia-Vega D AD - University of Santiago de Compostela, Spain; Cardiology Department, Clinical Hospital of Santiago de Compostela, Spain; Centro de Investigacion en Red en Enfermedades Cardiovasculares, Spain. Electronic address: david.garcia.vega@rai.usc.es. FAU - Cinza-Sanjurjo, Sergio AU - Cinza-Sanjurjo S AD - Centro de Investigacion en Red en Enfermedades Cardiovasculares, Spain; Centro de Salud de Milladoiro-Ames, Area Sanitaria de Santiago de Compostela, Spain. FAU - Tilves-Bellas, Carlos AU - Tilves-Bellas C AD - Cardiology Department, Clinical Hospital of Santiago de Compostela, Spain. FAU - Eiras, Sonia AU - Eiras S AD - Centro de Investigacion en Red en Enfermedades Cardiovasculares, Spain; Traslational Cardiology Group, Health Research Institute of Santiago de Compostela, Spain. FAU - Gonzalez-Juanatey, Jose Ramon AU - Gonzalez-Juanatey JR AD - University of Santiago de Compostela, Spain; Cardiology Department, Clinical Hospital of Santiago de Compostela, Spain; Centro de Investigacion en Red en Enfermedades Cardiovasculares, Spain; Traslational Cardiology Group, Health Research Institute of Santiago de Compostela, Spain. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20251202 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Male MH - Retrospective Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Sex Factors MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/blood MH - Treatment Outcome MH - Risk Factors MH - Time Factors MH - *Incretins/adverse effects/therapeutic use MH - Risk Assessment MH - Drug Therapy, Combination MH - Cause of Death MH - Spain/epidemiology MH - Biomarkers/blood MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes OT - GLP1ra OT - SGLT2i EDAT- 2026/01/04 00:32 MHDA- 2026/03/12 01:09 CRDT- 2026/01/03 22:04 PHST- 2025/06/23 00:00 [received] PHST- 2025/11/15 00:00 [revised] PHST- 2025/11/30 00:00 [accepted] PHST- 2026/03/12 01:09 [medline] PHST- 2026/01/04 00:32 [pubmed] PHST- 2026/01/03 22:04 [entrez] AID - S0939-4753(25)00638-6 [pii] AID - 10.1016/j.numecd.2025.104483 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2026 Apr;36(4):104483. doi: 10.1016/j.numecd.2025.104483. Epub 2025 Dec 2. PMID- 41482652 OWN - NLM STAT- MEDLINE DCOM- 20260519 LR - 20260813 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 111 IP - 6 DP - 2026 May 19 TI - GLP-1 receptor agonists in patients with cancer are associated with reduced all-cause mortality and hospitalization. PG - 1604-1612 LID - 10.1210/clinem/dgaf703 [doi] AB - CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been reported to decrease cancer incidence, but less is known about their potential in patients with active cancer. Preclinical studies have demonstrated that GLP-1RAs inhibit progression of solid tumor malignancies via downregulation of cellular proliferation pathways and improved glycemic control. Despite these promising findings, studies characterizing the effects of GLP-1RAs in patients with active cancer are limited. OBJECTIVE: To evaluate the effects of GLP-1RAs on mortality and hospitalization in patients with type 2 diabetes and active cancer compared to those receiving metformin. METHODS: Using TriNetX, a global database comprising more than 120 million patients, we identified an overall cohort of 3747 patients with type 2 diabetes who received GLP-1RAs within 3 months of starting systemic therapy and identified 52 061 patients receiving metformin in the same timeframe as a control cohort. Additional subanalyses stratified patients by glycated hemoglobin A1c (HbA1c) range, obesity, and by participants "newly started" on their first instance of GLP-1 RA within 3 months of starting cancer treatment. RESULTS: Patients receiving GLP-1RAs had significantly reduced mortality both in the overall monotherapy setting (hazard ratio [HR]: 0.875; 95% CI, 0.778-0.985; P = .0268) and the new-start setting (HR: 0.786; 95% CI, 0.662-0.934; P = .0062) cohorts. Secondary analyses found lower rates of all-cause hospitalization, sepsis, major adverse cardiovascular events, pulmonary embolism, and pneumonia in patients on GLP-1RAs. Subanalyses stratified by body mass index and HbA1c did not meet statistical significance. CONCLUSION: Patients with diabetes and cancer who received GLP-1RAs experienced superior survival outcomes and reduced rates of hospitalization compared to patients receiving metformin. Additionally, patients already on metformin and newly started on GLP-1RAs demonstrated superior survival outcomes compared to patients newly started on insulin. Further prospective, well-controlled studies are needed to evaluate the benefits of GLP-1RAs in patients with diabetes and cancer. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Mahadevan, Aditya AU - Mahadevan A AUID- ORCID: 0000-0002-2834-5487 AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Vosooghi, Aidan AU - Vosooghi A AD - Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Arora, Jagmeet S AU - Arora JS AD - School of Medicine, University of California, Irvine, CA 92617, USA. FAU - Kumar, Ruthvik Sunil AU - Kumar RS AD - Department of Medicine, University of Kentucky, Lexington, KY 40506, USA. FAU - Singh, Gagandeep AU - Singh G AD - Department of Computer Science, University of California, Davis, CA 95616, USA. FAU - Tsai, Katy K AU - Tsai KK AD - Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Quandt, Zoe AU - Quandt Z AUID- ORCID: 0000-0002-4568-4368 AD - Division of Endocrinology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. LA - eng GR - K12DK133995/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Neoplasms/complications/mortality/therapy MH - *Metformin/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Proportional Hazards Models MH - Hospitalization/statistics & numerical data MH - Treatment Outcome MH - Kaplan-Meier Estimate MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged MH - Retrospective Studies PMC - PMC13183429 OTO - NOTNLM OT - GLP-1RA OT - cancer OT - dulaglutide OT - exenatide OT - liraglutide OT - semaglutide OT - survival OT - tirzepatide EDAT- 2026/01/03 06:30 MHDA- 2026/05/19 06:20 PMCR- 2026/01/02 CRDT- 2026/01/03 00:33 PHST- 2025/09/10 00:00 [received] PHST- 2025/12/30 00:00 [accepted] PHST- 2026/05/19 06:20 [medline] PHST- 2026/01/03 06:30 [pubmed] PHST- 2026/01/03 00:33 [entrez] PHST- 2026/01/02 00:00 [pmc-release] AID - 8413119 [pii] AID - dgaf703 [pii] AID - 10.1210/clinem/dgaf703 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 May 19;111(6):1604-1612. doi: 10.1210/clinem/dgaf703. PMID- 41482395 OWN - NLM STAT- MEDLINE DCOM- 20260102 LR - 20260919 IS - 1791-7549 (Electronic) IS - 0258-851X (Print) IS - 0258-851X (Linking) VI - 40 IP - 1 DP - 2026 Jan-Feb TI - Sodium-Glucose Cotransporter 2 Inhibitors and Reduced Fibromyalgia Risk in Patients With Diabetes: A Target Trial Emulation Study. PG - 677-689 LID - 10.21873/invivo.14229 [doi] AB - BACKGROUND/AIM: Emerging evidence suggests that sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) may offer neuroprotective effects. This study aimed to compare the risk of new-onset fibromyalgia between diabetic patients starting SGLT2i versus those using GLP-1RA. PATIENTS AND METHODS: A target trial emulation was conducted using the TriNetX Global Collaborative Network. Adult patients with type 2 diabetes mellitus starting use of SGLT2i or GLP-1RA were included, excluding those with prior fibromyalgia or psychiatric disorders. Propensity score-matching (1:1) was applied to demographics, comorbidities, laboratory data, and co-medications. The primary outcome was incidence of fibromyalgia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. RESULTS: After matching, 297,937 patients per group were analyzed. During follow-up, fibromyalgia occurred in 6,963 (2.3%) of SGLT2i users and 7,855 (2.6%) of GLP-1RA users. SGLT2i use was associated with significantly lower fibromyalgia risk (HR=0.896, 95% CI=0.867-0.925). Findings remained robust in sensitivity analyses, including in 1-year (HR=0.884, 95% CI=0.855-0.914), 3-year (HR=0.880, 95% CI=0.850-0.912), and 5-year (HR=0.889, 95% CI=0.860-0.918) follow-up. CONCLUSION: In this large real-world cohort, SGLT2i use in diabetic patients was associated with a significantly reduced risk of fibromyalgia compared to GLP-1RA. CI - Copyright (c) 2026, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Jhang, Yi-Sheng AU - Jhang YS AD - Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. AD - Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. FAU - Lu, Hsin-Yo AU - Lu HY AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. FAU - Lin, Chen-Yu AU - Lin CY AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. FAU - Lee, Chien-Ying AU - Lee CY AD - Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. AD - Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. FAU - Su, Yu-Jung AU - Su YJ AD - Orthopedics Department, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C. FAU - Chang, Hui-Chin AU - Chang HC AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.; cshe215@gmail.com. AD - Evidence-based Medicine Center, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. AD - Library, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. FAU - Chen, Shiu-Jau AU - Chen SJ AD - Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C. AD - Department of Medicine, Mackay Medical Mackay Medical University, New Taipei City, Taiwan, R.O.C. FAU - Gau, Shuo-Yan AU - Gau SY AD - Department and Graduate Institute of Business Administration, National Taiwan, University, Taipei, Taiwan, R.O.C. AD - Department of Medical Education, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, R.O.C. LA - eng PT - Journal Article PL - Greece TA - In Vivo JT - In vivo (Athens, Greece) JID - 8806809 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Fibromyalgia/epidemiology/etiology/prevention & control MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects/administration & dosage MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Adult MH - Risk Factors MH - Hypoglycemic Agents/therapeutic use PMC - PMC12764255 OTO - NOTNLM OT - Fibromyalgia OT - SGLT2 inhibitors OT - electronic medical records OT - epidemiology OT - glucose-lowering drugs COIS- All Authors declare that no potential conflicts of interest exist. EDAT- 2026/01/03 00:30 MHDA- 2026/01/03 00:31 PMCR- 2026/01/02 CRDT- 2026/01/02 20:43 PHST- 2025/06/19 00:00 [received] PHST- 2025/07/10 00:00 [revised] PHST- 2025/07/17 00:00 [accepted] PHST- 2026/01/03 00:31 [medline] PHST- 2026/01/03 00:30 [pubmed] PHST- 2026/01/02 20:43 [entrez] PHST- 2026/01/02 00:00 [pmc-release] AID - 40/1/677 [pii] AID - 10.21873/invivo.14229 [doi] PST - ppublish SO - In Vivo. 2026 Jan-Feb;40(1):677-689. doi: 10.21873/invivo.14229. PMID- 41482188 OWN - NLM STAT- MEDLINE DCOM- 20260425 LR - 20260429 IS - 1878-1632 (Electronic) IS - 1529-9430 (Linking) VI - 26 IP - 5 DP - 2026 May TI - Glucagon-like peptide-1 receptor agonist use and perioperative outcomes after anterior cervical discectomy and fusion: a propensity-matched cohort study. PG - 882-892 LID - S1529-9430(25)00943-X [pii] LID - 10.1016/j.spinee.2025.12.019 [doi] AB - BACKGROUND CONTEXT: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a powerful treatment adjunct for type-2 diabetes mellitus (T2DM) and obesity by delaying gastric emptying and promoting early satiety. Previous studies have shown decreased complications associated with GLP-1 agonists after total hip and knee arthroplasty; however, the effects of GLP-1 agonists on outcomes following anterior cervical discectomy and fusion (ACDF) are not well known. PURPOSE: This study aimed to compare the risk of complications after ACDF in patients with T2DM and obesity (body mass index >30) who were on GLP-1 agonists with comparable patients who were not on these medications. We hypothesized that these medications reduce overall complications when compared to a matched cohort of diabetic and/or obese patients, but may place patients who undergo anterior cervical surgery at increased risk of aspiration due to the delayed gastric emptying. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Adult patients with T2DM and/or obesity undergoing single or 2-level ACDF between 2015 and 2022. OUTCOME MEASURES: Outcomes of the study included the incidence of 90-day and 1-year postoperative complications, including surgical site infections, wound dehiscence, hematoma, dysphagia, pulmonary aspiration, deep vein thrombosis or pulmonary embolism (DVT/PE), acute kidney injury, sepsis, hospital readmissions, extended hospital length of stay (>/=3 days), and pseudarthrosis or nonunion. METHODS: Adult patients with T2DM and/or obesity undergoing single or 2-level primary ACDF between 2015 and 2022 were reviewed utilizing an administrative claims database. Patients who had concurrent posterior decompression and fusion procedures were excluded. Propensity score matching was employed at a 1:1 ratio to match patients using GLP-1 agonists 6 months before and after surgery (treatment) to those who did not (control). Patients were matched on age, sex, Elixhauser comorbidity index, insulin-dependence and diabetic complications, presence of other diabetic medications, morbid obesity (body mass index >40), and active smoking status. Multivariable logistic regressions were performed to examine 90-day and 1-year outcomes between groups. RESULTS: In total, 20,941 patients with T2DM and/or obesity were queried from the database. 1,598 patients were included in both the treatment group and control group after propensity-score matching. There were no differences in rates of postoperative pulmonary aspiration in patients utilizing GLP-1 agonists compared to those who were not (0.81% vs 1.25%, p=.39). There were decreased rates of 90-day DVT/PE (0.44% vs 0.94%, p=.04), and acute kidney injury (0.94% vs 1.69%, p=.04) in the treatment group when compared to the control group. GLP-1 agonist use was associated with decreased rates of extended hospital stays (15.96% vs 18.65%, p=.04). At 1 year after ACDF, there were no differences in rates of DVT/PE (1.56% vs 2.00%, p=.36) or pseudarthrosis (2.82% vs 3.25%, p=.50). CONCLUSIONS: In this study, GLP-1 agonists have shown favorable outcomes without increasing the risk of aspiration in patients who undergo a single or 2-level ACDF. In addition to reducing postoperative medical complications, the medications also showed no increased risk of postoperative pulmonary aspiration or 1-year pseudarthrosis. Overall, while GLP-1 agonists provide benefits including increased glycemic control and weight loss, more data are needed to delineate the true effect of GLP-1 agonists on clinical outcomes following ACDF. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Heo, Kevin Y AU - Heo KY AD - Department of Orthopaedic Surgery, Emory University School of Medicine, 21 Ortho Ln, Atlanta, GA 30329, USA. Electronic address: kevin.heo@emory.edu. FAU - Barchick, Stephen R AU - Barchick SR AD - Department of Orthopaedic Surgery, Emory University School of Medicine, 21 Ortho Ln, Atlanta, GA 30329, USA. FAU - Sowa, Aubrie M AU - Sowa AM AD - Department of Orthopaedic Surgery, Emory University School of Medicine, 21 Ortho Ln, Atlanta, GA 30329, USA. FAU - Chao, Myra AU - Chao M AD - Emory University School of Medicine, 100 Woodruff Cir, Atlanta, GA 30322, USA. FAU - Rajan, Prashant V AU - Rajan PV AD - Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA. FAU - Goh, Brian C AU - Goh BC AD - Department of Orthopaedic Surgery, Emory University School of Medicine, 21 Ortho Ln, Atlanta, GA 30329, USA. FAU - Yoon, Sangwook T AU - Yoon ST AD - Department of Orthopaedic Surgery, Emory University School of Medicine, 21 Ortho Ln, Atlanta, GA 30329, USA. LA - eng PT - Journal Article DEP - 20251231 PL - United States TA - Spine J JT - The spine journal : official journal of the North American Spine Society JID - 101130732 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Spinal Fusion/adverse effects/methods MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Diskectomy/adverse effects/methods MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cervical Vertebrae/surgery MH - *Postoperative Complications/epidemiology MH - Propensity Score MH - Aged MH - Treatment Outcome MH - Cohort Studies MH - Adult OTO - NOTNLM OT - Anterior cervical discectomy and fusion OT - GLP-1 receptor agonist OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Postoperative medical complications OT - Postoperative surgical complications OT - Type-2 diabetes mellitus COIS- Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms. EDAT- 2026/01/03 00:30 MHDA- 2026/04/26 05:13 CRDT- 2026/01/02 19:31 PHST- 2025/09/08 00:00 [received] PHST- 2025/11/10 00:00 [revised] PHST- 2025/12/28 00:00 [accepted] PHST- 2026/04/26 05:13 [medline] PHST- 2026/01/03 00:30 [pubmed] PHST- 2026/01/02 19:31 [entrez] AID - S1529-9430(25)00943-X [pii] AID - 10.1016/j.spinee.2025.12.019 [doi] PST - ppublish SO - Spine J. 2026 May;26(5):882-892. doi: 10.1016/j.spinee.2025.12.019. Epub 2025 Dec 31. PMID- 41482136 OWN - NLM STAT- MEDLINE DCOM- 20260519 LR - 20260519 IS - 1879-3304 (Electronic) IS - 0039-6257 (Linking) VI - 71 IP - 4 DP - 2026 Jul-Aug TI - Glucagon-like peptide-1 receptor agonists: What ophthalmologists need to know. PG - 1090-1106 LID - S0039-6257(25)00236-X [pii] LID - 10.1016/j.survophthal.2025.12.007 [doi] AB - Initially designed for the treatment of type-2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RA) are multifaceted agents with promising neuroprotective and anti-inflammatory properties. The majority of the research exploring the relationship between GLP-1RA use and ophthalmic disease comes from large database studies or secondary-analysis of randomized controlled trials investigating GLP-1RAs in cardiovascular disease and obesity. Current evidence regarding the impact of GLP-1 receptor agonists on ophthalmic diseases remains inconsistent, with studies reporting both protective and detrimental effects. For example, there are conflicting findings of an effect on diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy, as well as age-related macular degeneration, with GLP-1RA use. In contrast, GLP-1RAs have more consistently demonstrated a protective effect against idiopathic intracranial hypertension, glaucoma and dry-eye disease. Importantly, the majority of the clinical ophthalmic studies are from large electronic health record databases. Overall, limitations in the design of these studies, such as the lack of manual chart review and potential miscoding of diagnosis or treatments, prohibit a more granular analysis of comprehensive ocular endpoints. As a heterogenous medication class with differing structures, potencies, and mechanisms of action, we outline the ophthalmic effects of all Food and Drug Administration-approved GLP-1RAs. We discuss the proposed mechanisms of ocular effects and GLP-1RA use, examine the current literature investigating the impact of GLP-1RAs on ophthalmic disease, discuss the effects of specific GLP-1RAs, and outline the perioperative considerations of this medication class. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Bala, Suraj AU - Bala S AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States; Hackensack Meridian School of Medicine, Nutley, NJ, United States. FAU - Allan, Kevin C AU - Allan KC AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Decker, Nicole L AU - Decker NL AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Abbass, Nadia J AU - Abbass NJ AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Joo, Julia H AU - Joo JH AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Zhao, Alison AU - Zhao A AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Talcott, Katherine E AU - Talcott KE AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Rachitskaya, Aleksandra V AU - Rachitskaya AV AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States. Electronic address: rachita@ccf.org. LA - eng PT - Journal Article PT - Review DEP - 20251231 PL - United States TA - Surv Ophthalmol JT - Survey of ophthalmology JID - 0404551 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Eye Diseases/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - *Ophthalmology OTO - NOTNLM OT - AMD OT - Age-related macular degeneration OT - DED OT - Dry eye disease OT - GLP-1 OT - GLP-1RA OT - Glaucoma OT - Glucagon-like peptide OT - IIH OT - Idiopathic intracranial hypertension OT - NAION OT - Non-arteritic anterior ischemic optic neuropathy OT - Perioperative management COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aleksandra V. Rachitskaya reports a relationship with Alcon that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Apellis Pharmaceuticals that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Regeneron that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Iveric that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Ocular Therapeutix that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Samsara that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with EyePoint that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Boehringer Ingelheim that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with 4D molecular therapeutics that includes: consulting or advisory. Katherine E. Talcott reports a relationship with Iveric that includes: funding grants. Katherine E. Talcott reports a relationship with Regeneron that includes: funding grants. Katherine E. Talcott reports a relationship with Zeiss that includes: funding grants. Katherine E. Talcott reports a relationship with Alimera that includes: consulting or advisory. Katherine E. Talcott reports a relationship with Genentech Roche that includes: consulting or advisory and funding grants. Katherine E. Talcott reports a relationship with Apellis that includes: consulting or advisory. Katherine E. Talcott reports a relationship with Bausch that includes: consulting or advisory. Katherine E. Talcott reports a relationship with Eyepoint that includes: consulting or advisory. Katherine E. Talcott reports a relationship with RegenxBio that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Abbvie Allergan that includes: consulting or advisory. Aleksandra V. Rachitskaya reports a relationship with Roche Genentech that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper EDAT- 2026/01/03 00:30 MHDA- 2026/05/20 00:33 CRDT- 2026/01/02 19:29 PHST- 2025/08/18 00:00 [received] PHST- 2025/12/17 00:00 [revised] PHST- 2025/12/30 00:00 [accepted] PHST- 2026/05/20 00:33 [medline] PHST- 2026/01/03 00:30 [pubmed] PHST- 2026/01/02 19:29 [entrez] AID - S0039-6257(25)00236-X [pii] AID - 10.1016/j.survophthal.2025.12.007 [doi] PST - ppublish SO - Surv Ophthalmol. 2026 Jul-Aug;71(4):1090-1106. doi: 10.1016/j.survophthal.2025.12.007. Epub 2025 Dec 31. PMID- 41480667 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - The importance of treatment sequencing with SGLT2 inhibitors and GLP-1 receptor agonists combination for kidney function preservation in type 2 diabetes. PG - 2713-2721 LID - 10.1111/dom.70445 [doi] AB - AIMS: To determine whether the sequence of initiation between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) influences kidney outcomes in people with type 2 diabetes (T2D) receiving these therapies in association. MATERIALS AND METHODS: We retrospectively included adults with T2D treated with both a SGLT2i and a GLP-1RA, stratified by treatment sequence: SGLT2i followed by GLP-1RA or GLP-1RA followed by SGLT2i. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from initiation of the first drug. Analyses used mixed models for repeated measures adjusted with inverse probability of treatment weighting (IPTW) and confirmed by propensity score matching (PSM). RESULTS: Among 565 participants (mean age 64 years, 29% women, diabetes duration 14 years, baseline eGFR 80 mL/min/1.73 m(2)), 210 initiated SGLT2i first and 355 GLP-1RA first. Over a median 4.3-year follow-up, eGFR declined more slowly in the SG group than in the GS group (adjusted difference 0.80 mL/min/1.73 m(2) per year; 95% CI 0.23-1.37; p = 0.006); this effect was more evident in patients with CKD at baseline. PSM analyses yielded consistent results. Changes in urine albumin-to-creatinine ratio, HbA1c, and body weight were similar between groups. CONCLUSIONS: In people with T2D receiving combination therapy, initiating treatment with a SGLT2i was associated with greater long-term preservation of kidney function compared with starting with a GLP-1RA. Early SGLT2i use may confer better renal protection even when GLP-1RA intensification is subsequently required, confirming SGLT2i as a foundational therapy for preventing the decline in renal function in T2D. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Morieri, Mario Luca AU - Morieri ML AD - Department of Medicine, University of Padova, Padua, Italy. AD - Unit of Internal Medicine 3, University Hospital of Padova, Padua, Italy. FAU - Vedovato, Monica AU - Vedovato M AD - Unit of Metabolic Diseases, University Hospital of Padova, Padua, Italy. FAU - Bonora, Benedetta Maria AU - Bonora BM AD - Department of Medicine, University of Padova, Padua, Italy. AD - Unit of Metabolic Diseases, University Hospital of Padova, Padua, Italy. FAU - Fioretto, Paola AU - Fioretto P AUID- ORCID: 0000-0003-3445-0387 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Unit of Internal Medicine 3, University Hospital of Padova, Padua, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Unit of Metabolic Diseases, University Hospital of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. LA - eng GR - University of Padova/ PT - Journal Article DEP - 20260102 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glomerular Filtration Rate/drug effects MH - Retrospective Studies MH - Aged MH - *Diabetic Nephropathies/prevention & control MH - *Kidney/drug effects/physiopathology MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - algorithm OT - combination OT - kidney disease OT - observational OT - prevention EDAT- 2026/01/02 06:29 MHDA- 2026/03/17 06:48 CRDT- 2026/01/02 04:55 PHST- 2025/12/22 00:00 [revised] PHST- 2025/11/15 00:00 [received] PHST- 2025/12/25 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/02 06:29 [pubmed] PHST- 2026/01/02 04:55 [entrez] AID - 10.1111/dom.70445 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2713-2721. doi: 10.1111/dom.70445. Epub 2026 Jan 2. PMID- 41478576 OWN - NLM STAT- MEDLINE DCOM- 20260110 LR - 20260813 IS - 1096-1186 (Electronic) IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 223 DP - 2026 Jan TI - IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes. PG - 108077 LID - S1043-6618(25)00502-X [pii] LID - 10.1016/j.phrs.2025.108077 [doi] AB - The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these diseases. While this current generation of incretin analogues show weight regain upon cessation of treatment, the amount of which can depend on the treatment and patient, iterative advancements may improve weight loss durability in the long term. In this review, we discuss the development of glucagon like peptide-1 receptor (GLP-1R) agonists and GLP-1R/ glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists, and how future generations will leverage this strategy. We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation. We rely on largely pre-clinical evidence for action because clinical data is extremely limited for GCGR agonism. Herein, we review mechanisms by which glucagon receptor agonists act to increase energy expenditure. Finally, we discuss future improvements to incretin-based therapeutics, and how they can include strategies that target the GCGR. The purpose of this review is to discuss mechanisms by which GCGR agonism can reduce body weight and put them in the context of the combination with incretin receptor agonists. Mechanistic data has only currently been evaluated in preclinical rodent models and evidence for similar processes in humans is limited. We also provide perspectives about how treatments can improve for future advancement of obesity treatment. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Elmendorf, Andrew J AU - Elmendorf AJ AD - Indiana University School of Medicine, Department of Biochemistry, Molecular Biology, and Pharmacology, Indianapolis, IN, United States. FAU - Yousefian, Mostafa AU - Yousefian M AD - Indiana University School of Medicine, Department of Biochemistry, Molecular Biology, and Pharmacology, Indianapolis, IN, United States. FAU - Kim, Il-Man AU - Kim IM AD - Indiana University School of Medicine, Department of Anatomy, Cell Biology, and Physiology, Indianapolis, IN, United States. FAU - Hardaway, J Andrew AU - Hardaway JA AD - University of Alabama at Birmingham, Department of Psychiatry and Behavioral Neurobiology, Birmingham, AL, United States. FAU - Habegger, Kirk AU - Habegger K AD - University of Alabama at Birmingham, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Birmingham, AL, United States. FAU - Flak, Jonathan N AU - Flak JN AD - Indiana University School of Medicine, Department of Biochemistry, Molecular Biology, and Pharmacology, Indianapolis, IN, United States. Electronic address: jflak@iu.edu. LA - eng GR - R01 HL180692/HL/NHLBI NIH HHS/United States GR - R01 DK136897/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States GR - T32 DK064466/DK/NIDDK NIH HHS/United States GR - P30 DK056336/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20251230 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 9007-92-5 (Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Obesity/drug therapy/metabolism MH - Animals MH - *Glucagon/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Repositioning MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Receptors, Glucagon/agonists/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Incretins/therapeutic use MH - Receptors, Gastrointestinal Hormone/agonists PMC - PMC12910462 MID - NIHMS2136191 OTO - NOTNLM OT - Body weight OT - Energy expenditure OT - GCGR OT - GIPR OT - GLP1-R COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JF has previously received research support from Eli Lilly for an associated project. EDAT- 2026/01/02 00:33 MHDA- 2026/01/11 00:34 PMCR- 2026/02/17 CRDT- 2026/01/01 19:40 PHST- 2025/09/30 00:00 [received] PHST- 2025/12/19 00:00 [revised] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/01/11 00:34 [medline] PHST- 2026/01/02 00:33 [pubmed] PHST- 2026/01/01 19:40 [entrez] PHST- 2026/02/17 00:00 [pmc-release] AID - S1043-6618(25)00502-X [pii] AID - 10.1016/j.phrs.2025.108077 [doi] PST - ppublish SO - Pharmacol Res. 2026 Jan;223:108077. doi: 10.1016/j.phrs.2025.108077. Epub 2025 Dec 30. PMID- 41475990 OWN - NLM STAT- MEDLINE DCOM- 20260212 LR - 20260212 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 36 IP - 3 DP - 2026 Mar TI - Sex specific responses to oral vs. subcutaneous semaglutide in type 2 diabetes mellitus: A 12-month real-world study. PG - 104462 LID - S0939-4753(25)00617-9 [pii] LID - 10.1016/j.numecd.2025.104462 [doi] AB - BACKGROUND AND AIM: Semaglutide therapy improves glycaemic control, weight loss, and cardiovascular risk reduction in patients with type 2 diabetes mellitus (T2D). Sex-specific differences in the response to oral versus subcutaneous formulation remain unexplored in real-world settings. This interventional pilot study compares the 12-month effectiveness of oral and subcutaneous semaglutide in a real-world cohort of T2D patients, with focus to sex-based differences in treatment outcomes. METHODS AND RESULTS: Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled. The primary endpoint was the change in HbA1c. Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach. Two-hundred and eight patients completed the study. In men, subcutaneous semaglutide resulted in significant reductions in delta(Delta)_weight (p = 0.010), Delta_HbA1c (p = 0.037), and Delta_LDL (p = 0.038) compared to the oral formulation. In women, subcutaneous semaglutide led to significantly lower Delta_hepatic steatosis index (p = 0.024). Additionally, women treated with subcutaneous semaglutide showed a significantly greater reduction in Delta_GOT (p = 0.035) compared to men. CONCLUSIONS: This real-world study suggests that subcutaneous semaglutide provides greater metabolic benefits than the oral formulation, particularly in men. Women treated with subcutaneous semaglutide experience more favorable liver responses, emphasizing the personalization of T2D treatment. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Piccione, Alessandra AU - Piccione A AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Bonsangue, Maria AU - Bonsangue M AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Barone, Martina AU - Barone M AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Vigneri, Enrica AU - Vigneri E AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Mineo, Mariagrazia Irene AU - Mineo MI AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Tomasello, Laura AU - Tomasello L AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. Electronic address: laura.tomasello@unipa.it. FAU - Maniscalco, Laura AU - Maniscalco L AD - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Via del Vespro 133, Palermo, 90127, Italy. FAU - Panto, Felicia AU - Panto F AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Arnaldi, Giorgio AU - Arnaldi G AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Guarnotta, Valentina AU - Guarnotta V AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251115 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Middle Aged MH - Administration, Oral MH - Treatment Outcome MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Aged MH - Glycated Hemoglobin/metabolism MH - Pilot Projects MH - *Blood Glucose/metabolism/drug effects MH - Sex Factors MH - Injections, Subcutaneous MH - Time Factors MH - Biomarkers/blood MH - Glycemic Control/adverse effects MH - Weight Loss/drug effects OTO - NOTNLM OT - Female OT - Gender OT - Glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - Male OT - Sex COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2026/01/01 00:35 MHDA- 2026/02/13 01:27 CRDT- 2025/12/31 22:04 PHST- 2025/07/05 00:00 [received] PHST- 2025/10/01 00:00 [revised] PHST- 2025/11/05 00:00 [accepted] PHST- 2026/02/13 01:27 [medline] PHST- 2026/01/01 00:35 [pubmed] PHST- 2025/12/31 22:04 [entrez] AID - S0939-4753(25)00617-9 [pii] AID - 10.1016/j.numecd.2025.104462 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2026 Mar;36(3):104462. doi: 10.1016/j.numecd.2025.104462. Epub 2025 Nov 15. PMID- 41474140 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261023 IS - 1469-0756 (Electronic) IS - 0032-5473 (Linking) VI - 102 IP - 1213 DP - 2026 Oct 22 TI - Pharmacogenetics of incretin-based therapies. PG - 989-997 LID - 10.1093/postmj/qgaf232 [doi] AB - Interindividual variability in the efficacy of various glucose-lowering drugs has been previously reported and partly explained by genetic variants. The aim of this review was to summarize currently available information on pharmacogenetic studies of the efficacy of incretin-based therapies such as glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1RA) and dipeptidyl peptidase 4 (DPP-4i) inhibitors. Several missense variants of the GLP1R gene have been associated with the effects of GLP1RA or DPP-4 inhibitors on glycaemic compensation or weight. Pharmacogenetic effects have also been reported for several type 2 diabetes-associated loci, such as TCF7L2, THADA, MTNR1B, CDKAL1, KCNQ1, KCNJ11, and PAM in candidate gene approach studies. Genome-wide pharmacogenetic studies have identified new genes with potentially relevant pharmacogenetic effects (CTRB1/2, ARRB1, PRKD1). Although none of these genetic associations are currently used in guiding the treatment choices in clinical practice, they offer valuable insights bringing us a little closer to precision medicine. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Fellowship of Postgraduate Medicine. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Yaluri, Alena Stancakova AU - Yaluri AS AD - 4th Department of Internal Medicine, P.J. Safarik University in Kosice, Medical Faculty, and L. Pasteur University Hospital, Rastislavova 43, 04001 Kosice, Slovakia. FAU - Urgeova, Anna AU - Urgeova A AD - 4th Department of Internal Medicine, P.J. Safarik University in Kosice, Medical Faculty, and L. Pasteur University Hospital, Rastislavova 43, 04001 Kosice, Slovakia. FAU - Marsalek, Michal AU - Marsalek M AD - 4th Department of Internal Medicine, P.J. Safarik University in Kosice, Medical Faculty, and L. Pasteur University Hospital, Rastislavova 43, 04001 Kosice, Slovakia. FAU - Javorsky, Martin AU - Javorsky M AD - 4th Department of Internal Medicine, P.J. Safarik University in Kosice, Medical Faculty, and L. Pasteur University Hospital, Rastislavova 43, 04001 Kosice, Slovakia. FAU - Tkac, Ivan AU - Tkac I AD - 4th Department of Internal Medicine, P.J. Safarik University in Kosice, Medical Faculty, and L. Pasteur University Hospital, Rastislavova 43, 04001 Kosice, Slovakia. LA - eng GR - 1/0050/24/The Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Science VEGA/ PT - Journal Article PT - Review PL - England TA - Postgrad Med J JT - Postgraduate medical journal JID - 0234135 RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Pharmacogenetics MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/genetics OTO - NOTNLM OT - dipeptidyl peptide 4 inhibitors OT - glucagon-like peptide 1 receptor agonists OT - pharmacogenetics OT - type 2 diabetes EDAT- 2025/12/31 12:54 MHDA- 2026/10/23 18:30 CRDT- 2025/12/31 07:43 PHST- 2025/09/11 00:00 [received] PHST- 2025/11/04 00:00 [revised] PHST- 2025/12/05 00:00 [accepted] PHST- 2026/10/23 18:30 [medline] PHST- 2025/12/31 12:54 [pubmed] PHST- 2025/12/31 07:43 [entrez] AID - 8407649 [pii] AID - 10.1093/postmj/qgaf232 [doi] PST - ppublish SO - Postgrad Med J. 2026 Oct 22;102(1213):989-997. doi: 10.1093/postmj/qgaf232. PMID- 41470212 OWN - NLM STAT- MEDLINE DCOM- 20251231 LR - 20260102 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 12 DP - 2025 Dec 15 TI - National Utilization and Expenditure Trends of GLP-1 Receptor Agonists and Dual GLP-1/GIP Agonist in Croatia, 2017-2024. LID - 10.3390/medicina61122210 [doi] LID - 2210 AB - Background and Objectives: GLP-1 receptor agonists (GLP-1 RAs; ATC A10BJ) and dual GLP-1/GIP agonist (ATC A10BX16) have expanded rapidly due to strong evidence in type 2 diabetes, obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Their high acquisition costs and accelerating uptake make them key drivers of pharmaceutical expenditure. This study quantified national utilization and expenditure trends for antihyperglycemic drugs in Croatia (2017-2024), with a focus on GLP-1 RA and dual GLP-1/GIP agonists. Materials and Methods: Aggregate national data on dispensed medicines, valued at wholesale pharmacy prices, were obtained from HALMED's annual ATC/DDD reports. Utilization was expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). We analyzed the total A10 and key subclasses. The dual GLP-1/GIP agonist was only marketed in 2024. Compound annual growth rates (CAGR) were calculated. Results: The total antihyperglycemic utilization increased from 66.9 to 96.8 DDD/1000/day (a 44.7% rise), while the total A10 expenditure increased from EUR 54.2 million to EUR 96.5 million, indicating that expenditure growth outpaced utilization growth. GLP-1 receptor agonist expenditure increased from EUR 5.2 million (2018) to EUR 28.6 million (2024) (CAGR 33.0%), reaching 29.8% of total A10 expenditure in 2024. Expenditure for GLP-1-based agents grew faster than their DDD volume because per-DDD acquisition costs are substantially higher than for SGLT-2 inhibitors. These growth patterns are consistent with trajectories reported in higher-uptake EU health systems, suggesting convergence rather than an outlier position for Croatia. Conclusions: Croatia experienced a rapid shift towards GLP-1 RA-based antihyperglycemic pharmacotherapy, with GLP-1-based therapies exerting a disproportionate budget impact. For payers, these surveillance data support budget forecasting and negotiation of pricing and reimbursement conditions; clinicians can use them to benchmark and optimize evidence-aligned prescribing; and policymakers can apply them to monitor the diffusion and fiscal impact of high-cost therapies. Routine national ATC/DDD analysis, complemented by HZZO claims and primary-care datasets, is essential for guiding future pricing, reimbursement and formulary decisions. FAU - Car, Mate AU - Car M AUID- ORCID: 0000-0002-7005-0500 AD - Department of Primary Care & Public Health, Imperial College London, London SW7 2AZ, UK. AD - Centre for Data-Driven Policy and Management, Catholic University of Croatia, 10000 Zagreb, Croatia. AD - School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia. FAU - Erceg, Damir AU - Erceg D AUID- ORCID: 0000-0003-0057-0946 AD - School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia. AD - Department of Allergology and Immunology, "Srebrnjak" Children's Hospital, 10000 Zagreb, Croatia. AD - Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia. FAU - Udovicic, Mario AU - Udovicic M AUID- ORCID: 0000-0001-9912-2179 AD - School of Medicine, University of Zagreb, 10000 Zagreb, Croatia. AD - Department of Cardiology, University Hospital Dubrava, 10000 Zagreb, Croatia. FAU - Bokun, Tomislav AU - Bokun T AUID- ORCID: 0000-0001-9605-2400 AD - Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, 10000 Zagreb, Croatia. AD - Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia. FAU - Rahelic, Dario AU - Rahelic D AUID- ORCID: 0000-0002-2901-0646 AD - School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia. AD - Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia. AD - Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Disorders, Merkur University Hospital, 10000 Zagreb, Croatia. LA - eng PT - Journal Article DEP - 20251215 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Croatia MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/economics MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - *Drug Utilization/statistics & numerical data/economics/trends MH - *Health Expenditures/trends/statistics & numerical data PMC - PMC12734843 OTO - NOTNLM OT - Croatia OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - antihyperglycemic drugs OT - drug utilization OT - dual GLP-1/GIP agonist OT - pharmaceutical expenditure OT - pharmacoepidemiology COIS- The authors declare no conflicts of interest. EDAT- 2025/12/31 07:37 MHDA- 2025/12/31 07:38 PMCR- 2025/12/15 CRDT- 2025/12/31 01:01 PHST- 2025/11/19 00:00 [received] PHST- 2025/12/08 00:00 [revised] PHST- 2025/12/10 00:00 [accepted] PHST- 2025/12/31 07:38 [medline] PHST- 2025/12/31 07:37 [pubmed] PHST- 2025/12/31 01:01 [entrez] PHST- 2025/12/15 00:00 [pmc-release] AID - medicina61122210 [pii] AID - medicina-61-02210 [pii] AID - 10.3390/medicina61122210 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Dec 15;61(12):2210. doi: 10.3390/medicina61122210. PMID- 41469686 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20261012 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 24 IP - 1 DP - 2025 Dec 31 TI - Association of GLP-1 receptor agonists with herpes risks in diabetes mellitus: a target trial emulation. LID - 10.1186/s12916-025-04606-w [doi] LID - 144 AB - BACKGROUND: GLP-1 receptor agonists (GLP-1RA) are effective for glycemic control and cardiometabolic outcomes, but their infectious safety, particularly regarding herpes simplex virus (HSV) and herpes zoster (HZ), is underexplored. This study evaluated the association between GLP-1RA therapy and risks of HSV and HZ infections in patients with DM, compared to sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i). METHODS: We conducted a retrospective cohort analysis using target trial emulation principles on de-identified electronic health records from the TriNetX U.S. Network (2015-2022). Adults aged >/= 18 years with diabetes prescribed biguanides were included. New users of GLP-1RA were compared to DPP-4i users in the first cohort and SGLT-2i users in the second cohort. Primary outcomes were HSV and HZ incidence, analyzed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Among 95,190 GLP-1RA vs. DPP-4i pairs and 82,789 GLP-1RA vs. SGLT-2i pairs, GLP-1RA therapy was associated with higher risks of HSV (HR = 1.387, 95% CI = 1.249-1.539) and HZ (HR = 1.294, 95% CI = 1.203-1.392) compared to DPP-4i and HSV (HR = 1.277, 95% CI = 1.132-1.442) and HZ (HR = 1.18, 95% CI = 1.085-1.284) compared to SGLT-2i. Younger patients (18-50 years) on GLP-1RAs had elevated risks for HSV (HR = 1.632) and HZ (HR = 1.553). Female GLP-1RA users showed increased HSV risk (HR = 1.51), and poorly controlled patients (HbA1c >/= 7%) had higher HSV risks (HR = 1.195). Herpes zoster vaccination mitigated these risks. CONCLUSIONS: GLP-1RA use is associated with an increased risk of HSV and HZ infections compared with SGLT-2i or a DPP-4i use, especially in younger, female, and poorly controlled T2DM patients. Vaccination against herpes zoster is essential in mitigating these risks. CI - (c) 2026. The Author(s). FAU - Huang, Chi-Hsien AU - Huang CH AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. AD - College of Nursing, Kaohsiung Medical University, Kaohsiung City, Taiwan. FAU - Chiang, I-Hui AU - Chiang IH AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. FAU - Lu, I-Cheng AU - Lu IC AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. FAU - Lai, Po-Hsuan AU - Lai PH AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. FAU - Liao, Pei-Lun AU - Liao PL AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hsieh, Ming-Ta AU - Hsieh MT AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. FAU - Lin, Chi-Wei AU - Lin CW AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. FAU - Liu, I-Ting AU - Liu IT AD - Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. claireliu627@gmail.com. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan. claireliu627@gmail.com. FAU - Wei, James Cheng-Chung AU - Wei JC AUID- ORCID: 0000-0002-1235-0679 AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. jccwei@gmail.com. AD - Department of Allergy, Chung Shan Medical University Hospital, Immunology & Rheumatology, Taichung, Taiwan. jccwei@gmail.com. AD - Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. jccwei@gmail.com. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. jccwei@gmail.com. AD - Office of Research and Development, Asia University, Taichung, Taiwan. jccwei@gmail.com. LA - eng GR - NSTC 112‑2314‑B‑650‑001‑MY3/National Science and Technology Council, Taiwan/ GR - EDAHP114016, EDAHS114019, EDAHJ113006, EDAHJ114008/E-Da Hospital/ PT - Journal Article PT - Observational Study DEP - 20251231 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - *Diabetes Mellitus/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Herpes Simplex/epidemiology/chemically induced MH - *Herpes Zoster/epidemiology/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Retrospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects PMC - PMC12964619 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Herpes simplex infection OT - Herpes zoster OT - Herpes zoster vaccination COIS- Declarations. Ethics approval and consent to participate: The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and received ethical approval from the Institutional Review Board of Chung Shan Medical University Hospital (IRB number: CS2-21176). Consent for publication: All authors have agreed to the submission and publication of this research. Competing interests: The authors declare no competing interests. EDAT- 2025/12/31 00:33 MHDA- 2026/03/07 18:37 PMCR- 2025/12/31 CRDT- 2025/12/30 23:33 PHST- 2025/05/20 00:00 [received] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/03/07 18:37 [medline] PHST- 2025/12/31 00:33 [pubmed] PHST- 2025/12/30 23:33 [entrez] PHST- 2025/12/31 00:00 [pmc-release] AID - 10.1186/s12916-025-04606-w [pii] AID - 4606 [pii] AID - 10.1186/s12916-025-04606-w [doi] PST - epublish SO - BMC Med. 2025 Dec 31;24(1):144. doi: 10.1186/s12916-025-04606-w. PMID- 41466578 OWN - NLM STAT- MEDLINE DCOM- 20260316 LR - 20260904 IS - 2326-5205 (Electronic) IS - 2326-5191 (Print) IS - 2326-5191 (Linking) VI - 78 IP - 3 DP - 2026 Mar TI - Glucagon-Like Peptide 1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, and Risk of Autoimmune Rheumatic Diseases. PG - 654-664 LID - 10.1002/art.70044 [doi] AB - OBJECTIVE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) facilitate weight loss and exhibit immunomodulatory effects, but their impact on the risk of developing autoimmune rheumatic diseases (ARDs) is unclear. We compared ARD incidence following initiation of GLP-1RAs or SGLT2i versus a weight-neutral comparator (dipeptidyl peptidase 4 inhibitors [DPP4i]). METHODS: We performed a population-based cohort study using administrative health data from a Canadian province with universal health care. We included adults with type 2 diabetes (T2D) and no prior ARD initiating a GLP-1RA, SGLT2i, or DPP4i between January 1, 2014, and December 31, 2022. Incident ARD cases, including rheumatoid arthritis, psoriatic disease, axial spondyloarthritis, and systemic ARDs (SARDs; systemic lupus erythematosus, systemic sclerosis, Sjogren disease, idiopathic inflammatory myopathies, and systemic vasculitides), were identified using validated algorithms. Propensity score (PS) weighting was used to balance cohorts at treatment initiation. Then hazard ratios (HRs) were estimated using Cox regression. RESULTS: Among 229,300 adults, 49,514 initiated GLP-1RAs, 101,925 initiated SGLT2i, and 77,861 initiated DPP4i. After PS weighting, ARD incidence per 10,000 person-years was 29.1 (95% confidence interval [CI] 23.5-35.5) with GLP-1RAs, 24.4 (95% CI 19.8-29.7) with SGLT2i, and 27.3 (95% CI 22.1-33.4) with DPP4i. Mean follow-up was 1.3 to 1.6 years. Relative to DPP4i, adjusted HRs (aHRs) of ARD were 1.04 (95% CI 0.81-1.33) with GLP-1RAs and 0.93 (95% CI 0.75-1.16) with SGLT2i. Risk of SARDs, but not other diseases, was lower with SGLT2i versus DPP4i (aHR 0.51 [95% CI 0.31-0.84]). CONCLUSION: Neither GLP-1RA nor SGLT2i treatment was associated with increased or decreased ARD risk versus DPP4i in adults with T2D; however, SGLT2i use was associated with significantly lower risk of SARDs, warranting further study. CI - (c) 2025 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. FAU - Karacabeyli, Derin AU - Karacabeyli D AUID- ORCID: 0000-0002-6597-0302 AD - Division of Rheumatology, University of British Columbia, Vancouver, British Columbia, Canada. AD - Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - Lacaille, Diane AU - Lacaille D AUID- ORCID: 0000-0002-4065-4151 AD - Division of Rheumatology, University of British Columbia, Vancouver, British Columbia, Canada. AD - Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - Lu, Na AU - Lu N AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - Xie, Hui AU - Xie H AUID- ORCID: 0000-0003-3328-7135 AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. AD - Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. FAU - Avina-Zubieta, J Antonio AU - Avina-Zubieta JA AUID- ORCID: 0000-0001-5526-663X AD - Division of Rheumatology, University of British Columbia, Vancouver, British Columbia, Canada. AD - Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. LA - eng GR - THC-135235/CIHR/Canada GR - THC-135235/CIHR/Canada PT - Journal Article DEP - 20260224 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Autoimmune Diseases/epidemiology/chemically induced MH - *Rheumatic Diseases/epidemiology MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Adult MH - Incidence MH - Cohort Studies MH - Canada/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Arthritis, Rheumatoid/epidemiology PMC - PMC12991922 EDAT- 2025/12/30 07:41 MHDA- 2026/03/17 00:34 PMCR- 2026/03/17 CRDT- 2025/12/30 04:11 PHST- 2025/11/28 00:00 [revised] PHST- 2025/06/28 00:00 [received] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/03/17 00:34 [medline] PHST- 2025/12/30 07:41 [pubmed] PHST- 2025/12/30 04:11 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - ART70044 [pii] AID - 10.1002/art.70044 [doi] PST - ppublish SO - Arthritis Rheumatol. 2026 Mar;78(3):654-664. doi: 10.1002/art.70044. Epub 2026 Feb 24. PMID- 41465555 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260102 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 24 DP - 2025 Dec 17 TI - The Influence of Glucagon-like Peptide-1 Receptor Agonists and Other Incretin Hormone Agonists on Body Composition. LID - 10.3390/ijms262412130 [doi] LID - 12130 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer incretin-based co-agonists have transformed obesity and type 2 diabetes (T2D) management, achieving unprecedented weight loss and cardiometabolic benefits. However, their effects on body composition, particularly lean and skeletal muscle mass, remain incompletely defined. In this current review, we examined the influence of GLP-1 RAs and incretin hormone agonists on lean tissue, integrating physiological, clinical, and mechanistic perspectives. We first outlined the physiology of incretin hormones, with emphasis on their metabolic roles and potential relevance to muscle health. We then discussed sarcopenia and sarcopenic obesity as conditions of rising clinical concern, given their overlap with obesity and metabolic disease. Evidence from preclinical studies and randomized clinical trials indicates that while GLP-1-based therapies predominantly reduce adipose tissue, including visceral and ectopic depots, but they also produce absolute reductions in lean mass, generally representing 20-30% of total weight loss. The extent to which these changes translate into impaired muscle function or increased vulnerability to frailty remains unclear. Preservation of lean and skeletal muscle mass is a critical yet underexplored aspect of incretin-based weight loss. Current studies are constrained by methodological heterogeneity, small sample sizes, and limited assessment of functional outcomes. Data on dual and triple agonists are emerging but remain limited. Future research should integrate standardized body-composition measures, mechanistic exploration, and adjunctive interventions such as resistance training or protein optimization. FAU - Chrysavgis, Lampros AU - Chrysavgis L AUID- ORCID: 0000-0003-2632-0742 AD - First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, 115 27 Athens, Greece. FAU - Mourelatou, Niki Gerasimoula AU - Mourelatou NG AD - First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, 115 27 Athens, Greece. FAU - Koloutsou, Maria-Evangelia AU - Koloutsou ME AUID- ORCID: 0000-0002-6898-1357 AD - First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, 115 27 Athens, Greece. FAU - Rozani, Sophia AU - Rozani S AUID- ORCID: 0000-0002-4465-022X AD - First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, 115 27 Athens, Greece. FAU - Cholongitas, Evangelos AU - Cholongitas E AUID- ORCID: 0000-0002-3645-582X AD - First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, 115 27 Athens, Greece. LA - eng PT - Journal Article PT - Review DEP - 20251217 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Body Composition/drug effects MH - *Incretins/agonists/pharmacology/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Obesity/drug therapy/metabolism MH - Muscle, Skeletal/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12733374 OTO - NOTNLM OT - body weight OT - glucagon-like peptide-1 (GLP-1) OT - incretin hormones OT - lean mass OT - metabolic dysfunction-associated steatotic liver disease (MASLD) OT - myosteatosis OT - sarcopenia OT - sarcopenic obesity OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/12/30 07:41 MHDA- 2025/12/30 07:42 PMCR- 2025/12/17 CRDT- 2025/12/30 02:10 PHST- 2025/11/19 00:00 [received] PHST- 2025/12/08 00:00 [revised] PHST- 2025/12/09 00:00 [accepted] PHST- 2025/12/30 07:42 [medline] PHST- 2025/12/30 07:41 [pubmed] PHST- 2025/12/30 02:10 [entrez] PHST- 2025/12/17 00:00 [pmc-release] AID - ijms262412130 [pii] AID - ijms-26-12130 [pii] AID - 10.3390/ijms262412130 [doi] PST - epublish SO - Int J Mol Sci. 2025 Dec 17;26(24):12130. doi: 10.3390/ijms262412130. PMID- 41456709 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20260805 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 284 DP - 2026 Apr TI - Association of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists With Risk of Cataract. PG - 66-77 LID - S0002-9394(25)00687-7 [pii] LID - 10.1016/j.ajo.2025.12.025 [doi] AB - PURPOSE: To evaluate the risk of age-related cataract (ARC) among patients with type 2 diabetes mellitus (T2DM) using sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1 RA) as second-line antihyperglycemic agents. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Adults aged over 40 years with a diagnosis of T2DM between January 2015 and June 2025 were identified from the TriNetX Global Network. The patients were categorized into three cohorts: (1) SGLT2i plus metformin, (2) GLP-1 RA plus metformin, and (3) metformin monotherapy. Patients with aphakia or pseudophakia, orbital injuries, secondary cataracts, or congenital ocular malformations were excluded. METHODS: Pairwise comparisons were performed with a 3-year follow-up. Baseline characteristics were balanced using 1:1 propensity score matching for demographics, comorbidities, T2DM severity, and cataract risk factors. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The primary outcome was the incidence of ARC events, defined as a diagnosis of ARC or cataract surgery, with stratified analyses conducted by demographics, glycemic control, and comorbidities. RESULTS: After matching, three pairwise comparisons included 34,259 (SGLT2i vs metformin; mean age, 62.8 years; 35.1% female), 50,877 (GLP-1 RA vs metformin; mean age, 58.3 years; 54.8% female), and 23,022 (SGLT2i vs GLP-1 RA; mean age, 61.0 years; 40.8% female) patients. Adjunctive SGLT2i or GLP-1 RA was associated with a reduced risk of ARC events (SGLT2i, HR: 0.82, 95% CI: 0.76-0.89; GLP-1 RA, HR: 0.93, 95% CI: 0.87-0.99). The protective effect of SGLT2i was greater than that of GLP-1 RA (HR: 0.84, 95% CI: 0.76-0.92). However, in patients with advanced age, obesity, or diabetic retinopathy, the association attenuated. When analyzed as separate outcomes, adjunctive use of SGLT2i and GLP-1 RA remained associated with a reduced risk of ARC diagnosis, while the risk of cataract surgery did not differ significantly (SGLT2i, HR: 1.14, 95% CI: 0.95-1.34; GLP-1 RA, HR: 1.01, 95% CI: 0.79-1.26). CONCLUSIONS: Adjunctive use of SGLT2i or GLP-1 RA was associated with a lower risk of ARC, with a stronger effect for SGLT2i; however, neither agent reduced the risk of cataract surgery. Further studies are needed to clarify the underlying biological pathways and validate our findings. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Lin, Bing-Hua AU - Lin BH AD - From the School of Medicine (B.H.L.), College of Medicine, Taipei Medical University, Taipei City, Taiwan. FAU - Chuang, Shu-Han AU - Chuang SH AD - Department of Ophthalmology (S.H.C. and C.H.C.), Changhua Christian Hospital, Changhua, Taiwan. FAU - Wu, Lien-Chen AU - Wu LC AD - Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; Graduate Institute of Biomedical Materials and Tissue Engineering (L.C.W.), College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan. FAU - Chen, Yu-Pin AU - Chen YP AD - Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. FAU - Kuo, Yi-Jie AU - Kuo YJ AD - Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; Department of Orthopedics (L.C.W., Y.P.C., Y.J.K.), School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. FAU - Chang, Cheng-Hsien AU - Chang CH AD - Department of Ophthalmology (S.H.C. and C.H.C.), Changhua Christian Hospital, Changhua, Taiwan; Department of Post-Baccalaureate Medicine (C.H.C.), College of Medicine, National Chung Hsing University, Taichung, Taiwan. Electronic address: 184040@cch.org.tw. LA - eng PT - Journal Article DEP - 20251226 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - Male MH - *Cataract/epidemiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors MH - Metformin/therapeutic use MH - Incidence MH - Follow-Up Studies MH - Adult EDAT- 2025/12/29 00:24 MHDA- 2026/03/20 00:59 CRDT- 2025/12/28 19:33 PHST- 2025/09/07 00:00 [received] PHST- 2025/12/14 00:00 [revised] PHST- 2025/12/24 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2025/12/29 00:24 [pubmed] PHST- 2025/12/28 19:33 [entrez] AID - S0002-9394(25)00687-7 [pii] AID - 10.1016/j.ajo.2025.12.025 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Apr;284:66-77. doi: 10.1016/j.ajo.2025.12.025. Epub 2025 Dec 26. PMID- 41456635 OWN - NLM STAT- MEDLINE DCOM- 20260214 LR - 20260214 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 294 DP - 2026 Apr TI - Dual versus monotherapy with SGLT2 inhibitor and GLP-1 receptor agonist: PRECIDENTD pragmatic randomized trial. PG - 107332 LID - S0002-8703(25)00394-1 [pii] LID - 10.1016/j.ahj.2025.107332 [doi] AB - BACKGROUND: Dual therapy with sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is frequently recommended. We compared rates of medication initiation and discontinuation between participants assigned to treatment with a single medication class or dual therapy in the feasibility phase of the PREvention of CardIovascular and DiabEtic kidNey disease in Type 2 Diabetes (PRECIDENTD) pragmatic trial. METHODS: PRECIDENTD randomly assigned participants with type 2 diabetes (T2D) and ASCVD or high ASCVD risk to fill prescriptions for SGLT2i, GLP-1RA, or dual therapy (1:1:1) using their own insurance. Analyses compared medication fill and discontinuation rates of assigned medication(s), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical and Mental Health Scores, and Modified Kansas City Cardiomyopathy Questionnaire (mKCCQ)-12 between the combined monotherapy (SGLT2i or GLP-1RA) and dual therapy (SGLT2i and GLP-1RA) groups. RESULTS: This report includes 173 insured participants [median age 67 years (IQR 62, 72), 46% female, 35% non-White, 67% with ASCVD]; 113 assigned to monotherapy and 60 to dual therapy. Monotherapy vs dual therapy fill rates were 84% vs 53% (P < .001) 4 months after randomization and 87% vs 68% overall (P = .004) during 10-month median follow-up. Of those who filled medication, 22% in monotherapy and 49% in dual therapy discontinued a study medication (P = .002), mostly due to side effects. PROMIS and mKCCQ-12 scores showed no change. CONCLUSIONS: Despite efforts to facilitate medication uptake in the feasibility phase of the PRECIDENTD pragmatic trial, barriers to initiation and ongoing use challenge the use of combination SGLT2i and GLP-1RA in T2D. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05390892, https://clinicaltrials.gov/study/NCT05390892. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: dwexler@mgh.harvard.edu. FAU - Mayberry, Lindsay S AU - Mayberry LS AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Nelson, Lyndsay A AU - Nelson LA AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Lema-Driscoll, Jeremy AU - Lema-Driscoll J AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Flores, Ligia C AU - Flores LC AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Malloy, Maureen AU - Malloy M AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - MacFadyen, Jean G AU - MacFadyen JG AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Shen, Joseph AU - Shen J AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Zaharris, Elaine AU - Zaharris E AD - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Karanchi, Harsha AU - Karanchi H AD - Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Charleston, SC. FAU - Chatterjee, Ranee AU - Chatterjee R AD - Duke University School of Medicine, Durham, NC. FAU - Benziger, Catherine P AU - Benziger CP AD - Heart and Vascular Center, Essentia Health, Duluth, MN. FAU - Decker, Jake E AU - Decker JE AD - Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee, WI. FAU - Kalyani, Rita AU - Kalyani R AD - Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Manrique-Acevedo, Camila AU - Manrique-Acevedo C AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO; Harry S. Truman Memorial Veteran's Hospital, Columbia, MO. FAU - Lonier, Jacqueline AU - Lonier J AD - Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY. FAU - Simeone, Edward AU - Simeone E AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Mieras, Kathleen AU - Mieras K AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Siqueira, Amanda R O AU - Siqueira ARO AD - Harvard Medical School, Boston, MA; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA; Paulista Institute of Cardiovascular Disease, Sao Paulo, SP, Brazil; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Rothman, Russell L AU - Rothman RL AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Jones, W Schuyler AU - Jones WS AD - Division of Cardiology, Duke University Health System, Duke Clinical Research Institute, Durham, NC. FAU - Glynn, Robert J AU - Glynn RJ AD - Harvard Medical School, Boston, MA; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Everett, Brendan M AU - Everett BM AD - Harvard Medical School, Boston, MA; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. LA - eng SI - ClinicalTrials.gov/NCT05390892 PT - Journal Article PT - Multicenter Study PT - Pragmatic Clinical Trial PT - Randomized Controlled Trial DEP - 20251226 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - Drug Therapy, Combination MH - Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology COIS- Declaration of competing interests This study was an investigator-initiated clinical trial funded by a grant from the Patient-Centered Outcomes Research Institute (PCORI). A contract was developed between PCORI and Brigham and Women's Hospital (primary investigators: D.J.W., R.J.G., and B.M.E.), which became the academic sponsor of the study. D.J.W. reports serving on Data Monitoring Committees for Novo Nordisk and has received royalties from UpToDate. C.P.B reports grant support to her institution from Amgen, Eli Lilly, and Novartis, and has acted as a consultant for Novartis. A.R.O.S. is supported by the Lemann Foundation Harvard Medical School Cardiovascular Postdoctoral Research Fellowship at Brigham and Women's Hospital. W.S.J. has received research support (to Duke Clinical Research Institute) from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, and Novartis, and has received royalties from Merck Manuals. R.J.G. has received research support (to Brigham and Women's Hospital) from Amarin, Kowa, Novartis, and Pfizer. B.M.E. has received research grant paid to the Brigham and Women's Hospital from Novo Nordisk; has acted as a consultant for Kowa Company, Novo Nordisk, Merck, the American Heart Association, NIDDK, and the FDA; and has received royalties from UpToDate. No relevant relationships have been disclosed by the other authors. EDAT- 2025/12/29 00:24 MHDA- 2026/02/15 00:31 CRDT- 2025/12/28 19:28 PHST- 2025/08/06 00:00 [received] PHST- 2025/12/09 00:00 [revised] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2025/12/29 00:24 [pubmed] PHST- 2025/12/28 19:28 [entrez] AID - S0002-8703(25)00394-1 [pii] AID - 10.1016/j.ahj.2025.107332 [doi] PST - ppublish SO - Am Heart J. 2026 Apr;294:107332. doi: 10.1016/j.ahj.2025.107332. Epub 2025 Dec 26. PMID- 41454299 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260630 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 26 IP - 1 DP - 2025 Dec 26 TI - SGLT2 inhibitors versus GLP-1 receptor agonists for major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. PG - 88 LID - 10.1186/s12872-025-05455-4 [doi] LID - 88 AB - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to reduce cardiovascular risk, but direct comparison is limited. Objective: Compare the effects of SGLT2 inhibitors and GLP-1 receptor agonist on major adverse cardiovascular events (MACE) in adults with T2DM using randomized controlled trials and indirect comparisons. METHODS: A systematic search of PubMed, Scopus, CENTRAL, and Google Scholar was conducted through October 20, 2025, following PRISMA 2020 guidelines. The protocol was registered with PROSPERO (CRD420251168485). We included randomized controlled trials (RCTs) of SGLT2i or GLP-1RA versus placebo in adults with T2DM that reported cardiovascular or renal outcomes. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using the generic inverse variance method with a random-effects model. An indirect treatment comparison was performed using the Bucher method. Risk of bias was assessed with the Cochrane RoB 1 tool. RESULTS: We reviewed twelve trials involving 99,261 individuals (5 SGLT2i, 7 GLP-1RA). Compared to placebo, SGLT2i significantly reduced MACE (HR 0.89, 95% CI 0.84-0.95; p = 0.0003), as did GLP-1RA (HR 0.82, 95% CI 0.78-0.87; p < 0.00001). The indirect comparison indicated a nominally greater MACE reduction with GLP-1RA (HR 1.09, 95% CI 1.00-1.18; p = 0.0497). SGLT2i demonstrated pronounced benefits for heart failure hospitalization (HR 0.68) and composite renal outcomes (HR 0.69), while GLP-1RA showed significant but more modest effects on these endpoints and greater benefits for atherosclerotic events and weight loss. CONCLUSION: Both SGLT2i and GLP-1RA are highly effective in reducing MACE in high-risk T2DM. Their markedly different secondary outcome profiles for heart failure, renal protection, atherosclerotic events, and weight loss underscore that they are complementary rather than interchangeable. The optimal choice should be individualized based on the patient's predominant comorbidities, treatment goals, and local access. FAU - Ahmed, Ali Abdelhaleem Omar AU - Ahmed AAO AD - Faculty of Medicine, National Ribat University, Khartoum, Sudan. ali7haleem@gmail.com. FAU - Ahmed, Omer Abdalhaleem Omer AU - Ahmed OAO AD - Faculty of Medicine, University of Khartoum, Khartoum, Sudan. FAU - Ahmed, Reem Abdelhaleem Omar AU - Ahmed RAO AD - Faculty of Medicine, National Ribat University, Khartoum, Sudan. FAU - Ahmed, Rana Abdelhaleem Omar AU - Ahmed RAO AD - Faculty of Medicine, National Ribat University, Khartoum, Sudan. FAU - Mohammed, Mawahib Ahmed Eltayeb Abdullah AU - Mohammed MAEA AD - Faculty of Medicine, University of Gezira, Wad Madani, Gezira, Sudan. FAU - Ahmed, Yara AU - Ahmed Y AD - Faculty of Medicine, University of Medical Sciences & Technology (UMST), Khartoum, Sudan. FAU - Abbas, Mahmood AU - Abbas M AD - Faculty of Medicine, National Ribat University, Khartoum, Sudan. FAU - Ibrahim, Mamdoh Abbas Ali AU - Ibrahim MAA AD - Faculty of Medicine, Sudan International University, Khartoum, Sudan. FAU - Abakar, Mugtaba Eltag Mohammed AU - Abakar MEM AD - Faculty of Medicine, Sudan International University, Khartoum, Sudan. FAU - Dahab, Kamal Eldeen M AU - Dahab KEM AD - Faculty of Medicine, University of Khartoum, Khartoum, Sudan. FAU - Elbashir, Roaa Mohamed Ali AU - Elbashir RMA AD - Barnsley Hospital NHS Foundation Trust, Barnsley, England. FAU - Mohamed, Khalid H AU - Mohamed KH AD - Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England. FAU - Mansour, Maram Adil AU - Mansour MA AD - National University Sudan, Khartoum, Sudan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251226 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology/mortality MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Risk Assessment MH - *Incretins/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Adult PMC - PMC12849425 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Major adverse cardiovascular events OT - Meta-analysis OT - SGLT2 inhibitors OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/12/27 00:54 MHDA- 2026/06/27 06:45 PMCR- 2025/12/26 CRDT- 2025/12/26 23:25 PHST- 2025/10/25 00:00 [received] PHST- 2025/12/15 00:00 [accepted] PHST- 2026/06/27 06:45 [medline] PHST- 2025/12/27 00:54 [pubmed] PHST- 2025/12/26 23:25 [entrez] PHST- 2025/12/26 00:00 [pmc-release] AID - 10.1186/s12872-025-05455-4 [pii] AID - 5455 [pii] AID - 10.1186/s12872-025-05455-4 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2025 Dec 26;26(1):88. doi: 10.1186/s12872-025-05455-4. PMID- 41453566 OWN - NLM STAT- MEDLINE DCOM- 20260111 LR - 20260111 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 231 DP - 2026 Jan TI - GLP-1 receptor agonist use during immune checkpoint inhibitor therapy is associated with mortality and Immune-Related adverse events across cancer types in People with type 2 Diabetes: A Target-Trial emulation. PG - 113073 LID - S0168-8227(25)01088-5 [pii] LID - 10.1016/j.diabres.2025.113073 [doi] AB - AIMS: To evaluate whether Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use at immune checkpoint inhibitor (ICI) start is associated with mortality, healthcare use, and immune-related adverse events in adults with type 2 diabetes (T2D). METHODS: A target-trial emulation was conducted in the TriNetX US Collaborative Network among adults with cancer and T2D starting an ICI, with or without overlapping GLP-1 RA at ICI start. A new-user 1:1 propensity-score-matched, intention-to-treat design yielded 2,903 per group and 36-month follow-up. Primary endpoint was all-cause mortality; key secondaries were hospitalization, and composite immune-related adverse events (irAEs). Prespecified per-protocol, 90-day landmark, and semaglutide-only analyses assessed robustness. RESULTS: GLP-1 RA co-exposure was associated with lower mortality (hazard ratio [HR] 0.55, 95 % CI 0.51-0.61; 36-month absolute risk difference [ARD] - 16.41 %; number needed to treat [NNT] 5). Hospitalization (HR 0.76; ARD - 7.06 %; NNT 11), and composite irAEs (43.93 % vs 51.51 %; ARD - 7.58 %; NNT 11) were also lower. Diabetic-retinopathy progression (HR 1.75; ARD + 2.71 %) and non-arteritic anterior ischemic optic neuropathy (HR 1.51) were higher; hypoglycaemia, acute kidney injury, and dehydration/orthostatic hypotension were lower. CONCLUSIONS: GLP-1 RA use during ICI therapy correlated with lower mortality, reduced acute care, fewer irAEs; ophthalmic signals warrant monitoring. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Chan, Shan-Ho AU - Chan SH AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan. Electronic address: shchan@ms.szmc.edu.tw. FAU - Li, Pei-Yun AU - Li PY AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: peiyunli@csh.org.tw. FAU - Li, Pin-Hung AU - Li PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: s0617034@gm.csmu.edu.tw. FAU - Lin, Yu-Jung AU - Lin YJ AD - Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan. Electronic address: tch32233@tzuchi.com.tw. FAU - Wang, Wei-Hsun AU - Wang WH AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan; Department of Golden-Ager Industry Management, Chaoyang University of Technology, Taichung, Taiwan. Electronic address: wangweihsun@nchu.edu.tw. FAU - Huang, Yu-Nan AU - Huang YN AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: yunanhuang@csh.org.tw. FAU - Chen, Jia-Yuh AU - Chen JY AD - Division of Neonatology, Changhua Christian Children's Hospital, Changhua, Taiwan; Division of Metabolism and Endocrinology, Yunlin Christian Hospital, Changhua, Taiwan. Electronic address: 182288@cch.org.tw. LA - eng PT - Journal Article DEP - 20251224 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Female MH - Male MH - *Immune Checkpoint Inhibitors/adverse effects/therapeutic use MH - *Neoplasms/drug therapy/mortality/complications/immunology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects OTO - NOTNLM OT - All-cause mortality OT - Diabetic retinopathy OT - GLP-1 receptor agonists OT - Immune checkpoint inhibitors OT - Immune-related adverse events COIS- Declaration of competing interest Shan-Ho Chan, Pei-Yun Li, Pin-Hung Li, Yu-Jung Lin, Wei-Hsun Wang, Yu-Nan Huang, and Jia-Yuh Chen declare no competing interests. The funding bodies had no role in the study design, data collection, analysis, interpretation, or manuscript preparation. The authors affirm independence in the conduct of this research and in the decision to publish. EDAT- 2025/12/27 00:54 MHDA- 2026/01/12 00:37 CRDT- 2025/12/26 19:34 PHST- 2025/11/07 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/23 00:00 [accepted] PHST- 2026/01/12 00:37 [medline] PHST- 2025/12/27 00:54 [pubmed] PHST- 2025/12/26 19:34 [entrez] AID - S0168-8227(25)01088-5 [pii] AID - 10.1016/j.diabres.2025.113073 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jan;231:113073. doi: 10.1016/j.diabres.2025.113073. Epub 2025 Dec 24. PMID- 41452441 OWN - NLM STAT- MEDLINE DCOM- 20260325 LR - 20261009 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 49 IP - 3 DP - 2026 Mar TI - Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients. PG - 689-696 LID - 10.1007/s40618-025-02756-5 [doi] AB - PURPOSE: This study aimed to evaluate the one-year metabolic and renal effects of combined therapy with SGLT-2 inhibitors and GLP-1 receptor (GLP-1R) agonists in patients with type 2 diabetes mellitus (T2DM), both with and without diabetic kidney disease (DKD). The primary objective was to assess changes in BMI, HbA1c, LDL-C, eGFR, and UACR in a real-world setting. METHODS: A retrospective analysis was conducted on 250 patients with type 2 diabetes mellitus (T2DM) treated with SGLT-2 inhibitors and GLP-1 receptor agonists at the Diabetology Service of CTO-Alesini Hospital, Rome, between 2022 and 2025. Metabolic and renal parameters were collected at baseline and after 12 months. Patients were stratified according to the presence of diabetic kidney disease (DKD). The primary outcomes included changes in BMI, HbA1c, LDL-C, eGFR, and UACR. Secondary analyses evaluated the impact of adding an SGLT-2 inhibitor to pre-existing GLP-1 receptor agonist therapy, or vice versa. RESULTS: After 12 months, we observed significant reductions in BMI (p = 0.03), HbA1c (p < 0.001), LDL-C (p < 0.01), and UACR (p < 0.001). In patients with DKD (46% of the cohort), UACR improved markedly (p < 0.001), while eGFR remained stable. Significant reductions in HbA1c (p < 0.001) and LDL-C (p < 0.01) were also observed. In non-DKD patients, HbA1c and LDL-C decreased after one year, with eGFR remaining within the normal range. Importantly, among DKD patients, the addition of an SGLT-2 inhibitor to GLP-1 receptor agonist therapy resulted in significant reductions in both HbA1c (p = 0.04) and UACR (p < 0.01), whereas the addition of a GLP-1 receptor agonist primarily reduced HbA1c (p < 0.01). In non-DKD patients, both treatment sequences improved HbA1c and LDL-C. CONCLUSION: Dual therapy with SGLT-2 inhibitors and GLP-1 receptor agonists was associated with improvements in glycemic control, lipid profile, and albuminuria, particularly among patients with DKD. The sequence of drug addition appeared to influence outcomes, with the addition of SGLT-2 inhibitors providing superior renal benefits in DKD. These findings may provide support for early combined use of both agents in high-risk patients with T2DM. CI - (c) 2025. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Mazzeo, L AU - Mazzeo L AD - Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Wolde Sellasie, S AU - Wolde Sellasie S AUID- ORCID: 0000-0002-2413-2388 AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. AD - PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Pecchioli, C AU - Pecchioli C AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Di Perna, P AU - Di Perna P AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Zaccaria, S AU - Zaccaria S AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. AD - PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Sperti, P AU - Sperti P AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Nardone, I AU - Nardone I AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. AD - PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Giurato, L AU - Giurato L AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. FAU - Della-Morte, D AU - Della-Morte D AD - Division of Geriatrics, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. AD - Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, 00133, Italy. AD - Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. FAU - Caprio, M AU - Caprio M AD - Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy. AD - Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Rome, 00166, Italy. FAU - Bellia, A AU - Bellia A AD - Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it. AD - Division of Endocrinology and Diabetology, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it. FAU - Uccioli, L AU - Uccioli L AD - Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy. LA - eng PT - Journal Article DEP - 20251226 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Nephropathies/drug therapy/metabolism/etiology MH - Middle Aged MH - Aged MH - Drug Therapy, Combination MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Glomerular Filtration Rate/drug effects MH - Follow-Up Studies MH - Blood Glucose/analysis MH - Kidney/drug effects MH - Biomarkers/analysis OTO - NOTNLM OT - Diabetic kidney disease OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - Type 2 diabetes mellitus COIS- Declaration. Conflicts of interest: The authors declare no conflicts of interest. Informed consent: Informed consent was not required in accordance with the Italian regulation for non-interventional (observational) retrospective studies concerning human beings (AIFA Guidelines for Observational Studies, see www.AIFA.gov). EDAT- 2025/12/26 13:39 MHDA- 2026/03/25 19:36 CRDT- 2025/12/26 11:07 PHST- 2025/07/08 00:00 [received] PHST- 2025/11/09 00:00 [accepted] PHST- 2026/03/25 19:36 [medline] PHST- 2025/12/26 13:39 [pubmed] PHST- 2025/12/26 11:07 [entrez] AID - 10.1007/s40618-025-02756-5 [pii] AID - 10.1007/s40618-025-02756-5 [doi] PST - ppublish SO - J Endocrinol Invest. 2026 Mar;49(3):689-696. doi: 10.1007/s40618-025-02756-5. Epub 2025 Dec 26. PMID- 41451880 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260129 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 2 DP - 2026 Feb TI - Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity. PG - 317-322 LID - 10.1002/oby.70105 [doi] AB - OBJECTIVE: This study compared the efficacy of a GLP-1 receptor agonist (GLP1-RA) (semaglutide, 0.5 mg/week), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and repetitive transcranial magnetic stimulation (rTMS), a new emerging treatment for obesity, in reducing body weight (BW) after 1 year in patients with obesity and type 2 diabetes (T2D). METHODS: We included 40 patients with T2D treated with a SGLT2i, 37 patients with T2D treated with the GLP1-RA semaglutide, and 30 patients treated with rTMS in this retrospective comparative analysis. rTMS was administered three times per week for 5 weeks. All patients received dietary advice about moderate caloric restriction (-300 kcal/day). RESULTS: After 12 months the weight loss with rTMS (-8.2 +/- 1.0 kg) was not significantly different from that with semaglutide (-5.7 +/- 0.9 kg). Weight loss with SGLT2i (-2.0 +/- 0.7 kg) was significantly less than with both semaglutide (p = 0.01) and rTMS (p < 0.0001). Individuals receiving SGLT2i therapy experienced weight regain from month 6 to month 12, while BW declined progressively in patients treated with semaglutide and rTMS. CONCLUSIONS: Treatment with rTMS produced a comparable reduction in BW to that observed with the GLP1-RA semaglutide (at the dose of 0.5 mg/week) and represents a promising intervention for the treatment of obesity and T2D. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03009695. CI - (c) 2025 The Obesity Society. FAU - Ferrulli, Anna AU - Ferrulli A AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Senesi, Pamela AU - Senesi P AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Sonaglioni, Andrea AU - Sonaglioni A AD - Division of Cardiology, IRCCS MultiMedica, Milan, Italy. FAU - Cannavaro, Daniele AU - Cannavaro D AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. FAU - Massarini, Stefano AU - Massarini S AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Macri, Concetta AU - Macri C AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. FAU - Cipponeri, Elisa AU - Cipponeri E AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - DeFronzo, Ralph A AU - DeFronzo RA AD - Division of Diabetes, UT Health San Antonio, San Antonio, Texas, USA. AD - Texas Diabetes Institute, San Antonio, Texas, USA. FAU - Luzi, Livio AU - Luzi L AUID- ORCID: 0000-0003-3183-0552 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. LA - eng SI - ClinicalTrials.gov/NCT03009695 GR - Ricerca Corrente-IRCCS MultiMedica/ GR - RF-2011-02349303/Italian Ministry of Health/ PT - Clinical Trial PT - Journal Article DEP - 20251226 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/therapy/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/therapy/drug therapy/complications MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Transcranial Magnetic Stimulation MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitors OT - obesity OT - transcranial magnetic stimulation OT - type 2 diabetes EDAT- 2025/12/26 13:38 MHDA- 2026/01/28 19:20 CRDT- 2025/12/26 06:54 PHST- 2025/10/28 00:00 [revised] PHST- 2025/08/12 00:00 [received] PHST- 2025/10/31 00:00 [accepted] PHST- 2026/01/28 19:20 [medline] PHST- 2025/12/26 13:38 [pubmed] PHST- 2025/12/26 06:54 [entrez] AID - 10.1002/oby.70105 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Feb;34(2):317-322. doi: 10.1002/oby.70105. Epub 2025 Dec 26. PMID- 41450584 OWN - NLM STAT- MEDLINE DCOM- 20251226 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. PG - 1646956 LID - 10.3389/fendo.2025.1646956 [doi] LID - 1646956 AB - OBJECTIVE: This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis. METHODS: Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity. Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes. RESULTS: Eight studies with low bias risk involving 1,454 participants were analysed. Meta-analysis results demonstrated that danuglipron significantly decreased HbA1c (mean difference [MD]: -0.90; 95% CI: -1.06, -0.74), FPG (MD: -24.66; 95% CI: -30.45, -18.86) and weight (MD: -2.17; 95% CI: -3.10, -1.23) and improved FPI (MD: 2.94; 95% CI: 1.50, 4.38). Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89). However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs). CONCLUSION: The oral GLP-1 RAs danuglipron and orforglipron are capable of improving blood glucose levels and reducing weight; however, they also pose an increased risk of gastrointestinal AEs. Further longitudinal studies are warranted to gain a deeper understanding of their efficacy, safety and tolerability. CI - Copyright (c) 2025 Zhou, Wang and Li. FAU - Zhou, Jingjing AU - Zhou J AD - Department of Epidemiology and Health Statistics, Shanxi University of Medicine, Fenyang, China. FAU - Wang, Fang AU - Wang F AD - Department of Endocrinology, Fenyang Hospital, Fenyang, Shanxi, China. FAU - Li, Sen AU - Li S AD - Department of Health Information, Shanxi University of Medicine, Fenyang, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251210 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Benzimidazoles) RN - 0 (Oxadiazoles) RN - 0 (Piperidines) RN - 0 (Fluorine Compounds) RN - 0 (orforglipron) RN - DN9IUI24GP (danuglipron) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Blood Glucose/drug effects MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Benzimidazoles MH - Oxadiazoles MH - Piperidines MH - Fluorine Compounds PMC - PMC12727569 OTO - NOTNLM OT - danuglipron OT - efficacy OT - meta-analysis OT - orforglipron OT - type 2 diabetes and obesity COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/12/26 07:40 MHDA- 2025/12/26 07:41 PMCR- 2025/12/10 CRDT- 2025/12/26 04:36 PHST- 2025/06/14 00:00 [received] PHST- 2025/11/03 00:00 [accepted] PHST- 2025/12/26 07:41 [medline] PHST- 2025/12/26 07:40 [pubmed] PHST- 2025/12/26 04:36 [entrez] PHST- 2025/12/10 00:00 [pmc-release] AID - 10.3389/fendo.2025.1646956 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Dec 10;16:1646956. doi: 10.3389/fendo.2025.1646956. eCollection 2025. PMID- 41448677 OWN - NLM STAT- MEDLINE DCOM- 20251225 LR - 20260926 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 12 DP - 2025 Dec 24 TI - Clinical characteristics and outcomes of patients with type 2 diabetes mellitus and chronic kidney disease from two new-user medication cohorts: a retrospective cohort study using regional electronic health records database in China. PG - e106126 LID - 10.1136/bmjopen-2025-106126 [doi] LID - e106126 AB - OBJECTIVES: Given the rapidly evolving therapeutic landscape for type 2 diabetes (T2D) and chronic kidney disease (CKD), this study aimed to characterise the clinical profiles and real-world outcomes of patients with T2D and CKD in China who initiated sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1 RA). DESIGN: Retrospective cohort study. SETTING: Demographic and clinical data of patients from a regional electronic health records database in Tianjin, China between 2012 and 2019 were used. PARTICIPANTS: Adult patients diagnosed with T2D and CKD who initiated SGLT2i or GLP-1 RA from 2012 to 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: Baseline demographic and disease characteristics, comorbidities and comedications, healthcare resource utilisation (HRU), and clinical outcomes were assessed using descriptive statistics. RESULTS: A total of 935 and 4821 patients were included in SGLT2i and GLP-1 RA cohorts, with the mean ages of 59 and 56 years, respectively. Both cohorts had similar durations of T2D (mean: 5 years) and CKD (mean: 3 years). In SGLT2i and GLP-1 RA cohorts, 54.4% and 56.9% of patients had hemoglobin A1c (HbA1c) >7%, and 50.5% and 54.1% were classified as CKD stage 1 at baseline. During the follow-up period (median 1.4 months for SGLT2i cohort and median 2.3 months for GLP-1 RA cohort), higher numbers of specialist visits compared with general practitioner visits were observed numerically for both cohorts. The incidence rates (95% CI) of kidney failure per 100 person-years were 3.1 (1.0, 7.3) for SGLT2i cohort, and 4.9 (3.9, 6.0) for GLP-1 RA cohort during follow-up. CONCLUSIONS: This study provides descriptive evidence regarding the clinical characteristics and outcomes of patients with T2D and CKD who initiated SGLT2i or GLP-1 RA in China. The results are important for understanding the existing HRU and residual risk of severe clinical outcomes in such patient populations. The findings also provide a solid foundation for future research aimed at examining the clinical outcomes of new therapeutic options for T2D and CKD. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Deng, Xiaoqing AU - Deng X AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Chen, Yanyan AU - Chen Y AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Xu, Zhe AU - Xu Z AD - Bayer Healthcare Company Ltd, Beijing, China. FAU - Wei, Huan AU - Wei H AD - Real-World Solutions, IQVIA Ltd, Shanghai, China. FAU - Liao, Yuqin AU - Liao Y AD - Bayer Healthcare Company Ltd, Beijing, China. FAU - Liu, Fangfang AU - Liu F AD - Bayer AG, Berlin, Germany. FAU - Farjat, Alfredo E AU - Farjat AE AD - Bayer AG, Berlin, Germany. FAU - Oberprieler, Nikolaus G AU - Oberprieler NG AD - Bayer AG, Berlin, Germany. FAU - Chen, Liming AU - Chen L AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China xfx22081@vip.163.com. LA - eng PT - Journal Article DEP - 20251224 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Renal Insufficiency, Chronic/drug therapy/epidemiology/complications MH - China/epidemiology MH - Electronic Health Records MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Databases, Factual MH - Adult MH - Glycated Hemoglobin MH - Treatment Outcome PMC - PMC12742173 OTO - NOTNLM OT - Chronic Disease OT - Diabetic nephropathy & vascular disease OT - Treatment Outcome COIS- Competing interests: FL, AEF and NGO are employees of Bayer AG, the study funder. FL, AEF and NGO contributed to the study design, data interpretation, manuscript review and the decision to submit the paper for publication. The funder didn't influence the results/outcomes of the study. ZX and YL are employees of Bayer Healthcare Company Ltd. HW is an employee of IQVIA Ltd. LC received research funding from AstraZeneca and Eli Lilly. Other authors declare no competing interests. EDAT- 2025/12/26 00:32 MHDA- 2025/12/26 00:33 PMCR- 2025/12/24 CRDT- 2025/12/25 20:43 PHST- 2025/12/26 00:33 [medline] PHST- 2025/12/26 00:32 [pubmed] PHST- 2025/12/25 20:43 [entrez] PHST- 2025/12/24 00:00 [pmc-release] AID - bmjopen-2025-106126 [pii] AID - 10.1136/bmjopen-2025-106126 [doi] PST - epublish SO - BMJ Open. 2025 Dec 24;15(12):e106126. doi: 10.1136/bmjopen-2025-106126. PMID- 41444586 OWN - NLM STAT- MEDLINE DCOM- 20251225 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Dec 24 TI - Glucagon-like peptide-1 receptor agonists and risk for cardiovascular events in older adults treated with levothyroxine: a target trial emulation. PG - 459 LID - 10.1186/s12933-025-02971-7 [doi] LID - 459 AB - BACKGROUND: Initiation of Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) treated with levothyroxine may decrease the required levothyroxine dose due to weight loss or enhance levothyroxine absorption through delayed gastric emptying. These changes may cause thyroid hormone over-replacement and increased risk of atrial fibrillation/flutter (AF/Aflutter) and stroke. Our study aims to investigate the impact of GLP-1RA initiation on risks of AF/Aflutter and stroke in patients with T2D treated with levothyroxine, compared to sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: Leveraging the target trial emulation framework, we conducted a retrospective study using observational data to emulate a new user, active comparator trial examining the effects of initiating GLP-1RA (exposure group) versus SGLT2 inhibitors (control group), with random treatment assignment emulated by propensity score matching with 1:1 ratio. We used a 15% nationally representative sample of U.S. Medicare beneficiaries to identify participants > 65 years, continuously on stable dose of levothyroxine for >/= 6 months before the index date (i.e., GLP-1RA or SGLT2 inhibitor initiation), with continuous Medicare enrollment, without malignant cancer or palliative care during 1 year before the index date. The primary outcome was AF/Aflutter, and secondary outcome was stroke, including ischemic stroke or transient ischemic attack. We assessed the per-protocol effects of GLP-1RA vs. SGLT2 inhibitors using inverse-probability-censoring weighted Cox proportional hazards models. RESULTS: After matching, the study cohort included 2,384 participants in both GLP-1RA and SGLT2 groups with mean age (SD): 73.3 (5.9) vs. 73.2 (5.8), and 71.5% and 71.8% of female. The median follow-up time was 1.05 years. Compared to SGLT2 inhibitors, initiation of GLP-1RA was associated with higher risk of AF/Aflutter (HR: 1.46; 95% CI: 1.28-1.67), while no statistically significant difference was observed between the two groups for stroke (HR: 1.17; 95% CI: 0.98-1.39). Sensitivity analyses showed consistent results, including restricting outcomes to inpatient visits, conducting an intention-to-treat analysis, applying a prevalent new user design, and substituting SGLT2 inhibitors with dipeptidyl peptidase-4 (DPP4) inhibitors as the active comparator. CONCLUSIONS: In patients with T2D historically treated with stable doses of levothyroxine, GLP-1RA initiation was associated with a higher risk of AF/Aflutter. Further research is warranted to investigate the potential roles of weight loss, TSH fluctuations, and levothyroxine dose adjustment after GLP-1RA in mediating the cardiovascular risk. CI - (c) 2025. The Author(s). FAU - Du, Fanxing AU - Du F AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA. FAU - Ospina, Naykky M Singh AU - Ospina NMS AD - Division of Endocrinology, Department of Medicine, University of Florida, Gainesville, USA. FAU - Chen, Yishan AU - Chen Y AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA. FAU - Brito, Juan P AU - Brito JP AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, USA. AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, USA. FAU - Liu, Qing AU - Liu Q AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA. FAU - Schmidt, Stephan AU - Schmidt S AD - Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA. AD - University of Maryland Institute for Health Computing, North Bethesda, USA. FAU - Cicali, Brian AU - Cicali B AD - Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA. FAU - Shao, Hui AU - Shao H AD - Emory Global Diabetes Research Center of Woodruff Health Sciences Center, Emory University, Atlanta, USA. AD - Hubert Department of Global Health, Rollin School of Public Health, Emory University, Atlanta, USA. FAU - Jiao, Tianze AU - Jiao T AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA. tianzejiao@ufl.edu. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, USA. tianzejiao@ufl.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20251224 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - Q51BO43MG4 (Thyroxine) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - Aged MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Thyroxine/adverse effects/therapeutic use MH - Risk Assessment MH - Treatment Outcome MH - Time Factors MH - *Incretins/adverse effects/therapeutic use MH - United States/epidemiology MH - Aged, 80 and over MH - Age Factors MH - Risk Factors MH - Atrial Fibrillation/epidemiology/diagnosis MH - *Stroke/epidemiology/diagnosis MH - Databases, Factual MH - Heart Disease Risk Factors MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12729143 OTO - NOTNLM OT - GLP-1RA OT - SGLT2 inhibitors OT - atrial fibrillation or flutter OT - levothyroxine OT - stroke OT - target trial emulation COIS- Declarations. Ethics approval and consent to participate: The study protocol received approval from the Institutional Review Board at the University of Florida, USA. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/12/25 00:29 MHDA- 2025/12/25 00:30 PMCR- 2025/12/24 CRDT- 2025/12/24 23:39 PHST- 2025/08/20 00:00 [received] PHST- 2025/10/06 00:00 [accepted] PHST- 2025/12/25 00:30 [medline] PHST- 2025/12/25 00:29 [pubmed] PHST- 2025/12/24 23:39 [entrez] PHST- 2025/12/24 00:00 [pmc-release] AID - 10.1186/s12933-025-02971-7 [pii] AID - 2971 [pii] AID - 10.1186/s12933-025-02971-7 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Dec 24;24(1):459. doi: 10.1186/s12933-025-02971-7. PMID- 41444101 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260920 IS - 1471-499X (Electronic) IS - 1471-4914 (Print) IS - 1471-4914 (Linking) VI - 32 IP - 7 DP - 2026 Jul TI - GLP-1 agonists in neurodegeneration: a multimodal biomarker-guided approach. PG - 711-725 LID - S1471-4914(25)00288-6 [pii] LID - 10.1016/j.molmed.2025.12.001 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP1-RAs), widely used for type 2 diabetes mellitus, are emerging as promising neuroprotective therapies in Alzheimer's disease (AD) and Parkinson's disease (PD). Agents such as exenatide, lixisenatide, and liraglutide have demonstrated disease-modifying potential in preclinical and clinical studies. However, translation remains hindered by the absence of validated biomarkers to guide patient selection, track target engagement, and monitor progression. Here, we review the mechanistic links between GLP1-RA signaling and neurodegeneration, summarize the evolving clinical evidence, and highlight emerging blood-based and molecular biomarkers, including those tied to insulin signaling, neurodegeneration, and metabolic and cardiovascular dysfunction, that may accelerate therapeutic development. Integrating these biomarkers with digital phenotyping and artificial intelligence could enable precision approaches to advance GLP1-RA research and clinical use in neurodegeneration. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Santiago, Jose A AU - Santiago JA AD - NeuroHub Analytics, LLC, Chicago, IL, USA; Department of Neurology and Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: jose.santiago@neurohubanalytics.com. FAU - Gutierrez-Silva, Jean C AU - Gutierrez-Silva JC AD - NeuroHub Analytics, LLC, Chicago, IL, USA. FAU - Hsu, Wei-Chuan AU - Hsu WC AD - NeuroHub Analytics, LLC, Chicago, IL, USA. FAU - Sanchez, Kameron AU - Sanchez K AD - NeuroHub Analytics, LLC, Chicago, IL, USA. FAU - Almanza, Cesar AU - Almanza C AD - NeuroHub Analytics, LLC, Chicago, IL, USA. FAU - Ramos, William AU - Ramos W AD - NeuroHub Analytics, LLC, Chicago, IL, USA. FAU - Haq, Ihtsham Ul AU - Haq IU AD - Department of Neurology and Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Rundek, Tatjana AU - Rundek T AD - Department of Neurology and Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA. LA - eng GR - T32 AG081170/AG/NIA NIH HHS/United States GR - T32 HL166609/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251223 PL - England TA - Trends Mol Med JT - Trends in molecular medicine JID - 100966035 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Neuroprotective Agents) SB - IM MH - Humans MH - *Biomarkers/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Neurodegenerative Diseases/drug therapy/metabolism MH - Parkinson Disease/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide 1/metabolism MH - Alzheimer Disease/drug therapy/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Neuroprotective Agents/therapeutic use/pharmacology PMC - PMC13005735 MID - NIHMS2149382 OTO - NOTNLM OT - Alzheimer's disease OT - Parkinson's disease OT - artificial intelligence OT - biomarkers OT - diabetes OT - glucagon-like peptide-1 agonist COIS- Declaration of interests J.A.S. is the founder and principal of NeuroHub Analytics LLC and a co-inventor on United States Patent US 9,970,056 B2, Methods and Kits for Diagnosing, Prognosing, and Monitoring Parkinson's Disease. Biomarkers identified by J.A.S. are included in the study protocol for the LIXIPARK trial (NCT03439943). J.C.G, W.H, K.S, C.A, W.R, I.H, and T.R declare no competing interests. EDAT- 2025/12/25 00:29 MHDA- 2026/07/09 00:40 PMCR- 2026/03/22 CRDT- 2025/12/24 22:02 PHST- 2025/10/25 00:00 [received] PHST- 2025/12/01 00:00 [revised] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/07/09 00:40 [medline] PHST- 2025/12/25 00:29 [pubmed] PHST- 2025/12/24 22:02 [entrez] PHST- 2026/03/22 00:00 [pmc-release] AID - S1471-4914(25)00288-6 [pii] AID - 10.1016/j.molmed.2025.12.001 [doi] PST - ppublish SO - Trends Mol Med. 2026 Jul;32(7):711-725. doi: 10.1016/j.molmed.2025.12.001. Epub 2025 Dec 23. PMID- 41443408 OWN - NLM STAT- MEDLINE DCOM- 20260502 LR - 20260502 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 10 IP - 5 DP - 2026 May TI - Impact of Glucagon-Like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center. PG - 480-489 LID - S2468-6530(25)00595-0 [pii] LID - 10.1016/j.oret.2025.12.014 [doi] AB - OBJECTIVE: There is ongoing debate in the literature on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on age-related macular degeneration (AMD). This study examines the effect of GLP-1RA on the risk of AMD development compared with other glucose-lowering medications at a single ophthalmology center. DESIGN: Retrospective cohort study. SUBJECTS: A total of 30 515 GLP-1RA users, 48 906 sodium-glucose transport protein 2 inhibitor (SGLT-2i) users, 286 066 metformin users, and 164 361 insulin users aged >/=50 years had a 1-year minimum drug duration between 2016 and 2025. After propensity score matching (PSM), each cohort included 7561 patients. Patients with diabetic macular edema, severe or proliferative diabetic retinopathy, and with history of prior retinal surgeries were excluded. METHODS: The relative risk (RR) of developing nonexudative AMD was measured at yearly drug duration intervals up to 3 years using logistic regression models controlling for age, sex, race, smoking status, and hemoglobin A1C percentage. Manual review was performed on a random sampling of AMD cases to optimize accuracy. Cox proportional hazards (CPHs) validation analyses in PSM cohorts were performed, matching additionally for body mass index, history of hypertension, chronic kidney disease, and diabetes duration. MAIN OUTCOME MEASURES: The primary outcome was the RR of nonexudative AMD up to 3 years on GLP-1RAs compared with alternative antihyperglycemic agents. RESULTS: Glucagon-like peptide-1 receptor agonist was associated with decreased risk of nonexudative AMD compared with metformin and insulin at all 3 years and compared with SGLT-2i only after 3 years of use (3 years: metformin relative risk [RR] = 0.25; 95% confidence interval [CI], 0.14-0.41; insulin RR = 0.28; 95% CI, 0.15-0.46; SGLT-2i RR = 0.42; 95% CI, 0.22-0.74). In PSM cohorts, CPH analyses showed a reduced risk only compared with insulin (hazards ratio = 0.45; 95% CI, 0.27-0.76). CONCLUSIONS: Glucagon-like peptide-1 receptor agonist use was associated with a lower risk of nonexudative AMD compared with metformin, insulin, and SGLT-2i in logistic regression models. The risk reduction persisted for insulin in CPH analyses in smaller PSM cohorts. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2025 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Joo, Julia H AU - Joo JH AD - Department of Ophthalmology, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio. FAU - Zhao, Alison H AU - Zhao AH AD - Department of Ophthalmology, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Chalasani, Meghana AU - Chalasani M AD - Department of Ophthalmology, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio. FAU - Allan, Kevin C AU - Allan KC AD - Department of Ophthalmology, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio. FAU - Rachitskaya, Aleksandra V AU - Rachitskaya AV AD - Department of Ophthalmology, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio. Electronic address: rachita@ccf.org. LA - eng PT - Journal Article DEP - 20251222 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - *Macular Degeneration/epidemiology/diagnosis MH - *Tertiary Care Centers/statistics & numerical data MH - Follow-Up Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Incidence MH - Risk Factors OTO - NOTNLM OT - Age-related macular degeneration OT - Drug repurposing OT - GLP-1 receptor agonist OT - SGLT-2 inhibitors EDAT- 2025/12/25 00:29 MHDA- 2026/05/03 05:27 CRDT- 2025/12/24 19:31 PHST- 2025/08/24 00:00 [received] PHST- 2025/12/15 00:00 [revised] PHST- 2025/12/16 00:00 [accepted] PHST- 2026/05/03 05:27 [medline] PHST- 2025/12/25 00:29 [pubmed] PHST- 2025/12/24 19:31 [entrez] AID - S2468-6530(25)00595-0 [pii] AID - 10.1016/j.oret.2025.12.014 [doi] PST - ppublish SO - Ophthalmol Retina. 2026 May;10(5):480-489. doi: 10.1016/j.oret.2025.12.014. Epub 2025 Dec 22. PMID- 41441832 OWN - NLM STAT- MEDLINE DCOM- 20251224 LR - 20251224 IS - 1972-6481 (Electronic) IS - 1827-6806 (Linking) VI - 27 IP - 1 DP - 2026 Jan TI - [Type 2 diabetes in patients with coronary artery disease: from an overlooked diagnosis to treatments with new glucose-lowering drugs]. PG - 37-47 LID - 10.1714/4618.46269 [doi] AB - Type 2 diabetes mellitus (T2DM) is a common risk factor for atherosclerotic cardiovascular disease. Although in patients with coronary artery disease T2DM has a non-negligible prevalence, it is often overlooked. Due to its prognostic impact and the availability of pharmacological intervention, as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA), able to improve the prognosis, an early diagnosis is crucial. T2DM diagnosis is based on three evaluations: fasting serum glucose levels; glycate hemoglobin levels; and oral glucose tolerance test. In addition, it is important to know the clinical significance of stress-induced hyperglycemia, commonly found in patients with an acute cardiovascular event. As regards T2DM therapy, SGLT2i and GLP1-RA represent two pillars to reduce cardiovascular disease risk but, despite international guidelines, their use remains rather low in routine cardiovascular care. This review reports indications for an appropriate use of these treatments with an analysis of benefits and precautions to consider in clinical practice. FAU - Guido, Vincenzo AU - Guido V AD - U.O.C. Cardiologia, Ospedale G.B. Grassi, ASL Roma 3, Roma. FAU - Di Fusco, Stefania Angela AU - Di Fusco SA AD - U.O.C. Cardiologia Clinica e Riabilitativa, Ospedale San Filippo Neri - ASL Roma 1, Roma. FAU - Morviducci, Lelio AU - Morviducci L AD - Unita di Diabetologia e Nutrizione, ASL Roma 1, Roma. FAU - Ammirati, Fabrizio AU - Ammirati F AD - U.O.C. Cardiologia, Ospedale G.B. Grassi, ASL Roma 3, Roma. FAU - Colivicchi, Furio AU - Colivicchi F AD - U.O.C. Cardiologia Clinica e Riabilitativa, Ospedale San Filippo Neri - ASL Roma 1, Roma. LA - ita PT - English Abstract PT - Journal Article PT - Review TT - Diabete mellito di tipo 2 nei pazienti con malattia coronarica: da una diagnosi troppo spesso trascurata alle terapie con i nuovi farmaci ipoglicemizzanti orali. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications MH - *Coronary Artery Disease/etiology/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose/analysis MH - Prognosis MH - Glucose Tolerance Test EDAT- 2025/12/24 12:55 MHDA- 2025/12/24 12:56 CRDT- 2025/12/24 10:33 PHST- 2025/12/24 12:56 [medline] PHST- 2025/12/24 12:55 [pubmed] PHST- 2025/12/24 10:33 [entrez] AID - 10.1714/4618.46269 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2026 Jan;27(1):37-47. doi: 10.1714/4618.46269. PMID- 41437637 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260129 IS - 1464-3677 (Electronic) IS - 1353-4505 (Linking) VI - 38 IP - 1 DP - 2026 Jan 10 TI - Income disparities and accessibility to Semaglutide: implications for diabetes management and policy reform. LID - mzaf131 [pii] LID - 10.1093/intqhc/mzaf131 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1(GLP-1) receptor agonist, is an effective treatment for type 2 diabetes and weight loss. However, its high cost poses a significant barrier to access for those who need it more. This study investigated if socioeconomic factors affected the use of semaglutide among patients with type 2 diabetes and if there are income disparities in its utilization. METHODS: This analysis utilized data from the 2022 Medical Expenditure Panel Survey (MEPS), focusing on US adults diagnosed with type 2 diabetes. The sample included 2542 individuals, representing approximately 30.3 million adults in the USA. Descriptive statistics were calculated to summarize demographic and socioeconomic characteristics. Bivariate associations between income, insurance status, and semaglutide use were assessed using chi-square tests. A multivariable logistic regression model was applied to identify the relationship between income levels and Semaglutide use while adjusting for potential confounders, including insurance status, education, and employment. RESULTS: The analysis revealed a significant association between income and semaglutide use. Individuals with incomes above the median were more likely to use semaglutide than those with lower incomes [odds ratio (OR) = 1.61, 95% CI: 1.14-2.26]. Private insurance also significantly increased the likelihood of semaglutide use (OR = 1.52, 95% CI: 1.04-2.22). Education level and employment status were additional significant predictors of access. Racial and ethnic disparities were observed but did not reach statistical significance after adjustment. DISCUSSION: These findings highlighted the significant barriers to accessing semaglutide for low-income individuals. Such individuals are disproportionately affected by diabetes. The affordability of drugs like semaglutide underlines the need for policy interventions to address income-related disparities in healthcare. Expanding insurance coverage, implementing subsidy programs, and introducing price regulation strategies, such as external reference pricing, are potential solutions to improve access to this essential treatment. This study emphasizes the importance of ensuring equitable access to such essential medications regardless of income level. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Vaidya, Varun AU - Vaidya V AUID- ORCID: 0000-0002-7943-3479 AD - Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States. FAU - Estep, Sophia AU - Estep S AD - College of Pharmacy & Pharmaceutical Sciences, The University of Toledo, Toledo, OH, United States. FAU - Gupte, Renuka AU - Gupte R AD - Humana Ohio Medicaid, Perrysburg, OH, United States. LA - eng PT - Journal Article PL - England TA - Int J Qual Health Care JT - International journal for quality in health care : journal of the International Society for Quality in Health Care JID - 9434628 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Female MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Male MH - Adult MH - *Hypoglycemic Agents/therapeutic use/economics MH - United States MH - *Income/statistics & numerical data MH - *Health Services Accessibility/statistics & numerical data MH - Aged MH - Socioeconomic Factors MH - *Healthcare Disparities/statistics & numerical data MH - Insurance Coverage/statistics & numerical data OTO - NOTNLM OT - Semaglutide OT - diabetes management OT - healthcare access OT - income disparities EDAT- 2025/12/24 07:43 MHDA- 2026/01/28 19:21 CRDT- 2025/12/24 02:03 PHST- 2025/05/09 00:00 [received] PHST- 2025/11/05 00:00 [revised] PHST- 2025/11/18 00:00 [accepted] PHST- 2026/01/28 19:21 [medline] PHST- 2025/12/24 07:43 [pubmed] PHST- 2025/12/24 02:03 [entrez] AID - 8403748 [pii] AID - 10.1093/intqhc/mzaf131 [doi] PST - ppublish SO - Int J Qual Health Care. 2026 Jan 10;38(1):mzaf131. doi: 10.1093/intqhc/mzaf131. PMID- 41429246 OWN - NLM STAT- MEDLINE DCOM- 20260214 LR - 20260214 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 283 DP - 2026 Mar TI - Potential Eye Disorders in People With and Without Type 2 Diabetes Mellitus Exposed to GLP-1 Receptor Agonists: An Examination of the FAERS (FDA Adverse Event Reporting System) Database. PG - 279-290 LID - S0002-9394(25)00666-X [pii] LID - 10.1016/j.ajo.2025.12.015 [doi] AB - PURPOSE: As use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Type 2 diabetes (T2DM) and weight management increases, emerging research identifies various adverse drug reactions. This study aimed to expand this research base, focusing on eye disorders in people with and without T2DM, a novel consideration. DESIGN: A retrospective clinical cohort disproportionality analysis of reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: FAERS was queried regarding selected GLP-1RAs. Python 3.11 was adopted to develop a program, quantifying reported cases between January 2017 - September 2025 (January 2022-September 2025 for tirzepatide) meeting the criteria for cases with and without T2DM. Main outcome measures Reporting Odds Ratios (RORs) >4.000 and 95% confidence intervals were calculated, with metformin and orlistat as controls. RESULTS: Compared to metformin, semaglutide showed increased reporting of optic ischemic neuropathy (ROR: 12.269 [0.915-1.967]), cataract (ROR: 31.879 [2.463-4.461]) and retinopathy (ROR: 5.185 [0.556-2.736]) in T2DM patients, and retinopathy (ROR: 9.424 [1.081-3.406]) and retinal hemorrhage (ROR: 10.253 [0.319-4.336]) in non-T2DM patients. Tirzepatide showed increased reporting of optic ischemic neuropathy (ROR: 4.619 [0.726-2.335]) and macular degeneration (ROR: 15.579 [0.554-4.938]) in T2DM patients and eye swelling (ROR: 6.475 [0.407-3.329]) in non-T2DM patients. Liraglutide showed increased reporting of cataract (ROR: 53.866 [2.945-5.028]), diabetic retinopathy (ROR: 18.162 [1.753-4.045]) and macular degeneration (ROR: 26.261 [1.076-5.460]) in T2DM patients and cataract (ROR: 9.628 [1.387-3.142]) and macular degeneration (ROR: 9.557 [0.110-4.405]) in non-T2DM patients. CONCLUSIONS: These results provide a signal of increased reporting of various eye disorders with GLP-1RA use compared to metformin across T2DM and non-T2DM patient cases. Further research is required to support these findings and confirm a biological causation. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Murray, Mya AU - Murray M AD - From Pharmacy, the Singleton Campus (M.M., A.G.), Swansea University, Wales, UK. FAU - Schifano, Fabrizio AU - Schifano F AD - Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit (F.S., J.M.C.), College Lane Campus, University of Hertfordshire, Hatfield, UK. FAU - Chiappini, Stefania AU - Chiappini S AD - Psychiatry, UniCamillus University (S.C.), Rome, Italy. FAU - Corkery, John Martin AU - Corkery JM AD - Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit (F.S., J.M.C.), College Lane Campus, University of Hertfordshire, Hatfield, UK. FAU - Guirguis, Amira AU - Guirguis A AD - From Pharmacy, the Singleton Campus (M.M., A.G.), Swansea University, Wales, UK. Electronic address: amira.guirguis@swansea.ac.uk. LA - eng PT - Journal Article DEP - 20251220 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Female MH - Male MH - Databases, Factual MH - Middle Aged MH - Aged MH - *Eye Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptides/adverse effects EDAT- 2025/12/23 00:27 MHDA- 2026/02/15 00:31 CRDT- 2025/12/22 19:28 PHST- 2025/10/23 00:00 [received] PHST- 2025/12/17 00:00 [revised] PHST- 2025/12/18 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2025/12/23 00:27 [pubmed] PHST- 2025/12/22 19:28 [entrez] AID - S0002-9394(25)00666-X [pii] AID - 10.1016/j.ajo.2025.12.015 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Mar;283:279-290. doi: 10.1016/j.ajo.2025.12.015. Epub 2025 Dec 20. PMID- 41427774 OWN - NLM STAT- MEDLINE DCOM- 20260119 LR - 20260130 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 11 DP - 2025 Nov TI - Racial/ethnic differences in the use of glucagon-like peptide-1 receptor agonists (GLP-1 agonists) for atherosclerotic cardiovascular disease (ASCVD) benefit in patients with type 2 diabetes. PG - 2067-2075 LID - 10.1080/03007995.2025.2606551 [doi] AB - PURPOSE: According to the current guidelines, glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are recommended for the treatment of Type II diabetes mellitus (T2DM) in patients who are at risk for developing atherosclerotic cardiovascular disease (ASCVD). The black population is at a greater risk of developing ASCVD. This research intends to investigate the prescribing patterns of GLP-1 agonists amongst blacks compared to patients of other races and ethnicities. METHODS: This is a retrospective study of patients who were 18 years or older with a diagnosis of T2DM and were prescribed GLP-1 agonists and at Ochsner Health System from January 2019 to July 2023. The primary outcome was comparison of major adverse cardiovascular events (MACE): myocardial infarction, stroke, and inpatient mortality among the three study groups. Secondary outcomes included differences in clinical outcomes (A1C reduction, BMI reduction) in patients using GLP-1 agonists compared to patients not receiving these agents. RESULTS: Of 92,861 patients who met the inclusion criteria, the proportion of patients prescribed GLP-1 agonists by race included black 12,225 (33.2%), white 17,931 (34.5%), and others 2,834 (71.5%). For the primary outcomes among patients prescribed GLP-1 agonists, there was a significant difference with patients with black race having a lower proportion of inpatient mortality and composite outcome [1.8%, 2.8%, respectively] compared to patients of white race [2.6%, 4%, respectively], (p < .0001). For the secondary outcomes, from baseline to 48 months, patients prescribed GLP-1 agonists with black race had a greater reduction in A1C than patients with white race [-0.80 vs-0.56] while patients with white race had a greater reduction in BMI [-1.74 vs -1.40], (p < .0001). CONCLUSION: The use of GLP-1 agonists has been shown to improve various clinical outcomes. Further research may reveal methods to increase the use of these agents, which may reduce disease-related complications especially for the minority population. FAU - Ahmed, Fahamina AU - Ahmed F AUID- ORCID: 0000-0001-7415-1117 AD - College of Pharmacy, Division of Clinical and Administrative Sciences, College of Pharmacy Xavier, University of Louisiana, Xavier University of Louisiana, New Orleans, LA, USA. FAU - Borghol, Amne AU - Borghol A AD - College of Pharmacy, Division of Clinical and Administrative Sciences, College of Pharmacy Xavier, University of Louisiana, Xavier University of Louisiana, New Orleans, LA, USA. FAU - Grady, Madison AU - Grady M AD - College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA. FAU - Rivera, Lauren AU - Rivera L AD - College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA. FAU - Meyers, Sierra AU - Meyers S AD - College of Pharmacy, Division of Clinical and Administrative Sciences, College of Pharmacy Xavier, University of Louisiana, Xavier University of Louisiana, New Orleans, LA, USA. FAU - Olet, Susan AU - Olet S AD - Ochsner Xavier Institute for Health Equity and Research, New Orleans, LA, USA. LA - eng PT - Journal Article DEP - 20251222 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Curr Med Res Opin. 2025 Dec;41(12):2391. doi: 10.1080/03007995.2026.2624991. PMID: 41614667 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Atherosclerosis/drug therapy/ethnology/etiology MH - *Black or African American/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/complications/ethnology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - *White/statistics & numerical data OTO - NOTNLM OT - ASCVD benefit OT - GLP-1 agonist OT - racial differences OT - type 2 diabetes mellitus EDAT- 2025/12/22 12:55 MHDA- 2026/01/19 18:33 CRDT- 2025/12/22 09:24 PHST- 2026/01/19 18:33 [medline] PHST- 2025/12/22 12:55 [pubmed] PHST- 2025/12/22 09:24 [entrez] AID - 10.1080/03007995.2025.2606551 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Nov;41(11):2067-2075. doi: 10.1080/03007995.2025.2606551. Epub 2025 Dec 22. PMID- 41424236 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260925 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation. PG - 1984-1996 LID - 10.1111/dom.70384 [doi] AB - AIM: Type 2 diabetes (T2D) is associated with increased dementia risk, but comparative data across newer glucose-lowering therapies remain limited. We examined whether the initiation of GLP-1 receptor agonists (GLP-1 RAs) was associated with incident dementia compared with DPP4 inhibitors (DPP4is) and SGLT2 inhibitors (SGLT2is) in older adults with T2D. MATERIALS AND METHODS: We conducted a retrospective cohort study emulating a target trial using electronic health records from the University of Pennsylvania Health System (2019-2024), with external validation in the TriNetX U.S. Collaborative Network. Adults aged >/=50 with T2D, no prior dementia, and no GLP-1 RA, DPP4i, or SGLT2i use in the previous year were eligible. New GLP-1 RA users were propensity-score matched (1:1) to DPP4i users (n = 6677 pairs) and SGLT2i users (n = 8434 pairs). The outcome was incident dementia, defined by ICD-10-CM codes. Cox proportional hazards models estimated hazard ratios (HRs), with multiple sensitivity and subgroup analyses performed. RESULTS: Over a median follow-up of 3.0 years (GLP-1 RA vs. DPP4i) and 2.4 years (GLP-1 RA vs. SGLT2i), GLP-1 RA use was associated with a lower dementia risk versus DPP4is (109 vs. 148 events; HR 0.76, 95% CI 0.59-0.97), but a higher risk versus SGLT2is (127 vs. 64 events; HR 1.53, 95% CI 1.13-2.07). Findings were consistent across sensitivity and subgroup analyses. External validation confirmed reduced dementia risk versus DPP4is but not versus SGLT2is. CONCLUSIONS: In this large real-world cohort, GLP-1 RAs were associated with lower dementia risk than DPP4is but higher risk than SGLT2is. Prospective, biomarker-informed studies are needed to clarify mechanisms and inform treatment choices in older adults with T2D. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zhou, Ting AU - Zhou T AUID- ORCID: 0000-0003-3392-2979 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhang, Dazheng AU - Zhang D AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Li, Lu AU - Li L AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Chen, Jiajie AU - Chen J AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0009-0006-9094-7012 AD - Pfizer, New York City, New York, USA. FAU - Asch, David A AU - Asch DA AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Division of General Internal Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence-Based Practice (CEP), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Institute for Biomedical Informatics (IBI), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - R01DK128237/NH/NIH HHS/United States GR - R01AG073435/NH/NIH HHS/United States GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - R21AI167418/NH/NIH HHS/United States GR - RF1 AG077820/AG/NIA NIH HHS/United States GR - R01 LM013519/LM/NLM NIH HHS/United States GR - U24 MH136069/MH/NIMH NIH HHS/United States GR - R56AG074604/NH/NIH HHS/United States GR - RF1AG077820/NH/NIH HHS/United States GR - R01LM013519/NH/NIH HHS/United States GR - R21 AI167418/AI/NIAID NIH HHS/United States GR - R21EY034179/NH/NIH HHS/United States GR - U01 TR003709/TR/NCATS NIH HHS/United States GR - U24MH136069/NH/NIH HHS/United States GR - R56 AG074604/AG/NIA NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - R21 EY034179/EY/NEI NIH HHS/United States GR - U01TR003709/NH/NIH HHS/United States PT - Journal Article DEP - 20251222 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Dementia/epidemiology/chemically induced MH - Female MH - Aged MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - Risk Factors MH - Aged, 80 and over MH - Incidence PMC - PMC12890729 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - cohort study OT - elderly OT - pharmaco-epidemiology OT - real-world evidence COIS- Dr. David Asch is a partner and part-owner of VAL Health and serves on the advisory boards of Thrive Global and Morpheus. Dr. Yong Chen (University of Pennsylvania) reported receiving personal fees from Merck & Co., Inc. and Pfizer Inc. outside the submitted work. Dr. Yong Chen (Pfizer, New York City, NY, USA) is a Pfizer employee and owns Pfizer stock. No potential conflicts of interest relevant to this article were reported by Ting Zhou, Huilin Tang, Bingyu Zhang, Dazheng Zhang, Yiwen Lu, Lu Li, and Jiajie Chen. EDAT- 2025/12/22 06:29 MHDA- 2026/02/11 00:40 PMCR- 2026/02/11 CRDT- 2025/12/22 04:43 PHST- 2025/12/04 00:00 [revised] PHST- 2025/09/16 00:00 [received] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/02/11 00:40 [medline] PHST- 2025/12/22 06:29 [pubmed] PHST- 2025/12/22 04:43 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - DOM70384 [pii] AID - 10.1111/dom.70384 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):1984-1996. doi: 10.1111/dom.70384. Epub 2025 Dec 22. PMID- 41424191 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260812 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Impact of glucagon-like peptide-1 receptor agonism-based therapies on limb outcomes in peripheral artery disease and type 2 diabetes: An updated systematic review and meta-analysis. PG - 2075-2084 LID - 10.1111/dom.70391 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonism (GLP1RA)-based therapies (GLP1RA-BTs) form the cornerstone for managing type 2 diabetes (T2D) and obesity. However, their impact on limb-specific outcomes in peripheral artery disease (PAD) remains unclear. This systematic-review and meta-analysis evaluated the safety and efficacy of GLP1RA-BTs on limb outcomes in PAD and T2D. MATERIALS AND METHODS: Electronic databases were searched for studies involving GLP1RA-BTs in PAD and/or T2D. Primary outcome was the major adverse limb events (MALEs). Secondary outcomes were all-cause mortality, revascularization, amputation, major adverse cardiovascular events (MACE), cardiovascular mortality, myocardial infarction (MI), stroke, hospitalization for heart-failure (HHF), and amputations. Analyses were performed separately for studies exclusively enrolling patients with PAD (PAD cohort) and for those in broader T2D populations reporting limb outcomes but not limited to PAD, in which PAD comprised <15% of participants (T2D cohort). RESULTS: Data from 10 studies for PAD cohort (352 743 patients) and 7 studies for T2D cohort (1 759 799 patients) were analysed. In PAD cohort, MALE [OR 0.66 (0.44, 1.00); p = 0.05; I(2) = 94%], all-cause mortality [OR 0.55 (0.38, 0.78); p = 0.0008; I(2) = 97%], MACE [OR 0.68 (0.52, 0.88); p = 0.004; I(2) = 85%], and MI [OR 0.68 (0.51, 0.91); p = 0.009; I(2) = 42%] were lower in patients on GLP1RA-BTs compared to controls. In the PAD cohort, need for revascularization was significantly lower in GLP1RA-BTs than in controls [OR 0.85 (0.80, 0.90); p < 0.001; I(2) = 0%]. In the T2D cohort, MALE [OR 0.70 (0.57, 0.85); p = 0.0005; I(2) = 0%], amputations [OR 0.58 (0.48, 0.69); p < 0.001; I(2) = 0%], and all-cause mortality [OR 0.55 (0.43, 0.69); p < 0.001; I(2) = 85%] were significantly lower in GLP1RA-BT compared to controls. CONCLUSIONS: GLP1RA-BTs are beneficial in PAD, especially in reducing the need for revascularization. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Dutta, Deep AU - Dutta D AUID- ORCID: 0000-0003-4915-8805 AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, New Delhi, India. FAU - Mahajan, Kunal AU - Mahajan K AUID- ORCID: 0000-0001-9378-6505 AD - Department of Cardiology, Himachal Heart Institute, Mandi, India. FAU - Kamrul-Hasan, Abul Bashar Mohammad AU - Kamrul-Hasan ABM AUID- ORCID: 0000-0002-5681-6522 AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. FAU - Mahajan, Nitin AU - Mahajan N AUID- ORCID: 0000-0002-0907-6410 AD - Translational Research and Data Science Consultant, USA. FAU - Sharma, Meha AU - Sharma M AD - Department of Rheumatology, CEDAR Superspeciality Healthcare, New Delhi, India. FAU - Vohra, Shekhar AU - Vohra S AUID- ORCID: 0009-0008-6909-5454 AD - Mount Sinai Morningside, Icahn School of Medicine at Mount Sinai, New York, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251222 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Peripheral Arterial Disease/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Amputation, Surgical/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - *Diabetic Angiopathies/drug therapy MH - Male OTO - NOTNLM OT - cardiovascular outcomes OT - liraglutide OT - peripheral artery disease OT - semaglutide OT - tirzepatide EDAT- 2025/12/22 06:29 MHDA- 2026/02/11 00:39 CRDT- 2025/12/22 04:23 PHST- 2025/12/02 00:00 [revised] PHST- 2025/11/05 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/02/11 00:39 [medline] PHST- 2025/12/22 06:29 [pubmed] PHST- 2025/12/22 04:23 [entrez] AID - 10.1111/dom.70391 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2075-2084. doi: 10.1111/dom.70391. Epub 2025 Dec 22. PMID- 41422027 OWN - NLM STAT- MEDLINE DCOM- 20260203 LR - 20261004 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2025 Dec 20 TI - Once-weekly semaglutide versus placebo for the treatment of type 2 diabetes and chronic kidney disease in Denmark: A long-term cost-effectiveness analysis based on FLOW. PG - 32 LID - 10.1186/s12933-025-03002-1 [doi] LID - 32 AB - BACKGROUND: The FLOW clinical trial recently demonstrated that the glucagon-like peptide-1 receptor agonist once-weekly semaglutide 1 mg was associated with kidney- and cardio-protective effects (the latter already shown in the SUSTAIN 6 trial) compared with placebo, both in addition to standard of care (SoC), in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study assessed the long-term cost-effectiveness of semaglutide versus placebo in people with T2D and CKD in Denmark, based on outcomes from FLOW. METHODS: Life expectancy, quality-adjusted life expectancy, cumulative incidence of diabetes-related complications, and costs were projected over a lifetime time horizon using the PRIME T2D Model. Baseline cohort characteristics and changes in risk factors with semaglutide and placebo were taken from FLOW, with extrapolation over patient lifetimes. Outcomes were assessed for the full population and subgroups receiving/not receiving sodium-glucose cotransporter-2 (SGLT-2) inhibitors at baseline. Quality-of-life disutilities and Denmark-specific costs (expressed in 2023 Danish Kroner [DKK]) were applied to capture the impact of diabetes-related complications and pharmacy costs. RESULTS: Treatment with semaglutide was projected to improve long-term quality-adjusted life expectancy by 0.60 quality-adjusted life years (QALYs) compared with placebo in the full population and by 0.44 and 0.62 QALYs in subgroups receiving/not receiving SGLT-2 inhibitors at baseline, respectively. Differences were predominantly driven by a reduced incidence of kidney failure with semaglutide versus placebo. Semaglutide was associated with long-term, per-person cost savings of DKK 6,068 in the full population and DKK 9,212 in those not receiving SGLT-2 inhibitors at baseline, leading to semaglutide being a dominant treatment compared with placebo. In patients receiving SGLT-2 inhibitors at baseline, semaglutide was cost-effective with an ICER of DKK 19,167 per QALY gained. CONCLUSIONS: Adding semaglutide to SoC was projected to be highly cost-effective over the long term in people with T2D and CKD in a Danish healthcare setting, based on patient characteristics and treatment effects from FLOW. Trial registration NCT03819153, first submitted on January 18, 2019. CI - (c) 2026. The Author(s). FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Complication Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Lindhardt, Morten AU - Lindhardt M AUID- ORCID: 0000-0001-6063-1718 AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Internal Medicine, Copenhagen University Hospital Holbaek, Holbaek, Denmark. FAU - Tikkanen, Christian Klyver AU - Tikkanen CK AUID- ORCID: 0000-0003-4474-6237 AD - Novo Nordisk Denmark A/S, Copenhagen, Denmark. FAU - Menon, Jyothi AU - Menon J AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Cattin, Juliette AU - Cattin J AUID- ORCID: 0009-0001-2528-4359 AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. hunt@ossianconsulting.com. FAU - Malkin, Samuel J P AU - Malkin SJP AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Chubb, Barrie AU - Chubb B AUID- ORCID: 0000-0001-7271-051X AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Damgaard, Tina AU - Damgaard T AUID- ORCID: 0009-0005-8595-6187 AD - Novo Nordisk Denmark A/S, Copenhagen, Denmark. FAU - Borg, Rikke AU - Borg R AUID- ORCID: 0000-0002-2283-3578 AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Medicine, Zealand University Hospital, Roskilde, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251220 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Cost-Benefit Analysis MH - Denmark/epidemiology MH - *Glucagon-Like Peptides/administration & dosage/economics/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/economics/diagnosis/epidemiology/mortality MH - Time Factors MH - *Renal Insufficiency, Chronic/economics/drug therapy/diagnosis/epidemiology/mortality MH - Treatment Outcome MH - Male MH - Female MH - *Hypoglycemic Agents/administration & dosage/adverse effects/economics MH - Quality-Adjusted Life Years MH - *Drug Costs MH - Middle Aged MH - Drug Administration Schedule MH - Models, Economic MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/economics/adverse effects/administration & dosage MH - Cost Savings MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Glucose/drug effects/metabolism MH - Life Expectancy MH - Cost-Effectiveness Analysis PMC - PMC12862915 OTO - NOTNLM OT - Chronic kidney disease OT - Cost-effectiveness analysis OT - End-stage kidney disease OT - GLP-1 receptor agonist OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Consent for publication: No individual patient data is included in the manuscript. Competing interests: PR has served as consultant on advisory boards for Astra Zeneca, Abbott, Bayer, Novartis, Boehringer Ingelheim, Gilead and Sanofi (honoraria to his institution); has received unrestricted grants (to his institution) from Astra Zeneca, Bayer, and Novo Nordisk; and grants from Bayer, Novo Nordisk and Lexicon pharmaceuticals (study medication to investigator initiated study). ML has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and GlaxoSmithKline. RB reports honoraria for education and consultancy from Astra Zeneca, Bayer, Novo Nordisk and Boehringer Ingelheim. She is an investigator in clinical studies sponsored by Boehringer Ingelheim, AstraZeneca or Bayer; and has received unrestricted research grants from Boehringer Ingelheim. JM and BC are employees of Novo Nordisk A/S. CKT and TD are employees of Novo Nordisk Denmark A/S. JC, BH and SJPM are employees of Ossian Health Economics and Communications. Ossian received consulting fees from Novo Nordisk A/S to support the preparation of the analysis. EDAT- 2025/12/21 01:48 MHDA- 2026/02/03 07:41 PMCR- 2025/12/20 CRDT- 2025/12/20 23:15 PHST- 2025/08/29 00:00 [received] PHST- 2025/10/28 00:00 [accepted] PHST- 2026/02/03 07:41 [medline] PHST- 2025/12/21 01:48 [pubmed] PHST- 2025/12/20 23:15 [entrez] PHST- 2025/12/20 00:00 [pmc-release] AID - 10.1186/s12933-025-03002-1 [pii] AID - 3002 [pii] AID - 10.1186/s12933-025-03002-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Dec 20;25(1):32. doi: 10.1186/s12933-025-03002-1. PMID- 41420258 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1758-9193 (Electronic) VI - 17 IP - 1 DP - 2025 Dec 20 TI - Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study. PG - 269 LID - 10.1186/s13195-025-01929-x [doi] LID - 269 AB - BACKGROUND: We aim to investigate comparative dementia risk associated with glucagon-like peptide-1 receptor agonists (GLP1-RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP4i) in adults aged >/= 60 years with type 2 diabetes. METHODS: This target trial emulation cohort study used primary care electronic health records from the UK Clinical Practice Research Datalink. Initiators of GLP1-RAs, SGLT2i, or DPP4i aged >/= 60 years with type 2 diabetes and without cognitive impairment were compared pairwise in three separate analyses. After propensity scores overlap weighting, 13,965 pairs of GLP1-RA versus DPP4i initiators (cohort entry: 2006-2022; mean age: 66.9 years), 25,533 pairs of SGLT2i versus DPP4i initiators (cohort entry: 2013-2022; mean age: 69.0 years), and 14,214 pairs of GLP1-RA versus SGLT2i initiators (cohort entry: 2013-2022; mean age: 67.9 years) were analyzed. The primary outcome was incident all-cause dementia. The primary analysis was an intention-to-treat analysis. A secondary as-treated analysis for continuous use was performed. RESULTS: In the intention-to-treat analysis, dementia risk was not different between GLP1-RA and DPP4i initiators (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.87-1.04; rates: 6.29 versus 6.64 per 1000 person-years; mean follow-up: 6.54 years); however, continuous GLP1-RA versus DPP4i use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64-0.97; rates: 3.64 versus 4.82; mean follow-up: 2.71 years). SGLT2i versus DPP4i initiation was associated with a 14% lower dementia risk in the intention-to-treat analysis (HR 0.86, 95% CI 0.79-0.94; rates: 4.83 versus 5.60; mean follow-up: 4.91 years), and the as-treated analysis showed greater risk reduction (HR 0.70, 95% CI 0.60-0.82; rates: 3.82 versus 5.46; mean follow-up: 2.43 years). Dementia risk was comparable between GLP1-RA versus SGLT2i in both intention-to-treat (HR 0.98, 95% CI 0.87-1.11; rates: 4.85 versus 4.95; mean follow-up: 5.09 years) and as-treated (HR 1.07, 95% CI 0.85-1.36; rates: 3.71 versus 3.56; mean follow-up: 2.40 years) analyses. CONCLUSIONS: In people with type 2 diabetes aged >/= 60 years, SGLT2i are associated with reduced dementia risk, but dementia risk reduction associated with the GLP1-RAs studied is less certain. FAU - Wu, Che-Yuan AU - Wu CY AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. AD - Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Alkabbani, Wajd AU - Alkabbani W AD - School of Pharmacy, University of Waterloo, Kitchener, ON, Canada. FAU - Shah, Baiju R AU - Shah BR AD - Division of Endocrinology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. AD - Department of Medicine, University of Toronto, Toronto, ON, Canada. AD - ICES, Toronto, ON, Canada. FAU - Kapral, Moira K AU - Kapral MK AD - ICES, Toronto, ON, Canada. AD - Division of General Internal Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada. AD - Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. FAU - Edwards, Jodi D AU - Edwards JD AD - School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada. AD - ICES uOttawa, Ottawa, ON, Canada. FAU - Maxwell, Colleen J AU - Maxwell CJ AD - School of Pharmacy, University of Waterloo, Kitchener, ON, Canada. AD - ICES, Toronto, ON, Canada. AD - School of Public Health Sciences, University of Waterloo, Waterloo, ON, Canada. FAU - Swardfager, Walter AU - Swardfager W AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. w.swardfager@utoronto.ca. AD - Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada. w.swardfager@utoronto.ca. AD - KITE University Health Network Toronto Rehabilitation Institute, Toronto, ON, Canada. w.swardfager@utoronto.ca. LA - eng GR - 202111FBD-47623-75801/CAPMC/CIHR/Canada GR - GC-202209-2024050/Alzheimer's Drug Discovery Foundation/ GR - CRC-2024-00213/Canada Excellence Research Chairs, Government of Canada/ GR - ER21-16-146/Ministry of Colleges and Universities/ PT - Comparative Study PT - Journal Article DEP - 20251220 PL - England TA - Alzheimers Res Ther JT - Alzheimer's research & therapy JID - 101511643 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Dementia/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Aged MH - Female MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - United Kingdom/epidemiology PMC - PMC12751920 OTO - NOTNLM OT - 1 (GLP1) receptor agonist, Dipeptidyl peptidase OT - 2 (SGLT2) inhibitor, Glucagon OT - 4 (DPP4) inhibitors, Diabetes, Dementia OT - Glucose cotransporter OT - Like peptide OT - Sodium COIS- Declarations. Ethics approval and consent for publication: The present study was approved by the CPRD Research Data Governance (#23_002545), the Research Ethics Board of Sunnybrook Health Sciences Centre (PIN: 6013), and the Research Ethics Board of University of Toronto (#46463). Competing interests: The authors declare no competing interests. EDAT- 2025/12/20 06:31 MHDA- 2026/06/27 00:55 PMCR- 2025/12/20 CRDT- 2025/12/20 00:18 PHST- 2025/08/18 00:00 [received] PHST- 2025/12/03 00:00 [accepted] PHST- 2026/06/27 00:55 [medline] PHST- 2025/12/20 06:31 [pubmed] PHST- 2025/12/20 00:18 [entrez] PHST- 2025/12/20 00:00 [pmc-release] AID - 10.1186/s13195-025-01929-x [pii] AID - 1929 [pii] AID - 10.1186/s13195-025-01929-x [doi] PST - epublish SO - Alzheimers Res Ther. 2025 Dec 20;17(1):269. doi: 10.1186/s13195-025-01929-x. PMID- 41419667 OWN - NLM STAT- MEDLINE DCOM- 20260122 LR - 20260902 IS - 2662-8465 (Electronic) IS - 2662-8465 (Linking) VI - 6 IP - 1 DP - 2026 Jan TI - Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders. PG - 56-67 LID - 10.1038/s43587-025-01029-3 [doi] AB - With therapeutic progress in Alzheimer's disease (AD), more molecular and mechanistic targets are coming into focus. Beyond amyloid, emerging targets include tau, neuroinflammation and neurotransmitters. Targeting neuroinflammation in neurodegenerative diseases has been explored using cyclooxygenase inhibitors, but it has mostly been unsuccessful. Among the drug classes under investigation for AD are the glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are approved for the treatment of type 2 diabetes (T2D), obesity and cardiovascular disease. GLP-1RAs are candidate treatments for AD based on several concepts. First, epidemiological data reveal that patients with T2D and cardiovascular disease receiving GLP-1RAs have substantial reductions in the risk of developing all-cause dementia. Second, GLP-1RAs reduce neuroinflammatory changes in preclinical models. Clinical trials have not yet shown that GLP-1RAs can slow the rate of cognitive decline in mild cognitive impairment and mild dementia due to AD. Here, we summarize data supporting the use of GLP-1RAs for the treatment of neurodegenerative diseases, with a focus on AD. CI - (c) 2025. Springer Nature America, Inc. FAU - Sabbagh, Marwan N AU - Sabbagh MN AUID- ORCID: 0000-0001-8139-3309 AD - Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA. marwan.sabbagh@barrowneuro.org. FAU - Cummings, Jeffrey L AU - Cummings JL AUID- ORCID: 0000-0001-8944-4158 AD - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV, USA. FAU - Ballard, Clive AU - Ballard C AUID- ORCID: 0000-0003-0022-5632 AD - Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK. FAU - van der Flier, Wiesje M AU - van der Flier WM AUID- ORCID: 0000-0001-8766-6224 AD - Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, Netherlands. AD - Amsterdam Neuroscience, Neurodegeneration, Amsterdam, Netherlands. AD - Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, Netherlands. FAU - Heneka, Michael T AU - Heneka MT AUID- ORCID: 0000-0003-4996-1630 AD - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg. FAU - Holst, Jens Juul AU - Holst JJ AD - Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Knudsen, Lotte Bjerre AU - Knudsen LB AD - Chief Scientific Advisor Office, Novo Nordisk A/S, Malov, Denmark. FAU - Salloway, Stephen AU - Salloway S AD - Warren Alpert Medical School, Brown University, Providence, RI, USA. FAU - Tansey, Malu Gamez AU - Tansey MG AUID- ORCID: 0000-0002-1719-4708 AD - Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. LA - eng GR - R01 AG059008/AG/NIA NIH HHS/United States GR - R35 AG071476/AG/NIA NIH HHS/United States GR - R25 AG083721/AG/NIA NIH HHS/United States GR - P30 AG072980/AG/NIA NIH HHS/United States GR - R01 NS139383/NS/NINDS NIH HHS/United States GR - P20 GM109025/GM/NIGMS NIH HHS/United States GR - RF1 NS128800/NS/NINDS NIH HHS/United States GR - R01 AG073212/AG/NIA NIH HHS/United States PT - Journal Article PT - Review DEP - 20251219 PL - United States TA - Nat Aging JT - Nature aging JID - 101773306 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neurodegenerative Diseases/drug therapy MH - *Alzheimer Disease/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - *Drug Repositioning MH - Animals MH - Cognitive Dysfunction/drug therapy PMC - PMC13528608 MID - NIHMS2134733 COIS- Competing interests: M.N.S. discloses ownership interest (stock or stock options) in Lighthouse Pharmaceuticals; he consults for Eisai, Lilly, NeuroTherapia, Signant Health, Novo Nordisk, Anavex Life Sciences, Alzheon, Cognito Therapeutics, GSK and AbbVie. M.N.S. is supported by the National Institutes of Health grants R01AG059008, R01AG073212 and P30AG072980, as well as by the Barrow Neurological Foundation. J.L.C. has provided consultation to Acadia Pharmaceuticals, Acumen Pharmaceuticals, ALZpath, Annovis, Aprinoia Therapeutics, Artery Therapeutics, Biogen, Biohaven, BioXcel, Bristol Myers Squibb, Eisai, Fosun, GAP Foundation, Green Valley, Janssen, Karuna, Kinoxis Therapeutics, Lighthouse Pharmaceuticals, Lilly, Lundbeck, LSP/EQT Life Sciences, Mangrove Therapeutics, Merck, MoCA Cognition, New Amsterdam, Novo Nordisk, OptoCeutics, Otsuka, Oxford Brain Diagnostics, Praxis, Prothena, reMYND, Roche, Scottish Brain Sciences, Signant Health, Simcere, Sinaptica, T-Neuro, TrueBinding and Vaxxinity pharmaceutical, assessment and investment companies. J.L.C. is supported by the National Institute of General Medical Sciences (NIGMS) grant P20GM109025, National Institute on Aging (NIA) grants R35AG71476 and R25AG083721-01, National Institute of Neurological Disorders and Stroke (NINDS) grant RO1NS139383, the Alzheimer's Drug Discovery Foundation (ADDF), Ted and Maria Quirk Endowment, and Joy Chambers-Grundy Endowment. C.B. has received contract grant funding from Acadia Pharmaceuticals, Lundbeck, Takeda and Axovant pharmaceutical companies, as well as honoraria from Lundbeck, Lilly, Otsuka and Orion pharmaceutical companies. W.M.v.d.F. declares having research programs that have been funded by ZonMw, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland (Topsector Life Sciences & Health), Stichting Dioraphte, Gieskes-Strijbis Fonds, Stichting Equilibrio, Edwin Bouw Fonds, Pasman Stichting, Stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc., Novartis-NL, Life-MI, AVID, Roche BV, Eli Lilly-NL, Fujifilm, Eisai and Combinostics. W.M.v.d.F. holds the Pasman chair. W.M.v.d.F. is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMw (#73305095007) and Health~Holland (Topsector Life Sciences & Health) (public-private partnership allowance; #LSHM20106). W.M.v.d.F. is a recipient of TAP-dementia ( www.tap-dementia.nl ), which receives funding from ZonMw (#10510032120003). TAP-dementia receives cofinancing from Avid Radiopharmaceuticals and Amprion. All funding is paid to her institution. W.M.v.d.F. has been an invited speaker at Biogen MA Inc., Danone, Eisai, WebMD Neurology (Medscape), Novo Nordisk, Springer Healthcare and European Brain Council. All funding is paid to her institution. W.M.v.d.F. is a consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc. and Eisai. All funding is paid to her institution. W.M.v.d.F. participated in the advisory boards of Biogen MA Inc., Roche and Eli Lilly. W.M.v.d.F. is a member of the steering committee of evoke/evoke+ (Novo Nordisk). All funding is paid to her institution. W.M.v.d.F. is a member of the steering committee of PAVE and Think Brain Health. W.M.v.d.F. was an associate editor of Alzheimer's Research & Therapy in 2020/2021 and is an associate editor at Brain. M.T.H. serves on the science advisory board of the UK Dementia Research Institute at Imperial College London, Life and Health Sciences Research Institute of the University of Minho School of Medicine, the Lyon Neuroscience Research Center, Alector, Muna Therapeutics and T3D Therapeutics. He has received speaking honoraria from Novo Nordisk, Novartis, Biogen and Eli Lilly. J.J.H. consults for Novo Nordisk and is the founder of Antag Pharmaceuticals. L.B.K. is an employee and a minor employee related shareholder of Novo Nordisk A/S. L.B.K. is an inventor on several patents related to GLP-1-based medicines and various uses of them. S.S. has provided consultation to Eisai, Biogen, Lilly, Roche, Genentech, Bolden, Novo Nordisk, Prothena, Acumen Pharmaceuticals, Labcorp, Alector, Corium, Kisbee, Neurophet, Icometrix and AbbVie. S.S. receives research support for clinical trials from Janssen, Lilly, Eisai, Genentech, Roche and Biogen. S.S. is an associate editor of the Journal of Prevention of Alzheimer's Disease and Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. M.G.T. is supported by NINDS grant RF1NS128800, the Michael J. Fox Foundation for Parkinson's Research and the Parkinson's Foundation. She has provided consultation to INmune Bio, Merck, Calico, Forward Therapeutics, Jaya, SciNeuro, NysnoBio, Longevity Biotech, Sanofi, iMetabolic Pharma, Novo Nordisk and iMMvention. She serves on advisory boards for the Weston Family Foundation, the Medical and Scientific Advisory Group of the Alzheimer's Association, Longeveron and the Parkinson's Foundation. D.J.D. has been a supported speaker or consultant for AstraZeneca, Boehringer Ingelheim, Kallyope, Merck, Novo Nordisk and Pfizer, as well as receives grant support for preclinical studies from Amgen, Zealand Pharma and Eli Lilly. EDAT- 2025/12/20 00:41 MHDA- 2026/01/22 07:43 PMCR- 2026/08/31 CRDT- 2025/12/19 23:33 PHST- 2025/03/25 00:00 [received] PHST- 2025/10/31 00:00 [accepted] PHST- 2026/01/22 07:43 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 23:33 [entrez] PHST- 2026/08/31 00:00 [pmc-release] AID - 10.1038/s43587-025-01029-3 [pii] AID - 10.1038/s43587-025-01029-3 [doi] PST - ppublish SO - Nat Aging. 2026 Jan;6(1):56-67. doi: 10.1038/s43587-025-01029-3. Epub 2025 Dec 19. PMID- 41419618 OWN - NLM STAT- MEDLINE DCOM- 20260322 LR - 20261009 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 69 IP - 5 DP - 2026 May TI - Efficacy of tirzepatide versus semaglutide in achieving therapeutic targets in type 2 diabetes: a post hoc analysis of the SURPASS-2 Trial. PG - 1216-1225 LID - 10.1007/s00125-025-06637-7 [doi] AB - AIMS/HYPOTHESIS: Simultaneous control of HbA(1c), lipid profile, BP and body weight is essential for preventing chronic complications of type 2 diabetes. Glucagon-like peptide-1 (GLP-1)-based therapies improve all these variables but whether the dual GLP-1 / glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide is superior to semaglutide in attaining therapeutic targets remains unclear. METHODS: We performed a post hoc analysis of the SURPASS-2 trial, a randomised phase 3 study including 1879 adults with type 2 diabetes. Participants were randomised to receive tirzepatide (5, 10 or 15 mg) or semaglutide (1 mg). In this analysis, we compared the effects of tirzepatide vs semaglutide on the attainment of standard (HbA(1c) <53 mmol/mol [7%], BP <140/90 mmHg, LDL-cholesterol <1.8 mmol/l, >10% weight loss) and intensive (HbA(1c) <48 mmol/mol [6.5%], BP <130/80 mmHg, LDL-cholesterol <1.4 mmol/l , >15% weight loss) therapeutic targets at 40 weeks. RESULTS: In the SURPASS-2 trial, at baseline, 19% of participants were on target for attaining no standard goals, 59% for one goal and 21% for two or more goals. For intensive therapeutic targets, 58% of participants were on target for attaining zero goals, 38% for one goal and 4% for two goals. All doses of tirzepatide increased the number of achieved standard and intensive targets compared with semaglutide. For standard targets, 34% of participants treated with semaglutide met three or more targets, compared with 42%, 53% and 57% with tirzepatide 5, 10 and 15 mg, respectively. For intensive targets, 8% of participants treated with semaglutide met three or more targets, vs 15%, 20% and 29% with tirzepatide. Regarding specific therapeutic goals, tirzepatide increased the odds of achieving standard and intensive targets for HbA(1c) (HbA(1c) <53 mmol/mol [7%], OR 1.50 [95% CI 1.12, 2.00]; HbA(1c) <48 mmol/mol [6.5%], OR 1.88 [95%CI 1.49, 2.36]) and weight loss (weight loss >10%, OR 2.72 [95% CI 2.14, 3.47]; weight loss >15%, OR 3.86 [95% CI 2.69, 5.55]) and the intensive target for BP (OR 1.45 [95% CI 1.17, 1.81]). CONCLUSIONS/INTERPRETATION: Tirzepatide improves therapeutic target attainment compared with semaglutide in type 2 diabetes. Longer trials are needed to confirm benefits on long-term prognosis. DATA AVAILABILITY: Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Neves, Joao Sergio AU - Neves JS AUID- ORCID: 0000-0002-8173-8255 AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. jsneves@med.up.pt. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. jsneves@med.up.pt. FAU - Leite, Ana Rita AU - Leite AR AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. FAU - Vale, Catarina AU - Vale C AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Marques, Pedro AU - Marques P AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Vasques-Novoa, Francisco AU - Vasques-Novoa F AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Leite-Moreira, Adelino AU - Leite-Moreira A AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Cardiothoracic Surgery, ULS Sao Joao, Porto, Portugal. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques - Plurithematique 14-33, Nancy, France. AD - Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20251219 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Aged MH - Blood Glucose/metabolism/drug effects MH - Adult MH - Gastric Inhibitory Polypeptide MH - Blood Pressure/drug effects MH - Treatment Outcome OTO - NOTNLM OT - GLP-1/GIP agonist OT - Glucagon-like peptide-1 therapies OT - Post hoc analysis OT - Semaglutide OT - Therapeutic goals OT - Tirzepatide OT - Type 2 diabetes COIS- Acknowledgements: This publication is based on research using data from data contributors Eli Lilly that have been made available through Vivli. Vivli has not contributed to or approved, and Vivli and Eli Lilly are not in any way responsible for, the contents of this publication. An abstract reporting part of the results presented here was submitted to the Endocrine Society's annual meeting ENDO 2025 (12 July 2025 to 15 July 2025, San Francisco, CA, USA). Data availability: Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors' relationships and activities: JSN reports having received consulting and speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Eli Lilly and Novo Nordisk and speaker fees from Merck. ARL reports having received consulting fees from BIAL. PM received salary support from an educational grant by Janssen. FVN has received consultancy fees and/or research support from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis and Ultragenyx. ALM has received research support from Boehringer Ingelheim, AstraZeneca, Novartis. JPF has received research support from Boehringer Ingelheim, AstraZeneca, Novartis, Bial, Salamandra and Bayer. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: JSN, ARL and JPF conceived and designed the study. JSN and ARL performed the data analysis. CV, PM, FVN, ALM and JPF provided methodological and statistical guidance. All authors contributed to the interpretation of the data. JSN and ARL drafted the first version of the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version to be submitted. JSN and ARL are the guarantors of this work and, as such, had full access to all the data in the analysis and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2025/12/20 00:41 MHDA- 2026/03/22 07:35 CRDT- 2025/12/19 23:31 PHST- 2025/05/17 00:00 [received] PHST- 2025/10/21 00:00 [accepted] PHST- 2026/03/22 07:35 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 23:31 [entrez] AID - 10.1007/s00125-025-06637-7 [pii] AID - 10.1007/s00125-025-06637-7 [doi] PST - ppublish SO - Diabetologia. 2026 May;69(5):1216-1225. doi: 10.1007/s00125-025-06637-7. Epub 2025 Dec 19. PMID- 41419187 OWN - NLM STAT- MEDLINE DCOM- 20260416 LR - 20260730 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 4 DP - 2026 Apr TI - Semaglutide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits. PG - 623-635 LID - S1530-891X(25)01331-X [pii] LID - 10.1016/j.eprac.2025.11.018 [doi] AB - OBJECTIVES: To evaluate semaglutide's multisystem therapeutic benefits across 12 health domains. Primary outcomes were major adverse cardiovascular events, resolution of metabolic dysfunction-associated steatohepatitis, and composite renal endpoints. METHODS: PubMed, Embase, and Cochrane Central were searched through June 30, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies included randomized controlled trials in adults (>/=18 years) with >/=24-week follow-up comparing semaglutide (>/=0.5 mg weekly subcutaneous or >/=7 mg daily oral) versus placebo or active comparators. Two reviewers independently extracted data and assessed bias (RoB 2) and certainty (GRADE). RESULTS: Thirty-five trials (n = 36 847; mean age 54.2 years; body mass index: 34.8 kg/m(2)) were included. Semaglutide reduced glycated hemoglobin (-1.52%, 95% confidence interval [CI]: -1.60 to -1.44) and weight (-12.4 kg, 95% CI: -13.0 to -11.8). Non-glycemic benefits included major adverse cardiovascular events reduction (16%, risk ratio [RR]: 0.84, 95% CI: 0.77-0.92), metabolic dysfunction-associated steatohepatitis resolution (62.9%, RR: 1.84, 95% CI: 1.49-2.27), renal protection (HR: 0.76, 95% CI: 0.68-0.85), improved vascular function (+87 m walking distance), favorable body composition (87:13 fat-to-lean ratio), and better quality of life (+3.8 SF-36 points). No increase was observed in psychiatric or cancer risk. CONCLUSIONS: Semaglutide confers robust, consistent multisystem benefits-including cardiovascular, hepatic, and renal protection-supporting its role as a transformative, disease-modifying therapy for metabolic disease beyond diabetes and obesity management. These findings support using semaglutide as a comprehensive, disease-modifying therapy for complex metabolic disorders, guiding clinicians to integrate it into patient-centered care for multisystem benefits beyond glycemic and obesity control. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Eisa, Naseem AU - Eisa N AD - Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Community Health Partners, Fresno, California. Electronic address: NEisa@communitymedical.org. FAU - Barood, Omar AU - Barood O AD - Damascus University, Faculty of Medicine, Damascus, Syria. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251217 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cardiovascular Diseases/prevention & control MH - Randomized Controlled Trials as Topic MH - Glycated Hemoglobin OTO - NOTNLM OT - GLP-1 receptor agonist OT - MASH OT - Semaglutide OT - cardiometabolic disease OT - obesity OT - type 2 diabetes COIS- Disclosure The authors declare no conflicts of interest related to this work. Neither author has received consulting fees, honoraria, stock ownership, or any other financial relationship with pharmaceutical companies or entities related to semaglutide or GLP-1 receptor agonists. EDAT- 2025/12/20 00:41 MHDA- 2026/04/19 17:41 CRDT- 2025/12/19 19:41 PHST- 2025/10/08 00:00 [received] PHST- 2025/11/05 00:00 [revised] PHST- 2025/11/21 00:00 [accepted] PHST- 2026/04/19 17:41 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 19:41 [entrez] AID - S1530-891X(25)01331-X [pii] AID - 10.1016/j.eprac.2025.11.018 [doi] PST - ppublish SO - Endocr Pract. 2026 Apr;32(4):623-635. doi: 10.1016/j.eprac.2025.11.018. Epub 2025 Dec 17. PMID- 41419094 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20260319 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 139 IP - 4 DP - 2026 Apr TI - Cardio-renal outcomes in type 2 diabetes patients with advanced chronic kidney disease on SGLT2 inhibitors or GLP-1 receptor agonists. PG - 465-474 LID - S0002-9343(25)00839-3 [pii] LID - 10.1016/j.amjmed.2025.12.011 [doi] AB - BACKGROUND: GLP-1 RA and SGLT2i have demonstrated cardio-renal protective effects in randomized clinical trials. However, their comparative cardio-renal benefits in diabetes patients with stage 4-5 chronic kidney disease remain underexplored. METHODS: This is a retrospective study with target trial emulation design using TriNetX platform. Adults type 2 diabetes mellitus, stage 4-5 chronic kidney disease patients who were new initiation of GLP-1 RA compared to SGLT2i were enrolled. OUTCOMES: major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), and all-cause mortality. Hazard ratios (HRs) were calculated for outcomes in 1:1 propensity score-matched patients. RESULTS: A total of 7,458 participants were included in each group, with a mean eGFR of 23-24 mL/min/1.73 m(2). New users of GLP-1 RAs had a higher HR for MAKE (HR 1.05, 95% CI 1.0-1.1) & dialysis (HR 1.09, 95% CI 1.03-1.15), but similar HRs for all-cause mortality (HR 0.98, 95% CI 0.91-1.05) and MACE (HR 0.97, 95% CI 0.93-1.01) compared with SGLT2i users, despite a lower HR for heart failure (HR 0.94, 95% CI 0.90-0.99). Among new GLP-1 RA users, higher HRs for MAKE occurred in subgroup of males and patients without heart failure. CONCLUSIONS: In patients with type 2 diabetes and stage 4-5 chronic kidney disease, initiating an SGLT2i, relative to a GLP-1 RA, was associated with a lower risk of adverse kidney events and comparable cardiovascular and mortality risks. Further studies are warranted to confirm these findings. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Chen, Jia-Jin AU - Chen JJ AD - Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: raymond110234@hotmail.com. FAU - Tsai, Ming-Hsien AU - Tsai MH AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: chaosmyth.tw@gmail.com. FAU - Ho, Wen-Yu AU - Ho WY AD - Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: dolaamon145@gmail.com. FAU - Fang, Yu-Wei AU - Fang YW AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: m005916@gmail.com. FAU - Chen, Meng-Ting AU - Chen MT AD - Department of Healthcare Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. Electronic address: ggracee67@yahoo.com.tw. FAU - Hsiao, Ching-Chung AU - Hsiao CC AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan. Electronic address: colinhua0123@gmail.com. LA - eng PT - Journal Article DEP - 20251217 PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/complications MH - Aged MH - *Cardiovascular Diseases/epidemiology MH - Glomerular Filtration Rate MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Cardiovascular outcome OT - Chronic kidney disease stage 4-5 OT - Dialysis OT - GLP-1 RA OT - SGLT2i OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors (Jia-Jin Chen, Ming-Hsien Tsai, Wen-Yu Ho, Yu-Wei, Meng-ting Chen, Ching-Chung Hsiao) declare that they have no competing interests EDAT- 2025/12/20 00:41 MHDA- 2026/03/20 00:59 CRDT- 2025/12/19 19:35 PHST- 2025/08/21 00:00 [received] PHST- 2025/12/03 00:00 [revised] PHST- 2025/12/06 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 19:35 [entrez] AID - S0002-9343(25)00839-3 [pii] AID - 10.1016/j.amjmed.2025.12.011 [doi] PST - ppublish SO - Am J Med. 2026 Apr;139(4):465-474. doi: 10.1016/j.amjmed.2025.12.011. Epub 2025 Dec 17. PMID- 41418910 OWN - NLM STAT- MEDLINE DCOM- 20260313 LR - 20260313 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 50 IP - 2 DP - 2026 Mar TI - Use of Second-line Diabetes Mellitus Medications and Adverse Events Among Older Adults After the Introduction of Glucagon-like Peptide-1 Receptor Agonists in Ontario, Canada: A Retrospective Cohort Study. PG - 88-96.e5 LID - S1499-2671(25)00421-6 [pii] LID - 10.1016/j.jcjd.2025.12.009 [doi] AB - OBJECTIVE: Our aim in this study was to describe incident use of second-line diabetes medications and serious adverse events among older adults before and after the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: We conducted a population-based cohort study from June 2011 to March 2023 using administrative data from Ontario, Canada. We identified individuals >/=66 years of age with a new prescription for a second-line diabetes medication and recent history of metformin use. We also calculated the number and proportion of individuals using medications monthly with hypoglycemia and gastrointestinal events, stratified by drug class. Joinpoint models were used to determine whether any significant changes aligned with the introduction of GLP-1RAs RESULTS: Metformin was initially the most dispensed diabetes drug (peak 105,245 individuals treated in 2016), but its use was overtaken by second-line medications in 2019. Among second-line drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors were dominant (peak 77,477 individuals in 2020). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors surpassed DPP-4 inhibitor use in 2022. Adverse events of interest were rare; however, insulin had the highest percentage of individuals affected with hypoglycemia (average 0.13% per month), while more individuals using second-line medications were affected with gastrointestinal outcomes (average 0.23% for diverticular disease in those using GLP-1RAs). Joinpoint models did not reveal any breaks in trend during the time of GLP-1RA introduction. CONCLUSIONS: Metformin was the most common drug class used, but the use of second-line medications, such as SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1RAs, exceeded the number of individuals using metformin in recent years---a major shift from historic trends. CI - Copyright (c) 2026 Diabetes Canada. Published by Elsevier Inc. All rights reserved. FAU - Chu, Cherry AU - Chu C AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada. FAU - Ghahramani, Dorsa AU - Ghahramani D AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. FAU - Giannakeas, Vasily AU - Giannakeas V AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada. FAU - Jeyaparan, Jeyani AU - Jeyaparan J AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada. FAU - Bhattacharyya, Onil AU - Bhattacharyya O AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. FAU - Gomes, Tara AU - Gomes T AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Ontario Drug Policy Research Network, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. FAU - Ivers, Noah AU - Ivers N AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. FAU - Tadrous, Mina AU - Tadrous M AD - Women's College Hospital Research and Innovation Institute, Women's College Hospital, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Ontario Drug Policy Research Network, Toronto, Ontario, Canada. Electronic address: mina.tadrous@wchospital.ca. LA - eng PT - Journal Article DEP - 20251217 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Ontario/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Aged, 80 and over MH - Hypoglycemia/chemically induced/epidemiology MH - Metformin/therapeutic use/adverse effects MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology MH - Follow-Up Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Prognosis OTO - NOTNLM OT - agonistes du recepteur du GLP-1 OT - diabetes OT - diabetes medication OT - diabete OT - drug safety OT - drug use OT - glucagon-like peptide-1 receptor agonist OT - medicaments antidiabetiques OT - pharmacoepidemiology OT - pharmacoepidemiologie OT - securite des medicaments OT - utilisation des medicaments EDAT- 2025/12/20 00:40 MHDA- 2026/03/14 00:32 CRDT- 2025/12/19 19:32 PHST- 2025/02/14 00:00 [received] PHST- 2025/12/04 00:00 [revised] PHST- 2025/12/10 00:00 [accepted] PHST- 2026/03/14 00:32 [medline] PHST- 2025/12/20 00:40 [pubmed] PHST- 2025/12/19 19:32 [entrez] AID - S1499-2671(25)00421-6 [pii] AID - 10.1016/j.jcjd.2025.12.009 [doi] PST - ppublish SO - Can J Diabetes. 2026 Mar;50(2):88-96.e5. doi: 10.1016/j.jcjd.2025.12.009. Epub 2025 Dec 17. PMID- 41417476 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Beyond diabetes and obesity: GLP-1 receptor agonists in disrupting the vicious cycle of metabolic dysfunction and neuroinflammation. PG - 1622-1637 LID - 10.1111/dom.70400 [doi] AB - Neurodegenerative diseases, including debilitating conditions like Alzheimer's and Parkinson's, are characterized by progressive neuronal loss, a process fundamentally driven by persistent chronic neuroinflammation and central metabolic dysfunction. In these disorders, persistent danger signals, such as the aggregation of misfolded proteins, activate resident microglial cells, leading to a functional shift toward a detrimental, pro-inflammatory phenotype. This damaging cycle is critically exacerbated by impaired Insulin/Insulin-like Growth Factor 1 signalling, which compromises neuronal mitochondrial homeostasis, decreases energy production, and severely diminishes synaptic plasticity, thereby establishing a self-perpetuating cycle of metabolic disturbance and neuroinflammation. This review examines the burgeoning therapeutic potential of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), a class of drugs traditionally used to manage type 2 diabetes mellitus and obesity, as neuroprotective agents. We discuss mechanistic insights demonstrating how GLP-1RAs operate through a crucial dual action: effectively mitigating central insulin resistance and directly suppressing the multi-faceted neuroinflammatory cascade. By activating specific neuronal and glial signalling pathways, GLP-1RAs are shown to restore mitochondrial function, increase neuronal resilience, and crucially, modulate adverse glial cell responses-inhibiting the release of major pro-inflammatory cytokines and significantly reducing cellular oxidative stress within the central nervous system. Clinical trials and comprehensive preclinical data, analysed through diverse experimental models of neurodegeneration, strongly support the translational potential relevance of these compounds. The accumulating evidence suggests that GLP-1RAs offer a promising, readily available therapeutic strategy to disrupt the core inflammatory and metabolic pathways common across many neurodegenerative conditions, warranting further investigation in large-scale human trials. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Spezani, Renata AU - Spezani R AUID- ORCID: 0000-0002-6144-8525 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Mandarim-de-Lacerda, Carlos A AU - Mandarim-de-Lacerda CA AUID- ORCID: 0000-0003-4134-7978 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. LA - eng GR - E-26/203.981/2024/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - 305993/2021-6/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ PT - Journal Article PT - Review DEP - 20251219 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Neuroprotective Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neuroinflammatory Diseases/drug therapy/metabolism MH - *Obesity/drug therapy/metabolism/complications MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications MH - *Neurodegenerative Diseases/drug therapy/metabolism MH - Insulin Resistance MH - *Neuroprotective Agents/therapeutic use/pharmacology MH - *Metabolic Diseases/drug therapy MH - Signal Transduction/drug effects PMC - PMC12890747 OTO - NOTNLM OT - insulin resistance OT - metabolic dysfunction OT - microglia/glial modulation OT - neurodegenerative diseases OT - synaptic resilience COIS- The authors declare no conflicts of interest. EDAT- 2025/12/19 18:33 MHDA- 2026/02/11 00:40 PMCR- 2026/02/11 CRDT- 2025/12/19 12:13 PHST- 2025/12/10 00:00 [revised] PHST- 2025/10/27 00:00 [received] PHST- 2025/12/13 00:00 [accepted] PHST- 2026/02/11 00:40 [medline] PHST- 2025/12/19 18:33 [pubmed] PHST- 2025/12/19 12:13 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - DOM70400 [pii] AID - 10.1111/dom.70400 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):1622-1637. doi: 10.1111/dom.70400. Epub 2025 Dec 19. PMID- 41417220 OWN - NLM STAT- MEDLINE DCOM- 20251219 LR - 20261009 IS - 1432-1459 (Electronic) IS - 0340-5354 (Linking) VI - 273 IP - 1 DP - 2025 Dec 19 TI - Peripheral nerve complications of weight loss associated with novel antihyperglycemic agents: a cohort study. PG - 33 LID - 10.1007/s00415-025-13566-3 [doi] AB - INTRODUCTION: Weight loss can cause or exacerbate peripheral nerve disorders, including peripheral neuropathy and entrapments. Novel antihyperglycaemic agents, including glucagon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors, may cause weight loss in addition to their effects on glucose levels. METHODS: Retrospective cohort review from 2020 to 2024 of adult patients undergoing electrodiagnostic evaluation for suspected peripheral nerve dysfunction. Cases were included if there was clinical and/or electrodiagnostic confirmation of peripheral nerve disorder with temporal association (onset < 12 months) to use of GLP1R agonists, SGLT2 inhibitors, or dipeptidyl peptidase-4 inhibitors. RESULTS: Five cases are described (78 M with femoral and fibular neuropathy, 58 F with fibular neuropathy, 85 M with fibular neuropathy, 48 M with median nerve entrapments and sensory peripheral neuropathy, 45 M with median and ulnar nerve entrapments and sensory peripheral neuropathy) all temporally associated with weight loss and use of GLP1R agonists or SGLT2 inhibitors. DISCUSSION: Neuropathy may develop following rapid weight loss or normalization of hyperglycaemia during treatment with GLP1R agonists or SGLT2 inhibitors. The underlying pathogenesis is unclear, but is unlikely due to direct effect of these medications on peripheral nerves. Caution is recommended and further work to establish safe targets for HbA1c and weight loss is needed. CI - (c) 2025. Springer-Verlag GmbH Germany, part of Springer Nature. FAU - O'Gorman, Cullen AU - O'Gorman C AUID- ORCID: 0000-0001-5262-9597 AD - Department of Neurology, Mater Hospital, Raymond Terrace, South Brisbane, QLD, Australia. c.ogorman@uq.edu.au. AD - University of Queensland, Brisbane, QLD, Australia. c.ogorman@uq.edu.au. LA - eng PT - Clinical Study PT - Journal Article DEP - 20251219 PL - Germany TA - J Neurol JT - Journal of neurology JID - 0423161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - *Peripheral Nervous System Diseases/chemically induced/etiology MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - *Weight Loss/drug effects OTO - NOTNLM OT - Complication OT - Diabetes OT - Entrapment OT - Neuropathy OT - Weight loss COIS- Declarations. Conflicts of interest: The author has no relevant disclosures or conflicts of interest. Ethical approval: I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. EDAT- 2025/12/19 15:03 MHDA- 2025/12/19 15:04 CRDT- 2025/12/19 11:26 PHST- 2025/10/02 00:00 [received] PHST- 2025/12/02 00:00 [accepted] PHST- 2025/11/27 00:00 [revised] PHST- 2025/12/19 15:04 [medline] PHST- 2025/12/19 15:03 [pubmed] PHST- 2025/12/19 11:26 [entrez] AID - 10.1007/s00415-025-13566-3 [pii] AID - 10.1007/s00415-025-13566-3 [doi] PST - epublish SO - J Neurol. 2025 Dec 19;273(1):33. doi: 10.1007/s00415-025-13566-3. PMID- 41417204 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260916 IS - 2520-8721 (Electronic) IS - 1109-3099 (Linking) VI - 25 IP - 2 DP - 2026 Jun TI - Dual target, dual benefit: real-world effects of SGLT2 inhibitors and GLP-1 receptor agonists on the FIB-4 score in people with type 2 diabetes mellitus. PG - 475-479 LID - 10.1007/s42000-025-00743-2 [doi] AB - BACKGROUND: Liver fibrosis is a serious comorbidity of type 2 diabetes mellitus (T2DM) in which non-invasive indices such as FIB-4 are used to monitor hepatic health. This study assesses the impact of GLP-1 receptor agonists (GLP-1RA), SGLT2 inhibitors (SGLT2i), and their combinations on FIB-4 scores in people with T2DM. METHODS: We conducted a retrospective analysis of 133 adults with T2DM on one of the three treatment regimens, with FIB-4 calculated at baseline and after 12 months. RESULTS: FIB-4 scores had significantly declined in all groups at 12-month follow-up. The GLP-1RA group exhibited the largest average reduction in FIB-4 (0.280, p < 0.001), followed by combination therapy (0.231, p = 0.001) and SGLT2i (0.206, p < 0.001). All treatment groups experienced significant improvements in glycemia and body weight. CONCLUSIONS: GLP-1RA and SGLT2i, either alone or in combination, may reduce liver fibrosis risk in T2DM patients as reflected by improved FIB-4 scores. CI - (c) 2025. The Author(s), under exclusive licence to Hellenic Endocrine Society. FAU - Markoutsaki, Virginia AU - Markoutsaki V AD - Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Health Center of Perama, Rethimo, Greece. FAU - Dimakopoulos, Georgios AU - Dimakopoulos G AD - BIOSTATS, Epirus Science and Technology Park Campus, University of Ioannina, Ioannina, Greece. FAU - Sinakos, Emmanouil AU - Sinakos E AD - Fourth Department of Internal Medicine, Hippokration General Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Kotsa, Kalliopi AU - Kotsa K AD - First Department of Internal Medicine, Division of Endocrinology and Metabolism and Diabetes Center, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54642, Thessaloniki, Greece. thkoyfak@auth.gr. LA - eng PT - Journal Article PT - Review DEP - 20251219 PL - Switzerland TA - Hormones (Athens) JT - Hormones (Athens, Greece) JID - 101142469 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Liver Cirrhosis/prevention & control/diagnosis/blood MH - *Hypoglycemic Agents/pharmacology/therapeutic use/administration & dosage MH - Aged MH - Drug Therapy, Combination MH - Blood Glucose/drug effects OTO - NOTNLM OT - FIB-4 OT - GLP-1 receptor agonists OT - MASLD OT - SGLT2 inhibitors OT - Type 2 diabetes mellitus COIS- Declarations. Informed consent statement: Written informed consent was obtained from all participants. Institutional review board statement: The study protocol was approved by the Ethics Committee of the Medical School of Aristotle University of Thessaloniki (approval number 3/14-1-2025), Greece. Conflict of interest: ES has received honoraria for lectures and for serving on advisory boards from Novo Nordisk and has participated in sponsored studies by Boehringer Ingelheim and Novo Nordisk. KK has received honoraria for lectures/serving on advisory boards and research support from Astra Zeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi-Aventis, ELPEN, MSD and Novo Nordisk; KK is an Associate Editor of Hormones and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. TK has received honoraria for lectures from AstraZeneca, Sanofi, Boehringer Ingelheim, Pharmaserve Lilly, ELPEN, Menarini, and Novo Nordisk, for serving on advisory boards from Novo Nordisk, Roche, Sanofi, and Boehringer Ingelheim and has participated in sponsored studies by Eli-Lilly, AstraZeneca, and Novo Nordisk. The other authors declare that no conflicts of interest or financial relationships relevant to this article exist. EDAT- 2025/12/19 15:03 MHDA- 2026/09/16 17:36 CRDT- 2025/12/19 11:25 PHST- 2025/07/31 00:00 [received] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/09/16 17:36 [medline] PHST- 2025/12/19 15:03 [pubmed] PHST- 2025/12/19 11:25 [entrez] AID - 10.1007/s42000-025-00743-2 [pii] AID - 10.1007/s42000-025-00743-2 [doi] PST - ppublish SO - Hormones (Athens). 2026 Jun;25(2):475-479. doi: 10.1007/s42000-025-00743-2. Epub 2025 Dec 19. PMID- 41410846 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261010 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 28 IP - 1 DP - 2025 Dec 18 TI - Semaglutide and Tirzepatide for the Treatment of Obesity and Weight-Related Comorbidities: A Narrative Review. PG - 2 LID - 10.1007/s11883-025-01369-w [doi] AB - PURPOSE OF REVIEW: This review provides practitioners with an up-to-date overview of the efficacy and safety data of the currently approved weekly Nutrient-Stimulated Hormone (NuSH) therapies, semaglutide and tirzepatide, in managing obesity and weight-related comorbidities. RECENT FINDINGS: In people with overweight/obesity without diabetes, semaglutide achieved 10.8-14.8% and tirzepatide 17.4-20.8% greater weight loss than placebo. These agents' pleotropic effects have translated into clinicals trials showing improvement in cardiovascular outcomes, improved quality of life and/or heart failure events in heart failure with preserved ejection fraction, resolution of steatohepatitis and improvement in liver fibrosis, prevention and treatment of type 2 diabetes, and improvement in renal function in chronic kidney disease. Semaglutide has additionally been shown to improve osteoarthritis symptoms and tirzepatide reduces obstructive sleep apnea severity. FAU - Saeed, Zeb Ijaz AU - Saeed ZI AUID- ORCID: 0000-0002-8195-5890 AD - Center for Weight Management and Wellness, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA. zisaeed@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. zisaeed@bwh.harvard.edu. AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, BL 347E, Boston, MA, 02115, USA. zisaeed@bwh.harvard.edu. FAU - Apovian, Caroline M AU - Apovian CM AUID- ORCID: 0000-0002-8029-1922 AD - Center for Weight Management and Wellness, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, BL 347E, Boston, MA, 02115, USA. LA - eng PT - Journal Article PT - Review DEP - 20251218 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Weight Loss/drug effects MH - Comorbidity MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use OTO - NOTNLM OT - Cardiometabolic outcomes OT - Nutrient-Stimulated hormone (NuSH) therapies OT - Safety and efficacy OT - Semaglutide OT - Tirzepatide OT - Weight-Related comorbidities COIS- Declarations. Competing interests: Dr. Saeed's receives research funding from Amylyx pharmaceutics and is a consultant for Alosa health. In the previous 36 months, Dr. Apovian has participated on advisory boards for AbbVie Inc., Altimmune, Inc., Arrowhead Pharmaceuticals, Inc., BioAge, Biolinq Incorporated, Caribou Biosciences, Inc., CinFina Pharma, Inc., Covidien LP, Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Keros Therapeutics, Inc., Lilly USA, LLC, L-Nutra, Inc., Mediflix Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine Biosciences, Inc., NodThera Limited, Novo Nordisk, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences Inc., Riverview School, Roman Health Ventures Inc., Scholar Rock, Inc., Terns, Inc., Verily Life Sciences LLC, Veru Inc., Vida Health, Inc., Wave Life Sciences, WondrHealth, Xeno Biosciences and Zyversa Therapeutics, Inc. Dr. Apovian has also received research funding from PCORI and GI Dynamics, Inc. All these conflicts are outside this paper.Dr. Saeed's receives research funding from Amylyx pharmaceutics and is a consultant for Alosa health. In the previous 36 months, Dr. Apovian has participated on advisory boards for AbbVie Inc., Altimmune, Inc., Arrowhead Pharmaceuticals, Inc., BioAge, Biolinq Incorporated, Caribou Biosciences, Inc., CinFina Pharma, Inc., Covidien LP, Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Keros Therapeutics, Inc., Lilly USA, LLC, L-Nutra, Inc., Mediflix Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine Biosciences, Inc., NodThera Limited, Novo Nordisk, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences Inc., Riverview School, Roman Health Ventures Inc., Scholar Rock, Inc., Terns, Inc., Verily Life Sciences LLC, Veru Inc., Vida Health, Inc., Wave Life Sciences, WondrHealth, Xeno Biosciences and Zyversa Therapeutics, Inc. Dr. Apovian has also received research funding from PCORI and GI Dynamics, Inc. All these conflicts are outside this paper. Human and Animal Rights and Informed Consent: No animal or human subjects by the authors were used in this study. EDAT- 2025/12/18 13:06 MHDA- 2026/06/27 06:45 CRDT- 2025/12/18 11:18 PHST- 2025/08/15 00:00 [received] PHST- 2025/11/15 00:00 [accepted] PHST- 2026/06/27 06:45 [medline] PHST- 2025/12/18 13:06 [pubmed] PHST- 2025/12/18 11:18 [entrez] AID - 10.1007/s11883-025-01369-w [pii] AID - 10.1007/s11883-025-01369-w [doi] PST - epublish SO - Curr Atheroscler Rep. 2025 Dec 18;28(1):2. doi: 10.1007/s11883-025-01369-w. PMID- 41410071 OWN - NLM STAT- MEDLINE DCOM- 20260213 LR - 20260607 IS - 1477-0377 (Electronic) IS - 1358-863X (Linking) VI - 31 IP - 1 DP - 2026 Feb TI - Benefits of glucagon-like peptide (GLP)-1 receptor agonists on 5-year risk of major amputation, all-cause mortality, myocardial infarction, and ischemic stroke in patients with chronic limb-threatening ischemia. PG - 47-53 LID - 10.1177/1358863X251393107 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM), but their effect on the risk of cardiovascular events and amputation in patients with chronic limb-threatening ischemia (CLTI) remains underexplored. This retrospective cohort study evaluated the association between GLP-1RA use and the 5-year risk of major amputation, all-cause mortality, and cardiovascular events in diabetic patients with CLTI. METHODS: The TriNetX real-world clinical data platform was used to identify patients with T2DM and CLTI, categorized by GLP-1RA prescription records. Propensity score matching was applied based on demographics, comorbidities, concurrent medications, and laboratory values. Cox proportional hazards, Kaplan-Meier curves, and the log-rank test were used for analysis. RESULTS: Among 139,173 patients with T2DM and CLTI, 17,306 patients were GLP-1RA users and 121,867 were non-GLP-1RA users. Following propensity score matching, 15,743 patients remained in each group (91% match rate). The mean age was 65.4 +/- 11 years and 58.9% were men. The mean follow-up duration was 753.7 days. GLP-1RA users had a significantly lower rate of major amputation (hazard ratio [HR]: 0.745; 95% CI: 0.679-0.816; log-rank p < 0.001), all-cause mortality (HR: 0.7; 95% CI: 0.663-0.738; log-rank p < 0.001), and myocardial infarction (MI) (HR: 0.838; 95% CI: 0.792-0.886; log-rank p < 0.001). There was no difference in the risk of ischemic stroke (HR: 0.969; 95% CI: 0.906-1.036; log-rank p = 0.353). CONCLUSION: The use of GLP-1RA medications is associated with a significant decrease in the 5-year risk of major amputations, all-cause mortality, and MI in diabetic patients with CLTI. FAU - Yahyavi, Ashkan AU - Yahyavi A AD - University Hospitals Harrington Heart & Vascular Institute, Cleveland, OH, USA. FAU - Zokaei Nikoo, Maedeh AU - Zokaei Nikoo M AD - Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. FAU - Hussein, Leen AU - Hussein L AD - University Hospitals Harrington Heart & Vascular Institute, Cleveland, OH, USA. FAU - Katara, Aarti AU - Katara A AD - Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA. FAU - Perez, Jaime A AU - Perez JA AD - University Hospitals Center for Clinical Research, Cleveland, OH, USA. FAU - Shishehbor, Mehdi H AU - Shishehbor MH AUID- ORCID: 0000-0002-4888-2431 AD - University Hospitals Harrington Heart & Vascular Institute, Cleveland, OH, USA. LA - eng PT - Journal Article DEP - 20251218 PL - England TA - Vasc Med JT - Vascular medicine (London, England) JID - 9610930 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - Male MH - Female MH - *Amputation, Surgical/mortality/adverse effects MH - Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Time Factors MH - Risk Assessment MH - *Myocardial Infarction/mortality/prevention & control/diagnosis MH - Treatment Outcome MH - Risk Factors MH - *Ischemic Stroke/mortality/prevention & control/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Peripheral Arterial Disease/mortality/diagnosis/therapy MH - *Incretins/therapeutic use/adverse effects MH - Databases, Factual MH - *Chronic Limb-Threatening Ischemia/mortality/diagnosis MH - Aged, 80 and over MH - *Ischemia/mortality/diagnosis MH - Cause of Death OTO - NOTNLM OT - chronic limb-threatening ischemia (CLTI) OT - glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - peripheral artery disease (PAD) OT - type 2 diabetes mellitus COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Mehdi Shishehbor serves as a global advisor for Boston Scientific, Medtronic, Abbott Vascular, Inquis, ANT, and Inari. The other authors report no conflicting interests. EDAT- 2025/12/18 07:20 MHDA- 2026/02/13 06:33 CRDT- 2025/12/18 05:12 PHST- 2026/02/13 06:33 [medline] PHST- 2025/12/18 07:20 [pubmed] PHST- 2025/12/18 05:12 [entrez] AID - 10.1177/1358863X251393107 [doi] PST - ppublish SO - Vasc Med. 2026 Feb;31(1):47-53. doi: 10.1177/1358863X251393107. Epub 2025 Dec 18. PMID- 41407860 OWN - NLM STAT- MEDLINE DCOM- 20260401 LR - 20261010 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 652 IP - 8108 DP - 2026 Apr TI - Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. PG - 181-188 LID - 10.1038/s41586-025-10031-z [doi] AB - Mazdutide is a once-weekly glucagon and glucagon-like peptide 1 receptor dual agonist developed for the treatment of type 2 diabetes (T2D)(1). Here we report on a randomized phase III trial assessing the efficacy and safety of mazdutide, compared with dulaglutide, in participants with T2D who were also treated with background oral anti-diabetic drugs. In this study, 731 participants with T2D were randomized 1:1:1 to receive 4 mg mazdutide, 6 mg mazdutide or 1.5 mg dulaglutide for 28 weeks. Both doses of mazdutide showed non-inferiority and superiority to the 1.5-mg dose of dulaglutide in terms of the mean change in the diagnostic marker glycated haemoglobin A1c (HbA(1c)) from baseline to week 28, with a least-squares mean treatment difference of -0.24% (P = 0.0032) for 4 mg mazdutide and -0.30% (P = 0.0003) for 6 mg mazdutide, relative to 1.5 mg dulaglutide. Significantly greater reductions in body weight were achieved with mazdutide than with dulaglutide, with a least-squares mean treatment difference of -3.78% for 4 mg mazdutide and -5.76% for 6 mg mazdutide (both P < 0.0001), relative to dulaglutide. Moreover, significantly more participants who received mazdutide 4 mg or 6 mg reached the composite end point of HbA(1c) < 7.0% with a body-weight reduction of at least 5% at week 28 (both P < 0.0001), compared with those who received dulaglutide. The most common treatment-emergent adverse events were diarrhoea, nausea and vomiting. In summary, we found that in Chinese participants with T2D, 28 weeks of treatment with mazdutide (4 mg and 6 mg) provided reductions in HbA(1c) and body weight that were superior to those attained with 1.5 mg dulaglutide. Mazdutide was generally safe, although the incidence of gastrointestinal adverse events was higher for mazdutide than for dulaglutide. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Guo, Lixin AU - Guo L AD - Department of Endocrinology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. FAU - Zhang, Bo AU - Zhang B AUID- ORCID: 0000-0003-3060-7850 AD - China-Japan Friendship Hospital, Beijing, China. FAU - Xue, Xia AU - Xue X AD - Central Hospital Affiliated to Shandong First Medical University, Jinan, China. FAU - Zhang, Xin AU - Zhang X AD - Genertec Liaoyou Gem Flower Hospital, Panjin, China. FAU - Cai, Hanqing AU - Cai H AD - Second Norman Bethune Hospital of Jilin University, Changchun, China. FAU - Jiang, Hongwei AU - Jiang H AD - First Affiliated Hospital, and College of Clinical Medicine, State Key Laboratory of Light Superalloys, Henan University of Science and Technology, Luoyang, China. FAU - Zhang, Lili AU - Zhang L AD - Jincheng General Hospital, Jincheng, China. FAU - Jin, Ping AU - Jin P AD - Third Xiangya Hospital of Central South University, Changsha, China. FAU - Wang, Xiaojing AU - Wang X AD - Yuncheng Central Hospital, Yuncheng, China. FAU - Cheng, Zhifeng AU - Cheng Z AD - Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Zhang, Suhe AU - Zhang S AD - Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Geng, Jianlin AU - Geng J AD - Hengshui People's Hospital (Harrison International Peace Hospital), Hengshui, China. FAU - Guo, Yushan AU - Guo Y AD - Affiliated Hospital of Bei-hua University, Jilin, China. FAU - Hu, Hanbo AU - Hu H AD - Innovent Biologics, Suzhou, China. FAU - Ma, Qingyang AU - Ma Q AD - Innovent Biologics, Suzhou, China. FAU - Li, Li AU - Li L AD - Innovent Biologics, Suzhou, China. FAU - Du, Haiwei AU - Du H AUID- ORCID: 0000-0001-6058-267X AD - Innovent Biologics, Suzhou, China. FAU - Han-Zhang, Han AU - Han-Zhang H AD - Innovent Biologics, Suzhou, China. FAU - Xue, Fengtai AU - Xue F AD - Innovent Biologics, Suzhou, China. FAU - Deng, Huan AU - Deng H AD - Innovent Biologics, Suzhou, China. FAU - Qian, Lei AU - Qian L AUID- ORCID: 0000-0001-8720-7140 AD - Innovent Biologics, Suzhou, China. FAU - Yang, Wenying AU - Yang W AD - China-Japan Friendship Hospital, Beijing, China. ywying_1010@126.com. CN - DREAMS-2 investigators LA - eng SI - ClinicalTrials.gov/NCT05606913 GR - Innovent Biologics/ PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251217 PL - England TA - Nature JT - Nature JID - 0410462 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) RN - Chinese people SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use/administration & dosage MH - *Recombinant Fusion Proteins/adverse effects/therapeutic use/administration & dosage MH - Male MH - Female MH - Glycated Hemoglobin/analysis/metabolism MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - Adult MH - Body Weight/drug effects MH - China MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - East Asian People MH - Peptides COIS- Competing interests: H.C. and H.J. serve as consultants to Innovent Biologics. H.H., Q.M., L.L., H. Du, H.H.-Z., F.X., H. Deng and L.Q. are employees of Innovent Biologics. The remaining authors declare no competing interests. EDAT- 2025/12/18 01:31 MHDA- 2026/04/02 00:28 CRDT- 2025/12/17 23:25 PHST- 2025/06/16 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/04/02 00:28 [medline] PHST- 2025/12/18 01:31 [pubmed] PHST- 2025/12/17 23:25 [entrez] AID - 10.1038/s41586-025-10031-z [pii] AID - 10.1038/s41586-025-10031-z [doi] PST - ppublish SO - Nature. 2026 Apr;652(8108):181-188. doi: 10.1038/s41586-025-10031-z. Epub 2025 Dec 17. PMID- 41407859 OWN - NLM STAT- MEDLINE DCOM- 20260401 LR - 20261010 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 652 IP - 8108 DP - 2026 Apr TI - Mazdutide versus placebo in Chinese adults with type 2 diabetes. PG - 174-180 LID - 10.1038/s41586-025-10026-w [doi] AB - Despite advances in type 2 diabetes (T2D) management, unmet needs remain for therapies that effectively control hyperglycaemia while addressing comorbid metabolic disorders(1,2). Here we assessed the efficacy and safety of the dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist mazdutide monotherapy versus placebo in Chinese adults with T2D controlled inadequately with diet and exercise alone. In this phase 3 trial, 320 participants (mean glycated haemoglobin A1c (HbA(1c)) of 8.24%, body mass index of 28.2 kg m(-2) and diabetes duration of 1.9 years) were randomized 1:1:1 to receive weekly subcutaneous injections of mazdutide (4 mg or 6 mg) or placebo for 24 weeks, followed by a 24-week extended mazdutide treatment. At week 24, mazdutide significantly reduced HbA(1c) versus placebo (primary endpoint): -1.57% with mazdutide 4 mg and -2.15% with mazdutide 6 mg, versus -0.14% with placebo, with treatment differences of -1.43% and -2.02% (both P < 0.0001). Weight loss from baseline at week 24 occurred with -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% (placebo) (both P < 0.0001). Furthermore, more participants with mazdutide achieved HbA(1c) < 7.0%, weight loss >/= 5% (all P < 0.0001) and composite endpoints (HbA(1c) < 7.0% and weight loss >/= 5%) versus placebo (P = 0.0006 for 4 mg; P < 0.0001 for 6 mg) at week 24. The most common adverse events-diarrhoea, decreased appetite and nausea-were consistent with GLP-1R agonists. These results establish mazdutide monotherapy as an effective intervention providing clinically meaningful glycaemic control and weight reduction alongside a favourable safety profile in this population. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Zhu, Dalong AU - Zhu D AUID- ORCID: 0000-0002-1064-1261 AD - Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. zhudalong@nju.edu.cn. FAU - Zhao, Jiajun AU - Zhao J AUID- ORCID: 0000-0003-3267-9292 AD - Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. jjzhao@sdu.edu.cn. FAU - Cai, Hanqing AU - Cai H AD - Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China. FAU - Chu, Xuan AU - Chu X AD - Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. FAU - Xiu, Shuangling AU - Xiu S AUID- ORCID: 0000-0002-8549-4374 AD - Department of Endocrinology, Xuanwu Hospital Capital Medical University, Beijing, China. FAU - Song, Chengwei AU - Song C AD - Department of Endocrinology, Jilin Province FAW General Hospital, Changchun, China. FAU - Cheng, Zhifeng AU - Cheng Z AD - Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Cao, Hongyi AU - Cao H AD - Department of Endocrinology and Metabolology, Chengdu Fifth People's Hospital, Chengdu, China. FAU - Jiang, Hongwei AU - Jiang H AD - Endocrinology and Metabolism Centre, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China. FAU - Zhang, Lili AU - Zhang L AD - Department of Endocrinology, Jincheng General Hospital, Jincheng, China. FAU - Wang, Haifang AU - Wang H AD - Department of Endocrinology, Handan First Hospital, Handan, China. FAU - Shi, Bimin AU - Shi B AD - Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Li, Yanbing AU - Li Y AD - Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Liu, Ming AU - Liu M AUID- ORCID: 0000-0003-2665-4072 AD - Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China. FAU - Feng, Bo AU - Feng B AD - Department of Endocrinology and Metabolology, Shanghai East Hospital, Tongji University, Shanghai, China. FAU - Xue, Fengtai AU - Xue F AD - Innovent Biologics, Suzhou, China. FAU - Deng, Huan AU - Deng H AD - Innovent Biologics, Suzhou, China. FAU - Li, Haoyu AU - Li H AD - Innovent Biologics, Suzhou, China. FAU - Li, Li AU - Li L AD - Innovent Biologics, Suzhou, China. FAU - Li, Yue AU - Li Y AUID- ORCID: 0009-0000-3793-5350 AD - Innovent Biologics, Suzhou, China. FAU - Ma, Qingyang AU - Ma Q AD - Innovent Biologics, Suzhou, China. FAU - Qian, Lei AU - Qian L AUID- ORCID: 0000-0001-8720-7140 AD - Innovent Biologics, Suzhou, China. cnradium@126.com. LA - eng GR - Innovent Biologics, Suzhou, China/ PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251217 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Placebos) RN - 0 (Receptors, Glucagon) RN - 0 (Peptides) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Placebos MH - Receptors, Glucagon/agonists/metabolism MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Peptides/therapeutic use MH - East Asian People COIS- Competing interests: D.Z., H. Cai and H.J. serve as consultants to Innovent Biologics. F.X., H.D., H.L., L.L., Yue Li, Q.M. and L.Q. are employees of Innovent Biologics. The other authors declare no competing interests. EDAT- 2025/12/18 01:31 MHDA- 2026/04/02 00:29 CRDT- 2025/12/17 23:25 PHST- 2025/06/16 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/04/02 00:29 [medline] PHST- 2025/12/18 01:31 [pubmed] PHST- 2025/12/17 23:25 [entrez] AID - 10.1038/s41586-025-10026-w [pii] AID - 10.1038/s41586-025-10026-w [doi] PST - ppublish SO - Nature. 2026 Apr;652(8108):174-180. doi: 10.1038/s41586-025-10026-w. Epub 2025 Dec 17. PMID- 41406444 OWN - NLM STAT- MEDLINE DCOM- 20251217 LR - 20260415 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 393 IP - 24 DP - 2025 Dec 18 TI - Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. PG - 2409-2420 LID - 10.1056/NEJMoa2505928 [doi] AB - BACKGROUND: Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain. METHODS: We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide. RESULTS: A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. The mean (+/-SD) age of the patients was 64.1+/-8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6+/-5.5, the mean glycated hemoglobin level was 8.4+/-0.9%, and the mean duration of diabetes was 14.7+/-8.8 years. A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group. CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke. (Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - Nicholls, Stephen J AU - Nicholls SJ AD - Victorian Heart Institute, Monash University, Melbourne, VIC, Australia. FAU - Pavo, Imre AU - Pavo I AD - Eli Lilly, Indianapolis. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York. FAU - Buse, John B AU - Buse JB AD - University of North Carolina, Chapel Hill. FAU - Del Prato, Stefano AU - Del Prato S AD - Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Kahn, Steven E AU - Kahn SE AD - Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland. FAU - McGuire, Darren K AU - McGuire DK AD - University of Texas Southwestern Medical Center, Dallas. AD - Parkland Health and Hospital System, Dallas. FAU - Miller, Debra AU - Miller D AD - Eli Lilly, Indianapolis. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, and Metabolism Section, Department of Medicine, St. Josef-Hospital, Katholisches Klinikum Bochum, Ruhr University of Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Nishiyama, Hiroshi AU - Nishiyama H AD - Eli Lilly, Indianapolis. FAU - Nissen, Steven E AU - Nissen SE AUID- ORCID: 0000-0002-7231-6464 AD - Cleveland Clinic Coordinating Center for Clinical Research (C5 Research), Cleveland Clinic, Cleveland. AD - Department of Medicine, Cleveland Clinic, Cleveland. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular Medicine and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. FAU - Weerakkody, Govinda AU - Weerakkody G AD - Eli Lilly, Indianapolis. FAU - Wiese, Russell J AU - Wiese RJ AD - Eli Lilly, Indianapolis. FAU - Zinman, Bernard AU - Zinman B AD - Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto. AD - Mount Sinai Hospital, University of Toronto, Toronto. FAU - Zoungas, Sophia AU - Zoungas S AD - Victorian Heart Institute, Monash University, Melbourne, VIC, Australia. AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. FAU - Basile, Jan AU - Basile J AD - Medical University of South Carolina, Charleston. AD - Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. AD - National Institute for Health and Care Research Leicester Biomedical Research Centre, Leicester, United Kingdom. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy. FAU - Kellerer, Monika AU - Kellerer M AD - Department of Medicine 1, Marienhospital Stuttgart, Stuttgart, Germany. AD - Tubingen University Hospital, Tubingen, Germany. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing. FAU - Varkonyi, Tamas AU - Varkonyi T AD - Department of Internal Medicine, Albert Szent-Gyorgyi Medical School, University of Szeged, Szeged, Hungary. FAU - Menon, Venu AU - Menon V AD - Cleveland Clinic Coordinating Center for Clinical Research (C5 Research), Cleveland Clinic, Cleveland. AD - Department of Medicine, Cleveland Clinic, Cleveland. FAU - Broder, Jonathan C AU - Broder JC AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. AD - Monash University Clinical Trials Centre, Monash University, Melbourne, VIC, Australia. FAU - Herschtal, Alan AU - Herschtal A AD - Monash University Clinical Trials Centre, Monash University, Melbourne, VIC, Australia. FAU - D'Alessio, David AU - D'Alessio D AD - Duke University Medical Center, Durham, NC. CN - SURPASS-CVOT Investigators LA - eng SI - ClinicalTrials.gov/NCT04255433 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - N Engl J Med. 2026 Apr 16;394(15):1550. doi: 10.1056/NEJMc2600572. PMID: 41985142 CIN - N Engl J Med. 2026 Apr 16;394(15):1550-1551. doi: 10.1056/NEJMc2600572. PMID: 41985143 CIN - N Engl J Med. 2026 Apr 16;394(15):1551. doi: 10.1056/NEJMc2600572. PMID: 41985144 CIN - N Engl J Med. 2026 Apr 16;394(15):1551. doi: 10.1056/NEJMc2600572. PMID: 41985145 CIN - N Engl J Med. 2026 Apr 16;394(15):1551-1553. doi: 10.1056/NEJMc2600572. PMID: 41985146 CIN - N Engl J Med. 2026 Apr 16;394(15):10.1056/NEJMc2600572#sa6. doi: 10.1056/NEJMc2600572. PMID: 41985147 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis MH - *Cardiovascular Diseases/complications/drug therapy/mortality/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality/blood MH - Double-Blind Method MH - Glucagon-Like Peptides/administration & dosage/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects MH - Injections, Subcutaneous MH - Intention to Treat Analysis MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects MH - *Tirzepatide/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Treatment Outcome FIR - MacKinnon, Ignacio IR - MacKinnon I FIR - Zaidman, Cesar IR - Zaidman C FIR - Romeo, Alejandra IR - Romeo A FIR - Vico, Marisa IR - Vico M FIR - Abalos, Franklin IR - Abalos F FIR - Sassone, Sonia IR - Sassone S FIR - Aizenberg, Diego IR - Aizenberg D FIR - Majul, Claudio IR - Majul C FIR - Lanchiotti, Paulina IR - Lanchiotti P FIR - Sessa, Horacio IR - Sessa H FIR - Chertkoff, Alejandro IR - Chertkoff A FIR - Waitman, Jorge IR - Waitman J FIR - Dominguez, Andrea IR - Dominguez A FIR - Montana, Oscar IR - Montana O FIR - Nardone, Lucrecia IR - Nardone L FIR - Fretes, Jose IR - Fretes J FIR - Sicer, Maximiliano IR - Sicer M FIR - Frechtel, Gustavo IR - Frechtel G FIR - Serra, Leonardo IR - Serra L FIR - Gutnisky, Lucas IR - Gutnisky L FIR - Maldonado, Natacha IR - Maldonado N FIR - Prado, Aldo IR - Prado A FIR - Steinacher, Maria IR - Steinacher M FIR - Ulla, Maria IR - Ulla M FIR - Gelersztein, Elizabeth IR - Gelersztein E FIR - Saavedra, Silvia IR - Saavedra S FIR - Valdez, Maria IR - Valdez M FIR - Koretzky, Martin IR - Koretzky M FIR - Gorban de Lapertosa, Silvia IR - Gorban de Lapertosa S FIR - Vallejos, Julio IR - Vallejos J FIR - Carrozza, Diego Alberto IR - Carrozza DA FIR - Yee, Ming Li IR - Yee ML FIR - d'Emden, Michael IR - d'Emden M FIR - Rahman, Atifur IR - Rahman A FIR - Hamilton, Andrew IR - Hamilton A FIR - Morbey, Claire IR - Morbey C FIR - Ekinci, Elif IR - Ekinci E FIR - Caterson, Ian IR - Caterson I FIR - Williams, Kathryn IR - Williams K FIR - Choy, Kay Hau IR - Choy KH FIR - Colquhoun, David IR - Colquhoun D FIR - Purnell, Peter IR - Purnell P FIR - Sangla, Kunwarjit IR - Sangla K FIR - Davis, Timothy IR - Davis T FIR - Ho, Jui IR - Ho J FIR - Phillips, Liza IR - Phillips L FIR - Pape, Alexia IR - Pape A FIR - Worthley, Matthew IR - Worthley M FIR - Nicholls, Stephen IR - Nicholls S FIR - Cooke, Duncan IR - Cooke D FIR - Hanusch, Ursula IR - Hanusch U FIR - Ludvik, Bernhard IR - Ludvik B FIR - Sourij, Harald IR - Sourij H FIR - Stulnig, Thomas IR - Stulnig T FIR - Stechemesser, Lars IR - Stechemesser L FIR - Kautzky-Willer, Alexandra IR - Kautzky-Willer A FIR - Nobels, Frank IR - Nobels F FIR - Coremans, Peter IR - Coremans P FIR - Debroye, Corinne IR - Debroye C FIR - De Block, Christophe IR - De Block C FIR - Verhaegen, Ann IR - Verhaegen A FIR - Mertens, Ann IR - Mertens A FIR - Duyck, Francis IR - Duyck F FIR - Taes, Youri IR - Taes Y FIR - Crenier, Laurent IR - Crenier L FIR - Vercammen, Chris IR - Vercammen C FIR - Winne, Linsey IR - Winne L FIR - Vanhaverbeke, Gerd IR - Vanhaverbeke G FIR - Radermecker, Regis IR - Radermecker R FIR - Cools, Frank IR - Cools F FIR - Franco, Denise IR - Franco D FIR - Santomauro Junior, Augusto Cezar IR - Santomauro Junior AC FIR - Salles, Joao IR - Salles J FIR - Alves, Breno Balabem IR - Alves BB FIR - Rea, Rosangela IR - Rea R FIR - Cercato, Cintia IR - Cercato C FIR - Saraiva, Jose IR - Saraiva J FIR - Vidotti, Maria Helena IR - Vidotti MH FIR - Augusto, Gustavo IR - Augusto G FIR - Hissa, Miguel IR - Hissa M FIR - Russo, Luis IR - Russo L FIR - Canani, Luis Henrique IR - Canani LH FIR - Santos, Queulla IR - Santos Q FIR - de Oliveira, Gabriela IR - de Oliveira G FIR - Pereira, Marcio IR - Pereira M FIR - Dumas, Richard IR - Dumas R FIR - Abitbol, Alexander IR - Abitbol A FIR - Bajaj, Harpreet IR - Bajaj H FIR - Woo, Vincent IR - Woo V FIR - Liu, Selina IR - Liu S FIR - Noronha, Luis IR - Noronha L FIR - Twum-Barima, David IR - Twum-Barima D FIR - Khandwala, Hasnain IR - Khandwala H FIR - Chehayeb, Raja IR - Chehayeb R FIR - Shukla, Dinkar IR - Shukla D FIR - Cha, James IR - Cha J FIR - Constance, Christian IR - Constance C FIR - Tailor, Chetna IR - Tailor C FIR - Filteau, Pierre IR - Filteau P FIR - Vallieres, Gerald IR - Vallieres G FIR - Schlosser, Robert IR - Schlosser R FIR - Alasaad, Hani IR - Alasaad H FIR - Hartleib, Michael IR - Hartleib M FIR - Conway, James IR - Conway J FIR - Yip, Churn-Ern IR - Yip CE FIR - Elliott, Thomas IR - Elliott T FIR - Jones, Michael IR - Jones M FIR - Pliamm, Lew IR - Pliamm L FIR - Ajala, Buki IR - Ajala B FIR - Pandey, A Shekhar IR - Pandey AS FIR - Aggarwal, Naresh IR - Aggarwal N FIR - Dzongowski, Peter IR - Dzongowski P FIR - O'Mahony, John IR - O'Mahony J FIR - Gupta, Anil IR - Gupta A FIR - Verma, Subodh IR - Verma S FIR - Shen, Aidong IR - Shen A FIR - Zheng, Ziqi IR - Zheng Z FIR - Jiang, Jie IR - Jiang J FIR - Dong, Xiaoying IR - Dong X FIR - Tang, Xulei IR - Tang X FIR - Zhang, Junqing IR - Zhang J FIR - Dong, Xiaolin IR - Dong X FIR - Peng, Jianqiang IR - Peng J FIR - Ma, Changsheng IR - Ma C FIR - Ji, Linong IR - Ji L FIR - Guo, Hui IR - Guo H FIR - Ma, Jianhua IR - Ma J FIR - Dong, Yugang IR - Dong Y FIR - Sun, Yuemin IR - Sun Y FIR - Ma, Genshan IR - Ma G FIR - Xu, Biao IR - Xu B FIR - Huang, Wen Jun IR - Huang WJ FIR - Lu, Weiping IR - Lu W FIR - Yuan, Guoyue IR - Yuan G FIR - Lu, Yibing IR - Lu Y FIR - Cheng, ZhiFeng IR - Cheng Z FIR - Liu, Ying IR - Liu Y FIR - Bai, Feng IR - Bai F FIR - Yang, Ping IR - Yang P FIR - Kopecka, Sarka IR - Kopecka S FIR - Bartaskova, Dagmar IR - Bartaskova D FIR - Edelsberger, Tomas IR - Edelsberger T FIR - Malicherova, Emilia IR - Malicherova E FIR - Hron, Jakub IR - Hron J FIR - Pelikanova, Michala IR - Pelikanova M FIR - Diepoltova, Barbora IR - Diepoltova B FIR - Vachova, Alena IR - Vachova A FIR - Ceska, Richard IR - Ceska R FIR - Sejvlova, Petra IR - Sejvlova P FIR - Cariou, Bertrand IR - Cariou B FIR - Bully, Chantal IR - Bully C FIR - Agopian, Bermione IR - Agopian B FIR - Potier, Louis IR - Potier L FIR - Penfornis, Alfred IR - Penfornis A FIR - Verges, Bruno IR - Verges B FIR - Gourdy, Pierre IR - Gourdy P FIR - Larroumet, Alice IR - Larroumet A FIR - Gautier, Jean-Francois IR - Gautier JF FIR - Guerci, Bruno IR - Guerci B FIR - Dupuy, Olivier IR - Dupuy O FIR - Sauter, Joachim IR - Sauter J FIR - Busch, Klaus IR - Busch K FIR - Rose, Ludger IR - Rose L FIR - Simon, Joerg IR - Simon J FIR - Kraft, Martina IR - Kraft M FIR - Segner, Alexander IR - Segner A FIR - Hagenow, Andreas IR - Hagenow A FIR - Wenzl-Bauer, Veronika IR - Wenzl-Bauer V FIR - Milek, Karsten IR - Milek K FIR - Lee-Barkey, Young-Hee IR - Lee-Barkey YH FIR - Schaum, Thomas IR - Schaum T FIR - Dahl, Dominik IR - Dahl D FIR - Kempe, Hans-Peter IR - Kempe HP FIR - Meyhofer, Svenja IR - Meyhofer S FIR - Marck, Cornelia IR - Marck C FIR - Tews, Dietrich IR - Tews D FIR - Luedemann, Joerg IR - Luedemann J FIR - Klausmann, Gerhard IR - Klausmann G FIR - Simon-Wagner, Ilka IR - Simon-Wagner I FIR - Derwahl, Karl-Michael IR - Derwahl KM FIR - Sarnighausen, Hans-Eckart IR - Sarnighausen HE FIR - Paschen, Bjoern IR - Paschen B FIR - Schlichthaar, Heike IR - Schlichthaar H FIR - Zeller, Helga IR - Zeller H FIR - Weigmann, Ingo IR - Weigmann I FIR - Denger, Ralf IR - Denger R FIR - Serban, Pavel Marcel IR - Serban PM FIR - Bieler, Tasso IR - Bieler T FIR - Kosch, Christine IR - Kosch C FIR - Jung, Thomas IR - Jung T FIR - Segiet, Thomas IR - Segiet T FIR - Kellerer, Monika IR - Kellerer M FIR - Lorra, Babette IR - Lorra B FIR - Becker, Bernd IR - Becker B FIR - Braun, Hermann IR - Braun H FIR - Jacob, Stephan IR - Jacob S FIR - Schwarz, Toralf IR - Schwarz T FIR - Henkel, Elena IR - Henkel E FIR - Taeschner, Heidrun IR - Taeschner H FIR - Schaefer, Axel IR - Schaefer A FIR - Mehltretter, Kai IR - Mehltretter K FIR - Witzel, Peter IR - Witzel P FIR - Hartard, Manfred IR - Hartard M FIR - Stahl, Hans-Detlev IR - Stahl HD FIR - Weimer, Joachim IR - Weimer J FIR - Haas, Johannes IR - Haas J FIR - Winkelmann, Bernhard IR - Winkelmann B FIR - Stephan, Uta IR - Stephan U FIR - Pagkalos, Emmanouil IR - Pagkalos E FIR - Tzatzagou, Glykeria IR - Tzatzagou G FIR - Benroubi, Marianna IR - Benroubi M FIR - Kotsa, Kalliopi IR - Kotsa K FIR - Mouslech, Zadalla IR - Mouslech Z FIR - Markou, Athina IR - Markou A FIR - Lambadiari, Vaia IR - Lambadiari V FIR - Bargiota, Alexandra IR - Bargiota A FIR - Zografou, Ioanna IR - Zografou I FIR - Doupis, John IR - Doupis J FIR - Noori, Ebrahim IR - Noori E FIR - Pauer, Jozsef IR - Pauer J FIR - Kesmarki, Nora IR - Kesmarki N FIR - Bujtor, Zoltan IR - Bujtor Z FIR - Wudi, Krisztina IR - Wudi K FIR - Salamon, Csaba IR - Salamon C FIR - Kajetan, Miklos IR - Kajetan M FIR - Beke, Eleonora IR - Beke E FIR - Berhes, Istvan IR - Berhes I FIR - Mohacsi, Attila IR - Mohacsi A FIR - Hevesi, Judit IR - Hevesi J FIR - Varkonyi, Tamas IR - Varkonyi T FIR - Petro, Gizella IR - Petro G FIR - Revesz, Katalin IR - Revesz K FIR - Pap, Gizella IR - Pap G FIR - Pall, Denes IR - Pall D FIR - Kis, Janos Tibor IR - Kis JT FIR - Kaul, Upendra IR - Kaul U FIR - Mohan, Viswanathan IR - Mohan V FIR - Mehta, Ashwani IR - Mehta A FIR - Sethi, Bipin IR - Sethi B FIR - Mehta, Vimal IR - Mehta V FIR - Banerjee, Suvro IR - Banerjee S FIR - Ambuj, Roy IR - Ambuj R FIR - Bandgar, Tushar IR - Bandgar T FIR - Parikh, Keyur IR - Parikh K FIR - Shah, Parag IR - Shah P FIR - Bhagwat, Nikhil IR - Bhagwat N FIR - Julka, Sandeep IR - Julka S FIR - Gandhi, Pramod IR - Gandhi P FIR - Shamanna, Paramesh IR - Shamanna P FIR - Mazen, Elias IR - Mazen E FIR - Tirosh, Amir IR - Tirosh A FIR - Roguin, Ariel IR - Roguin A FIR - Hochberg, Irit IR - Hochberg I FIR - Zornitzki, Taiba IR - Zornitzki T FIR - Adawi, Faiad IR - Adawi F FIR - Dicker, Dror IR - Dicker D FIR - Sofer, Yael IR - Sofer Y FIR - Tsur, Anat IR - Tsur A FIR - Darawsha, Mahmud IR - Darawsha M FIR - Liberty, Idit IR - Liberty I FIR - Leibowitz, David IR - Leibowitz D FIR - Bashkin, Amir IR - Bashkin A FIR - Vishlitzky, Victor IR - Vishlitzky V FIR - Sabbah, Muhammad IR - Sabbah M FIR - Munter, Gavriel IR - Munter G FIR - Durst, Ronen IR - Durst R FIR - Yosefy, Chaim IR - Yosefy C FIR - Aharon Hananel, Genya IR - Aharon Hananel G FIR - Francis, Adi IR - Francis A FIR - Grossman, Alon IR - Grossman A FIR - Shechter, Michael IR - Shechter M FIR - Dobrecky Mery, Idit IR - Dobrecky Mery I FIR - Wainstein, Julio IR - Wainstein J FIR - Haddad, Elie IR - Haddad E FIR - Picconi, Fabiana IR - Picconi F FIR - Zoppini, Giacomo IR - Zoppini G FIR - Esposito, Katherine IR - Esposito K FIR - Orsi, Emanuela IR - Orsi E FIR - Mannucci, Edoardo IR - Mannucci E FIR - Giaccari, Andrea IR - Giaccari A FIR - Pagotto, Uberto IR - Pagotto U FIR - Giorgino, Francesco IR - Giorgino F FIR - Giordano, Carla IR - Giordano C FIR - Lauro, Davide IR - Lauro D FIR - De Cata, Pasquale IR - De Cata P FIR - Arturi, Franco IR - Arturi F FIR - Trevisan, Roberto IR - Trevisan R FIR - Tonolo, Giancarlo IR - Tonolo G FIR - Dei Cas, Alessandra IR - Dei Cas A FIR - Genovese, Stefano IR - Genovese S FIR - Consoli, Agostino IR - Consoli A FIR - Romeo, Francesco IR - Romeo F FIR - Del Prato, Stefano IR - Del Prato S FIR - Frittitta, Lucia IR - Frittitta L FIR - Sato, Nobuyuki IR - Sato N FIR - Onishi, Yukiko IR - Onishi Y FIR - Onaka, Haruhiko IR - Onaka H FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Fukushima, Yasushi IR - Fukushima Y FIR - Yamasaki, Yoshimitsu IR - Yamasaki Y FIR - Jinnouchi, Hideaki IR - Jinnouchi H FIR - Iwanaga, Yoshitaka IR - Iwanaga Y FIR - Sueyoshi, Atsushi IR - Sueyoshi A FIR - Bayram Llamas, Edmundo IR - Bayram Llamas E FIR - Nevarez, Luis IR - Nevarez L FIR - Fajardo Campos, Pedro IR - Fajardo Campos P FIR - Alpizar Salazar, Melchor IR - Alpizar Salazar M FIR - Vidrio, Maricela IR - Vidrio M FIR - Banda Elizondo, Ramiro IR - Banda Elizondo R FIR - Lopez, Agustin IR - Lopez A FIR - Sauque Reyna, Leobardo IR - Sauque Reyna L FIR - Garcia Hernandez, Pedro IR - Garcia Hernandez P FIR - Nunez Fragoso, Juan IR - Nunez Fragoso J FIR - Garcia Cantu, Elias Alberto IR - Garcia Cantu EA FIR - Gonzalez Galvez, Guillermo IR - Gonzalez Galvez G FIR - Pascoe, Sara IR - Pascoe S FIR - Medina, Carlos IR - Medina C FIR - Stobschinski de Alba, Carlos Alejandro IR - Stobschinski de Alba CA FIR - de Los Rios Ibarra, Manuel IR - de Los Rios Ibarra M FIR - Arechavaleta Granell, Maria IR - Arechavaleta Granell M FIR - Calvo Vargas, Cesar IR - Calvo Vargas C FIR - Gonzalez Gonzalez, Jose Gerardo IR - Gonzalez Gonzalez JG FIR - Pelayo Orozco, Emilia IR - Pelayo Orozco E FIR - Llamas Esperon, Guillermo Antonio IR - Llamas Esperon GA FIR - Violante Ortiz, Rafael IR - Violante Ortiz R FIR - Ramirez Diaz, Santiago IR - Ramirez Diaz S FIR - Alcocer Gamba, Marco IR - Alcocer Gamba M FIR - Lopez Rosas, Enrique IR - Lopez Rosas E FIR - Kuijper, Aaf IR - Kuijper A FIR - Abbink, Evertine IR - Abbink E FIR - Alhakim, Mazin IR - Alhakim M FIR - Drost, J IR - Drost J FIR - Oude Ophuis, Anthonius Josephus Maria IR - Oude Ophuis AJM FIR - Houtgraaf, Jaco IR - Houtgraaf J FIR - Nieuwdorp, Max IR - Nieuwdorp M FIR - van Eck, Martijn IR - van Eck M FIR - Nierop, Pieter IR - Nierop P FIR - van Raalte, Daniel IR - van Raalte D FIR - Bemelmans, Remy IR - Bemelmans R FIR - Kooy, Adriaan IR - Kooy A FIR - Constandse, Jan IR - Constandse J FIR - Kievit, Chris IR - Kievit C FIR - Monajemi, Houshang IR - Monajemi H FIR - Jaspers Focks, Jeroen IR - Jaspers Focks J FIR - Spiering, Wilko IR - Spiering W FIR - Broeyer, Freerk IR - Broeyer F FIR - Rudzki, Henryk IR - Rudzki H FIR - Jozefowska, Malgorzata IR - Jozefowska M FIR - Lukaszewicz, Monika IR - Lukaszewicz M FIR - Szyprowska, Ewa IR - Szyprowska E FIR - Jusiak, Katarzyna IR - Jusiak K FIR - Modzelewska, Anna IR - Modzelewska A FIR - Sowinski, Dariusz IR - Sowinski D FIR - Matyjaszek-Matuszek, Beata IR - Matyjaszek-Matuszek B FIR - Skokowska, Ewa IR - Skokowska E FIR - Pankowska, Ewa IR - Pankowska E FIR - Kwiatkowska, Magdalena IR - Kwiatkowska M FIR - Opiela, Jaroslaw IR - Opiela J FIR - Krzyzagorska, Ewa IR - Krzyzagorska E FIR - Laszewska, Grazyna IR - Laszewska G FIR - Witek, Robert IR - Witek R FIR - Pisarczyk-Wiza, Dorota IR - Pisarczyk-Wiza D FIR - Tiuryn-Petrulewicz, Agnieszka IR - Tiuryn-Petrulewicz A FIR - Stasinska, Teresa IR - Stasinska T FIR - Madej, Andrzej IR - Madej A FIR - Mindrescu, Nicoleta IR - Mindrescu N FIR - Ciomos, Daniela IR - Ciomos D FIR - Pletea, Noemi IR - Pletea N FIR - Valerica, Nafornita IR - Valerica N FIR - Popa, Bogdan IR - Popa B FIR - Neacsu, Valentina IR - Neacsu V FIR - Onaca, Adriana IR - Onaca A FIR - Hortensia, Barbonta Diana IR - Hortensia BD FIR - Vacaru, Georgeta IR - Vacaru G FIR - Popescu, Alexandrina IR - Popescu A FIR - Vladu, Ionela Mihaela IR - Vladu IM FIR - Cosma, Dana IR - Cosma D FIR - Morosanu, Magdalena IR - Morosanu M FIR - Guja, Cristian IR - Guja C FIR - Pop, Lavinia IR - Pop L FIR - Pintilei, Ella IR - Pintilei E FIR - Pascu, Marlena IR - Pascu M FIR - Gutu, Olimpia IR - Gutu O FIR - Negrisanu, Gabriela IR - Negrisanu G FIR - Thury-Burileanu, Amalia IR - Thury-Burileanu A FIR - Chazova, Irina IR - Chazova I FIR - Khalimov, Yury IR - Khalimov Y FIR - Kunitsyna, Marina IR - Kunitsyna M FIR - Vorokhobina, Natalia IR - Vorokhobina N FIR - Yakushin, Sergey IR - Yakushin S FIR - Dvoryashina, Irina IR - Dvoryashina I FIR - Samoylova, Julia IR - Samoylova J FIR - Glinkina, Irina IR - Glinkina I FIR - Mkrtumyan, Ashot IR - Mkrtumyan A FIR - Markova, Tatiana IR - Markova T FIR - Vorobyev, Sergey IR - Vorobyev S FIR - Petunina, Nina IR - Petunina N FIR - Khokhlov, Alexander IR - Khokhlov A FIR - Dreval, Alexander IR - Dreval A FIR - Kharakhulakh, Marina IR - Kharakhulakh M FIR - Ipatko, Irina IR - Ipatko I FIR - Ershova, Olga IR - Ershova O FIR - Filippov, Evgeny IR - Filippov E FIR - Ermakova, Polina IR - Ermakova P FIR - Startseva, Maria IR - Startseva M FIR - Gonchar, Natalia IR - Gonchar N FIR - Galstyan, Gagik IR - Galstyan G FIR - Bondar, Irina IR - Bondar I FIR - Demidova, Irina IR - Demidova I FIR - Litvin, Alexander IR - Litvin A FIR - Drapkina, Oxana IR - Drapkina O FIR - Merciakova, Martina IR - Merciakova M FIR - Teplanova, Miriam IR - Teplanova M FIR - Kubincova, Ludmila IR - Kubincova L FIR - Zobokova, Barbora IR - Zobokova B FIR - Macko, Marek IR - Macko M FIR - Zakovicova, Eva IR - Zakovicova E FIR - Lachova, Beata IR - Lachova B FIR - Gabrisova, Alena IR - Gabrisova A FIR - Tomasova, Livia IR - Tomasova L FIR - Sosovec, Dalibor IR - Sosovec D FIR - Lee, Joonyub IR - Lee J FIR - Yu, Jae Myung IR - Yu JM FIR - Lee, Byung Wan IR - Lee BW FIR - Ahn, Kyu Jeung IR - Ahn KJ FIR - Cho, Young Min IR - Cho YM FIR - Namgoong, Ilseong IR - Namgoong I FIR - Kim, Hye Soon IR - Kim HS FIR - Chung, Choon Hee IR - Chung CH FIR - Lee, Woo Je IR - Lee WJ FIR - Kim, Sin Gon IR - Kim SG FIR - Fajardo, Carmen IR - Fajardo C FIR - Gonzalez-Juanatey, Jose Ramon IR - Gonzalez-Juanatey JR FIR - Beltran Robles, Manuel IR - Beltran Robles M FIR - Soto Gonzalez, Alfonso IR - Soto Gonzalez A FIR - de la Cuesta, Carmen IR - de la Cuesta C FIR - Jodar Gimeno, Esteban IR - Jodar Gimeno E FIR - Lopez de la Torre Casares, Martin IR - Lopez de la Torre Casares M FIR - Tinahones Madueno, Francisco IR - Tinahones Madueno F FIR - Merino-Torres, Juan IR - Merino-Torres J FIR - Rivas Fernandez, Margarita IR - Rivas Fernandez M FIR - Bellido Guerrero, Diego IR - Bellido Guerrero D FIR - Rico Corral, Miguel Angel IR - Rico Corral MA FIR - Manzano Espinosa, Luis IR - Manzano Espinosa L FIR - Ferrer Garcia, Juan Carlos IR - Ferrer Garcia JC FIR - Mezquita-Raya, Pedro IR - Mezquita-Raya P FIR - Botella Serrano, Marta IR - Botella Serrano M FIR - Garcia Del Rio, Enrique IR - Garcia Del Rio E FIR - Delgado, Elias IR - Delgado E FIR - De Luis Roman, Daniel IR - De Luis Roman D FIR - Castro, Almudena IR - Castro A FIR - Larnefeldt, Hans IR - Larnefeldt H FIR - Eliasson, Bjorn IR - Eliasson B FIR - Tengmark, Bengt-Olov IR - Tengmark BO FIR - Mooe, Thomas IR - Mooe T FIR - Eliasson, Ken IR - Eliasson K FIR - Luts, Anders IR - Luts A FIR - Sung, Shih-Hsien IR - Sung SH FIR - Lee, I-Te IR - Lee IT FIR - Hsieh, I-Chang IR - Hsieh IC FIR - Huang, Wei-Fu IR - Huang WF FIR - Tu, Shih-Te IR - Tu ST FIR - Chao, Ting-Hsing IR - Chao TH FIR - Chen, Jung-Fu IR - Chen JF FIR - Liu, Ming-En IR - Liu ME FIR - Wang, Ji-Hung IR - Wang JH FIR - Araz, Mustafa IR - Araz M FIR - Sertbas, Meltem IR - Sertbas M FIR - Sezer, Kerem IR - Sezer K FIR - Yaylali, Guzin IR - Yaylali G FIR - Guney, Engin IR - Guney E FIR - Dogruel, Fatma IR - Dogruel F FIR - Celik, Ozlem IR - Celik O FIR - Deyneli, Oguzhan IR - Deyneli O FIR - Mert, Meral IR - Mert M FIR - Comlekci, Abdurrahman IR - Comlekci A FIR - Saygili, Fusun IR - Saygili F FIR - Kebabci, Nur IR - Kebabci N FIR - Evren, Bahri IR - Evren B FIR - Bilen, Habib IR - Bilen H FIR - Sargin, Mehmet IR - Sargin M FIR - Bakiner, Okan IR - Bakiner O FIR - Sari, Ramazan IR - Sari R FIR - Canturk, Zeynep IR - Canturk Z FIR - Tuzcu, Alpaslan IR - Tuzcu A FIR - Orlenko, Valeriia IR - Orlenko V FIR - Kaydashev, Igor IR - Kaydashev I FIR - Berenfus, Vadym IR - Berenfus V FIR - Panina, Svitlana IR - Panina S FIR - Prystupa, Lyudmila IR - Prystupa L FIR - Katerenchuk, Vitaliy IR - Katerenchuk V FIR - Zinych, Olesia IR - Zinych O FIR - Vlasenko, Maryna IR - Vlasenko M FIR - Pashkovska, Nataliia IR - Pashkovska N FIR - Pertseva, Nataliia IR - Pertseva N FIR - Vizir, Vadym IR - Vizir V FIR - Pererva, Larysa IR - Pererva L FIR - Kopytsya, Mykola IR - Kopytsya M FIR - Kuznietsova, Olena IR - Kuznietsova O FIR - Tseluyko, Vira IR - Tseluyko V FIR - Mankovsky, Borys IR - Mankovsky B FIR - Reshotko, Dmytro IR - Reshotko D FIR - Serhiyenko, Olexandr IR - Serhiyenko O FIR - Zlova, Tetiana IR - Zlova T FIR - Teliatnikova, Zinaida IR - Teliatnikova Z FIR - Postol, Svitlana IR - Postol S FIR - Browne, Duncan IR - Browne D FIR - McCrimmon, Rory IR - McCrimmon R FIR - Davies, Melanie IR - Davies M FIR - Tatovic, Danijela IR - Tatovic D FIR - Garstang, Jonathan IR - Garstang J FIR - Sathyapalan, Thozhukat IR - Sathyapalan T FIR - Philip, Sam IR - Philip S FIR - Wilding, John IR - Wilding J FIR - Sharma, Sanjeev IR - Sharma S FIR - Stephens, Jeffrey IR - Stephens J FIR - Boyle, James IR - Boyle J FIR - Gunstone, Anthony IR - Gunstone A FIR - Tan, Anjanette IR - Tan A FIR - Chang, Anna IR - Chang A FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Gangi, Sumana IR - Gangi S FIR - Bressler, Peter IR - Bressler P FIR - Aslam, Shamaila IR - Aslam S FIR - Wiebel, Jaime IR - Wiebel J FIR - Palal, Betsy IR - Palal B FIR - Nakhle, Samer IR - Nakhle S FIR - Tripathy, Devjit IR - Tripathy D FIR - Gabriel, John IR - Gabriel J FIR - Lillestol, Michael IR - Lillestol M FIR - Pullman, John IR - Pullman J FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Soufer, Joseph IR - Soufer J FIR - Agarwal, Shubham IR - Agarwal S FIR - Poremba, John IR - Poremba J FIR - Tanzer, Adam IR - Tanzer A FIR - Cortes-Maisonet, Gregorio IR - Cortes-Maisonet G FIR - Smith, Timothy IR - Smith T FIR - Wynne, Alan IR - Wynne A FIR - Comulada-Rivera, Angel IR - Comulada-Rivera A FIR - Ortiz-Carrasquillo, Ramon IR - Ortiz-Carrasquillo R FIR - Schuchard, Timothy IR - Schuchard T FIR - Biscoveanu, Mihaela IR - Biscoveanu M FIR - Brautigam, Donald IR - Brautigam D FIR - Vazquez-Tanus, Jose IR - Vazquez-Tanus J FIR - Palchick, Bryce IR - Palchick B FIR - Bhargava, Anuj IR - Bhargava A FIR - Correia, Marcelo IR - Correia M FIR - Samal, Aditya IR - Samal A FIR - Busch, Robert IR - Busch R FIR - Cavale, Arvind IR - Cavale A FIR - Oliver, Michael IR - Oliver M FIR - French, William IR - French W FIR - Hansen, Darrin IR - Hansen D FIR - Woolman, Michael IR - Woolman M FIR - Chow, Christopher IR - Chow C FIR - Bitar, Fahed IR - Bitar F FIR - Chochinov, Ronald IR - Chochinov R FIR - Johnson, David IR - Johnson D FIR - Soucie, Gary IR - Soucie G FIR - Boeder, Schafer IR - Boeder S FIR - Mello, Curtis IR - Mello C FIR - Ledger, Gregory IR - Ledger G FIR - Norwood, Paul IR - Norwood P FIR - Bailey, Timothy IR - Bailey T FIR - Gaudiani, Linda IR - Gaudiani L FIR - Rabin, Mara Lee IR - Rabin ML FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Madu, Ivy-Joan IR - Madu IJ FIR - Firek, Anthony IR - Firek A FIR - Grasch, Anton IR - Grasch A FIR - Utzschneider, Kristina IR - Utzschneider K FIR - Barkhuizen, Andre IR - Barkhuizen A FIR - Khachikian, Sonalika IR - Khachikian S FIR - Desouza, Cyrus IR - Desouza C FIR - Youssef, Rasha IR - Youssef R FIR - Foucauld, Jean IR - Foucauld J FIR - Vedere, Amarnath IR - Vedere A FIR - Forgosh, Les IR - Forgosh L FIR - Cox, Michael IR - Cox M FIR - Suh, David IR - Suh D FIR - Singh, Narendra IR - Singh N FIR - Odugbesan, Ola IR - Odugbesan O FIR - Robbins, David IR - Robbins D FIR - Mangual Garcia, Michelle IR - Mangual Garcia M FIR - Rodbard, Helena IR - Rodbard H FIR - Brusco, Osvaldo IR - Brusco O FIR - Ong, Stephen IR - Ong S FIR - Koren, Michael IR - Koren M FIR - Jabbour, Serge IR - Jabbour S FIR - Chu, James IR - Chu J FIR - Rovner, Sergio IR - Rovner S FIR - Park, Jean IR - Park J FIR - Bode, Bruce IR - Bode B FIR - Cole, Jeffrey IR - Cole J FIR - Jones, Thomas IR - Jones T FIR - Nadar, Venkatesh IR - Nadar V FIR - Luo, Lan IR - Luo L FIR - Canadas, Rafael IR - Canadas R FIR - Saba, Fadi IR - Saba F FIR - Rowell, Jennifer IR - Rowell J FIR - Cohen, Alan IR - Cohen A FIR - Haddad, Tariq IR - Haddad T FIR - Miao, Simeng IR - Miao S FIR - Parker, John IR - Parker J FIR - Koilpillai, Robinson IR - Koilpillai R FIR - Whiles, Rick IR - Whiles R FIR - Ranadive, Nadakishore IR - Ranadive N FIR - Mills, Richard IR - Mills R FIR - Manning, Rickey IR - Manning R FIR - Barker, Timothy IR - Barker T FIR - Welch, Michelle IR - Welch M FIR - Mayfield, Ronald IR - Mayfield R FIR - Ovalle, Fernando IR - Ovalle F FIR - Rasouli, Neda IR - Rasouli N FIR - Chaychi, Leila IR - Chaychi L FIR - Hotchkiss, David IR - Hotchkiss D FIR - Magee, James IR - Magee J FIR - Berk, Martin IR - Berk M FIR - Wysham, Carol IR - Wysham C FIR - Upadhyay, Shital Hiten IR - Upadhyay SH FIR - Hamdy, Osama IR - Hamdy O FIR - Aroda, Vanita IR - Aroda V FIR - Bays, Harold IR - Bays H FIR - Gonzalez-Orozco, Luis IR - Gonzalez-Orozco L FIR - Sugimoto, Danny IR - Sugimoto D FIR - Lupovitch, Steven IR - Lupovitch S FIR - Agaiby, John IR - Agaiby J FIR - Fraser, Neil IR - Fraser N FIR - Sartore, J Christopher IR - Sartore JC FIR - Widicus, Diana IR - Widicus D FIR - Barzilay, Joshua IR - Barzilay J FIR - Slim, Ahmad IR - Slim A FIR - Rosenstock, Julio IR - Rosenstock J FIR - Shikuma Lee, Kelsey IR - Shikuma Lee K FIR - Pantalone, Kevin IR - Pantalone K FIR - Hermayer, Kathie IR - Hermayer K FIR - Bekwelem, Wobo IR - Bekwelem W FIR - Connery, Lisa IR - Connery L FIR - Prier, Kevin IR - Prier K FIR - Grena, Paul IR - Grena P FIR - Perez, Rodolfo IR - Perez R EDAT- 2025/12/17 19:11 MHDA- 2025/12/17 19:12 CRDT- 2025/12/17 16:53 PHST- 2025/12/17 19:12 [medline] PHST- 2025/12/17 19:11 [pubmed] PHST- 2025/12/17 16:53 [entrez] AID - 10.1056/NEJMoa2505928 [doi] PST - ppublish SO - N Engl J Med. 2025 Dec 18;393(24):2409-2420. doi: 10.1056/NEJMoa2505928. PMID- 41405672 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20261009 IS - 1708-0428 (Electronic) IS - 0960-8923 (Linking) VI - 36 IP - 2 DP - 2026 Feb TI - Preoperative GLP-1 Receptor Agonists Exposure and Risk of Postoperative Acute Kidney Injury after Metabolic and Bariatric Surgery: A Retrospective Study. PG - 418-428 LID - 10.1007/s11695-025-08436-w [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) are increasingly prescribed for patients with type 2 diabetes mellitus (T2DM) and obesity undergoing metabolic and bariatric surgery (MBS). This study evaluated the association between preoperative GLP-1-RAs exposure and the risk of acute kidney injury (AKI) following MBS. METHODS: This retrospective cohort study utilized the TriNetX Research Network to identify adults with T2DM and a body mass index exceeding 35 kg/m(2) who underwent elective laparoscopic MBS (2010-2024). Patients were stratified by preoperative GLP-1-RAs exposure and matched using propensity score analysis. The primary outcome was the incidence of AKI within 90 days after surgery, and the secondary outcomes included mortality, intensive care unit (ICU) admission, sepsis, and events of postoperative hyperglycemia (i.e., serum glucose > 180 mg/dL). RESULTS: After propensity score matching, 5,480 patients were included in each cohort. Preoperative GLP-1-RAs exposure was associated with a significantly reduced 90-day AKI risk (1.6% versus 2.3%; hazard ratio [HR]: 0.68, 95% confidence interval [CI] 0.52-0.89, p = 0.005, absolute risk reduction [ARR]:0.73%, number needed to treat [NNT]:137) and 30-day risk (HR: 0.58, p = 0.001). GLP-1-RAs exposure also correlated with a lower risk of postoperative hyperglycemia (24.5% versus 26.6%, HR:0.91, 95% CI: 0.85-0.99, p = 0.013, ARR 2.04%, NNT 49). No significant differences were observed in mortality, ICU admission, or sepsis. Sensitivity analyses confirmed these consistent findings. CONCLUSION: Preoperative GLP-1-RAs exposure was associated with a reduced AKI risk following MBS, with concurrent improvement in perioperative glycemic control. Future randomized controlled studies are required to validate these observational findings and clarify the underlying mechanisms. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Hung, Kuo-Chuan AU - Hung KC AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan. FAU - Chang, Li-Chen AU - Chang LC AD - Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan. FAU - Tan, Ping-Heng AU - Tan PH AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AD - Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan. FAU - Lai, Yi-Chen AU - Lai YC AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan City, Taiwan. FAU - Chen, I-Wen AU - Chen IW AD - Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan City, Taiwan. cheniwena60912@gmail.com. LA - eng PT - Journal Article DEP - 20251217 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - *Acute Kidney Injury/epidemiology/etiology/prevention & control MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Bariatric Surgery/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/surgery MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - *Postoperative Complications/epidemiology/etiology/prevention & control MH - Propensity Score MH - Risk Factors OTO - NOTNLM OT - Acute kidney injury OT - Bariatric surgery OT - Glucagon-like peptide-1 receptor agonists OT - Metabolic surgery OT - Perioperative outcomes OT - Type 2 diabetes mellitus COIS- Declarations. Competing Interests: The authors declare no competing interests. EDAT- 2025/12/17 13:03 MHDA- 2026/03/06 13:44 CRDT- 2025/12/17 11:07 PHST- 2025/10/01 00:00 [received] PHST- 2025/12/05 00:00 [accepted] PHST- 2025/11/28 00:00 [revised] PHST- 2026/03/06 13:44 [medline] PHST- 2025/12/17 13:03 [pubmed] PHST- 2025/12/17 11:07 [entrez] AID - 10.1007/s11695-025-08436-w [pii] AID - 10.1007/s11695-025-08436-w [doi] PST - ppublish SO - Obes Surg. 2026 Feb;36(2):418-428. doi: 10.1007/s11695-025-08436-w. Epub 2025 Dec 17. PMID- 41402646 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1590-3478 (Electronic) IS - 1590-1874 (Linking) VI - 47 IP - 1 DP - 2025 Dec 17 TI - Effect of Tirzepatide on arrhythmic, major cardiovascular, and neurological outcomes in patients with type 2 diabetes: A systematic review and meta-analysis. PG - 10 LID - 10.1007/s10072-025-08680-z [doi] AB - BACKGROUND: Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective for glycemic control in type 2 diabetes (T2D), but its impact on cardiovascular (CV) and neurological safety remains uncertain. This meta-analysis evaluated the risks of arrhythmic, major CV, and neurological outcomes associated with tirzepatide. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane databases was conducted to identify eligible randomized controlled trials (RCTs) reporting arrhythmic, major CV, and neurological outcomes published up to February 2025. Additionally, subgroup analyses were conducted by age, BMI, diabetes duration, and comparator type. RESULTS: Twelve RCTs involving 10,615 patients with T2D were included. Tirzepatide was not associated with a statistically significant increase in arrhythmic outcomes, including atrial fibrillation (AF) (RR 1.39, 95% CI 0.53 to 3.67) and atrial flutter (AFL) (RR 1.14, 95% CI 0.20 to 6.55). For major CV outcomes, no significant differences were observed for acute myocardial infarction (RR 0.66, 95% CI 0.38 to 1.17) or coronary artery disease (RR 0.62, 95% CI 0.32 to 1.18). Neurologically, tirzepatide significantly increased the risk of dizziness (RR 1.64, 95% CI 1.04 to 2.57), whereas the risks of headache (RR 1.00, 95% CI 0.65 to 1.55) and transient ischemic attack (RR 1.43, 95% CI 0.44 to 4.61) were not significant. Subgroup analyses suggested higher dizziness risk in patients aged 10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from nationwide health-data registries. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, gastroesophageal reflux disease, obesity, alcohol overconsumption, and tobacco smoking. RESULTS: This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with nonusers (adjusted OR 1.3, 95% CI 1.1-1.5). Instead, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8). DISCUSSION: Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. The validity of the observed decreased risk of esophageal squamous cell carcinoma is uncertain. CI - Copyright (c) 2025 by The American College of Gastroenterology. FAU - Hardvik Akerstrom, Johan AU - Hardvik Akerstrom J AUID- ORCID: 0000-0003-2199-7965 AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Santoni, Giola AU - Santoni G AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - von Euler-Chelpin, My AU - von Euler-Chelpin M AUID- ORCID: 0000-0003-2204-7048 AD - Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Birgisson, Helgi AU - Birgisson H AD - The Icelandic Cancer Registry, Reykjavik, Iceland. FAU - Ness-Jensen, Eivind AU - Ness-Jensen E AUID- ORCID: 0000-0001-6005-0729 AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. AD - Department of Public Health and Nursing, HUNT Research Centre, NTNU, Norwegian University of Science and Technology, Trondheim/Levanger, Norway. AD - Medical Department, Levanger Hospital, Nord-Trondelag Hospital Trust, Levanger, Norway. FAU - Kauppila, Joonas H AU - Kauppila JH AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. AD - Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland. FAU - Holmberg, Dag AU - Holmberg D AUID- ORCID: 0000-0003-1000-5422 AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Lagergren, Jesper AU - Lagergren J AUID- ORCID: 0000-0002-5143-5448 AD - Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. AD - School of Cancer and Pharmaceutical Sciences, King's College London, London, UK . LA - eng GR - 24 3414/Cancerfonden/ PT - Journal Article PT - Multicenter Study DEP - 20251212 PL - United States TA - Am J Gastroenterol JT - The American journal of gastroenterology JID - 0421030 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Adenocarcinoma Of Esophagus SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Adenocarcinoma/epidemiology/prevention & control MH - Case-Control Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Esophageal Neoplasms/epidemiology/prevention & control MH - *Esophageal Squamous Cell Carcinoma/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Obesity/complications/drug therapy/epidemiology OTO - NOTNLM OT - GLP-1 OT - esophageal neoplasm OT - incretin OT - obesity-associated malignancy EDAT- 2025/12/12 17:55 MHDA- 2026/09/02 11:39 CRDT- 2025/12/12 10:13 PHST- 2025/06/05 00:00 [received] PHST- 2025/12/04 00:00 [accepted] PHST- 2026/09/02 11:39 [medline] PHST- 2025/12/12 17:55 [pubmed] PHST- 2025/12/12 10:13 [entrez] AID - 00000434-202609000-00019 [pii] AID - 10.14309/ajg.0000000000003885 [doi] PST - ppublish SO - Am J Gastroenterol. 2026 Sep 1;121(9):2158-2165. doi: 10.14309/ajg.0000000000003885. Epub 2025 Dec 12. PMID- 41380027 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 2 DP - 2026 Feb 1 TI - Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. PG - 257-265 LID - 10.2337/dc25-1080 [doi] AB - OBJECTIVE: To examine the effects of oral semaglutide on kidney outcomes in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: SOUL (NCT03914326), a double-blind randomized controlled trial, compared oral semaglutide with placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse cardiovascular (CV) events. Prespecified kidney outcomes included a five-point composite (>/=50% decrease in estimated glomerular filtration rate [eGFR], persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy, or death from kidney or CV causes); a four-point composite (excluding CV death); and eGFR decline. Prespecified subgroups were also assessed, including those with eGFR <60 mL/min/1.73 m2 at baseline. RESULTS: Among 9,650 participants, mean eGFR was 73.8 mL/min/1.73 m2, and follow-up was 47.5 months. The five-point outcome occurred in 403 (8.4%) and 435 (9.0%) participants taking oral semaglutide versus placebo, respectively (hazard ratio [HR] 0.91; 95% CI 0.80, 1.05; P = 0.19). The four-point outcome occurred in 112 (2.3%) and 129 (2.7%) participants, respectively (HR 0.86; 95% CI 0.66, 1.10; P = 0.22). Mean annual eGFR decline was less with oral semaglutide than placebo (-1.67 vs. -2.06 mL/min/1.73 m2; estimated treatment difference 0.40 [95% CI 0.27, 0.53; P < 0.0001). These effects were similar across most subgroups, including those with eGFR <60 mL/min/1.73 m2. Serious adverse events occurred at similar rates in both groups. CONCLUSIONS: In people with T2D and ASCVD and/or CKD but with overall mostly preserved eGFR, orally administered semaglutide, compared with placebo, did not significantly reduce adverse kidney outcomes but did slow the decline in eGFR. CI - (c) 2025 by the American Diabetes Association. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University, Erlangen, Germany. FAU - Marx, Nikolaus AU - Marx N AD - RWTH Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London, U.K. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT. FAU - McGuire, Darren K AU - McGuire DK AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX. AD - Parkland Health and Hospital System, Dallas, TX. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland, OR. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London, U.K. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Tubingen, Germany. AD - German Center for Diabetes Research and Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, Germany. FAU - Amod, Aslam AU - Amod A AD - Life Chatsmed Garden Hospital and University of KwaZulu-Natal, Durban, South Africa. FAU - Mankovsky, Boris AU - Mankovsky B AD - Institute of Gerontology, Kyiv, Ukraine. FAU - Desouza, Cyrus AU - Desouza C AD - Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE. FAU - Gorgojo-Martinez, Juan J AU - Gorgojo-Martinez JJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Fundacion Alcorcon, Madrid, Spain. FAU - Arechavaleta, Rosario AU - Arechavaleta R AD - Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico. FAU - Tu, Shih-Te AU - Tu ST AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, NC. CN - SOUL Study Group* LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - n/a/Novo Nordisk/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Middle Aged MH - Glomerular Filtration Rate/drug effects MH - Double-Blind Method MH - Aged MH - *Renal Insufficiency, Chronic/drug therapy MH - Administration, Oral MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Kidney/drug effects PMC - PMC12824789 COIS- Duality of Interest. J.F.E.M. reports grants from Novo Nordisk, the European Union, and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; participation on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim; authorship for UpToDate; and a leadership role in the Kidney Disease: Improving Global Outcomes (KDIGO) group. N.M. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TRR 219; Project-ID 322900939 [M03, M05]) and has given lectures for Bayer, Boehringer Ingelheim, Sanofi Aventis, MSD, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, and Novo Nordisk; received unrestricted research grants from Boehringer Ingelheim; served as an advisor for Bayer, Boehringer Ingelheim, Sanofi Aventis, MSD, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk; and served in trial leadership for Boehringer Ingelheim and Novo Nordisk. N.M. declines all personal compensation from pharma or device companies. J.E.D. reports grants or contracts in 2022-2025 from Alzheimer's Research UK and in 2019-2022 from the British Heart Foundation and consulting fees/honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. S.S.E. declares consulting fees from Novo Nordisk for steering committee participation and from Boehringer Ingelheim for consulting for veterinary CHF; support for attending or travel from meetings and/or travel from Novo Nordisk; and participation on advisory boards for Novo Nordisk, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GlaxoSmithKline, Eli Lilly, Novartis, Bristol-Myers Squibb, and Sanofi. S.E.I. has served as a consultant or on advisory boards for Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, and Bayer; given lectures sponsored by AstraZeneca and Boehringer Ingelheim/Lilly; received royalties from McGraw-Hill and Wolters Kluwer Health; and received support for attending meetings and/or travel from Novo Nordisk, AstraZeneca, Boehringer Ingelheim/Lilly, and Bayer. D.K.M. has received consulting fees from Novo Nordisk, AstraZeneca, Pfizer, Altimmune, Ventyx Pharmaceuticals, Bayer, Lexicon, Applied Therapeutics, Intercept Pharmaceuticals, Esperion, Lilly USA, Boehringer Ingelheim, New Amsterdam, CSL Behring, Amgen, Neurotronics, Metsera, Kailera, and Alveus Pharma. S.L.M. has served as a consultant or on advisory boards for Novo Nordisk and Merck. R.P.-B. has received research grant support to her institutions from the National Institute of Diabetes and Digestive and Kidney Diseases, Breakthrough T1D (formerly JDRF), Bayer, Lexicon Pharmaceuticals, and Novo Nordisk; consulting fees from Averitas Pharma, Biogen, Lexicon Pharmaceuticals, Nevro Inc., Novo Nordisk, and Roche Diagnostic; support for attending meetings and/or travel from Roche; participation on an advisory board for Biogen/Reata; and membership on the board of directors of the American Diabetes Association. N.R.P. has received financial support from several pharmaceutical companies that manufacture blood pressure-lowering, lipid-lowering, and glucose-lowering agents for consultancy fees, research projects and staff, and for arranging and speaking at educational meetings, including Servier, Pfizer, AstraZeneca, Amgen, Sanofi, and Novo Nordisk; he holds no stocks and shares in any such companies. M.D.M.E., N.B., T.I., and O.K.J. are employees and shareholders of Novo Nordisk. G.K.H. has received funding from the Klinkerpadfonds, paid out to his former academic institution (Amsterdam UMC, the Netherlands) and is an employee and shareholder of Novo Nordisk. A.L.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; GRK2816; BI1292/12-1; 10-1; 9-1) and the German Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.); has given lectures for Novo Nordisk and Daiichi Sankyo; has received unrestricted research grants from Boehringer Ingelheim and AstraZeneca; has served as an advisor for Bayer and Novo Nordisk; and has served in trial leadership for Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. A.L.B. declines all personal compensation from pharma or device companies. A.A. reports contract research fees, advisory board fees, and lecture fees from Novo Nordisk, and advisory board fees and lecture fees from Aspen Pharma (SA) and Lilly (SA). B.M. has served on advisory boards and received speaking fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi, Servier, and Worwag Pharma. C.D. reports Novo Nordisk research grants (payments to institution) and has personally received consulting fees from Eli Lilly and consulting fees and support for attending meetings and/or travel from Novo Nordisk. J.J.G.-M. has the following financial relationships: advisor on scientific boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and Novo Nordisk; lectures for Amarin, AstraZeneca, Boehringer Ingelheim, Menarini, and Novo Nordisk; and research activities for AstraZeneca, Mundipharma, and Novo Nordisk. R.A. has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk and Eli Lilly. S.-T.T. has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. J.B.B. reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns Inc., Vertex, and Zealand; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. No other potential conflicts of interest relevant to this article were reported. FIR - McGuire, D K IR - McGuire DK FIR - Buse, J B IR - Buse JB FIR - Mann, J F E IR - Mann JFE FIR - Marx, N IR - Marx N FIR - Deanfield, J E IR - Deanfield JE FIR - Emerson, S S IR - Emerson SS FIR - Inzucchi, S E IR - Inzucchi SE FIR - Mulvagh, S L IR - Mulvagh SL FIR - Pop-Busui, R IR - Pop-Busui R FIR - Poulter, N R IR - Poulter NR FIR - Engelmann, M D M IR - Engelmann MDM FIR - Hovingh, G K IR - Hovingh GK FIR - Schelde, P B IR - Schelde PB FIR - Birkenfeld, A L IR - Birkenfeld AL FIR - Amod, A IR - Amod A FIR - Mankovsky, B IR - Mankovsky B FIR - Desouza, C IR - Desouza C FIR - Gorgojo-Martinez, J J IR - Gorgojo-Martinez JJ FIR - Arechavaleta, R IR - Arechavaleta R FIR - Tu, S-T IR - Tu ST FIR - Francisco, J IR - Francisco J FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Chow, F Chun Chung IR - Chow FCC FIR - Watada, Hirotaka IR - Watada H FIR - Yoon, Kun Ho IR - Yoon KH FIR - Singh, Pardeep Jhund IR - Singh PJ FIR - Matthew IR - Matthew FIR - Perez Manghi, F IR - Perez Manghi F FIR - Pozzi, J M IR - Pozzi JM FIR - Lorenzatti, A J IR - Lorenzatti AJ FIR - Visco, V E IR - Visco VE FIR - Piskorz, D IR - Piskorz D FIR - Nardone, L IR - Nardone L FIR - Chahin, M I IR - Chahin MI FIR - Bustamante Labarta, M IR - Bustamante Labarta M FIR - Luquez, C IR - Luquez C FIR - MacKinnon, I J IR - MacKinnon IJ FIR - Pieber, T IR - Pieber T FIR - Prager, R IR - Prager R FIR - Fliesser-Gorzer, E IR - Fliesser-Gorzer E FIR - Ebenbichler, C IR - Ebenbichler C FIR - Fasching, P IR - Fasching P FIR - Mathieu, C IR - Mathieu C FIR - De Block, C IR - De Block C FIR - Duyck, F IR - Duyck F FIR - Heyns, E IR - Heyns E FIR - Lapauw, B IR - Lapauw B FIR - Turatti, L A A IR - Turatti LAA FIR - Franco, D R IR - Franco DR FIR - Rea, R R IR - Rea RR FIR - Kurtz Lisboa, R IR - Kurtz Lisboa R FIR - Salles, J E IR - Salles JE FIR - Saraiva, J F K IR - Saraiva JFK FIR - Fonseca, A G T IR - Fonseca AGT FIR - Vidotti, M H IR - Vidotti MH FIR - Leite, S O IR - Leite SO FIR - Aggarwal, N IR - Aggarwal N FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Noronha, L IR - Noronha L FIR - Pedersen, S IR - Pedersen S FIR - Peterson, S IR - Peterson S FIR - Tellier, G IR - Tellier G FIR - Weisnagel, J IR - Weisnagel J FIR - Beca, S IR - Beca S FIR - Alasaad, H IR - Alasaad H FIR - Punthakee, Z IR - Punthakee Z FIR - Mancini, J G B IR - Mancini JGB FIR - Tytus, R IR - Tytus R FIR - Ransom, T P P IR - Ransom TPP FIR - Connelly, K IR - Connelly K FIR - Husain, M IR - Husain M FIR - Tsoukas, M IR - Tsoukas M FIR - Ji, L IR - Ji L FIR - Liu, J IR - Liu J FIR - Yuan, G IR - Yuan G FIR - Ye, X IR - Ye X FIR - Dong, X IR - Dong X FIR - Bian, F IR - Bian F FIR - Angelo, A A IR - Angelo AA FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Hernandez Erazo, I D IR - Hernandez Erazo ID FIR - Hernandez Ruiz, E A IR - Hernandez Ruiz EA FIR - Gomez Mesa, J E IR - Gomez Mesa JE FIR - Canecki-Varzic, S IR - Canecki-Varzic S FIR - Vucak Loncar, J IR - Vucak Loncar J FIR - Simegi-Djekic, V IR - Simegi-Djekic V FIR - Ticinovic Kurir, T IR - Ticinovic Kurir T FIR - Tusek, S IR - Tusek S FIR - Rahelic, D IR - Rahelic D FIR - Marusic, S IR - Marusic S FIR - Kruljac, I IR - Kruljac I FIR - Fabris Vitkovic, D IR - Fabris Vitkovic D FIR - Oznerova, M IR - Oznerova M FIR - Vrkoc, J IR - Vrkoc J FIR - Dolezalova, B IR - Dolezalova B FIR - Haluzik, M IR - Haluzik M FIR - Jankovec, Z IR - Jankovec Z FIR - Olsovsky, J IR - Olsovsky J FIR - Zemanova, J IR - Zemanova J FIR - Kyselova, P IR - Kyselova P FIR - Smahelova, A IR - Smahelova A FIR - Gregersen, S IR - Gregersen S FIR - Olsen, A-M Z IR - Olsen AZ FIR - Mikkelsen, D IR - Mikkelsen D FIR - Egstrup, K IR - Egstrup K FIR - Pedersen-Bjergaard, U IR - Pedersen-Bjergaard U FIR - Potier, L IR - Potier L FIR - Borot, S IR - Borot S FIR - Gaborit, B IR - Gaborit B FIR - Monier, A IR - Monier A FIR - Pradignac, A IR - Pradignac A FIR - Verges, B IR - Verges B FIR - Larroumet, A IR - Larroumet A FIR - Thuan, J-F IR - Thuan JF FIR - Kellerer, M IR - Kellerer M FIR - Ludemann, J IR - Ludemann J FIR - Esser, M IR - Esser M FIR - Kahrmann, G IR - Kahrmann G FIR - Kempe, H-P IR - Kempe HP FIR - Koch, T IR - Koch T FIR - Axthelm, C IR - Axthelm C FIR - Paschen, B IR - Paschen B FIR - Rose, L IR - Rose L FIR - Schaum, T IR - Schaum T FIR - Schulze, J IR - Schulze J FIR - Staudenmeyer, A IR - Staudenmeyer A FIR - Wenzl-Bauer, V IR - Wenzl-Bauer V FIR - Ma, R C W IR - Ma RCW FIR - Thomas, N IR - Thomas N FIR - Mohan, V IR - Mohan V FIR - Reddy, V S IR - Reddy VS FIR - Rao, P V IR - Rao PV FIR - Sahay, R IR - Sahay R FIR - Singh, J IR - Singh J FIR - Prakash, A IR - Prakash A FIR - Tandon, N IR - Tandon N FIR - Marwah, T IR - Marwah T FIR - Chaudhury, T IR - Chaudhury T FIR - Ghosh, S IR - Ghosh S FIR - Kanungo, A K IR - Kanungo AK FIR - Mittal, N IR - Mittal N FIR - Jacob, J J IR - Jacob JJ FIR - Chadha, M IR - Chadha M FIR - Chawla, M IR - Chawla M FIR - Bhagwat, N M IR - Bhagwat NM FIR - Jain, S M IR - Jain SM FIR - Thulaseedharan, N K IR - Thulaseedharan NK FIR - Girithara, G IR - Girithara G FIR - Desai, A IR - Desai A FIR - Sharma, S K IR - Sharma SK FIR - Murthy, S IR - Murthy S FIR - Sethi, B K IR - Sethi BK FIR - Kadam, Y IR - Kadam Y FIR - Kesavadev, J IR - Kesavadev J FIR - Daxini, B IR - Daxini B FIR - Chawla, R IR - Chawla R FIR - Gopalakrishnan, U A IR - Gopalakrishnan UA FIR - Baruah, M P IR - Baruah MP FIR - Reddy, S P IR - Reddy SP FIR - Suryanarayana, K M IR - Suryanarayana KM FIR - Singh, K P IR - Singh KP FIR - Saboo, B IR - Saboo B FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Hochberg, I IR - Hochberg I FIR - Sofer, Y IR - Sofer Y FIR - Tirosh, A IR - Tirosh A FIR - Shimon, I IR - Shimon I FIR - Vishlitzky, V IR - Vishlitzky V FIR - Bashkin, A IR - Bashkin A FIR - Tsur, A IR - Tsur A FIR - Shechter, M IR - Shechter M FIR - Andreozzi, F IR - Andreozzi F FIR - Setola, E IR - Setola E FIR - Consoli, A IR - Consoli A FIR - Lupoli, R IR - Lupoli R FIR - Genovese, S IR - Genovese S FIR - Maranghi, M IR - Maranghi M FIR - Lauro, D IR - Lauro D FIR - Citarrella, R IR - Citarrella R FIR - Fadini, G P IR - Fadini GP FIR - Murdolo, G IR - Murdolo G FIR - Di Carlo, A IR - Di Carlo A FIR - Giorgino, F IR - Giorgino F FIR - Buscemi, S IR - Buscemi S FIR - Hanaoka, K IR - Hanaoka K FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Ezaki, H IR - Ezaki H FIR - Yuki, H IR - Yuki H FIR - Kiyosue, A IR - Kiyosue A FIR - Hata, Y IR - Hata Y FIR - Sugawara, M IR - Sugawara M FIR - Domae, H IR - Domae H FIR - Iwata, H IR - Iwata H FIR - Nishida, Y IR - Nishida Y FIR - Igarashi, M IR - Igarashi M FIR - Fujino, S IR - Fujino S FIR - Oiwa, A IR - Oiwa A FIR - Oh, F IR - Oh F FIR - Sueyoshi, A IR - Sueyoshi A FIR - Murakami, T IR - Murakami T FIR - Tanaka, M IR - Tanaka M FIR - Idogaki, A IR - Idogaki A FIR - Onaka, H IR - Onaka H FIR - Mizote, I IR - Mizote I FIR - Doi, M IR - Doi M FIR - Ebisui, O IR - Ebisui O FIR - Tanabe, M IR - Tanabe M FIR - Natsuaki, M IR - Natsuaki M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Wan Mohamed, W M I IR - Wan Mohamed WMI FIR - Yahaya, N IR - Yahaya N FIR - Ratnasingam, J IR - Ratnasingam J FIR - Ong, T K IR - Ong TK FIR - Mohamad, M IR - Mohamad M FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Abdul Ghani, R IR - Abdul Ghani R FIR - Adam, N L IR - Adam NL FIR - Fam, T L IR - Fam TL FIR - Tan, F H S IR - Tan FHS FIR - Morales Villegas, E C IR - Morales Villegas EC FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Espinoza Peralta, D IR - Espinoza Peralta D FIR - Medina Pech, C E IR - Medina Pech CE FIR - Garcia Ulloa, A C IR - Garcia Ulloa AC FIR - Laviada Molina, H A IR - Laviada Molina HA FIR - Banda Elizondo, R G IR - Banda Elizondo RG FIR - Garza Ruiz, J A IR - Garza Ruiz JA FIR - Garcia Cantu, E A IR - Garcia Cantu EA FIR - van Bemmel, T IR - van Bemmel T FIR - de Valk, H W IR - de Valk HW FIR - Kooy, A IR - Kooy A FIR - Lieverse, L IR - Lieverse L FIR - Landewe-Cleuren, S A N T IR - Landewe-Cleuren SANT FIR - Hoogenberg, K IR - Hoogenberg K FIR - van Raalte, D IR - van Raalte D FIR - Jebbink, M IR - Jebbink M FIR - Oldenburg-Ligtenberg, C IR - Oldenburg-Ligtenberg C FIR - Abbink-Zandbergen, E IR - Abbink-Zandbergen E FIR - Mihai, B IR - Mihai B FIR - Crisan, C IR - Crisan C FIR - Filip, I IR - Filip I FIR - Busegeanu, M M IR - Busegeanu MM FIR - Roman, G IR - Roman G FIR - Mot, A C IR - Mot AC FIR - Nicoara, A IR - Nicoara A FIR - Anghel, V IR - Anghel V FIR - Pletea, N N IR - Pletea NN FIR - Suciu, M IR - Suciu M FIR - Strajer, D IR - Strajer D FIR - Cernea, S IR - Cernea S FIR - Zilov, A IR - Zilov A FIR - Kobalava, Z IR - Kobalava Z FIR - Ruyatkina, L A IR - Ruyatkina LA FIR - Suplotova, L A IR - Suplotova LA FIR - Sergeeva-Kondrachenko, M Y IR - Sergeeva-Kondrachenko MY FIR - Yanovskaya, M E IR - Yanovskaya ME FIR - Kargina, L IR - Kargina L FIR - Ignatyeva, A IR - Ignatyeva A FIR - Astamirova, K IR - Astamirova K FIR - Zalevskaya, A IR - Zalevskaya A FIR - Zagrebelnaya, O IR - Zagrebelnaya O FIR - Frolova, E V IR - Frolova EV FIR - Peskov, A B IR - Peskov AB FIR - Mishchenko Golinskaya, O IR - Mishchenko Golinskaya O FIR - Otroshchenko, O IR - Otroshchenko O FIR - Gaysina, L IR - Gaysina L FIR - Shabelnikova, O Y IR - Shabelnikova OY FIR - Saprina, T V IR - Saprina TV FIR - Lysenko, T A IR - Lysenko TA FIR - Kunitsyna, M IR - Kunitsyna M FIR - Zyangirova, S T IR - Zyangirova ST FIR - Lalic, N IR - Lalic N FIR - Lalic, K IR - Lalic K FIR - Beljic Zivkovic, T IR - Beljic Zivkovic T FIR - Kikovic, S IR - Kikovic S FIR - Djukic, A IR - Djukic A FIR - Pesic, M IR - Pesic M FIR - Dimic, D IR - Dimic D FIR - Stokic, E IR - Stokic E FIR - Mitrovic, M IR - Mitrovic M FIR - Polovina, S IR - Polovina S FIR - Djordjevic, M IR - Djordjevic M FIR - Sosovec, D IR - Sosovec D FIR - Pella, D IR - Pella D FIR - Donicova, V IR - Donicova V FIR - Hanackova Prasekova, S IR - Hanackova Prasekova S FIR - Koleny, D IR - Koleny D FIR - Culak, J IR - Culak J FIR - Cerna, K IR - Cerna K FIR - Hundza, V IR - Hundza V FIR - Gmitrov, J IR - Gmitrov J FIR - Lacka, J IR - Lacka J FIR - Plasil, R IR - Plasil R FIR - Bacus, H B IR - Bacus HB FIR - Bhorat, Q E IR - Bhorat QE FIR - Joshi, P IR - Joshi P FIR - Lakha, D R IR - Lakha DR FIR - Makan, V IR - Makan V FIR - Ntusi, N IR - Ntusi N FIR - Padayachee, T IR - Padayachee T FIR - Seeber, M E IR - Seeber ME FIR - Pillay, D IR - Pillay D FIR - Joshi, M IR - Joshi M FIR - Mayet, L IR - Mayet L FIR - Lee, J IR - Lee J FIR - Kim, S G IR - Kim SG FIR - Min, K W IR - Min KW FIR - Kang, E S IR - Kang ES FIR - Lee, W J IR - Lee WJ FIR - Choi, S H IR - Choi SH FIR - Lee, C B IR - Lee CB FIR - Lopez Suarez, A IR - Lopez Suarez A FIR - Garcia Ordonez, M A IR - Garcia Ordonez MA FIR - Garcia Quintana, A IR - Garcia Quintana A FIR - Mazon Ramos, P IR - Mazon Ramos P FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soto Gonzalez, A IR - Soto Gonzalez A FIR - Jodar, E IR - Jodar E FIR - Delgado Lista, J IR - Delgado Lista J FIR - Morales Portillo, C IR - Morales Portillo C FIR - Montalban Carrasco, C IR - Montalban Carrasco C FIR - Tinahones, F IR - Tinahones F FIR - Cigarran, S IR - Cigarran S FIR - Huang, C-N IR - Huang CN FIR - Chen, S-T IR - Chen ST FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Buranapin, S IR - Buranapin S FIR - Suwanagool, A IR - Suwanagool A FIR - Tantiwong, P IR - Tantiwong P FIR - Boonyavarakul, A IR - Boonyavarakul A FIR - Benjachareonwong, S IR - Benjachareonwong S FIR - Leelawattana, R IR - Leelawattana R FIR - Vathesatogkit, P IR - Vathesatogkit P FIR - Deerochanawong, C IR - Deerochanawong C FIR - Sonmez, Y A IR - Sonmez YA FIR - Oguz, A IR - Oguz A FIR - Tabak, O IR - Tabak O FIR - Kocak, M IR - Kocak M FIR - Sariakcali, B IR - Sariakcali B FIR - Bayram, F IR - Bayram F FIR - Guclu, M IR - Guclu M FIR - Gurkan, E IR - Gurkan E FIR - Kebapci, N IR - Kebapci N FIR - Comlekci, A IR - Comlekci A FIR - Acibucu, F IR - Acibucu F FIR - Ahbab, S IR - Ahbab S FIR - Bilen, H IR - Bilen H FIR - Urbanovych, A IR - Urbanovych A FIR - Kuskalo, P IR - Kuskalo P FIR - Bondarets, I IR - Bondarets I FIR - Petrosyan, O IR - Petrosyan O FIR - Pashkovska, N IR - Pashkovska N FIR - Oleksyk, O IR - Oleksyk O FIR - Kaydashev, I IR - Kaydashev I FIR - Maliar, K IR - Maliar K FIR - Myshanych, G IR - Myshanych G FIR - Bain, S C IR - Bain SC FIR - Black, D IR - Black D FIR - Johnston, P IR - Johnston P FIR - Dang, C IR - Dang C FIR - Dhatariya, K IR - Dhatariya K FIR - English, P IR - English P FIR - Field, B IR - Field B FIR - Grimmer, P IR - Grimmer P FIR - Gunstone, A IR - Gunstone A FIR - Ray, S IR - Ray S FIR - Tatovic, D IR - Tatovic D FIR - Kernohan, A IR - Kernohan A FIR - Lindsay, R IR - Lindsay R FIR - Mcknight, J A IR - Mcknight JA FIR - Park, A IR - Park A FIR - Patel, D IR - Patel D FIR - Philip, S IR - Philip S FIR - Randeva, H IR - Randeva H FIR - Sathyapalan, T IR - Sathyapalan T FIR - Turner, W IR - Turner W FIR - Wyatt, N IR - Wyatt N FIR - Allison, D C IR - Allison DC FIR - Awasty, V IR - Awasty V FIR - Ayele, E IR - Ayele E FIR - Bajaj, C IR - Bajaj C FIR - Budoff, M J IR - Budoff MJ FIR - Busch, R IR - Busch R FIR - Casaubon, L IR - Casaubon L FIR - Chaidarun, S S IR - Chaidarun SS FIR - Chochinov, R H IR - Chochinov RH FIR - Chu, J W IR - Chu JW FIR - Daboul, N Y IR - Daboul NY FIR - Dang, A H IR - Dang AH FIR - Everhart, B G IR - Everhart BG FIR - Arambasick, J IR - Arambasick J FIR - Fink, R I IR - Fink RI FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Fogarty, C M IR - Fogarty CM FIR - Gilbert, M P IR - Gilbert MP FIR - Johnson, D M IR - Johnson DM FIR - Krishnasamy, S S IR - Krishnasamy SS FIR - Lane, W S IR - Lane WS FIR - Nakhle, S N IR - Nakhle SN FIR - Levenson, D IR - Levenson D FIR - O'Donnell, P IR - O'Donnell P FIR - Weiss, D IR - Weiss D FIR - Risser, J A IR - Risser JA FIR - Wierum, C IR - Wierum C FIR - Sivalingam, K IR - Sivalingam K FIR - Gupta, D IR - Gupta D FIR - Philis-Tsimikas, A IR - Philis-Tsimikas A FIR - Pratley, R E IR - Pratley RE FIR - Mirza, L IR - Mirza L FIR - Snyder, B IR - Snyder B FIR - Rasouli, N IR - Rasouli N FIR - Porter, J IR - Porter J FIR - Ledesma, G N IR - Ledesma GN FIR - Powell, T IR - Powell T FIR - Tandron, I J IR - Tandron IJ FIR - Lingvay, I IR - Lingvay I FIR - Reed, J C H IR - Reed JCH FIR - Patel, M B IR - Patel MB FIR - Lovre, D IR - Lovre D FIR - Chaicha-Brom, T IR - Chaicha-Brom T FIR - Jantzi, C IR - Jantzi C FIR - Brautigam, D IR - Brautigam D FIR - Bao, S IR - Bao S FIR - Mbogua, C N IR - Mbogua CN FIR - Zemel, L R IR - Zemel LR FIR - Hasan, S IR - Hasan S FIR - Rosenstock, J IR - Rosenstock J FIR - Tran, H IR - Tran H FIR - Poremba, J IR - Poremba J FIR - Baker, C IR - Baker C FIR - Prier, K IR - Prier K FIR - Chilka, S IR - Chilka S FIR - Agaiby, J M IR - Agaiby JM FIR - Condit, J IR - Condit J FIR - Eagerton, D C IR - Eagerton DC FIR - Huffman, D IR - Huffman D FIR - Cornett, G M IR - Cornett GM FIR - Traylor, H IR - Traylor H FIR - Brinson, C IR - Brinson C FIR - Bays, H E IR - Bays HE FIR - Jerkins, T IR - Jerkins T FIR - Nicol, P R IR - Nicol PR FIR - Siddiqui, I A IR - Siddiqui IA FIR - Hewitt, M IR - Hewitt M FIR - Odugbesan, A O IR - Odugbesan AO FIR - Lillestol, M J IR - Lillestol MJ FIR - Thrasher, J R IR - Thrasher JR FIR - Gandy, W H IR - Gandy WH FIR - Pant, N IR - Pant N FIR - Nagelberg, S IR - Nagelberg S FIR - Cannon, K IR - Cannon K FIR - Anderson, M W IR - Anderson MW FIR - Bhargava, A IR - Bhargava A FIR - Doshi, A IR - Doshi A FIR - Jardula, M F IR - Jardula MF FIR - Montero, M IR - Montero M FIR - Purighalla, R S IR - Purighalla RS FIR - Warren, M L IR - Warren ML FIR - Harris, K IR - Harris K FIR - Jackson, R A IR - Jackson RA FIR - Khaira, A S IR - Khaira AS FIR - Gonzalez-Orozco, B L IR - Gonzalez-Orozco BL FIR - Gagianas, P J IR - Gagianas PJ FIR - Pantalone, K IR - Pantalone K FIR - Murray, A V IR - Murray AV EDAT- 2025/12/11 19:42 MHDA- 2026/01/20 19:20 PMCR- 2025/12/04 CRDT- 2025/12/11 15:03 PHST- 2025/05/08 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2026/01/20 19:20 [medline] PHST- 2025/12/11 19:42 [pubmed] PHST- 2025/12/11 15:03 [entrez] PHST- 2025/12/04 00:00 [pmc-release] AID - 163945 [pii] AID - 251080 [pii] AID - 10.2337/dc25-1080 [doi] PST - ppublish SO - Diabetes Care. 2026 Feb 1;49(2):257-265. doi: 10.2337/dc25-1080. PMID- 41372397 OWN - NLM STAT- MEDLINE DCOM- 20260116 LR - 20260118 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 16 IP - 1 DP - 2025 Dec 11 TI - Erythrocytosis and thromboembolic risks associated with SGLT2 inhibitors in type 2 diabetes. PG - 2000 LID - 10.1038/s41598-025-31726-3 [doi] LID - 2000 AB - This study aimed to determine if sodium-glucose co-transporter-2 inhibitors (SGLT2i) use in diabetic patients leads to erythrocytosis and increases the incidence of arterial and venous thrombosis events. This is a retrospective cohort study using records from over 50 U.S. healthcare organizations. Adults with type 2 diabetes who received SGLT2i therapy were compared to those on glucagon-like peptide-1 receptor agonists (GLP1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i). The primary outcome was the risk of erythrocytosis, defined by elevated hemoglobin and hematocrit levels. Secondary outcomes included arterial and venous thromboembolic events. Propensity score matching was applied to balance baseline characteristics, and Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results demonstrated that compared to SGLT2i use, DPP4i use was associated with a significantly higher risk of erythrocytosis in both male (hemoglobin > 16.5 g/dL: HR 1.954 [1.909-2.001]) and female (hemoglobin > 16 g/dL: HR 1.873 [1.803-1.947]) patients with type 2 diabetes. Similarly, GLP1RA use was associated with a significantly higher risk of erythrocytosis in both male (HR 1.605 [1.573, 1.636] and female (HR 1.697 [1.640, 1.755]) patients compared to SGLT2i use. Compared with DPP4i users, SGLT2i users had less cardiovascular events, except for increased stroke/TIA in females (HR 1.744 [1.654-1.839]). Compared with GLP1RA, SGLT2i use was associated with a decrease risk of MACE in both men and women, but higher risk for other cardiovascular and peripheral vascular events. Among SGLT2i users, those who developed erythrocytosis had increased incidence of thromboembolic events compared to those without erythrocytosis. Lastly, among SGLT2i patients treated for their erythrocytosis, the men who discontinued SGLT2i had increased risks of stroke/TIA, MI, and limb ischemia, while women had increased risk of stroke/TIA, MI, and venous thrombosis. Those who received anti-platelet therapy were associated with elevated risks of stroke/TIA, MI, venous thrombosis, and limb ischemia. In contrast, patients who receive phlebotomy had no significant difference in the outcomes. Therefore, regular monitoring of hematologic parameters is recommended for early detection and modified therapeutic strategies should be considered to reduce complication risks. Further studies are needed to establish effective strategies to reduce complications in this population. CI - (c) 2025. The Author(s). FAU - Chen, Yu-Han AU - Chen YH AD - Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA. FAU - Hsieh, Tina Yi Jin AU - Hsieh TYJ AD - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. AD - Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA. FAU - Sun, Andrea Yue-En AU - Sun AY AD - College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chen, Kayleigh AU - Chen K AD - Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA. FAU - Choi, Ellen AU - Choi E AD - Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA. FAU - Rastogi, Natasha AU - Rastogi N AD - Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA. FAU - Cheng, James AU - Cheng J AD - Department of Internal Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. wei3228@gmail.com. AD - Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. wei3228@gmail.com. FAU - Lee, Cho-Hao AU - Lee CH AD - Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan. LA - eng PT - Journal Article DEP - 20251211 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Polycythemia/chemically induced/epidemiology MH - Retrospective Studies MH - Aged MH - *Thromboembolism/chemically induced/epidemiology/etiology MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence PMC - PMC12808242 OTO - NOTNLM OT - Erythrocytosis OT - SGLT2 inhibitors OT - Thromboembolic events OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/12/11 01:22 MHDA- 2026/01/16 07:07 PMCR- 2025/12/11 CRDT- 2025/12/10 23:28 PHST- 2025/07/04 00:00 [received] PHST- 2025/12/04 00:00 [accepted] PHST- 2026/01/16 07:07 [medline] PHST- 2025/12/11 01:22 [pubmed] PHST- 2025/12/10 23:28 [entrez] PHST- 2025/12/11 00:00 [pmc-release] AID - 10.1038/s41598-025-31726-3 [pii] AID - 31726 [pii] AID - 10.1038/s41598-025-31726-3 [doi] PST - epublish SO - Sci Rep. 2025 Dec 11;16(1):2000. doi: 10.1038/s41598-025-31726-3. PMID- 41371743 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 12 DP - 2025 Dec 10 TI - Effects of glucagon-like peptide-1 analogues on hard binary outcomes for patients at increased risk of cardiovascular events: a protocol for a systematic review with network meta-analysis and Trial Sequential Analysis. PG - e098205 LID - 10.1136/bmjopen-2024-098205 [doi] LID - e098205 AB - BACKGROUND: Cardiovascular diseases, overweight, type 2 diabetes and chronic kidney disease increase the risk of cardiovascular events.Glucagon-like peptide-1 analogues are recommended by the European Society of Cardiology and the American College of Cardiology to lower the risk of death and progression of cardiovascular disease in patients with cardiovascular disease and type 2 diabetes. Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight. CagriSema is currently not approved, but several phase III trials are ongoing.No previous systematic review has investigated the effects of semaglutide, tirzepatide, CagriSema and liraglutide, which may not be disease-specific, on hard binary outcomes for all trial populations at increased risk of cardiovascular events. METHODS AND ANALYSES: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science) and clinical trial registries from their inception and onwards to identify relevant randomised trials. We expect to perform the literature search in December 2025. Two review authors will independently extract data and assess the risk of bias. We will include randomised trials assessing the effects of semaglutide, tirzepatide, CagriSema and/or liraglutide in participants with an increased risk of cardiovascular events. The primary outcome will be all-cause mortality. Secondary outcomes will be myocardial infarction, stroke and all-cause hospitalisation. Data will be synthesised by aggregate data meta-analyses, Trial Sequential Analyses and network meta-analysis, risk of bias will be assessed with Cochrane Risk of Bias tool V. 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations and the Confidence in Network Meta-Analysis approach. ETHICS AND DISSEMINATION: This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD42024623312. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AUID- ORCID: 0009-0004-9247-5245 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark christina.sillassen@ctu.dk. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Faltermeier, Pascal AU - Faltermeier P AUID- ORCID: 0000-0002-6684-2070 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Petersen, Johanne Juul AU - Petersen JJ AUID- ORCID: 0000-0001-9837-1958 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. FAU - Kamp, Caroline Barkholt AU - Kamp CB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. FAU - Grand, Johannes AU - Grand J AUID- ORCID: 0000-0002-5511-4668 AD - Department of Cardiology, Copenhagen University Hospital - Amager-Hvidovre Hospital, Hvidovre, Denmark. FAU - Dominguez, Helena AU - Dominguez H AD - Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Frolich, Anne AU - Frolich A AD - Innovation and Research Centre for Multimorbidity, Slagelse Hospital, Slagelse, Denmark. AD - Section of General Practice, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gaede, Peter Haulund AU - Gaede PH AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Gluud, Christian AU - Gluud C AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Mathiesen, Ole AU - Mathiesen O AD - Centre for Anaesthesiological Research, Department of Anaesthesiology, Zealand University Hospital, Koge, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Jakobsen, Janus C AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article DEP - 20251210 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Systematic Reviews as Topic MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Network Meta-Analysis as Topic MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - Research Design MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Meta-Analysis as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC12699605 OTO - NOTNLM OT - Meta-Analysis OT - Network Meta-Analysis OT - PUBLIC HEALTH OT - Safety OT - Systematic Review COIS- Competing interests: CDBS's husband was employed at Novo Nordisk, Kalundborg, Denmark, as a 'facility manager' and 'sprinkler technician' from 1 September 2024 to 31 August 2025. PHG has received lecture fees for Novo Nordisk, AstraZeneca, Eli Lilly, Bayer and MSD, and has served in Advisory Boards for Novo Nordisk, AstraZeneca and Bayer. All other authors have no known competing interests. EDAT- 2025/12/11 01:22 MHDA- 2025/12/11 01:23 PMCR- 2025/12/10 CRDT- 2025/12/10 20:43 PHST- 2025/12/11 01:23 [medline] PHST- 2025/12/11 01:22 [pubmed] PHST- 2025/12/10 20:43 [entrez] PHST- 2025/12/10 00:00 [pmc-release] AID - bmjopen-2024-098205 [pii] AID - 10.1136/bmjopen-2024-098205 [doi] PST - epublish SO - BMJ Open. 2025 Dec 10;15(12):e098205. doi: 10.1136/bmjopen-2024-098205. PMID- 41370744 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20251210 IS - 1526-632X (Electronic) IS - 0028-3878 (Linking) VI - 106 IP - 1 DP - 2026 Jan 13 TI - Association Between GLP-1 Receptor Agonist Use and Epilepsy Risk in Type 2 Diabetes. PG - e214509 LID - 10.1212/WNL.0000000000214509 [doi] AB - BACKGROUND AND OBJECTIVES: Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk of developing epilepsy, particularly in later life. While preclinical studies suggest neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), real-world comparative effectiveness data remain limited. We aimed to evaluate whether GLP-1 RA use is associated with a lower risk of incident epilepsy compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) use in adults with T2DM. METHODS: We conducted a retrospective cohort study using the TriNetX network from 2015 to 2023, including adults aged 18 years or older with T2DM who were new users of either GLP-1 RAs or DPP-4is. Patients with a previous diagnosis of epilepsy or seizure, or those using antiepileptic drugs, were excluded. The primary outcome was incident epilepsy, identified using ICD-10-CM codes. Propensity score matching (1:1) was performed based on demographics, socioeconomic status, body mass index, comorbidities, and baseline medications. Cox proportional hazard models estimated hazard ratios (HRs) with 95% CIs. We also conducted prespecified subgroup and sensitivity analyses to assess the robustness of the findings. RESULTS: After matching, 452,766 patients were included (226,383 in each group; mean age 60.5 years; 47.1% female). During follow-up, 1,670 individuals in the GLP-1 RA group and 1,886 in the DPP-4i group developed epilepsy, corresponding to cumulative incidences of 2.35% vs 2.41%. GLP-1 RA use was associated with a significantly lower risk of epilepsy (HR 0.84, 95% CI 0.78-0.90), with protective associations evident at 1 year (HR 0.71, 95% CI 0.62-0.80), 3 years (HR 0.81, 95% CI 0.74-0.88), and 5 years (HR 0.82, 95% CI 0.76-0.88). Among individual agents, semaglutide showed the strongest association (HR 0.68, 95% CI 0.60-0.77). The results were consistent across major subgroups, including both age and sex. Sensitivity analyses excluding patients with overlapping or switching exposure yielded similar findings (HR 0.71, 95% CI 0.64-0.78). DISCUSSION: GLP-1 RA therapy was associated with a significantly lower epilepsy risk compared with DPP-4i use in adults with T2DM. These results support the hypothesis that GLP-1 RAs may exert neurologic benefits beyond glycemic control. Limitations include the observational design and potential residual confounding. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the use of GLP-1 RAs in people with T2DM results in a lower risk of developing epilepsy compared with those treated with DPP-4i. FAU - Cheng, Ching-Yang AU - Cheng CY AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. FAU - Lo, Shih-Chang AU - Lo SC AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. FAU - Huang, Chien-Ning AU - Huang CN AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. AD - Chung Shan Medical University, Institute of Medicine, Taichung, Taiwan; and. FAU - Yang, Yi-Sun AU - Yang YS AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. FAU - Wang, Yu-Hsun AU - Wang YH AD - Chung Shan Medical University Hospital, Department of Medical Research, Taichung, Taiwan. FAU - Kornelius, Edy AU - Kornelius E AUID- ORCID: 0000-0002-9342-5467 AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20251210 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Retrospective Studies MH - *Epilepsy/epidemiology MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Cohort Studies MH - Risk Factors EDAT- 2025/12/10 19:22 MHDA- 2025/12/10 19:23 CRDT- 2025/12/10 16:03 PHST- 2025/12/10 19:23 [medline] PHST- 2025/12/10 19:22 [pubmed] PHST- 2025/12/10 16:03 [entrez] AID - 10.1212/WNL.0000000000214509 [doi] PST - ppublish SO - Neurology. 2026 Jan 13;106(1):e214509. doi: 10.1212/WNL.0000000000214509. Epub 2025 Dec 10. PMID- 41370018 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20261010 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 31 IP - 1 DP - 2025 Dec 10 TI - The impact of oral semaglutide on cardiovascular events in patients with type 2 diabetes: review of results from the SOUL trial. PG - 11 LID - 10.1007/s10741-025-10579-y [doi] AB - Subcutaneous glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce risk of major adverse cardiac events (MACE) for patients with type 2 diabetes (T2DM) who have or are at high risk of cardiovascular disease, but the evaluation of cardiovascular efficacy of oral GLP-1 RAs has yet to be performed. This article reviews results from the SOUL (Semaglutide Cardiovascular Outcomes) trial, whose aim was to assess the cardiovascular benefit in oral semaglutide in high-risk individuals. SOUL was a randomized, double blind, parallel-group, placebo-controlled superiority trial that enrolled 9,650 adults with T2DM who had established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or both, to receive a maximum daily dose of 14 mg oral semaglutide or placebo. The primary outcome in this study was a composite of time to first CV death, non-fatal MI, or non-fatal stroke. In prespecified secondary analyses, treatment groups were analyzed for an expanded list of CV, CKD, PAD, and HF outcomes. Over a median follow-up of 49.5 months, the risk for MACE was significantly lower in the oral semaglutide compared with the placebo group (HR 0.86; 95% CI, 0.77; 0.96; p = 0.006), and these results were consistent across subgroup analysis, including by sodium glucose co-transporter 2 inhibitor (SGLT2i) drug use. Oral semaglutide reduces the risk of MACE in high-risk patients with T2DM. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Lehenbauer, Katy S AU - Lehenbauer KS AD - University of Colorado, Aurora, CO, USA. FAU - Nelson, Adam J AU - Nelson AJ AD - University of Adelaide, Adelaide, South Australia. FAU - Nodari, Savina AU - Nodari S AD - University and ASST Spedali Civili of Brescia, Brescia, Italy. FAU - Sverdlov, Aaron L AU - Sverdlov AL AD - University of Newcastle, Callaghan, Australia. FAU - Harrington, Josephine AU - Harrington J AD - University of Colorado, Aurora, CO, USA. Josephine.harrington@cuanschutz.edu. LA - eng PT - Journal Article PT - Review DEP - 20251210 PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage MH - *Cardiovascular Diseases/prevention & control/etiology/epidemiology MH - Administration, Oral MH - Hypoglycemic Agents/administration & dosage MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Disclosures: AN has served as a consultant or as a speaker for Amgen, Boehringer Ingelheim, Eli Lilly, GSK, Novartis, Novo Nordisk, Pfizer and VAXXINITY. SN has received grants and/or speakers' fees from Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, AMGEN, Menarini. AS has received grants and/or speakers' fees and/or advisory board fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Galaxo Smith Kline, Janssen, Novartis, Novo Nordisk and RACE Oncology. He is supported by the National Heart Foundation of Australia Future Leader Fellowship (Award ID: 106025). JH has served as a consultant for Novo Nordisk. Competing interests: The authors declare no competing interests. EDAT- 2025/12/10 13:52 MHDA- 2025/12/10 19:21 CRDT- 2025/12/10 11:53 PHST- 2025/06/10 00:00 [received] PHST- 2025/10/14 00:00 [accepted] PHST- 2025/10/13 00:00 [revised] PHST- 2025/12/10 19:21 [medline] PHST- 2025/12/10 13:52 [pubmed] PHST- 2025/12/10 11:53 [entrez] AID - 10.1007/s10741-025-10579-y [pii] AID - 10.1007/s10741-025-10579-y [doi] PST - epublish SO - Heart Fail Rev. 2025 Dec 10;31(1):11. doi: 10.1007/s10741-025-10579-y. PMID- 41366934 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20260513 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 104 IP - 49 DP - 2025 Dec 5 TI - Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation. PG - e46173 LID - 10.1097/MD.0000000000046173 [doi] LID - e46173 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 agonist) have revolutionized the treatment of obesity. However, regulatory agencies have reported an association with suicidality. To the best of our knowledge, this is the first meta-analysis to assess the association between GLP-1 agonist use, suicidal ideation, and suicide completion. We aimed to assess the same in patients with diabetes and obesity. METHODS: We searched 6 databases for relevant articles, from the first published article to October 2024. The keywords used were GLP-1 agonists, suicidal ideation, suicide, suicidal behavior, semaglutide, liraglutide, tripeptide, exenatide, and lixisenatide. We identified 354 studies and 126 stands after the removal of duplicates, of which 23 were eligible, and only 12 studies were included in the final meta-analysis. RESULTS: No significant statistical difference was found in suicidal ideations in patients on GLP-1 agonists compared to their counterparts on other obesity and diabetes drugs (odds ratio [OR], 1.0; 95% confidence interval [CI]: 1.0-1.0). No significant difference was observed between patients on GLP-1 agonists and their counterparts regarding complete suicide (OR, 1.77; 95% CI: 0.80-3.91). In a subgroup analysis, suicide was higher among patients on liraglutide compared to their counterparts on semaglutide (OR, 1.48; 95% CI: 1.17-1.89). No significant statistical difference was observed when comparing monjaro and semaglutide (OR, 0.98; 95% CI: 0.94-1.03). CONCLUSION: No significant statistical difference was found between GLP-1 agonists and other obesity and diabetes drugs regarding suicide/suicidal ideation. In a subgroup analysis, suicide was higher in patients on liraglutide compared to semaglutide, with no significant difference between semaglutide and monjaro. Randomized controlled trials that assess the association between GLP-1 agonists and suicidality are highly recommended. CI - Copyright (c) 2025 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Alansari, Amal Omar AU - Alansari AO AUID- ORCID: 0009-0001-9022-1389 AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alharbi, Ahlam Saleem AU - Alharbi AS AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alshehri, Khaled Mohammad AU - Alshehri KM AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alhabib, Ali Tareq AU - Alhabib AT AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alsalmi, Bodour Saleh AU - Alsalmi BS AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Almosfer, Waleed Abdulaziz AU - Almosfer WA AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - AlAjlan, Fadiyah Abdullah AU - AlAjlan FA AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alharbi, Abeer Abdullah AU - Alharbi AA AD - Department of Family Medicine, Madinah Health Cluster, Ministry of Health, Madinah, Saudi Arabia. FAU - Alzahrani, Basmah Saleh AU - Alzahrani BS AD - Saudi Commission for Health Specialties, Riyadh, Saudi Arabia. FAU - Alamer, Bader AU - Alamer B AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alatawi, Amirah M AU - Alatawi AM AD - Department of Family Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Suicidal Ideation MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/psychology MH - Liraglutide/adverse effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12688971 OTO - NOTNLM OT - glucagon-like receptors-1 agonists OT - liraglutide OT - semaglutide OT - suicidal ideation OT - suicide OT - tirzepatide COIS- The authors have no conflicts of interest to disclose. EDAT- 2025/12/10 06:28 MHDA- 2025/12/10 06:29 PMCR- 2026/05/12 CRDT- 2025/12/10 01:00 PHST- 2025/07/22 00:00 [received] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/12/10 06:29 [medline] PHST- 2025/12/10 06:28 [pubmed] PHST- 2025/12/10 01:00 [entrez] PHST- 2026/05/12 00:00 [pmc-release] AID - 00005792-202512050-00050 [pii] AID - MD-D-25-09174 [pii] AID - 10.1097/MD.0000000000046173 [doi] PST - ppublish SO - Medicine (Baltimore). 2025 Dec 5;104(49):e46173. doi: 10.1097/MD.0000000000046173. PMID- 41364427 OWN - NLM STAT- MEDLINE DCOM- 20260826 LR - 20260826 IS - 1529-4242 (Electronic) IS - 0032-1052 (Linking) VI - 158 IP - 3 DP - 2026 Sep 1 TI - Impact of GLP-1 Agonist on Surgical Wound Complications after Plastic and Reconstructive Surgery: A Propensity-Matched Cohort Large Database Analysis. PG - 481e-490e LID - 10.1097/PRS.0000000000012703 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained Food and Drug Administration approval for management of type 2 diabetes. However, they have been increasingly used for their weight loss side effect profile. Surgical site wound complications have been observed in patients using these medications (although with a low incidence rate). Given the paucity of literature on weight loss medications and their implications in plastic surgery, this study evaluates the impact of weight loss medication use on postoperative surgical site outcomes in patients undergoing common plastic and reconstructive procedures. METHODS: The TriNetX National Health Research database was queried to identify patients undergoing panniculectomy, abdominoplasty, or breast reduction. Patients with diabetes; peripheral vascular diseases; nutritional, metabolic, or endocrine diseases; a history of cancer; or smoking were excluded. Propensity matching analysis was performed to balance the cohorts. Postoperative outcomes, specifically surgical wound infections, breakdown, or dehiscence within 30 days after the procedure, were assessed based on GLP-1 RA use status. RESULTS: The risk of surgical site wound healing complications in patients taking GLP-1 RAs compared with those not on these medications was statistically significantly higher before cohort matching as well as after matching. Matched cohort results were as follows: 4.7% versus 2.7% for panniculectomy ( P = 0.05), 9.8% versus 3.6% for abdominoplasty ( P = 0.001), and 2.6% versus 1.3% for breast reduction ( P = 0.035), respectively. CONCLUSIONS: Use of GLP-1 RAs was associated with higher rates of surgical site complications across all evaluated procedures. This underscores the necessity of patient counseling regarding the implications of these weight loss medications before surgery, along with the potential need for a strategic perioperative management plan to enhance surgical outcomes. CI - Copyright (c) 2025 by the American Society of Plastic Surgeons. FAU - Lee, Charles C AU - Lee CC AD - From the Division of Plastic Surgery. FAU - Newland, Mary AU - Newland M AD - College of Medicine, Penn State Milton S. Hershey Medical Center. FAU - Yau, Alice AU - Yau A AD - From the Division of Plastic Surgery. FAU - Chroneos, Rea AU - Chroneos R AD - From the Division of Plastic Surgery. FAU - Johnson, T Shane AU - Johnson TS AD - From the Division of Plastic Surgery. LA - eng PT - Journal Article DEP - 20251209 PL - United States TA - Plast Reconstr Surg JT - Plastic and reconstructive surgery JID - 1306050 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Propensity Score MH - Male MH - Databases, Factual MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Surgical Wound Infection/epidemiology/etiology MH - Abdominoplasty/adverse effects MH - Mammaplasty/adverse effects MH - Adult MH - *Plastic Surgery Procedures/adverse effects MH - Aged MH - *Surgical Wound Dehiscence/epidemiology MH - Retrospective Studies MH - Wound Healing/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects EDAT- 2025/12/09 13:09 MHDA- 2026/08/26 23:35 CRDT- 2025/12/09 11:28 PHST- 2026/08/26 23:35 [medline] PHST- 2025/12/09 13:09 [pubmed] PHST- 2025/12/09 11:28 [entrez] AID - 00006534-990000000-02967 [pii] AID - 10.1097/PRS.0000000000012703 [doi] PST - ppublish SO - Plast Reconstr Surg. 2026 Sep 1;158(3):481e-490e. doi: 10.1097/PRS.0000000000012703. Epub 2025 Dec 9. PMID- 41361010 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20261009 IS - 1432-1459 (Electronic) IS - 0340-5354 (Linking) VI - 273 IP - 1 DP - 2025 Dec 8 TI - Impact of GLP-1 receptor agonists on cranial nerve palsies in type 2 diabetes: a retrospective cohort study. PG - 16 LID - 10.1007/s00415-025-13560-9 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as key agents in managing type 2 diabetes mellitus (T2DM), with proven benefits in glycemic control, weight loss, and cardiovascular risk reduction. However, their neurologic safety profile remains underexplored. OBJECTIVE: To evaluate the association between GLP-1 receptor agonist use and the incidence of cranial nerve (CN) palsies in patients with T2DM. METHODS: This retrospective cohort study utilized the TriNetX Global Collaborative Network, comprising de-identified records from 160 healthcare organizations. Patients with T2DM treated with GLP-1 receptor agonists were compared to propensity-score-matched T2DM controls who never received GLP-1 therapy. Exclusion criteria included prior CN palsy diagnoses, CNS malignancy, type 1 diabetes, and neurological comorbidities. Outcomes assessed over a 10-year period included third nerve palsy (H49.0), sixth nerve palsy (H49.2), and Bell's palsy (G51.0). Propensity score matching was applied for age, sex, hypertension, dyslipidemia, insulin exposure, metformin use, and SGL2 inhibitor use. RESULTS: After matching (n = 841,219 per group), GLP-1 users had a significantly reduced incidence of CN III palsy (RR: 0.86, 95% CI: 0.76-0.98) and Bell's palsy (RR: 0.92, 95% CI: 0.87-0.96), with p < 0.05 for both. CN VI palsy demonstrated a moderately elevated risk ratio (RR: 1.15, 95% CI: 1.03-1.28), but long-term hazard favored GLP-1 therapy (HR: 0.76, 95% CI: 0.68-0.84). Hazard ratios showed consistent protective ratios across all three outcomes, supported by Kaplan-Meier survival analysis (log-rank p < 0.001). CONCLUSION: While absolute risks remain low, GLP-1 receptor agonist use was associated with a statistically significant decrease in cranial nerve palsies, demonstrating a potential protective pattern across multiple cranial nerve palsies. These findings suggest possible neuroprotective or microvascular benefits of GLP-1 signaling and warrant further investigation, particularly in ophthalmological and neurological domains. CI - (c) 2025. Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Bhatia, Ronak AU - Bhatia R AD - Howard University College of Medicine, Washington, DC, USA. FAU - Al-Bana, Huda AU - Al-Bana H AD - Howard University College of Medicine, Washington, DC, USA. FAU - Mohamed, Khalid AU - Mohamed K AD - Howard University College of Medicine, Washington, DC, USA. FAU - Amaefuna, Chimezie AU - Amaefuna C AD - Howard University College of Medicine, Washington, DC, USA. FAU - Johnson, Stephanie AU - Johnson S AD - Howard University College of Medicine, Washington, DC, USA. FAU - Munasinghe, Banuja AU - Munasinghe B AD - Howard University College of Medicine, Washington, DC, USA. FAU - Elkomi, Rawan AU - Elkomi R AUID- ORCID: 0000-0002-3707-544X AD - Department of Internal Medicine, Howard University, Washington, DC, USA. rawan.elkomi@gmail.com. FAU - Gillani, Syed Fahad AU - Gillani SF AD - Department of Internal Medicine, Howard University, Washington, DC, USA. FAU - Beyene, Elizabeth AU - Beyene E AD - Department of Internal Medicine, Howard University, Washington, DC, USA. FAU - Bisrat, Mekdem AU - Bisrat M AD - Department of Internal Medicine, Howard University, Washington, DC, USA. FAU - Michael, Miriam AU - Michael M AD - Department of Internal Medicine, Howard University, Washington, DC, USA. AD - Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, USA. LA - eng PT - Journal Article DEP - 20251208 PL - Germany TA - J Neurol JT - Journal of neurology JID - 0423161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Cranial Nerve Diseases/epidemiology MH - Incidence MH - Cohort Studies OTO - NOTNLM OT - Bell's palsy OT - Cranial nerve palsy OT - GLP-1 receptor agonists OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interests: The authors declare that they have no competing interests (financial or non-financial) relevant to this work. Ethics approval and consent to participate: This retrospective analysis used only de-identified data from the TriNetX Global Collaborative Network. Because no identifiable private information was accessed, this work did not constitute human subjects research and institutional review board approval and informed consent were not required. Prior presentations: None. Use of generative AI: Generative artificial intelligence (OpenAI ChatGPT) was used only for language editing and formatting. No AI tool was used to generate data, perform analyses, or draw scientific conclusions. All content was reviewed and approved by the authors. EDAT- 2025/12/09 00:31 MHDA- 2025/12/09 00:32 CRDT- 2025/12/08 23:26 PHST- 2025/08/30 00:00 [received] PHST- 2025/12/01 00:00 [accepted] PHST- 2025/11/30 00:00 [revised] PHST- 2025/12/09 00:32 [medline] PHST- 2025/12/09 00:31 [pubmed] PHST- 2025/12/08 23:26 [entrez] AID - 10.1007/s00415-025-13560-9 [pii] AID - 10.1007/s00415-025-13560-9 [doi] PST - epublish SO - J Neurol. 2025 Dec 8;273(1):16. doi: 10.1007/s00415-025-13560-9. PMID- 41360342 OWN - NLM STAT- MEDLINE DCOM- 20260214 LR - 20260820 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 283 DP - 2026 Mar TI - Tirzepatide is Associated With Reduced Risk of Primary Open-Angle Glaucoma and Ocular Hypertension in Patients With Type 2 Diabetes. PG - 120-128 LID - S0002-9394(25)00653-1 [pii] LID - 10.1016/j.ajo.2025.12.003 [doi] AB - PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has shown superior efficacy in glycemic control, weight loss, and cardiometabolic outcomes compared to GLP-1 RAs alone. While GLP-1 RAs may offer neuroprotective effects relevant to glaucoma, the impact of dual-incretin therapies like tirzepatide on glaucoma remains unknown. This study investigates the association between tirzepatide initiation and the risk of primary open-angle glaucoma (POAG), ocular hypertension (OHTN), and glaucoma treatment initiation in patients with type 2 diabetes mellitus (T2DM), compared to those initiating selective GLP-1 RAs. DESIGN: Retrospective clinical cohort study using a nationwide electronic health records network from June 2022 to May 2025. SUBJECTS: Adults with T2DM who initiated tirzepatide or selective GLP-1 RA therapy. Patients with prior exposure to either drug class, recent addition of second-line antihyperglycemic agents, previous glaucoma diagnosis or surgery, or ocular trauma were excluded. METHODS: Data from 71 U.S. healthcare organizations were analyzed. Propensity score matching (1:1) was conducted to balance cohorts for demographics, comorbidities, medication use, and ophthalmic encounters. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. MAIN OUTCOME MEASURES: Incidence of POAG, OHTN, and first-line glaucoma treatments (medications or surgery). RESULTS: We identified 41,850 patients who initiated tirzepatide and 147,828 patients who initiated selective GLP-1 RAs. After matching, 41,849 patients remained in each cohort. Tirzepatide use was associated with a significantly lower risk of POAG (RR 0.50, 95% CI 0.34-0.74), OHTN (RR 0.59, 95% CI 0.40-0.88), and need for glaucoma treatment (RR 0.54, 95% CI 0.45-0.64) compared to selective GLP-1 RAs. Risk reductions persisted in subgroups with concomitant metformin or insulin use. Sensitivity analyses limited to patients aged >/=60 years and comparisons with individual GLP-1 RAs (semaglutide and dulaglutide) yielded consistent trends. CONCLUSIONS: Tirzepatide use was associated with a significantly reduced risk of developing POAG, OHTN, and need for first-line glaucoma treatment compared to selective GLP-1 RAs in patients with T2DM. These findings suggest a potential additional ocular benefit of tirzepatide and support further investigation into its role in glaucoma management. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Hong, Alexander T AU - Hong AT AD - From the Keck School of Medicine of University of Southern California (A.T.H. and F.L.), Los Angeles, California, USA. FAU - Lin, Forest AU - Lin F AD - From the Keck School of Medicine of University of Southern California (A.T.H. and F.L.), Los Angeles, California, USA. FAU - Baxter, Sally AU - Baxter S AD - Hamilton Glaucoma Center (S.B. and R.N.W.), Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California, USA; Division of Biomedical Informatics (S.B.), Department of Medicine, University of California San Diego, La Jolla, California, USA. FAU - Weinreb, Robert N AU - Weinreb RN AD - Hamilton Glaucoma Center (S.B. and R.N.W.), Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California, USA. Electronic address: rweinreb@health.ucsd.edu. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20251206 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glaucoma, Open-Angle/epidemiology/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Retrospective Studies MH - Female MH - *Ocular Hypertension/epidemiology/prevention & control/etiology MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Intraocular Pressure/physiology/drug effects MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Incidence MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incretins/therapeutic use MH - United States/epidemiology MH - Tirzepatide EDAT- 2025/12/09 00:31 MHDA- 2026/02/15 00:31 CRDT- 2025/12/08 19:34 PHST- 2025/06/23 00:00 [received] PHST- 2025/12/01 00:00 [revised] PHST- 2025/12/03 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2025/12/09 00:31 [pubmed] PHST- 2025/12/08 19:34 [entrez] AID - S0002-9394(25)00653-1 [pii] AID - 10.1016/j.ajo.2025.12.003 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Mar;283:120-128. doi: 10.1016/j.ajo.2025.12.003. Epub 2025 Dec 6. PMID- 41359966 OWN - NLM STAT- MEDLINE DCOM- 20260216 LR - 20260730 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 2 DP - 2026 Feb TI - Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists : A Systematic Review and Meta-analysis. PG - 216-229 LID - 10.7326/ANNALS-25-02237 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus (T2DM) and overweight or obesity, but their association with cancer is unclear. PURPOSE: To investigate the risk for obesity-related cancer associated with GLP-1RAs. DATA SOURCES: PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials from inception to August 2025. STUDY SELECTION: Randomized placebo-controlled trials reporting any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. DATA EXTRACTION: Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis. DATA SYNTHESIS: The review included 48 trials involving 94 245 participants. GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty). GLP-1RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. Results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1RA class, weight loss profile, dose, and duration of action. LIMITATION: The included trials were not designed to evaluate cancer outcomes and had short follow-up. CONCLUSION: GLP-1RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42024608365). FAU - Ko, Albert AU - Ko A AUID- ORCID: 0009-0004-5939-1947 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K., S.-W.L.). FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut (Y.-C.C., R.J.-L.H.). FAU - Bahar, Furkan AU - Bahar F AUID- ORCID: 0000-0002-4672-5977 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts (F.B., N.X.). FAU - Wang, Tsu Hsien AU - Wang TH AD - Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, New York (T.H.W.). FAU - Xanthavanij, Nutchapon AU - Xanthavanij N AUID- ORCID: 0000-0003-3198-0657 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts (F.B., N.X.). FAU - Yu, Chun-Chiao AU - Yu CC AD - Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York (C.-C.Y.). FAU - Hsieh, Rebecca Jen-Ling AU - Hsieh RJ AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut (Y.-C.C., R.J.-L.H.). FAU - See, Xin Ya AU - See XY AUID- ORCID: 0000-0001-5388-9112 AD - School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (X.Y.S.). FAU - Lo, Shao-Wei AU - Lo SW AUID- ORCID: 0009-0004-7027-3132 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K., S.-W.L.). FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York (J.S.). FAU - Hsia, Yuan Ping AU - Hsia YP AD - Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan (Y.P.H.). FAU - Chiang, Cho-Hung AU - Chiang CH AUID- ORCID: 0000-0002-7910-2338 AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (Cho-Hung Chiang). FAU - Xu, Xiaocao AU - Xu X AUID- ORCID: 0000-0003-1895-7428 AD - Division of Hematology and Oncology, Department of Medicine, University of Vermont Medical Center, Burlington, Vermont (X.X.). FAU - Lin, Shuwen AU - Lin S AUID- ORCID: 0009-0003-9197-7887 AD - Department of Oncology, Montefiore Medical Center, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York (S.L.). FAU - Chiang, Cho-Han AU - Chiang CH AUID- ORCID: 0000-0002-5757-6161 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, and Northwell Health Cancer Institute, New Hyde Park, New York (Cho-Han Chiang). LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251209 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/12/08 19:23 MHDA- 2026/02/16 18:34 CRDT- 2025/12/08 17:03 PHST- 2026/02/16 18:34 [medline] PHST- 2025/12/08 19:23 [pubmed] PHST- 2025/12/08 17:03 [entrez] AID - 10.7326/ANNALS-25-02237 [doi] PST - ppublish SO - Ann Intern Med. 2026 Feb;179(2):216-229. doi: 10.7326/ANNALS-25-02237. Epub 2025 Dec 9. PMID- 41359407 OWN - NLM STAT- MEDLINE DCOM- 20260402 LR - 20260402 IS - 1758-1095 (Electronic) IS - 0141-0768 (Print) IS - 0141-0768 (Linking) VI - 119 IP - 2 DP - 2026 Feb TI - The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression, dementia and coma: evidence from a network meta-analysis. PG - 46-54 LID - 10.1177/01410768251395877 [doi] AB - OBJECTIVES: Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors may exert neuroprotective effects. However, the comparative efficacy of individual agents remains unclear. This network meta-analysis (NMA) aimed to evaluate the differential impacts of these therapies on the incidence of mental status changes, specifically delirium, depression, dementia and coma. DESIGN: A frequentist NMA was conducted using data from randomised controlled trials (RCTs) investigating GLP-1 receptor agonists or SGLT2 inhibitors. The robustness of the findings was verified through a Bayesian NMA framework. SETTING: This study adopted a confirmatory framework focusing on pre-defined neuropsychiatric adverse outcomes in alignment with Cochrane recommendations. PARTICIPANTS: Included trials enrolled individuals without baseline cognitive or psychiatric disorders. MAIN OUTCOME MEASURES: The primary endpoint was the incidence of delirium, depression, dementia or coma during treatment. Secondary endpoints included changes in cognitive performance and drop-out rates. RESULTS: A total of 62 RCTs comprising 200,068 participants were included. Among all treatments, only high-dose dapagliflozin (10 mg/day) significantly reduced the occurrence of delirium and depression, particularly in patients with type 2 diabetes. Dulaglutide and liraglutide were the only agents associated with cognitive improvement. No significant benefits were observed for dementia or coma across all agents. CONCLUSIONS: This analysis highlights agent-specific neuroprotective profiles: SGLT2 inhibitors, especially high-dose dapagliflozin, may mitigate the onset of delirium and depression, while GLP-1 receptor agonists, notably dulaglutide and liraglutide, may enhance cognitive function. These findings warrant consideration in selecting antihyperglycemic therapies for individuals at elevated neuropsychiatric risk. TRIAL REGISTRATION: PROSPERO CRD42024601021.The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB E202516007). FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan. AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 807, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AUID- ORCID: 0000-0002-8650-4060 AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. FAU - Suen, Mein-Woei AU - Suen MW AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan. AD - Gender Equality Education and Research Center, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, Asia University Hospital, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 840, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3220, Australia. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK. AD - Department of Sport, University of Vienna, Vienna 1010, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AD - Department of Psychiatry, Tri-Service General Hospital, National Defense Medical University, Taipei 114, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei 114, Taiwan. FAU - Lei, Wei-Te AU - Lei WT AD - Division of Pediatric Allergy, Immunology, and Rheumatology, Department of Pediatrics, Hsinchu Municipal MacKay Children's Hospital, Hsinchu 300, Taiwan. AD - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan. FAU - Lin, Pao-Yen AU - Lin PY AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. AD - Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Su, Kuan-Pin AU - Su KP AUID- ORCID: 0000-0002-4501-2502 AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK. AD - Office of Research and Development, Asia University, Taichung 404, Taiwan. AD - College of Medicine, China Medical University, Taichung 404, Taiwan. AD - An-Nan Hospital, China Medical University, Tainan 709, Taiwan. FAU - Wang, Hung-Yu AU - Wang HY AD - Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City 802, Taiwan. FAU - Zeng, Bing-Syuan AU - Zeng BS AD - Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Shiue, Yow-Ling AU - Shiue YL AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AUID- ORCID: 0000-0003-1138-5586 AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical University, Taipei 114, Taiwan. AD - Department of Psychiatry, National Defense Medical University, Taipei 114, Taiwan. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20251208 PL - England TA - J R Soc Med JT - Journal of the Royal Society of Medicine JID - 7802879 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Neuroprotective Agents) SB - IM MH - Humans MH - *Dementia/prevention & control MH - *Delirium/prevention & control MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Coma/prevention & control MH - *Depression/prevention & control MH - Network Meta-Analysis as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - Dose-Response Relationship, Drug MH - *Neuroprotective Agents/therapeutic use PMC - PMC12685696 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Network meta-analysis OT - SGLT2 inhibitor OT - delirium OT - depression OT - mental status COIS- The authors report no financial interests or potential conflicts of interest. EDAT- 2025/12/08 19:23 MHDA- 2026/04/02 12:37 PMCR- 2025/12/08 CRDT- 2025/12/08 12:23 PHST- 2026/04/02 12:37 [medline] PHST- 2025/12/08 19:23 [pubmed] PHST- 2025/12/08 12:23 [entrez] PHST- 2025/12/08 00:00 [pmc-release] AID - 10.1177_01410768251395877 [pii] AID - 10.1177/01410768251395877 [doi] PST - ppublish SO - J R Soc Med. 2026 Feb;119(2):46-54. doi: 10.1177/01410768251395877. Epub 2025 Dec 8. PMID- 41359186 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20260902 IS - 1432-1750 (Electronic) IS - 0341-2040 (Print) IS - 0341-2040 (Linking) VI - 203 IP - 1 DP - 2025 Dec 8 TI - State of the Art Review: Glucagon-Like Peptide-1 in Obesity-Related Asthma. PG - 108 LID - 10.1007/s00408-025-00861-z [doi] LID - 108 AB - Asthma is a heterogeneous condition characterized by chronic airway inflammation, airway hyperresponsiveness, and mucin hypersecretion. Obesity-related asthma is one phenotype of asthma with significant metabolic dysregulation. A complete understanding of obesity-related asthma remains elusive, but it is most often characterized by the absence of hallmark features of Type-2 (T2) high asthma, such as eosinophilia or elevated exhaled nitric oxide (NO) levels. Patients with obesity-related and T2 low asthma with or without type 2 diabetes mellitus (T2DM) experience worse clinical outcomes, including more severe acute exacerbations. Among the Food and Drug Administration (FDA) approved drug classes for T2DM, there is a growing interest in glucagon-like peptide 1 receptor agonists' (GLP-1RAs) ability to potentially exert effects in the airway. Previous studies found that individuals with T2DM and asthma who were prescribed GLP-1RAs, had decreased asthma exacerbations and improved lung function. However, there remains a gap in understanding GLP-1RAs mechanism of action in the lung and airways to improve pulmonary function. In this review we discuss the potential mechanisms by which GLP-1RAs may impact T2 low asthma and offer a therapeutic option for this highly prevalent disorder. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Gomez, Destiny R AU - Gomez DR AUID- ORCID: 0000-0002-6757-5621 AD - UC Davis Lung Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Davis, CA, USA. FAU - Swartzman, Isaac AU - Swartzman I AUID- ORCID: 0000-0003-3203-6625 AD - Department of Internal Medicine, UC Davis School of Medicine, Sacramento, CA, USA. FAU - Linderholm, Angela AU - Linderholm A AUID- ORCID: 0000-0002-8561-3089 AD - UC Davis Lung Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Davis, CA, USA. FAU - Cummings, Bethany P AU - Cummings BP AUID- ORCID: 0000-0002-0610-9870 AD - Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA. AD - Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, Sleep Medicine, Department of Medicine, University of California, School of Medicine, Sacramento, CA, 95817, USA. FAU - Zeki, Amir A AU - Zeki AA AUID- ORCID: 0000-0001-8901-588X AD - UC Davis Lung Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Davis, CA, USA. AD - Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, Sleep Medicine, Department of Medicine, University of California, School of Medicine, Sacramento, CA, 95817, USA. FAU - Sundar, Krishna M AU - Sundar KM AUID- ORCID: 0000-0001-7220-5767 AD - UC Davis Lung Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Davis, CA, USA. FAU - Kenyon, Nicholas J AU - Kenyon NJ AD - UC Davis Lung Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California, Davis School of Medicine, Davis, CA, USA. njkenyon@health.ucdavis.edu. LA - eng GR - R01 HL148715/HL/NHLBI NIH HHS/United States GR - T32 HL007013/HL/NHLBI NIH HHS/United States GR - #HL007013-46/T32 Training Program in Comparative Lung Biology and Medicine/ PT - Journal Article PT - Review DEP - 20251208 PL - United States TA - Lung JT - Lung JID - 7701875 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Asthma/drug therapy/physiopathology/etiology/metabolism MH - *Obesity/complications/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Lung/physiopathology/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13379408 OTO - NOTNLM OT - Airway inflammation OT - Asthma OT - Glucagon-Like peptide-1 OT - Obesity OT - Weight loss COIS- Declarations. Competing Interests: The authors declare no competing interests. EDAT- 2025/12/08 13:19 MHDA- 2025/12/08 13:20 PMCR- 2025/12/08 CRDT- 2025/12/08 11:14 PHST- 2025/11/04 00:00 [received] PHST- 2025/11/21 00:00 [accepted] PHST- 2025/12/08 13:20 [medline] PHST- 2025/12/08 13:19 [pubmed] PHST- 2025/12/08 11:14 [entrez] PHST- 2025/12/08 00:00 [pmc-release] AID - 10.1007/s00408-025-00861-z [pii] AID - 861 [pii] AID - 10.1007/s00408-025-00861-z [doi] PST - epublish SO - Lung. 2025 Dec 8;203(1):108. doi: 10.1007/s00408-025-00861-z. PMID- 41355396 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1542-6270 (Electronic) IS - 1060-0280 (Print) IS - 1060-0280 (Linking) VI - 60 IP - 8 DP - 2026 Aug TI - Association of Baseline Comorbidities With First-Year Adherence to GLP-1 Receptor Agonists in Patients With Diabetes or Obesity: A Retrospective Cohort Study. PG - 733-744 LID - 10.1177/10600280251384637 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for diabetes and obesity. Yet, the role of comorbidities on adherence, and variability due to drug subtype or indication remains understudied. OBJECTIVE: Study objective was to (a) evaluate association between baseline comorbidities and digestive system adverse events on first-year GLP-1 RA adherence and (b) assess how associations differ across GLP-1 RA subtypes and between patients with diabetes and obesity. METHOD: We conducted a retrospective cohort study of adults with type 1 or type 2 or obesity initiating GLP-1 RAs between 2018 and 2023 using the University of California Health Data Warehouse. Primary outcome was first-year adherence association with baseline comorbidity and digestive system adverse event status. Adherence odds ratios based on exposure were estimated using regression. Analyses were stratified by indication and drug type. RESULT: Among 69 049 adults who initiated a GLP-1 RAs between 2018 and 2023, 59.3% had diabetes and 74.4% had obesity. Among patients with diabetes, hypertensive disorder (OR: 1.06, 95% CI: 1.01-1.10), hyperlipidemia (OR: 1.17, 95% CI: 1.12-1.22), and chronic kidney disease (CKD) (OR: 1.14, 95% CI: 1.08-1.21) increased adherence likelihood. Among patients with obesity, hyperlipidemia (OR: 1.10, 95% CI: 1.05-1.15) and CKD (OR: 1.09, 95% CI: 1.02-1.16) were associated with increased adherence. In patients with diabetes, atherosclerotic cardiovascular disease (ASCVD) and digestive system adverse events reduced adherence likelihood (OR: 0.90, 95% CI: 0.86-0.95) and (OR: 0.94, 95% CI: 0.90-0.98), respectively. Results were similar for patients with obesity. Findings remained consistent overall in brand-specific analyses. CONCLUSION AND RELEVANCE: Comorbidities affected GLP-1 RA adherence with variation by drug and indication. Further research is needed to understand drivers of these patterns and how they may inform future strategies to support adherence. FAU - Mai, Ziyang AU - Mai Z AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. FAU - Kornak, John AU - Kornak J AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. FAU - Dufault, Suzanne M AU - Dufault SM AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. FAU - Strand, Michael W AU - Strand MW AD - Department of Clinical Pharmacy, University of California, San Francisco, CA, USA. FAU - Reikes, Andrew R AU - Reikes AR AD - Divisions of General Internal Medicine and Endocrinology, Department of Medicine, UC Irvine School of Medicine, Irvine, CA, USA. FAU - Watanabe, Jonathan H AU - Watanabe JH AUID- ORCID: 0000-0002-2543-5305 AD - Department of Clinical Pharmacy, University of California, San Francisco, CA, USA. LA - eng PT - Journal Article DEP - 20251207 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Obesity/drug therapy/epidemiology MH - Male MH - Middle Aged MH - Comorbidity MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - *Drug Monitoring MH - Adult MH - *Diabetes Mellitus, Type 1/drug therapy/epidemiology MH - Cohort Studies PMC - PMC13332170 OTO - NOTNLM OT - GLP-1 RA OT - adherence OT - comorbidity OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - type 2 diabetes COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/12/08 06:27 MHDA- 2026/07/08 01:11 PMCR- 2026/07/04 CRDT- 2025/12/08 02:53 PHST- 2026/07/08 01:11 [medline] PHST- 2025/12/08 06:27 [pubmed] PHST- 2025/12/08 02:53 [entrez] PHST- 2026/07/04 00:00 [pmc-release] AID - 10.1177_10600280251384637 [pii] AID - 10.1177/10600280251384637 [doi] PST - ppublish SO - Ann Pharmacother. 2026 Aug;60(8):733-744. doi: 10.1177/10600280251384637. Epub 2025 Dec 7. PMID- 41354136 OWN - NLM STAT- MEDLINE DCOM- 20251207 LR - 20260127 IS - 1748-1716 (Electronic) IS - 1748-1708 (Linking) VI - 242 IP - 1 DP - 2026 Jan TI - Effect of Weight-Neutral Treatment With Semaglutide or Tirzepatide on beta-Cell Identity in db/db Mice. PG - e70141 LID - 10.1111/apha.70141 [doi] AB - AIM: Insulin resistance and pancreatic beta-cell failure are key characteristics of type 2 diabetes (T2D). Impaired beta-cell function is associated with loss of beta-cell identity, resulting in beta-cell dedifferentiation or trans-differentiation to other endocrine cells. We have shown that beta-cell dedifferentiation can be reversed, restoring insulin secretion. The aim of this study was to investigate whether semaglutide or tirzepatide treatment can reverse early stages of beta-cell dedifferentiation in db/db mice independent of their effect on body weight. METHODS: After 4 weeks of treatment, 12-week-old db/db mice were assessed by oral glucose tolerance test and immunofluorescence to evaluate glucose clearance capacity and effects on pancreatic beta-cell. Body weight, fasting blood glucose, and plasma insulin levels were monitored weekly. Bulk RNA sequencing from islets was performed to identify potential targets. RESULTS: At the doses employed, tirzepatide stabilized, whereas semaglutide was unable to reverse the weight gain of db/db mice. After a 4-week course, both groups showed comparable glucose lowering and increased insulin levels. However, both treatments failed to reverse pancreatic beta-cell dedifferentiation, as assessed by either the percentage of cells expressing the dedifferentiation marker ALDH1A3(+) or FOXO1 translocation. Furthermore, the number of beta-cells expressing low levels of PDX1 was higher in both treatment groups than in controls. Gene expression analyses showed a muted transcriptional response in overlapping patterns in islets treated with either compound but no obvious candidate target genes. CONCLUSION: The findings highlight that the early glucose-lowering effects of semaglutide and tirzepatide in db/db mice occur independently of changes to beta-cell identity. CI - (c) 2025 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. FAU - Deng, Zhaobin AU - Deng Z AUID- ORCID: 0009-0009-4278-8178 AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Zheng, Dongxu AU - Zheng D AD - Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands. FAU - Son, Jinsook AU - Son J AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Du, Wen AU - Du W AD - School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, People's Republic of China. FAU - McKimpson, Wendy M AU - McKimpson WM AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Liu, Qingli AU - Liu Q AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Accili, Domenico AU - Accili D AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. LA - eng GR - DK63618/NH/NIH HHS/United States GR - DK64819/NH/NIH HHS/United States PT - Journal Article PL - England TA - Acta Physiol (Oxf) JT - Acta physiologica (Oxford, England) JID - 101262545 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology MH - Mice MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Blood Glucose/drug effects/metabolism MH - Insulin/blood/metabolism MH - Mice, Inbred C57BL MH - Body Weight/drug effects MH - *Hypoglycemic Agents/pharmacology MH - Insulin Resistance MH - Cell Dedifferentiation/drug effects MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - insulin OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - beta-Cell dedifferentiation EDAT- 2025/12/08 01:37 MHDA- 2025/12/08 01:38 CRDT- 2025/12/07 19:33 PHST- 2025/10/29 00:00 [revised] PHST- 2025/08/19 00:00 [received] PHST- 2025/11/21 00:00 [accepted] PHST- 2025/12/08 01:38 [medline] PHST- 2025/12/08 01:37 [pubmed] PHST- 2025/12/07 19:33 [entrez] AID - 10.1111/apha.70141 [doi] PST - ppublish SO - Acta Physiol (Oxf). 2026 Jan;242(1):e70141. doi: 10.1111/apha.70141. PMID- 41351656 OWN - NLM STAT- MEDLINE DCOM- 20260113 LR - 20261009 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 86 IP - 1 DP - 2026 Jan TI - Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists: A State-of-the-Art Narrative Review. PG - 11-36 LID - 10.1007/s40265-025-02263-0 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs)-along with the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA tirzepatide-are widely acknowledged for their efficacy in managing both type 2 diabetes mellitus and obesity, with expanding indications in cardiometabolic risk reduction. While their glycemic, weight-lowering, and cardiovascular benefits are well established through randomized trials and meta-analyses, concerns remain regarding their safety and tolerability across diverse populations and clinical settings. Gastrointestinal (GI) adverse events-particularly nausea, vomiting, diarrhea, and constipation-are the most common side effects, generally emerging during dose escalation and resolving over time. However, accumulating evidence has identified additional GI complications, including cholelithiasis, cholecystitis, gastroparesis, and bowel obstruction, which may warrant caution in susceptible individuals. Injection-site reactions and worsening of pre-existing diabetic retinopathy are also relevant clinical concerns. Although rare, associations with nonarteritic anterior ischemic optic neuropathy, pancreatitis, medullary thyroid carcinoma, and acute kidney injury (AKI) have been reported, primarily through pharmacovigilance and case-based evidence. Importantly, large-scale randomized trials, meta-analyses, and observational studies suggest that GLP-1RAs do not significantly increase AKI risk and may even confer renal benefits in high-risk populations. There is no confirmed elevated risk of suicidality, but surveillance remains warranted. Safety data in special populations-such as pregnant or lactating women, pediatric patients, and those with advanced renal or hepatic impairment-remain limited and require further study. This state-of-the-art narrative review synthesizes current evidence from clinical trials, pharmacovigilance databases, and real-world cohorts to provide a comprehensive evaluation of the safety and tolerability of GLP-1RAs and tirzepatide. We present clinical strategies for adverse event mitigation, monitoring recommendations, contraindications, and practical considerations for treatment discontinuation or switching. Although these agents offer transformative therapeutic potential, their optimal use requires individualized care, careful patient selection, and ongoing safety surveillance. Future research should prioritize long-term safety in underrepresented populations and strategies to mitigate lean mass loss during therapy. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Kunutsor, Setor K AU - Kunutsor SK AUID- ORCID: 0000-0002-2625-0273 AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, St. Boniface Hospital, University of Manitoba, 409 Tache Avenue, Winnipeg, MB, R2H 2A6, Canada. skk31@cantab.net. AD - Cardiovascular Real-World Evidence (CARDIO-RWE) Research Group, Section of Cardiology, I.H. Asper Institute, St. Boniface Hospital, 369 Tache Avenue, Winnipeg, MB, R2H 2A6, Canada. skk31@cantab.net. AD - Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. skk31@cantab.net. FAU - Seidu, Samuel AU - Seidu S AUID- ORCID: 0000-0002-8335-7018 AD - Leicester Real World Evidence Unit, Diabetes Research Centre, Leicester General Hospital, University of Leicester, Gwendolen Road, Leicester, LE5 4WP, UK. LA - eng PT - Journal Article PT - Review DEP - 20251206 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Obesity/drug therapy MH - Gastrointestinal Diseases/chemically induced COIS- Declarations. Conflict of Interest: The authors declare that they have no conflicts of interest. Authors' Contributions: Setor K. Kunutsor: conceptualization, methodology, data curation, formal analysis, investigation, original draft, writing-review and editing. Samuel Seidu: methodology, data curation, formal investigation, writing-review and editing. Data Availability Statement: This is a narrative review; no new scientific data was generated, and all data are within the paper. Ethics Approval: Not applicable. Code Availability: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. EDAT- 2025/12/06 12:51 MHDA- 2026/01/14 00:37 CRDT- 2025/12/06 11:03 PHST- 2025/06/17 00:00 [received] PHST- 2025/11/10 00:00 [accepted] PHST- 2026/01/14 00:37 [medline] PHST- 2025/12/06 12:51 [pubmed] PHST- 2025/12/06 11:03 [entrez] AID - 10.1007/s40265-025-02263-0 [pii] AID - 10.1007/s40265-025-02263-0 [doi] PST - ppublish SO - Drugs. 2026 Jan;86(1):11-36. doi: 10.1007/s40265-025-02263-0. Epub 2025 Dec 6. PMID- 41349614 OWN - NLM STAT- MEDLINE DCOM- 20260111 LR - 20260111 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 231 DP - 2026 Jan TI - Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes. PG - 113041 LID - S0168-8227(25)01056-3 [pii] LID - 10.1016/j.diabres.2025.113041 [doi] AB - AIMS: To identify whether genetic predisposition to obesity influences the weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes (T2D). METHODS: This study evaluated 52-week weight loss trajectories. Genetic exposures comprised: 1) a BMI polygenic risk score (PRS) incorporating 935,416 single-nucleotide polymorphisms (SNPs) and stratified into low (bottom 20 %), intermediate (middle 60 %), and high (top 20 %) categories; and 2) five major genetic variants for BMI PRS. Linear mixed models were applied to assess the associations between genetic factors and weight loss percentage, and the interaction effect between genetic factors and follow-up time was further considered. RESULTS: Among the 1,055 included adults (mean age 59 +/- 11 years, 55 % female), intermediate and high BMI PRS groups were modestly associated with less weight loss over 52 weeks (0.7 % and 1.5 %, P = 0.0017 and 0.0023, respectively) than the low BMI PRS group. Individual SNPs showed no significant association with weight loss. BMI PRS modified response over time-intermediate PRS showed less early weight loss, whereas high PRS showed less late weight loss; several genotypes also showed significant time-varying effects. CONCLUSIONS: BMI PRS could potentially be used to personalize obesity management with GLP-1RAs. Large-scale, multi-ancestry studies are needed to validate the application. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Zheng, Yulu AU - Zheng Y AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: yulu.zheng@vumc.org. FAU - Guo, Zheng AU - Guo Z AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: zheng.guo@vumc.org. FAU - Jeong, Eugene AU - Jeong E AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: eugene.jeong.1@vumc.org. FAU - Xu, Shuai AU - Xu S AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: shuai.xu.1@Vanderbilt.Edu. FAU - Samuels, Jason M AU - Samuels JM AD - Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: jason.m.samuels@vumc.org. FAU - Dawwas, Ghadeer K AU - Dawwas GK AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: ghadeer.dawwas@vumc.org. FAU - Tao, Ran AU - Tao R AD - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: r.tao@vumc.org. FAU - Srivastava, Gitanjali AU - Srivastava G AD - Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: gitanjali.srivastava@vumc.org. FAU - Chen, You AU - Chen Y AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: you.chen@vumc.org. FAU - Yu, Danxia AU - Yu D AD - Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: danxia.yu@vumc.org. LA - eng PT - Journal Article DEP - 20251203 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - Female MH - Middle Aged MH - *Weight Loss/genetics/drug effects MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Polymorphism, Single Nucleotide MH - Aged MH - Body Mass Index MH - Genetic Predisposition to Disease MH - *Obesity/genetics/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - GLP-1RA OT - Genetic factors OT - T2D OT - Weight loss COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/12/06 00:32 MHDA- 2026/01/12 00:37 CRDT- 2025/12/05 19:32 PHST- 2025/10/28 00:00 [received] PHST- 2025/12/01 00:00 [revised] PHST- 2025/12/02 00:00 [accepted] PHST- 2026/01/12 00:37 [medline] PHST- 2025/12/06 00:32 [pubmed] PHST- 2025/12/05 19:32 [entrez] AID - S0168-8227(25)01056-3 [pii] AID - 10.1016/j.diabres.2025.113041 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jan;231:113041. doi: 10.1016/j.diabres.2025.113041. Epub 2025 Dec 3. PMID- 41348220 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 49 IP - 2 DP - 2026 Feb 1 TI - Socioeconomic Factors and Initiation of Semaglutide or Tirzepatide Among Medicare Beneficiaries With Type 2 Diabetes. PG - 277-281 LID - 10.2337/dc25-1619 [doi] AB - OBJECTIVE: Identifying social and economic factors associated with initiation of semaglutide or tirzepatide may inform strategies to support equitable uptake. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted using 100% of Medicare claims of patients >/=65 years with type 2 diabetes mellitus (T2DM). The outcome was initiation of semaglutide or tirzepatide. We calculated adjusted odds ratios (aORs) for each exposure (self-reported race and ethnicity, dual enrollment in Medicare and Medicaid, rurality, and social vulnerability index), accounting for demographic and clinical characteristics. RESULTS: Among 13,922,387 patients with T2DM, 673,776 (4.8%) initiated semaglutide or tirzepatide in 2023. Minoritized racial and ethnic identity (e.g., non-Hispanic Black compared with White; aOR 0.72; 95% CI 0.71-0.72), dual enrollment (aOR 0.90; 0.89-0.91), and residence in the most versus least vulnerable socially vulnerable neighborhoods (aOR 0.93; 0.92-0.93) were associated with lower initiation. CONCLUSIONS: Minoritized racial and ethnic identity and adverse socioeconomic factors were associated with lower odds of initiation among Medicare beneficiaries with T2DM. CI - (c) 2025 by the American Diabetes Association. FAU - Decker, Sergio R R AU - Decker SRR AUID- ORCID: 0000-0001-6989-3079 AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Department of Internal Medicine and MOVE Outcomes Research Lab, Moinhos de Vento Hospital, Porto Alegre, Brazil. FAU - Chaudhary, Richard S AU - Chaudhary RS AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. FAU - Inoue, Kosuke AU - Inoue K AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Department of Health Promotion and Behavioral Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Hakubi Center, Kyoto University, Kyoto, Japan. FAU - Song, Yang AU - Song Y AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. FAU - Ndumele, Chiadi E AU - Ndumele CE AUID- ORCID: 0000-0002-1603-282X AD - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Khan, Sadiya S AU - Khan SS AUID- ORCID: 0000-0003-0643-1859 AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. FAU - Kazi, Dhruv S AU - Kazi DS AUID- ORCID: 0000-0002-9510-2979 AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Harvard T.H. Chan School of Public Health, Boston, MA. LA - eng PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - United States MH - *Medicare/statistics & numerical data MH - Aged MH - Male MH - Cross-Sectional Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Socioeconomic Factors MH - *Hypoglycemic Agents/therapeutic use MH - Aged, 80 and over MH - Tirzepatide EDAT- 2025/12/05 13:07 MHDA- 2026/01/20 19:20 CRDT- 2025/12/05 11:13 PHST- 2025/07/05 00:00 [received] PHST- 2025/10/27 00:00 [accepted] PHST- 2026/01/20 19:20 [medline] PHST- 2025/12/05 13:07 [pubmed] PHST- 2025/12/05 11:13 [entrez] AID - 163978 [pii] AID - 10.2337/dc25-1619 [doi] PST - ppublish SO - Diabetes Care. 2026 Feb 1;49(2):277-281. doi: 10.2337/dc25-1619. PMID- 41346258 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Unintentional periconceptional exposure to glucagon-like peptide-1 receptor agonists and adverse pregnancy outcomes: A nationwide cohort study in Taiwan. PG - 1420-1430 LID - 10.1111/dom.70334 [doi] AB - AIMS: To assess whether periconceptional exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with adverse outcomes in women with pregestational type 2 diabetes. MATERIALS AND METHODS: We linked Taiwan's Birth Certificate Application and National Health Insurance claims (2013-2022) to assemble a nationwide cohort of singleton births to mothers (18-50 years) with pregestational diabetes. Exposure was any GLP-1 RA dispensed during the 90 days before and after the last menstrual period; insulin without GLP-1 RA was the active comparator. Outcomes were major congenital malformations, stillbirth, preterm birth (<37 weeks) and small for gestational age (SGA, <10th percentile). We used 1:4 propensity-score matching and Poisson generalised estimating equation (GEE); sensitivity analyses required >/=2 prescriptions and restricted exposure to the first trimester. RESULTS: We identified 3351 comparison pregnancies (GLP-1 RA 160; insulin 3191); matching yielded 160 versus 606. Risk ratios (GLP-1 RA vs. insulin) were malformations 0.64 (95% confidence interval 0.11-3.83), stillbirth 2.05 (0.82-5.13), preterm birth 1.09 (0.85-1.39) and SGA 0.86 (0.31-2.41). Sensitivity analyses were similar. CONCLUSIONS: Periconceptional GLP-1 RA exposure was not associated with increased risks of malformations, stillbirth, preterm birth or SGA versus insulin use. These preliminary data require confirmation in larger agent-specific studies; until then, intentional GLP-1 RA use in planned pregnancy is not advised. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chou, Yi-Chang AU - Chou YC AUID- ORCID: 0000-0002-7478-0105 AD - Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan. AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. AD - University of Taipei, Taipei, Taiwan. AD - Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Weng, Shih-Han AU - Weng SH AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. AD - University of Taipei, Taipei, Taiwan. AD - Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Cheng, Feng-Shiang AU - Cheng FS AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. AD - University of Taipei, Taipei, Taiwan. AD - Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Tseng, Chih-Hao AU - Tseng CH AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. FAU - Hu, Hsiao-Yun AU - Hu HY AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. AD - University of Taipei, Taipei, Taiwan. AD - Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Liu, Chieh-Hsing AU - Liu CH AD - Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan. LA - eng GR - 11401-62-007/Department of Health, Taipei City Government/ PT - Journal Article DEP - 20251205 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - Female MH - Pregnancy MH - Adult MH - Taiwan/epidemiology MH - *Pregnancy Outcome/epidemiology MH - Young Adult MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Adolescent MH - Infant, Newborn MH - Middle Aged MH - Cohort Studies MH - *Pregnancy in Diabetics/drug therapy/epidemiology MH - Premature Birth/epidemiology/chemically induced MH - Infant, Small for Gestational Age MH - Stillbirth/epidemiology MH - Congenital Abnormalities/epidemiology MH - Insulin/therapeutic use/adverse effects PMC - PMC12803572 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - periconceptional exposure OT - pregnancy outcomes OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/12/05 06:27 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/12/05 03:13 PHST- 2025/11/05 00:00 [revised] PHST- 2025/10/03 00:00 [received] PHST- 2025/11/13 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/12/05 06:27 [pubmed] PHST- 2025/12/05 03:13 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70334 [pii] AID - 10.1111/dom.70334 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1420-1430. doi: 10.1111/dom.70334. Epub 2025 Dec 5. PMID- 41344888 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 7 DP - 2026 Jun 30 TI - Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes. PG - 1262-1273 LID - 10.1093/ndt/gfaf258 [doi] AB - BACKGROUND AND HYPOTHESIS: In patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), there remains a paucity of data from large, high-quality, real-world studies on the efficacy of weight-lowering interventions, including the glucagon-like peptide-1-based therapies semaglutide and tirzepatide, as well as bariatric surgery (BS). This retrospective cohort study evaluates these interventions on cardiorenal outcomes and mortality using health records from TriNetX US Collaborative Network. METHODS: Three cohorts with T2DM and CKD living with overweight or obesity, prescribed semaglutide or tirzepatide, or with a BS procedure were propensity-score matched with a cohort receiving dipeptidyl peptidase 4 inhibitors (DPP4i, weight-neutral control). We investigated the hazard ratio (HR) of: (i) end-stage renal disease (ESRD); (ii) myocardial infarction (MI); (iii) stroke; and (iv) all-cause mortality. RESULTS: Cohorts included 17 749 (semaglutide, age 64.1 +/- 10.9 years, 57.4% female), 4211 (tirzepatide, 63.7 +/- 10.8, 58.1%) and 2603 (BS, 56.1 +/- 11.2, 74.1%) patients. Compared with DPP4i, semaglutide reduced the risk of ESRD [HR 0.78 (95% confidence interval 0.71 to 0.85)], while tirzepatide showed a reduction of 42% (0.0.58, 0.45 to 0.75). BS lowered ESRD risk (0.79, 0.67 to 0.92). Semaglutide reduced MI (0.80, 0.72 to 0.88) and stroke (0.85, 0.77 to 0.95) risk, while tirzepatide lowered MI and stroke by 24%. BS was associated with reduced MI (0.45, 0.35 to 0.58) and stroke (0.57, 0.44 to 0.74) risk. All-cause mortality risk was reduced by semaglutide (0.64, 0.59 to 0.70), tirzepatide (0.47, 0.35 to 0.63) and BS (0.68, 0.57 to 0.81). CONCLUSIONS: Using a real-world dataset, semaglutide, tirzepatide and BS-interventions shown to elicit weight loss and improve glycaemic control-have a myriad of benefits on cardio-renal outcomes and mortality, supporting their use as disease-modifying therapy options in T2DM and CKD. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Wilkinson, Thomas J AU - Wilkinson TJ AUID- ORCID: 0000-0002-7855-7752 AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Goldney, Jonathan AU - Goldney J AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Yates, Thomas AU - Yates T AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Henson, Joseph AU - Henson J AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Khunti, Kamlesh AU - Khunti K AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. FAU - Webb, David AU - Webb D AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - University of Hospitals Leicester NHS Trust, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AUID- ORCID: 0000-0001-5044-1515 AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. LA - eng GR - NIHR Leicester Biomedical Research Centre/ PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy MH - Female MH - Semaglutide MH - Retrospective Studies MH - Male MH - Tirzepatide MH - *Weight Loss MH - Middle Aged MH - *Renal Insufficiency, Chronic/complications/therapy MH - *Bariatric Surgery MH - Aged MH - Glucagon-Like Peptides/therapeutic use MH - Follow-Up Studies MH - *Obesity/complications/therapy MH - Prognosis MH - Glomerular Filtration Rate MH - Kidney Function Tests MH - Risk Factors PMC - PMC13314376 OTO - NOTNLM OT - bariatric surgery OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- M.J.D. receives funding from AstraZeneca, Boehringer Ingelheim and Novo Nordisk; consulting fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi and Eli Lilly; support for meetings/travel from Boehringer Ingelheim, Novo Nordisk, Lilly, Amgen, AstraZeneca, Biomea Fusion, Regeneron and Zealand Pharma; and participation on advisory boards for Amgen, AstraZeneca, Biomea Fusion, Sanofi, Zealand Pharma, Carmot/Roche and Regeneron. K.K. receives funding from AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, Servier, Oramed Pharmaceuticals, Roche, Daiichi-Sankyo and Applied Therapeutics; consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Servier, Pfizer, Roche, Daiichi-Sankyo, Embecta and Nestle Health Science; and honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Servier, Pfizer, Roche, Daiichi-Sankyo, Embecta and Nestle Health Science. D.P. receives funding from Novo Nordisk A/S, National Institute for Health and Care Research and Novo Nordisk UK Research Foundation; and honoraria from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Johnson and Johnson, and Academy of Medical Sciences/Diabetes UK. EDAT- 2025/12/05 01:01 MHDA- 2026/06/30 06:31 PMCR- 2025/12/04 CRDT- 2025/12/04 21:32 PHST- 2025/05/16 00:00 [received] PHST- 2025/11/26 00:00 [accepted] PHST- 2026/06/30 06:31 [medline] PHST- 2025/12/05 01:01 [pubmed] PHST- 2025/12/04 21:32 [entrez] PHST- 2025/12/04 00:00 [pmc-release] AID - 8365542 [pii] AID - gfaf258 [pii] AID - 10.1093/ndt/gfaf258 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Jun 30;41(7):1262-1273. doi: 10.1093/ndt/gfaf258. PMID- 41343723 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20251204 IS - 1442-2050 (Electronic) IS - 1120-8694 (Linking) VI - 38 IP - 6 DP - 2025 Nov 1 TI - Esophageal high-resolution manometry can be safely and effectively performed with concurrent glucagon-like peptide-1 receptor agonist use. LID - doaf109 [pii] LID - 10.1093/dote/doaf109 [doi] AB - Esophageal high-resolution manometry (HRM) is the gold standard for evaluating esophageal motility disorders but can be limited by patient intolerance. With increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for obesity and type 2 diabetes, delayed gastric emptying raises concerns for HRM feasibility and safety. This study assessed HRM tolerability in patients on GLP-1RAs. We conducted a retrospective case-control study of adult patients who underwent HRM at our tertiary care center between January 2014 and November 2024. Patients actively taking GLP-1RAs during HRM were identified as cases, while an equal number of consecutive eligible patients not on GLP-1RAs served as controls. Patients with established gastrointestinal dysmotility, prior foregut surgery, esophageal mechanical obstruction, large hiatal hernias, malignancy, or recent opioid use were excluded. From a prospective database of 7194 HRM attempts, 83 cases and 83 matched controls were identified. Among 166 patients, 15 (9.0%) had incomplete HRM due to intolerance, with similar rates between GLP-1RA users and controls (10.84% vs. 7.2%, P = 0.59). Predictors of incomplete HRM included younger age (44.9 +/- 17.4 vs. 60.4 +/- 13.7 years, P < 0.01), globus (P = 0.02), dyspepsia (P = 0.02), and depression (P = 0.04). No aspiration or adverse events occurred in either group. Duration of HRM before abortion was similar between cases and controls. GLP-1RA use was not associated with increased risk of HRM abortion or adverse events, suggesting these medications do not significantly impact HRM feasibility or safety. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the International Society for Diseases of the Esophagus. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Gala, Khushboo AU - Gala K AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Chopra, Preeyati AU - Chopra P AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Ohri, Ashwariya AU - Ohri A AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Goyal, Mayank AU - Goyal M AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Marek, George AU - Marek G AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Camilleri, Michael AU - Camilleri M AUID- ORCID: 0000-0001-6472-7514 AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Ravi, Karthik AU - Ravi K AD - Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. LA - eng PT - Journal Article PL - United States TA - Dis Esophagus JT - Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus JID - 8809160 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Manometry/methods/adverse effects MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - Case-Control Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Esophageal Motility Disorders/diagnosis MH - Aged MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Esophagus/physiopathology/drug effects OTO - NOTNLM OT - GLP-1RA OT - esophageal motility OT - high-resolution manometry OT - incomplete procedure OT - obesity EDAT- 2025/12/04 19:37 MHDA- 2025/12/04 19:38 CRDT- 2025/12/04 15:42 PHST- 2025/10/13 00:00 [received] PHST- 2025/11/15 00:00 [accepted] PHST- 2025/12/04 19:38 [medline] PHST- 2025/12/04 19:37 [pubmed] PHST- 2025/12/04 15:42 [entrez] AID - 8365034 [pii] AID - 10.1093/dote/doaf109 [doi] PST - ppublish SO - Dis Esophagus. 2025 Nov 1;38(6):doaf109. doi: 10.1093/dote/doaf109. PMID- 41340366 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260802 IS - 1467-789X (Electronic) IS - 1467-7881 (Linking) VI - 27 IP - 4 DP - 2026 Apr TI - GLP-1 Receptor Agonist Medications for Obesity and Type 2 Diabetes Treatment: A Rapid Review of Changes in Eating Behaviors and Eating Disorder Risk. PG - e70049 LID - 10.1111/obr.70049 [doi] AB - This rapid review aimed to evaluate the effects of GLP-1 RAs on eating behaviors and eating disorder risk. Databases were searched to January 2025 to identify studies evaluating GLP-1 RA treatment for adolescents or adults with obesity or Type 2 diabetes. Eligible studies reported adverse events, changes in eating disorder risk, or eating behaviors post-intervention or follow-up. Data were synthesized narratively. Of 1597 records screened, 25 studies (k) were included (two adolescent, n = 275; 23 adult, n = 8722). Two studies reported eating disorder adverse events, and two reported no binge eating adverse events. Liraglutide reduced global eating disorder risk scores, with no differences between groups (k = 1). Binge eating episodes and prevalence reduced following liraglutide and semaglutide, respectively. Binge eating scores improved with liraglutide compared to placebo (k = 2). Food cravings following liraglutide (k = 1) or semaglutide (k = 6) were improved (k = 6) or unchanged (k = 1). There was no difference in disinhibition between liraglutide and comparator (k = 2) with one study reporting a reduction in both groups. Three non-RCTs reported reduced disinhibition with liraglutide. Limited data are available on GLP-1 RAs, eating behaviors and eating disorders. For most, eating behaviors may improve or remain unchanged. Comprehensive assessment of eating behaviors is needed to understand the benefits and risks of treatment. CI - (c) 2025 World Obesity Federation. FAU - Jebeile, Hiba AU - Jebeile H AUID- ORCID: 0000-0002-8623-6174 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. FAU - Danielsen, Yngvild Sorebo AU - Danielsen YS AUID- ORCID: 0000-0002-4117-8900 AD - Department of Clinical Psychology, University of Bergen, Bergen, Norway. AD - Regional Department of Eating Disorders, Haukeland University Hospital, Bergen, Norway. FAU - Sumithran, Priya AU - Sumithran P AUID- ORCID: 0000-0002-9576-1050 AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. AD - Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Australia. FAU - Lorien, Sasha AU - Lorien S AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. FAU - Jardine, Isabelle R AU - Jardine IR AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. FAU - Baur, Louise A AU - Baur LA AUID- ORCID: 0000-0002-4521-9482 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. FAU - Lister, Natalie B AU - Lister NB AUID- ORCID: 0000-0002-9148-8632 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251203 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - Liraglutide/therapeutic use MH - *Feeding and Eating Disorders MH - *Feeding Behavior/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adolescent MH - Adult OTO - NOTNLM OT - binge eating OT - disordered eating OT - liraglutide OT - obesity treatment OT - semaglutide OT - tirzepatide EDAT- 2025/12/04 06:27 MHDA- 2026/03/24 00:30 CRDT- 2025/12/04 02:05 PHST- 2025/09/18 00:00 [revised] PHST- 2025/04/07 00:00 [received] PHST- 2025/11/06 00:00 [accepted] PHST- 2026/03/24 00:30 [medline] PHST- 2025/12/04 06:27 [pubmed] PHST- 2025/12/04 02:05 [entrez] AID - 10.1111/obr.70049 [doi] PST - ppublish SO - Obes Rev. 2026 Apr;27(4):e70049. doi: 10.1111/obr.70049. Epub 2025 Dec 3. PMID- 41338557 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260127 IS - 0578-1426 (Print) IS - 0578-1426 (Linking) VI - 64 IP - 12 DP - 2025 Dec 1 TI - [Effect of semaglutide on serum metabolomics in obese patients with type 2 diabetes mellitus complicated with metabolic-associated fatty liver disease]. PG - 1218-1225 LID - 10.3760/cma.j.cn112138-20250424-00235 [doi] AB - Objective: To investigate the effect of semaglutide on the metabolomics of obese patients with type 2 diabetes mellitus (T2DM) complicated by metabolic-associated fatty liver disease (MAFLD). Methods: A prospective non-randomized controlled study was conducted. Obese patients with T2DM complicated by MAFLD who attended the Department of Endocrinology of Shijiazhuang People's Hospital from October 2022 to June 2023 were selected as the semaglutide group, and healthy individuals from the physical examination center were selected as the control group. Clinical data of both groups were collected. The semaglutide group was subcutaneously injected with semaglutide following a basic hypoglycemic regimen (starting dose of 0.25 mg once a week, which was changed to 0.5 mg once a week after 1 week for 12 weeks). Liquid chromatography-tandem mass spectrometry was used for qualitative and quantitative analyses of plasma metabolites, and multivariate analysis methods were used to analyze the metabolomics data. Results: In total, 69 patients in the semaglutide group completed the treatment, with 49 males (71%) and a median age of 46 (36, 54) years, and the healthy control group consisted of 100 individuals, with 38 males (38%) and a median age of 40 (35, 45) years. The body mass index and levels of fasting blood glucose, alanine aminotransferase, and interleukin-6 (IL-6) in the semaglutide group before treatment were significantly higher than those in the control group (all P<0.001). The body mass index [23.65 (22.33, 24.45) vs. 28.72 (27.50, 32.07) kg/m(2)], liver stiffness measurement [1.61 (0.91, 2.00) vs. 5.78 (5.51, 6.10) kPa], and homeostasis model assessment of insulin resistance index [5.10 (2.90, 7.95) vs. 9.00 (6.25, 11.80)] in the semaglutide group were significantly lower after treatment than before treatment (all P<0.001), and the blood glucose, blood lipid, liver function indicator, and IL-6 levels all significantly decreased after treatment. Metabolomics analysis revealed that there were 219 differential metabolites (131 up-regulated and 88 down-regulated) between the semaglutide group (n=27) before treatment and the control group (n=12), with glycerophospholipids and free fatty acids being significantly up-regulated. The semaglutide group showed 203 differential metabolites (121 up-regulated and 82 down-regulated) after treatment compared with before, with significant down-regulation of long-chain fatty acids and significant up-regulation of metabolites including carnitines, branched-chain amino acids, and taurine. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differential metabolites identified before and after semaglutide treatment were involved in several signaling pathways, such as biosynthesis of unsaturated fatty acids, linoleic acid metabolism, aldosterone synthesis and secretion, and the mTOR signaling pathway, etc. Conclusion: Semaglutide alters the serum metabolite levels in obese patients with T2DM complicated by MAFLD. FAU - Niu, S AU - Niu S AD - Department of Endocrinology, Shijiazhuang People's Hospital, Shijiazhuang 050081, China. FAU - Wang, C X AU - Wang CX AD - Hebei Medical University, Shijiazhuang 050017, China. FAU - Zhao, Y B AU - Zhao YB AD - Department of Gastroenterology, Shijiazhuang People's Hospital, Shijiazhuang 050081, China. FAU - Wu, D AU - Wu D AD - Department of Gastroenterology, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang 050051, China. FAU - Yang, K L AU - Yang KL AD - Hebei Medical University, Shijiazhuang 050017, China. LA - chi GR - 2024127/2024 Annual Instructional Project of Hebei Administration of Traditional Chinese Medicine/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Nei Ke Za Zhi JT - Zhonghua nei ke za zhi JID - 16210490R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/blood/metabolism MH - Male MH - Middle Aged MH - Female MH - Metabolomics MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/complications/blood/drug therapy MH - Prospective Studies MH - Adult MH - *Fatty Liver/complications/blood/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/12/04 02:11 MHDA- 2025/12/04 02:12 CRDT- 2025/12/03 19:47 PHST- 2025/12/04 02:12 [medline] PHST- 2025/12/04 02:11 [pubmed] PHST- 2025/12/03 19:47 [entrez] AID - 10.3760/cma.j.cn112138-20250424-00235 [doi] PST - ppublish SO - Zhonghua Nei Ke Za Zhi. 2025 Dec 1;64(12):1218-1225. doi: 10.3760/cma.j.cn112138-20250424-00235. PMID- 41335431 OWN - NLM STAT- MEDLINE DCOM- 20260204 LR - 20260813 IS - 2168-6238 (Electronic) IS - 2168-622X (Print) IS - 2168-622X (Linking) VI - 83 IP - 2 DP - 2026 Feb 1 TI - Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial. PG - 128-138 LID - 10.1001/jamapsychiatry.2025.3639 [doi] AB - IMPORTANCE: Individuals with schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs) are at heightened risk for obesity, prediabetes, and type 2 diabetes, contributing to increased cardiovascular morbidity and premature mortality. Early intervention with glucagon-like peptide-1 receptor agonists (GLP-1RAs) may help mitigate long-term cardiometabolic risk. OBJECTIVE: To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, double-blind, placebo-controlled, randomized clinical trial. Participants were enrolled from 3 clinical sites in Denmark between September 2021 and August 2024. Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years. Participants had early-stage glycemic dysregulation (hemoglobin A1c [HbA1c], 5.4%-7.4%) and were not receiving antidiabetic therapy. INTERVENTIONS: Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks. MAIN OUTCOMES AND MEASURES: The prespecified primary outcome was change in HbA1c level from baseline to week 26. The primary analysis adhered to the intention-to-treat principle. RESULTS: Of 104 individuals screened, 73 were randomized and 57 (78%) completed the trial. Baseline characteristics were comparable between groups. Mean (SD) age was 35 (12) years, 48 were female (65%), and mean (SD) body mass index was 36.1 (7.9). At week 26, semaglutide significantly reduced HbA1c level compared with placebo (mean difference, -0.25%; 95% CI, -0.33 to -0.16; P < .001); 43% of participants (12 of 28) treated with semaglutide achieved low-risk HbA1c levels (<5.4%) vs 3% with placebo. Greater reductions in body weight (-9.2 kg; 95% CI, -13.3 to -5.1 kg; P < .001), waist circumference (-7.0 cm; 95% CI, -10.6 to -3.3 cm; P < .001), and fat mass (-6.1 kg; 95% CI, -10.2 to -1.9 kg; P = .006) were observed with semaglutide. No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed. Gastrointestinal adverse events were common but mild and transient; psychiatric adverse events were similar across groups. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial show that adjunctive semaglutide significantly improved glycemic control and weight outcomes in individuals with schizophrenia spectrum disorders. Secondary outcomes were exploratory. These findings support the use of GLP-1RAs as a potential early intervention strategy to reduce cardiometabolic risk in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04892199. FAU - Sass, Marie R AU - Sass MR AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. AD - Now with Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Klausen, Mette Kruse AU - Klausen MK AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Schwarz, Christine R AU - Schwarz CR AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. FAU - Rasmussen, Line AU - Rasmussen L AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Giver, Malte E B AU - Giver MEB AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Hviid, Malthe AU - Hviid M AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Schilling, Christoffer AU - Schilling C AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Zamorski, Alexandra AU - Zamorski A AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Jensen, Andreas AU - Jensen A AD - Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark. FAU - Gefke, Maria AU - Gefke M AD - Mental Health Centre, Northern Zealand, Copenhagen University Hospital-Mental Health Services CPH, Copenhagen, Denmark. AD - The Early Multimodular Prevention and Intervention Research Institution, Hillerod, Denmark. FAU - Storgaard, Heidi AU - Storgaard H AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. FAU - Oturai, Peter S AU - Oturai PS AD - Department of Clinical Physiology and Nuclear Medicine, Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. FAU - Kjaer, Andreas AU - Kjaer A AD - Department of Clinical Physiology and Nuclear Medicine, Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens J AU - Holst JJ AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Ekstrom, Claus T AU - Ekstrom CT AD - Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. FAU - Vinberg, Maj AU - Vinberg M AD - Mental Health Centre, Northern Zealand, Copenhagen University Hospital-Mental Health Services CPH, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. FAU - Correll, Christoph U AU - Correll CU AD - The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, New York. AD - Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofsta/Northwell, Hempstead, New York. AD - Department of Child and Adolescent Psychiatry, Charite Universitatsmedizin, Berlin, Germany. AD - German Center for Mental Health, partner site Berlin, Berlin, Germany. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. FAU - Fink-Jensen, Anders AU - Fink-Jensen A AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04892199 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA Psychiatry JT - JAMA psychiatry JID - 101589550 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antipsychotic Agents) RN - N7U69T4SZR (Olanzapine) RN - 0 (Glycated Hemoglobin) RN - J60AR2IKIC (Clozapine) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Adult MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/pharmacology MH - *Schizophrenia/drug therapy MH - Double-Blind Method MH - *Antipsychotic Agents/adverse effects/therapeutic use MH - Olanzapine/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Young Adult MH - Clozapine/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adolescent MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Diabetes Mellitus, Type 2/chemically induced MH - Drug Therapy, Combination PMC - PMC12676471 COIS- Conflict of Interest Disclosures: Dr Sass reported institution received unrestricted grants from Novo Nordisk A/S, Mental Health Services in the Capital Region of Denmark, The Lundbeck Foundation, the Novo Nordisk Foundation, and P. Carl Petersen Foundation and being a full-time employee of Novo Nordisk A/S outside the submitted work. Dr Schwarz reported receiving personal fees from Novo Nordisk and Eli Lilly outside the submitted work. Dr Rasmussen reported receiving a pregraduate fellowship grant from Novo Nordisk Foundation during the conduct of the study. Dr Giver reported receiving grants from Novo Nordisk during the conduct of the study. Dr Hviid reported receiving grants from Dagmar Foundation and The Lundbeck Foundation during the conduct of the study. Dr Schilling reported institution received grants from Novo Nordisk A/S, Mental Health Services in the Capital Region of Denmark, The Lundbeck Foundation, Novo Nordisk Foundation, and P. Carl Petersen Foundation during the conduct of the study. Dr Gefke reported receiving grants from Jascha Foundation during the conduct of the study. Dr Kjaer reported receiving consultant fees from Novo Nordisk A/S outside the submitted work. Dr Holst reported receiving grants from Novo Nordisk Foundation during the conduct of the study. Dr Vinberg reported receiving grants from Jascha Foundation during the conduct of the study. Dr Correll reported receiving royalties from UpToDate; consultant and/or advisor fees from AbbVie, Alkermes, Allergan, Angelini, Aristo, Autobahn, Boehringer Ingelheim, Bristol Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Draig, Eli Lilly, Eumentis Therapeutics, Gedeon Richter, GH, Hikma, Holmusk, Intra-Cellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedInCell, Med-Link, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neuraxpharm, Neurocrine, Neurelis, NeuShen, Newron, Noven, Novo Nordisk, Orion Pharma, Otsuka, PPD Biotech, Recognify Life Science, Recordati, Relmada, Response Pharmaceutical, Re-viva, Rovi, Saladax, Sanofi, Seqirus, Servier, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Terran, Tolmar, Vertex, Viatris and Xenon Pharmaceuticals; providing expert testimony for Janssen, Lundbeck, Neurocrine, and Otsuka; serving on a Data Safety Monitoring Board for Compass Pathways, Intra-Cellular Therapies, Relmada, Reviva, and Rovi; receiving grant support from Boehringer-Ingelheim, Janssen, and Takeda; and having stock options for Cardio Diagnostics, Kuleon Biosciences, LB Pharma, MedLink Global, Mindpax, Quantic, and Terran. Dr Vilsboll reported receiving advisory fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mass Medicine, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals, and Zealand Pharma Global outside the submitted work. Dr Fink-Jensen reported receiving an unrestricted research grant from Novo Nordisk A/S during the conduct of the study and serving as an unpaid member of the advisory board for Novo Nordisk A/S outside the submitted work. No other disclosures were reported. EDAT- 2025/12/03 14:10 MHDA- 2026/02/04 15:12 PMCR- 2026/12/03 CRDT- 2025/12/03 11:33 PHST- 2026/02/04 15:12 [medline] PHST- 2025/12/03 14:10 [pubmed] PHST- 2025/12/03 11:33 [entrez] PHST- 2026/12/03 00:00 [pmc-release] AID - 2842202 [pii] AID - yoi250062 [pii] AID - 10.1001/jamapsychiatry.2025.3639 [doi] PST - ppublish SO - JAMA Psychiatry. 2026 Feb 1;83(2):128-138. doi: 10.1001/jamapsychiatry.2025.3639. PMID- 41334697 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260609 IS - 1099-1557 (Electronic) IS - 1053-8569 (Linking) VI - 34 IP - 12 DP - 2025 Dec TI - Cardiovascular Effectiveness of Semaglutide Versus Dulaglutide in Type 2 Diabetes. PG - e70276 LID - 10.1002/pds.70276 [doi] AB - OBJECTIVE: Randomized clinical trials show that subcutaneous semaglutide is modestly superior to dulaglutide in reducing HbA1c and body weight, but no trial has compared their effectiveness on hard cardiovascular outcomes. This study aimed to examine whether semaglutide and dulaglutide differ in cardiovascular effectiveness. RESEARCH DESIGN AND METHODS: This new-user, active-comparator cohort study used nationwide population-based Danish healthcare data to emulate a target trial of adults with type 2 diabetes receiving standard care who initiated subcutaneous semaglutide compared with dulaglutide. Up to five semaglutide initiators were matched to one dulaglutide initiator on a propensity score estimated from 52 variables. The outcome was a major adverse cardiovascular event (MACE), including myocardial infarction, ischemic stroke, heart failure, coronary revascularization, and cardiovascular death. In per-protocol analyses, Aalen-Johansen estimates were used to calculate risks, risk differences, and risk ratios at 3 years, accounting for informative censoring at nonadherence to the assigned treatment via time-varying inverse probability of censoring weights. RESULTS: The semaglutide group included 2535 individuals, and the dulaglutide group 569 (median age [IQR], 61 [52-71] years; 1105 female individuals [36%]). Within 3 years, the risk of MACE was 6.0% (95% CI, 4.5%-7.8%) in the semaglutide group and 6.2% (95% CI, 4.0%-8.9%) in the dulaglutide group, corresponding to a risk difference of -0.2% (95% CI, -3.2% to 2.8%) and a risk ratio of 0.97 (95% CI, 0.59-1.61). CONCLUSIONS: This target trial emulation did not provide evidence for a substantial difference in cardiovascular outcomes between individuals with type 2 diabetes initiating semaglutide and dulaglutide. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Bonnesen, Kasper AU - Bonnesen K AUID- ORCID: 0000-0002-8626-2372 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Clinical Pharmacology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Heide-Jorgensen, Uffe AU - Heide-Jorgensen U AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Christensen, Diana H AU - Christensen DH AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Lash, Timothy L AU - Lash TL AD - Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. FAU - Pedersen, Lars AU - Pedersen L AUID- ORCID: 0000-0002-9341-3888 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Thomsen, Reimar W AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Matthews, Anthony A AU - Matthews AA AUID- ORCID: 0000-0002-1290-271X AD - Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Schmidt, Morten AU - Schmidt M AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Cardiology, Godstrup Hospital, Herning, Denmark. LA - eng GR - Danish Diabetes and Endocrine Academy/ GR - NNF22SA0079901/Novo Nordisk Foundation/ GR - NNF19OC0054908/Novo Nordisk Foundation/ GR - 2018-03028/Swedish Research Council/ GR - 2021-02236/Swedish Research Council/ GR - 2020-00029/Forte/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM EIN - Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70333. doi: 10.1002/pds.70333. PMID: 41566767 MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Recombinant Fusion Proteins/administration & dosage/therapeutic use/adverse effects MH - *Immunoglobulin Fc Fragments/administration & dosage/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - Denmark/epidemiology MH - Cohort Studies MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - Injections, Subcutaneous MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - cardiovascular diseases OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus EDAT- 2025/12/03 14:11 MHDA- 2025/12/03 14:12 CRDT- 2025/12/03 06:53 PHST- 2025/11/13 00:00 [revised] PHST- 2025/04/09 00:00 [received] PHST- 2025/11/18 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/12/03 14:11 [pubmed] PHST- 2025/12/03 06:53 [entrez] AID - 10.1002/pds.70276 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2025 Dec;34(12):e70276. doi: 10.1002/pds.70276. PMID- 41326727 OWN - NLM STAT- MEDLINE DCOM- 20260122 LR - 20261009 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 40 IP - 1 DP - 2026 Jan TI - Bariatric surgery vs. GLP-1 receptor agonists among primarily medicare and medicaid patients with diabetes: a 3-year analysis. PG - 671-678 LID - 10.1007/s00464-025-12403-y [doi] AB - BACKGROUND: Bariatric surgery has long been established as an effective treatment option for obesity and diabetes [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025] and Ogden et al. in JAMA 311(8):806-806, 2025. 10.1001/jama.2014.732]. Recently, GLP-1 Receptor Agonists' (GLP-1RAs) use has expanded as an alternative therapy for weight loss and diabetes management. While GLP1RAs are known to be safe and effective, few have compared long term outcomes of GLP-1RAs versus the "gold standard" of bariatric surgery among Medicare/Medicaid patients, who make up the largest payer group in the U.S. [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025]. METHODS: This was a retrospective, multicenter study of obese, type-2 diabetic patients (T2D) >/= 18 years old, who initiated weekly injectable semaglutide or tirzepatide or underwent bariatric surgery between January 1st, 2018 to July 31st, 2024. Patients with a baseline BMI /=1% alongside BW reductions of >/=3% or >/=5%, respectively. Treatment satisfaction increased significantly (mean change in DTSQs +8.7 and DTSQc 14.9; both p < 0.0001). At EoS, 49.5% of participants remained on oral semaglutide, of whom 47.4% were receiving the 14.0 mg dose. CONCLUSIONS: This real-world population of adults with T2D in Saudi Arabia experienced clinically significant reductions in HbA1c and BW, increased treatment satisfaction and a favourable safety profile, consistent with previously published PIONEER REAL studies. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - ElBadawi, Hussein AU - ElBadawi H AD - Wayne State University School of Medicine, Detroit, Michigan, USA. FAU - Albalkhi, Nader AU - Albalkhi N AD - Specialized Medical Center Hospital, Riyadh, Saudi Arabia. FAU - Al Kadhim, Ibrahim AU - Al Kadhim I AD - Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia. FAU - Elsadig, Ahmed AU - Elsadig A AD - Dr Suliaman Al Habib Hospitals, Riyadh, Saudi Arabia. FAU - Baltzis, Dimitrios AU - Baltzis D AD - Mouwasat Hospital, Khobar, Saudi Arabia. FAU - Hatahet, Mohamed Hassan AU - Hatahet MH AD - Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia. FAU - Ismail, Mahmoud AU - Ismail M AUID- ORCID: 0000-0002-3164-6969 AD - Novo Nordisk Saudia Arabia, Riyadh, Saudi Arabia. FAU - Khader, Said AU - Khader S AD - Dr Suliaman Al Habib Hospitals, Riyadh, Saudi Arabia. FAU - Rasmussen, Christina Louise AU - Rasmussen CL AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Scheuer, Stine Hedegaard AU - Scheuer SH AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Shalaby, Ahmed AU - Shalaby A AD - Novo Nordisk Saudia Arabia, Riyadh, Saudi Arabia. FAU - Almehthel, Mohammed AU - Almehthel M AD - Obesity, Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia. AD - Division of Endocrinology, University of British Columbia, Vancouver, British Columbia, Canada. LA - eng GR - Novo Nordisk Saudi Arabia/ PT - Journal Article PT - Multicenter Study DEP - 20251127 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Saudi Arabia/epidemiology MH - Female MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Middle Aged MH - Male MH - Prospective Studies MH - Adult MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Administration, Oral MH - Treatment Outcome MH - Patient Satisfaction MH - Drug Administration Schedule MH - Blood Glucose MH - Aged MH - Body Weight/drug effects MH - Waist Circumference/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803558 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- Ibrahim Al Kadhim: lecturer/advisory panel member: Novo Nordisk, AstraZeneca, Novartis, Sanofi, Eli Lilly, MSD, Spimaco. Research support: Novo Nordisk, Eli Lilly, IQVIA. Mahmoud Ismail is an employee of Novo Nordisk Saudi Arabia. Christina Louise Rasmussen is an employee of Novo Nordisk A/S. Stine Hedegaard Scheuer is an employee of Novo Nordisk A/S. Ahmed Shalaby is an employee of Novo Nordisk Saudi Arabia. Mohammed Almehthel received lecturing and consultation fees from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Novartis, MSD, Merk, Bayer, Boeringer Ingelheim, Abbott, Vital Aire, Dexcom, Sibionics, Syai, and research support from Vital Aire, Novo Nordisk, Eli Lilly, Sanofi, Syai and Bayer. EDAT- 2025/11/28 00:26 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/27 21:43 PHST- 2025/11/12 00:00 [revised] PHST- 2025/06/04 00:00 [received] PHST- 2025/11/12 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/28 00:26 [pubmed] PHST- 2025/11/27 21:43 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70317 [pii] AID - 10.1111/dom.70317 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1304-1314. doi: 10.1111/dom.70317. Epub 2025 Nov 27. PMID- 41307691 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 2 DP - 2026 Feb TI - Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes. PG - 303-311 LID - 10.1007/s00592-025-02626-9 [doi] AB - AIMS: Glucagon-like peptide-1 receptor (GLP-1R) has become one of the most promising ligand-receptor systems to target for type 2 diabetes mellitus (T2DM) treatment. Over the last two decades, several GLP-1 receptor agonists (GLP-1RAs) have been developed and semaglutide is the first and only GLP-1RA available as an oral formulation. GLP1R single nucleotide polymorphisms may affect GLP-1R response to oral semaglutide. Here we aimed to evaluate the impact of rs6923761 and rs761387 GLP1R polymorphisms on the response to oral semaglutide. METHODS: This is a retrospective cohort study including adult patients with T2DM who had been treated with oral semaglutide for at least one year. Patients were enrolled between November 2023 and April 2024, and then genotyped. RESULTS: We selected 210 adult patients with a median age of 71 years. Their median BMI was 29.1 kg/m2, HbA1c was 7.2% (55 mmol/mol), duration of diabetes was 12 years. After a median follow-up of 18 months, oral semaglutide reduced HbA1c by -0.3% (-3 mmol/mol), BMI by -1.1 kg/m2, SBP by -5 mmHg, total cholesterol by -8 mg/dL, triglycerides by -6.5 mg/dL. In addition, a reduction of ACR by -44.02 mg/g was observed in patients with baseline ACR > 30 mg/g, along with a decrease of liver transaminases in patients with baseline levels >/= 35 U/L. Multivariate linear regression did not show any significant association between rs6923761 or rs761387 GLP1R genotypes and changes in HbA1c, BMI, SBP and DBP. CONCLUSIONS: Our findings confirm the effectiveness of oral semaglutide in improving metabolic control and providing cardiorenal protection in different clinical scenarios. Conversely, they fail to show a clear benefit of GLP1R genotyping to guide treatment decisions, at least in patients with HbA1c < 7.5% (< 58 mmol/mol). Further studies are needed to confirm and extend our findings. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. AD - SC Patologie Diabetiche, ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Via Sai 7, 34128, Trieste, Italy. FAU - Toffoli, Barbara AU - Toffoli B AUID- ORCID: 0000-0002-6854-5782 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Baccichetto, Gabriele AU - Baccichetto G AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Marchese, Francesca AU - Marchese F AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Carpene, Silvia AU - Carpene S AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Gaiotti, Sara AU - Gaiotti S AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Fabris, Bruno AU - Fabris B AUID- ORCID: 0000-0001-5226-1833 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. AD - SS Endocrinologia (Medicina Clinica), ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Bernardi, Stella AU - Bernardi S AUID- ORCID: 0000-0002-7429-3075 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. stella.bernardi@units.it. AD - SS Endocrinologia (Medicina Clinica), ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. stella.bernardi@units.it. LA - eng PT - Journal Article DEP - 20251127 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Female MH - Male MH - Aged MH - *Polymorphism, Single Nucleotide MH - Middle Aged MH - Retrospective Studies MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Blood Glucose MH - Genotype PMC - PMC12957030 OTO - NOTNLM OT - rs6923761 OT - rs761387 OT - GLP1R OT - Oral semaglutide OT - Polymorphism OT - Type 2 diabetes COIS- Declarations. Conflict of interest: All the authors have no conflict of interests. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the Institutional Review Board of the University of Trieste, Trieste, Italy (University of Trieste Comitato Etico di Ateneo #136 date 30/11/2023). Informed consent: Informed consent was obtained from all subjects involved in this study, prior to study enrollment and genotyping. EDAT- 2025/11/27 12:29 MHDA- 2026/06/27 10:10 PMCR- 2025/11/27 CRDT- 2025/11/27 11:13 PHST- 2025/09/14 00:00 [received] PHST- 2025/11/17 00:00 [accepted] PHST- 2026/06/27 10:10 [medline] PHST- 2025/11/27 12:29 [pubmed] PHST- 2025/11/27 11:13 [entrez] PHST- 2025/11/27 00:00 [pmc-release] AID - 10.1007/s00592-025-02626-9 [pii] AID - 2626 [pii] AID - 10.1007/s00592-025-02626-9 [doi] PST - ppublish SO - Acta Diabetol. 2026 Feb;63(2):303-311. doi: 10.1007/s00592-025-02626-9. Epub 2025 Nov 27. PMID- 41307513 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260911 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 3 DP - 2026 Sep TI - Efficacy and safety of oral semaglutide as add-on therapy in poorly controlled type 2 diabetes on background SGLT2 inhibitors: a real-world, multi-center, retrospective, observational study (RYS2). PG - 248-256 LID - 10.23736/S2724-6507.25.04376-3 [doi] AB - BACKGROUND: Treatment of type 2 diabetes mellitus (T2DM) relies on diverse glucose-lowering medications, championing sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists as viable options to address concurrent cardiovascular risk. An oral formulation of semaglutide (Rybelsus((R)), Novo Nordisk) has been recently introduced to clinical use for managing T2DM. Accordingly, there is a paucity of practice evidence while building experience on its combination with SGLT2i. METHODS: In this observational, single-arm, retrospective study, data collected from 142 T2DM patients (66% males, 68% older than 60 years, 85% overweight/obese) treated with oral semaglutide in combination with SGLT2i were analyzed. RESULTS: After 6.8+/-2.6 months of treatment, both glycosylated hemoglobin (HbA1c) and fasting plasma glucose levels significantly improved: 39.6% of patients achieved HbA1cDCCT IFCC /=1% and a weight loss >/=5%. In addition, body weight, body mass index, waist circumference, triglycerides, and total cholesterol levels were significantly reduced. Regarding safety, 94.7% of reported adverse events were non-serious gastrointestinal symptoms and 1 patient experienced hypoglycemia. CONCLUSIONS: The herein presented real-world data suggest that oral semaglutide can be regarded as safe and effective, when used as add-on medication for uncontrolled T2DM on background SGLT2i. FAU - Malighetti, Maria E AU - Malighetti ME AD - Ambulatory of Diabetology, Casa di Cura Ambrosiana, Cesano Boscone, Milan, Italy. FAU - Vescini, Fabio AU - Vescini F AD - Section of Endocrinology, Azienda Sanitaria-Universitaria Friuli Centrale, Udine, Italy. FAU - Carpentieri, Maria AU - Carpentieri M AD - Section of Endocrinology, Azienda Sanitaria-Universitaria Friuli Centrale, Udine, Italy. FAU - Altomari, Anna AU - Altomari A AD - Center of Diabetology, S. Maria del Prato Hospital, Feltre, Belluno, Italy. FAU - Turchi, Federica AU - Turchi F AD - Metabolic Diseases and Diabetology Unit, IRCCS INRCA, Ancona, Italy. FAU - DA Porto, Andrea AU - DA Porto A AD - Clinica Medica, University of Udine, Udine, Italy. FAU - Dauriz, Marco AU - Dauriz M AD - Section of Endocrinology and Diabetes, Department of Internal Medicine, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy - marco.dauriz@sabes.it. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251127 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Therapy, Combination MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use EDAT- 2025/11/27 12:29 MHDA- 2026/09/07 11:37 CRDT- 2025/11/27 10:18 PHST- 2026/09/07 11:37 [medline] PHST- 2025/11/27 12:29 [pubmed] PHST- 2025/11/27 10:18 [entrez] AID - S2724-6507.25.04376-3 [pii] AID - 10.23736/S2724-6507.25.04376-3 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Sep;51(3):248-256. doi: 10.23736/S2724-6507.25.04376-3. Epub 2025 Nov 27. PMID- 41303737 OWN - NLM STAT- MEDLINE DCOM- 20251127 LR - 20251130 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 11 DP - 2025 Oct 23 TI - Small-Molecule GLP-1 Receptor Agonists: A Promising Pharmacological Approach. LID - 10.3390/medicina61111902 [doi] LID - 1902 AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists are injectable peptide-based therapies that have become a focal point in the medical community due to their significant therapeutic efficacy in type 2 diabetes and obesity treatment. Recent advancements in medicinal chemistry have enabled the development of small-molecule GLP-1R agonists, presenting advantages such as oral administration, improved patient adherence, and cost-effectiveness. These compounds demonstrate promising efficacy in enhancing insulin secretion and promoting weight loss, in a similar way to peptide agonists. This narrative review focuses on the pharmacodynamic profiles and the current progress in clinical and preclinical research on small-molecule GLP-1R agonists. As this class of agents continues to evolve, it represents a compelling therapeutic alternative with the potential to reshape the treatment for metabolic disorders. FAU - Seremet, Oana Cristina AU - Seremet OC AUID- ORCID: 0000-0002-0816-0012 AD - Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. FAU - Puscasu, Ciprian AU - Puscasu C AUID- ORCID: 0009-0003-7259-7942 AD - Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. FAU - Andrei, Corina AU - Andrei C AUID- ORCID: 0000-0002-1789-742X AD - Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. FAU - Nitulescu, Georgiana AU - Nitulescu G AUID- ORCID: 0000-0002-2162-3069 AD - Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. FAU - Zbarcea, Cristina Elena AU - Zbarcea CE AUID- ORCID: 0000-0001-9905-5957 AD - Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. FAU - Olaru, Octavian Tudorel AU - Olaru OT AUID- ORCID: 0000-0001-6904-3066 AD - Department of Pharmaceutical Botany and Cell Biology, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania. LA - eng GR - PN-IV-P2-2.1-TE-2023-1680-70TE/03.01.2025/Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii/ PT - Journal Article PT - Review DEP - 20251023 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use PMC - PMC12654632 OTO - NOTNLM OT - obesity OT - small-molecule GLP-1 receptor agonists OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/11/27 06:28 MHDA- 2025/11/27 06:29 PMCR- 2025/10/23 CRDT- 2025/11/27 01:15 PHST- 2025/09/11 00:00 [received] PHST- 2025/10/17 00:00 [revised] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/27 06:29 [medline] PHST- 2025/11/27 06:28 [pubmed] PHST- 2025/11/27 01:15 [entrez] PHST- 2025/10/23 00:00 [pmc-release] AID - medicina61111902 [pii] AID - medicina-61-01902 [pii] AID - 10.3390/medicina61111902 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Oct 23;61(11):1902. doi: 10.3390/medicina61111902. PMID- 41301492 OWN - NLM STAT- MEDLINE DCOM- 20251127 LR - 20260327 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 11 DP - 2025 Nov 10 TI - Current and Emerging Roles of GLP1 Receptor Agonists Across the Spectrum of Left Ventricular Ejection Fraction in Heart Failure. LID - 10.3390/biom15111574 [doi] LID - 1574 AB - Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant cardiometabolic benefits, particularly in patients with type 2 diabetes and obesity. Their role in heart failure (HF) is gaining increasing attention, with growing evidence supporting their efficacy in HF with preserved ejection fraction (HFpEF). Recent trials have shown that semaglutide improves symptoms, functional capacity, and weight loss in patients with HFpEF. However, these trials did not demonstrate a reduction in HF hospitalizations or mortality. In contrast, tirzepatide has revealed a significant reduction in cardiovascular death and worsening HF events in patients with obesity-related HFpEF, suggesting broader cardioprotective effects. Concordantly, the benefit of GLP1-RAs in the setting of HF with reduced ejection fraction (HFrEF) remains uncertain. Although their mechanisms suggest potential advantages, particularly for patients with a cardiometabolic phenotype, clinical evidence supporting improvements in major clinical outcomes is lacking. Additionally, concerns regarding risk of increased HF hospitalizations, fluid retention and arrhythmic risk have led to a cautious approach in this population. As HF management continues to evolve, GLP1-RAs emerge as a promising yet complex therapeutic option. This review synthesizes the current evidence, highlights key knowledge gaps, and explores how these medications might be integrated into guideline-directed medical therapy (GDMT) to determine their optimal role across the LVEF spectrum in HF. FAU - Crispino, Simone Pasquale AU - Crispino SP AUID- ORCID: 0000-0002-0051-5253 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. AD - Department of Biomedical Engineering, Intelligent Technology Laboratory for Health and Wellbeing, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Nusca, Annunziata AU - Nusca A AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Ferro, Aurora AU - Ferro A AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Cricco, Riccardo AU - Cricco R AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Ciancio, Martina AU - Ciancio M AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Segreti, Andrea AU - Segreti A AUID- ORCID: 0000-0003-2631-8642 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. AD - Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", 00135 Rome, Italy. FAU - Cavallari, Ilaria AU - Cavallari I AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Sabatino, Mario AU - Sabatino M AD - Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Potena, Luciano AU - Potena L AD - Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Ussia, Gian Paolo AU - Ussia GP AUID- ORCID: 0000-0001-8849-3097 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Grigioni, Francesco AU - Grigioni F AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251110 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Stroke Volume/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Ventricular Function, Left/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12650310 OTO - NOTNLM OT - cardio-kidney-metabolic syndrome OT - cardiometabolic disease OT - cardiovascular prevention OT - glucagon-like peptide 1 receptor agonists OT - heart failure OT - heart failure with preserved ejection fraction OT - heart failure with reduced ejection fraction COIS- The authors declare no conflicts of interest. EDAT- 2025/11/27 06:28 MHDA- 2025/11/27 06:29 PMCR- 2025/11/10 CRDT- 2025/11/27 01:07 PHST- 2025/10/09 00:00 [received] PHST- 2025/10/28 00:00 [revised] PHST- 2025/10/30 00:00 [accepted] PHST- 2025/11/27 06:29 [medline] PHST- 2025/11/27 06:28 [pubmed] PHST- 2025/11/27 01:07 [entrez] PHST- 2025/11/10 00:00 [pmc-release] AID - biom15111574 [pii] AID - biomolecules-15-01574 [pii] AID - 10.3390/biom15111574 [doi] PST - epublish SO - Biomolecules. 2025 Nov 10;15(11):1574. doi: 10.3390/biom15111574. PMID- 41297910 OWN - NLM STAT- MEDLINE DCOM- 20260424 LR - 20260926 IS - 2287-285X (Electronic) IS - 2287-2728 (Print) IS - 2287-2728 (Linking) VI - 32 IP - 2 DP - 2026 Apr TI - Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders. PG - 464-486 LID - 10.3350/cmh.2025.0744 [doi] AB - Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the development of engineered multi-agonist therapies targeting additional nutrient-stimulated hormonal (NUSH) pathways. Dual and triple peptide-based co-agonists combining glucagon-like peptide-1 (GLP-1) with glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, or peptide YY have demonstrated superior metabolic efficacy in preclinical and clinical studies. Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1 RAs such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence. Multi-agonist incretin-based therapies represent a paradigm shift in the management of obesity and metabolic diseases. These agents offer broad clinical utility beyond glucose lowering by mimicking the pleiotropic hormonal responses observed after bariatric surgery. These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists. FAU - Cho, Yun Kyung AU - Cho YK AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. AD - Asan Diabetes Center, Asan Medical Center, Seoul, Korea. FAU - Jung, Chang Hee AU - Jung CH AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. AD - Asan Diabetes Center, Asan Medical Center, Seoul, Korea. LA - eng PT - Journal Article PT - Review DEP - 20251126 PL - Korea (South) TA - Clin Mol Hepatol JT - Clinical and molecular hepatology JID - 101586730 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Metabolic Diseases/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - Incretins/therapeutic use MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13129745 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Nutrient-stimulated hormonal multi-agonist OT - Obesity and metabolic disorders OT - Precision metabolic medicine COIS- Conflicts of Interest The authors have no conflicts to disclose. EDAT- 2025/11/27 00:27 MHDA- 2026/04/24 06:33 PMCR- 2026/04/01 CRDT- 2025/11/26 19:57 PHST- 2025/07/07 00:00 [received] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/04/24 06:33 [medline] PHST- 2025/11/27 00:27 [pubmed] PHST- 2025/11/26 19:57 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - cmh.2025.0744 [pii] AID - cmh-2025-0744 [pii] AID - 10.3350/cmh.2025.0744 [doi] PST - ppublish SO - Clin Mol Hepatol. 2026 Apr;32(2):464-486. doi: 10.3350/cmh.2025.0744. Epub 2025 Nov 26. PMID- 41297885 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20260319 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 3 DP - 2026 Mar TI - Cardiovascular Outcomes in Adults With Type 2 Diabetes Treated With Tirzepatide: A Systematic Review and Meta-Analysis of Real-World Studies. PG - 369-379 LID - S1530-891X(25)01292-3 [pii] LID - 10.1016/j.eprac.2025.11.010 [doi] AB - OBJECTIVE: Tirzepatide shows benefits on cardiovascular (CV) parameters and major adverse cardiovascular events (MACE) in clinical trials, but real-world data, especially for type 2 diabetes (T2D), are limited. This systematic review and meta-analysis seeks to address this gap. METHODS: Multiple databases and registries were searched for real-world observational studies involving individuals with T2D receiving tirzepatide. The co-primary outcomes were acute coronary syndrome (ACS), heart failure (HF), sudden cardiac death, and stroke. RevMan Web was used to conduct meta-analyses employing random-effects models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Eight retrospective cohort studies (N = 118 252) were included. Compared to the control group, tirzepatide reduced risks of ACS (HR 0.74 [0.62-0.89], P = .001), HF (HR 0.65 [0.53-0.82], P = .0002), stroke (HR 0.71 [0.62-0.81], P < .00001), MACE (HR 0.72 [0.60-0.86], P = .0004), and all-cause mortality (HR 0.49 [0.37-0.67], P < .00001). However, the risk of sudden cardiac death was similar between groups. The risk of composite outcomes of all-cause mortality plus CV outcomes was also lower with tirzepatide (HR 0.65 [0.54-0.79], P < .0001). Compared to semaglutide, tirzepatide had lower risks of stroke and MACE but similar risks for ACS, HF, sudden cardiac death, all-cause mortality, and composite outcomes. CONCLUSIONS: Tirzepatide offers the potential to reduce the risks of ACS, HF, stroke, MACE, and death in real-world patients with T2D, suggesting CV benefits. Larger trials are needed to confirm long-term CV effects and define its role in T2D and CV management. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Kamrul-Hasan, A B M AU - Kamrul-Hasan ABM AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. Electronic address: rangassmc@gmail.com. FAU - Chatterjee, Subhankar AU - Chatterjee S AD - Department of Endocrinology, Medical College and Hospital, Kolkata, West Bengal, India. FAU - Ashraf, Hamid AU - Ashraf H AD - Rajiv Gandhi Centre for Diabetes and Endocrinology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India. FAU - Nagendra, Lakshmi AU - Nagendra L AD - Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India. FAU - Dutta, Deep AU - Dutta D AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, Dwarka, New Delhi, Delhi, India. FAU - Pappachan, Joseph M AU - Pappachan JM AD - Faculty of Science, Manchester Metropolitan University, Manchester, United Kingdom; Department of Endocrinology, Countess of Chester Hospital NHS Foundation Trust, Chester, Cheshire, United Kingdom; Department of Endocrinology, Kasturba Medical College, Manipal and Manipal Academy of Higher Education, Manipal, Karnataka, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251124 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Adult MH - Tirzepatide OTO - NOTNLM OT - Acute coronary syndrome OT - All-cause mortality OT - Major adverse cardiovascular events OT - Real-world study OT - Tirzepatide OT - Type 2 diabetes COIS- Disclosure The authors assert the absence of any identifiable financial conflicts or personal relationships that could be perceived as impacting the integrity of the findings reported in this manuscript. EDAT- 2025/11/27 00:27 MHDA- 2026/03/20 00:59 CRDT- 2025/11/26 19:34 PHST- 2025/09/16 00:00 [received] PHST- 2025/11/12 00:00 [revised] PHST- 2025/11/12 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2025/11/27 00:27 [pubmed] PHST- 2025/11/26 19:34 [entrez] AID - S1530-891X(25)01292-3 [pii] AID - 10.1016/j.eprac.2025.11.010 [doi] PST - ppublish SO - Endocr Pract. 2026 Mar;32(3):369-379. doi: 10.1016/j.eprac.2025.11.010. Epub 2025 Nov 24. PMID- 41297711 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260127 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 445 DP - 2026 Feb 15 TI - Early glucagon-like peptide-1 receptor agonist use after myocardial infarction in patients with type 2 diabetes. PG - 134042 LID - S0167-5273(25)01085-X [pii] LID - 10.1016/j.ijcard.2025.134042 [doi] AB - AIMS: Acute myocardial infarction (AMI) is among the leading causes of mortality in patients with type 2 diabetes (T2DM). This study evaluated whether initiation of glucagon-like peptide-1 receptor agonists (GLP1RAs) post-AMI improves cardiovascular outcomes in this population. METHODS: This retrospective cohort study used the TriNetX Research Network to identify adult patients with T2DM who experienced an AMI between January 1, 2017, and December 31, 2023. Patients were included if they initiated tirzepatide or semaglutide within 14 days post-AMI. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was recurrent coronary events, and secondary outcomes included all-cause mortality and hospitalizations, heart failure (HF) hospitalizations, acute kidney injury (AKI), and cardiac arrest. Hazard ratios (HR) were estimated using Cox proportional hazard models. RESULTS: 5338 patients were included in each cohort. Mean follow-up was 327.7 days (GLP1RA group) vs. 307.9 days (non-GLP1RA group). GLP1RA use did not significantly reduce recurrent coronary events (3.7 % vs 3.8 %; HR 0.913, 95 % CI 0.750-1.111). GLP1RA use was associated with significantly lower all-cause mortality (HR 0.484, 95 % CI 0.413-0.567), HF hospitalizations (HR 0.578, 95 % CI 0.531-0.630), AKI (HR 0.688, 95 % CI 0.610-0.732), cardiac arrest (HR 0.549, 95 % CI 0.418-0.722), and all-cause hospitalizations (HR 0.673, 95 % CI 0.636-0.713). CONCLUSIONS: GLP1RA initiation in patients with T2DM post-AMI was not associated with a reduction in recurrent coronary events, but was linked to improvements in other cardiovascular outcomes, suggesting a potential role for GLP1RAs as part of a secondary prevention strategy. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Ahmad, Omar AU - Ahmad O AD - College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. Electronic address: Ibrahim.ramzi@mayo.edu. FAU - Pham, Hoang Nhat AU - Pham HN AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Medicine, University of Arizona, Tucson, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Elbenawi, Hossam AU - Elbenawi H AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Salih, Mohammed AU - Salih M AD - Department of Cardiology, Baylor Scott and White-The Heart Hospital, Plano, TX, United States of America. FAU - Farina, Juan AU - Farina J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Bhakta, Mayurkumar D AU - Bhakta MD AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Sell-Dottin, Kristen A AU - Sell-Dottin KA AD - Department of Cardiothoracic Surgery, Mayo Clinic, Phoenix, AZ, United States of America. FAU - Yang, Eric H AU - Yang EH AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Sweeney, John P AU - Sweeney JP AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Fortuin, F David AU - Fortuin FD AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Simper, David AU - Simper D AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Al-Kindi, Sadeer AU - Al-Kindi S AD - Center for CV Computational and Precision Health, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. FAU - Lee, Kwan AU - Lee K AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Nasir, Khurram AU - Nasir K AD - Center for CV Computational and Precision Health, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. FAU - Ayoub, Chadi AU - Ayoub C AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article DEP - 20251124 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications/epidemiology MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Myocardial Infarction/drug therapy/diagnosis/mortality/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Follow-Up Studies MH - Cohort Studies MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of competing interest None. EDAT- 2025/11/27 00:27 MHDA- 2025/12/19 01:45 CRDT- 2025/11/26 19:13 PHST- 2025/08/07 00:00 [received] PHST- 2025/11/08 00:00 [revised] PHST- 2025/11/23 00:00 [accepted] PHST- 2025/12/19 01:45 [medline] PHST- 2025/11/27 00:27 [pubmed] PHST- 2025/11/26 19:13 [entrez] AID - S0167-5273(25)01085-X [pii] AID - 10.1016/j.ijcard.2025.134042 [doi] PST - ppublish SO - Int J Cardiol. 2026 Feb 15;445:134042. doi: 10.1016/j.ijcard.2025.134042. Epub 2025 Nov 24. PMID- 41296333 OWN - NLM STAT- MEDLINE DCOM- 20260212 LR - 20260923 IS - 2168-619X (Electronic) IS - 2168-6181 (Print) IS - 2168-6181 (Linking) VI - 152 IP - 2 DP - 2026 Feb 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Chronic Cough. PG - 163-171 LID - 10.1001/jamaoto.2025.4181 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become substantially more popular as a medication to treat obesity and type 2 diabetes (T2D). Despite their known association with gastroesophageal reflux disease and vagal nerve stimulation, the association between GLP-1RAs and chronic cough has not been previously studied. OBJECTIVE: To assess the clinical association between GLP-1RAs and chronic cough. DESIGN, SETTING, AND PARTICIPANTS: This large, multicenter cohort study used clinical records from a US-based collection of electronic medical record data from April 28, 2005, to April 15, 2025, from 70 health care organizations. Adults (>/=18 years) with T2D and prescription of a GLP-1RA were identified. Additionally, groups with T2D and prescription of another second-line diabetes medication, including dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and sulfonylureas were created. After propensity score matching for various demographic and clinical characteristics, adjusted hazard ratios (aHRs) and 95% CIs were calculated using Cox regression analyses to estimate the risk of new chronic cough or gastroesophageal reflux disease diagnosis. EXPOSURE: GLP-1RAs or other second-line diabetes medication. MAIN OUTCOMES AND MEASURES: Chronic cough. RESULTS: Cohorts included 427 555 individuals (mean [SD] age, 55.8 [13.8] years; 251 928 female individuals [58.9%]) with T2D who were prescribed a GLP-1RA and 1 614 495 individuals (mean [SD] age, 63.7 [13.3] years; 712 946 female individuals [44.4%]) with T2D who were prescribed another second-line diabetes medication. After propensity score matching, individuals prescribed a GLP-1RA had significantly increased risk of new chronic cough compared with individuals prescribed any non-GLP-1RA second-line medication (aHR, 1.12; 95% CI, 1.08-1.16), DPP-4 inhibitor (aHR, 1.18; 95% CI, 1.11-1.26), or sulfonylurea (aHR, 1.32; 95% CI, 1.24-1.40) but not compared with SLGT2 inhibitors (aHR, 1.03; 95% CI, 0.98-1.09). After removing patients with a previous diagnosis of gastroesophageal reflux disease from analysis, patients prescribed GLP-1RAs had significantly increased risk of chronic cough compared with those prescribed any non-GLP-1RA (aHR, 1.29; 95% CI, 1.17-1.42), DPP4 inhibitor (aHR, 1.36; 95% CI, 1.17-1.58), SGLT2 inhibitor (aHR, 1.14; 95% CI, 1.02-1.28), or sulfonylurea (aHR, 1.25; 95% CI, 1.09-1.42). CONCLUSIONS AND RELEVANCE: This cohort study suggests an association between GLP-1RA use and chronic cough. Further research is needed to confirm the existence, strength, and mechanisms of this association. FAU - Gallagher, Tyler J AU - Gallagher TJ AD - Caruso Department of Otolaryngology-Head & Neck Surgery, Keck School of Medicine of the University of Southern California, Los Angeles. FAU - Razura, Diego E AU - Razura DE AD - Department of Otolaryngology-Head & Neck Surgery, Mayo Clinic Arizona, Phoenix. FAU - Li, Albert AU - Li A AD - Keck School of Medicine of the University of Southern California, Los Angeles. FAU - Kim, Ian AU - Kim I AD - Department of Pediatrics, Stanford University, Palo Alto, California. FAU - Vukkadala, Neelaysh AU - Vukkadala N AD - Division of Otolaryngology-Head and Neck Surgery, Cedars Sinai Medical Center, Los Angeles, California. FAU - Barbu, Anca M AU - Barbu AM AD - Division of Otolaryngology-Head and Neck Surgery, Cedars Sinai Medical Center, Los Angeles, California. LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - JAMA Otolaryngol Head Neck Surg JT - JAMA otolaryngology-- head & neck surgery JID - 101589542 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - doi: 10.1001/jama.2025.20026 MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Cough/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Chronic Disease MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Adult MH - United States/epidemiology MH - Retrospective Studies MH - Cohort Studies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Chronic Cough PMC - PMC12658766 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/11/26 13:11 MHDA- 2026/02/12 12:50 PMCR- 2026/11/26 CRDT- 2025/11/26 11:32 PHST- 2026/02/12 12:50 [medline] PHST- 2025/11/26 13:11 [pubmed] PHST- 2025/11/26 11:32 [entrez] PHST- 2026/11/26 00:00 [pmc-release] AID - 2842204 [pii] AID - ooi250075 [pii] AID - 10.1001/jamaoto.2025.4181 [doi] PST - ppublish SO - JAMA Otolaryngol Head Neck Surg. 2026 Feb 1;152(2):163-171. doi: 10.1001/jamaoto.2025.4181. PMID- 41296314 OWN - NLM STAT- MEDLINE DCOM- 20251126 LR - 20251202 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 31 IP - 12 DP - 2025 Dec TI - Differences in GLP-1 RA medication adherence across place-based variables in patients with diabetes living in Wisconsin. PG - 1311-1319 LID - 10.18553/jmcp.2025.31.12.1311 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications are efficacious in improving health outcomes in patients with type 2 diabetes mellitus (T2DM). As demand and costs have increased, questions have arisen around socioeconomic and geographic differences in adherence. OBJECTIVE: To understand these differences, pharmacy claims data were used to examine medication fills across urban and rural areas and Census tract-level income and racial make-up. METHODS: Data obtained from the Wisconsin Health Information Organization database included adults (aged >/=18 years) diagnosed with T2DM, with a prescription fill for a GLP-1 RA medication between January 1, 2020, and September 30, 2022. Adherence was defined as proportion of prescription days covered of 80% or greater for 1 year from first fill. Unadjusted and adjusted logistic regression was performed. Adherence was compared across urban and rural residence and Census tract-level median household income quintiles and race (majority Black residents vs nonmajority, majority Hispanic residents vs nonmajority, and majority White residents vs nonmajority). Adjusted models included age, sex, insurance provider, and number of comorbidities. RESULTS: Patients (N = 7,265) were 56.3% female with a mean age of 55.3 (SD = 12.1) years. Place-based variables showed 38.2% lived in rural areas, 5.8% lived in areas with majority Black population, 2.0% with majority Hispanic population, and 87.9% with majority White population. Overall, 40.1% of patients were adherent 1 year following first prescription fill. Adjusted models showed that patients in tracts with the lowest incomes had lower odds of adherence compared with those living in the highest income tracts (odds ratio [OR] = 0.76; 95% CI = 0.59-0.98). Patients in areas with majority Black residents had lower odds of adherence (OR = 0.67; 95% CI = 0.52-0.85) than areas with less than a majority of Black residents, whereas patients living in areas with majority White residents had higher odds of adherence (OR = 1.31; 95% CI = 1.11-1.56) than areas with less than a majority of White residents. CONCLUSIONS: This analysis highlights geographic differences in medication adherence in patients with T2DM. Patients living in high-income areas and areas with higher percentages of White residents had higher odds of adherence to GLP-1 RA medications. As demand for GLP-1 RA medications grow, future work that identifies reasons for disparities in adherence and potential strategies to improve adherence is critical. FAU - Gavin, Kara L AU - Gavin KL AD - Center for Advancing Population Health, Medical College of Wisconsin, Milwaukee. FAU - Amjad, Rabia AU - Amjad R AD - Center for Advancing Population Health, Medical College of Wisconsin, Milwaukee. FAU - Makris, Vaia AU - Makris V AD - Center for Advancing Population Health, Medical College of Wisconsin, Milwaukee. FAU - Neuner, Joan M AU - Neuner JM AD - Center for Advancing Population Health, Medical College of Wisconsin, Milwaukee. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Wisconsin/epidemiology MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Rural Population/statistics & numerical data MH - Urban Population/statistics & numerical data MH - Socioeconomic Factors MH - *Medication Adherence/ethnology PMC - PMC12653633 EDAT- 2025/11/26 13:12 MHDA- 2025/11/26 13:13 PMCR- 2025/12/01 CRDT- 2025/11/26 11:23 PHST- 2025/11/26 13:13 [medline] PHST- 2025/11/26 13:12 [pubmed] PHST- 2025/11/26 11:23 [entrez] PHST- 2025/12/01 00:00 [pmc-release] AID - 10.18553/jmcp.2025.31.12.1311 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2025 Dec;31(12):1311-1319. doi: 10.18553/jmcp.2025.31.12.1311. PMID- 41291666 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260114 IS - 1471-2490 (Electronic) IS - 1471-2490 (Linking) VI - 25 IP - 1 DP - 2025 Nov 25 TI - Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis. PG - 311 LID - 10.1186/s12894-025-02005-0 [doi] LID - 311 AB - INTRODUCTION: Testosterone plays a central role in endocrine and metabolic functions. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely prescribed for type 2 diabetes and obesity, have been proposed to modulate testosterone levels. Although this association is not yet covered by clinical guidelines, emerging studies suggest favorable effects, possibly due to weight loss and improved insulin sensitivity. This systematic review and meta-analysis aim to synthesize current evidence on how GLP-1 RAs influence testosterone levels and highlight areas for future investigation. MATERIALS AND METHODS: A systematic search was conducted using Embase, PubMed, Scopus, Cochrane, and Google Scholar databases through December 2024. Eligible studies included RCTs, cohort studies, and retrospective analyses comparing testosterone levels before and after GLP-1 RA administration. Primary and secondary outcomes included total, free, and bioavailable testosterone, SHBG, and HbA1c. All included studies reported baseline hormone values and used validated measurement techniques. Data analysis was performed using RStudio. RESULTS: Four studies comprising 219 patients pre-treatment and 216 post-treatment were included. GLP-1 RA use was significantly associated with increased bioavailable testosterone (MD -57.18; 95% CI -87.60 to -26.76; p < 0.001; I(2) = 86%) and decreased HbA1c (MD 0.79; 95% CI 0.58 to 1.00; p < 0.001; I(2) = 0%). Free testosterone (MD -1.62; p = 0.051) and SHBG (MD -6.62; p = 0.120) showed no significant changes. Sensitivity and Baujat analyses were used to explore heterogeneity. CONCLUSIONS: GLP-1 RAs appear to elevate bioavailable testosterone and improve glycemic control, while effects on free testosterone and SHBG remain inconclusive. These findings suggest possible endocrine benefits of GLP-1 therapy; however, further well-powered studies are warranted. CI - (c) 2025. The Author(s). FAU - Orra, Soraya Hussein AU - Orra SH AUID- ORCID: 0009-0002-0136-8432 AD - Ninth of July University, Sao Paulo, SP, Brazil. FAU - Martinez, Juan Victor Nabhan AU - Martinez JVN AUID- ORCID: 0009-0008-0609-5799 AD - Ninth of July University, Sao Paulo, SP, Brazil. FAU - Porto, Breno Cordeiro AU - Porto BC AUID- ORCID: 0000-0002-4004-4089 AD - Surgical Technique and Experimental Surgery Department, University of Sao Paulo School of Medicine, Cincinato Braga St. 37 - Cj 32 , Sao Paulo, SP, 01333-011, Brazil. AD - International Teaching and Research Institute, Hapvida NotreDame Intermedica, Sao Paulo, Brazil. FAU - Passerotti, Carlo Camargo AU - Passerotti CC AD - Surgical Technique and Experimental Surgery Department, University of Sao Paulo School of Medicine, Cincinato Braga St. 37 - Cj 32 , Sao Paulo, SP, 01333-011, Brazil. FAU - Sardenberg, Rodrigo A S AU - Sardenberg RAS AUID- ORCID: 0000-0002-6010-1829 AD - International Teaching and Research Institute, Hapvida NotreDame Intermedica, Sao Paulo, Brazil. FAU - Da Cruz, Jose Arnaldo Shiomi AU - Da Cruz JAS AUID- ORCID: 0000-0003-4203-3196 AD - Surgical Technique and Experimental Surgery Department, University of Sao Paulo School of Medicine, Cincinato Braga St. 37 - Cj 32 , Sao Paulo, SP, 01333-011, Brazil. arnaldoshiomi@yahoo.com.br. AD - International Teaching and Research Institute, Hapvida NotreDame Intermedica, Sao Paulo, Brazil. arnaldoshiomi@yahoo.com.br. AD - Ninth of July University, Sao Paulo, SP, Brazil. arnaldoshiomi@yahoo.com.br. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251125 PL - England TA - BMC Urol JT - BMC urology JID - 100968571 RN - 3XMK78S47O (Testosterone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Testosterone/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood PMC - PMC12752444 OTO - NOTNLM OT - Erectile Dysfunction OT - Functional Hypogonadism OT - Glucagon-like Peptide-1 Receptor Agonists COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have reviewed and approved the manuscript for publication. Competing interests: The authors declare no competing interests. EDAT- 2025/11/26 06:29 MHDA- 2025/12/30 07:41 PMCR- 2025/11/25 CRDT- 2025/11/26 00:08 PHST- 2025/04/29 00:00 [received] PHST- 2025/11/19 00:00 [accepted] PHST- 2025/12/30 07:41 [medline] PHST- 2025/11/26 06:29 [pubmed] PHST- 2025/11/26 00:08 [entrez] PHST- 2025/11/25 00:00 [pmc-release] AID - 10.1186/s12894-025-02005-0 [pii] AID - 2005 [pii] AID - 10.1186/s12894-025-02005-0 [doi] PST - epublish SO - BMC Urol. 2025 Nov 25;25(1):311. doi: 10.1186/s12894-025-02005-0. PMID- 41287923 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260813 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 27 IP - 4 DP - 2026 Apr TI - GLP-1 Receptor Agonists for the Prevention of New-Onset Heart Failure: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials. PG - e70043 LID - 10.1111/obr.70043 [doi] LID - e70043 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve outcomes in heart failure (HF) with preserved ejection fraction. Whether GLP-1 RA prevent new-onset HF in Type 2 diabetes or obesity requires further investigation. METHODS: We performed an updated meta-analysis of randomized placebo-controlled trials (RCT) of treatment with GLP-1 RA in participants without HF. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the group without HF in each study. The primary outcome was time to first HF event (HF hospitalization or urgent visit for HF). The correlation between the effect of GLP-1 RA on HF events and the effects on HbA1c, weight and major atherosclerotic cardiovascular events (MACE) was also investigated. We also evaluated the heterogeneity of effect according to study characteristics. RESULTS: A total of 52,752 participants without HF from six RCTs were included. Treatment with GLP-1 RA (vs. placebo) decreased the risk of new-onset HF (HR = 0.77 [95% CI 0.65-0.93], p < 0.001) and the composite of HF events or cardiovascular death (HR = 0.82 [95% CI 0.76-0.89], p < 0.001). The effect of GLP-1 RA on HF events was independent of its effects on HbA1c or weight, but was correlated with its protective effects on MACE. The effects on HF prevention were more pronounced in studies restricted to patients with atherosclerotic cardiovascular disease and in trials with higher incidence rate of HF events. CONCLUSION: Treatment with GLP-1 RA decreases the risk of new-onset HF in patients with Type 2 diabetes or obesity. CI - (c) 2025 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Neves, Joao Sergio AU - Neves JS AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. FAU - Lobato, Carolina B AU - Lobato CB AUID- ORCID: 0000-0003-3708-6859 AD - Section of Endocrinology, Department of Medicine, Copenhagen University Hospital, Amager and Hvidovre, Section of Endocrinology, Hvidovre, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Leite, Ana Rita AU - Leite AR AUID- ORCID: 0000-0002-4111-3787 AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. FAU - Vale, Catarina AU - Vale C AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Vasques-Novoa, Francisco AU - Vasques-Novoa F AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Saraiva, Francisca AU - Saraiva F AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. FAU - Leite-Moreira, Adelino AU - Leite-Moreira A AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Cardiothoracic Surgery, ULS Sao Joao, Porto, Portugal. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Inserm, Centre d'Investigations Cliniques, - Plurithematique 14-33, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Universite de Lorraine, Nancy, France. LA - eng GR - PhD013-20/Danish Diabetes and Endocrine Academy/ GR - NNF18CC0034900/Novo Nordisk Foundation Center for Basic Metabolic Research/ GR - NNF23SA0084103/Novo Nordisk Foundation Center for Basic Metabolic Research/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20251125 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Heart Failure/prevention & control MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/complications/drug therapy PMC - PMC13008604 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - heart failure OT - obesity OT - type 2 diabetes COIS- J.S.N. reports having received consulting or speaker fees from AstraZeneca, Bayer, BIAL, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Menarini and Merck. C.B.L. has received research support from the Danish Diabetes Academy (Novo Nordisk Foundation) and from Dexcom. F.V.N. has received consulting or speaker fees from AstraZeneca, Bayer, Daiichi Sankyo and Ultragenyx. A.L.M. has received research support from Boehringer-Ingelheim, AstraZeneca and Novartis. J.J.H. has in the recent three years been an advisory/consultant for, been on the advisory board of, and/or received research support from Eli Lilly, Novo Nordisk, Zealand Pharma, MSD Denmark, Structure Therapeutics, Scohia., HealthCap, Morgan Stanley, MEDACorp Inc., Arix Bioscience, Alphasights, Alcimed, Google Ventures Management, Guidepoint, Tema, Jefferies International Limited, Amgen, Sofinnova Partners, Thinks Insight & Strategy, AstraZeneca, Septerna; is co-founder of Antag Therapeutics and Villus (Bainan Biotech). J.P.F. has received research support from Boehringer-Ingelheim, AstraZeneca, Novartis, Bayer, Salamandra, Bial, Abbott. EDAT- 2025/11/25 06:26 MHDA- 2026/03/24 00:30 PMCR- 2026/03/24 CRDT- 2025/11/25 05:07 PHST- 2025/09/15 00:00 [revised] PHST- 2025/01/07 00:00 [received] PHST- 2025/11/06 00:00 [accepted] PHST- 2026/03/24 00:30 [medline] PHST- 2025/11/25 06:26 [pubmed] PHST- 2025/11/25 05:07 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - OBR70043 [pii] AID - 10.1111/obr.70043 [doi] PST - ppublish SO - Obes Rev. 2026 Apr;27(4):e70043. doi: 10.1111/obr.70043. Epub 2025 Nov 25. PMID- 41287564 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Assessment of thyroid cancer risk associated with glucagon-like peptide 1 receptor agonist use. PG - 1499-1507 LID - 10.1111/dom.70291 [doi] AB - AIMS: Published literature has raised concerns regarding a causal association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and thyroid cancer risk in adults. In this analysis, we evaluated the association between thyroid cancer risk and GLP-1RA use. MATERIALS AND METHODS: Our evaluation included data from (i) 93 liraglutide or semaglutide phase 2 and 3 clinical trials, of which six were cardiovascular outcome trials (CVOTs); (ii) post-marketing surveillance from the Novo Nordisk safety database (evaluating data for liraglutide and semaglutide); and (iii) the US Merative MarketScan(R) Commercial Database. Hazard ratios (HRs) were estimated for overall thyroid cancer risk for treatment groups in the clinical trials and for individuals with type 2 diabetes treated with any GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) for the real-world data. RESULTS: Data from all clinical trials across 101 732 participants (totalling 206 950 patient-years of exposure [PYE]) reported low numbers of thyroid cancer events; across all trials, HRs were 1.70 (95% confidence interval [CI] 0.99, 3.03) and 1.83 (0.70, 6.71) for pooled GLP-1RA versus pooled placebo and active comparator, respectively. For CVOTs, the HR (95% CI) for pooled GLP-1RA versus pooled placebo was 1.41 (0.72, 2.81). Post-marketing surveillance data showed a low thyroid cancer reporting rate of 0.001 cases/100 PYE and did not support an association between liraglutide or semaglutide exposure and the number of thyroid cancer events. Analysis of the US Merative MarketScan(R) Commercial Database reported an HR of 0.87 (95% CI 0.58, 1.29) for the occurrence of thyroid cancer in individuals using any GLP-1RAs versus SGLT2is. CONCLUSIONS: The totality of data analysed did not suggest an association between liraglutide or semaglutide use and thyroid cancer risk in adults. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Clinical Research, Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Stellfeld, Michael AU - Stellfeld M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Dandanell, Sune AU - Dandanell S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kristiansen, Ceyda T P AU - Kristiansen CTP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Roberts, Fiona L AU - Roberts FL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hegedus, Laszlo AU - Hegedus L AD - Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, Denmark. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article DEP - 20251125 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Thyroid Neoplasms/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Liraglutide/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Adult MH - Risk Assessment MH - Clinical Trials, Phase II as Topic MH - Aged MH - Product Surveillance, Postmarketing MH - Risk Factors MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803555 OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - real-world evidence OT - type 2 diabetes OT - weight management COIS- Tina Vilsboll has served on scientific advisory panels and/or speakers' bureaus for or has served as a consultant to and/or received research support from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD/Merck, Novo Nordisk, Regor, Roche/Carmot, Zealand Pharma, Sanofi, and Sun Pharmaceuticals. Michael Stellfeld, Sune Dandanell, Jens-Peter David, Ceyda T. P. Kristiansen, Soren Rasmussen, and Fiona L. Roberts are employees of, and shareholders in, Novo Nordisk. Vanita R. Aroda reports research grant support (to institution) from Amgen, Applied Therapeutics, AstraZeneca, Biomea, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Fractyl Health, Novo Nordisk A/S, Pfizer, Recordati, Rhythm Pharmaceuticals, and Servier, and consulting fees from Mediflix and Sanofi. Laszlo Hegedus has served on scientific advisory panels and/or speakers' bureaus or has served as a consultant to and/or received research support from Amgen, Berlin-Chemie, Horizon, IBSA, Linical, Merck, and Novo Nordisk. EDAT- 2025/11/25 06:27 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/25 04:36 PHST- 2025/10/27 00:00 [revised] PHST- 2025/07/25 00:00 [received] PHST- 2025/10/28 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 04:36 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70291 [pii] AID - 10.1111/dom.70291 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1499-1507. doi: 10.1111/dom.70291. Epub 2025 Nov 25. PMID- 41286875 OWN - NLM STAT- MEDLINE DCOM- 20251125 LR - 20261022 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 23 IP - 1 DP - 2025 Nov 24 TI - The adverse effects associated with semaglutide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis. PG - 654 LID - 10.1186/s12916-025-04486-0 [doi] LID - 654 AB - BACKGROUND: Semaglutide's disease-specific weight-reducing effects are well established, but its adverse effects, which may not be disease-specific, have not been systematically assessed. The aim of this review was to assess the adverse effects associated with semaglutide use compared with placebo in patients at increased risk of cardiovascular events. METHODS: We searched six electronic databases and other sources from inception to 31/03/2025. Randomized trials comparing semaglutide (oral or subcutaneous) with placebo in patients at increased risk of cardiovascular events were eligible. The search identified 8370 records. Two review authors independently screened all studies for eligibility. Data were synthesized using meta-analysis and Trial Sequential Analysis (TSA). Risk of bias was assessed with the Cochrane Risk of Bias tool - version 2; our eight-step procedure was used to assess if the thresholds for statistical significance were crossed, and the certainty of the evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations. Primary outcomes were all-cause mortality and serious adverse events (SAEs). Secondary outcomes included myocardial infarction and non-serious adverse events (AEs). RESULTS: The analysis included 50 trials, with a total of 54,972 participants randomized. Nineteen (38%) enrolled participants with type 2 diabetes (T2DM), 17 (34%) with overweight, 5 (10%) with T2DM and chronic kidney disease, 5 (10%) with T2DM and overweight, and 4 (8%) involved other patient populations. Meta-analysis and TSA showed evidence of beneficial effects of semaglutide on all-cause mortality (relative risk (RR) 0.85; 95% CI 0.79 to 0.91; I(2) = 0.0%; p < 0.01) and myocardial infarction (RR 0.77, 95% CI 0.69 to 0.85; I(2) = 0.0%; p < 0.01). None of these analyses showed signs of heterogeneity, and the evidence was of high certainty. Meta-analysis showed that semaglutide decreased the risk of SAEs (RR 0.93, 95% CI 0.88 to 0.98; I(2) = 24.1%; p < 0.01), but increased the risk of several non-serious gastrointestinal AEs including nausea (RR 3.00, 95% CI 2.63 to 3.42), vomiting (RR 4.12, 95% CI 3.47 to 4.90), and diarrhea (RR 1.88, 95% CI 1.68 to 2.11). CONCLUSIONS: In patients at increased risk of cardiovascular events, semaglutide reduced the risk of mortality, SAEs, and myocardial infarction but increased the risk of several non-serious gastrointestinal AEs. REGISTRATION: PROSPERO, CRD42024499511. CI - (c) 2025. The Author(s). FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. christina.sillassen@ctu.dk. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. christina.sillassen@ctu.dk. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. christina.sillassen@ctu.dk. FAU - Petersen, Johanne Juul AU - Petersen JJ AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Faltermeier, Pascal AU - Faltermeier P AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Yucel, Delal AU - Yucel D AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Siddiqui, Faiza AU - Siddiqui F AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Andersen, Rebecca Kjaer AU - Andersen RK AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Graever, Leonardo AU - Graever L AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Bjerg, Jonas Leth AU - Bjerg JL AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Kamp, Caroline Barkholt AU - Kamp CB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Grand, Johannes AU - Grand J AD - Department of Cardiology, Copenhagen University Hospital - Amager-Hvidovre Hospital, Copenhagen, Denmark. FAU - Dominguez, Helena AU - Dominguez H AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. FAU - Frolich, Anne AU - Frolich A AD - Innovation and Research Centre for Multimorbidity, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. AD - Section of General Practice, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gaede, Peter AU - Gaede P AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Gluud, Christian AU - Gluud C AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Mathiesen, Ole AU - Mathiesen O AD - Department of Anaesthesiology, Centre for Anaesthesiological Research, Zealand University Hospital, Koge, Denmark. AD - Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark. FAU - Jakobsen, Janus Christian AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251124 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Cardiovascular Diseases/epidemiology MH - Randomized Controlled Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12642075 OTO - NOTNLM OT - Meta-analysis OT - Placebo OT - Safety OT - Semaglutide OT - Systematic review OT - Trial sequential analysis COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: CDBS's husband has previously been employed at Novo Nordisk, Kalundborg, as 'facility manager' and 'sprinkler technician' (employed from September 1, 2024, to August 31, 2025). PG has received lecture fees for Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, and MSD and has served in Advisory Boards for Novo Nordisk, AstraZeneca, and Bayer. The remaining authors declare no known competing interests. EDAT- 2025/11/25 06:27 MHDA- 2025/11/25 06:28 PMCR- 2025/11/24 CRDT- 2025/11/25 03:28 PHST- 2025/06/07 00:00 [received] PHST- 2025/10/27 00:00 [accepted] PHST- 2025/11/25 06:28 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 03:28 [entrez] PHST- 2025/11/24 00:00 [pmc-release] AID - 10.1186/s12916-025-04486-0 [pii] AID - 4486 [pii] AID - 10.1186/s12916-025-04486-0 [doi] PST - epublish SO - BMC Med. 2025 Nov 24;23(1):654. doi: 10.1186/s12916-025-04486-0. PMID- 41286734 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Nov 24 TI - Temporal and subgroup disparities in mediation effects on cardiovascular outcomes with liraglutide and semaglutide: a post-hoc analysis of LEADER and SUSTAIN-6 trials. PG - 465 LID - 10.1186/s12933-025-03007-w [doi] LID - 465 AB - BACKGROUND: It is unclear whether the time-varying mediation effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the three-point major adverse cardiovascular event (3P-MACE) outcomes, including nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death, via HbA(1c), urine albumin-to-creatinine ratio (UACR), and systolic blood pressure (SBP) vary by types of GLP-1RAs, and patient subgroups. METHODS: A causal mediation analysis was applied to assess the mediation effects of HbA(1c), UACR, and SBP on the 3P-MACE with liraglutide and semaglutide over time, using the LEADER and SUSTAIN-6 trials. We further explored the heterogeneity in mediation effects in subsets of vulnerable patients, including those with an estimated glomerular filtration rate (eGFR) level of < 60 ml/min/1.73 m(2) or established cardiovascular diseases (CVDs). RESULTS: Individual-level data consisting of 9340 (liraglutide: 4668; placebo: 4672) and 3297 (semaglutide: 1648; placebo: 1649) subjects from the LEADER and SUSTAIN-6 trials, respectively, was utilized for this study. The study population aged around 64.2-64.4/64.4-64.8 years old, with 64.0%-64.5%/58.5%-63.0% of males, and having a diabetes duration of 12.8-12.9/13.2-14.3 years in the LEADER/SUSTAIN-6 trials, respectively. Among study populations, those established CVDs (e.g., heart failure, stroke, myocardial infarction) accounted for 14.0%-35.4% in the LEADER trial, whereas 13.7%-61.9% in the SUSTAIN-6 trial. At the end of each trial, HbA(1c) contributed the most to liraglutide's/semaglutide's effect on 3P-MACE (38.2%, 95% confidence interval: 13.8%-194.5%/51.8%, 29.6%-86.7%), followed by UACR (17.9%, 8.5%-61.9%/12.4%, 6.1%-32.4%) and SBP (6.8%, 2.2%-31.0%/6.7%, 2.9%-11.7%), respectively. Over the trial period, the effect of liraglutide mediated by HbA(1c) increased from 31.3% to 38.2%, whereas the effects of semaglutide mediated by HbA(1c) remained stable from 52.5% to 51.8%. For patients with eGFR < 60 ml/min/1.73 m(2), HbA(1c) was the leading mediator (35.2%) of semaglutide-associated 3P-MACE, while the mediation effects via HbA(1c) (7.2%), UACR (11.8%), and SBP (5.1%) on liraglutide-associated 3P-MACE seemed similar and smaller. For patients with established CVDs, HbA(1c) was the leading mediator of liraglutide- (25.3%) and semaglutide-associated 3P-MACE (51.2%). CONCLUSIONS: The HbA(1c)-mediated effects of liraglutide and semaglutide varied over time and across patient subgroups. HbA(1c) consistently explained a larger proportion of mediation compared to UACR and SBP, with patterns suggesting that mediation through HbA(1c) may differ by underlying risk factors. CI - (c) 2025. The Author(s). FAU - Peng, Zi-Yang AU - Peng ZY AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lee, Yu-Hsuan AU - Lee YH AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Ou, Huang-Tz AU - Ou HT AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. AD - Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. FAU - Kuo, Shihchen AU - Kuo S AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. LA - eng GR - grant NSTC 112-2628-B-006-008-MY3/National Science and Technology Council in Taiwan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251124 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Liraglutide/adverse effects/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Time Factors MH - Male MH - Treatment Outcome MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/mortality/diagnosis/physiopathology/prevention & control MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - *Incretins/adverse effects/therapeutic use MH - Risk Assessment MH - Biomarkers/blood/urine MH - Aged MH - *Blood Glucose/metabolism/drug effects MH - Randomized Controlled Trials as Topic MH - Glomerular Filtration Rate/drug effects MH - Albuminuria MH - Blood Pressure/drug effects MH - *Kidney/physiopathology MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12751512 COIS- Declarations. Ethics approval and consent to participate: To comply with the Declaration of Helsinki, both trials adhered to the policy of the institutional review board or ethics committee at the corresponding study site, with written informed consent provided to the trial participants at enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/11/25 06:27 MHDA- 2025/12/30 07:41 PMCR- 2025/11/24 CRDT- 2025/11/25 03:10 PHST- 2025/08/05 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2025/12/30 07:41 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 03:10 [entrez] PHST- 2025/11/24 00:00 [pmc-release] AID - 10.1186/s12933-025-03007-w [pii] AID - 3007 [pii] AID - 10.1186/s12933-025-03007-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Nov 24;24(1):465. doi: 10.1186/s12933-025-03007-w. PMID- 41283270 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20260707 IS - 2076-3271 (Electronic) IS - 2076-3271 (Linking) VI - 13 IP - 4 DP - 2025 Nov 14 TI - Incretin-Based Therapies Through the Decades: Molecular Innovations and Clinical Impact. LID - 10.3390/medsci13040269 [doi] LID - 269 AB - The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice. FAU - Lee, Arthur Anatolievich AU - Lee AA AUID- ORCID: 0009-0001-3341-4248 AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. FAU - Khotina, Victoria Alexandrovna AU - Khotina VA AUID- ORCID: 0000-0003-2096-3237 AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. FAU - Kashirskikh, Dmitry Alexandrovich AU - Kashirskikh DA AUID- ORCID: 0000-0002-0748-9238 AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. FAU - Voronko, Olga Evgenevna AU - Voronko OE AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. FAU - Gasanov, Vagif Ali Oglu AU - Gasanov VAO AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. FAU - Vasiliev, Andrey Valentinovich AU - Vasiliev AV AD - Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia. LA - eng GR - No.0088-2025-0005/Ministry of Science and Higher Education of the Russian Federation/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251114 PL - Switzerland TA - Med Sci (Basel) JT - Medical sciences (Basel, Switzerland) JID - 101629322 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Obesity/drug therapy/metabolism MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals PMC - PMC12641833 OTO - NOTNLM OT - GIP OT - GLP-1 OT - GLP-1RA OT - T2DM OT - cardiometabolic diseases OT - incretins OT - obesity COIS- The authors declare no conflicts of interest. EDAT- 2025/11/24 12:39 MHDA- 2025/11/24 18:38 PMCR- 2025/11/14 CRDT- 2025/11/24 09:21 PHST- 2025/09/30 00:00 [received] PHST- 2025/11/11 00:00 [revised] PHST- 2025/11/12 00:00 [accepted] PHST- 2025/11/24 18:38 [medline] PHST- 2025/11/24 12:39 [pubmed] PHST- 2025/11/24 09:21 [entrez] PHST- 2025/11/14 00:00 [pmc-release] AID - medsci13040269 [pii] AID - medsci-13-00269 [pii] AID - 10.3390/medsci13040269 [doi] PST - epublish SO - Med Sci (Basel). 2025 Nov 14;13(4):269. doi: 10.3390/medsci13040269. PMID- 41283266 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20260707 IS - 2076-3271 (Electronic) IS - 2076-3271 (Linking) VI - 13 IP - 4 DP - 2025 Nov 12 TI - Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders. LID - 10.3390/medsci13040265 [doi] LID - 265 AB - BACKGROUND/OBJECTIVES: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. METHODS: We conducted a detailed analysis of preclinical data sets, Phase I-III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. RESULTS: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved beta-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. CONCLUSIONS: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. FAU - Weiskirchen, Ralf AU - Weiskirchen R AUID- ORCID: 0000-0003-3888-0931 AD - Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany. FAU - Lonardo, Amedeo AU - Lonardo A AUID- ORCID: 0000-0001-9886-0698 AD - Ospedale Civile di Baggiovara (-2023), Department of Internal Medicine, AOU Modena, 41100 Modena, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251112 PL - Switzerland TA - Med Sci (Basel) JT - Medical sciences (Basel, Switzerland) JID - 101629322 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Humans MH - Animals MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Liver Diseases/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12642005 OTO - NOTNLM OT - GLP-1 receptor agonist OT - MACE OT - MASLD/MASH OT - STEP and SUSTAIN clinical trials OT - heart failure OT - obesity OT - semaglutide OT - translational pharmacology OT - type 2 diabetes OT - weight management COIS- A.L. is member of the Editorial Board of Medical Sciences. However, he was not involved in any phase of the Editorial processing of this manuscript. R.W. declares no conflicts of interest. EDAT- 2025/11/24 12:39 MHDA- 2025/11/24 18:38 PMCR- 2025/11/12 CRDT- 2025/11/24 09:21 PHST- 2025/10/25 00:00 [received] PHST- 2025/11/10 00:00 [revised] PHST- 2025/11/11 00:00 [accepted] PHST- 2025/11/24 18:38 [medline] PHST- 2025/11/24 12:39 [pubmed] PHST- 2025/11/24 09:21 [entrez] PHST- 2025/11/12 00:00 [pmc-release] AID - medsci13040265 [pii] AID - medsci-13-00265 [pii] AID - 10.3390/medsci13040265 [doi] PST - epublish SO - Med Sci (Basel). 2025 Nov 12;13(4):265. doi: 10.3390/medsci13040265. PMID- 41277213 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20251215 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 73 IP - 11 DP - 2025 Nov TI - The Weight of the Matter in Diabetes Care. PG - 87-88 LID - 10.59556/japi.73.1201 [doi] AB - The weight of the matter in diabetes care challenges the traditional glucose-centric model of diabetes management and argues for a paradigm shift toward prioritizing weight-specifically fat reduction-as the central lever in achieving metabolic health. Drawing insights from landmark trials such as SURMOUNT and Diabetes Remission Clinical Trial (DiRECT), as well as real-world Indian experience with agents like oral semaglutide, the article emphasizes that visceral adiposity is a root cause driving insulin resistance, beta-cell dysfunction, and multiorgan complications. Addressing weight early can lead to improved glycemic control, cardiorenal protection, and even disease remission-outcomes that far exceed glucose lowering alone. In the Indian context, where the "thin-fat" phenotype and central obesity present unique challenges, this weight-first approach demands culturally sensitive strategies and redefined success metrics beyond body mass index (BMI) or hemoglobin A1c (HbA1c). With the advent of incretin-based therapies, clinicians now have the tools to treat upstream rather than manage symptoms downstream. The piece calls for a unified therapeutic strategy that targets excess adiposity to deliver both glycemic and vascular legacy benefits-reframing weight not merely as a number but as a powerful determinant of risk, response, and recovery. CI - (c) Journal of The Association of Physicians of India 2025. FAU - Bhattacharyya, Supratik AU - Bhattacharyya S AD - Consultant Endocrinologist, SKN Diabetes and Endocrine Centre, Kolkata, West Bengal, India, Orcid: https://orcid.org/0000-0002-2351-7470, Corresponding Author. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/therapy/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - India MH - Insulin Resistance EDAT- 2025/11/24 06:27 MHDA- 2025/11/24 06:28 CRDT- 2025/11/24 02:47 PHST- 2025/11/24 06:28 [medline] PHST- 2025/11/24 06:27 [pubmed] PHST- 2025/11/24 02:47 [entrez] AID - 10.59556/japi.73.1201 [doi] PST - ppublish SO - J Assoc Physicians India. 2025 Nov;73(11):87-88. doi: 10.59556/japi.73.1201. PMID- 41276951 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20260127 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 6 DP - 2025 Nov TI - Safety and Efficacy of Semaglutide in Patients With Chronic Kidney Disease, With or Without Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - e70136 LID - 10.1002/edm2.70136 [doi] LID - e70136 AB - BACKGROUND: Chronic kidney disease (CKD) affects over half a billion people globally and significantly increases the risk of cardiovascular complications, particularly in those with type 2 diabetes mellitus (T2DM). Although semaglutide, a glucagon-like peptide-1 receptor agonist, has shown favourable cardiorenal effects in T2DM patients, prior meta-analyses were limited by small sample sizes and few studies. This updated meta-analysis includes both diabetic and non-diabetic CKD patients, incorporates recently published RCTs and addresses gaps in the literature to enhance result generalizability. METHODS: MEDLINE, Embase and Cochrane CENTRAL were searched from inception to May 2025 following PRISMA and AMSTAR guidelines. Studies comparing semaglutide with placebo or standard care in adults (>/= 18 years) with CKD, with or without T2DM were included. Primary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), major kidney-related adverse events, nonfatal myocardial infarction and nonfatal stroke. Risk of bias was assessed using Cochrane RoB 2.0. RESULTS: Five RCTs involving 12,785 participants were included. The findings showed that semaglutide substantially decreased major kidney-related adverse events (defined as a composite outcome encompassing the onset of kidney failure (including long-term dialysis, kidney transplantation or a sustained eGFR reduction to < 15 mL/min/1.73 m(2)), a sustained 50% or greater reduction in eGFR from baseline, or death due to kidney-related causes) (RR: 0.79; 95% CI: 0.71-0.87; p < 0.00001; I(2) = 0%), cardiovascular mortality (RR: 0.74; 95% CI: 0.62-0.88; p = 0.0008; I(2) = 36%) and MACE (defined as a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) (RR: 0.78; 95% CI: 0.70-0.87; p < 0.00001; I(2) = 0%). CONCLUSION: Semaglutide demonstrates a favourable safety profile and significant cardiorenal benefits in CKD patients, with or without T2DM. Further research is needed to confirm its effects in non-diabetic CKD populations. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251019235. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Abdullah, Ali AU - Abdullah A AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Sagreeka, F N U AU - Sagreeka FNU AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Aniket, Gurdas Alias AU - Aniket GA AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Lal, Rohan AU - Lal R AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Geeta, F N U AU - Geeta FNU AD - Chandka Medical College, Larkana, Pakistan. FAU - Bai, Anusha AU - Bai A AD - Chandka Medical College, Larkana, Pakistan. FAU - Ahmed, Ghazi Uddin AU - Ahmed GU AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Raza, Ahmed Asad AU - Raza AA AUID- ORCID: 0009-0004-2930-8188 AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Shaikh, Varisha Fatima AU - Shaikh VF AD - Dow Medical College, Karachi, Pakistan. FAU - Sanaullah, Owais AU - Sanaullah O AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Sabahat, Syeda Elezeh AU - Sabahat SE AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Ghori, Ahzam Khan AU - Ghori AK AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Bhutto, Seema Habib AU - Bhutto SH AD - Jinnah Medical and Dental College, Karachi, Pakistan. FAU - Tesfaye, Mahir AU - Tesfaye M AUID- ORCID: 0009-0003-7324-5121 AD - Addis Ababa University, Addis Ababa, Ethiopia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cardiovascular Diseases/prevention & control MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12640882 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular outcomes OT - chronic kidney disease OT - major adverse cardiovascular events OT - major kidney adverse events OT - meta-analysis OT - renal outcomes OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/11/24 06:27 MHDA- 2025/11/24 06:28 PMCR- 2025/11/23 CRDT- 2025/11/24 00:33 PHST- 2025/07/29 00:00 [revised] PHST- 2025/05/23 00:00 [received] PHST- 2025/11/07 00:00 [accepted] PHST- 2025/11/24 06:28 [medline] PHST- 2025/11/24 06:27 [pubmed] PHST- 2025/11/24 00:33 [entrez] PHST- 2025/11/23 00:00 [pmc-release] AID - EDM270136 [pii] AID - 10.1002/edm2.70136 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 Nov;8(6):e70136. doi: 10.1002/edm2.70136. PMID- 41276236 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260806 IS - 1532-8406 (Electronic) IS - 0883-5403 (Linking) VI - 41 IP - 8 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists, Readmission, and Postoperative Complications in Arthroplasty: A Systematic Review and Meta-Analysis. PG - 2530-2538.e6 LID - S0883-5403(25)01490-1 [pii] LID - 10.1016/j.arth.2025.11.036 [doi] AB - BACKGROUND: Agonists targeting the glucagon-like peptide-1 receptor have gained prominence in treating individuals who have type 2 diabetes and obesity. However, their influence on postoperative medical complications following total joint arthroplasty remains poorly characterized. METHODS: A systematic review and meta-analysis were conducted using data from eight retrospective cohort studies encompassing 76,091 patients who underwent total hip or knee arthroplasty. The primary outcome was hospital readmission within 90 days. Additional postoperative events assessed included deep vein thrombosis, pulmonary embolism, pneumonia, acute kidney injury, surgical site infection, cerebrovascular accident, urinary tract infection, and hypoglycemic event. Pooled odds ratios were calculated using a random-effects model to account for interstudy variability. RESULTS: Patients who received glucagon-like peptide-1 receptor agonists (GLP-1 RAs) before surgery exhibited a significantly lower likelihood of 90-day readmission (odds ratio 0.73; 95% confidence interval: 0.64 to 0.82). There were no statistically significant differences observed in other postoperative medical complications. Sensitivity and trim-and-fill analyses revealed modest variability in select outcomes, but did not substantially alter overall conclusions. CONCLUSIONS: Preoperative glucagon-like peptide-1 receptor agonist use may be linked to reduced readmission risk following joint arthroplasty, without evidence of increased postoperative medical harm. Further prospective studies are warranted to validate these associations and guide perioperative care protocols. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Chan, Yi-Chuan AU - Chan YC AD - Division of General Practice, Department of Medical Education, Changhua Christian Hospital, Changhua, Taiwan. FAU - Chuang, Shu-Han AU - Chuang SH AD - Division of General Practice, Department of Medical Education, Changhua Christian Hospital, Changhua, Taiwan. FAU - Wu, Lien-Chen AU - Wu LC AD - Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan. FAU - Kuo, Yi-Jie AU - Kuo YJ AD - Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Lian, Yu-Zhi AU - Lian YZ AD - School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan. FAU - Chen, Yu-Pin AU - Chen YP AD - Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251121 PL - United States TA - J Arthroplasty JT - The Journal of arthroplasty JID - 8703515 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Postoperative Complications/epidemiology/prevention & control MH - *Patient Readmission/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Arthroplasty, Replacement, Knee/adverse effects MH - *Arthroplasty, Replacement, Hip/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - medical complications OT - meta-analysis OT - systematic review OT - total hip arthroplasty OT - total knee arthroplasty EDAT- 2025/11/24 00:49 MHDA- 2026/07/15 12:36 CRDT- 2025/11/23 19:17 PHST- 2025/07/09 00:00 [received] PHST- 2025/11/16 00:00 [revised] PHST- 2025/11/17 00:00 [accepted] PHST- 2026/07/15 12:36 [medline] PHST- 2025/11/24 00:49 [pubmed] PHST- 2025/11/23 19:17 [entrez] AID - S0883-5403(25)01490-1 [pii] AID - 10.1016/j.arth.2025.11.036 [doi] PST - ppublish SO - J Arthroplasty. 2026 Aug;41(8):2530-2538.e6. doi: 10.1016/j.arth.2025.11.036. Epub 2025 Nov 21. PMID- 41276093 OWN - NLM STAT- MEDLINE DCOM- 20260325 LR - 20260823 IS - 1097-6809 (Electronic) IS - 0741-5214 (Print) IS - 0741-5214 (Linking) VI - 83 IP - 4 DP - 2026 Apr TI - Glucagon-like peptide-1 receptor agonists are associated with reduced abdominal aortic aneurysm-related events. PG - 1079-1088.e2 LID - S0741-5214(25)02006-3 [pii] LID - 10.1016/j.jvs.2025.11.021 [doi] AB - OBJECTIVE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown to possess cardiovascular protective effects, with preclinical data, suggesting potential benefits in slowing abdominal aortic aneurysm (AAA) growth. However, their effect on AAA in humans remains underexplored. This study evaluates the effects of GLP-1RAs on all-cause mortality, AAA repair, and acute abdominal aortic syndrome in patients with unruptured AAA. METHODS: We used the US collaborative network of the TriNetX platform to identify patients aged >/=18 years with unruptured AAA, based on International Classification of Disease, 10th Revision (ICD-10), codes from January 1, 2015, to March 1, 2020. Patients with prior AAA rupture, dissection, repair, and connective tissue disorders were excluded. The remaining cohort was stratified by type 2 diabetes (T2D) status and divided into two cohorts: patients who had GLP-1RA prescription within 6 months before or any time after their first AAA encounter diagnosis during the study period and non-GLP-1RA users who were never prescribed GLP-1RAs. Propensity score matching (1:1) adjusted for demographics, tobacco use, comorbidities, and medications. Five-year odds ratios (ORs) and Kaplan-Meier survival analyses assessed outcomes. RESULTS: Of the 1407 patients prescribed GLP-1RAs and 38,994 not prescribed GLP-1RAs with T2D, 1401 patients were matched and analyzed. Similarly, among 336 patient prescribed GLP-1RAs and 129,790 not prescribed non-GLP-1RAs without T2D, 336 matched pairs were analyzed. Patient prescribed GLP-1RAs had significantly lower risks of the composite outcome of mortality, AAA repair, and acute abdominal aortic syndrome in both T2D (OR, 0.56; 95% confidence interval [CI], 0.47-0.66) and non-T2D cohorts (OR, 0.42; 95% CI, 0.28-0.63). Specifically, those prescribed GLP-1RAs had reduced mortality (T2D: OR, 0.54; 95% CI, 0.45-0.65; non-T2D: OR, 0.47; 95% CI, 0.30-0.74) and were less likely to undergo AAA repair (T2D: OR, 0.66; 95% CI, 0.45-0.95; non-T2D: OR, 0.45; 95% CI, 0.21-0.96). Kaplan-Meier analysis also demonstrated the benefits of GLP-1RAs in delaying outcome. CONCLUSIONS: GLP-1RA prescriptions were associated with a lower risk of clinically important events in patients with unruptured AAA. These findings suggest potential benefits of GLP-1RAs in AAA management, warranting further research on their effect on aneurysm growth and progression. CI - Copyright (c) 2025 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved. FAU - Ahn, Hyunjun AU - Ahn H AD - Lerner College of Medicine, Cleveland Clinic, Cleveland, OH. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Case Western Reserve University, Cleveland, OH; Department of Internal Medicine, Case Western Reserve University, Cleveland, OH. FAU - Hoell, Nicholas AU - Hoell N AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Ambani, Ravi AU - Ambani R AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Quatromoni, Jon G AU - Quatromoni JG AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Khalifeh, Ali AU - Khalifeh A AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Kirksey, Lee AU - Kirksey L AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Hanak, Courtney AU - Hanak C AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Cameron, Scott J AU - Cameron SJ AD - Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Lyden, Sean P AU - Lyden SP AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. FAU - Caputo, Francis J AU - Caputo FJ AD - Department of Vascular Surgery and Aortic Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. Electronic address: caputof@ccf.org. LA - eng GR - R01 HL158801/HL/NHLBI NIH HHS/United States GR - U54 HL119810/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251121 PL - United States TA - J Vasc Surg JT - Journal of vascular surgery JID - 8407742 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Aortic Aneurysm, Abdominal/mortality/diagnostic imaging/surgery MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/complications MH - Risk Factors MH - Retrospective Studies MH - Time Factors MH - Risk Assessment MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use MH - Aged, 80 and over MH - Protective Factors MH - Databases, Factual MH - United States/epidemiology PMC - PMC13395541 MID - NIHMS2189139 OTO - NOTNLM OT - Abdominal aortic aneurysm OT - Aneurysm growth OT - Aneurysm repair OT - Glucagon-like peptide receptor agonists OT - Medical management COIS- Disclosures S.P.L. is a consultant for BD, Boston Scientific, Contego Medical, Cordis, Endologix, Inspire MD, Medtronic, Rapid Medical, Shockwave, Penumbra, Vivasure, and Nectero; has stock options with Inspire MD, Reva Medical, and Centerline Biomedical; is a board member for VIVA Physicians; and conducts research studies for Abbott, Endologix, Surmodics, W.L. Gore, Terumo Aortic, NIH, Boston Scientific, Merit, Contego Medical, Inspire MD, Reva Medical, Penumbra, Medalliance, and Nectero. EDAT- 2025/11/24 00:49 MHDA- 2026/03/26 01:03 PMCR- 2026/07/23 CRDT- 2025/11/23 19:15 PHST- 2025/09/29 00:00 [received] PHST- 2025/11/12 00:00 [revised] PHST- 2025/11/15 00:00 [accepted] PHST- 2026/03/26 01:03 [medline] PHST- 2025/11/24 00:49 [pubmed] PHST- 2025/11/23 19:15 [entrez] PHST- 2026/07/23 00:00 [pmc-release] AID - S0741-5214(25)02006-3 [pii] AID - 10.1016/j.jvs.2025.11.021 [doi] PST - ppublish SO - J Vasc Surg. 2026 Apr;83(4):1079-1088.e2. doi: 10.1016/j.jvs.2025.11.021. Epub 2025 Nov 21. PMID- 41275875 OWN - NLM STAT- MEDLINE DCOM- 20251220 LR - 20260923 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 406 IP - 10522 DP - 2026 Dec 20 TI - Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. PG - 2927-2944 LID - S0140-6736(25)02165-8 [pii] LID - 10.1016/S0140-6736(25)02165-8 [doi] AB - BACKGROUND: Obesity is a chronic disease that significantly contributes to type 2 diabetes and its complications. We aimed to evaluate orforglipron, an oral small-molecule (non-peptide) GLP-1 receptor agonist, for obesity treatment in adults with type 2 diabetes. METHODS: This 72-week, phase 3, double-blind, placebo-controlled trial was conducted across 136 sites in ten countries. Participants with a BMI of 27 kg/m(2) or higher and glycated haemoglobin (HbA(1c)) of 7-10% (53-86 mmol/mol) were randomly assigned (1:1:1:2) to once-daily orforglipron 6 mg, 12 mg, 36 mg, or placebo. The primary endpoint was the mean percent change in bodyweight from baseline to week 72. The treatment regimen estimand (using data from all randomly assigned participants, regardless of intercurrent events) was the primary estimand, with the efficacy estimand considered supportive. Safety was assessed in all patients who received at least one dose of study drug. This trial was registered at ClinicalTrials.gov (NCT05872620) and is completed. FINDINGS: From June 5, 2023, to Feb 15, 2024, 2859 participants were screened, and 1613 (757 [46.9%] female) were randomly assigned, following a dose-escalation phase, to receive orforglipron 6 mg (n=329), 12 mg (n=332), 36 mg (n=322), or placebo (n=630), as an adjunct to lifestyle modification; 1444 (89.5%) completed the study. Baseline bodyweight was 101.4 kg (SD 22.5), BMI 35.6 kg/m(2) (SD 6.6), and HbA(1c) 8.05% (SD 0.75; 64.4 mmol/mol [SD 8.2]). For the treatment regimen estimand, the mean percent change in bodyweight from baseline to week 72 was -5.1% (95% CI -6.0 to -4.2) with 6 mg (estimated treatment difference [ETD] -2.7 [95% CI -3.7 to -1.6]; p<0.0001), -7.0% (-7.8 to -6.2) with 12 mg (ETD -4.5 [-5.5 to -3.6]; p<0.0001), and -9.6% (-10.5 to -8.7) with 36 mg orforglipron (ETD -7.1 [-8.2 to -6.1]; p<0.0001), versus -2.5% (-3.0 to -1.9) with placebo (all p<0.0001 compared with placebo). All prespecified weight and cardiometabolic measures including HbA(1c) statistically significantly improved with orforglipron. Treatment discontinuations due to adverse events (mainly gastrointestinal-related) were higher for orforglipron (6.1-9.9%) versus placebo (4.1%). The most common adverse events with orforglipron were mild-to-moderate gastrointestinal events, predominantly occurring during dose escalation. Ten deaths were reported during the study: six with orforglipron and four with placebo. Investigators deemed all deaths unrelated to the study treatment, except for one case in the placebo group and one case in the 12 mg orforglipron group. For the case in the orforglipron group, no treatment-related association was reported. INTERPRETATION: In adults with obesity or overweight and type 2 diabetes, statistically superior reduction in bodyweight compared with placebo was demonstrated by once-daily orforglipron as an adjunct to lifestyle modification, with a safety profile similar to other GLP-1 receptor agonists. FUNDING: Eli Lilly and Company. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Horn, Deborah B AU - Horn DB AD - Department of Surgery, University of Texas McGovern Medical School, and Center for Obesity Medicine and Metabolic Performance, Houston, TX, USA. Electronic address: deborah.b.horn@uth.tmc.edu. FAU - Ryan, Donna H AU - Ryan DH AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. FAU - Kis, Sanja Giljanovic AU - Kis SG AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Alves, Breno AU - Alves B AD - Centro Paulista De Investigacao Clinica (Cepic), Sao Paulo, Brazil. FAU - Mu, Yiming AU - Mu Y AD - Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing, China. FAU - Kim, Sin Gon AU - Kim SG AD - Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea. FAU - Aberle, Jens AU - Aberle J AD - University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, UK. FAU - Allen, Sheryl AU - Allen S AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Sarker, Elizabeth AU - Sarker E AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Wu, Qiwei AU - Wu Q AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Stefanski, Adam AU - Stefanski A AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Jouravskaya, Irina AU - Jouravskaya I AD - Eli Lilly and Company, Indianapolis, IN, USA. CN - ATTAIN-2 Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT05872620 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251120 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (orforglipron) RN - 0 (Fluorine Compounds) RN - 0 (Oxadiazoles) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Hypoglycemic Agents MH - *Obesity/drug therapy/complications MH - Treatment Outcome MH - *Fluorine Compounds/therapeutic use MH - *Oxadiazoles/therapeutic use COIS- Declaration of interests DBH reports consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Roche, Kailera, and Zealand Pharmaceuticals; honoraria for presentations and support for meeting attendance from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Zealand, Vindico, Haymarket, and Novo Nordisk; institutional research support from Eli Lilly, Novo Nordisk, KVK Tech, and Weight Watchers; roles in advisory boards for Eli Lilly, AstraZeneca, Amgen, Novo Nordisk, Zealand, and Boehringer Ingelheim, and in speaker bureaus for Eli Lilly and Novo Nordisk; and volunteer services for The Obesity Society, Obesity Medicine Association, and the World Obesity Federation. BA reports research grants and support for attending meetings from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, and Arrowhead Pharmaceuticals. SGKim reports support for the present manuscript from Eli Lilly; grants from Abbott, Novo Nordisk, and Viatris; consulting fees from AstraZeneca, Novo Nordisk, Celltrion, and Eli Lilly; payments or honoraria from Boehringer Ingelheim, Eli Lilly, Celltrion, Viatris, Sanofi, Daewoong, and AstraZeneca; and support for attending meetings from Eli Lilly and Novo Nordisk. JA reports consulting fees from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; payments or honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; support for attending meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and a role as a board member and commission speaker of the German Obesity Association. SCB reports payments or honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Menarini, and Novo Nordisk. DHR reports consulting fees for advisory services from AbbVie, Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Calibrate, Carmot/Roche, CinRx, Currax, eMedd, Epitomee, Fractyl, Gila, Eli Lilly, Nestle, Novo Nordisk, Pfizer, Regeneron, Source Bio, Structure Therapeutics, Tenvie, Wondr Health, and Zealand; payments or honoraria for presentations from Novo Nordisk, Eli Lilly, and PPD; participation on data monitoring committees for IQVIA, Eli Lilly, and CinRx; volunteer service for The Obesity Society, World Obesity Federation, Stop Obesity Alliance, and Obesity Action Coalition; and stock or stock options from Calibrate, Scientific Intake, Epitomee, Roman, and Xeno Bioscience. AS, SA, ES, QW, SGKis, and IJ are employees and stockholders of Eli Lilly and Company. YM declares no competing interests. EDAT- 2025/11/24 00:49 MHDA- 2025/12/21 01:48 CRDT- 2025/11/23 18:54 PHST- 2025/09/10 00:00 [received] PHST- 2025/10/20 00:00 [revised] PHST- 2025/10/21 00:00 [accepted] PHST- 2025/12/21 01:48 [medline] PHST- 2025/11/24 00:49 [pubmed] PHST- 2025/11/23 18:54 [entrez] AID - S0140-6736(25)02165-8 [pii] AID - 10.1016/S0140-6736(25)02165-8 [doi] PST - ppublish SO - Lancet. 2026 Dec 20;406(10522):2927-2944. doi: 10.1016/S0140-6736(25)02165-8. Epub 2025 Nov 20. PMID- 41275408 OWN - NLM STAT- MEDLINE DCOM- 20251226 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 18 IP - 11 DP - 2025 Nov TI - Orforglipron in type 2 diabetes mellitus and obesity: an overview. PG - 883-898 LID - 10.1080/17512433.2025.2594493 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes mellitus (T2DM) and obesity. AREAS COVERED: An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Orforglipron is a novel oral non-peptide GLP-1RA. In T2DM individuals, it has led to reductions in glycated hemoglobin (HbA(1c)) by up to 2.10%, in weight by up to 10.1 kg and in waist circumference by up to 8.7 cm. In studies on overweight or obesity, a weight loss up to 13.0 kg has been reported. In meta-analyses, orforglipron was the most efficient GLP-1RA in terms of weight loss. Significant decreases in systolic blood pressure have also been found in individuals with and without T2DM. Untoward effects include mild-to-moderate vomiting and nausea, particularly in those receiving high doses and after rapid-dose escalation. EXPERT OPINION: Orforglipron is a promising treatment option for T2DM and overweight or obesity, in terms of glucose control and weight loss. The increased frequency of adverse events, particularly in those receiving high doses and after rapid-dose escalation, requires caution before widespread use. FAU - Panou, Theodoros AU - Panou T AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Gouveri, Evanthia AU - Gouveri E AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Novi Sad, Serbia. AD - Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Review DEP - 20251130 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Obesity/drug therapy/physiopathology MH - *Hypoglycemic Agents/pharmacology/adverse effects/administration & dosage MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/metabolism MH - Dose-Response Relationship, Drug MH - Waist Circumference/drug effects MH - Overweight/drug therapy MH - Blood Pressure/drug effects MH - Animals MH - Oxadiazoles MH - Fluorine Compounds OTO - NOTNLM OT - LY3502970 OT - Orforglipron OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - type 2 diabetes mellitus EDAT- 2025/11/23 14:04 MHDA- 2025/12/26 07:40 CRDT- 2025/11/23 09:52 PHST- 2025/12/26 07:40 [medline] PHST- 2025/11/23 14:04 [pubmed] PHST- 2025/11/23 09:52 [entrez] AID - 10.1080/17512433.2025.2594493 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2025 Nov;18(11):883-898. doi: 10.1080/17512433.2025.2594493. Epub 2025 Nov 30. PMID- 41272444 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260423 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 25 IP - 1 DP - 2025 Nov 21 TI - Cardiovascular benefits of semaglutide: a systematic review and meta-analysis of randomized controlled trials. PG - 881 LID - 10.1186/s12872-025-05278-3 [doi] LID - 881 AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist (GLP-1RA), has shown potential in controlling type 2 diabetes due to their ability to lower blood glucose and improve cardiovascular outcomes. Although semaglutide is the newest GLP-1RA available, its cardiovascular effects have not yet been systematically reviewed. METHODS: This meta-analysis adhered to a pre-registered protocol (PROSPERO ID: CRD42024538847). PubMed, Scopus, and Web of Science were searched comprehensively on February 26, 2024, to locate randomized controlled trials (RCTs) assessing semaglutide's impact on cardiovascular outcomes. A random effects model was used to analyze the data and the Cochrane risk of bias 2 tool was used to assess the quality of included studies. RESULTS: There were four RCTs involving 27,617 individuals (13,809 receiving semaglutide and 13,808 receiving placebo). There was a significant reduction in the risk of major adverse cardiovascular events (MACE) after administration of semaglutide (RR: 0.81, 95% CI: 0.74-0.88, p < 0.001, I(2): 0.00%). Additionally, benefits were observed for particular findings such as cardiovascular death and nonfatal myocardial infarction. However, semaglutide showed no significant effect on nonfatal stroke, heart failure hospitalizations, or admissions for unstable angina. The treatment also led to fewer serious adverse events (RR: 0.91, 95% CI: 0.88-0.94, p < 0.001, I(2): 0.01%), though it was linked to a higher rate of treatment discontinuation (RR: 1.67, 95% CI: 1.27-2.21, p < 0.001, I(2): 91.09%), which was underemphasized in its clinical implications and should be interpreted more cautiously considering the trade-off with benefits. CONCLUSION: Semaglutide effectively reduces the risk of MACE and modestly improves cardiovascular mortality rates and nonfatal myocardial infarction, without significantly affecting nonfatal stroke incidence and hospitalizations (for angina and heart failure). While it lowers the occurrence of serious adverse events, it also increases the likelihood of discontinuing treatment. CI - (c) 2025. The Author(s). FAU - Sadraei, Samin AU - Sadraei S AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Aarabi, Aryan AU - Aarabi A AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Rajai Firouzabadi, Shahryar AU - Rajai Firouzabadi S AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Alinejadfard, Mohammadreza AU - Alinejadfard M AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Mohammadi, Ida AU - Mohammadi I AUID- ORCID: 0000-0002-0662-0329 AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. idamohammadi2000@gmail.com. FAU - Jolfayi, Amir Ghaffari AU - Jolfayi AG AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251121 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis/epidemiology MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Assessment MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Glucose/drug effects/metabolism MH - Female MH - Male MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12752371 OTO - NOTNLM OT - Cardiovascular mortality OT - GLP-1 receptor agonist OT - Major Adverse Cardiac Events OT - Myocardial infarction OT - Semaglutide OT - Stroke COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/11/22 06:29 MHDA- 2025/12/30 07:41 PMCR- 2025/11/21 CRDT- 2025/11/22 00:06 PHST- 2025/05/23 00:00 [received] PHST- 2025/10/10 00:00 [accepted] PHST- 2025/12/30 07:41 [medline] PHST- 2025/11/22 06:29 [pubmed] PHST- 2025/11/22 00:06 [entrez] PHST- 2025/11/21 00:00 [pmc-release] AID - 10.1186/s12872-025-05278-3 [pii] AID - 5278 [pii] AID - 10.1186/s12872-025-05278-3 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2025 Nov 21;25(1):881. doi: 10.1186/s12872-025-05278-3. PMID- 41271442 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260813 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 IP - 2 DP - 2026 Feb TI - Weight Changes From Glucagon-Like Peptide-1 Receptor Agonist Use and Discontinuation: A Retrospective Cohort Study. PG - 482-490 LID - 10.1002/oby.70076 [doi] AB - OBJECTIVE: This study aimed to quantify the effect of glucagon-like peptide-1 receptor agonists (GLP-1s) on weight loss and weight gain following GLP-1 discontinuation. METHODS: This retrospective cohort study using electronic health records from TriNetX included individuals age 18 years or older with various lengths of continuous GLP-1 use between September 2014 and November 2023. Applying an intention-to-treat framework, we used linear mixed effects models and propensity score adjustment to model changes in BMI after GLP-1 discontinuation while accounting for correlated within-person observations and potential confounders. RESULTS: A total of 78,076 (19.7%) individuals used GLP-1s continuously for 3 months, 23,861 (6.0%) for 6 months, and 12,642 (3.2%) for 9 months. The median BMI prior to initiation was 36.38 (IQR 36.30-36.46), which declined by 2.15% (IQR 2.10%-2.21%) to 35.81 (IQR 35.7-35.92) among individuals with 3 months of continuous GLP-1 use. Median BMI declines were greater among individuals with 6 months (4.38%, IQR 4.27%-4.48%) and 9 months (5.56%, IQR 5.34%-5.78%) of continuous use. On average, weight loss among discontinuers at months 3, 6, and 9 slowed in comparison to their counterparts. CONCLUSIONS: Among this real-world sample, GLP-1 use was associated with more modest weight loss than has been demonstrated in randomized controlled trials. CI - (c) 2025 The Obesity Society. FAU - Alexander, G Caleb AU - Alexander GC AUID- ORCID: 0000-0002-5622-2986 AD - Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, Maryland, USA. FAU - Xu, Yizhen AU - Xu Y AD - Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Xiao, Xuya AU - Xiao X AD - Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Lewis, Sydney V AU - Lewis SV AD - Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Zeger, Scott AU - Zeger S AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Mehta, Hemalkumar B AU - Mehta HB AD - Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. LA - eng GR - K01 AG070329/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20251121 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Weight Loss/drug effects MH - Adult MH - *Weight Gain/drug effects MH - Body Mass Index MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy PMC - PMC13463575 MID - NIHMS2199415 OTO - NOTNLM OT - glucagon-like peptide-1 (GLP-1) inhibitors OT - medication discontinuation OT - obesity COIS- Disclosures: Dr. Alexander is past Chair of FDA's Peripheral and Central Nervous System Advisory Committee and a co-founding Principal and equity holder in Stage Analytics. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. EDAT- 2025/11/22 00:28 MHDA- 2026/01/28 19:21 PMCR- 2026/08/12 CRDT- 2025/11/21 21:22 PHST- 2025/09/11 00:00 [revised] PHST- 2025/03/18 00:00 [received] PHST- 2025/09/28 00:00 [accepted] PHST- 2026/01/28 19:21 [medline] PHST- 2025/11/22 00:28 [pubmed] PHST- 2025/11/21 21:22 [entrez] PHST- 2026/08/12 00:00 [pmc-release] AID - 10.1002/oby.70076 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Feb;34(2):482-490. doi: 10.1002/oby.70076. Epub 2025 Nov 21. PMID- 41270831 OWN - NLM STAT- MEDLINE DCOM- 20260116 LR - 20261022 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 103 DP - 2026 Jan TI - Additive effects of GLY-200 (oral pharmacologic duodenal exclusion therapy) and GLP-1R agonist in obesity management. PG - 102287 LID - S2212-8778(25)00194-2 [pii] LID - 10.1016/j.molmet.2025.102287 [doi] LID - 102287 AB - Type 2 diabetes and obesity impact billions of people and the global prevalence is only growing. Current treatment options, which include pharmacotherapy, e.g., GLP-1 receptor agonists (GLP-1RA) and bariatric surgical approaches have limitations. GLY-200 is an investigational clinical-stage oral non-absorbed polymeric drug designed to target proximal intestinal mucin and enhance its barrier function, emulating duodenal exclusion physiology for the treatment of diabetes and obesity. The efficacy of GLY-200 as a monotherapy and in combination with semaglutide, a leading GLP-1 receptor agonist (GLP-1RA) for obesity weight management was evaluated in diet-induced obesity (DIO) mice. Significant improvements in metabolic parameters were seen in mice treated with GLY-200 monotherapy. Moreover, an additive effect was observed when GLY-200 was combined with semaglutide, resulting in enhanced weight loss and metabolic improvements beyond those achieved with either treatment alone. GLY-200 showed promise as a weight maintenance drug, significantly blunting the weight rebound seen after GLP-1RA discontinuation. Phase 2a data from patients with type 2 diabetes (T2D) showed reductions in fasting and postprandial blood glucose, improved fasting lipid profiles, and progressive weight loss with GLY-200 treatment. These findings suggest that GLY-200, in combination with GLP-1RAs, holds promise as a novel therapeutic strategy for obesity, potentially offering a valuable approach for GLP-1RA dose reduction or weight maintenance following GLP-1RA discontinuation. CI - Copyright (c) 2025 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Carlson, Taylor L AU - Carlson TL AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Fineman, Mark AU - Fineman M AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Kernodle, Stace AU - Kernodle S AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Hutch, Chelsea R AU - Hutch CR AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Bryant, Christine AU - Bryant C AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Colbert, Kevin AU - Colbert K AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Seeley, Randy J AU - Seeley RJ AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Nimgaonkar, Ashish AU - Nimgaonkar A AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA; Center for Bioengineering Innovation and Design, Department of Biomedical Engineering, The Johns Hopkins Hospital, Baltimore, MD, USA; Division of Gastroenterology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: animgao1@jh.edu. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - P30 DK089503/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251119 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Animals MH - Humans MH - Male MH - Mice MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Duodenum/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Mice, Inbred C57BL MH - *Obesity/drug therapy/metabolism MH - Obesity Management/methods MH - Weight Loss/drug effects PMC - PMC12719563 OTO - NOTNLM OT - Bariatric surgery OT - Combination therapy OT - Duodenal exclusion OT - GLP-1RA OT - GLY-200 OT - Weight loss OT - Weight maintenance COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TLC, MF, CB, KC, AN report equity or stock options in Glyscend. RJS has received research support from Novo Nordisk, Fractyl, AstraZeneca, Congruence Therapeutics, Eli Lilly, Bullfrog AI, Glyscend Therapeutics, Diasome and Amgen. RJS has been a paid consultant for Novo Nordisk, Eli Lilly, CinRx, Fractyl, Structure Therapeutics, Crinetics, Amgen, Congruence Therapeutics, Heliocore, Gallant and Nuanced Health. RJS has equity in Nuanced Health, Coro Bio, Eccogene, Fractyl and Rewind. The research was funded by Glyscend Therapeutics. There are no patents or intellectual property to report. EDAT- 2025/11/22 00:28 MHDA- 2026/01/17 00:37 PMCR- 2025/11/19 CRDT- 2025/11/21 19:12 PHST- 2025/07/24 00:00 [received] PHST- 2025/11/09 00:00 [revised] PHST- 2025/11/16 00:00 [accepted] PHST- 2026/01/17 00:37 [medline] PHST- 2025/11/22 00:28 [pubmed] PHST- 2025/11/21 19:12 [entrez] PHST- 2025/11/19 00:00 [pmc-release] AID - S2212-8778(25)00194-2 [pii] AID - 102287 [pii] AID - 10.1016/j.molmet.2025.102287 [doi] PST - ppublish SO - Mol Metab. 2026 Jan;103:102287. doi: 10.1016/j.molmet.2025.102287. Epub 2025 Nov 19. PMID- 41266905 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260918 IS - 1420-908X (Electronic) IS - 1023-3830 (Print) IS - 1023-3830 (Linking) VI - 74 IP - 1 DP - 2025 Nov 21 TI - The potential role of GLP-1 receptor agonists in the management of psoriatic disease: a scoping review. PG - 167 LID - 10.1007/s00011-025-02140-2 [doi] LID - 167 AB - BACKGROUND: Psoriatic disease (PsD) is a chronic systemic inflammatory condition associated with significant cardiometabolic comorbidities, including obesity, type 2 diabetes mellitus (T2DM), and cardiovascular (CV) disease. These comorbidities are interlinked via shared immunopathogenic mechanisms, notably chronic low-grade inflammation driven by Th1/Th17 cytokines such as TNF, IL-6, and IL-17. Obesity, in particular, exacerbates PsD severity and treatment resistance, underscoring the need for integrated therapeutic strategies. This scoping review investigates the biological rationale and evidence for the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in PsD. FINDINGS: Originally developed for T2DM, GLP-1RAs have demonstrated efficacy in reducing weight and improving glycemic control and CV outcomes. Evidence also suggests immunomodulatory properties through modulation of key inflammatory pathways and immune cell activity. We examined studies addressing: (1) the impact of obesity, T2DM, and CV disease on PsD; (2) outcomes of GLP-1RAs in these comorbidities; and (3) their potential in related rheumatologic and dermatologic diseases. GLP-1RAs show promise in reducing PsD burden by improving metabolic parameters and reducing systemic inflammation. Early clinical and preclinical data suggest benefits also in rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis, and hidradenitis suppurativa. IMPLICATIONS: GLP-1RAs represent a novel, multifaceted therapeutic option in PsD, targeting both metabolic and inflammatory components. Further clinical trials are warranted to define their role in comprehensive PsD management and validate their disease-modifying potential. CI - (c) 2025. The Author(s). FAU - Buonanno, Simona AU - Buonanno S AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. FAU - Gaggiano, Carla AU - Gaggiano C AUID- ORCID: 0000-0003-1401-8343 AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. cgaggiano132@gmail.com. FAU - Terribili, Riccardo AU - Terribili R AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. FAU - Cantarini, Luca AU - Cantarini L AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. FAU - Frediani, Bruno AU - Frediani B AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. FAU - Gentileschi, Stefano AU - Gentileschi S AD - Rheumatology Section, Department of Medical Sciences, Surgery and Neuroscience, Siena University Hospital, University of Siena, Policlinico "Le Scotte", Viale Mario Bracci 16, 53100, Siena, Italy. LA - eng PT - Journal Article PT - Scoping Review DEP - 20251121 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Psoriasis/drug therapy/immunology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy/complications MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Cardiovascular Diseases/drug therapy/complications PMC - PMC12634801 OTO - NOTNLM OT - Cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Psoriasis OT - Psoriatic disease OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Not required. Human participants and/or animals: Not applicable. Informed consent: Not applicable. EDAT- 2025/11/21 00:27 MHDA- 2025/11/21 06:27 PMCR- 2025/11/21 CRDT- 2025/11/20 23:53 PHST- 2025/07/29 00:00 [received] PHST- 2025/11/03 00:00 [accepted] PHST- 2025/10/01 00:00 [revised] PHST- 2025/11/21 06:27 [medline] PHST- 2025/11/21 00:27 [pubmed] PHST- 2025/11/20 23:53 [entrez] PHST- 2025/11/21 00:00 [pmc-release] AID - 10.1007/s00011-025-02140-2 [pii] AID - 2140 [pii] AID - 10.1007/s00011-025-02140-2 [doi] PST - epublish SO - Inflamm Res. 2025 Nov 21;74(1):167. doi: 10.1007/s00011-025-02140-2. PMID- 41266832 OWN - NLM STAT- MEDLINE DCOM- 20251223 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 1 DP - 2026 Jan TI - Semaglutide Versus Dulaglutide and Liraglutide in Chinese Patients With T2DM: A Multicenter Real-World Study. PG - 101-113 LID - 10.1002/oby.70065 [doi] AB - OBJECTIVE: We aimed to compare the effectiveness and safety of semaglutide 1.0 mg versus dulaglutide 1.5 mg and liraglutide 1.8 mg in patients with type 2 diabetes mellitus (T2DM) under routine clinical care. METHODS: This multicenter, retrospective, real-world study enrolled Chinese adults with T2DM who initiated GLP-1 receptor agonist therapy in endocrinology clinics between January 1, 2022, and August 31, 2024. We compared the effectiveness of these agents on HbA1c and weight loss, with safety as a key exploratory endpoint. Additionally, the UK Prospective Diabetes Study Outcomes Model 2.1 was utilized to project long-term health outcomes. RESULTS: This multicenter retrospective study included 111, 74, and 107 patients treated with semaglutide 1.0 mg, dulaglutide 1.5 mg, and liraglutide 1.8 mg, respectively. After 1:1 propensity score matching, semaglutide demonstrated significantly greater HbA1c reduction compared to both dulaglutide (-0.27% +/- 0.70%, p = 0.008) and liraglutide (-0.39% +/- 0.87%, p < 0.001), along with higher glycemic target achievement rates. Semaglutide was associated with improved outcomes in all death, cardiovascular death, and other death endpoints. No significant differences in safety profiles were observed among the three treatment groups. CONCLUSIONS: Semaglutide demonstrated superior glycemic control and weight loss compared to both dulaglutide and liraglutide, whereas dulaglutide and liraglutide exhibited comparable clinical efficacy. CI - (c) 2025 The Obesity Society. FAU - Xie, Zeyu AU - Xie Z AUID- ORCID: 0000-0002-1609-4377 AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Gan, Bin AU - Gan B AD - Department of Pharmacy, Shenzhen Baoan People's Hospital, Shenzhen, Guangdong, China. FAU - Cao, Weiling AU - Cao W AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Liu, Jiang AU - Liu J AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Chen, Jisheng AU - Chen J AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China. LA - eng GR - SZSM201801060/Sanming Project of Medicine in Shenzen Municipality/ GR - 2024-0808-03/the 2024 "Real-World Evidence and Health Technology Assessment for Clinical Use of Medicines" Special Project/ PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20251120 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Chinese people SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Liraglutide/therapeutic use/adverse effects/administration & dosage MH - Male MH - Female MH - Middle Aged MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects/administration & dosage MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis MH - *Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Aged MH - China MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Blood Glucose/drug effects MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People OTO - NOTNLM OT - GLP-1 receptor agonists OT - effectiveness OT - observational OT - real-world OT - safety OT - semaglutide EDAT- 2025/11/21 00:27 MHDA- 2025/12/23 12:48 CRDT- 2025/11/20 23:51 PHST- 2025/08/19 00:00 [revised] PHST- 2025/07/26 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/12/23 12:48 [medline] PHST- 2025/11/21 00:27 [pubmed] PHST- 2025/11/20 23:51 [entrez] AID - 10.1002/oby.70065 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jan;34(1):101-113. doi: 10.1002/oby.70065. Epub 2025 Nov 20. PMID- 41264828 OWN - NLM STAT- MEDLINE DCOM- 20251120 LR - 20251215 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 12 DP - 2025 Dec 1 TI - Additive Benefits of Control-IQ+ AID to GLP-1 Receptor Agonist Use in Adults With Type 2 Diabetes. PG - 2154-2159 LID - 10.2337/dc25-1753 [doi] AB - OBJECTIVE: To assess the effect of automated insulin delivery (AID) on glycemic and insulin outcomes in adults with insulin-treated type 2 diabetes using a glucagon-like peptide-1 receptor agonist (GLP-1 RA). RESEARCH DESIGN AND METHODS: In a randomized trial comparing Control-IQ+ AID versus continuation of prestudy insulin delivery method plus continuous glucose monitoring (CGM group), 143 (45%) of the 319 participants were using a GLP-1 RA at baseline, which was continued during the trial. RESULTS: Among GLP-1 RA users, mean HbA1c decreased by 0.8% from a baseline of 8.0 +/- 1.2% with AID, which represented a mean improvement of -0.5% (95% CI -0.8 to -0.3, P < 0.001) compared with the CGM group. Time-in-range 70-180 mg/dL and other CGM metrics reflective of hyperglycemia also showed comparable statistically significant improvements using AID when added to GLP-1 RA use. For GLP-1 RA users, there was no significant difference in weight after 13 weeks with AID compared with the CGM group (0.9 kg, 95% CI -0.2 to 2.1, P = 0.10), whereas, in GLP-1 RA nonusers, there was a mean weight gain of 1.9 kg with AID compared with CGM (95% CI 0.5 to 3.2, P = 0.007). CONCLUSIONS: The benefits of AID appear to be substantial for a broad spectrum of insulin-treated patients with type 2 diabetes, including those already receiving contemporary and guideline-directed therapy, such as a GLP-1 RA medication. These additive benefits of AID in GLP-1 RA users included significant reductions in HbA1c levels with simultaneous reduction in insulin use, along with no statistical increase in weight despite very significant improvements in glycemic control. CI - (c) 2025 by the American Diabetes Association. FAU - Graham, Timothy E AU - Graham TE AD - Utah Diabetes & Endocrine Treatment Specialists, Sandy, UT. FAU - Raghinaru, Dan AU - Raghinaru D AD - Jaeb Center for Health Research, Tampa, FL. FAU - Afreen, Samina AU - Afreen S AD - Division of Endocrinology, Center for Diabetes Technology, University of Virginia, Charlottesville, VA. FAU - Ahmann, Andrew AU - Ahmann A AD - Harold Schnitzer Diabetes Health Center, Oregon Health & Science University, Portland, OR. FAU - Haidar, Ahmad AU - Haidar A AD - Department of Biomedical Engineering and Division of Endocrinology, McGill University, Montreal, Quebec, Canada. FAU - Raskin, Philip AU - Raskin P AD - UT Southwestern Medical Center, University of Texas, Southwestern, Dallas, TX. FAU - Tsoukas, Michael A AU - Tsoukas MA AD - Department of Biomedical Engineering and Division of Endocrinology, McGill University, Montreal, Quebec, Canada. FAU - Lum, John W AU - Lum JW AD - Jaeb Center for Health Research, Tampa, FL. FAU - Sasson-Katchalski, Ravid AU - Sasson-Katchalski R AD - Tandem Diabetes Care, San Diego, CA. FAU - Pinsker, Jordan E AU - Pinsker JE AUID- ORCID: 0000-0003-4080-9034 AD - Tandem Diabetes Care, San Diego, CA. FAU - Beck, Roy W AU - Beck RW AUID- ORCID: 0000-0002-5194-8446 AD - Jaeb Center for Health Research, Tampa, FL. CN - 2IQP Study Group* LA - eng GR - Tandem Diabetes Care/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Insulin/administration & dosage/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Glycated Hemoglobin/metabolism MH - Aged MH - Adult MH - *Insulin Infusion Systems PMC - PMC12635876 COIS- Duality of Interest. S.A. reports receiving grants from Tandem Diabetes Care. A.A. reports receiving consultancy payments from Medtronic MiniMed. A.H. reports receiving consultancy fees from Eli Lilly and Abbott and research support from Dexcom, Tandem Diabetes Care, Ypsomed, and BetaBionics. M.A.T. reports receiving speaker fees from Boehringer Ingelheim Canada, Eli Lilly, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi. J.W.L. reports receiving grants from Dexcom and grants and consultancy payments from Tandem Diabetes Care. R.S.-K. is an employee of Tandem Diabetes Care. J.E.P. is an employee and shareholder of Tandem Diabetes Care. R.W.B. reports that his institution has received funding on his behalf as follows: grant funding, study supplies, and consulting fees from Insulet, Tandem Diabetes Care, and Beta Bionics; grant funding and study supplies from Dexcom and Abbott; grant funding from Bigfoot Biomedical, embecta, Sequel Med Tech, and MannKind; study supplies from Medtronic; consulting fees and study supplies from Novo Nordisk; and consulting fees from Vertex, Hagar, DreaMed Diabetes, Ypsomed, Abata Therapeutics, Eli Lilly, and Zucara Therapeutics. No other potential conflicts of interest relevant to this article were reported. FIR - Kudva, Yogish C IR - Kudva YC FIR - Desjardins, Donna IR - Desjardins D FIR - Kurek, Corey IR - Kurek C FIR - Kaur, Ravinder Jeet IR - Kaur RJ FIR - Livingood, Daine IR - Livingood D FIR - Rizvi, Shafaq IR - Rizvi S FIR - Graham, Timothy E IR - Graham TE FIR - Terry, Adrienne IR - Terry A FIR - Luker, Ryan IR - Luker R FIR - Mellenthin, Melanie IR - Mellenthin M FIR - Rezac, Stephanie IR - Rezac S FIR - Liljenquist, David R IR - Liljenquist DR FIR - Rogers, Justin IR - Rogers J FIR - Smith, Joshua IR - Smith J FIR - Williams, Jonathan IR - Williams J FIR - Christensen, Rochelle IR - Christensen R FIR - Lee, Inkyoung IR - Lee I FIR - Malone, Joann IR - Malone J FIR - Spanakis, Elias K IR - Spanakis EK FIR - Singh, Lakshmi IR - Singh L FIR - Churchill, Jade IR - Churchill J FIR - Comen, Kathleen IR - Comen K FIR - Scott, William IR - Scott W FIR - Pasquel, Francisco J IR - Pasquel FJ FIR - Davis, Georgia M IR - Davis GM FIR - Tajrishi, Farbod Z IR - Tajrishi FZ FIR - Arroyo, Lizda Guerrero IR - Arroyo LG FIR - Oladejo, Omolade IR - Oladejo O FIR - Usman, Sabeena IR - Usman S FIR - Ahmann, Andrew IR - Ahmann A FIR - Schmid, Caleb IR - Schmid C FIR - Dean, Ariel IR - Dean A FIR - Branigan, Deborah IR - Branigan D FIR - Caswell, Brittany IR - Caswell B FIR - Howard, Matthew IR - Howard M FIR - Heyerman, Tess IR - Heyerman T FIR - Tessman, Brian IR - Tessman B FIR - Vander-Heide, Jesse IR - Vander-Heide J FIR - Ahn, David IR - Ahn D FIR - Dennis, Brittany IR - Dennis B FIR - Hendricks, Laurie IR - Hendricks L FIR - Reyes-Rodriguez, Clemente IR - Reyes-Rodriguez C FIR - Wolf, Valerie IR - Wolf V FIR - Aleppo, Grazia IR - Aleppo G FIR - Coyne, Kasey IR - Coyne K FIR - Kravarusic, Jelena IR - Kravarusic J FIR - Fronczyk, Evelyn IR - Fronczyk E FIR - Herrmann, Stefanie IR - Herrmann S FIR - Penn, Samsam IR - Penn S FIR - Blevins, Thomas IR - Blevins T FIR - Casaubon, Luis IR - Casaubon L FIR - Espinosa, Valerie IR - Espinosa V FIR - Pandit, Keta IR - Pandit K FIR - Perez, Jennifer IR - Perez J FIR - Stewart, Ana IR - Stewart A FIR - Assir, Courtney IR - Assir C FIR - Fields, Cory IR - Fields C FIR - Kruger, Davida IR - Kruger D FIR - Estrada, Kathleen IR - Estrada K FIR - Jones, J Kimberly IR - Jones JK FIR - Mukhashen, Shereen IR - Mukhashen S FIR - Corker, Natalie IR - Corker N FIR - Hunter, Heather IR - Hunter H FIR - Layton, Paula IR - Layton P FIR - Brown, Sue A IR - Brown SA FIR - Afreen, Samina IR - Afreen S FIR - Dhillon, Jasmeen IR - Dhillon J FIR - Emory, Emma IR - Emory E FIR - Fulkerson, David IR - Fulkerson D FIR - Fuller, Morgan IR - Fuller M FIR - Holmes, Viola IR - Holmes V FIR - Kollar, Laura IR - Kollar L FIR - Oliveri, Mary IR - Oliveri M FIR - Toole, Elyse IR - Toole E FIR - Levy, Carol J IR - Levy CJ FIR - Levister, Camilla M IR - Levister CM FIR - O'Malley, Grenye IR - O'Malley G FIR - Ipek, Aslihan IR - Ipek A FIR - Alabi, Denise IR - Alabi D FIR - Ellis, Emily IR - Ellis E FIR - Hassan, Shaziah IR - Hassan S FIR - Ogyaadu, Selassie IR - Ogyaadu S FIR - Tamarez, Denisa IR - Tamarez D FIR - Weinstock, Ruth S IR - Weinstock RS FIR - Stone, Sheri IR - Stone S FIR - Bzdick, Suzan IR - Bzdick S FIR - Agostini, Lynn IR - Agostini L FIR - Bulger, Jane IR - Bulger J FIR - Steenkamp, Devin W IR - Steenkamp DW FIR - Wolpert, Howard IR - Wolpert H FIR - Atakov-Castillo, Astrid IR - Atakov-Castillo A FIR - Sullivan, Asya IR - Sullivan A FIR - Aia, Corinne IR - Aia C FIR - Brouillard, Elizabeth IR - Brouillard E FIR - Spaic, Tamara IR - Spaic T FIR - Liu, Selina IR - Liu S FIR - Driscoll, Marsha IR - Driscoll M FIR - Lapier, Heather IR - Lapier H FIR - Payra, Sherryl IR - Payra S FIR - Vancer, Louise IR - Vancer L FIR - Hirsch, Irl B IR - Hirsch IB FIR - Averkiou, Xenia IR - Averkiou X FIR - Baran, Jesica IR - Baran J FIR - Holod, Rosanna IR - Holod R FIR - Litvicov, Patrisia IR - Litvicov P FIR - Mandava, Patali IR - Mandava P FIR - Swinton, Sydney IR - Swinton S FIR - Khakpour, Dori IR - Khakpour D FIR - Broyles, Frances IR - Broyles F FIR - Marks, Sheryl IR - Marks S FIR - Mitchell, Tina IR - Mitchell T FIR - Hairston, Babette IR - Hairston B FIR - Costello, Reilly IR - Costello R FIR - Curtis, Stella IR - Curtis S FIR - Rickels, Michael R IR - Rickels MR FIR - Kamimoto, Jorge Jo IR - Kamimoto JJ FIR - Peleckis, Amy J IR - Peleckis AJ FIR - Sultan, Rahaf IR - Sultan R FIR - Dalton-Bakes, Cornelia IR - Dalton-Bakes C FIR - Bourne, Patricia IR - Bourne P FIR - Tsoukas, Michael IR - Tsoukas M FIR - Haidar, Ahmad IR - Haidar A FIR - Pasqua, Melissa IR - Pasqua M FIR - Tardio, Vanessa IR - Tardio V FIR - Moore, Adelyn IR - Moore A FIR - Kemp, Gabrielle IR - Kemp G FIR - Raskin, Philip IR - Raskin P FIR - Jordan, Lin Fan IR - Jordan LF FIR - Shao, Baomei IR - Shao B FIR - DoNguyen, Trang IR - DoNguyen T FIR - Meeks, Tram IR - Meeks T FIR - Phan, Michael IR - Phan M FIR - Hatipoglu, Betul IR - Hatipoglu B FIR - Lesniak, Amanda IR - Lesniak A FIR - Becerra, Mario IR - Becerra M FIR - Bellini, Natalie IR - Bellini N FIR - Denallo, Erica IR - Denallo E FIR - Howard, Quiana IR - Howard Q FIR - Lewis, Claudia IR - Lewis C FIR - Tribout, Jerry IR - Tribout J FIR - Tribout, Megan IR - Tribout M FIR - DiFrancesco, Kathryn IR - DiFrancesco K FIR - Phillips, Kylie IR - Phillips K FIR - Lum, John W IR - Lum JW FIR - Raghinaru, Dan IR - Raghinaru D FIR - Campos, Tiffany IR - Campos T FIR - Morrell, Beth IR - Morrell B FIR - Oduah, Vanessa IR - Oduah V FIR - Cardenas-Villamil, Gabriela IR - Cardenas-Villamil G FIR - Morales, Amanda IR - Morales A FIR - Murphy, Carlos IR - Murphy C FIR - Strayer, Heidi IR - Strayer H FIR - Spanbauer, Charles IR - Spanbauer C FIR - Kanapka, Lauren IR - Kanapka L FIR - Kollman, Craig IR - Kollman C FIR - Beck, Roy W IR - Beck RW FIR - Pinsker, Jordan E IR - Pinsker JE FIR - Sasson-Katchalski, Ravid IR - Sasson-Katchalski R FIR - Piquette, Nicole IR - Piquette N FIR - Wheatcroft, Alex IR - Wheatcroft A FIR - White, Kirstin IR - White K FIR - Carmelo, K C IR - Carmelo KC FIR - Janicek, Robert IR - Janicek R FIR - Gabrielson, Deanna IR - Gabrielson D FIR - Le, Van IR - Le V FIR - Mercado, Kevin IR - Mercado K EDAT- 2025/11/20 18:28 MHDA- 2025/11/20 18:29 PMCR- 2025/11/20 CRDT- 2025/11/20 15:02 PHST- 2025/07/18 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/11/20 18:29 [medline] PHST- 2025/11/20 18:28 [pubmed] PHST- 2025/11/20 15:02 [entrez] PHST- 2025/11/20 00:00 [pmc-release] AID - 163808 [pii] AID - 251753 [pii] AID - 10.2337/dc25-1753 [doi] PST - ppublish SO - Diabetes Care. 2025 Dec 1;48(12):2154-2159. doi: 10.2337/dc25-1753. PMID- 41260459 OWN - NLM STAT- MEDLINE DCOM- 20251226 LR - 20260127 IS - 1559-2030 (Electronic) IS - 1551-7144 (Linking) VI - 160 DP - 2026 Jan TI - Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial. PG - 108150 LID - S1551-7144(25)00344-1 [pii] LID - 10.1016/j.cct.2025.108150 [doi] AB - BACKGROUND: Effective weight management and glycemic control are both important in people with type 2 diabetes (T2D) and obesity. Despite the proven benefits of GLP-1 receptor agonists, there is a persistent need for more effective weight management strategies in the treatment of T2D and obesity. Glucagon receptor-based co-agonists, such as mazdutide, represent a promising therapeutic class with the potential for enhanced weight loss compared to current standards of care. However, robust clinical evidence for these agents in populations with T2D and obesity is still lacking. The DREAMS-3 trial is designed to address this gap by directly comparing the efficacy and safety of mazdutide against semaglutide, a widely used GLP-1 receptor agonist, in Chinese adults with T2D and obesity. The results will provide crucial evidence to inform clinical decision-making for this large patient population. METHODS: DREAMS-3 is a randomized, open-label phase 3 trial. Obese Participants (BMI >/= 28 kg/m(2)) diagnosed with T2D (/=10 % at week 32. RESULTS: A total of 349 participants were enrolled and randomized, the overall mean age was 42.4 years, 44.7 % of participants were male. The mean baseline duration of T2D was 1.8 years, and 39.5 % of participants were on metformin. The mean glycated hemoglobin was 8.0 %, body weight was 90.5 kg, BMI was 33.0 kg/m(2). Most participants had at least one comorbidity. The prevalence of some comorbidities (such as metabolic associated fatty liver disease, gout/hyperuricemia) showed strong association of BMI. CONCLUSION: DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Luo, Yingying AU - Luo Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Jiang, Hongwei AU - Jiang H AD - Department of Endocrinology, The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang, China. FAU - Shi, Bimin AU - Shi B AD - Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Cai, Hanqing AU - Cai H AD - Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China. FAU - Wang, Haifang AU - Wang H AD - Department of Endocrinology, Handan First Hospital, Handan, China. FAU - Li, Shu AU - Li S AD - Department of Endocrinology, Huizhou Municipal Central Hospital, Huizhou, China. FAU - Qiu, Wei AU - Qiu W AD - Department of Endocrinology, Huzhou Central Hospital, Huzhou, China. FAU - Li, Yunfeng AU - Li Y AD - Department of Endocrinology, Inner Mongolia People's Hospital, Hohhot, China. FAU - Zhou, Runze AU - Zhou R AD - Innovent Biologics, Inc., Suzhou, China. FAU - Deng, Huan AU - Deng H AD - Innovent Biologics, Inc., Suzhou, China. FAU - Guo, Qun AU - Guo Q AD - Innovent Biologics, Inc., Suzhou, China. FAU - Li, Li AU - Li L AD - Innovent Biologics, Inc., Suzhou, China. FAU - Pei, Lijuan AU - Pei L AD - Innovent Biologics, Inc., Suzhou, China. FAU - Zhang, Han Han AU - Zhang HH AD - Innovent Biologics, Inc., Suzhou, China. FAU - Qian, Lei AU - Qian L AD - Innovent Biologics, Inc., Suzhou, China. Electronic address: cnradium@126.com. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. LA - eng PT - Clinical Trial Protocol PT - Journal Article DEP - 20251117 PL - United States TA - Contemp Clin Trials JT - Contemporary clinical trials JID - 101242342 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 0 (Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - MB76Z4IBZ5 (mazdutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Obesity/drug therapy/complications MH - Male MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Female MH - Middle Aged MH - Adult MH - Clinical Trials, Phase III as Topic MH - Glycated Hemoglobin MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose MH - Metformin/therapeutic use MH - Peptides MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Mazdutide OT - Obesity OT - Semaglutide OT - Study design OT - Type 2 diabetes COIS- Declaration of competing interest Linong Ji, and Yingying Luo, Hongwei Jiang, Bimin Shi, Hanqing Cai, Haifang Wang, Shu Li, Wei Qiu, and Yunfeng Li report personal fees from Innovent Biologics, Inc., during the conduct of the study. Runze Zhou, Huan Deng, Qun Guo, Li Li, Lijuan Pei, HanHan Zhang, and Lei Qian are employees of Innovent Biologics, Inc. EDAT- 2025/11/20 00:29 MHDA- 2025/12/27 00:54 CRDT- 2025/11/19 19:19 PHST- 2025/06/26 00:00 [received] PHST- 2025/11/10 00:00 [revised] PHST- 2025/11/16 00:00 [accepted] PHST- 2025/12/27 00:54 [medline] PHST- 2025/11/20 00:29 [pubmed] PHST- 2025/11/19 19:19 [entrez] AID - S1551-7144(25)00344-1 [pii] AID - 10.1016/j.cct.2025.108150 [doi] PST - ppublish SO - Contemp Clin Trials. 2026 Jan;160:108150. doi: 10.1016/j.cct.2025.108150. Epub 2025 Nov 17. PMID- 41259721 OWN - NLM STAT- MEDLINE DCOM- 20251219 LR - 20251224 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 1 DP - 2026 Jan 1 TI - Metabolic Improvement Mediates the Causal Relationship Between GLP-1 Receptor Agonists and Myocardial Infarction: A Mendelian Randomization and Mediation Analysis Study. PG - 171-178 LID - 10.2337/dc25-1822 [doi] AB - OBJECTIVE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular benefits, but whether this is via metabolic improvements or direct effect remains controversial. This study aimed to explore the causal link between GLP-1RAs and myocardial infarction (MI) and quantify the contribution of metabolic improvements. RESEARCH DESIGN AND METHODS: Mendelian randomization (MR) was applied to assess the causal relationship between GLP-1RAs and MI, and two-step MR analysis was applied to quantify the mediating role of metabolic traits. The direct effect of GLP-1RAs on MI was evaluated by multivariate Mendelian randomization (MVMR). Genetic variants associated with GLP-1 receptor (GLP-1R) expression (proxying GLP-1RAs) were used as instrumental variables. Genome-wide association studies (GWAS) data for metabolic traits glycated hemoglobin (HbA1c), BMI, lipid profile, and blood pressure were sourced from the Million Veteran Program, serving as mediators. GWAS data for type 2 diabetes mellitus (T2DM) were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and data for MI were sourced from the UK Biobank/Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease (CARDIoGRAMplusC4D), serving as outcomes. All GWAS data were restricted to European ancestry. RESULTS: Higher GLP-1R expression was correlated with a lower risk of T2DM (odds ratio 0.94 [95% CI 0.92, 0.97]) and MI (0.97 [0.95, 1.00]). Metabolic improvements mediated this association: HbA1c (36.67% [3.89, 69.44]), BMI (28.86% [2.62, 55.10]), triglycerides (18.52% [1.47, 35.57]), HDL-cholesterol (18.28% [1.45, 35.12]), and systolic blood pressure (11.55% [0.33, 22.76]). No direct effect of GLP-1R expression on MI was observed after adjusting for metabolic traits (beta = -0.003, P = 0.12). CONCLUSIONS: GLP-1RAs protect against MI primarily through metabolic improvements, with no direct effect independent of these pathways. These findings support prioritizing metabolic improvements to reduce cardiovascular risk with GLP-1RAs. CI - (c) 2025 by the American Diabetes Association. FAU - Tong, Jingkai AU - Tong J AD - Department of Endocrinology, Tianjin First Central Hospital, Tianjin, China. FAU - Li, Nana AU - Li N AD - Teaching Research Department, Tianjin First Central Hospital, Tianjin, China. FAU - Hu, Fang AU - Hu F AUID- ORCID: 0009-0006-2750-7145 AD - Department of Cardiology, Tianjin First Central Hospital, Tianjin, China. FAU - Yue, Yingying AU - Yue Y AD - Clinical Laboratory, Tianjin First Central Hospital, Tianjin, China. LA - eng GR - 82202802/Foundation of China/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Myocardial Infarction/metabolism/genetics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Genome-Wide Association Study MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/genetics MH - Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Glycated Hemoglobin/metabolism MH - Mediation Analysis MH - Polymorphism, Single Nucleotide PMC - PMC12719715 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2025/11/19 18:27 MHDA- 2025/12/19 18:32 PMCR- 2025/11/19 CRDT- 2025/11/19 15:42 PHST- 2025/07/31 00:00 [received] PHST- 2025/10/24 00:00 [accepted] PHST- 2025/12/19 18:32 [medline] PHST- 2025/11/19 18:27 [pubmed] PHST- 2025/11/19 15:42 [entrez] PHST- 2025/11/19 00:00 [pmc-release] AID - 163853 [pii] AID - 251822 [pii] AID - 10.2337/dc25-1822 [doi] PST - ppublish SO - Diabetes Care. 2026 Jan 1;49(1):171-178. doi: 10.2337/dc25-1822. PMID- 41257737 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Nov 19 TI - Risk of all-cause death and pancreatic events following GLP-1 RA initiation in people with obesity or type 2 diabetes: observations from a federated research network. PG - 438 LID - 10.1186/s12933-025-02986-0 [doi] LID - 438 AB - BACKGROUND: Limited data are available on the risk of pancreatic adverse events among people with obesity or type 2 diabetes mellitus (T2DM) initiating glucagon-like peptide-1 receptor agonist (GLP-1 RA). METHODS: Retrospective study utilizing data from a federated research network (TriNetX). Adult people (>/= 18 years) with a diagnosis of obesity (body mass index >/= 30 kg/m(2)) or T2DM (ICD-10-CM: E11) between 2018 and 2024 were subdivided in two mutually exclusive cohorts: (1) GLP-1 RA Users; and (2) Non-GLP-1 RA Users. Primary outcomes were 1-year risk of all-cause death and a composite outcome (acute pancreatitis, chronic pancreatitis). Secondary outcomes included the individual components of the composite outcome and pancreatic cancer. Cox regression analyses were employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) before and after 1:1 propensity score matching (PSM). Sensitivity analyses stratified follow-up into early (first 6 months) and late (last 6 months) phases. Subgroup analyses were performed based on age (>/= 65 or < 65 years), sex, and the history of smoking and alcohol use, hypertriglyceridemia, cholelithiasis, heart failure, and chronic kidney disease. RESULTS: We identified 1,562,626 people who initiated treatment with GLP-1 RA (mean age 55.3 +/- 14.0 years; 59.2% female) and 18,652,572 those who did not (mean age 50.6 +/- 18.7 years; 54.5% female). Before PSM, GLP-1 RA Users were older, more frequently female, and exhibited a higher burden of endocrine, metabolic and gastrointestinal disorders. After PSM, GLP-1 RA use was associated with a substantially lower risk of all-cause death (HR 0.554, 95% CI 0.542-0.566), and small increased risk of the composite outcome (HR 1.062, 95% CI 1.023-1.102) and acute pancreatitis (HR 1.058, 95% CI 1.015-1.103), with no differences in chronic pancreatitis or pancreatic cancer. The excess risk of acute pancreatitis was more pronounced during the early phase of follow-up (first 6 months). Subgroup analyses showed a higher reduction in death and composite outcome among people aged < 65 years. Additional significant interactions were observed for all-cause death in females and in people with a history of smoking, alcohol use, heart failure, chronic kidney disease, or cholelithiasis. CONCLUSION: GLP-1 RA use was associated with substantially reduced all-cause death but a small increased risk of acute pancreatitis, particularly during early treatment. The survival benefit was more pronounced in younger people and those with cardiometabolic comorbidities, highlighting the need for a careful risk-benefit evaluation when prescribing GLP-1 RAs in high-risk individuals. CI - (c) 2025. The Author(s). FAU - Tartaglia, Enrico AU - Tartaglia E AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy. FAU - Bucci, Tommaso AU - Bucci T AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Perugia, Italy. FAU - Rossi, Michele AU - Rossi M AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy. AD - Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy. FAU - Rigutini, Andrea Galeazzo AU - Rigutini AG AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Perugia, Italy. FAU - Askarinejad, Amir AU - Askarinejad A AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK. AD - Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent,, UK. FAU - Nabrdalik, Katarzyna AU - Nabrdalik K AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. AD - Department of Internal Medicine, Diabetology and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland. FAU - Boriani, Giuseppe AU - Boriani G AD - Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy. AD - University of Modena and Reggio Emilia, Modena, Italy. FAU - Lip, Gregory Y H AU - Lip GYH AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool, UK. gregory.lip@liverpool.ac.uk. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. gregory.lip@liverpool.ac.uk. AD - Department of Cardiology, Lipidology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland. gregory.lip@liverpool.ac.uk. LA - eng PT - Journal Article PT - Observational Study DEP - 20251119 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cause of Death MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Incretins/adverse effects/therapeutic use MH - *Obesity/mortality/diagnosis/drug therapy MH - *Pancreatic Neoplasms/mortality/diagnosis MH - *Pancreatitis/mortality/diagnosis/chemically induced MH - Pancreatitis, Chronic/mortality/diagnosis/chemically induced MH - Retrospective Studies MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome PMC - PMC12628983 OTO - NOTNLM OT - Death OT - GLP-1 receptor agonists OT - Obesity OT - Pancreatic outcomes OT - Propensity score matching OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was conducted using de-identified data from the TriNetX Research Network. All patient data are anonymized in compliance with the Health Insurance Portability and Accountability Act (HIPAA) and US federal law. No patient-level identifiers are accessible within TriNetX. In accordance with these conditions, institutional review board (IRB) approval and informed consent were not required. Competing interests: G.Y.H.L. has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos, and Daiichi-Sankyo. No fees are directly received personally. All the disclosures happened outside the submitted work. He is a National Institute for Health and Care Research (NIHR) Senior Investigator Emeritus and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalized management of atrial fibrillation and stroke (grant agreement No 101136244), and ARISTOTELES project on artificial intelligence for management of chronic long-term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research and Innovation program. G.B. reported small speaker fees from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Janssen, and Sanofi outside of the submitted work. G.B. is the Principal Investigator of the ARISTOTELES project (Applying ARtificial Intelligence to define clinical trajectorieS for personalized predicTiOn and early deTEction of comorbidity and muLti-morbidity pattErnS) that received funding from the European Union within the Horizon 2020 research and innovation programme (grant no. 101080189). U.A. has received honoraria from Viatris, Grunenthal, Eli Lilly, Sanofi and Procter & Gamble for educational meetings, investigator-led funding from Proctor & Gamble and received sponsorship to attend educational meetings from Daiichi Sankyo and Sanofi. The other authors did not report conflicts of interest to disclose outside of the submitted work. EDAT- 2025/11/19 12:28 MHDA- 2025/11/19 12:29 PMCR- 2025/11/19 CRDT- 2025/11/19 08:19 PHST- 2025/08/26 00:00 [received] PHST- 2025/10/13 00:00 [accepted] PHST- 2025/11/19 12:29 [medline] PHST- 2025/11/19 12:28 [pubmed] PHST- 2025/11/19 08:19 [entrez] PHST- 2025/11/19 00:00 [pmc-release] AID - 10.1186/s12933-025-02986-0 [pii] AID - 2986 [pii] AID - 10.1186/s12933-025-02986-0 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Nov 19;24(1):438. doi: 10.1186/s12933-025-02986-0. PMID- 41255528 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Development of a risk prediction model for gastrointestinal adverse events associated with semaglutide administration in patients with type 2 diabetes mellitus. PG - 1684395 LID - 10.3389/fendo.2025.1684395 [doi] LID - 1684395 AB - OBJECTIVE: This study aims to identify the risk factors associated with gastrointestinal adverse events induced by semaglutide in patients with type 2 diabetes mellitus (T2DM) and to develop a predictive risk model. METHODS: A total of 215 patients with T2DM admitted to our hospital between June 2022 and December 2024 were enrolled. Participants were divided into two groups based on the presence (n = 41) or absence (n = 174) of gastrointestinal adverse events associated with semaglutide use. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for these adverse events. Subsequently, a nomogram was developed using R software to predict the likelihood of gastrointestinal adverse events in this patient population. The predictive performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration plots, and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: In a cohort of 215 patients with T2DM, 41 individuals (19.07%) experienced gastrointestinal adverse events attributed to semaglutide administration. Logistic regression analysis identified concomitant gastrointestinal disorders [95% confidence interval (CI): 2.074-9.808, P < 0.001], alcohol consumption (95% CI: 1.304-6.633, P = 0.009), and concurrent use of alpha-glucosidase inhibitors (95% CI: 1.368-6.460, P = 0.006) as independent risk factors for semaglutide-induced gastrointestinal adverse events in this population. The predictive model demonstrated an area under the ROC curve of 0.763 (95% CI: 0.691-0.836). Calibration assessment revealed a slope approximating unity, and the Hosmer-Lemeshow goodness-of-fit test indicated an adequate model fit (chi(2) = 5.633, P = 0.228). CONCLUSION: Patients with T2DM exhibit a significant incidence of gastrointestinal adverse events associated with semaglutide use. The presence of gastrointestinal comorbidities, alcohol consumption, and alpha-glucosidase inhibitor therapy are independent risk factors. The developed nomogram effectively predicts the likelihood of semaglutide-related gastrointestinal adverse events in this patient population. CI - Copyright (c) 2025 Yue, Hua, Zhu, Wang, Gu, Yuan, Jian, Chen and Meng. FAU - Yue, Deyong AU - Yue D AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. AD - Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China. FAU - Hua, Xuesheng AU - Hua X AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Zhu, Ling AU - Zhu L AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Wang, Jun AU - Wang J AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Gu, Lihua AU - Gu L AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Yuan, Zhengxia AU - Yuan Z AD - Nantong University Xinglin College, Nantong, Jiangsu, China. FAU - Jian, Wenle AU - Jian W AD - Nantong University Xinglin College, Nantong, Jiangsu, China. FAU - Chen, Yirong AU - Chen Y AD - General Surgery Department of Wuxi No.8 People's Hospital, Wuxi, Jiangsu, China. FAU - Meng, Guoliang AU - Meng G AD - Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China. LA - eng PT - Journal Article DEP - 20251103 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Female MH - Male MH - Middle Aged MH - Aged MH - Risk Factors MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Nomograms MH - Risk Assessment MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12620217 OTO - NOTNLM OT - alcohol OT - gastrointestinal adverse events OT - risk prediction model OT - semaglutide OT - type 2 diabetes mellitus OT - alpha-glucosidase inhibitors COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/11/19 06:32 MHDA- 2025/11/19 06:33 PMCR- 2025/11/03 CRDT- 2025/11/19 05:15 PHST- 2025/09/09 00:00 [received] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/19 06:33 [medline] PHST- 2025/11/19 06:32 [pubmed] PHST- 2025/11/19 05:15 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 10.3389/fendo.2025.1684395 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Nov 3;16:1684395. doi: 10.3389/fendo.2025.1684395. eCollection 2025. PMID- 41255131 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Efficacy and safety of glucagon-like peptide 1 receptor agonists across all health outcomes in type 2 diabetes: An umbrella review and evidence map of randomised controlled trials. PG - 1136-1149 LID - 10.1111/dom.70298 [doi] AB - AIM: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been established as effective treatments for type 2 diabetes, offering benefits beyond glycaemic control; however, their associations across multiple health outcomes remain insufficiently assessed. Thus, we conducted an umbrella review of meta-analyses of randomised controlled trials (RCTs) to comprehensively evaluate the broad spectrum of their effects. MATERIALS AND METHODS: We conducted a systematic search of PubMed/MEDLINE, Embase, CINAHL, and Google Scholar through June 13, 2025, to identify meta-analyses of RCTs assessing the effects of GLP-1RAs on various health outcomes, including cardiovascular, renal, metabolic, oncologic, gastrointestinal and other domains. Effect sizes were recalculated using random-effects models and converted to equivalent odds ratios (eORs) with 95% confidence intervals (CIs) for consistency. The methodological quality of each review was assessed using the AMSTAR 2, and the certainty of evidence for each association was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation framework (high, moderate, low or very low certainty). We preregistered our study protocol with PROSPERO (CRD420251112823). RESULTS: After applying predefined inclusion and exclusion criteria, 17 studies comprising 432 RCTs were included, covering 65 unique outcomes across 6 clinical domains. GLP-1RAs use was associated with reduced risks of heart failure (eOR, 0.71 [95% CI, 0.64-0.79]; low certainty) and peripheral artery disease (0.75 [0.67-0.84]; low certainty). Drug-specific analyses exhibited protective effects of liraglutide (eOR, 0.86 [95% CI, 0.80-0.91]), albiglutide (0.65 [0.47-0.89]), and dulaglutide (0.78 [0.68-0.90]) for major cardiovascular events, myocardial infarction and stroke, respectively. Renal outcomes indicated that GLP-1RAs use was associated with reducing the risk of kidney-specific composite outcomes (eOR, 0.76 [95% CI, 0.66-0.87]; low certainty), including nephropathy (0.74 [0.61-0.92]; low certainty) and albuminuria (0.73 [0.55-0.97]; very low certainty). GLP-1RAs were also associated with reductions in body weight (eOR, 0.46 [95% CI, 0.36-0.60]; moderate certainty) and glycated haemoglobin A1c (0.83 [0.71-0.97]; high certainty), but no substantial association with cancer risk was found. Gastrointestinal adverse events, including nausea (9.62 [4.60-20.10]; high certainty), dyspepsia (4.85 [1.52-15.45]; moderate certainty), and constipation (3.39 [1.54-7.47]; high certainty), were consistently reported. GLP-1RAs use was associated with higher lumbar spine (eOR, 1.99 [95% CI, 1.38-2.85]; low certainty) and hip-neck bone mineral density (1.79 [1.08-2.98]; low certainty). CONCLUSIONS: In this study, GLP-1RAs were associated with cardiovascular, renal, and metabolic benefits in type 2 diabetes without increasing cancer risk, though gastrointestinal adverse events were common. Our findings support the clinical use of GLP-1RAs, with attention to individual risk profiles and treatment tolerability. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yeo, Dongjin AU - Yeo D AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Jo, Yeona AU - Jo Y AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Jeong, Jinyoung AU - Jeong J AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Jeong, Yi Deun AU - Jeong YD AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Woo, Ho Geol AU - Woo HG AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Neurology, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Son, Yejun AU - Son Y AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Kim, Sunyoung AU - Kim S AD - Department of Family Medicine, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Rhee, Sang Youl AU - Rhee SY AUID- ORCID: 0000-0003-0119-5818 AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, South Korea. FAU - Yon, Dong Keon AU - Yon DK AUID- ORCID: 0000-0003-1628-9948 AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea. LA - eng GR - IITP-2024-RS-2024-00438239/Ministry of Science and ICT, South Korea/ GR - RS-2024-00509257/Ministry of Science and ICT, South Korea/ PT - Journal Article PT - Systematic Review DEP - 20251119 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Cardiovascular Diseases/prevention & control PMC - PMC12803684 OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonists OT - meta-analysis OT - randomised controlled trials OT - type 2 diabetes OT - umbrella review COIS- All the authors declared no competing interests. EDAT- 2025/11/19 06:32 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/19 03:33 PHST- 2025/10/15 00:00 [revised] PHST- 2025/09/11 00:00 [received] PHST- 2025/11/06 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/19 06:32 [pubmed] PHST- 2025/11/19 03:33 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70298 [pii] AID - 10.1111/dom.70298 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1136-1149. doi: 10.1111/dom.70298. Epub 2025 Nov 19. PMID- 41252314 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260715 IS - 1875-8908 (Electronic) IS - 1387-2877 (Linking) VI - 109 IP - 2 DP - 2026 Jan TI - Incidence of dementia in patients with type 2 diabetes using SGLT2 inhibitors versus GLP-1 receptor agonists or DPP-4 inhibitors: A systematic review and meta-analysis of cohort studies. PG - 594-603 LID - 10.1177/13872877251395086 [doi] AB - BackgroundIndividuals with type 2 diabetes mellitus (T2DM) have a higher incidence of dementia than those without the disease, possibly due to overlapping pathophysiological mechanisms. While glycemic control is essential to reduce dementia risk, recent studies suggest that newer antidiabetic agents, SGLT2i, GLP-1 RA, and DPP-4i, may offer neuroprotective effects.ObjectiveTo investigate the incidence of dementia in T2DM patients treated with SGLT2i compared to GLP-1 RA or DPP-4i.MethodsA systematic search of PubMed, Embase, and Cochrane databases was conducted for cohort studies published up to June 2025 that assessed dementia incidence in T2DM patients using SGLT2i versus DPP-4i or GLP-1 RA. Risk ratios (RRs) were calculated using the Mantel-Haenszel random-effects model, with variance estimated via restricted maximum likelihood in R version 4.3.0.ResultsTen studies met inclusion criteria. Four compared SGLT2i with GLP-1 RA, and seven with DPP-4i; one study contributed to both comparisons. The pooled RR for dementia in SGLT2i versus GLP-1 RA users was 0.91 (95% CI: 0.73-1.12; p < 0.003; I(2) = 78.7%). When comparing SGLT2i to DPP-4i, the RR was 0.39 (95% CI: 0.28-0.56; p < 0.00001; I(2) = 96.4%).ConclusionsUse of SGLT2i was associated with a lower risk of dementia compared to DPP-4i, with no significant difference observed when compared to GLP-1 RA. FAU - Milori, Pedro Henrique AU - Milori PH AUID- ORCID: 0000-0003-3307-0956 AD - Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Armelin, Larissa Maria AU - Armelin LM AUID- ORCID: 0000-0002-9389-3586 AD - Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Mutarelli, Antonio AU - Mutarelli A AUID- ORCID: 0000-0002-5595-9433 AD - Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Caramelli, Paulo AU - Caramelli P AUID- ORCID: 0000-0002-4786-6990 AD - Behavioral and Cognitive Neurology Unit, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20251118 PL - United States TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Cohort Studies MH - *Dementia/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use OTO - NOTNLM OT - Alzheimer's disease OT - dementia OT - diabetes mellitus OT - dipeptidyl-peptidase IV inhibitors OT - glucagon-like peptide-1 receptor agonists OT - meta-analysis OT - sodium-glucose transporter 2 inhibitors COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Paulo Caramelli: Preparation of CME materials and speaker in symposium sponsored by Ache, Biogen, Danone, Fleury, Lilly, Lundbeck, Novo Nordisk and Pratti-Donaduzzi. Consulting activities for para Ache, Danone and Knight Therapeutics. Investigator in clinical trials sponsored by Passage Bio and Roche.Paulo Caramelli is an Editorial Board Member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review. EDAT- 2025/11/18 18:30 MHDA- 2026/01/20 07:43 CRDT- 2025/11/18 13:22 PHST- 2026/01/20 07:43 [medline] PHST- 2025/11/18 18:30 [pubmed] PHST- 2025/11/18 13:22 [entrez] AID - 10.1177/13872877251395086 [doi] PST - ppublish SO - J Alzheimers Dis. 2026 Jan;109(2):594-603. doi: 10.1177/13872877251395086. Epub 2025 Nov 18. PMID- 41251628 OWN - NLM STAT- MEDLINE DCOM- 20260702 LR - 20260919 IS - 1537-2677 (Electronic) IS - 0740-9303 (Print) IS - 0740-9303 (Linking) VI - 42 IP - 4 DP - 2026 Jul-Aug 01 TI - Periorbital Changes Following Glucagon-Like Peptide-1 Receptor Agonist Use: A Retrospective Cohort Study of Oculofacial Complications and Interventions. PG - 414-419 LID - 10.1097/IOP.0000000000003129 [doi] AB - PURPOSE: The purpose of this study is to evaluate whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with periorbital changes in patients with type 2 diabetes mellitus (T2DM) or obesity. METHODS: A retrospective cohort study was conducted using the TriNetX Research Network database. Patients with T2DM treated with insulin or other antidiabetic agents and who were GLP-1RA naive served as the T2DM control group. The obesity control group included patients with obesity (body mass index >/=30 kg/m 2 ) who neither had bariatric surgery nor T2DM and were GLP-1RA naive. Study groups included patients with T2DM or obesity treated with GLP-1RAs. Rates of blepharoptosis, brow ptosis, dermatochalasis, ectropion, and entropion were recorded alongside their respective rates of surgical repair as well as the frequency of rhytidectomy and botulinum A toxin use. Outcomes were assessed at 3 and 20 years postdrug approval for the obesity and T2DM study groups, respectively. RESULTS: Patients with T2DM using any GLP-1RA were significantly more likely to develop brow ptosis ( p < 0.001) and receive botulinum toxin A ( p = 0.001) compared to controls. Patients with obesity using a GLP-1RA were significantly more likely to develop brow ptosis ( p = 0.004), dermatochalasis ( p < 0.001), and receive botulinum toxin A ( p < 0.001). Patients with obesity on a GLP-1RA were significantly more likely to undergo brow ptosis repair ( p = 0.001), blepharoptosis repair ( p < 0.001), blepharoplasty ( p < 0.001), and rhytidectomy ( p = 0.011) compared to controls. CONCLUSIONS: GLP-1RA use by patients with obesity or T2DM resulted in significant periorbital changes and subsequent repair. When compared to their respective controls, patients using GLP-1RAs for obesity observed more periorbital changes than those with TD2M, likely secondary to excess adipose tissue accumulation and loss. CI - Copyright (c) 2025 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. FAU - Saffari, Persiana S AU - Saffari PS AD - Division of Ophthalmic Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, U.S.A. FAU - Davila, Natalia AU - Davila N AD - Division of Ophthalmic Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, U.S.A. AD - Division of Oculoplastics, University of Texas Medical Branch, Galveston, Texas, U.S.A. FAU - Pradeep, Tejus AU - Pradeep T AD - Division of Ophthalmic Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, U.S.A. FAU - Wong, Brian AU - Wong B AD - Division of Oculoplastics, University of Texas Medical Branch, Galveston, Texas, U.S.A. FAU - Lee, Wendy W AU - Lee WW AD - Division of Ophthalmic Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, U.S.A. LA - eng GR - P30 EY014801/EY/NEI NIH HHS/United States GR - UL1 TR001439/TR/NCATS NIH HHS/United States GR - P30EY014801/NIH Core Grant/ PT - Journal Article DEP - 20251117 PL - United States TA - Ophthalmic Plast Reconstr Surg JT - Ophthalmic plastic and reconstructive surgery JID - 8508431 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/complications/drug therapy MH - Aged MH - Blepharoptosis/chemically induced MH - Rhytidoplasty PMC - PMC12743635 MID - NIHMS2129173 EDAT- 2025/11/18 12:28 MHDA- 2026/07/03 03:37 PMCR- 2025/12/29 CRDT- 2025/11/18 10:23 PHST- 2026/07/03 03:37 [medline] PHST- 2025/11/18 12:28 [pubmed] PHST- 2025/11/18 10:23 [entrez] PHST- 2025/12/29 00:00 [pmc-release] AID - 00002341-202607000-00008 [pii] AID - 10.1097/IOP.0000000000003129 [doi] PST - ppublish SO - Ophthalmic Plast Reconstr Surg. 2026 Jul-Aug 01;42(4):414-419. doi: 10.1097/IOP.0000000000003129. Epub 2025 Nov 17. PMID- 41251033 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260323 IS - 1528-1167 (Electronic) IS - 0013-9580 (Linking) VI - 67 IP - 3 DP - 2026 Mar TI - Seizure recurrence after GLP-1 receptor agonist initiation in adults with epilepsy. PG - 1246-1255 LID - 10.1111/epi.70022 [doi] AB - OBJECTIVE: To examine whether initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with seizure recurrence and related outcomes in adults with epilepsy and type 2 diabetes. METHODS: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX Research Network (January 2003-August 2025), including adults >/=18 years with >/=3 epilepsy or recurrent seizure diagnoses. Patients initiating a GLP-1 RA (exenatide, liraglutide, dulaglutide, lixisenatide, semaglutide, or tirzepatide) without prior comparator therapy were compared with those initiating other glucose-lowering agents (sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase 4 inhibitors, sulfonylureas, or insulin) without GLP-1 RA exposure. Propensity score matching (1:1) was performed on 82 covariates, yielding 8688 matched pairs. Outcomes were assessed using Cox proportional hazards models. RESULTS: After matching, the mean age was 52.6 years, and 67.6% were female. Median follow-up was 514 days (interquartile range [IQR] 671) for GLP-1 RA initiators and 415 days (IQR 769) for comparators. GLP-1 RA initiation was associated with lower risk of seizure recurrence (HR .82, 95% confidence interval [CI] .78-.86; RD -2.1%), hospitalization (HR .35, 95% CI .29-.43; RD -2.6%), and all-cause mortality (HR .40, 95% CI .34-.47; RD -4.8%). Associations with status epilepticus (HR .75, 95% CI .66-.85; RD -.7%) and ICU admission (HR .82, 95% CI .69-.96; RD -.3%) were smaller; the latter was not statistically significant. SIGNIFICANCE: In this large multinational cohort, GLP-1 RA initiation was associated with reduced risks of seizure recurrence, hospitalization, and mortality compared with other glucose-lowering therapies. These hypothesis-generating findings warrant confirmation in prospective studies before translation into clinical practice. CI - (c) 2025 International League Against Epilepsy. FAU - AbuAlrob, Majd A AU - AbuAlrob MA AUID- ORCID: 0000-0002-9707-9266 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. FAU - Hussein, Abdullah AU - Hussein A AUID- ORCID: 0000-0002-2408-2691 AD - Department of Internal Medicine, Virtua Health, Camden, USA. FAU - Abdellatif, Rand AU - Abdellatif R AUID- ORCID: 0000-0001-5879-1990 AD - Department of Internal Medicine, Jenin Governmental Hospital, Palestinian Health Ministry, Nablus, Palestine. FAU - Itbaisha, Adham AU - Itbaisha A AUID- ORCID: 0009-0007-2630-0107 AD - Department of Internal Medicine, Jenin Governmental Hospital, Palestinian Health Ministry, Nablus, Palestine. FAU - Zammar, Khaled AU - Zammar K AUID- ORCID: 0009-0006-5530-1136 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. FAU - Mesraoua, Boulenouar AU - Mesraoua B AUID- ORCID: 0000-0001-8625-7365 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. LA - eng PT - Journal Article DEP - 20251118 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Recurrence MH - Adult MH - *Epilepsy/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Seizures/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Cohort Studies OTO - NOTNLM OT - GLP-1 receptor agonists OT - epilepsy OT - real-world evidence OT - seizure recurrence OT - type 2 diabetes EDAT- 2025/11/18 06:26 MHDA- 2026/03/23 19:54 CRDT- 2025/11/18 05:13 PHST- 2025/10/31 00:00 [revised] PHST- 2025/08/22 00:00 [received] PHST- 2025/11/03 00:00 [accepted] PHST- 2026/03/23 19:54 [medline] PHST- 2025/11/18 06:26 [pubmed] PHST- 2025/11/18 05:13 [entrez] AID - 10.1111/epi.70022 [doi] PST - ppublish SO - Epilepsia. 2026 Mar;67(3):1246-1255. doi: 10.1111/epi.70022. Epub 2025 Nov 18. PMID- 41250965 OWN - NLM STAT- MEDLINE DCOM- 20251118 LR - 20260811 IS - 1478-3231 (Electronic) IS - 1478-3223 (Print) IS - 1478-3223 (Linking) VI - 45 IP - 12 DP - 2025 Dec TI - GLP-1RA and Liver Fibrosis Progression in MASLD and Type 2 Diabetes: Target Trial Emulation Using Propensity Score Matching. PG - e70447 LID - 10.1111/liv.70447 [doi] LID - e70447 AB - BACKGROUND AND AIMS: GLP-1 receptor agonists (GLP-1RA) are widely used in type 2 diabetes mellitus (T2DM) and may confer hepatoprotective effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Their impact on liver fibrosis progression in real-world clinical settings remains unclear. This study evaluated the link between GLP-1RA use and liver fibrosis progression in T2DM patients with early-stage MASLD. METHODS: We conducted a retrospective cohort study emulating a target trial using electronic health records from the Mass General Brigham (MGB) system between 2010 and 2023. Adults with MASLD and T2DM who initiated GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy and had baseline Fibrosis-4 (FIB-4) scores < 2.67 were included. Propensity score matching (1:1) was applied to balance baseline covariates between groups. The primary outcome was progression to high-risk FIB-4 (> 2.67), confirmed by two consecutive values >/= 90 days apart within a one-year period. The secondary outcome was a composite of cirrhosis, hepatic decompensation, hepatocellular carcinoma, or liver transplantation. RESULTS: A total of 2238 matched pairs were analysed. GLP-1RA use was associated with a lower risk of fibrosis progression compared to DPP-4i (incidence rate 3.25 vs. 4.29 per 100 person-years; HR 0.75, 95% CI 0.65-0.87). Results were consistent in per-protocol (HR 0.80) and landmark sensitivity analyses. The risk reduction was also observed across subgroups, including those with low baseline FIB-4, BMI < 30, and users of statins, aspirin or metformin. No significant difference was found in secondary liver-related outcomes (HR 0.98, 95% CI 0.72-1.34). CONCLUSION: GLP-1RA use significantly reduced the risk of liver fibrosis progression in patients with MASLD and T2DM, supporting its potential role in early disease modification. CI - (c) 2025 The Author(s). Liver International published by John Wiley & Sons Ltd. FAU - Choi, Jonggi AU - Choi J AD - Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Kamath, Tushar AU - Kamath T AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Nguyen, Vy H AU - Nguyen VH AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Przybyszewski, Eric AU - Przybyszewski E AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Song, Jiunn AU - Song J AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Carroll, Allison AU - Carroll A AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Michta, Megan AU - Michta M AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Almazan, Erik AU - Almazan E AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Simon, Tracey G AU - Simon TG AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Chung, Raymond T AU - Chung RT AD - Liver Center, Gastroenterology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - R01 CA255621/CA/NCI NIH HHS/United States GR - U01 CA288375/CA/NCI NIH HHS/United States GR - U01 CA288375/NH/NIH HHS/United States GR - R01 CA255621/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Liver Cirrhosis/etiology/prevention & control/epidemiology MH - Middle Aged MH - Retrospective Studies MH - Disease Progression MH - Propensity Score MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Fatty Liver/complications/drug therapy PMC - PMC12625798 OTO - NOTNLM OT - GLP-1RA OT - MASLD OT - liver fibrosis COIS- Access to Data and Data Analysis: Jonggi Choi and Raymond T. Chung had full access to the data used in this study and took responsibility for its integrity and the accuracy of the analyses. Jonggi Choi received a Gilead Sciences research grant. No other authors have disclosures. EDAT- 2025/11/18 06:26 MHDA- 2025/11/18 06:27 PMCR- 2025/11/18 CRDT- 2025/11/18 04:53 PHST- 2025/11/03 00:00 [revised] PHST- 2025/09/15 00:00 [received] PHST- 2025/11/07 00:00 [accepted] PHST- 2025/11/18 06:27 [medline] PHST- 2025/11/18 06:26 [pubmed] PHST- 2025/11/18 04:53 [entrez] PHST- 2025/11/18 00:00 [pmc-release] AID - LIV70447 [pii] AID - 10.1111/liv.70447 [doi] PST - ppublish SO - Liver Int. 2025 Dec;45(12):e70447. doi: 10.1111/liv.70447. PMID- 41249646 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260408 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 3 DP - 2026 Feb TI - Effects of Glucagon-Like Peptide-1 Receptor Agonists After Treatment Withdrawal: A Systematic Review and Meta-Analysis. PG - 807-818 LID - 10.1007/s11606-025-09950-4 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively promote weight reduction and improve glycemic control, blood pressure, and lipid profiles in individuals with overweight or obesity. This systematic review and meta-analysis evaluates the durability of these therapeutic benefits following treatment discontinuation. METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP from inception to June 2024, to identify randomized controlled trials that assessed the effects of GLP-1RAs with a follow-up period of at least six months after treatment discontinuation. The outcomes were changes in weight, body mass index (BMI), waist circumference (WC), glycemia, blood pressure, and lipid profiles. RESULTS: We screened 10,670 studies and ultimately identified 5 eligible studies, encompassing 719 patients. Compared to the control group, GLP-1RAs were associated with significant reductions in weight (mean difference (MD) = -5.70 kg, 95% confidence interval (CI): -9.52 to -1.88), BMI (MD = -2.94 kg/m(2), 95% CI: -5.60 to -0.28), WC (MD = -3.66 cm, 95% CI: -4.89 to -2.43), glycated hemoglobin A1c (HbA1c) (standardized mean difference (SMD) = -0.73, 95% CI: -1.14 to -0.32), and systolic blood pressure (SBP) (MD = -3.62 mm Hg, 95% CI: -5.51 to -1.73) after cessation of therapy. After discontinuation, there was a pronounced rebound in weight (MD = 4.13 kg, 95% CI: 1.60 to 6.65), BMI (MD = 0.84 kg/m(2), 95% CI: 0.37 to 1.32), WC (MD = 3.64 cm, 95% CI: 2.27 to 5.01), and HbA1c (SMD = 0.69, 95% CI: 0.50 to 0.89). From study baseline to the end of follow-up, GLP-1RAs treatment resulted in statistically significant decreases in weight (MD = -2.32 kg, 95% CI: -4.21 to -0.43) and BMI (MD = -0.82 kg/m(2), 95% CI: -1.47 to -0.17). CONCLUSIONS: This meta-analysis demonstrated that although statistically significant weight reduction persists after GLP-1RAs discontinuation, the clinical significance and durability of this effect are limited. To achieve sustained therapeutic benefits, continued treatment with these agents may be necessary. CI - (c) 2025. The Author(s), under exclusive licence to Society of General Internal Medicine. FAU - Zhou, Lei AU - Zhou L AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China. FAU - Wei, Aiming AU - Wei A AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China. FAU - Pan, Chongsheng AU - Pan C AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China. FAU - Zhang, Jing AU - Zhang J AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China. FAU - Hu, Peiqun AU - Hu P AD - School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610000, Sichuan, China. FAU - Li, Xiaoyi AU - Li X AD - School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. FAU - Zhao, Xinyu AU - Zhao X AD - School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. FAU - Hu, Yushi AU - Hu Y AD - School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610000, Sichuan, China. FAU - He, Benxiang AU - He B AD - Sichuan Academy of Chinese Medicine Science, Chengdu, Sichuan, China. FAU - Liu, Yunlu AU - Liu Y AD - School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610000, Sichuan, China. FAU - Dan, Ranlin AU - Dan R AD - School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610000, Sichuan, China. FAU - Xu, Wen AU - Xu W AD - Affiliated Sport Hospital of Chengdu Sport University, Chengdu, Sichuan, China. FAU - Liang, Xinyue AU - Liang X AD - Affiliated Sport Hospital of Chengdu Sport University, Chengdu, Sichuan, China. FAU - Pan, Xiongfei AU - Pan X AD - Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Zhu, Tianmin AU - Zhu T AD - School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China. tianminzhu@cdutcm.edu.cn. FAU - Li, Hui AU - Li H AUID- ORCID: 0000-0002-6171-4934 AD - School of Preclinical Medicine, Chengdu University, Chengdu, 610000, Sichuan, China. ttlihui@163.com. FAU - Wang, Yang AU - Wang Y AD - School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610000, Sichuan, China. wangyang@cdsu.edu.cn. AD - Affiliated Sport Hospital of Chengdu Sport University, Chengdu, Sichuan, China. wangyang@cdsu.edu.cn. LA - eng GR - SCZJJCC 02/the Innovation Project of Key Laboratory for Sports Medicine of Sichuan Province & General Administration of Sport/ GR - 22KJCX009/the Scientific and Technological Innovation Project of the General Administration of Sport of China/ GR - 2022NSFSC1529/the Natural Science Foundation of Sichuan Province/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20251117 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic/methods MH - *Obesity/drug therapy MH - *Withholding Treatment/trends MH - *Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Blood Glucose/drug effects PMC - PMC12960891 OTO - NOTNLM OT - GLP-1 receptor agonists OT - meta-analysis OT - obesity OT - overweight COIS- Declarations:. Conflict of Interest:: The authors declare that they do not have a conflict of interest. Human Ethics and Consent to Participate:: Not applicable. EDAT- 2025/11/18 00:28 MHDA- 2026/03/07 01:37 PMCR- 2027/02/01 CRDT- 2025/11/17 23:51 PHST- 2025/01/29 00:00 [received] PHST- 2025/09/15 00:00 [accepted] PHST- 2026/03/07 01:37 [medline] PHST- 2025/11/18 00:28 [pubmed] PHST- 2025/11/17 23:51 [entrez] PHST- 2027/02/01 00:00 [pmc-release] AID - 10.1007/s11606-025-09950-4 [pii] AID - 9950 [pii] AID - 10.1007/s11606-025-09950-4 [doi] PST - ppublish SO - J Gen Intern Med. 2026 Feb;41(3):807-818. doi: 10.1007/s11606-025-09950-4. Epub 2025 Nov 17. PMID- 41247648 OWN - NLM STAT- MEDLINE DCOM- 20260422 LR - 20260422 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 26 IP - 3 DP - 2026 May TI - Cardiovascular Pharmacotherapy and Glucose Metabolism: The Good, the Bad and the Unsightly. PG - 269-281 LID - 10.1007/s40256-025-00777-2 [doi] AB - Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are two prevalent and interrelated conditions that share common pathophysiological mechanisms, including insulin resistance and chronic inflammation. While newer glucose-lowering agents such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in improving insulin sensitivity and cardiovascular outcomes, a number of commonly used cardiovascular pharmacologic agents such as thiazide diuretics, beta-blockers, and statins have been associated with adverse effects on glucose metabolism, including increased insulin resistance and elevated risk of T2DM. This narrative review examines both the detrimental and beneficial metabolic effects of various cardiovascular drugs, explores their underlying mechanisms, and discusses the implications for the prevention and management of metabolic dysfunction in patients at high cardiometabolic risk. A clearer understanding of these effects is crucial for optimizing therapeutic strategies in individuals with or at risk for both CVD and T2DM. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Bianchettin, Rosana G AU - Bianchettin RG AD - Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. FAU - Poirier, Paul AU - Poirier P AD - Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite Laval, 2725 Chemin Ste-Foy, Quebec, QC, G1V 4G5, Canada. AD - Faculte de Pharmacie, Universite Laval, Quebec, QC, Canada. FAU - Lopez-Jimenez, Francisco AU - Lopez-Jimenez F AD - Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. FAU - Lavie, Carl J AU - Lavie CJ AD - John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, USA. FAU - Piche, Marie-Eve AU - Piche ME AUID- ORCID: 0000-0001-5349-8234 AD - Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite Laval, 2725 Chemin Ste-Foy, Quebec, QC, G1V 4G5, Canada. marie-eve.piche.1@ulaval.ca. AD - Faculte de Medecine, Universite Laval, Quebec, QC, Canada. marie-eve.piche.1@ulaval.ca. LA - eng PT - Journal Article PT - Review DEP - 20251117 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Hypoglycemic Agents) RN - 0 (Cardiovascular Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - IY9XDZ35W2 (Glucose) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Cardiovascular Diseases/drug therapy/metabolism MH - Insulin Resistance MH - *Hypoglycemic Agents/adverse effects/therapeutic use/pharmacology MH - *Cardiovascular Agents/adverse effects/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucose/metabolism MH - *Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Declarations. Conflict of Interest: Rosana G. Bianchettin, Paul Poirier, Francisco Lopez Jimenez, Carl J. Lavie, and Marie-Eve Piche declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Authors' Contributions: All authors contributed to writing and reviewing this manuscript. Data Availability Statement: Data sharing not applicable to this manuscript as no datasets were generated for it. Ethics Approval: Not applicable. Code Availability: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. EDAT- 2025/11/17 17:29 MHDA- 2026/04/22 18:32 CRDT- 2025/11/17 11:17 PHST- 2025/04/17 00:00 [received] PHST- 2025/11/03 00:00 [accepted] PHST- 2026/04/22 18:32 [medline] PHST- 2025/11/17 17:29 [pubmed] PHST- 2025/11/17 11:17 [entrez] AID - 10.1007/s40256-025-00777-2 [pii] AID - 10.1007/s40256-025-00777-2 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2026 May;26(3):269-281. doi: 10.1007/s40256-025-00777-2. Epub 2025 Nov 17. PMID- 41246137 OWN - NLM STAT- MEDLINE DCOM- 20251117 LR - 20251120 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2025 DP - 2025 TI - Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal and Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Retrospective Study. PG - 2663671 LID - 10.1155/jdr/2663671 [doi] LID - 2663671 AB - AIMS: This research explores the impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) on key risk factors associated with kidney and cardiovascular diseases in Indigenous (Aboriginal and/or Torres Strait Islander) and non-Indigenous adults living with Type 2 diabetes, receiving care at a regional health facility in North Queensland, Australia. METHODS: This retrospective study included patients who attended the diabetes clinic at a regional hospital between January 2016 and January 2020. Data was extracted from electronic medical records. Basic demographic characteristics along with blood pressure, body weight, BMI, urine albumin creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate (eGFR), HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels were retrieved from initial presentation, 6 months, and 12 months post. Data was analyzed using IBM SPSS 28 with appropriate statistical tests applied. RESULTS: The study involved a total of 164 patients. GLP-1RA use resulted in a significant reduction of HbA1c between 0 and 6 months (8.7%-7.9%, p < 0.01) and 0 and 12 months (8.7%-8.1%, p < 0.01). Significant reduction in weight between 0 and 6 months (115.9-114.0 kg, p < 0.001), 6 and 12 months (114.0-112.5 kg, p = 0.004), and 0 and 12 months (115.9-112.5 kg, p < 0.001) was also seen. However, there were no statistically significant differences in all measures of lipid profile and no significant changes in UACR and eGFR. CONCLUSIONS: This study affirms the effectiveness of GLP-1RAs as a glycemic control agent with an additional benefit of weight reduction across a 12-month period in adult T2DM patients. No effect on other cardiovascular parameters apart from weight or renal risk factors was observed. Further investigation into the influence of GLP-1RAs on these would be beneficial. CI - Copyright (c) 2025 Daniel Yuan et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Yuan, Daniel AU - Yuan D AD - Translational Research in Endocrinology and Diabetes (TREAD), College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. FAU - Vangaveti, Venkat N AU - Vangaveti VN AD - Translational Research in Endocrinology and Diabetes (TREAD), College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. AD - Townsville University Hospital, Townsville, Queensland, Australia. FAU - Arojojoye, Oluwatosin A AU - Arojojoye OA AUID- ORCID: 0000-0002-2300-0658 AD - Translational Research in Endocrinology and Diabetes (TREAD), College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. FAU - Malabu, Usman H AU - Malabu UH AUID- ORCID: 0000-0003-4899-7228 AD - Translational Research in Endocrinology and Diabetes (TREAD), College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. AD - Townsville University Hospital, Townsville, Queensland, Australia. LA - eng PT - Journal Article DEP - 20251104 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Cardiovascular Diseases/prevention & control MH - Glycated Hemoglobin/metabolism MH - Heart Disease Risk Factors MH - Glomerular Filtration Rate/drug effects MH - *Diabetic Nephropathies/prevention & control MH - Risk Factors MH - Adult MH - Blood Glucose/drug effects/metabolism MH - Kidney/drug effects PMC - PMC12614731 OTO - NOTNLM OT - Australia OT - North Queensland OT - Type 2 diabetes mellitus OT - cardiovascular OT - glucagon-like peptide-1 receptor agonist OT - renal COIS- The authors declare no conflicts of interest. EDAT- 2025/11/17 17:29 MHDA- 2025/11/17 17:30 PMCR- 2025/11/04 CRDT- 2025/11/17 06:26 PHST- 2024/09/10 00:00 [received] PHST- 2025/08/25 00:00 [revised] PHST- 2025/09/23 00:00 [accepted] PHST- 2025/11/17 17:30 [medline] PHST- 2025/11/17 17:29 [pubmed] PHST- 2025/11/17 06:26 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 10.1155/jdr/2663671 [doi] PST - epublish SO - J Diabetes Res. 2025 Nov 4;2025:2663671. doi: 10.1155/jdr/2663671. eCollection 2025. PMID- 41243611 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Real-world evaluation of clinical outcomes in Dutch patients with type 2 diabetes treated with oral semaglutide: A retrospective, observational cohort study using the PHARMO data network. PG - 895-905 LID - 10.1111/dom.70251 [doi] AB - AIM: A retrospective observational cohort study, in the Netherlands, evaluated clinical outcomes with oral semaglutide. METHODS: Glucagon-like peptide-1 receptor agonists (GLP-1ra) naive type 2 diabetes (T2D) patients who initiated oral semaglutide between 1 January 2020 and 31 December 2022 were identified from the PHARMO Data Network. Change from baseline was evaluated in glycated haemoglobin (HbA1c), body weight, blood lipids, and blood pressure over 12 months of follow-up. Outcomes were analysed in patients with at least a baseline and >/=1 follow-up measurement, using mixed-effect models for repeated measurements. RESULTS: Of 932 T2D patients initiating oral semaglutide identified, 731 were GLP-1ra naive (mean [standard deviation] age, 62 [11] years; baseline HbA1c, 70 [14] mmol/mol; baseline body weight, 102 [19] kg). In 320 patients with an average follow-up of 8.1 months the mean (95% confidence interval) change in HbA1c from baseline was -16.05 (-12.57, -19.54) mmol/mol at 12 months, of whom 70% achieved personalized HbA1c targets. Body weight was reduced by -4.73 (-3.63, -5.83) kg at 12 months in 260 patients over an average of 8.2 months follow-up. Minimal changes were observed in blood lipid parameters and diastolic blood pressure, with moderate changes in systolic blood pressure. CONCLUSIONS: Among Dutch T2D patients who were GLP-1ra naive and initiated oral semaglutide, significant reductions in HbA1c and body weight were observed over 12 months, consistent with prospective clinical trial data. These results provide a first-look insight into real-world glycaemic control and body weight reduction in early adopters of oral semaglutide in the Netherlands. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Postema, Abigail AU - Postema A AUID- ORCID: 0009-0006-4897-827X AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Gaspersz, Jordy AU - Gaspersz J AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Baak, Brenda N AU - Baak BN AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Huisman, Eline L AU - Huisman EL AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Hoogstraten, Charlotte AU - Hoogstraten C AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Hagelund, Lise Meinicke AU - Hagelund LM AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Penning-van Beest, Fernie J A AU - Penning-van Beest FJA AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Overbeek, Jetty A AU - Overbeek JA AD - The PHARMO Institute, Utrecht, The Netherlands. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Observational Study DEP - 20251117 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Lipids) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Retrospective Studies MH - Netherlands/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Administration, Oral MH - Treatment Outcome MH - Blood Glucose/analysis MH - Blood Pressure/drug effects MH - Body Weight/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Lipids/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803591 OTO - NOTNLM OT - body weight OT - glucagon-like peptide-1 receptor agonist OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- Abigail Postema, Jordy Gaspersz, Brenda N. Baak, Fernie J. A. Penning-van Beest, and Jetty A. Overbeek are employees of the PHARMO Institute, part of Lumanity. This independent research institute performs financially supported studies for government and related health care authorities and several pharmaceutical companies. Eline L. Huisman, Charlotte Hoogstraten, and Lise Meinicke Hagelund are employees and shareholders of Novo Nordisk. EDAT- 2025/11/17 09:07 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/17 03:42 PHST- 2025/10/14 00:00 [revised] PHST- 2025/07/25 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/17 09:07 [pubmed] PHST- 2025/11/17 03:42 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70251 [pii] AID - 10.1111/dom.70251 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):895-905. doi: 10.1111/dom.70251. Epub 2025 Nov 17. PMID- 41243582 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260803 IS - 1532-6535 (Electronic) IS - 0009-9236 (Linking) VI - 119 IP - 2 DP - 2026 Feb TI - Advances in Incretin-Based Therapies for MAFLD: Mechanisms and Clinical Evidence. PG - 336-349 LID - 10.1002/cpt.70131 [doi] AB - The global prevalence and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD), including its progressive form metabolic dysfunction-associated steatohepatitis (MASH), are steadily rising, making them the most common chronic liver diseases worldwide. However, therapeutic options for MAFLD are currently limited. Glucolipid dysregulation drives MAFLD pathogenesis through intertwined glucose metabolic imbalance and lipid accumulation. Patients with type 2 diabetes mellitus (T2DM) are particularly prone to developing MASH and are at a higher risk of progressing to cirrhosis and hepatocellular carcinoma. The coexistence of MAFLD and T2DM correlates with clinical prognosis and elevates the risk of extrahepatic complications. Given the close association between MAFLD and T2DM, glucagon-like peptide-1 receptor agonists (GLP-1RAs), which have been approved for the treatment of T2DM and obesity, were the first to be investigated in patients with MAFLD/MASH. Recently, beyond GLP-1RAs, novel combination agents integrating glucose-dependent insulinotropic peptide receptor (GIPR) and/or glucagon receptor (GCR) agonists have also been explored. A large number of phase II randomized clinical trials have demonstrated significant improvements in body weight, insulin resistance, and liver parameters. Thus, GLP-1RAs and dual/triple agonists are promising for MAFLD/MASH, especially in those with obesity or T2DM. This study explores mechanisms and clinical evidence of incretin-based therapies for MAFLD by targeting its core pathogenesis-glucolipid disorders. With growing evidence, it also forecasts the broad clinical prospects on MAFLD treatment. CI - (c) 2025 The Author(s). Clinical Pharmacology & Therapeutics (c) 2025 American Society for Clinical Pharmacology and Therapeutics. FAU - Dong, Wenqi AU - Dong W AUID- ORCID: 0009-0005-3319-8089 AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Haiming AU - Zhang H AUID- ORCID: 0000-0001-7669-5353 AD - Department of Integrated Traditional Chinese and Western Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Mu, Shaowei AU - Mu S AUID- ORCID: 0009-0004-7810-0690 AD - Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China. FAU - Shi, Shuyi AU - Shi S AUID- ORCID: 0009-0001-2265-0114 AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Junli AU - Zhang J AUID- ORCID: 0000-0003-2792-3094 AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Keshu AU - Xu K AUID- ORCID: 0009-0009-4600-0034 AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng GR - 82370589/National Natural Science Foundation of China/ GR - 82270609/National Natural Science Foundation of China/ GR - 82105009/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251117 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Fatty Liver/drug therapy/epidemiology MH - *Non-alcoholic Fatty Liver Disease/drug therapy/epidemiology MH - Hypoglycemic Agents/therapeutic use EDAT- 2025/11/17 09:08 MHDA- 2026/01/20 07:44 CRDT- 2025/11/17 03:34 PHST- 2025/06/08 00:00 [received] PHST- 2025/10/24 00:00 [accepted] PHST- 2026/01/20 07:44 [medline] PHST- 2025/11/17 09:08 [pubmed] PHST- 2025/11/17 03:34 [entrez] AID - 10.1002/cpt.70131 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 Feb;119(2):336-349. doi: 10.1002/cpt.70131. Epub 2025 Nov 17. PMID- 41239945 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20251203 IS - 1754-9485 (Electronic) IS - 1754-9477 (Linking) VI - 69 IP - 8 DP - 2025 Dec TI - The Ozempic Generation: What the Interventional Radiologist Needs to Know About GLP-1 Agonists. PG - 836-843 LID - 10.1111/1754-9485.70045 [doi] AB - Glucagon-like peptide 1 receptor (GLP-1) agonists have been traditionally used in the treatment of type II diabetes. However, in recent times they have become a cornerstone in the pharmacological management of weight loss, and their use is increasing rapidly. Interventional Radiologists (IRs) need to understand GLP-1 agonists as they will increasingly encounter patients taking these medications in their daily practice, with implications for quality of care. These drugs have the potential to impact fasting glucose levels and gastric emptying, with implications for peri-procedural management when giving conscious sedation for an IR procedure. There is a need for IRs to adapt to the modern landscape. This review discusses the pharmacological effects, peri-procedural implications, and the need for IR-specific guidance in managing patients taking GLP-1 agonists. CI - (c) 2025 Royal Australian and New Zealand College of Radiologists. FAU - Wani, Suhail AU - Wani S AD - Department of Radiology, Alfred Health, Melbourne, Australia. FAU - Findakly, Salam AU - Findakly S AUID- ORCID: 0000-0002-1177-2052 AD - Department of Radiology, Alfred Health, Melbourne, Australia. FAU - Phan, Tuan AU - Phan T AUID- ORCID: 0000-0003-3402-4011 AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. FAU - Lukies, Matthew W AU - Lukies MW AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. AD - Department of Medical Imaging, Monash Health, Melbourne, Australia. FAU - Goh, Gerard S AU - Goh GS AUID- ORCID: 0000-0002-1552-5470 AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. AD - National Trauma Research Institute, Melbourne, Australia. FAU - Venn, Georgina AU - Venn G AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Radiology, Western Health, Footscray, Melbourne, Australia. FAU - Joseph, Tim AU - Joseph T AD - Department of Radiology, Alfred Health, Melbourne, Australia. FAU - Koukounaras, Jim AU - Koukounaras J AUID- ORCID: 0000-0001-9795-9477 AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. FAU - Clements, Warren AU - Clements W AUID- ORCID: 0000-0003-1859-5850 AD - Department of Radiology, Alfred Health, Melbourne, Australia. AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. AD - National Trauma Research Institute, Melbourne, Australia. LA - eng PT - Journal Article PT - Review DEP - 20251115 PL - Australia TA - J Med Imaging Radiat Oncol JT - Journal of medical imaging and radiation oncology JID - 101469340 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Radiology, Interventional MH - *Glucagon-Like Peptide 1/agonists MH - *Radiography, Interventional OTO - NOTNLM OT - GLP-1 OT - fasting OT - mounjaro OT - ozempic OT - sedation EDAT- 2025/11/15 12:32 MHDA- 2025/12/04 02:11 CRDT- 2025/11/15 07:42 PHST- 2025/10/31 00:00 [revised] PHST- 2025/06/11 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2025/12/04 02:11 [medline] PHST- 2025/11/15 12:32 [pubmed] PHST- 2025/11/15 07:42 [entrez] AID - 10.1111/1754-9485.70045 [doi] PST - ppublish SO - J Med Imaging Radiat Oncol. 2025 Dec;69(8):836-843. doi: 10.1111/1754-9485.70045. Epub 2025 Nov 15. PMID- 41238166 OWN - NLM STAT- MEDLINE DCOM- 20260123 LR - 20260126 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) VI - 87 IP - 2 DP - 2026 Feb TI - Glucagon-like Peptide-1 Receptor Agonists and Risk of Major Adverse Cardiovascular Events in Patients With CKD. PG - 211-229.e1 LID - S0272-6386(25)01149-7 [pii] LID - 10.1053/j.ajkd.2025.09.010 [doi] AB - RATIONALE & OBJECTIVE: There are limited real-world data describing the cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP1-RAs) across the spectrum of chronic kidney disease (CKD) severity. This study evaluated the association of GLP1-RAs with major adverse cardiovascular events (MACE) in comparison with dipeptidyl peptidase-4 (DPP-4) inhibitors in the setting of CKD. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: 24,576 new users of GLP1-RA and 44,367 new users of DPP-4 inhibitors with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m(2) in Ontario, Canada. EXPOSURE: New use of GLP1-RAs versus DPP-4 inhibitors. OUTCOME: The primary outcome was MACE, comprising nonfatal myocardial infarction, unstable angina, nonfatal ischemic stroke or transient ischemic attack, coronary revascularization, and cardiovascular death. Secondary outcomes included individual components of the composite outcome, hospitalization or emergency department visits for congestive heart failure, peripheral vascular disease revascularization, lower limb amputation, and all-cause mortality. ANALYTICAL APPROACH: Inverse probability of treatment weighting using propensity scores was used to minimize confounding. Multivariable Fine-Gray subdistribution hazard models stratified by eGFR subgroup were fit to evaluate the primary outcome. FINDINGS: Mean age of study participants was 69 years, 50% were female, 92% had type 2 diabetes mellitus, 40% were taking a sodium/glucose cotransporter 2 (SGLT2) inhibitor, and 41% had CKD stages 3-5. MACE occurred among 1,296 (31.6 per 1,000 person-years) GLP1-RA users versus 1,374 (36.5 per 1,000 person-years) DPP-4 inhibitor users (subdistribution hazard ratio [SHR], 0.88 [95% CI, 0.80-0.97]). The lower rate of MACE among GLP1-RA users was largely related to a lower rate of cardiovascular death (SHR, 0.72 [95% CI, 0.62-0.85]). In subgroup analyses, there was no effect modification between the association of GLP1-RA initiation and lower rates of MACE by CKD stages, degree of albuminuria, or concomitant use of SGLT2 inhibitors. LIMITATIONS: Retrospective design. A substantial amount of missing information on albuminuria. CONCLUSIONS: In a population-based study of individuals across the spectrum of kidney disease, GLP1-RA initiation was associated with a lower rate of MACE than initiation of DPP-4 inhibitors. PLAIN-LANGUAGE SUMMARY: A class of medications called glucagon-like peptide-1 receptor agonists (GLP1-RA) is now used for the treatment of diabetes. This study explored the association of GLP1-RA administration with cardiac health in people with kidney disease compared with another common class of diabetes medication, dipeptidyl peptidase-4 (DPP-4) inhibitors. In this study of nearly 69,000 individuals in Ontario, Canada, with a wide range of kidney function, people taking GLP1-RA experienced a lower rate of heart disease than those taking DPP-4 inhibitors. The lower rate was mainly related to fewer deaths from heart disease. Differences were consistent across different levels of kidney disease and regardless of whether people were also taking other medications that protect the heart. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yau, Kevin AU - Yau K AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada. Electronic address: kevin.yau@mail.utoronto.ca. FAU - Ray, Joel G AU - Ray JG AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. FAU - Jeyakumar, Nivethika AU - Jeyakumar N AD - ICES, Toronto, Ontario, Canada. FAU - Luo, Bin AU - Luo B AD - ICES, Toronto, Ontario, Canada; Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada. FAU - Abdullah, Sheikh AU - Abdullah S AD - ICES, Toronto, Ontario, Canada; Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada. FAU - Dixon, Stephanie N AU - Dixon SN AD - ICES, Toronto, Ontario, Canada; Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada. FAU - Wing, Sara AU - Wing S AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Clemens, Kristin K AU - Clemens KK AD - ICES, Toronto, Ontario, Canada; Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada; Department of Medicine and Epidemiology and Biostatistics, Western University, London, Ontario; Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, London, Ontario, Canada. FAU - Castrillon-Ramirez, Fabio AU - Castrillon-Ramirez F AD - Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. FAU - Udell, Jacob A AU - Udell JA AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada. FAU - Meraz-Munoz, Alejandro AU - Meraz-Munoz A AD - University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada. FAU - Young, Ann AU - Young A AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. FAU - Harel, Ziv AU - Harel Z AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. FAU - Perl, Jeffrey AU - Perl J AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. FAU - Leiter, Lawrence A AU - Leiter LA AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Garg, Amit X AU - Garg AX AD - ICES, Toronto, Ontario, Canada; Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada; Department of Medicine and Epidemiology and Biostatistics, Western University, London, Ontario. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada. FAU - Wald, Ron AU - Wald R AD - Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Observational Study DEP - 20251112 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/drug therapy/complications/epidemiology MH - Female MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/epidemiology MH - Aged MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glomerular Filtration Rate MH - Cohort Studies MH - Ontario/epidemiology OTO - NOTNLM OT - Cardiovascular disease OT - diabetes mellitus OT - epidemiologic studies OT - glucagon-like peptide-1 receptor agonist OT - heart disease OT - kidney disease EDAT- 2025/11/15 00:29 MHDA- 2026/01/24 00:32 CRDT- 2025/11/14 19:17 PHST- 2025/02/07 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/13 00:00 [accepted] PHST- 2026/01/24 00:32 [medline] PHST- 2025/11/15 00:29 [pubmed] PHST- 2025/11/14 19:17 [entrez] AID - S0272-6386(25)01149-7 [pii] AID - 10.1053/j.ajkd.2025.09.010 [doi] PST - ppublish SO - Am J Kidney Dis. 2026 Feb;87(2):211-229.e1. doi: 10.1053/j.ajkd.2025.09.010. Epub 2025 Nov 12. PMID- 41236578 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20260918 IS - 1438-2199 (Electronic) IS - 0939-4451 (Print) IS - 0939-4451 (Linking) VI - 57 IP - 1 DP - 2025 Nov 14 TI - Decoding incretin resistance: a mechanistic framework to reclassify therapeutic variability for GLP-1 receptor agonist therapy. PG - 55 LID - 10.1007/s00726-025-03488-9 [doi] LID - 55 AB - This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance-receptor-level, post-receptor, and secretory-highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified 'non-responder' classification. CI - (c) 2025. The Author(s). FAU - Fajkic, Almir AU - Fajkic A AUID- ORCID: 0000-0002-3722-9701 AD - Department of Pathophysiology, Faculty of Medicine, University of Sarajevo, Sarajevo, 71000, Bosnia and Herzegovina. almir.fajkic@mf.unsa.ba. FAU - Lam, Yun Wah AU - Lam YW AUID- ORCID: 0000-0001-8929-5965 AD - Department of Health Sciences, School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong SAR, China. FAU - Belancic, Andrej AU - Belancic A AUID- ORCID: 0000-0001-7848-6600 AD - Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. andrej.belancic@uniri.hr. LA - eng PT - Journal Article PT - Review DEP - 20251114 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Incretins/metabolism/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Drug Resistance PMC - PMC12618332 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Incretin resistance OT - Mechanistic classification OT - Personalized medicine OT - Therapeutic variability OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: All authors declare that they do not have any conflict of interest concerning the content of this manuscript. Ethical approval: Not applicable. EDAT- 2025/11/14 12:32 MHDA- 2025/11/14 12:33 PMCR- 2025/11/14 CRDT- 2025/11/14 11:04 PHST- 2025/07/29 00:00 [received] PHST- 2025/10/24 00:00 [accepted] PHST- 2025/11/14 12:33 [medline] PHST- 2025/11/14 12:32 [pubmed] PHST- 2025/11/14 11:04 [entrez] PHST- 2025/11/14 00:00 [pmc-release] AID - 10.1007/s00726-025-03488-9 [pii] AID - 3488 [pii] AID - 10.1007/s00726-025-03488-9 [doi] PST - epublish SO - Amino Acids. 2025 Nov 14;57(1):55. doi: 10.1007/s00726-025-03488-9. PMID- 41235513 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20251114 IS - 0040-3660 (Print) IS - 0040-3660 (Linking) VI - 97 IP - 10 DP - 2025 Nov 11 TI - [The perspectives in obesity and type 2 diabetes therapy: the present and future of incretin therapy]. PG - 823-829 LID - 10.26442/00403660.2025.10.203366 [doi] AB - The rates of increase in the incidence of type 2 diabetes mellitus (T2DM) and obesity in the world are steadily increasing and exceed even the wildest forecasts, which forces specialists to seek, develop and implement more effective therapeutic methods for these two interrelated non-communicable pandemics. This article discusses promising areas in the pharmacotherapy of obesity and T2DM with an emphasis on the development of a class of incretin hormone receptor agonists. Monoagonists (liraglutide, dulaglutide, semaglutide) and dual incretin receptor agonists (tirzepatide), as well as triple- and tetra-agonists of gastrointestinal hormones currently under development, which are expected to be even more effective in the complex treatment of both type T2DM and obesity, are being discussed. FAU - Shestakova, M V AU - Shestakova MV AUID- ORCID: 0000-0002-5057-127X AD - Endocrinology Research Centre. FAU - Bashlykova, R O AU - Bashlykova RO AUID- ORCID: 0009-0006-0444-3732 AD - Endocrinology Research Centre. LA - rus PT - English Abstract PT - Journal Article PT - Review DEP - 20251111 PL - Russia (Federation) TA - Ter Arkh JT - Terapevticheskii arkhiv JID - 2984818R RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Incretins/pharmacology/therapeutic use MH - *Obesity/drug therapy/epidemiology MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives OTO - NOTNLM OT - diabetes mellitus OT - glucagon OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - glycemic control OT - incretins OT - metabolic process OT - multiagnestics OT - obesity OT - pharmacotherapy OT - weight EDAT- 2025/11/14 06:28 MHDA- 2025/11/14 06:29 CRDT- 2025/11/14 05:43 PHST- 2025/07/02 00:00 [received] PHST- 2025/07/02 00:00 [accepted] PHST- 2025/11/14 06:29 [medline] PHST- 2025/11/14 06:28 [pubmed] PHST- 2025/11/14 05:43 [entrez] AID - 10.26442/00403660.2025.10.203366 [doi] PST - epublish SO - Ter Arkh. 2025 Nov 11;97(10):823-829. doi: 10.26442/00403660.2025.10.203366. PMID- 41233973 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20251126 IS - 2309-4990 (Electronic) IS - 1022-5536 (Linking) VI - 33 IP - 3 DP - 2025 Sep-Dec TI - Impact of glucagon-like peptide-1 receptor agonists on postoperative complications after total joint arthroplasty: A systematic review and meta-analysis. PG - 10225536251391959 LID - 10.1177/10225536251391959 [doi] AB - BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for obesity and type 2 diabetes mellitus (T2DM). While their metabolic benefits are well-established, their impact on postoperative outcomes following total joint arthroplasty (TJA) remains controversial. This study aimed to systematically evaluate the association between GLP-1 RA use and postoperative outcomes in patients undergoing total hip (THA), knee (TKA), or shoulder arthroplasty (TSA).MethodsWe conducted a PRISMA-compliant systematic review and meta-analysis across PubMed, Embase, Web of Science, and Scopus through April 24, 2025. Eligible retrospective cohort studies compared adults undergoing TJA with and without preoperative GLP-1 RA exposure. Primary outcomes were 90-day readmission and all-cause revision. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated under random-effects models. Subgroup analysis based on the type of arthroplasty was conducted where applicable.ResultsFourteen studies (total sample size of 365,154; including 62,117 (17.01%) GLP-1 consumers, and 303,037 (82.98%) control cases) met the inclusion criteria (All studies included primary TJA cases). GLP-1 RA use was associated with lower 90-day readmission (OR = 0.86, 95% CI: 0.74-0.99, p = 0.033) and reduced sepsis incidence (OR = 0.63, 95% CI: 0.46-0.88, p = 0.006). No significant differences were observed for all-cause revision, thromboembolic events, and other medical and surgical complications. Length of stay was marginally shorter in GLP-1 users (SMD = -0.09, p = 0.048). Subgroup analyses showed the strongest sepsis reduction in TSA.ConclusionGLP-1 RA use before TJA is associated with reduced readmission and sepsis risk without increasing surgical or thromboembolic complications. These findings support the potential perioperative benefits of GLP-1 RAs, warranting prospective trials to confirm causality and define optimal perioperative strategies for high-risk arthroplasty patients. FAU - Mashayekhi, Yashar AU - Mashayekhi Y AUID- ORCID: 0000-0002-1784-8556 AD - Department of Orthopaedic, Leicester University Hospital, Leicester, UK. RINGGOLD: 4490 FAU - Asgari, Amir-Mohammad AU - Asgari AM AUID- ORCID: 0000-0001-7123-1576 AD - School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. RINGGOLD: 48464 FAU - Pahlevan-Fallahy, Mohammad-Taha AU - Pahlevan-Fallahy MT AUID- ORCID: 0000-0003-2426-6340 AD - School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. RINGGOLD: 48439 FAU - Karimi, Mohammad Amin AU - Karimi MA AUID- ORCID: 0000-0002-0638-1743 AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. RINGGOLD: 556492 FAU - Jalali, Ronak AU - Jalali R AUID- ORCID: 0009-0004-4717-4013 AD - School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. RINGGOLD: 125691 FAU - Shaker, Farhad AU - Shaker F AUID- ORCID: 0009-0003-5987-9873 AD - School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. RINGGOLD: 48439 LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251113 PL - England TA - J Orthop Surg (Hong Kong) JT - Journal of orthopaedic surgery (Hong Kong) JID - 9440382 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Postoperative Complications/epidemiology/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Patient Readmission/statistics & numerical data MH - Arthroplasty, Replacement, Hip MH - *Arthroplasty, Replacement/adverse effects MH - Arthroplasty, Replacement, Knee MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - postoperative complications OT - readmission rates OT - total joint arthroplasty COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/11/14 06:28 MHDA- 2025/11/14 06:29 CRDT- 2025/11/14 00:52 PHST- 2025/11/14 06:29 [medline] PHST- 2025/11/14 06:28 [pubmed] PHST- 2025/11/14 00:52 [entrez] AID - 10.1177/10225536251391959 [doi] PST - ppublish SO - J Orthop Surg (Hong Kong). 2025 Sep-Dec;33(3):10225536251391959. doi: 10.1177/10225536251391959. Epub 2025 Nov 13. PMID- 41232081 OWN - NLM STAT- MEDLINE DCOM- 20251219 LR - 20260919 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 1 DP - 2026 Jan 1 TI - Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-Like Peptide 1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes. PG - 147-151 LID - 10.2337/dc25-1031 [doi] AB - OBJECTIVE: Older adults with type 2 diabetes are at high risk for frailty. The effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) on frailty remain uncertain. RESEARCH DESIGN AND METHODS: Using a 7% random sample of Medicare data, we compared new users of dipeptidyl peptidase 4 inhibitors (DPP-4is), GLP-1RAs, SGLT-2is, and sulfonylureas on 1-year frailty progression, measured by a claims-based frailty index (CFI) (range: 0-1; higher scores indicate greater frailty). Mediation analyses assessed whether cardiovascular or safety events explained differences in frailty progression. RESULTS: Compared with DPP-4i users, the mean CFI change (95% CI) was significantly lower for GLP-1RA (-0.007 [-0.011, -0.004]) and SGLT-2i (-0.005 [-0.008, -0.002]) users; no difference was found for sulfonylurea users. These associations were minimally mediated by cardiovascular or safety events. CONCLUSIONS: GLP-1RAs and SGLT-2is may slow frailty progression through mechanisms independent of cardiovascular benefits. Future trials should confirm these preliminary findings. CI - (c) 2025 by the American Diabetes Association. FAU - Park, Chan Mi AU - Park CM AUID- ORCID: 0000-0003-1880-048X AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Department of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA. FAU - Thanapluetiwong, Saran AU - Thanapluetiwong S AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. AD - Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. FAU - Chen, Xiecheng AU - Chen X AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. FAU - Oh, Gahee AU - Oh G AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. FAU - Ko, Darae AU - Ko D AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. AD - Harvard Medical School, Boston, MA. FAU - Kim, Dae Hyun AU - Kim DH AD - Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Department of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA. LA - eng GR - K24 AG073527/AG/NIA NIH HHS/United States GR - R01 AG071809/AG/NIA NIH HHS/United States GR - K24AG073527/National Institute on Aging of the National Institutes of Health/ GR - R01AG071809/National Institute on Aging of the National Institutes of Health/ PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Aged, 80 and over MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Frailty MH - *Hypoglycemic Agents/therapeutic use MH - Disease Progression MH - Sulfonylurea Compounds/therapeutic use PMC - PMC12643794 MID - NIHMS2123347 COIS- Duality of Interest. C.M.P. has received grants from the National Institute on Aging of the National Institutes of Health outside the submitted work. D.K. has received grants from the National Institutes of Health and consulting fees from Regeneron and Bayer outside the submitted work. D.H.K. received personal fees in 2022 from Alosa Health and VillageMD for unrelated work. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/11/13 18:30 MHDA- 2025/12/19 18:33 PMCR- 2025/11/13 CRDT- 2025/11/13 16:33 PHST- 2025/05/02 00:00 [received] PHST- 2025/10/19 00:00 [accepted] PHST- 2025/12/19 18:33 [medline] PHST- 2025/11/13 18:30 [pubmed] PHST- 2025/11/13 16:33 [entrez] PHST- 2025/11/13 00:00 [pmc-release] AID - 163841 [pii] AID - 251031 [pii] AID - 10.2337/dc25-1031 [doi] PST - ppublish SO - Diabetes Care. 2026 Jan 1;49(1):147-151. doi: 10.2337/dc25-1031. PMID- 41230897 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20260904 IS - 1473-5598 (Electronic) IS - 0263-6352 (Linking) VI - 44 IP - 1 DP - 2026 Jan 1 TI - Ambulatory blood pressure monitoring strengthens the cardiovascular signal of GLP-1RA: a meta-analysis of blood pressure and weight mediation. PG - 123-129 LID - 10.1097/HJH.0000000000004158 [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1RA) and dual GLP-1/GIP agonists reduce cardiovascular events in patients with type 2 diabetes and obesity. The extent to which these benefits are mediated by blood pressure (BP) reduction vs. weight loss, especially in hypertensive patients, remains unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials published from January 2015 to April 2025 evaluating GLP-1RA or dual agonists. Eligible trials reported major adverse cardiovascular events (MACE) and changes in SBP and/or weight. Random-effects meta-analyses and meta-regressions were used to assess associations between MACE and reductions in BP or weight. Subgroup analyses were performed according to BP measurement method (clinical vs. ambulatory). RESULTS: Twenty-one trials including 145 322 participants were analyzed. GLP-1RA significantly reduced MACE (pooled hazard ratio 0.86; 95% confidence interval 0.81-0.91). Meta-regression revealed that both SBP and weight reductions were independently associated with MACE risk reduction, with BP reduction showing a stronger relationship in trials using ambulatory BP monitoring. CONCLUSION: The cardiovascular benefits of GLP-1RA are likely influenced by both BP and weight reductions. Ambulatory BP monitoring strengthens the observed association between BP control and cardiovascular outcomes, although causality cannot be definitively established. These findings support the use of GLP-1RA in individuals with hypertension, including those with resistant phenotypes. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Renna, Nicolas F AU - Renna NF AD - Department of Cardiology, Hospital Espanol de Mendoza. AD - Department of Basic Health Sciences, National University of Cuyo. FAU - Ramirez, Eliel Ivan AU - Ramirez EI AD - Department of Cardiology, Hospital Espanol de Mendoza. FAU - Arrupe, Matias Fernando AU - Arrupe MF AD - Department of Cardiology, Hospital Espanol de Mendoza. FAU - Ramirez, Jesica Magali AU - Ramirez JM AD - Department of Cardiology, Hospital Espanol de Mendoza. AD - Department of Internal Medicine, Genetic Unit, Hospital Central de Mendoza, Mendoza, Argentina. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251022 PL - Netherlands TA - J Hypertens JT - Journal of hypertension JID - 8306882 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Blood Pressure Monitoring, Ambulatory MH - *Blood Pressure/drug effects MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypertension/drug therapy/physiopathology MH - *Cardiovascular Diseases/prevention & control MH - Randomized Controlled Trials as Topic MH - Obesity/drug therapy OTO - NOTNLM OT - GLP-1 receptor agonists OT - ambulatory blood pressure monitoring OT - blood pressure OT - cardiovascular outcomes OT - meta-analysis OT - resistant hypertension EDAT- 2025/11/13 12:32 MHDA- 2025/12/04 13:39 CRDT- 2025/11/13 08:32 PHST- 2025/06/16 00:00 [received] PHST- 2025/08/27 00:00 [accepted] PHST- 2025/12/04 13:39 [medline] PHST- 2025/11/13 12:32 [pubmed] PHST- 2025/11/13 08:32 [entrez] AID - 00004872-990000000-00782 [pii] AID - 10.1097/HJH.0000000000004158 [doi] PST - ppublish SO - J Hypertens. 2026 Jan 1;44(1):123-129. doi: 10.1097/HJH.0000000000004158. Epub 2025 Oct 22. PMID- 41228390 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 17 IP - 21 DP - 2025 Oct 22 TI - Exploring Dietary Intake in Adults with Type 2 Diabetes Using GLP-1 Receptor Agonists: A Cross-Sectional Analysis. LID - 10.3390/nu17213318 [doi] LID - 3318 AB - Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in type 2 diabetes (T2D) management for their glycemic and weight benefits. However, their appetite-suppressing effects may influence dietary intake and nutrient adequacy, yet real-world evidence is scarce. Objective: To evaluate dietary intake and adherence to the Mediterranean diet in adults with T2D treated with GLP-1RAs compared to those receiving other oral hypoglycemic agents. Methods: In this cross-sectional study, 103 adults with T2D (mean age 66 +/- 8 years; 65% male) attending a diabetes clinic in Turin, Italy, were enrolled between February and June 2025. Dietary habits were assessed using a validated food frequency questionnaire, and adherence to the Mediterranean diet was evaluated via the Mediterranean Diet Score (MDS). Anthropometric, biochemical, and lifestyle data were collected. Results: Fifty-two participants (50.5%) were treated with GLP-1RAs (semaglutide 55.8%, dulaglutide 40.4%). No significant differences in energy intake, macronutrient distribution, or MDS were observed between groups. Overall, diets were characterized by low carbohydrate intake (~44% of energy), inadequate fiber ( approximately 11 g/1000 kcal), and high fat intake ( approximately 39-40% of energy), with saturated fat below 10%. None of the GLP-1RA users met fiber recommendations. Subgroup analysis by treatment duration (<1 year, 1-2 years, >2 years) revealed no significant differences in dietary patterns. Conclusions: Patients with T2D, regardless of pharmacological treatment, exhibited poor adherence to dietary guidelines. These findings highlight the need for structured nutritional counseling alongside GLP-1RA therapy to optimize metabolic outcomes and prevent nutritional deficiencies. FAU - Ponzo, Valentina AU - Ponzo V AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Vitale, Marilena AU - Vitale M AUID- ORCID: 0000-0001-9951-4674 AD - Nutrition, Diabetes and Metabolism Research Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy. FAU - Bo, Simona AU - Bo S AUID- ORCID: 0000-0001-6862-8628 AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Broglio, Fabio AU - Broglio F AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Goitre, Ilaria AU - Goitre I AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Cioffi, Iolanda AU - Cioffi I AUID- ORCID: 0000-0002-1408-209X AD - Division of Human Nutrition, Department of Food, Environmental and Nutritional Sciences-DeFENS, University of Milan, Via G. Celoria 2, 20133 Milan, Italy. LA - eng PT - Journal Article DEP - 20251022 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Cross-Sectional Studies MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diet, Mediterranean MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Italy MH - Energy Intake MH - *Eating MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC12610383 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Mediterranean diet OT - Pharmacotherapy OT - Type 2 diabetes OT - diet quality OT - dietary intake OT - nutritional adequacy COIS- The authors declare no conflicts of interest. EDAT- 2025/11/13 06:30 MHDA- 2025/11/13 18:29 PMCR- 2025/10/22 CRDT- 2025/11/13 01:11 PHST- 2025/09/10 00:00 [received] PHST- 2025/10/18 00:00 [revised] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/13 18:29 [medline] PHST- 2025/11/13 06:30 [pubmed] PHST- 2025/11/13 01:11 [entrez] PHST- 2025/10/22 00:00 [pmc-release] AID - nu17213318 [pii] AID - nutrients-17-03318 [pii] AID - 10.3390/nu17213318 [doi] PST - epublish SO - Nutrients. 2025 Oct 22;17(21):3318. doi: 10.3390/nu17213318. PMID- 41226444 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 21 DP - 2025 Oct 26 TI - Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes. LID - 10.3390/ijms262110404 [doi] LID - 10404 AB - The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine the effects of semaglutide and dipeptidyl peptidase-4 inhibitor sitagliptin therapy on serum levels of IGFBP-1, IGFBP-3, and IGFBP-rp1, and to analyze their associations with anthropometric variables and markers of carbohydrate and lipid metabolism. In this prospective study, we enrolled 34 patients with type 2 diabetes mellitus (T2DM) on metformin monotherapy and 31 age-, sex- and BMI-matched controls. Among the patients, 18 received semaglutide, and 16 were treated with sitagliptin. Anthropometric and laboratory assessments were performed at baseline, 26 and 52 weeks. IGFBP levels were measured using ELISA. Both semaglutide and sitagliptin treatment significantly increased IGFBP-1 levels. IGFBP-3 levels were significantly decreased following sitagliptin therapy. No significant change in IGFBP-rp1 levels was observed with either treatment. Based on multiple regression analysis, the best predictors of IGFBP-1 were insulin and hsCRP, while the best predictor of IGFBP-3 was LDL-C level. Our findings suggest that semaglutide and sitagliptin may exert favorable effects on the GH/IGF-1 axis, potentially contributing to their beneficial metabolic outcomes in patients with T2DM. FAU - Daniel, Eszter AU - Daniel E AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Sztanek, Ferenc AU - Sztanek F AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Csiha, Sara AU - Csiha S AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - Department of Clinical Basics, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Ratku, Balazs AU - Ratku B AUID- ORCID: 0000-0002-0991-8622 AD - Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Somodi, Sandor AU - Somodi S AD - Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Paragh, Gyorgy AU - Paragh G AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harangi, Mariann AU - Harangi M AUID- ORCID: 0000-0001-9761-9595 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Lorincz, Hajnalka AU - Lorincz H AUID- ORCID: 0009-0000-5303-3082 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. LA - eng GR - K142273/National Research, Development and Innovation Office/ GR - Hungarian Society for Endocrinology and Metabolism/ PT - Journal Article DEP - 20251026 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Insulin-Like Growth Factor Binding Protein 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Insulin-Like Growth Factor Binding Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (IGFBP1 protein, human) RN - 0 (IGFBP3 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Sitagliptin Phosphate/therapeutic use/pharmacology MH - Male MH - Female MH - Middle Aged MH - *Insulin-Like Growth Factor Binding Protein 1/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Insulin-Like Growth Factor Binding Protein 3/blood MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Metformin/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Insulin-Like Growth Factor Binding Proteins/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12609315 OTO - NOTNLM OT - C-peptide OT - C-reactive protein OT - insulin OT - insulin-like growth factor-binding protein OT - lipid parameters OT - semaglutide OT - sitagliptin OT - type 2 diabetes mellitus OT - waist circumference COIS- The authors declare no conflicts of interest. EDAT- 2025/11/13 06:29 MHDA- 2025/11/13 18:29 PMCR- 2025/10/26 CRDT- 2025/11/13 01:04 PHST- 2025/09/12 00:00 [received] PHST- 2025/10/18 00:00 [revised] PHST- 2025/10/25 00:00 [accepted] PHST- 2025/11/13 18:29 [medline] PHST- 2025/11/13 06:29 [pubmed] PHST- 2025/11/13 01:04 [entrez] PHST- 2025/10/26 00:00 [pmc-release] AID - ijms262110404 [pii] AID - ijms-26-10404 [pii] AID - 10.3390/ijms262110404 [doi] PST - epublish SO - Int J Mol Sci. 2025 Oct 26;26(21):10404. doi: 10.3390/ijms262110404. PMID- 41220901 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260901 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2025 DP - 2025 TI - SGLT2 Inhibitor and GLP-1 Receptor Agonist Prescriptions in Newly Diagnosed Type 2 Diabetes Patients With Cardiorenal Risks: A Cross-Sectional Study. PG - 6656982 LID - 10.1155/jdr/6656982 [doi] LID - 6656982 AB - AIMS: The aim of this study is to evaluate the real-world prescribing patterns of SGLT2 inhibitors and GLP-1 receptor agonists (GLP-1RA) in patients with newly diagnosed Type 2 diabetes (T2DM), particularly among those with high cardiovascular risks or chronic kidney disease, and to identify demographic, clinical, and system-level factors associated with receiving these medications. MATERIALS AND METHODS: This cross-sectional study analyzed electronic medical records (EMRs) of patients with newly diagnosed T2DM from 60 primary care clinics in West Michigan between April 2021 and January 2023. We assessed the documented prescription rates of SGLT2 inhibitors and GLP-1RAs within 3 months of diagnosis based on EMRs, particularly in high-risk subgroups. RESULTS: Overall, 19.9% of n = 5783 patients with newly diagnosed T2DM had either an SGLT2 inhibitor or GLP-1RA prescribed. Prescription rates for these agents were 20.0% for patients with chronic ischemic heart disease and 19.3% for those with impaired kidney function. In adjusted analyses, higher BMI (aOR 2.92 for BMI > 40 kg/m(2), 95% CI 1.58-5.42, ref BMI < 24 kg/m(2)), hyperlipidemia (aOR 1.89, 95% CI 1.28-2.79), chronic ischemic heart disease (aOR 1.55, 95% CI 1.11-2.18), and higher HbA1c (aOR 1.32 per 1% increase, 95% CI 1.22-1.42) were associated with higher odds of receiving prescription of these medications. CONCLUSIONS: Despite guideline recommendations, SGLT2 inhibitors and GLP-1RAs are prescribed to only a minority of patients with newly diagnosed T2DM, even among those with clear indications. Efforts to improve guideline-adherent care in primary care settings are needed. CI - Copyright (c) 2025 Frank Muller et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Muller, Frank AU - Muller F AUID- ORCID: 0000-0002-9496-9423 AD - Department of Family Medicine, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. AD - Corewell Health Family Medicine Residency Center, Corewell Health, Grand Rapids, Michigan, USA. AD - Department of General Practice, University Medical Center Gottingen, Gottingen, Germany. FAU - Bouthillier, Michael J AU - Bouthillier MJ AD - Department of Family Medicine, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. AD - Corewell Health Family Medicine Residency Center, Corewell Health, Grand Rapids, Michigan, USA. FAU - Alshaarawy, Omayma AU - Alshaarawy O AUID- ORCID: 0000-0002-5968-0245 AD - Department of Family Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA. FAU - Azhary, Hend AU - Azhary H AD - Department of Family Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA. FAU - Holman, Harland T AU - Holman HT AUID- ORCID: 0000-0003-3835-9193 AD - Department of Family Medicine, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. AD - Corewell Health Family Medicine Residency Center, Corewell Health, Grand Rapids, Michigan, USA. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20251103 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/diagnosis MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Cross-Sectional Studies MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Renal Insufficiency, Chronic MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Cardiovascular Diseases MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Drug Prescriptions/statistics & numerical data PMC - PMC12602036 COIS- The authors declare no conflicts of interest. EDAT- 2025/11/12 06:31 MHDA- 2025/11/13 18:29 PMCR- 2025/11/03 CRDT- 2025/11/12 04:28 PHST- 2025/01/07 00:00 [received] PHST- 2025/07/06 00:00 [revised] PHST- 2025/10/04 00:00 [accepted] PHST- 2025/11/13 18:29 [medline] PHST- 2025/11/12 06:31 [pubmed] PHST- 2025/11/12 04:28 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 10.1155/jdr/6656982 [doi] PST - epublish SO - J Diabetes Res. 2025 Nov 3;2025:6656982. doi: 10.1155/jdr/6656982. eCollection 2025. PMID- 41219651 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260408 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 3 DP - 2026 Feb TI - Ethical Considerations in the Use of Weight Loss Medications. PG - 852-855 LID - 10.1007/s11606-025-10026-6 [doi] AB - The emergence of GLP-1 receptor agonists, such as semaglutide and tirzepatide, has transformed the landscape of weight management and diabetes treatment. Initially developed for type 2 diabetes mellitus, these medications have gained widespread popularity due to their weight-loss effects, spurred by media attention and celebrity endorsements. However, their increasing demand raises ethical concerns regarding accessibility, affordability, and medical necessity. Patients with genuine clinical indications often struggle to obtain these medications due to shortages and high costs, while wealthier individuals use them for cosmetic weight loss. Additionally, unregulated alternatives, such as compounded injections and celebrity-endorsed supplements, further complicate the landscape by introducing safety risks and misinformation. Physicians face the challenge of balancing evidence-based prescribing with resource allocation, ensuring medications reach those in need. Patients have a responsibility to critically evaluate information and engage in informed decision-making. Policymakers must address disparities by implementing equitable policies that prioritize medical necessity over commercial interests. As the use of GLP-1 agonists continues to rise, a collaborative approach, rooted in ethical responsibility, patient education, and regulatory oversight, is essential to prevent healthcare inequities and uphold the integrity of medical practice. CI - (c) 2025. The Author(s), under exclusive licence to Society of General Internal Medicine. FAU - Savla, Riya AU - Savla R AUID- ORCID: 0009-0001-4073-3829 AD - Hackensack Meridian School of Medicine, Nutley, NJ, USA. riya.savla@hmhn.org. FAU - Van Hoven, Anne Marie AU - Van Hoven AM AD - Office of Medical Education, Hackensack Meridian School of Medicine, Nutley, NJ, USA. FAU - Pilkington, Bryan AU - Pilkington B AD - Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA. LA - eng PT - Editorial DEP - 20251111 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use/economics MH - *Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12960898 COIS- Declarations. Human Ethics and Consent to Participate: Not applicable. Conflict of interest: The authors declare that they do not have a conflict of interest. EDAT- 2025/11/12 00:26 MHDA- 2026/03/07 06:40 PMCR- 2027/02/01 CRDT- 2025/11/11 23:38 PHST- 2025/02/20 00:00 [received] PHST- 2025/10/31 00:00 [accepted] PHST- 2026/03/07 06:40 [medline] PHST- 2025/11/12 00:26 [pubmed] PHST- 2025/11/11 23:38 [entrez] PHST- 2027/02/01 00:00 [pmc-release] AID - 10.1007/s11606-025-10026-6 [pii] AID - 10026 [pii] AID - 10.1007/s11606-025-10026-6 [doi] PST - ppublish SO - J Gen Intern Med. 2026 Feb;41(3):852-855. doi: 10.1007/s11606-025-10026-6. Epub 2025 Nov 11. PMID- 41218687 OWN - NLM STAT- MEDLINE DCOM- 20251129 LR - 20251129 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 230 DP - 2025 Dec TI - Association of tirzepatide use with risk of osteoporosis compared with other GLP-1 receptor agonists: A retrospective cohort study using the TriNetX database. PG - 112995 LID - S0168-8227(25)01010-1 [pii] LID - 10.1016/j.diabres.2025.112995 [doi] AB - AIMS: To determine whether tirzepatide use is associated with a higher risk of osteoporosis or fragility fractures compared with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs). METHODS: In a retrospective cohort study using the TriNetX network, we identified 459,886 eligible patients with type 2 diabetes or obesity who initiated tirzepatide or other GLP-1 RAs between June 2022 and May 2024. We performed 1:1 propensity score matching to balance baseline characteristics. The primary outcome was a composite of new-onset osteoporosis or fragility fracture, assessed within a 14-month follow-up period. RESULTS: The matched study included 66,329 participants per group. Compared with other GLP-1 RAs, tirzepatide was associated with a higher risk of the primary outcome (hazard ratio [HR], 1.44; 95 % confidence interval [CI], 1.22-1.69) and of initiating osteoporosis therapy (HR, 1.61; 95 % CI, 1.22-2.12). Compared with the nonusers, tirzepatide users were associated with a significantly higher risk of the primary composite outcome of osteoporosis or fragility fracture (HR, 1.48; 95 % CI, 1.26-1.75) but not with other GLP-1 RAs (HR, 1.07; 95 % CI, 1.00-1.15). CONCLUSIONS: In this large real-world cohort study, initiation of tirzepatide was associated with a significantly higher risk of osteoporosis or fragility fractures compared to other GLP-1 RAs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Hsu, Yung-Han AU - Hsu YH AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Liang, Yu-Cheng AU - Liang YC AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Tong Yuan Diabetes Center, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Chan, Ka-Chon AU - Chan KC AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Chou, Yu-Hsuan AU - Chou YH AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Wu, Hung-Tsung AU - Wu HT AD - Tong Yuan Diabetes Center, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Ou, Horng-Yih AU - Ou HY AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Tong Yuan Diabetes Center, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: wahoryi@mail.ncku.edu.tw. LA - eng PT - Journal Article DEP - 20251109 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoporosis/epidemiology/chemically induced MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Tirzepatide/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Databases, Factual MH - Risk Factors OTO - NOTNLM OT - Diabetes mellitus OT - Fracture OT - Obesity OT - Osteoporosis OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/11/12 00:26 MHDA- 2025/11/30 00:30 CRDT- 2025/11/11 19:10 PHST- 2025/09/21 00:00 [received] PHST- 2025/10/30 00:00 [revised] PHST- 2025/11/08 00:00 [accepted] PHST- 2025/11/30 00:30 [medline] PHST- 2025/11/12 00:26 [pubmed] PHST- 2025/11/11 19:10 [entrez] AID - S0168-8227(25)01010-1 [pii] AID - 10.1016/j.diabres.2025.112995 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Dec;230:112995. doi: 10.1016/j.diabres.2025.112995. Epub 2025 Nov 9. PMID- 41217382 OWN - NLM STAT- MEDLINE DCOM- 20260505 LR - 20260724 IS - 1930-613X (Electronic) IS - 0026-4075 (Linking) VI - 191 IP - 5-6 DP - 2026 May 1 TI - Semaglutide Decreases Risk of Non-Arteritic Anterior Ischemic Optic Neuroapthy in Type 2 Diabetic Patients. PG - e1020-e1025 LID - 10.1093/milmed/usaf522 [doi] AB - INTRODUCTION: Although the association between semaglutide use for diabetes or obesity and non-arteritic ischemic optic neuropathy (NAION) has been investigated, the relative risk has not been established in large, racially diverse populations. Given the increasing use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications, it is vital to study the odds of this serious adverse event. MATERIALS AND METHODS: We conducted a retrospective cohort study to investigate the relationship between semaglutide use and NAION in Military Health System beneficiaries ages 18 and older with diabetes or overweight and obesity who received care from December 7, 2017 to September 30, 2023. A subset analysis was performed using phosphodiesterase-5 inhibitors. This study was carried out as part of the Burden of Diseases and Injuries in the U.S. Military Health System, 2001-2018: Incidence, Prevalence, and Years Lived project and was found exempt by the Institutional Review Board at the Uniformed Services University of the Health Sciences. RESULTS: A total of 1,212,775 individuals (973,529 patients with type 2 diabetes and 239,246 with overweight or obesity) were included. There were 2,447 NAION events identified. After adjusting for comorbidities, patients with type 2 diabetes prescribed semaglutide had a significantly lower risk of NAION (OR = 0.36, 95% CI = 0.25-0.51) compared to those prescribed non-GLP-1 RA medications. Among patients who had overweight or obesity, there was no significant difference in the odds of receiving a NAION diagnosis (OR = 0.10, 95% CI = 0.01-1.35). Use of phosphodiesterase-5 inhibitors was associated with lower odds of NAION in both populations (Type 2 diabetes: OR = 0.78, 95% CI = 0.69-0.87; overweight/obesity: OR = 0.49, 95% CI = 0.26-0.93) compared with those who did not use these medications. CONCLUSION: This retrospective cohort study found a lower risk of NAION in patients with type 2 diabetes taking semaglutide compared with those taking non-GLP-1 RA medications in a large, diverse population. There was no association between NAION and semaglutide use in patients with overweight or obesity. These findings suggest that the risk of NAION should not preclude the use of this medication. CI - Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US. FAU - Lieberman, Rachel A AU - Lieberman RA AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - Walter Reed National Military Medical Center, Bethesda, MD 20814, United States. FAU - Korona-Bailey, Jessica AU - Korona-Bailey J AUID- ORCID: 0000-0002-0314-5171 AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD 20817, United States. FAU - Banaag, Amanda AU - Banaag A AUID- ORCID: 0000-0001-6660-1229 AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD 20817, United States. FAU - Furhman, Barbara AU - Furhman B AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. FAU - Corrado, Richele AU - Corrado R AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. FAU - Koehlmoos, Tracey Perez AU - Koehlmoos TP AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. LA - eng GR - # HU0001-11-1-0023/Department of Defense, Defense Health Agency/ PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Mil Med JT - Military medicine JID - 2984771R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Retrospective Studies MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Adult MH - Aged MH - *Optic Neuropathy, Ischemic/epidemiology/prevention & control/drug therapy MH - Cohort Studies MH - United States/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - Obesity EDAT- 2025/11/11 12:29 MHDA- 2026/05/06 00:34 CRDT- 2025/11/11 10:34 PHST- 2026/05/06 00:34 [medline] PHST- 2025/11/11 12:29 [pubmed] PHST- 2025/11/11 10:34 [entrez] AID - 8320596 [pii] AID - 10.1093/milmed/usaf522 [doi] PST - ppublish SO - Mil Med. 2026 May 1;191(5-6):e1020-e1025. doi: 10.1093/milmed/usaf522. PMID- 41216778 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Baseline characteristics in the SYNCHRONIZE-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes. PG - 1490-1498 LID - 10.1111/dom.70263 [doi] AB - AIMS: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528). MATERIALS AND METHODS: Participants aged >/=18 years with a body mass index (BMI) >/=27 kg/m(2) and T2D were randomized 1:1:1 to weekly subcutaneous survodutide (up-titrated to 3.6 or 6.0 mg) or placebo with recommendations for modified diet and physical activity. The primary endpoints are the percentage change in body weight (BW) and achievement of BW reduction of >/=5% from baseline to Week 76. RESULTS: SYNCHRONIZE-2 includes 752 treated participants from 133 sites across 19 countries. At baseline, participants had a mean age of 55.7 years, BMI 36.5 kg/m(2), BW 104.1 kg, waist circumference 115.5 cm and haemoglobin A1c 7.4%; 50.7% were female. Overall, 36.2% are from Europe, 32.8% from North America and 22.3% from East Asia. The most common obesity complications included hypertension (69.0%), dyslipidaemia (67.6%), obstructive sleep apnoea (17.3%) and arteriosclerotic cardiovascular disease (10.9%); 78.7% were treated with metformin, 34.2% with sodium-glucose co-transporter-2 inhibitors and 58.6% with lipid-lowering medications. CONCLUSIONS: SYNCHRONIZE-2 will determine the efficacy, safety and tolerability of survodutide for BW reduction in people with obesity and T2D, whose baseline characteristics suggest a representative, diverse cohort. CI - (c) 2025 Boehringer Ingelheim International GmbH and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - McMaster University, Hamilton, Ontario, Canada. AD - University of Toronto, Toronto, Ontario, Canada. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - University College Dublin School of Medicine, Dublin, Ireland. AD - Ulster University, Coleraine, UK. FAU - Bozkurt, Biykem AU - Bozkurt B AUID- ORCID: 0000-0002-6362-0253 AD - Winters Center for Heart Failure Research, Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, USA. FAU - Platz, Elke AU - Platz E AUID- ORCID: 0000-0002-8604-0710 AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Bleckert, Gabriele AU - Bleckert G AUID- ORCID: 0000-0002-4341-9042 AD - Staburo GmbH, Munich, Germany, on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. FAU - Ajaz Hussain, Samina AU - Ajaz Hussain S AUID- ORCID: 0009-0002-4849-0363 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Brueckmann, Martina AU - Brueckmann M AUID- ORCID: 0000-0003-1215-0746 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. AD - First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Startseva, Elena AU - Startseva E AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Kloer, Isabel M AU - Kloer IM AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Kaplan, Lee M AU - Kaplan LM AUID- ORCID: 0000-0002-6301-2696 AD - Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. LA - eng SI - ClinicalTrials.gov/NCT06066528 GR - Boehringer Ingelheim/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20251111 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Glucagon) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - Middle Aged MH - Male MH - *Obesity/drug therapy/complications MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Treatment Outcome MH - Weight Loss/drug effects MH - Body Mass Index MH - Receptors, Glucagon/agonists MH - *Anti-Obesity Agents/therapeutic use PMC - PMC12803687 OTO - NOTNLM OT - diabetes mellitus, type 2 OT - glucagon OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - randomized controlled trial COIS- Sean Wharton reports research funding from Novo Nordisk and Bausch Health Canada. He reports honoraria for academic talks and advisory boards from Amgen, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Regeneron, Bausch Health Canada, Merck, iNova and Currax. Carel W. le Roux has received personal fees from Boehringer Ingelheim, GI Dynamics, Herbalife, Johnson and Johnson, Keyron, Eli Lilly and Novo Nordisk outside the submitted work. Biykem Bozkurt has received consulting fees from Abbott, Abiomed, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardurion, Cytokinetics, Daiichi Sankyo, Johnson and Johnson, Lantheus, Liva Nova, Merck, Regeneron, Renovacor, Respicardia/Zoll, Roche, Sanofi-Aventis and Vifor. Elke Platz's employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals. She has received research support from the NIH and AstraZeneca, and she serves on the clinical trial steering committee of the SYNCHRONIZE-1 and -2 trials and SYNCHRONIZE-CVOT funded by Boehringer Ingelheim. Gabriele Bleckert is an employee of Staburo GmbH, which was contracted by Boehringer Ingelheim. Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva and Isabel M. Kloer are employees of Boehringer Ingelheim. Lee M. Kaplan reports serving as a consultant to Altimmune, Amgen, AstraZeneca, Bain Capital, Boehringer Ingelheim, Cytoki, Gelesis, Gilead Sciences, Intellihealth, Johnson and Johnson, Kallyope, Eli Lilly, Metsera, Novo Nordisk, Optum Health, Perspectum, Pfizer, Sidekick Health, Skye Bioscience, Structure Therapeutics and Twenty30 Health. EDAT- 2025/11/11 06:31 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/11 05:33 PHST- 2025/10/23 00:00 [revised] PHST- 2025/09/01 00:00 [received] PHST- 2025/10/24 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/11 06:31 [pubmed] PHST- 2025/11/11 05:33 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70263 [pii] AID - 10.1111/dom.70263 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1490-1498. doi: 10.1111/dom.70263. Epub 2025 Nov 11. PMID- 41213390 OWN - NLM STAT- MEDLINE DCOM- 20260821 LR - 20260821 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 24 IP - 9 DP - 2026 Sep TI - Glucagon-Like Peptide-1 Receptor Agonist Use Is Associated With and May Lead to Esophageal Motility Abnormalities. PG - 2620-2622 LID - S1542-3565(25)00941-3 [pii] LID - 10.1016/j.cgh.2025.11.003 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the treatment of obesity and type 2 diabetes mellitus (T2D). GLP1-RA use has grown exponentially, with a recent survey reporting 1 in 8 adults (12%) in the United States have ever taken a GLP-1RA.(1) GLP-1RAs are known to cause a variety of effects on gastrointestinal motility, including increased gastric accommodation, delayed gastric motility, and decreased small intestinal transit. However, little is known regarding the direct effects of GLP-1RAs on esophageal function beyond reported increased risk of gastroesophageal reflux disease (GERD).(2) The primary aim of this study was to assess the association of GLP-1RA exposure with findings on esophageal high-resolution manometry (HRM). CI - Published by Elsevier Inc. FAU - Gala, Khushboo AU - Gala K AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. FAU - Camilleri, Michael AU - Camilleri M AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. FAU - Goyal, Mayank AU - Goyal M AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. FAU - Ohri, Ashwariya AU - Ohri A AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. FAU - Marek, George AU - Marek G AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. FAU - Ravi, Karthik AU - Ravi K AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: ravi.karthik@mayo.edu. LA - eng PT - Journal Article DEP - 20251108 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Manometry MH - *Esophageal Motility Disorders/chemically induced MH - Female MH - Male MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - United States EDAT- 2025/11/11 00:27 MHDA- 2026/08/21 23:37 CRDT- 2025/11/10 19:12 PHST- 2025/07/29 00:00 [received] PHST- 2025/10/31 00:00 [revised] PHST- 2025/11/05 00:00 [accepted] PHST- 2026/08/21 23:37 [medline] PHST- 2025/11/11 00:27 [pubmed] PHST- 2025/11/10 19:12 [entrez] AID - S1542-3565(25)00941-3 [pii] AID - 10.1016/j.cgh.2025.11.003 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2026 Sep;24(9):2620-2622. doi: 10.1016/j.cgh.2025.11.003. Epub 2025 Nov 8. PMID- 41212550 OWN - NLM STAT- MEDLINE DCOM- 20260113 LR - 20260629 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 335 IP - 2 DP - 2026 Jan 13 TI - Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review. PG - 163-174 LID - 10.1001/jama.2025.19615 [doi] AB - IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction-associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. OBSERVATIONS: The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (>/=50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor beta-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis. CONCLUSIONS: A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis. FAU - Tilg, Herbert AU - Tilg H AD - Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria. FAU - Petta, Salvatore AU - Petta S AD - Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties Promise, University of Palermo, Palermo, Italy. FAU - Stefan, Norbert AU - Stefan N AD - Department of Internal Medicine IV, Division of Endocrinology, Diabetology, and Nephrology, University of Tubingen, Tubingen, Germany. AD - Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Tubingen, Germany. FAU - Targher, Giovanni AU - Targher G AD - Department of Medicine, University of Verona, Verona, Italy. AD - Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy. LA - eng PT - Journal Article PT - Review PL - United States TA - JAMA JT - JAMA JID - 7501160 SB - IM EIN - JAMA. 2026 Jul 28;336(4):347. doi: 10.1001/jama.2026.11797. PMID: 42371640 MH - Adult MH - Female MH - Humans MH - Male MH - Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology MH - *Metabolic Syndrome/complications/diagnosis/epidemiology/therapy MH - Obesity/complications/diagnosis/epidemiology MH - Risk Factors MH - *Non-alcoholic Fatty Liver Disease/complications/diagnosis/epidemiology/therapy MH - Carcinoma, Hepatocellular/epidemiology/etiology/prevention & control MH - Liver Neoplasms/epidemiology/etiology/prevention & control MH - Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - Liver/metabolism/pathology MH - Liver Cirrhosis/epidemiology/etiology/pathology/prevention & control MH - Age Factors MH - Sex Factors EDAT- 2025/11/10 12:35 MHDA- 2026/01/13 13:15 CRDT- 2025/11/10 11:33 PHST- 2026/01/13 13:15 [medline] PHST- 2025/11/10 12:35 [pubmed] PHST- 2025/11/10 11:33 [entrez] AID - 2841071 [pii] AID - 10.1001/jama.2025.19615 [doi] PST - ppublish SO - JAMA. 2026 Jan 13;335(2):163-174. doi: 10.1001/jama.2025.19615. PMID- 41211586 OWN - NLM STAT- MEDLINE DCOM- 20251112 LR - 20260708 IS - 2090-0716 (Electronic) IS - 2090-0708 (Print) IS - 2090-0708 (Linking) VI - 2025 DP - 2025 TI - Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Obesity Management in Adults With and Without Type 2 Diabetes: A Systematic Review. PG - 3897161 LID - 10.1155/jobe/3897161 [doi] LID - 3897161 AB - OBJECTIVE: This systematic review aimed to assess the efficacy and safety of GLP-1 RAs in adults with obesity or overweight, by comparing different GLP-1 RAs, identifying the most effective agents, and evaluating adverse effects. METHODS: We systematically searched Embase, MEDLINE, and Cochrane for phase 3 and 4 randomized controlled trials (RCTs) with a minimum duration of 40 weeks. Included studies compared GLP-1 RAs to placebo or to each other in adults with obesity (BMI >/= 30 kg/m(2)) or overweight (BMI >/= 27 kg/m(2)), with or without type 2 diabetes (T2DM). We excluded crossover trials, open-label studies, early-phase trials, and studies focusing on specific subpopulations. RESULTS: A total of 22 RCTs involving 41,757 participants were included. Among adults with T2DM, the greatest weight reductions were observed with tirzepatide 15 mg (-9.5 kg at 40 weeks; 72% lost >/= 5% of baseline weight) and semaglutide 2.4 mg (-9.6% body weight at 68 weeks; 69% lost >/= 5%). In participants without T2DM, semaglutide 2.4 mg (-14.9% body weight at 68 weeks) and tirzepatide 15 mg (-20.9% at 72 weeks) produced the most substantial effects, while semaglutide 50 mg was also effective in nondiabetic patients. Liraglutide 3 mg showed modest efficacy. Across trials, GLP-1 RAs were consistently associated with a higher frequency of gastrointestinal adverse events compared to placebo, including nausea (14%-28% vs. 5%-10%), vomiting (6%-12% vs. 2%-4%), and diarrhea (8%-20% vs. 4%-7%). The risk of pancreatitis and serious adverse events remained comparable to placebo. CONCLUSIONS: GLP-1 RAs, especially semaglutide and tirzepatide, are effective for weight management. Liraglutide may remain a viable, cost-effective alternative. CI - Copyright (c) 2025 Jena Velji-Ibrahim et al. Journal of Obesity published by John Wiley & Sons Ltd. FAU - Velji-Ibrahim, Jena AU - Velji-Ibrahim J AUID- ORCID: 0000-0002-5282-0727 AD - Gastroenterology and Liver Center, Prisma Health-Upstate, University of South Carolina School of Medicine, Greenville, South Carolina, USA. FAU - Radadiya, Dhruvil AU - Radadiya D AD - Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA. FAU - Devani, Kalpit AU - Devani K AD - Gastroenterology and Liver Center, Prisma Health-Upstate, University of South Carolina School of Medicine, Greenville, South Carolina, USA. FAU - Patel, Harsh AU - Patel H AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Nathani, Piyush AU - Nathani P AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Hassan, Cesare AU - Hassan C AD - Department of Gastroenterology and Hepatology, Humanitas Research Hospital, Milan, Italy. FAU - Pugliese, Nicola AU - Pugliese N AUID- ORCID: 0000-0001-6466-1412 AD - Department of Gastroenterology and Hepatology, Humanitas Research Hospital, Milan, Italy. FAU - Thompson, Christopher AU - Thompson C AD - Department of Advanced Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Sharma, Prateek AU - Sharma P AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. AD - Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20251019 PL - United States TA - J Obes JT - Journal of obesity JID - 101526295 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - J Obes. 2026 Feb 03;2026:9821679. doi: 10.1155/jobe/9821679. PMID: 41641176 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Adult MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12591819 OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - tirzepatide OT - weight loss COIS- Dhruvil Radadiya: Consultant: Castle Biosciences. Prateek Sharma: Consultant: Boston Scientific, Olympus Inc. Grant support: US Endoscopy, Medtronics, Fujifilms, Ironwood, Cosmo Pharmaceuticals, Erbe. Christopher Thompson: Consultant and Research Support from Apollo Endosurgery; Founder, Board Member, Ownership Interest with Bariendo; Founder and General Partner with BlueFlame Healthcare Venture Fund; Consultant and Research Support from Boston Scientific; Consultant with Medtronic; Founder, Board Member, Ownership Interest with ELLES; Consultant and Research Support from Endoquest Robotics; Founder, Consultant, Board Member, Ownership Interest with Enterasense Ltd; Founder, Board Member, Consultant, Ownership Interest with EnVision Endoscopy; Research Support from ERBE; Consultant, Advisory Board Member, Research Support from Fractyl; Consultant and Research Support from FujiFilm; Consultant and Research Support from GI Dynamics; Founder, Board Member, Ownership interest with GI Windows; Consultant and Research Support from Lumendi; Consultant and Research Support from Olympus/Spiration; Founder, President, Ownership Interest with Society for Metabolic and Bariatric Endoscopy; Consultant and Ownership Interest with Softac; Consultant, Advisory Board Member, Research Support from USGI Medical; and Consultant, Scientific Advisory Board, Ownership Interest with Xenter. No other disclosures were reported. EDAT- 2025/11/10 18:15 MHDA- 2025/11/13 00:31 PMCR- 2025/10/19 CRDT- 2025/11/10 06:18 PHST- 2025/05/05 00:00 [received] PHST- 2025/09/14 00:00 [revised] PHST- 2025/09/23 00:00 [accepted] PHST- 2025/11/13 00:31 [medline] PHST- 2025/11/10 18:15 [pubmed] PHST- 2025/11/10 06:18 [entrez] PHST- 2025/10/19 00:00 [pmc-release] AID - 10.1155/jobe/3897161 [doi] PST - epublish SO - J Obes. 2025 Oct 19;2025:3897161. doi: 10.1155/jobe/3897161. eCollection 2025. PMID- 41210503 OWN - NLM STAT- MEDLINE DCOM- 20251112 LR - 20251205 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - GLP1 receptor agonists and SGLT2 inhibitors for the prevention or delay of type 2 diabetes mellitus onset: a systematic review and meta-analysis. PG - 1627909 LID - 10.3389/fendo.2025.1627909 [doi] LID - 1627909 AB - BACKGROUND: SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1 RA) are two widely used classes of medications in the treatment of diabetes, each demonstrating significant efficacy and adoption. These medications have shown promising results in glycemic control and offer additional health benefits such as weight loss and cardiovascular protection. The objective of our meta-analysis is to systematically assess the effectiveness of SGLT-2 inhibitors and GLP-1 receptor agonists in slowing down or preventing the progression of prediabetic patients into diabetics. By synthesizing the existing evidence, we aim to determine whether early intervention with these medications can effectively mitigate the risk of developing diabetes in prediabetic individuals. This analysis will provide critical insights into their comparative effectiveness and inform clinical decision-making for early diabetes prevention strategies. METHODS: In this meta-analysis we primarily focused on randomized control trials (RCTs) that included the use of either SGLT-2 inhibitors, GLP-1 receptor agonists, or both. The database search was conducted using PubMed, Embase, and Cochrane. Statistical analysis was performed using IBM SPSS, and the results were reported with a 95% confidence interval (CI). RESULTS: The meta-analysis included 14 studies with the majority being double blinded (13/14). Effective randomization was evident from balanced baseline characteristics between treatment and control groups. Both SGLT-2 inhibitors and GLP-1 receptor agonists demonstrated significant reductions in body weight when given individually. This effect is also amplified when given as a combination therapy (SMD: -23, 95% CI: [-27.9, -18.10]). Also, fasting plasma glucose levels decreased in patients receiving treatment (SMD: -5.40, 95% CI: [-10.70, 2.24]) compared to control groups. Moreover, HbA1c levels were assessed in seven studies, where significant reductions in treatment groups were reported with a standardized mean difference of -6.95 (95% CI: [-14.24, 2.98], p-value= 0.06) for the overall effect size. Furthermore, three studies showed that SGLT-2 inhibitors reduced diabetes mellitus (DM) onset, though statistical significance was not achieved (p-value = 0.08, SMD: -2.21, CI: [-5.11, 0.69]). Finally, no significant change in fasting insulin levels was noticed with an overall SMD of -1.74 (95% CI: [-6.84, 3.37]), which was also not statistically significant (p-value: 0.55). These findings highlight the efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing HbA1C, fasting blood glucose, and body weight, while also potentially delaying the progression to type 2 diabetes mellitus in prediabetic patients. CONCLUSION: Early medical intervention at the prediabetic stage with SGLT-2i or GLP-1 RA shows potential in modifying progression to the onset of T2DM and its adverse effects. However, more studies are needed to reliably assess which of the two yields better results and further investigate the potential of combination therapy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024565439. CI - Copyright (c) 2025 Ghobar, Tarhini, Osman, Sbeih, Ghayda, Matar, Haddad, Kanaan, Eid, Azar, Ghadieh and Harb. FAU - Ghobar, Farah AU - Ghobar F AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Tarhini, Ali AU - Tarhini A AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Osman, Zeinab AU - Osman Z AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Sbeih, Sergio AU - Sbeih S AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Ghayda, Ralph Abou AU - Ghayda RA AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Matar, Patena AU - Matar P AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Haddad, Gaelle AU - Haddad G AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Kanaan, Amjad AU - Kanaan A AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. FAU - Eid, Assaad AU - Eid A AD - AUB Diabetes, American University of Beirut, Beirut, Lebanon. AD - Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. FAU - Azar, Sami AU - Azar S AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. AD - AUB Diabetes, American University of Beirut, Beirut, Lebanon. FAU - Ghadieh, Hilda E AU - Ghadieh HE AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. AD - AUB Diabetes, American University of Beirut, Beirut, Lebanon. FAU - Harb, Frederic AU - Harb F AD - Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Lebanon. AD - AUB Diabetes, American University of Beirut, Beirut, Lebanon. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251023 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/prevention & control/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC12588854 OTO - NOTNLM OT - Glucagon-like peptide-1 (GLP-1) OT - HbA1c OT - fasting glucose OT - fasting insulin OT - prediabetes OT - sodium-glucose transport protein 2 (SGLT-2) OT - type two diabetes mellitus (T2DM) COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/11/10 18:15 MHDA- 2025/11/12 23:30 PMCR- 2025/10/23 CRDT- 2025/11/10 06:08 PHST- 2025/05/13 00:00 [received] PHST- 2025/10/07 00:00 [accepted] PHST- 2025/11/12 23:30 [medline] PHST- 2025/11/10 18:15 [pubmed] PHST- 2025/11/10 06:08 [entrez] PHST- 2025/10/23 00:00 [pmc-release] AID - 10.3389/fendo.2025.1627909 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Oct 23;16:1627909. doi: 10.3389/fendo.2025.1627909. eCollection 2025. PMID- 41207920 OWN - NLM STAT- MEDLINE DCOM- 20260121 LR - 20260127 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 32 IP - 1 DP - 2026 Jan TI - Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. PG - 342-352 LID - 10.1038/s41591-025-04102-x [doi] AB - Cardiovascular outcome trials of the incretin-based medicines tirzepatide and semaglutide have shown benefits in populations with varying levels of cardiovascular risk. However, without direct head-to-head comparisons, treatment decisions rely on indirect evidence from heterogeneous trial populations, leaving optimal treatment choices uncertain. Here we conducted five cohort studies to assess the effectiveness of tirzepatide and semaglutide in patients with elevated cardiovascular risk, including obesity and type 2 diabetes, enrolled in insurance programs in the USA between 2018 and 2025. First, we emulated two cardiovascular outcome trials, SUSTAIN-6 (semaglutide versus sitagliptin as placebo proxy) and SURPASS-CVOT (tirzepatide versus dulaglutide), to benchmark and critically evaluate our design, data and analytic framework. Second, we assessed each drug in expanded populations reflective of patients routinely seen in clinical practice. Third, we directly compared tirzepatide versus semaglutide. Baseline confounders were balanced using propensity score matching. For the primary composite endpoint of myocardial infarction, stroke or all-cause mortality, benchmarking identified high agreement between the reference trials and their emulations for all individual endpoints except for all-cause mortality in SUSTAIN-6, informing subsequent analyses. In expanded populations, comparing semaglutide versus sitagliptin for the composite outcome of myocardial infarction or stroke yielded a hazard ratio of 0.82 (95% confidence interval (CI) 0.74 to 0.91), and comparing tirzepatide versus dulaglutide for the composite outcome including mortality yielded a hazard ratio of 0.87 (95% CI 0.75 to 1.01). In the head-to-head comparison of tirzepatide versus semaglutide, the hazard ratio was 1.06 (95% CI 0.95 to 1.18). These findings support a comparable cardiovascular benefit of tirzepatide and semaglutide in clinical practice and demonstrate how rigorously designed real-world evidence can complement randomized clinical trials. ClinicalTrials.gov registration: NCT06659744 , NCT07088718 , NCT07096063 . CI - (c) 2026. The Author(s). FAU - Kruger, Nils AU - Kruger N AUID- ORCID: 0009-0008-3190-0462 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. nkruger1@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. nkruger1@bwh.harvard.edu. AD - Department of Cardiology, TUM University Hospital German Heart Center, Technical University of Munich, Munich, Germany. nkruger1@bwh.harvard.edu. AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. nkruger1@bwh.harvard.edu. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Desai, Rishi J AU - Desai RJ AUID- ORCID: 0000-0003-0299-7273 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Sreedhara, Sushama Kattinakere AU - Sreedhara SK AUID- ORCID: 0000-0002-9182-304X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. FAU - Kehoe, Anna R AU - Kehoe AR AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Fuse, Kenshiro AU - Fuse K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Hahn, Georg AU - Hahn G AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Schunkert, Heribert AU - Schunkert H AUID- ORCID: 0000-0001-6428-3001 AD - Department of Cardiology, TUM University Hospital German Heart Center, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. FAU - Wang, Shirley V AU - Wang SV AUID- ORCID: 0000-0001-7761-7090 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. LA - eng SI - ClinicalTrials.gov/NCT06659744 SI - ClinicalTrials.gov/NCT07096063 SI - ClinicalTrials.gov/NCT07088718 GR - R01-HL141505/U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ GR - R01 HL141505/HL/NHLBI NIH HHS/United States GR - S/02/24/Deutsche Herzstiftung (German Heart Foundation)/ GR - SRF-HF/24/Deutsche Herzstiftung (German Heart Foundation)/ GR - R01-AR080194/U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ GR - R01 AR080194/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20251109 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Sitagliptin Phosphate/therapeutic use MH - *Tirzepatide/therapeutic use MH - Treatment Outcome MH - Observational Studies as Topic PMC - PMC12823426 COIS- Competing interests: S.S. reports personal fees from Aetion Inc., a software-enabled analytics company, and grants from Bayer, UCB and Boehringer Ingelheim to Brigham and Women's Hospital outside the submitted work. H.S. reports personal fees from AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Pharmacosmos, Sanofi, Servier, Synlab, Amgen and Amarin outside the submitted work. S.V.W. reports personal fees from MITRE, a federally funded research and development center for the Centers for Medicare and Medicaid Services and personal fees from Cytel Inc. during the conduct of the study. The other authors declare no competing interests. EDAT- 2025/11/10 00:53 MHDA- 2026/01/22 01:09 PMCR- 2025/11/09 CRDT- 2025/11/09 23:14 PHST- 2025/09/03 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2026/01/22 01:09 [medline] PHST- 2025/11/10 00:53 [pubmed] PHST- 2025/11/09 23:14 [entrez] PHST- 2025/11/09 00:00 [pmc-release] AID - 10.1038/s41591-025-04102-x [pii] AID - 4102 [pii] AID - 10.1038/s41591-025-04102-x [doi] PST - ppublish SO - Nat Med. 2026 Jan;32(1):342-352. doi: 10.1038/s41591-025-04102-x. Epub 2025 Nov 9. PMID- 41207620 OWN - NLM STAT- MEDLINE DCOM- 20260104 LR - 20260922 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 109 IP - 1 DP - 2026 Jan TI - REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. PG - 6-16 LID - S0085-2538(25)00861-0 [pii] LID - 10.1016/j.kint.2025.10.005 [doi] AB - Chronic kidney disease poses a major global health burden and is one of the most common complications of type 2 diabetes. Drug trials have demonstrated that treatments, including sodium-glucose cotransporter-2 inhibitors, a glucagon-like peptide-1 receptor agonist, and a nonsteroidal mineralocorticoid receptor antagonist, mitigate chronic kidney disease progression, but the underlying nephroprotective mechanisms of action remain incompletely understood, partly ascribed to their pleiotropic actions. New innovative trial designs are needed to tackle simultaneously the hemodynamic and structural effects induced by these drugs. The REMODEL trial (REnal MODE of action of semagLutide in patients with type 2 diabetes and chronic kidney disease; ClinicalTrials.gov identifier: NCT04865770) is designed to explore the mechanisms of action of semaglutide with a novel multiparametric approach, integrating functional magnetic resonance imaging and research kidney biopsies for structural and molecular interrogation and blood and urine biomarker analysis. Better understanding of these mechanisms will help explain semaglutide's beneficial effects on kidney disease outcomes, reported in the FLOW (Evaluate Renal Function with Semaglutide Once Weekly; ClinicalTrials.gov identifier: NCT03819153) trial, and may identify patient subpopulations to optimize treatment strategies. By combining diverse and state-of-the-art methods, REMODEL aims to pave the way to a larger use of mechanism of action trials in the near future. To this purpose, this article describes the REMODEL framework, methods, technical challenges, and lessons learned as a platform for future mechanistic trials of chronic kidney disease therapies and beyond. CI - Copyright (c) 2025 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Pruijm, Menno AU - Pruijm M AD - Service of Nephrology, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. Electronic address: menno.pruijm@chuv.ch. FAU - Belmar, Nicolas AU - Belmar N AD - Global Medical Affairs, Product and Portfolio Strategy, Novo Nordisk A/S, Soborg, Denmark. FAU - Bjornstad, Petter AU - Bjornstad P AD - Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington Medicine Diabetes Institute, Seattle, Washington, USA; Department of Pediatrics, Division of Endocrinology, University of Washington, Seattle, Washington, USA; Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Department of Pediatrics, Section of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. FAU - Das, Vivek AU - Das V AD - Clinical Omics Science, Data Science, Research & Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Gunnarsson, Thomas AU - Gunnarsson T AD - Global Medical Affairs, Product and Portfolio Strategy, Novo Nordisk A/S, Soborg, Denmark. FAU - Hodgin, Jeffrey B AU - Hodgin JB AD - Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, Michigan, USA. FAU - Schytz, Philip A AU - Schytz PA AD - Medical and Science, Research & Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence, Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA; Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle, Washington, USA. FAU - Kretzler, Matthias AU - Kretzler M AD - Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: kretzler@umich.edu. LA - eng SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT04865770 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251107 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Biomarkers/urine/blood MH - Biopsy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/drug therapy/etiology MH - Disease Progression MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney/drug effects/pathology/diagnostic imaging/physiopathology MH - Magnetic Resonance Imaging MH - *Renal Insufficiency, Chronic/drug therapy/etiology/pathology MH - Multicenter Studies as Topic MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - clinical trials OT - type 2 diabetes EDAT- 2025/11/10 00:53 MHDA- 2026/01/05 00:49 CRDT- 2025/11/09 19:15 PHST- 2025/08/01 00:00 [received] PHST- 2025/10/27 00:00 [revised] PHST- 2025/10/27 00:00 [accepted] PHST- 2026/01/05 00:49 [medline] PHST- 2025/11/10 00:53 [pubmed] PHST- 2025/11/09 19:15 [entrez] AID - S0085-2538(25)00861-0 [pii] AID - 10.1016/j.kint.2025.10.005 [doi] PST - ppublish SO - Kidney Int. 2026 Jan;109(1):6-16. doi: 10.1016/j.kint.2025.10.005. Epub 2025 Nov 7. PMID- 41207615 OWN - NLM STAT- MEDLINE DCOM- 20251219 LR - 20260805 IS - 1532-8600 (Electronic) IS - 0026-0495 (Linking) VI - 175 DP - 2026 Feb TI - GLP-1RAs and tirzepatide may reduce heart failure risk in obese but not in non-obese patients with cardiovascular or renal disease: A systematic review and meta-analysis. PG - 156433 LID - S0026-0495(25)00302-6 [pii] LID - 10.1016/j.metabol.2025.156433 [doi] AB - BACKGROUND: Cardiovascular disease (CVD) and chronic kidney disease (CKD) frequently coexist, with obesity and type 2 diabetes (T2D) being major contributors to adverse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide have shown cardiorenal benefits beyond glycemic control, but their efficacy across metabolic phenotypes remains unclear. METHODS: This review was prospectively registered in PROSPERO (CRD420251088042). PubMed, Embase, Web of Science, and Cochrane Library were searched (January 2015-July 2025) for RCTs comparing GLP-1RAs or tirzepatide with placebo in patients with cardiovascular or renal disease. Subgroup analyses were performed according to T2D and obesity status. RESULTS: A total of 18 RCTs (n = 97,800) involving eight GLP-1RAs and tirzepatide were included, primarily enrolling patients with established cardiovascular or renal disease. GLP-1RAs significantly reduced the risk of the primary composite outcome (RR 0.88, 95 % CI 0.84-0.91, P < 0.001). GLP-1RAs and tirzepatide also significantly reduced the risk of death from any cause (RR 0.88, 95 % CI 0.84-0.92, P < 0.001), and death from cardiovascular causes (RR 0.88, 95 % CI 0.83-0.93, P < 0.001). Although the overall effect of GLP-1RAs on hospitalization for heart failure was not statistically significant (RR 0.92, 95 % CI 0.78-1.08), a potential benefit was observed in obese patients (P for interaction = 0.02), warranting further investigation. GLP-1RAs showed favorable overall safety profile, with a lower incidence of serious adverse events (RR 0.93, 95 % CI 0.89-0.99, P = 0.01) and cardiac adverse events (RR 0.90, 95 % CI 0.85-0.96, P < 0.01) compared with placebo. CONCLUSION: In patients with cardiovascular or renal disease, GLP-1RAs and tirzepatide provide consistent cardiovascular and renal protection, with a possible benefit in reducing hospitalization for heart failure among individuals with obesity. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Zhang, Ju AU - Zhang J AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. FAU - Guan, Xiangfeng AU - Guan X AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. FAU - Kong, Mowei AU - Kong M AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. FAU - Xia, Meng AU - Xia M AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. FAU - Yu, Yang AU - Yu Y AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address: dr.yangyuself@gmail.com. FAU - Zhang, Chunxiang AU - Zhang C AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address: zhangchunxiang2121@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20251108 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Obesity/complications/drug therapy MH - *Heart Failure/prevention & control/epidemiology/etiology MH - *Cardiovascular Diseases/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Tirzepatide OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1RAs OT - Obesity OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2025/11/10 00:53 MHDA- 2025/12/20 00:41 CRDT- 2025/11/09 19:15 PHST- 2025/07/27 00:00 [received] PHST- 2025/10/31 00:00 [revised] PHST- 2025/11/03 00:00 [accepted] PHST- 2025/12/20 00:41 [medline] PHST- 2025/11/10 00:53 [pubmed] PHST- 2025/11/09 19:15 [entrez] AID - S0026-0495(25)00302-6 [pii] AID - 10.1016/j.metabol.2025.156433 [doi] PST - ppublish SO - Metabolism. 2026 Feb;175:156433. doi: 10.1016/j.metabol.2025.156433. Epub 2025 Nov 8. PMID- 41206745 OWN - NLM STAT- MEDLINE DCOM- 20260429 LR - 20260607 IS - 2058-1742 (Electronic) IS - 2058-1742 (Linking) VI - 12 IP - 3 DP - 2026 Apr 29 TI - GLP-1 receptor agonists and clinical outcomes in patients with type 2 diabetes undergoing transcatheter aortic valve implantation. PG - 405-418 LID - 10.1093/ehjqcco/qcaf135 [doi] AB - AIMS: We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. METHODS AND RESULTS: We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (>/=18 years) with T2D who underwent TAVI (2015-2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 +/- 1.1 and 2.6 +/- 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583-0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706-0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749-0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677-0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719-0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510-0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. CONCLUSION: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Pham, Hoang Nhat AU - Pham HN AUID- ORCID: 0000-0001-8412-0082 AD - Department of Medicine, University of Arizona-Tucson, 1625 N. Campbell Ave, Tucson, AZ 85719, USA. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Bcharah, George AU - Bcharah G AD - Mayo Clinic Alix School of Medicine, Phoenix, AZ 85259, USA. FAU - Mahmoud, Ahmed K AU - Mahmoud AK AD - Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. FAU - Allam, Mohamed AU - Allam M AUID- ORCID: 0000-0002-7687-9344 AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Farina, Juan AU - Farina J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Lee, Justin Z AU - Lee JZ AD - Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. FAU - Singh, Amitoj AU - Singh A AUID- ORCID: 0000-0003-1977-1270 AD - Sarver Heart Center, University of Arizona-Tucson, Tucson, AZ 85724, USA. FAU - Ayoub, Chadi AU - Ayoub C AUID- ORCID: 0000-0001-5877-7478 AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Alsidawi, Said AU - Alsidawi S AUID- ORCID: 0000-0001-8750-7880 AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Sell-Dottin, Kristen A AU - Sell-Dottin KA AD - Department of Cardiothoracic Surgery, Mayo Clinic, Phoenix, AZ 85259, USA. FAU - Chahal, Anwar AU - Chahal A AD - Wellspan Health, York, PA 17403, USA. AD - Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA. FAU - Sorajja, Dan AU - Sorajja D AUID- ORCID: 0000-0003-1976-6420 AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Lee, Kwan AU - Lee K AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Alkhouli, Mohamad AU - Alkhouli M AD - Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article PT - Multicenter Study PL - England TA - Eur Heart J Qual Care Clin Outcomes JT - European heart journal. Quality of care & clinical outcomes JID - 101677796 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - *Transcatheter Aortic Valve Replacement/methods MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Aortic Valve Stenosis/surgery/complications MH - Treatment Outcome MH - Aged, 80 and over MH - Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - Follow-Up Studies OTO - NOTNLM OT - Cardiovascular outcome OT - GLP-1 RA OT - SGLT2 inhibitor OT - Transcatheter aortic-valve implantation OT - Type 2 diabetes COIS- Conflict of interest: none declared. EDAT- 2025/11/09 14:46 MHDA- 2026/04/29 06:34 CRDT- 2025/11/09 06:22 PHST- 2025/05/24 00:00 [received] PHST- 2025/07/21 00:00 [revised] PHST- 2025/10/26 00:00 [accepted] PHST- 2026/04/29 06:34 [medline] PHST- 2025/11/09 14:46 [pubmed] PHST- 2025/11/09 06:22 [entrez] AID - 8314650 [pii] AID - 10.1093/ehjqcco/qcaf135 [doi] PST - ppublish SO - Eur Heart J Qual Care Clin Outcomes. 2026 Apr 29;12(3):405-418. doi: 10.1093/ehjqcco/qcaf135. PMID- 41204831 OWN - NLM STAT- MEDLINE DCOM- 20251229 LR - 20260127 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 1 DP - 2026 Jan TI - GLP-1 agonist-associated presentations to unscheduled care: An opportunistic pilot study. PG - 312-316 LID - 10.1002/bcp.70335 [doi] AB - The impact of GLP-1 or GIP/GLP-1 receptor agonist use on unscheduled care is not well-described. We conducted a prospective, observational study using opportunistic screening by clinicians as a first step to understanding the effect of GLP-1 or GIP/GLP-1 agonists on Emergency Department presentations and to guide future studies. Data were collected from April to August 2025 at a single centre for any nontrauma adult patient who self-reported GLP-1 or GIP/GLP-1 agonist exposure. Fifty-six cases were identified, 51 reported tirzepatide use, three subcutaneous semaglutide, one oral semaglutide and one dulaglutide. In 79% of cases (CI95% 66% to 88%), the presenting features were due to GLP-1 or agonist use. Presentations were greatest in the lowest and highest deprivation quintiles and a significant number had coexisting depression. There is a need for formal observational studies to assess the impact of GLP-1 or GIP/GLP-1 agonists on unscheduled care and explore these tentative associations. CI - (c) 2025 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Thomas, Oliver AU - Thomas O AUID- ORCID: 0009-0002-9448-2639 AD - Cardiff & Vale University Health Board, University Hospital of Wales, Heath Park Campus, Cardiff, UK. FAU - Coulson, James Michael AU - Coulson JM AD - All Wales Therapeutics & Toxicology Centre, Cardiff & Vale University Health Board, University Hospital, Llandough, Penarth, UK. AD - School of Medicine, Cardiff University, Cardiff, UK. LA - eng PT - Journal Article PT - Observational Study DEP - 20251108 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Pilot Projects MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/administration & dosage MH - Aged MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Recombinant Fusion Proteins/adverse effects/administration & dosage MH - Adult MH - *Emergency Service, Hospital/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Immunoglobulin Fc Fragments/adverse effects/administration & dosage MH - Gastric Inhibitory Polypeptide/agonists MH - Semaglutide PMC - PMC12746371 OTO - NOTNLM OT - GIP/GLP-1 OT - GLP-1 receptor agonist OT - unscheduled care COIS- The authors declare no conflicts of interest. EDAT- 2025/11/08 12:45 MHDA- 2025/12/29 13:02 PMCR- 2025/11/08 CRDT- 2025/11/08 06:02 PHST- 2025/10/11 00:00 [revised] PHST- 2025/09/16 00:00 [received] PHST- 2025/10/15 00:00 [accepted] PHST- 2025/12/29 13:02 [medline] PHST- 2025/11/08 12:45 [pubmed] PHST- 2025/11/08 06:02 [entrez] PHST- 2025/11/08 00:00 [pmc-release] AID - BCP70335 [pii] AID - 10.1002/bcp.70335 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Jan;92(1):312-316. doi: 10.1002/bcp.70335. Epub 2025 Nov 8. PMID- 41204644 OWN - NLM STAT- MEDLINE DCOM- 20260108 LR - 20260111 IS - 2191-0251 (Electronic) IS - 0334-018X (Print) IS - 0334-018X (Linking) VI - 39 IP - 1 DP - 2026 Jan 23 TI - Exploratory real-world experience with GLP-1 receptor agonists vs. metformin in youth with new-onset type 2 diabetes: a single-center retrospective study. PG - 56-64 LID - 10.1515/jpem-2025-0493 [doi] AB - OBJECTIVES: In youth with type 2 diabetes (YT2D), glucagon-like peptide 1 receptor agonists (GLP1) are recommended as adjuncts to metformin (Met) when glycemic targets are not achieved. Early GLP1 use may improve weight and glycemic control, but its efficacy as monotherapy in treatment-naive YT2D remains unstudied. This exploratory study compares GLP1 and Met monotherapy for glycemic and weight outcomes in newly diagnosed YT2D. METHODS: This retrospective study analyzed patients<21 diagnosed with T2D between January 2022 and March 2024 at a single center. Data were collected for up to 1 year following diagnosis for patients prescribed GLP1 or Met alone. Records were excluded if additional diabetes medication or bariatric surgery was introduced. A mixed effects linear regression model adjusted for baseline BMI, HbA(1c), age, and gender. RESULTS: The cohort included 12 GLP1 and 113 Met patients. About 83 % GLP1 patients were female (vs. Met 51 %). All were publicly insured. Median age at diagnosis was 14.8 years. Baseline and final HbA(1c) were similar: GLP1 (52-36 mmol/mol) and Met (52-44 mmol/mol), with 83 % GLP1 and 67 % Met patients achieving HbA(1c)/= 65 years old (0.82 [0.78 to 0.87]) or < 65 years old (0.84 [0.70 to 1.00]), and in those initiating semaglutide (0.75 [0.67 to 0.84]), liraglutide (0.77 [0.70 to 0.84]), or dulaglutide (0.82 [0.77 to 0.88]). The hazard ratios for dementia, Alzheimer's disease, vascular dementia, and Parkinson's disease onset were 0.76 [0.72 to 0.81], 0.77 [0.68 to 0.87], 0.75 [0.67 to 0.85], and 1.04 [0.93 to 1.17] with GLP-1 RAs versus DPP4i, respectively. The results were in the same direction when comparing individuals initiating GLP-1 RAs with those initiating basal insulin. CONCLUSIONS: In a real-world cohort of people living with T2D with a multinational representation, the initiation of GLP-1 RAs, compared to DPP4i or basal insulin, was associated with a lower risk of new-onset neurodegeneration. These data support the rationale for dedicated clinical trials to assess the potential neuroprotective properties of GLP-1 RAs in this population. CI - (c) 2025. The Author(s). FAU - Schechter, Meir AU - Schechter M AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. meir.schechter@mail.huji.ac.il. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. meir.schechter@mail.huji.ac.il. AD - The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan, Israel. meir.schechter@mail.huji.ac.il. AD - Dina Recanati School of Medicine, Reichman University, Herzliya, Israel. meir.schechter@mail.huji.ac.il. FAU - Fishkin, Alisa AU - Fishkin A AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Regeneron Pharmaceuticals Inc., New York, NY, USA. FAU - Sehtman-Shachar, Dvora R AU - Sehtman-Shachar DR AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. AD - Department of Epidemiology and Preventive Medicine, School of Public Health, Dear Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, Israel. FAU - Leibowitz, Gil AU - Leibowitz G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Aharon-Hananel, Genya AU - Aharon-Hananel G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20251107 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Neurodegenerative Diseases/epidemiology/diagnosis/prevention & control MH - Risk Factors MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Time Factors MH - Treatment Outcome MH - Risk Assessment MH - Biomarkers/blood MH - *Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Electronic Health Records MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12595915 OTO - NOTNLM OT - Alzheimer's disease OT - Dementia OT - Glucagon-like peptide-1 receptor agonists OT - Neurodegeneration OT - Neuroprotection OT - Parkinson's disease COIS- Declarations. Conflict of interest: MS reports travel support from Novo Nordisk and AstraZeneca through Hadassah Medical Center, and lecturing fees from AstraZeneca (2022). AF and DRSS report no conflict of interest. OM reports Advisory Board membership for Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and BOL Pharma, research grant support through Hadassah Hebrew University Hospital from Novo Nordisk and AstraZeneca, and Speaker's Bureau participation for AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, and Boehringer Ingelheim. From May 1st, 2023, OM has been an employee of Regeneron Pharmaceuticals Inc. This work was not funded by Regeneron Pharmaceuticals, Inc.; it was not part of OM's job responsibilities; and the company had no role in conception, data acquisition, analysis, interpretation, or manuscript preparation. TCY reports receiving research support from Medtronic, Regeneron, Novo Nordisk, and Merck Sharp & Dohme. Honorarium for lecture/advisory board from Medtronic, Sanofi, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, and Amgen. GL reports participation in previous Advisory Boards: Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Medtronic. He reports travel support from Novo Nordisk, Boehringer Ingelheim and AstraZeneca through Hadassah Medical Center. Speaker's Bureau: AstraZeneca, Novo Nordisk, Eli Lilly, Boehringer Ingelheim. GAH reported previous Advisory Board: Sanofi and Eli Lilly. She is a current PI in several RCTs conducted by Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca and Bayer including the CONFIDENCE study, through Hadassah Medical Center. GAH reports travel support from Novo Nordisk and Medetronic through Hadassah Medical Center and AstraZeneca through Sheba medical center. Speaker's Bureau: AstraZeneca, Novo Nordisk, Eli Lilly and Sanofi. EDAT- 2025/11/08 00:28 MHDA- 2025/11/08 06:29 PMCR- 2025/11/07 CRDT- 2025/11/07 23:53 PHST- 2025/08/02 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/11/08 06:29 [medline] PHST- 2025/11/08 00:28 [pubmed] PHST- 2025/11/07 23:53 [entrez] PHST- 2025/11/07 00:00 [pmc-release] AID - 10.1186/s12933-025-02962-8 [pii] AID - 2962 [pii] AID - 10.1186/s12933-025-02962-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Nov 7;24(1):426. doi: 10.1186/s12933-025-02962-8. PMID- 41201615 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260920 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 2 DP - 2026 Feb TI - Muscle loss and GLP-1R agonists use. PG - 333-342 LID - 10.1007/s00592-025-02611-2 [doi] AB - Skeletal muscle wasting is a major yet often overlooked determinant of adverse outcomes in diabetes mellitus and obesity. Loss of muscle mass and strength not only impairs mobility and quality of life, but also worsens insulin resistance, accelerates cardiometabolic decline and increases mortality risk. The convergence of chronic inflammation, mitochondrial dysfunction and altered protein metabolism makes individuals with metabolic diseases particularly vulnerable to sarcopenia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the therapeutic landscape of type 2 diabetes (T2D) and obesity by offering substantial weight loss and cardiometabolic protection. However, clinical trials and real-world evidence consistently show that weight reduction with GLP-1RAs is accompanied by decrease in lean body mass, raising concern in patients already predisposed to muscle wasting and underscoring the need for integrated management strategies. By including all English-language studies on muscle mass loss during GLP-1RA therapy in T2D and obesity from major scientific databases and clinical trial registries, this narrative review synthesizes the current knowledge on the epidemiology and mechanisms of muscle loss in diabetes and obesity, with a focus on the impact of GLP-1RAs therapy. It further examines preventive and therapeutic strategies to preserve muscle health during pharmacological weight loss, with the ultimate aim of providing clinicians and researchers with practical insights and future directions to maximize the benefits of GLP-1RAs while mitigating the risk of sarcopenia. CI - (c) 2025. The Author(s). FAU - Rossi, Giada AU - Rossi G AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita degli Studi di Milano, Milan, Italy. AD - Division of Endocrinology, ASST Fatebenefratelli Sacco, Milan, Italy. FAU - Bucciarelli, Loredana AU - Bucciarelli L AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita degli Studi di Milano, Milan, Italy. AD - Pio Albergo Trivulzio, Milan, Italy. FAU - Mananguite, Chyrell-Lyn AU - Mananguite CL AD - Internal Medicine Department, Clemenceau Hospital, Johns Hopkins International, Dubai, UAE. FAU - Giovarelli, Matteo AU - Giovarelli M AD - Department of Biomedical and Clinical Sciences (DIBIC), Universita degli Studi di Milano, Milan, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita degli Studi di Milano, Milan, Italy. paolo.fiorina@childrens.harvard.edu. AD - Division of Endocrinology, ASST Fatebenefratelli Sacco, Milan, Italy. paolo.fiorina@childrens.harvard.edu. AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave. Enders Building, Boston, MA, 02115, USA. paolo.fiorina@childrens.harvard.edu. AD - Brigham and Women's Hospital, Transplantation Research Center, Harvard Medical School, Boston, MA, USA. paolo.fiorina@childrens.harvard.edu. LA - eng GR - 20229ZA2YF/Ministero dell'Istruzione, dell'Universita e della Ricerca/ PT - Journal Article PT - Review DEP - 20251107 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Obesity/drug therapy/complications/metabolism MH - *Sarcopenia MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Muscle, Skeletal/drug effects/metabolism MH - Weight Loss/drug effects PMC - PMC12957034 OTO - NOTNLM OT - Diabetes mellitus OT - GLP-1RA OT - Muscle loss OT - Obesity OT - Prevention OT - Treatment COIS- Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. EDAT- 2025/11/07 12:46 MHDA- 2026/03/06 08:58 PMCR- 2025/11/07 CRDT- 2025/11/07 11:16 PHST- 2025/10/10 00:00 [received] PHST- 2025/10/26 00:00 [accepted] PHST- 2026/03/06 08:58 [medline] PHST- 2025/11/07 12:46 [pubmed] PHST- 2025/11/07 11:16 [entrez] PHST- 2025/11/07 00:00 [pmc-release] AID - 10.1007/s00592-025-02611-2 [pii] AID - 2611 [pii] AID - 10.1007/s00592-025-02611-2 [doi] PST - ppublish SO - Acta Diabetol. 2026 Feb;63(2):333-342. doi: 10.1007/s00592-025-02611-2. Epub 2025 Nov 7. PMID- 41200927 OWN - NLM STAT- MEDLINE DCOM- 20260601 LR - 20260605 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 25 IP - 6 DP - 2026 Jun TI - The efficacy and safety of dual GIP/GLP1 receptor agonists (tirzepatide) in diabetes and obesity: a systematic review and network meta-analysis. PG - 1031-1046 LID - 10.1080/14740338.2025.2586703 [doi] AB - BACKGROUND: Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear. METHODS: We conducted a PROSPERO-registered systematic review and network meta-analysis of randomized controlled trials up to July 2024. Trials comparing tirzepatide (5, 10, or 15 mg weekly) with placebo, insulin, or GLP-1 receptor agonists in adults with type 2 diabetes and/or obesity were included. Random-effects models estimated mean differences (MDs) or relative risks (RRs), with treatment ranking assessed by SUCRA and evidence certainty rated with CINeMA. RESULTS: Thirteen RCTs (14,007 participants) were included. Tirzepatide produced dose-dependent weight reductions versus insulin (MD -14.5 kg for 15 mg; -12.5 kg for 10 mg; -10.2 kg for 5 mg; all p < 0.0001). The likelihood of >/=15% weight loss (RR 4.83 for 15 mg), HbA1c reduction (MD -12.6 mmol/mol), and normoglycemia (RR 11.3) was significantly higher with tirzepatide. Safety analyses showed fewer serious adverse events (RR 0.71-0.77) and hypoglycemia (RR 0.44-0.50) than insulin, but more gastrointestinal events. CONCLUSIONS: Tirzepatide provides superior weight loss, glycemic improvements, and favorable safety versus insulin and other comparators, supporting its role as a leading therapy for type 2 diabetes and obesity. FAU - Hoffmann, Karolina AU - Hoffmann K AD - Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland. FAU - Michalak, Michal AU - Michalak M AD - Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland. FAU - Rizzo, Manfredi AU - Rizzo M AD - School of Medicine, Promise Department, University of Palermo, Palermo, Italy. AD - Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Maggio, Viviana AU - Maggio V AD - School of Medicine, Promise Department, University of Palermo, Palermo, Italy. FAU - Paczkowska, Anna AU - Paczkowska A AD - Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20251111 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/blood/drug therapy/physiopathology MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Insulin/administration & dosage/adverse effects MH - *Obesity/drug therapy/physiopathology MH - Randomized Controlled Trials as Topic MH - *Tirzepatide/adverse effects/administration & dosage MH - Weight Loss/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - obesity OT - tirzepatide OT - type 2 diabetes OT - weight loss EDAT- 2025/11/07 12:47 MHDA- 2026/06/01 12:38 CRDT- 2025/11/07 06:23 PHST- 2026/06/01 12:38 [medline] PHST- 2025/11/07 12:47 [pubmed] PHST- 2025/11/07 06:23 [entrez] AID - 10.1080/14740338.2025.2586703 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2026 Jun;25(6):1031-1046. doi: 10.1080/14740338.2025.2586703. Epub 2025 Nov 11. PMID- 41196662 OWN - NLM STAT- MEDLINE DCOM- 20251219 LR - 20260721 IS - 1939-327X (Electronic) IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 75 IP - 1 DP - 2026 Jan 1 TI - Additive Effects of Dorzagliatin and Glucagon-Like Peptide 1 Receptor Agonism in a Novel Mouse Model of GCK-MODY and in Obese db/db Mice. PG - 99-114 LID - 10.2337/db25-0520 [doi] AB - Glucokinase (GK) catalyzes the key regulatory step in glucose-stimulated insulin secretion (GSIS). Correspondingly, hetero- and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes mellitus, respectively. To explore the possible utility of GK activators (GKAs) and of glucagon-like peptide 1 (GLP-1) receptor agonists in these diseases, we have developed a novel hypomorphic Gck allele in mice encoding an aberrantly spliced mRNA. In islets from homozygous knock-in (GckKI/KI) mice, GK immunoreactivity was reduced by >85%, and GSIS eliminated. Homozygous GckKI/KI mice displayed frank diabetes (fasting blood glucose >18 mmol/L; HbA1c approximately 108 mmol/mol), ketosis, and nephropathy. Heterozygous GckKI/+ mice were glucose intolerant (HbA1c approximately 37 mmol/mol). Abnormal glucose-stimulated Ca2+ dynamics in GckKI/+ islets were completely reversed by the GKA dorzagliatin, which was largely inactive in homozygous GckKI/KI mouse islets. The GLP-1 receptor agonist exendin-4 improved glucose tolerance in male GckKI/+ mice, an action potentiated by dorzagliatin. Sex-dependent additive effects of these agents were also observed on insulin secretion in vitro. Similar additive effects of the drugs were observed in obese hyperglycemic db/db mice. Combined treatment with GKA and incretin mimetics may thus be useful in GCK-MODY and in more common forms of type 2 diabetes. ARTICLE HIGHLIGHTS: Glucokinase (GK) deficiency can drive maturity-onset diabetes of the young (GCK-MODY) in heterozygotes and permanent neonatal diabetes in homozygotes. We describe a hypomorphic Gck allele that results in aberrant splicing in islets and liver lowering GK activity by approximately 85%. Whereas heterozygous mutant mice are mildly hyperglycemic, homozygotes have frank diabetes but survive to adulthood. Dorzagliatin potentiates the effects of glucagon-like receptor-1 receptor activation sex dependently in heterozygous Gck mice and in obese hyperglycemic db/db mice. Combined use of these drugs may be useful in some forms of GCK-MODY and in obesity-related type 2 diabetes. CI - (c) 2025 by the American Diabetes Association. FAU - Salazar, Shadai AU - Salazar S AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Delgadillo-Silva, Luis Fernando AU - Delgadillo-Silva LF AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Carapeto, Priscila AU - Carapeto P AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Kenfaoui, Mohamed Mourad AU - Kenfaoui MM AD - Department of Biochemistry and Molecular Medicine, Universite de Montreal, Quebec, Canada. FAU - Dakessian, Karen AU - Dakessian K AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Melhem, Rana AU - Melhem R AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Provencher-Girard, Audrey AU - Provencher-Girard A AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Ostinelli, Giada AU - Ostinelli G AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Turgeon, Julie AU - Turgeon J AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. FAU - Kaci, Imane AU - Kaci I AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. AD - Departement de Medecine, Universite de Montreal, Montreal, Quebec, Canada. FAU - Migneault, Francis AU - Migneault F AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. AD - Departement de Microbiologie, Infectiologie et Immunologie, Faculte de Medecine, Universite de Montreal, Montreal, Quebec, Canada. FAU - Huising, Mark O AU - Huising MO AD - Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA. AD - Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA. FAU - Hebert, Marie-Josee AU - Hebert MJ AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. AD - Departement de Medecine, Universite de Montreal, Montreal, Quebec, Canada. FAU - Chaker-Margot, Malik AU - Chaker-Margot M AD - Department of Biochemistry and Molecular Medicine, Universite de Montreal, Quebec, Canada. FAU - Rutter, Guy A AU - Rutter GA AUID- ORCID: 0000-0001-6360-0343 AD - Research Center of the Hospital Center of the University of Montreal and University of Montreal, Quebec, Canada. AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, U.K. AD - Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. AD - Lee Kong Chian School of Medicine, Nanyang Technological College, Singapore. LA - eng GR - 333916/CIHR/Canada GR - WT212625/Z/18/Z/WT_/Wellcome Trust/United Kingdom GR - R01 DK135268/DK/NIDDK NIH HHS/United States GR - JDRF 4-SRA-2023-1182-S-N/CIHR-JDRF Team/ GR - 353239/CIHR/Canada GR - R01DK135268/NIH-NIDDK/ GR - WT_/Wellcome Trust/United Kingdom GR - CFI 42649/CIHR-JDRF Team/ GR - 489982/CIHR/Canada GR - BDA 16/0005485/DUK_/Diabetes UK/United Kingdom GR - 353239/Fonds de Recherche du Qubec - Nature, Science/ GR - R01 DK110276/DK/NIDDK NIH HHS/United States GR - MR/R022259/1/MRC Programme/ GR - 333390/Fonds de Recherche du Qubec - Sant/ GR - CIHR-IRSC TDP-186358/CIHR-JDRF Team/ PT - Journal Article PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - EC 2.7.1.2 (Glucokinase) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM UOF - bioRxiv. 2024 Nov 11:2024.11.09.622781. doi: 10.1101/2024.11.09.622781. PMID: 39605321 MH - Animals MH - Mice MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/genetics MH - *Glucokinase/genetics/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Disease Models, Animal MH - Male MH - Islets of Langerhans/metabolism/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Insulin Secretion/drug effects MH - Female MH - *Hypoglycemic Agents/pharmacology/therapeutic use PMC - PMC12716621 COIS- Duality of Interest. G.A.R. has received grant funding from, and is a consultant for, Sun Pharmaceuticals Inc. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/11/06 18:26 MHDA- 2025/12/19 18:32 PMCR- 2025/11/06 CRDT- 2025/11/06 12:12 PHST- 2025/06/02 00:00 [received] PHST- 2025/10/09 00:00 [accepted] PHST- 2025/12/19 18:32 [medline] PHST- 2025/11/06 18:26 [pubmed] PHST- 2025/11/06 12:12 [entrez] PHST- 2025/11/06 00:00 [pmc-release] AID - 163756 [pii] AID - 250520 [pii] AID - 10.2337/db25-0520 [doi] PST - ppublish SO - Diabetes. 2026 Jan 1;75(1):99-114. doi: 10.2337/db25-0520. PMID- 41196592 OWN - NLM STAT- MEDLINE DCOM- 20251106 LR - 20260726 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 11 DP - 2025 Nov 3 TI - Cost-Effectiveness of MASH Diagnosis and Management Approaches Among Those With Type 2 Diabetes. PG - e2542750 LID - 10.1001/jamanetworkopen.2025.42750 [doi] LID - e2542750 AB - IMPORTANCE: Metabolic dysfunction-associated steatohepatitis (MASH) represents a high, underprioritized burden among noncommunicable diseases (NCDs) and people living with type 2 diabetes (T2D). OBJECTIVE: To identify cost-effective management approaches to prevent, detect, and treat MASH and liver fibrosis in people living with T2D. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation consisted of a generalized cost-effectiveness analysis (GCEA) that was conducted for 12 countries (Brazil, Chile, Germany, Italy, Japan, Saudi Arabia, South Africa, Spain, Sweden, Tanzania, Thailand, and the United States), across all 6 World Health Organization (WHO) regions. A cohort state-transition model simulated liver disease development and its impact on a synthetic cohort, aged 19 years and older and living with T2D, over their lifespan across 10 liver health states. EXPOSURES: Using an 80% coverage level, 14 management approaches were compared, including screening via the Fibrosis-4 (FIB-4) test and Enhanced Liver Fibrosis (ELF) test or vibration-controlled transient elastography (VCTE) as well as treatment with pharmacological and nonpharmacological interventions. MAIN OUTCOMES AND MEASURES: The main outcomes were the average cost-effectiveness ratios (ACERs) and the incremental cost-effectiveness ratios (ICERs), which were used to construct care expansion paths by ranking the management approaches in order of cost-effectiveness. The main measures were the total incremental costs and the total incremental quality-adjusted life-years (QALYs) of each intervention. RESULTS: In this GCEA, the outcomes were evaluated with respect to country-specific willingness-to-pay thresholds. The standard of care had the lowest ACERs in 8 countries (not in Chile, Germany, Saudi Arabia, or the United States). Treatment with intensive lifestyle interventions (ILIs), after screening via ELF or VCTE, was cost-effective in all countries. ILIs and treatment with semaglutide was cost-effective in 11 countries (not in Tanzania); ILIs and treatment with resmetirom was cost-effective in 8 countries (not in Brazil, South Africa, Tanzania, or Thailand). CONCLUSION AND RELEVANCE: In this economic evaluation, screening followed by ILIs was found to be a cost-effective management approach for MASH and liver fibrosis among people living with T2D in all countries. Screening followed by pharmacological treatment was cost-effective in most countries. These results can inform health policy decision-making and further the development of WHO recommended interventions to address NCDs. FAU - Lazarus, Jeffrey V AU - Lazarus JV AD - City University of New York Graduate School of Public Health and Health Policy (CUNY SPH), New York. AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. AD - Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain. FAU - Agirre-Garrido, Leire AU - Agirre-Garrido L AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. FAU - Diaz, Luis Antonio AU - Diaz LA AD - Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. AD - Observatorio Multicentrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile. AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla. FAU - Danpanichkul, Pojsakorn AU - Danpanichkul P AD - Department of Internal Medicine, Texas Tech University Health Science Center, Lubbock. FAU - Kivuyo, Sokoine L AU - Kivuyo SL AD - Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain. AD - National Institutes for Medical Research, Dar es Salaam, Tanzania. FAU - Kondili, Loreta A AU - Kondili LA AD - National Center for Global Health, Istituto Superiore di Sanita, Rome, Italy. FAU - Hagstrom, Hannes AU - Hagstrom H AD - Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. AD - Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden. FAU - Takahashi, Hirokazu AU - Takahashi H AD - Liver Center, Saga University Hospital, Saga City, Saga, Japan. FAU - Pericas, Juan M AU - Pericas JM AD - Liver Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute for Research, Universitat Autonoma de Barcelona, Centros de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain. FAU - Spearman, C Wendy AU - Spearman CW AD - Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. FAU - Oliveira, Claudia P AU - Oliveira CP AD - Department of Gastroenterology, Faculdade de Medicina da Universidade de Sao Paulo (LIM07), Sao Paulo, Brazil. FAU - Villela-Nogueira, Cristiane A AU - Villela-Nogueira CA AD - School of Medicine, Hepatology Division, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Schattenberg, Jorn M AU - Schattenberg JM AD - Department of Internal Medicine II, Saarland University Medical Centre, Homburg, Germany. AD - Faculty of Medicine, Saarland University, Saarbrucken, Germany. FAU - Toresson Grip, Emilie AU - Toresson Grip E AD - Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. FAU - Alkhouri, Naim AU - Alkhouri N AD - Steatotic Liver Disease Program, Arizona Liver Health, Phoenix. FAU - Marcellusi, Andrea AU - Marcellusi A AD - Department of Pharmaceutical Sciences, University of Milan, Milan, Italy. FAU - Mark, Henry E AU - Mark HE AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. FAU - Allen, Alina M AU - Allen AM AD - Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Carvalho Leite, Nathalie AU - Carvalho Leite N AD - Hepatology Division, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Al-Omar, Hussain A AU - Al-Omar HA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alqahtani, Saleh A AU - Alqahtani SA AD - King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. FAU - Brachowicz, Nicolai AU - Brachowicz N AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251103 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/economics MH - *Cost-Benefit Analysis MH - Female MH - Middle Aged MH - Male MH - Liver Cirrhosis/economics/diagnosis/therapy MH - Adult MH - *Non-alcoholic Fatty Liver Disease/therapy/economics/diagnosis MH - Aged MH - Quality-Adjusted Life Years PMC - PMC12593099 COIS- Conflict of Interest Disclosures: Dr Lazarus reported receiving grants to the institution (ISGlobal) from Gilead Science, Echosens, Novo Nordisk, Pfizer, Madrigal Pharmaceuticals, Boehringer Ingelheim, AbbVie, Moderna, MSD, and Roche Diagnostics; receiving personal fees from GSK, Echosens, Novovax, Novo Nordisk, and Pfizer; having held a paid leadership role at the Global NASH/MASH Council; receiving honoraria from AbbVie, Echosens, Gilead Science, GSK, Moderna, MSD, Novo Nordisk, Pfizer and Prosciento; participating on a data safety monitoring board for the QuickStart Study; having a leadership role in Healthy Livers, Health Lives; and serving as director of the Global Think-tank on Steatotic Liver Disease and MASH Cities outside the submitted work. Dr Kondili reported receiving grants to her institution from Gilead Science and personal fees from Gilead Science for participation in a scientific meeting outside the submitted work. Dr Hagstrom reported receiving grants to his institution from AstraZeneca, Echosens, Gilead Science, Intercept, MSD, Novo Nordisk and Pfizer; receiving consulting fees from AstraZeneca and Novo Nordisk; receiving payment for lectures from Gilead Science and Novo Nordisk; and participating on hepatic events adjudication committees for Arrowhead, KOWA, GW Pharma, and Boehringer Ingelheim outside of the submitted work. Dr Takahashi reported receiving honoraria for lectures from Novo Nordisk, Tisho Pharma, and Kowa outside of the submitted work. Dr Pericas reported receiving consulting fees from MSD, Madrigal Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk; receiving speaking fees from Madrigal Pharmaceuticals, Gilead Science, Intercept, Boehringer Ingelheim, Novo Nordisk, Asociacion Espanola para el Estudio del Higado, and International Meeting on Therapy in Liver Diseases; travel expenses from Gilead Science, Rubio, Pfizer, Astellas, MSD, and Novo Nordisk; receiving educational and research support from Madrigal Pharmaceuticals, Boehringe Ingelheim, Gilead Science, Pfizer, Astellas, Accelerate, Novartis, AbbVie, ViiV, Siemens and MSD; and receiving competitive funding from Vall d'Hebron University Hospital Campus (research intensification grant 2024-2025), ISCIII PI19/01898, PI22/01770, European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, HLTH-2023-TOOL-05-03, MICIN IBEC_ProyectCompl22, DTS24/00035, and "La Caixa" Foundation and Barcelona City Council (COVID-SHINE and StopALD) outside of the submitted work. Dr Spearman reported receiving honoraria for lectures from Novo Nordisk, Gilead Science, and Sanofi; receiving travel support from Gilead Science, and having a leadership or fiduciary role for the Society on Liver Disease in Africa (SOLDA) outside the submitted work. Dr Oliveira reported receiving consulting fees from Novo Nordisk, Boehringer Ingelheim, Inventiva AstraZeneca, and Pfizer; receiving payment or honoraria for lectures from Novo Nordisk, Boehringer Ingelheim, Inventiva, AstraZeneca, and Pfizer, and receiving support for attending meetings from Novo Nordisk and Mertz outside of the submitted work. Dr Villela-Nogueira reported receiving honoraria from Novo Nordisk, Boehringer Ingelheim, and Mantecorp; receiving travel support from Novo Nordisk; and serving on the advisory boards of Novo Nordisk and Boehringer Ingelheim outside of the submitted work. Dr Schattenberg reported receiving speaker fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Science, Ipsen, Eli Lilly and Co, Madrigal Pharmaceuticals, MedScape, MSD, and Novo Nordisk; receiving personal fees from Akero, Alentis, Alexion, Altimmune, AstraZeneca, 89Bio, Bionorica, Boehringer Ingelheim, Boston Pharmaceuticals, Gilead Science, GSK, HistoIndex, Ipsen, Inventiva Pharma, Madrigal Pharmaceuticals, Kriya Therapeutics, Eli Lilly and Co, MSD Sharp & Dohme GmbH, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; and having stock options in Hepta Bio outside the submitted work. Mrs Grip reported receiving consulting fees from Quantify Research outside of the submitted work. Dr Alkhouri reported receiving grants to Arizona Liver Health from 89bio, Akero Therapeutics, Allergan, Arbutus Biopharma, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, CymaBay Therapeutics, DSM, Galectin Therapeutics, Genentech, Genfit, Gilead Science, Healio, Hepagene Therapeutics, Intercept Pharmaceuticals, Inventiva Pharma, Ionis Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Noom, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking Therapeutics, and Zydus Pharmaceuticals during the conduct of the study as well as receiving personal fees from 89bio, Akero, Boehringer Ingelheim, Echosens, Fibronostics, Gilead Science, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, Regeneron, and Zydus Pharmaceuticals; receiving honoraria for lectures from AbbVie, AstraZeneca, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, and Perspectum outside the submitted work. Mr Mark reported being a director of HEM Consultancy and receiving consulting fees from Panorma Global, Barcelona Institute for Global Health, the European Association for the Study of the Liver, GBCHealth, and the United Nations University-IIGH outside of the submitted work. Dr Allen reported receiving grants to Mayo Clinic from the National Institutes of Health, Novo Nordisk, Madrigal Pharmaceuticals, Target Pharma, Siemens, Oncoustics, Escopics, and Pfizer as well as receiving consulting fees from Boehringer Ingelheim, Madrigal Pharmaceuticals, Novo Nordisk, and GSK outside the submitted work. Mr Brachowicz reported receiving support from the Ministerio de Ciencia, Innovacion y Universidades/Agencia Estatal de Investigacion (MCIN/AEI) and the Generalitat de Catalunya, through the CERCA Programme. No other disclosures were reported. EDAT- 2025/11/06 12:33 MHDA- 2025/11/06 12:34 PMCR- 2025/11/06 CRDT- 2025/11/06 11:33 PHST- 2025/11/06 12:34 [medline] PHST- 2025/11/06 12:33 [pubmed] PHST- 2025/11/06 11:33 [entrez] PHST- 2025/11/06 00:00 [pmc-release] AID - 2841038 [pii] AID - zoi251164 [pii] AID - 10.1001/jamanetworkopen.2025.42750 [doi] PST - epublish SO - JAMA Netw Open. 2025 Nov 3;8(11):e2542750. doi: 10.1001/jamanetworkopen.2025.42750. PMID- 41196232 OWN - NLM STAT- MEDLINE DCOM- 20251209 LR - 20251209 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 34 IP - 11 DP - 2025 Nov TI - Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions. PG - 929-941 LID - 10.1080/13543784.2025.2587277 [doi] AB - INTRODUCTION: This review evaluates the potential of glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs) - first developed for type 2 diabetes and later approved for chronic weight management and additional indications - to be repurposed as neuroprotective and remyelinating therapies in multiple sclerosis (MS). We synthesize emerging pre‑clinical and early clinical evidence, highlight practical barriers to translation, and outline directions for future research. AREAS COVERED: In experimental autoimmune encephalomyelitis and toxin-induced demyelination mouse models, GLP-1RAs have been shown to reduce oxidative stress, preserve axonal integrity, suppress microglial and astrocytic activation, and, in some cases, promote remyelination. Early observational data in people with MS suggest GLP-1RAs are well tolerated, provide expected metabolic benefits, and do not exacerbate disease activity. Moreover, signals of reduced neurological impairment and lower dementia incidence in broader diabetic cohorts further support their translational promise. However, to date, there are no published randomized controlled trials of GLP-1RAs in MS. EXPERT OPINION: Pre‑clinical and early clinical signals support GLP‑1RAs as promising candidates for neuroprotection in MS, yet definitive evidence of disease‑modifying efficacy is lacking. Practical barriers, such as drug availability and cost, together with unresolved mechanistic questions underscore the need for biomarker‑rich mechanistic trials. Rigorous prospective studies are essential to establish whether GLP‑1RAs can meaningfully alter the trajectory of MS. FAU - Shirani, Afsaneh AU - Shirani A AD - Saint Luke's Marion Bloch Neuroscience Institute, Kansas City, MO, USA. AD - Department of Neurology, University of Missouri-Kansas City, Kansas City, MO, USA. FAU - Stuve, Olaf AU - Stuve O AD - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA. AD - Neurology Section, VA North Texas Health Care System, Dallas, TX, USA. AD - Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. LA - eng PT - Journal Article PT - Review DEP - 20251110 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Neuroprotective Agents) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Multiple Sclerosis/drug therapy/physiopathology MH - *Neuroprotective Agents/pharmacology/adverse effects/therapeutic use MH - Mice MH - Disease Models, Animal MH - Encephalomyelitis, Autoimmune, Experimental/drug therapy/physiopathology MH - Diabetes Mellitus, Type 2/drug therapy MH - Drug Repositioning OTO - NOTNLM OT - Glucagon-Like Peptide-1 receptor agonists OT - medication repurposing OT - multiple sclerosis OT - neurodegenerative disorders OT - neuroprotection EDAT- 2025/11/06 12:33 MHDA- 2025/12/09 07:38 CRDT- 2025/11/06 10:22 PHST- 2025/12/09 07:38 [medline] PHST- 2025/11/06 12:33 [pubmed] PHST- 2025/11/06 10:22 [entrez] AID - 10.1080/13543784.2025.2587277 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2025 Nov;34(11):929-941. doi: 10.1080/13543784.2025.2587277. Epub 2025 Nov 10. PMID- 41192940 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20251203 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 6 DP - 2025 Nov 4 TI - Combination therapy with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in heart failure patients with type 2 diabetes. LID - 10.1136/bmjdrc-2025-005364 [doi] LID - e005364 AB - INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiovascular outcomes in type 2 diabetes (T2D), and SGLT2i reduces events in heart failure (HF). However, the benefit of their combination in patients with both conditions remains unclear. This study assessed the risk of all-cause death and hospitalization with combination therapy versus SGLT2i monotherapy. RESEARCH DESIGN AND METHODS: This multicenter, retrospective, observational study used the TriNetX database between January 1, 2018, and December 31, 2021. We identified 928,981 patients aged >/=18 years with HF and T2D. Of these, 168,422 received an SGLT2i. The exposure group comprised patients who initiated a GLP-1 RA within 6 months of SGLT2i initiation, while the control group included those who did not receive a GLP-1 RA after SGLT2i initiation. The index date was defined as 6 months after SGLT2i. 25,989 patients received SGLT2i and GLP-1 RA and 54,619 received SGLT2i monotherapy. Following propensity score matching, each group comprised 23,240 patients. RESULTS: Over 1 year, the risk of all-cause death in patients who received SGLT2i and GLP-1 RA relative to those who received SGLT2i monotherapy was significantly lower (2.8% vs 6.3%, p<0.001; HR 0.43; 95% CI 0.39 to 0.48). Similarly, the risk of hospitalization in patients who received SGLT2i and GLP-1 RA was also lower (32.9% vs 36.4%, p<0.001; HR, 0.87; 95% CI 0.84 to 0.90). CONCLUSIONS: The risk of all-cause death and hospitalization in patients who received combination therapy with SGLT2i and GLP-1 RA relative to those who received SGLT2i monotherapy was significantly lower in patients with HF and T2D. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Kyoto, Japan tkato75@kuhp.kyoto-u.ac.jp. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Matsumoto, Takahiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Shiga Prefecture, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251104 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Heart Failure/drug therapy/complications/mortality MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Middle Aged MH - Drug Therapy, Combination MH - Hospitalization/statistics & numerical data MH - Follow-Up Studies PMC - PMC12588009 OTO - NOTNLM OT - Heart Failure OT - Type 2 Diabetes COIS- Competing interests: None declared. EDAT- 2025/11/06 00:27 MHDA- 2025/11/06 00:28 PMCR- 2025/11/04 CRDT- 2025/11/05 20:33 PHST- 2025/06/28 00:00 [received] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/06 00:28 [medline] PHST- 2025/11/06 00:27 [pubmed] PHST- 2025/11/05 20:33 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 13/6/e005364 [pii] AID - bmjdrc-2025-005364 [pii] AID - 10.1136/bmjdrc-2025-005364 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Nov 4;13(6):e005364. doi: 10.1136/bmjdrc-2025-005364. PMID- 41192935 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260429 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 6 DP - 2025 Nov 4 TI - Semaglutide and diabetic retinopathy: an OHDSI network study. LID - 10.1136/bmjdrc-2025-005424 [doi] LID - e005424 AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from 1 December 2017 to 31 December 2023 were included. The association between semaglutide and PDR or treatment-requiring DR/DME was assessed using an active-comparator cohort design comparing new users of semaglutide as second-line T2D treatment to those on other GLP-1RAs and non-GLP-1RAs. Propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs). Network-wide HR estimates were generated using a random-effects meta-analysis. RESULTS: The study included 810 390 new semaglutide users for T2D. PDR risk for semaglutide was similar to dulaglutide (HR 0.81, 95% CI 0.42 to 1.54, p=0.51), empagliflozin (HR 0.83, 95% CI 0.53 to 1.30, p=0.41) and sitagliptin (HR 0.83, 95% CI 0.45 to 1.55, p=0.57) but was lower than glipizide (HR 0.59, 95% CI 0.39 to 0.88, p=0.01). The risk for treatment-requiring DR/DME for semaglutide was similar to empagliflozin (HR 0.66, 95% CI 0.43 to 1.02, p=0.06) but lower than dulaglutide (HR 0.53, 95% CI 0.31 to 0.91, p=0.02), sitagliptin (HR 0.46, 95% CI 0.26 to 0.81, p=0.008) and glipizide (HR 0.55, 95% CI 0.33 to 0.91, p=0.02). CONCLUSIONS AND RELEVANCE: We did not identify increased risk for either PDR or treatment-requiring DR/DME comparing semaglutide with other GLP-1RAs or non-GLP-1RAs. Patients with T2D should still undergo close eye care follow-up, particularly when initiating new antihyperglycemic medications. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Cai, Cindy Xinji AU - Cai CX AUID- ORCID: 0000-0003-3752-7239 AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA ccai6@jhmi.edu. AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California, USA. AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA. FAU - Goetz, Kerry AU - Goetz K AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. FAU - Hribar, Michelle AU - Hribar M AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. AD - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. FAU - Barkmeier, Andrew AU - Barkmeier A AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California, USA. FAU - Swaminathan, Swarup AU - Swaminathan S AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Flowers, Alexis AU - Flowers A AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Brown, Eric AU - Brown E AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Xu, Benjamin AU - Xu B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. FAU - Chen, John AU - Chen J AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California, USA. FAU - Boland, Michael AU - Boland M AD - Department of Ophthalmology, Mass Eye and Ear, Boston, Massachusetts, USA. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, Jazan University, Jazan, Jazan, Saudi Arabia. AD - Pharmacy Practice Research Unit, Jazan University, Jazan, Saudi Arabia. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Wilcox, Adam AU - Wilcox A AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Lai, Albert AU - Lai A AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Stocking, Jacqueline C AU - Stocking JC AUID- ORCID: 0000-0003-0775-684X AD - Department of Internal Medicine, University of California Davis, Davis, California, USA. FAU - Xie, Yangyiran AU - Xie Y AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Lee, Lok Hin AU - Lee LH AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Dorr, David AU - Dorr D AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - McCoy, David AU - McCoy D AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Adibuzzaman, Mohammad AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Areaux, Raymond Jr AU - Areaux R Jr AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA. FAU - Brash, James AU - Brash J AD - IQVIA, Real World Solutions, Brighton, England, UK. FAU - Weiskopf, Nicole AU - Weiskopf N AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Stanford, California, USA. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Stanford, California, USA. FAU - Tran, Diep AU - Tran D AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Rustam, Zainab AU - Rustam Z AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Zhu, Gina AU - Zhu G AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Swerdel, Joel AU - Swerdel J AD - Janssen Research & Development, Titusville, New Jersey, USA. FAU - Sena, Anthony AU - Sena A AD - Janssen Research & Development, Titusville, New Jersey, USA. AD - Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands. FAU - Nagy, Paul AU - Nagy P AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Suchard, Marc AU - Suchard M AD - Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, California, USA. AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, UT, USA. FAU - Schuemie, Martijn AU - Schuemie M AD - Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, California, USA. AD - Johnson and Johnson, Horsham, PA, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. FAU - Ryan, Patrick AU - Ryan P AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. AD - Johnson and Johnson, Horsham, PA, USA. LA - eng GR - K01 HL168222/HL/NHLBI NIH HHS/United States GR - P30 DK092950/DK/NIDDK NIH HHS/United States GR - P30 EY010572/EY/NEI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - T15 LM011271/LM/NLM NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - R01 LM013426/LM/NLM NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251104 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/chemically induced/epidemiology MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587949 OTO - NOTNLM OT - Diabetes Complications OT - Diabetic Retinopathy COIS- Competing interests: CXC: Regeneron Pharmaceuticals, Inc. (grant support), Optomed USA (equipment support), Boehringer Ingelheim (travel), 4D Molecular Therapeutics (travel). AN: none. SB: Consulting fees Topcon, Equipment support Optomed. KG: none. MH: none. BT: none. AB: none. SW: none. SS: Heidelberg Engineering (support), Lumata Health (Consulting, Equity), AbbVie (Consulting); Topcon (Consulting), Elios Vision (Consulting). AF: none. EB: none. BX: none. JC: none. AC: none. TL: Grants: Astellas, Consultant: Astellas, Boehringer Ingelheim, Roche/Genentech, Toku, Topcon, Virtual Field. MB: Carl Zeiss Meditec-consulting, speaking; Topcon healthcare, consulting; AbbVie-consulting; TA: none. FB: none. TF: none. BM: none. EW: none. NM: none. LZ: none. RF: none. AW: none. AL: none. JCS: none. YX: none. LHL: none. DD: none. IH: none. DM: none. MA: none. RA: none. JB: Employee of IQVIA. NW: none. HM-C: none. PD: none. DT: none. ZR: none. GZ: none. JS: Employee and Stockholder of Johnson & Johnson. AS: Employee and Stockholder of Johnson & Johnson. PN: none. MSu: Contracts and grants from Johnson & Johnson, Gilead and the US Food & Drug Administration. MSc: Employee and Stockholder of Johnson & Johnson. GH: none. PR: is an employee and shareholder of Johnson & Johnson. EDAT- 2025/11/06 00:27 MHDA- 2025/11/06 00:28 PMCR- 2025/11/04 CRDT- 2025/11/05 20:33 PHST- 2025/07/14 00:00 [received] PHST- 2025/10/11 00:00 [accepted] PHST- 2025/11/06 00:28 [medline] PHST- 2025/11/06 00:27 [pubmed] PHST- 2025/11/05 20:33 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 13/6/e005424 [pii] AID - bmjdrc-2025-005424 [pii] AID - 10.1136/bmjdrc-2025-005424 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Nov 4;13(6):e005424. doi: 10.1136/bmjdrc-2025-005424. PMID- 41189335 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - One-year usage patterns of SGLT-2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes in a real-world population. PG - 972-981 LID - 10.1111/dom.70269 [doi] AB - AIMS: Real-world studies of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) typically assess adherence and discontinuation as separate outcomes. We applied a novel approach that integrates these measures to categorize patterns of drug usage. We describe patterns across individual subclasses, and in overall class-level models, we examined clinical characteristics associated with each category with particular interest in poor adherence and intolerance. MATERIALS AND METHODS: We conducted an observational cohort study using electronic health records from the Scottish Care Information Diabetes Collaboration database, including individuals with type 2 diabetes who initiated a SGLT2i or GLP-1RA. Each initiation was followed for 1 year and classified into five mutually exclusive groups: adherent, poor adherence and three discontinuation categories including a proxy for intolerance. RESULTS: Among SGLT2is, poor adherence was more common in younger individuals, with greater socioeconomic deprivation, and higher HbA(1c), while intolerance was more frequent in older, leaner females and in those with prior genital thrush. For GLP-1RAs, newer agents were associated with more favourable usage patterns. Poor adherence was more frequent with liraglutide, lixisenatide, and exenatide compared to semaglutide, and intolerance was more common with lixisenatide. In addition, poor adherence was associated with younger age and prior GLP-1RA use, while intolerance was linked to lower BMI, female sex, and more advanced CKD. CONCLUSIONS: Distinct clinical and biochemical characteristics are associated with poor adherence versus discontinuation. Understanding these patterns is crucial for developing targeted strategies to improve sustained use, ultimately enhancing treatment outcomes for people with type 2 diabetes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Donnelly, Louise A AU - Donnelly LA AUID- ORCID: 0000-0003-4902-1040 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - Singh, Katyayeni AU - Singh K AUID- ORCID: 0000-0002-2702-3611 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - McCrimmon, Rory J AU - McCrimmon RJ AUID- ORCID: 0000-0002-3957-1981 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - Pearson, Ewan R AU - Pearson ER AUID- ORCID: 0000-0001-9237-8585 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. LA - eng GR - 875534/Innovative Medicines Initiative 2 Joint Undertaking/ PT - Journal Article PT - Observational Study DEP - 20251104 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Scotland/epidemiology MH - Glycated Hemoglobin/analysis MH - Cohort Studies MH - Medication Adherence PMC - PMC12803620 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - cohort study OT - database research OT - real-world evidence OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/11/05 06:29 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/05 01:52 PHST- 2025/10/24 00:00 [revised] PHST- 2025/09/10 00:00 [received] PHST- 2025/10/25 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/05 06:29 [pubmed] PHST- 2025/11/05 01:52 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70269 [pii] AID - 10.1111/dom.70269 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):972-981. doi: 10.1111/dom.70269. Epub 2025 Nov 4. PMID- 41188987 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260127 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 30 IP - 1 DP - 2025 Nov 4 TI - Semaglutide reduces cardiovascular events in type 2 diabetes: a systematic review and meta-analysis highlighting enhanced benefits in chronic kidney disease. PG - 1059 LID - 10.1186/s40001-025-03241-8 [doi] LID - 1059 AB - BACKGROUND: Cardiovascular disease (CVD) disproportionately affects type 2 diabetes (T2D) patients with chronic kidney disease (CKD). Although semaglutide shows cardiometabolic benefits, its efficacy across CVD endpoints and high-risk CKD subgroups remains underexplored. METHODS: We systematically reviewed PubMed, Embase, Cochrane, Web of Science (through September 2025) for randomized trials and observational studies evaluating oral semaglutide versus placebo in T2D. Data synthesis employed hazard ratios (HRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Across 17 studies (n = 40, 632 patients), semaglutide significantly reduced the risk of cardiovascular (CV) death by 23% [HR 0.77, 95% CI (0.68, 0.88)], major adverse cardiovascular events (MACE) by 18% [HR 0.82, 95% CI (0.75, 0.90)], expanded MACE by 22% [HR 0.78, 95% CI (0.70, 0.85)], nonfatal myocardial infarction (MI) by 18% [HR 0.82, 95% CI (0.68, 0.92)], and nonfatal stroke by 32% [HR 0.68, 95% CI (0.56, 0.83)]. The reductions in CV events were most pronounced in T2D patients with CKD (24-37% risk reduction vs. 13-35% in T2D alone or with CVD). Semaglutide also significantly improved modifiable CV risk factors, reducing systolic/diastolic blood pressure (SBP/DBP) decreased by 8.02/3.71 mmHg, and low-density Lipoprotein (LDL) decreased by 12.62 mg/dL, while increasing high-density lipoprotein (HDL) by 1.44 mg/dL. However, semaglutide had no significant effect on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). CONCLUSION: Semaglutide confers robust cardiovascular protection in T2D, with amplified benefits in patients with comorbid CKD. It confers a collective advantage by simultaneously addressing multiple risk factors including blood pressure and lipoprotein, positioning it as a comprehensive treatment strategy for high-risk populations. This analysis is the first to synthesize evidence across CKD subgroups, supporting prioritizing semaglutide in T2D patients with CKD. Further research should clarify mechanisms underlying CKD-specific benefits and refine risk-stratified treatment algorithms. CI - (c) 2025. The Author(s). FAU - Yao, Yanni AU - Yao Y AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Liu, Nairong AU - Liu N AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Chen, Siyan AU - Chen S AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Sun, Meng AU - Sun M AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Guo, Yanjie AU - Guo Y AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. yaoyanni-2021@qq.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251104 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12584374 OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - Meta-analysis OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Formal ethics committee approval was not required for this study, as it involves the secondary analysis of publicly available, de-identified data from previously published clinical trials. All original trials included in our analysis have been documented to have adhered to the Good Clinical Practice guidelines and/or the principles of the Declaration of Helsinki. Competing interests: The authors declare no competing interests. EDAT- 2025/11/05 00:28 MHDA- 2025/11/05 06:29 PMCR- 2025/11/04 CRDT- 2025/11/04 23:57 PHST- 2025/06/16 00:00 [received] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 23:57 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 10.1186/s40001-025-03241-8 [pii] AID - 3241 [pii] AID - 10.1186/s40001-025-03241-8 [doi] PST - epublish SO - Eur J Med Res. 2025 Nov 4;30(1):1059. doi: 10.1186/s40001-025-03241-8. PMID- 41187967 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE-1). PG - 337-346 LID - 10.1111/dom.70196 [doi] AB - AIMS: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515). MATERIALS AND METHODS: Participants aged >/=18 years with BMI >/=30 or >/=27 kg/m(2) with >/=1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks. The primary endpoints are percent body weight change and achievement of body weight reduction >/=5% from baseline to Week 76. Efficacy and safety analyses will include all randomized and treated participants. RESULTS: At baseline, participants (n = 725 from 14 countries) had a mean age of 47.1 years, BMI 37.9 kg/m(2), and waist circumference 115.2 cm. Most participants (59.4%) were female; 47.3% were from North America, 21.0% from Europe, and 20.0% from East Asia. Obesity complications included hypertension (40.0%), dyslipidaemia (33.7%), and prediabetes (30.2%). Mean haemoglobin A1c was 5.5%, estimated glomerular filtration rate 93.0 mL/min/1.73 m(2), systolic/diastolic blood pressure 127.0/82.7 mmHg, and low-density lipoprotein cholesterol 116.4 mg/dL; 21.8% were taking lipid-lowering drugs. CONCLUSIONS: SYNCHRONIZE-1 will determine the efficacy, safety, and tolerability of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for weight loss in a representative cohort of people with obesity without T2D. CI - (c) 2025 Boehringer Ingelheim and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - University College Dublin School of Medicine, Dublin, Ireland. AD - Ulster University, Coleraine, UK. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - McMaster University, Hamilton, Ontario, Canada. AD - University of Toronto, Toronto, Ontario, Canada. FAU - Bozkurt, Biykem AU - Bozkurt B AUID- ORCID: 0000-0002-6362-0253 AD - Winters Center for Heart Failure Research, Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, USA. FAU - Platz, Elke AU - Platz E AUID- ORCID: 0000-0002-8604-0710 AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Bleckert, Gabriele AU - Bleckert G AUID- ORCID: 0000-0002-4341-9042 AD - Staburo GmbH, on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. FAU - Ajaz Hussain, Samina AU - Ajaz Hussain S AUID- ORCID: 0009-0002-4849-0363 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Brueckmann, Martina AU - Brueckmann M AUID- ORCID: 0000-0003-1215-0746 AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. AD - First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Startseva, Elena AU - Startseva E AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Kloer, Isabel M AU - Kloer IM AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Kaplan, Lee M AU - Kaplan LM AUID- ORCID: 0000-0002-6301-2696 AD - Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. LA - eng SI - ClinicalTrials.gov/NCT06066515 GR - Boehringer Ingelheim/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20251104 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Double-Blind Method MH - *Obesity/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - Adult MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Aged MH - Diabetes Mellitus, Type 2 MH - Injections, Subcutaneous PMC - PMC12673442 OTO - NOTNLM OT - glucagon OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - randomized controlled trial COIS- CWlR has received personal fees from Boehringer Ingelheim, GI Dynamics, Herbalife, Johnson & Johnson, Keyron, Eli Lilly, and Novo Nordisk outside the submitted work. SW reports research funding from Novo Nordisk and Bausch Health Canada. He reports honoraria for academic talks and advisory board from Amgen, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Regeneron, Bausch Health Canada, Merck, iNova and Currax. BB has received consulting fees from Abbott, Abiomed, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardurion, Cytokinetics, Daiichi Sankyo, Johnson & Johnson, Lantheus, Liva Nova, Merck, Regeneron, Renovacor, Respicardia/Zoll, Roche, Sanofi-Aventis, and Vifor. EP's employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals. She has received research support from AstraZeneca, and she serves on the clinical trial steering committee of the SYNCHRONIZE-1 and -2 trials and SYNCHRONIZE-CVOT funded by Boehringer Ingelheim. GB is an employee of Staburo GmbH, which was contracted by Boehringer Ingelheim. SAH, MB, ES, and IMK are employees of Boehringer Ingelheim. LMK reports serving as a consultant to Altimmune, Amgen, AstraZeneca, Bain Capital, Boehringer Ingelheim, Cytoki, Gelesis, Gilead Sciences, Intellihealth, Johnson & Johnson, Kallyope, Eli Lilly, Novo Nordisk, Optum Health, Perspectum, Pfizer, Sidekick Health, Skye Bioscience, Structure Therapeutics, and Twenty30 Health. EDAT- 2025/11/05 00:28 MHDA- 2025/12/03 14:12 PMCR- 2025/12/03 CRDT- 2025/11/04 19:52 PHST- 2025/09/22 00:00 [revised] PHST- 2025/09/01 00:00 [received] PHST- 2025/10/02 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 19:52 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70196 [pii] AID - 10.1111/dom.70196 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):337-346. doi: 10.1111/dom.70196. Epub 2025 Nov 4. PMID- 41187787 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260307 IS - 1439-3646 (Electronic) IS - 0947-7349 (Linking) VI - 134 IP - 2 DP - 2026 Feb TI - The Impact of Semaglutide on Weight Loss and Inflammation in People with HIV. An Observational Prospective Study in Greek Population. PG - 29-35 LID - 10.1055/a-2737-6227 [doi] AB - The existing literature on the effects of semaglutide in people with HIV (PWH) and diabetes mellitus remains limited. In this study, the effects of semaglutide on weight control and inflammation in PWH were evaluated.This is a prospective observational study that included PWH with type 2 diabetes mellitus monitored at the HIV Unit of the University General Hospital of Alexandroupolis and a matched control group of non-HIV individuals. Demographic, anthropometric, and clinical characteristics, including HIV-related data and comorbidities, were reported. All participants received semaglutide with a gradual dose increase to 1 mg once weekly. Body Mass Index (BMI), glycosylated haemoglobin (HbA1c), and inflammatory markers (IL-6, TNF, hsCRP, sCD14, CD4/CD8 ratio) were recorded at baseline and at 6, 12, 18, and 24 months.Fifty participants (PWH: n=25; non-HIV: n=25) were included. At baseline, the mean BMI was 35.2+/-8.0 kg/m(2) for PWH and 36.1+/-6.0 kg/m(2) for non-HIV controls. Semaglutide treatment resulted in significant and sustained weight loss in both groups (p<0.001). At 24 months, the median weight loss was -14.6 kg in the PWH group and -18.8 kg in the non-HIV group for those with a baseline BMI>35 kg/m(2). Glycemic control also improved significantly, with mean HbA1c decreasing from 7.7%+/-1.23 to 5.2%+/-1.02 in PWH (p<0.001), and from 7.9%+/-1.16 to 5.6%+/-1.21 in non-HIV controls (p<0.001). Significant reductions were observed in hsCRP and sCD14 levels in both cohorts. A unique finding was the significant increase in the CD4/CD8 ratio in the PWH group, from a mean baseline of 0.54+/-0.12 to 0.83+/-0.14 at 24 months (p<0.001), a change not seen in the non-HIV controls.Semaglutide appears to be an effective and safe option for weight reduction and inflammation control in PWHIV. Further studies with a larger number of patients are necessary to substantiate these findings. CI - Thieme. All rights reserved. FAU - Petrakis, Vasileios AU - Petrakis V AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, Democritus University of Thrace, General University Hospital of Alexandroupolis, Alexandroupolis, Greece. FAU - Rafailidis, Petros AU - Rafailidis P AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Panopoulou, Maria AU - Panopoulou M AD - Univeristy Laboratory of Microbiology, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Konstantinidis, Theocharis AU - Konstantinidis T AD - Univeristy Laboratory of Microbiology, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Tsantes, Andreas G AU - Tsantes AG AUID- ORCID: 0000-0002-3695-0759 AD - Laboratory of Haematology and Blood Bank Unit, School of Medicine, National and Kapodistrian University of Athens, Panepistemiako Geniko Nosokomeio Attikon, Athens, Greece. AD - Microbiology Department, Agios Savvas General Cancer and Oncology Hospital of Athens, Athens, Greece. FAU - Babaka, Nikoleta AU - Babaka N AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Papazoglou, Dimitrios AU - Papazoglou D AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Panagopoulos, Periklis AU - Panagopoulos P AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Observational Study DEP - 20251104 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - *HIV Infections/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Inflammation/drug therapy/blood MH - Greece MH - Adult MH - Prospective Studies MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - Glycated Hemoglobin COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2025/11/05 00:28 MHDA- 2026/03/07 06:38 CRDT- 2025/11/04 18:53 PHST- 2026/03/07 06:38 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 18:53 [entrez] AID - 10.1055/a-2737-6227 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2026 Feb;134(2):29-35. doi: 10.1055/a-2737-6227. Epub 2025 Nov 4. PMID- 41187492 OWN - NLM STAT- MEDLINE DCOM- 20251211 LR - 20260902 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 55 DP - 2025 Dec TI - Glucagon-like peptide-1 receptor agonists and sarcopenia-related markers in diabetes: A systematic review and meta-analysis. PG - 42-56 LID - S0261-5614(25)00277-8 [pii] LID - 10.1016/j.clnu.2025.10.006 [doi] AB - AIMS: GLP-1 receptor agonists (GLP-1RAs) are first-line therapies for type 2 diabetes (T2DM) due to their additional weight-lowering and cardiovascular benefits. However, their impact on muscle mass is debated, posing a concern for sarcopenia in older adults with T2DM. This systematic review and meta-analysis aimed to evaluate the effects of GLP-1RAs on body composition and sarcopenia-related markers in diabetic patients and relevant preclinical models, and to explore the underlying mechanisms. METHODS: We systematically searched PubMed, Web of Science, MEDLINE, Cochrane Library, and EMBASE to identify relevant randomized controlled trials and animal studies on the impact of GLP-1 RAs on muscle in diabetic participants. Standardized Mean Difference (SMD) or Mean Difference (MD) with 95 % confidence intervals (CI) were calculated using random-effects or fixed-effect models to synthesize the effects on anthropometric, functional, and molecular endpoints. RESULTS: A total of 254 articles were retrieved, yielding 18 eligible studies after screening against the inclusion criteria. These comprised six human studies measuring lean mass, four clinical trials assessing Skeletal Muscle Mass Index (SMI), and eight animal studies. The animal studies investigated parameters including muscle mass, muscle fiber cross-sectional area, grip strength, lean mass percentage, myogenin, MyoD, Atrogin-1, MuRF-1, myostatin, GLUT4, SIRT1, and inflammatory cytokines (IL-1beta, IL-6, TNF-alpha). CONCLUSIONS: GLP-1 RAs were found to increase the percentage of lean body mass in animal models, improve body composition, enhance skeletal muscle strength, elevate concentrations of muscle growth factors, and reduce muscle growth inhibitory factors and inflammatory factors. These effects promote muscle cell proliferation and differentiation, accelerate muscle protein synthesis, leading to better overall muscle function. Confirming these promising preclinical findings requires large-scale randomized controlled trials in humans. CI - Copyright (c) 2025 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Chen, Wenjie AU - Chen W AD - Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, 410011, PR China. FAU - Qin, Hongzhuo AU - Qin H AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, PR China. FAU - Zhou, Zhaokai AU - Zhou Z AD - Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China; Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, PR China. FAU - Chen, Yun AU - Chen Y AD - Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, 410011, PR China. FAU - Xu, Xiaowei AU - Xu X AD - Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, 410011, PR China. FAU - Chen, Yajun AU - Chen Y AD - Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China. FAU - He, Jieyu AU - He J AD - Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China. FAU - Xu, Ran AU - Xu R AD - Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, PR China. FAU - Gao, Hua AU - Gao H AD - Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, 750004, PR China. Electronic address: gaohualike@163.com. FAU - Lu, Qiong AU - Lu Q AD - Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, 410011, PR China. Electronic address: christy_luq@csu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20251025 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Sarcopenia/chemically induced MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Biomarkers/blood MH - Body Composition/drug effects MH - Animals MH - Muscle, Skeletal/drug effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged OTO - NOTNLM OT - Diabetes mellitus OT - Elderly OT - GLP-1 receptor agonist OT - Meta-analysis OT - Sarcopenia COIS- Conflict of interest The authors declare that they have no competing interests. EDAT- 2025/11/05 00:28 MHDA- 2025/12/12 03:28 CRDT- 2025/11/04 18:05 PHST- 2025/06/19 00:00 [received] PHST- 2025/09/11 00:00 [revised] PHST- 2025/10/19 00:00 [accepted] PHST- 2025/12/12 03:28 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 18:05 [entrez] AID - S0261-5614(25)00277-8 [pii] AID - 10.1016/j.clnu.2025.10.006 [doi] PST - ppublish SO - Clin Nutr. 2025 Dec;55:42-56. doi: 10.1016/j.clnu.2025.10.006. Epub 2025 Oct 25. PMID- 41186740 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260813 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 2 DP - 2026 Feb TI - GLP-1 receptor agonists and coronary plaques regression in diabetic patients after acute coronary syndromes. PG - 179-191 LID - 10.1007/s00592-025-02606-z [doi] AB - BACKGROUND: Despite advances in therapeutic strategies a significant proportion of acute coronary syndrome (ACS) patients experience early coronary artery disease (CAD) progression, particularly those with diabetes. AIM: To evaluate CAD progression in diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1Ra) over 1 year after an ACS. METHODS: Patients presenting with non-ST-elevation ACS between 2019 and 2022 were enrolled in a prospective registry and underwent serial coronary computed tomography angiography (CCTA) at baseline (after revascularization, during the index hospitalization) and at 1-year follow-up. The primary endpoint was the absolute change (1 year - baseline) in non-culprit lesion plaque burden (DeltaPB) on CCTA, with the absolute change in patient percent atheroma volume (DeltaPAV) as a key secondary endpoint. A comprehensive lipidomic, metabolomic, and proteomic plasma assessment was also performed in all GLP-1Ra-treated patients and four randomly selected controls. RESULTS: Of 28 diabetic patients, 7 (25%) with 22 coronary plaques were treated with GLP-1Ra, and 21 (75%) with 65 plaques received other antidiabetic agents. In the 1-year observation frame, both DeltaPB (-5.8 +/- 12.8% vs. -1.1 +/- 13.6%, p = 0.041) and DeltaPAV (-6.1% [-7.3, -1.8] vs. -0.7% [-2.4, 9.8], p = 0.039) were significantly lower in GLP-1Ra-treated patients. Total atheroma volume also showed a numerically greater reduction in the GLP-1Ra cohort (0.7 mm(3) [-2.5-8.7] vs. 25.0 mm(3) [4.8-39.7]), primarily due to a decrease in plaque fibrofatty volume percentage (-2.9 +/- 10.1% vs. 1.0 +/- 6.8%, p = 0.042). Lipidomic, metabolomic, and proteomic analyses identified reductions in monoacylglycerols and triacylglycerols, increases in diacylglycerols and phosphatidylethanolamine, a shift from carbohydrate metabolism toward lipid metabolism and hormone regulation, and differential expression of proteins involved in complement activation, endothelial function, and cytoskeletal organization in GLP-1Ra-treated patients compared with controls. CONCLUSIONS: In diabetic patients with ACS, GLP-1Ra therapy was associated with a significant regression in coronary plaque burden at 1 year, supported by favorable lipidomic, metabolomic, and proteomic changes. These findings suggest a potential role for GLP-1Ra in modifying atherosclerosis progression beyond glycemic control. CI - (c) 2025. The Author(s). FAU - Gitto, Mauro AU - Gitto M AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Catapano, Federica AU - Catapano F AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Francone, Marco AU - Francone M AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Mincione, Gianluca AU - Mincione G AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Scialo, Vincenzo AU - Scialo V AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Pivato, Carlo A AU - Pivato CA AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Lisi, Costanza AU - Lisi C AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Regazzoli, Damiano AU - Regazzoli D AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Cao, Davide AU - Cao D AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Fiorina, Roberta Maria AU - Fiorina RM AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. FAU - Petrelli, Alessandra AU - Petrelli A AD - International Center for T1D, Pediatric Clinical Research Center Romeo Ed Enrica Invernizzi, DIBIC, Universita Degli Studi di Milano, Milan, Italy. AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Bucciarelli, Loredana AU - Bucciarelli L AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Loretelli, Cristian AU - Loretelli C AD - International Center for T1D, Pediatric Clinical Research Center Romeo Ed Enrica Invernizzi, DIBIC, Universita Degli Studi di Milano, Milan, Italy. AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Condorelli, Gianluigi AU - Condorelli G AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - International Center for T1D, Pediatric Clinical Research Center Romeo Ed Enrica Invernizzi, DIBIC, Universita Degli Studi di Milano, Milan, Italy. AD - Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Stefanini, Giulio AU - Stefanini G AUID- ORCID: 0000-0002-3558-6967 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. giulio.stefanini@hunimed.eu. AD - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. giulio.stefanini@hunimed.eu. LA - eng GR - Ricerca Finalizzata 2016, grant GR-2016-02363223/Ministero della Salute/ PT - Journal Article DEP - 20251104 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - *Acute Coronary Syndrome/drug therapy/complications MH - Middle Aged MH - *Plaque, Atherosclerotic/drug therapy/diagnostic imaging MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - *Coronary Artery Disease/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Computed Tomography Angiography PMC - PMC12957045 OTO - NOTNLM OT - Acute coronary syndrome OT - Coronary artery disease OT - Diabetes mellitus OT - GLP-1 receptor agonists OT - Plaque regression COIS- Declarations. Conflict of interest: The authors declare no conflicts of interest to disclose. Ethical approval and consent to participate: Ethical approval was granted by the local Institutional Review Board, and the study was registered on ClinicalTrials.gov (NCT03890822). Consent for publication: Not Applicable. EDAT- 2025/11/04 12:27 MHDA- 2026/03/06 09:06 PMCR- 2025/11/04 CRDT- 2025/11/04 11:15 PHST- 2025/10/04 00:00 [received] PHST- 2025/10/15 00:00 [accepted] PHST- 2026/03/06 09:06 [medline] PHST- 2025/11/04 12:27 [pubmed] PHST- 2025/11/04 11:15 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 10.1007/s00592-025-02606-z [pii] AID - 2606 [pii] AID - 10.1007/s00592-025-02606-z [doi] PST - ppublish SO - Acta Diabetol. 2026 Feb;63(2):179-191. doi: 10.1007/s00592-025-02606-z. Epub 2025 Nov 4. PMID- 41183330 OWN - NLM STAT- MEDLINE DCOM- 20260119 LR - 20260919 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 179 IP - 1 DP - 2026 Jan TI - Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes. PG - 1-11 LID - 10.7326/ANNALS-25-01724 [doi] AB - BACKGROUND: The comparative gastrointestinal safety across glucagon-like peptide-1 receptor agonists and tirzepatide is still unclear. OBJECTIVE: To compare the risk for severe gastrointestinal adverse events across dulaglutide, subcutaneous semaglutide, and tirzepatide in patients with type 2 diabetes (T2D) in routine clinical practice. DESIGN: New-user, active-comparator cohort study. SETTING: Population-based study. PARTICIPANTS: Adults with T2D initiating dulaglutide, subcutaneous semaglutide, and tirzepatide between 1 January 2019 and 30 August 2024 in 3 cohorts corresponding to 3 pairwise comparisons. MEASUREMENTS: The primary outcome was a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Secondary outcomes of interest were the individual components of the primary outcome. Patients were 1:1 propensity score matched within each comparison. We calculated hazard ratios (HRs) with 95% CIs. RESULTS: There were 65 238 matched pairs in the semaglutide versus dulaglutide cohort, 20 893 in the tirzepatide versus dulaglutide cohort, and 46 620 in the tirzepatide versus semaglutide cohort. The HR of gastrointestinal events was 0.96 (95% CI, 0.87 to 1.06) in the semaglutide versus dulaglutide cohort, 0.96 (CI, 0.77 to 1.20) in the tirzepatide versus dulaglutide cohort, and 1.07 (CI, 0.90 to 1.26) in the tirzepatide versus semaglutide cohort. LIMITATION: Possible residual confounding by glycemic control and body mass index. CONCLUSION: These findings suggest that dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles in adults with T2D. This study provides clinicians with evidence to weigh the benefits and risks of these medications. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases. FAU - Crisafulli, Salvatore AU - Crisafulli S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and Department of Diagnostics and Public Health, University of Verona, Verona, Italy (S.C.). FAU - Alkabbani, Wajd AU - Alkabbani W AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada (W.A.). FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital; and New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts (J.M.P.). FAU - Bykov, Katsiaryna AU - Bykov K AUID- ORCID: 0000-0003-3336-5412 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Tavakkoli, Ali AU - Tavakkoli A AUID- ORCID: 0000-0002-7430-1848 AD - Division of General and Gastrointestinal Surgery, Brigham and Women's Hospital, Boston, Massachusetts (A.T.). FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Htoo, Phyo T AU - Htoo PT AUID- ORCID: 0000-0003-4742-8306 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Yu, Elaine W AU - Yu EW AD - Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, and Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts (E.W.Y.). FAU - Trifiro, Gianluca AU - Trifiro G AUID- ORCID: 0000-0003-1147-7296 AD - Department of Diagnostics and Public Health, University of Verona, Verona, Italy (G.T.). FAU - Wexler, Deborah J AU - Wexler DJ AUID- ORCID: 0000-0001-6979-402X AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (D.J.W.). FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - K01 AG068365/AG/NIA NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251104 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Recombinant Fusion Proteins/adverse effects/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use MH - *Tirzepatide/adverse effects/therapeutic use MH - Aged MH - *Gastrointestinal Diseases/chemically induced MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12718079 MID - NIHMS2125278 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/11/03 18:30 MHDA- 2026/01/19 18:33 PMCR- 2025/12/21 CRDT- 2025/11/03 17:02 PHST- 2026/01/19 18:33 [medline] PHST- 2025/11/03 18:30 [pubmed] PHST- 2025/11/03 17:02 [entrez] PHST- 2025/12/21 00:00 [pmc-release] AID - 10.7326/ANNALS-25-01724 [doi] PST - ppublish SO - Ann Intern Med. 2026 Jan;179(1):1-11. doi: 10.7326/ANNALS-25-01724. Epub 2025 Nov 4. PMID- 41182904 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260925 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 8 DP - 2025 Nov TI - Long-Term Glucagon-Like Peptide 1 Receptor Agonist Use Is Not Associated With Increased Risk of Thyroid Cancer in Adults With Type 2 Diabetes. PG - e70104 LID - 10.1002/dmrr.70104 [doi] LID - e70104 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes (T2DM) and obesity, but their potential association with thyroid cancer remains a concern. This study assessed thyroid cancer risk with long-term GLP-1RA use in a large real-world cohort. METHODS: We conducted a propensity score matched cohort study using electronic health records from TriNetX, including 89,646 adults with T2DM who initiated GLP-1RA therapy between 2014 and 2020, and demonstrated continued use for at least 1 year. Active comparator controls included users of insulin, metformin, sodium-glucose transporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, sulfonylureas, and thiazolidinediones. The primary outcome was the incidence of thyroid cancer. RESULTS: During a median follow-up of 4.5 +/- 2.3 years, GLP-1RA use was not associated with an increased risk of thyroid cancer compared with any of the other antidiabetic medications. As expected, GLP-1RA use was associated with a greater reduction in HbA1c levels, while the negative control outcome remained unaffected. Findings remained consistent across subgroups stratified by sex, age, obesity-status, glycaemic-control, and GLP-1RA type and in multiple sensitivity analyses. CONCLUSIONS: In this large real-world cohort study, long-term GLP-1RA use was not associated with an increased risk of thyroid cancer. These findings provide reassurance for the safety of GLP-1RAs and support their continued evidence-based use in clinical practice. CI - (c) 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Pollack, Rena AU - Pollack R AUID- ORCID: 0000-0001-6771-337X AD - Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Stokar, Joshua AU - Stokar J AUID- ORCID: 0000-0003-4939-5800 AD - Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng PT - Journal Article PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Thyroid Neoplasms/epidemiology/chemically induced/pathology MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Follow-Up Studies MH - Aged MH - Adult MH - Risk Factors MH - Prognosis MH - Incidence MH - Biomarkers/analysis PMC - PMC12582397 OTO - NOTNLM OT - diabetes mellitus type 2 OT - glucagon-like peptide 1 OT - thyroid cancer COIS- The authors declare no conflicts of interest. EDAT- 2025/11/03 18:30 MHDA- 2025/11/03 18:31 PMCR- 2025/11/03 CRDT- 2025/11/03 12:53 PHST- 2025/10/23 00:00 [revised] PHST- 2025/06/18 00:00 [received] PHST- 2025/10/28 00:00 [accepted] PHST- 2025/11/03 18:31 [medline] PHST- 2025/11/03 18:30 [pubmed] PHST- 2025/11/03 12:53 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - DMRR70104 [pii] AID - 10.1002/dmrr.70104 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 Nov;41(8):e70104. doi: 10.1002/dmrr.70104. PMID- 41182046 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20251204 IS - 1758-1095 (Electronic) IS - 0141-0768 (Print) IS - 0141-0768 (Linking) VI - 118 IP - 11 DP - 2025 Nov TI - SGLT2 inhibitors for primary prevention of macrovascular and major microvascular complications in type 2 diabetes: an island-wide cohort study. PG - 347-357 LID - 10.1177/01410768251375906 [doi] AB - OBJECTIVE: This study aimed to evaluate the different risks of developing cardiovascular disease and major microvascular complications between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and non-SGLT2i users in patients with type 2 diabetes (T2D) who do not have existing macrovascular or microvascular diseases. DESIGN: This study employed a retrospective, population-based cohort study design. SETTING: Data were obtained from Taiwan's National Health Insurance Research Database, covering the period from January 1, 2008, to December 31, 2021. Propensity score matching was used to identify 91,327 matched pairs of SGLT2 inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor users, 91,673 pairs of SGLT2 inhibitor and sulfonylurea users, and 20,857 pairs of SGLT2 inhibitor and glucagon-like peptide-1 receptor agonist (GLP-1 RA) users. PARTICIPANTS: The study included 1,145,035 patients diagnosed with T2D from the NHIRD. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to assess the risk of outcomes. RESULTS: SGLT2i users showed a lower risk of coronary artery disease (0.80 (0.73-0.87), 0.78 (0.72-0.85) and 0.74 (0.64-0.86)), heart failure (0.44 (0.38-0.49), 0.56 (0.50-0.62) and 0.66 (0.55-0.78)), cardiovascular death (0.47 (0.40-0.56), 0.47 (0.40-0.55) and 0.68 (0.53-0.87)), dialysis (0.03 (0.02-0.05), 0.13 (0.10-0.17) and 0.16 (0.11-0.23)), vision-threatening retinopathy (0.58 (0.51-0.67), 0.59 (0.51-0.67) and 0.78 (0.62-0.98)), amputation (0.29 (0.20-0.41), 0.28 (0.21-0.38) and 0.61 (0.46-0.89)) and all-cause mortality (0.42 (0.39-0.445), 0.39 (0.37-0.42) and 0.68 (0.61-0.76]))when compared to DPP-4 inhibitors, sulfonylureas, and GLP-1 RA users, respectively. CONCLUSIONS: This study showed that SGLT2i use was associated with a lower risk of incident cardiovascular diseases, major microvascular complications and mortality compared with the use of DPP-4 inhibitors, sulfonylureas and GLP-1 RA in patients with T2D, who did not have macrovascular and microvascular diseases. FAU - Cheng, Wan-Yin AU - Cheng WY AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Yen, Fu-Shun AU - Yen FS AUID- ORCID: 0000-0002-4677-2415 AD - Dr. Yen's Clinic, Taoyuan, Taiwan. FAU - Hung, Yao-Min AU - Hung YM AUID- ORCID: 0000-0001-6920-8799 AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. FAU - Lin, Heng-Jun AU - Lin HJ AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Huang, Yu-Han AU - Huang YH AD - College of Medicine, China Medical University, Taichung, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan. AD - Department of Health Services Administration, China Medical University, Taichung, Taiwan. AD - Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan. AD - National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AUID- ORCID: 0000-0002-8209-9627 AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan. LA - eng PT - Journal Article DEP - 20251103 PL - England TA - J R Soc Med JT - Journal of the Royal Society of Medicine JID - 7802879 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - Taiwan/epidemiology MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Diabetic Angiopathies/prevention & control/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Primary Prevention/methods MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Sulfonylurea Compounds/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Proportional Hazards Models MH - Cohort Studies MH - Hypoglycemic Agents/therapeutic use PMC - PMC12583002 OTO - NOTNLM OT - Drugs: cardiovascular system OT - Ischaemic heart disease OT - cardiovascular medicine OT - clinical OT - heart failure EDAT- 2025/11/03 13:42 MHDA- 2025/12/04 19:37 PMCR- 2025/11/03 CRDT- 2025/11/03 08:43 PHST- 2025/12/04 19:37 [medline] PHST- 2025/11/03 13:42 [pubmed] PHST- 2025/11/03 08:43 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 10.1177_01410768251375906 [pii] AID - 10.1177/01410768251375906 [doi] PST - ppublish SO - J R Soc Med. 2025 Nov;118(11):347-357. doi: 10.1177/01410768251375906. Epub 2025 Nov 3. PMID- 41178728 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes. PG - 803-816 LID - 10.1111/dom.70229 [doi] AB - Treatment with GLP-1 receptor agonists (GLP-1 RAs) is effective in reducing body weight in individuals with overweight and type 2 diabetes (T2D). However, measurements indicate that a considerable portion of the weight loss derives from fat-free mass (FFM), including skeletal muscle, which may compromise metabolic health and physical function. We aimed to evaluate the evidence for the ability of pharmacological interventions to preserve or increase lean body mass (LBM) during weight loss with GLP-1 RAs, assess their clinical potential and limitations, and identify knowledge gaps requiring further research. A literature review was conducted using PubMed, JAMA, Wiley, ResearchGate, The Royal Danish Library, and ClinicalTrials.gov. Included were preclinical and clinical studies on compounds with documented anabolic effects and established safety profiles. The primary outcomes assessed were changes in LBM, fat mass (FM), physical function, and adverse events. Activin II receptor inhibition with bimagrumab demonstrated significant preservation and increases in LBM, along with FM reduction, in both preclinical and phase 2 studies in individuals with overweight and T2D. Similar effects were observed for myostatin and activin A inhibitors (trevogrumab, garetosmab), latent myostatin inhibitors (apitegromab, SRK-439), and Selective Androgen Receptor Modulators (enobosarm). Notably, enobosarm also improved physical function. Adverse events were generally mild and reversible; however, long-term data remain limited. Pharmacological adjunct therapies show potential for improving body composition and physical function during GLP-1 RA-induced weight loss. Preliminary findings are promising, but larger, controlled trials are necessary to confirm efficacy and safety before clinical implementation can be considered. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aimelet, Viktor AU - Aimelet V AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens Juul AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Review DEP - 20251103 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Humans MH - *Overweight/drug therapy/complications MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Body Composition/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome PMC - PMC12803604 OTO - NOTNLM OT - GLP-1 analogue OT - anti-obesity drug OT - obesity therapy OT - weight management COIS- VA: no conflicts. JJH: scientific advisory panels and/or speaker/consultant for several companies including Novo Nordisk, Eli Lilly, MSD. He is co-founder and owns stock in Antag Therapeutics. EDAT- 2025/11/03 13:42 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/03 06:05 PHST- 2025/10/12 00:00 [revised] PHST- 2025/08/18 00:00 [received] PHST- 2025/10/17 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/03 13:42 [pubmed] PHST- 2025/11/03 06:05 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70229 [pii] AID - 10.1111/dom.70229 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):803-816. doi: 10.1111/dom.70229. Epub 2025 Nov 3. PMID- 41178720 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260619 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 21 DP - 2025 Nov 3 TI - GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research. LID - 10.1172/JCI194743 [doi] LID - e194743 AB - Cancer diagnoses are prevalent in people with obesity and type 2 diabetes, and abundant clinical evidence supports the protective effects of weight loss for cancer prevention. Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized obesity and type 2 diabetes medicine and alleviate many comorbidities of these metabolic diseases. In this Review, we summarize the current clinical evidence for GLP-1 receptor agonists and cancer risk, including thyroid, pancreatic, gastrointestinal, and hormone-dependent malignancies. With few exceptions, recent meta-analyses report that GLP-1 receptor therapies do not increase cancer incidence and may lower risk in some cases. Preclinical studies reinforce the anticancer effects of GLP-1 receptor therapies, even in non-obese models. However, there are still many opportunities for translational insight as the field grows. Immune-modulating effects of GLP-1 receptor agonists are reported in several preclinical cancer studies, which may reflect direct action on immune cells or result from improved metabolic function. We highlight ongoing clinical trials for GLP-1 receptor therapies in cancer patients, and offer considerations for preclinical studies, including perspectives on the timing and duration of GLP-1 receptor agonist treatment, concurrent use of standard anticancer therapies, and interpretation of models of cancer risk versus progression. FAU - Valencia-Rincon, Estefania AU - Valencia-Rincon E AD - Department of Pathology, College of Medicine, and. FAU - Rai, Rajani AU - Rai R AD - Gynecologic Oncology Section, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. AD - Stephenson Cancer Center, Oklahoma City, Oklahoma, USA. FAU - Chandra, Vishal AU - Chandra V AD - Gynecologic Oncology Section, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. AD - Stephenson Cancer Center, Oklahoma City, Oklahoma, USA. FAU - Wellberg, Elizabeth A AU - Wellberg EA AD - Department of Pathology, College of Medicine, and. AD - Stephenson Cancer Center, Oklahoma City, Oklahoma, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251103 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Neoplasms/drug therapy/metabolism/pathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Translational Research, Biomedical MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Obesity/drug therapy/metabolism PMC - PMC12578377 COIS- Conflict of interest: The authors have declared that no conflict of interest exists. EDAT- 2025/11/03 13:42 MHDA- 2025/11/03 13:43 PMCR- 2025/11/03 CRDT- 2025/11/03 06:03 PHST- 2025/11/03 13:43 [medline] PHST- 2025/11/03 13:42 [pubmed] PHST- 2025/11/03 06:03 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 194743 [pii] AID - 10.1172/JCI194743 [doi] PST - epublish SO - J Clin Invest. 2025 Nov 3;135(21):e194743. doi: 10.1172/JCI194743. eCollection 2025 Nov 3. PMID- 41178712 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260620 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 21 DP - 2025 Nov 3 TI - GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity. LID - 10.1172/JCI194749 [doi] LID - e194749 AB - Glucagon-like peptide-1 (GLP-1) was initially considered to be a hormone with a predominant role in regulating glucose metabolism by inducing insulin secretion, reducing glucagon secretion, and ameliorating insulin resistance, with the last effect being largely dependent on the induction of weight loss. In more recent years, the role of this peptide beyond metabolism has progressively been explored, including its impact on kidney physiology and kidney clinical outcomes in people with obesity with or without diabetes. Indeed, despite only modest expression of the GLP-1 receptor in the kidney, the renoprotective actions of GLP-1 and its receptor agonists have become an area of intensive investigation. This Review appraises the current status of GLP-1 peptide and its receptor agonists and focuses on the preclinical as well as recent seminal clinical findings defining the kidney benefits conferred by GLP-1 receptor agonist treatment in people living with type 2 diabetes and obesity. FAU - Cooper, Mark E AU - Cooper ME AD - Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251103 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Obesity/drug therapy/complications/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Glucagon-Like Peptide 1/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetic Nephropathies/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12578383 COIS- Conflict of interest: MEC has received speaking fees from Novo Nordisk. DHVR has acted as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, and Novo Nordisk and has received research funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, and Novo Nordisk. EDAT- 2025/11/03 13:42 MHDA- 2025/11/03 13:43 PMCR- 2025/11/03 CRDT- 2025/11/03 06:03 PHST- 2025/11/03 13:43 [medline] PHST- 2025/11/03 13:42 [pubmed] PHST- 2025/11/03 06:03 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 194749 [pii] AID - 10.1172/JCI194749 [doi] PST - epublish SO - J Clin Invest. 2025 Nov 3;135(21):e194749. doi: 10.1172/JCI194749. eCollection 2025 Nov 3. PMID- 41178710 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260620 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 21 DP - 2025 Nov 3 TI - Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits. LID - 10.1172/JCI194751 [doi] LID - e194751 AB - Therapies based on glucagon-like peptide-1 (GLP-1) reduce rates of cardiovascular and chronic kidney disease in people with type 2 diabetes and/or obesity, with ongoing clinical trials investigating their effects in people with metabolic liver disease, arthritis, and both substance use and neurodegenerative disorders. Acute and chronic activation of GLP-1 receptor signaling also reduces systemic and tissue inflammation in mice and humans, through weight loss-dependent and -independent mechanisms, actions that may contribute to the expanding spectrum of clinical benefits ascribed to GLP-1 medicines. In this Review, we highlight current understanding of the direct and indirect antiinflammatory effects and mechanisms of GLP-1 medicines in both preclinical and clinical studies, covering emerging concepts, clinical relevance, and areas of uncertainty that require further investigation. FAU - Wong, Chi Kin AU - Wong CK AD - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. FAU - Drucker, Daniel J AU - Drucker DJ AD - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251103 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptide 1/therapeutic use/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/pathology MH - Mice MH - *Anti-Inflammatory Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/drug therapy/metabolism/pathology MH - Inflammation/drug therapy/metabolism MH - Signal Transduction/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12578379 COIS- Conflict of interest: DJD has received consulting fees from Anylam, Amgen, AstraZeneca Inc., Crinetics, Eli Lilly, Insulet, Kallyope, Metsara, and Pfizer Inc. and speaking fees from Novo Nordisk. Mount Sinai Hospital has received investigator-initiated grant support from Amgen, Eli Lilly, Novo Nordisk, Pfizer Inc., and Zealand Pharmaceuticals Inc. to support preclinical studies in the Drucker laboratory. EDAT- 2025/11/03 13:42 MHDA- 2025/11/03 13:43 PMCR- 2025/11/03 CRDT- 2025/11/03 06:03 PHST- 2025/11/03 13:43 [medline] PHST- 2025/11/03 13:42 [pubmed] PHST- 2025/11/03 06:03 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 194751 [pii] AID - 10.1172/JCI194751 [doi] PST - epublish SO - J Clin Invest. 2025 Nov 3;135(21):e194751. doi: 10.1172/JCI194751. eCollection 2025 Nov 3. PMID- 41178701 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Synergistic associations of metformin and GLP-1 receptor agonist use with adiposity-related cancer incidence in people living with type 2 diabetes. PG - 946-959 LID - 10.1111/dom.70267 [doi] AB - BACKGROUND: Metformin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of adiposity-related cancers in patients with type 2 diabetes (T2D). The potential synergistic effects of these treatments on cancer incidence remain unclear, considering their distinct biological mechanisms and their associated effects on body weight. METHODS: A retrospective cohort analysis was conducted using a large global database (TriNetX) of patients with T2D. Three cohorts: single agent use with metformin or GLP-1 RAs, and dual/combination metformin/GLP-1 RA use, were compared with a reference group treated with DPP4 inhibitors (DPP4i). Propensity score matching (1:1) was applied to control for confounders. Cancer incidence and all cause mortality were assessed over 5 years of follow up. RESULTS: After matching, metformin and GLP-1 RA treatment were both associated with a lower risk of all adiposity-related cancers and all-cause mortality; the latter was associated with greater reductions in both. Cancer rates were (hazard ratio) 0.96 [95% CI 0.92, 0.99] and 0.86 [0.82, 0.89], while mortality rates were 0.78 [0.76, 0.80] and 0.61 [0.59, 0.63] for metformin and GLP-1 RA, respectively. Dual therapy showed the strongest association with lower cancer incidence (0.61 [0.57, 0.65]) and mortality (0.33 [0.32, 0.35]). Results were more significant in younger, male patients with obesity. CONCLUSION: In patients with T2D, dual metformin and GLP-1 RA treatment was associated with a 39% lower incidence of adiposity-related cancers and a 67% lower mortality, with a striking impact on cancer-related outcomes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Heague, Megan AU - Heague M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Hydes, Theresa J AU - Hydes TJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Anson, Matthew AU - Anson M AUID- ORCID: 0000-0001-9991-7369 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Visiting Fellow, Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. LA - eng PT - Journal Article DEP - 20251103 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - *Neoplasms/epidemiology/prevention & control/etiology/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Adiposity/drug effects MH - Aged MH - Drug Therapy, Combination MH - Drug Synergism MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Obesity/complications PMC - PMC12803636 OTO - NOTNLM OT - GLP-1 analogue OT - cohort study OT - metformin OT - real-world evidence OT - type 2 diabetes COIS- Matthew Anson receives a fellowship from the Novo Nordisk UK research foundation and JDRF. CAR has acted as a consultant for Boehringer Ingelheim, and has received grant funding from Unilever. Daniel J Cuthbertson has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool. GHI is an employee of TriNetX LLC. Uazman Alam has received honoraria from Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Diiachi Sankyo. Uazman Alam has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2025/11/03 06:27 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/03 05:53 PHST- 2025/10/14 00:00 [revised] PHST- 2025/04/08 00:00 [received] PHST- 2025/10/16 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/03 06:27 [pubmed] PHST- 2025/11/03 05:53 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70267 [pii] AID - 10.1111/dom.70267 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):946-959. doi: 10.1111/dom.70267. Epub 2025 Nov 3. PMID- 41177923 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Evolving trends of antidiabetic agents stratified by age, kidney function and body mass index: Insights from a nationwide claims database. PG - 701-710 LID - 10.1111/dom.70255 [doi] AB - AIMS: To analyse prescribing trends in antidiabetic agents stratified by background characteristics among individuals with type 2 diabetes. MATERIALS AND METHODS: This retrospective study used a large-scale database between 2015 and 2024 in Japan. Adults with type 2 diabetes receiving at least one antidiabetic prescription were included, and annual prescription rates were assessed by drug class. Trends were evaluated overall and stratified by age, sex, heart failure (HF) status, estimated glomerular filtration rate (eGFR), body mass index, haemoglobin A1c and clinical setting, because these factors are important determinants of efficacy and safety in prescribing antidiabetic agents. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prescriptions showed a marked increase, rising from 4.1% (95% confidence interval [CI], 4.0%-4.2%) in 2015 to 38.9% (95% CI, 38.7%-39.0%) in 2024. Particularly high prescription rates were seen in individuals aged <65 years, with HF, eGFR <30 mL/min/1.73 m(2), and obesity. A temporal increase was also noted among individuals aged >/=80 years, reaching 33.1% (95% CI, 32.8%-33.3%) in 2024. Glucagon-like peptide-1 receptor agonists were prescribed at a relatively low rate, reaching only 8.0% (95% CI, 7.9%-8.1%) in 2024; however, an upward trend was observed among individuals aged <65 years and with obesity, especially after the launch of oral semaglutide in 2021. CONCLUSIONS: In this large-scale analysis, SGLT2i use increased substantially across diverse individual traits, supporting their integration into diverse clinical contexts in real-world practice. Our findings may provide valuable insights into diabetes care in the forthcoming era of super-aged societies. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aoyama, Kazuki AU - Aoyama K AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Okada, Akira AU - Okada A AUID- ORCID: 0000-0001-6480-3388 AD - Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kaneko, Hidehiro AU - Kaneko H AUID- ORCID: 0000-0003-2553-6170 AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan. FAU - Azegami, Tatsuhiko AU - Azegami T AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Suzuki, Yuta AU - Suzuki Y AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health, Saitama, Japan. FAU - Meguro, Shu AU - Meguro S AUID- ORCID: 0000-0003-3528-128X AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Fujiu, Katsuhito AU - Fujiu K AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan. FAU - Takeda, Norifumi AU - Takeda N AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Morita, Hiroyuki AU - Morita H AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Node, Koichi AU - Node K AUID- ORCID: 0000-0002-2534-0939 AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Nangaku, Masaomi AU - Nangaku M AD - Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Takeda, Norihiko AU - Takeda N AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yasunaga, Hideo AU - Yasunaga H AD - Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. FAU - Hayashi, Kaori AU - Hayashi K AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. LA - eng GR - 2024-YNG-031/Japan Association for Diabetes Education and Care/ GR - 23AA2003/Ministry of Health, Labour and Welfare, Japan/ GR - 20H03907/Ministry of Education, Culture, Sports, Science and Technology, Japan/ GR - 21H03159/Ministry of Education, Culture, Sports, Science and Technology, Japan/ GR - 21K08123/Ministry of Education, Culture, Sports, Science and Technology, Japan/ PT - Journal Article DEP - 20251102 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications/physiopathology MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Body Mass Index MH - Aged, 80 and over MH - Japan/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Databases, Factual MH - Age Factors MH - Glomerular Filtration Rate MH - Adult MH - *Practice Patterns, Physicians'/trends MH - Glycated Hemoglobin/analysis MH - Kidney/physiopathology PMC - PMC12673422 OTO - NOTNLM OT - antidiabetic drug OT - pharmaco-epidemiology OT - real-world evidence OT - type 2 diabetes COIS- Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan Co., Ltd., Abbott Medical Japan Co., Ltd., Boston Scientific Japan Co., Ltd., and Fukuda Denshi, Central Tokyo Co., Ltd. Akira Okada is a member of the Department of Prevention of Diabetes and Lifestyle-Related Diseases, which is a cooperative programme between the University of Tokyo and Asahi Mutual Life Insurance Company. Hidehiro Kaneko holds shares in PrevMed Co., Ltd. and Japan Preventive Medical Development Institute Co., Ltd. Norihiko Takeda has received collaborative research funding from AstraZeneca and Ono Pharmaceutical. Koichi Node has received honoraria from Boehringer Ingelheim, research grants from Astellas, and scholarship funds from Daiichi Sankyo and Mitsubishi Tanabe Pharma. Masaomi Nangaku has received scholarship funds from Boehringer Ingelheim. Kaori Hayashi has received scholarship funds from Boehringer Ingelheim. The remaining authors have nothing to disclose. EDAT- 2025/11/03 00:26 MHDA- 2025/12/03 07:41 PMCR- 2025/12/03 CRDT- 2025/11/02 23:33 PHST- 2025/10/13 00:00 [revised] PHST- 2025/08/09 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2025/12/03 07:41 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 23:33 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70255 [pii] AID - 10.1111/dom.70255 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):701-710. doi: 10.1111/dom.70255. Epub 2025 Nov 2. PMID- 41177308 OWN - NLM STAT- MEDLINE DCOM- 20260330 LR - 20260918 IS - 1872-8227 (Electronic) IS - 0168-8227 (Print) IS - 0168-8227 (Linking) VI - 230 DP - 2025 Dec TI - Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease. PG - 112982 LID - S0168-8227(25)00996-9 [pii] LID - 10.1016/j.diabres.2025.112982 [doi] AB - AIMS: To compare the association of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) therapies on lower extremity vascular complications and mortality in PAD. METHODS: We conducted a retrospective cohort study using a nationwide U.S. electronic health records database. Adults with PAD and type 2 diabetes who initiated GLP-1RA, SGLT2i, or DPP4i therapy (May 2013-January 2025) were included. Propensity score matching (1:1) balanced baseline characteristics. Cox models estimated hazard ratios (HR) with 95 % confidence intervals (CI) for major amputation (primary outcome), lower extremity revascularization (LER), and all-cause mortality over 3 years follow-up. Subgroup analyses included symptomatic PAD, prior LER, and drug-level comparisons. RESULTS: GLP-1RAs were associated with lower risks of major amputation (HR 0.79 [95 % CI 0.70-0.90]), LER (HR 0.82 [0.76-0.88]), and mortality (HR 0.71 [0.68-0.73]) compared with SGLT2i (n = 77,393 each). Similar reductions were seen versus DPP-4is (n = 39,907 each); SGLT2is and DPP-4is showed comparable risks (n = 42,924 each). GLP-1RA benefits remained significant in symptomatic PAD (p < 0.05) and were associated with lower mortality in LER patients (p < 0.05). Semaglutide and tirzepatide showed the greatest benefit. CONCLUSION: GLP-1RAs were associated with lower limb complication and mortality risks in PAD, supporting a potential vascular benefit that warrants prospective evaluation. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Hong, Alexander T AU - Hong AT AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Lin, Forest AU - Lin F AD - University of South Florida Health Morsani College of Medicine, Tampa, FL, USA. FAU - Luu, Ivan Y AU - Luu IY AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Shin, Laura AU - Shin L AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Han, Sukgu M AU - Han SM AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Armstrong, David G AU - Armstrong DG AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Tan, Tze-Woei AU - Tan TW AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: tze-woei.tan@med.usc.edu. LA - eng GR - K23 DK122126/DK/NIDDK NIH HHS/United States GR - R03 DK140420/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20251101 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Peripheral Arterial Disease/complications/drug therapy/mortality MH - *Glucagon-Like Peptide-1 Receptor MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Amputation, Surgical/statistics & numerical data MH - Hypoglycemic Agents/therapeutic use PMC - PMC12645714 MID - NIHMS2121410 OTO - NOTNLM OT - Diabetes mellitus OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Limb amputation OT - Peripheral artery disease OT - Sodium-glucose cotransporter-2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/11/03 00:26 MHDA- 2025/11/30 00:30 PMCR- 2025/12/03 CRDT- 2025/11/02 19:13 PHST- 2025/09/12 00:00 [received] PHST- 2025/10/20 00:00 [revised] PHST- 2025/10/28 00:00 [accepted] PHST- 2025/11/30 00:30 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 19:13 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - S0168-8227(25)00996-9 [pii] AID - 10.1016/j.diabres.2025.112982 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Dec;230:112982. doi: 10.1016/j.diabres.2025.112982. Epub 2025 Nov 1. PMID- 41176849 OWN - NLM STAT- MEDLINE DCOM- 20251128 LR - 20251218 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 9 DP - 2025 Sep TI - Compounded incretins in clinical practice: An opinion of the endocrine and metabolism practice and research network of the American College of Clinical Pharmacy. PG - 103314 LID - S1871-4021(25)00131-6 [pii] LID - 10.1016/j.dsx.2025.103314 [doi] AB - AIMS: This article aims to summarize the role of compounded incretin mimetics in clinical practice and in the context of drug shortages. METHODS: The Endocrine and Metabolism Practice and Research Network, a focused group of the American College of Clinical Pharmacy members, convened an independent committee to evaluate the role of compounded incretin mimetics. RESULTS: There is limited data demonstrating positive clinical outcomes in small cohorts of patients receiving compounded semaglutide and tirzepatide. However, there remain significant legal and safety concerns since compounded incretins do not undergo approval by the Food and Drug Administration. CONCLUSION: Whenever possible, healthcare providers should make every effort to assist patients with obtaining approved medications. If patients choose to obtain compounded incretins, providers can encourage safety by ensuring use of reputable compounding pharmacies and routinely monitoring patients for safety and efficacy of the compounded product. CI - Copyright (c) 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Courtney, Lindsay A AU - Courtney LA AD - Texas Tech University Health Sciences Center Jerry H. Hodge School of Pharmacy, Amarillo, TX, USA. Electronic address: lindsay.courtney@ttuhsc.edu. FAU - Clements, Jennifer N AU - Clements JN AD - University of South Carolina College of Pharmacy, Greenville, SC, USA. FAU - Isaacs, Diana AU - Isaacs D AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Pitlick, Jamie M AU - Pitlick JM AD - Drake University College of Pharmacy and Health Sciences, Des Moines, IA, USA. FAU - Reece, Sara Mandy AU - Reece SM AD - Philadelphia College of Osteopathic Medicine Georgia School of Pharmacy, Suwanee, GA, USA. FAU - Whitley, Heather P AU - Whitley HP AD - Auburn University, Harrison College of Pharmacy, Auburn, AL, USA. LA - eng PT - Journal Article PT - Review DEP - 20251021 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/therapeutic use/chemistry MH - *Drug Compounding/standards MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Endocrinology MH - United States OTO - NOTNLM OT - Compounding OT - Glucagon-like peptide-1 receptor agonist OT - Incretin mimetic OT - Obesity OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer N. Clements is a speaker for Eli Lilly and Novo Nordisk and a consultant for Sanofi. Diana Isaacs is a speaker for Eli Lilly and Novo Nordisk. Sara Reece is a speaker for Novo Nordisk and serves on the Eli Lilly advisory board. Jamie M. Pitlick reports that a family member began employment with Novo Nordisk in January 2024, after her involvement with this manuscript. Lindsay A. Courtney and Heather P. Whitley have no relevant conflicts of interest. EDAT- 2025/11/03 00:26 MHDA- 2025/11/29 02:21 CRDT- 2025/11/02 18:02 PHST- 2024/12/14 00:00 [received] PHST- 2025/10/17 00:00 [revised] PHST- 2025/10/21 00:00 [accepted] PHST- 2025/11/29 02:21 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 18:02 [entrez] AID - S1871-4021(25)00131-6 [pii] AID - 10.1016/j.dsx.2025.103314 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Sep;19(9):103314. doi: 10.1016/j.dsx.2025.103314. Epub 2025 Oct 21. PMID- 41174643 OWN - NLM STAT- MEDLINE DCOM- 20251101 LR - 20260903 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Oct 31 TI - Benefits of glucagon-like peptide-1 receptor agonists versus pioglitazone for cardio-hepatic outcomes: a territory-wide target trial emulation. PG - 416 LID - 10.1186/s12933-025-02973-5 [doi] LID - 416 AB - BACKGROUND: Both glucagon-like peptide 1 receptor agonist (GLP1RA) and pioglitazone are associated with cardiovascular and hepatic benefits in patients with type 2 diabetes (T2D). However, studies that directly compare their cardio-hepatic effects are lacking. We emulated a target trial to compare their effects on adverse liver and cardiovascular outcomes in T2D patients. METHODS: We adopted an "active comparator, new user" design involving T2D patients newly prescribed GLP1RA or pioglitazone between January 2008 and December 2022. The primary outcomes were major adverse liver outcomes (MALO) and cardiovascular events (MACE), with their individual outcomes and heart failure (HF) as secondary outcomes. Cox proportional hazards models were used to estimate hazard ratios (HRs) via intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: A total of 8922 patients (N = 4461 each group) were included. Compared to pioglitazone users, GLP1RA users had comparable risks of incident MALO (ITT: HR 0.94, 95% CI 0.66-1.34; PP: HR 1.13, 95% CI 0.60-2.15) and MACE (ITT: HR 0.99, 95% CI 0.80-1.22; PP: HR 1.10, 95% CI 0.77-1.58). The risk of HF was significantly lower in GLP1RA users in ITT analysis (HR 0.65, 95% CI 0.51-0.83). The results were consistent across most subgroup and sensitivity analyses. CONCLUSIONS: The effects on incident major adverse liver and cardiovascular outcomes were comparable between GLP1RA and pioglitazone, although the risk of incident HF was lower with GLP1RA. Treatment decisions for T2D patients at risk of adverse cardio-hepatic events should be individualized, considering HF risk and the need for weight loss, which if present, GLP1RA may be preferred. CI - (c) 2025. The Author(s). FAU - Li, Lanlan AU - Li L AD - Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Lui, David Tak-Wai AU - Lui DT AD - Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China. FAU - Fong, Carol Ho-Yi AU - Fong CH AD - Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Chow, Wing-Sun AU - Chow WS AD - Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Au, Ivan Chi-Ho AU - Au IC AD - School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Patrick Manson Building, 7 Sassoon Road, Hong Kong SAR, China. FAU - Xiong, Xi AU - Xiong X AD - Laboratory of Data Discovery for Health (D24H), Hong Kong SAR, China. AD - Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK. FAU - Lang, Brian Hung-Hin AU - Lang BH AD - Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Wong, Carlos King-Ho AU - Wong CK AD - School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Patrick Manson Building, 7 Sassoon Road, Hong Kong SAR, China. carlosho@hku.hk. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong SAR, China. carlosho@hku.hk. AD - Department of Infectious Disease Epidemiology & Dynamics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. carlosho@hku.hk. FAU - Lee, Chi-Ho AU - Lee CH AD - Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. pchlee@hku.hk. AD - State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China. pchlee@hku.hk. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251031 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - X4OV71U42S (Pioglitazone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Pioglitazone/adverse effects/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Middle Aged MH - Treatment Outcome MH - Aged MH - Risk Assessment MH - *Incretins/adverse effects/therapeutic use MH - Time Factors MH - *Cardiovascular Diseases/epidemiology/diagnosis/prevention & control MH - Risk Factors MH - Chemical and Drug Induced Liver Injury/epidemiology/diagnosis MH - Heart Failure/epidemiology/prevention & control/diagnosis MH - Incidence MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12577280 OTO - NOTNLM OT - Adverse liver diseases OT - Cardiovascular OT - GLP1RA OT - Glucose-lowering medications OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committee of the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Reference Number: UW 15-613). Informed consent was not required as all data was anonymous. Consent for publication: Not applicable. Competing interests: C.H.L received advisory board and lecture honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Echosens, Eli Lilly, Gilead, GSK, Novo Nordisk and Sanofi Aventis. C.K.H.W and X.X were supported by the AIR@InnoHK administered by Innovation and Technology Commission, Government of Hong Kong Special Administrative Region, China. EDAT- 2025/11/01 05:37 MHDA- 2025/11/01 06:32 PMCR- 2025/10/31 CRDT- 2025/11/01 01:10 PHST- 2025/06/11 00:00 [received] PHST- 2025/10/07 00:00 [accepted] PHST- 2025/11/01 06:32 [medline] PHST- 2025/11/01 05:37 [pubmed] PHST- 2025/11/01 01:10 [entrez] PHST- 2025/10/31 00:00 [pmc-release] AID - 10.1186/s12933-025-02973-5 [pii] AID - 2973 [pii] AID - 10.1186/s12933-025-02973-5 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Oct 31;24(1):416. doi: 10.1186/s12933-025-02973-5. PMID- 41173399 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20251209 IS - 1532-2742 (Electronic) IS - 0163-4453 (Linking) VI - 91 IP - 5 DP - 2025 Nov TI - Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis. PG - 106645 LID - S0163-4453(25)00245-2 [pii] LID - 10.1016/j.jinf.2025.106645 [doi] AB - OBJECTIVE: To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs). METHODS: Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool. RESULTS: A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86-0.93; absolute risk difference, -30 per 10,000 persons/year; I(2) = 0%), non-serious (RR, 0.90; 95% CI, 0.85-0.97; I(2) = 77%), and total infections (RR, 0.89; 95% CI, 0.84-0.94; I(2) = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79-0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68-0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65-0.97), vascular (RR, 0.65; 95% CI, 0.47-0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72-0.92), all with I(2) = 0%. Meta-regression showed greater weight loss (beta = -0.011; P =.045), hemoglobin A1c reduction (beta = -0.229; P =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83-0.92) were associated with lower risk. CONCLUSION: GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Han, Shumeng AU - Han S AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Liu, Yiwen AU - Liu Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Xing, Baodi AU - Xing B AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Yang, Yucheng AU - Yang Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Liu, Zijun AU - Liu Z AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Li, Yixuan AU - Li Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Wang, Xuechen AU - Wang X AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Yu, Jie AU - Yu J AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Ping, Fan AU - Ping F AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Li, Wei AU - Li W AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Xu, Lingling AU - Xu L AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. FAU - Qi, Tao AU - Qi T AD - State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, China; School of Computer Science, Beijing University of Posts and Telecommunications, China. FAU - Zhang, Yuelun AU - Zhang Y AD - Center for Prevention and Early Intervention, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. FAU - Li, Yuxiu AU - Li Y AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: liyuxiu@medmail.com.cn. FAU - Zhang, Huabing AU - Zhang H AD - Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: huabingzhangchn@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251029 PL - England TA - J Infect JT - The Journal of infection JID - 7908424 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - COVID-19 MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Infections/epidemiology MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - COVID-19 OT - Drug safety OT - Glucagon-like peptide-1 receptor agonists OT - Infection OT - Meta-analysis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/11/01 05:37 MHDA- 2025/11/20 00:30 CRDT- 2025/10/31 20:19 PHST- 2025/09/04 00:00 [received] PHST- 2025/10/18 00:00 [revised] PHST- 2025/10/25 00:00 [accepted] PHST- 2025/11/20 00:30 [medline] PHST- 2025/11/01 05:37 [pubmed] PHST- 2025/10/31 20:19 [entrez] AID - S0163-4453(25)00245-2 [pii] AID - 10.1016/j.jinf.2025.106645 [doi] PST - ppublish SO - J Infect. 2025 Nov;91(5):106645. doi: 10.1016/j.jinf.2025.106645. Epub 2025 Oct 29. PMID- 41166543 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20251121 IS - 1479-683X (Electronic) IS - 0804-4643 (Linking) VI - 193 IP - 5 DP - 2025 Oct 30 TI - Glucagon-like peptide-1 receptor agonists and muscle health: potential role in sarcopenia prevention and treatment. PG - R31-R44 LID - 10.1093/ejendo/lvaf223 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone therapy for weight loss and glycemic control in type 2 diabetes mellitus and obesity. Moreover, robust cardiometabolic benefits and favorable safety profiles have positioned GLP-1RAs at the forefront of modern obesity pharmacotherapy. However, findings from large-scale trials (eg, SUSTAIN, STEP, SURPASS) have raised concerns that a significant proportion of the weight loss achieved with GLP-1RA treatment may derive from lean body mass-particularly skeletal muscle-which could be detrimental in populations already at risk for sarcopenia. However, emerging preclinical evidence suggests that GLP-1RAs may directly and indirectly influence skeletal muscle through anti-inflammatory, antioxidant, and mitochondrial-supportive mechanisms. These include modulation of key signaling pathways such as PI3K/Akt/mammalian target of rapamycin (mTOR) and AMP-activated protein kinase-PGC-1alpha, suppression of proteolytic activity, and promotion of myogenic differentiation. In experimental models of aging, sarcopenic obesity, and chronic disease, GLP-1RAs have shown muscle-preserving properties. Nevertheless, the balance between adipose tissue reduction and lean mass preservation remains incompletely understood in clinical settings. This review examines the existing experimental and clinical evidence and identify critical research directions to determine whether GLP-1RAs confer overall benefit or carry unintended risks for skeletal muscle integrity in the context of weight loss. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Gonzalez-Luis, Ainhoa AU - Gonzalez-Luis A AD - Research Unit, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - Doctoral and Graduate School, University of La Laguna, San Cristobal de La Laguna 38200, Spain. FAU - Llinares-Arvelo, Vicente AU - Llinares-Arvelo V AD - Doctoral and Graduate School, University of La Laguna, San Cristobal de La Laguna 38200, Spain. AD - Escuela de Enfermeria Nuestra Senora de Candelaria, Carretera General del Rosario, 145, Santa Cruz de Tenerife 38010, Spain. FAU - Martinez-Alberto, Carlos E AU - Martinez-Alberto CE AD - Escuela de Enfermeria Nuestra Senora de Candelaria, Carretera General del Rosario, 145, Santa Cruz de Tenerife 38010, Spain. FAU - Hernandez-Carballo, Carolina AU - Hernandez-Carballo C AD - Research Unit, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - Internal Medicine Service, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. FAU - Mora-Fernandez, Carmen AU - Mora-Fernandez C AD - Research Unit, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - Internal Medicine Service, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - GEENDIAB (Grupo Espanol Para el Estudio de la Nefropatia Diabetica), Sociedad Espanola de Nefrologia, Santander 39000, Spain. FAU - Navarro-Gonzalez, Juan F AU - Navarro-Gonzalez JF AD - Research Unit, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - GEENDIAB (Grupo Espanol Para el Estudio de la Nefropatia Diabetica), Sociedad Espanola de Nefrologia, Santander 39000, Spain. AD - RICORS2040 (RD24/004/0022), Instituto de Salud Carlos III, Madrid 28000, Spain. AD - Instituto de Tecnologias Biomedicas, Universidad de La Laguna, Santa Cruz de Tenerife 38000, Spain. AD - Nephrology Service, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria 35450, Spain. FAU - Donate-Correa, Javier AU - Donate-Correa J AUID- ORCID: 0000-0001-7389-7347 AD - Research Unit, University Hospital Nuestra Senora de Candelaria (UHNSC), Santa Cruz de Tenerife 38010, Spain. AD - GEENDIAB (Grupo Espanol Para el Estudio de la Nefropatia Diabetica), Sociedad Espanola de Nefrologia, Santander 39000, Spain. AD - RICORS2040 (RD24/004/0022), Instituto de Salud Carlos III, Madrid 28000, Spain. AD - Instituto de Tecnologias Biomedicas, Universidad de La Laguna, Santa Cruz de Tenerife 38000, Spain. LA - eng GR - PI24/00218/Instituto de Salud Carlos III/ GR - PI21/01037/Instituto de Salud Carlos III/ GR - CP20/00122/Instituto de Salud Carlos III/ GR - FI22/00213/Instituto de Salud Carlos III/ GR - PIFIISC24/12/Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias (FIISC)/ GR - PIFIISC21/08/Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias (FIISC)/ PT - Journal Article PT - Review PL - England TA - Eur J Endocrinol JT - European journal of endocrinology JID - 9423848 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sarcopenia/prevention & control/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Muscle, Skeletal/drug effects/metabolism MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - GLP-1RAs OT - diabetes OT - muscle homeostasis OT - obesity OT - sarcopenia COIS- Conflict of interest: The authors have no conflicts of interest to declare that are relevant to the content of this article. EDAT- 2025/10/30 18:26 MHDA- 2025/11/21 12:50 CRDT- 2025/10/30 14:24 PHST- 2025/08/04 00:00 [received] PHST- 2025/10/06 00:00 [revised] PHST- 2025/10/22 00:00 [accepted] PHST- 2025/11/21 12:50 [medline] PHST- 2025/10/30 18:26 [pubmed] PHST- 2025/10/30 14:24 [entrez] AID - 8306985 [pii] AID - 10.1093/ejendo/lvaf223 [doi] PST - ppublish SO - Eur J Endocrinol. 2025 Oct 30;193(5):R31-R44. doi: 10.1093/ejendo/lvaf223. PMID- 41165079 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Glucagon-like peptide-1 receptor agonist versus sodium-glucose cotransporter-2 inhibitor persistence in Medicare Advantage beneficiaries with type 2 diabetes, cardiovascular risk, and obesity. PG - 472-484 LID - 10.1111/dom.70219 [doi] AB - AIMS: To compare treatment persistence and augmentation in adults with type 2 diabetes initiating glucagon-like peptide-1 receptor agonist versus sodium-glucose cotransporter-2 inhibitor therapy, including subgroups with cardiovascular disease and obesity. MATERIALS AND METHODS: Using Humana Healthcare Research claims data, we identified adults with type 2 diabetes newly initiating GLP-1 RA or SGLT2i therapy between 1 January, 2018, and 30 June 2022. Eligible patients had >12 months of continuous enrollment before and after the index date (first GLP-1 RA or SGLT2i claim). Persistence was measured over 12 months post-index, defined by a therapy gap <45 days, with additional 30- and 90-day gap assessments. Days on therapy until discontinuation were calculated. Augmentation was defined as the initiation of a new glucose-lowering class not used pre- or at-index. RESULTS: The 1:1 matched cohort included 22 167 GLP-1 RA and 22 267 SGLT2i initiators (mean age 68.2 years; 52.2% female; 73.4% White; 18.6% Black). At 1 year, persistence was 37.6% for GLP-1 RA versus 47.0% for SGLT2i (p <0.001). Augmentation occurred in 23.4% versus 27.4%, respectively (p <0.001). GLP-1 RA users were more likely to discontinue (HR = 1.39, p <0.001) therapy. Cardiovascular and obesity subgroup findings were consistent with overall study findings. A higher percentage of patients were persistent with increasing allowable gap (30-day: 31.4% vs. 41.1%; 90-day: 50.1% vs. 59.1%, GLP-1 RA vs. SGLT2i, respectively). CONCLUSIONS: At 1 year, SGLT2i users showed higher persistence and augmentation than GLP-1 RA users. This may reflect better tolerance, fewer side effects, improved glucose control, preferences for oral medications, lower patient costs, and easier access to SGLT2i medications. Providers may support improved persistence by addressing patient-specific factors influencing therapy choices. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Bowe, Andy AU - Bowe A AD - Humana Healthcare Research, Inc, Louisville, Kentucky, USA. FAU - Hayes, Mary AU - Hayes M AD - Humana Pharmacy Solutions, Humana Inc, Louisville, Kentucky, USA. FAU - John, Isha AU - John I AD - Humana Pharmacy Solutions, Humana Inc, Louisville, Kentucky, USA. FAU - Diaz, Monica AU - Diaz M AD - Humana Pharmacy Solutions, Humana Inc, Louisville, Kentucky, USA. FAU - Dixon, Suzanne AU - Dixon S AUID- ORCID: 0000-0003-4173-9103 AD - Humana Healthcare Research, Inc, Louisville, Kentucky, USA. FAU - Poonawalla, Insiya AU - Poonawalla I AD - Humana Healthcare Research, Inc, Louisville, Kentucky, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251030 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Obesity/complications/epidemiology MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Middle Aged MH - United States/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Heart Disease Risk Factors OTO - NOTNLM OT - GLP-1 OT - SGLT2 inhibitor OT - antidiabetic drug OT - antiobesity drug OT - cardiovascular disease OT - real-world evidence EDAT- 2025/10/30 12:28 MHDA- 2025/12/03 14:10 CRDT- 2025/10/30 07:04 PHST- 2025/10/03 00:00 [revised] PHST- 2025/08/20 00:00 [received] PHST- 2025/10/11 00:00 [accepted] PHST- 2025/12/03 14:10 [medline] PHST- 2025/10/30 12:28 [pubmed] PHST- 2025/10/30 07:04 [entrez] AID - 10.1111/dom.70219 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):472-484. doi: 10.1111/dom.70219. Epub 2025 Oct 30. PMID- 41163197 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 68 IP - 21 DP - 2025 Nov 13 TI - Chemoenzymatic Synthesis of Rhamnolipid-Modified Exendin-4: A Dual Approach for Long-Acting Glycemic Control through Endogenous Antibody Recruitment and Albumin Interaction. PG - 23324-23334 LID - 10.1021/acs.jmedchem.5c02146 [doi] AB - Effective management of Type 2 diabetes requires therapies that balance potency with sustained action. Glycosylation of glucagon-based drugs improves stability and reduces aggregation but does not significantly enhance pharmacokinetics. This study develops a novel glycosylation strategy horizontal line a rhamnolipid conjugation platform horizontal line to address this challenge. Using sortase A-mediated enzymatic ligation, we synthesized Ex4-rhamnolipid bioconjugates that prolong action through a dual mechanism: carbohydrate-mediated antibody engagement and lipophilic albumin binding. These conjugates potently activated GLP-1 receptors (EC(50) = 0.14-0.21 nM) and elicited rapid blood glucose reduction in diabetic rodent models. In immunized subjects, glucose-lowering effects persisted for 24 h, reflecting a 6.7-fold improvement in circulation half-life. In extended-duration studies, once-daily administration of the lead conjugate achieved glycemic control and pancreatic beta-cell protection comparable to semaglutide without adverse effects. This methodology capitalizes on natural immune components and plasma protein interactions to address the challenges of peptide-based treatments, offering a promising platform for sustained-release antidiabetic drugs. FAU - Dai, Shijie AU - Dai S AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. AD - State Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. FAU - Liu, Haiyan AU - Liu H AD - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. FAU - Mi, Baojing AU - Mi B AD - State Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. FAU - Li, Yanchu AU - Li Y AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Zhao, Kai AU - Zhao K AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Hong, Haofei AU - Hong H AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Wu, Zhimeng AU - Wu Z AUID- ORCID: 0000-0001-7583-7268 AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. LA - eng PT - Journal Article DEP - 20251029 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Glycolipids) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (rhamnolipid) RN - 0 (Blood Glucose) RN - EC 2.3.2.- (sortase A) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - EC 2.3.2.- (Aminoacyltransferases) RN - 0 (Bacterial Proteins) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - Animals MH - *Glycolipids/chemistry MH - *Exenatide/chemistry/pharmacology/therapeutic use/chemical synthesis MH - *Hypoglycemic Agents/pharmacology/therapeutic use/chemical synthesis/chemistry MH - Humans MH - Mice MH - Diabetes Mellitus, Experimental/drug therapy MH - Rats MH - Blood Glucose/drug effects MH - Male MH - Diabetes Mellitus, Type 2/drug therapy MH - Glycemic Control MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Aminoacyltransferases/metabolism MH - Bacterial Proteins MH - Cysteine Endopeptidases EDAT- 2025/10/30 06:29 MHDA- 2025/11/13 18:29 CRDT- 2025/10/30 01:00 PHST- 2025/11/13 18:29 [medline] PHST- 2025/10/30 06:29 [pubmed] PHST- 2025/10/30 01:00 [entrez] AID - 10.1021/acs.jmedchem.5c02146 [doi] PST - ppublish SO - J Med Chem. 2025 Nov 13;68(21):23324-23334. doi: 10.1021/acs.jmedchem.5c02146. Epub 2025 Oct 29. PMID- 41162256 OWN - NLM STAT- MEDLINE DCOM- 20260104 LR - 20260112 IS - 1471-6771 (Electronic) IS - 0007-0912 (Linking) VI - 136 IP - 1 DP - 2026 Jan TI - Managing patients taking glucagon-like peptide-1 receptor agonists: proceed with caution. PG - 12-14 LID - S0007-0912(25)00685-3 [pii] LID - 10.1016/j.bja.2025.10.004 [doi] AB - The use of glucagon-like peptide-1 (GLP-1) receptor agonists for managing type 2 diabetes mellitus has increased, but concerns have arisen about potential risks of perioperative pulmonary aspiration. A recent study by Huang and colleagues analysed the US Food and Drug Administration Adverse Event Reporting System database, and found a significant association between GLP-1 receptor agonist use and impaired gastric emptying events, which can lead to aspiration. Recent guidelines suggest that most patients can continue taking GLP-1 receptor agonists before surgery, and those at high risk for gastrointestinal issues should follow a 24-hour liquid diet beforehand, but determining which patients are at high risk for aspiration remains a challenge for clinicians. CI - Copyright (c) 2025. Published by Elsevier Ltd. FAU - Ovsak, Gavin G AU - Ovsak GG AD - Division of Anesthesiology, Critical Care and Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ggovsak@mdanderson.org. FAU - Gan, Tong J AU - Gan TJ AD - Division of Anesthesiology, Critical Care and Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: tjgan@mdanderson.org. LA - eng PT - Editorial DEP - 20251028 PL - England TA - Br J Anaesth JT - British journal of anaesthesia JID - 0372541 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Gastric Emptying/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - gastric emptying OT - gastric ultrasound OT - guidelines OT - preoperative fasting OT - pulmonary aspiration EDAT- 2025/10/30 00:27 MHDA- 2026/01/05 00:49 CRDT- 2025/10/29 22:54 PHST- 2024/11/22 00:00 [received] PHST- 2025/09/24 00:00 [revised] PHST- 2025/10/02 00:00 [accepted] PHST- 2026/01/05 00:49 [medline] PHST- 2025/10/30 00:27 [pubmed] PHST- 2025/10/29 22:54 [entrez] AID - S0007-0912(25)00685-3 [pii] AID - 10.1016/j.bja.2025.10.004 [doi] PST - ppublish SO - Br J Anaesth. 2026 Jan;136(1):12-14. doi: 10.1016/j.bja.2025.10.004. Epub 2025 Oct 28. PMID- 41161770 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 5 DP - 2025 Oct 29 TI - Using real-world data to predict findings of an ongoing phase IV trial: glycemic control of semaglutide versus standard of care. LID - 10.1136/bmjdrc-2025-005180 [doi] LID - e005180 AB - OBJECTIVE: Using national claims databases, we sought to emulate the design of the ongoing SEPRA trial and predict its findings, comparing the effects of once weekly semaglutide to SoC medications on glycemic control (A1C <7%) in type-2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: Using Optum Clinformatics (July 2017 - May 2022), we identified a 1:1 propensity score-matched (PSM) cohort of adults with T2D on metformin monotherapy, who had recorded A1C and initiated either injectable semaglutide or SoC medications (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, SUs, or glucagon-like peptide-1 agonists) and met eligibility criteria adapted from the SEPRA trial. The primary outcome was the proportion of patients achieving A1C <7%. The study protocol was preregistered (NCT05577728, ClinicalTrials.gov) before any etiologic analyses. Risk ratios and corresponding 95% CIs were estimated. RESULTS: We identified 1,144 PSM pairs of injectable semaglutide and SoC initiators with balance in pre-exposure covariates. Semaglutide initiators were 30% (risk ratio (95% CI), 1.30 (1.16 to 1.45)) more likely to achieve glycemic control (A1C <7%) than those initiating SoC. Additionally, semaglutide initiators had a 1.3% reduction in A1C, compared with a 1.1% reduction in the SoC group. These results were consistent with interim results of the SEPRA trial, which were released after the protocol for our database study was preregistered. CONCLUSION: This claims database study, designed to predict the results of the SEPRA trial, found results consistent with interim trial results. Our findings support the notion that well-designed non-randomized studies using fit-for-purpose data can effectively complement pragmatic randomized controlled trials. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. FAU - Kattinakere Sreedhara, Sushama AU - Kattinakere Sreedhara S AUID- ORCID: 0000-0002-9182-304X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA skattinakeresreedhara@bwh.harvard.edu. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AUID- ORCID: 0000-0003-2575-467X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - D'Andrea, Elvira AU - D'Andrea E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Weberpals, Janick G AU - Weberpals JG AUID- ORCID: 0000-0003-0404-7394 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - DiCesare, Elyse C AU - DiCesare EC AUID- ORCID: 0009-0000-2244-6378 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Tsacogianis, Theodore AU - Tsacogianis T AUID- ORCID: 0009-0003-4529-5287 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Bradley, Marie AU - Bradley M AUID- ORCID: 0000-0002-6266-4414 AD - Office of Medical Policy, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Concato, John AU - Concato J AUID- ORCID: 0000-0003-2846-0503 AD - Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Wang, Shirley V AU - Wang SV AUID- ORCID: 0000-0001-7761-7090 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT05577728 GR - R01 HL141505/HL/NHLBI NIH HHS/United States GR - R01 AR080194/AR/NIAMS NIH HHS/United States GR - R01 AG053302/AG/NIA NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article DEP - 20251029 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - *Glycemic Control/methods/statistics & numerical data MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - *Standard of Care/statistics & numerical data MH - Aged MH - Metformin/therapeutic use MH - Biomarkers/analysis MH - Adult MH - Clinical Trials, Phase IV as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12574359 OTO - NOTNLM OT - Cohort Studies OT - Database OT - Glycated Hemoglobin A OT - Pharmacoepidemiology COIS- Competing interests: Dr. Wang has been an ad hoc consultant to Exponent Inc, Cytel Inc, and MITRE, a federally funded research and development center for the Centers for Medicare and Medicaid Services. Dr. Schneeweiss is principal investigator of the FDA Sentinel Innovation Center funded by the FDA and co-principal investigator of an investigator-initiated grant to the Brigham and Women's Hospital from UCB Pharma unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women's Hospital and MGB HealthCare System in accordance with their institutional compliance policies. Dr.D'Andrea is currently an employee and owns stocks of AbbVie Inc. and not related to the topic of this work. Dr. Patorno is principal investigator of a research grant to the Brigham and Women's Hospital from Boehringer Ingelheim, not related to the topic of this work. She receives royalties from UpToDate. EDAT- 2025/10/30 00:26 MHDA- 2025/10/30 00:27 PMCR- 2025/10/29 CRDT- 2025/10/29 21:24 PHST- 2025/04/22 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/10/30 00:27 [medline] PHST- 2025/10/30 00:26 [pubmed] PHST- 2025/10/29 21:24 [entrez] PHST- 2025/10/29 00:00 [pmc-release] AID - 13/5/e005180 [pii] AID - bmjdrc-2025-005180 [pii] AID - 10.1136/bmjdrc-2025-005180 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Oct 29;13(5):e005180. doi: 10.1136/bmjdrc-2025-005180. PMID- 41161090 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20260325 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 789 DP - 2025 Nov 14 TI - GLP-1 receptor agonists and inflammatory pathway modulation: Dual targeting of metabolic and immune dysfunction in insulin resistance. PG - 152822 LID - S0006-291X(25)01538-4 [pii] LID - 10.1016/j.bbrc.2025.152822 [doi] AB - Because of their extensive effects on glycaemic management and weight loss, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are showing promise as therapeutic agents in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Their therapeutic use over the past few years is no longer restricted to glucose metabolism only, but increasingly, more evidence is suggesting their anti-inflammatory actions. Low-grade inflammation for prolonged periods is a important participant in the pathogenesis of insulin resistance and metabolic syndrome. It has been demonstrated that GLP-1RAs influence immune functions and suppress inflammation via influencing key signalling pathways, such as c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-kappaB), and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. These signaling pathways are involved in cellular stress responses and cytokine production resulting in insulin resistance. By modulating both inflammatory and metabolic targets, GLP-1RAs are a potential class of immunometabolic modulators. This mini-review emphasizes the dual impact of GLP-1RAs and their therapeutic application in the overall management of insulin resistance and metabolic disorders. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Ngabea, Murtala A AU - Ngabea MA AD - Department of Medicine Maitama District Hospital/ College of Medicine Baze University, Abuja, Nigeria. FAU - Dimeji, Igbayilola Yusuff AU - Dimeji IY AD - Department of Human Physiology, College of Medicine and Health Sciences, Baze University, Nigeria. Electronic address: yusuff.igbayilola@bazeuniversity.edu.ng. LA - eng PT - Journal Article PT - Review DEP - 20251016 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Insulin Resistance/immunology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Inflammation/drug therapy/immunology/metabolism MH - Animals MH - Signal Transduction/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/immunology/metabolism MH - Glucagon-Like Peptide-1 Receptor MH - Metabolic Syndrome/drug therapy/immunology MH - *Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - And NLRP3. this dual mechanism improves insulin sensitivity and may prevent further metabolic complications OT - Cytokines OT - Due to their broad effects OT - Enabling more individualized and effective treatments for type 2 diabetes. GLP-1RAs provide a dual-action approach to treating insulin resistance by addressing both metabolic and immunological factors. in addition to lowering blood glucose OT - Especially in patients with inflammatory conditions OT - GLP-1 receptor agonists OT - GLP-1RAs OT - Glucose metabolism OT - Inflammatory pathway OT - Insulin resistance OT - JNK OT - Or GLP-1 receptor agonists OT - Show promise for integrated therapies OT - Significant statement OT - They reduce systemic inflammation by modulating pathways like NF-kappaB COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DR IGBAYILOLA YUSUFF DIMEJI reports administrative support was provided by Baze University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/10/30 00:26 MHDA- 2025/11/15 00:29 CRDT- 2025/10/29 19:06 PHST- 2025/08/29 00:00 [received] PHST- 2025/10/16 00:00 [revised] PHST- 2025/10/16 00:00 [accepted] PHST- 2025/11/15 00:29 [medline] PHST- 2025/10/30 00:26 [pubmed] PHST- 2025/10/29 19:06 [entrez] AID - S0006-291X(25)01538-4 [pii] AID - 10.1016/j.bbrc.2025.152822 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2025 Nov 14;789:152822. doi: 10.1016/j.bbrc.2025.152822. Epub 2025 Oct 16. PMID- 41160742 OWN - NLM STAT- MEDLINE DCOM- 20260127 LR - 20260128 IS - 1545-326X (Electronic) IS - 0066-4219 (Linking) VI - 77 IP - 1 DP - 2026 Jan TI - Glucagon-Like Peptide 1 Receptor Agonists and Cardiovascular Disease. PG - 1-15 LID - 10.1146/annurev-med-043024-011141 [doi] AB - Glucagon-like peptide 1 receptor (GLP-1R) agonists were originally developed as treatments for diabetes and subsequently evolved into weight management medications. These drugs have recently been shown to demonstrate remarkable efficacy in cardiovascular disease, kidney disease, and heart failure with preserved ejection fraction (HFpEF). In this review, we focus on the cardiovascular protective effects of GLP-1R agonists identified from basic studies and outcome trials, including a brief description of those forthcoming soon. FAU - Ibe, Tatsuro AU - Ibe T AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; email: borlaug.barry@mayo.edu. FAU - Borlaug, Barry A AU - Borlaug BA AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; email: borlaug.barry@mayo.edu. LA - eng PT - Journal Article PT - Review DEP - 20251029 PL - United States TA - Annu Rev Med JT - Annual review of medicine JID - 2985151R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide MH - Heart Failure/drug therapy OTO - NOTNLM OT - cardiovascular disease OT - glucagon-like peptide 1 receptor agonist OT - heart failure OT - heart failure with preserved ejection fraction OT - metabolic inflammation OT - vascular disease EDAT- 2025/10/29 18:27 MHDA- 2026/01/28 19:20 CRDT- 2025/10/29 14:53 PHST- 2026/01/28 19:20 [medline] PHST- 2025/10/29 18:27 [pubmed] PHST- 2025/10/29 14:53 [entrez] AID - 10.1146/annurev-med-043024-011141 [doi] PST - ppublish SO - Annu Rev Med. 2026 Jan;77(1):1-15. doi: 10.1146/annurev-med-043024-011141. Epub 2025 Oct 29. PMID- 41155271 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 20 DP - 2025 Oct 14 TI - GLP-1 Receptor Agonists Are Associated with Reduced Ascending Aorta Dilatation in Patients with Type 2 Diabetes: A Prospective Study. LID - 10.3390/ijms26209977 [doi] LID - 9977 AB - The aim was to assess the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RA) treatment on the progression of ascending aorta dilatation in patients with type 2 diabetes mellitus (T2DM). A total of 127 T2DM patients with subclinical ascending aortic dilatation (35-45 mm) were prospectively enrolled. Fifty-seven initiated GLP-1 RA therapy (liraglutide, semaglutide, or dulaglutide), while 70 continued on standard care. Ascending aortic diameter was measured by computed tomography angiography (CTA) at baseline and 24 months, alongside circulating markers of vascular remodeling: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), C-reactive protein (CRP), and osteoprotegerin (OPG). Progression of aortic dilatation was significantly lower in the GLP-1 RA group compared with controls (+0.36 +/- 0.20 mm vs. +1.05 +/- 0.28 mm; p < 0.001). Therapy correlated with decreased MMP-9 and CRP (p < 0.01) and increased TIMP-1 and OPG (p < 0.05). The use of GLP-1 RA was an independent predictor of low progression, even in multivariate models after adjusting for demographic, metabolic, and biomarker data. GLP-1 RA therapy was associated with reduced progression of ascending aortic dilatation in T2DM, supporting a potential vasoprotective role beyond glucose lowering. FAU - Sardu, Celestino AU - Sardu C AUID- ORCID: 0000-0001-5099-3790 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. FAU - Marfella, Ludovica Vittoria AU - Marfella LV AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Fumagalli, Carlo AU - Fumagalli C AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Rinaldi, Luca AU - Rinaldi L AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Sasso, Ferdinando Carlo AU - Sasso FC AUID- ORCID: 0000-0002-9142-7848 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. FAU - Cozzolino, Domenico AU - Cozzolino D AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Nappo, Francesco AU - Nappo F AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Sellitto, Ausilia AU - Sellitto A AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Romano, Ciro AU - Romano C AUID- ORCID: 0000-0002-5807-6601 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Carusone, Caterina AU - Carusone C AUID- ORCID: 0009-0007-8644-9843 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Russo, Pasquale AU - Russo P AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Marfella, Lorenza AU - Marfella L AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Tarantino, Nicola Maria AU - Tarantino NM AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Carpinella, Gerardo AU - Carpinella G AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Furbatto, Fulvio AU - Furbatto F AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Gentile, Sandro AU - Gentile S AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Guarino, Giuseppina AU - Guarino G AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Satta, Ersilia AU - Satta E AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Bellis, Alessandro AU - Bellis A AUID- ORCID: 0000-0003-3476-5696 AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Marinelli, Luca AU - Marinelli L AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Donisi, Isabella AU - Donisi I AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - D'Onofrio, Nunzia AU - D'Onofrio N AUID- ORCID: 0000-0002-5300-9530 AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Mauro, Ciro AU - Mauro C AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Cappabianca, Salvatore AU - Cappabianca S AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Balestrieri, Maria Luisa AU - Balestrieri ML AUID- ORCID: 0000-0001-6001-1789 AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Marfella, Raffaele AU - Marfella R AUID- ORCID: 0000-0003-3960-9270 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. LA - eng PT - Journal Article DEP - 20251014 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Osteoprotegerin) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - EC 3.4.24.35 (MMP9 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prospective Studies MH - *Aorta/drug effects/pathology/diagnostic imaging MH - Matrix Metalloproteinase 9/blood/metabolism MH - Aged MH - Tissue Inhibitor of Metalloproteinase-1/blood MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - C-Reactive Protein/metabolism MH - Osteoprotegerin/blood MH - Biomarkers/blood MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12563610 OTO - NOTNLM OT - GLP-1 receptor agonists OT - ascending aortic dilatation OT - computed tomography angiography OT - inflammation OT - type 2 diabetes mellitus OT - vascular biomarkers COIS- The authors declare no conflicts of interest. EDAT- 2025/10/29 06:27 MHDA- 2025/10/29 06:28 PMCR- 2025/10/14 CRDT- 2025/10/29 01:14 PHST- 2025/09/15 00:00 [received] PHST- 2025/10/09 00:00 [revised] PHST- 2025/10/12 00:00 [accepted] PHST- 2025/10/29 06:28 [medline] PHST- 2025/10/29 06:27 [pubmed] PHST- 2025/10/29 01:14 [entrez] PHST- 2025/10/14 00:00 [pmc-release] AID - ijms26209977 [pii] AID - ijms-26-09977 [pii] AID - 10.3390/ijms26209977 [doi] PST - epublish SO - Int J Mol Sci. 2025 Oct 14;26(20):9977. doi: 10.3390/ijms26209977. PMID- 41153084 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Effectiveness and safety of GLP-1 receptor agonists in craniopharyngioma patients with obesity: A multicentre real-world study. PG - 443-451 LID - 10.1111/dom.70216 [doi] AB - AIMS: Acquired hypothalamic obesity (aHO) following craniopharyngioma (CP) is a challenging condition with limited therapeutic options. This study aimed to assess the real-world effectiveness and safety of GLP-1 RAs in this population. MATERIALS AND METHODS: CranioGLP1 is a retrospective multicentre study including 116 adults with aHO treated with one or more GLP-1 RAs across 16 French obesity centres. Demographic, clinical, and therapeutic data were collected from medical records. Weight outcomes, adverse events, and predictors of response were analysed. RESULTS: Patients had a mean age of 44.4 +/- 13.5 years and a mean BMI of 40.1 +/- 8.6 kg/m(2), 42% had type 2 diabetes. Over a mean follow-up of 44 months, mean weight loss was -4.6% (+/-12.5), with high interindividual variability; 51% achieved >/=5% weight loss, and 28% >/=10%. Semaglutide (mean dose 1.2 mg/week) was associated with the greatest reduction (-6.8%), particularly in patients without diabetes (-8.5% +/- 12.3 vs. -3.9% +/- 10.0 in those with diabetes; p = 0.032). Endocrine adverse events occurred in 12% and 10% of patients with adrenal or vasopressin deficiency decompensation, respectively, with 8% requiring hospitalisation. Gastrointestinal intolerance led to treatment discontinuation in 13% of cases. CONCLUSIONS: GLP-1 RAs at submaximal doses induce moderate, yet clinically meaningful weight loss in adults with aHO, with semaglutide showing the highest efficacy. Given the non-negligible risk of hormonal decompensation, specific endocrine monitoring is essential. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lambert, Flora AU - Lambert F AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. FAU - Guillon, Emilie AU - Guillon E AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Gatta-Cherifi, Blandine AU - Gatta-Cherifi B AD - Endocrinology, Diabetology, Nutrition and Metabolic Diseases Department, Haut-Leveque Hospital, Bordeaux, France. CN - CranioGLP1_FORCE Group FAU - Soula, Hedi AU - Soula H AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Poitou, Christine AU - Poitou C AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Faucher, Pauline AU - Faucher P AUID- ORCID: 0000-0001-5472-3851 AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20251028 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Craniopharyngioma/complications/drug therapy MH - Male MH - Female MH - Adult MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications/etiology MH - *Pituitary Neoplasms/complications/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/adverse effects MH - Weight Loss/drug effects MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications MH - France/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12673446 OTO - NOTNLM OT - GLP-1 analogue OT - anti-obesity drug OT - obesity therapy OT - real-world evidence OT - semaglutide COIS- The authors declare no conflicts of interest. FIR - Lambert, Flora IR - Lambert F FIR - Guillon, Emilie IR - Guillon E FIR - Soula, Hedi IR - Soula H FIR - Poitou, Christine IR - Poitou C FIR - Faucher, Pauline IR - Faucher P FIR - Albarel, Frederique IR - Albarel F FIR - Bonnet, Jean-Baptiste IR - Bonnet JB FIR - Borel, Anne-Laure IR - Borel AL FIR - Brindisi, Marie-Claude IR - Brindisi MC FIR - Carette, Claire IR - Carette C FIR - Drui, Delphine IR - Drui D FIR - Fagour, Cedric IR - Fagour C FIR - Farigon, Nicolas IR - Farigon N FIR - Gaborit, Benedicte IR - Gaborit B FIR - Gatta-Cherifi, Blandine IR - Gatta-Cherifi B FIR - Illouz, Frederic IR - Illouz F FIR - Jouini-Bouhamri, Ryme IR - Jouini-Bouhamri R FIR - Maiga, Ibrahima IR - Maiga I FIR - Montastier, Emilie IR - Montastier E FIR - Mosbah, Helena IR - Mosbah H FIR - Vitellius, Geraldine IR - Vitellius G FIR - Ziegler, Olivier IR - Ziegler O EDAT- 2025/10/29 06:28 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/29 00:59 PHST- 2025/10/09 00:00 [revised] PHST- 2025/06/30 00:00 [received] PHST- 2025/10/09 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/29 06:28 [pubmed] PHST- 2025/10/29 00:59 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70216 [pii] AID - 10.1111/dom.70216 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):443-451. doi: 10.1111/dom.70216. Epub 2025 Oct 28. PMID- 41147324 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials. PG - 518-528 LID - 10.1111/dom.70224 [doi] AB - AIMS: To investigate the renal outcomes of dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose transport protein-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) with chronic renal disease (CKD). MATERIALS AND METHODS: PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched through July 2025 for randomized controlled trials with >/=24 weeks of follow-up in patients with T2DM and CKD. Outcomes included composite renal outcome, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). A network meta-analysis was conducted, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation used to evaluate evidence certainty (GRADE). RESULTS: Twenty RCTs enrolling 80,670 participants were included. Compared with placebo, several agents significantly reduced composite renal outcomes, with dapagliflozin 10 mg showing the greatest efficacy (OR 0.55, 95% CI 0.42-0.72; high-certainty evidence), followed by canagliflozin, empagliflozin, efpeglenatide, sotagliflozin 400 mg, semaglutide, and dulaglutide 1.5 mg. Canagliflozin 100-300 mg significantly reduced UACR, whereas dapagliflozin had no effect. None of the novel antidiabetic agents significantly altered eGFR. Certainty of evidence ranged from high for placebo-controlled comparisons to low or very low for indirect estimates. CONCLUSIONS: In patients with T2DM and CKD, SGLT2 inhibitors provide the most consistent renal protection, while GLP-1 receptor agonists offer additional but variable benefits. Dapagliflozin showed the greatest efficacy, and canagliflozin most strongly reduced albuminuria, highlighting meaningful heterogeneity across agents. DPP-4 inhibitors conferred no renal benefit. Overall, evidence from placebo-controlled trials was robust, whereas certainty was lower for indirect estimates, highlighting the need for drug-specific evaluation in clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lin, Rong AU - Lin R AD - Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. FAU - Hsu, Chia-Li AU - Hsu CL AD - Ministry of Health and Welfare Shuang-Ho Hospital, New Taipei City, Taiwan. FAU - Shih, Ming-Chieh AU - Shih MC AD - School of Medicine, National Tsing Hua University, Hsinchu, Taiwan. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. FAU - Wu, Hon-Yen AU - Wu HY AUID- ORCID: 0000-0003-3121-3351 AD - Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. LA - eng GR - NHRI-EX112-11026PI/National Health Research Institutes/ GR - NHRI-EX114-11433PI/National Health Research Institutes/ GR - FEMH-2022-C-014/Far Eastern Memorial Hospital/ GR - FEMH-2023-C-010/Far Eastern Memorial Hospital/ GR - FEMH-2025-C-019/Far Eastern Memorial Hospital/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20251028 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Diabetic Nephropathies/prevention & control MH - Glomerular Filtration Rate/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome PMC - PMC12673457 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - diabetic nephropathy OT - network meta-analysis COIS- The authors declare that there are no conflicts of interest related to this manuscript. EDAT- 2025/10/28 12:29 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/28 06:13 PHST- 2025/09/26 00:00 [revised] PHST- 2025/06/11 00:00 [received] PHST- 2025/10/11 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/28 12:29 [pubmed] PHST- 2025/10/28 06:13 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70224 [pii] AID - 10.1111/dom.70224 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):518-528. doi: 10.1111/dom.70224. Epub 2025 Oct 28. PMID- 41145374 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm. PG - 826-839 LID - 10.1111/dom.70240 [doi] AB - Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder usually caused by the variant m.3243A>G in the MT-TL1 gene. We have proposed that diabetes in MIDD arises from a combination of insulin resistance and impaired beta-cell function that is more likely to occur in the presence of high skeletal muscle heteroplasmy and moderate beta-cell heteroplasmy for m.3243A>G and to be driven by oxidative stress as a major pathophysiologic mechanism. There are no randomised trials specifically on the management of MIDD. An approach to MIDD informed by its pathophysiology could optimise management and be a framework for future trials. In this narrative review, we discuss the effects of existing anti-hyperglycaemic medications on oxidative stress, mitochondrial function, and cardiorenal protection. We also review the published case reports and series on the management of diabetes associated with MIDD, and the safety of insulin and non-insulin medications in MIDD. We found that glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors have favourable properties in addressing oxidative stress and mitochondrial function. They also harbour cardiorenal protection properties independent from their effect on glucose control that are fully relevant in MIDD, making them ideal candidates as first-line agents for the management of MIDD. Accordingly, we share our perspective on a disease-specific algorithm for the management of MIDD diabetes that could delay or prevent the development of cardiovascular and renal complications associated with this mitochondrial disease. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chaudhry, Ahsen AU - Chaudhry A AUID- ORCID: 0009-0003-0136-4869 AD - Division of Endocrinology, Department of Medicine, Clinician Investigator Program, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Thompson, David M AU - Thompson DM AUID- ORCID: 0000-0002-8597-2356 AD - Division of Endocrinology, Department of Medicine, Clinician Investigator Program, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Chanoine, Jean-Pierre AU - Chanoine JP AUID- ORCID: 0000-0002-5167-2064 AD - Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada. LA - eng GR - 1-SRA-2025-1785-A-N/Breakthrough T1D Canada/ GR - University of British Columbia Clinician Investigator Program/ PT - Journal Article PT - Review DEP - 20251027 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Noninsulin-dependent diabetes mellitus with deafness SB - IM MH - Humans MH - *Deafness/genetics/complications MH - *Mitochondrial Diseases/complications/genetics/drug therapy MH - Algorithms MH - *Hypoglycemic Agents/therapeutic use MH - Oxidative Stress/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus/genetics/drug therapy MH - Insulin Resistance MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12803549 OTO - NOTNLM OT - algorithm OT - dipeptidyl peptidase 4 (DPP-4) inhibitors OT - glucagon-like peptide-1 receptor (GLP-1R) agonists OT - insulin OT - management OT - maternally inherited diabetes and deafness (MIDD) OT - metformin OT - pregnancy OT - sodium-glucose cotransporter-2 (SGLT2) inhibitors OT - thiazolidinediones COIS- Ahsen Chaudhry, David M. Thompson and Jean-Pierre Chanoine report no conflict of interest relevant to this work. EDAT- 2025/10/28 00:26 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/10/27 23:32 PHST- 2025/10/15 00:00 [revised] PHST- 2025/08/01 00:00 [received] PHST- 2025/10/17 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/10/28 00:26 [pubmed] PHST- 2025/10/27 23:32 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70240 [pii] AID - 10.1111/dom.70240 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):826-839. doi: 10.1111/dom.70240. Epub 2025 Oct 27. PMID- 41144235 OWN - NLM STAT- MEDLINE DCOM- 20251120 LR - 20260921 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 12 DP - 2025 Dec 1 TI - Risk of Acute Pancreatitis and Biliary Events After Initiation of Incretin-Based Medications in Patients With Type 2 Diabetes. PG - 2127-2137 LID - 10.2337/dc25-1840 [doi] AB - OBJECTIVE: Patients with type 2 diabetes (T2D) are at increased risk of acute pancreatitis (AP) and biliary events. Evidence remains mixed regarding the association between incretin-based therapies, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is), and these outcomes. We examined the association between incretin medication use and risk of incident AP or biliary disease in patients with T2D. RESEARCH DESIGN AND METHODS: Using Medicare Fee-for-Service (FFS) and two U.S. commercial claims databases (2014-2021), we identified three pairwise cohorts of propensity score (PS)-based fine stratification-weighted patients aged >/=18 years (>/=65 years in Medicare FFS) with T2D without prior AP or biliary disease who initiated treatment with GLP-1RAs versus sodium-glucose cotransporter 2 inhibitors (SGLT2is), DPP-4is versus SGLT2is, or GLP-1RAs versus DPP-4is. PS was estimated using 92 covariates. Weighted hazard ratios (HRs) with 95% CIs for hospitalization because of AP and biliary events were estimated using Cox models. RESULTS: Each cohort included >1.2 million patients. After weighting, GLP-1RA and DPP-4i initiators had similar risk of AP compared with SGLT2i initiators (HR 1.01; 95% CI 0.90-1.13 and HR 1.00; 95% CI 0.85-1.15, respectively). However, both GLP-1RA and DPP-4i initiators showed a modestly increased risk of biliary disease compared with SGLT2i initiators (HR 1.15; 95% CI 1.05-1.26 and HR 1.22; 95% CI 1.03-1.46, respectively), equivalent to fewer than one additional event per 1,000 person-years. There was no difference in risk of AP (HR 1.08; 95% CI 0.95-1.22) or biliary disease (HR 0.95; 95% CI 0.86-1.04) between GLP-1RAs and DPP-4is. CONCLUSIONS: In patients with T2D, GLP-1RAs and DPP-4is were associated with a small increase in risk of biliary disease, but not of AP, compared with SGLT2is. CI - (c) 2025 by the American Diabetes Association. FAU - Fang, Yichen E AU - Fang YE AUID- ORCID: 0000-0001-7323-2716 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Paik, Julie M AU - Paik JM AUID- ORCID: 0000-0002-1315-5445 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA. FAU - Ortega-Montiel, Janinne AU - Ortega-Montiel J AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Clinical Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. LA - eng GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - DB-2020C2-20326/PCORI/Patient-Centered Outcomes Research Institute/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Pancreatitis/epidemiology/chemically induced MH - Male MH - *Incretins/therapeutic use/adverse effects MH - Female MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - United States/epidemiology PMC - PMC12718078 MID - NIHMS2125281 COIS- Duality of Interest. D.J.W. reported receiving personal fees from Novo Nordisk outside the submitted work. E.P. reported receiving grants to her institution from Boehringer Ingelheim, Astra Zeneca, and Bayer outside the submitted work and receiving royalties from UpToDate. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/10/27 18:25 MHDA- 2025/11/20 18:27 PMCR- 2025/10/27 CRDT- 2025/10/27 12:24 PHST- 2025/07/28 00:00 [received] PHST- 2025/09/19 00:00 [accepted] PHST- 2025/11/20 18:27 [medline] PHST- 2025/10/27 18:25 [pubmed] PHST- 2025/10/27 12:24 [entrez] PHST- 2025/10/27 00:00 [pmc-release] AID - 163686 [pii] AID - 251840 [pii] AID - 10.2337/dc25-1840 [doi] PST - ppublish SO - Diabetes Care. 2025 Dec 1;48(12):2127-2137. doi: 10.2337/dc25-1840. PMID- 41132144 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260626 IS - 1532-5415 (Electronic) IS - 0002-8614 (Print) IS - 0002-8614 (Linking) VI - 74 IP - 1 DP - 2026 Jan TI - GLP-1 Receptor Agonist Therapy and Cardiorenal Outcomes in Patients >/= 80 Years Old With Type 2 Diabetes. PG - 96-106 LID - 10.1111/jgs.70187 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated potential in improving glycemic control and reducing adverse outcomes in patients with Type 2 diabetes mellitus (T2DM); however, their efficacy in individuals aged 80 years and older remains understudied. To evaluate the efficacy of GLP-1 RAs compared with dipeptidyl peptidase-4 inhibitors (DPP4i) in patients aged >/= 80 years with T2DM. PARTICIPANT AND SETTING: De-identified records from the TriNetX United States database identified 284,417 patients aged >/= 80 years with T2DM, including 12,032 new GLP-1 RA users and 28,230 new DPP4i users, analyzed from January 2018 to December 2022. METHODS: This retrospective cohort study utilized a new-user and active comparator design to evaluate clinical outcomes between GLP-1 RA and DPP4i users during a follow-up period of up to 5 years. Propensity score matching, incorporating all the baseline covariates, was used to minimize baseline differences. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for clinical outcomes. Sensitivity analyses were performed to validate the findings. RESULTS: After 1:1 propensity score matching, 11,464 patients were included in each group. Both cohorts had a mean age of 81.6 years; 47.7% were female, and 67% were White. GLP-1 RA users had significantly lower risks of major adverse cardiovascular events (HR: 0.86, 95% CI: 0.81-0.91), major adverse kidney events (HR: 0.86, 95% CI: 0.82-0.91), all-cause hospitalization (HR: 0.91, 95% CI: 0.84-0.97), and all-cause mortality (HR: 0.82, 95% CI: 0.77-0.88) compared with DPP4i users. No significant differences were observed between the groups in the rate of heart failure or bone fractures. CONCLUSIONS: GLP-1 RAs may offer substantial cardiorenal and survival benefits in patients aged 80 years and older with T2DM. These findings support the use of GLP-1 RAs as a therapeutic option in this high-risk, older population. CI - (c) 2025 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. FAU - Chen, Jui-Cheng AU - Chen JC AD - Department of General Medicine, Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Liu, Ya-Fang AU - Liu YF AD - Data Analysis Group, Artificial Intelligence Research Center, Research Department, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Chen, Mon-Ting AU - Chen MT AD - Department of Healthcare Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AUID- ORCID: 0000-0003-3561-4689 AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. LA - eng GR - 2023SKHADR036/Shin Kong Wu Ho-Su Memorial Hospital/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251024 PL - United States TA - J Am Geriatr Soc JT - Journal of the American Geriatrics Society JID - 7503062 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Aged, 80 and over MH - Female MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Propensity Score MH - Cardiovascular Diseases/epidemiology MH - United States/epidemiology PMC - PMC12774297 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - cardiovascular outcomes OT - glucagon-like peptide-1 receptor agonists OT - older adults OT - renal outcomes COIS- The authors declare no conflicts of interest. EDAT- 2025/10/24 06:26 MHDA- 2026/01/06 19:17 PMCR- 2026/01/06 CRDT- 2025/10/24 04:43 PHST- 2025/09/26 00:00 [revised] PHST- 2025/04/22 00:00 [received] PHST- 2025/10/05 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2025/10/24 06:26 [pubmed] PHST- 2025/10/24 04:43 [entrez] PHST- 2026/01/06 00:00 [pmc-release] AID - JGS70187 [pii] AID - 10.1111/jgs.70187 [doi] PST - ppublish SO - J Am Geriatr Soc. 2026 Jan;74(1):96-106. doi: 10.1111/jgs.70187. Epub 2025 Oct 24. PMID- 41130867 OWN - NLM STAT- MEDLINE DCOM- 20260104 LR - 20260917 IS - 1879-0828 (Electronic) IS - 0953-6205 (Print) IS - 0953-6205 (Linking) VI - 143 DP - 2026 Jan TI - Contemporary management of advanced chronic kidney disease: An evidence-based review. PG - 106557 LID - S0953-6205(25)00434-0 [pii] LID - 10.1016/j.ejim.2025.106557 [doi] AB - Chronic kidney disease (CKD) is a major contributor to global morbidity and mortality, traditionally managed through renin-angiotensin system (RAS) inhibition and supportive care. Recent therapeutic advances have transformed this landscape, offering targeted interventions that modify disease progression and improve cardiovascular and renal outcomes. This review summarizes emerging treatments across key domains of CKD management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated robust cardiorenal benefits, particularly in patients with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors are now widely used in CKD and heart failure, including among non-diabetic populations. GLP-1 receptor agonists are approved for T2DM and cardiovascular risk reduction, with recent expansion to CKD in T2DM. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), particularly finerenone, provide additional cardiorenal protection with a lower risk of hyperkalemia than traditional steroidal agents. In autosomal dominant polycystic kidney disease (ADPKD), tolvaptan remains the only approved disease-modifying therapy, with clinical trials and real-world data supporting its efficacy across a range of disease stages. Emerging regenerative strategies, including mesenchymal stem cell (MSC) therapy and xenotransplantation using genetically modified pig kidneys, have shown early promise in preclinical models and limited human studies. While further research is needed to optimize patient selection and long-term outcomes, these approaches represent important future directions in nephrology. Together, these developments mark a shift toward mechanism-based, precision therapies in CKD care. Internal medicine clinicians are pivotal in identifying appropriate candidates for these treatments and integrating evolving evidence into practice to improve patient outcomes. CI - Copyright (c) 2025 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Baker, Lyle W AU - Baker LW AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA. FAU - Ovincy, Cene AU - Ovincy C AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA. FAU - Souvalian, Levon AU - Souvalian L AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA; Mayo Clinic Florida PKD Center of Excellence, Jacksonville, FL, USA. FAU - Hickson, LaTonya J AU - Hickson LJ AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA. FAU - Chebib, Fouad T AU - Chebib FT AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA; Mayo Clinic Florida PKD Center of Excellence, Jacksonville, FL, USA. Electronic address: Chebib.fouad@mayo.edu. LA - eng GR - R01 DK142878/DK/NIDDK NIH HHS/United States GR - U54 DK144863/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20251023 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 21G72T1950 (Tolvaptan) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/therapy/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tolvaptan/therapeutic use MH - Polycystic Kidney, Autosomal Dominant/drug therapy PMC - PMC12560998 MID - NIHMS2119074 OTO - NOTNLM OT - ADPKD OT - Autosomal dominant polycystic kidney disease OT - CKD OT - Chronic kidney disease OT - Disease modifying treatment OT - ESKD OT - End stage kidney disease OT - MSC OT - Mesenchymal stem cell OT - Nonsteroidal mineralocorticoid receptor antagonists OT - SGLT2i OT - Sodium-glucose cotransporter-2 inhibitors OT - Vaptans OT - Xenotransplant OT - nsMRAs COIS- Declaration of competing interest The authors declare no relevant conflicts of interest related to the content of this manuscript. Dr. Fouad T. Chebib has received research funding from Otsuka Pharmaceuticals, Natera, Mezzion, Vertex, AbbVie, and Regulus Therapeutics. He serves on the Board of Directors for the PKD Foundation. He also serves on the Advisory Board for Vertex, Otsuka, Hikma and AstraZeneca. Dr. Fouad T. Chebib received research funding from the National Institutes of Health (NIDDK). Dr. LaTonya J. Hickson has received research funding from the National Institutes of Health (NIDDK and NIA) and from Regenerative Medicine Minnesota. She has served as a consultant for ETTA Biotechnology and Resolution Therapeutics. All other authors declare no conflicts of interest. EDAT- 2025/10/24 00:26 MHDA- 2026/01/05 03:53 PMCR- 2026/09/01 CRDT- 2025/10/23 21:58 PHST- 2025/07/02 00:00 [received] PHST- 2025/10/05 00:00 [revised] PHST- 2025/10/14 00:00 [accepted] PHST- 2026/01/05 03:53 [medline] PHST- 2025/10/24 00:26 [pubmed] PHST- 2025/10/23 21:58 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - S0953-6205(25)00434-0 [pii] AID - 10.1016/j.ejim.2025.106557 [doi] PST - ppublish SO - Eur J Intern Med. 2026 Jan;143:106557. doi: 10.1016/j.ejim.2025.106557. Epub 2025 Oct 23. PMID- 41130371 OWN - NLM STAT- MEDLINE DCOM- 20251207 LR - 20260127 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 281 DP - 2026 Jan TI - Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development. PG - 666-673 LID - S0002-9394(25)00558-6 [pii] LID - 10.1016/j.ajo.2025.10.021 [doi] AB - OBJECTIVE: To evaluate the risk of developing age-related cataract among nondiabetic patients who are overweight or obese prescribed glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared to other weight loss drugs (OWLD). DESIGN: Retrospective cohort study using the TriNetX Global Collaborative Network. SUBJECTS: Overweight or obese patients aged 55 years and greater were included. Patients with a diabetes mellitus or prior age-related cataract were excluded. METHODS: Patients in the GLP-1RA group were prescribed either semaglutide or liraglutide. Patients in the OWLD group were lorcaserin, setmelanotide, diethylpropion, sibutramine, fenfluramine, mazindol, phentermine, or orlistat A third cohort included patients not prescribed any weight loss medications. Propensity score matching was performed to minimize baseline differences between cohorts. MAIN OUTCOME MEASURES: The primary outcome was development of age-related cataract at 5-, 7-, and 10-year intervals. Risk ratios with 95% confidence intervals and corresponding P-values were reported. Standardized mean differences (SMDs) were calculated to assess covariate balance. RESULTS: In the primary analysis of GLP-1RA vs OWLD usage, covariate balance was achieved across all matched variables with SMDs < 0.2. In this primary analysis, GLP-1RA use was associated with a decreased risk of age-related cataract at 5 (RR: 0.278; 95% CI: 0.246-0.314; P < .0001), 7 (RR: 0.269; 95% CI: 0.241-0.299; P < .0001), and 10 (RR: 0.198; 95% CI: 0.176-0.222; P < .0001) years compared to OWLD use. GLP-1RA use was also associated with decreased risk at 5 (RR: 0.605; 95% CI: 0.553-0.661; P < .0001), 7 (RR: 0.499; 95% CI: 0.458-0.542; P < .0001), and 10 (RR: 0.437; 95% CI: 0.403-0.475; P < .0001) years compared to no drug use. Conversely, OWLD use was associated with increased risk at 5 (RR: 2.142; 95% CI: 1.957-2.345; P < .0001), 7 (RR: 2.093; 95% CI: 1.931-2.268; P < .0001) and 10 (RR: 2.111; 95% CI: 1.961-2.273; P < .0001) years compared to no drug use. CONCLUSIONS: GLP-1RA use was associated with a significantly reduced risk of age-related cataract compared to OWLD use and no pharmacologic treatment. These findings support the need for randomized prospective trials and mechanistic studies to better understand this observed association. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Ahuja, Abhimanyu S AU - Ahuja AS AD - From the Department of Ophthalmology (A.S.A., B.K.Y.), Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Paredes, Alfredo A 3rd AU - Paredes AA 3rd AD - Charles E. Schmidt College of Medicine (A.A.P.), Florida Atlantic University, Boca Raton, FL, USA. FAU - Ahuja, Sejal A AU - Ahuja SA AD - Windsor University School of Medicine (S.A.A.), Oakbrook, IL, USA. FAU - Young, Benjamin K AU - Young BK AD - From the Department of Ophthalmology (A.S.A., B.K.Y.), Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. Electronic address: youngbe@ohsu.edu. LA - eng PT - Journal Article DEP - 20251021 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - *Cataract/epidemiology/chemically induced/diagnosis MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Overweight/drug therapy/complications MH - Incidence MH - Diabetes Mellitus, Type 2/drug therapy MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/10/24 00:26 MHDA- 2025/12/08 01:37 CRDT- 2025/10/23 19:34 PHST- 2025/06/16 00:00 [received] PHST- 2025/10/16 00:00 [revised] PHST- 2025/10/17 00:00 [accepted] PHST- 2025/12/08 01:37 [medline] PHST- 2025/10/24 00:26 [pubmed] PHST- 2025/10/23 19:34 [entrez] AID - S0002-9394(25)00558-6 [pii] AID - 10.1016/j.ajo.2025.10.021 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Jan;281:666-673. doi: 10.1016/j.ajo.2025.10.021. Epub 2025 Oct 21. PMID- 41129847 OWN - NLM STAT- MEDLINE DCOM- 20251128 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 9 DP - 2025 Sep TI - Effects of GLP-1 agonists on 10-year cardiovascular risk reduction in primary prevention: A 44-week open label prospective study. PG - 103312 LID - S1871-4021(25)00129-8 [pii] LID - 10.1016/j.dsx.2025.103312 [doi] AB - AIMS: Patients with Type 2 diabetes mellitus face elevated cardiovascular risk. We assessed the effect of GLP-1 receptor agonists on 10-year CVR in a primary prevention cohort. METHODS: In this 44-week prospective, non-randomized study, 135 patients with type 2 diabetes mellitus and obesity were included across 13 healthcare centers. The primary endpoint was the change in 10-year cardiovascular risk, estimated using the AHA ASCVD Risk Estimator Plus tool at baseline and week 44. Secondary endpoints included weight loss, HbA1c, fasting plasma glucose, and lipid profiles. Patients received subcutaneous semaglutide, oral semaglutide, dulaglutide, or other GLP-1RAs. RESULTS: In the primary prevention cohort (n = 105), mean 10-year CVR decreased by 3.28 percentage points, a relative reduction of 13.45 % (p < 0.001). Subcutaneous semaglutide showed the greatest weight loss (-8.1 kg), followed by oral semaglutide (-6.5 kg) and dulaglutide (-5.6 kg). HbA1c improved from 8.1 % to 6.6 %, and fasting plasma glucose decreased by 45.8 mg/dL (both p < 0.001). CONCLUSIONS: GLP-1 receptor agonists reduce 10-year cardiovascular risk in primary prevention and improve metabolic control. Findings support early use in high-risk people with type 2 diabetes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT05136287. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Universidade de Santiago de Compostela, Spain. Electronic address: jose.seijas@rai.usc.es. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologia y Salud Publica CIBERESP), Carlos III Health Institute, Madrid, Spain. Electronic address: angel.salgado.barreira@usc.es. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Centro de Salud, Ribeira, A Coruna, Spain. FAU - Perez-Alvarez, Maria Teresa AU - Perez-Alvarez MT AD - Centro de Salud de Culleredo, A Coruna, Spain. FAU - Ponce-Pinon, Belen AU - Ponce-Pinon B AD - Centro de Salud de Fene, A Coruna, Spain. FAU - Fernandez-Silva, Marlen AU - Fernandez-Silva M AD - Centro de Salud O Ventorillo, A Coruna, Spain. FAU - Rodriguez-Barreiro, Marta AU - Rodriguez-Barreiro M AD - Centro de Salud. Virxe Peregrina, Pontevedra, Spain. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Centro de Salud de San Roque, Lugo, Spain. FAU - Iglesias-Moreno, Jose Manuel AU - Iglesias-Moreno JM AD - Centro de Salud de Val Minor, Nigran, Pontevedra, Spain. FAU - Gago-Garcia, Mar AU - Gago-Garcia M AD - Centro de Salud de Ribadeo, Lugo, Spain. FAU - Montans-Garcia, Raquel AU - Montans-Garcia R AD - Centro de Salud de Cee, A Coruna, Spain. FAU - Fernandez-Perez, Agustina AU - Fernandez-Perez A AD - Centro de Salud Vilalba, Lugo, Spain. FAU - Fraga-Gayoso, Dolores AU - Fraga-Gayoso D AD - Centro de Salud de Sarria, Lugo, Spain. FAU - Fernandez-Montenegro, Montse AU - Fernandez-Montenegro M AD - Centro de Salud de O Carballino, Ourense, Spain. FAU - Riveiro-Barciela, Beatriz AU - Riveiro-Barciela B AD - Centro de Salud O Temple, A Coruna, Spain. FAU - Rilla-Villar, Natalia AU - Rilla-Villar N AD - Centro de Salud de Arriondas, Asturias, Spain. FAU - Cardeso-Paredes, Begona AU - Cardeso-Paredes B AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Ribeiro-Ferreiro, Marta AU - Ribeiro-Ferreiro M AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain. FAU - Rodriguez-Penas, Diego AU - Rodriguez-Penas D AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain. FAU - Cordero, Alberto AU - Cordero A AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Department, Hospital IMED Elche, Alicante, Spain; Grupo de Investigacion Cardiovascular (GRINCAVA), Universidad Miguel Hernandez, Elche, Spain. FAU - Rodriguez-Manero, Moises AU - Rodriguez-Manero M AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. CN - SEVERAL INVESTIGATORS LA - eng SI - ClinicalTrials.gov/NCT05136287 PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251019 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Biomarkers/analysis MH - Blood Glucose/analysis MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Follow-Up Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/analysis MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - *Primary Prevention/methods MH - Prognosis MH - Prospective Studies MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular risk OT - GLP-1 receptor agonists OT - Primary prevention OT - Type 2 diabetes OT - Weight loss COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/10/23 18:26 MHDA- 2025/11/29 02:21 CRDT- 2025/10/23 17:59 PHST- 2024/11/19 00:00 [received] PHST- 2025/10/15 00:00 [revised] PHST- 2025/10/18 00:00 [accepted] PHST- 2025/11/29 02:21 [medline] PHST- 2025/10/23 18:26 [pubmed] PHST- 2025/10/23 17:59 [entrez] AID - S1871-4021(25)00129-8 [pii] AID - 10.1016/j.dsx.2025.103312 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Sep;19(9):103312. doi: 10.1016/j.dsx.2025.103312. Epub 2025 Oct 19. PMID- 41129133 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20261024 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 12 DP - 2025 Dec 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration. PG - 999-1003 LID - 10.1001/jamaophthalmol.2025.3821 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown. OBJECTIVE: To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025. EXPOSURES: Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion. MAIN OUTCOMES AND MEASURES: The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching. RESULTS: A total of 91 408 patients were included. After propensity score matching for the primary analysis, 45 704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35 753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35 732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P < .001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P < .001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P < .001). No differences were observed in progression to exudative AMD. CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations. FAU - Ahuja, Abhimanyu S AU - Ahuja AS AD - Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland. FAU - Paredes, Alfredo A 3rd AU - Paredes AA 3rd AD - Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. FAU - Young, Benjamin K AU - Young BK AD - Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Dec 1;143(12):1004-1005. doi: 10.1001/jamaophthalmol.2025.4090. PMID: 41129138 MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use MH - *Macular Degeneration/epidemiology MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Disease Progression MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12550735 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/10/23 12:28 MHDA- 2026/01/06 19:17 PMCR- 2026/10/23 CRDT- 2025/10/23 11:33 PHST- 2026/01/06 19:17 [medline] PHST- 2025/10/23 12:28 [pubmed] PHST- 2025/10/23 11:33 [entrez] PHST- 2026/10/23 00:00 [pmc-release] AID - 2840121 [pii] AID - eoi250061 [pii] AID - 10.1001/jamaophthalmol.2025.3821 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Dec 1;143(12):999-1003. doi: 10.1001/jamaophthalmol.2025.3821. PMID- 41128495 OWN - NLM STAT- MEDLINE DCOM- 20260415 LR - 20260813 IS - 1941-7225 (Electronic) IS - 0895-7061 (Print) IS - 0895-7061 (Linking) VI - 39 IP - 5 DP - 2026 May 1 TI - GLP-1 Receptor Agonists and Blood Pressure: A State-of-the-Art Review of Mechanisms, Evidence, and Clinical Implications. PG - 611-622 LID - 10.1093/ajh/hpaf205 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes and, more recently, for weight management among individuals without diabetes. AIM: This review synthesizes the current evidence on the mechanisms by which GLP-1 RAs affect BP, their clinical effects across populations, and the implications for patient care. We discuss subpopulations who may benefit from their BP-lowering effects, identify limitations in the existing evidence, and explore future directions for research. RESULTS: Beyond their metabolic effects, growing evidence suggests that GLP-1 RAs produce modest reductions in BP, typically 2-5 mm Hg systolic, across diverse populations with diabetes, obesity, or at high cardiovascular risk. These reductions appear to be driven primarily by weight loss, with additional contributions from potential weight-independent mechanisms such as natriuresis, improved endothelial function, and attenuation of vascular inflammation. Although smaller in magnitude than those achieved with traditional antihypertensive drugs, the BP-lowering effects of GLP-1 RAs can translate into meaningful cardiovascular risk reduction at the population level and provide additive BP benefit when used alongside conventional therapies. Among individuals with hypertension, GLP-1 RAs are generally well tolerated, although small increases in heart rate and potential interactions with volume-regulating medications may warrant clinical attention. CONCLUSION: As newer GLP-based therapies continue to emerge, a clearer understanding of their effects on BP may inform more integrated approaches to cardiometabolic care. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. FAU - Moiz, Areesha AU - Moiz A AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, QC, Canada. FAU - Zolotarova, Tetiana AU - Zolotarova T AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, QC, Canada. FAU - Filion, Kristian B AU - Filion KB AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, QC, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. AD - Faculty of Medicine, McGill University, Montreal, QC, Canada. FAU - Eisenberg, Mark J AU - Eisenberg MJ AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, QC, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. AD - Faculty of Medicine, McGill University, Montreal, QC, Canada. AD - Division of Cardiology, Jewish General Hospital/McGill University, Montreal, QC, Canada. LA - eng GR - Fond de recherche du Quebec-Sante/ GR - McGill University/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Am J Hypertens JT - American journal of hypertension JID - 8803676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Antihypertensive Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Pressure/drug effects MH - *Hypertension/drug therapy/physiopathology/diagnosis/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Treatment Outcome MH - *Antihypertensive Agents/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Animals MH - Obesity/drug therapy/physiopathology PMC - PMC13080269 OTO - NOTNLM OT - antihypertensive OT - blood pressure OT - cardiometabolic risk OT - glucagon-like peptide-1 receptor agonists OT - hypertension COIS- The authors have no conflicts of interest to disclose. EDAT- 2025/10/23 12:28 MHDA- 2026/04/15 06:29 PMCR- 2025/10/23 CRDT- 2025/10/23 09:04 PHST- 2025/09/29 00:00 [received] PHST- 2025/10/07 00:00 [revised] PHST- 2025/10/11 00:00 [accepted] PHST- 2026/04/15 06:29 [medline] PHST- 2025/10/23 12:28 [pubmed] PHST- 2025/10/23 09:04 [entrez] PHST- 2025/10/23 00:00 [pmc-release] AID - 8300155 [pii] AID - hpaf205 [pii] AID - 10.1093/ajh/hpaf205 [doi] PST - ppublish SO - Am J Hypertens. 2026 May 1;39(5):611-622. doi: 10.1093/ajh/hpaf205. PMID- 41127972 OWN - NLM STAT- MEDLINE DCOM- 20251125 LR - 20251215 IS - 1365-2036 (Electronic) IS - 0269-2813 (Print) IS - 0269-2813 (Linking) VI - 62 IP - 11-12 DP - 2025 Dec TI - Effects of Resmetirom on Metabolic-Dysfunction Associated Steatohepatitis in Patients With Weight Loss and/or Diabetes Taking Glucagon-Like Peptide-1 Receptor Agonists and Other Diabetes Therapies: A Secondary Analysis of the MAESTRO-NASH Trial. PG - 1089-1099 LID - 10.1111/apt.70382 [doi] AB - BACKGROUND: MAESTRO-NASH, a randomised, double-blind, placebo-controlled, 54-month phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed metabolic-dysfunction associated steatohepatitis (MASH) and liver fibrosis achieved primary endpoints of MASH resolution with no worsening of fibrosis, and >/= 1-stage improvement in fibrosis with no worsening of MASH at 52-weeks. AIMS: The effects of resmetirom (80 or 100 mg) versus placebo were evaluated on Week 52 histological and biomarker endpoints in relation to background treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i), GLP-1 receptor agonists (GLP-1 RA), and/or >/= 5% weight loss at Week 52. METHODS: At baseline, 13%-17% of patients (all with type 2 diabetes mellitus [T2DM]) were on stable GLP-1 RA or SGLT2i therapy. Changes in liver histology, MRI-proton density fat fraction (MRI-PDFF), and liver stiffness were examined after 52 weeks of treatment. RESULTS: No weight loss above baseline occurred with GLP-1 RA or SGLT2i therapy. SGLT2 and GLP-1 RA treated patients showed similar rates of MASH resolution and fibrosis improvement in combination with resmetirom as patients not on these therapies. Resmetirom-treated patients (100 mg) with weight loss (>/= 5%) compared with those with weight loss < 5% had higher rates of MASH resolution (56.6% vs. 33.8%), fibrosis improvement (40.6% vs. 31.5%), MRI-PDFF reduction (-69% vs. -46%), and liver stiffness reduction after 52 weeks of treatment (-4.6 kPa vs. -2.3 kPa). CONCLUSIONS: The efficacy of resmetirom on multiple MASH endpoints was not impacted by background SGLT2i or GLP-1 RA treatment. Weight loss (>/= 5%) enhanced the efficacy of resmetirom. TRIAL REGISTRATION: MAESTRO-NASH ClinicalTrials.gov number, NCT03900429. CI - (c) 2025 Madrigal Pharmaceuticals. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. FAU - Noureddin, Mazen AU - Noureddin M AD - Houston Methodist Hospital, Houston, Texas, USA. AD - Houston Research Institute, Houston, Texas, USA. FAU - Rinella, Mary AU - Rinella M AD - University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA. FAU - Taub, Rebecca AU - Taub R AD - Madrigal Pharmaceuticals, West Conshohocken, Pennsylvania, USA. FAU - Labriola, Dominic AU - Labriola D AD - Madrigal Pharmaceuticals, West Conshohocken, Pennsylvania, USA. FAU - Camacho, Raul C AU - Camacho RC AD - Madrigal Pharmaceuticals, West Conshohocken, Pennsylvania, USA. FAU - Alkhouri, Naim AU - Alkhouri N AUID- ORCID: 0000-0001-9872-2391 AD - Summit Clinical Research, San Antonio, Texas, USA. FAU - Loomba, Rohit AU - Loomba R AUID- ORCID: 0000-0002-4845-9991 AD - MASLD Research Center, University of California at San Diego, La Jolla, California, USA. FAU - Bansal, Meena B AU - Bansal MB AUID- ORCID: 0000-0002-7501-2191 AD - Icahn School of Medicine at Mount Sinai, New York, New York, USA. LA - eng SI - ClinicalTrials.gov/NCT03900429 GR - Madrigal Pharmaceuticals/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20251023 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Fatty Liver/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Liver Cirrhosis/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - *Weight Loss/drug effects PMC - PMC12646629 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MASH resolution OT - fibrosis improvement OT - resmetirom OT - weight loss COIS- M.N. serves on an advisory board/consulting for Akero, Altimmune, Alligos, AstraZeneca, BI, Boston Pharma, Cytodyn, GSK, Lilly, Madrigal, Merck, Novo Nordisk, Sagimet, Terns, and Takeda and as a Principal Investigator for a Drug Study: Allergan, Altimmune, Akero, BI, BMS, Boston Pharma, Conatus, Corcept, Gilead, Galectin, Genfit, GSK, Kowa, Enanta, Madrigal, Lilly, Merck, Novartis, Novo Nordisk, Rivus, Shire, Takeda, Terns, Viking, and Zydus. M.N. is a stockholder of Rivus Pharma and Akero and serves on a speaking bureau for Madrigal. M.R. has served as a scientific consultant in the last 24 months for Akero, 89Bio, Boehringer Ingelheim, Boston Pharmaceuticals, Intercept Pharmaceuticals, Histoindex, Madrigal, NGM Biopharmaceuticals, Novo Nordisk, Eli Lilly, Sagimet Biosciences, Sonic Incytes, Cytodyn, GSK. R.T., D.L., and R.C.C. are employees and stockholders of Madrigal Pharmaceuticals Inc. N.A. has received grant/research support from 89bio, Akero Therapeutics, Arbutus Biopharma, AstraZeneca, BioAge, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, Galectin Therapeutics, Genentech, Gilead Sciences, Hepagene Therapeutics, Intercept Pharmaceuticals, Inventiva Pharma, Ionis Pharmaceuticals, Ipsen, Lilly, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, PharmaIN, Poxel, Regeneron, Viking Therapeutics, and Zydus Pharmaceuticals; reports speaker's fees from AbbVie, AstraZeneca, Echosens, Gilead Sciences, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, and Perspectum; and reports consulting for 89bio, AbbVie, Akero, Boehringer Ingelheim, Echosens, Fibronostics, Gilead Sciences, HistoIndex, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, and Regeneron. R.L. serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics. R.L. has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals, and is co-founder of LipoNexus Inc. M.B.B. has received Grant Support from NIH, CDC/NIOSH, Pfizer, The Kinetix Group, Histoindex, Siemens and has served as a consultant for The Kinetix Group, Madrigal, Pfizer, Fibronostics, NOVO Nordisk, GSK, Boston Pharma, Merck, Boehringer-Ingelheim, CurveBio, and mBIOTA. EDAT- 2025/10/23 06:28 MHDA- 2025/11/25 18:30 PMCR- 2025/11/25 CRDT- 2025/10/23 05:32 PHST- 2025/08/04 00:00 [revised] PHST- 2025/07/18 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2025/11/25 18:30 [medline] PHST- 2025/10/23 06:28 [pubmed] PHST- 2025/10/23 05:32 [entrez] PHST- 2025/11/25 00:00 [pmc-release] AID - APT70382 [pii] AID - 10.1111/apt.70382 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2025 Dec;62(11-12):1089-1099. doi: 10.1111/apt.70382. Epub 2025 Oct 23. PMID- 41127515 OWN - NLM STAT- MEDLINE DCOM- 20251023 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Severe euglycemic ketoacidosis following combined therapy with GLP-1 receptor agonist and SGLT-2 inhibitor, refractory to standard treatment: a case report. PG - 1649270 LID - 10.3389/fendo.2025.1649270 [doi] LID - 1649270 AB - BACKGROUND: Euglycemic diabetic ketoacidosis (euDKA) is a rare but potentially life-threatening complication of diabetes, increasingly linked to SGLT-2 inhibitors (SGLT-2i) and, less frequently, GLP-1 receptor agonists (GLP-1 RA), especially in combination. CASE PRESENTATION: We present the case of a 36-year-old man with newly diagnosed type 2 diabetes who developed severe euDKA within days of starting combined therapy with semaglutide and dapagliflozin. Despite prior patient education and adherence to antidiabetic therapy, persistent vomiting and carbohydrate deficiency-likely related to GLP-1 RA side effects-led to decreased insulin administration and metabolic decompensation. This case was characterized by very early onset after initiation of therapy, absence of infection or other common triggers, and resistance to standard treatment with insulin, glucose, and fluid resuscitation. Intensive care with continuous veno-venous hemodiafiltration was required, resulting in full recovery. CONCLUSION: This case emphasizes the potential severity of euDKA induced by GLP-1 RA and SGLT-2i combination therapy and highlights the risk of treatment resistance. The decision to initiate SGLT2i and GLP-1RA concurrently should be individualized or possibly spread apart in time, weighing the potential therapeutic benefits against the risk of rare but severe complication such as euDKA. Comprehensive education on ketone monitoring and insulin administration during intercurrent illness are essential to prevent this rare but serious complication. CI - Copyright (c) 2025 Gandecka-Pempera, Naskret, Adamska and Zozulinska-Ziolkiewicz. FAU - Gandecka-Pempera, Agnieszka AU - Gandecka-Pempera A AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Naskret, Dariusz AU - Naskret D AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Adamska, Anna AU - Adamska A AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Zozulinska-Ziolkiewicz, Dorota AU - Zozulinska-Ziolkiewicz D AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Case Reports PT - Journal Article DEP - 20251007 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucosides) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Humans MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage MH - Adult MH - *Diabetic Ketoacidosis/chemically induced/pathology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Benzhydryl Compounds/adverse effects/administration & dosage MH - Drug Therapy, Combination/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Glucosides/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12537370 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT-2 inhibitor OT - adverse drug reaction OT - euglycemic diabetic ketoacidosis (euDKA) OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/23 11:46 MHDA- 2025/10/23 12:29 PMCR- 2025/10/07 CRDT- 2025/10/23 04:55 PHST- 2025/06/18 00:00 [received] PHST- 2025/09/22 00:00 [accepted] PHST- 2025/10/23 12:29 [medline] PHST- 2025/10/23 11:46 [pubmed] PHST- 2025/10/23 04:55 [entrez] PHST- 2025/10/07 00:00 [pmc-release] AID - 10.3389/fendo.2025.1649270 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Oct 7;16:1649270. doi: 10.3389/fendo.2025.1649270. eCollection 2025. PMID- 41126551 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260925 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Psychiatric effects of GLP-1 receptor agonists: A systematic review of emerging evidence. PG - 50-59 LID - 10.1111/dom.70198 [doi] AB - This systematic review examines the current literature on glucagon-like peptide-1 receptor agonists (GLP-1RAs)-associated psychiatric manifestations, including depression, suicidality, eating disorders, substance use disorders (SUD) and schizophrenia spectrum disorders. A comprehensive literature search was conducted to identify studies evaluating the association between GLP-1RAs and psychiatric outcomes. The electronic databases systematically searched were PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase and Web of Science. GLP-1RAs are increasingly recognised for their potential neuropsychiatric effects beyond glycaemic control and weight loss. Findings suggest modest antidepressant effects, inconsistent associations with suicidality and potential therapeutic benefit in disorders of reward regulation. These findings are constrained by limited sample diversity, variability in outcome measures and the consistent underrepresentation of individuals with psychiatric comorbidities, factors that warrant targeted future research. This review highlights key findings on the neuropsychiatric effects of GLP-1RAs. The heterogeneity among the studies in terms of dosing, clinical indications and baseline psychiatric status complicates interpretation, but preliminary evidence suggests modest antidepressant effects and potential therapeutic roles in eating and SUD. Concerns regarding suicidality remain unresolved. In schizophrenia, GLP-1RAs provide clear metabolic benefits but have not demonstrated consistent effects on psychiatric symptomatology. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Sa, Brianna AU - Sa B AUID- ORCID: 0009-0006-5229-185X AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Maristany, Anthony AU - Maristany A AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Subramaniam, Ashwin AU - Subramaniam A AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Guillen, Ryan AU - Guillen R AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Buonocore, Brooke AU - Buonocore B AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Smith, Audrey AU - Smith A AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Oldak, Sean E AU - Oldak SE AD - Department of Psychiatry, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. FAU - Padilla, Vanessa AU - Padilla V AD - Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20251022 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Mental Disorders/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Schizophrenia/chemically induced MH - Feeding and Eating Disorders/chemically induced/psychology MH - Depression/chemically induced MH - Suicide/psychology MH - Substance-Related Disorders PMC - PMC12673456 OTO - NOTNLM OT - GLP-1 OT - systematic review OT - type 2 diabetes OT - weight control COIS- All authors state no conflicts of interest. EDAT- 2025/10/23 06:28 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/23 02:02 PHST- 2025/10/05 00:00 [revised] PHST- 2025/06/21 00:00 [received] PHST- 2025/10/05 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/23 06:28 [pubmed] PHST- 2025/10/23 02:02 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70198 [pii] AID - 10.1111/dom.70198 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):50-59. doi: 10.1111/dom.70198. Epub 2025 Oct 22. PMID- 41125326 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260819 IS - 2047-9956 (Print) IS - 2047-9956 (Linking) VI - 33 IP - 5 DP - 2026 Aug 19 TI - Hypoglycaemic coma induced by a falsified semaglutide product: a case report. PG - 486-489 LID - 10.1136/ejhpharm-2025-004656 [doi] AB - Semaglutide (Ozempic, Rybelsus, Wegovy) is a GLP-1 receptor agonist used for the treatment of type 2 diabetes and, more recently, weight management. Due to its efficacy in weight loss, semaglutide has gained worldwide popularity, particularly the branded version Ozempic, resulting in off-label use by people seeking rapid weight loss. The resulting high demand has led to an increase in falsified products sold by unregulated online marketplaces. We present a case of a 31-year-old woman who was admitted to the emergency room in a hypoglycaemic coma after self-administrating semaglutide (Ozempic) obtained from a website. Toxicological analysis showed that the vial contained insulin instead of semaglutide, therefore leading to severe hypoglycaemia. This case highlights the growing concern regarding falsified medicines sold in the online drug market and the associated risk of severe adverse events. We reported the case to the Italian Medicines Agency (AIFA) and local authorities. We propose regulatory measures to mitigate similar incidents in the future. CI - (c) European Association of Hospital Pharmacists 2026. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Antonacci, Giulia AU - Antonacci G AUID- ORCID: 0009-0007-6968-6337 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Bortignon, Erika AU - Bortignon E AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Bolognesi, Massimo AU - Bolognesi M AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Piano, Salvatore Silvio AU - Piano SS AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Cadore, Alessandro AU - Cadore A AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Camuffo, Laura AU - Camuffo L AUID- ORCID: 0009-0001-8710-486X AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Venturini, Francesca AU - Venturini F AUID- ORCID: 0000-0003-0396-4377 AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Faoro, Sonia AU - Faoro S AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Favretto, Donata AU - Favretto D AD - Forensic Toxicologist, Universita degli Studi di Padova, Padua, Italy. FAU - Romano, Antonietta AU - Romano A AD - Department of Medicine, University of Padova, Padua, Italy antonietta.romano@aopd.veneto.it. FAU - Mengato, Daniele AU - Mengato D AUID- ORCID: 0000-0003-1374-1505 AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20260819 PL - England TA - Eur J Hosp Pharm JT - European journal of hospital pharmacy : science and practice JID - 101578294 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Adult MH - *Hypoglycemia/chemically induced/diagnosis MH - Diabetes Mellitus, Type 2/drug therapy MH - *Coma/chemically induced/diagnosis OTO - NOTNLM OT - Diabetes Mellitus OT - Drug Monitoring OT - Metabolic Side Effects of Drugs and Substances OT - PHARMACISTS OT - PUBLIC HEALTH COIS- Competing interests: None declared. EDAT- 2025/10/23 00:26 MHDA- 2026/08/19 23:42 CRDT- 2025/10/22 21:03 PHST- 2025/07/10 00:00 [received] PHST- 2025/10/13 00:00 [accepted] PHST- 2026/08/19 23:42 [medline] PHST- 2025/10/23 00:26 [pubmed] PHST- 2025/10/22 21:03 [entrez] AID - ejhpharm-2025-004656 [pii] AID - 10.1136/ejhpharm-2025-004656 [doi] PST - epublish SO - Eur J Hosp Pharm. 2026 Aug 19;33(5):486-489. doi: 10.1136/ejhpharm-2025-004656. PMID- 41123870 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20261009 IS - 1179-1942 (Electronic) IS - 0114-5916 (Linking) VI - 49 IP - 4 DP - 2026 Apr TI - Incretin-Based Drugs and the Risk of Dementia Among Patients with Type 2 Diabetes. PG - 419-434 LID - 10.1007/s40264-025-01623-9 [doi] AB - BACKGROUND: Incretin-based drugs, namely glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may have neuroprotective effects. Thus, we assessed whether these drugs are associated with a decreased risk of dementia among patients with type 2 diabetes. METHODS: Using the Clinical Practice Research Datalink from the UK, we formed two new user cohorts of patients at least 50 years of age with type 2 diabetes starting incretin-based drugs or sulfonylureas between 2007 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were estimated separately for GLP-1 RAs and DPP-4 inhibitors using Cox proportional hazards models with propensity score fine-stratification weighting and inverse probability of censoring weights. RESULTS: Among 275,144 initiators of DPP-4 inhibitors or sulfonylureas, followed for 750,846 person-years, DPP-4 inhibitors were associated with a reduced dementia risk compared with sulfonylureas (4.4 vs. 5.7 events per 1000 person-years; HR 0.77, 95% CI 0.71-0.85). HRs decreased with increasing cumulative duration of use and dose. Similar associations were observed across dementia subtypes and individual DPP-4 inhibitors molecules. Among 181,215 initiators of GLP-1 RAs or sulfonylureas, followed for 530,415 person-years, GLP-1 RAs were associated with a similar reduction in dementia risk compared with sulfonylureas, although with high uncertainty (2.3 vs. 3.1 events per 1000 person-years; HR 0.74, 95% CI 0.46-1.18). The magnitude of the association increased with cumulative duration of use and dose but with high uncertainty. CONCLUSIONS: In this population-based study, DPP-4 inhibitors, and possibly GLP-1 RAs, were associated with a reduced dementia risk compared with sulfonylureas. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Wang, Yun-Han AU - Wang YH AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. FAU - Johnson, Kyle AU - Johnson K AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. FAU - Beradid, Sarah AU - Beradid S AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. FAU - Yin, Hui AU - Yin H AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. FAU - Yu, Oriana H Y AU - Yu OHY AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, Canada. FAU - Suissa, Samy AU - Suissa S AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. AD - Department of Medicine, McGill University, Montreal, Canada. FAU - Azoulay, Laurent AU - Azoulay L AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada. FAU - Renoux, Christel AU - Renoux C AUID- ORCID: 0000-0002-4691-9579 AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. christel.renoux@mcgill.ca. AD - Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine H 416.1, Montreal, QC, H3T 1E2, Canada. christel.renoux@mcgill.ca. AD - Department of Medicine, McGill University, Montreal, Canada. christel.renoux@mcgill.ca. AD - Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. christel.renoux@mcgill.ca. LA - eng GR - PJT-180357/CAPMC/CIHR/Canada GR - PJT-180357/CAPMC/CIHR/Canada PT - Journal Article DEP - 20251022 PL - New Zealand TA - Drug Saf JT - Drug safety JID - 9002928 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (Sulfonylurea Compounds) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Dementia/epidemiology/prevention & control MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage MH - *Incretins/therapeutic use/administration & dosage MH - Female MH - Aged MH - Middle Aged MH - Sulfonylurea Compounds/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies MH - United Kingdom/epidemiology COIS- Declarations. Conflict of Interest: SS attended scientific advisory committee meetings for Atara, Bristol-Myers-Squibb, Merck, Novartis, Pfizer and Seqirus, and received speaking fees from Boehringer-Ingelheim and Novartis. LA served as a consultant for Roche and Pfizer for work unrelated to this study. LA is an Editorial Board member of Drug Safety. LA was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. The other authors have no conflicts of interest to declare. Data Availability: This study is based in part on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Because electronic health records are classified as "sensitive data" by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval through the individual constituent entities controlling access to the data. Specifically, the primary-care data can be requested via application to the Clinical Practice Research Datalink ( https://www.cprd.com ). Ethics Approval: The study protocol was approved by the CPRD Research Data Governance (No. 22_001853) and the Research Ethics Board of the Jewish General Hospital, Montreal, Canada. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Codes may be made privately available upon reasonable request to the corresponding author. Author Contributions: YHW, LA, and CR conceived and designed the study and were involved in the analysis and interpretation of the results. All authors contributed to the study design, analysis, and interpretation of the results. Analyses were performed by YHW and SB. The first draft of the manuscript was written by YHW, with editing by KJ and CR. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. CR and LA obtained funding and CR supervised the study. EDAT- 2025/10/22 12:30 MHDA- 2026/03/19 21:44 CRDT- 2025/10/22 11:25 PHST- 2025/05/26 00:00 [received] PHST- 2025/09/24 00:00 [accepted] PHST- 2026/03/19 21:44 [medline] PHST- 2025/10/22 12:30 [pubmed] PHST- 2025/10/22 11:25 [entrez] AID - 10.1007/s40264-025-01623-9 [pii] AID - 10.1007/s40264-025-01623-9 [doi] PST - ppublish SO - Drug Saf. 2026 Apr;49(4):419-434. doi: 10.1007/s40264-025-01623-9. Epub 2025 Oct 22. PMID- 41122783 OWN - NLM STAT- MEDLINE DCOM- 20251211 LR - 20251230 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 10 DP - 2025 Oct TI - Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD. PG - 1787-1798 LID - 10.1080/03007995.2025.2577762 [doi] AB - OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as glucose-lowering therapies for people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited comparing cardiovascular (CV) outcomes between once-weekly (OW) GLP-1 RAs vs other non-insulin glucose lowering therapies (ONIGLTs) including SGLT2is. This study aimed to compare CV outcomes among Medicare Advantage (MA) beneficiaries with T2D and ASCVD initiating OW GLP-1 RAs or ONIGLTs. METHODS: This observational cohort study included MA beneficiaries with T2D and ASCVD within Optum's de-identified Clinformatics Data Mart Database (01/2007-03/2024). Propensity score matching was used to compare adults initiating OW GLP-1 RAs or ONIGLTs. Incidence rates and time to the first event of ischemic stroke (IS), myocardial infarction (MI), 2-, 3-, and 5-point major adverse cardiovascular event (MACE) during follow-up were assessed. Individual OW GLP-1 RAs were compared with SGLT2is. RESULTS: Post-matching, 41,835 adults were treated with OW GLP-1 RAs and 77,599 with ONIGLTs. Compared with ONIGLTs, OW GLP-1 RAs had 18% lower risk for IS, 14% lower for MI, 17% lower for 2-point MACE, 28% lower for 3-point MACE, and 27% lower for 5-point MACE. Compared with SGLT2is, OW GLP-1 RAs had 14% lower risk of 2-point MACE, 15% lower risk of 3-point MACE, and 14% lower risk of 5-point MACE. Semaglutide had lower risk of all CV outcomes vs SGLT2is. CONCLUSION: Among MA beneficiaries with T2D and ASCVD, risk of CV outcomes was lower with OW GLP-1 RAs, particularly semaglutide, vs ONIGLTs including SGLT2is. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, Connecticut, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20251106 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology/blood MH - Female MH - Male MH - Aged MH - United States/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Medicare Part C/statistics & numerical data MH - *Atherosclerosis/drug therapy/epidemiology MH - Aged, 80 and over MH - Cardiovascular Diseases/epidemiology MH - Treatment Outcome OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Medicare Advantage OT - atherosclerotic cardiovascular disease OT - major adverse cardiovascular events OT - semaglutide OT - sodium-glucose co-transporter-2 inhibitors OT - type 2 diabetes EDAT- 2025/10/22 06:33 MHDA- 2025/12/11 07:42 CRDT- 2025/10/22 04:24 PHST- 2025/12/11 07:42 [medline] PHST- 2025/10/22 06:33 [pubmed] PHST- 2025/10/22 04:24 [entrez] AID - 10.1080/03007995.2025.2577762 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Oct;41(10):1787-1798. doi: 10.1080/03007995.2025.2577762. Epub 2025 Nov 6. PMID- 41122011 OWN - NLM STAT- MEDLINE DCOM- 20260108 LR - 20260108 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 64 IP - 1 DP - 2026 Jan TI - Association between incretin-related drugs and fractures in patients treated with pioglitazone: A pharmacovigilance study using the FDA Adverse Event Reporting System. PG - 1-8 LID - 10.5414/CP204789 [doi] AB - OBJECTIVE: Diabetes mellitus (DM) causes various long-term complications and has, e.g., a direct negative effect on bone metabolism. Pioglitazone, which is used to treat DM, increases the risk of fractures. Reduced bone metabolism in patients with DM substantially impairs their quality of life. Therefore, this study aimed to determine the association of fractures with incretin-related drugs, dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients treated with pioglitazone using a pharmacovigilance database. MATERIALS AND METHODS: Data from the U.S. Food and Drug Administration Adverse Event Reporting System from the first quarter of 2013 to the end of 2019 were analyzed. The reporting odds ratio and information component values were used to evaluate the positive and inverse associations between the abovementioned drugs and fractures. RESULTS: Inverse associations were observed between incretin-related drugs and fractures in patients treated with DPP-4Is (sitagliptin) and GLP-1RAs (dulaglutide, exenatide, and liraglutide). A subgroup analysis revealed inverse associations between fractures and GLP-1RAs (exenatide and liraglutide) in patients treated with pioglitazone. CONCLUSION: Our results suggest that incretin-related drugs, especially GLP-1RAs, reduce the risk of fractures in patients treated with diabetes medications such as pioglitazone. FAU - Ohyama, Katsuhiro AU - Ohyama K FAU - Abe, Nonoka AU - Abe N FAU - Okamoto, Takumi AU - Okamoto T FAU - Hori, Yusuke AU - Hori Y LA - eng PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Fractures, Bone/chemically induced/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - Incretins/pharmacology MH - Pharmacovigilance MH - *Pioglitazone/adverse effects MH - Adverse Drug Reaction Reporting Systems EDAT- 2025/10/22 06:32 MHDA- 2026/01/02 06:29 CRDT- 2025/10/22 03:33 PHST- 2025/12/17 00:00 [accepted] PHST- 2026/01/02 06:29 [medline] PHST- 2025/10/22 06:32 [pubmed] PHST- 2025/10/22 03:33 [entrez] AID - 192456 [pii] AID - 10.5414/CP204789 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2026 Jan;64(1):1-8. doi: 10.5414/CP204789. PMID- 41118557 OWN - NLM STAT- MEDLINE DCOM- 20251021 LR - 20251024 IS - 2474-7661 (Electronic) IS - 2474-7661 (Linking) VI - 9 IP - 10 DP - 2025 Oct 1 TI - Effect of Glucagon-like Peptide-1 Receptor Agonists on Outcomes After Hip Hemiarthroplasty for Femoral Neck Fractures in Patients With Type 2 Diabetes. LID - e25.00312 AB - The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes mellitus (T2DM) has increased substantially over the past several years. The purpose of this study was to determine whether GLP-1RA use affects outcomes after hip hemiarthroplasty (HA) for femoral neck fractures (FNFs). A retrospective cross-sectional analysis of a local hospital system database was conducted between 2016 and 2023 to identify patients with T2DM aged at least 18 years who underwent HA for FNFs and were on a GLP-1RA at the time of injury. A 1:1 random patient sample of those who underwent HA and were not on a GLP-IRA was used as a control. Patient characteristics and Elixhauser comorbidity index were recorded. Outcomes included hospital length of stay, aspiration pneumonitis during index hospitalization, inpatient readmissions and emergency department encounters within 365 days, medical complications, surgical site infection, implant complications, revision hip surgery, and in-hospital mortality/discharge to hospice within 30, 90, and 365 days. Binary logistic regression was done to assess the 30-day risk of medical and the 365-day risk of implant postoperative outcomes. Four hundred ninety-nine patients (GLP-1RA, N = 248; No GLP-1RA, N = 251), with T2DM, who underwent HA for FNF were included for analysis. GLP-1RA use was not markedly associated with medical complications within 30, 90, or 365 days; implant complications or revision surgery within 365 days; in-hospital mortality/discharge to hospice within 30 or 90 days; postoperative aspiration; length of stay; or inpatient readmissions or emergency department encounters. GLP-IRA use was associated with a decreased risk of in-hospital mortality/discharge to hospice within 365 days. When controlling for confounding variables, the use of GLP-IRA was not associated with any adverse outcome measured in the study (P > 0.05). GLP-1RA use in T2DM patients undergoing HA for FNF is not associated with an increased risk of early postoperative medical and surgical complications. CI - Copyright (c) 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons. FAU - Box, McKenna W AU - Box MW AUID- ORCID: 0000-0002-5037-9544 AD - From the Department of Orthopaedic Surgery, Medical City Denton, Denton, TX (Dr. Box, Dr. Puga, Dr. Werthmann, and Dr. Riehl), and the Physician Services Group, Graduate Medical Education, HCA Healthcare, Brentwood, TN (Ms. Liu). FAU - Puga, Troy B AU - Puga TB FAU - Werthmann, Neil J AU - Werthmann NJ FAU - Liu, Yingxian AU - Liu Y FAU - Riehl, John T AU - Riehl JT AUID- ORCID: 0000-0003-4527-1747 LA - eng GR - HCA Healthcare/ PT - Journal Article DEP - 20251017 PL - United States TA - J Am Acad Orthop Surg Glob Res Rev JT - Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews JID - 101724868 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Femoral Neck Fractures/surgery/complications MH - Female MH - Male MH - Aged MH - Retrospective Studies MH - *Hemiarthroplasty/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cross-Sectional Studies MH - Postoperative Complications/epidemiology MH - Aged, 80 and over MH - Middle Aged MH - Length of Stay/statistics & numerical data MH - Treatment Outcome MH - *Arthroplasty, Replacement, Hip PMC - PMC12543238 EDAT- 2025/10/21 18:29 MHDA- 2025/10/21 18:30 PMCR- 2025/10/17 CRDT- 2025/10/21 15:22 PHST- 2025/08/23 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/10/21 18:30 [medline] PHST- 2025/10/21 18:29 [pubmed] PHST- 2025/10/21 15:22 [entrez] PHST- 2025/10/17 00:00 [pmc-release] AID - 01979360-202510000-00014 [pii] AID - JAAOSGlobal-D-25-00312 [pii] AID - 10.5435/JAAOSGlobal-D-25-00312 [doi] PST - epublish SO - J Am Acad Orthop Surg Glob Res Rev. 2025 Oct 17;9(10):e25.00312. doi: 10.5435/JAAOSGlobal-D-25-00312. eCollection 2025 Oct 1. PMID- 41117973 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20260701 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 69 IP - 1 DP - 2026 Jan TI - Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies. PG - 36-49 LID - 10.1007/s00125-025-06565-6 [doi] AB - AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiorenal risk in type 2 diabetes. However, the effect of combining these drugs remains uncertain. This systematic review aimed to evaluate the potential effectiveness and safety of combination therapy compared with monotherapy in individuals with type 2 diabetes. METHOD: We systematically searched PubMed and Embase from inception to 1 May 2025 for cohort studies comparing the effect of combination therapy with SGLT2 inhibitor or GLP-1 RA monotherapy on (cardiovascular) mortality and cardiovascular or kidney endpoints in individuals with type 2 diabetes. Studies enrolling individuals with type 1 diabetes or a maximum follow-up of less than 1 year were excluded. The primary outcome was a composite of major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalisation for heart failure, a kidney composite endpoint and serious adverse events. Risk of bias was assessed with ROBINS-I. Risk ratios (RRs) and 95% CIs were pooled in random effects meta-analyses. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 18 cohort studies (1,164,774 participants). In cohort studies, combination therapy was associated with a lower risk of MACE (RR 0.56 [95% CI 0.43, 0.71]; low certainty of evidence) and the kidney composite endpoint (RR 0.48 [95% CI 0.32, 0.73]; very low certainty of evidence) relative to SGLT2 inhibitor or GLP-1 RA monotherapy. Combination therapy was also associated with a lower risk of all-cause mortality (RR 0.50 [95% CI 0.40, 0.63]; low certainty of evidence), cardiovascular mortality (RR 0.26 [95% CI 0.16, 0.43]; low certainty of evidence) and hospitalisation for heart failure (RR 0.67 [95% CI 0.64, 0.71]; moderate certainty of evidence). Although safety data could not be pooled due to lack of events, no differences were observed in the risk of severe hypoglycaemia, diabetic ketoacidosis, genitourinary infections and gastrointestinal side effects. No data were reported on the risk of serious adverse events or major adverse limb events. CONCLUSIONS/INTERPRETATION: Observational studies suggest that combining an SGLT2 inhibitor and a GLP-1 RA in type 2 diabetes may lower the risk of MACE, all-cause and cardiovascular mortality, hospitalisation for heart failure and kidney composite endpoints compared with monotherapy with either drug. Of course, residual confounding cannot be overcome but results support the need for future randomised trials of combined vs monotherapy. REGISTRATION: PROSPERO registration no. CRD42024532383. CI - (c) 2025. The Author(s). FAU - Colombijn, Julia M T AU - Colombijn JMT AUID- ORCID: 0000-0002-9022-5937 AD - Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands. AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. FAU - de Leijer, Jan F AU - de Leijer JF AUID- ORCID: 0000-0003-4254-8923 AD - Department of Vascular Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands. FAU - Visseren, Frank L J AU - Visseren FLJ AUID- ORCID: 0000-0003-3951-5223 AD - Department of Vascular Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands. FAU - Verhaar, Marianne C AU - Verhaar MC AUID- ORCID: 0000-0002-3276-6428 AD - Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands. FAU - van Raalte, Daniel H AU - van Raalte DH AUID- ORCID: 0000-0003-2894-6124 AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Vernooij, Robin W M AU - Vernooij RWM AUID- ORCID: 0000-0001-5734-4566 AD - Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands. AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. FAU - van Sloten, Thomas T AU - van Sloten TT AUID- ORCID: 0000-0003-2870-482X AD - Department of Vascular Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands. t.t.vansloten@umcutrecht.nl. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251021 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - Cardiovascular Diseases MH - Cohort Studies PMC - PMC12686040 OTO - NOTNLM OT - Cardiovascular disease OT - Combination therapy OT - GLP-1 RA OT - Heart failure OT - Kidney failure OT - Meta-analysis OT - Mortality OT - SGLT2 inhibitor OT - Systematic review OT - Type 2 diabetes COIS- Data availability: The dataset is available in the ESM Dataset file. Code availability: Code/syntax is available in the ESM Syntax file. Funding: JC, MV and RV are supported by grant 2020B008 RECONNEXT from the Dutch CardioVascular Alliance, an initiative supported by the Dutch Heart Foundation. Authors' relationships and activities: DvR reports receiving personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and MSD, outside this manuscript. NS reported receiving personal fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novartis, Novo Nordisk, Pfizer and Roche, and research grants from AstraZeneca, Boehringer Ingelheim, Novartis and Roche, outside this manuscript. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: JC, JdL, RV and TvS designed the study. JC and JdL acquired the data. JC performed the data analysis and drafted the manuscript. JC and JdL drafted the tables, figures and graphical abstract. All authors contributed to the interpretation of the data, critically revised the manuscript, provided intellectual input and approved the final version to be published. JC and TvS are responsible for the integrity of the work as a whole. EDAT- 2025/10/21 12:36 MHDA- 2025/12/08 13:19 PMCR- 2025/10/21 CRDT- 2025/10/21 11:15 PHST- 2025/03/09 00:00 [received] PHST- 2025/07/21 00:00 [accepted] PHST- 2025/12/08 13:19 [medline] PHST- 2025/10/21 12:36 [pubmed] PHST- 2025/10/21 11:15 [entrez] PHST- 2025/10/21 00:00 [pmc-release] AID - 10.1007/s00125-025-06565-6 [pii] AID - 6565 [pii] AID - 10.1007/s00125-025-06565-6 [doi] PST - ppublish SO - Diabetologia. 2026 Jan;69(1):36-49. doi: 10.1007/s00125-025-06565-6. Epub 2025 Oct 21. PMID- 41117588 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20261005 IS - 1897-9483 (Electronic) IS - 0032-3772 (Linking) VI - 135 IP - 12 DP - 2025 Dec 18 TI - Assessment of noninferiority of oral vs subcutaneous semaglutide: a systematic review and meta-analysis. LID - 17141 [pii] LID - 10.20452/pamw.17141 [doi] AB - INTRODUCTION: This systematic review and meta‑analysis is the first to comprehensively compare oral and subcutaneous semaglutide for type 2 diabetes (T2D) management. OBJECTIVES: Our aim was to determine whether oral semaglutide is noninferior to the subcutaneous preparation, assess potential superiority, and provide evidence‑based guidance for clinical decisions. PATIENTS AND METHODS: We searched clinical trial registries and bibliographic databases through April 30, 2025. Twelve randomized controlled trials involving 6253 adults with T2D were analyzed. Following the PRISMA and Cochrane guidelines (PROSPERO, CRD420251017953), the data were extracted on efficacy, safety, and clinical outcomes. Noninferiority was assessed using predefined margins, and post hoc superiority analyses examined secondary end points. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Both formulations of semaglutide significantly reduced the level of glycated hemoglobin (HbA1c), that is, oral by 1.16 percentage points (95% CI, -1.22 to -1.09) and subcutaneous by 1.4 percentage points (95% CI, -1.47 to -1.33). Oral semaglutide met the noninferiority margin at 50% of the subcutaneous effect. Subcutaneous semaglutide was superior for weight loss (2.19 kg; 95% CI, -3.57 to -0.81; P <0.002), body mass index (BMI) reduction (0.88 kg/m2; 95% CI, -1.55 to -0.21; P <0.011), and triglyceride level lowering (0.09 mmol/l; 95% CI, -0.14 to -0.04; P <0.001). CONCLUSIONS: Both forms of semaglutide effectively improve glycemic control in T2D. Oral semaglutide is noninferior to subcutanous semaglutide in lowering HbA1c level, while subcutaneous semaglutide is superior in weight, BMI, and triglyceride reduction. Given similar safety profiles and modest differences in other outcomes, treatment selection should be guided by clinical goals and patient preferences. FAU - Drygalski, Krzysztof AU - Drygalski K AUID- ORCID: 0000-0003-0645-7020 AD - Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland. FAU - Pastuszak, Krzysztof AU - Pastuszak K AD - Department of Algorithms and System Modeling, Gdansk University of Technology, Gdansk, Poland. AD - Department of Translational Oncology, Medical University of Gdansk, Gdansk, Poland. AD - Centre of Biostatistics and Bioinformatics Analysis, Medical University of Gdansk, Gdansk, Poland. FAU - Modzelewska, Beata AU - Modzelewska B AD - Department of Biophysics, Medical University of Bialystok, Bialystok, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251021 PL - Poland TA - Pol Arch Intern Med JT - Polish archives of internal medicine JID - 101700960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Injections, Subcutaneous MH - Glycated Hemoglobin/analysis MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/10/21 12:35 MHDA- 2025/12/18 07:20 CRDT- 2025/10/21 09:31 PHST- 2025/12/18 07:20 [medline] PHST- 2025/10/21 12:35 [pubmed] PHST- 2025/10/21 09:31 [entrez] AID - 17141 [pii] AID - 10.20452/pamw.17141 [doi] PST - ppublish SO - Pol Arch Intern Med. 2025 Dec 18;135(12):17141. doi: 10.20452/pamw.17141. Epub 2025 Oct 21. PMID- 41117521 OWN - NLM STAT- MEDLINE DCOM- 20260330 LR - 20260813 IS - 2641-7650 (Electronic) IS - 2641-7650 (Linking) VI - 7 IP - 3 DP - 2026 Mar 1 TI - Sodium-Glucose Cotransporter 2 Inhibitors Prevent Nephrolithiasis in Patients with Diabetes: A TriNetX-Based Real-World Global Comparison. PG - 633-641 LID - 10.34067/KID.0000000981 [doi] AB - KEY POINTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) were associated with lower nephrolithiasis risk compared with dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 receptor agonist in patients with diabetes. Risk reduction with SGLT2i was consistent across age, glycemic control, body mass index, and renal function subgroups. Findings support potential use of SGLT2i as a preventive strategy for kidney stones in high-risk diabetic populations. BACKGROUND: Nephrolithiasis (NL) is a prevalent condition associated with diabetes mellitus (DM) and obesity, yet effective pharmacologic preventive options remain limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), primarily used to manage type 2 DM, have shown potential lithoprotective effects. METHODS: This retrospective multinational cohort study used electronic health records from the TriNetX database. Adults with DM initiating SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4is), or glucagon-like peptide-1 receptor agonists (GLP-1RAs) were included. Propensity score matching was conducted to balance baseline covariates, yielding 358,096 matched pairs (SGLT2i versus DPP4i) and 371,374 pairs (SGLT2i versus GLP-1RA). The primary outcome was incidence of NL. RESULTS: SGLT2i use was associated with a significantly lower risk of NL compared with DPP4i (1.5% versus 1.9%; hazard ratio, 0.825; 95% confidence interval, 0.795 to 0.855; P < 0.001) and GLP-1RA (1.6% versus 2.0%; hazard ratio, 0.812; 95% confidence interval, 0.784 to 0.840; P < 0.001). Subgroup analyses showed consistent protective effects across age, hemoglobin A1c, body mass index, and renal function strata, although the association was slightly attenuated in older adults, those with suboptimal glycemic control, or impaired renal function. CONCLUSIONS: SGLT2is may reduce the risk of NL among patients with DM. Possible mechanisms include increased urinary citrate excretion, urinary alkalinization, and anti-inflammatory effects. These findings suggest that SGLT2i may reduce the risk of incident NL in diabetic populations, particularly those with additional metabolic risk factors for NL. CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology. FAU - Liu, Chia-Min AU - Liu CM AUID- ORCID: 0000-0002-1722-3564 AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Department of Urology, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan. FAU - Tsai, Daniel Hsiang-Te AU - Tsai DH AUID- ORCID: 0000-0003-2841-0338 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Tung, Hsiu-Ting AU - Tung HT AUID- ORCID: 0009-0006-7668-9256 AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lu, Ze-Hong AU - Lu ZH AUID- ORCID: 0000-0002-3605-2369 AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AUID- ORCID: 0000-0002-5852-7652 AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Liu, Chan-Jung AU - Liu CJ AUID- ORCID: 0000-0002-3929-286 AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Department of Urology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20251020 PL - United States TA - Kidney360 JT - Kidney360 JID - 101766381 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Nephrolithiasis/prevention & control/epidemiology/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult PMC - PMC13065125 OTO - NOTNLM OT - SGLT2 inhibitors OT - kidney stones COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/B331. EDAT- 2025/10/21 12:35 MHDA- 2026/03/30 12:50 PMCR- 2025/10/20 CRDT- 2025/10/21 09:03 PHST- 2025/06/28 00:00 [received] PHST- 2025/09/30 00:00 [accepted] PHST- 2026/03/30 12:50 [medline] PHST- 2025/10/21 12:35 [pubmed] PHST- 2025/10/21 09:03 [entrez] PHST- 2025/10/20 00:00 [pmc-release] AID - 02200512-990000000-00776 [pii] AID - K360-2025-000714 [pii] AID - 10.34067/KID.0000000981 [doi] PST - ppublish SO - Kidney360. 2026 Mar 1;7(3):633-641. doi: 10.34067/KID.0000000981. Epub 2025 Oct 20. PMID- 41116700 OWN - NLM STAT- MEDLINE DCOM- 20251106 LR - 20260925 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 10 IP - Suppl 10 DP - 2025 Nov TI - iGlarLixi: A titrateable fixed-ratio combination of basal insulin + GLP-1 receptor agonist-An effective type 2 diabetes treatment option in China. PG - 15-23 LID - 10.1111/dom.70192 [doi] AB - Five years ago, the overall prevalence of diabetes in China was reported to be as high as 10.6%, and it is especially concerning that type 2 diabetes (T2DM) is developing in younger age groups. Glycaemic control rates (both HbA1c and post-prandial glucose control) are worryingly low among patients with T2DM in China, and 'clinical inertia' is a major challenge, in particular a reluctance among clinicians to initiate injectable therapy when oral antidiabetic therapies (OADs) are no longer achieving target levels of glucose control. Within the Chinese guidelines, clinicians now have the option to use a fixed-ratio combination of basal insulin (Glargine) and GLP-1 receptor agonist (lixisenatide), iGlarLixi, as a convenient, safe, and effective treatment for patients with T2DM. This review summarises the key clinical trials with iGlarLixi in Chinese and Asia-Pacific people, for example, the LixiLan-O-AP and LixiLan-L-CN trials, and highlights the advantages of this treatment for lowering HbA1c and post-prandial glucose. iGlarLixi is preferable to premixed insulin and can be combined with OADs among typical people with T2DM and poor glycaemic control. The safety, efficacy, and practical convenience of iGlarLixi are summarised in the Chinese healthcare context. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yu, Miao AU - Yu M AUID- ORCID: 0000-0003-1450-9011 AD - Department of Endocrinology, Peking Union Medical College Hospital, Beijing, People's Republic of China. LA - eng PT - Journal Article PT - Review DEP - 20251020 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Drug Combinations) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - China/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Combinations MH - *Peptides/administration & dosage/therapeutic use MH - *Insulin Glargine/administration & dosage/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/metabolism MH - Treatment Outcome MH - Glucagon-Like Peptide-2 Receptor PMC - PMC12590520 OTO - NOTNLM OT - iGlarLixi OT - insulin therapy OT - residual hyperglycaemia OT - type 2 diabetes COIS- The author declares no conflicts of interest. EDAT- 2025/10/21 06:27 MHDA- 2025/11/06 12:33 PMCR- 2025/11/06 CRDT- 2025/10/21 02:43 PHST- 2025/10/01 00:00 [revised] PHST- 2025/07/17 00:00 [received] PHST- 2025/10/01 00:00 [accepted] PHST- 2025/11/06 12:33 [medline] PHST- 2025/10/21 06:27 [pubmed] PHST- 2025/10/21 02:43 [entrez] PHST- 2025/11/06 00:00 [pmc-release] AID - DOM70192 [pii] AID - 10.1111/dom.70192 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27 Suppl 10(Suppl 10):15-23. doi: 10.1111/dom.70192. Epub 2025 Oct 20. PMID- 41110425 OWN - NLM STAT- MEDLINE DCOM- 20251130 LR - 20260105 IS - 1095-9157 (Electronic) IS - 0896-8411 (Linking) VI - 157 DP - 2025 Dec TI - Comparative risk of rheumatoid arthritis between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in type 2 diabetes. PG - 103493 LID - S0896-8411(25)00138-6 [pii] LID - 10.1016/j.jaut.2025.103493 [doi] AB - INTRODUCTION: Rheumatoid arthritis (RA) causes disability, chronic pain, and reduced quality of life. Preclinical studies suggest glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce inflammation and protect joint tissues. This study compared GLP-1 RAs with non-GLP-1 RAs on the risk of RA in patients with type 2 diabetes mellitus (T2DM). METHODS: Using the TriNetX network (2016-2023), we identified 2,688,327 patients with T2DM. Propensity score matching yielded 89,938, 111,074, and 88,054 pairs of GLP-1 RA users versus dipeptidyl peptidase-4 inhibitors (DPP-4i), basal insulin, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), respectively. Analyses followed an as-treated approach. Relative hazards of RA were estimated with Kaplan-Meier methods. Subgroup analyses were performed, and a sensitivity analysis used the intention-to-treat approach. RESULTS: In matched cohorts, GLP-1 RAs showed no significant difference in 7-year RA risk versus DPP-4i (HR 1.06, 95 % CI 0.98-1.15) or basal insulin (HR 0.98, 95 % CI 0.89-1.08). By contrast, SGLT2i use was associated with lower RA risk compared with GLP-1 RAs (HR 0.88, 95 % CI 0.80-0.96). Kaplan-Meier curves confirmed a significantly lower cumulative incidence of RA in SGLT2i users (log-rank p = 0.007). CONCLUSIONS: In this multicenter cohort study of patients with T2DM, GLP-1 RAs did not significantly alter RA risk compared with DPP-4i or basal insulin. In contrast, SGLT2i was associated with a significantly reduced risk of new-onset RA, suggesting potential anti-inflammatory benefits. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, Taoyuan, Taiwan. FAU - Wang, Shiow-Ing AU - Wang SI AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan. FAU - Huang, Chien-Wei AU - Huang CW AD - Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chang, Renin AU - Chang R AD - Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan; Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan. Electronic address: cch@nhri.edu.tw. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Office of Research and Development, Asia University, Taichung, Taiwan. Electronic address: jccwei@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251018 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Arthritis, Rheumatoid/epidemiology/etiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Basal insulins OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Rheumatoid arthritis OT - Sodium-glucose cotransporter-2 inhibitors COIS- Declaration of competing interests None declared. EDAT- 2025/10/20 00:27 MHDA- 2025/12/01 00:30 CRDT- 2025/10/19 18:08 PHST- 2025/07/31 00:00 [received] PHST- 2025/10/13 00:00 [revised] PHST- 2025/10/14 00:00 [accepted] PHST- 2025/12/01 00:30 [medline] PHST- 2025/10/20 00:27 [pubmed] PHST- 2025/10/19 18:08 [entrez] AID - S0896-8411(25)00138-6 [pii] AID - 10.1016/j.jaut.2025.103493 [doi] PST - ppublish SO - J Autoimmun. 2025 Dec;157:103493. doi: 10.1016/j.jaut.2025.103493. Epub 2025 Oct 18. PMID- 41107882 OWN - NLM STAT- MEDLINE DCOM- 20251018 LR - 20260903 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Oct 17 TI - Stratifying cardiovascular benefits from GLP-1RA: a multisource analysis of patient-level CVOT and real-world data using AI-driven methods. PG - 401 LID - 10.1186/s12933-025-02952-w [doi] LID - 401 AB - BACKGROUND: It remains unclear whether certain individuals with type 2 diabetes (T2D) derive greater cardiovascular benefit from GLP-1 receptor agonists (GLP-1RAs). Here, we integrate individual-level data from cardiovascular outcome trials (CVOTs) and electronic health records (EHRs), applying machine learning methods to confirm the cardiovascular benefits of GLP-1RAs in real-world populations and to identify subgroups with enhanced treatment response. METHODS: Data from two CVOTs (LEADER and SUSTAIN-6) and a large real-world study (DARWIN-T2D) were analyzed. We first transposed the hazard ratio (HR) for 3-point major adverse cardiovascular event (3P-MACE) from CVOTs to the real-world population. Then, we used PRISM (Patient Response Identifiers for Stratified Medicine) against 3P-MACE reduction by GLP-1RA in a training/test setting. Findings were validated with external cohorts of new-users of GLP-1RA or comparators (DPP-4 inhibitors or basal insulin). RESULTS: Despite notable differences in clinical characteristics between CVOT and real-world patients, the real-world-transposed HRs for 3P-MACE closely paralleled those from CVOTs. PRISM identified subgroups with differential treatment responses, based on history of myocardial infarction (MI) or stroke and age. Participants aged over 71 years without MI/stroke (41% of the real-world population) had the greatest relative benefit (HR 0.46; 95% CI 0.24-0.89 in the test set) and a greater absolute risk reduction (ARR 4.5%, 95% CI 1.2-7.7) than other subgroups (Gail-Simon p = 0.02). The external validation cohort confirmed these results (HR 0.67; 95% CI 0.51-0.89 and ARR 3.8%, 95% CI 1.5-6.1) showing significant differences in absolute risk reduction (p < 0.05). CONCLUSIONS: This study supports the integration of individual data from CVOT with those from EHR to confirm the transposition of results from CVOT to real-world populations, and enables the identification and validation of subgroups with greater cardiovascular benefits from cardioprotective treatment such as GLP-1RA treatment. This precision medicine approach represents a new framework for deploying cardiovascular prevention strategies in T2D. CI - (c) 2025. The Author(s). FAU - Morieri, Mario Luca AU - Morieri ML AD - Department of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy. marioluca.morieri@unipd.it. FAU - Longato, Enrico AU - Longato E AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Sciannameo, Veronica AU - Sciannameo V AD - Centre for Biostatistics, Epidemiology and Public Health, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, Italy. FAU - Donatiello, Emily AU - Donatiello E AD - Novo Nordisk Italia, SpA, Roma, Italy. FAU - Berchialla, Paola AU - Berchialla P AD - Centre for Biostatistics, Epidemiology and Public Health, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, Italy. FAU - Avogaro, Angelo AU - Avogaro A AD - Department of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti- Pescara, Chieti, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy. gianpaolo.fadini@unipd.it. AD - Veneto Institute of Molecular Medicine, Padova, Italy. gianpaolo.fadini@unipd.it. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20251017 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality/blood MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Aged MH - Risk Assessment MH - Middle Aged MH - Electronic Health Records MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - *Machine Learning MH - Time Factors MH - Heart Disease Risk Factors MH - *Decision Support Techniques MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12535053 OTO - NOTNLM OT - Cardiovascular prevention OT - GLP-1RA OT - Precision medicine OT - Randomized clinical trial OT - Real-world evidence COIS- Declarations. Competing interests: MLM has received lecture or consultancy fee from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Guidotti, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi and Servier. ED is an employee of Novo Nordisk Italia SpA. AA received research grants and lecture or advisory board fees from MSD, AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier and Takeda. AC received research grants and/or lecture and/or advisory board and/or consultancy fees from AstraZeneca, Boehringer Ingelheim, Sanofi, Novo Nordisk, Lilly, Abbot and Bayer. MR received speaker fees from Lilly. GPF received grants, honoraria or lecture fees from AstraZeneca, Boehringer, Lilly, Guidotti, Mundipharma, Novartis, Novo Nordisk, Servier, Sanofi. EL, VS and PB have nothing to disclose. Ethical approval: The DARWIN-T2D, SUSTAIN-6, and LEADER studies were approved by competent ethical committees. EDAT- 2025/10/18 00:30 MHDA- 2025/10/18 06:28 PMCR- 2025/10/17 CRDT- 2025/10/17 23:52 PHST- 2025/07/02 00:00 [received] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/10/18 06:28 [medline] PHST- 2025/10/18 00:30 [pubmed] PHST- 2025/10/17 23:52 [entrez] PHST- 2025/10/17 00:00 [pmc-release] AID - 10.1186/s12933-025-02952-w [pii] AID - 2952 [pii] AID - 10.1186/s12933-025-02952-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Oct 17;24(1):401. doi: 10.1186/s12933-025-02952-w. PMID- 41107649 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20261010 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 64 IP - 12 DP - 2025 Dec TI - Exposure-Response Analysis of Efsubaglutide Alfa in Patients with Type 2 Diabetes Mellitus. PG - 1785-1797 LID - 10.1007/s40262-025-01570-9 [doi] AB - BACKGROUND: Efsubaglutide alfa is a novel glucagon-like peptide-1 receptor agonist composed of dual GLP-1 molecules fused with the fragment crystallizable (Fc) region of human immunoglobulin G2. It is designed for the treatment of type 2 diabetes mellitus (T2DM) and metabolic diseases. OBJECTIVES: This study aimed to quantitatively describe the exposure-response (E-R) relationship between efsubaglutide alfa exposure and efficacy and safety endpoints in patients with T2DM and to assess the impact of baseline characteristics on the E-R relationship. METHODS: An E-R analysis was conducted using data from 465 drug-naive participants with T2DM in a phase IIb/III trial (YN011-301), which included a 24-week double-blind period followed by a 28-week open-label period. Participants received once-weekly subcutaneous injections of efsubaglutide alfa 1 mg, 2 mg, or 3 mg or placebo. Regression analysis was performed against the steady-state pharmacokinetic exposure, including steady state peak concentration (C(max,ss)), steady state minimum concentration (C(min,ss)), steady state average concentration (C(avg,ss)), and their logarithms. RESULTS: The median age was 51.0 years, and the mean baseline glycated hemoglobin (HbA1c) was 8.71%. At weeks 24 and 52, reductions in HbA1c, fasting plasma glucose, area under the concentration-time curve for glucose during the mixed-meal tolerance test, body weight, waist circumference, and body mass index correlated positively with drug exposure. The E-R model indicated that a 10-fold increase in C(min,ss) led to a 1.150% decrease in HbA1c at week 24. Baseline HbA1c, age, and neutralizing anti-drug antibody influenced the E-R relationship for HbA1c. Safety analysis showed a positive correlation between drug exposure and the incidence of treatment-related adverse events, particularly nausea and diarrhea, with tolerance developing over time. CONCLUSIONS: Efsubaglutide alfa demonstrates a strong E-R relationship for glycemic control and weight reduction in drug-naive participants with T2DM. The extended half-life and favorable safety profile of efsubaglutide alfa make it well-suited for once weekly or biweekly monotherapy in patients with newly diagnosed T2DM. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (identifier: NCT04994288). CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Wang, Qinghua AU - Wang Q AD - Innogen Pharmaceutical Technology Co., Ltd., No. 501, Building 10, 299 Bi Bo Road, Shanghai, 201203, China. qh_wang@fudan.edu.cn. AD - Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China. qh_wang@fudan.edu.cn. FAU - Jiang, Fan AU - Jiang F AD - Innogen Pharmaceutical Technology Co., Ltd., No. 501, Building 10, 299 Bi Bo Road, Shanghai, 201203, China. FAU - Xu, Yulong AU - Xu Y AD - Innogen Pharmaceutical Technology Co., Ltd., No. 501, Building 10, 299 Bi Bo Road, Shanghai, 201203, China. FAU - Lei, Yuyang AU - Lei Y AD - Innogen Pharmaceutical Technology Co., Ltd., No. 501, Building 10, 299 Bi Bo Road, Shanghai, 201203, China. FAU - Zhang, Li AU - Zhang L AD - Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China. FAU - Sun, Xiaodong AU - Sun X AD - Department of Endocrinology and Metabolism, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China. LA - eng SI - ClinicalTrials.gov/NCT04994288 PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251017 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Middle Aged MH - Female MH - Male MH - Double-Blind Method MH - *Hypoglycemic Agents/pharmacokinetics/administration & dosage/therapeutic use/adverse effects MH - Adult MH - *Glucagon-Like Peptide 1/pharmacokinetics/analogs & derivatives/administration & dosage MH - Aged MH - Glycated Hemoglobin/analysis MH - Blood Glucose/drug effects MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments MH - *Recombinant Fusion Proteins/pharmacokinetics/administration & dosage/therapeutic use/adverse effects COIS- Declarations. Conflict of Interests: QW is the founder and actual controller of Innogen Pharmaceutical Co. Ltd. FJ and YX are employees of the company. All the remaining authors declare no competing interests. Data Availability Statement: All data are available upon reasonable request. Data will be made available upon reasonable request, subject to the protection of research participants' privacy. Author Contributions: YX and LZ drafted the manuscript. YX, YL, and FJ analyzed the data and produced the figures. QW and XS reviewed and edited the manuscript. Ethical Approval: All studies included in this analysis were approved by the relevant ethics committees and conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonisation guidelines for Good Clinical Practice (ICH-GCP). Code Availability: The model codes that support the findings of this study are accessible upon reasonable request by contacting the corresponding author. Consent for Publication: Not applicable. Consent to Participate: Written, informed consent was obtained from all participants. EDAT- 2025/10/18 00:29 MHDA- 2025/12/18 13:07 CRDT- 2025/10/17 23:41 PHST- 2025/03/06 00:00 [received] PHST- 2025/08/14 00:00 [accepted] PHST- 2025/12/18 13:07 [medline] PHST- 2025/10/18 00:29 [pubmed] PHST- 2025/10/17 23:41 [entrez] AID - 10.1007/s40262-025-01570-9 [pii] AID - 10.1007/s40262-025-01570-9 [doi] PST - ppublish SO - Clin Pharmacokinet. 2025 Dec;64(12):1785-1797. doi: 10.1007/s40262-025-01570-9. Epub 2025 Oct 17. PMID- 41105066 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260418 IS - 1531-6564 (Electronic) IS - 0363-5023 (Linking) VI - 50 IP - 12 DP - 2025 Dec TI - Endoscopic and Open Carpal Tunnel Release in Patients With Type II Diabetes Mellitus: Influence of Preoperative Semaglutide Use on Postoperative Outcomes. PG - 1467-1475 LID - S0363-5023(25)00504-0 [pii] LID - 10.1016/j.jhsa.2025.09.003 [doi] AB - PURPOSE: Patients with type II diabetes mellitus are at greater risk of carpal tunnel syndrome and of complications following carpal tunnel release (CTR). Although recent orthopedic literature suggests preoperative semaglutide use may reduce complication and reoperation rates, its impact has not been studied in hand surgery. Given the overall favorable complication profile of CTR, it remains unknown if similar risk modification exists. METHODS: Type II diabetes mellitus patients undergoing endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) were identified from the PearlDiver database. Exclusion criteria included the following: age <18, revision CTR, traumatic, neoplastic, or infectious diagnoses within 90 days before surgery, <90 days follow-up, and other concurrent upper-extremity procedures. Patients using semaglutide within 1 year before surgery were identified and matched 1:4 with (-)semaglutide controls. Ninety-day complications were compared by multivariable logistic regression, and 2-year reoperation was assessed by Kaplan-Meier survival analysis and log-rank test. RESULTS: Semaglutide was used by 689 (1.2%) of ECTR and 1,966 (0.8%) of OCTR patients. Once matched, there were 426 ECTR and 1,673 OCTR patients receiving semaglutide. Relative to ECTR (-)semaglutide controls, semaglutide reduced the odds of pneumonia (OR, 0.30 [0.13-0.58]) and urinary tract infection (OR, 0.28 [0.18-0.44]). Relative to OCTR (-)semaglutide controls, semaglutide reduced the odds of surgical site infection (SSI) (OR, 0.31 [0.18-0.51]), sepsis (OR, 0.61 [0.43-0.85]), wound dehiscence (OR, 0.25 [0.13-0.42]), pneumonia (OR, 0.26 [0.19-0.35]), and urinary tract infection (OR, 0.33 [0.27-0.40]). For both ECTR and OCTR, 2-year reoperation rates were similar for those with versus without semaglutide. CONCLUSIONS: The current study reinforces the low overall incidence of complications following CTR. The most clinically relevant findings were observed in OCTR patients, including reduced odds of SSI and wound dehiscence. However, 2-year reoperation rates were similar across both surgical approaches regardless of semaglutide use. These findings may have implications in the context of perioperative risk stratification. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. CI - Copyright (c) 2025 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Day, Wesley AU - Day W AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Rancu, Albert L AU - Rancu AL AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Modrak, Maxwell AU - Modrak M AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Joo, Peter Y AU - Joo PY AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Grauer, Jonathan N AU - Grauer JN AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. Electronic address: jonathan.grauer@yale.edu. LA - eng PT - Journal Article DEP - 20251017 PL - United States TA - J Hand Surg Am JT - The Journal of hand surgery JID - 7609631 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - Male MH - *Carpal Tunnel Syndrome/surgery/complications MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Middle Aged MH - *Postoperative Complications/prevention & control/epidemiology MH - Reoperation/statistics & numerical data MH - Aged MH - *Endoscopy MH - Treatment Outcome MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Preoperative Care MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Carpal tunnel release OT - complications OT - preoperative optimization OT - surgical site infection OT - wound dehiscence COIS- Conflicts of Interest No benefits in any form have been received or will be received related directly to this article. EDAT- 2025/10/17 12:29 MHDA- 2025/12/04 02:11 CRDT- 2025/10/17 10:31 PHST- 2025/02/27 00:00 [received] PHST- 2025/08/03 00:00 [revised] PHST- 2025/09/03 00:00 [accepted] PHST- 2025/12/04 02:11 [medline] PHST- 2025/10/17 12:29 [pubmed] PHST- 2025/10/17 10:31 [entrez] AID - S0363-5023(25)00504-0 [pii] AID - 10.1016/j.jhsa.2025.09.003 [doi] PST - ppublish SO - J Hand Surg Am. 2025 Dec;50(12):1467-1475. doi: 10.1016/j.jhsa.2025.09.003. Epub 2025 Oct 17. PMID- 41104525 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Effects of GLP-1 receptor agonists on cognitive function in patients with type 2 diabetes: A systematic review and meta-analysis based on randomized controlled trials. PG - 3396-3407 LID - 10.1111/dom.70201 [doi] AB - AIMS: Patients with type 2 diabetes mellitus (T2DM) have a significantly increased risk of cognitive impairment, and the protective effects of traditional hypoglycaemic drugs on cognitive function remain unclear. This study systematically evaluated the neuroprotective effects of GLP-1 receptor agonists (GLP-1RAs) based on randomized controlled trial (RCT) evidence, aiming to provide key evidence-based insights for optimizing diabetes management strategies. MATERIALS AND METHODS: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and ClinicalTrials.gov databases to identify studies investigating the impact of GLP-1RAs on cognitive function in T2DM patients, with the search timeframe extending up to July 2025. The analysis focused on RCTs comparing the effects of GLP-1RAs versus placebo (or conventional therapy) on neurocognitive function in T2DM patients. RESULTS: Based on the inclusion criteria, 18 RCTs involving 11 114 participants were included in the primary meta-analysis. Pooled results demonstrated that, compared to the placebo group, GLP-1RA treatment significantly increased Mini-Mental State Examination (MMSE) scores by a weighted mean difference (WMD) of 1.33 (95% CI: 0.67-1.99; I(2) = 82%) and Montreal Cognitive Assessment (MoCA) scores by a WMD of 1.70 (95% CI: 0.83-2.56; I(2) = 96%). The effect size on MMSE was significantly greater with long-term GLP-1RA use (>/=24 weeks) compared to short-term use (<24 weeks) (mean difference = 3.74; t = 6.52, df = 269, p < 0.0001; Cohen's d = 0.79). Sensitivity analyses yielded results closely aligned with the primary analysis, indicating robust stability. Jadad scale assessment confirmed that all included studies achieved a score >/=3. CONCLUSIONS: Current evidence indicates that GLP-1 RA-based therapy may improve cognitive function in patients with type 2 diabetes mellitus compared with placebo. Furthermore, long-term administration or early initiation of GLP-1 RA treatment may offer greater cognitive benefits. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Wan, Suxin AU - Wan S AD - Department of Pharmacy, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China. FAU - Yan, He AU - Yan H AD - Department of Endocrinology and Metabolism, Three Gorges Hospital, Chongqing University, Chongqing, China. FAU - Sun, Qiu-Yan AU - Sun QY AD - Department of Pharmacy, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China. FAU - Zhu, Jia-Quan AU - Zhu JQ AD - Fengdu General Hospital & Department of Pharmacy, Chongqing, China. FAU - Wang, Hui-Hong AU - Wang HH AD - Department of Pharmacy, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China. FAU - Qu, Ke-Yi AU - Qu KY AUID- ORCID: 0009-0003-0402-1570 AD - Fengdu General Hospital & Department of Stomatology, Chongqing, China. FAU - Yi, Xiang AU - Yi X AD - Department of Liver Disease, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China. LA - eng GR - YXQN202401/Chongqing Medical Young Elite Talent Program/ PT - Journal Article PT - Meta-Analysis PT - Retracted Publication PT - Systematic Review DEP - 20251017 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM RIN - Diabetes Obes Metab. 2026 Apr;28(4):3451. doi: 10.1111/dom.70552. PMID: 41667890 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Cognition/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Cognitive Dysfunction/prevention & control/etiology OTO - NOTNLM OT - GLP-1 receptor agonists OT - cognitive impairment OT - meta-analysis OT - systematic review OT - type 2 diabetes mellitus EDAT- 2025/10/17 06:26 MHDA- 2026/03/17 06:47 CRDT- 2025/10/17 05:42 PHST- 2025/10/03 00:00 [revised] PHST- 2025/07/31 00:00 [received] PHST- 2025/10/04 00:00 [accepted] PHST- 2026/03/17 06:47 [medline] PHST- 2025/10/17 06:26 [pubmed] PHST- 2025/10/17 05:42 [entrez] AID - 10.1111/dom.70201 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3396-3407. doi: 10.1111/dom.70201. Epub 2025 Oct 17. PMID- 41104517 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260919 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - GLP-1RA and the risk of non-arteritic anterior ischaemic optic neuropathy in patients with type 2 diabetes: A population-based study. PG - 1517-1528 LID - 10.1111/dom.70200 [doi] AB - AIMS: Evidence on the safety of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RA) concerning non-arteritic anterior ischemic optic neuropathy (NAION) is inconclusive, with several studies published to date presenting methodological challenges. We sought to compare the risk of presumed NAION in patients with type 2 diabetes (T2D), initiating a GLP-1RA versus a sodium-glucose cotransporter-2 inhibitor (SGLT2i), using a new-user active comparator cohort study design within a target trial emulation framework. MATERIALS AND METHODS: Using insurance claims data from three databases (01/2016-08/2024), we identified 482 912 propensity score matched (1:1) pairs of GLP-1RA and SGLT2i adult initiators with T2D and without prior ischemic optic neuropathy (ION) or other optic nerve disorders. NAION was defined as a diagnosis of ION without other causes of optic neuropathy, combined with an ophthalmologist or optometrist visit on the same day. We estimated pooled hazard ratios (HRs) and rate differences (RDs). RESULTS: Over a median follow-up of 6.7 months on treatment, the risk of incident NAION was higher among initiators of GLP-1RA compared with SGLT2i [HR, 1.85; 95% CI (1.51-2.27); RD, 0.29 (0.19, 0.39) per 1000 person-years]. Results were consistent across subgroups and sensitivity analyses. A meta-analysis of our semaglutide analysis with previously published results also showed an elevated risk, with a HR of 2.78 (1.39-5.56). CONCLUSIONS: In this large observational study, the initiation of GLP-1RA was associated with an 85% increase in the risk of presumed NAION, compared with the initiation of SGLT2is, though incidence rates and absolute increase in risk were small. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, USA. FAU - Wexler, Deborah J AU - Wexler DJ AD - MGH Diabetes Center, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Hathaway, Jimena Tatiana AU - Hathaway JT AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. FAU - Yu, Elaine W AU - Yu EW AD - Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Freedman, Ariel AU - Freedman A AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Rizzo, Joseph F 3rd AU - Rizzo JF 3rd AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20251017 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - Female MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Adult MH - Incidence MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12718077 MID - NIHMS2125282 OTO - NOTNLM OT - GLP-1 analogue OT - pharmacoepidemiology OT - real-world evidence OT - type 2 diabetes EDAT- 2025/10/17 06:27 MHDA- 2026/01/16 04:07 PMCR- 2025/12/21 CRDT- 2025/10/17 05:32 PHST- 2025/10/02 00:00 [revised] PHST- 2025/08/13 00:00 [received] PHST- 2025/10/03 00:00 [accepted] PHST- 2026/01/16 04:07 [medline] PHST- 2025/10/17 06:27 [pubmed] PHST- 2025/10/17 05:32 [entrez] PHST- 2025/12/21 00:00 [pmc-release] AID - 10.1111/dom.70200 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1517-1528. doi: 10.1111/dom.70200. Epub 2025 Oct 17. PMID- 41103643 OWN - NLM STAT- MEDLINE DCOM- 20251017 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Multi-omics analysis of hepatic outcomes in T2DM-MAFLD patients treated with semaglutide: a single-centre, longitudinal, data-driven study. PG - 1650729 LID - 10.3389/fendo.2025.1650729 [doi] LID - 1650729 AB - BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease and is closely linked to type 2 diabetes mellitus (T2DM). The pathogenesis of MAFLD involves complex metabolic imbalances, including impaired fatty acid beta-oxidation and chronic inflammation. GLP-1 receptor agonists (GLP-1 RAs) have shown promise in improving metabolic outcomes, but their specific effects on MAFLD remain unclear. This study aims to investigate the molecular mechanisms underlying the hepatic benefits of semaglutide, a GLP-1 RA, in T2DM patients with MAFLD using serum proteomics and metabolomics. METHODS: We conducted a single-centre, longitudinal, data-driven study involving 75 T2DM patients with MAFLD (pre-treatment, PT) and 100 healthy controls (health control, HC). Patients received semaglutide treatment (0.25 mg/week initially, escalated to 0.5 mg/week) for 12 weeks. Serum proteomic and metabolomic profiles were analyzed using 4D-DIA proteomics and LC-MS before and after treatment. Biomarker discovery involved the identification of differential metabolites and proteins, pathway analysis, and integration of proteomic and metabolomic data. Clinical and biochemical parameters were also assessed. RESULTS: Semaglutide significantly improved metabolic and liver parameters, including HbA1c, BMI, HOMA-IR, liver function, IL-6, and liver stiffness (p < 0.01). Multivariate analysis revealed distinct proteomic and metabolomic profiles between baseline and post-treatment groups. A total of 203 differential metabolites and 61 proteins were identified, with key changes including reductions in long-chain fatty acids and inflammatory mediators, alongside increases in carnitine derivatives and anti-inflammatory proteins. Pathway analysis highlighted effects on fatty acid metabolism, PPAR signaling, and NAFLD-related pathways. CONCLUSION: Our study provides a comprehensive multi-omics analysis revealing that semaglutide modulates serum proteomic and metabolomic profiles in T2DM-MAFLD patients, potentially through enhancing mitochondrial beta-oxidation, reducing lipid toxicity, and suppressing inflammation. These findings offer mechanistic insights into the hepatic benefits of semaglutide and support its potential as a therapeutic agent for MAFLD. This innovative approach advances our understanding of GLP-1 RAs' multi-organ protective effects and provides a foundation for developing precision medicine strategies for MAFLD. CI - Copyright (c) 2025 Niu, Chen, Wu, Wang, Xu, Yin and Zhao. FAU - Niu, Shu AU - Niu S AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. FAU - Chen, Shuchun AU - Chen S AD - Department of Endocrine, Hebei Provincial People's Hospital, Shijiazhuang, Hebei, China. FAU - Wu, Di AU - Wu D AD - Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, China. FAU - Wang, Chenxi AU - Wang C AD - Department of Endocrine, Medical University, Shijiazhuang, Hebei, China. FAU - Xu, Jianchao AU - Xu J AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. FAU - Yin, Jiantong AU - Yin J AD - Department of Endocrine, Medical University, Shijiazhuang, Hebei, China. FAU - Zhao, Yubin AU - Zhao Y AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. LA - eng PT - Journal Article DEP - 20251001 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Longitudinal Studies MH - Metabolomics/methods MH - Proteomics/methods MH - *Liver/metabolism/drug effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Biomarkers/blood MH - Aged MH - Treatment Outcome MH - Multiomics MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12521249 OTO - NOTNLM OT - MAFLD-T2DM OT - hepatic outcomes OT - multi-omics analysis OT - proteomics OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/17 06:27 MHDA- 2025/10/17 06:28 PMCR- 2025/10/01 CRDT- 2025/10/17 04:49 PHST- 2025/06/20 00:00 [received] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/10/17 06:28 [medline] PHST- 2025/10/17 06:27 [pubmed] PHST- 2025/10/17 04:49 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1650729 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Oct 1;16:1650729. doi: 10.3389/fendo.2025.1650729. eCollection 2025. PMID- 41102421 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20260423 IS - 1348-4214 (Electronic) IS - 0916-9636 (Print) IS - 0916-9636 (Linking) VI - 48 IP - 12 DP - 2025 Dec TI - Risk management of cardiovascular disease in older patients with diabetes. PG - 3179-3186 LID - 10.1038/s41440-025-02424-4 [doi] AB - The number of older patients with diabetes has been increasing due to Japan's rapidly aging population. As aging and diabetes are independent risk factors for cardiovascular disease, older adults face a higher risk of cardiovascular disease, with the incidence of heart failure and stroke increasing significantly with age. Preventing cardiovascular events is critical for this population to maintain their activities of daily living and improve their quality of life. To achieve this challenging purpose, it is essential to prioritize the use of glucose-lowering medications with proven cardiovascular benefits and to comprehensively manage risk factors, including blood pressure, as with younger patients. However, considering the vulnerability and divergent health status of older patients, population-specific effects and precautions regarding medications, such as sodium-glucose cotransporter (SGLT) 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RA) should be considered. In particular, we must deliberate their impact on frailty when administering these medications to this population. In this mini review, we discuss the characteristics of older patients with diabetes and update the evidence on the consistent efficacy and safety of SGLT2 inhibitors and GLP-1RA in older patients. In addition, recent clinical trials that examined the effect of stricter blood pressure control in older patients with diabetes have been reconsidered to accomplish comprehensive risk management for preventing cardiovascular disease. Heterogeneity of older patients with diabetes and principles of cardiovascular risk management in this population. SGLT2: sodium glucose cotransporter 2, GLP-1RA: glucagon-like peptide 1 receptor agonist. CI - (c) 2025. The Author(s). FAU - Sawami, Kosuke AU - Sawami K AD - Department of Frontier Cardiovascular Science, The University of Tokyo Hospital, Tokyo, Japan. sawami-kosuke915@g.ecc.u-tokyo.ac.jp. AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. sawami-kosuke915@g.ecc.u-tokyo.ac.jp. FAU - Tanaka, Atsushi AU - Tanaka A AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. FAU - Node, Koichi AU - Node K AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251016 PL - England TA - Hypertens Res JT - Hypertension research : official journal of the Japanese Society of Hypertension JID - 9307690 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Risk Management MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use PMC - PMC12678176 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Implemental hypertension OT - Older adults OT - Sodium-glucose cotransporter 2 inhibitor OT - Type 2 diabetes COIS- Compliance with ethical standards. Conflict of interest: KS is affiliated with an endowed department by Nexera Pharma, Novo Nordisk, Toa Eiyo, Takara Bio, Boehringer Ingelheim Japan and BioStream. AT has received honoraria from Amgen, Boehringer Ingelheim Japan, Mochida, and Novo Nordisk, as well as research funding from Bristol-Myers Squibb, GlaxoSmithKline, and Novo Nordisk. KN has received honoraria from MSD, AstraZeneca, Novartis, Novo Nordisk, Bayer, Kowa, Mochida, Otsuka, Daiichi Sankyo, Mitsubishi Tanabe, Eli Lilly Japan, Boehringer Ingelheim Japan; Research grant from Fuji, Astellas, Novartis, Bayer, Mochida; Scholarship from Abbott Medical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Teijin Pharma, Boehringer Ingelheim Japan. EDAT- 2025/10/17 00:31 MHDA- 2025/12/05 01:02 PMCR- 2025/10/16 CRDT- 2025/10/16 23:41 PHST- 2025/08/23 00:00 [received] PHST- 2025/10/02 00:00 [accepted] PHST- 2025/09/21 00:00 [revised] PHST- 2025/12/05 01:02 [medline] PHST- 2025/10/17 00:31 [pubmed] PHST- 2025/10/16 23:41 [entrez] PHST- 2025/10/16 00:00 [pmc-release] AID - 10.1038/s41440-025-02424-4 [pii] AID - 2424 [pii] AID - 10.1038/s41440-025-02424-4 [doi] PST - ppublish SO - Hypertens Res. 2025 Dec;48(12):3179-3186. doi: 10.1038/s41440-025-02424-4. Epub 2025 Oct 16. PMID- 41102420 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20261010 IS - 1348-4214 (Electronic) IS - 0916-9636 (Linking) VI - 48 IP - 12 DP - 2025 Dec TI - Possible mechanisms of action of glucagon-like peptide-1 receptor agonists on blood pressure beyond body weight. PG - 3159-3171 LID - 10.1038/s41440-025-02418-2 [doi] AB - Glucagon-like petide-1 (GLP-1) potentiates insulin and suppresses glucagon secretion from the pancreas in response to the ingestion of nutrients. Due to a short plasma half-life of native GLP-1, several synthesized GLP-1 receptor agonists (RAs) were developed for type 2 diabetes mellitus (DM) treatment. In clinical trials, GLP-1 RAs were shown to significantly lower blood pressure (BP) in addition to HbA1c and body weight (BW), indicating the possibility as anti-hypertensive medication of type 2 DM individuals. Although the hypotensive effect of GLP-1 RAs seems to be manifested by BW losing, other mechanisms not related to BW might be implied by the mediation meta-analysis, which suggests an existence of BW-independent hypotensive effect of GLP-1 RA, along with the clinical evidence of weak or no correlations, and difference in time course between BP lowering and BW reducing effects. Both human and animal studies reported inconsistent BP response to acute administration but showed hypotensive effect of chronic administration of GLP-1/ GLP-1 RAs. As for the mechanisms of hypotensive effect beyond BW, augmentation of natriuresis by inhibiting sodium hydrogen exchanger at proximal tubule, ameliorating angiotensin II activity, and enhancing vasodilation can be postulated. Since GLP-1 RAs improve both morning surge and nocturnal hypertension, they are expected as promising remedies for morning hypertension. GLP-1 RAs exert three properties, that are glucose, BW and BP lowering actions, all of which are expected to exert potent and coordinated effects for conquering noncommunicable diseases, including type 2 DM and hypertension. CI - (c) 2025. The Author(s), under exclusive licence to The Japanese Society of Hypertension. FAU - Tanaka, Masami AU - Tanaka M AD - Midtown Clinic East, Minato-ku, Tokyo, Japan. FAU - Itoh, Hiroshi AU - Itoh H AD - Specially-appointed Professor, Center for Preventive Medicine, Keio University, Minato-ku, Tokyo, Japan. hiito@keio.jp. LA - eng PT - Journal Article PT - Review DEP - 20251016 PL - England TA - Hypertens Res JT - Hypertension research : official journal of the Japanese Society of Hypertension JID - 9307690 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Antihypertensive Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Pressure/drug effects MH - *Body Weight/drug effects MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - *Antihypertensive Agents/pharmacology/therapeutic use MH - Hypertension/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use OTO - NOTNLM OT - Blood pressure OT - Body weight OT - Diabetes mellitus OT - Glucagon-like petide-1 OT - Morning hypertension COIS- Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. EDAT- 2025/10/17 00:31 MHDA- 2025/12/05 01:02 CRDT- 2025/10/16 23:41 PHST- 2025/03/25 00:00 [received] PHST- 2025/09/02 00:00 [accepted] PHST- 2025/07/28 00:00 [revised] PHST- 2025/12/05 01:02 [medline] PHST- 2025/10/17 00:31 [pubmed] PHST- 2025/10/16 23:41 [entrez] AID - 10.1038/s41440-025-02418-2 [pii] AID - 10.1038/s41440-025-02418-2 [doi] PST - ppublish SO - Hypertens Res. 2025 Dec;48(12):3159-3171. doi: 10.1038/s41440-025-02418-2. Epub 2025 Oct 16. PMID- 41102137 OWN - NLM STAT- MEDLINE DCOM- 20251028 LR - 20251031 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 11 DP - 2025 Nov TI - Comparative Weight Change With Initiation and Adherence to Common Medications for Type 2 Diabetes. PG - 2205-2213 LID - 10.1002/oby.70022 [doi] AB - OBJECTIVE: This study aimed to estimate population-level effects on weight change of initiating/adhering to additional glucose-lowering medications in adults with type 2 diabetes prescribed metformin. METHODS: We conducted a target trial using electronic health record data from 22,601 patients (age 20 to < 80 years) prescribed metformin to determine initiation/adherence to dipeptidyl peptidase IV (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, long-acting insulin, or sulfonylureas. Inverse probability weighting of marginal structural models with standardization by baseline covariates was used to estimate population-level effects of initiating/adhering to different medications on average 24-month weight change. RESULTS: At 24 months, a mean -5.15 kg (95% CI -10.6, -1.36) and -6.71 kg (95% CI -8.38, -4.34) weight loss would be observed for initiation/adherence to GLP-1RAs and SGLT-2s respectively. At 6 months, weight loss for DPP4s would be observed (-0.89 kg, 95% CI -1.41, -0.32) though not at 12 or 24 months. Glimepiride would be associated with weight gain at 6 and 12 months (0.88 kg, 95% CI 0.44, 1.22; 1.01 kg, 95% CI 0.32, 1.51) but not at 24 months. CONCLUSIONS: Initiation/adherence to GLP-1RAs and SGLT-2s over 24 months could result in average weight losses of 5.15 kg and 6.71 kg, respectively. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Sneed, Nadia M AU - Sneed NM AUID- ORCID: 0000-0001-9973-6672 AD - School of Nursing, Vanderbilt University, Nashville, Tennessee, USA. FAU - Rifas-Shiman, Sheryl L AU - Rifas-Shiman SL AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. FAU - Petimar, Joshua AU - Petimar J AUID- ORCID: 0000-0002-3025-5931 AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Young, Jessica G AU - Young JG AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Bailey, L Charles AU - Bailey LC AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Daley, Matthew F AU - Daley MF AD - Institute for Health Research, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Janicke, David M AU - Janicke DM AUID- ORCID: 0000-0002-8493-610X AD - Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Jones, W Schuyler AU - Jones WS AD - Department of Medicine, Duke University Health System, Durham, North Carolina, USA. FAU - Prentice, Carly AU - Prentice C AD - Faith Family Medical Center, Nashville, Tennessee, USA. FAU - Block, Jason P AU - Block JP AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. FAU - Heerman, William J AU - Heerman WJ AD - Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. LA - eng GR - R01 DK120598/DK/NIDDK NIH HHS/United States GR - T32HS026122/HS/AHRQ HHS/United States GR - KL2 TR002245/TR/NCATS NIH HHS/United States GR - T32 HS026122/HS/AHRQ HHS/United States GR - 5KL2TR002245/TR/NCATS NIH HHS/United States GR - 5R01DK120598/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20251016 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin, Long-Acting) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged MH - *Weight Loss/drug effects MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Metformin/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Medication Adherence MH - Aged, 80 and over MH - Insulin, Long-Acting/therapeutic use MH - Young Adult MH - Weight Gain/drug effects PMC - PMC12559777 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - sodium-glucose cotransporter 2 OT - target trial OT - type 2 diabetes COIS- W.J.S. reports grant funding from Boehringer Ingelheim, Bayer, Merck, and Novartis outside the submitted work. The other authors declare no conflicts of interest. EDAT- 2025/10/17 00:31 MHDA- 2025/10/28 06:30 PMCR- 2025/10/28 CRDT- 2025/10/16 23:02 PHST- 2025/07/07 00:00 [revised] PHST- 2025/03/08 00:00 [received] PHST- 2025/07/10 00:00 [accepted] PHST- 2025/10/28 06:30 [medline] PHST- 2025/10/17 00:31 [pubmed] PHST- 2025/10/16 23:02 [entrez] PHST- 2025/10/28 00:00 [pmc-release] AID - OBY70022 [pii] AID - 10.1002/oby.70022 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Nov;33(11):2205-2213. doi: 10.1002/oby.70022. Epub 2025 Oct 16. PMID- 41100333 OWN - NLM STAT- MEDLINE DCOM- 20251016 LR - 20251216 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 73 IP - 10 DP - 2025 Oct TI - Achieving Diabetes Remission: Current Guidelines and Emerging Pharmacotherapies in India. PG - 83-86 LID - 10.59556/japi.73.1184 [doi] AB - Type 2 diabetes mellitus (T2DM) remission has emerged as a critical area of research and clinical interest, especially in India, where diabetes prevalence is rising at an alarming rate. Achieving remission through pharmacologic, dietary, and surgical interventions is now an attainable goal for a subset of patients. This systematic review synthesizes evidence from clinical trials, emerging pharmacologic interventions, and current guidelines for diabetes remission. We explore the mechanisms of diabetes reversal, highlighting novel agents such as glucagon-like peptide-1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. This review also addresses the long-term sustainability of remission, epidemiological trends in India, and current treatment recommendations, integrating data from major studies. The findings underscore the need for a patient-centered, evidence-based approach to diabetes management. Additionally, we discuss the role of continuous glucose monitoring (CGM), dietary interventions, and the benefits of millet consumption in diabetes remission. CI - (c) Journal of The Association of Physicians of India 2025. FAU - Arpan AU - Arpan AD - Intern, Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar, Punjab, India, Orcid: https://orcid.org/0009-0006-1246-4007. FAU - Singh, Navrajbir AU - Singh N AD - Intern, Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar, Punjab, India, Corresponding Author, Orcid: https://orcid.org/0009-0003-7071-659X. FAU - Bali, Kusum AU - Bali K AD - Professor and Head of Department, Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar, Punjab, India, Orcid: https://orcid.org/0009-0000-1134-734X. FAU - Singh, Tarundeep AU - Singh T AD - Associate Professor, Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar, Punjab, India, Orcid: https://orcid.org/0009-0008-1723-5128. LA - eng PT - Journal Article PT - Systematic Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - India/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Remission Induction MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Practice Guidelines as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2025/10/16 18:36 MHDA- 2025/10/16 18:37 CRDT- 2025/10/16 12:45 PHST- 2025/10/16 18:37 [medline] PHST- 2025/10/16 18:36 [pubmed] PHST- 2025/10/16 12:45 [entrez] AID - 10.59556/japi.73.1184 [doi] PST - ppublish SO - J Assoc Physicians India. 2025 Oct;73(10):83-86. doi: 10.59556/japi.73.1184. PMID- 41096554 OWN - NLM STAT- MEDLINE DCOM- 20251016 LR - 20251019 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 19 DP - 2025 Sep 23 TI - Effects of Combined Therapy with SGLT2i and GLP-1RAs on Atrial Fibrillation Recurrence After Catheter Ablation in Diabetic Cohorts: One-Year Outcomes from Continuous Monitoring. LID - 10.3390/ijms26199285 [doi] LID - 9285 AB - To evaluate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and their combination on atrial fibrillation (AF) recurrence after catheter ablation in patients with type 2 diabetes mellitus (T2DM). In a prospective cohort study, patients with T2DM undergoing AF ablation were stratified into three groups: SGLT2i-users, GLP-1RAs-users, and combined SGLT2i/GLP-1RAs users. Diabetics under SGLT2i/GLP-1RAs therapy had worse glycemic control (HbA1c > 7%). AF recurrence was assessed over 12 months using implantable continuous monitoring (ICM). Secondary outcomes included the inflammatory/oxidative stress markers measured at the 12-month follow-up. At the follow-up end, patients treated with SGLT2i/GLP-1RAs versus monotherapy patients showed significantly lower AF recurrence and serum inflammatory/oxidative stress markers, despite having higher HbA1c levels (p < 0.05). Combined SGLT2i/GLP-1RAs therapy reduced AF recurrence following catheter ablation and inflammatory/oxidative stress in T2DM patients. FAU - Sardu, Celestino AU - Sardu C AUID- ORCID: 0000-0001-5099-3790 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. FAU - Marfella, Raffaele AU - Marfella R AUID- ORCID: 0000-0003-3960-9270 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania Luigi Vanvitelli, 80138 Naples, Italy. LA - eng PT - Journal Article DEP - 20250923 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Atrial Fibrillation/drug therapy/etiology/surgery/therapy MH - Male MH - *Catheter Ablation MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Recurrence MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prospective Studies MH - Treatment Outcome MH - Drug Therapy, Combination MH - Oxidative Stress/drug effects MH - Glycated Hemoglobin MH - Biomarkers PMC - PMC12524772 OTO - NOTNLM OT - GLP-1Ras OT - SGLT2i OT - atrial fibrillation OT - diabetes mellitus type 2 COIS- The authors declare no conflicts of interest. EDAT- 2025/10/16 06:30 MHDA- 2025/10/16 06:31 PMCR- 2025/09/23 CRDT- 2025/10/16 01:11 PHST- 2025/08/26 00:00 [received] PHST- 2025/09/18 00:00 [revised] PHST- 2025/09/19 00:00 [accepted] PHST- 2025/10/16 06:31 [medline] PHST- 2025/10/16 06:30 [pubmed] PHST- 2025/10/16 01:11 [entrez] PHST- 2025/09/23 00:00 [pmc-release] AID - ijms26199285 [pii] AID - ijms-26-09285 [pii] AID - 10.3390/ijms26199285 [doi] PST - epublish SO - Int J Mol Sci. 2025 Sep 23;26(19):9285. doi: 10.3390/ijms26199285. PMID- 41094027 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 69 IP - 1 DP - 2026 Jan TI - Pre-stroke weight loss by glucagon-like peptide 1 receptor and neuropeptide Y receptor Y2 activation improves post-stroke functional recovery in male diabetic mouse models. PG - 230-243 LID - 10.1007/s00125-025-06567-4 [doi] AB - AIMS/HYPOTHESIS: Type 2 diabetes is associated with worsened stroke outcome and lasting disability. The underlying mechanisms are undetermined, and no therapy is available. We experimentally investigated whether pharmacologically targeting obesity, which is highly prevalent in type 2 diabetes, before stroke enhances neurological recovery in type 2 diabetes. To induce weight loss, we employed the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide and the neuropeptide Y receptor Y2 (NPY2R) agonist BI8271, which potentiates GLP-1R-mediated weight loss. We also investigated potential acute neuroprotective effects induced by these treatments, independently of metabolic regulation. METHODS: C57BL/6J mice were fed with a high-fat diet for 5 months to induce obesity and features of type 2 diabetes (i.e. hyperglycaemia and insulin resistance). Weight loss was induced by 4-week administration of semaglutide and/or BI8271. As a control for the effect of weight loss, a vehicle (PBS)-treated group was switched to standard diet to achieve the same weight range and the same percentage weight loss within the same time frame as those receiving semaglutide/BI8271. Thereafter, mice were subjected to stroke by transient middle cerebral artery occlusion (tMCAO). Stroke recovery (the primary outcome) was assessed by measuring the recovery of grip strength and the lateralised sensorimotor integration. Brains and serum were collected, and stroke volume and serum IGF-1 levels were quantified (secondary outcomes). In additional studies, type 2 diabetic mice were subjected to tMCAO and injected with semaglutide and/or BI8271 1 and 24 h after reperfusion. Acute neuroprotection (the primary outcome) was assessed by a grip strength test and by quantifying stroke volume and the number of surviving neuronal nuclear marker (NeuN)-positive neurons. RESULTS: We report that pre-stroke weight loss by GLP-1R activation, and more potently by dual co-activation of GLP-1 and NPY2 receptors, is a pharmacologically targetable mechanism, upstream of glycaemic regulation, through which post-stroke recovery is achieved. Moreover, we show that post-stroke recovery in type 2 diabetes is inversely associated with peripheral IGF-1 levels. Finally, GLP-1R and NPY2R activation can also improve stroke recovery through acute neuroprotection if they are given acutely after stroke, independently of their metabolic effects. CONCLUSIONS/INTERPRETATION: The diabetes and obesity epidemics are increasing the incidence of stroke, and consequently the need for treatments to improve stroke outcome. Our results indicate that clinically used type 2 diabetes treatments could be employed in a preventive role to improve stroke outcome by exerting dual pharmacological action: weight loss and acute neuroprotection. These findings could have novel therapeutic implications for many people. CI - (c) 2025. The Author(s). FAU - Vercalsteren, Ellen AU - Vercalsteren E AUID- ORCID: 0000-0002-9425-4209 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Karampatsi, Dimitra AU - Karampatsi D AUID- ORCID: 0000-0002-5316-088X AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Neicu, Maria AU - Neicu M AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Romanitan, Mihaela Oana AU - Romanitan MO AUID- ORCID: 0009-0001-4719-6624 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Haebel, Peter AU - Haebel P AUID- ORCID: 0009-0000-5861-9613 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Bleymehl, Katherin AU - Bleymehl K AUID- ORCID: 0009-0007-6269-1061 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Nystrom, Thomas AU - Nystrom T AUID- ORCID: 0000-0002-3462-7990 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Klein, Thomas AU - Klein T AUID- ORCID: 0000-0001-5762-9166 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Darsalia, Vladimer AU - Darsalia V AUID- ORCID: 0000-0002-6693-934X AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. vladimer.darsalia@ki.se. FAU - Patrone, Cesare AU - Patrone C AUID- ORCID: 0000-0003-0470-4606 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. cesare.patrone@ki.se. LA - eng PT - Journal Article DEP - 20251015 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Receptors, Neuropeptide Y) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (neuropeptide Y2 receptor) SB - IM MH - Animals MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Weight Loss/drug effects/physiology MH - *Stroke/metabolism/physiopathology/drug therapy MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - *Receptors, Neuropeptide Y/metabolism/agonists MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Recovery of Function/drug effects MH - Diet, High-Fat MH - *Diabetes Mellitus, Experimental/metabolism MH - Obesity/metabolism MH - Disease Models, Animal MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12686085 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor OT - Neuropeptide Y receptor Y2 OT - Stroke OT - Type 2 diabetes OT - Weight loss COIS- Acknowledgements: We thank F. Bahram (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for technical assistance, and H. Pettersson (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for advice on statistical analyses. Data availability: The data that support the findings of this study are not openly available for reasons of sensitivity, but are available from the corresponding author upon reasonable request. Data are located in controlled-access data storage (data repository) at the Karolinska Institutet. Funding: Open access funding provided by Karolinska Institute. Funding was provided by the Swedish Medical Research Council (to CP), the FANG Foundation and the Swedish Brain Foundation (to CP), the Swedish Heart-Lung Foundation (to TN), the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (to TN), the Ulla Hamberg Angeby och Lennart Angebys Stiftelse (to VD and EV), the Swedish Stroke Foundation (to CP, VD and EV), the Foundation for Geriatric Diseases at Karolinska Institutet (to EV), ALF Stockholm (to TN) and by a grant from Boehringer Ingelheim Pharma GmbH & Co. KG. Authors' relationships and activities: TN has received consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Merck and Sanofi. TK, PH and KB are employed at Boehringer Ingelheim Pharma GmbH & Co. KG. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: EV substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1-3, and part of the immunohistochemical and stereology analysis. Moreover, she drafted and critically reviewed the article with DK, and approved the final version of the manuscript. DK substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1 and 3 and part of the immunohistochemical and stereology analysis, and acquired/processed images. Moreover, she drafted and critically reviewed the article with EV, and approved the final version of the manuscript. MN performed part of the immunohistochemical studies and reviewed the article critically. MOR provided resources and contributed to the conception of the work. She also reviewed the manuscript. TN contributed to the conception of the study, provided resources, and critically revised the manuscript. PH synthesised the BI8271 compound and substantially contributed to the analysis and interpretation of data and critically reviewed the article. KB provided the data used to determine the doses of the compounds, contributed to the analysis and interpretation of data and critically reviewed the article. TK conceived the study and provided resources, including semaglutide/BI8271, and revised the manuscript. VD conceived and designed the study, performed the stroke experiments and part of the diabetic/functional tests, and edited the manuscript. CP conceived, designed and coordinated the research plan, and wrote the manuscript. All authors approved the final version to be published. EV, VD and CP are responsible for the integrity of the work as a whole. EDAT- 2025/10/16 05:31 MHDA- 2025/12/08 13:20 PMCR- 2025/10/15 CRDT- 2025/10/15 23:31 PHST- 2025/05/13 00:00 [received] PHST- 2025/07/23 00:00 [accepted] PHST- 2025/12/08 13:20 [medline] PHST- 2025/10/16 05:31 [pubmed] PHST- 2025/10/15 23:31 [entrez] PHST- 2025/10/15 00:00 [pmc-release] AID - 10.1007/s00125-025-06567-4 [pii] AID - 6567 [pii] AID - 10.1007/s00125-025-06567-4 [doi] PST - ppublish SO - Diabetologia. 2026 Jan;69(1):230-243. doi: 10.1007/s00125-025-06567-4. Epub 2025 Oct 15. PMID- 41093600 OWN - NLM STAT- MEDLINE DCOM- 20251015 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 5 DP - 2025 Oct 15 TI - Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial. LID - 10.1136/bmjdrc-2025-005161 [doi] LID - e005161 AB - INTRODUCTION: This study evaluated the long-term effectiveness of once-weekly subcutaneous semaglutide versus alternative treatment in adults with type 2 diabetes (T2D) in routine clinical practice. RESEARCH DESIGN AND METHODS: The SEmaglutide PRAgmatic (SEPRA) was a 2-year, randomized, open-label, pragmatic clinical trial (NCT03596450). Adults with T2D and inadequate glycemic control on one or two oral antidiabetic medications were randomized to receive once-weekly subcutaneous semaglutide or alternative treatment (chosen by the treating physician) as add-on therapy. Endpoints included proportion of participants achieving glycated hemoglobin (HbA(1c))<7.0% at year 1 (primary endpoint) and year 2; changes in HbA(1c) (percentage point), body weight, and patient-reported outcomes (PROs) at years 1 and 2; and treatment changes (baseline to year 2). Missing data were imputed for some analyses. RESULTS: Participants were randomized to semaglutide (n=644) or alternative treatment (n=634). Proportions of participants achieving HbA(1c) <7.0% were significantly higher with semaglutide versus alternative treatment at years 1 (53.1% vs 45.5%; OR (95% CI): 1.36 (1.03 to 1.79); p=0.033) and 2 (49.9% vs 38.9%; OR (95% CI): 1.56 (1.13 to 2.16); p=0.007). Mean HbA(1c) decreases were larger with semaglutide versus alternative treatment at year 1 (-1.35% vs -1.16%; estimated treatment difference (ETD) (95% CI): -0.20% (-0.39% to 0.00%); p=0.046) and year 2 (-1.27% vs -0.96%; ETD (95% CI): -0.31% (-0.57% to -0.05%); p=0.018). Semaglutide was associated with larger reductions in body weight at year 1 (-3.57% vs -1.91%; ETD (95% CI): -1.65% (-2.92% to -0.39%); p=0.010) but not year 2 (p=0.175). Treatment changes occurred less frequently with semaglutide than with alternative treatments. Some PROs indicated greater improvement with semaglutide versus alternative treatment. No new safety concerns were identified. CONCLUSIONS: SEPRA demonstrates that semaglutide is an appropriate choice for treatment intensification among individuals with T2D in the USA who are receiving 1-2 antidiabetic medications. Findings support semaglutide as an effective and well-tolerated option in clinical practice. TRIAL REGISTRATION NUMBER: NCT03596450. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA jbuse@med.unc.edu. FAU - Nordahl Christensen, Helene AU - Nordahl Christensen H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Harty, Brian J AU - Harty BJ AD - Carelon Research, Newton, Massachusetts, USA. FAU - Cziraky, Mark J AU - Cziraky MJ AD - Carelon Research, Wilmington, Delaware, USA. FAU - Willey, Vincent J AU - Willey VJ AD - Carelon Research, Wilmington, Delaware, USA. FAU - Skibsted, Simon AU - Skibsted S AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03596450 PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Pragmatic Clinical Trial PT - Randomized Controlled Trial DEP - 20251015 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - United States/epidemiology MH - Blood Glucose/analysis MH - Aged MH - Adult MH - Drug Administration Schedule MH - Follow-Up Studies MH - Treatment Outcome MH - *Biomarkers/analysis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12530410 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Glucagon-Like Peptide 1 COIS- Competing interests: JBB reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns, Vertex, and Zealand Pharma; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. HNC received support for the present manuscript from Novo Nordisk as an employee and holds stock or stock options for Novo Nordisk A/S. BJH received support for the present manuscript from Novo Nordisk as sponsor of the SEPRA trial; and contracted with his employer, Carelon Research, to serve as the data coordinating center for the trial, performing all data collection and analysis and supporting manuscript writing activities. MJC received support for the present manuscript from his employer, Carelon Research, which received funding from Novo Nordisk to perform the study services. He also holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of Carelon Research. VJW received support for the present manuscript from his employer, Carelon Research, which received funding from Novo Nordisk to perform the study services. He also holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of Carelon Research. SS received support for the present manuscript from Novo Nordisk as a full-time employee and holds stock or stock options for Novo Nordisk. EDAT- 2025/10/16 05:32 MHDA- 2025/10/16 05:33 PMCR- 2025/10/15 CRDT- 2025/10/15 21:22 PHST- 2025/04/09 00:00 [received] PHST- 2025/09/06 00:00 [accepted] PHST- 2025/10/16 05:33 [medline] PHST- 2025/10/16 05:32 [pubmed] PHST- 2025/10/15 21:22 [entrez] PHST- 2025/10/15 00:00 [pmc-release] AID - 13/5/e005161 [pii] AID - bmjdrc-2025-005161 [pii] AID - 10.1136/bmjdrc-2025-005161 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Oct 15;13(5):e005161. doi: 10.1136/bmjdrc-2025-005161. PMID- 41091469 OWN - NLM STAT- MEDLINE DCOM- 20251015 LR - 20261016 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 10 DP - 2025 Oct 1 TI - Glucose-Lowering Medication Classes and Cardiovascular Outcomes in Patients With Type 2 Diabetes. PG - e2536100 LID - 10.1001/jamanetworkopen.2025.36100 [doi] LID - e2536100 AB - IMPORTANCE: Major adverse cardiovascular events (MACEs) are primary causes of morbidity and mortality in adults with type 2 diabetes (T2D), yet few head-to-head randomized trials have compared the effects of glucose-lowering medications on MACEs, and most observational analyses are limited by inadequate bias adjustment methods. OBJECTIVE: To compare the effectiveness of sustained exposure to 4 classes of glucose-lowering medications (sulfonylureas, dipeptidyl peptidase-4 inhibitors [DPP4is], sodium-glucose cotransporter-2 inhibitors [SGLT2is], and glucagon-like peptide-1 receptor agonists [GLP-1RAs]) on MACEs in US adults with T2D using modern causal methods combined with machine learning. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study included adults with T2D who were members of 6 large US health care delivery systems and initiated treatment with 1 of 4 medication classes (sulfonylureas, DPP4is, SGLT2is, and GLP-1RAs) between January 1, 2014, and December 31, 2021. Data analysis was conducted from May 1 to December 31, 2024. EXPOSURE: New use of a sulfonylurea, DPP4i, SGLT2i, or GLP-1RA based on filled prescriptions. MAIN OUTCOMES AND MEASURES: The primary outcome was MACEs defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Analyses were conducted using targeted learning within a trial emulation framework. Heterogeneity of treatment effects was assessed for prespecified subgroups. RESULTS: This study included 296 676 adults. The cohort for emulating a 4-arm trial included a subset of 241 981 adults (mean [SD] age, 57.2 [12.9] years; 54.3% male) with T2D. In adjusted analyses, 2.5-year MACE risk was lowest in patients with sustained exposure to GLP-1RAs, followed by SGLT2is , sulfonylureas, and DPP4is. Comparing DPP4is with sulfonylureas and SGLT2is with GLP-1RAs, the 2.5-year cumulative risk difference was 1.9% (95% CI, 1.1%-2.7%) and 1.5% (1.1%-1.9%), respectively. Risk differences in patients with vs without atherosclerotic cardiovascular disease (ASCVD) were similar in direction but typically much smaller for patients without ASCVD. Evidence of a benefit of GLP-1RAs over SGLT2is was most pronounced in patients with baseline ASCVD or heart failure (HF), age 65 years or older, or low to moderate kidney impairment but was not found in patients younger than 50 years. CONCLUSIONS AND RELEVANCE: In this study, MACE risk varied significantly by medication class, with most protection achieved with sustained treatment with GLP-1RAs followed by SGLT2is, sulfonylureas, and DPP4is. The magnitude of benefit of GLP-1RAs over SGLT2is depended on baseline age, ASCVD, HF, and kidney impairment. These results, along with consideration of cost, availability, and collateral clinical benefits, may inform treatment decisions for adults with T2D. FAU - Neugebauer, Romain AU - Neugebauer R AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - An, Jaejin AU - An J AD - Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena. FAU - Dombrowski, Sarah Krahe AU - Dombrowski SK AD - Center for Pharmacy Innovation and Outcomes, Geisinger, Danville, Pennsylvania. FAU - Oshiro, Caryn AU - Oshiro C AD - Center for Integrated Health Care Research, Kaiser Permanente Hawaii, Honolulu. FAU - Cassidy-Bushrow, Andrea AU - Cassidy-Bushrow A AD - Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan. AD - Michigan State University Health Sciences, Detroit. AD - Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing. FAU - Gilliam, Lisa AU - Gilliam L AD - Endocrinology and Internal Medicine, Kaiser Permanente Northern California, South San Francisco. FAU - Simonson, Gregg AU - Simonson G AD - HealthPartners Institute, International Diabetes Center, Minneapolis, Minnesota. FAU - Karter, Andrew J AU - Karter AJ AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Bergenstal, Richard AU - Bergenstal R AD - HealthPartners Institute, International Diabetes Center, Minneapolis, Minnesota. FAU - Finertie, Holly AU - Finertie H AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Yassin, Maher M AU - Yassin MM AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Knowlton, Greg AU - Knowlton G AD - HealthPartners Institute, Minneapolis, Minnesota. FAU - Lin, Sharon R AU - Lin SR AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Dyer, Wendy AU - Dyer W AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Pimentel, Noel AU - Pimentel N AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Izadian, Keanu AU - Izadian K AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Schmittdiel, Julie AU - Schmittdiel J AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Thomas, Tainayah W AU - Thomas TW AD - Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California. FAU - Hooker, Stephanie A AU - Hooker SA AD - HealthPartners Institute, Minneapolis, Minnesota. FAU - Nolan, Margaret B AU - Nolan MB AD - HealthPartners Institute, Minneapolis, Minnesota. FAU - Wright, Eric AU - Wright E AD - Center for Pharmacy Innovation and Outcomes, Geisinger, Danville, Pennsylvania. FAU - Aurora, Lindsey AU - Aurora L AD - Division of Cardiology, Department of Medicine, Henry Ford Health, Detroit, Michigan. FAU - Rodriguez, Luis A AU - Rodriguez LA AD - Division of Research, Kaiser Permanente Northern California, Pleasanton. FAU - Kaur, Jasleen AU - Kaur J AD - Department of Endocrinology, HealthPartners, St Paul, Minnesota. FAU - Adams, Alyce S AU - Adams AS AD - Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California. AD - Department of Health Policy, Stanford University School of Medicine, Stanford, California. FAU - van der Laan, Mark J AU - van der Laan MJ AD - Division of Biostatistics, School of Public Health, University of California, Berkeley. FAU - O'Connor, Patrick J AU - O'Connor PJ AD - HealthPartners Institute, Minneapolis, Minnesota. LA - eng GR - P30 DK092924/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/classification MH - *Cardiovascular Diseases/epidemiology/mortality/etiology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Sulfonylurea Compounds/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Comparative Effectiveness Research MH - United States/epidemiology PMC - PMC12529185 COIS- Conflict of Interest Disclosures: Dr Neugebauer reported receiving grants from the Patient Centered Outcomes Research Institute (PCORI) and the National Institutes of Health (NIH) during the conduct of the study. Dr An reported receiving grants (to Kaiser Permanente Southern California) from PCORI during the conduct of the study and grants from AstraZeneca, Merck LLC, and Bayer outside the submitted work. Dr Dombrowski reported receiving grants from PCORI during the conduct of the study. Dr Oshiro reported receiving grants from PCORI during the conduct of the study. Dr Simonson reported receiving grants from HealthPartners Institute during the conduct of the study and grants from Novo Nordisk, Abbott Diabetes Care, Dexcom, and Sanofi outside the submitted work. Dr Karter reported receiving grants from PCORI during the conduct of the study. Dr Bergenstal reported receiving grants (to HealthPartners Institute) from Abbott Diabetes Care, Eli Lilly, Novo Nordisk, DexCom, and Zealand outside the submitted work. In additional, Dr Bergenstal reported consulting for or serving on advisory boards (with support to HealthPartners Institute) to Abbott Diabetes Care, Eli Lilly, Novo Nordisk, DexCom, Zealand, Sanofi, and Roche outside the submitted work. Mr Yassin reported receiving grants from PCORI during the conduct of the study. Ms Dyer reported receiving grants from PCORI during the conduct of the study. Dr Schmittdiel reported receiving grants from PCORI during the conduct of the study. Dr Thomas reported receiving grants from PCORI during the conduct of the study and grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Minority Health and Disparities outside the submitted work. Dr Wright reported receiving grants from PCORI during the conduct of the study and personal fees from AstraZeneca outside the submitted work. Dr Adams reported receiving grants from PCORI and the NIDDK during the conduct of the study. Dr O'Connor reported receiving grants from the NIH outside the submitted work. No other disclosures were reported. EDAT- 2025/10/15 12:31 MHDA- 2025/10/15 18:28 PMCR- 2025/10/15 CRDT- 2025/10/15 11:33 PHST- 2025/10/15 18:28 [medline] PHST- 2025/10/15 12:31 [pubmed] PHST- 2025/10/15 11:33 [entrez] PHST- 2025/10/15 00:00 [pmc-release] AID - 2840139 [pii] AID - zoi251004 [pii] AID - 10.1001/jamanetworkopen.2025.36100 [doi] PST - epublish SO - JAMA Netw Open. 2025 Oct 1;8(10):e2536100. doi: 10.1001/jamanetworkopen.2025.36100. PMID- 41090945 OWN - NLM STAT- MEDLINE DCOM- 20251028 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 28 IP - 1 DP - 2025 Dec TI - The cost-effectiveness of subcutaneous semaglutide 2.4 mg in the management of people living with obesity and prediabetes in England. PG - 1887-1898 LID - 10.1080/13696998.2025.2575692 [doi] AB - BACKGROUND: Prediabetes and type 2 diabetes (T2D) are more prevalent amongst people living with obesity (PwO). T2D and obesity increase the risk of cardiovascular disease. In the STEP clinical development program, once-weekly subcutaneous semaglutide (2.4 mg) reduced body weight by 10-15% and reversed prediabetes in about 80% of patients. The aim of this study was to assess the cost-effectiveness of semaglutide plus diet and exercise (D&E) compared with D&E alone in PwO and prediabetes in England based on the STEP-10 trial. METHODS: The published Core Obesity Model was populated with baseline characteristics and treatment efficacy from STEP-10. This study assessed the reversal of prediabetes at 52 weeks. Baseline age and body mass index (BMI) were 53 (SD = 11) years and 40.1 (6.9) kg/m(2). At 52 weeks, semaglutide plus D&E and D&E alone reversed prediabetes in 80% and 12% of patients, and decreased BMI by 13.9% and 2.7%, respectively. The perspective of the NHS was considered using annual discounting rates of 3.5% on costs and outcomes. Several subgroups were assessed: Different baseline BMI, number of comorbidities, proportions of prediabetes and different treatment durations. Individuals losing >/= 5% of body weight after 20 weeks (responders) were analysed separately. RESULTS: The treatment duration in the base case analysis was 20 years. The use of semaglutide resulted in 1.105 QALY gained at an additional cost of 19,391 GBP. The resulting ICER was 17,547 GBP/QALY gained. Treatment with semaglutide extended life expectancy by 1.68 years. Ranging treatment duration between 1 year as per STEP 10 trial and lifelong resulted in an ICER of 7,152 to 17,695 GBP/QALY. Results did not differ significantly by subgroup. The probabilistic sensitivity analysis indicated a 90% chance of semaglutide being cost-effective at a willingness-to-pay threshold of 20,000 GBP/QALY. CONCLUSION: Semaglutide is a cost-effective treatment option for PwO and prediabetes in England based on the results of the STEP-10 trial. FAU - Ramos, Mafalda AU - Ramos M AUID- ORCID: 0000-0002-8472-3841 AD - Th(is)2Modeling bv, Asse, Belgium. FAU - Larsen, Sara AU - Larsen S AUID- ORCID: 0000-0002-3887-4948 AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Fusco, Francesco AU - Fusco F AUID- ORCID: 0000-0001-5515-3977 AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Lamotte, Mark AU - Lamotte M AD - Th(is)2Modeling bv, Asse, Belgium. FAU - Capehorn, Matthew AU - Capehorn M AUID- ORCID: 0000-0002-8196-2505 AD - Rotherham Institute for Obesity, Rotherham, UK. LA - eng PT - Journal Article DEP - 20251028 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Cost-Benefit Analysis MH - *Glucagon-Like Peptides/economics/administration & dosage/therapeutic use MH - *Prediabetic State/drug therapy/therapy/complications MH - Female MH - Middle Aged MH - England MH - *Obesity/drug therapy/complications/therapy MH - Male MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy MH - Quality-Adjusted Life Years MH - Adult MH - *Hypoglycemic Agents/economics/therapeutic use/administration & dosage MH - Injections, Subcutaneous MH - Exercise Therapy/economics MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - B41 OT - Core Obesity Model OT - Cost-effectiveness OT - I10 OT - I15 OT - Markov model OT - cardiovascular disease OT - obesity OT - prediabetes OT - semaglutide EDAT- 2025/10/15 12:31 MHDA- 2025/10/28 18:27 CRDT- 2025/10/15 09:04 PHST- 2025/10/28 18:27 [medline] PHST- 2025/10/15 12:31 [pubmed] PHST- 2025/10/15 09:04 [entrez] AID - 10.1080/13696998.2025.2575692 [doi] PST - ppublish SO - J Med Econ. 2025 Dec;28(1):1887-1898. doi: 10.1080/13696998.2025.2575692. Epub 2025 Oct 28. PMID- 41090391 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Comparative healthcare resource utilization and costs of empagliflozin and GLP-1 receptor agonists in type 2 diabetes. PG - 324-336 LID - 10.1111/dom.70195 [doi] AB - AIMS: Understanding the real-world impact of treatment with empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) on healthcare resource utilization (HCRU) and costs could help inform clinical decision-making and healthcare policy. MATERIALS AND METHODS: We conducted a comparative-effectiveness cohort study comparing HCRU and costs following empagliflozin versus GLP-1RA treatment in adults with type 2 diabetes (>/=18 years) using US Medicare and commercial claims (08/2014-09/2019). We estimated rate ratios (RR) for HCRU outcomes using zero-inflated negative binomial regression and cost differences per member per year (PMPY) using gamma regression after adjusting for 143 baseline covariates via propensity score matching. RESULTS: We identified 146,341 matched pairs across all databases. After matching, the rates of hospital days, hospitalizations, emergency department (ED) visits, and physician office visits were similar between treatments. Empagliflozin had lower rates of dispensed medication classes versus GLP-1RA across most databases (RRs ranged from 0.91 to 0.95, RDs from -1246 to -709 per 1000 PY, reflecting varying degrees of precision). Total costs of care were lower with empagliflozin versus GLP-1RA. PMPY ratios ranged from 0.93 to 0.97 and differences from -$1425 to -$847. Inpatient and outpatient costs were comparable between treatments. Empagliflozin had lower pharmacy costs than GLP-1RA, mainly driven by glucose-lowering medications (PMPY ratios ranging from 0.91 to 0.95; PMPY differences from -$799 to -$441). CONCLUSIONS: Among adults with diabetes, empagliflozin was associated with similar rates of inpatient days, hospitalizations, ED, and office visits, with lower dispensed medication rates compared with GLP-1RA. Empagliflozin initiators incurred lower total costs, driven by lower glucose-lowering medication costs. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Htoo, Phyo Than AU - Htoo PT AUID- ORCID: 0000-0003-4742-8306 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - DiCesare, Elyse AU - DiCesare E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Freedman, Ariel AU - Freedman A AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Schmedt, Niklas AU - Schmedt N AD - Global Epidemiology, Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Shay, Christina AU - Shay C AD - Global Epidemiology, Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - 116283/Boehringer Ingelheim/ GR - 4-22-PDFPM-15/American Diabetes Association/ GR - 5K08AG055670/AG/NIA NIH HHS/United States GR - 5U01FD007213/FD/FDA HHS/United States GR - 5K08AG055670/AG/NIA NIH HHS/United States GR - 5U01FD007213/FD/FDA HHS/United States PT - Comparative Study PT - Journal Article DEP - 20251015 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Benzhydryl Compounds) RN - HDC1R2M35U (empagliflozin) RN - 0 (Glucosides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Benzhydryl Compounds/therapeutic use/economics MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucosides/therapeutic use/economics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - Aged MH - *Patient Acceptance of Health Care/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use/economics MH - *Health Care Costs/statistics & numerical data MH - United States/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - *Health Resources/statistics & numerical data/economics MH - Adult MH - Comparative Effectiveness Research MH - Hospitalization/economics/statistics & numerical data OTO - NOTNLM OT - Medicare OT - RWD OT - diabetes mellitus, type 2 OT - empagliflozin OT - glucagon-like peptide-1 receptor agonists OT - health care costs OT - health services utilization OT - real-world data OT - real-world evidence OT - sodium-glucose transporter 2 inhibitors EDAT- 2025/10/15 12:32 MHDA- 2025/12/03 14:12 CRDT- 2025/10/15 06:13 PHST- 2025/09/23 00:00 [revised] PHST- 2025/06/20 00:00 [received] PHST- 2025/10/02 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/10/15 12:32 [pubmed] PHST- 2025/10/15 06:13 [entrez] AID - 10.1111/dom.70195 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):324-336. doi: 10.1111/dom.70195. Epub 2025 Oct 15. PMID- 41088952 OWN - NLM STAT- MEDLINE DCOM- 20260102 LR - 20260127 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 40 IP - 6 DP - 2025 Dec TI - Early Dose Escalation of Tirzepatide after Switching from Semaglutide in Type 2 Diabetes Mellitus. PG - 1012-1015 LID - 10.3803/EnM.2025.2420 [doi] AB - Tirzepatide has demonstrated greater efficacy than semaglutide in improving glycemic control and reducing body weight in patients with type 2 diabetes mellitus (T2DM). However, the optimal tirzepatide dose following a switch from 1.0 mg of semaglutide remains unclear. This retrospective study included 15 T2DM patients who switched to tirzepatide due to inadequate weight loss. All patients started tirzepatide at 2.5 mg, with escalation to either 7.5 mg (n=10) or 10 mg (n=5). Changes in glycated hemoglobin (HbA1c) and body weight were assessed over a 3-month period. The 10 mg group experienced a significant reduction in HbA1c (-0.7%+/-0.3%, P<0.01) and a non-significant trend toward weight loss (-6.6+/-5.4 kg, P=0.07). In contrast, no significant changes were observed in the 7.5 mg group. There were no statistically significant differences between groups. Since 10 mg of tirzepatide significantly improved glycemic control after switching from 1.0 mg of semaglutide, early escalation to 10 mg may be beneficial for patients who respond inadequately to semaglutide. FAU - Kurinami, Noboru AU - Kurinami N AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. AD - Kurinami Clinic, Kanzaki, Kumamoto, Japan. FAU - Takada, Masafumi AU - Takada M AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Sugiyama, Seigo AU - Sugiyama S AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Cardiovascular Medicine, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Yoshida, Akira AU - Yoshida A AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Hieshima, Kunio AU - Hieshima K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Suzuki, Tomoko AU - Suzuki T AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Miyamoto, Fumio AU - Miyamoto F AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Kajiwara, Keizo AU - Kajiwara K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Jinnouchi, Katsunori AU - Jinnouchi K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Ashida, Kenji AU - Ashida K AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Nomura, Masatoshi AU - Nomura M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Jinnouchi, Hideaki AU - Jinnouchi H AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital, Kumamoto, Japan. LA - eng PT - Journal Article DEP - 20251015 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Tirzepatide MH - Blood Glucose/analysis MH - Drug Substitution MH - Dose-Response Relationship, Drug MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12765867 OTO - NOTNLM OT - Body weight reduction OT - Diabetes mellitus, type 2 OT - Dose escalation OT - Semaglutide OT - Tirzepatide COIS- CONFLICTS OF INTEREST Hideaki Jinnouchi has received honoraria from Novo Nordisk, Sanofi, Eli Lilly, Mitsubishi Tanabe Pharma, and Otsuka Pharmaceutical. Seigo Sugiyama has received honoraria from Astra-Zeneca Pharmaceuticals and Ono Pharmaceutical. All other authors declare no conflicts of interest. EDAT- 2025/10/15 06:30 MHDA- 2026/01/02 06:28 PMCR- 2025/12/01 CRDT- 2025/10/15 03:40 PHST- 2025/04/18 00:00 [received] PHST- 2025/06/09 00:00 [accepted] PHST- 2026/01/02 06:28 [medline] PHST- 2025/10/15 06:30 [pubmed] PHST- 2025/10/15 03:40 [entrez] PHST- 2025/12/01 00:00 [pmc-release] AID - EnM.2025.2420 [pii] AID - enm-2025-2420 [pii] AID - 10.3803/EnM.2025.2420 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2025 Dec;40(6):1012-1015. doi: 10.3803/EnM.2025.2420. Epub 2025 Oct 15. PMID- 41086442 OWN - NLM STAT- MEDLINE DCOM- 20251201 LR - 20251201 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 103 IP - 12 DP - 2025 Dec 1 TI - Anti-inflammatory properties of GLP-1 receptor agonists and other ancillary benefits from a pharmacological perspective. PG - 369-377 LID - 10.1139/cjpp-2025-0148 [doi] AB - Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), exert a wide range of beneficial effects beyond glycemic control, largely mediated by their anti-inflammatory properties. Chronic low-grade inflammation is a common pathological mechanism underlying metabolic, cardiovascular, hepatic, and neurodegenerative diseases. GLP-1RAs reduce systemic and tissue-specific inflammation through both direct and indirect mechanisms, including inhibition of nuclear factor kappa B signaling, reduction of proinflammatory cytokines, and modulation of immune cell activity, such as that of macrophages and microglia. In type 2 diabetes and obesity, GLP-1RAs improve insulin sensitivity and endothelial function by attenuating inflammation. In metabolic dysfunction-associated steatotic liver disease, GLP-1RAs reduce hepatic steatosis and fibrosis by modulating inflammation in hepatocytes and Kupffer cells. In cardiovascular disease, they mitigate atherosclerosis progression and improve vascular health. GLP-1RAs also exert direct nephroprotective effects by reducing renal inflammation, oxidative stress, and glomerular hyperfiltration in both diabetic and nondiabetic models. GLP-RAs have been also associated with the preservation of cognitive and motor function. Preclinical studies suggest that these neuroprotective effects may involve the attenuation of neuroinflammation and reduced aggregation of pathological proteins. Overall, these pleiotropic actions position incretin-based therapies as promising tools for the management of complex chronic diseases with an inflammatory component. FAU - Ros-Madrid, Inmaculada AU - Ros-Madrid I AUID- ORCID: 0000-0001-6862-1012 AD - Department of Endocrinology and Nutrition, Virgen de la Arrixaca University Hospital, 30120 Murcia, Spain. RINGGOLD: 16518 AD - Obesity, Diabetes and Metabolism Research Group, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. FAU - Cano-Marmol, Rosario Paloma AU - Cano-Marmol R AD - Department of Endocrinology and Nutrition, Virgen de la Arrixaca University Hospital, 30120 Murcia, Spain. RINGGOLD: 16518 AD - Obesity, Diabetes and Metabolism Research Group, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. FAU - Ferrer-Gomez, Mercedes AU - Ferrer-Gomez M AD - Department of Endocrinology and Nutrition, Virgen de la Arrixaca University Hospital, 30120 Murcia, Spain. RINGGOLD: 16518 AD - Obesity, Diabetes and Metabolism Research Group, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. FAU - Ramos-Molina, Bruno AU - Ramos-Molina B AD - Obesity, Diabetes and Metabolism Research Group, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. LA - eng PT - Journal Article PT - Review DEP - 20251118 PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Anti-Inflammatory Agents/therapeutic use/pharmacology MH - *Inflammation/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Incretins/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - chronic inflammation OT - metabolic diseases OT - neuroprotection COIS- The authors declare there are no competing interests. EDAT- 2025/10/14 18:29 MHDA- 2025/12/01 12:28 CRDT- 2025/10/14 17:43 PHST- 2025/12/01 12:28 [medline] PHST- 2025/10/14 18:29 [pubmed] PHST- 2025/10/14 17:43 [entrez] AID - 10.1139/cjpp-2025-0148 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2025 Dec 1;103(12):369-377. doi: 10.1139/cjpp-2025-0148. Epub 2025 Nov 18. PMID- 41085793 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20261010 IS - 1573-4986 (Electronic) IS - 0282-0080 (Linking) VI - 42 IP - 5-6 DP - 2025 Dec TI - The effects of DPP4 inhibitors, SGLT2 inhibitors and GLP1-RA on the AGE/RAGE pathway: implications for diabetes and its complications. PG - 225-238 LID - 10.1007/s10719-025-10197-8 [doi] AB - It is predicted that by 2045, diabetes will affect approximately 700 million individuals worldwide with increased morbidity, mortality and healthcare costs. Diabetes results in both microvascular and macrovascular complications, resulting in end-organ damage of blindness, renal failure, neuropathy and amputations, and increased cardiovascular disease, resulting in an enhanced mortality rate. The pathophysiology of diabetic complications involves the development of advanced glycation end products (AGEs) through nonenzymatic glycation interactions with proteins and nucleic acids, which is exacerbated by the persistent hyperglycemic state in type 2 diabetes mellitus. A key player in this process is the cellular receptor for AGEs, known as RAGE. AGEs activate RAGE by initiating various signalling pathways that contribute to increased oxidative stress and inflammation. These detrimental effects include impaired insulin signalling, disruption of metabolic homeostasis, toxicity to pancreatic beta cells, and epigenetic changes. To address diabetes glycemic control and its associated complications, several classes of drugs have been introduced to the market. Among them are GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors. These medications employ different mechanisms of action to achieve glycemic control and have additional benefits. One such mechanism involves targeting the AGE/RAGE pathway, which reduces oxidative stress and inflammation by decreasing the formation of AGEs and suppressing RAGE expression in various organs. This approach shows potential in improving diabetes management and mitigating its resultant diabetes-related complications. FAU - Abolfazli, Sajad AU - Abolfazli S AD - Student Research Committee, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran. FAU - Atkin, Stephen L AU - Atkin SL AD - Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain. FAU - Jamialahmadi, Tannaz AU - Jamialahmadi T AD - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. amir_saheb2000@yahoo.com. AD - Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India. amir_saheb2000@yahoo.com. AD - Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. amir_saheb2000@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20251014 PL - United States TA - Glycoconj J JT - Glycoconjugate journal JID - 8603310 RN - 0 (Glycation End Products, Advanced) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glycation End Products, Advanced/metabolism MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/pharmacology MH - *Receptor for Advanced Glycation End Products/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Signal Transduction/drug effects MH - *Diabetes Complications/metabolism/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Oxidative Stress/drug effects OTO - NOTNLM OT - AGE OT - DPP-4 inhibitors OT - Diabetes OT - GLP-1RA OT - RAGE OT - SGLT-2 inhibitors COIS- Declarations. Ethics approval: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/10/14 12:30 MHDA- 2026/06/27 00:52 CRDT- 2025/10/14 11:18 PHST- 2024/09/01 00:00 [received] PHST- 2025/09/08 00:00 [accepted] PHST- 2025/07/24 00:00 [revised] PHST- 2026/06/27 00:52 [medline] PHST- 2025/10/14 12:30 [pubmed] PHST- 2025/10/14 11:18 [entrez] AID - 10.1007/s10719-025-10197-8 [pii] AID - 10.1007/s10719-025-10197-8 [doi] PST - ppublish SO - Glycoconj J. 2025 Dec;42(5-6):225-238. doi: 10.1007/s10719-025-10197-8. Epub 2025 Oct 14. PMID- 41083699 OWN - NLM STAT- MEDLINE DCOM- 20251014 LR - 20251120 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Oct 13 TI - Association between glucagon-like peptide-1 receptor agonist therapy and respiratory illness in patients with type 2 diabetes: a retrospective observational cohort study. PG - 35625 LID - 10.1038/s41598-025-19657-5 [doi] LID - 35625 AB - Studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide lung benefits beyond glycemic control, including reduced risks of lung malignancy, pulmonary infection and chronic obstructive pulmonary disease exacerbations. A retrospective cohort study with a new-user and active-comparator design was conducted using the TriNetX US Network. Adults (>/= 18 years) with Type 2 diabetes mellitus (T2DM) (n = 3,389,059) from January 1, 2005, to December 31, 2020, were identified. Two cohorts of new GLP-1 RA (n = 201,153) and new dipeptidyl peptidase-4 inhibitor (DPP4i) (n = 323,114) users were created. Propensity score matching was used to create comparable cohorts. The primary outcome was lung cancer, while other pulmonary conditions were secondary outcomes over a 10-year follow-up. Through 1:1 propensity score matching, two balanced cohorts of GLP-1 RA and DPP4i (n = 158,224) users were created. GLP-1 RA users had a significantly lower risk of lung cancer than did DPP4i users (hazard ratios [HR] 0.86; 95% confidence interval [CI] 0.80-0.94). Reduced risk of influenza and pneumonia (HR 0.94; 95% CI 0.92-0.96) and pulmonary fibrosis (HR 0.92; 95% CI 0.87-0.98) were also noted in GLP-1 RA users. Our findings indicate that GLP-1 RAs may lower the risks of lung cancer, pulmonary fibrosis, and respiratory infections, meriting further prospective study. CI - (c) 2025. The Author(s). FAU - Ho, Li-Ti AU - Ho LT AD - Department of General Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Department of Medicine, Fu-Jen Catholic University School of Medicine, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 242062, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. FAU - Hsu, Pei-Sung AU - Hsu PS AD - Department of General Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. AD - Division of Pulmonology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. FAU - Wang, Jing-Tong AU - Wang JT AD - Department of Healthcare Management, National Taipei University of Nursing and Health Sciences, No. 89, Neijiang St., Wanhua Dist., Taipei City, 108306, Taiwan. AD - Data Analysis Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AD - Department of General Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. chaosmyth.tw@gmail.com. AD - Department of Medicine, Fu-Jen Catholic University School of Medicine, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 242062, Taiwan. chaosmyth.tw@gmail.com. AD - Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-Chang Rd, Shih-Lin Dist., Taipei, 11101, Taiwan. chaosmyth.tw@gmail.com. LA - eng PT - Journal Article PT - Observational Study DEP - 20251013 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Lung Neoplasms/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - Pulmonary Disease, Chronic Obstructive MH - Adult PMC - PMC12518849 OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitor OT - Glucagon-like peptide-1 receptor agonist OT - Lung cancer OT - Real-world evidence OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/10/14 00:29 MHDA- 2025/10/14 06:28 PMCR- 2025/10/13 CRDT- 2025/10/14 00:01 PHST- 2025/07/08 00:00 [received] PHST- 2025/09/09 00:00 [accepted] PHST- 2025/10/14 06:28 [medline] PHST- 2025/10/14 00:29 [pubmed] PHST- 2025/10/14 00:01 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - 10.1038/s41598-025-19657-5 [pii] AID - 19657 [pii] AID - 10.1038/s41598-025-19657-5 [doi] PST - epublish SO - Sci Rep. 2025 Oct 13;15(1):35625. doi: 10.1038/s41598-025-19657-5. PMID- 41082229 OWN - NLM STAT- MEDLINE DCOM- 20251013 LR - 20260723 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 10 DP - 2025 Oct 1 TI - Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes. PG - e2537297 LID - 10.1001/jamanetworkopen.2025.37297 [doi] LID - e2537297 AB - IMPORTANCE: The head-to-head comparative effectiveness and safety of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) are not well understood. OBJECTIVE: To compare risks of kidney, cardiovascular, and death outcomes among patients with type 2 diabetes initiating GLP-1RAs in the Department of Veterans Affairs (VA) health system. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study used an active-comparator, new-user target trial-emulation design with national data linked among the VA, Medicare, and US Renal Data System. Participants were GLP-1RA-naive veterans with type 2 diabetes and without end-stage kidney disease treated with metformin who started liraglutide, semaglutide, or dulaglutide between January 1, 2018, and December 31, 2021. Data were analyzed from September 2024 to June 2025. EXPOSURE: Liraglutide, semaglutide, or dulaglutide. MAIN OUTCOMES AND MEASURES: Kidney failure (sustained estimated glomerular filtration rate <15 mL/min/1.73 m2 or initiation of kidney replacement therapy), composite cardiovascular and kidney metabolic (CKM) events (kidney failure or major adverse cardiovascular events [MACE]; myocardial infarction, heart failure, or stroke/transient ischemic attack), MACE, all-cause death, and adverse gastrointestinal events (gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis) were evaluated separately through March 31, 2023. RESULTS: Of 21 790 included veterans (mean [SD] age, 63.5 [10.8] years, 19 823 [91.0%] male), 5425 (24.9%), 10 838 (49.7%), and 5527 (24.9%) initiated liraglutide, semaglutide, and dulaglutide, respectively. In weighted Cox regression models, compared with initiation of semaglutide, liraglutide initiation had similar hazards for kidney failure (hazard ratio [HR], 0.93; 95% CI, 0.60-1.44), the CKM composite outcome (HR, 0.96; 95% CI, 0.84-1.10), and MACE (HR, 0.95; 95% CI, 0.83-1.09). Results were similar with liraglutide vs dulaglutide and dulaglutide vs semaglutide comparisons. Liraglutide had significantly lower hazard of all-cause death compared with semaglutide under intent-to-treat analyses (HR, 0.83; 95% CI, 0.69-0.99), which lost significance in per-protocol models. Compared with dulaglutide, liraglutide was associated with a lower risk of all-cause mortality in both the intent-to-treat (HR, 0.69; 95% CI, 0.58-0.83) and per-protocol (HR, 0.50; 95% CI, 0.31-0.82) analyses, but compared with semaglutide, dulaglutide had higher hazard of mortality only in the per-protocol model (HR, 1.72; 95% CI, 1.20-2.47). The only observed difference for the gastrointestinal adverse events was a decreased risk for gallstones and acute cholecystitis with dulaglutide vs semaglutide (gallstones: HR, 0.72; 95% CI, 0.54-0.95; acute cholecystitis: HR, 0.62; 95% CI, 0.39-0.99). CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study in veterans with diabetes, liraglutide, semaglutide, and dulaglutide initiators had similar risks for kidney and cardiovascular outcomes. Head-to-head randomized trials are needed to confirm these findings. FAU - Derington, Catherine G AU - Derington CG AD - Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora. AD - Adult & Child Center for Outcomes Research & Delivery Science, University of Colorado Anschutz Medical Campus, Aurora. FAU - Sarwal, Amara AU - Sarwal A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Wei, Guo AU - Wei G AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Hartsell, Sydney E AU - Hartsell SE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, Salt Lake City. FAU - Throolin, Michael AU - Throolin M AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. FAU - Singh, Ravinder AU - Singh R AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. FAU - Nevers, McKenna R AU - Nevers MR AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Informatics, Decision-Enhancement, and Analytic Sciences Center of Innovation, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Zhang, Chong AU - Zhang C AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Katkam, Niharika AU - Katkam N AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Takyi, Augustine AU - Takyi A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Chakravartula, Akhil R AU - Chakravartula AR AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Babu, Poorvika AU - Babu P AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Deshmukh, Vikrant G AU - Deshmukh VG AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Boucher, Robert E AU - Boucher RE AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Drakos, Stavros G AU - Drakos SG AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, Salt Lake City. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Greene, Tom AU - Greene T AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Shen, Jincheng AU - Shen J AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Beddhu, Srinivasan AU - Beddhu S AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.37304 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liraglutide/therapeutic use/adverse effects MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Veterans/statistics & numerical data MH - Middle Aged MH - United States MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Comparative Effectiveness Research MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12519307 COIS- Conflict of Interest Disclosures: Dr Hartsell reported receiving grants from National Kidney Foundation, Bayer, and Women in Nephrology outside the submitted work. Dr Drakos reported receiving personal fees from Abbott and Novartis outside the submitted work. Dr Greene reported receiving research funding from National Kidney Foundation, The Collaborative Study Group, National Institutes of Health (NIH), and Patient-Centered Outcomes Research Institute outside the submitted work. No other disclosures were reported. EDAT- 2025/10/13 12:30 MHDA- 2025/10/13 18:29 PMCR- 2025/10/13 CRDT- 2025/10/13 11:33 PHST- 2025/10/13 18:29 [medline] PHST- 2025/10/13 12:30 [pubmed] PHST- 2025/10/13 11:33 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - 2840010 [pii] AID - zoi251028 [pii] AID - 10.1001/jamanetworkopen.2025.37297 [doi] PST - epublish SO - JAMA Netw Open. 2025 Oct 1;8(10):e2537297. doi: 10.1001/jamanetworkopen.2025.37297. PMID- 41079186 OWN - NLM STAT- MEDLINE DCOM- 20251013 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Predictive factors of body weight loss in patients with type 2 diabetes treated with GLP-1 receptor agonists: a 52-week prospective real-life study. PG - 1674308 LID - 10.3389/fendo.2025.1674308 [doi] LID - 1674308 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for their efficacy in glycemic control and weight reduction, but patient response is heterogeneous and predictors of weight loss remain insufficiently defined. This 52-week prospective, observational study aimed to identify predictors of weight reduction (>/=5% from baseline) in patients with type 2 diabetes mellitus (T2D) undergoing GLP-1RA therapy (semaglutide or dulaglutide, including oral formulations). METHODS: A total of 194 adults with T2D initiating GLP-1RA therapy were evaluated at baseline, and after 6, and 12 months of therapy. To identify predictors of weight loss, variables differing between Responders (weight loss >/=5% than baseline) and Non-Responders were evaluated by ROC analysis and tested in univariate and multivariate logistic regression models adjusted for age, gender, GLP-1RA type and dosage. RESULTS: At 6 and 12 months, 58% and 49% of patients, respectively, achieved the primary outcome. Responders at 12 months exhibited elevated BMI, waist circumference, hepatic steatosis indices, fat mass, and insulin levels at baseline, along with reduced muscle-to-fat and muscle-to-visceral adipose tissue ratios. Moreover, female gender, younger age, shorter disease duration, and non-use of metformin prior to enrollment were significantly associated with response. Notably, early response at 6 months strongly predicted 12-month success. CONCLUSIONS: Our results highlight a valuable interplay between body composition, liver involvement, and the incretin response, also suggesting a maximal synergistic effect between metformin and GLP-1RAs when treatments are initiated concurrently rather than sequentially. These data provide valuable insights for the development of individualized treatment strategies. CI - Copyright (c) 2025 Vozza, Triggiani, Fanelli, Lisco, Coletto, Custodero, Volpe, Racaniello, Colaianni, Lavarra, Maggipinto, Portacci, Tortorella, Moschetta and Piazzolla. FAU - Vozza, Alfredo AU - Vozza A AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Fanelli, Margherita AU - Fanelli M AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lisco, Giuseppe AU - Lisco G AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Coletto, Deborah AU - Coletto D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Custodero, Carlo AU - Custodero C AD - Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy. FAU - Volpe, Sara AU - Volpe S AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Racaniello, Davide AU - Racaniello D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lavarra, Valentina AU - Lavarra V AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Maggipinto, Rosselia AU - Maggipinto R AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Portacci, Andrea AU - Portacci A AD - Department of Translational Biomedicine and Neuroscience, University of Bari "Aldo Moro", Bari, Italy. FAU - Tortorella, Cosimo AU - Tortorella C AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Moschetta, Antonio AU - Moschetta A AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20250925 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prospective Studies MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Recombinant Fusion Proteins/therapeutic use MH - Prognosis MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12507565 OTO - NOTNLM OT - GLP-1 receptor agonists OT - body weight loss OT - fat mass OT - hepatic steatosis OT - metformin OT - predictive factors OT - skeletal muscle mass OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/10/13 12:31 MHDA- 2025/10/13 12:32 PMCR- 2025/09/25 CRDT- 2025/10/13 07:23 PHST- 2025/07/27 00:00 [received] PHST- 2025/09/08 00:00 [accepted] PHST- 2025/10/13 12:32 [medline] PHST- 2025/10/13 12:31 [pubmed] PHST- 2025/10/13 07:23 [entrez] PHST- 2025/09/25 00:00 [pmc-release] AID - 10.3389/fendo.2025.1674308 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Sep 25;16:1674308. doi: 10.3389/fendo.2025.1674308. eCollection 2025. PMID- 41076575 OWN - NLM STAT- MEDLINE DCOM- 20251031 LR - 20260127 IS - 1752-2978 (Electronic) IS - 1752-296X (Linking) VI - 32 IP - 6 DP - 2025 Dec 1 TI - Effect of GLP-1 receptor agonists on body composition. PG - 279-285 LID - 10.1097/MED.0000000000000934 [doi] AB - PURPOSE OF REVIEW: Obesity is present in up to 85% of individuals with type 2 diabetes mellitus (T2DM) and poses a major therapeutic challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, are now widely used for obesity management and increasingly recognized for their impact on body composition beyond weight reduction. This review summarizes evidence on the effects of GLP-1RAs, particularly semaglutide and liraglutide, on fat mass, lean body mass (LBM), visceral adipose tissue (VAT), and resting energy expenditure (REE). RECENT FINDINGS: Clinical trials and meta-analyses show GLP-1RAs achieve marked fat mass loss, preferentially reducing VAT, with modest proportional declines in LBM. Despite reductions in absolute LBM, relative preservation or improvement is observed, and REE is largely maintained, with some reports of increases during prolonged therapy. In both diabetic and nondiabetic populations, GLP-1RAs improve metabolic health without accelerating sarcopenia. Rodent data support protective muscle effects through anti-inflammatory and myogenic mechanisms. Withdrawal, however, predictably results in weight regain, primarily as fat mass, highlighting the importance of continued therapy or supportive lifestyle strategies. SUMMARY: GLP-1RAs confer favourable body composition outcomes, with clinical implications for obesity, sarcopenic obesity, and broader metabolic disease management. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Bhandarkar, Akhila AU - Bhandarkar A AD - Nitte (deemed to be University) KS Hegde Medical Academy (KSHEMA), Mangalore Department of Endocrinology and Metabolism. FAU - Bhat, Sowrabha AU - Bhat S AD - Department of Endocrinology and Metabolism, Yenepoya Medical College, Faculty of Center for Nutrition Studies, Yenepoya University, Mangalore, Karnataka, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India; Noncommunicable Disease Unit, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20251010 PL - England TA - Curr Opin Endocrinol Diabetes Obes JT - Current opinion in endocrinology, diabetes, and obesity JID - 101308636 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Body Composition/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Obesity/drug therapy/metabolism/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Liraglutide/therapeutic use/pharmacology MH - Animals MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1RA OT - body composition OT - fat mass OT - lean body mass OT - visceral adipose tissue EDAT- 2025/10/12 12:31 MHDA- 2025/10/31 17:30 CRDT- 2025/10/12 07:43 PHST- 2025/10/31 17:30 [medline] PHST- 2025/10/12 12:31 [pubmed] PHST- 2025/10/12 07:43 [entrez] AID - 01266029-990000000-00143 [pii] AID - 10.1097/MED.0000000000000934 [doi] PST - ppublish SO - Curr Opin Endocrinol Diabetes Obes. 2025 Dec 1;32(6):279-285. doi: 10.1097/MED.0000000000000934. Epub 2025 Oct 10. PMID- 41075815 OWN - NLM STAT- MEDLINE DCOM- 20251212 LR - 20260704 IS - 1538-9375 (Electronic) IS - 1525-8610 (Linking) VI - 26 IP - 12 DP - 2025 Dec TI - Glucagon-Like Peptide-1 Receptor Agonists and Dementia Risk Reduction in Older Adults With Type 2 Diabetes: A Retrospective Cohort Study. PG - 105901 LID - S1525-8610(25)00418-9 [pii] LID - 10.1016/j.jamda.2025.105901 [doi] AB - OBJECTIVE: To evaluate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on dementia risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) among older adults with type 2 diabetes (T2D). DESIGN: Retrospective cohort study using an active-comparator, new-user design with propensity score matching. SETTING AND PARTICIPANTS: Data were obtained from the TriNetX Global Collaborative Network, which includes electronic health records from 134 health care organizations worldwide. Participants were adults aged >/=65 years with T2D who initiated GLP-1RA or DPP-4i therapy between January 2017 and November 2024. METHODS: Eligible participants were matched 1:1 on baseline characteristics using propensity score matching (PSM). The primary outcome was incident dementia. Secondary outcomes included prescriptions for dementia-related drugs, Alzheimer's disease, and vascular dementia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, and subgroup and sensitivity analyses were performed. RESULTS: After PSM, 82,689 patients were included in each treatment group. GLP-1RA use was associated with a lower risk of dementia compared with DPP-4i (HR, 0.58; 95% CI, 0.55-0.61; P < .0001). Stratified analyses revealed consistent risk reductions across age, sex, and GLP-1RA type. In addition, GLP-1RA was also associated with lower risks of dementia-related drug prescriptions (HR, 0.76; 95% CI, 0.70-0.81), Alzheimer's disease (HR, 0.62; 95% CI, 0.56-0.70), and vascular dementia (HR, 0.62; 95% CI, 0.55-0.70). Sensitivity analyses supported the robustness of these findings. CONCLUSIONS AND IMPLICATIONS: GLP-1RA use in older adults with T2D is associated with a significantly lower risk of dementia compared with DPP-4i. These findings suggest the potential neuroprotective benefits of GLP-1RAs and highlight their importance in managing T2D with a view toward reducing dementia risk. Further studies are warranted to explore the underlying mechanisms and validate these observations in randomized controlled trials. CI - Copyright (c) 2025 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Yu-Min AU - Lin YM AD - Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Hsu, Wan-Hsuan AU - Hsu WH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan Taiwan. FAU - Liu, Ting-Hui AU - Liu TH AD - Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan. FAU - Tsai, Ya-Wen AU - Tsai YW AD - Division of Preventive Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan Taiwan. FAU - Yu, Tsung AU - Yu T AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: dtmed141@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251029 PL - United States TA - J Am Med Dir Assoc JT - Journal of the American Medical Directors Association JID - 100893243 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Retrospective Studies MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dementia/prevention & control/epidemiology MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged, 80 and over MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - *Risk Reduction Behavior OTO - NOTNLM OT - Dementia OT - dipeptidyl peptidase-4 inhibitors OT - glucagon-like peptide-1 receptor agonists OT - neuroprotection OT - older adults OT - type 2 diabetes COIS- Disclosure The authors declare no conflicts of interest. EDAT- 2025/10/12 00:34 MHDA- 2025/12/13 00:32 CRDT- 2025/10/11 19:21 PHST- 2025/06/12 00:00 [received] PHST- 2025/08/12 00:00 [revised] PHST- 2025/08/12 00:00 [accepted] PHST- 2025/12/13 00:32 [medline] PHST- 2025/10/12 00:34 [pubmed] PHST- 2025/10/11 19:21 [entrez] AID - S1525-8610(25)00418-9 [pii] AID - 10.1016/j.jamda.2025.105901 [doi] PST - ppublish SO - J Am Med Dir Assoc. 2025 Dec;26(12):105901. doi: 10.1016/j.jamda.2025.105901. Epub 2025 Oct 29. PMID- 41075262 OWN - NLM STAT- MEDLINE DCOM- 20251011 LR - 20260127 IS - 1399-0012 (Electronic) IS - 0902-0063 (Linking) VI - 39 IP - 10 DP - 2025 Oct TI - Bridging the Gap to Waitlist Activation: Semaglutide's Weight Loss Efficacy and Safety in Patients With Obesity on Dialysis Seeking Kidney Transplantation. PG - e70344 LID - 10.1111/ctr.70344 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated efficacy for weight loss and glycemic control in patients with obesity and type 2 diabetes mellitus, but data are limited for patients with end-stage kidney disease on dialysis. We examined the weight loss efficacy and safety of semaglutide when prescribed to patients on dialysis to improve transplant candidacy and activation status. We conducted a retrospective chart review of 36 patients on dialysis who were prescribed semaglutide through a metabolic clinic between September 2021 and December 2023. Outcomes included weight loss efficacy, safety, and change in waitlist status at 1 year. Patients achieved a mean total body weight loss of 7.8% (SD 6.1). Of patients who were ineligible for transplant due to elevated body mass index, 48.2% achieved waitlist activation after successful weight loss. Treatment-limiting gastrointestinal side effects occurred in 16.7% of patients. Patients on peritoneal dialysis (PD, 30.8%) versus hemodialysis (8.7%) discontinued therapy more frequently. In a single-center cohort, patients who received semaglutide experienced significantly greater weight loss and increased rates of waitlist activation compared with a lifestyle-only intervention. Semaglutide was generally well-tolerated. Prospective studies should examine whether patients on PD experience severe GI side effects more frequently on semaglutide. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Wade, Francis G AU - Wade FG AUID- ORCID: 0009-0002-1313-8335 AD - Division of General Internal Medicine, Department of Internal Medicine, SSM Health/Saint Louis University, St. Louis, Missouri, USA. FAU - Lentine, Krista L AU - Lentine KL AUID- ORCID: 0000-0002-9423-4849 AD - SSM Health Saint Louis University Hospital Transplant Center, Saint Louis University, St. Louis, Missouri, USA. FAU - Turk, David AU - Turk D AUID- ORCID: 0009-0009-3534-6283 AD - School of Medicine, Saint Louis University, St. Louis, Missouri, USA. FAU - Kirbach, Kyleigh AU - Kirbach K AUID- ORCID: 0000-0002-4513-3662 AD - Division of General Internal Medicine, Department of Internal Medicine, SSM Health/Saint Louis University, St. Louis, Missouri, USA. FAU - Knobloch, Taylor AU - Knobloch T AUID- ORCID: 0009-0005-6778-4633 AD - Department of Nutrition & Dietetics, SSM Health Saint Louis University Hospital, St. Louis, Missouri, USA. FAU - Schnitzler, Mark AU - Schnitzler M AUID- ORCID: 0000-0001-8547-5643 AD - SSM Health Saint Louis University Hospital Transplant Center, Saint Louis University, St. Louis, Missouri, USA. FAU - Qureshi, Kamran AU - Qureshi K AUID- ORCID: 0000-0002-0389-7269 AD - Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. FAU - Syn, Wing-Kin AU - Syn WK AUID- ORCID: 0000-0001-7966-0500 AD - Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. AD - Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country, UPV/EHU, Vizcaya, Spain. FAU - Fleetwood, Vidya A AU - Fleetwood VA AUID- ORCID: 0000-0002-7655-9375 AD - Division of Transplantation, Michael E. DeBakey Department of Surgery, Baylor Medical College, Houston, Texas, USA. LA - eng GR - R01DK102981/Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation and National Institute of Diabetes and Digestive and Kidney Diseases/ PT - Journal Article PL - Denmark TA - Clin Transplant JT - Clinical transplantation JID - 8710240 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Waiting Lists/mortality MH - Male MH - *Kidney Transplantation MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Loss/drug effects MH - *Renal Dialysis MH - *Kidney Failure, Chronic/therapy/complications MH - *Obesity/drug therapy/complications MH - Follow-Up Studies MH - Prognosis MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide 1 receptor agonist OT - kidney transplantation OT - obesity OT - patient selection OT - renal dialysis OT - semaglutide EDAT- 2025/10/11 22:19 MHDA- 2025/10/11 22:20 CRDT- 2025/10/11 12:52 PHST- 2025/09/04 00:00 [revised] PHST- 2025/07/03 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/10/11 22:20 [medline] PHST- 2025/10/11 22:19 [pubmed] PHST- 2025/10/11 12:52 [entrez] AID - 10.1111/ctr.70344 [doi] PST - ppublish SO - Clin Transplant. 2025 Oct;39(10):e70344. doi: 10.1111/ctr.70344. PMID- 41075111 OWN - NLM STAT- MEDLINE DCOM- 20251011 LR - 20261010 IS - 1941-6636 (Electronic) VI - 56 IP - 1 DP - 2025 Oct 11 TI - Do Incretin-Based Therapies Influence the Risk of Cholangiocarcinoma in Type 2 Diabetes Patients? Insights from a Systematic Review and Meta-Analysis. PG - 198 LID - 10.1007/s12029-025-01330-9 [doi] AB - INTRODUCTION: Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is), are widely used in the management of type 2 diabetes mellitus (T2DM). However, concerns have emerged regarding their potential association with an increased risk of cholangiocarcinoma (CCA), and current evidence remains inconclusive. This review aims to evaluate and clarify the association between incretin-based therapies and the risk of CCA in patients with T2DM. METHODS: This review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025641616). A comprehensive search was performed across PubMed, ProQuest, EBSCOhost, Wiley, and SAGE databases. Eligible observational studies reporting the association between incretin-based therapies and CCA were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using RevMan with a random-effects model. RESULT: Four studies (three cohort and one case-control) were included. The pooled HRs showed no significant association between incretin-based therapies and CCA risk, with estimates of 1.07 (95% CI: 0.70-1.63) for GLP-1RAs and 1.05 (95% CI: 0.83-1.34) for DPP-4Is. Pooled RR analyses yielded similarly non-significant results. All included studies were assessed as having a low risk of bias according to the NOS. CONCLUSION: Incretin-based therapies do not significantly increase the risk of CCA in T2DM patients. Within the limitations of the available observational evidence, these findings provide reassurance regarding their safety profile, while highlighting the need for ongoing pharmacovigilance and further large-scale studies to confirm these results. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Yonatan, Eric Ricardo AU - Yonatan ER AD - School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, North Jakarta, Indonesia. ericr.yonatan@gmail.com. FAU - Jusni, Louis Fabio Jonathan AU - Jusni LFJ AD - School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, North Jakarta, Indonesia. FAU - Alvianto, Steven AU - Alvianto S AD - School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, North Jakarta, Indonesia. FAU - Widjanarko, Nicolas Daniel AU - Widjanarko ND AD - School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, North Jakarta, Indonesia. FAU - Usman, Steven Yulius AU - Usman SY AD - School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, North Jakarta, Indonesia. FAU - Muzellina, Virly Nanda AU - Muzellina VN AD - Division of Gastroenterology, Pancreatobiliary, and Digestive Endoscopy, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine , Universitas Indonesia, Jakarta, Indonesia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251011 PL - United States TA - J Gastrointest Cancer JT - Journal of gastrointestinal cancer JID - 101479627 RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Incretins/adverse effects/therapeutic use MH - *Cholangiocarcinoma/epidemiology/chemically induced MH - *Bile Duct Neoplasms/epidemiology/chemically induced MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Cholangiocarcinoma OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Incretin-based therapies OT - Type 2 diabetes mellitus COIS- Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests. EDAT- 2025/10/11 12:32 MHDA- 2025/10/11 12:33 CRDT- 2025/10/11 11:18 PHST- 2025/10/05 00:00 [accepted] PHST- 2025/10/11 12:33 [medline] PHST- 2025/10/11 12:32 [pubmed] PHST- 2025/10/11 11:18 [entrez] AID - 10.1007/s12029-025-01330-9 [pii] AID - 10.1007/s12029-025-01330-9 [doi] PST - epublish SO - J Gastrointest Cancer. 2025 Oct 11;56(1):198. doi: 10.1007/s12029-025-01330-9. PMID- 41074575 OWN - NLM STAT- MEDLINE DCOM- 20251229 LR - 20260807 IS - 1532-6535 (Electronic) IS - 0009-9236 (Linking) VI - 119 IP - 1 DP - 2026 Jan TI - Ocular Complications of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors in T2DM Treatments: A Retrospective Real-World Cohort Study. PG - 255-266 LID - 10.1002/cpt.70087 [doi] AB - Glaucoma is a leading cause of irreversible vision loss worldwide, and type 2 diabetes mellitus (T2DM) is increasingly recognized as a risk factor for glaucoma. This study compared the effects of 3 classes of antidiabetic drugs-sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is)-on ocular and systemic complications in adults with T2DM. Using the TriNetX database from 2015 to 2025, adults aged >/= 40 years initiating SGLT-2is, GLP-1 RAs, or DPP-4is were identified and matched through propensity score methods to create three cohorts. The primary outcomes included open-angle glaucoma and ocular hypertension, with secondary outcomes of cataract, diabetic retinopathy, macular edema, and various systemic events. The matched cohorts included 68,283 patients (SGLT-2is vs. GLP-1 RAs), 69,765 patients (SGLT-2is vs. DPP-4is), and 55,760 patients (GLP-1 RAs vs. DPP-4is). Compared with GLP-1 RAs and DPP-4is, SGLT-2i use was associated with significantly lower risks of open-angle glaucoma (HR: 0.88 and 0.90), ocular hypertension (HR: 0.78 and 0.90), cataract (HR: 0.84 and 0.87), diabetic retinopathy (HR: 0.84 and 0.87), and macular edema (HR: 0.77 and 0.71). Conversely, GLP-1 RAs demonstrated stronger protective effects against systemic complications, such as diabetic nephropathy or chronic kidney disease, liver cirrhosis, dementia, cerebral infarction, and ischemic heart disease. These findings suggest that SGLT-2is may be prioritized in T2DM patients at higher risk for ocular complications, while GLP-1 RAs may be preferred when systemic risk reduction is the primary therapeutic goal. CI - (c) 2025 The Author(s). Clinical Pharmacology & Therapeutics (c) 2025 American Society for Clinical Pharmacology and Therapeutics. FAU - Lin, Lee-Yuan AU - Lin LY AUID- ORCID: 0009-0007-7212-3535 AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Wu, Jie-Syuan AU - Wu JS AUID- ORCID: 0009-0001-8164-3299 AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Jeng, Wei-Jung AU - Jeng WJ AUID- ORCID: 0009-0006-2400-9626 AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Tsai, Chen-Hsin AU - Tsai CH AD - Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Sun, Jia-Wei AU - Sun JW AUID- ORCID: 0009-0004-8018-8847 AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Kuo, Cheng-Hao AU - Kuo CH AUID- ORCID: 0009-0006-0399-3329 AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. AD - Ph.D. Program of Interdisciplinary Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Yuliani, Fara Silvia AU - Yuliani FS AD - Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. FAU - Lin, Shyh-Hsiang AU - Lin SH AUID- ORCID: 0000-0002-3723-560X AD - School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan. AD - School of Nutrition, College of Nutrition, Taipei Medical University, Taipei, Taiwan. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251011 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications MH - Male MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetic Retinopathy/epidemiology MH - Glaucoma, Open-Angle/epidemiology/chemically induced MH - Adult MH - Databases, Factual MH - Ocular Hypertension/epidemiology/chemically induced MH - Risk Factors EDAT- 2025/10/11 06:31 MHDA- 2025/12/29 13:02 CRDT- 2025/10/11 03:44 PHST- 2025/07/17 00:00 [received] PHST- 2025/09/19 00:00 [accepted] PHST- 2025/12/29 13:02 [medline] PHST- 2025/10/11 06:31 [pubmed] PHST- 2025/10/11 03:44 [entrez] AID - 10.1002/cpt.70087 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 Jan;119(1):255-266. doi: 10.1002/cpt.70087. Epub 2025 Oct 11. PMID- 41070406 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 18 IP - 10 DP - 2025 Oct TI - Semaglutide for the treatment of MASH: reaching into the ESSENCE of cardio-metabolic health? PG - 1-5 LID - 10.1080/17512433.2025.2573785 [doi] AB - Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis poses a significant clinical challenge, especially given its strong association with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated impressive results in managing obesity and T2DM, prompting interest in their potential therapeutic role for MASH with fibrosis. The ESSENCE trial recently investigated the effectiveness of once-weekly semaglutide in patients with biopsy-proven MASH and moderate-to-advanced fibrosis. Interim analysis at 72 weeks demonstrated that semaglutide substantially improved liver histology, effectively resolving steatohepatitis and showing improvement in liver fibrosis, compared to placebo. Consistent with these findings, the U.S. Food and Drug Administration has granted accelerated approval to semaglutide (Wegovy) for adults with noncirrhotic MASH and stage 2 or 3 fibrosis. Those hepatic benefits were accompanied with notable improvements in body weight, insulin sensitivity and inflammatory markers. While these preliminary results are encouraging, their clinical relevance will depend on whether they translate into reduced long-term liver complications and amelioration of overall cardio-renal risk. Thus, semaglutide represents a highly promising therapeutic strategy for patients with MASH and fibrosis, addressing critical unmet needs by simultaneously targeting liver pathology and cardiometabolic health. FAU - Mademlis, Christos AU - Mademlis C AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Teperikidis, Eleftherios AU - Teperikidis E AD - Clinical Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Giouleme, Olga AU - Giouleme O AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Doumas, Michael AU - Doumas M AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20251013 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Liver Cirrhosis/drug therapy/etiology/pathology/physiopathology MH - Obesity/drug therapy/complications MH - Hypoglycemic Agents/pharmacology/administration & dosage MH - *Fatty Liver/drug therapy/physiopathology/pathology/etiology MH - Animals MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Fibrosis OT - glucagon-like peptide-1 receptor agonist OT - metabolic dysfunction-associated Steatohepatitis OT - semaglutide OT - steatohepatitis resolution EDAT- 2025/10/10 06:28 MHDA- 2025/11/13 12:32 CRDT- 2025/10/10 05:00 PHST- 2025/11/13 12:32 [medline] PHST- 2025/10/10 06:28 [pubmed] PHST- 2025/10/10 05:00 [entrez] AID - 10.1080/17512433.2025.2573785 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2025 Oct;18(10):1-5. doi: 10.1080/17512433.2025.2573785. Epub 2025 Oct 13. PMID- 41069284 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Glucagon-like peptide-1 receptor agonist and respiratory complications after endoscopy: A Japanese nationwide cohort study. PG - 316-323 LID - 10.1111/dom.70194 [doi] AB - AIMS: While discontinuation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) before esophagogastroduodenoscopy (EGD) is not universally mandated, safety concerns persist. Evidence remains insufficient for managing specific patient subgroups, particularly in Asian populations. We aimed to provide evidence for stratified risk assessment in a large Japanese cohort. MATERIALS AND METHODS: This nationwide retrospective cohort study used the Japan Medical Data Center database. We performed 1:4 propensity score matching based on age, sex, insulin use, HbA1c level, chronic respiratory disease, and body mass index to compare patients with diabetes receiving GLP-1RAs (n = 3568) with non-users (n = 14 246). Respiratory and severe complications within 14 days post-EGD were assessed via logistic regression. RESULTS: GLP-1RA was not associated with an increased risk of overall (0.39% vs. 0.50%; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.44-1.40; p = 0.41) or severe (0.11% vs. 0.077%; 1.45, 0.46-4.56; p = 0.52) respiratory complications. While no subgroup analysis reached statistical significance, numerical trends towards a higher risk were observed in new users (OR 1.43; 95% CI, 0.51-3.98) and patients with severe diabetes (OR 1.28; 95% CI, 0.64-2.52). CONCLUSIONS: GLP-1RA was not associated with increased post-EGD respiratory complications, suggesting that routine discontinuation may be unnecessary for many stable, long-term users. However, our findings do not support a uniform conclusion of safety for all subgroups. The non-significant trends in new users and patients with severe diabetes warrant a cautious, individualised approach for these potentially vulnerable populations. Further research is needed to definitively clarify this risk. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hisada, Hiroyuki AU - Hisada H AUID- ORCID: 0000-0002-6184-2215 AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Ikeuchi, Kazuhiko AU - Ikeuchi K AD - Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Tsuji, Yosuke AU - Tsuji Y AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Next-Generation Endoscopic Computer Vision, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yamamichi, Nobutake AU - Yamamichi N AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kakushima, Naomi AU - Kakushima N AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Okushin, Kazuya AU - Okushin K AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yakabi, Seiichi AU - Yakabi S AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Takeuchi, Chihiro AU - Takeuchi C AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Ohki, Daisuke AU - Ohki D AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Mizutani, Hiroya AU - Mizutani H AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Next-Generation Endoscopic Computer Vision, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Miura, Yuko AU - Miura Y AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kubota, Dai AU - Kubota D AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Tsutsumi, Takeya AU - Tsutsumi T AD - Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Fujishiro, Mitsuhiro AU - Fujishiro M AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. LA - eng GR - JPMJPR23R1/JST, PRESTO/ PT - Journal Article DEP - 20251010 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - Japanese people SB - IM MH - Humans MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Japan/epidemiology MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Endoscopy, Digestive System/adverse effects MH - *Respiratory Tract Diseases/epidemiology/etiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Respiration Disorders/epidemiology MH - Adult MH - East Asian People PMC - PMC12673464 OTO - NOTNLM OT - complications OT - esophagogastroduodenoscopy OT - glucagon-like peptide-1 receptor agonist OT - poor glycaemic control COIS- Yosuke Tsuji and Hiroya Mizutani are affiliated with an endowed chair by AI Medical Service Inc., which is not relevant to this research. EDAT- 2025/10/10 06:28 MHDA- 2025/12/03 07:41 PMCR- 2025/12/03 CRDT- 2025/10/10 04:23 PHST- 2025/09/28 00:00 [revised] PHST- 2025/08/04 00:00 [received] PHST- 2025/10/01 00:00 [accepted] PHST- 2025/12/03 07:41 [medline] PHST- 2025/10/10 06:28 [pubmed] PHST- 2025/10/10 04:23 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70194 [pii] AID - 10.1111/dom.70194 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):316-323. doi: 10.1111/dom.70194. Epub 2025 Oct 10. PMID- 41068996 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study. PG - 112-121 LID - 10.1111/dom.70141 [doi] AB - AIMS: Semaglutide, a GLP-1 receptor agonist, has shown efficacy in promoting weight loss. However, limited data exist on its impact on lean mass, muscle function, and metabolic adaptations. The SEMALEAN study aims to evaluate these parameters in patients with obesity treated with Semaglutide (2.4 mg). MATERIALS AND METHODS: This prospective study enrolled 115 patients with obesity between February 2022 and November 2024. Body weight, body composition (measured by DXA), muscle function (handgrip strength), and resting energy expenditure (REE) were assessed at baseline (M0), 7 months (M7), and 12 months (M12). Subgroup analyses examined the impact of sex, type 2 diabetes, previous GLP-1 use, and history of bariatric surgery. RESULTS: A total of 106 patients (68.9% female; mean BMI 46.3 kg/m(2)) completed the study. Weight loss was significant, with mean reductions of 10% at M7 and 13% at M12; 59% of patients achieved >/=10% weight loss. Total fat mass decreased by 14% at M7 and 18% at M12, while lean mass initially declined (-3 kg at M7) but stabilised thereafter. Handgrip strength improved significantly (+4.5 kg at M12), and the prevalence of sarcopenic obesity decreased from 49% at baseline to 33% at M12. REE normalised to lean mass increased significantly from M7 to M12. Subgroup analyses revealed greater weight and fat mass loss in women, while patients with type 2 diabetes or prior GLP-1 analogue use showed attenuated responses. Patients with a history of bariatric surgery exhibited the most pronounced reductions in body composition parameters. CONCLUSIONS: The SEMALEAN study highlights the significant impact of Semaglutide 2.4 mg on weight loss, fat mass reduction, and muscle function improvement, with preserved lean mass and metabolic efficiency. These findings underscore the importance of a comprehensive approach to obesity management, addressing not only weight loss but also functional and metabolic adaptation. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Alissou, Mathieu AU - Alissou M AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Demangeat, Thomas AU - Demangeat T AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Folope, Vanessa AU - Folope V AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Van Elslande, Helene AU - Van Elslande H AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Lelandais, Helene AU - Lelandais H AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Blanchemaison, Julia AU - Blanchemaison J AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Cailleaux, Pierre-Emmanuel AU - Cailleaux PE AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Guney, Suzan AU - Guney S AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Aupetit, Alexandra AU - Aupetit A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Aubourg, Agnes AU - Aubourg A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Rapp, Clement AU - Rapp C AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Petit, Andre AU - Petit A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Godin, Morgane AU - Godin M AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Vignal, Luc AU - Vignal L AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Grigioni, Sebastien AU - Grigioni S AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Dechelotte, Pierre AU - Dechelotte P AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Colange, Guillaume AU - Colange G AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Coeffier, Moise AU - Coeffier M AUID- ORCID: 0000-0002-7469-2682 AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Achamrah, Najate AU - Achamrah N AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. LA - eng PT - Journal Article DEP - 20251009 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Obesity/drug therapy/physiopathology/metabolism MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Prospective Studies MH - *Body Composition/drug effects MH - Weight Loss/drug effects MH - Adult MH - Hand Strength MH - *Muscle, Skeletal/drug effects/physiopathology MH - *Adipose Tissue/drug effects MH - Diabetes Mellitus, Type 2 MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12673431 OTO - NOTNLM OT - Semaglutide OT - antiobesity drug OT - body composition OT - obesity care COIS- Vanessa Folope is currently employed by Novo Nordisk. However, her involvement in the study design occurred before joining the company. The other authors declare no conflicts of interest related to this publication. EDAT- 2025/10/10 06:29 MHDA- 2025/12/03 14:12 PMCR- 2025/12/03 CRDT- 2025/10/10 00:19 PHST- 2025/09/09 00:00 [revised] PHST- 2025/06/25 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/10/10 06:29 [pubmed] PHST- 2025/10/10 00:19 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70141 [pii] AID - 10.1111/dom.70141 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):112-121. doi: 10.1111/dom.70141. Epub 2025 Oct 9. PMID- 41065947 OWN - NLM STAT- MEDLINE DCOM- 20251009 LR - 20251012 IS - 1534-6242 (Electronic) IS - 1523-3804 (Print) IS - 1523-3804 (Linking) VI - 27 IP - 1 DP - 2025 Oct 9 TI - Current Perspectives on GLP-1 Agonists in Contemporary Clinical Practice from Science and Mechanistic Foundations To Optimal Translation. PG - 99 LID - 10.1007/s11883-025-01350-7 [doi] LID - 99 AB - PURPOSE OF REVIEW: This review provides a comprehensive and scholarly examination of glucagon-like peptide-1 receptor (GLP-1R) agonists, tracing their evolution from glycemic control agents in diabetes mellitus (DM) to multifaceted therapeutics with expanding indications in cardiovascular, renal, and metabolic health. We explore the underlying biological mechanisms, summarize clinical trial evidence, and highlight emerging applications in non-diabetic populations. Recent developments underscore the relevance of GLP-1R agonists in addressing the complex interplay of cardiovascular-kidney-metabolic (CKM) syndrome, microvascular dysfunction, and metabolic-associated steatohepatitis (MASH). We also discuss combination therapies and strategies to mitigate muscle mass loss during treatment and calls for targeted research, improved clinical education, and policy reforms to optimize the translational potential of GLP-1R agonists in both individualized care and population health. RECENT FINDINGS: Diabetes mellitus currently affects over 422 million individuals worldwide, with projections indicating a rise to 783 million by 2045, representing 10.5% of the global adult population. Common comorbidities include chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD), which collectively impact nearly one-third of individuals with DM. The growing prevalence of metabolic disease, CKD, and ASCVD have prompted investigation into the role of GLP-1R agonists in mitigating cardiovascular and metabolic risks, particularly within the framework of Cardiovascular-Kidney-Metabolic (CKM) Syndrome, irrespective of diabetic status. Emerging evidence, foundational science, and transformative knowledge of mechanisms of action further support the expansion of therapeutic indications for this drug class. Although GLP-1R agonists were originally developed for glycemic control in DM, their mechanistic versatility has enabled broader application across a spectrum of cardiovascular, cerebrovascular and metabolic disorders. This review traces the trajectory of their development and highlights opportunities for more expansive translational use in both clinical and population health settings. We also address current barriers to implementation and evidence-based use, ongoing clinical trials, and future directions, including combination therapies that may enhance efficacy and patient outcomes. CI - (c) 2025. The Author(s). FAU - Abu-Nejim, Husam AU - Abu-Nejim H AD - The Warren Alpert Medical School of Brown University, Providence, RI, USA. FAU - Becker, Richard C AU - Becker RC AD - University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA. Richard.becker@uc.edu. LA - eng PT - Journal Article PT - Review DEP - 20251009 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cardiovascular Diseases/drug therapy PMC - PMC12511252 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Chronic kidney disease OT - Diabetes mellitus OT - GLP-1R agonists OT - Microvascular disease OT - Thrombosis COIS- Declarations. Competing Interests: The authors declare no competing interests. Human and Animal Rights and Informed Consent: No animal or human subjects were used in this study by the authors. EDAT- 2025/10/09 12:31 MHDA- 2025/10/09 12:32 PMCR- 2025/10/09 CRDT- 2025/10/09 11:19 PHST- 2025/04/03 00:00 [received] PHST- 2025/09/20 00:00 [accepted] PHST- 2025/10/09 12:32 [medline] PHST- 2025/10/09 12:31 [pubmed] PHST- 2025/10/09 11:19 [entrez] PHST- 2025/10/09 00:00 [pmc-release] AID - 10.1007/s11883-025-01350-7 [pii] AID - 1350 [pii] AID - 10.1007/s11883-025-01350-7 [doi] PST - epublish SO - Curr Atheroscler Rep. 2025 Oct 9;27(1):99. doi: 10.1007/s11883-025-01350-7. PMID- 41064855 OWN - NLM STAT- MEDLINE DCOM- 20251118 LR - 20260127 IS - 1941-3084 (Electronic) IS - 1941-3084 (Linking) VI - 18 IP - 11 DP - 2025 Nov TI - Effect of Semaglutide on Atrial Arrhythmias Recurrence Following Ablation for Atrial Fibrillation: A Prospective Study. PG - e014069 LID - 10.1161/CIRCEP.125.014069 [doi] AB - BACKGROUND: Recurrence of atrial arrhythmias remains a significant challenge following catheter ablation for atrial fibrillation. The potential role of semaglutide in reducing atrial arrhythmia recurrence postablation is unclear. METHODS: A consecutive sample of 437 patients with a body mass index >/=24 kg/m(2) and type 2 diabetes who underwent their first atrial fibrillation ablation procedure between January 2022 and March 2024 were enrolled. Participants were divided into a semaglutide group and a control group based on patient preference. The primary outcome was the freedom from atrial arrhythmia recurrence during the 12-month follow-up period after the 3-month blanking period postablation. RESULTS: Of the 437 enrolled patients, 158 opted for semaglutide therapy and 279 declined. At baseline, the semaglutide group had higher body mass index (27.5 [2.2] versus 27.0 [2.4]; P=0.038) and glycated hemoglobin levels (8.0 [1.0] versus 7.6 [1.1]; P<0.001) compared with controls. During the 12-month follow-up, the semaglutide group showed a higher event-free rate for recurrent atrial arrhythmias (hazard ratio, 0.68 [95% CI, 0.49-0.95]; P=0.030), greater weight loss (-8.2% [3.2] versus -4.6% [2.9]; P<0.001), and larger reductions in glycated hemoglobin (-1.3% [0.8] versus -0.6% [0.8]; P<0.001). CONCLUSIONS: Semaglutide treatment following catheter ablation for atrial fibrillation is associated with a lower rate of atrial arrhythmia recurrence over 12 months and may lead to improvements in weight and glycated hemoglobin levels. FAU - Guo, Jiongchao AU - Guo J AUID- ORCID: 0009-0002-7957-878X AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Song, Ziliang AU - Song Z AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Wang, Shiyi AU - Wang S AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Yao, Die AU - Yao D AUID- ORCID: 0009-0003-8021-7479 AD - Department of Nutrition, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (D.Y.). FAU - Hong, Yu AU - Hong Y AD - Department of Cardiology, Anhui Second Provincial People's Hospital, Hefei, China (Y.H.). FAU - Fu, Minmin AU - Fu M AD - Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University (Hefei First People's Hospital) (M.F.). FAU - Chen, Min AU - Chen M AD - Department of Cardiology, Hefei Second People's Hospital, China (M.C.). FAU - Jiang, Weifeng AU - Jiang W AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Zhang, Yu AU - Zhang Y AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Wu, Shaohui AU - Wu S AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Liu, Xu AU - Liu X AUID- ORCID: 0009-0001-4219-5606 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Hou, Xumin AU - Hou X AUID- ORCID: 0009-0005-6506-7083 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Qin, Mu AU - Qin M AUID- ORCID: 0000-0002-1645-4758 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). LA - eng PT - Journal Article DEP - 20251009 PL - United States TA - Circ Arrhythm Electrophysiol JT - Circulation. Arrhythmia and electrophysiology JID - 101474365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Circ Arrhythm Electrophysiol. 2025 Nov;18(11):e014508. doi: 10.1161/CIRCEP.125.014508. PMID: 41159264 MH - Humans MH - *Atrial Fibrillation/surgery/physiopathology/diagnosis MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - Prospective Studies MH - *Catheter Ablation/adverse effects MH - Recurrence MH - Treatment Outcome MH - Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Time Factors MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - atrial fibrillation OT - body mass index OT - catheter ablation OT - glycated hemoglobin OT - semaglutide COIS- None. EDAT- 2025/10/09 06:28 MHDA- 2025/11/18 18:30 CRDT- 2025/10/09 05:09 PHST- 2025/11/18 18:30 [medline] PHST- 2025/10/09 06:28 [pubmed] PHST- 2025/10/09 05:09 [entrez] AID - 10.1161/CIRCEP.125.014069 [doi] PST - ppublish SO - Circ Arrhythm Electrophysiol. 2025 Nov;18(11):e014069. doi: 10.1161/CIRCEP.125.014069. Epub 2025 Oct 9. PMID- 41063381 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Histological efficacy of anti-diabetic agents in MASH and the mediating role of weight loss: A network meta-analysis. PG - 287-295 LID - 10.1111/dom.70187 [doi] AB - BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with rising global prevalence, closely linked to type 2 diabetes. While several anti-diabetic agents show promise, a comprehensive analysis comparing their efficacy on biopsy-confirmed histological outcomes, including dose-dependent effects and the mediating role of weight loss, remains unexplored. METHODS: A frequentist random-effects network meta-analysis (NMA) was conducted to explore histological efficacy of anti-diabetic agents in biopsy-confirmed MASH without cirrhosis. The primary outcome was fibrosis improvement (>/=1 stage) without worsening steatohepatitis; the secondary outcome was MASH resolution without fibrosis worsening. Incretin-based agents were dose-stratified. Treatment ranking used surface-under the cumulative-ranking curve (SUCRA). Meta-regression investigated the impact of percentage weight loss and baseline covariates on the proportion of individuals achieving histological end-points. RESULTS: Data from five RCTs (N = 1667) were included. All active treatments, including Dapagliflozin 10 mg, Survodutide (2.4 mg/wk, 4.8-6 mg/wk), Tirzepatide (5 mg/wk, 10-15 mg/wk), and Semaglutide (0.7-1.4 mg/wk, 2.4 or 2.8 mg/wk), improved fibrosis versus placebo (I(2) = 0%). For MASH resolution, dose-dependent effects led to significant heterogeneity (I(2) = 73%), with lower-dose Semaglutide demonstrating no benefits and Dapagliflozin showing benefits in the F2-F3 subgroup only on sensitivity analysis. Survodutide exhibited the highest ranking (SUCRA = 0.822-0.849), followed by Tirzepatide (SUCRA = 0.622-0.681) and higher-dose Semaglutide (SUCRA = 0.327) for MASH resolution. Meta-regression using data from 16 interventions, including placebo arms, showed that weight loss significantly explained heterogeneity in treatment effects on fibrosis improvement (R(2) = 54.26%) and MASH resolution (R(2) = 78.16%). CONCLUSIONS: SGLT2 inhibitor and incretin-based agents improved fibrosis in MASH, with weight loss being a significant mediator. Targeting multiple incretin pathways, especially involving glucagon receptors, may offer greater MASH resolution. Dose-dependent effects were more prominent for MASH resolution than fibrosis improvement, indicating potential weight-loss-independent anti-fibrotic pathways. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Banerjee, Mainak AU - Banerjee M AUID- ORCID: 0000-0002-6656-8569 AD - Department of Endocrinology, R N Tagore Hospital, Kolkata, India. AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Pal, Rimesh AU - Pal R AUID- ORCID: 0000-0003-4859-9393 AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. FAU - Pal, Sandip AU - Pal S AD - Department of Gastroenterology, R N Tagore Hospital, Kolkata, India. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20251008 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use MH - Liver/pathology/drug effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - MAFLD OT - MASH OT - SGLT2 inhibitors OT - diabetes OT - fibrosis OT - incretin agents OT - weight loss EDAT- 2025/10/09 06:28 MHDA- 2025/12/03 14:11 CRDT- 2025/10/09 00:33 PHST- 2025/09/29 00:00 [revised] PHST- 2025/08/01 00:00 [received] PHST- 2025/09/29 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/09 06:28 [pubmed] PHST- 2025/10/09 00:33 [entrez] AID - 10.1111/dom.70187 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):287-295. doi: 10.1111/dom.70187. Epub 2025 Oct 8. PMID- 41062312 OWN - NLM STAT- MEDLINE DCOM- 20260517 LR - 20260813 IS - 1349-7235 (Electronic) IS - 0918-2918 (Print) IS - 0918-2918 (Linking) VI - 65 IP - 10 DP - 2026 May 15 TI - Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study. PG - 1334-1341 LID - 10.2169/internalmedicine.6239-25 [doi] AB - Objective To investigate the additive effects of semaglutide on liver function indicators in patients with type 2 diabetes mellitus (T2DM) complicated by metabolic dysfunction-associated steatotic liver disease (MASLD), who received sodium-glucose cotransporter 2 inhibitors (SGLT2-Is). Methods Liver function indicators at baseline were compared with those 6 months after the initiation of semaglutide. Patients Forty-seven patients (mean age, 56.2+/-10.4 years; 74.5% men) with T2DM complicated by MASLD who were prescribed SGLT2-Is continuously for at least 12 months were retrospectively selected. Results Six months of semaglutide treatment significantly decreased body weight (BW; 80.9+/-16.4 kg to 77.3+/-17.0 kg, p<0.001), body mass index (BMI; 28.9+/-4.5 kg/m(2) to 27.7+/-4.6 kg/m(2), p<0.001), and the levels of glycated hemoglobin (HbA1c; 7.4+/-0.7% to 6.9+/-0.7%, p<0.001), aspartate aminotransferase (AST; 30.4+/-15.9 U/L to 26.3+/-12.5 U/L, p=0.014), alanine aminotransferase (ALT; 42.4+/-28.7 U/L to 35.7+/-22.8 U/L, p=0.022), and gamma-glutamyl transpeptidase (gamma-GTP; 46.5+/-36.8 U/L to 38.0+/-30.0 U/L, p=0.001). The fibrosis-4 index, an indicator of liver fibrosis, did not improve. Changes in ALT levels were significantly correlated with changes in metabolic parameters, including BW (p=0.004), BMI (p=0.004), HbA1c (p=0.005), and triglycerides (p=0.011). Conclusion The addition of semaglutide to SGLT2-Is reduced liver enzyme levels in patients with T2DM complicated with MASLD. Future randomized controlled trials are needed to investigate the additive effects of semaglutide on MASLD in patients with T2DM receiving SGLT2-Is. FAU - Sato, Kanako AU - Sato K AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Irie, Yoko AU - Irie Y AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Asai, Hiroaki AU - Asai H AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Yoshioka, Saori AU - Yoshioka S AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Murakawa, Keisuke AU - Murakawa K AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Sho, Hiroyuki AU - Sho H AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Inui, Ryoko AU - Inui R AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Kosugi, Motohiro AU - Kosugi M AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Hazama, Yoji AU - Hazama Y AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Yasuda, Tetsuyuki AU - Yasuda T AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20251009 PL - Japan TA - Intern Med JT - Internal medicine (Tokyo, Japan) JID - 9204241 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - *Liver/enzymology/drug effects MH - *Fatty Liver/drug therapy/complications/enzymology MH - Drug Therapy, Combination MH - Aspartate Aminotransferases/blood MH - Alanine Transaminase/blood MH - Glycated Hemoglobin/metabolism PMC - PMC13265098 OTO - NOTNLM OT - Type 2 diabetes OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide OT - sodium-glucose cotransporter 2 inhibitors COIS- Tetsuyuki Yasuda received lecture fees from Eli Lilly Japan K.K., Sumitomo Pharma, Novo Nordisk Pharma, and Mitsubishi Tanabe Pharma. The authors declare that they have no conflicts of interest. EDAT- 2025/10/09 00:30 MHDA- 2026/05/18 00:30 PMCR- 2026/05/15 CRDT- 2025/10/08 21:43 PHST- 2026/05/18 00:30 [medline] PHST- 2025/10/09 00:30 [pubmed] PHST- 2025/10/08 21:43 [entrez] PHST- 2026/05/15 00:00 [pmc-release] AID - 10.2169/internalmedicine.6239-25 [doi] PST - ppublish SO - Intern Med. 2026 May 15;65(10):1334-1341. doi: 10.2169/internalmedicine.6239-25. Epub 2025 Oct 9. PMID- 41058255 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Addressing the risk of ocular complications of GLP-1RAs; a multi-disciplinary expert consensus. PG - 7535-7543 LID - 10.1111/dom.70160 [doi] AB - AIMS: There is current apprehension among some clinicians and conflicting evidence regarding ocular complications in relation to Glucagon-like peptide-1 receptor agonists (GLP-1RAs). We aimed to generate multi-disciplinary, expert-led consensus recommendations relating to ocular complications to facilitate optimum prescribing of GLP-1RAs. MATERIALS AND METHODS: A modified Delphi was conducted following the ACcurate COnsensus Reporting Document (ACCORD) for Delphi research. A structured literature review informed an anonymous online Delphi questionnaire, followed by a virtual consensus meeting. Eligible participants included ophthalmologists, diabetologists, and obesity specialists practising in Europe. RESULTS: Responses from 58 participants across 17 countries were analysed. Respondents agreed that diabetic retinopathy (DR) worsening events are primarily linked to rapid blood glucose-lowering, rather than a direct drug effect. The benefits of GLP-1RAs were deemed to outweigh potential ocular risks and should not limit access to these medicines. Prescribers should ensure that people with diabetes are screened for diabetic retinopathy before commencing GLP-1RAs, particularly in high-risk populations (>10 years duration and/or poor glucose control, (haemoglobin A1c [HbA1c] >10% or 86 mmol/mol)). When prescribing GLP-1RA to those with sight loss in one eye and/or prior history of non-arteritic anterior ischaemic optic neuropathy (NAION), the risk of ocular complications should be discussed. The Delphi study highlighted current uncertainty in the evidence, with some topics on the relationship between GLP-1RAs and ocular complications reaching limited consensus. CONCLUSIONS: Further research is needed into the direct effects of GLP-1RAs on the retina and ocular complications. New evidence should be disseminated rapidly to optimise outcomes and safety. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Carter, Patrice AU - Carter P AUID- ORCID: 0000-0003-3445-6754 AD - Evidence Review & Synthesis, Health Economics & Outcomes Research Ltd., Cardiff, UK. FAU - Simo, Rafael AU - Simo R AUID- ORCID: 0000-0003-0475-3096 AD - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Campus Vall d'Hebron and CIBERDEM, Barcelona, Spain. FAU - Lovestam-Adrian, Monica AU - Lovestam-Adrian M AD - Department of Ophthalmology, Lund University, Lund, Sweden. FAU - Pearce, Ian AU - Pearce I AD - St Pauls Eye Unit, Liverpool University Hospitals, NHS Foundation Trust, Liverpool, UK. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - School of Medicine, Swansea University, Swansea, UK. FAU - Dinah, Christiana AU - Dinah C AD - Ophthalmology Department, London North West University Healthcare NHS Trust, Harrow, UK. FAU - Davies, Sarah Jane AU - Davies SJ AD - Woodlands Medical Centre, Cardiff, UK. FAU - Strain, W David AU - Strain WD AUID- ORCID: 0000-0002-6826-418X AD - Diabetes and Vascular Research Centre, University of Exeter, Exeter, UK. FAU - Burgess, Philip AU - Burgess P AD - St Pauls Eye Unit, Liverpool University Hospitals, NHS Foundation Trust, Liverpool, UK. AD - Department of Eye and Vision Science, University of Liverpool, Liverpool, UK. FAU - Gamble, Amy AU - Gamble A AD - Evidence Review & Synthesis, Health Economics & Outcomes Research Ltd., Cardiff, UK. FAU - Hembury, Chloe AU - Hembury C AD - Evidence Review & Synthesis, Health Economics & Outcomes Research Ltd., Cardiff, UK. FAU - Evans, Marc AU - Evans M AUID- ORCID: 0000-0003-0671-0778 AD - Diabetes Resource Centre, University Hospital Llandough, Cardiff, UK. LA - eng PT - Consensus Statement PT - Journal Article DEP - 20251008 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Retinopathy/chemically induced/epidemiology/prevention & control MH - Delphi Technique MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Eye Diseases/chemically induced MH - Risk Factors OTO - NOTNLM OT - Delphi OT - consensus recommendations OT - diabetic retinopathy OT - glucagon-like peptide-1 receptor agonists OT - non-arteritic anterior ischemic optic neuropathy EDAT- 2025/10/08 06:29 MHDA- 2025/11/05 06:29 CRDT- 2025/10/08 03:03 PHST- 2025/09/17 00:00 [revised] PHST- 2025/08/08 00:00 [received] PHST- 2025/09/17 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/10/08 06:29 [pubmed] PHST- 2025/10/08 03:03 [entrez] AID - 10.1111/dom.70160 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7535-7543. doi: 10.1111/dom.70160. Epub 2025 Oct 8. PMID- 41058240 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach. PG - 137-150 LID - 10.1111/dom.70169 [doi] AB - AIMS: There is growing evidence that the GLP-1 system is implicated in alcohol and other substance use disorders, and that GLP-1-based therapies may have therapeutic relevance in alcohol use disorder (AUD). We aimed to determine the impact of GLP-1 based therapies on incident AUDs in a real-world setting in patients with T2D. MATERIAL AND METHODS: We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America. Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i). First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses. Four target trial cohorts were generated and compared with a reference arm of patients treated with DPP4i: cohort (1) treatment with tirzepatide; cohort (2) treatment with semaglutide; cohort (3) treatment with liraglutide; and cohort (4) treatment with dulaglutide. Cohorts underwent propensity score matching 1:1 for confounders. We examined rates of incident AUD (ICD-10 code F10) and performed head-to-head analyses of the incretin-based therapies. We also performed sensitivity analyses relating to whether treatment was adjunctive therapy with metformin and by treatment adherence. RESULTS: After propensity-score matching, we identified four target trials of patients treated with tirzepatide (n = 7165), semaglutide (n = 20 198), liraglutide (n = 6565), and dulaglutide (n = 19 061); 1:1 with the reference (DPP4i) patients. Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively). Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]). CONCLUSION: In patients with T2D, tirzepatide and semaglutide treatment is associated with a lower incidence of AUD; robust randomised, controlled evidence for the use of these drugs for this novel indication is appropriate. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Heague, Megan AU - Heague M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Roberts, Carl A AU - Roberts CA AD - Department of Psychology, Institute of Population Health, University of Liverpool, Merseyside, UK. FAU - Hydes, Theresa J AU - Hydes TJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Hughes, David M AU - Hughes DM AD - Deparment of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. LA - eng PT - Journal Article DEP - 20251007 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Incretins) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Liraglutide/therapeutic use MH - Female MH - Middle Aged MH - *Alcoholism/prevention & control/epidemiology MH - Recombinant Fusion Proteins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide 1/agonists/analogs & derivatives/therapeutic use MH - Tirzepatide/therapeutic use MH - Adult MH - Aged MH - Treatment Outcome MH - Drug Therapy, Combination MH - Incretins/therapeutic use MH - Receptors, Gastrointestinal Hormone MH - Semaglutide PMC - PMC12673470 OTO - NOTNLM OT - GLP-1 analogue OT - cohort study OT - real-world evidence OT - type 2 diabetes COIS- MA receives a fellowship from the Novo Nordisk UK research foundation and JDRF. CAR has acted as a consultant for Boehringer Ingelheim and has received grant funding from Unilever. DJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum, with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool, and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. GHI is an employee of TriNetX LLC. UA has received honoraria from Procter & Gamble, Viatris, Grunenthal, and Sanofi for educational meetings and funding for attendance at an educational meeting from Daiichi Sankyo. UA has also received investigator-led funding from Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2025/10/08 06:29 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/08 03:03 PHST- 2025/09/15 00:00 [revised] PHST- 2025/04/08 00:00 [received] PHST- 2025/09/21 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/08 06:29 [pubmed] PHST- 2025/10/08 03:03 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70169 [pii] AID - 10.1111/dom.70169 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):137-150. doi: 10.1111/dom.70169. Epub 2025 Oct 7. PMID- 41055617 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260418 IS - 1531-6564 (Electronic) IS - 0363-5023 (Linking) VI - 50 IP - 11 DP - 2025 Nov TI - Glucagon-like peptide-1 Agonists and Common Hand Procedures: Perioperative and Postoperative Risks and Complications. PG - 1297-1303 LID - S0363-5023(25)00442-3 [pii] LID - 10.1016/j.jhsa.2025.08.004 [doi] AB - PURPOSE: Glucagon-like peptide-1 (GLP-1) receptor agonists have recently become a cornerstone in managing type 2 diabetes mellitus and obesity given their ability to improve glycemic control and promote weight loss. However, the postoperative safety profile of these medications in patients undergoing common hand procedures remains poorly studied. The purpose of this study was to evaluate the effects of preoperative GLP-1 agonists use on postoperative complications, readmission, and reoperation following several commonly performed hand procedures. METHODS: A retrospective study using a large insurance claims database was performed from 2015 to 2022. Patients undergoing six common hand procedures were queried. Individuals taking GLP-1 agonists at the time of surgery were propensity score-matched to those not taking the medications in a 1:4 fashion controlling for numerous clinical variables. Postoperative complications, 90-day readmission, 90-day reoperation for infection, and 2-year all-cause revision rates were then calculated between both groups using multivariable logistic regression. RESULTS: Patients taking GLP-1 agonists had equal or lower odds of postoperative infections including lower rates of surgical site infections and equal rates of wound dehiscence. These patients also had lower risk of postoperative pneumonia, acute kidney injury, hematoma, pulmonary embolism, and deep vein thrombosis. Risk of all-cause 90-day readmission was significantly lower for patients taking GLP-1 agonists. Rates of 90-day reoperation for infection and 2-year all-cause revision were equal between both cohorts. CONCLUSION: This study found that patients taking GLP-1 agonists were at no higher risk for 90-day postoperative infections including surgical site infections and wound dehiscence. Furthermore, these patients demonstrated equal or lower rates of overall perioperative complications, reoperation, and readmission compared to their matched controls. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IIc. CI - Copyright (c) 2025 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved. FAU - Amen, Troy B AU - Amen TB AD - Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY. Electronic address: ament@hss.edu. FAU - Ibrahim, Lina I AU - Ibrahim LI AD - Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY. FAU - Gillinov, Stephen M AU - Gillinov SM AD - Department of Orthopedic Surgery, Yale New Haven Hospital, New Haven, CT. FAU - Torabian, Kaveh A AU - Torabian KA AD - Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL. FAU - Dean, Michael C AU - Dean MC AD - Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN. FAU - Liimakka, Adriana AU - Liimakka A AD - Harvard Medical School, Boston, MA. FAU - Lee, Steve K AU - Lee SK AD - Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY. LA - eng PT - Journal Article DEP - 20251006 PL - United States TA - J Hand Surg Am JT - The Journal of hand surgery JID - 7609631 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Retrospective Studies MH - Female MH - Middle Aged MH - *Postoperative Complications/epidemiology MH - Reoperation/statistics & numerical data MH - Patient Readmission/statistics & numerical data MH - Aged MH - *Hand/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Adult MH - Propensity Score OTO - NOTNLM OT - Common Hand Procedures OT - GLP-1 OT - Glucagon-like peptide-1 Agonist OT - Hand Surgery OT - Perioperative Complications OT - Postoperative Complications COIS- Conflicts of Interest No benefits in any form have been received or will be received related directly to this article. The authors have no relevant conflicts to disclose. EDAT- 2025/10/07 12:30 MHDA- 2025/11/06 00:27 CRDT- 2025/10/07 10:53 PHST- 2025/01/07 00:00 [received] PHST- 2025/07/30 00:00 [revised] PHST- 2025/08/07 00:00 [accepted] PHST- 2025/11/06 00:27 [medline] PHST- 2025/10/07 12:30 [pubmed] PHST- 2025/10/07 10:53 [entrez] AID - S0363-5023(25)00442-3 [pii] AID - 10.1016/j.jhsa.2025.08.004 [doi] PST - ppublish SO - J Hand Surg Am. 2025 Nov;50(11):1297-1303. doi: 10.1016/j.jhsa.2025.08.004. Epub 2025 Oct 6. PMID- 41054801 OWN - NLM STAT- MEDLINE DCOM- 20260311 LR - 20260614 IS - 1945-7189 (Electronic) IS - 0163-769X (Linking) VI - 47 IP - 2 DP - 2026 Mar 11 TI - Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. PG - 159-177 LID - 10.1210/endrev/bnaf036 [doi] AB - The approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. Building on their success, novel glucagon-like peptide-1 (GLP-1)-based therapeutics are rapidly advancing. These next-generation agents engage not only GLP-1 receptors but also those for other gastro-entero-pancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, and peptide YY to enhance energy uptake, storage, and expenditure through synergistic mechanisms. Both GIP receptor agonism and antagonism, particularly in combination with GLP-1 receptor agonism, have shown promise. Maridebart cafraglutide, combining GLP-1 receptor agonism with GIP receptor antagonism, exemplifies this innovative approach. Glucagon coagonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multireceptor agonists and oral GLP-1-based therapies may reshape the future landscape of obesity and type 2 diabetes treatment by offering more effective and better-tolerated options. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Son, Jang Won AU - Son JW AUID- ORCID: 0000-0003-0339-0131 AD - Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, University College Dublin, Dublin D04 C1P1, Ireland. FAU - Bluher, Matthias AU - Bluher M AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum, St. Josef Hospital (Ruhr University Bochum), Bochum 44791, Germany. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea. LA - eng PT - Journal Article PT - Review PL - United States TA - Endocr Rev JT - Endocrine reviews JID - 8006258 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Animals OTO - NOTNLM OT - amylin OT - glucagon OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - obesity EDAT- 2025/10/07 06:29 MHDA- 2026/03/11 19:00 CRDT- 2025/10/07 04:32 PHST- 2025/05/10 00:00 [received] PHST- 2025/09/24 00:00 [accepted] PHST- 2026/03/11 19:00 [medline] PHST- 2025/10/07 06:29 [pubmed] PHST- 2025/10/07 04:32 [entrez] AID - 8276515 [pii] AID - 10.1210/endrev/bnaf036 [doi] PST - ppublish SO - Endocr Rev. 2026 Mar 11;47(2):159-177. doi: 10.1210/endrev/bnaf036. PMID- 41053738 OWN - NLM STAT- MEDLINE DCOM- 20251007 LR - 20260903 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Oct 6 TI - Real-world cardiovascular effectiveness of sustained glucagon-like peptide 1 GLP-1 receptor agonist usage in type 2 diabetes. PG - 385 LID - 10.1186/s12933-025-02915-1 [doi] LID - 385 AB - BACKGROUND: Cardiovascular outcome trials have shown that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular event rates more effectively than placebo and in patients with type 2 diabetes at increased cardiovascular risk. However, the generalizability of these findings to real-world settings remains uncertain. AIM: This study aimed to evaluate the real-world cardiovascular effectiveness of sustained GLP1-RA use compared to dipeptidyl peptidase 4 inhibitor (DPP-4i) over 3.5 years. METHODS: Using Danish nationwide registries, we emulated a target trial to assess the real-world effectiveness of GLP1-RAs in a population of individuals with type 2 diabetes mirroring the inclusion and exclusion criteria from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. The study period was 2012-2022. Outcomes included the composite of myocardial infarction, stroke, and cardiovascular mortality (3P-MACE), as well as each component individually, alongside all-cause mortality, heart failure, angina pectoris, and revascularization. Longitudinal Targeted Minimum Loss-based Estimation, a method that adjusts for both baseline and time-varying confounding, was used to estimate absolute risks of cardiovascular outcomes under sustained use of GLP1-RA and DPP 4i (active comparator), adjusting for baseline and time-varying confounding. RESULTS: We included 6,681 people initiating GLP1-RA and 19,072 initiating DPP-4i. Accounting for baseline and time-varying confounding, sustained GLP1-RA use showed a 2.5% (95% CI 0.8-4.1%) risk reduction of 3P-MACEover 3.5 years. Risk reductions for cardiovascular mortality, all-cause mortality, heart failure, and unstable angina pectoris were 2.3% (95% CI 1.4-3.1%), 2.5% (95% CI 0.7-4.3%), 0.9% (95% CI 0.01-1.8%), and 0.7% (95% CI 0.01-1.3%), respectively. No significant differences were observed for myocardial infarction, stroke, or revascularization with risk differences of 0.1% (95% CI -1.0 to 0.8%), 0.8% (95% CI -0.2 to 1.7%), and 0.2% (95% CI -0.7-1.1%), respectively. CONCLUSIONS: This real-world study confirms the cardiovascular benefits of GLP1-RAs over DPP-4is, particularly for reducing cardiovascular and all-cause mortality under continuous treatment exposure in patients with type 2 diabetes at increased cardiovascular risk. CI - (c) 2025. The Author(s). FAU - Sorensen, Kathrine Kold AU - Sorensen KK AUID- ORCID: 0000-0002-9402-1317 AD - Clinical and Translational Research, Copenhagen University Hospital, Steno Diabetes Center Herlev, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark. kathrine.kold.soerensen@regionh.dk. FAU - Yazdanfard, Puriya Daniel Wurtz AU - Yazdanfard PDW AD - Clinical and Translational Research, Copenhagen University Hospital, Steno Diabetes Center Herlev, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark. FAU - Zareini, Bochra AU - Zareini B AD - Clinical and Translational Research, Copenhagen University Hospital, Steno Diabetes Center Herlev, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark. FAU - Pedersen-Bjergaard, Ulrik AU - Pedersen-Bjergaard U AD - Department of Endocrinology and Nephrology, North Zealand University Hospital, Hillerod, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Kosjerina, Vanja AU - Kosjerina V AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Andersen, Mikkel Porsborg AU - Andersen MP AD - Clinical and Translational Research, Copenhagen University Hospital, Steno Diabetes Center Herlev, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark. AD - The Prehospital Center, Region Zealand, Naestved, Denmark. FAU - Munch, Anders AU - Munch A AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Ohlendorff, Johan Sebastian AU - Ohlendorff JS AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Schmid, Stefanie AU - Schmid S AD - Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. AD - German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. FAU - Lanzinger, Stefanie AU - Lanzinger S AD - Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. AD - German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. FAU - Choudhary, Pratik AU - Choudhary P AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Gillies, Clare AU - Gillies C AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Gharibzadeh, Safoora AU - Gharibzadeh S AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Lind, Marcus AU - Lind M AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. AD - Department of Medicine, NU-Hospital Group, Uddevalla, Sweden. FAU - Tasselius, Viktor AU - Tasselius V AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Michelsen, Jens AU - Michelsen J AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Gerds, Thomas Alexander AU - Gerds TA AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Torp-Pedersen, Christian AU - Torp-Pedersen C AD - Clinical and Translational Research, Copenhagen University Hospital, Steno Diabetes Center Herlev, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark. AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251006 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Denmark/epidemiology MH - Middle Aged MH - Treatment Outcome MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis/epidemiology MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use/administration & dosage MH - *Incretins/adverse effects/therapeutic use/administration & dosage MH - Time Factors MH - Risk Assessment MH - Registries MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Heart Disease Risk Factors MH - Biomarkers/blood MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12502128 COIS- Declarations. Ethics approval: Danish registry-based studies performed for statistics and scientific research do not require patient consent or ethical committee approval, as stated in the Danish Data Protection Act. Approval to use the data sources for research purposes was granted by the data responsible institute of the Capital Region of Denmark under the General Data Protection Regulation (GDPR). Danish legislation states that data is accessed on secure servers under Statistics Denmark and cannot be shared [39]. Competing interests: The authors declare no competing interests. EDAT- 2025/10/07 00:29 MHDA- 2025/10/07 06:29 PMCR- 2025/10/06 CRDT- 2025/10/07 00:00 PHST- 2025/04/28 00:00 [received] PHST- 2025/08/21 00:00 [accepted] PHST- 2025/10/07 06:29 [medline] PHST- 2025/10/07 00:29 [pubmed] PHST- 2025/10/07 00:00 [entrez] PHST- 2025/10/06 00:00 [pmc-release] AID - 10.1186/s12933-025-02915-1 [pii] AID - 2915 [pii] AID - 10.1186/s12933-025-02915-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Oct 6;24(1):385. doi: 10.1186/s12933-025-02915-1. PMID- 41053152 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20251009 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Oct 6 TI - Disproportionality analysis of GLP-1 receptor agonists combined with metformin based on the FAERS database. PG - 34673 LID - 10.1038/s41598-025-02394-0 [doi] LID - 34673 AB - This study analyzed adverse events (AEs) of GLP-1RA and metformin combination therapy using FAERS data (2004-2024). A retrospective disproportionality analysis was conducted using the reporting odds ratio (ROR) on FAERS data (2004-2024), with Bayesian confidence propagation neural network (BCPNN) employed for sensitivity analysis. Adverse reactions were compared between combination therapy and monotherapy (GLP-1 RAs or metformin alone), followed by stratified analyses by gender, age, and body weight. Among 48,214 reports (57.5% female), common AEs included nausea and weight loss. Unexpected signals included kidney injury and pancreatic cancer. Monotherapy showed higher AE rates. Males reported more renal calculi and early-onset AEs ( 360 days). Weight loss was consistent across all demographics. The combination therapy of GLP-1 receptor agonists and metformin demonstrates superior safety over monotherapy, while revealing novel adverse events and demographic-specific risk patterns, thereby offering reliable evidence to inform clinical practice. CI - (c) 2025. The Author(s). FAU - Liu, Boyi AU - Liu B AD - The First Clinical College, Changsha Medical University, Changsha, 410219, China. FAU - Huang, Ruizhe AU - Huang R AD - The First Clinical College, Changsha Medical University, Changsha, 410219, China. FAU - Zhang, Wenchao AU - Zhang W AD - The First Clinical College, Changsha Medical University, Changsha, 410219, China. FAU - Tian, Jie AU - Tian J AD - The First Clinical College, Changsha Medical University, Changsha, 410219, China. FAU - Yao, Xian AU - Yao X AD - The First Clinical College, Changsha Medical University, Changsha, 410219, China. FAU - Chen, Danna AU - Chen D AD - Department of Basic Medical Sciences, Changsha Medical University, 1501 Leifeng Street, Changsha, 410219, Hunan, China. chendanna007@gmail.com. AD - Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha, China. chendanna007@gmail.com. LA - eng GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - S202410823011/National Undergraduate Innovation and Entrepreneurship Training Program 2024 (Letter No. 13 [2024] from the Department of Higher Education)/ GR - 23A0667/Hunan Provincial Department of Education Fund Project/ GR - kq2106074/Changsha Outstanding Youth Innovation Talent Development Program/ GR - Clinical Medicine/The "14th Five-Year Plan" Applied Characteristic Discipline of Hunan Province/ PT - Journal Article DEP - 20251006 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Metformin/adverse effects/administration & dosage/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - Drug Therapy, Combination/adverse effects MH - Retrospective Studies MH - Adult MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy PMC - PMC12500926 OTO - NOTNLM OT - Disproportionality analysis OT - Drug safety OT - GLP-1 receptor agonists OT - Metformin OT - Pharmacovigilance COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/10/07 00:29 MHDA- 2025/10/07 00:30 PMCR- 2025/10/06 CRDT- 2025/10/06 23:25 PHST- 2025/02/21 00:00 [received] PHST- 2025/05/13 00:00 [accepted] PHST- 2025/10/07 00:30 [medline] PHST- 2025/10/07 00:29 [pubmed] PHST- 2025/10/06 23:25 [entrez] PHST- 2025/10/06 00:00 [pmc-release] AID - 10.1038/s41598-025-02394-0 [pii] AID - 2394 [pii] AID - 10.1038/s41598-025-02394-0 [doi] PST - epublish SO - Sci Rep. 2025 Oct 6;15(1):34673. doi: 10.1038/s41598-025-02394-0. PMID- 41052622 OWN - NLM STAT- MEDLINE DCOM- 20260424 LR - 20260519 IS - 1098-8785 (Electronic) IS - 0735-1631 (Linking) VI - 43 IP - 7 DP - 2026 May TI - Glucagon-Like Peptide-1 Receptor Agonists among Pregnancies with Pregestational Diabetes and Its Relationship with Congenital Malformations. PG - 984-988 LID - 10.1055/a-2716-1639 [doi] AB - OBJECTIVE: Pregestational diabetes is a common complication seen in pregnancy, with significant increase seen in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for diabetes management in reproductive-age individuals. The objective of this study was to describe the perinatal outcomes and prevalence of congenital malformations associated with the use of GLP-1 RA in individuals with pregestational diabetes using a national dataset. STUDY DESIGN: This study was a retrospective cohort study of patients with pregestational diabetes and pregnancies using data obtained from the Epic Cosmos database between May 1, 2022 and April 30, 2025. Demographics, perinatal outcomes, and prevalence of congenital malformations were compared by GLP-1 RA exposure in pregnancy. Categorical variables were compared with Chi-square and continuous variables were compared using student t-tests for two comparisons. No individual level data were available, so covariate adjustment was not performed. RESULTS: The total sample population was 143,593 patients with pregestational diabetes, with 24.4% (n = 35,083) of patients using a GLP-1 RA at some time point in pregnancy. Patients with GLP-1 RA usage were more likely to develop pre-eclampsia (13.1 versus 11.9%, p < 0.00001), have a cesarean delivery (44.4 vs. 38.9%, p < 0.0001), have a first trimester pregnancy loss/termination (9.8 vs. 7.5%, p < 0.00001), and a preterm delivery (23.1 vs. 20.8%, p < 0.0001) when compared with patients without GLP-1 RA use. There was no statistically significant difference in the overall rate of any congenial malformation by GLP-1 RA use (3.3% in both groups, p = 0.63). However, patients with GLP-1 RA usage were more likely to have fetuses with genital malformations (0.7 vs. 0.6%, p = 0.02) and urinary malformations (0.5 vs. 0.4%, p = 0.01) compared with patients without GLP-1 RA use. CONCLUSION: GLP-1 RA therapy in a large cohort of pregnant patients with pregestational diabetes was associated with an overall low rate of malformations but found to have a possible increase in genital and urinary malformations. Counseling of patients prior to use of this medication in the preconception period is required. KEY POINTS: . GLP-1 receptor agonist therapy exposure is common in pregnancy among patients with diabetes.. . GLP-1 receptor agonist therapy was not associated with an increased risk of overall malformations.. . GLP-1 receptor agonist therapy was associated with increased genital and urinary malformations.. CI - Thieme. All rights reserved. FAU - Lewin, Zoe AU - Lewin Z AD - Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts, United States. FAU - Snow, Shani AU - Snow S AUID- ORCID: 0009-0000-3934-1740 AD - Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts, United States. FAU - Lee, Jung Ae AU - Lee JA AD - Department of Population and Quantitative Health Sciences, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts, United States. FAU - Wilkie, Gianna AU - Wilkie G AUID- ORCID: 0000-0002-1712-0514 AD - Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts, United States. LA - eng GR - K23HD111526/Eunice Kennedy Shriver National Institute of Child Health and Human Development/ PT - Journal Article DEP - 20251006 PL - United States TA - Am J Perinatol JT - American journal of perinatology JID - 8405212 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Pregnancy MH - Retrospective Studies MH - *Pregnancy in Diabetics/drug therapy MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Congenital Abnormalities/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Infant, Newborn MH - Pregnancy Outcome MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Abnormalities, Drug-Induced/epidemiology MH - Prevalence COIS- G.W. provides consulting services for VentureWell. All other authors report no conflicts of interest. EDAT- 2025/10/07 00:29 MHDA- 2026/04/25 00:34 CRDT- 2025/10/06 19:14 PHST- 2026/04/25 00:34 [medline] PHST- 2025/10/07 00:29 [pubmed] PHST- 2025/10/06 19:14 [entrez] AID - 10.1055/a-2716-1639 [doi] PST - ppublish SO - Am J Perinatol. 2026 May;43(7):984-988. doi: 10.1055/a-2716-1639. Epub 2025 Oct 6. PMID- 41051803 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20260127 IS - 1997-7298 (Print) IS - 1997-7298 (Linking) VI - 125 IP - 9 DP - 2025 TI - [Effects of semaglutide on mental health]. PG - 28-36 LID - 10.17116/jnevro202512509128 [doi] AB - Semaglutide is a glucagon-like peptide-1 receptor agonist, approved and currently actively used worldwide for the treatment of type 2 diabetes mellitus and obesity. With the growing popularity of the drug, reports of both adverse and beneficial effects of the drug on mental health have become more frequent. The purpose of this study is to review the impact of semaglutide on mental health by collecting, analyzing, and synthesizing current scientific evidence. The authors conclude that currently there is no unequivocal opinion on this matter, which opens up new horizons for future research. FAU - Rozhdestvenskaya, V A AU - Rozhdestvenskaya VA AUID- ORCID: 0009-0000-8348-4706 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Yuzbashyan, P G AU - Yuzbashyan PG AUID- ORCID: 0000-0002-7441-5546 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Romanov, D V AU - Romanov DV AUID- ORCID: 0000-0002-1822-8973 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. AD - Centre for Mental Health Research, Moscow, Russia. FAU - Shchurenkov, A V AU - Shchurenkov AV AUID- ORCID: 0009-0005-7128-0171 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Kazaryan, P A AU - Kazaryan PA AUID- ORCID: 0009-0009-8501-9336 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Sheyanov, A M AU - Sheyanov AM AUID- ORCID: 0009-0009-9601-0193 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Zubacheva, E O AU - Zubacheva EO AUID- ORCID: 0009-0004-8702-3834 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Fedyainova, I K AU - Fedyainova IK AUID- ORCID: 0009-0006-3281-6962 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. LA - rus PT - English Abstract PT - Journal Article PT - Review TT - Vliyanie semaglutida na psikhicheskoe zdorov'e. PL - Russia (Federation) TA - Zh Nevrol Psikhiatr Im S S Korsakova JT - Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova JID - 9712194 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy MH - *Mental Health MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 agonists OT - addiction OT - alcohol dependence OT - anxiety OT - autoaggression OT - cognitive functions OT - depression OT - diabetes mellitus OT - obesity OT - semaglutide OT - suicidal behavior OT - weight loss EDAT- 2025/10/06 12:31 MHDA- 2025/10/06 12:32 CRDT- 2025/10/06 11:46 PHST- 2025/10/06 12:32 [medline] PHST- 2025/10/06 12:31 [pubmed] PHST- 2025/10/06 11:46 [entrez] AID - 10.17116/jnevro202512509128 [doi] PST - ppublish SO - Zh Nevrol Psikhiatr Im S S Korsakova. 2025;125(9):28-36. doi: 10.17116/jnevro202512509128. PMID- 41047964 OWN - NLM STAT- MEDLINE DCOM- 20251031 LR - 20260703 IS - 2042-6313 (Electronic) IS - 2042-6305 (Print) IS - 2042-6305 (Linking) VI - 14 IP - 11 DP - 2025 Nov TI - Healthcare costs and treatment patterns associated with glucagon-like peptide 1 receptor agonist use among patients with metabolic dysfunction-associated steatohepatitis. PG - e240223 LID - 10.57264/cer-2024-0223 [doi] LID - e240223 AB - Aim: While only recently approved for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), many patients with MASH have taken glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of comorbid Type 2 diabetes (T2D) or obesity. This real-world study evaluated treatment patterns, weight loss, healthcare resource utilization, and costs among patients with MASH who initiated GLP-1 RAs. Materials & methods: In a linked electronic health records (Veradigm Network EHR) and claims (Komodo Health) dataset, we identified adults (>/=18 years old) with a MASH diagnosis who initiated GLP-1 RA treatment (1 July 2018 to 30 April 2023; index date = date of the first GLP-1 RA claim). Patients with other causes of liver disease or severe complications from MASH were excluded. We required >/=12 months of continuous enrollment pre- (baseline) and post-index (follow-up). Patients were stratified into high and low-dose subgroups. We also identified a comparator cohort of patients who initiated a different class of T2D medication (DPP4, SGLT2, or sulfonylurea) during the same time period. We captured patient characteristics, change in BMI, GLP-1 RA treatment patterns, liver-related events, healthcare utilization, and costs. Results: We identified 10,316 patients with MASH who initiated a GLP-1 RA (high dose: 2043 [19.8%]; low dose: 8273 [80.2%]) and 2915 who initiated a non-GLP-1 RA T2D medication. GLP-1 RA users were 52.7 years old and 64.3% female. A 5.8% decrease in the percentage of patients with class III obesity was observed among GLP-1 RA users (10.7% among high-dose users; 0.8% among non-users). Overall, 56.1% of GLP-1 RA users discontinued during the 12-month follow-up. Total costs among GLP-1 RA users and non users were $20,912 and $19,019 in the baseline period and $27,586 and $24,917 in the follow-up period, respectively. Medical costs among GLP-1 RA users were $16,293 (baseline) and $16,886 (follow-up). Results were similar for high and low-dose subgroups. Conclusion: Although some patients with MASH on GLP-1 RAs, particularly those taking higher dosages, may achieve weight loss, outcomes remain suboptimal with frequent discontinuation and high healthcare costs. Real-world GLP-1 RA utilization may be insufficient for resolving chronic metabolic issues, including MASH. FAU - Tapper, Elliot B AU - Tapper EB AUID- ORCID: 0000-0002-0839-1515 AD - Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Ryan, Taylor AU - Ryan T AD - Veradigm, Chicago, IL 60654, USA. FAU - Zeng, Ni AU - Zeng N AUID- ORCID: 0000-0003-2368-5279 AD - Veradigm, Chicago, IL 60654, USA. FAU - Carter, Renee AU - Carter R AD - Veradigm, Chicago, IL 60654, USA. FAU - Winer-Jones, Jessamine P AU - Winer-Jones JP AUID- ORCID: 0000-0002-6412-4139 AD - Veradigm, Chicago, IL 60654, USA. FAU - Bonafede, Machaon AU - Bonafede M AUID- ORCID: 0000-0001-6330-6718 AD - Veradigm, Chicago, IL 60654, USA. FAU - Kim, Yestle AU - Kim Y AUID- ORCID: 0009-0007-0263-9384 AD - Madrigal Pharmaceuticals, Inc., West Conshohocken, PA 19428, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251006 PL - England TA - J Comp Eff Res JT - Journal of comparative effectiveness research JID - 101577308 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Health Care Costs/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use/economics MH - Adult MH - Obesity/drug therapy/complications MH - Aged MH - *Fatty Liver/drug therapy/economics MH - Weight Loss/drug effects MH - Patient Acceptance of Health Care/statistics & numerical data PMC - PMC12580915 OAB - What is this article about? Metabolic dysfunction-associated steatohepatitis (MASH) is a liver disease that gets worse over time. MASH can lead to serious complications such as liver failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat obesity and Type 2 diabetes, which are common among people with MASH. This article is about the usage of GLP-1 RAs among people diagnosed with MASH. We looked at patient characteristics, BMI, patterns of medication treatment, reasons for discontinuation and changes in healthcare use and costs after starting GLP-1 RA. We also captured similar data for people who started a different Type 2 diabetes treatment to provide additional context. What were the results? People with MASH who took GLP-1 RA tended to lose weight, measured as a decrease in the percentage of patients with a very high BMI (>/=40). This was not observed in people who started a different Type 2 diabetes treatment. More than half of people who started GLP-1 RAs stopped treatment for at least 45 days within 1 year. Roughly half of people who stopped treatment did not restart treatment. Side effects were the most common reason for stopping treatment. Total healthcare costs were $27,586, and nonmedicine-related costs were $16,886 in the year after starting treatment. What do the results mean? GLP-1 RA may be effective in promoting weight loss among people with MASH, but these medications may not address other issues among people with MASH as healthcare use and costs remain high. OABL- eng OTO - NOTNLM OT - GLP-1 RA OT - MASH OT - NAFLD OT - healthcare costs OT - treatment patterns COIS- Competing interests disclosure T Marlin, N Zeng, R Carter, JP Winer-Jones and M Bonafede are employees of Veradigm, which received fees from Madrigal Pharmaceuticals related to this work. Y Kim is an employee of Madrigal Pharmaceuticals. EB Tapper is an employee at the University of Michigan, which received unrestricted financial support to the institution related to this work. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed. EDAT- 2025/10/06 06:30 MHDA- 2025/10/31 17:31 PMCR- 2025/10/06 CRDT- 2025/10/06 04:23 PHST- 2025/10/31 17:31 [medline] PHST- 2025/10/06 06:30 [pubmed] PHST- 2025/10/06 04:23 [entrez] PHST- 2025/10/06 00:00 [pmc-release] AID - 10.57264/cer-2024-0223 [doi] PST - ppublish SO - J Comp Eff Res. 2025 Nov;14(11):e240223. doi: 10.57264/cer-2024-0223. Epub 2025 Oct 6. PMID- 41045922 OWN - NLM STAT- MEDLINE DCOM- 20251015 LR - 20261022 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 58 IP - 10 DP - 2025 Oct 14 TI - Obesity, diabetes, and inflammation: Pathophysiology and clinical implications. PG - 2373-2382 LID - S1074-7613(25)00422-4 [pii] LID - 10.1016/j.immuni.2025.09.011 [doi] AB - Obesity and its related disorders, including type 2 diabetes and liver, kidney, and cardiovascular diseases, are now recognized as chronic inflammatory conditions. Here, we review the mechanisms underlying inflammation in these settings and how they may contribute to pathology. Nutrient excess triggers immune activation through pattern recognition receptors and the NLRP3 inflammasome, leading to interleukin (IL)-1beta production and downstream cytokine cascades. Initially adaptive, this inflammation promotes tissue remodeling and metabolic compensation, but chronic activation contributes to insulin resistance, beta cell dysfunction, and end-organ damage. We discuss the current therapeutic options, with a focus on glucagon-like peptide-1 (GLP-1) receptor agonists, which, alone or combined with additional bioactive moieties, exert notable anti-inflammatory effects. Some effects of GLP-1 medicines are independent of glucose control or weight loss, and they are attributed to direct signaling via the immune GLP-1 receptor (GLP-1R) and, indirectly, via central nervous system circuits. Understanding these mechanisms may unlock further therapeutic potential in chronic inflammatory diseases. CI - Crown Copyright (c) 2025. Published by Elsevier Inc. All rights reserved. FAU - Donath, Marc Y AU - Donath MY AD - Integrated Centre of Excellence in Metabolic Health and Endocrine Division, Department of Medicine and Centre de Recherche, Centre hospitalier de l'Universite de Montreal, Montreal, QC, Canada. Electronic address: marc.donath@umontreal.ca. FAU - Drucker, Daniel J AU - Drucker DJ AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: drucker@lunenfeld.ca. LA - eng SI - ClinicalTrials.gov/NCT06047262 PT - Journal Article PT - Review DEP - 20251003 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Inflammasomes) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Inflammation/immunology/metabolism/physiopathology/drug therapy MH - *Obesity/immunology/physiopathology/metabolism/drug therapy MH - Animals MH - *Diabetes Mellitus, Type 2/immunology/physiopathology/drug therapy/metabolism MH - Inflammasomes/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Insulin Resistance MH - Signal Transduction MH - Glucagon-Like Peptide 1/metabolism OTO - NOTNLM OT - GLP-1 OT - IL-1 OT - NLRP3 OT - diabetes OT - inflammation OT - obesity COIS- Declaration of interests D.J.D. has received consulting fees from Anylam, Amgen, AstraZeneca Inc., Crinetics, Eli Lilly Inc., Insulet, Kailera Therapeutics, Kallyope, Metsara, and Pfizer Inc. and speaking fees from Novo Nordisk Inc. Mount Sinai Hospital has received investigator-initiated grant support from Amgen, Eli Lilly Inc., Novo Nordisk, Pfizer, and Zealand Pharmaceuticals Inc. to support preclinical studies in the Drucker laboratory. M.Y.D. has received consulting fees from Eli Lilly Inc. and Novo Nordisk and is a member of the clinical advisory board of Olatec. EDAT- 2025/10/05 00:33 MHDA- 2025/10/16 05:31 CRDT- 2025/10/04 18:41 PHST- 2025/05/01 00:00 [received] PHST- 2025/08/04 00:00 [revised] PHST- 2025/09/16 00:00 [accepted] PHST- 2025/10/16 05:31 [medline] PHST- 2025/10/05 00:33 [pubmed] PHST- 2025/10/04 18:41 [entrez] AID - S1074-7613(25)00422-4 [pii] AID - 10.1016/j.immuni.2025.09.011 [doi] PST - ppublish SO - Immunity. 2025 Oct 14;58(10):2373-2382. doi: 10.1016/j.immuni.2025.09.011. Epub 2025 Oct 3. PMID- 41039650 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 12 DP - 2025 Dec TI - Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice. PG - 2296-2303 LID - 10.1002/oby.70058 [doi] AB - OBJECTIVE: This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice. METHODS: This cross-sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year. RESULTS: We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance-related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record. CONCLUSIONS: High cost or insurance-related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AUID- ORCID: 0000-0001-7137-9423 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Criswell, Victoria AU - Criswell V AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Fox, Jacqueline AU - Fox J AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Renner, Holly AU - Renner H AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Alpert, Jordan AU - Alpert J AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - RPC8755/Cleveland Clinic Research Program Committees/ PT - Journal Article DEP - 20251002 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/economics/administration & dosage/adverse effects MH - Male MH - Female MH - Middle Aged MH - Cross-Sectional Studies MH - *Obesity/drug therapy MH - Adult MH - *Tirzepatide/therapeutic use/economics/administration & dosage/adverse effects MH - *Anti-Obesity Agents/therapeutic use/economics MH - Aged MH - Diabetes Mellitus, Type 2 MH - Ohio MH - Florida MH - Electronic Health Records MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12636059 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - obesity pharmacotherapy OT - treatment discontinuation COIS- Dr. Butsch reported advisory board fees from Novo Nordisk A/S, Eli Lilly and Co., Boehringer Ingelheim, and Abbott and research funding from Eli Lilly and Co. outside the submitted work. Dr. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. Other authors declare no conflicts of interest. EDAT- 2025/10/03 06:31 MHDA- 2025/11/21 12:50 PMCR- 2025/11/21 CRDT- 2025/10/03 00:03 PHST- 2025/08/26 00:00 [revised] PHST- 2025/06/16 00:00 [received] PHST- 2025/08/27 00:00 [accepted] PHST- 2025/11/21 12:50 [medline] PHST- 2025/10/03 06:31 [pubmed] PHST- 2025/10/03 00:03 [entrez] PHST- 2025/11/21 00:00 [pmc-release] AID - OBY70058 [pii] AID - 10.1002/oby.70058 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Dec;33(12):2296-2303. doi: 10.1002/oby.70058. Epub 2025 Oct 2. PMID- 41036780 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20260918 IS - 1935-3227 (Electronic) IS - 1932-0620 (Print) IS - 1932-0620 (Linking) VI - 20 IP - 4 DP - 2026 Jul-Aug 01 TI - Trends in Newly Filled GLP-1 Receptor Agonist Prescriptions for US Patients With Versus Without Comorbid Alcohol Use Disorder, 2016-2024. PG - 472-479 LID - 10.1097/ADM.0000000000001575 [doi] AB - OBJECTIVES: To evaluate trends in newly filled GLP-1 receptor agonist (GLP-1RA) prescriptions among U.S. adults with type 2 diabetes (T2DM) and/or obesity, comparing those with and without comorbid alcohol use disorder (AUD), and to assess differences in their demographic and clinical characteristics. METHODS: We used national claims data from Optum Labs Data Warehouse, which includes de-identified administrative and pharmacy claims from commercially insured and Medicare Advantage (MA) enrollees throughout the U.S., to identify adults who newly filled GLP-1RA-based prescriptions between April 1, 2016, and March 31, 2024. We calculated quarterly rates of new GLP-1RA fills per 100 person-years and compared the characteristics of individuals with T2DM and/or obesity with and without comorbid AUD. RESULTS: From 2016 to 2024, 555,224 individuals with T2DM and/or obesity newly filled prescriptions for GLP-1RAs, of whom 6606 had comorbid AUD. The rate of new GLP-1RA fills for individuals with comorbid AUD increased from 1.27 to 6.02 per 100 person-years between 2016-2024 [incident rate ratio (IRR): 4.73 (95% CI 3.38, 6.79)], compared with an increase of 2.21 to 6.55 per 100 person-years among individuals without comorbid AUD [IRR: 2.96 (95% CI 2.88, 3.05)]. Individuals with AUD were more likely to be MA enrollees under age 65, male, have had a recent emergency department visit, and have co-occurring psychiatric and medical conditions compared with those without comorbid AUD. CONCLUSIONS: From 2016 to 2024, the rate of newly filled GLP-1RA prescriptions increased among individuals with T2DM and/or obesity and comorbid AUD. Individuals with comorbid AUD were more likely to be male and to have clinical characteristics linked to greater AUD severity. Additional clinical studies on the efficacy and safety of GLP-1RAs for AUD are needed to guide their appropriate use. CI - Copyright (c) 2025 American Society of Addiction Medicine. FAU - Wallach, Joshua D AU - Wallach JD FAU - O'Malley, Stephanie S AU - O'Malley SS FAU - Lipska, Kasia J AU - Lipska KJ FAU - Ross, Joseph S AU - Ross JS FAU - Jeffery, Molly M AU - Jeffery MM FAU - Savitz, Samuel T AU - Savitz ST LA - eng GR - K01 AA028258/AA/NIAAA NIH HHS/United States GR - R01 AA032254/AA/NIAAA NIH HHS/United States PT - Journal Article DEP - 20251002 PL - Netherlands TA - J Addict Med JT - Journal of addiction medicine JID - 101306759 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - United States/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Aged MH - *Obesity/epidemiology/drug therapy MH - Comorbidity MH - *Alcoholism/epidemiology MH - Middle Aged MH - *Drug Prescriptions/statistics & numerical data MH - Adult MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12636227 MID - NIHMS2106615 OTO - NOTNLM OT - GLP-1 receptor agonists OT - alcohol use disorder OT - anti-obesity medications COIS- JDW reported receiving grants from Arnold Ventures, Johnson & Johnson (through the Yale Open Data Access Project) and the FDA (through the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation), as well as former consulting fees from Hagen Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. SOS reported receiving grants from the NIH during the conduct of the study; personal fees from the American Society of Clinical Psychopharmacology ACTUVE work group supported by Alkermes, Dicerna, Eli Lilly and Company, Ethypharm, Imbrium Therapeutics, Indivior, Pear Therapeutics, and Kinnov Therapeutics; nonfinancial support from Novartis (study medication), Stalicla (study medication), and Amygdala (study medication); personal fees from Dicerna; and personal fees from the University of New Mexico (consultant on NIH grant), and Indiana University (DSMB member), outside the submitted work; in addition, SOS had a patent for Mavoglurant for gambling disorder with Yale and Novartis pending and contracts with Altimmune and Tempero Bi. KJL reported receiving personal fees from UpToDate to write and edit content and other fees from Centers for Medicare and Medicaid Services Support to develop and evaluate publicly reported quality measures outside the submitted work. JSR reported receiving grants from the FDA, Arnold Ventures, Johnson & Johnson, Medical Devices Innovation Consortium, Agency for Healthcare Research and Quality, and National Heart, Lung, and Blood Institute; and having been an expert witness at the request of realtor's attorney, the Greene Law Firm, in a qui tam lawsuit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc that was Settled in September 2022. All authors report receiving funding from the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (1R01AA032254). The remaining authors did not have any conflicts of interest to disclose. EDAT- 2025/10/02 12:33 MHDA- 2026/08/05 18:38 PMCR- 2025/11/22 CRDT- 2025/10/02 08:03 PHST- 2025/03/31 00:00 [received] PHST- 2025/08/06 00:00 [accepted] PHST- 2026/08/05 18:38 [medline] PHST- 2025/10/02 12:33 [pubmed] PHST- 2025/10/02 08:03 [entrez] PHST- 2025/11/22 00:00 [pmc-release] AID - 01271255-990000000-00586 [pii] AID - 10.1097/ADM.0000000000001575 [doi] PST - ppublish SO - J Addict Med. 2026 Jul-Aug 01;20(4):472-479. doi: 10.1097/ADM.0000000000001575. Epub 2025 Oct 2. PMID- 41036135 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Predictive factors for HbA1c and weight loss associated with semaglutide treatment in type 2 diabetes mellitus: real-world clinical evidence. PG - 1621892 LID - 10.3389/fendo.2025.1621892 [doi] LID - 1621892 AB - OBJECTIVE: This study aimed to identify clinical predictors associated with reductions in HbA1c and weight among patients with type 2 diabetes mellitus (T2DM) treated with semaglutide in real-world clinical settings in Bulgaria. METHODS: A retrospective analysis was conducted on 168 T2DM patients receiving dispensary monitoring at the University Specialized Hospital for Active Treatment in Endocrinology "Acad. Ivan Penchev," Sofia. Clinical data, including comorbidities, HbA1c, weight, and BMI, were collected from medical records at baseline and after one year of treatment. Patients were administered subcutaneous semaglutide beginning at 0.25 mg weekly, titrated to 0.5 mg after four weeks, and to 1 mg thereafter, maintained over a one-year period. RESULTS: At baseline, 92.3% of patients had obesity (BMI >/=30 kg/m(2)), with 53.6% categorized as Obesity Class 1. After one year of GLP - 1RA therapy, significant improvements in metabolic parameters were observed. Median weight reduced from 100.0 kg to 91.5 kg (p<0.001), and median BMI decreased from 33.6 to 30.9 kg/m(2) (p<0.001). HbA1c levels declined from 7.80% to 6.90% (p<0.001). Transitions to lower obesity classes occurred in 81 patients, while 15 remained in Class 3 obesity. CONCLUSIONS: Semaglutide significantly improves glycemic control and promotes weight and BMI reduction in T2DM patients in routine clinical practice. These findings suggest that structured follow-up under endocrinologist supervision, as required by national protocols, may enhance therapeutic response. Further prospective studies with extended follow-up are warranted to evaluate the long-term sustainability of these effects and to identify predictors of optimal patient response. CI - Copyright (c) 2025 Milushewa, Mitreva, Chakarova, Tankova, Naseva and Petkova. FAU - Milushewa, Petya AU - Milushewa P AD - Department of Organization and Economics of Pharmacy, Medical University of Sofia, Sofia, Bulgaria. FAU - Mitreva, Yoanna AU - Mitreva Y AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Chakarova, Nevena AU - Chakarova N AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Tankova, Tsvetalina AU - Tankova T AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Naseva, Emilia AU - Naseva E AD - Department of Health Management and Health Economics, Medical University of Sofia, Sofia, Bulgaria. FAU - Petkova, Valentina AU - Petkova V AD - Department of Organization and Economics of Pharmacy, Medical University of Sofia, Sofia, Bulgaria. LA - eng PT - Journal Article DEP - 20250916 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - *Glycated Hemoglobin/analysis/metabolism MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Obesity/drug therapy MH - Adult MH - Follow-Up Studies MH - Body Mass Index MH - Prognosis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12479283 OTO - NOTNLM OT - glycemic control OT - obesity OT - real-world data OT - semaglutide OT - type 2 diabetes OT - weight loss COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/02 06:28 MHDA- 2025/10/02 06:29 PMCR- 2025/09/16 CRDT- 2025/10/02 04:54 PHST- 2025/05/02 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/10/02 06:29 [medline] PHST- 2025/10/02 06:28 [pubmed] PHST- 2025/10/02 04:54 [entrez] PHST- 2025/09/16 00:00 [pmc-release] AID - 10.3389/fendo.2025.1621892 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Sep 16;16:1621892. doi: 10.3389/fendo.2025.1621892. eCollection 2025. PMID- 41034888 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20251005 IS - 1472-6963 (Electronic) IS - 1472-6963 (Linking) VI - 25 IP - 1 DP - 2025 Oct 1 TI - Information pharmacists assist in the construction of GLP-1RA prescription review rules in a tertiary hospital in China. PG - 1276 LID - 10.1186/s12913-025-13377-2 [doi] LID - 1276 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for type 2 diabetes mellitus (T2DM) due to their multifaceted benefits, including glycemic control and cardiovascular protection. However, variations in prescribing practices and potential adverse drug events (ADEs) necessitate standardized prescription review protocols to ensure medication safety and efficacy. OBJECTIVE: This study aimed to develop and implement GLP-1RA prescription review rules through a multidisciplinary information pharmacist team, evaluate their impact on prescription rationality, and identify ADE risk signals using real-world data, thereby promoting rational clinical medication use and ensuring patient safety. METHODS: A multidisciplinary information pharmacist team was established at a tertiary hospital to develop GLP-1RA prescription review protocols. China-approved GLP-1RA formulations and their clinical parameters were systematically reviewed to establish standardized prescribing criteria, including indications, dosing, and safety considerations. Adverse drug events were analyzed using FDA Adverse Event Reporting System data (2018-2023) to identify risk patterns. A dual review system integrating prospective prescription screening and retrospective evaluation was implemented. The intervention's efficacy was evaluated by comparing prescription approval rates pre- (2022) and post-implementation (2023). RESULTS: The GLP-1RA audit rules represented by liraglutide and semaglutide were successfully created, as well as their potential adverse event signals were successfully obtained. The process of prescription review and medication monitoring enabled them to be put into clinical practice. After the rules were put in place in 2023, the pass rates of GLP-1RA prescriptions significantly improved, and the rationalization of these prescriptions was also notably enhanced compared to the same period in 2022 (p < 0.001). CONCLUSIONS: Standardized GLP-1RA review rules enhanced prescription rationality and ADE risk awareness, demonstrating the value of information pharmacists in optimizing clinical decision-making. This model is scalable for other high-risk medications, promoting safer drug use and pharmacist-led innovation in healthcare. CI - (c) 2025. The Author(s). FAU - Zhou, Li AU - Zhou L AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. zhouli1007@126.com. FAU - Duanmu, Wenjing AU - Duanmu W AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Tan, Feilong AU - Tan F AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Gu, Xi AU - Gu X AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Che, Hongyi AU - Che H AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Yin, Wenjie AU - Yin W AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. yinwj123@126.com. LA - eng GR - NO.2024J0277/Scientific Research Fund Project of Education Department of Yunnan Province/ GR - NO.2021-SW (reserve)-08/Kunming Health Science and Technology "Thousand Project" Talents Project/ PT - Journal Article DEP - 20251001 PL - England TA - BMC Health Serv Res JT - BMC health services research JID - 101088677 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - China MH - Tertiary Care Centers/organization & administration MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pharmacists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Retrospective Studies PMC - PMC12487512 OTO - NOTNLM OT - Adverse drug events OT - Glucagon-like peptide-1 receptor agonist OT - Information pharmacists OT - Prescription review rules OT - Rational drug use COIS- Declarations. Ethics approval and consent to participate: The information on prior prescription data involved in this study was obtained from our hospital's prescription audit management system, and the ADEs data information was obtained from the FAERS database. Ethical approval was not considered necessary given the use of the identified data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/10/02 06:28 MHDA- 2025/10/02 06:29 PMCR- 2025/10/01 CRDT- 2025/10/02 00:03 PHST- 2024/06/11 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/10/02 06:29 [medline] PHST- 2025/10/02 06:28 [pubmed] PHST- 2025/10/02 00:03 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 10.1186/s12913-025-13377-2 [pii] AID - 13377 [pii] AID - 10.1186/s12913-025-13377-2 [doi] PST - epublish SO - BMC Health Serv Res. 2025 Oct 1;25(1):1276. doi: 10.1186/s12913-025-13377-2. PMID- 41034339 OWN - NLM STAT- MEDLINE DCOM- 20251023 LR - 20261010 IS - 1759-4804 (Electronic) IS - 1759-4790 (Linking) VI - 21 IP - 11 DP - 2025 Nov TI - Glucagon-like peptide-1 receptor agonists in arthritis: current insights and future directions. PG - 671-683 LID - 10.1038/s41584-025-01302-0 [doi] AB - Obesity affects nearly one in six adults worldwide. Excess adiposity is a pro-inflammatory state associated with increased risk of several types of arthritis, increased arthritis disease activity and/or severity, and poorer response to certain treatments. Obesity is a major risk factor for cardiovascular disease, the leading cause of death in people with common arthritides such as osteoarthritis (OA), gout, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a promising therapeutic option for people with arthritis and obesity or type 2 diabetes mellitus owing to their pleiotropic effects, including weight loss, improved survival and reduced risk of major cardiovascular and renal events. In vitro and preclinical in vivo experiments in arthritis have uncovered weight-loss-independent anti-inflammatory and chondroprotective properties of GLP-1RAs. In knee OA, clinical data suggest that GLP-1RAs improve pain and function and reduce the risk of surgical intervention; however, their effects on OA incidence remain incompletely understood. Evidence suggests that GLP-1RAs do not directly prevent gout attacks, but are effective in managing cardiometabolic conditions commonly associated with gout and other arthritides. More research is needed to clarify the effects of GLP-1RAs on incidence, disease activity, and progression of rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. CI - (c) 2025. Springer Nature Limited. FAU - Karacabeyli, Derin AU - Karacabeyli D AUID- ORCID: 0000-0002-6597-0302 AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. dkaracabeyli@arthritisresearch.ca. AD - Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. dkaracabeyli@arthritisresearch.ca. AD - Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. dkaracabeyli@arthritisresearch.ca. FAU - Lacaille, Diane AU - Lacaille D AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. AD - Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. LA - eng PT - Journal Article PT - Review DEP - 20251001 PL - United States TA - Nat Rev Rheumatol JT - Nature reviews. Rheumatology JID - 101500080 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Arthritis/drug therapy/complications MH - Arthritis, Rheumatoid/drug therapy COIS- Competing interests: The authors declare no competing interests. EDAT- 2025/10/02 00:29 MHDA- 2025/10/23 06:27 CRDT- 2025/10/01 23:30 PHST- 2025/09/02 00:00 [accepted] PHST- 2025/10/23 06:27 [medline] PHST- 2025/10/02 00:29 [pubmed] PHST- 2025/10/01 23:30 [entrez] AID - 10.1038/s41584-025-01302-0 [pii] AID - 10.1038/s41584-025-01302-0 [doi] PST - ppublish SO - Nat Rev Rheumatol. 2025 Nov;21(11):671-683. doi: 10.1038/s41584-025-01302-0. Epub 2025 Oct 1. PMID- 41032189 OWN - NLM STAT- MEDLINE DCOM- 20260219 LR - 20260219 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 26 IP - 2 DP - 2026 Mar TI - Effect of Tirzepatide on Cardiovascular Outcomes. PG - 157-163 LID - 10.1007/s40256-025-00767-4 [doi] AB - Patients with type 2 diabetes mellitus and obesity have a higher risk of cardiovascular disease and major adverse cardiovascular events. It is important that medication options for these disease states are either cardioprotective or cardioneutral so that the health of the patient is not worsened. Medications in the glucagon-like peptide-1 receptor agonists class decrease cardiovascular risk in those at high or increased risk of cardiovascular events. This review presents and discusses the current clinical and scientific evidence pertaining to tirzepatide, a glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor co-agonist. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Huston, Jessica AU - Huston J AD - Department of Pharmacy Education and Practice, College of Pharmacy, University of Florida, Jacksonville, FL, 32209, USA. FAU - Orey, Dontia AU - Orey D AD - East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, 32216, FL, USA. FAU - Ashchi, Andrew AU - Ashchi A AD - East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, 32216, FL, USA. FAU - Lachapelle, Andrea Ashchi AU - Lachapelle AA AD - East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, 32216, FL, USA. FAU - Genovese, Ariana AU - Genovese A AD - Florida State University College of Medicine, Tallahassee, FL, 32304, USA. FAU - Jackson, Jenna AU - Jackson J AD - Department of Pharmacy Education and Practice, College of Pharmacy, University of Florida, Jacksonville, FL, 32209, USA. FAU - Ashchi, Ramsey AU - Ashchi R AD - East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, 32216, FL, USA. FAU - Ashchi, Towfeeq AU - Ashchi T AD - Lake Erie College of Osteopathic Medicine-Bradenton, Bradenton, FL, 34211, USA. FAU - Ashchi, Majdi AU - Ashchi M AD - Ashchi Heart and Vascular Center, Jacksonville, FL, 32216, USA. FAU - Sutton, David AU - Sutton D AD - Northeast Florida Endocrine & Diabetes Associates, Jacksonville, FL, USA. FAU - Deeb, Wasim AU - Deeb W AD - First Choice Endocrinology, Jacksonville, FL, USA. FAU - Goldfaden, Rebecca F AU - Goldfaden RF AUID- ORCID: 0000-0002-6401-4888 AD - East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, 32216, FL, USA. rg@roviaclinical.com. LA - eng PT - Journal Article PT - Review DEP - 20251001 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/etiology/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Tirzepatide COIS- Declarations. Conflicts of Interest: Jessica Huston, Dontia Orey, Andrew Ashchi, Andrea Ashchi Lachapelle, Ariana Genovese, Jenna Jackson, Ramsey Ashchi, Towfeeq Ashchi, Majdi Ashchi, David Sutton, Wasim Deeb, and Rebecca F. Goldfaden have no potential conflicts of interest that might be relevant to the contents of this manuscript. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Not applicable. Data Availability Statement: Data sharing is not applicable to this article as no datasets were generated. Author Contributions: Jessica Huston was involved in supervision, data curation, analysis, reviewing, editing, and writing. Dontia Orey, Andrea Ashchi Lachapelle, Andrew Ashchi, Ariana Genovese, Jenna Jackson, Ramsey Ashchi, and Towfeeq Ashchi were involved in data curation, analysis, and writing. Majdi Ashchi, David Sutton, and Wasim Deeb were involved in reviewing and editing. Rebecca Goldfaden was involved in conceptualization, project administration, reviewing and editing. EDAT- 2025/10/01 12:30 MHDA- 2026/02/19 19:02 CRDT- 2025/10/01 11:16 PHST- 2025/04/14 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2026/02/19 19:02 [medline] PHST- 2025/10/01 12:30 [pubmed] PHST- 2025/10/01 11:16 [entrez] AID - 10.1007/s40256-025-00767-4 [pii] AID - 10.1007/s40256-025-00767-4 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2026 Mar;26(2):157-163. doi: 10.1007/s40256-025-00767-4. Epub 2025 Oct 1. PMID- 41030857 OWN - NLM STAT- MEDLINE DCOM- 20251001 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Case Report: Efficacy and safety of dose-escalated Mazdutide, a GLP-1/GCGR dual agonist, in an adolescent with obesity, type 2 diabetes, and hyperuricemia. PG - 1654506 LID - 10.3389/fendo.2025.1654506 [doi] LID - 1654506 AB - OBJECTIVE: Mazdutide, a glucagon-like peptide-1/glucagon receptor (GLP - 1/GCGR) dual agonist, has shown marked efficacy in glycemic control, weight loss, and metabolic improvement in adults. However, data in adolescents remain limited. This report explores its therapeutic potential in an adolescent with obesity-related type 2 diabetes mellitus (T2DM) and hyperuricemia (HUA). STUDY DESIGN AND METHODS: We report the case of a 15-year-old male patient diagnosed with obesity (BMI: 30.64 kg/m(2)), type 2 diabetes mellitus (HbA1c: 9.60%), and hyperuricemia (serum uric acid: 511 mumol/L). The patient underwent a dose-escalation regimen of Mazdutide (2 mg --> 4 mg --> 6 mg, administered subcutaneously once weekly) in combination with metformin and insulin to evaluate therapeutic efficacy and safety outcomes. RESULTS: After 36 weeks, the patient showed significant improvement: weight decreased by 16.8 kg (18.89% BMI reduction), uric acid dropped by 37.00%, and HbA1c fell by 21.88%. No hypoglycemic episodes occurred. Lipid levels improved notably: triglycerides fell by 69.02%, total cholesterol by 13.65%, and LDL cholesterol by 17.27%. Hepatic steatosis resolved by week 14, as confirmed by ultrasound. No adverse events were reported, and benefits were sustained post-treatment. CONCLUSIONS: Mazdutide exhibited robust metabolic efficacy and good tolerability in an adolescent with obesity, T2DM, and HUA. It improved glycemic control, reduced weight and uric acid, reversed steatosis, and modulated lipid profiles. These findings support its potential as a comprehensive treatment for adolescent metabolic disorders. CI - Copyright (c) 2025 Cheng, Chen, Li, Zhang, Ma, Liu and Jiang. FAU - Cheng, Wenfei AU - Cheng W AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Chen, Zilong AU - Chen Z AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Li, Puyu AU - Li P AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Zhang, Yingyu AU - Zhang Y AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Ma, Yujin AU - Ma Y AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Liu, Peng AU - Liu P AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. FAU - Jiang, Hongwei AU - Jiang H AD - Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China. LA - eng PT - Case Reports PT - Journal Article DEP - 20250915 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Glucagon) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adolescent MH - *Hyperuricemia/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - *Receptors, Glucagon/agonists MH - Peptides PMC - PMC12477040 OTO - NOTNLM OT - GLP-1/GCGR dual agonist OT - Mazdutide OT - adolescent obesity OT - adolescent treatment OT - hyperuricemia OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/01 12:01 MHDA- 2025/10/01 12:02 PMCR- 2025/09/15 CRDT- 2025/10/01 05:00 PHST- 2025/06/26 00:00 [received] PHST- 2025/08/20 00:00 [accepted] PHST- 2025/10/01 12:02 [medline] PHST- 2025/10/01 12:01 [pubmed] PHST- 2025/10/01 05:00 [entrez] PHST- 2025/09/15 00:00 [pmc-release] AID - 10.3389/fendo.2025.1654506 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Sep 15;16:1654506. doi: 10.3389/fendo.2025.1654506. eCollection 2025. PMID- 41029853 OWN - NLM STAT- MEDLINE DCOM- 20251001 LR - 20260903 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Sep 30 TI - Cardiovascular and renal outcomes of dual combination therapies with glucagon-like peptide-1 receptor agonists and sodium-glucose transport protein 2 inhibitors: a systematic review and meta-analysis. PG - 370 LID - 10.1186/s12933-025-02900-8 [doi] LID - 370 AB - BACKGROUND: Combination therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and/or finerenone offers a strategy to reduce the risk of adverse cardiovascular and renal outcomes. This study aimed to quantify the cardiorenal benefits of combination regimens with GLP-1RA, SGLT2i, and/or finerenone versus corresponding monotherapies. METHODS: MEDLINE and Embase were systematically searched, yielding four post hoc analyses of randomized controlled trials (RCTs) and ten observational studies that met prespecified inclusion criteria. Among RCTs, a random-effects meta-regression was performed to assess whether the effect of GLP-1RAs on cardiorenal outcomes differed based on baseline SGLT2i use. Additionally, for observational studies, random-effects meta-analyses were performed to estimate the effect of combination therapy versus monotherapy on the risk of cardiorenal outcomes. RESULTS: Across RCTs, p for interaction was > 0.05 for major adverse cardiac events (MACE) (p = 0.730), cardiovascular (CV) mortality (p = 0.889), non-fatal myocardial infarction (MI) (p = 0.237), non-fatal stroke (p = 0.696), all-cause mortality (p = 0.682), heart failure (HF) hospitalization (p = 0.257), and renal composite outcome (p = 0.890), supporting that GLP-1RAs result in a consistent reduction in outcomes irrespective of baseline SGLT2i use. In observational trials, compared to SGLT2i monotherapy, GLP-1RA and SGLT2i combination therapy significantly reduced MACE (HR 0.59, 95% CI 0.47-0.75), MI (HR 0.73, 95% CI 0.61-0.88), stroke (HR 0.72, 95% CI 0.53-0.97), all-cause mortality (HR 0.57, 95% CI 0.48-0.67), and HF hospitalization/events (HR 0.71, 95% CI 0.59-0.86). Compared to GLP-1RA monotherapy, SGLT2i and GLP-1RA combination therapy significantly reduced CV mortality (HR 0.35, 95% CI 0.15-0.81), MI (HR 0.93, 95% CI 0.88-0.97), stroke (HR 0.92, 95% CI 0.88-0.96), all-cause mortality (HR 0.59, 95% 0.49-0.70), HF hospitalization/events (HR 0.84, 95% CI 0.81-0.88), and serious renal events (HR 0.43, 95% CI 0.23-0.80). Compared to either SGLT2i or finerenone monotherapy, SGLT2i and finerenone combination therapy significantly reduced all-cause mortality and major adverse kidney events. CONCLUSION: Combination therapy with GLP-1RA, SGLT2i, or finerenone confers cardiorenal protection beyond monotherapy in T2D, as supported by concordant evidence from RCTs and large real-world cohorts. These findings support broader clinical adoption of dual-agent strategies but also underscore the need for dedicated prospective trials powered to assess hard clinical outcomes with dual-agent strategies. CI - (c) 2025. The Author(s). FAU - Shokravi, Arveen AU - Shokravi A AD - Department of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. shokravi@student.ubc.ca. FAU - Seth, Jayant AU - Seth J AD - Department of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. FAU - Mancini, G B John AU - Mancini GBJ AD - Department of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. AD - Centre for Cardiovascular Innovation, Dilwari Cardiovascular Institute, Division of Cardiology, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250930 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Blood Glucose) RN - 0 (finerenone) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Naphthyridines) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Blood Glucose/metabolism/drug effects MH - *Cardiovascular Diseases/mortality/diagnosis/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Incretins/adverse effects/therapeutic use MH - *Kidney/drug effects/physiopathology MH - *Kidney Diseases/mortality/diagnosis/prevention & control MH - Observational Studies as Topic MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor MH - Naphthyridines PMC - PMC12487346 OTO - NOTNLM OT - Cardiometabolic risk OT - Cardiovascular outcomes OT - Chronic kidney disease OT - Combination therapy OT - Finerenone OT - GLP-1 receptor agonist OT - Meta-analysis OT - Renal outcomes OT - SGLT2 inhibitor OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. This study is a meta-analysis and did not involve direct recruitment of human participants. Competing interests: Arveen Shokravi, and Jayant Seth, have no conflicts of interest to declare. G.B. John Mancini reports receiving honoraria from Eli Lilly, Boehringer Ingelheim, Novo Nordisk, GlaxoSmithKline, and Bayer. EDAT- 2025/10/01 06:30 MHDA- 2025/10/01 06:31 PMCR- 2025/09/30 CRDT- 2025/10/01 01:46 PHST- 2025/07/16 00:00 [received] PHST- 2025/08/10 00:00 [accepted] PHST- 2025/10/01 06:31 [medline] PHST- 2025/10/01 06:30 [pubmed] PHST- 2025/10/01 01:46 [entrez] PHST- 2025/09/30 00:00 [pmc-release] AID - 10.1186/s12933-025-02900-8 [pii] AID - 2900 [pii] AID - 10.1186/s12933-025-02900-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Sep 30;24(1):370. doi: 10.1186/s12933-025-02900-8. PMID- 41028671 OWN - NLM STAT- MEDLINE DCOM- 20251217 LR - 20261010 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 39 IP - 12 DP - 2025 Dec TI - Analysis of the long-term impact of glucagon-like peptide-1 (GLP-1) receptor agonists for control of obesity and obesity-related comorbidities: a meta-analysis. PG - 8580-8589 LID - 10.1007/s00464-025-12086-5 [doi] AB - INTRODUCTION: GLP-1 receptor agonist medications are a promising new medical weight loss therapy and have been shown to reduce rates of obesity-related comorbidities. The aim of this meta-analysis was to examine the long-term effects of these medications. METHODS: A meta-analysis was performed following PRISMA guidelines. Data were collected on weight change, type 2 diabetes, and hypertension prevalence with GLP-1 or placebo therapy in studies meeting inclusion criteria per study protocol. RESULTS: A total of 54 articles and 59,856 patients were included in this study. GLP-1-treated patients were noted to lose an average of 10.6% of total body weight (TBW) compared to placebo at 3.9%, with a peak occurring at 12-18 months of treatment. When subdivided into intention-to-treat and adherent patients, those maintaining medication use lost more weight at a peak of 12% TBW loss. Weight regain with medication discontinuation was found to occur within weeks at a rate of 0.55% original TBW per month. The incident rate of type 2 diabetes was reduced sevenfold by GLP therapy over placebo. Hypertension resolution was also noted to be higher in the GLP-1-treated patients at a peak of 23% reduction compared to 11% for placebo. CONCLUSION: GLP-1 medications are effective at weight reduction and can produce diabetes and hypertension remission. Medication adherence is critical for efficacy, and non-compliance dramatically reduces the impact of these therapies. Additionally, medication discontinuation results in rapid weight regain within weeks; however, longer-term data are needed to qualify the durability of GLP-1-mediated weight loss. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Jia, Iwanger-I-Ter T AU - Jia IT AD - Georgetown University, School of Medicine, Washington, DC, USA. FAU - Bloomfield, Grace C AU - Bloomfield GC AD - Georgetown University, School of Medicine, Washington, DC, USA. FAU - Chen, Mike Y AU - Chen MY AD - Georgetown University, School of Medicine, Washington, DC, USA. FAU - Cunningham, Marcus H AU - Cunningham MH AD - Georgetown University, School of Medicine, Washington, DC, USA. FAU - Azagury, Dan E AU - Azagury DE AD - Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA. FAU - Alimi, Yewande R AU - Alimi YR AD - Department of Surgery, MedStar Georgetown University Hospital, Washington, DC, 20007, USA. FAU - Prindeze, Nicholas J AU - Prindeze NJ AUID- ORCID: 0000-0002-0928-1799 AD - Department of Surgery, MedStar Georgetown University Hospital, Washington, DC, 20007, USA. nickprindeze@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20250930 PL - Germany TA - Surg Endosc JT - Surgical endoscopy JID - 8806653 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Obesity/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/epidemiology/prevention & control/drug therapy MH - Weight Loss/drug effects MH - Hypertension/epidemiology/prevention & control/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Diabetes OT - GLP-1 outcomes OT - Meta-analysis OT - Weight loss COIS- Declarations. Conflict of interest: All authors, including Mrs. Iwanger-T-Ter Jia, Mrs. Grace Bloomfield, Mr. Mike Chen, Mr. Marcus Cunningham, Dr. Dan Azagury, Dr. Yewande Alimi, and Dr. Nicholas Prindeze, have no financial disclosures, commercial associations, or other conditions posing a conflict of interest to report. EDAT- 2025/10/01 06:30 MHDA- 2025/12/17 06:41 CRDT- 2025/10/01 00:12 PHST- 2025/03/28 00:00 [received] PHST- 2025/08/08 00:00 [accepted] PHST- 2025/12/17 06:41 [medline] PHST- 2025/10/01 06:30 [pubmed] PHST- 2025/10/01 00:12 [entrez] AID - 10.1007/s00464-025-12086-5 [pii] AID - 10.1007/s00464-025-12086-5 [doi] PST - ppublish SO - Surg Endosc. 2025 Dec;39(12):8580-8589. doi: 10.1007/s00464-025-12086-5. Epub 2025 Sep 30. PMID- 41028652 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 85 IP - 12 DP - 2025 Dec TI - Mazdutide: First Approval. PG - 1621-1627 LID - 10.1007/s40265-025-02249-y [doi] AB - Mazdutide (Xinermei((R))) is a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist being developed by Eli Lilly and Company along with Innovent Biologics for use in weight management in adults with obesity or overweight and for the treatment of type 2 diabetes (T2D). In June 2025, mazdutide received its first approval, in China, for use (in combination with diet control and increased physical activity) in long-term body weight management in adults with a body-mass index (BMI) of >/= 28 kg/m(2) or with a BMI >/= 24 kg/m(2) together with one or more weight-related comorbidity. Subsequently, in September 2025, mazdutide also received approval in China for use in glycaemic control in adults with T2D. Additionally, mazdutide is under clinical evaluation for use in the treatment of metabolic dysfunction-associated fatty liver disease, obstructive sleep apnoea and alcohol use disorder. This article summarises the milestones in the development of mazdutide leading to this first approval for long-term body weight management in adults with obesity or overweight. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Shirley, Matt AU - Shirley M AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com. LA - eng PT - Journal Article PT - Review DEP - 20250930 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Glucagon) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - Drug Approval MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Overweight/drug therapy MH - Receptors, Glucagon/agonists MH - China MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Anti-Obesity Agents/therapeutic use MH - Peptides COIS- Declarations. Authorship and Conflict of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content. Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability: Not applicable. EDAT- 2025/10/01 06:29 MHDA- 2025/11/13 18:30 CRDT- 2025/10/01 00:10 PHST- 2025/09/04 00:00 [received] PHST- 2025/09/22 00:00 [accepted] PHST- 2025/11/13 18:30 [medline] PHST- 2025/10/01 06:29 [pubmed] PHST- 2025/10/01 00:10 [entrez] AID - 10.1007/s40265-025-02249-y [pii] AID - 10.1007/s40265-025-02249-y [doi] PST - ppublish SO - Drugs. 2025 Dec;85(12):1621-1627. doi: 10.1007/s40265-025-02249-y. Epub 2025 Sep 30. PMID- 41026313 OWN - NLM STAT- MEDLINE DCOM- 20250930 LR - 20261010 IS - 1573-2630 (Electronic) IS - 0165-5701 (Linking) VI - 45 IP - 1 DP - 2025 Sep 30 TI - Blinded by the drug? A vigilyze signal linking semaglutide to NAION. PG - 398 LID - 10.1007/s10792-025-03760-7 [doi] AB - INTRODUCTION: Semaglutide, available widely as Ozempic, Wegovy, and Rybelsus, has significantly improved the management of type 2 diabetes and obesity due to its beneficial adverse drug reactions and safer use in diverse population. However, as its use grows widely, rare but serious side effects are coming to light. One such emerging concern is Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION), a condition causing sudden, often irreversible vision loss. METHODOLOGY: A retrospective, post-market observational study was conducted using data collected from VigiBase(R) until June 2025, using mapped terms under Medical Dictionary for Regulatory Activities (MedDRA). RESULT: Of 73,636 global Individual Case Safety Reports (ICSRs) related to Semaglutide reported adverse reactions globally, 91 were associated with the adverse reaction NAION. The cases were reported globally with increased number of cases reported by Denmark (N = 38, 41.80%), Australia (N = 9, 9.90%) and France (N = 7, 7.70%), primarily affected patients aged 45-74 years (N = 50, 54.90%). Most cases (97.80%) were classified as serious with a significant of the cases reported of males. The co-reported reactions involved serious 'eye-related' conditions like Visual Impairment (N = 12,13.20%), Blindness (N = 9, 9.90%), Visual field defect (N = 5, 5.50%), Optic atrophy (N = 4, 4.40%), Vision blurred (N = 4, 4.40%) among other serious reactions. CONCLUSION: This study raises awareness of a rare yet significant safety concern with Semaglutide. Early detection of NAION symptoms and timely drug discontinuation may be critical in preventing permanent vision loss. Moreover, the reaction should be mentioned in the patient information leaflet/ summary of the product characteristic of the drug to create awareness among the healthcare providers as well as the consumers taking the drug. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Suresh, Jaishree AU - Suresh J AD - Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector-23, Raj Nagar, Ghaziabad, Uttar Pradesh, 201002, India. drjaishreesuresh@gmail.com. FAU - Vivekanandan, Kalaiselvan AU - Vivekanandan K AD - Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector-23, Raj Nagar, Ghaziabad, Uttar Pradesh, 201002, India. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250930 PL - Netherlands TA - Int Ophthalmol JT - International ophthalmology JID - 7904294 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - *Glucagon-Like Peptides/adverse effects MH - Male MH - Middle Aged MH - Female MH - Aged MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Global data OT - NAION OT - Non-arteritic anterior ischemic optic neuropathy OT - Pharmacovigilance OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declare no competing interests EDAT- 2025/09/30 14:16 MHDA- 2025/09/30 14:17 CRDT- 2025/09/30 11:19 PHST- 2025/07/10 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2025/09/30 14:17 [medline] PHST- 2025/09/30 14:16 [pubmed] PHST- 2025/09/30 11:19 [entrez] AID - 10.1007/s10792-025-03760-7 [pii] AID - 10.1007/s10792-025-03760-7 [doi] PST - epublish SO - Int Ophthalmol. 2025 Sep 30;45(1):398. doi: 10.1007/s10792-025-03760-7. PMID- 41026248 OWN - NLM STAT- MEDLINE DCOM- 20250930 LR - 20261009 IS - 1544-2241 (Electronic) IS - 1544-1873 (Linking) VI - 23 IP - 1 DP - 2025 Sep 30 TI - Headline: Fracture Risk in Type 2 Diabetes: Systematic Review of Cardiovascular Outcome Trials with Glucagon Like Peptide Receptor Agonists. PG - 38 LID - 10.1007/s11914-025-00937-y [doi] AB - PURPOSE OF REVIEW: This systematic review examined the available evidence on fracture risk in people with type 2 diabetes (T2D) using cardiovascular outcome trials with glucagon-like peptide-1 receptor agonist (GLP-1RA). RECENT FINDINGS: A systematic Literature search identified 797 records, of which 643 remained after duplicate removal. Following screening, 20 studies met the criteria for inclusion. Although GLP-1 RAs have demonstrated well-established benefits in glycaemic control, weight reduction, and cardiovascular protection, their impact on bone health remains incompletely understood. Preclinical studies suggest potential bone-protective effects, including increased bone mass, improved microarchitecture, and reduced bone resorption. However, evidence from human studies has been inconsistent. While some findings indicate a possible reduction in fracture risk with long-term GLP-1 RA therapy, further research is needed to clarify their role in bone metabolism and fracture prevention among people with T2D, particularly within the context of cardiovascular outcome trials. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Mahalingasivam, Aksayan Arunanthy AU - Mahalingasivam AA AUID- ORCID: 0000-0003-0406-9702 AD - Steno Diabetes Centre North Denmark, Aalborg University Hospital, Aalborg, Denmark. aksayan.mahalingasivam@rn.dk. FAU - Rasmussen, Nicklas Hojgaard-Hessellund AU - Rasmussen NH AD - Steno Diabetes Centre North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250930 PL - United States TA - Curr Osteoporos Rep JT - Current osteoporosis reports JID - 101176492 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Curr Osteoporos Rep. 2025 Dec 2;23(1):52. doi: 10.1007/s11914-025-00946-x. PMID: 41326915 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Fractures, Bone/prevention & control/epidemiology/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Cardiovascular Diseases/prevention & control MH - Bone Density/drug effects OTO - NOTNLM OT - BMD OT - Cardiovascular disease OT - Diabetes mellitus type 2 OT - Fracture OT - GLP1-RA COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/09/30 14:17 MHDA- 2025/09/30 14:18 CRDT- 2025/09/30 11:16 PHST- 2025/05/01 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/09/30 14:18 [medline] PHST- 2025/09/30 14:17 [pubmed] PHST- 2025/09/30 11:16 [entrez] AID - 10.1007/s11914-025-00937-y [pii] AID - 10.1007/s11914-025-00937-y [doi] PST - epublish SO - Curr Osteoporos Rep. 2025 Sep 30;23(1):38. doi: 10.1007/s11914-025-00937-y. PMID- 41025406 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction-associated steatotic liver disease, and other cardio-kidney-metabolic conditions. PG - 6869-6883 LID - 10.1111/dom.70148 [doi] AB - Glucagon is a pancreatic peptide hormone whose receptor (GCGR) is expressed in the liver, kidney, and, to a lesser extent, various other tissues. Glucagon is well known as the counterpart to insulin in glucose homeostasis. However, recent evidence has revealed other potential roles of glucagon, which include the regulation of amino acid metabolism via a liver-pancreatic alpha cell axis, stimulation of lipolysis and mitochondrial fat oxidation in the liver (and possibly in other tissues), reduction of caloric intake, and an increase in energy expenditure (at least in animal models). These advances in basic science-together with clinical trials that found GCGR antagonists increased body weight, hepatic fat, and serum lipids in people with type 2 diabetes-are driving the development of GCGR-based agonists for the treatment of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and other cardio-kidney-metabolic diseases. Due to the hyperglycaemic effects of glucagon, these unimolecular compounds also incorporate moieties that activate the glucagon-like peptide-1 (GLP-1) receptor, which stimulates insulin secretion to lower blood glucose levels. In early clinical trials, several GCGR-based multi-agonists (mazdutide, survodutide [being developed by the sponsor of this review], retatrutide) demonstrated substantial efficacy for eliciting weight loss in people with obesity while improving liver health in those with MASLD. However, the physiological and molecular pathways modulated by chronic pharmacological activation of the GCGR in humans remain to be delineated, as do its potential risks. Thus, there is great interest in the ongoing phase 3 clinical trials of these compounds. As data for their safety and efficacy emerge, glucagon's role in energy regulation and lipid metabolism will become clearer, along with warranting a potential new therapeutic option for obesity and MASLD. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Neff, Guy W AU - Neff GW AUID- ORCID: 0009-0008-1408-2162 AD - Covenant Metabolic Specialists, Sarasota, Florida, USA. LA - eng GR - Boehringer Ingelheim Pharmaceuticals, Inc./ PT - Journal Article PT - Review DEP - 20250930 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9007-92-5 (Glucagon) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon/metabolism MH - *Obesity/drug therapy/metabolism/complications MH - Signal Transduction/drug effects MH - Animals MH - Receptors, Glucagon/agonists/metabolism/antagonists & inhibitors MH - *Fatty Liver/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/metabolism/drug therapy OTO - NOTNLM OT - MASH OT - MASLD OT - NAFLD OT - NASH OT - anti-obesity agents OT - glucagon OT - glucagon receptors OT - metabolic dysfunction-associated steatotic liver disease OT - non-alcoholic fatty liver disease OT - obesity EDAT- 2025/09/30 13:53 MHDA- 2025/11/05 06:29 CRDT- 2025/09/30 06:23 PHST- 2025/09/05 00:00 [revised] PHST- 2025/06/01 00:00 [received] PHST- 2025/09/13 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/30 13:53 [pubmed] PHST- 2025/09/30 06:23 [entrez] AID - 10.1111/dom.70148 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):6869-6883. doi: 10.1111/dom.70148. Epub 2025 Sep 30. PMID- 41022666 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260825 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 1 DP - 2025 Dec 18 TI - GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischemic Optic Neuropathy: What an Endocrinologist Needs to Know. PG - e308-e313 LID - 10.1210/clinem/dgaf541 [doi] AB - CONTEXT: There is emerging evidence suggesting a possible association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) and non-arteritic anterior ischemic optic neuropathy (NAION). Retrospective cohort studies supporting this association report hazard ratios ranging from 2.19 to 7.74 when comparing exposed vs unexposed groups. This article explores the current research surrounding the risk of NAION with GLP-1 RA use in patients with type 2 diabetes and obesity, analyses patient factors that may increase susceptibility and highlights key areas warranting further research to guide endocrinologists in future prescribing. CONCLUSION: Whilst the emerging evidence suggests a possible association between commencement of GLP-1 RAs and NAION, absolute risk remains low and needs to be balanced with the known substantial benefits of GLP-1 RAs. Further research is needed to investigate whether specific patient characteristics such as optic disc parameters, blood pressure changes, degree of weight loss, or improvement of glycemic control can assist clinicians in identifying those at higher risk. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Liu, Livia AU - Liu L AUID- ORCID: 0009-0007-7034-1635 AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. FAU - Mohan, Sharanya AU - Mohan S AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. FAU - Wu, Linda AU - Wu L AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. AD - Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney 2065, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia. LA - eng PT - Journal Article PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy/complications MH - Endocrinologists MH - Risk Factors OTO - NOTNLM OT - GLP-1 agonists OT - non-arteritic ischemic optic neuropathy OT - obesity OT - semaglutide OT - type 2 diabetes EDAT- 2025/09/30 05:16 MHDA- 2025/12/18 13:06 CRDT- 2025/09/29 22:43 PHST- 2025/08/14 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/12/18 13:06 [medline] PHST- 2025/09/30 05:16 [pubmed] PHST- 2025/09/29 22:43 [entrez] AID - 8268255 [pii] AID - 10.1210/clinem/dgaf541 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 Dec 18;111(1):e308-e313. doi: 10.1210/clinem/dgaf541. PMID- 41022269 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20251030 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - GLP-1 receptor agonists and sarcopenia: Weight loss at a cost? A brief narrative review. PG - 112924 LID - S0168-8227(25)00938-6 [pii] LID - 10.1016/j.diabres.2025.112924 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual agonists targeting both GLP-1 and glucose-dependent insulinotropic polypeptide receptors (GLP-1/GIP RAs) are established therapies for type 2 diabetes mellitus (T2DM) and obesity. However, there is evidence that treatment with these agents may lead to significant loss of muscle mass, potentially resulting in sarcopenia or sarcopenic obesity. This brief narrative review explores the complex relationship between GLP-1 based therapies and muscle health. Some studies have linked GLP-1 RAs and dual GLP-1/GIP RAs with significant reductions in lean mass, and sarcopenia. However, preclinical evidence suggests that these agents can attenuate skeletal muscle atrophy, improve muscle function, and enhance mitochondrial health. Moreover, limited clinical data indicate a potential role in preserving muscle mass under certain conditions. Management includes optimised diet, targeted exercise, and novel pharmacological interventions, such as blockade of growth differentiation factor-8 (GDF8) and activin A (ActA). These measures hold potential to preserve muscle mass and to improve patient outcomes. Further research is warranted to clarify these mechanisms and to evaluate combination therapies aimed at preventing sarcopenia in patients receiving GLP-1 RAs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Pantazopoulos, Dimitrios AU - Pantazopoulos D AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis 68100, Alexandroupolis, Greece. FAU - Gouveri, Evanthia AU - Gouveri E AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis 68100, Alexandroupolis, Greece. FAU - Papazoglou, Dimitrios AU - Papazoglou D AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis 68100, Alexandroupolis, Greece. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis 68100, Alexandroupolis, Greece. Electronic address: papanasnikos@yahoo.gr. LA - eng PT - Journal Article PT - Review DEP - 20250927 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sarcopenia/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Obesity/drug therapy MH - Muscle, Skeletal/drug effects OTO - NOTNLM OT - GLP-1 RAs OT - GLP-1/GIP RAs OT - Sarcopenia OT - T2DM OT - Weight loss COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dimitrios Pantazopoulos has no conflicts of interest. Evanthia Gouveri has attended conferences sponsored by Berlin-Chemie, Sanofi, AstraZeneca, Novo Nordisk, Lilly, Boehringer Ingelheim, Menarini, Petsiavas and KRKA Hellas; received speaker honoraria by AstraZeneca, Boehringer-Ingelheim, Sanofi, Menarini. Dimitrios Papazoglou declares associations with Menarini, Novo Nordisk, Astra-Zeneca, Boehringer Ingelheim and Sanofi-Aventis. Nikolaos Papanas has been an advisory board member of Astra-Zeneca, Bayer, Boehringer Ingelheim, Menarini, MSD, Novo Nordisk, Pfizer, Takeda and TrigoCare International; has participated in sponsored studies by Astra-Zeneca, Eli-Lilly, GSK, MSD, Novo Nordisk, Novartis and Sanofi-Aventis; has received honoraria as a speaker for Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, ELPEN, Galenica, Menarini, MSD, Mylan, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda and Vianex; and attended conferences sponsored by TrigoCare International, Bayer, Eli-Lilly, Galenica, Novo Nordisk, Pfizer and Sanofi-Aventis. EDAT- 2025/09/30 05:16 MHDA- 2025/10/31 00:29 CRDT- 2025/09/29 19:28 PHST- 2025/08/18 00:00 [received] PHST- 2025/09/23 00:00 [revised] PHST- 2025/09/25 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/30 05:16 [pubmed] PHST- 2025/09/29 19:28 [entrez] AID - S0168-8227(25)00938-6 [pii] AID - 10.1016/j.diabres.2025.112924 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112924. doi: 10.1016/j.diabres.2025.112924. Epub 2025 Sep 27. PMID- 41022246 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20251222 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 258 DP - 2026 Jan 1 TI - GLP-1 Receptor Agonists and Cardiovascular Outcomes in Adults With Diabetes and Peripheral Artery Disease: An Updated Systematic Review and Meta-Analysis. PG - 268-275 LID - S0002-9149(25)00595-8 [pii] LID - 10.1016/j.amjcard.2025.09.039 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide proven cardiovascular benefits in type 2 diabetes mellitus (T2DM) and heart failure, but their effects in patients with peripheral artery disease (PAD) remain unclear. PAD is common in T2DM and increases the risk of adverse cardiovascular and limb outcomes. This meta-analysis assessed the impact of GLP-1 RAs on cardiovascular and limb-related outcomes in patients with T2DM and PAD. A systematic search of PubMed, Cochrane CENTRAL, ScienceDirect, and ClinicalTrials.gov was conducted through May 24, 2025. Primary outcomes included all-cause mortality (ACM) and cardiovascular mortality (CVM). Secondary outcomes were major adverse cardiovascular events (MACE), myocardial infarction, stroke, major adverse limb events (MALE), glycemic control (HbA1c), body weight, and adverse events. Pooled risk ratios and mean differences were calculated using random-effects models. Six randomized controlled trials, including 7,645 participants met the inclusion criteria. GLP-1 RAs significantly reduced ACM (RR 0.83, 95% CI 0.70 to 0.99, p = 0.04, I(2) = 0%), MACE (RR 0.86, 95% CI 0.76 to 0.98, p = 0.02, I(2) = 0%), and improved HbA1c (MD -0.72%, p = 0.02), with no significant effect on weight, major adverse limb events (MALE), CVM, myocardial infarction, or stroke. In conclusion, GLP-1 RAs lower MACE and ACM in patients with T2DM and PAD but do not clearly benefit limb-specific outcomes, highlighting the need for larger, PAD-focused trials to clarify their role in limb protection. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Shuja, Syed Hasan AU - Shuja SH AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Shuja, Muhammad Hamza AU - Shuja MH AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Shaukat, Ayesha AU - Shaukat A AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Hannat, Ramish AU - Hannat R AD - Services institute of Medical sciences, Lahore, Pakistan. FAU - Ahmed, Ilsa AU - Ahmed I AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Adam, Siad AU - Adam S AD - Rosalind Franklin University- Northwestern McHenry Hospital, McHenry, Illinois. FAU - Abdelkhalek, Ahmed AU - Abdelkhalek A AD - Rosalind Franklin University- Northwestern McHenry Hospital, McHenry, Illinois. FAU - Changez, Mah I Kan AU - Changez MIK AD - Department of General Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas. FAU - Ullah, Irfan AU - Ullah I AD - Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio; DCB Academy, Milan, Italy; Fondazione Ricerca e Innovazione Cardiovascolare, Milan, Italy. FAU - Ahmed, Raheel AU - Ahmed R AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. FAU - Cortese, Bernardo AU - Cortese B AD - Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio; DCB Academy, Milan, Italy; Fondazione Ricerca e Innovazione Cardiovascolare, Milan, Italy. Electronic address: bcortese@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250927 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peripheral Arterial Disease/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/mortality OTO - NOTNLM OT - GLP-1 Receptor Agonists OT - Major Adverse Cardiovascular Events (MACE) OT - Major Adverse Limb Events (MALE) OT - Meta-Analysis OT - PAD OT - Peripheral Artery Disease OT - Type-2 Diabetes Mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/30 05:16 MHDA- 2025/12/09 00:31 CRDT- 2025/09/29 19:28 PHST- 2025/08/10 00:00 [received] PHST- 2025/09/14 00:00 [revised] PHST- 2025/09/22 00:00 [accepted] PHST- 2025/12/09 00:31 [medline] PHST- 2025/09/30 05:16 [pubmed] PHST- 2025/09/29 19:28 [entrez] AID - S0002-9149(25)00595-8 [pii] AID - 10.1016/j.amjcard.2025.09.039 [doi] PST - ppublish SO - Am J Cardiol. 2026 Jan 1;258:268-275. doi: 10.1016/j.amjcard.2025.09.039. Epub 2025 Sep 27. PMID- 41021225 OWN - NLM STAT- MEDLINE DCOM- 20250929 LR - 20260718 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 9 DP - 2025 Sep 2 TI - SGLT2 Inhibitors and External Genital Infection in Male Patients With Type 2 Diabetes. PG - e2534485 LID - 10.1001/jamanetworkopen.2025.34485 [doi] LID - e2534485 AB - IMPORTANCE: New medications for type 2 diabetes (T2D) control, such as sodium-glucose cotransporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), have emerged. However, the US Food and Drug Administration has warned about potential risks of Fournier gangrene, a severe genital infection associated with SGLT2I use. OBJECTIVE: To determine comparative risks of male external genital infections (MEGIs) in adult male patients with T2D treated with SGLT2Is. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study analyzing Taiwan's National Health Insurance Research Database was conducted to evaluate the MEGI risk in adult male patients with T2D newly treated with SGLT2Is between January 1, 2009, and December 31, 2020. Patients newly treated with GLP-1RAs were chosen during the same period for the active-comparator group, and propensity scores with inverse probability of treatment weighting were applied to balance the baseline characteristics between the 2 treatment groups. Data analyses were conducted between February 2023 and April 2025. EXPOSURES: Treatment with SGLT2Is or GLP-1RAs. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of MEGI, identified using International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. To examine the result consistency, subgroup analyses based on age (older or younger than 60 years), diabetes severity (insulin use or not), and kidney function were conducted. RESULTS: The study included 239 757 patients; 224 360 initiated SGLT2Is (mean [SD] age, 58.4 [12.3] years) and 15 397 initiated GLP-1RAs (mean [SD] age, 58.1 [13.6] years). Compared with the GLP-1RA group, the SGLT2I group had a significantly increased risk of MEGI (hazard ratio [HR], 1.65; 95% CI, 1.59-1.71). The subgroup analyses indicated an increased risk of MEGI in the SGLT2I group among patients younger than 60 years (HR, 2.04; 95% CI, 1.58-2.65), those with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 (HR, 1.69; 95% CI, 1.34-2.15), and those with hemoglobin A1c below 7% (HR, 3.22; 95% CI, 1.71-6.03). CONCLUSIONS AND RELEVANCE: These findings suggest that SGLT2Is are associated with a higher risk of MEGI in adult male patients with T2D, compared with GLP-1RAs. Clinicians should be cautious when prescribing SGLT2Is in male patients with T2D. FAU - Cheng, Tsung-Han AU - Cheng TH AD - Division of Urology, Department of Surgery, Kaohsiung Show Chwan Memorial Hospital, Kaohsiung, Taiwan. FAU - Lin, Kun-Che AU - Lin KC AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Chuang, Albert Tzu-Ming AU - Chuang AT AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Cheng, Michael Chun-Yuan AU - Cheng MC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Shao, Shih-Chieh AU - Shao SC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. AD - Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. FAU - Lin, Swu-Jane AU - Lin SJ AD - Department of Pharmacy Systems, Outcomes & Policy, College of Pharmacy, University of Illinois at Chicago, Chicago. FAU - Lin, Tsung-Yen AU - Lin TY AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - National Cheng Kung University Hospital Douliu Branch, Yunlin, Taiwan. FAU - Tsai, Yuh-Shyan AU - Tsai YS AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Hu, Che-Yuan AU - Hu CY AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Wu, Kuan-Yu AU - Wu KY AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250902 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Middle Aged MH - Taiwan/epidemiology MH - Aged MH - Cohort Studies MH - *Fournier Gangrene/epidemiology/chemically induced MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - *Genital Diseases, Male/epidemiology/chemically induced PMC - PMC12481227 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/09/29 13:19 MHDA- 2025/09/29 13:20 PMCR- 2025/09/29 CRDT- 2025/09/29 11:32 PHST- 2025/09/29 13:20 [medline] PHST- 2025/09/29 13:19 [pubmed] PHST- 2025/09/29 11:32 [entrez] PHST- 2025/09/29 00:00 [pmc-release] AID - 2839404 [pii] AID - zoi250963 [pii] AID - 10.1001/jamanetworkopen.2025.34485 [doi] PST - epublish SO - JAMA Netw Open. 2025 Sep 2;8(9):e2534485. doi: 10.1001/jamanetworkopen.2025.34485. PMID- 41021211 OWN - NLM STAT- MEDLINE DCOM- 20260221 LR - 20261009 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 49 IP - 2 DP - 2026 Feb TI - Multi-database pharmacovigilance assessment of GLP-1 receptor agonist-related ophthalmic risks using advanced signal detection in FAERS and vigibase. PG - 425-433 LID - 10.1007/s40618-025-02712-3 [doi] AB - BACKGROUND: The expanding clinical use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and obesity has raised concerns about underrecognized ocular adverse events (AEs). Despite their metabolic benefits, fragmented evidence and methodological limitations in pharmacovigilance systems hinder comprehensive risk characterization. This study aimed to systematically evaluate ocular toxicity signals associated with GLP-1 RAs using advanced signal mining across the FDA Adverse Event Reporting System (FAERS) and VigiBase. METHODS: Data from FAERS (2005-2025 Q1) and VigiBase (1987-2025 Q1) were analyzed for ocular AEs linked to five GLP-1 RAs (exenatide, liraglutide, dulaglutide, semaglutide, lixisenatide). Disproportionality analyses using Bayesian (Information Component, IC(025) > 0) and frequentist (Reporting Odds Ratio, ROR 95% CI > 1) methods identified significant signals. Duplicate reports and incomplete data were excluded, with statistical processing performed in R packages and Excel software. RESULTS: Across both databases, ocular AEs predominantly occurred in individuals aged 45-64 and females. Semaglutide exhibited the strongest signals, notably for NAION (ROR = 40.18, IC(025) = 2.06 in VigiBase and ROR = 31.46, IC(025) = 4.84 in FAERS), with 2,878 cases in VigiBase and 2,047 in FAERS. Dulaglutide showed high rates of visual impairment and diabetic retinopathy. Early-onset AEs ( 360 days. Discrepancies between databases emerged, such as absent liraglutide/lixisenatide signals in VigiBase but moderate activity in FAERS. Furthermore, review of the prescribing information for these GLP-1RAs indicates that ocular adverse events are incompletely characterized. Diabetic retinopathy is reported solely for semaglutide and dulaglutide, while blurred vision is the only ocular event listed for lixisenatide. Other potential ocular risks are not mentioned in any of the respective drug labels. CONCLUSION: This large-scale pharmacovigilance analysis suggests underrecognized ocular safety signals associated with GLP-1 RAs, most prominently NAION with semaglutide and visual impairment/diabetic retinopathy with dulaglutide. The distinct AE profiles, temporal patterns (early vs. late onset), and database discrepancies highlight the complexity of GLP-1 RA ocular toxicity. These findings underscore the need for enhanced clinical vigilance, targeted post-marketing surveillance, and consideration of label updates to reflect these emerging ocular safety concerns. CI - (c) 2025. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Cheng, Xiao AU - Cheng X AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Jiang, Ziwei AU - Jiang Z AD - Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China. FAU - Li, Guangyao AU - Li G AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Wang, Jiawei AU - Wang J AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. wangjw2023@126.com. FAU - Han, Furong AU - Han F AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. furonghan@mail.ccmu.edu.cn. LA - eng PT - Journal Article DEP - 20250929 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Pharmacovigilance MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - Databases, Factual/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Male MH - Recombinant Fusion Proteins/adverse effects MH - United States/epidemiology MH - Middle Aged MH - United States Food and Drug Administration/statistics & numerical data MH - *Eye Diseases/chemically induced/epidemiology MH - Adult MH - Exenatide/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects OTO - NOTNLM OT - Disproportionality analysis OT - GLP-1 receptor agonists OT - NAION OT - Ocular adverse events OT - Pharmacovigilance COIS- Declarations. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/29 13:19 MHDA- 2026/02/21 12:29 CRDT- 2025/09/29 11:26 PHST- 2025/07/08 00:00 [received] PHST- 2025/09/20 00:00 [accepted] PHST- 2026/02/21 12:29 [medline] PHST- 2025/09/29 13:19 [pubmed] PHST- 2025/09/29 11:26 [entrez] AID - 10.1007/s40618-025-02712-3 [pii] AID - 10.1007/s40618-025-02712-3 [doi] PST - ppublish SO - J Endocrinol Invest. 2026 Feb;49(2):425-433. doi: 10.1007/s40618-025-02712-3. Epub 2025 Sep 29. PMID- 41020937 OWN - NLM STAT- MEDLINE DCOM- 20260129 LR - 20260201 IS - 1130-0108 (Print) IS - 1130-0108 (Linking) VI - 118 IP - 1 DP - 2026 Jan TI - GLP-1 receptor agonists and acute pancreatitis: fact or overstated risk? PG - 64-65 LID - 10.17235/reed.2025.11499/2025 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and weight management. These medications mimic the effects of the intestinal hormone GLP-1, thereby enhancing insulin secretion, reducing glucagon release, inducing satiety, and slowing gastric emptying. Their therapeutic scope now extends to cardiometabolic conditions and metabolic-associated steatotic liver disease (MASLD). Despite their clinical utility, GLP-1 RAs are frequently associated with gastrointestinal adverse effects-including nausea, vomiting, and diarrhoea-reported in up to 80% of patients, often in a dose-dependent manner. Concerns have also emerged regarding a potential association with acute pancreatitis. FAU - Dominguez Munoz, Juan Enrique AU - Dominguez Munoz JE AUID- ORCID: 0000-0001-8283-3185 AD - Gastroenterology and Hepatology, Fundacion Instituto de Investigacion Sanitaria de Santiago (IDIS), Espana. FAU - Larino Noia, Jose AU - Larino Noia J AUID- ORCID: 0000-0003-4892-6702 AD - Gastroenterology and Hepatology, Fundacion Instituto de Investigacion Sanitaria de Santiago (IDIS), espana. FAU - Dominguez Novoa, Yessica AU - Dominguez Novoa Y AD - Gastroenterology and Hepatology, Fundacion Instituto de Investigacion Sanitaria de Santiago (IDIS), Espana. FAU - Iglesias-Garcia, Julio AU - Iglesias-Garcia J AD - Gastroenterology and Hepatology, Fundacion Instituto de Investigacion Sanitaria de Santiago (IDIS), Espana. LA - eng PT - Journal Article PT - Review PL - Spain TA - Rev Esp Enferm Dig JT - Revista espanola de enfermedades digestivas JID - 9007566 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Pancreatitis/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Acute Disease EDAT- 2025/09/29 13:18 MHDA- 2026/01/29 07:34 CRDT- 2025/09/29 11:13 PHST- 2026/01/29 07:34 [medline] PHST- 2025/09/29 13:18 [pubmed] PHST- 2025/09/29 11:13 [entrez] AID - 10.17235/reed.2025.11499/2025 [doi] PST - ppublish SO - Rev Esp Enferm Dig. 2026 Jan;118(1):64-65. doi: 10.17235/reed.2025.11499/2025. PMID- 41017578 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260925 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study. PG - 197-209 LID - 10.1111/dom.70175 [doi] AB - AIMS: The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and depression remains uncertain due to contradictory evidence. We compared the risk of incident depression between GLP-1 RAs and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in overweight or obese adults with type 2 diabetes. MATERIALS AND METHODS: We conducted a new-user, active-comparator cohort study using a deidentified electronic health record network from January 2016 to July 2024. After 1:1 propensity score matching, we compared 25 704 new GLP-1 RA users to 25 704 SGLT2i users with newly diagnosed type 2 diabetes and overweight/obesity, excluding those with prior mood disorders. The primary outcome was a composite of incident depression diagnosis or antidepressant initiation, assessed from 1 month to 1 year post-initiation using Cox models and time-varying analyses. RESULTS: In 51 408 patients (mean age 56.8 years, 48.9% male), GLP-1 RA use was associated with higher depression incidence versus SGLT2i use (17.0% vs. 14.8%; hazard ratio 1.09, 95% CI 1.04-1.14; p < 0.001), with an absolute risk difference of 2.2%. The association was stronger in adults >/=65 years (HR 1.15) and plateaued after approximately 6 months. In secondary analysis, GLP-1 RA use was associated with a lower rate of all-cause mortality (HR 0.74, 95% CI 0.63-0.88). CONCLUSIONS: GLP-1 RA initiation was associated with a statistically significant increase in depression risk compared to SGLT2i use (9% relative increase, 2.2% absolute risk difference over 1 year), particularly during the subacute period and in older adults. This observed association must be balanced against substantial mortality benefits. Enhanced monitoring and shared decision-making are warranted. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chang, Yu AU - Chang Y AUID- ORCID: 0000-0001-9954-921X AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hsieh, Ming-Hong AU - Hsieh MH AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Ju, Po-Chung AU - Ju PC AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chang, Cheng-Chen AU - Chang CC AD - Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20250929 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/psychology/epidemiology MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Depression/epidemiology/chemically induced MH - *Obesity/complications/psychology/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Overweight/complications/psychology MH - Aged MH - Cohort Studies MH - Incidence MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors PMC - PMC12673450 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - depression OT - neuropsychiatric adverse effects OT - pharmacovigilance OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/09/29 09:27 MHDA- 2025/12/03 07:41 PMCR- 2025/12/03 CRDT- 2025/09/29 05:23 PHST- 2025/09/15 00:00 [revised] PHST- 2025/08/29 00:00 [received] PHST- 2025/09/23 00:00 [accepted] PHST- 2025/12/03 07:41 [medline] PHST- 2025/09/29 09:27 [pubmed] PHST- 2025/09/29 05:23 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70175 [pii] AID - 10.1111/dom.70175 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):197-209. doi: 10.1111/dom.70175. Epub 2025 Sep 29. PMID- 41014747 OWN - NLM STAT- MEDLINE DCOM- 20251206 LR - 20260428 IS - 1578-8989 (Electronic) IS - 0025-7753 (Linking) VI - 165 IP - 6 DP - 2025 Dec TI - Clinical factors influencing the systolic blood pressure benefits of once-weekly semaglutide in patients with type 2 diabetes. PG - 107179 LID - S0025-7753(25)00407-5 [pii] LID - 10.1016/j.medcli.2025.107179 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM), a major cardiovascular risk, is often associated with obesity and hypertension. Once-weekly subcutaneous semaglutide (OWS-Sema) can improve these conditions, but factors influencing blood pressure (BP) effects are not well studied. This study aimed to assess the impact of OWS-Sema on systolic BP (SBP) and identify clinical factors associated with its reduction in patients with T2DM. METHODS: Sub-analysis of the REALSEM-SP study involving OWS-Sema-naive patients with T2DM. Changes in SBP and diastolic BP (DBP) and influencing factors were analyzed over 12 months. RESULTS: One hundred seventy-eight patients were included (mean age 61+/-10 years, 43.8% female, 79.2% with hypertension). Median baseline SBP and DBP were 132 [122-145] and 80 [72-88]mmHg, respectively. SBP decreased by -4mmHg at 6 months and -2mmHg at 12 months (p=0.014), while DBP showed no significant change (p=0.395). Factors independently associated with SBP reduction at 6 months included uncontrolled BP and a glomerular filtration rate >/=60mL/min/1.73m(2), while at 12 months, only uncontrolled BP remained significant. A SBP >/=10mmHg reduction was associated with uncontrolled BP, dyslipidemia and renal function at 6-month, and only with uncontrolled BP at 12-month. CONCLUSION: OWS-Sema was associated with significant reductions in office SBP in T2DM patients, especially those with uncontrolled baseline BP, independent of BMI changes or dose. Patients with baseline uncontrolled BP appear to benefit the most. CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Ruiz-Sanchez, Jorge Gabriel AU - Ruiz-Sanchez JG AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez-Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), Hospital Universitario Fundacion Jimenez Diaz, Madrid 28040, Spain. Electronic address: jorgeg.ruiz@quironsalud.es. FAU - Sierra Poyatos, Roberto Miguel AU - Sierra Poyatos RM AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario General de Villalba, Madrid, Spain. FAU - Luiza Luca, Bogdana AU - Luiza Luca B AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Sanchez-Lechuga, Begona AU - Sanchez-Lechuga B AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Modrono Mostoles, Naiara AU - Modrono Mostoles N AD - Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Montoya Alvarez, Teresa AU - Montoya Alvarez T AD - Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Meneses, Diego AU - Meneses D AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Sanchez-Lopez, Raquel AU - Sanchez-Lopez R AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Casado Cases, Carlos AU - Casado Cases C AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Perez de Arenaza Pozo, Victor AU - Perez de Arenaza Pozo V AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Vazquez, Clotilde AU - Vazquez C AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez-Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), Hospital Universitario Fundacion Jimenez Diaz, Madrid 28040, Spain; Endocrinology Department, Hospital Universitario General de Villalba, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain; Endocrinology Department, Hospital Universitario Rey Juan Carlos, Madrid, Spain. FAU - Cardenas-Salas, Jersy Jair AU - Cardenas-Salas JJ AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. LA - eng LA - spa PT - Journal Article DEP - 20250926 PL - Spain TA - Med Clin (Barc) JT - Medicina clinica JID - 0376377 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Blood Pressure/drug effects MH - *Hypertension/drug therapy/complications/etiology MH - Aged MH - Drug Administration Schedule MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Blood pressure OT - Diabetes tipo 2 OT - Hipertension arterial OT - Hypertension OT - Obesidad OT - Obesity OT - Presion arterial OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/09/28 01:02 MHDA- 2025/12/07 00:40 CRDT- 2025/09/27 18:04 PHST- 2025/03/30 00:00 [received] PHST- 2025/06/12 00:00 [revised] PHST- 2025/06/17 00:00 [accepted] PHST- 2025/12/07 00:40 [medline] PHST- 2025/09/28 01:02 [pubmed] PHST- 2025/09/27 18:04 [entrez] AID - S0025-7753(25)00407-5 [pii] AID - 10.1016/j.medcli.2025.107179 [doi] PST - ppublish SO - Med Clin (Barc). 2025 Dec;165(6):107179. doi: 10.1016/j.medcli.2025.107179. Epub 2025 Sep 26. PMID- 41011082 OWN - NLM STAT- MEDLINE DCOM- 20250927 LR - 20250930 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 9 DP - 2025 Sep 18 TI - Impact of Incretin-Based Therapy on Skeletal Muscle Health. LID - 10.3390/medicina61091691 [doi] LID - 1691 AB - Skeletal muscle is the largest insulin-sensitive tissue in the human body, playing a crucial role in glucose homeostasis, body mobility and overall metabolic health. In obesity and type 2 diabetes (T2D), skeletal muscle undergoes structural, functional, and metabolic alterations, including reduced muscle mass, impaired contractile function, increased myosteatosis, mitochondrial dysfunction, and chronic low-grade inflammation. Incretin-based therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are highly effective treatments for T2D and obesity, producing substantial weight loss. While clinical trials suggest proportional loss of fat and lean mass when using incretin-based therapies, emerging preclinical and translational data indicate potential muscle-specific beneficial effects such as attenuation of atrophy, improved myogenesis, enhanced mitochondrial function and reduced myosteatosis. This review comprehensively summarizes the current preclinical and clinical evidence on the impact of incretin-based therapies on skeletal muscle mass, composition, metabolism, and performance, focusing on mechanistic insights from animal models and translational findings from human studies. FAU - Koceva, Andrijana AU - Koceva A AD - Department of Endocrinology and Diabetology, University Medical Center Maribor, 2000 Maribor, Slovenia. AD - Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia. FAU - Janez, Andrej AU - Janez A AUID- ORCID: 0000-0002-6594-5254 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. FAU - Jensterle, Mojca AU - Jensterle M AUID- ORCID: 0000-0002-8861-8803 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. LA - eng PT - Journal Article PT - Review DEP - 20250918 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - *Muscle, Skeletal/drug effects/physiopathology MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12471476 OTO - NOTNLM OT - incretin-based treatment OT - liraglutide OT - muscle function OT - muscle quality OT - obesity OT - semaglutide OT - tirzepatide COIS- A.K. reports receiving lecture honoraria from Eli Lilly, Novo Nordisk, Pfeizer, AstraZeneca, Boehringer Ingelheim and Sanofi and having served as a consultant for Novo Nordisk. A.J. has served as a consultant and is on Speakers Bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Abbott, Novo Nordisk, Medtronic, and Sanofi. M.J. reports receiving lecture honoraria from Novo Nordisk, Eli Lilly, Pfeizer, Amgen, Novartis and Sanofi and being an advisory board member of Novo Nordisk, Eli Lilly, Amgen and Pfeizer. EDAT- 2025/09/27 06:34 MHDA- 2025/09/27 06:35 PMCR- 2025/09/18 CRDT- 2025/09/27 01:21 PHST- 2025/08/14 00:00 [received] PHST- 2025/09/11 00:00 [revised] PHST- 2025/09/15 00:00 [accepted] PHST- 2025/09/27 06:35 [medline] PHST- 2025/09/27 06:34 [pubmed] PHST- 2025/09/27 01:21 [entrez] PHST- 2025/09/18 00:00 [pmc-release] AID - medicina61091691 [pii] AID - medicina-61-01691 [pii] AID - 10.3390/medicina61091691 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Sep 18;61(9):1691. doi: 10.3390/medicina61091691. PMID- 41008649 OWN - NLM STAT- MEDLINE DCOM- 20250927 LR - 20260329 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 9 DP - 2025 Sep 19 TI - Role of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) in Patients with Chronic Heart Failure. LID - 10.3390/biom15091342 [doi] LID - 1342 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes and obesity due to their metabolic benefits. Beyond weight loss and glycemic control, emerging evidence suggests they may also exert cardioprotective effects. In the context of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF), GLP-1RAs have been associated with improvement in symptoms, physical capacity, biomarkers, and structural cardiac remodeling. These benefits appear to be independent of weight loss, suggesting additional mechanisms including anti-inflammatory effects, improved myocardial metabolism or modulation of epicardial adipose tissue. However, current data largely come from non-HF dedicated trials, with limited standardization of the HF phenotype. Results are overall inconsistent and may suggest potential harm in some cases, particularly in HF with reduced ejection fraction (HFrEF). This review aims to summarize the current evidence on the role of GLP-1RAs in heart failure, explore possible underlying mechanisms and highlight key gaps in knowledge. FAU - Llongueras-Espi, Pasqual AU - Llongueras-Espi P AUID- ORCID: 0009-0008-1906-7519 AD - Advanced Heart Failure and Heart Transplant Program, Cardiology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. FAU - Garcia-Romero, Elena AU - Garcia-Romero E AUID- ORCID: 0000-0003-4090-6571 AD - Advanced Heart Failure and Heart Transplant Program, Cardiology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. AD - Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, 08908 Barcelona, Spain. AD - Biomedical Research Networking Center on Cardiovascular Diseases (CIBER-CV), Carlos III Health Institute, 28029 Madrid, Spain. FAU - Comin-Colet, Josep AU - Comin-Colet J AUID- ORCID: 0000-0001-8780-720X AD - Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, 08908 Barcelona, Spain. AD - Biomedical Research Networking Center on Cardiovascular Diseases (CIBER-CV), Carlos III Health Institute, 28029 Madrid, Spain. AD - Community Heart Failure Program, Cardiology and Internal Medicine Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. AD - Department of Clinical Sciences, School of Medicine, University of Barcelona, 08036 Barcelona, Spain. FAU - Gonzalez-Costello, Jose AU - Gonzalez-Costello J AUID- ORCID: 0000-0002-7437-3630 AD - Advanced Heart Failure and Heart Transplant Program, Cardiology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. AD - Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, 08908 Barcelona, Spain. AD - Biomedical Research Networking Center on Cardiovascular Diseases (CIBER-CV), Carlos III Health Institute, 28029 Madrid, Spain. AD - Department of Clinical Sciences, School of Medicine, University of Barcelona, 08036 Barcelona, Spain. LA - eng PT - Journal Article PT - Review DEP - 20250919 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Heart Failure/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - Chronic Disease MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals PMC - PMC12466965 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiometabolic disease OT - heart failure OT - obesity OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/09/27 06:33 MHDA- 2025/09/27 06:34 PMCR- 2025/09/19 CRDT- 2025/09/27 01:09 PHST- 2025/08/08 00:00 [received] PHST- 2025/09/12 00:00 [revised] PHST- 2025/09/16 00:00 [accepted] PHST- 2025/09/27 06:34 [medline] PHST- 2025/09/27 06:33 [pubmed] PHST- 2025/09/27 01:09 [entrez] PHST- 2025/09/19 00:00 [pmc-release] AID - biom15091342 [pii] AID - biomolecules-15-01342 [pii] AID - 10.3390/biom15091342 [doi] PST - epublish SO - Biomolecules. 2025 Sep 19;15(9):1342. doi: 10.3390/biom15091342. PMID- 41008590 OWN - NLM STAT- MEDLINE DCOM- 20250927 LR - 20260925 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 9 DP - 2025 Sep 5 TI - The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe? LID - 10.3390/biom15091284 [doi] LID - 1284 AB - Erectile dysfunction (ED) is a common yet frequently underrecognized microvascular complication of diabetes, affecting up to three out of four individuals. Key contributing factors include advancing age, long-standing disease duration, and suboptimal glycemic control, as well as insulin resistance and androgen deficiency-the latter being particularly common in men with type 2 diabetes (T2D) and obesity. While numerous studies have investigated the effects of various antidiabetic therapies on diabetes-related ED, the results remain inconsistent, limiting definitive conclusions. In recent years, increasing attention has focused on a novel class of antidiabetic medications, namely glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These agents have become central to the treatment of T2D due to their potent glucose-lowering properties and well-documented benefits on cardiovascular outcomes, and weight loss. Given these pleiotropic effects, GLP-1 RAs have been presumed to positively influence erectile function-a hypothesis supported by a growing body of experimental and clinical research. However, preliminary reports have also raised concerns about a possible association between GLP-1 RA use and ED. This narrative review aims to synthesize current evidence regarding the impact of GLP-1 RAs on erectile function, providing a platform for future research in this evolving field. FAU - Kounatidis, Dimitris AU - Kounatidis D AUID- ORCID: 0000-0003-4338-4879 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Vallianou, Natalia G AU - Vallianou NG AUID- ORCID: 0000-0003-3874-5393 AD - First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece. FAU - Rebelos, Eleni AU - Rebelos E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. AD - Turku PET Centre, University of Turku, 20014 Turku, Finland. AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Vallianou, Kalliopi AU - Vallianou K AD - Clinic of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Diakoumopoulou, Evanthia AU - Diakoumopoulou E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Makrilakis, Konstantinos AU - Makrilakis K AUID- ORCID: 0000-0002-4160-0577 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Tentolouris, Nikolaos AU - Tentolouris N AUID- ORCID: 0000-0003-0615-2534 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. LA - eng PT - Journal Article PT - Review DEP - 20250905 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Erectile Dysfunction/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Penile Erection/drug effects PMC - PMC12467596 OTO - NOTNLM OT - GIP OT - GLP-1 receptor agonists OT - diabetes OT - dulaglutide OT - erectile dysfunction OT - hypogonadism OT - liraglutide OT - semaglutide OT - testosterone OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2025/09/27 06:33 MHDA- 2025/09/27 06:34 PMCR- 2025/09/05 CRDT- 2025/09/27 01:09 PHST- 2025/07/28 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/04 00:00 [accepted] PHST- 2025/09/27 06:34 [medline] PHST- 2025/09/27 06:33 [pubmed] PHST- 2025/09/27 01:09 [entrez] PHST- 2025/09/05 00:00 [pmc-release] AID - biom15091284 [pii] AID - biomolecules-15-01284 [pii] AID - 10.3390/biom15091284 [doi] PST - epublish SO - Biomolecules. 2025 Sep 5;15(9):1284. doi: 10.3390/biom15091284. PMID- 41004212 OWN - NLM STAT- MEDLINE DCOM- 20250926 LR - 20251002 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 31 IP - 10 DP - 2025 Oct TI - Patterns and costs associated with glucagon-like peptide-1 receptor agonist use in US adults with type 2 diabetes. PG - 1029-1038 LID - 10.18553/jmcp.2025.31.10.1029 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer cardiorenal benefits in diabetes management. Since 2020, public awareness of GLP-1 RAs for diabetes, weight loss, and the prevention of cardiovascular disease has led to a surge in their utilization. However, the high cost of GLP-1 RAs and limitations in insurance coverage have been considered significant barriers to access. Current knowledge regarding how GLP-1 RA use affects total health care costs in diabetes care after 2020 in the United States remains limited. Consequently, further research is needed to examine the financial burden of GLP-1 RA use on patients and payers, as well as its overall impact on total health care costs at the national level. OBJECTIVE: To examine GLP-1 RA utilization and association with health care costs among US adults with type 2 diabetes. METHODS: Using data from the 2021-2022 Medical Expenditure Panel Survey, the study sample included individuals (aged >/=18 years) with a diagnosis of type 2 diabetes. Outcomes included GLP-1 RA use and all-cause and diabetes-related health care costs, including medical and prescription drug costs paid by patients and insurers. Generalized linear regression with a log link and gamma distribution was used to assess the effect of GLP-1 RA use on health care costs, adjusting for sociodemographic and health-related characteristics. RESULTS: Among 3,587 eligible adults with type 2 diabetes, 637 (18.8%) used GLP-1 RAs, representing an estimated 3.66 million US adults-a marked increase compared with pre-2020 estimates of less than 10%. Fewer older adults (aged >/=65 years) used GLP-1 RAs (35.1%) compared with adults aged 45-64 years (50.6%). The average annual per-person cost of GLP-1 RA was $6,947. Although insurance covered more than 95% of GLP-1 RA cost, these medications represented a substantial proportion of diabetes care costs: 63.3% of antidiabetic drug costs and 55.7% of total diabetes-related costs among GLP-1 RA users. After adjustment, GLP-1 RA use was associated with a 219% increase in diabetes-related costs and a 55.3% increase in total all-cause health care costs. CONCLUSIONS: GLP-1 RA utilization among US adults with type 2 diabetes has substantially increased, with use in 2021-2022 nearly double that of the period prior to 2020. The higher health care costs associated with taking GLP-1 RAs were largely attributable to high drug costs, of which over 95% were covered by insurance. FAU - Wu, Jun AU - Wu J AD - Department of Sociobehavioral and Administrative Pharmacy, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL. FAU - Perez, Alexandra AU - Perez A AD - Department of Sociobehavioral and Administrative Pharmacy, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL. FAU - Sullivan, Patrick W AU - Sullivan PW AD - Department of Sociobehavioral and Administrative Pharmacy, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - United States MH - Male MH - *Hypoglycemic Agents/economics/therapeutic use MH - Aged MH - Adult MH - *Health Care Costs/statistics & numerical data MH - Health Expenditures MH - Drug Costs MH - Young Adult PMC - PMC12467763 EDAT- 2025/09/26 12:33 MHDA- 2025/09/26 18:29 PMCR- 2025/10/01 CRDT- 2025/09/26 11:43 PHST- 2025/09/26 18:29 [medline] PHST- 2025/09/26 12:33 [pubmed] PHST- 2025/09/26 11:43 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 10.18553/jmcp.2025.31.10.1029 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2025 Oct;31(10):1029-1038. doi: 10.18553/jmcp.2025.31.10.1029. PMID- 40998218 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20251030 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - End-stage renal diseases associated with SGLT2 inhibitors versus GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease. PG - 112921 LID - S0168-8227(25)00935-0 [pii] LID - 10.1016/j.diabres.2025.112921 [doi] AB - AIMS: To compare the renal effectiveness of SGLT2 inhibitors (SGLT2i) versus GLP-1 receptor agonists (GLP-1RA) in metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Using nationwide healthcare claims (2014-2023) of Korea, we constructed a cohort of MASLD patients who initiated SGLT2i or GLP-1RA. Patients were stratified on baseline status of chronic kidney disease (CKD). New-users of SGLT2i and GLP-1RA were 1:1 propensity score (PS) matched. Incidence rates (IRs) per 1,000 person-years, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for a composite of end-stage renal diseases (ESRD). RESULTS: Of 333,082 MASLD patients who initiated SGLT2i or GLP-1RA, a total of 1,268 SGLT2i-GLP-1RA pairs were PS-matched in cohort with CKD, while 10,996 pairs were matched in cohort without CKD. For the cohort with CKD, SGLT2i presented 33% lower risk of ESRD compared to GLP-1RA (20.3 vs. 30.0 events per 1,000 person-years; HR 0.67, 95% CI 0.45-1.00). For the cohort without CKD, SGLT2i presented a 68% lowered risk of ESRD compared to GLP-1RA (0.9 vs. 2.5 events per 1,000 person-years; HR 0.32, 95% CI 0.19-0.53). CONCLUSIONS: The use of SGLT2i was associated with lower risk of ESRD compared to GLP-1RA in MASLD. The protective association was presented regardless of CKD status. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Ko, Hwa Yeon AU - Ko HY AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. Electronic address: hy12@g.skku.edu. FAU - Hong, Bin AU - Hong B AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. Electronic address: hongbin@g.skku.edu. FAU - Bea, Sungho AU - Bea S AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: sbea@bwh.harvard.edu. FAU - Bae, Jae Hyun AU - Bae JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: fermatah@gmail.com. FAU - Cho, Young Min AU - Cho YM AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: ymchomd@snu.ac.kr. FAU - Chang, Yoosoo AU - Chang Y AD - Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea. Electronic address: yoosoo.chang@gmail.com. FAU - Ryu, Seungho AU - Ryu S AD - Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea. Electronic address: sh703.yoo@gmail.com. FAU - Byrne, Christopher D AU - Byrne CD AD - Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom. Electronic address: C.D.Byrne@soton.ac.uk. FAU - Shin, Ju-Young AU - Shin JY AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea; Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea. Electronic address: shin.jy@skku.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250923 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Republic of Korea/epidemiology MH - *Fatty Liver/complications/drug therapy/epidemiology MH - *Kidney Failure, Chronic/epidemiology/chemically induced MH - Adult MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - End Stage Liver Disease/epidemiology COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/26 00:30 MHDA- 2025/10/31 00:29 CRDT- 2025/09/25 19:43 PHST- 2025/09/15 00:00 [received] PHST- 2025/09/21 00:00 [revised] PHST- 2025/09/22 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/26 00:30 [pubmed] PHST- 2025/09/25 19:43 [entrez] AID - S0168-8227(25)00935-0 [pii] AID - 10.1016/j.diabres.2025.112921 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112921. doi: 10.1016/j.diabres.2025.112921. Epub 2025 Sep 23. PMID- 40996853 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260527 IS - 1744-6880 (Electronic) IS - 1744-6872 (Linking) VI - 36 IP - 1 DP - 2026 Jan 1 TI - GLP1R and OCT1 variants modulate semaglutide and metformin response in type 2 diabetes. PG - 9-17 LID - 10.1097/FPC.0000000000000577 [doi] AB - BACKGROUND: Large consortia link variants in SLC22A1 , SLC47A1 , and GLP1R to antidiabetic response, yet few data confirm these effects in small real-world cohorts. We tested whether three common polymorphisms translate into measurable 3-month metabolic changes. METHODS: Twenty-seven Bulgarian adults with type 2 diabetes [BMI >/= 25 kg/m(2); mean glycated hemoglobin (HbA1c): 8.3 +/- 0.9%] received metformin XR 2000 mg ( n = 17) or oral semaglutide 14 mg ( n = 10). Sanger sequencing identified SLC22A1 rs628031, SLC47A1 rs2252281, and GLP1R rs6923761. Primary endpoints were 3-month changes (Delta) in weight and HbA1c; analysis of variance and ordinary least squares regression assessed genotype and treatment effects, as well as covariate-adjusted linear models of 3-month change (Delta). RESULTS: Semaglutide produced greater weight loss than metformin [-6.5 +/- 3.6 vs. -1.6 +/- 2.5 kg; 95% confidence interval (CI) -7.6 to -2.2; P = 0.001] and larger BMI reduction (-2.0 +/- 1.2 vs. -0.3 +/- 0.9 kg/m(2); P = 0.001). At an exploratory 10% FDR, only OCT1 rs34130495 dosage was associated with high-density lipoprotein (HDL) change in metformin-treated participants ( beta = +0.340 mmol/L per minor allele; P = 0.0026; q = 0.063; N = 16). GLP1R rs6923761 showed nominal trends for weight and BMI change in semaglutide users that did not survive FDR ( P approximately 0.06-0.07; q approximately 0.29; N = 10). CONCLUSION: Semaglutide outperformed metformin for short-term weight loss. An HDL signal for OCT1 rs34130495 at an exploratory 10% FDR warrants replication. These hypothesis-generating data support the feasibility of genotype-guided studies in local clinical settings. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Tourtourikov, Ivan AU - Tourtourikov I AD - Department of Chemistry and Biochemistry, Medical Faculty, Medical University. AD - Genetic Medico-Diagnostic Laboratory Genica and Genome Center Bulgaria. FAU - Kalinkova, Maria AU - Kalinkova M AD - Department of Pharmacology and Toxicology. FAU - Ivanov, Peter AU - Ivanov P AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Mileva-Popova, Rene AU - Mileva-Popova R AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Tafradjiiska-Hadjiolova, Radka AU - Tafradjiiska-Hadjiolova R AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Handjieva-Darlenska, Teodora AU - Handjieva-Darlenska T AD - Department of Pharmacology and Toxicology. FAU - Kadiyska, Tanya AU - Kadiyska T AD - Genetic Medico-Diagnostic Laboratory Genica and Genome Center Bulgaria. AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. LA - eng PT - Journal Article DEP - 20251028 PL - United States TA - Pharmacogenet Genomics JT - Pharmacogenetics and genomics JID - 101231005 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Octamer Transcription Factor-1) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (POU2F1 protein, human) SB - IM MH - Humans MH - *Metformin/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Octamer Transcription Factor-1/genetics MH - Glycated Hemoglobin MH - Polymorphism, Single Nucleotide MH - Aged MH - Adult MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - metformin OT - pharmacogenetics OT - semaglutide OT - type 2 diabetes EDAT- 2025/09/25 18:30 MHDA- 2025/11/03 06:27 CRDT- 2025/09/25 12:23 PHST- 2025/05/29 00:00 [received] PHST- 2025/09/06 00:00 [accepted] PHST- 2025/11/03 06:27 [medline] PHST- 2025/09/25 18:30 [pubmed] PHST- 2025/09/25 12:23 [entrez] AID - 01213011-990000000-00099 [pii] AID - 10.1097/FPC.0000000000000577 [doi] PST - ppublish SO - Pharmacogenet Genomics. 2026 Jan 1;36(1):9-17. doi: 10.1097/FPC.0000000000000577. Epub 2025 Oct 28. PMID- 40995652 OWN - NLM STAT- MEDLINE DCOM- 20250925 LR - 20260501 IS - 1731-2531 (Electronic) IS - 1642-5758 (Print) IS - 1642-5758 (Linking) VI - 57 IP - 1 DP - 2025 Sep 17 TI - New therapeutic agents for type 2 diabetes: anaesthetic considerations. A narrative review. PG - 231-238 LID - 208895 [pii] LID - 10.5114/ait/208895 [doi] AB - An increasing number of patients treated with novel antidiabetic drugs, including glucagon-like-peptide-1 receptor agonists (GLP-1RA), dual glucose-dependent insulinotropic polypeptide receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors, are presenting in the perioperative period. GLP-1RAs are known to delay gastric emptying, although current data remain preliminary and somewhat conflicting. SGLT2 inhibitors may be associated with euglycemic ketoacidosis in the perioperative period. To assess residual gastric content, gastric ultrasound may serve as a valuable tool in stratifying aspiration risk. Various recommendations are available for the perioperative management of patients on GLP-1RAs or SGLT2 inhibitors. These are based largely on expert opinion and multi-society consensus. This review aims to summarise the key perioperative considerations related to these drug classes and to familiarise practitioners with their pharmacological profiles. We highlight their potential adverse effects and present current recommendations from professional organisations to support safe and effective perioperative management. FAU - Doroba, Oliwia AU - Doroba O AD - 2nd Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Poland. FAU - Czupryniak, Leszek AU - Czupryniak L AD - Department of Diabetology and Internal Medicine, Medical University of Warsaw, Poland. FAU - Sanfilippo, Filippo AU - Sanfilippo F AD - Department of Anaesthesia and Intensive Care, A.O.U. Policlinico-San Marco, Site "Policlinico G. Rodolico", Catania, Italy. AD - Section of Anaesthesia, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy. FAU - Andruszkiewicz, Pawel AU - Andruszkiewicz P AD - 2nd Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Poland. FAU - Zawadka, Mateusz AU - Zawadka M AD - 2nd Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Poland. LA - eng PT - Journal Article PT - Review PL - Poland TA - Anaesthesiol Intensive Ther JT - Anaesthesiology intensive therapy JID - 101472620 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Perioperative Care/methods MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Anesthesia/methods PMC - PMC12793977 OTO - NOTNLM OT - GIP OT - GLP-1 receptor agonists OT - GLP-1RA OT - SGLT-2 inhibitors OT - aspiration risk OT - gastric ultrasound OT - perioperative management EDAT- 2025/09/25 06:28 MHDA- 2025/09/25 12:42 PMCR- 2025/09/17 CRDT- 2025/09/25 05:15 PHST- 2025/09/25 12:42 [medline] PHST- 2025/09/25 06:28 [pubmed] PHST- 2025/09/25 05:15 [entrez] PHST- 2025/09/17 00:00 [pmc-release] AID - 208895 [pii] AID - 10.5114/ait/208895 [doi] PST - ppublish SO - Anaesthesiol Intensive Ther. 2025 Sep 17;57(1):231-238. doi: 10.5114/ait/208895. PMID- 40994370 OWN - NLM STAT- MEDLINE DCOM- 20251220 LR - 20251220 IS - 1759-7390 (Electronic) IS - 1750-8460 (Linking) VI - 86 IP - 9 DP - 2025 Sep 25 TI - Obesity and Metabolic Syndrome: Current Insights and Future Directions. PG - 1-20 LID - 10.12968/hmed.2025.0127 [doi] AB - Obesity and metabolic syndrome are global health challenges, significantly increasing risks for type 2 diabetes, cardiovascular and cerebrovascular diseases, and overall mortality. This narrative review aims to discuss the relationship between obesity and metabolic syndrome; the past, present and future of anti-obesity medications including new advances in incretin-based therapies which have enabled patients to achieve significant weight loss and improvement in metabolic parameters; and the role of metabolic/bariatric surgery which remains the most effective durable treatment for severe obesity, with high remission rates of metabolic comorbidities like type 2 diabetes. Multimodal approaches involving the combination of lifestyle, medical and surgical advances will revolutionise our approach to treating obesity and metabolic syndrome in the future. FAU - Zarkasi, Zaiem AU - Zarkasi Z AD - Endocrinology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK. FAU - Mudaliar, Rajshekhar N AU - Mudaliar RN AD - Endocrinology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK. AD - Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. FAU - Majeed, Waseem A AU - Majeed WA AD - Endocrinology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK. AD - Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. FAU - Syed, Akheel A AU - Syed AA AD - Endocrinology, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK. AD - Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. LA - eng PT - Journal Article PT - Review DEP - 20250905 PL - Singapore TA - Br J Hosp Med (Lond) JT - British journal of hospital medicine (London, England : 2005) JID - 101257109 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - *Metabolic Syndrome/epidemiology/metabolism/therapy MH - *Obesity/epidemiology/metabolism/therapy MH - *Bariatric Surgery/methods MH - Weight Loss/drug effects MH - *Anti-Obesity Agents/pharmacology/therapeutic use MH - Comorbidity MH - Diabetes Mellitus, Type 2/epidemiology/metabolism/therapy MH - Risk Factors MH - Prevalence MH - Humans MH - Healthy Lifestyle MH - Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Incretins/metabolism/pharmacology/therapeutic use MH - Gastric Inhibitory Polypeptide/metabolism MH - Receptors, Gastrointestinal Hormone/agonists/metabolism MH - Treatment Outcome OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - incretins OT - metabolic syndrome OT - metabolic/bariatric surgery OT - obesity OT - weight loss EDAT- 2025/09/25 06:29 MHDA- 2025/09/25 06:30 CRDT- 2025/09/25 04:22 PHST- 2025/09/25 06:30 [medline] PHST- 2025/09/25 06:29 [pubmed] PHST- 2025/09/25 04:22 [entrez] AID - 10.12968/hmed.2025.0127 [doi] PST - ppublish SO - Br J Hosp Med (Lond). 2025 Sep 25;86(9):1-20. doi: 10.12968/hmed.2025.0127. Epub 2025 Sep 5. PMID- 40994310 OWN - NLM STAT- MEDLINE DCOM- 20260316 LR - 20260904 IS - 2326-5205 (Electronic) IS - 2326-5191 (Print) IS - 2326-5191 (Linking) VI - 78 IP - 3 DP - 2026 Mar TI - Glucagon-Like Peptide-1 Receptor Agonist Use and the Risk of Adverse Cardiac and Kidney Outcomes Among Patients With Systemic Lupus Erythematosus and Lupus Nephritis. PG - 665-671 LID - 10.1002/art.43403 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardioprotective and kidney-protective benefits among patients with type 2 diabetes (T2D). We sought to determine whether GLP-1RA use improves cardiovascular (CV) and kidney outcomes among patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). METHODS: We emulated a pragmatic target trial to evaluate the impact of GLP-1RA versus comparator hypoglycemic agents, dipeptidyl peptidase 4 inhibitors (DPP4i), on CV and kidney outcomes among patients with SLE and T2D using a large, US multicenter electronic health record database. We used propensity score overlap weighting to emulate randomization among treatment groups. Outcomes included major adverse CV events, venous thromboembolism (VTE), kidney disease progression (estimated glomerular filtration rate decline >/= 30% or new onset end-stage kidney disease), and all-cause mortality. We used Cox regression to compare hazard ratios (HR) based on the weighted populations. In a secondary analysis, we only included patients with LN. RESULTS: There were 910 and 1,004 initiators of GLP-1RA and DPP4i, respectively, including 267 and 324 patients with LN, respectively. Baseline covariates were balanced after propensity score overlap weighting. The risks of major adverse cardiac events (MACEs; hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.48-0.91), VTE (HR 0.49, 95% CI 0.24-0.97), kidney disease progression (HR 0.77, 95% CI 0.60-0.98), and all-cause mortality (HR 0.26, 95% CI 0.10-0.68) were lower with GLP-1RA versus DPP4i use. GLP-1RA use was similarly associated with lower risks of MACE and kidney disease progression among patients with LN. CONCLUSION: We found lower risks of adverse CV and kidney outcomes and mortality with GLP-1RA use compared with DPP4i use among patients with lupus and T2D. CI - (c) 2025 American College of Rheumatology. FAU - Jorge, April AU - Jorge A AUID- ORCID: 0000-0001-6935-880X AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston. AD - Harvard Medical School, Boston, Massachusetts. FAU - Patel, Aakash V AU - Patel AV AUID- ORCID: 0000-0002-4253-0822 AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston. AD - Harvard Medical School, Boston, Massachusetts. FAU - Zhou, Baijun AU - Zhou B AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston. FAU - Zhang, Lingxiao AU - Zhang L AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston. FAU - Choi, Hyon AU - Choi H AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston. AD - Harvard Medical School, Boston, Massachusetts. LA - eng GR - P50-AR-060772/AR/NIAMS NIH HHS/United States GR - R01 AR065944/AR/NIAMS NIH HHS/United States GR - K23-AR-079040/AR/NIAMS NIH HHS/United States GR - R01-AR-065944/AR/NIAMS NIH HHS/United States GR - K23 AR079040/AR/NIAMS NIH HHS/United States GR - P50 AR060772/AR/NIAMS NIH HHS/United States GR - K supplement/Rheumatology Research Foundation/ PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251217 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Lupus Nephritis/complications/drug therapy MH - Adult MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Lupus Erythematosus, Systemic/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Disease Progression MH - Venous Thromboembolism/epidemiology MH - Proportional Hazards Models PMC - PMC13501418 MID - NIHMS2202332 COIS- Conflicts of Interest: The authors declare no conflicts of interest. EDAT- 2025/09/25 06:28 MHDA- 2026/03/17 00:34 PMCR- 2026/08/24 CRDT- 2025/09/25 03:53 PHST- 2025/07/25 00:00 [revised] PHST- 2025/03/30 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2026/03/17 00:34 [medline] PHST- 2025/09/25 06:28 [pubmed] PHST- 2025/09/25 03:53 [entrez] PHST- 2026/08/24 00:00 [pmc-release] AID - 10.1002/art.43403 [doi] PST - ppublish SO - Arthritis Rheumatol. 2026 Mar;78(3):665-671. doi: 10.1002/art.43403. Epub 2025 Dec 17. PMID- 40994081 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Genetic evidence for repurposing GLP-1 receptor agonists in chronic kidney disease and IgA nephropathy: Metabolic and anti-inflammatory pathways beyond glycaemic control. PG - 7395-7407 LID - 10.1111/dom.70144 [doi] AB - AIMS: Despite observational links between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and kidney benefits, causal mechanisms remain unclear. This study aims to dissect genetic causality and mediation pathways underlying the effects of GLP-1RAs on chronic kidney disease (CKD) and related renal outcomes. MATERIALS AND METHODS: Using large-scale Genome - Wide Association Study (GWAS) data, we applied two-sample Mendelian randomisation (MR) to estimate the causal effects of GLP-1RAs on CKD, estimated glomerular filtration rate (eGFR) and subtypes (IgA nephropathy, membranous nephropathy, nephrotic syndrome and chronic glomerulonephritis), with sensitivity analyses. The glycaemic markers (glycated haemoglobin [HbA1c] and blood glucose), type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) served as positive controls. Mediation MR assessed body mass index (BMI), lipids, glycaemic markers and inflammatory proteins. Data were sourced from MRC Integrative Epidemiology Unit Open Genome - Wide Association Studies OpenGWAS, FinnGen, GWAS Catalogue and cohort-specific studies. RESULTS: Positive control analyses revealed that genetically predicted GLP-1R activation was associated with reduced levels of HbA1c (p = 4.93E-15) and blood glucose (p = 9.73E-5), as well as a decreased risk of T2DM (p = 2.45E-4) and DN (p = 6.35E-4), fully validating the reliability of the genetic instruments. Genetic proxies for GLP-1R activation lowered risks of CKD (odds ratio [OR] = 0.83, p = 9.22E-9), immunoglobulin A nephropathy (IgAN) (OR = 0.70, p = 2.11E-3) and kidney function preservation (beta = 0.01, p = 9.11E-3), but showed null effects on other CKD subtypes. Mediation analyses indicated that fibroblast growth factor 23 (FGF23) suppression mediated 26.57% of the effect on eGFR and 13.50% of CKD protection, whereas metabolic traits (BMI: 2.08% for CKD, 5.51% for eGFR; high-density lipoprotein: 0.79% for CKD, 2.34% for eGFR; HbA1c: 8.25% for eGFR) partially explained the benefits on CKD and eGFR. Only BMI exhibited a mediation effect on IgAN. Sensitivity analyses confirmed minimal pleiotropy. CONCLUSIONS: This study provides robust genetic evidence for repurposing GLP-1RAs in CKD and IgAN through anti-inflammatory (FGF23) and metabolic pathways, extending their utility beyond glucose control. While European ancestry data limit generalisability, our framework prioritises FGF23 and metabolic modulation as key targets for clinical trials in renal protection. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Yang, Xueying AU - Yang X AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. FAU - Tang, Wenhao AU - Tang W AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. FAU - Chan, Han AU - Chan H AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. FAU - Wang, Mo AU - Wang M AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. FAU - Yang, Haiping AU - Yang H AUID- ORCID: 0000-0002-0456-9304 AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. FAU - Li, Qiu AU - Li Q AD - Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. AD - Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China. LA - eng GR - 2022YFC2705101/National Key Research and Development Program of China/ GR - 2023GGXM001/The Joint Medical Research Programs of Chongqing Science and Technology Bureau and Health Commission Foundation/ GR - W0098/Programme for Youth Innovation in Future Medicine, and Chongqing Medical University/ PT - Journal Article DEP - 20250924 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/genetics/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Genome-Wide Association Study MH - Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glomerulonephritis, IGA/genetics/drug therapy/metabolism MH - Glycemic Control MH - *Drug Repositioning MH - Mendelian Randomization Analysis MH - Diabetic Nephropathies/genetics/drug therapy MH - Glycated Hemoglobin MH - Male MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Blood Glucose/metabolism MH - Middle Aged MH - Female OTO - NOTNLM OT - GLP-1 receptor agonists OT - IgA nephropathy OT - Mendelian randomisation OT - chronic kidney disease OT - mediation analysis EDAT- 2025/09/25 06:28 MHDA- 2025/11/05 06:29 CRDT- 2025/09/25 02:23 PHST- 2025/09/10 00:00 [revised] PHST- 2025/06/19 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/25 06:28 [pubmed] PHST- 2025/09/25 02:23 [entrez] AID - 10.1111/dom.70144 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7395-7407. doi: 10.1111/dom.70144. Epub 2025 Sep 24. PMID- 40991141 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20261010 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 64 IP - 12 DP - 2025 Dec TI - Exposure-Response Analysis of Efsubaglutide Alfa in Patients with Type 2 Diabetes Treated with Metformin. PG - 1799-1809 LID - 10.1007/s40262-025-01569-2 [doi] AB - BACKGROUND AND OBJECTIVES: Efsubaglutide alfa is a long-acting GLP-1 receptor agonist and is designed by fusion of two human GLP-1 molecules with IgG2 Fc via a natural immunoglobulin hinge region. This study evaluates the exposure-response (E-R) relationship of efsubaglutide alfa in patients with type 2 diabetes (T2D) treated with metformin. METHODS: Data were derived from an operational seamless design of randomized, double blind, placebo clinical trial (YN011-302) involving 406 subjects with T2D on stable metformin therapy. Participants received weekly subcutaneous injections of 1 mg or 3 mg efsubaglutide alfa, or placebo. The trial included a 24-week double-blind period and a 28-week open-label period. RESULTS: Participants had a median age of 55.0 years, mean body weight of 73.7 kg, fasting plasma glucose (FPG) of 9.72 mmol/L, and glycated hemoglobin (HbA1c) of 8.63%. A robust inverse correlation was observed between efsubaglutide alfa exposure and improvements in HbA1c, FPG, glucose area under the curve (AUC) during mixed-meal tolerance test (MMTT), body weight, and body mass index. Efsubaglutide alfa exposure also positively correlated with C-peptide AUC during MMTT, indicating improved beta-cell function. The E-R model indicates that doubling steady-state trough concentrations (C(min,ss)) reduced HbA1c by 0.211%, while every 100 ng/mL increase in C(avg,ss) led to 0.5 kg reduction in body weight at Week 24. Baseline HbA1c was a predictor of treatment response. Safety analysis revealed a positive correlation between exposure and gastrointestinal adverse events, which decreased over time, suggesting tolerance development. CONCLUSIONS: Efsubaglutide alfa, combined with metformin, significantly improves glycemic control and weight management, with an acceptable safety profile. This E-R model provides insights for dose optimization and trial design, and supports its use as an effective add-on therapy for patients with T2D, as indicated in the drug specification. TRIAL REGISTRATION: The trials were registered at Clinicaltrials.gov (identifier: NCT04998032). CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Wang, Qinghua AU - Wang Q AD - Innogen Pharmaceutical Technology Co., Ltd, Shanghai, 201203, China. qh_wang@fudan.edu.cn. AD - Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China. qh_wang@fudan.edu.cn. FAU - Jiang, Fan AU - Jiang F AD - Innogen Pharmaceutical Technology Co., Ltd, Shanghai, 201203, China. FAU - Xu, Yulong AU - Xu Y AD - Innogen Pharmaceutical Technology Co., Ltd, Shanghai, 201203, China. FAU - Lei, Yuyang AU - Lei Y AD - Innogen Pharmaceutical Technology Co., Ltd, Shanghai, 201203, China. FAU - Zhang, Li AU - Zhang L AD - Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China. FAU - Sun, Xiaodong AU - Sun X AD - Department of Endocrinology and Metabolism, Affiliated Hospital of Shandong Second Medical University, Weifang, China. LA - eng SI - ClinicalTrials.gov/NCT04998032 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250924 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Metformin/therapeutic use/administration & dosage MH - Middle Aged MH - Male MH - Female MH - *Hypoglycemic Agents/pharmacokinetics/therapeutic use/administration & dosage MH - Double-Blind Method MH - Glycated Hemoglobin/analysis/metabolism MH - Blood Glucose/drug effects MH - Aged MH - Adult MH - *Recombinant Fusion Proteins/pharmacokinetics/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide 1/analogs & derivatives/pharmacokinetics/administration & dosage/therapeutic use MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Declarations. Funding: This study was sponsored by Shanghai Innogen Pharmaceutical Technology Co., Ltd. Conflict of interest: F. Jiang, Y. Xu, Y. Lei, and Q. Wang are employees of Shanghai Innogen Pharmaceutical Technology Co., Ltd. Contribution statement: Y. Xu and L. Zhang drafted the manuscript. Y. Xu, Y. Lei and F. Jiang analyzed data and produced figures. Q. Wang and X. Sun reviewed and edited the manuscript. Ethical approval: All studies included in this analysis were approved by the relevant ethics committees and conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonisation guidelines for Good Clinical Practice (ICH-GCP). Data availability statement: Data will be made available upon reasonable request, subject to the protection of research participants' privacy. Code availability: The model codes that support the findings of this study are accessible upon reasonable request by contacting the corresponding author. Consent for publication: Not applicable. Consent to participate: Written, informed consent was obtained from all participants. Rights and permissions: Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. EDAT- 2025/09/24 13:02 MHDA- 2025/12/18 13:06 CRDT- 2025/09/24 11:19 PHST- 2025/03/06 00:00 [received] PHST- 2025/08/14 00:00 [accepted] PHST- 2025/12/18 13:06 [medline] PHST- 2025/09/24 13:02 [pubmed] PHST- 2025/09/24 11:19 [entrez] AID - 10.1007/s40262-025-01569-2 [pii] AID - 10.1007/s40262-025-01569-2 [doi] PST - ppublish SO - Clin Pharmacokinet. 2025 Dec;64(12):1799-1809. doi: 10.1007/s40262-025-01569-2. Epub 2025 Sep 24. PMID- 40990658 OWN - NLM STAT- MEDLINE DCOM- 20260123 LR - 20260124 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 112 IP - 1 DP - 2026 Jan 1 TI - The different colorectal tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 68 randomized controlled trials. PG - 443-459 LID - 10.1097/JS9.0000000000003450 [doi] AB - BACKGROUND: Recent evidence has raised concerns about potential pro-oncogenic effects associated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly regarding gastrointestinal malignancies. Colorectal tumors, the third most diagnosed cancer globally, already show increased incidence in patients with metabolic disorders who typically require these medications. For example, obese subjects had a significantly higher risk of colorectal tumors than healthy subjects. However, existing evidence on this association remains inconsistent. This network meta-analysis (NMA) evaluated the comparative incidence of colorectal tumors associated with specific GLP-1 receptor agonists and SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a confirmatory NMA focused specifically on colorectal tumor incidence as an adverse effect, following Cochrane methodological recommendations. We performed a frequentist-based NMA of randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was colorectal tumor incidence, with safety profiles assessed by dropout rates as a secondary outcome. RESULTS: This NMA encompassing 68 RCTs with 207 200 participants found that only semaglutide was associated with increased incidence of colorectal tumors compared to controls. A dose-stratified analysis revealed that high-dose injectable semaglutide (2.4 mg/week) was the only regimen associated with increased incidence. Furthermore, when focusing on RCTs of obese subjects, the increased colorectal tumor rate related to semaglutide still existed. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. CONCLUSION: Our study provides the first comprehensive NMA addressing the incidence of colorectal tumors related to individual GLP-1 receptor agonists and SGLT2 inhibitors, suggesting a dose-dependent relationship to semaglutide, particularly in its high-dose injectable form (2.4 mg/week). These findings represent a potential risk signal that requires further validation, given the already elevated baseline colorectal tumor risk in the target population, especially in subjects with obesity. Future research should focus on long-term follow-up studies to better characterize the mechanisms and clinical implications of this semaglutide-specific risk signal. WHAT THIS ADDS TO THE EXISTING LITERATURE: This network meta-analysis, based on 68 randomized controlled trials, suggested that only semaglutide, especially in highdose injectable form (2.4 mg/week), was associated with increased incidence of colorectal tumors compared to controls, especially in obese patients. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. LEARNING POINTS: Our study provides evidence regarding the increased incidence of colorectal tumors related to semaglutide in a dose dependent way (2.4 mg/week). CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chen, Po-Huang AU - Chen PH AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital; School of Medicine, National Defense Medical University, Taipei, Taiwan. AD - School of Medicine, National Defense Medical Center, Taipei, Taiwan. FAU - Sun, Cheuk-Kwan AU - Sun CK AD - Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan. AD - School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. AD - Department of Sport, University of Vienna, Vienna, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AD - School of Medicine, National Defense Medical Center, Taipei, Taiwan. AD - Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei, Taiwan. FAU - Lei, Wei-Te AU - Lei WT AD - Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Munipical MacKay Children's Hospital, Hsinchu, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Shiue, Yow-Ling AU - Shiue YL AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Su, Kuan-Pin AU - Su KP AD - Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan. AD - College of Medicine, China Medical University, Taichung, Taiwan. AD - An-Nan Hospital, China Medical University, Tainan, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan. AD - Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan. FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20250911 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Colorectal Neoplasms/epidemiology/chemically induced MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Incidence MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects PMC - PMC12825905 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - colorectal malignancy OT - colorectal tumor OT - network meta-analysis OT - semaglutide COIS- The authors report no financial interests or potential conflicts of interest. EDAT- 2025/09/24 13:01 MHDA- 2026/01/23 06:30 PMCR- 2026/01/22 CRDT- 2025/09/24 09:53 PHST- 2025/04/14 00:00 [received] PHST- 2025/08/27 00:00 [accepted] PHST- 2026/01/23 06:30 [medline] PHST- 2025/09/24 13:01 [pubmed] PHST- 2025/09/24 09:53 [entrez] PHST- 2026/01/22 00:00 [pmc-release] AID - 01279778-990000000-03299 [pii] AID - IJS-D-25-01794 [pii] AID - 10.1097/JS9.0000000000003450 [doi] PST - ppublish SO - Int J Surg. 2026 Jan 1;112(1):443-459. doi: 10.1097/JS9.0000000000003450. Epub 2025 Sep 11. PMID- 40990044 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER-2 trial emulation with real-world data. PG - 7431-7440 LID - 10.1111/dom.70151 [doi] AB - BACKGROUND AND AIMS: Oral semaglutide and empagliflozin are commonly used for the management of type 2 diabetes (T2D), but head-to-head comparisons in real-world settings are limited. We aimed to emulate the PIONEER-2 trial using electronic health records to compare the effectiveness and persistence of oral semaglutide versus empagliflozin. METHODS: This was a retrospective multicentre study using electronic health records from Italian diabetes clinics. New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months. The primary outcome was HbA1c change; secondary outcomes included weight change and treatment persistence. Analyses used mixed models for repeated measures under both treatment policy and trial product estimands. RESULTS: After matching, we included new users of oral semaglutide (n = 105) or empagliflozin (n = 207). Mean age was 65 years, diabetes duration 10 years, baseline HbA1c 7.6%, BMI 29 kg/m(2), and 94% were on metformin. Only 28.6% of new users of oral semaglutide reached the 14 mg dose and 31.4% of empagliflozin new users reached the 25 mg dose. HbA1c reduction was significantly greater with oral semaglutide than with empagliflozin (mean difference - 0.35%, p <0.001). Weight loss over time was similar, with oral semaglutide showing a modest advantage at 18 months among persistent patients. Persistence was lower for semaglutide (HR for discontinuation 1.47, p = 0.007). CONCLUSIONS: Under routine care, new users of oral semaglutide achieved better glycaemic control compared with empagliflozin new users, with similar weight loss but lower treatment persistence. These findings support the results of PIONEER-2 and its transferability to clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Laboratory of Experimental Diabetology, Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Longato, Enrico AU - Longato E AD - Department of Information Engineering, University of Padova, Padua, Italy. FAU - Poletto, Sara AU - Poletto S AD - Department of Information Engineering, University of Padova, Padua, Italy. FAU - Giaccari, Andrea AU - Giaccari A AUID- ORCID: 0000-0002-7462-7792 AD - Endocrine and Metabolic Center, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Ghiani, Mariangela AU - Ghiani M AD - Diabetology Unit, Azienda Sanitaria Locale 8 Cagliari Quartu S. Elena, Cagliari, Italy. FAU - Strazzabosco, Marco AU - Strazzabosco M AD - Diabetology and Metabolic Diseases Unit, S. Bortolo Hospital, Vicenza, Italy. FAU - Trombetta, Maddalena AU - Trombetta M AUID- ORCID: 0000-0002-0825-1117 AD - Endocrinology, Diabetology and Metabolic Diseases, University of Verona and University Hospital of Verona, Verona, Italy. FAU - Penno, Giuseppe AU - Penno G AUID- ORCID: 0000-0002-2834-4847 AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Solini, Anna AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy. AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. CN - GLIMPLES study investigators and DARWIN-Renal study investigators LA - eng GR - Italian Diabetes Society/ PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20250924 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucosides) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucosides/administration & dosage/therapeutic use MH - *Benzhydryl Compounds/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Treatment Outcome MH - Blood Glucose MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Weight Loss/drug effects MH - Italy/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587239 OTO - NOTNLM OT - cohort study OT - empagliflozin OT - real-world evidence OT - semaglutide COIS- GPF received honoraria, lecture, or advisory board fees from AstraZeneca, Boehringer, Guidotti, Lilly, Novartis, Novo Nordisk, and Sanofi. AG has received lecture fees from AstraZeneca, Lilly, and Novo Nordisk. GP reports consulting, advisory board, or speaking honoraria from Eli Lilly, consulting or participation on advisory boards for Bayer, and consulting for Novo Nordisk. AA received research grants, lecture, or advisory board fees from Merck Sharp & Dohme, AstraZeneca, Novartis, Boehringer-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. AS served on the advisory board of Novo Nordisk, Sankyo, and Sanofi and received speaker fees from AstraZeneca, Bayer, Lilly, Novo Nordisk, and Sanofi. AC received grants from AstraZeneca, Lilly, and Novo Nordisk. He also received speaker fees and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dohme, Menarini, Novo Nordisk, Sanofi, Sigma-Tau, and Takeda. EL, SP, MG, MS, and MT have nothing to disclose. FIR - Baldassarre, Maria Antonia Pompea IR - Baldassarre MAP FIR - Formoso, Gloria IR - Formoso G FIR - Consoli, Agostino IR - Consoli A FIR - Leto, Gaetano IR - Leto G FIR - Leonetti, Frida IR - Leonetti F FIR - Fazion, Stefano IR - Fazion S FIR - Meregalli, Giancarla IR - Meregalli G FIR - Zavattaro, Marco IR - Zavattaro M FIR - Aimaretti, Gianluca IR - Aimaretti G FIR - Melchionda, Elena IR - Melchionda E FIR - Barale, Cristina IR - Barale C FIR - Cau, Rosella IR - Cau R FIR - Ghiani, Mariangela IR - Ghiani M FIR - Muscara, Andrea IR - Muscara A FIR - Russo, Giuseppina IR - Russo G FIR - Anichini, Roberto IR - Anichini R FIR - Fattor, Bruno IR - Fattor B FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Avogaro, Angelo IR - Avogaro A FIR - Nollino, Laura IR - Nollino L FIR - Paccagnella, Agostino IR - Paccagnella A FIR - Strazzabosco, Marco IR - Strazzabosco M FIR - Baldassarre, Mariella IR - Baldassarre M FIR - Consoli, Agostino IR - Consoli A FIR - Morganet, Sara IR - Morganet S FIR - Zugaro, Antonella IR - Zugaro A FIR - Baroni, Marco Giorgio IR - Baroni MG FIR - Andreozzi, Francesco IR - Andreozzi F FIR - Gatti, Adriano IR - Gatti A FIR - De Riu, Stefano IR - De Riu S FIR - Del Buono, Andrea IR - Del Buono A FIR - Aldigeri, Raffaella IR - Aldigeri R FIR - Bonadonna, Riccardo IR - Bonadonna R FIR - Cas, Alessandra Dei IR - Cas AD FIR - Vazzana, Angela IR - Vazzana A FIR - Antonini, Monica IR - Antonini M FIR - Moretti, Valentina IR - Moretti V FIR - Volsi, Patrizia Li IR - Volsi PL FIR - Cesare, Miranda IR - Cesare M FIR - Zanette, Giorgio IR - Zanette G FIR - Carletti, Silvia IR - Carletti S FIR - D'Angelo, Paola IR - D'Angelo P FIR - Leto, Gaetano IR - Leto G FIR - Leonetti, Frida IR - Leonetti F FIR - D'Onofrio, Luca IR - D'Onofrio L FIR - Maddaloni, Ernesto IR - Maddaloni E FIR - Buzzetti, Raffaella IR - Buzzetti R FIR - Picconi, Fabiana IR - Picconi F FIR - Frontoni, Simona IR - Frontoni S FIR - Cavallo, Gisella IR - Cavallo G FIR - Morano, Susanna IR - Morano S FIR - Filardi, Tiziana IR - Filardi T FIR - Cinti, Francesca IR - Cinti F FIR - Giaccari, Andrea IR - Giaccari A FIR - Bossi, Antonio C IR - Bossi AC FIR - Meregalli, Giancarla IR - Meregalli G FIR - Querci, Fabrizio IR - Querci F FIR - Gaglio, Alessia IR - Gaglio A FIR - Resi, Veronica IR - Resi V FIR - Orsi, Emanuela IR - Orsi E FIR - Fazion, Stefano IR - Fazion S FIR - Franzetti, Ivano G IR - Franzetti IG FIR - Berra, Cesare IR - Berra C FIR - Manfrini, Silvia IR - Manfrini S FIR - Garrapa, Gabriella IR - Garrapa G FIR - Lucarelli, Giulio IR - Lucarelli G FIR - Riccialdelli, Lara IR - Riccialdelli L FIR - Tortato, Elena IR - Tortato E FIR - Zavattaro, Marco IR - Zavattaro M FIR - Aimaretti, Gianluca IR - Aimaretti G FIR - Cavalot, Franco IR - Cavalot F FIR - Beccuti, Guglielmo IR - Beccuti G FIR - Broglio, Fabio IR - Broglio F FIR - Fattor, Bruno IR - Fattor B FIR - Cazzetta, Giuliana IR - Cazzetta G FIR - Lamacchia, Olga IR - Lamacchia O FIR - Rauseo, Anna IR - Rauseo A FIR - De Cosmo, Salvatore IR - De Cosmo S FIR - Cau, Rosella IR - Cau R FIR - Ghiani, Mariangela IR - Ghiani M FIR - Di Benedetto, Antonino IR - Di Benedetto A FIR - Di Pino, Antonino IR - Di Pino A FIR - Piro, Salvatore IR - Piro S FIR - Purrello, Francesco IR - Purrello F FIR - Frittitta, Lucia IR - Frittitta L FIR - Milluzzo, Agostino IR - Milluzzo A FIR - Russo, Giuseppina IR - Russo G FIR - Solini, Anna IR - Solini A FIR - Garofolo, Monia IR - Garofolo M FIR - Penno, Giuseppe IR - Penno G FIR - Del Prato, Stefano IR - Del Prato S FIR - Anichini, Roberto IR - Anichini R FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Avogaro, Angelo IR - Avogaro A FIR - Gottardo, Lucia IR - Gottardo L FIR - Rigato, Mauro IR - Rigato M FIR - Paccagnella, Agostino IR - Paccagnella A FIR - Strazzabosco, Marco IR - Strazzabosco M FIR - Cigolini, Massimo IR - Cigolini M FIR - Bonora, Enzo IR - Bonora E EDAT- 2025/09/24 06:29 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/24 05:33 PHST- 2025/09/04 00:00 [revised] PHST- 2025/07/22 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/24 06:29 [pubmed] PHST- 2025/09/24 05:33 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70151 [pii] AID - 10.1111/dom.70151 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7431-7440. doi: 10.1111/dom.70151. Epub 2025 Sep 24. PMID- 40988251 OWN - NLM STAT- MEDLINE DCOM- 20250924 LR - 20250930 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 104 IP - 38 DP - 2025 Sep 19 TI - Genetically proxied glucagon-like peptide-1 receptor agonist is associated with risk of tubulo-interstitial nephritis: A network Mendelian randomization study. PG - e44742 LID - 10.1097/MD.0000000000044742 [doi] LID - e44742 AB - Glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are widely used in type 2 diabetes mellitus (T2DM) management due to their glycemic and cardiorenal benefits, yet emerging evidence suggests potential renal adverse effects, particularly tubulo-interstitial nephritis (TIN). We conducted a 2-sample Mendelian randomization (MR) analysis to investigate causal relationships between GLP1RA use and TIN risks. Genetic proxies for GLP1RA effects were derived from cis-eQTLs for GLP1R. Proteome-wide MR and mediation analyses with UK Biobank Pharma Proteomics Project data were also used to identify mediating plasma proteins and biological pathways. MR analyses showed a significant causal link between GLP1RA use and chronic tubulo-interstitial nephritis (CTIN; OR = 2.32, 95% CI = 1.39-3.85, P = .001), with no significant association for acute tubulo-interstitial nephritis (ATIN; OR = 0.93, 95% CI = 0.83-1.04, P = .216). Colocalization analysis strongly supported the MR findings, showing a high posterior probability of shared genetic variants between GLP1R expression and CTIN (PP.H4 = 0.99). Mediation analysis identified 4 plasma proteins (HYAL1, NMNAT1, IL12RB2, and DPP6) as partial mediators of the effect. Genetic evidence from this study indicated an association between GLP1R agonists and higher risk of chronic tubulo-interstitial nephritis. Potential risks need to be evaluated when prescribing GLP1RAs in in clinical practice. CI - Copyright (c) 2025 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Xu, Xu-Chun AU - Xu XC AD - Department of Nephrology, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang Province, China. FAU - Huang, Fang-Zhong AU - Huang FZ AD - Department of Nephrology, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang Province, China. FAU - Ying, Jun AU - Ying J AD - Department of Nephrology, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang Province, China. FAU - Zhang, Ting-Ting AU - Zhang TT AD - Department of Nephrology, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang Province, China. FAU - Huang, Hua-Ying AU - Huang HY AUID- ORCID: 0009-0004-6432-6322 AD - Department of Endocrinology and Metabolism, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang Province, China. LA - eng PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Nephritis, Interstitial/genetics/chemically induced MH - *Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor/genetics PMC - PMC12459490 OTO - NOTNLM OT - Mendelian randomization OT - genome-wide association study OT - glucagon-like peptide-1 receptor agonists OT - tubulo-interstitial nephritis COIS- The authors have no conflicts of interest to disclose. EDAT- 2025/09/24 06:29 MHDA- 2025/09/24 06:30 PMCR- 2025/09/19 CRDT- 2025/09/24 01:01 PHST- 2025/05/15 00:00 [received] PHST- 2025/08/25 00:00 [accepted] PHST- 2025/09/24 06:30 [medline] PHST- 2025/09/24 06:29 [pubmed] PHST- 2025/09/24 01:01 [entrez] PHST- 2025/09/19 00:00 [pmc-release] AID - 00005792-202509190-00095 [pii] AID - MD-D-25-05486 [pii] AID - 10.1097/MD.0000000000044742 [doi] PST - ppublish SO - Medicine (Baltimore). 2025 Sep 19;104(38):e44742. doi: 10.1097/MD.0000000000044742. PMID- 40988099 OWN - NLM STAT- MEDLINE DCOM- 20250924 LR - 20250927 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 5 DP - 2025 Sep TI - Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. PG - e70113 LID - 10.1002/edm2.70113 [doi] LID - e70113 AB - AIMS: This meta-analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomised controlled trials (RCTs). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP-1 RA RCTs that evaluated pancreatitis/pancreatic cancer. A meta-analysis was conducted to evaluate this risk; subgroup analysis was performed with and without background medications. RESULTS: 62 studies utilising dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, or tirzepatide, with 66,232 patients, mean age of 58.3 years (14.4 to 68), and mean follow-up of 43.5 weeks (1 to 198) were included in this study. Meta-analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09-1.89, p = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87-1.87) and without background medications (RR: 1.37, 95% CI 0.91-2.05). Pancreatic cancer and GLP-1 RA use showed no significant association (RR: 1.30, 95% CI 0.86-1.97). However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05-3.26, p = 0.03), but not without (RR: 0.81, 95% CI 0.43-1.55). CONCLUSION: GLP-1 RAs carry a slightly increased risk of pancreatitis, which is not significant when stratified by background medication use. Overall risk for pancreatic cancer was not observed, but a slight association was found when stratified with background medications. However, this difference is likely minimal, given the numerous studies excluded from the meta-analysis where both treatment arms had zero events. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AUID- ORCID: 0009-0007-7510-2246 AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Joy, Bethany AU - Joy B AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Kou, Megan AU - Kou M AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Muttalib, Zohaer AU - Muttalib Z AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Alam, Arsh AU - Alam A AD - University of California, Davis, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - College of Medicine, California Northstate University, Elk Grove, California, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Pancreatic Neoplasms/epidemiology/chemically induced MH - *Pancreatitis/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic PMC - PMC12457091 OTO - NOTNLM OT - GLP-1 RA OT - pancreatic cancer OT - pancreatitis COIS- The authors declare no conflicts of interest. EDAT- 2025/09/24 06:29 MHDA- 2025/09/24 06:30 PMCR- 2025/09/23 CRDT- 2025/09/24 00:03 PHST- 2025/09/09 00:00 [revised] PHST- 2025/06/18 00:00 [received] PHST- 2025/09/13 00:00 [accepted] PHST- 2025/09/24 06:30 [medline] PHST- 2025/09/24 06:29 [pubmed] PHST- 2025/09/24 00:03 [entrez] PHST- 2025/09/23 00:00 [pmc-release] AID - EDM270113 [pii] AID - 10.1002/edm2.70113 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 Sep;8(5):e70113. doi: 10.1002/edm2.70113. PMID- 40986866 OWN - NLM STAT- MEDLINE DCOM- 20250923 LR - 20260812 IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 14 DP - 2025 Sep 23 TI - Effect of Adherence to Oral Semaglutide on Glycemic Control in People With Type 2 Diabetes Treated With Metformin: Protocol for an Open-Label Clinical Trial. PG - e64899 LID - 10.2196/64899 [doi] LID - e64899 AB - BACKGROUND: Treatment adherence by people with type 2 diabetes (T2D) is overall suboptimal, which can hinder glycemic control. Multiple adherence barriers have been identified, such as the dislike and fear of injections. Several of the recommended antidiabetic drugs are available in oral formulations, which may be a good alternative to injection therapy when possible. However, strict dosing instruction could pose adherence barriers; for example, oral semaglutide requires predose and postdose fasting and restricted water intake at dosing time. Currently, oral semaglutide is the only oral glucagon-like peptide-1 receptor agonist and has only been available for a few years; therefore, limited knowledge exists on adherence to it. OBJECTIVE: The aim of this study is to investigate the effect of adherence to oral semaglutide dosing instructions on glycemic control in people with T2D who are dysregulated on metformin and optionally a sodium-glucose cotransporter-2 inhibitor and naive to oral semaglutide. METHODS: This prospective, noninterventional, open-label, clinical trial with a duration of 12 weeks will be conducted in Denmark. Eligible participants are adults (aged >/=18 years) with dysregulated T2D (hemoglobin A1c of 53-75 mmol/mol) currently treated with metformin and optionally a sodium-glucose cotransporter-2 inhibitor for whom the next natural step in the treatment is to add an antidiabetic drug to the treatment regimen. Potential participants are recruited through announcements on social media and digital mail sent to their official digital mailbox (e-boks). During the trial, 20 participants will be initiated on oral semaglutide and escalated in dosage in accordance with the label. Information on the participants' behavior related to the dosing instructions will be collected using the following devices: a smartwatch to track activity and sleep time, a smart pill bottle to track dosing time, a smart bottle to track time and volume of water intake at dosing time, and a smartphone to take a photo of their breakfast to log time of breakfast. Glycemic control will be assessed using an unblinded continuous glucose monitoring sensor that the participants will wear. Participants are asked to report any cases of nausea or vomiting in terms of time of occurrence, duration, and severity. The primary endpoint is change from baseline to end-of-study time-in-range derived from continuous glucose monitoring data. RESULTS: The first participant visit was in April 2024. Three months of high frequency temporal data on adherence behavior will be collected, despite the relatively few expected participants included. CONCLUSIONS: Participants may change their behavior due to awareness of being observed. Regardless, the knowledge gained from this trial might be integrated into a decision support system, providing people with diabetes with guidance on how to increase adherence and potentially improving glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT06333080.; https://clinicaltrials.gov/study/NCT06333080. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64899. CI - (c)Nynne Sophie Holdt-Caspersen, Claus Dethlefsen, Ole Hejlesen, Erik Christiansen, Stine Hangaard, Peter Vestergaard, Morten Hasselstrom Jensen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.09.2025. FAU - Holdt-Caspersen, Nynne Sophie AU - Holdt-Caspersen NS AUID- ORCID: 0000-0003-3263-0966 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. FAU - Dethlefsen, Claus AU - Dethlefsen C AUID- ORCID: 0000-0003-3994-6189 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark. FAU - Hejlesen, Ole AU - Hejlesen O AUID- ORCID: 0000-0003-3578-8750 AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AUID- ORCID: 0000-0002-0291-8136 AD - Department of Medical & Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Hangaard, Stine AU - Hangaard S AUID- ORCID: 0000-0003-0395-3563 AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. FAU - Vestergaard, Peter AU - Vestergaard P AUID- ORCID: 0000-0002-9046-2967 AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Jensen, Morten Hasselstrom AU - Jensen MH AUID- ORCID: 0000-0002-6649-8644 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT06333080 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250923 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Metformin/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - *Glycemic Control/methods MH - Blood Glucose/drug effects/analysis MH - Prospective Studies MH - Female MH - Adult MH - Male MH - Middle Aged MH - Denmark MH - Glycated Hemoglobin/analysis MH - *Medication Adherence MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12504889 OTO - NOTNLM OT - continuous glucose monitoring OT - dosing instructions OT - medication adherence OT - observational study OT - oral antidiabetic drug OT - oral semaglutide COIS- Conflicts of Interest: Authors EC, CD, NSH-C, and MHJ are employees and shareholders of Novo Nordisk. PV is Head of Research at Steno Diabetes Center North Denmark funded by the Novo Nordisk Foundation. EDAT- 2025/09/23 18:28 MHDA- 2025/09/23 18:29 PMCR- 2025/09/23 CRDT- 2025/09/23 16:53 PHST- 2024/08/01 00:00 [received] PHST- 2025/07/02 00:00 [accepted] PHST- 2025/03/31 00:00 [revised] PHST- 2025/09/23 18:29 [medline] PHST- 2025/09/23 18:28 [pubmed] PHST- 2025/09/23 16:53 [entrez] PHST- 2025/09/23 00:00 [pmc-release] AID - v14i1e64899 [pii] AID - 10.2196/64899 [doi] PST - epublish SO - JMIR Res Protoc. 2025 Sep 23;14:e64899. doi: 10.2196/64899. PMID- 40986735 OWN - NLM STAT- MEDLINE DCOM- 20250923 LR - 20260707 IS - 1538-9766 (Electronic) IS - 1042-895X (Linking) VI - 48 IP - 5 DP - 2025 Sep-Oct 01 TI - Glucagon-Like Peptide-1 (GLP-1a) Receptor Agonist Use in Patients Presenting for Gastroenterology Procedures: A Review of Concerns. PG - 389-395 LID - 10.1097/SGA.0000000000000891 [doi] AB - Glucagon-like peptide-1 receptor agonist (GLP1a) agonists are one of the most recent discoveries to improve blood glucose control and provide satiety. The U.S. Food and Drug Administration (FDA) approved the first of these therapeutics for the management of type 2 diabetes in 2005 (Dungan et al., 2023). In 2014, the FDA approved semaglutide, a GLP1a, for weight management of patients with a BMI of 27 kg/m2 or greater and one weight-related ailment for patients with a BMI of at least 30 kg/m2. Although these pharmacologic agents provide many benefits, there is a growing concern for patients who currently use GLP1a medication during the perioperative period, especially relating to delayed gastric emptying. With the increasing use of GLP1a, health care practitioners require in-depth knowledge of implications and treatment for these patients to provide an evidence-based safety net for those requiring endoscopic services. CI - Copyright (c) 2025 Society of Gastroenterology Nurses and Associates. FAU - Wunder, Linda AU - Wunder L AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. FAU - Lee, Rebecca AU - Lee R AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. FAU - Dalpe Welliver, Dawn AU - Dalpe Welliver D AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. LA - eng PT - Journal Article PT - Review DEP - 20250923 PL - United States TA - Gastroenterol Nurs JT - Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates JID - 8915377 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use MH - Gastric Emptying/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors declare no conflict of interest. EDAT- 2025/09/23 18:28 MHDA- 2025/09/23 18:29 CRDT- 2025/09/23 14:54 PHST- 2023/01/30 00:00 [received] PHST- 2024/01/06 00:00 [accepted] PHST- 2025/09/23 18:29 [medline] PHST- 2025/09/23 18:28 [pubmed] PHST- 2025/09/23 14:54 [entrez] AID - 00001610-202509000-00007 [pii] AID - 10.1097/SGA.0000000000000891 [doi] PST - ppublish SO - Gastroenterol Nurs. 2025 Sep-Oct 01;48(5):389-395. doi: 10.1097/SGA.0000000000000891. Epub 2025 Sep 23. PMID- 40983112 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial. PG - 112910 LID - S0168-8227(25)00924-6 [pii] LID - 10.1016/j.diabres.2025.112910 [doi] AB - AIM: To compare the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes mellitus (T2D) at moderate cardiovascular risk. METHODS: We emulated a target trial using claims data of adults with T2D at moderate cardiovascular risk who initiated dulaglutide, exenatide, liraglutide, or semaglutide between 01/01/2014-12/31/2021. Random treatment assignment was emulated by propensity scores and incorporated into inverse probability of treatment weighted (IPTW) Cox models. Outcomes were time to composite major adverse cardiovascular events (MACE: myocardial infarction, stroke, and all-cause mortality), expanded MACE (MACE, hospitalization for heart failure, and revascularization) and its components, and severe hypoglycemia. RESULTS: After IPTW, 35,572 patients initiated dulaglutide, 4376 initiated exenatide, 8843 initiated liraglutide, and 33,063 initiated semaglutide. Compared to dulaglutide, semaglutide was associated with lower risk of MACE (HR 0.85, 95CI % 0.78-0.93), expanded MACE (HR 0.92, 95CI % 0.87-0.96), all-cause mortality (HR 0.81, 95CI % 0.71-0.92), stroke (HR 0.82, 95CI % 0.70-0.97), and revascularization (HR 0.93, 95CI % 0.88-0.99), while liraglutide was associated with lower risk of MACE (HR 0.84, 95CI % 0.72-0.97) and all-cause mortality (HR 0.79, 95CI % 0.64-0.99). CONCLUSIONS: Among GLP-1RAs, semaglutide and liraglutide were associated with the greatest cardiovascular risk reduction in patients with T2D at moderate cardiovascular risk. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Sklepinski, Stacey M AU - Sklepinski SM AD - University of Maryland School of Medicine, 655 W Baltimore St, Baltimore, MD 21201, USA. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Swarna, Kavya Sindu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave MC2000, Chicago, IL 60637, USA. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, 412 East Spokane Falls Blvd., PBS 130, Spokane, WA 99202-2131, USA; Providence Medical Research Center, 105 W 8th Ave, Suite 250E, Spokane, WA 99204, USA. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA; Department of Health Policy and Management, Yale School of Public Health, 60 College St, New Haven, CT 06510, USA. FAU - Borah, Bijan J AU - Borah BJ AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA. FAU - Maron, Bradley A AU - Maron BA AD - University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 655 W Baltimore St, Baltimore, MD 21201, USA. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA; University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, 670 W Baltimore St, Baltimore, MD 21201, USA. Electronic address: Rozalina.McCoy@som.umaryland.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250920 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - Exenatide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use MH - Heart Disease Risk Factors MH - Treatment Outcome MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Comparative effectiveness OT - Glucagon-like peptide-1 receptor agonists OT - Hypoglycemia OT - Major adverse cardiovascular event OT - Target trial emulation OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last 36 months, JH received support from the Centers for Medicare and Medicaid Services, NIH, Agency for Healthcare Research and Quality, PCORI, and the American Heart Association. JJN is supported by a NIH research grant and a foundation grant from the American College of Clinical Pharmacy, serves as a consultant to Bayer, Eli Lilly, Boehringer Ingelheim, and Proteomics International, and receives support from the American Diabetes Association for projects unrelated to this work. RJG is supported by grants from NIDDK of NIH. RJG received research support from Novo Nordisk, Boehringer, Eli Lilly, and Dexcom, and consulting/advisory from Abbott Diabetes, Astra-Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, and Novo Nordisk, and Medtronic. GEU is supported by research grants from NIH and National Center for Research Resources and has received research support (to Emory University) from Abbott, Dexcom, Corcept, and Bayer, and served as a member of advisory boards for Dexcom, Glucotrack and GlyCare. JSR receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from FDA for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), and from Arnold Ventures; formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology; and was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled September 2022. BJB serves as a consultant to Boehringer-Ingelheim on projects unrelated to this study. RGM has received support from the NIDDK of NIH, the National Institute on Aging of the NIH, the National Center for Advancing Translational Sciences, and the American Diabetes Association for projects unrelated to this work. She also served as a consultant to EmmiEducate(R) (Wolters Kluwer) and the Yale-New Haven Health System and received speaking honoraria and travel support from the American Diabetes Association. EDAT- 2025/09/23 03:17 MHDA- 2025/10/31 00:29 CRDT- 2025/09/22 19:29 PHST- 2025/07/21 00:00 [received] PHST- 2025/08/31 00:00 [revised] PHST- 2025/09/17 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/23 03:17 [pubmed] PHST- 2025/09/22 19:29 [entrez] AID - S0168-8227(25)00924-6 [pii] AID - 10.1016/j.diabres.2025.112910 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112910. doi: 10.1016/j.diabres.2025.112910. Epub 2025 Sep 20. PMID- 40982219 OWN - NLM STAT- MEDLINE DCOM- 20260331 LR - 20260813 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 4 DP - 2026 Mar 31 TI - The effect of GLP-1 receptor agonists on renal outcomes: a systematic review and meta-analysis. PG - 681-691 LID - 10.1093/ndt/gfaf193 [doi] AB - BACKGROUND AND HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are anti-hyperglycaemic agents, with cardioprotective effects, however their renal protective effects remain unclear. We aimed to assess the effects of GLP1-RAs on renal outcomes in patients with or without diabetes. METHODS: We performed a systematic review and meta-analysis with Medline, EMBASE and the Cochrane Register searched to December 2024. The primary outcome was the composite of kidney failure (defined as estimated glomerular filtration rate <15 mL/min/1.73 m2) or dialysis requirement, worsening of renal function and changes in proteinuria. Subgroup analysis was performed based on diabetic status, a (CKD) and individual GLP1-RA drugs. Relative risks (RR) with 95% confidence intervals (CI) for individual trials were pooled using random effects models. RESULTS: We identified 19 trials including 90 882 patients. Mean age was 60.8 years and mean follow-up was 25.9 months. GLP1-RAs were associated with a 19% reduction in the risk of primary renal outcome (RR 0.81, 95% CI 0.73-0.89), a 12% reduction in renal functional decline (RR 0.88, 95% CI 0.81-0.95) and a 0.45 mL/min/1.73 m2 reduction in yearly loss [16 trials, mean difference (MD) 0.45, 95% CI 0.10-0.81]. GLP1-RAs also reduced microalbuminuria by 24% (RR 0.76, 95% CI 0.71-0.82), HbA1c (units: %) by 0.61 (MD -0.61, 95% CI -0.76 to -0.49) and body weight by 5 kg (MD -5.24, 95% CI -7.46 to -3.02). Although there were no significant differences in progression to kidney failure (RR 0.86, 95% CI 0.71-1.05), GLP1-RAs reduced the incidence of major adverse cardiovascular events by 15% (RR 0.85, 95% CI 0.81-0.90) and all-cause mortality by 14% (RR 0.86, 95% CI 0.82-0.91). No significant differences were seen in severe adverse events (RR 0.96, 95% CI 0.90-1.01). However, there were more gastroenterological side effects. CONCLUSIONS: GLP1-RAs demonstrated cardiovascular and renal benefits. Further high-quality randomized trials assessing their effects in patients without diabetes, with or without proteinuria and/or CKD are needed. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Sasaki, Takaya AU - Sasaki T AUID- ORCID: 0000-0001-9525-2638 AD - Renal and Metabolic Division, George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Giang, Samantha My-Linh AU - Giang SM AD - Department of Nephrology, Concord Repatriation General Hospital, Sydney, NSW, Australia. AD - Concord Clinical School, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia. FAU - Wu, Jiajia AU - Wu J AD - Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China. FAU - Yokoo, Takashi AU - Yokoo T AD - Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Gallagher, Martin AU - Gallagher M AD - Renal and Metabolic Division, George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. FAU - Bellomo, Rinaldo AU - Bellomo R AUID- ORCID: 0000-0002-1650-8939 AD - Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia. FAU - Wang, Amanda Ying AU - Wang AY AD - Renal and Metabolic Division, George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. AD - Concord Clinical School, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia. AD - The Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. LA - eng GR - National Heart Foundation Vanguard Grant/ GR - Royal Australasian College of Physicians Jacquot Research Establishment Fellowship/ GR - Uehara Memorial Foundation/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies PMC - PMC13037467 OTO - NOTNLM OT - chronic kidney disease OT - glucagon-like peptide-1 receptor agonists OT - systematic review COIS- T.Y. has received lecture honoraria from Novo Nordisk Pharma Ltd for presentations. EDAT- 2025/09/22 12:46 MHDA- 2026/03/31 18:49 PMCR- 2025/09/22 CRDT- 2025/09/22 11:23 PHST- 2025/04/08 00:00 [received] PHST- 2025/08/19 00:00 [accepted] PHST- 2026/03/31 18:49 [medline] PHST- 2025/09/22 12:46 [pubmed] PHST- 2025/09/22 11:23 [entrez] PHST- 2025/09/22 00:00 [pmc-release] AID - 8261545 [pii] AID - gfaf193 [pii] AID - 10.1093/ndt/gfaf193 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Mar 31;41(4):681-691. doi: 10.1093/ndt/gfaf193. PMID- 40980971 OWN - NLM STAT- MEDLINE DCOM- 20250922 LR - 20260925 IS - 1478-3231 (Electronic) IS - 1478-3223 (Print) IS - 1478-3223 (Linking) VI - 45 IP - 10 DP - 2025 Oct TI - Target Trial Emulations of GLP-1 and Dual GLP-1/GIP Agonists to Reduce Major Adverse Liver Outcomes in Type 2 Diabetes. PG - e70367 LID - 10.1111/liv.70367 [doi] LID - e70367 AB - BACKGROUND: Clinical trials suggest GLP-1 receptor agonists (RAs) and dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) RAs improve metabolic dysfunction associated with steatohepatitis (MASH) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to compare the estimate of the relative effect of tirzepatide, semaglutide, and liraglutide in reducing the risk of major adverse liver outcomes (MALOs) in patients with type 2 diabetes (T2D). DESIGN, SETTING AND PARTICIPANTS: We emulated target trials based on a real-world network of electronic health records (EHRs) from over 150 million patients. Three target trials were emulated, among eligible patients with T2D who had no prior MALO diagnosis, by comparing therapy involving tirzepatide, semaglutide, and liraglutide versus DPP4 inhibitor (DPP4i) therapy. We identified the first-ever diagnosis of MALO occurring within a 2-year follow-up period and compared across the treatment groups using Kaplan-Meier survival analyses. Cohorts underwent propensity score matching 1:1 for confounders. We performed sensitivity analyses relating to geographical location, combination with metformin, and by treatment adherence. We also performed head-to-head analyses of the incretin-based therapies. RESULTS: After matching, we identified three target trials comprised of 10 165, 56 702, and 8 301 patients treated with tirzepatide, semaglutide, and liraglutide, respectively (1:1 with reference patients) for a 2-year period. Tirzepatide (HR 0.53 [95% CI 0.40, 0.71]) and semaglutide (HR 0.81 [0.72, 0.90]) were associated with a significant reduction in the risk of incident MALO compared with DPP4i, whereas liraglutide was not (HR 1.04 [95% CI 0.79, 1.36]). In head-to-head comparisons, tirzepatide was associated with a significantly lower risk of incident MALO compared with liraglutide (HR 0.56 [95% CI 0.39, 0.79]), but not semaglutide (HR 0.83 [95% CI 0.63, 1.09]). Semaglutide was not associated with a reduced risk compared with liraglutide (HR 0.77 [95% CI 0.57, 1.05]). CONCLUSION: Treatment with tirzepatide and, to a lesser extent, semaglutide, in patients with T2D, was associated with a lower incidence of MALO compared with DPP4i after 2 years; largely driven by a reduction in the rates of compensated and decompensated cirrhosis. A reduction in MALO was not demonstrated with the use of liraglutide. These findings highlight a comparative benefit of tirzepatide (and semaglutide) versus DPP4i and should prompt more robust, longer-term randomised controlled studies to evaluate their role in preventing MALO in this increasingly prevalent patient population with co-existing T2D and MASLD. CI - (c) 2025 The Author(s). Liver International published by John Wiley & Sons Ltd. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Azmi, Shazli AU - Azmi S AD - Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Centre for Musculoskeletal Research, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Liraglutide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Tirzepatide/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Gastric Inhibitory Polypeptide/agonists MH - Glucagon-Like Peptide 1/agonists MH - Incretins/therapeutic use MH - Semaglutide PMC - PMC12452214 COIS- M.A. receives a fellowship from the Novo Nordisk UK research foundation and JDRF. D.J.C. has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. G.H.I. is an employee of TriNetX LLC. U.A. has received honoraria from Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Diiachi Sankyo. U.A. has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2025/09/22 12:46 MHDA- 2025/09/22 12:47 PMCR- 2025/09/22 CRDT- 2025/09/22 08:48 PHST- 2025/09/09 00:00 [revised] PHST- 2025/04/22 00:00 [received] PHST- 2025/09/16 00:00 [accepted] PHST- 2025/09/22 12:47 [medline] PHST- 2025/09/22 12:46 [pubmed] PHST- 2025/09/22 08:48 [entrez] PHST- 2025/09/22 00:00 [pmc-release] AID - LIV70367 [pii] AID - 10.1111/liv.70367 [doi] PST - ppublish SO - Liver Int. 2025 Oct;45(10):e70367. doi: 10.1111/liv.70367. PMID- 40977363 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Efficacy and safety of Efsubaglutide Alfa in "overrun" patients in the SUPER2 trial: A post-hoc analysis for comprehensive evaluation. PG - 7123-7132 LID - 10.1111/dom.70112 [doi] AB - AIMS: Efsubaglutide Alfa is a novel, long-acting, once-weekly GLP-1 receptor agonist. In the pivotal phase 2b/3 SUPER2 trial, Efsubaglutide Alfa 3 mg plus metformin showed significant efficacy and favourable safety in patients with type 2 diabetes (T2D) inadequately controlled on metformin. This post-hoc analysis evaluated the 1 mg dose. MATERIALS AND METHODS: In phase 2b, patients with T2D on metformin were randomized (1:1:1) to once-weekly Efsubaglutide Alfa 1 mg, 3 mg, or placebo for 12 weeks. After interim analysis, 3 mg was selected as the phase 3 dose. However, 155 patients already randomized (the "overrun" cohort) completed 24 weeks of double-blind treatment with 1 mg, then entered 28 weeks of open-label 3 mg and 4 weeks of follow-up. This analysis focused on the 1 mg cohort. The primary endpoint was change in HbA1c at week 24; secondary endpoints included fasting plasma glucose (FPG), body weight, HbA1c <7.0%, and subgroup analyses. RESULTS: At week 24, HbA1c decreased by -1.69% (95% CI -1.91 to -1.47) with Efsubaglutide Alfa 1 mg versus -0.74% (-0.96 to -0.52) with placebo, a placebo-corrected difference of -0.95% (95% CI -1.25 to -0.65; p < 0.0001). FPG decreased by -2.09 mmol/L versus -0.50 mmol/L with placebo (difference - 1.59 mmol/L; p < 0.001). Body weight reduction was modest and not significant (-2.8% vs. -1.3%; LSM -0.72 kg; p = 0.137). HbA1c <7.0% was achieved by 56.3% versus 11.1% with placebo (p < 0.0001; odds ratio 8.3). Gastrointestinal adverse events were most common, generally mild and transient, and no drug-related serious events occurred. CONCLUSIONS: Efsubaglutide Alfa 1 mg provided clinically meaningful glucose lowering with good tolerability but without significant weight loss. These results support a lower-dose strategy for elderly or frail patients, those with low BMI, or individuals sensitive to gastrointestinal effects, and as a possible lead-in step before escalation. Confirmatory trials are warranted to establish long-term outcomes. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Jia, Weiping AU - Jia W AUID- ORCID: 0000-0002-6244-2168 AD - Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China. FAU - Jiang, Fan AU - Jiang F AD - Innogen Pharmaceutical Technology Co., Ltd., Shanghai, China. FAU - Xu, Yulong AU - Xu Y AD - Innogen Pharmaceutical Technology Co., Ltd., Shanghai, China. FAU - Li, Yiming AU - Li Y AD - Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China. FAU - Bao, Yuqian AU - Bao Y AUID- ORCID: 0000-0002-4754-3470 AD - Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China. FAU - Wang, Qinghua AU - Wang Q AUID- ORCID: 0000-0002-6478-0988 AD - Innogen Pharmaceutical Technology Co., Ltd., Shanghai, China. AD - Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China. LA - eng GR - Innogen Pharmaceutical Co. Ltd., Shanghai, China/ PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250922 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Double-Blind Method MH - Glycated Hemoglobin/analysis/metabolism MH - Metformin/therapeutic use/administration & dosage MH - Blood Glucose/drug effects/metabolism MH - Aged MH - Treatment Outcome MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Drug Administration Schedule OTO - NOTNLM OT - Efsubaglutide Alfa OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - pharmacodynamics OT - safety OT - tolerability EDAT- 2025/09/22 06:31 MHDA- 2025/11/05 06:29 CRDT- 2025/09/22 04:44 PHST- 2025/08/29 00:00 [revised] PHST- 2025/07/16 00:00 [received] PHST- 2025/09/02 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/22 06:31 [pubmed] PHST- 2025/09/22 04:44 [entrez] AID - 10.1111/dom.70112 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7123-7132. doi: 10.1111/dom.70112. Epub 2025 Sep 22. PMID- 40977256 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260114 IS - 1879-0844 (Electronic) IS - 1388-9842 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Effect of glucagon-like peptide-1 receptor agonists on heart failure outcomes and cardiovascular death across varying cardiovascular-kidney-metabolic comorbidity. PG - 2844-2854 LID - 10.1002/ejhf.70048 [doi] AB - AIMS: Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart failure hospitalization (HFH) and cardiovascular (CV) death among patients with varying overlap of cardiovascular-kidney-metabolic (CKM) comorbidity are not well characterized. This study aimed to assess effects GLP-1RAs on HFH and CV death across populations with varying type and number of CKM comorbidity. METHODS AND RESULTS: Online databases were queried through November 2024 for primary and secondary analyses of clinical outcome trials of GLP-1RAs in patients with heart failure (HF), type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), obesity, and combinations of these diseases. Primary outcome was a composite HFH or CV death. Secondary outcomes were first HFH and CV death. Hazard ratios (HRs), risk ratios (RRs), and their 95% confidence intervals (CI) were derived using random-effects models. Fifteen trials (n = 87 549) were included. Compared with placebo, GLP-1RAs reduced the relative risk of composite HFH/CV death in HF (HR 0.81, 95% CI 0.69-0.96), T2DM (HR 0.85, 95% CI 0.78-0.93), and obesity (HR 0.70, 95% CI 0.58-0.86), with a non-significant risk reduction in CKD (HR 0.79, 95% CI 0.61-1.01). GLP-1RAs reduced the risk of HFH in T2DM (HR 0.89, 95% CI 0.80-0.99) and obesity (HR 0.63, 95% CI 0.45-0.87), with a non-significant risk reduction among patients with HF (HR 0.85, 95% CI 0.69-1.04) and CKD (HR 0.82, 95% CI 0.64-1.06). GLP-1RAs also significantly reduced CV death in HF (HR 0.88, 95% CI 0.77-0.99), T2DM (HR 0.85, 95% CI 0.78-0.93), and in obesity (HR 0.83, 95% CI 0.73-0.93), with a non-significant risk reduction in CKD (HR 0.80, 95% CI 0.60-1.08). Effects were consistent across subgroups, except for HF with reduced ejection fraction (HFrEF), where GLP-1RAs showed a non-significant risk increase in HFH (HR 1.17, 95% CI 0.93-1.47) but significantly reduced CV death (HR 0.67, 95% CI 0.50-0.90). GLP-1RAs were not associated with increased risk for serious adverse events (RR 0.94, 95% CI 0.89-1.00). CONCLUSIONS: Glucagon-like peptide-1 receptor agonists reduce HFH and CV death across CKM conditions, with generally consistent effects in varying combinations of these diseases. The potential exception is among patients with HFrEF, where a reduction in risk of CV death, but a numeric increase in HFH, was observed. Definitive CV outcome trials are needed to definitively determine effects of GLP-1RAs in patients with established HFrEF. CI - (c) 2025 European Society of Cardiology. FAU - Siddiqi, Tariq Jamal AU - Siddiqi TJ AD - Department of Internal Medicine, Baylor University Medical Center, Dallas, TX, USA. FAU - Khan, Muhammad Shahzeb AU - Khan MS AD - Baylor College of Medicine, Temple, TX, USA. AD - Baylor Scott and White Heart Hospital, Plano, TX, USA. AD - Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, TX, USA. FAU - Waqas, Saad Ahmed AU - Waqas SA AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Van Spall, Harriette G C AU - Van Spall HGC AD - Division of Cardiology, Department of Medicine, McMaster University, Hamilton, ON, Canada. FAU - Shapiro, Michael D AU - Shapiro MD AD - Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. FAU - Fonarow, Gregg C AU - Fonarow GC AD - Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan-UCLA Medical Center, Los Angeles, CA, USA. FAU - Januzzi, James L AU - Januzzi JL AD - Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. AD - Baim Institute for Clinical Research, Boston, MA, USA. FAU - Afzal, Aasim M AU - Afzal AM AD - Baylor Scott and White Heart Hospital, Plano, TX, USA. FAU - Pandey, Ambarish AU - Pandey A AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, TX, USA. AD - Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Greene, Stephen J AU - Greene SJ AD - Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. LA - eng PT - Journal Article DEP - 20250922 PL - England TA - Eur J Heart Fail JT - European journal of heart failure JID - 100887595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Heart Failure/drug therapy/epidemiology/mortality/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Renal Insufficiency, Chronic/epidemiology MH - Comorbidity MH - *Obesity/epidemiology MH - Hospitalization/statistics & numerical data MH - Male MH - Hypoglycemic Agents/therapeutic use MH - Female OTO - NOTNLM OT - Chronic kidney disease OT - Diabetes OT - GLP-1 receptor agonists OT - Heart failure OT - Obesity EDAT- 2025/09/22 06:31 MHDA- 2026/01/18 21:01 CRDT- 2025/09/22 03:33 PHST- 2025/08/26 00:00 [revised] PHST- 2025/02/28 00:00 [received] PHST- 2025/08/29 00:00 [accepted] PHST- 2026/01/18 21:01 [medline] PHST- 2025/09/22 06:31 [pubmed] PHST- 2025/09/22 03:33 [entrez] AID - 10.1002/ejhf.70048 [doi] PST - ppublish SO - Eur J Heart Fail. 2025 Dec;27(12):2844-2854. doi: 10.1002/ejhf.70048. Epub 2025 Sep 22. PMID- 40976663 OWN - NLM STAT- MEDLINE DCOM- 20250921 LR - 20250926 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 9 DP - 2025 Sep 21 TI - Cardiovascular effects of incretin-based drugs in patients with and without a history of heart failure: a protocol for a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials. PG - e103668 LID - 10.1136/bmjopen-2025-103668 [doi] LID - e103668 AB - BACKGROUND: Incretin-based drugs, including glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, are increasingly used in the management of type 2 diabetes mellitus and obesity. While these agents have shown cardiovascular benefits, their effects on both cardiovascular outcomes and cardiac structure and function remain uncertain-particularly in patients with and without a history of heart failure (HF). METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S)), as well as clinical trial registries from their inception and onwards to identify relevant randomised trials. The literature search is scheduled for July 2025. Two review authors will independently extract data and assess risk of bias. We will include randomised controlled trials assessing the effects of cagrilintide/semaglutide, liraglutide, semaglutide and tirzepatide in patients with and without a history of HF. The primary outcome will be cardiovascular mortality. Secondary outcomes will include HF hospitalisation, myocardial infarction, stroke, heart rate, systolic blood pressure, N-terminal pro B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume. Data will be synthesised by aggregate data meta-analyses and trial sequential analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool, version 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). ETHICS AND DISSEMINATION: As this study is a systematic review based on secondary analysis of published data, ethical approval is not required. Findings will be published in international peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD420251003374. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - El-Sheikh, Mohammed AU - El-Sheikh M AUID- ORCID: 0000-0003-0549-2203 AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark mo-sheikh@hotmail.com. FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AUID- ORCID: 0009-0004-9247-5245 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ̶ Rigshospitalet, Copenhagen, Denmark, Rigshospitalet, Copenhagen, Denmark. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, University of Southern Denmark, Odense, Denmark. FAU - Wisborg, Frederik Dencker AU - Wisborg FD AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Hove, Jens Dahlgaard AU - Hove JD AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Dirksen, Carsten AU - Dirksen C AD - Department of Respiratory Diseases and Endocrinology, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Lee, Matthew Meng Yang AU - Lee MMY AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, University of Glasgow, Glasgow, UK. FAU - Jakobsen, Janus C AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ̶ Rigshospitalet, Copenhagen, Denmark, Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, University of Southern Denmark, Odense, Denmark. FAU - Grand, Johannes AU - Grand J AUID- ORCID: 0000-0002-5511-4668 AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. LA - eng PT - Journal Article DEP - 20250921 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Heart Failure/drug therapy/complications MH - Systematic Reviews as Topic MH - *Incretins/therapeutic use/pharmacology MH - Randomized Controlled Trials as Topic MH - Meta-Analysis as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Research Design MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12458674 OTO - NOTNLM OT - Cardiovascular Disease OT - Drug Therapy OT - Heart failure OT - Meta-Analysis OT - Safety OT - Systematic Review COIS- Competing interests: ME-S and JDH have received lecture fees from Novo Nordisk. CDBS's husband was employed at Novo Nordisk, Kalundborg site, as a sprinkler technician from September 1, 2024, to August 31, 2025. CD has received research funding from the Novo Nordisk Foundation, and over the past three years received personal fees (lecturer, consultant) from Novo Nordisk, AstraZeneca and Amylyx, and served in various unpaid roles (lecturer, chairperson, investigator) for Novo Nordisk, Amgen, AstraZeneca and Eli Lilly. MMYL has received research grants through his institution, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim and Roche Diagnostics; is a member of Trial Steering Committees for Amgen and Cytokinetics; and Clinical Event Committees for Bayer and GSK. All other authors have no known competing interests. EDAT- 2025/09/22 00:30 MHDA- 2025/09/22 00:31 PMCR- 2025/09/21 CRDT- 2025/09/21 21:53 PHST- 2025/09/22 00:31 [medline] PHST- 2025/09/22 00:30 [pubmed] PHST- 2025/09/21 21:53 [entrez] PHST- 2025/09/21 00:00 [pmc-release] AID - bmjopen-2025-103668 [pii] AID - 10.1136/bmjopen-2025-103668 [doi] PST - epublish SO - BMJ Open. 2025 Sep 21;15(9):e103668. doi: 10.1136/bmjopen-2025-103668. PMID- 40976497 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20251208 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - Association of SGLT2 inhibitors and GLP-1 receptor agonists with the risk of Parkinson's disease in patients with type 2 diabetes: A propensity score-matched cohort study with meta-analysis. PG - 112914 LID - S0168-8227(25)00928-3 [pii] LID - 10.1016/j.diabres.2025.112914 [doi] AB - AIMS: This study aimed to investigate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and the risk of Parkinson's disease (PD) in patients with type 2 diabetes (T2D). METHODS: We conducted a real-world cohort study using the TriNetX U.S. Research Network. Adults aged >/= 50 years with T2D initiating SGLT2is, GLP-1RAs, or dipeptidyl peptidase-4 inhibitors (DPP4is) between 2015 and 2022 were included. A landmark analysis using a new-user, active-comparator design with propensity score matching was applied. The primary outcome was incident PD. A meta-analysis incorporating additional real-world studies was also performed. RESULTS: In total, 93,872, 110,366, and 95,838 patients were included in the SGLT2i vs. DPP4i, GLP-1RA vs. DPP4i, and SGLT2i vs. GLP-1RA comparisons, respectively. SGLT2i users had a significantly lower risk of PD compared with both DPP4i users (HR = 0.80, 95 % CI: 0.69-0.93, p = 0.003) and GLP-1RA users (HR = 0.80, 95 % CI: 0.69-0.93, p = 0.003). No significant difference was observed between GLP-1RA and DPP4i users (HR = 0.97, 95 % CI: 0.85-1.10, p = 0.656). The meta-analysis further supported the reduced PD risk associated with SGLT2i use. CONCLUSIONS: SGLT2i use was associated with a significantly lower risk of PD compared with both DPP4i and GLP-1RA use in patients with T2D. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Yeh, Jia-Ai AU - Yeh JA AD - School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Lin, Shu-Man AU - Lin SM AD - Department of Physical Medicine and Rehabilitation, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. FAU - Liu, Yu-Chang AU - Liu YC AD - Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Hsu, Ji-Ze AU - Hsu JZ AD - Center for Clinical Epidemiology and Biostatistics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. FAU - Huang, Amy Huaishiuan AU - Huang AH AD - Department of Internal Medicine, University of Connecticut School of Medicine, Farmington, USA. FAU - Munir, Kashif M AU - Munir KM AD - Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Peng, Carol Chiung-Hui AU - Peng CC AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Loh, Ching-Hui AU - Loh CH AD - School of Medicine, Tzu Chi University, Hualien, Taiwan; Center for Aging and Health, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. FAU - Huang, Huei-Kai AU - Huang HK AD - School of Medicine, Tzu Chi University, Hualien, Taiwan; Center for Clinical Epidemiology and Biostatistics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Family Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. Electronic address: drhkhuang@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250919 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Parkinson Disease/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Propensity Score MH - Male MH - Female MH - Aged MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Cohort Studies MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Diabetes OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Parkinson's disease OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/22 00:30 MHDA- 2025/10/31 00:29 CRDT- 2025/09/21 20:00 PHST- 2025/06/12 00:00 [received] PHST- 2025/09/08 00:00 [revised] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/22 00:30 [pubmed] PHST- 2025/09/21 20:00 [entrez] AID - S0168-8227(25)00928-3 [pii] AID - 10.1016/j.diabres.2025.112914 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112914. doi: 10.1016/j.diabres.2025.112914. Epub 2025 Sep 19. PMID- 40975962 OWN - NLM STAT- MEDLINE DCOM- 20251011 LR - 20260127 IS - 1768-3254 (Electronic) IS - 0223-5234 (Linking) VI - 300 DP - 2025 Dec 15 TI - Unraveling the safety profile of GLP-1 receptor agonists: Mechanistic insights with a focus on semaglutide. PG - 118163 LID - S0223-5234(25)00928-6 [pii] LID - 10.1016/j.ejmech.2025.118163 [doi] AB - Semaglutide, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated remarkable therapeutic efficacy in managing type 2 diabetes (T2D) and obesity in recent years, emerging as a focal point in clinical research. However, with the expansion of its clinical application, there is increasing evidence that semaglutide can cause multisystem adverse reactions, leading to reduced patient compliance and safety. Recent research findings indicate that adverse events associated with semaglutide involve pathological changes across multiple systems (digestive, cardiovascular, neurological, reproductive, immune and respiratory) and organs (liver, kidneys, thyroid and retina). The precise mechanisms underlying these effects remain incompletely characterized, hindering early detection and targeted intervention in clinical practice. This review integrates evidence from preclinical studies, randomized controlled trials (RCTs), and real-world data to systematically evaluate the safety profile of GLP-1RAs, with semaglutide as the primary focus. It elucidates the biological mechanisms underlying organ/system-specific adverse effects broadly applicable to the GLP-1RA class. Furthermore, we propose a stratified management framework to guide personalized treatment strategies aligned with precision medicine principles, aiming to optimize the dynamic equilibrium between therapeutic efficacy and safety risks. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - He, Xinyi AU - He X AD - Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China; Clinical Department I, China Medical University, Shenyang, 110122, Liaoning Province, China. Electronic address: neveah_he@163.com. FAU - Zhao, Zimo AU - Zhao Z AD - First Clinical Medical College, China Medical University, Shenyang, 110122, Liaoning Province, China. FAU - Sun, Yan AU - Sun Y AD - Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China. Electronic address: suny6@sj-hospital.org. FAU - Jiang, Xi AU - Jiang X AD - Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China. Electronic address: xijiang1985@126.com. LA - eng PT - Journal Article PT - Review DEP - 20250910 PL - France TA - Eur J Med Chem JT - European journal of medicinal chemistry JID - 0420510 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/pharmacology/therapeutic use/chemistry MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - *Hypoglycemic Agents/adverse effects/pharmacology/chemistry/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse reactions OT - Clinical applications OT - GLP-1 receptor agonists OT - Mechanisms OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/22 00:30 MHDA- 2025/10/12 00:33 CRDT- 2025/09/21 18:02 PHST- 2025/07/13 00:00 [received] PHST- 2025/08/31 00:00 [revised] PHST- 2025/09/09 00:00 [accepted] PHST- 2025/10/12 00:33 [medline] PHST- 2025/09/22 00:30 [pubmed] PHST- 2025/09/21 18:02 [entrez] AID - S0223-5234(25)00928-6 [pii] AID - 10.1016/j.ejmech.2025.118163 [doi] PST - ppublish SO - Eur J Med Chem. 2025 Dec 15;300:118163. doi: 10.1016/j.ejmech.2025.118163. Epub 2025 Sep 10. PMID- 40975854 OWN - NLM STAT- MEDLINE DCOM- 20251202 LR - 20261010 IS - 1970-9366 (Electronic) IS - 1828-0447 (Linking) VI - 20 IP - 8 DP - 2025 Nov TI - GLP-1 and GIP agonists in diabetes and obesity and the rise of dyspepsia. PG - 2291-2294 LID - 10.1007/s11739-025-04117-9 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, such as tirzepatide, have transformed the management of type 2 diabetes and obesity through durable glycemic control, weight reduction, and cardiovascular protection. However, their widespread use has revealed a high incidence of gastrointestinal adverse events, particularly dyspepsia and gastroparesis-like symptoms. While most effects are transient, a significant subset of patients develop persistent intolerance, often leading to misdiagnosis, unnecessary investigations, or premature treatment discontinuation. Current therapeutic options remain limited, with guidelines offering little direction for managing symptoms, in this subset of dyspeptic patients. This growing clinical challenge highlights the urgent need for structured strategies, including risk stratification, tailored dose titration, and multidisciplinary care, to balance metabolic efficacy with gastrointestinal tolerability. CI - (c) 2025. The Author(s), under exclusive licence to Societa Italiana di Medicina Interna (SIMI). FAU - Masulli, Maria AU - Masulli M AD - Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Via Pansini 5, Naples, Italy. FAU - Tack, Jan AU - Tack J AD - Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. FAU - Esposito, Giuseppe AU - Esposito G AD - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy. FAU - Sarnelli, Giovanni AU - Sarnelli G AUID- ORCID: 0000-0002-1467-1134 AD - Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Via Pansini 5, Naples, Italy. sarnelli@unina.it. LA - eng PT - Journal Article PT - Review DEP - 20250921 PL - Italy TA - Intern Emerg Med JT - Internal and emergency medicine JID - 101263418 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Dyspepsia/chemically induced/etiology MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Inhibitory Polypeptide/therapeutic use/agonists MH - *Glucagon-Like Peptide 1/therapeutic use/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Tirzepatide OTO - NOTNLM OT - Functional dyspepsia OT - GIP OT - GLP-1 receptor agonists OT - Gastric emptying OT - Gastrointestinal symptoms OT - Gastroparesis OT - Obesity OT - Tirzepatide OT - Type 2 diabetes COIS- Declarations. Conflict of interest: The authors hereby affirm that there are no conflicts of interest to disclose. Human and animal rights statement and Informed consent: Not applicable. EDAT- 2025/09/21 13:06 MHDA- 2025/12/02 12:57 CRDT- 2025/09/21 11:03 PHST- 2025/08/07 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/12/02 12:57 [medline] PHST- 2025/09/21 13:06 [pubmed] PHST- 2025/09/21 11:03 [entrez] AID - 10.1007/s11739-025-04117-9 [pii] AID - 10.1007/s11739-025-04117-9 [doi] PST - ppublish SO - Intern Emerg Med. 2025 Nov;20(8):2291-2294. doi: 10.1007/s11739-025-04117-9. Epub 2025 Sep 21. PMID- 40968755 OWN - NLM STAT- MEDLINE DCOM- 20251020 LR - 20251205 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 11 DP - 2025 Nov 1 TI - Impact of Baseline GLP-1 Receptor Agonist Use on Albuminuria Reduction and Safety With Simultaneous Initiation of Finerenone and Empagliflozin in Type 2 Diabetes and Chronic Kidney Disease (CONFIDENCE Trial). PG - 1904-1913 LID - 10.2337/dc25-1673 [doi] AB - OBJECTIVE: The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium-glucose cotransporter 2 (SGLT2) inhibitor compared with monotherapy in reducing the urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide 1 receptor agonist (GLP-1 RA) use. RESEARCH DESIGN AND METHODS: Adults with chronic kidney disease (UACR >/=100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30-90 mL/min/1.73 m2) and type 2 diabetes (glycated hemoglobin <11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin. RESULTS: Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was -51% (95% CI -59 to -40%) with combination therapy, -34% (-48 to -18%) with finerenone, and -36% (-48 to -21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were -56% (-62 to -50%), -37% (-45 to -28%), and -33% (-41 to -23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy. CONCLUSIONS: In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA. CI - (c) 2025 by the American Diabetes Association. FAU - Agarwal, Rajiv AU - Agarwal R AUID- ORCID: 0000-0001-8355-7100 AD - Division of Nephrology, Richard L. Roudebush VA Medical Center, Indianapolis, IN. AD - Indiana University School of Medicine, Indianapolis, IN. FAU - Green, Jennifer B AU - Green JB AUID- ORCID: 0000-0002-9967-5352 AD - Division of Endocrinology, Department of Medicine and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AUID- ORCID: 0000-0002-3126-3730 AD - Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany. AD - Department of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Germany. FAU - McGill, Janet B AU - McGill JB AD - Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis School of Medicine, St. Louis, MO. FAU - Mottl, Amy K AU - Mottl AK AUID- ORCID: 0000-0002-4258-1726 AD - University of North Carolina Kidney Center, University of North Carolina School of Medicine, Chapel Hill, NC. FAU - Nangaku, Masaomi AU - Nangaku M AD - Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas, TX. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AUID- ORCID: 0000-0003-0885-1953 AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. AD - Harvard Medical School, Boston, MA. FAU - Brinker, Meike AU - Brinker M AD - Cardiology and Nephrology Clinical Development, Bayer AG, Wuppertal, Germany. FAU - Scott, Charlie AU - Scott C AD - Clinical Statistics and Analytics, Bayer US LLC, Whippany, NJ. FAU - Li, Li AU - Li L AD - Bayer AG, Berlin, Germany. FAU - Li, Na AU - Li N AD - Bayer Healthcare, Chaoyang District, Beijing, China. FAU - Rohwedder, Katja AU - Rohwedder K AD - Bayer AG, Berlin, Germany. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Pharmaceuticals Bayer/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (finerenone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Naphthyridines) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Benzhydryl Compounds/therapeutic use/adverse effects MH - *Glucosides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - *Albuminuria/drug therapy MH - Middle Aged MH - *Renal Insufficiency, Chronic/drug therapy MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Naphthyridines/therapeutic use/adverse effects MH - Drug Therapy, Combination MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glomerular Filtration Rate/drug effects MH - Hypoglycemic Agents/therapeutic use PMC - PMC12583382 COIS- Duality of Interest. R.A. has received nonfinancial support and consulting fees from Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, and Novartis; has received royalties or licenses from UptoDate and Wolters Kluwer; is a member of data safety monitoring committees for Chinook and Vertex; has served as an associate editor of the American Journal of Nephrology and Nephrology Dialysis Transplantation; has been an author and editor for UpToDate; and has received research grants from the National Institutes of Health and the US Veterans Administration. J.B.G. has received funds for research, paid to her institution, from Bluedrop, Boehringer Ingelheim, Eli Lilly, Merck, and Roche and is a consultant for Anji, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Eli Lilly, Mineralys, Novo Nordisk, Valo, and Vertex. H.J.L.H. has received consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, BioCity, Dimerix, Eli Lilly, Janssen, Novartis, Novo Nordisk, Roche, and Travere Therapeutics, all paid to his employer; research support from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, and Novo Nordisk, all paid to his employer; honoraria from AstraZeneca and Novo Nordisk; and travel expenses from AstraZeneca and Eli Lilly. J.F.E.M. has received grants from McMaster University, Novo Nordisk, and the European Union; has received consulting fees from Bayer and Novo Nordisk; has received honoraria from AstraZeneca, Bayer, Novartis, UpToDate, and Novo Nordisk; has participated on a data safety monitoring board for Cytel, IQVIA, Parexel, WCG, and Sanofi; and had a leadership role in the Kidney Disease: Improving Global Outcomes group. J.B.M. is the principal investigator on grants to Washington University from Biomea Fusion, Diamyd, Breakthrough T1D (formerly JDRF), Lexicon, the National Institutes of Health, and Novo Nordisk; has received royalties or licenses from Washington University; has received consulting fees from Bayer, ClearNote Health, Eli Lilly, Mannkind, Novo Nordisk, and Thermo Fisher Scientific; has received payment or honoraria from Medscape, Thermo Fisher Scientific, Bayer, Med Learning Group, and Baylor; has participated on a data safety monitoring board for the Jaeb Center, Washington University, and the National Institutes of Health; has received support for attending meetings and/or travel from the Endocrine Society, Mannkind, Western Endocrine Society, and Kansas Diabetes Symposium; and holds a leadership or fiduciary role with the Diabetes Technology Access Group. A.K.M. has received research support and personal fees from Alexion, Boehringer Ingelheim, Bayer, Chinook Therapeutics, and Novartis, paid to her institution; royalties from UpToDate; consulting fees from Bayer, Otsuka, Vera, and Chinook/Novartis; and travel support and payment for an educational symposium from Novo Nordisk. M.N. has received research grants from Astellas, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, JT, Kyowa-Kirin, Takeda, Tanabe-Mitsubishi, and Torii; consulting fees from Astellas, Boehringer Ingelheim, Daiichi Sankyo, JT, Kyowa-Kirin, and Tanabe-Mitsubishi; and honoraria from Astellas, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, GSK, Kyowa-Kirin, and Tanabe-Mitsubishi. J.R. has received research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Carmot, Corcept, Eli Lilly, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Regeneron, Pfizer, and Sanofi; has served on scientific advisory boards and received honoraria or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Eli Lilly, Hanmi, Novo Nordisk, Oramed, Regeneron, Regor, Roche, Sanofi, and Structure Therapeutics; and has received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. M.V. has received research grant support, served on advisory boards, or had speaker engagements with Alnylam Pharmaceuticals, American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health and participates on clinical trial committees for studies sponsored by Amgen, AstraZeneca, Boehringer Ingelheim, Galmed, Novartis, Bayer AG, Occlutech, Pharmacosmos, and Impulse Dynamics. M.B. is an employee of Bayer AG, Germany, and is named on a planned, issued, or pending finerenone patent. C.S. is an employee of Bayer Healthcare Inc, USA. L.L. is an employee of Bayer AG, Germany. N.L. is an employee of Bayer Healthcare, China. K.R. is an employee of Bayer AG, Germany. P.R. has received research support from AstraZeneca, Bayer, and Novo Nordisk, all to his institution; consulting fees from Abbott, Amgen, Astellas, Bayer, Boehringer Ingelheim, Eli Lilly, Roche, and Gilead, all to his institution; payment or honoraria from Daiichi Sankyo to his institution; support for attending meetings and/or travel from Bayer; and receipt of study drug for an investigator-initiated study from Bayer, AstraZeneca, Novo Nordisk, and Lexicon Pharma. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/09/19 06:33 MHDA- 2025/10/20 18:29 PMCR- 2025/09/19 CRDT- 2025/09/19 04:04 PHST- 2025/07/11 00:00 [received] PHST- 2025/08/07 00:00 [accepted] PHST- 2025/10/20 18:29 [medline] PHST- 2025/09/19 06:33 [pubmed] PHST- 2025/09/19 04:04 [entrez] PHST- 2025/09/19 00:00 [pmc-release] AID - 163403 [pii] AID - 251673 [pii] AID - 10.2337/dc25-1673 [doi] PST - ppublish SO - Diabetes Care. 2025 Nov 1;48(11):1904-1913. doi: 10.2337/dc25-1673. PMID- 40966636 OWN - NLM STAT- MEDLINE DCOM- 20250918 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 9 DP - 2025 Sep TI - Navigating compounded semaglutide: what health care providers need to know. PG - 480-484 LID - 10.37765/ajmc.2025.89787 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, is FDA approved under the brand names Ozempic for treatment of type 2 diabetes and Wegovy for the treatment of overweight or obesity. The soaring popularity of these drugs, driven by social media and their overall efficacy, has resulted in nationwide shortages. The high costs associated with the FDA-approved products for both insurers and patients have also led to additional restrictions in access. In response to the unmet growing demand for semaglutide, suppliers have started to sell compounded versions of these products, both legally and illegally. This narrative review examines the implications of these compounded products on our health care system, highlighting concerns regarding their safety, efficacy, and regulatory status. Compounding, when done following federal and state regulations, can fill an important need in our health care marketplace. However, the compounded semaglutide products currently available to patients may lack the quality controls historically seen with compounded formulations, resulting in risks for dosing errors and adverse health outcomes. In addition, the compounded semaglutide market worldwide has seen batches of fraudulent products. Pharmacists and other health care providers have a unique opportunity to help guide patients in navigating this compounded semaglutide market, including directing them to lawful sources of compounded semaglutide, providing counseling on dosage and administration, and minimizing safety concerns. FAU - Liu, Grace AU - Liu G FAU - Jarema, Marissa AU - Jarema M AD - Blue Cross Blue Shield of Michigan, 600 E Lafayette Blvd, Mail Code 512C, Detroit, MI 48226. Email: mjarema@bcbsm.com. FAU - Mo, Millie AU - Mo M FAU - Stievater, Trish AU - Stievater T LA - eng PT - Journal Article PT - Review PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Compounding/standards MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - United States Food and Drug Administration MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/09/18 18:32 MHDA- 2025/09/18 18:33 CRDT- 2025/09/18 16:35 PHST- 2025/09/18 18:33 [medline] PHST- 2025/09/18 18:32 [pubmed] PHST- 2025/09/18 16:35 [entrez] AID - 89787 [pii] AID - 10.37765/ajmc.2025.89787 [doi] PST - ppublish SO - Am J Manag Care. 2025 Sep;31(9):480-484. doi: 10.37765/ajmc.2025.89787. PMID- 40962119 OWN - NLM STAT- MEDLINE DCOM- 20260129 LR - 20260130 IS - 2162-0989 (Electronic) IS - 2162-0989 (Linking) VI - 15 IP - 1 DP - 2026 Jan-Feb TI - Does semaglutide increase the risk of non-arteritic anterior ischemic optic neuropathy? A systematic review and meta-analysis of emerging evidence. PG - 100245 LID - S2162-0989(25)00112-4 [pii] LID - 10.1016/j.apjo.2025.100245 [doi] AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist widely prescribed for type 2 diabetes and obesity, has recently been linked to rare ocular adverse events, including non-arteritic anterior ischemic optic neuropathy (NAION). Given the growing concerns and limited clarity, this systematic review and meta-analysis aims to critically assess the potential association between semaglutide use and NAION risk. OBJECTIVES: To evaluate the association between semaglutide use and the development of NAION. METHODS: A comprehensive literature search was conducted via different databases from inception to June 3rd, 2025. A reviewer screened the potential articles against prespecified eligibility criteria. The risk of bias in the eligible studies was then evaluated using the Newcastle Ottawa Scale (NOS). Data were then systematically extracted and analyzed. RESULTS: The database search yielded 3539 records, of which 10 research articles investigating the association between Semaglutide and NAION were included in this study. Semaglutide use was associated with a significantly increased risk of NAION compared to control medications, with a pooled hazard ratio of 2.620 (95 % CI: 1.808-3.795, P < 0.001). Risk elevation showed time-dependency, becoming statistically significant after 2 years of exposure. Identified risk factors included older age, male sex, prolonged diabetes duration, elevated HbA1c, diabetic retinopathy, and obesity. Among GLP-1 receptor agonists, semaglutide accounted for 86.5 % of reported NAION cases. Clinical presentations featured optic disc edema, intraretinal fluid on OCT, and crowded optic discs. Cumulative incidence rates were substantially higher in semaglutide users versus non-GLP-1 receptor agonist comparators. CONCLUSIONS: Semaglutide use shows association with increased NAION risk, particularly with prolonged exposure and in patients with predisposing factors. Risk-benefit assessment and targeted ophthalmologic monitoring are recommended while maintaining appropriate therapeutic use. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Chen, Kai-Yang AU - Chen KY AD - Department of General Medicine, Chang Gung Memorial Hospital (Linkou branch), Taoyuan, Taiwan. FAU - Chan, Hoi-Chun AU - Chan HC AD - School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Chan, Chi-Ming AU - Chan CM AD - Department of Ophthalmology, Cardinal Tien Hospital, New Taipei CityTaiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: m212092001@tmu.edu.tw. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250915 PL - United States TA - Asia Pac J Ophthalmol (Phila) JT - Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) JID - 101583622 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Risk Factors MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Diabetic retinopathy OT - NAION OT - Non-Arteritic Anterior Ischemic Optic Neuropathy OT - Optic nerve ischemia OT - Semaglutide COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2025/09/18 00:31 MHDA- 2026/01/30 00:54 CRDT- 2025/09/17 19:15 PHST- 2025/06/25 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/08 00:00 [accepted] PHST- 2026/01/30 00:54 [medline] PHST- 2025/09/18 00:31 [pubmed] PHST- 2025/09/17 19:15 [entrez] AID - S2162-0989(25)00112-4 [pii] AID - 10.1016/j.apjo.2025.100245 [doi] PST - ppublish SO - Asia Pac J Ophthalmol (Phila). 2026 Jan-Feb;15(1):100245. doi: 10.1016/j.apjo.2025.100245. Epub 2025 Sep 15. PMID- 40961953 OWN - NLM STAT- MEDLINE DCOM- 20251016 LR - 20260925 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 11 DP - 2025 Nov TI - Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. PG - 935-948 LID - S2213-8587(25)00225-6 [pii] LID - 10.1016/S2213-8587(25)00225-6 [doi] AB - BACKGROUND: Semaglutide 2.4 mg is approved for weight management in adults with obesity or overweight in the presence of at least one obesity-related complication; however, many people with obesity and type 2 diabetes do not reach their bodyweight reduction goals with this dose. We aimed to investigate the efficacy and safety of a new 7.2 mg maintenance dose of once-weekly subcutaneous semaglutide in people with obesity and type 2 diabetes. METHODS: STEP UP T2D was a randomised, phase 3b, double-blind controlled, three-arm, parallel-group trial conducted at 68 hospitals, specialist clinics, and medical centres in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa, and the USA. Adults aged 18 years or older (BMI >/=30.0 kg/m(2), HbA(1c) 7.0-10.0% [53-86 mmol/mol]) were randomly assigned (3:1:1) to receive once-weekly subcutaneous semaglutide 7.2 mg, 2.4 mg, or placebo, alongside a lifestyle intervention, for 72 weeks. Coprimary endpoints were the percentage change in bodyweight and the proportion of participants reaching a bodyweight reduction of 5% or greater with semaglutide 7.2 mg versus placebo. Confirmatory secondary endpoints were the proportion of participants reaching a bodyweight reduction of 10% or greater, 15% or greater, and 20% or greater, and changes in waist circumference (cm) and HbA(1c) (%) with semaglutide 7.2 mg versus placebo. Efficacy was assessed in all randomly assigned participants, and safety was assessed in all randomly assigned participants who received at least one dose of the trial product. This trial is registered with ClinicalTrials.gov (NCT05649137) and is now closed and completed. FINDINGS: Between Jan 4 and May 4, 2023, 512 participants were randomly assigned to receive semaglutide 7.2 mg (n=307), semaglutide 2.4 mg (n=103), or placebo (n=102). 265 (51.8%) of 512 participants were female, the mean age was 56 (SD 10) years, mean bodyweight was 110.1 (22.9) kg, mean BMI was 38.6 (7.1) kg/m(2), and mean HbA(1c) was 8.1% (0.9). Compared with placebo, semaglutide 7.2 mg led to greater reductions in mean bodyweight (-13.2% vs -3.9%; estimated treatment difference [ETD] -9.3% [95% CI -11.0 to -7.7]; p<0.0001); more participants reaching bodyweight reductions of 5% or greater (odds ratio 10.0 [95% CI 6.0 to 16.9]; p<0.0001), 10% or greater (11.3 [5.9 to 21.4]; p<0.0001), 15% or greater (8.1 [3.7 to 17.7]; p<0.0001), and 20% or greater (12.3 [3.0 to 51.0]; p=0.0006); and reduced waist circumference (ETD -6.5 cm [95% CI -9.0 to -4.1]; p<0.0001) and HbA(1c) (ETD -1.5% [95% CI -1.8 to -1.2]; p<0.0001). Level 2-3 hypoglycaemia risk was low and comparable between semaglutide doses and placebo. Gastrointestinal events were reported by 163 (53.1%) of 307 participants with semaglutide 7.2 mg, 53 (51.5%) of 103 participants with semaglutide 2.4 mg, 26 (25.5%) of 102 participants with placebo; and serious adverse events were reported by 28 (9.1%) participants with semaglutide 7.2 mg, nine (8.7%) participants with semaglutide 2.4 mg, and nine (8.8%) participants with placebo. Dysaesthesia was more common with semaglutide 7.2 mg (58 [18.9%] of 307) versus 2.4 mg (five [4.9%] of 103) and placebo (none). INTERPRETATION: Among people with obesity and type 2 diabetes, semaglutide 7.2 mg was superior to placebo in reducing bodyweight, waist circumference, and HbA(1c). Safety and tolerability were comparable between semaglutide 7.2 mg and 2.4 mg, except for the imbalance in dysaesthesia. FUNDING: Novo Nordisk. TRANSLATIONS: For the Bulgarian, Hungarian and Polish translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ildiko.lingvay@utsouthwestern.edu. FAU - Bergenheim, Sara J AU - Bergenheim SJ AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Freitas, Paula AU - Freitas P AD - Department of Medicine, Faculty of Medicine and I3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Integrated Responsibility Center for Obesity, Sao Joao Local Health Unit, Porto, Portugal. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Harder-Lauridsen, Nina M AU - Harder-Lauridsen NM AD - Novo Nordisk, Soborg, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AD - Velocity Clinical Research at Medical City, Dallas, TX, USA. FAU - Sahu, Kushal AU - Sahu K AD - Novo Nordisk, Bangalore, India. FAU - Wharton, Sean AU - Wharton S AD - Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Faculty of Health and Kinesiology, York University, Toronto, ON, Canada; Faculty of Medicine, McMaster University, Hamilton, ON, Canada; Wharton Medical Clinic Weight and Diabetes Management, Burlington, ON, Canada. CN - STEP UP T2D trial group LA - eng SI - ClinicalTrials.gov/NCT05649137 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250914 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Lancet Diabetes Endocrinol. 2026 Jun;14(6):e9. doi: 10.1016/S2213-8587(26)00078-1. PMID: 41932351 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Drug Administration Schedule MH - *Obesity/drug therapy/complications MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Semaglutide COIS- Declaration of interests IL has received grants from Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Roche, and Pfizer, with all payments made to her institution; has received payment or honoraria from AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bayer, Betagenon, Bioio, Biomea, Boehringer Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Therapeutics, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, Terns Pharma, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma; and has received support to attend meetings from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. SJB is a full-time employee of, and has received gifts from, Novo Nordisk and holds an unpaid affiliation with the University of Copenhagen. JBB has received grants or consulting fees, or both, from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns, Vertex, and Zealand, with all payments made to his institution; has received payment for expert testimony from Medtronic MiniMed and Novo Nordisk, with all payments made to his institution; has participated on a data safety monitoring board or advisory board for Altimmune, AstraZeneca, and Tandem Diabetes Care; holds stock or options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health; and has an unpaid leadership role for the Association for Clinical and Translational Science. PF has received payment or honoraria from Amryt, Bial, Boehringer Ingelheim, FaesFarma, Janssen, Lilly, Merck, Novartis, Novo Nordisk, Pronokal, and Sanofi, along with support to attend meetings from Bial, Medinfar, Novo Nordisk, and Sanofi. WTG has received grants as a principal investigator from Novo Nordisk, Eli Lilly & Co, Pfizer, Epitomee, Neurovalens, Zealand, Carmot/Roche, Terns Pharmaceuticals, and Viking Therapeutics; has received grants for research from the UAB Diabetes Research Center (DK079626) funded by the US National Institutes of Health (NIH) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), with all payments made to his institution; has received consulting fees as an advisory board member from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, Gan & Lee, NodThera, and Regeneron; has received fees to participate on a data safety monitoring board or advisory board for Boehringer Ingelheim and Eli Lilly; and is an unpaid member for the Lancet Commission on Obesity, American Association of Clinical Endocrinology (AACE) update of obesity treatment algorithm, American Diabetes Association (ADA) nutrition recommendations update, and ADA Standards of Care for Obesity. NMHL and KS are full-time employees of, and hold shares in, Novo Nordisk. JR has received research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Carmot, Corcept, Eli Lilly, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Regeneron, Pfizer, Sanofi, Structure Therapeutics, and TERNS; and has served on scientific advisory boards and received honorarium or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Eli Lilly, Hanmi, Novo Nordisk, Oramed, Regeneron, Regor, Roche, Sanofi, Structure Therapeutics, and TERNS; and received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. SW has received payment or honoraria from AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Metsera, Neurogastrix, Novo Nordisk, and Regeneron for academic talks to colleagues; has been provided with medical writing support from AstraZeneca, Boehringer Ingelheim, Bausch Health Canada, Eli Lilly, and Novo Nordisk; and has an unpaid leadership role in The Obesity Society and Obesity Canada. EDAT- 2025/09/18 00:31 MHDA- 2025/10/17 00:31 CRDT- 2025/09/17 18:52 PHST- 2025/06/05 00:00 [received] PHST- 2025/07/11 00:00 [revised] PHST- 2025/07/17 00:00 [accepted] PHST- 2025/10/17 00:31 [medline] PHST- 2025/09/18 00:31 [pubmed] PHST- 2025/09/17 18:52 [entrez] AID - S2213-8587(25)00225-6 [pii] AID - 10.1016/S2213-8587(25)00225-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Nov;13(11):935-948. doi: 10.1016/S2213-8587(25)00225-6. Epub 2025 Sep 14. PMID- 40957960 OWN - NLM STAT- MEDLINE DCOM- 20251017 LR - 20261010 IS - 1546-170X (Electronic) IS - 1078-8956 (Linking) VI - 31 IP - 10 DP - 2025 Oct TI - Macrovascular and microvascular outcomes of metabolic surgery versus GLP-1 receptor agonists in patients with diabetes and obesity. PG - 3341-3349 LID - 10.1038/s41591-025-03893-3 [doi] AB - Both metabolic surgery and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) improve cardiometabolic outcomes, but their long-term outcomes have not been directly compared. Here, we compared macrovascular and microvascular outcomes in 1,657 patients (65.7% female) with type 2 diabetes and obesity who underwent metabolic surgery with 2,275 similar patients (53.5% female) who received treatment with GLP-1 RAs. Using a doubly robust estimation method to balance baseline characteristics between groups, we examined the time to all-cause mortality, incident major adverse cardiovascular events (MACE), nephropathy and retinopathy over a median follow-up of 5.9 years. The 10-year cumulative incidence of all-cause mortality was 9.0% (95% confidence interval (CI) 6.8-10.8%) in the metabolic surgery group and 12.4% (95% CI 9.9-15.2%) in the GLP-1 RA group (adjusted hazard ratio (HR) 0.68 (95% CI 0.48-0.96), P = 0.028). Compared with the GLP-1 RA group, metabolic surgery was also associated with a lower risk of MACE (adjusted HR 0.65; 95% CI 0.51-0.82; P < 0.001), nephropathy (adjusted HR 0.53; 95% CI 0.43-0.67; P < 0.001) and retinopathy (adjusted HR 0.46; 95% CI 0.29-0.75; P = 0.002). These findings indicate that even with the availability of GLP-1 RAs, metabolic surgery remains superior to medical treatment. Future studies should compare the cardiometabolic outcomes of metabolic surgery with newer GLP-1 RAs that are more effective for weight reduction. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Alavi, Mohammad Hesam AU - Alavi MH AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Zajichek, Alexander AU - Zajichek A AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AUID- ORCID: 0000-0003-2291-835X AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Al Jabri, Abdullah AU - Al Jabri A AUID- ORCID: 0000-0001-7838-9261 AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Bena, James AU - Bena J AUID- ORCID: 0000-0002-7592-0480 AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Feng, Xiaoxi AU - Feng X AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Wilson, Rickesha AU - Wilson R AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Corcelles, Ricard AU - Corcelles R AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Butsch, W Scott AU - Butsch WS AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. FAU - Singh, Rishi P AU - Singh RP AD - Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Das, Nikhil AU - Das N AD - Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Jeong, Hejin AU - Jeong H AUID- ORCID: 0009-0001-7903-0792 AD - Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Mentias, Amgad AU - Mentias A AD - Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Tang, W H Wilson AU - Tang WHW AUID- ORCID: 0000-0002-8335-735X AD - Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Burguera, Bartolome AU - Burguera B AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Rosenthal, Raul J AU - Rosenthal RJ AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Weston, FL, USA. FAU - Nissen, Steven E AU - Nissen SE AUID- ORCID: 0000-0002-7231-6464 AD - Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. nissens@ccf.org. FAU - Rothberg, Michael B AU - Rothberg MB AUID- ORCID: 0000-0002-2063-1876 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Aminian, Ali AU - Aminian A AUID- ORCID: 0000-0001-5756-9917 AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA. aminiaa@ccf.org. LA - eng PT - Journal Article DEP - 20250916 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/surgery/drug therapy/complications/mortality MH - *Obesity/surgery/drug therapy/complications MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor MH - Aged MH - Treatment Outcome MH - *Bariatric Surgery MH - Cardiovascular Diseases MH - Hypoglycemic Agents/therapeutic use MH - Microvessels/drug effects COIS- Competing interests: W.S.B. has received honoraria and paid consultancy from Novo Nordisk, Abbott Nutrition, Medscape, Alfie Health and the Med Learning Group. R.P.S. reported receiving personal fees from Alcon, Apellis, Bausch + Lomb, EyePoint, Genentech, Iveric Bio, Regeneron, Regenxbio and ZEISS, and research grants from Janssen. W.H.W.T. received consulting fees from Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, WhiteSwell, Boston Scientific, CardiaTec Biosciences, Intellia Therapeutics, Bristol Myers Squibb, Alleviant Medical, Alexion Pharmaceuticals, Salubris Biotherapeutics and BioCardia, and received honoraria from Springer, Belvoir Media Group and the American Board of Internal Medicine. B.B. received an honorarium from Novo Nordisk. R.J.R. reported receiving personal fee from Medtronic, Diagnostic Green, mediCAD and Dendrite Imaging, and serving as the CEO of Dendrite Imaging. S.E.N. received grants to perform clinical trials from AbbVie, AstraZeneca, Amgen, Bristol Myers Squibb, Eli Lilly, Esperion Therapeutics, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis and Silence Therapeutics. M.B.R. has a consulting relationship with the Blue Cross Blue Shield Association. A.A. received research grants from Medtronic and Ethicon, and serves as a consultant for Medtronic, Ethicon and Eli Lilly. The other authors declare no competing interests. EDAT- 2025/09/17 00:31 MHDA- 2025/10/17 06:28 CRDT- 2025/09/16 23:18 PHST- 2024/10/25 00:00 [received] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/10/17 06:28 [medline] PHST- 2025/09/17 00:31 [pubmed] PHST- 2025/09/16 23:18 [entrez] AID - 10.1038/s41591-025-03893-3 [pii] AID - 10.1038/s41591-025-03893-3 [doi] PST - ppublish SO - Nat Med. 2025 Oct;31(10):3341-3349. doi: 10.1038/s41591-025-03893-3. Epub 2025 Sep 16. PMID- 40954547 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260918 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 Suppl 2 IP - Suppl 2 DP - 2026 Sep TI - GLP-1 Receptor Agonists and Substance Use Disorders in Older Adults With Type 2 Diabetes: A Target Trial Emulation. PG - 88-100 LID - 10.1002/oby.70024 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for type 2 diabetes (T2D) and obesity, may modulate reward pathways and reduce substance-related behaviors. This study assessed the association between GLP-1RA use and substance use-related hospitalization in older adults with coexisting T2D and substance use disorders (SUD). METHODS: A retrospective cohort study using 2016-2020 Medicare data compared GLP-1RA initiators with new users of SGLT2 inhibitors (SGLT2is) or DPP-4 inhibitors (DPP4is) among adults aged >/= 65. The primary outcome was hospitalization for any SUD; secondary outcomes included hospitalizations for alcohol use disorder (AUD) and opioid use disorder (OUD). Propensity score 1:1 matching and Cox proportional hazards models were used under an intention-to-treat approach. RESULTS: In the GLP-1RA versus DPP4i cohort (n = 4920), GLP-1RA users had a lower risk of SUD hospitalization (HR 0.76; 95% CI, 0.67-0.86) and OUD hospitalization (HR 0.64; 95% CI, 0.43-0.96), with a nonsignificant trend for AUD (HR 0.76; 95% CI, 0.53-1.08). No significant differences were observed compared to SGLT2is (n = 4620). CONCLUSIONS: Among older adults with T2D, GLP-1RA use was associated with reduced SUD-related hospitalization versus DPP4i use, suggesting potential repurposing for SUD management. CI - (c) 2025 The Obesity Society. FAU - Dai, Hao AU - Dai H AUID- ORCID: 0000-0001-7950-3759 AD - Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. FAU - Radwan, Rotana M AU - Radwan RM AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Scheiffele, Grant D AU - Scheiffele GD AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Tang, Huilin AU - Tang H AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Sheer, Amy AU - Sheer A AD - Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Lin, Hsin-Yueh AU - Lin HY AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Zhang, Pengyue AU - Zhang P AD - Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. FAU - Adirika, Darlene AU - Adirika D AD - College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Luong, Kate AU - Luong K AD - College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. AD - Regenstrief Institute, Indianapolis, Indiana, USA. AD - Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, Indiana, USA. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250915 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Retrospective Studies MH - Medicare/statistics & numerical data MH - United States/epidemiology MH - Randomized Controlled Trials as Topic MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy/psychology MH - *Hospitalization/statistics & numerical data MH - *Substance-Related Disorders/complications/epidemiology MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - Proportional Hazards Models MH - Alcoholism/complications/epidemiology MH - Opioid-Related Disorders/complications/epidemiology MH - Humans MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use PMC - PMC12701773 MID - NIHMS2122877 OTO - NOTNLM OT - glucagon-like peptide 1 (GLP-1) OT - older adults OT - subtance use disorder OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/09/16 06:36 MHDA- 2026/09/02 05:36 PMCR- 2026/09/02 CRDT- 2025/09/16 00:23 PHST- 2025/07/12 00:00 [revised] PHST- 2025/05/08 00:00 [received] PHST- 2025/07/14 00:00 [accepted] PHST- 2026/09/02 05:36 [medline] PHST- 2025/09/16 06:36 [pubmed] PHST- 2025/09/16 00:23 [entrez] PHST- 2026/09/02 00:00 [pmc-release] AID - OBY70024 [pii] AID - 10.1002/oby.70024 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Sep;34 Suppl 2(Suppl 2):88-100. doi: 10.1002/oby.70024. Epub 2025 Sep 15. PMID- 40954421 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20251103 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 40 IP - 11 DP - 2025 Nov TI - Unmasking Aspiration Risks: A Propensity-Matched Odyssey of GLP-1 Receptor Agonists and Colonoscopy. PG - 2732-2737 LID - 10.1111/jgh.70071 [doi] AB - BACKGROUND AND AIMS: The use of glucagon-like peptide-1(GLP-1) receptor agonists has revolutionized the treatment of Type 2 diabetes mellitus and morbid obesity. They are known to slow gastric emptying and potentially increase the risk of pulmonary aspiration perioperatively. We aim to conduct a retrospective study to evaluate the risk of aspiration pneumonia in patients on GLP-1 receptor agonists undergoing colonoscopy. METHODS: A large research network (TriNetX LLC) comprising over 100 million patients was leveraged to obtain data from 2016 to 2024. Patients who underwent colonoscopy during the study period were divided into GLP-1 users and non-users. The primary outcomes were aspiration pneumonia and hospitalization following colonoscopy. The secondary outcomes were respiratory failure and the need for mechanical ventilation within 7 days of colonoscopy. RESULTS: Before propensity score matching, the study included 126 663 patients on GLP-1 agonists and 1 380 652 not on GLP-1 agonists. Propensity score matching resulted in balanced cohorts of 126 663 patients per group. After propensity score matching, the risk ratio for aspiration pneumonia in the GLP-1 agonist group was 0.70 (95% confidence interval, 0.50-0.98), suggesting a trend towards reduced risk and does not suggest increased risk of aspiration pneumonia. Similarly, no significant differences were observed in mechanical ventilation, respiratory failures, or hospitalization rates between the two groups. CONCLUSIONS: This large retrospective study shows no increased risk of aspiration pneumonia with GLP-1 agonist use, in patients undergoing screening colonoscopy. These findings suggest that minimally sedated gastroscopy prior to colonoscopy, routine GLP-1 agonist withholding, and overly restrictive fasting are not required. CI - (c) 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Chhabra, Puneet AU - Chhabra P AD - Department of Gastroenterology, Royal Hobart Hospital, Hobart, Australia. FAU - Bhandari, Ritesh AU - Bhandari R AD - Department of Gastroenterology, Royal Hobart Hospital, Hobart, Australia. FAU - Singh, Rituraj AU - Singh R AD - College of Medicine, University of Illinois, Peoria, Illinois, USA. LA - eng PT - Journal Article DEP - 20250915 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Colonoscopy/adverse effects MH - Propensity Score MH - *Pneumonia, Aspiration/etiology/epidemiology MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Hospitalization/statistics & numerical data MH - Risk Factors MH - Respiration, Artificial/statistics & numerical data OTO - NOTNLM OT - GLP-1 receptor agonists OT - aspiration pneumonia OT - colonoscopy EDAT- 2025/09/16 00:34 MHDA- 2025/11/03 13:49 CRDT- 2025/09/15 23:28 PHST- 2025/08/14 00:00 [revised] PHST- 2025/06/02 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/11/03 13:49 [medline] PHST- 2025/09/16 00:34 [pubmed] PHST- 2025/09/15 23:28 [entrez] AID - 10.1111/jgh.70071 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2025 Nov;40(11):2732-2737. doi: 10.1111/jgh.70071. Epub 2025 Sep 15. PMID- 40952752 OWN - NLM STAT- MEDLINE DCOM- 20251201 LR - 20260916 IS - 2168-6211 (Electronic) IS - 2168-6203 (Print) IS - 2168-6203 (Linking) VI - 179 IP - 12 DP - 2025 Dec 1 TI - Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - 1308-1317 LID - 10.1001/jamapediatrics.2025.3243 [doi] AB - IMPORTANCE: Obesity affects 1 in 5 children and adolescents, increasing the risk of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the few pharmacotherapy options available for this population, necessitating a comprehensive evaluation of efficacy and safety. OBJECTIVE: To assess the efficacy and safety of GLP-1 RAs in children and adolescents (<18 years) with obesity, prediabetes, or T2D. DATA SOURCES: A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized clinical trials (RCTs) published from inception until February 28, 2025. Data analysis was completed from January 2025 to April 2025. STUDY SELECTION: RCTs comparing GLP-1 RAs to placebo in children and adolescents with obesity, overweight, prediabetes, or T2D with reported safety and efficacy data were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data on sample size, population, interventions, follow-up, and outcomes. Risk of bias was assessed using version 2 of the Cochrane risk of bias tool (RoB2). Efficacy outcomes (except lipids) were analyzed as estimated treatment differences, lipids as estimated treatment ratios, and safety via rate ratios. A random-effects inverse variance model was used for all outcomes. MAIN OUTCOMES AND MEASURES: The primary efficacy outcomes were change in hemoglobin A1c (HbA1c) (in percentage points), fasting glucose (in milligrams per deciliter), body weight (in kilograms), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), BMI z scores or percentiles, BMI standard deviation score (SDS), lipid outcomes, and blood pressure. Exploratory efficacy outcomes included obstructive sleep apnea and metabolic dysfunction-associated steatohepatitis or metabolic dysfunction-associated steatotic liver disease. Safety outcomes included gastrointestinal adverse effects (GI AEs), infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations. RESULTS: A total of 18 RCTs (11 in obesity, 6 in T2D, and 1 in prediabetes) with 1402 participants (838 GLP-1 RA users and 564 placebo) were included (mean [range] age, 13.7 [6-17] years; 831 female participants (59.3%); median [IQR] treatment duration, 0.51 [0.25-1.00] years). GLP-1 RAs significantly reduced HbA1c (-0.44%; 95% CI, -0.68% to -0.21%), fasting glucose (-9.92 mg/dL; 95% CI, -16.20 to -3.64), body weight (-3.02 kg; 95% CI, -4.98 to -1.06), BMI (-1.45; 95% CI, -2.40 to -0.49), BMI SDS (-0.20; 95% CI, -0.36 to -0.05), BMI percentile (-7.24%; 95% CI, -12.97% to -1.51%), and systolic blood pressure (-2.73 mm Hg; 95% CI, -4.04 to -1.43) and increased GI AE (log[rate ratio] [RR], 0.75). Other AEs, including suicidal ideation or behaviors, showed no significant differences. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of 18 trials, GLP-1 RAs significantly improved glycemic, weight, and cardiometabolic outcomes in children and adolescents with T2D or obesity. Available data over a relatively short follow-up suggested suicidal ideation or behaviors were not significantly different, although GI AEs warrant attention in long-term management. FAU - Kotecha, Pareeta AU - Kotecha P AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville. AD - College of Pharmacy, University of Florida, Gainesville. FAU - Huang, Wenxi AU - Huang W AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville. AD - College of Pharmacy, University of Florida, Gainesville. FAU - Yeh, Ya-Yun AU - Yeh YY AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville. AD - College of Pharmacy, University of Florida, Gainesville. FAU - Narvaez, Valerie Martino AU - Narvaez VM AD - College of Pharmacy, University of Florida, Gainesville. FAU - Adirika, Darlene AU - Adirika D AD - College of Pharmacy, University of Florida, Gainesville. FAU - Tang, Huilin AU - Tang H AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia. FAU - Bernier, Angelina V AU - Bernier AV AD - Division of Pediatric Endocrinology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville. FAU - Westen, Sarah C AU - Westen SC AD - Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville. FAU - Smith, Steven M AU - Smith SM AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville. AD - College of Pharmacy, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville. FAU - Bian, Jiang AU - Bian J AD - Regenstrief Institute, Indianapolis, Indiana. AD - Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville. AD - College of Pharmacy, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - JAMA Pediatr JT - JAMA pediatrics JID - 101589544 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Child MH - Adolescent MH - *Pediatric Obesity/drug therapy/complications MH - *Prediabetic State/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC12439189 MID - NIHMS2122880 COIS- Conflict of Interest Disclosures: Dr Kotecha reported personal fees from Merck Sharp & Dohme for service as a summer intern, Novo Nordisk India for service as a regulatory medical writer, and Takeda Pharmaceuticals for service as a summer intern outside the submitted work. Dr Westen reported salary support through a contract with the University of Florida from Blue Circle Health; consulting fees from the American Diabetes Association and Breakthrough T1D; and being the sole proprietor of Wisdom of Meraki outside the submitted work. No other disclosures were reported. EDAT- 2025/09/15 12:34 MHDA- 2025/12/01 12:28 PMCR- 2026/09/15 CRDT- 2025/09/15 11:33 PHST- 2025/12/01 12:28 [medline] PHST- 2025/09/15 12:34 [pubmed] PHST- 2025/09/15 11:33 [entrez] PHST- 2026/09/15 00:00 [pmc-release] AID - 2838307 [pii] AID - poi250049 [pii] AID - 10.1001/jamapediatrics.2025.3243 [doi] PST - ppublish SO - JAMA Pediatr. 2025 Dec 1;179(12):1308-1317. doi: 10.1001/jamapediatrics.2025.3243. PMID- 40952016 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260925 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 21 IP - 9 DP - 2025 Sep TI - GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes. PG - e70621 LID - 10.1002/alz.70621 [doi] LID - e70621 AB - INTRODUCTION: To address gaps in current research, this study aims to compare the impact of exposure to glucagon-like peptide-1 receptor agonists (GLP-1RA) versus sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), and sulfonylureas (SU) on reducing the risk of dementia, using a rigorous targeted learning causal inference approach. METHODS: Using clinical and claims data from four diverse US health-care systems, we emulated three two-arm trials contrasting sustained treatment with GLP-1RA versus SGLT2i, DPP4i, and SU on dementia diagnosis. We included diabetes patients aged >/= 60 years who initiated medication between 2014 and 2022. We estimated cumulative risk differences at 2.5 years. RESULTS: In Cohort 1, there was no evidence of differential dementia risk between sustained exposure to GLP1-RA versus SGLT2i (adjusted risk difference [aRD] -0.001, 95% confidence interval [CI] -0.004, 0.001). In Cohorts 2 and 3, GLP-1RA was associated with reduced risk of dementia diagnosis compared to DPP4i and SU, respectively (aRD -0.013, 95% CI -0.017, -0.009; aRD -0.016, 95% CI -0.018, -0.015). DISCUSSION: Rigorous causal inference analysis suggests that sustained exposure to GLP-1RA may modestly reduce risk of dementia, compared to DPP4i or SU exposure-but not compared to SGLT2i. HIGHLIGHTS: We researched the comparative effects of diabetes medications on dementia. We studied a large, diverse observational cohort of patients with diabetes in the United States. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may modestly reduce risk of dementia compared to dipeptidyl peptidase 4 inhibitor or sulfonylurea exposure. GLP-1RAs do not show evidence of dementia risk reduction compared to sodium-glucose cotransporter 2 inhibitors. Physicians may consider this when making prescription decisions with patients. CI - (c) 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Nance, Nerissa AU - Nance N AUID- ORCID: 0000-0002-8407-2364 AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. AD - University of California, Berkeley School of Public Health, Berkeley, California, USA. AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Gilsanz, Paola AU - Gilsanz P AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - Karter, Andrew J AU - Karter AJ AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - Finertie, Holly AU - Finertie H AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - Schmittdiel, Julie A AU - Schmittdiel JA AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. AD - Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA. FAU - An, JaeJin AU - An J AD - Kaiser Permanente Southern California Research and Evaluation, Pasadena, California, USA. FAU - Adams, Alyce S AU - Adams AS AD - Stanford University, Stanford, California, USA. FAU - Oshiro, Caryn AU - Oshiro C AD - Kaiser Permanente Hawaii, Honolulu, Hawai'i, USA. FAU - Cassidy-Bushrow, Andrea E AU - Cassidy-Bushrow AE AD - Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan, USA. AD - Henry Ford Health + Michigan State University Health Sciences, Detroit, Michigan, USA. AD - Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA. FAU - Krahe-Dombrowski, Sarah AU - Krahe-Dombrowski S AD - Geisinger Research, Danville, Pennsylvania, USA. FAU - Yassin, Maher AU - Yassin M AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - Lin, Sharon AU - Lin S AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - Izadian, Keanu AU - Izadian K AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. FAU - O'Connor, Patrick J AU - O'Connor PJ AD - HealthPartners Institute, Bloomington, Minnesota, USA. FAU - Neugebauer, Romain AU - Neugebauer R AD - Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA. AD - Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA. LA - eng GR - P30 DK092924/DK/NIDDK NIH HHS/United States GR - R01 AG067199/AG/NIA NIH HHS/United States GR - DB-2020C2-20318/Patient-Centered Outcomes Research Institute (PCORI)/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - *Dementia/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - United States MH - Retrospective Studies PMC - PMC12434700 OTO - NOTNLM OT - causal inference OT - diabetes OT - diabetes medications OT - glucagon-like peptide-1 receptor agonist OT - longitudinal data OT - targeted learning COIS- Nerissa Nance conducted this research while employed as a graduate student researcher at University of California Berkeley through a financial gift to University of California Berkeley from Novo Nordisk. After completing this research as part of their graduate studies, Nerissa Nance accepted a position at Novo Nordisk. No other authors state disclosures. EDAT- 2025/09/15 12:32 MHDA- 2025/09/16 20:01 PMCR- 2025/09/15 CRDT- 2025/09/15 08:13 PHST- 2025/07/11 00:00 [revised] PHST- 2025/03/17 00:00 [received] PHST- 2025/07/24 00:00 [accepted] PHST- 2025/09/16 20:01 [medline] PHST- 2025/09/15 12:32 [pubmed] PHST- 2025/09/15 08:13 [entrez] PHST- 2025/09/15 00:00 [pmc-release] AID - ALZ70621 [pii] AID - 10.1002/alz.70621 [doi] PST - ppublish SO - Alzheimers Dement. 2025 Sep;21(9):e70621. doi: 10.1002/alz.70621. PMID- 40947139 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20250918 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 34 IP - 9 DP - 2025 Sep TI - Comparative Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1-RAs) in Type 2 Diabetes and Chronic Weight Management: A Real-World Data Study. PG - e70214 LID - 10.1002/pds.70214 [doi] LID - e70214 AB - PURPOSE: This study assessed serious clinical outcomes comparing glucagon-like peptide 1 receptor agonists (GLP-1-RAs) with sodium glucose co-transporter 2 inhibitors (SGLT2-Is) in patients with type 2 diabetes (T2DM) and patients without diabetes using two chronic weight management (CWM) regimens. METHODS: We performed a new user, active comparator cohort study in a large, national U.S. claims database. Adults who initiated GLP-1-RAs, SGLT2-Is, naltrexone/bupropion (NalBup), or phentermine/topiramate (PhenTop) from 1 January 2016 to 31 December 2023 were included. Potential confounding was controlled using propensity score weighting for 82 clinical and demographic covariates, and risk ratios (RRs) were estimated. RESULTS: This study included 330,684 GLP-1-RA users and 264,277 SGLT2-I users with T2DM. Among CWM patients without diabetes, we studied over 25,000 GLP-1-RA users, 5019 NalBup users, and 3841 PhenTop users. In both indications, GLP-1-RA users had higher rates of hospitalizations for gallbladder and biliary diseases with RRs ranging from 1.14 (95% CI: 1.06-1.22) in T2DM patients to 3.32 (95% CI: 1.44-7.64) in CWM patients. No reduction in the rate of cardiovascular events was observed for GLP-1-RA users with RRs ranging from 0.92 (95% CI: 0.37-2.25) in CWM patients to 1.03 (95% CI: 0.99-1.08) in T2DM patients. In T2DM patients, GLP-1-RA users had a lower rate of acute liver injury (RR: 0.76; 95% CI: 0.64-0.91). CONCLUSIONS: This study corroborates an increased risk of hospitalization for gall bladder and biliary conditions among users of GLP-1-RAs and found similar rates as comparators of MI or stroke when GLP-1-RAs were used for T2DM or CWM. This real-world study complements placebo-controlled trials and can further inform prescribing decisions. PROTOCOL REGISTRATION: The study protocol was pre-registered at the Center for Open Science's Real-World Evidence Registry and is publicly accessible online (https://doi.org/10.17605/OSF.IO/PSY74). CI - (c) 2025 Carelon Research Inc. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Hurwitz, Sarah Ruth AU - Hurwitz SR AUID- ORCID: 0000-0001-5629-160X AD - Carelon Research, Wilmington, Delaware, USA. FAU - Lanes, Stephan AU - Lanes S AD - Carelon Research, Wilmington, Delaware, USA. FAU - Quimbo, Tracey AU - Quimbo T AD - Carelon Research, Wilmington, Delaware, USA. FAU - Papazian, Anahit AU - Papazian A AD - Carelon Research, Wilmington, Delaware, USA. FAU - White, Jeff AU - White J AD - CarelonRx, Morristown, New Jersey, USA. FAU - Fisher, Vicki AU - Fisher V AD - CarelonRx, Morristown, New Jersey, USA. FAU - Cziraky, Mark J AU - Cziraky MJ AD - Carelon Research, Wilmington, Delaware, USA. FAU - Crowley, Matthew J AU - Crowley MJ AD - Duke University Medical Center, Durham, North Carolina, USA. FAU - Willey, Vincent J AU - Willey VJ AD - Carelon Research, Wilmington, Delaware, USA. LA - eng GR - CarelonRX/ PT - Comparative Study PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Aged MH - Adult MH - Databases, Factual MH - United States/epidemiology MH - Cohort Studies MH - Hospitalization/statistics & numerical data MH - Retrospective Studies PMC - PMC12433752 OTO - NOTNLM OT - GLP-1-RA OT - SGLT2 OT - diabetes OT - naltrexone-bupropion OT - phentermine-topiramate OT - safety OT - weight management COIS- This work was funded by CarelonRx, a pharmacy benefit manager. This study was designed and led by Carelon Research, a healthcare research company that frequently does contract research for pharmaceutical companies, including companies that manufacture or market the medications in this study. Both CarelonRx and Carelon Research are part of Elevance Health, a health insurance provider. The authors have declare no conflicts of interest. EDAT- 2025/09/15 00:33 MHDA- 2025/09/16 20:02 PMCR- 2025/09/15 CRDT- 2025/09/14 20:52 PHST- 2025/06/06 00:00 [revised] PHST- 2025/01/08 00:00 [received] PHST- 2025/08/22 00:00 [accepted] PHST- 2025/09/16 20:02 [medline] PHST- 2025/09/15 00:33 [pubmed] PHST- 2025/09/14 20:52 [entrez] PHST- 2025/09/15 00:00 [pmc-release] AID - PDS70214 [pii] AID - 10.1002/pds.70214 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70214. doi: 10.1002/pds.70214. PMID- 40945896 OWN - NLM STAT- MEDLINE DCOM- 20251010 LR - 20251010 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 1006 DP - 2025 Nov 5 TI - YN1548: A novel small-molecule agonist of human glucagon-like peptide-1 receptor for the treatment of type 2 diabetes mellitus and obesity. PG - 178143 LID - S0014-2999(25)00897-0 [pii] LID - 10.1016/j.ejphar.2025.178143 [doi] AB - Type 2 diabetes mellitus (T2DM) and obesity are the major global health concerns. Glucagon-like peptide-1 (GLP-1) receptor agonists are effective incretin-based treatments for T2DM and obesity. The patient compliance of peptide-based GLP-1 receptor agonists is limited due to subcutaneous administration. This study aimed to develop small-molecule GLP-1 receptor agonists that can be administered orally. Pharmacological properties of YN1548 were evaluated using in vitro assays in Chinese hamster ovary (CHO) cells expressing GLP-1 receptor and diabetic monkey models. YN1548 demonstrated potent binding to human GLP-1 receptor and activation of the cyclic adenosine monophosphate (cAMP) signaling pathway at a half-maximal effective concentration of 4.59, 24.28, and 2.20 nM in CHO cells expressing various levels of human GLP-1 receptor. The maximal efficacy, ranging from 101.0 % to 103.9 %, was comparable to GLP-1 (7-36) amide. YN1548 exhibited biased agonism, preferentially activating cAMP response over beta-arrestin recruitment, as well as selectivity for primate GLP-1 receptor. Pharmacokinetic evaluations indicated that YN1548 is suitable for oral administration. In diabetic monkeys, oral administration of YN1548 reduced blood glucose levels and enhanced insulin secretion in a concentration-dependent manner. YN1548 also reduced food intake and induced weight loss comparable to liraglutide, injectable GLP-1 receptor agonists. Toxicological studies in rats and monkeys revealed that YN1548 was well-tolerated up to 1000 and 500 mg/kg/day, respectively, with reversible and non-adverse changes in clinical pathology parameters. YN1548, a novel small-molecule GLP-1 receptor agonist, is a promising therapeutic candidate for the management of T2DM and obesity, addressing the unmet need for long-term and convenient oral treatments. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Je, In-Gyu AU - Je IG AD - Research Laboratories, Ildong Pharmaceutical Co., Ltd, Hwaseong-si, Republic of Korea; Yunovia Co., Ltd, Hwaseong-si, Republic of Korea; Graduate School of Biotechnology, Kyung Hee University, Yongin-si, Republic of Korea. FAU - Kim, Tae-Kwang AU - Kim TK AD - Research Laboratories, Ildong Pharmaceutical Co., Ltd, Hwaseong-si, Republic of Korea. FAU - Lee, Hyeong Jun AU - Lee HJ AD - Research Laboratories, Ildong Pharmaceutical Co., Ltd, Hwaseong-si, Republic of Korea. FAU - Lee, Mi-Young AU - Lee MY AD - Yunovia Co., Ltd, Hwaseong-si, Republic of Korea. FAU - An, Kyung-Mi AU - An KM AD - Yunovia Co., Ltd, Hwaseong-si, Republic of Korea. FAU - Park, Joon-Tae AU - Park JT AD - Yunovia Co., Ltd, Hwaseong-si, Republic of Korea. FAU - Kim, Ki-Young AU - Kim KY AD - Graduate School of Biotechnology, Kyung Hee University, Yongin-si, Republic of Korea. Electronic address: kiyoung@khu.ac.kr. LA - eng PT - Journal Article DEP - 20250911 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - E0399OZS9N (Cyclic AMP) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - CHO Cells MH - *Obesity/drug therapy/metabolism MH - Cricetulus MH - Male MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Rats MH - Cyclic AMP/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Cricetinae MH - Blood Glucose/metabolism/drug effects OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Small-molecule OT - Type 2 diabetes mellitus OT - YN1548 COIS- Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/14 00:29 MHDA- 2025/10/11 00:31 CRDT- 2025/09/13 19:18 PHST- 2025/05/13 00:00 [received] PHST- 2025/08/29 00:00 [revised] PHST- 2025/09/08 00:00 [accepted] PHST- 2025/10/11 00:31 [medline] PHST- 2025/09/14 00:29 [pubmed] PHST- 2025/09/13 19:18 [entrez] AID - S0014-2999(25)00897-0 [pii] AID - 10.1016/j.ejphar.2025.178143 [doi] PST - ppublish SO - Eur J Pharmacol. 2025 Nov 5;1006:178143. doi: 10.1016/j.ejphar.2025.178143. Epub 2025 Sep 11. PMID- 40945659 OWN - NLM STAT- MEDLINE DCOM- 20260108 LR - 20260108 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 1 DP - 2026 Jan TI - Comparative Risk of Adverse Pancreatic Events With GLP-1 Receptor Agonists, SGLT2 Inhibitors, DPP4 Inhibitors, and Sulfonylureas Among Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk. PG - 23-30 LID - S1530-891X(25)01021-3 [pii] LID - 10.1016/j.eprac.2025.09.004 [doi] AB - OBJECTIVE: Evidence on acute pancreatitis and pancreatic cancer with glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy is mixed, and no studies examined this risk directly across all commonly used classes of type 2 diabetes medications, particularly sodium-glucose cotransporter 2 inhibitors (SGLT2is) and sulfonylureas. METHODS: De-identified claims data from OptumLabs Data Warehouse and fee-for-service Medicare were used to emulate a target trial examining the risks of incident acute pancreatitis and pancreatic cancer among adults with type 2 diabetes and moderate cardiovascular risk. Propensity scores (estimated using the SuperLearner ensemble method) and inverse probability of treatment weighting emulated random treatment assignment to GLP-1RA, DPP-4i, SGLT2i, or sulfonylurea. RESULTS: The weighted study cohort included 388 262 patients starting GLP-1RA (N = 44 084), DPP-4i (N = 82 079), SGLT2i (N = 56 463), or a sulfonylurea (N = 205 636). SGLT2i was associated with a lower risk of acute pancreatitis compared with DPP-4i (hazard ratio [HR], 0.82; 95% CI, 0.68-0.98). Conversely, sulfonylurea was associated with a higher risk compared with GLP-1RA (HR, 1.28; 95% CI, 1.03-1.56) and SGLT2i (HR, 1.32; 95% CI, 1.12-1.57). There was no difference in acute pancreatitis risk between GLP-1RA and DPP-4i or GLP-1RA and SGLT2i. The risk of pancreatic cancer was lower with GLP-1RA compared with DPP-4i (HR, 0.56; 95% CI, 0.40-0.77). In contrast, risk was higher with SGLT2i and sulfonylurea compared with GLP-1RA (HR, 1.67; 95% CI, 1.12-2.49 and HR, 1.60; 95% CI, 1.17-2.19, respectively). CONCLUSION: GLP-1RA and DPP-4i therapy was not associated with increased risk of adverse pancreatic events. The lower risk of acute pancreatitis with SGLT2i therapy warrants further exploration. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Kalathiya, Urja N AU - Kalathiya UN AD - University of Maryland School of Medicine, Baltimore, Maryland. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Swarna, Kavya Sindu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington; Providence Medical Research Center, Spokane, Washington. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut; Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairie, Minnesota; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; University of Maryland Institute for Health Computing, North Bethesda, Maryland. Electronic address: Rozalina.McCoy@som.umaryland.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250911 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Sulfonylurea Compounds/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Male MH - Female MH - *Pancreatitis/chemically induced/epidemiology MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Pancreatic Neoplasms/epidemiology/chemically induced MH - *Cardiovascular Diseases/epidemiology MH - Adult MH - United States/epidemiology OTO - NOTNLM OT - DPP-4 inhibitor OT - GLP-1 receptor agonist OT - causal inference OT - incretin OT - target trial OT - type 2 diabetes COIS- Disclosure In the last 36 months, R.G.M. has received unrelated research support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institute of Health (NIH), the National Institute on Aging (NIA) of the NIH, the National Center for Advancing Translational Sciences (NCATS), and the American Diabetes Association (ADA). R.G.M. also served as a consultant to EmmiEducate (Wolters Kluwer) and the Yale-New Haven Health System and received speaking honoraria and travel support from the ADA. J.H. currently receives unrelated research support from the Centers for Medicare and Medicaid Services, the NIH, Agency for Healthcare Research and Quality (AHRQ), Patient-centered Outcomes Research Institute (PCORI), and the American Heart Association (AHA) (all unrelated to this work). J.J.N. receives unrelated research support from the NIH and the American College of Clinical Pharmacy; serves as a consultant to Bayer, Eli Lilly, Boehringer Ingelheim, and Proteomics International; and received other support from the ADA (all unrelated to this work). R.J.G. receives unrelated research supported by the NIH, Novo Nordisk, Dexcom, and Eli Lilly and consulting/advisory/honoraria fees from Abbott, Dexcom, Eli Lilly, Novo Nordisk, Bayer, Boehringer, Medtronic, and AstraZeneca, outside of this work. G.E.U. is partly supported by unrelated research grants from the NIH, Bayer, Abbott, and Dexcom and has served as a member of advisory boards for Dexcom, Corcept, and GlyCare Health, all unrelated to this work. J.S.R. currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program, AHRQ, and Arnold Ventures; J.S.R. formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST). In addition, J.S.R. was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc that was settled in September 2022. The other authors have no conflicts of interest to disclose. EDAT- 2025/09/14 00:29 MHDA- 2026/01/09 00:26 CRDT- 2025/09/13 19:14 PHST- 2025/06/19 00:00 [received] PHST- 2025/08/07 00:00 [revised] PHST- 2025/09/05 00:00 [accepted] PHST- 2026/01/09 00:26 [medline] PHST- 2025/09/14 00:29 [pubmed] PHST- 2025/09/13 19:14 [entrez] AID - S1530-891X(25)01021-3 [pii] AID - 10.1016/j.eprac.2025.09.004 [doi] PST - ppublish SO - Endocr Pract. 2026 Jan;32(1):23-30. doi: 10.1016/j.eprac.2025.09.004. Epub 2025 Sep 11. PMID- 40940281 OWN - NLM STAT- MEDLINE DCOM- 20260104 LR - 20260131 IS - 1471-6771 (Electronic) IS - 0007-0912 (Print) IS - 0007-0912 (Linking) VI - 136 IP - 1 DP - 2026 Jan TI - Risk of perioperative cardiorespiratory complications and mortality associated with preoperative glucagon-like peptide-1 receptor agonist use in type 2 diabetes mellitus: a nationwide propensity-score matched study. PG - 86-97 LID - S0007-0912(25)00531-8 [pii] LID - 10.1016/j.bja.2025.08.003 [doi] AB - BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has raised concerns about delayed gastric emptying, pulmonary aspiration, and respiratory complications. This study aimed to investigate the association between preoperative GLP-1 RA use and perioperative respiratory complications in type 2 diabetes mellitus. METHODS: We conducted a nationwide propensity-score matched cohort study using the TriNetX database to analyse adults with type 2 diabetes mellitus undergoing surgery in the USA from January 1, 2016, to December 31, 2024. The exposure of interest was use of GLP-1 RA (prescription within 90 days before surgery) compared with individuals not receiving GLP-1 RA. The primary outcome was postoperative respiratory complications within 30 days of surgery, including aspiration. RESULTS: After propensity matching in 296 389 matched pairs (mean [sd] age, 58 [12] yr; 57% female), 259/296 389 (0.09%) receiving GLP-1 RA before surgery had fewer respiratory complications, compared with 1017/296 389 (0.34%) individuals who were not prescribed GLP-1 RA (relative risk, 0.26 [95% confidence interval, 0.22-0.29]; P<0.0001). Pulmonary aspiration occurred in 24/296 389 (0.01%) individuals receiving GLP-1 RA, compared with 78/296 389 (0.03%) not receiving GLP-1 RA (relative risk, 0.31 [95% confidence interval, 0.20-0.49]; P<0.0001). Both long- and short-acting GLP-1 RA use was associated with fewer respiratory complications. CONCLUSIONS: Preoperative glucagon-like peptide-1 receptor agonists use was associated with reduced risks of perioperative respiratory complications in people with type 2 diabetes mellitus. These findings were observed in a real-world cohort, with uncertainty about whether measures were undertaken to reduce the risk of aspiration. CI - Copyright (c) 2025 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved. FAU - Wu, Hsiang-Ling AU - Wu HL AD - Department of Anaesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chen, Jui-Tai AU - Chen JT AD - Department of Anaesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Anaesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Cata, Juan Pablo AU - Cata JP AD - Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Hsieh, Chia-Hsing AU - Hsieh CH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan. FAU - Cherng, Yih-Giun AU - Cherng YG AD - Department of Anaesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Anaesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Tai, Ying-Hsuan AU - Tai YH AD - Department of Anaesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Anaesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: 18045@s.tmu.edu.tw. LA - eng PT - Journal Article DEP - 20250911 PL - England TA - Br J Anaesth JT - British journal of anaesthesia JID - 0372541 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Propensity Score MH - *Postoperative Complications/mortality/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cohort Studies MH - *Respiration Disorders/mortality MH - United States/epidemiology PMC - PMC12851884 OTO - NOTNLM OT - aspiration pneumonitis OT - diabetes mellitus OT - gastroparesis OT - pneumonia OT - postoperative outcomes OT - pulmonary aspiration COIS- Declaration of interest The authors declare that they have no conflicts of interest. EDAT- 2025/09/13 00:29 MHDA- 2026/01/05 00:49 PMCR- 2027/01/01 CRDT- 2025/09/12 21:55 PHST- 2025/05/01 00:00 [received] PHST- 2025/08/05 00:00 [revised] PHST- 2025/08/06 00:00 [accepted] PHST- 2026/01/05 00:49 [medline] PHST- 2025/09/13 00:29 [pubmed] PHST- 2025/09/12 21:55 [entrez] PHST- 2027/01/01 00:00 [pmc-release] AID - S0007-0912(25)00531-8 [pii] AID - 10.1016/j.bja.2025.08.003 [doi] PST - ppublish SO - Br J Anaesth. 2026 Jan;136(1):86-97. doi: 10.1016/j.bja.2025.08.003. Epub 2025 Sep 11. PMID- 40938549 OWN - NLM STAT- MEDLINE DCOM- 20260513 LR - 20260517 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 40 IP - 3 DP - 2026 Jun TI - Superior Cerebrovascular Outcomes with Tirzepatide versus Semaglutide in Diabetic CABG Patients: A Global Network Study of Propensity-Matched Patients. PG - 1001-1011 LID - 10.1007/s10557-025-07757-3 [doi] AB - PURPOSE: To compare the effectiveness of tirzepatide (a dual GLP-1/GIP receptor agonist) versus semaglutide (a GLP-1 receptor agonist) in improving postoperative outcomes among patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG). METHODS: We conducted a retrospective analysis using the TriNetX global research network, identifying 226,742 adults with T2DM who underwent isolated CABG between 2022 and 2024. Among these, 3,669 received tirzepatide and 19,521 received semaglutide. After 1:1 propensity score matching, 3,667 matched pairs were analyzed. Primary outcomes included cerebrovascular and cardiovascular events, postoperative complications, healthcare utilization, and all-cause mortality, assessed at 6-month and 3-year intervals. P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. RESULTS: Tirzepatide was associated with significantly lower risks of cerebrovascular events at both follow-up points, including reduced incidence of cerebrovascular disease (11.8% vs. 17.5%; HR = 0.831), cerebral infarction (4.6% vs. 7.3%; HR = 0.788), and cerebral occlusion without infarction (6.8% vs. 10.4%; HR = 0.838)-all of which remained statistically significant after multiple comparison correction (adjusted p = 0.0024). Cardiovascular outcomes also favored tirzepatide, with significant reductions in major adverse cardiovascular events (MACE) (39.7% vs. 49.5%; HR = 0.911), myocardial infarction (7.0% vs. 10.8%; HR = 0.838), and acute coronary disease (1.1% vs 2.3%; HR = 0.691); several of these remained significant after correction at both timepoints. While tirzepatide was associated with lower rates of surgical site infection, venous thrombosis, and CABG-specific complications, only venous thrombosis remained statistically significant after adjustment (adjusted p = 0.021). Additionally, tirzepatide users had reduced healthcare utilization and lower all-cause mortality, with 3-year readmission (16.4% vs. 23.4%; HR = 0.871) and mortality (1.9% vs. 4.7%; HR = 0.595) both remaining significant after adjustment (adjusted p = 0.002). Kaplan-Meier analysis confirmed sustained survival benefit. CONCLUSION: In patients with T2DM undergoing CABG, tirzepatide was associated with improved cerebrovascular and cardiovascular outcomes, reduced venous thrombotic complications, and lower long-term mortality and healthcare utilization compared to semaglutide. These findings support the therapeutic potential of dual GLP-1/GIP receptor agonism in high-risk post-CABG populations. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chunduri, Shriya AU - Chunduri S AD - Tulane University School of Medicine, New Orleans, LA, USA. FAU - Bidaoui, Ghassan AU - Bidaoui G AD - Tulane Research Innovation for Arrhythmia Discovery (TRIAD) Center, Tulane University School of Medicine, New Orleans, LA, USA. FAU - Hussein, Mohammad H AU - Hussein MH AD - Ochsner Clinic Foundation, New Orleans, LA, USA. FAU - Patel, Milee AU - Patel M AD - Tulane University School of Medicine, New Orleans, LA, USA. FAU - Abdelmaksoud, Ahmed AU - Abdelmaksoud A AD - Department of Internal Medicine, University of California, Riverside, CA, 92521, USA. FAU - Mohamed, Mohamed AU - Mohamed M AD - Department of Internal Medicine, University of California, Riverside, CA, 92521, USA. FAU - Attia, Abdallah AU - Attia A AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Tatum, Danielle AU - Tatum D AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Borgi, Jamil AU - Borgi J AUID- ORCID: 0000-0001-9267-3787 AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Toraih, Eman A AU - Toraih EA AD - Department of Cardiovascular Perfusion, College of Health Professions, Upstate Medical University, New York, NY, USA. etoraih@tulane.edu. AD - Genetics Unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. etoraih@tulane.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250912 PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Coronary Artery Bypass/adverse effects/mortality MH - Middle Aged MH - Aged MH - Retrospective Studies MH - *Cerebrovascular Disorders/prevention & control/mortality/epidemiology/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Coronary Artery Disease/surgery/mortality MH - Propensity Score MH - Risk Factors MH - Risk Assessment MH - Time Factors MH - Postoperative Complications/prevention & control MH - Tirzepatide OTO - NOTNLM OT - CABG OT - Cardiovascular outcomes OT - Cerebrovascular disease OT - GLP-1/GIP receptor agonist OT - Mortality OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes COIS- Declarations. Ethics Approval: This study utilized de-identified data from the TriNetX global federated health research network, therefore, ethics committee approval and informed consent were waived. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Consent to Participate: This study used de-identified patient data from TriNetX. As such, individual informed consent was not required. Consent for Publication: This study used de-identified patient data from TriNetX. As such, individual consent for publication was not required. Competing interests: The authors have no relevant financial or non-financial interests to disclose. EDAT- 2025/09/12 12:30 MHDA- 2026/05/13 12:32 CRDT- 2025/09/12 11:20 PHST- 2025/08/04 00:00 [accepted] PHST- 2026/05/13 12:32 [medline] PHST- 2025/09/12 12:30 [pubmed] PHST- 2025/09/12 11:20 [entrez] AID - 10.1007/s10557-025-07757-3 [pii] AID - 10.1007/s10557-025-07757-3 [doi] PST - ppublish SO - Cardiovasc Drugs Ther. 2026 Jun;40(3):1001-1011. doi: 10.1007/s10557-025-07757-3. Epub 2025 Sep 12. PMID- 40937414 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20250915 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review. PG - 1656884 LID - 10.3389/fendo.2025.1656884 [doi] LID - 1656884 AB - The development of once-weekly basal insulin analogues, such as insulin icodec and efsitora alfa, represents a promising strategy to reduce injection burden and improve adherence in diabetes management. This mini-review summarizes the recent findings from clinical trials evaluating once-weekly insulin therapies in both type 1 and type 2 diabetes. In type 1 diabetes, available data remain limited; however, the ONWARDS 6 and QWINT-5 trials demonstrated that once-weekly icodec and efsitora, respectively, achieved comparable reductions in HbA1c to once-daily insulin degludec, when used in combination with prandial insulin. In type 2 diabetes, accumulating evidences from randomized clinical trials supports the efficacy of once-weekly icodec and efsitora, showing non-inferiority-and in some cases, superiority-compared to once-daily basal insulin, both in insulin-naive individuals and in those previously treated with insulin. Safety profiles of once-weekly insulins in type 2 diabetes are reassuring, with similar rates of clinically significant and severe hypoglycemia compared to once-daily regimens. In contrast, trials in type 1 diabetes reported higher hypoglycemia rates with once-weekly insulins. Recent findings from the COMBINE program demonstrated that the fixed-ratio combination of icodec and semaglutide (IcoSema) produced superior HbA1c reductions compared to either agent alone, though not superior to a basal-bolus regimen with glargine and aspart insulin. However, several important questions remain to be addressed regarding once-weekly insulins, including their long-term efficacy on cardiovascular outcomes and overall long-term safety. CI - Copyright (c) 2025 Denimal. FAU - Denimal, Damien AU - Denimal D AD - Universite Bourgogne Europe, CHU Dijon Bourgogne, Department of Clinical Biochemistry, INSERM, CTM UMR 1231, PADYS team, Dijon, France. LA - eng PT - Journal Article PT - Review DEP - 20250827 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Long-Acting) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetes Mellitus, Type 1/drug therapy MH - *Hypoglycemic Agents/administration & dosage MH - Drug Administration Schedule MH - Insulin, Long-Acting/administration & dosage MH - Randomized Controlled Trials as Topic PMC - PMC12420296 OTO - NOTNLM OT - diabetes mellitus OT - glycemic control OT - insulin efsitora OT - insulin icodec OT - long-acting insulin COIS- The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/12 06:29 MHDA- 2025/09/16 00:32 PMCR- 2025/08/27 CRDT- 2025/09/12 04:44 PHST- 2025/06/30 00:00 [received] PHST- 2025/08/11 00:00 [accepted] PHST- 2025/09/16 00:32 [medline] PHST- 2025/09/12 06:29 [pubmed] PHST- 2025/09/12 04:44 [entrez] PHST- 2025/08/27 00:00 [pmc-release] AID - 10.3389/fendo.2025.1656884 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 27;16:1656884. doi: 10.3389/fendo.2025.1656884. eCollection 2025. PMID- 40936218 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Comparative efficacy and safety of Glucagon-like pepetide-1 receptor agonists with metformin in Asian versus non-Asian patients with type 2 diabetes: A systematic review and meta-analysis. PG - 6727-6736 LID - 10.1111/dom.70084 [doi] AB - AIMS: In type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin show better efficacy than metformin alone. Nevertheless, the reactions of different ethnic groups, especially Asian and non-Asian populations, are still controversial. To give clinical medication usage an evidence-based foundation, this meta-analysis examined GLP-1RAs' safety and efficacy when combined with metformin in the treatment of type 2 diabetes mellitus. MATERIALS AND METHODS: Up to January 2025, systematic searches for randomised controlled trials were carried out in PubMed, Embase, the Cochrane Library, SinoMed and Wanfang comparing GLP-1RA/metformin combination versus metformin alone in type 2 diabetes, with subgroup analyses for Asian versus non-Asian cohorts. RevMan version 5.3 was used for analyses, and the Cochrane tools for risk of bias were used for quality assessment. RESULTS: This meta-analysis comprised 11 papers in total (6 Asian trials: 750 people; 5 non-Asian trials: 1096 people). After treatment of GLP-1RAs combined with metformin, the Asian group showed greater improvement in glycosylated haemoglobin (HbA1c) (weighted mean differences [WMD], -1.09; 95% confidence intervals [CI], -1.48 to -0.71; subgroup heterogeneity: I(2) = 77.7%, p < 0.05) and weight (WMD, -4.16; 95% CI -6.11 to -2.22; subgroup heterogeneity: I(2) = 89.5%, p < 0.05) with a lower gastrointestinal (GI) events risk (relative risks, 0.76; 95% CI, 0.47 to 1.22; subgroup heterogeneity: I(2) = 93.7%, p < 0.00001). There were no racial variations in fasting glucose levels (p = 0.78) or hypoglycaemia (p = 0.16). CONCLUSIONS: This meta-analysis suggested potential ethnic variations in the treatment combining GLP-1RAs with metformin, with Asian populations achieving superior HbA1c reduction and weight loss alongside better GI tolerance. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Li, Wenxuan AU - Li W AUID- ORCID: 0009-0000-8704-9592 AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Huang, Linyan AU - Huang L AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Wang, Ruixue AU - Wang R AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Peng, Peiyan AU - Peng P AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Song, Aowen AU - Song A AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Zeng, Yi AU - Zeng Y AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. FAU - Zhang, Zhen AU - Zhang Z AUID- ORCID: 0000-0002-1252-7972 AD - Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. LA - eng GR - 81770804/The National Natural Science Foundation of China/ GR - 2023A1515012507/The Basic and Applied Basic Research Foundation of Guangdong Province/ GR - 82470846/The National Natural Science Foundation of China/ PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250911 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Asian People/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Metformin/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Treatment Outcome OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - metformin OT - type 2 diabetes EDAT- 2025/09/12 06:28 MHDA- 2025/10/13 00:27 CRDT- 2025/09/12 00:53 PHST- 2025/08/02 00:00 [revised] PHST- 2025/06/12 00:00 [received] PHST- 2025/08/21 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/09/12 06:28 [pubmed] PHST- 2025/09/12 00:53 [entrez] AID - 10.1111/dom.70084 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6727-6736. doi: 10.1111/dom.70084. Epub 2025 Sep 11. PMID- 40935040 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260820 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 328 IP - Pt 1 DP - 2025 Nov TI - Development of a potent Xenopus GLP-1-derived GLP-1/GIP/Y(2) receptor tri-agonist for obesity and type 2 diabetes. PG - 147553 LID - S0141-8130(25)08110-3 [pii] LID - 10.1016/j.ijbiomac.2025.147553 [doi] AB - The drug development strategy of combining the complementary effects of different endogenous metabolism related hormones into one molecule is receiving increasing attention. In this study, we developed the unimolecular GLP-1/GIP/Y(2) receptor triple agonist, aiming to simultaneously activating the GLP-1 and GIP receptors together with the appetite-curbing Y(2) receptor to achieve better weight loss and blood glucose control. One strategy for constructing this triple agonist peptide involves coupling the GLP-1/GIP receptor dual agonist moiety with the PYY moiety through a maleimide-thiol specific reaction. Another strategy is to directly synthesize peptides with essentially identical sequences through solid-phase synthesis. Through long-acting modifications and comprehensive receptor screening, we identified a novel triple agonist, GP-38, exhibiting potent and balanced activity at GIP, GLP-1, and Y(2) receptor. In diet-induced obesity mice, GP-38 showed favourable effects on lipid metabolism, weight reduction, and glucose homeostasis with semaglutide and cagrisema used as control. Collectively, these data demonstrate that GP-38, a highly potent triple agonist targeting GLP-1, GIP, and Y(2) receptor, significantly outperforms GLP-1 receptor monotherapy in improving glucose homeostasis and reducing body weight, offers a promising pathway for the development of new treatments for obesity and type 2 diabetes. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Liu, Xiyu AU - Liu X AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China. FAU - Gong, Binbin AU - Gong B AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310000, China. FAU - Wang, Ting AU - Wang T AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China. FAU - Hu, Guoqiang AU - Hu G AD - Taizhou Hospital, Zhejiang University, Taizhou, 317000, China. FAU - Han, Jing AU - Han J AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, 221116, China. FAU - Sun, Lidan AU - Sun L AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China; Taizhou Hospital, Zhejiang University, Taizhou, 317000, China. Electronic address: slidan89@zjxu.edu.cn. LA - eng PT - Journal Article DEP - 20250909 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Neuropeptide Y) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (neuropeptide Y2 receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) SB - IM MH - Animals MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Obesity/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Glucagon-Like Peptide 1/chemistry MH - Mice MH - *Receptors, Neuropeptide Y/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Semaglutide MH - Hypoglycemic Agents/pharmacology/chemistry MH - Male MH - Gastric Inhibitory Polypeptide MH - Blood Glucose OTO - NOTNLM OT - Glucagon-like peptide-1 OT - Glucose dependent insulinotropic polypeptide OT - Obesity OT - Peptide YY OT - Triple agonist COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/12 00:29 MHDA- 2026/08/20 11:41 CRDT- 2025/09/11 19:12 PHST- 2025/06/13 00:00 [received] PHST- 2025/08/26 00:00 [revised] PHST- 2025/09/07 00:00 [accepted] PHST- 2026/08/20 11:41 [medline] PHST- 2025/09/12 00:29 [pubmed] PHST- 2025/09/11 19:12 [entrez] AID - S0141-8130(25)08110-3 [pii] AID - 10.1016/j.ijbiomac.2025.147553 [doi] PST - ppublish SO - Int J Biol Macromol. 2025 Nov;328(Pt 1):147553. doi: 10.1016/j.ijbiomac.2025.147553. Epub 2025 Sep 9. PMID- 40934962 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20251202 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - Comparative effectiveness of OW GLP-1 RAs and other glucose-lowering therapies among Medicare beneficiaries with T2D and ASCVD. PG - 112473 LID - S0168-8227(25)00487-5 [pii] LID - 10.1016/j.diabres.2025.112473 [doi] AB - AIMS: To compare the incidence rates for cardiovascular (CV) outcomes and healthcare resource utilization (HCRU) and costs among patients treated with once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared with other non-insulin glucose lowering therapies (ONIGLTs). METHODS: This was an observational cohort study using Medicare fee-for-service claims data (2006-2022). Medicare beneficiaries with T2D and ASCVD treated with OW GLP-1 RAs or ONIGLTs were matched using propensity score matching. RESULTS: Among the total 398,470 Medicare beneficiaries, OW GLP-1 RAs were associated with reduced risk of CV events (hazard ratios [HRs] range: 0.72 to 0.88, P < 0.05 for all) compared with ONIGLTs, in addition to lower HCRU and costs including ASCVD-related total medical visits (incidence rate ratio [95 % CI]: 0.91 [0.90-0.93]; P < 0.001) and total medical costs (mean cost ratio [95 %CI]: 0.88 [0.86-0.91]; P < 0.001). Among OW GLP-1 RAs, semaglutide had the lowest risk of all CV outcomes when compared with SGLT2is (HRs range: 0.80 to 0.85, P < 0.05 for all) and DPP-4is (HRs range: 0.58 to 0.73; P < 0.001 for all). CONCLUSION: The study findings corroborate current guideline recommendations for GLP-1 RAs in people with T2D and ASCVD, and extend findings to lower HCRU and costs in a real-world setting, most notably for semaglutide. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, 111 River St Ste 1120, Hoboken, NJ 07030, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, 111 River St Ste 1120, Hoboken, NJ 07030, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, 15 York St, New Haven, CT 06510, USA. Electronic address: adam.dehavenon@yale.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250909 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - United States/epidemiology MH - Medicare/statistics & numerical data MH - Female MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use/economics/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications/economics/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Aged, 80 and over OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Healthcare cost OT - Major adverse cardiovascular events OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest AdH reports NIH/NINDS funding (K23NS105924, R01NS130189, UG3NS130228, R21NS138995), has received investigator-initiated clinical research funding from the AAN, receives consultant fees from Novo Nordisk, receives royalty fees from UpToDate, and has equity in Titin KM and Certus. XT, YL, LX, CM, and CS are employees of Novo Nordisk Inc. JH and CG are employees of Genesis Research Group. EDAT- 2025/09/12 00:29 MHDA- 2025/10/31 00:29 CRDT- 2025/09/11 19:11 PHST- 2025/04/30 00:00 [received] PHST- 2025/08/28 00:00 [revised] PHST- 2025/09/07 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/12 00:29 [pubmed] PHST- 2025/09/11 19:11 [entrez] AID - S0168-8227(25)00487-5 [pii] AID - 10.1016/j.diabres.2025.112473 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112473. doi: 10.1016/j.diabres.2025.112473. Epub 2025 Sep 9. PMID- 40933383 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Effect of semaglutide on arrhythmic, major cardiovascular, and microvascular outcomes in patients with type 2 diabetes: a systematic review and meta-analysis. PG - 1554795 LID - 10.3389/fendo.2025.1554795 [doi] LID - 1554795 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in managing hyperglycemia and reducing cardiovascular (CV) outcomes. However, its effects on arrhythmic, major CV, and microvascular outcomes remain uncertain. This systematic review and meta-analysis aimed to evaluate these outcomes in patients with type 2 diabetes (T2D) treated with semaglutide. METHODS: We searched the PubMed, Embase, and Cochrane databases for eligible randomized controlled trials (RCTs) reported up to November 2024. We performed a meta-analysis via a random-effects model to estimate overall relative risks (RRs) with 95% confidence intervals (CIs) for arrhythmic, major CV, and microvascular outcomes. We conducted subgroup analyses on the basis of different administration types, treatment comparisons, and treatment durations. Additionally, we performed a meta-regression for retinopathy complications on the basis of baseline patient characteristics. RESULTS: This meta-analysis included 30 RCTs encompassing 32490 patients with T2D. Compared with the controls, semaglutide significantly reduced the incidence of atrial fibrillation (AF) (RR 0.73, 95% CI 0.54 to 0.98), complete atrioventricular (AV) block (RR 0.22, 95% CI 0.06 to 0.80), death from CV causes (RR 0.76, 95% CI 0.58 to 0.98), and revascularization (RR 0.68, 95% CI 0.52 to 0.88). Subgroup analyses revealed that semaglutide (long-term treatment) reduced the risk of AF, supraventricular tachycardia, and complete AV block. Meta-regression analysis revealed that the heterogeneity of retinopathy complications was not associated with baseline patient characteristics. CONCLUSION: Semaglutide reduces the risk of AF, complete AV block, death from CV causes, and revascularization in patients with T2D, with long-term treatment showing greater benefits for arrhythmic outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024618146. CI - Copyright (c) 2025 Wu, Xing, Huang, Zhou, Sun, Yu and Wang. FAU - Wu, Rui AU - Wu R AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Xing, Bo AU - Xing B AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Huang, Yuting AU - Huang Y AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Zhou, Zijun AU - Zhou Z AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Sun, Boxuan AU - Sun B AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Yu, Liming AU - Yu L AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Wang, Huishan AU - Wang H AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/etiology/drug therapy/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - *Arrhythmias, Cardiac/drug therapy/etiology/prevention & control MH - Randomized Controlled Trials as Topic MH - *Microvessels/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12417197 OTO - NOTNLM OT - arrhythmic OT - cardiovascular OT - meta-analysis OT - microvascular OT - semaglutide OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/11 18:29 MHDA- 2025/09/16 00:32 PMCR- 2025/08/26 CRDT- 2025/09/11 12:35 PHST- 2025/01/10 00:00 [received] PHST- 2025/08/15 00:00 [accepted] PHST- 2025/09/16 00:32 [medline] PHST- 2025/09/11 18:29 [pubmed] PHST- 2025/09/11 12:35 [entrez] PHST- 2025/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1554795 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 26;16:1554795. doi: 10.3389/fendo.2025.1554795. eCollection 2025. PMID- 40933382 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - The impact of oral semaglutide on glycemic control and weight reduction: a database analysis of dosing effects in Japanese individuals with type 2 diabetes. PG - 1615516 LID - 10.3389/fendo.2025.1615516 [doi] LID - 1615516 AB - OBJECTIVE: GLP-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events in type 2 diabetes (T2D), and oral formulations improve accessibility. However, their real-world effectiveness and predictors of response remain unclear. This study assessed the proportions of individuals achieving HbA1c < 7.0% and experiencing >/=3.0% weight reduction after 180 days of maintenance-dose therapy (no dose modification for >/=180 days). METHODS: We retrospectively analyzed 169 participants with T2D (3 mg: n=45; 7 mg: n=92; 14 mg: n=32) treated at a single medical care center in Japan. The cohort included participants with HbA1c >/= 7.0% at baseline. We evaluated semaglutide changes in HbA1c and weight, and predictors of glycemic response after 180 days of maintenance therapy using logistic regression. RESULTS: Baseline characteristics included median age 63.0 years, body mass index (BMI) 27.2 kg/m(2), diabetes duration 10.0 years, and HbA1c 7.7%. Oral semaglutide was initiated as the first or second choice in 45.0% of participants. HbA1c < 7.0% was achieved in 60.0%, 53.3%, and 46.9% of the 3 mg, 7 mg, and 14 mg groups, respectively. Weight reduction >/= 3.0% occurred in approximately half of participants across all groups. Lower baseline HbA1c (B = -1.330, p < 0.001) and earlier semaglutide use (first/second choice; B = 1.070, p = 0.013) were significant predictors of HbA1c < 7.0%. CONCLUSION: Approximately 50% of participants across all dosing groups achieved HbA1c < 7.0% after 180 days of maintenance therapy. Weight reduction (>/= 3.0%) occurred frequently in parallel with HbA1c reduction. Early semaglutide use (first/second choice) and lower baseline HbA1c predicted HbA1c < 7.0% on maintenance therapy. CI - Copyright (c) 2025 Ishiguro and Nishimura. FAU - Ishiguro, Mizuki AU - Ishiguro M AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20250826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Japan/epidemiology MH - Retrospective Studies MH - *Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12417148 OTO - NOTNLM OT - GLP-1 receptor agonists OT - HbA1c OT - oral antidiabetic drugs OT - semaglutide OT - type 2 diabetes COIS- The authors of this manuscript have the following competing interests: RN has received honoraria from Sanofi Co., Ltd., Japan Medtronic Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Teijin, Kissei Pharmaceutical Co., Ltd., Abbott, Eli Lilly Japan Co., Ltd., Novo Nordisk Pharma Co., Ltd., and Astellas Pharma Inc. RN has also received research funding from Kowa Co., Ltd. and Mitsubishi Electric Corporation. In addition, commercial entities have endowed departments with which RN is affiliated, including Taisho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Abbott, Arkley Co., Ltd., and Kowa Co., Ltd. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/11 18:30 MHDA- 2025/09/15 18:34 PMCR- 2025/08/26 CRDT- 2025/09/11 12:35 PHST- 2025/04/21 00:00 [received] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/15 18:34 [medline] PHST- 2025/09/11 18:30 [pubmed] PHST- 2025/09/11 12:35 [entrez] PHST- 2025/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1615516 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 26;16:1615516. doi: 10.3389/fendo.2025.1615516. eCollection 2025. PMID- 40933374 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20250916 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Comparative effectiveness and safety of sodium-glucose cotransporter 2 inhibitors vs glucagon-like peptide 1 receptor agonists in elderly patients with type 2 diabetes mellitus: a meta-analysis. PG - 1486655 LID - 10.3389/fendo.2025.1486655 [doi] LID - 1486655 AB - OBJECTIVE: This systematic review aimed to evaluate the cardiovascular effectiveness and safety of initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) in comparison to glucagon-like peptide 1 receptor agonists (GLP-1RA) among elderly patients with diabetes. METHODS: A comprehensive search of the PubMed, Embase, and Web of Science databases was conducted up to March 2024. The summary standard mean differences and odds ratios were calculated. RESULTS: Twelve studies of eleven articles were included in the analysis. Older patients receiving SGLT2i had a greater incidence of euglycemic ketoacidosis (EKA) (OR 1.622, 95% CI 1.276-2.062, p = 0.000) and genitourinary infection (GUI) (OR 3.59, 95% CI 3.31-3.89, p = 0.00) than did those receiving GLP-1RA, and the opposite was true for acute kidney injury (AKI) (OR 0.902, 95% CI 0.854 - 0.952, p = 0.00). However, no significant differences were detected for major adverse cardiovascular events (MACE) (OR 1.04, 95% CI 0.95-1.13, p = 0.386), hospitalization for heart failure (HHF) (OR 0.98 95% CI 0.83-1.16, p = 0.825), myocardial infarction (MI) (OR 1.09, 95% CI 0.94-1.26, p = 0.265), stroke (OR 1.22, 95% CI 1.02-1.45, p = 0.028), total adverse events (AEs), (OR 0.98, 95% CI 0.83-1.16, p = 0.825), serious AEs (OR 1.02, 95% CI 0.94 -1.11, p = 0.594), fractures (OR 1.07, 95% CI 0.92-1.24, p = 0.394) or hypoglycemia (OR 0.95, 95% CI 0.88-1.02, p = 0.141). CONCLUSION: In conclusion, although SGLT2i increase the risk of EKA and GUI and GLP-1RA decrease the risk of AKI, SGLT2i are at comparable risk of MACE, HHF, MI, stroke, hypoglycemia, and fracture to GLP-1RA. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518348. CI - Copyright (c) 2025 Wang, Wu, Yang, Ma, Li, He, Xiao and Pan. FAU - Wang, Yao AU - Wang Y AD - Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China. AD - College of Pharmacy, Chengdu University, Chengdu, Sichuan, China. FAU - Wu, Haoming AU - Wu H AD - School of Preclinical Medicine of Chengdu University, Chengdu University, Chengdu, Sichuan, China. FAU - Yang, Jingxian AU - Yang J AD - Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China. FAU - Ma, Jun AU - Ma J AD - West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Li, Hongling AU - Li H AD - College of Pharmacy, Chengdu University, Chengdu, Sichuan, China. FAU - He, Xinyu AU - He X AD - Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China. FAU - Xiao, Yibo AU - Xiao Y AD - Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China. FAU - Pan, Yan AU - Pan Y AD - Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome PMC - PMC12417164 OTO - NOTNLM OT - GLP-1RA OT - SGLT-2i OT - elderly OT - meta-analysis OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. EDAT- 2025/09/11 18:29 MHDA- 2025/09/15 18:33 PMCR- 2025/08/26 CRDT- 2025/09/11 12:35 PHST- 2024/11/19 00:00 [received] PHST- 2025/06/23 00:00 [accepted] PHST- 2025/09/15 18:33 [medline] PHST- 2025/09/11 18:29 [pubmed] PHST- 2025/09/11 12:35 [entrez] PHST- 2025/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1486655 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 26;16:1486655. doi: 10.3389/fendo.2025.1486655. eCollection 2025. PMID- 40932602 OWN - NLM STAT- MEDLINE DCOM- 20251216 LR - 20251216 IS - 1827-1669 (Electronic) IS - 0026-4806 (Linking) VI - 116 IP - 6 DP - 2025 Dec TI - Glucagon-like peptide-1 receptor agonists and its possible nephroprotective role: a systematic review. PG - 454-460 LID - 10.23736/S0026-4806.25.09709-5 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used to manage type 2 diabetes (T2DM), offering benefits not only for blood sugar control but also potentially for kidney health. While some studies have looked at kidney function, no review has specifically focused on how these medications impact kidney health in people with diabetes. EVIDENCE ACQUISITION: We conducted a review of existing studies following established guidelines. We searched databases like PubMed, Embase, Web of Science, and the Cochrane Library for studies that examined kidney outcomes - such as estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) - in T2DM patients treated with GLP-1RAs. We also assessed the quality of these studies using well-known bias risk tools. EVIDENCE SYNTHESIS: We included 13 studies, including clinical trials and observational research. Overall, the findings suggest that GLP-1RAs may help slow the decline in kidney function, reduce proteinuria and improve other kidney health markers in people with T2DM. However, the results weren't consistent - some studies showed clear benefits, while others found little to no effect. CONCLUSIONS: This review highlights the potential for GLP-1RAs to protect kidney function in people with type 2 diabetes. Although the evidence is encouraging, the differences between studies suggest the need for more large-scale, well-designed trials to confirm these effects and help guide treatment decisions. FAU - Perencin, Alessandro AU - Perencin A AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - Ceolin, Chiara AU - Ceolin C AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. AD - Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden. FAU - Papa, Mario V AU - Papa MV AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy - mariovirgilio.papa@phd.unipd.it. FAU - DI Marzio, Benedetta AU - DI Marzio B AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - Zanforlini, Bruno M AU - Zanforlini BM AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - Devita, Maria AU - Devita M AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. AD - Department of General Psychology (DPG), University of Padua, Padua, Italy. FAU - Curreri, Chiara AU - Curreri C AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - Gasparini, Giulia AU - Gasparini G AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - Sergi, Giuseppe AU - Sergi G AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. FAU - DE Rui, Marina AU - DE Rui M AD - Department of Medicine (DIMED) Geriatrics Division, University of Padua, Padua, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250911 PL - Italy TA - Minerva Med JT - Minerva medica JID - 0400732 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glomerular Filtration Rate/drug effects MH - Kidney/drug effects EDAT- 2025/09/11 12:31 MHDA- 2025/12/16 13:13 CRDT- 2025/09/11 11:11 PHST- 2025/12/16 13:13 [medline] PHST- 2025/09/11 12:31 [pubmed] PHST- 2025/09/11 11:11 [entrez] AID - S0026-4806.25.09709-5 [pii] AID - 10.23736/S0026-4806.25.09709-5 [doi] PST - ppublish SO - Minerva Med. 2025 Dec;116(6):454-460. doi: 10.23736/S0026-4806.25.09709-5. Epub 2025 Sep 11. PMID- 40932012 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Sex differences in the efficacy of GLP-1 receptor agonists: A systematic review and meta-analysis of cardiovascular and renal outcome trials. PG - 6847-6856 LID - 10.1111/dom.70123 [doi] AB - Sex-based differences in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on cardiovascular, renal, and cerebrovascular outcomes remain unclear. This systematic review and meta-analysis evaluated sex-specific effects of GLP-1RAs in patients with type 2 diabetes mellitus and related comorbidities. Randomised controlled trials and secondary analyses comparing GLP-1RAs with placebo and reporting sex-stratified data were included. Outcomes assessed included composite kidney outcomes, 3-point major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke), individual components of MACE, and hospitalization for heart failure (HHF). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Eleven trials comprising 85,273 patients (43, 339 receiving GLP-1RAs; 41, 934 placebo) were analysed. GLP-1RAs significantly reduced the risk of composite kidney outcomes by 20% in males (HR: 0.80; 95% CI: 0.69-0.92) and 31% in females (HR: 0.69; 95% CI: 0.54-0.87), with no significant sex interaction (p = 0.31). The risk of 3-point MACE was reduced by 14% in males (HR: 0.86; 95% CI: 0.79-0.93) and 18% in females (HR: 0.82; 95% CI: 0.75-0.90; p = 0.47). Stroke risk decreased by 21% in males and 25% in females. No significant sex-based differences were observed for cardiovascular death, myocardial infarction, or HHF. GLP-1RAs reduce the risk of major cardiovascular, kidney, and cerebrovascular outcomes in both sexes, with consistent benefits across men and women. While variations between sexes were observed in certain outcomes, these differences did not reach statistical significance for interaction. Future trials should improve female representation and explore sex-specific effects further. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Siddiqui, Hasan Fareed AU - Siddiqui HF AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Ali, Dua AU - Ali D AUID- ORCID: 0009-0003-9925-2098 AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Sajid, Maryam AU - Sajid M AUID- ORCID: 0009-0007-3544-3513 AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Qureshi, Shaheer AU - Qureshi S AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Siddiqui, Hibah AU - Siddiqui H AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Hasan, Ali AU - Hasan A AD - Department of Medicine, National Heart and Lung Institute, Imperial College London, London, UK. FAU - Ripley, David AU - Ripley D AD - Department of Medicine, Northumbria Hospitals NHS Foundation Trust, Tyneside, Tyne and Wear, UK. FAU - Ahmed, Raheel AU - Ahmed R AD - Department of Medicine, National Heart and Lung Institute, Imperial College London, London, UK. AD - Department of Medicine, Newcastle University, Newcastle upon Tyne, UK. AD - Department of Medicine, University of Sunderland, Sunderland, UK. AD - Department of Medicine, Freeman Hospital, Newcastle upon Tyne, UK. FAU - Waqas, Saad Ahmed AU - Waqas SA AUID- ORCID: 0009-0008-9051-6081 AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250911 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Sex Factors MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Randomized Controlled Trials as Topic MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - Treatment Outcome PMC - PMC12587241 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MACE OT - gender differences OT - hospitalization for heart failure OT - myocardial infarction OT - stroke COIS- The authors declare that they have no conflicts of interest. EDAT- 2025/09/11 12:30 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/11 07:13 PHST- 2025/08/12 00:00 [revised] PHST- 2025/07/17 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/11 12:30 [pubmed] PHST- 2025/09/11 07:13 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70123 [pii] AID - 10.1111/dom.70123 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):6847-6856. doi: 10.1111/dom.70123. Epub 2025 Sep 11. PMID- 40931739 OWN - NLM STAT- MEDLINE DCOM- 20250911 LR - 20250912 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 80 IP - 9 DP - 2025 Sep TI - [Tirzepatide (Mounjaro(R)) : a GIP/GLP-1 receptor dual agonist for the treatment of type 2 diabetes]. PG - 618-624 AB - Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, recently commercialized and reimbursed in Belgium for the treatment of type 2 diabetes (T2D). Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg as a once-weekly subcutaneous injection), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. Tirzepatide tolerance is almost similar to that of pure GLP-1 receptor agonists, with digestive adverse events, most often during the first weeks after initiation, which justifies the recommendation of progressive titration every four weeks. Tirzepatide is now refunded under conditions in Belgium for the treatment of TD2 in patients with a body mass index >/= 30 kg/m(2) and a HbA1c level > 7.5 % with antihyperglycaemic therapy including metformin. These reimbursement conditions are similar to those of pure GLP-1 receptor agonists but are more restrictive than the indications validated by the European Medicines Agency and the latest guidelines by international scientific societies. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), Liege Universite, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Le medicament du mois. Le tirzepatide (Mounjaro(R))▼: un agoniste double des recepteurs GIP/GLP-1 pour le traitement du diabete de type 2. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Tirzepatide MH - *Gastric Inhibitory Polypeptide/therapeutic use/analogs & derivatives MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use OTO - NOTNLM OT - Body Weight OT - GIP/GLP-1 dual agonist OT - Glycated Haemoglobin OT - Obesity OT - Tirzepatide OT - Type 2 diabetes EDAT- 2025/09/11 06:28 MHDA- 2025/09/11 06:29 CRDT- 2025/09/11 03:52 PHST- 2025/09/11 06:29 [medline] PHST- 2025/09/11 06:28 [pubmed] PHST- 2025/09/11 03:52 [entrez] PST - ppublish SO - Rev Med Liege. 2025 Sep;80(9):618-624. PMID- 40926380 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Cardiovascular risk reduction with glucagon-like peptide-1 receptor agonists is proportional to HbA1c lowering in type 2 diabetes: An updated meta-regression analysis incorporating FLOW and SOUL trials. PG - 7210-7220 LID - 10.1111/dom.70121 [doi] AB - AIMS: To evaluate relationships of cardiovascular and kidney outcomes with glycemic or bodyweight reductions in randomised placebo-controlled trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs), incorporating data from FLOW and SOUL trials. MATERIALS AND METHODS: PubMed and EMBASE were searched up to 22 August 2025 for placebo-controlled randomized trials of oral or bolus-type, subcutaneous GLP-1RAs reporting major adverse cardiovascular events (MACE; a composite of cardiovascular death, myocardial infarction, and stroke) in adults with type 2 diabetes. The primary outcome was MACE; secondary outcomes included heart failure (HF) and kidney outcomes. Random-effects meta-analyses were followed by meta-regression evaluating associations with HbA1c and bodyweight reduction. RESULTS: A total of 73 263 individuals were included from 10 trials (ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, PIONEER 6, REWIND, AMPLITUDE-O, FLOW, and SOUL). GLP-1RAs reduced MACE by 14% (hazard ratio: 0.86; 95% CI: 0.82 to 0.91; p <0.001), as well as hospitalisation for HF and the composite kidney outcome (both p <0.001). Meta-regression showed that every 1% extra reduction in HbA1c corresponded to a 27% lower HR for MACE (p = 0.015; R(2) = 0.61). While HbA1c reduction was not significantly associated with secondary outcomes, the directionality was consistent with MACE. Bodyweight change was not associated with any of the analysed endpoints, including MACE (p = 0.13; R(2) = 0.21). CONCLUSIONS: HbA1c reduction, not bodyweight change, was significantly and proportionally associated with MACE risk reduction. HbA1c lowering may serve as a useful surrogate for the cardiovascular improvements associated with GLP-1RAs in type 2 diabetes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hasebe, Masashi AU - Hasebe M AUID- ORCID: 0000-0001-7031-2446 AD - Canada Excellence Research Chair in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Su, Chen-Yang AU - Su CY AUID- ORCID: 0000-0001-6071-4660 AD - Canada Excellence Research Chair in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada. FAU - Keidai, Yamato AU - Keidai Y AUID- ORCID: 0000-0001-6271-9609 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Minamino, Hiroto AU - Minamino H AUID- ORCID: 0000-0002-9113-4690 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Inagaki, Nobuya AU - Inagaki N AUID- ORCID: 0000-0001-8261-2593 AD - Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan. FAU - Yoshiji, Satoshi AU - Yoshiji S AUID- ORCID: 0000-0001-8863-2413 AD - Canada Excellence Research Chair in Genomic Medicine, McGill University, Montreal, Quebec, Canada. AD - Department of Human Genetics, McGill University, Montreal, Quebec, Canada. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycated Hemoglobin/analysis MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss PMC - PMC12587236 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular disease OT - meta-analysis OT - type 2 diabetes COIS- DY received clinically commissioned or joint research grants from Novo Nordisk, Ono Pharmaceutical, Taisho Pharmaceutical, Terumo, and Arklay. DY also received consulting or speaker fees from Sumitomo Dainippon Pharma, Boehringer Ingelheim, Astellas Pharma, MSD, Novo Nordisk, Ono Pharmaceutical, Eli Lilly, and Takeda Pharmaceutical. NI received joint research grants from Asken Inc.; speaker honoraria from Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co., Ltd., Sanofi K.K., and Mitsubishi Tanabe Pharma Corporation; and scholarship grants from Mitsubishi Tanabe Pharma Corporation, Sumitomo Pharma Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. SY serves as an Analytical Consultant for the Broad Institute of MIT and Harvard under contract with Precision Global Consulting. All other authors declare no conflicts of interest. EDAT- 2025/09/10 06:29 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/10 01:13 PHST- 2025/08/25 00:00 [revised] PHST- 2025/07/26 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/10 06:29 [pubmed] PHST- 2025/09/10 01:13 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70121 [pii] AID - 10.1111/dom.70121 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7210-7220. doi: 10.1111/dom.70121. Epub 2025 Sep 9. PMID- 40926360 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World). PG - 6691-6704 LID - 10.1111/dom.70080 [doi] AB - AIMS: In this first interim analysis of the SCORE study, we investigated the risk of major adverse cardiovascular events (MACE) among individuals with atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity but without diabetes who initiated semaglutide 2.4 mg in real-world settings. MATERIALS AND METHODS: Individuals initiating semaglutide 2.4 mg aged >/=45 years with ASCVD and overweight/obesity but without diabetes were identified in a US database (01/01/2016-12/31/2023) and matched 1:2 to those not on semaglutide based on a non-parsimonious propensity-score model. The primary outcomes included revised 3-point MACE (rMACE-3: myocardial infarction, stroke, and all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, coronary revascularisation, and hospitalisation for heart failure). Secondary outcomes included MACE-3 and MACE-5, defined similarly to rMACE-3 and rMACE-5 but replacing all-cause mortality with cardiovascular-related mortality. Exploratory outcomes included incident type 2 diabetes, major adverse kidney events, and major obesity-related adverse events. RESULTS: A total of 9321 individuals on semaglutide 2.4 mg were matched to 18,642 individuals not on semaglutide; patient characteristics were well-balanced between cohorts. Over a mean follow-up of 200 days, semaglutide 2.4 mg was associated with significantly lower risks of rMACE-5 (hazard ratio: 0.55; p < 0.001), rMACE-3 (0.43; p < 0.001), MACE-5 (0.65; p < 0.001), and MACE-3 (0.58; p < 0.01). Semaglutide 2.4 mg was also associated with lower risks of all-cause mortality, cardiovascular-related mortality, hospitalisation for heart failure, and all exploratory outcomes. CONCLUSIONS: In this real-world study of US individuals with ASCVD and overweight/obesity but without diabetes, semaglutide 2.4 mg was associated with significantly reduced risk of MACEs and other obesity-related morbidities (NCT06874751). CI - (c) 2025 Novo Nordisk Inc and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Smolderen, Kim G AU - Smolderen KG AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Section of Psychology, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Mena-Hurtado, Carlos AU - Mena-Hurtado C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Michalak, Wojciech AU - Michalak W AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Faurby, Mads AU - Faurby M AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Smolarz, B Gabriel AU - Smolarz BG AUID- ORCID: 0000-0002-8591-3858 AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Chen, Yan AU - Chen Y AUID- ORCID: 0000-0002-5317-1909 AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Boland, Joanna AU - Boland J AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. LA - eng SI - ClinicalTrials.gov/NCT06874751 GR - K76 AG088428/AG/NIA NIH HHS/United States GR - P30 AG021342/AG/NIA NIH HHS/United States GR - Novo Nordisk, Inc./ PT - Journal Article PT - Observational Study DEP - 20250909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Atherosclerosis/complications/epidemiology MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Obesity/complications/drug therapy/epidemiology MH - *Overweight/complications/drug therapy/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12515752 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - cohort study OT - observational study OT - real-world evidence OT - semaglutide COIS- Zhenxiang Zhao, Wojciech Michalak, Mads Faurby, and B. Gabriel Smolarz are employees of Novo Nordisk, Inc. and hold stock/options. Jinlin Song, Yan Chen, and Joanna Boland are employees of Analysis Group, Inc., which has received consulting fees from Novo Nordisk, Inc. for this work. Kim G. Smolderen receives research grants from Johnson & Johnson, Merck, and Abbott. She is a consultant for Dario Health, Terumo, Novo Nordisk, and Merck. She is the owner of BoboDream LLC. She receives funding from the National Institutes of Health (R01HL163640-03S1; R01HL163640-02S1; R21AT012430-01). Carlos Mena-Hurtado is a consultant for Terumo, Novo Nordisk, and Cook. He receives research grants from Merck, Shockwave, and the National Institutes of Health. Michael G. Nanna: Dr. Nanna reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging (K76AG088428). Dr. Nanna also reports being a consultant for Novo Nordisk, Heartflow, and Merck. Mikhail N. Kosiborod has served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Regeneron, Roche, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor, and Youngene Therapeutics; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stock options in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; has received other research support from AstraZeneca and Vifor; and is employed by AstraZeneca R&D, effective January 6, 2025. EDAT- 2025/09/10 06:29 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/09/10 01:03 PHST- 2025/08/18 00:00 [revised] PHST- 2025/07/17 00:00 [received] PHST- 2025/08/20 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/09/10 06:29 [pubmed] PHST- 2025/09/10 01:03 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70080 [pii] AID - 10.1111/dom.70080 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6691-6704. doi: 10.1111/dom.70080. Epub 2025 Sep 9. PMID- 40925137 OWN - NLM STAT- MEDLINE DCOM- 20251102 LR - 20260502 IS - 1578-1275 (Electronic) IS - 0212-6567 (Print) IS - 0212-6567 (Linking) VI - 57 IP - 11 DP - 2025 Nov TI - [Effectiveness of GLP-1 receptor agonists in managing patients with type 2 diabetes]. PG - 103354 LID - S0212-6567(25)00140-4 [pii] LID - 10.1016/j.aprim.2025.103354 [doi] LID - 103354 AB - OBJECTIVE: To evaluate the effectiveness of GLP-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus and to describe their clinical characteristics. DESIGN: Retrospective cohort study based on electronic health records. SITE: Health centres of the Primary and Community Care Management (GAPiC) Camp de Tarragona. PARTICIPANTS: Patients aged >/=18 years with a diagnosis of type 2 diabetes mellitus on treatment with an GLP-1 RA. MAIN MEASUREMENTS: Demographic variables, glycosylated haemoglobin (HbA1c) and weight/BMI were collected to assess effectiveness; and clinical variables were recorded to assess safety. RESULTS: A total of 1227 patients (50.2% male) were included. A mean average HbA1c% reduction of 0.50% in HbA1c (p<0.001), weight reduction of 3.08kg weight (p<0.001) and BMI reduction of 0.99kg/m(2) (p<0,001) were observed after 472 days of average treatment. CONCLUSIONS: GLP-1 RAs are effective in glycemic control and weight reduction in clinical practice. The results are consistent with international studies, although somewhat lower than pivotal trials. CI - Copyright (c) 2025 The Authors. Publicado por Elsevier Espana S.L.U. All rights reserved. FAU - Bejarano Romero, Ferran AU - Bejarano Romero F AD - Gerencia Atencion Primaria y a la Comunidad Camp de Tarragona, Tarragona, Espana; Grup de Recerca Emergent en Intervencions Sanitaries i Activitats Comunitaries-GRE ISAC (2021 SGR 00884). IDIAP Jordi Gol i Gurina, Barcelona, Espana; Grup de recerca en Qualitat i Seguretat dels Pacients de Tarragona (2022 6G22/035). IDIAP Jordi Gol i Gurina, Barcelona, Espana. Electronic address: fbejarano.tgn.ics@gencat.cat. FAU - Arago Moles, Vicente AU - Arago Moles V AD - Facultad de Medicina, Universidad Rovira i Virgili, Tarragona, Espana. FAU - Moron Porrua, Daniel AU - Moron Porrua D AD - Facultad de Medicina, Universidad Rovira i Virgili, Tarragona, Espana. FAU - Lopez Guerrero, Eva AU - Lopez Guerrero E AD - Gerencia Atencion Primaria y a la Comunidad Camp de Tarragona, Tarragona, Espana. FAU - Suner Barriga, Helena AU - Suner Barriga H AD - Hospital Universitario Joan 23, Tarragona, Espana. FAU - Canadell Vilarrasa, Laura AU - Canadell Vilarrasa L AD - Hospital Universitario Joan 23, Tarragona, Espana. LA - spa PT - English Abstract PT - Journal Article TT - Efectividad de los agonistas del receptor GLP-1 en el manejo de pacientes diabeticos tipo 2. DEP - 20250908 PL - Spain TA - Aten Primaria JT - Atencion primaria JID - 9111075 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - Weight Loss MH - Adult MH - Exenatide/therapeutic use PMC - PMC12454283 OTO - NOTNLM OT - Agonistas del receptor GLP-1 OT - Diabetes mellitus tipo 2 OT - Efectividad OT - Effectiveness OT - GLP-1 receptor agonists OT - Obesidad OT - Obesity OT - Safety OT - Seguridad OT - Type 2 diabetes mellitus EDAT- 2025/09/10 00:28 MHDA- 2025/11/03 00:26 PMCR- 2025/09/08 CRDT- 2025/09/09 18:05 PHST- 2025/06/20 00:00 [received] PHST- 2025/07/07 00:00 [revised] PHST- 2025/07/07 00:00 [accepted] PHST- 2025/11/03 00:26 [medline] PHST- 2025/09/10 00:28 [pubmed] PHST- 2025/09/09 18:05 [entrez] PHST- 2025/09/08 00:00 [pmc-release] AID - S0212-6567(25)00140-4 [pii] AID - 103354 [pii] AID - 10.1016/j.aprim.2025.103354 [doi] PST - ppublish SO - Aten Primaria. 2025 Nov;57(11):103354. doi: 10.1016/j.aprim.2025.103354. Epub 2025 Sep 8. PMID- 40923457 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260921 IS - 1944-7876 (Electronic) IS - 1071-1007 (Linking) VI - 46 IP - 11 DP - 2025 Nov TI - Preoperative GLP-1 Receptor Agonist Use and Postoperative Outcomes Following Operative Ankle Fracture Repair in Patients With Type 2 Diabetes: A National Database Study. PG - 1265-1274 LID - 10.1177/10711007251364187 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in management of type 2 diabetes mellitus (T2DM) and obesity. Beyond glycemic control, these agents may influence orthopaedic outcomes. This study aimed to assess the relationship between preoperative GLP-1 RA use and postoperative complications in T2DM patients undergoing operative ankle fracture repair. METHODS: A retrospective cohort study was conducted using the TriNetX database, identifying adult patients with T2DM who underwent operative ankle fracture repair from 2005 to 2024. Patients were stratified based on preoperative GLP-1 RA exposure within 180 days of surgery. Propensity score matching (1:1) was performed on demographics, medications, comorbidities, and laboratory values. Postoperative outcomes were analyzed in 3 domains: (1) medical complications within 90 days, (2) operative and implant-related complications from 90 to 180 days, and (3) health care utilization at 30, 90, and 180 days. RESULTS: A total of 1,107 patients were analyzed in each group after matching. After false discovery rate correction, GLP‑1 RA use was associated only with lower all‑cause mortality (odds ratio [OR] 0.33, 95% CI 0.16-0.67, adjusted P = .011; number needed to treat = 56) and higher fall‑related injuries (OR 1.32, 95% CI 1.12-1.57, adjusted P = .011; number needed to harm = 15). No significant differences were observed in infection, posttraumatic arthritis, persistent opioid use, and wound healing complications. CONCLUSION: Preoperative GLP-1 RA use in T2DM patients undergoing operative ankle fracture repair may reduce postoperative all-cause mortality but increase fall-related injuries. These findings underscore a complex risk-benefit profile of GLP-1 RA therapy in orthopaedic care. FAU - White, Carter J K AU - White CJK AUID- ORCID: 0009-0009-8093-3516 AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Choudhury, Ankit AU - Choudhury A AUID- ORCID: 0000-0001-9863-9862 AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Bollepalli, Harshavardhan AU - Bollepalli H AUID- ORCID: 0009-0003-6454-324X AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Kodra, Jacob D AU - Kodra JD AUID- ORCID: 0009-0001-4330-8393 AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Burton, Alex T AU - Burton AT AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Kraus, Jonathan C AU - Kraus JC AD - Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. LA - eng PT - Journal Article DEP - 20250909 PL - United States TA - Foot Ankle Int JT - Foot & ankle international JID - 9433869 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Ankle Fractures/surgery/complications MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - *Postoperative Complications/epidemiology MH - Aged MH - Databases, Factual MH - *Hypoglycemic Agents/therapeutic use MH - Adult OTO - NOTNLM OT - GLP-1 receptor agonists OT - ankle fracture OT - foot and ankle surgery OT - orthopaedic trauma OT - type 2 diabetes mellitus COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online. EDAT- 2025/09/09 12:32 MHDA- 2025/11/21 06:27 CRDT- 2025/09/09 06:43 PHST- 2025/11/21 06:27 [medline] PHST- 2025/09/09 12:32 [pubmed] PHST- 2025/09/09 06:43 [entrez] AID - 10.1177/10711007251364187 [doi] PST - ppublish SO - Foot Ankle Int. 2025 Nov;46(11):1265-1274. doi: 10.1177/10711007251364187. Epub 2025 Sep 9. PMID- 40920377 OWN - NLM STAT- MEDLINE DCOM- 20250908 LR - 20260720 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 9 DP - 2025 Sep 2 TI - GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes. PG - e2530952 LID - 10.1001/jamanetworkopen.2025.30952 [doi] LID - e2530952 AB - IMPORTANCE: The cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may vary by body mass index (BMI), but evidence on BMI-specific outcomes remains limited. OBJECTIVE: To investigate the associations of GLP-1 RA use with cardiovascular and kidney outcomes across BMI categories in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Chang Gung Research Database, a clinical dataset covering multiple hospitals in Taiwan. Patients with type 2 diabetes who received GLP-1 RAs or dipeptidyl peptidase-4 (DPP-4) inhibitors between 2011 and 2022 were identified. DPP-4 inhibitors were selected as the comparator due to their widespread use as a second-line oral hypoglycemic agent and their relatively neutral cardiovascular and kidney effects reported in previous studies. Propensity score matching was applied separately within BMI categories less than 25 and 25 or greater using a comprehensive set of demographic, clinical, and biochemical variables to balance baseline characteristics between treatment groups. The analysis was conducted from December 15, 2023, to July 5, 2024. EXPOSURES: Initiation of GLP-1 RAs compared with DPP-4 inhibitors. MAIN OUTCOMES AND MEASURES: Primary outcomes included major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, ischemic stroke, or hospitalization for heart failure) and composite kidney outcomes (defined as estimated glomerular filtration rate decline >/=50% or progression to dialysis). RESULTS: Among 97 156 patients with diabetes identified, a total of 7200 matched patients (mean [SD] age, 57.4 [14.2] years; 7473 [51.9%] female) were included (1841 pairs with BMI <25 and 5359 pairs with BMI >/=25). Among patients with BMI 25 or greater, GLP-1 RAs were associated with lower risks of cardiovascular death (hazard ratio [HR], 0.62; 95% CI, 0.46-0.83) and hospitalization for heart failure (subdistribution HR, 0.77; 95% CI, 0.62-0.94). Kidney outcomes were consistent across BMI strata. Restricted cubic spline analysis revealed increasing cardiovascular benefit associated with GLP-1 RAs among patients with higher BMI. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with type 2 diabetes, GLP-1 RAs use was associated with BMI-dependent cardiovascular benefits and consistent kidney protection, suggesting the importance of BMI stratification in guiding treatment decisions. FAU - Chen, Tien-Hsing AU - Chen TH AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hu, En-Hao AU - Hu EH AD - Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Dong-Yi AU - Chen DY AD - Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Lin, Yuan AU - Lin Y AD - Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chou, Tien-Shin AU - Chou TS AD - Division of Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Lin, Ming-Shyan AU - Lin MS AD - Division of Cardiology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Yang, Ning-I AU - Yang NI AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Wang, Chao-Yung AU - Wang CY AD - Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hung, Ming-Jui AU - Hung MJ AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Tsai, Ming-Lung AU - Tsai ML AD - Division of Cardiology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - College of Management, Chang Gung University, Taoyuan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250902 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.30969 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Body Mass Index MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Taiwan/epidemiology PMC - PMC12418133 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/09/08 12:43 MHDA- 2025/09/08 12:44 PMCR- 2025/09/08 CRDT- 2025/09/08 11:33 PHST- 2025/09/08 12:44 [medline] PHST- 2025/09/08 12:43 [pubmed] PHST- 2025/09/08 11:33 [entrez] PHST- 2025/09/08 00:00 [pmc-release] AID - 2838602 [pii] AID - zoi250869 [pii] AID - 10.1001/jamanetworkopen.2025.30952 [doi] PST - epublish SO - JAMA Netw Open. 2025 Sep 2;8(9):e2530952. doi: 10.1001/jamanetworkopen.2025.30952. PMID- 40915058 OWN - NLM STAT- MEDLINE DCOM- 20251015 LR - 20251203 IS - 1879-0267 (Electronic) IS - 0020-1383 (Linking) VI - 56 IP - 11 DP - 2025 Nov TI - Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up. PG - 112746 LID - S0020-1383(25)00604-7 [pii] LID - 10.1016/j.injury.2025.112746 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for Type 2 diabetes and obesity due to their cardiometabolic benefits. However, their effects on fracture healing remain controversial. This study investigates perioperative GLP-1 RA use and outcomes following surgical treatment of lower extremity (LE) fractures. METHODS: A retrospective analysis utilizing a large multicenter database compared patients on GLP-1 RAs within one year prior to and after lower extremity index surgery (+GLP) with those not on GLP-1 RAs (-GLP). Propensity score matching was performed on 275,970 included patients, matching 1:1 on age, sex, tobacco use, diabetes mellitus, primary hypertension, hyperlipidemia, chronic ischemic heart disease, chronic lower respiratory disease, and body mass index (BMI), resulting in 6125 "best-matched" patients per group. This was conducted utilizing multivariate logistic regression with a 0.1 caliper. Outcomes were assessed at 1 month, 3 months, and 1 year. RESULTS: At 1-year follow-up, GLP-1 RA users demonstrated a significantly higher rate of nonunion compared to matched controls (5.4% vs 4.4%, Risk Ratio 1.2, 95% CI 1.0-1.4, P < 0.05) when assessing patients who also continued GLP-1 RAs postoperatively. There were no significant differences in wound dehiscence, deep or superficial surgical site infections, or hematoma. Importantly, the +GLP group experienced significantly lower rates of cardiac arrest (0.8% vs 1.6%, RR 0.5, 95% CI 0.3-0.7, P < 0.01) and all-cause mortality (4.4% vs 8.0%, RR 0.5, 95% CI 0.4-0.6, P < 0.01). CONCLUSIONS: Perioperative GLP-1 RA use was associated with a higher risk of nonunion following lower extremity fracture surgery, though without increased wound complication rates. Importantly, GLP-1 RA use was linked to reduced cardiac arrest and mortality within one year. These findings suggest that while the increased rate of nonunion is statistically significant, its clinically significance is limited. Thus, the mortality reduction may be more clinically meaningful for patient counseling and perioperative management. Further study is required to clarify the balance between systemic benefits and surgical outcomes of GLP-1 RAs in orthopedic trauma. CI - Published by Elsevier Ltd. FAU - Pereira, Daniel E AU - Pereira DE AD - Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. FAU - Tummala, Sri AU - Tummala S AD - University of Texas Southwestern Medical Center, Department of Orthopaedics, Dallas, TX, USA. FAU - Mittal, Mehul M AU - Mittal MM AD - University of Texas Southwestern Medical Center, Department of Orthopaedics, Dallas, TX, USA. FAU - Obey, Mitchel AU - Obey M AD - Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. FAU - Berkes, Marschall B AU - Berkes MB AD - Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. FAU - McAndrew, Christopher M AU - McAndrew CM AD - Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. FAU - Wilson, Jenna L AU - Wilson JL AD - Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. Electronic address: wjenna@wustl.edu. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250902 PL - Netherlands TA - Injury JT - Injury JID - 0226040 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Follow-Up Studies MH - *Fracture Healing/drug effects MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Propensity Score MH - *Fracture Fixation MH - Adult OTO - NOTNLM OT - Fracture fixation OT - GLP1-RA, glucagon like peptide 1 receptor agonist OT - Infection OT - Nonunion OT - Trinetx OT - database OT - lower extremity OT - trauma COIS- Declaration of competing interest None. EDAT- 2025/09/07 18:30 MHDA- 2025/10/16 05:31 CRDT- 2025/09/07 18:04 PHST- 2025/08/02 00:00 [received] PHST- 2025/08/30 00:00 [revised] PHST- 2025/08/31 00:00 [accepted] PHST- 2025/10/16 05:31 [medline] PHST- 2025/09/07 18:30 [pubmed] PHST- 2025/09/07 18:04 [entrez] AID - S0020-1383(25)00604-7 [pii] AID - 10.1016/j.injury.2025.112746 [doi] PST - ppublish SO - Injury. 2025 Nov;56(11):112746. doi: 10.1016/j.injury.2025.112746. Epub 2025 Sep 2. PMID- 40914786 OWN - NLM STAT- MEDLINE DCOM- 20251115 LR - 20261010 IS - 2190-3948 (Electronic) IS - 2190-393X (Linking) VI - 15 IP - 12 DP - 2025 Dec TI - Current status of Liraglutide delivery systems for the management of type 2 diabetes mellitus. PG - 4479-4500 LID - 10.1007/s13346-025-01965-y [doi] AB - Diabetes is a metabolic disorder of increasing global concern. Characterized by constantly elevated levels of glucose, severe beta-cell dysfunction, and insulin resistance, it is the cause of a major burden on patients if not managed with therapeutic and lifestyle changes. The human body is slowly developing tolerance to many marketed antidiabetic drugs and the quest for the discovery of newer molecules continues. Liraglutide is a prominent GLP-1 receptor agonist which is administered daily via subcutaneous injection. In addition to lowering HbA1c levels, it is also known for promoting weight loss and improving cardiovascular outcomes. A variety of novel formulation strategies have been explored to improve its bioavailability and patient compliance. To address these limitations, various advanced drug delivery systems have been investigated, including polymeric nanoparticles, lipid-based nanocarriers, biodegradable microparticles, hydrogels, and dissolvable microneedles. These systems aim to prolong drug release, enhance mucosal penetration, increase stability, and reduce dosing frequency. While many of these platforms show promise in preclinical and early clinical studies, critical translational barriers remain. These include challenges in large-scale manufacturing, ensuring formulation sterility, achieving regulatory approval, and maintaining stability during storage and distribution.This review provides a comprehensive overview of the formulation strategies developed for liraglutide delivery, critically examines their pharmacokinetic and pharmacodynamic profiles, and evaluates the current state of clinical translation. By identifying both the potential and the limitations of these delivery technologies, the article aims to inform future research directions in GLP-1-based therapeutics and improve treatment outcomes for patients with T2DM. CI - (c) 2025. Controlled Release Society. FAU - Chatterjee, Riti AU - Chatterjee R AD - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333031, India. FAU - Galave, Vishal Sangita Babasaheb AU - Galave VSB AD - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333031, India. FAU - Jindal, Anil B AU - Jindal AB AUID- ORCID: 0000-0003-3856-869X AD - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333031, India. anil_jndl@yahoo.co.in. LA - eng PT - Journal Article PT - Review DEP - 20250906 PL - United States TA - Drug Deliv Transl Res JT - Drug delivery and translational research JID - 101540061 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Liraglutide/administration & dosage/pharmacokinetics/therapeutic use/chemistry MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/therapeutic use/chemistry MH - Animals MH - *Drug Delivery Systems MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Challenges OT - Formulation strategies OT - GLP-1 agonists OT - Liraglutide OT - Market status OT - Regulatory control COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/07 00:37 MHDA- 2025/11/16 00:27 CRDT- 2025/09/06 23:33 PHST- 2025/05/06 00:00 [received] PHST- 2025/08/25 00:00 [accepted] PHST- 2025/11/16 00:27 [medline] PHST- 2025/09/07 00:37 [pubmed] PHST- 2025/09/06 23:33 [entrez] AID - 10.1007/s13346-025-01965-y [pii] AID - 10.1007/s13346-025-01965-y [doi] PST - ppublish SO - Drug Deliv Transl Res. 2025 Dec;15(12):4479-4500. doi: 10.1007/s13346-025-01965-y. Epub 2025 Sep 6. PMID- 40912924 OWN - NLM STAT- MEDLINE DCOM- 20251008 LR - 20260127 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 34 IP - 10 DP - 2025 Oct TI - Real-World Prescribing of Renal and Cardiovascular Protective Drugs in Patients With Type 2 Diabetes and Chronic Kidney Disease: Analysis of Data From a Western Australian Quaternary Hospital. PG - 1089-1097 LID - S1443-9506(25)01554-9 [pii] LID - 10.1016/j.hlc.2025.07.007 [doi] AB - BACKGROUND: In patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), sodium-glucose cotransporter 2 (SGLT2) inhibitors, semaglutide (glucagon-like peptide-1 [GLP-1] agonist), and finerenone (non-steroidal mineralocorticoid receptor antagonist) improve renal and cardiovascular outcomes. We assessed real-world prescribing of these drugs in patients with T2D and CKD. METHOD: The ReDiCare project retrospectively identified patients with T2D and CKD admitted to an Australian hospital between January 2020 and September 2024 using International Statistical Classification of Diseases and Related Health Problems 10th Revision Australian Modification codes. CKD was also defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) for >3 months. Patients with an eGFR <15 mL/min/1.73 m(2), acute kidney injury, renal transplant, or those receiving dialysis were excluded. Drugs prescribed at discharge were obtained. RESULTS: Of 2,216 patients (mean age 78.2+/-10.9 years and 41.3% female), an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was prescribed in 1,243 (56.1%) patients, an SGLT2 inhibitor in 472 (21.3%), a GLP-1 agonist in 163 (7.4%), and a mineralocorticoid receptor antagonist in 305 (13.8%). Specifically, semaglutide was prescribed in 79 (3.6%) patients and finerenone in three (0.1%). Overall, 735 (33.2%) patients were prescribed none, 919 (41.5%) one, 433 (19.5%) two, 115 (5.2%) three, and 14 (0.6%) all four drug groups. From January to March 2020 to July to September 2024, there was an increased prescribing of SGLT2 inhibitors (7.9%-38.7%; p<0.001) and GLP-1 agonists (6.3%-11.7%; p=0.007). CONCLUSIONS: In patients admitted to the hospital with T2D and CKD, one-quarter were prescribed an SGLT2 inhibitor and/or a GLP-1 agonist at discharge. Further studies are required to identify barriers and enablers to prescribing these drugs. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Lan, Nick S R AU - Lan NSR AD - Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, WA, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, The University of Western Australia, Perth, WA, Australia; Harry Perkins Institute of Medical Research, Perth, WA, Australia. Electronic address: nick.lan@uwa.edu.au. FAU - McFadden, Ben AU - McFadden B AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Johnson, Andrew AU - Johnson A AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Shedden, Phillip AU - Shedden P AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Fegan, P Gerry AU - Fegan PG AD - Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, Curtin University, Perth, WA, Australia. FAU - Puttagunta, Harish AU - Puttagunta H AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Ho, Sharon AU - Ho S AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia; Department of Pharmacy, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Gillett, Richard AU - Gillett R AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Swaminathan, Ramyasuda AU - Swaminathan R AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Dwivedi, Girish AU - Dwivedi G AD - Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, WA, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, The University of Western Australia, Perth, WA, Australia; Harry Perkins Institute of Medical Research, Perth, WA, Australia; CardioInnovate Translational Lab - Western Australia, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia. LA - eng PT - Journal Article DEP - 20250905 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (finerenone) RN - 0 (Naphthyridines) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - Aged MH - *Renal Insufficiency, Chronic/drug therapy/complications/epidemiology/physiopathology MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glomerular Filtration Rate MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - Western Australia/epidemiology MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Drug Prescriptions/statistics & numerical data MH - Follow-Up Studies MH - Naphthyridines OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - Diabetes OT - Implementation OT - Prevention OT - Risk factors COIS- Declaration of Competing Interests N.S.R.L. has received research funding from Sanofi as part of a Clinical Fellowship in Endocrinology and Diabetes, education support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Seqirus, Eli Lilly, Novartis, and Pfizer; speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, and Sanofi; and has participated in advisory boards for Eli Lilly. S.H. has provided consultancy services to CSL Seqirus and has received education support from CSL Seqirus. G.D. reports paid lectures from AstraZeneca, Pfizer, and Amgen and provides consultancy services and has equity interest in Artrya Ltd. All other authors have no conflicts of interest to disclose. EDAT- 2025/09/06 00:35 MHDA- 2025/10/09 00:30 CRDT- 2025/09/05 21:51 PHST- 2025/04/29 00:00 [received] PHST- 2025/07/04 00:00 [revised] PHST- 2025/07/06 00:00 [accepted] PHST- 2025/10/09 00:30 [medline] PHST- 2025/09/06 00:35 [pubmed] PHST- 2025/09/05 21:51 [entrez] AID - S1443-9506(25)01554-9 [pii] AID - 10.1016/j.hlc.2025.07.007 [doi] PST - ppublish SO - Heart Lung Circ. 2025 Oct;34(10):1089-1097. doi: 10.1016/j.hlc.2025.07.007. Epub 2025 Sep 5. PMID- 40912462 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20250917 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 228 DP - 2025 Oct TI - Effects of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on CRT response and clinical outcomes in in type 2 diabetes mellitus patients receiving chronic anti-diabetic medications: A multicenter observational study. PG - 112452 LID - S0168-8227(25)00466-8 [pii] LID - 10.1016/j.diabres.2025.112452 [doi] AB - BACKGROUND: Type-2-diabetes-mellitus (T2DM) impairs outcomes in patients undergoing cardiac-resynchronization-therapy-with-defibrillator (CRTd).While both sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardiovascular benefits, their combination impact in CRTd-treated T2DM patients remains unclear. METHODS: In this prospective multicenter observational study, 2,257 T2DM patients treated with CRTd were stratified into three groups: SGLT2i monotherapy (n 874), GLP-1RAs monotherapy (n 808), and combination therapy with GLP-1RAs/SGLT2i (n 575). Primary endpoints were CRT-response and heart failure (HF) hospitalizations at 1-year follow-up. Secondary endpoints included changes in glycemic control, renal function, inflammatory/oxidative markers, and cardiac deaths. RESULTS: At 1 year, the combination therapy group had significantly higher CRT-response rate (66.3 %) compared to SGLT2i (59.6 %) and GLP-1RAs (59.2 %) groups (p = 0.014), and lower HF-hospitalization rates (15.7 % vs. 23.5 % and 24.4 %, respectively; p = 0.001). Multivariate Cox analysis confirmed combination therapy as an independent predictor of CRT response (HR 1.659, CI 95 % [1.320-2.085]; p 0.001) and reduced HF hospitalizations (0.822, CI 95 % [0.751-0.966]; p0.012) at 1 year of follow-up. CONCLUSIONS: In T2DM patients receiving CRTd, combination therapy with GLP-1RAs/SGLT2i was associated with improvements in cardiac function and clinical outcomes compared to monotherapy. GLP-1RAs/SGLT2i could optimize CRT responsiveness and reduce HF-hospitalizations in T2DM patients. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Sardu, Celestino AU - Sardu C AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", Naples, Italy; Department of Cardiovascular Sciences, Responsible Research Hospital, Campobasso, Italy; Department of Neuro-Cardiological Sciences, IRCCS Neuromed, Pozzilli, Italy. Electronic address: drsarducele@gmail.com. FAU - Marfella, Ludovica Vittoria AU - Marfella LV AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Rinaldi, Luca AU - Rinaldi L AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Sasso, Ferdinando Carlo AU - Sasso FC AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Cozzolino, Domenico AU - Cozzolino D AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Nappo, Francesco AU - Nappo F AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Sellitto, Ausilia AU - Sellitto A AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Romano, Ciro AU - Romano C AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Carusone, Caterina AU - Carusone C AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - D'Onofrio, Nunzia AU - D'Onofrio N AD - Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Trotta, Maria Consiglia AU - Trotta MC AD - Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Riccio, Joshua AU - Riccio J AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Cioffi, Domenico AU - Cioffi D AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Volpicelli, Mario AU - Volpicelli M AD - Department of Cardiovascular Sciences, Santa Maria della Pieta Hospital, Nola, Naples, Italy. FAU - Marca, Carmine La AU - Marca C AD - Department of Cardiovascular Sciences, Santa Maria della Pieta Hospital, Nola, Naples, Italy. FAU - Marrazzo, Natale AU - Marrazzo N AD - Department of Cardiovascular Sciences, Responsible Research Hospital, Campobasso, Italy. FAU - Giordano, Valerio AU - Giordano V AD - Department of Cardiovascular Sciences, San Luca Hospital Hospital, Vallo della Lucania, Italy. FAU - Fumagalli, Carlo AU - Fumagalli C AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; Department of Neuro-Cardiological Sciences, IRCCS Neuromed, Pozzilli, Italy. FAU - Landolfi, Alessandro AU - Landolfi A AD - Department of Neuro-Cardiological Sciences, IRCCS Neuromed, Pozzilli, Italy. FAU - Abitabile, Marianna AU - Abitabile M AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Marfella, Lorenza AU - Marfella L AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Balestrieri, Maria Luisa AU - Balestrieri ML AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", Naples, Italy; Department of Cardiovascular Sciences, Responsible Research Hospital, Campobasso, Italy. FAU - Marfella, Raffaele AU - Marfella R AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250903 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Middle Aged MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Treatment Outcome MH - *Cardiac Resynchronization Therapy MH - Heart Failure/therapy MH - Hospitalization/statistics & numerical data OTO - NOTNLM OT - CRTd OT - Heart failure OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/06 00:35 MHDA- 2025/09/16 13:04 CRDT- 2025/09/05 19:15 PHST- 2025/06/26 00:00 [received] PHST- 2025/08/27 00:00 [revised] PHST- 2025/08/31 00:00 [accepted] PHST- 2025/09/16 13:04 [medline] PHST- 2025/09/06 00:35 [pubmed] PHST- 2025/09/05 19:15 [entrez] AID - S0168-8227(25)00466-8 [pii] AID - 10.1016/j.diabres.2025.112452 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Oct;228:112452. doi: 10.1016/j.diabres.2025.112452. Epub 2025 Sep 3. PMID- 40911751 OWN - NLM STAT- MEDLINE DCOM- 20250905 LR - 20250916 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 24 IP - 9 DP - 2025 Sep 1 TI - Glucagon-Like Peptide-1 Receptor Agonists Reduce Surgeries and Hospitalizations in Hidradenitis Suppurativa: A Multicenter TriNetX Cohort Study. PG - 869-874 LID - 10.36849/jdd.8926 [doi] AB - BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin condition frequently associated with type 2 diabetes mellitus and obesity. Glucagon-like peptide-1 receptor agonists have emerged as promising agents for managing type 2 diabetes mellitus due to their potent effects on glycemic control and weight reduction. Recent evidence suggests that glucagon-like peptide-1 receptor agonists may also possess anti-inflammatory properties, potentially making them effective in treating inflammatory conditions, such as hidradenitis suppurativa. OBJECTIVE: To determine if glucagon-like peptide-1 receptor agonists reduce surgeries and hospitalizations in patients with hidradenitis suppurativa. METHODS: We utilized the TriNetX platform to evaluate the rate of surgical abscess repairs performed and hospitalizations in a propensity score-matched cohort of patients with hidradenitis suppurativa who were prescribed glucagon-like peptide-1 receptor agonists. RESULTS: Our analysis revealed that patients prescribed glucagon-like peptide-1 receptor agonists had significantly lower rates of surgeries with a HR of 0.35 (95% CI: 0.25, 0.50) and hospitalizations with a HR of 0.87 (95% CI: 0.82, 0.92) compared to a control cohort of patients who did not receive glucagon-like peptide-1 receptor agonists. CONCLUSIONS: Glucagon-like peptide-1 receptor agonists reduce surgeries and hospitalizations in hidradenitis suppurativa, demonstrating their potential therapeutic value in dermatology patient care. FAU - Gupta, Neal AU - Gupta N FAU - Zafar, Kayla AU - Zafar K FAU - Patel, Paras AU - Patel P FAU - Kabakova, Margaret AU - Kabakova M FAU - Collins, Alexia AU - Collins A FAU - Ray, Maile AU - Ray M FAU - Shayya, Ashley AU - Shayya A FAU - McGinnis, Sandra AU - McGinnis S FAU - Kurtti, Alana AU - Kurtti A FAU - Cohen, Marc AU - Cohen M FAU - Austin, Evan AU - Austin E FAU - Derrick, Kristina AU - Derrick K FAU - Glick, Sharon AU - Glick S FAU - Jagdeo, Jared AU - Jagdeo J LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Hidradenitis Suppurativa/drug therapy/surgery/complications MH - *Hospitalization/statistics & numerical data MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Cohort Studies MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score EDAT- 2025/09/05 18:33 MHDA- 2025/09/05 18:34 CRDT- 2025/09/05 14:40 PHST- 2025/09/05 18:34 [medline] PHST- 2025/09/05 18:33 [pubmed] PHST- 2025/09/05 14:40 [entrez] AID - S1545961625P8926X [pii] AID - 10.36849/jdd.8926 [doi] PST - ppublish SO - J Drugs Dermatol. 2025 Sep 1;24(9):869-874. doi: 10.36849/jdd.8926. PMID- 40908778 OWN - NLM STAT- MEDLINE DCOM- 20250905 LR - 20260127 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 5 DP - 2025 Sep-Oct TI - US eligibility and preventable cardiovascular disease events from semaglutide in type 2 diabetes. PG - 14791641251376551 LID - 10.1177/14791641251376551 [doi] LID - 14791641251376551 AB - BackgroundThe SUSTAIN-6 trial showed the cardiovascular disease (CVD) benefits of semaglutide among patients with type 2 diabetes mellitus (T2DM). We estimated the US population eligibility and preventable CVD events from semaglutide.MethodsUS adults with T2DM were selected from the National Health and Nutrition Examination Survey 2011-2020 based on SUSTAIN-6 eligibility criteria. We estimated composite and secondary CVD events from SUSTAIN-6 treated and placebo published event rates multiplied by the weighted US eligible population, the difference being the number of preventable events which was then divided by 2.1 years to provide annualized estimates.ResultsAmong 4755 (projected to 33.6 million [M]) adults with T2DM, 1132 (6.9 million) fit SUSTAIN-6 criteria. Compared to SUSTAIN-6, our sample more likely had female and black patients, shorter diabetes duration, and was less likely with prior CVD. We estimated 75,681 primary outcome CVD events, 128,329 expanded composite CVD events, 72,390 combined nonfatal MI, nonfatal stroke, and all-cause deaths, 36,195 non-fatal stroke events, 85,552 revascularizations, and 75,681 cases of nephropathy could be prevented annually if eligible T2DM subjects were on semaglutide.ConclusionSemaglutide may prevent over 75,000 CVD events annually if provided to eligible T2DM US adults. Efforts to improve use of these therapies are needed. FAU - Karthikeyan, Hridhay AU - Karthikeyan H AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. FAU - Fan, Wenjun AU - Fan W AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. AD - Center for Global Cardiometabolic Health and Nutrition, University of California, Irvine, CA, USA. FAU - Wong, Nathan D AU - Wong ND AUID- ORCID: 0000-0003-1102-7324 AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. AD - Center for Global Cardiometabolic Health and Nutrition, University of California, Irvine, CA, USA. LA - eng PT - Journal Article DEP - 20250904 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology/mortality MH - Female MH - Middle Aged MH - United States/epidemiology MH - Male MH - *Eligibility Determination MH - Treatment Outcome MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Time Factors MH - Risk Assessment MH - Nutrition Surveys MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12413520 OTO - NOTNLM OT - GLP1 receptor agonists OT - cardiovascular disease OT - diabetes OT - semaglutide COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Wong receives research support from Amgen, Novartis, Novo Nordisk, and Regeneron and is an advisory board member for Amgen and consultant for Heart Lung, Novartis and Ionis. No other authors have any disclosures. EDAT- 2025/09/05 06:34 MHDA- 2025/09/05 06:35 PMCR- 2025/09/04 CRDT- 2025/09/05 02:54 PHST- 2025/09/05 06:35 [medline] PHST- 2025/09/05 06:34 [pubmed] PHST- 2025/09/05 02:54 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - 10.1177_14791641251376551 [pii] AID - 10.1177/14791641251376551 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Sep-Oct;22(5):14791641251376551. doi: 10.1177/14791641251376551. Epub 2025 Sep 4. PMID- 40906565 OWN - NLM STAT- MEDLINE DCOM- 20260427 LR - 20260427 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 39 IP - 3 DP - 2026 Jun TI - Glucagon-like Peptide-1 Receptor Agonists and Reproductive Health: Current Evidence and Clinical Implications. PG - 239-250 LID - 10.1177/08971900251376795 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have experienced rapid growth in recent years as treatments for type 2 diabetes mellitus and obesity. These medications offer promising benefits, including weight loss and improved glycemic control; however, their implications for reproductive health warrant attention. While tirzepatide has been shown to impact absorption of oral contraceptives due to delayed gastric emptying, other GLP-1RAs do not appear to have clinically significant interactions with oral contraception. Fertility outcomes may improve with GLP-1RAs and dual GLP-1/GIP agonists due to weight loss and related metabolic benefits. Despite their widespread use, data on GLP-1RAs in pregnancy and lactation remain limited, leaving significant gaps in guidance for clinicians. This review synthesizes current literature on GLP-1RAs to highlight reproductive health considerations, including their potential impacts on contraception, fertility, pregnancy, and lactation. Greater awareness and understanding of these factors can support informed decision-making and optimize care for individuals using GLP-1RAs. FAU - Kettner, Jordyn AU - Kettner J AUID- ORCID: 0000-0001-8155-7043 AD - Ambulatory Care Clinical Pharmacist, University of Wisconsin Health, Middleton, WI, USA. FAU - Donnelly, Elizabeth AU - Donnelly E AUID- ORCID: 0009-0006-8168-4767 AD - PGY2 Ambulatory Care Clinical Pharmacist, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Maes, Marina L AU - Maes ML AUID- ORCID: 0000-0003-0608-0729 AD - Pharmacy Practice and Translational Research Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. RINGGOLD: 5228 LA - eng PT - Journal Article PT - Review DEP - 20250904 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Pregnancy MH - Female MH - *Reproductive Health MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Lactation/drug effects MH - Obesity/drug therapy OTO - NOTNLM OT - contraception OT - fertility OT - glucagon-like peptide-1 receptor agonist OT - pregnancy lactation OT - reproductive health COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/09/04 18:35 MHDA- 2026/04/27 06:32 CRDT- 2025/09/04 12:42 PHST- 2026/04/27 06:32 [medline] PHST- 2025/09/04 18:35 [pubmed] PHST- 2025/09/04 12:42 [entrez] AID - 10.1177/08971900251376795 [doi] PST - ppublish SO - J Pharm Pract. 2026 Jun;39(3):239-250. doi: 10.1177/08971900251376795. Epub 2025 Sep 4. PMID- 40903861 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Weight loss interventions and obesity-associated cancers in people with type 2 diabetes and overweight/obesity: A real-world observational study. PG - 6914-6926 LID - 10.1111/dom.70090 [doi] AB - AIMS: To evaluate whether weight-loss interventions are associated with obesity-associated cancers (OAC) in individuals with overweight/obesity and type 2 diabetes (T2D). MATERIALS AND METHODS: This retrospective cohort study utilised the TriNetX federated research network. Three cohorts of adults with overweight/obesity and T2D, treated with either semaglutide, tirzepatide or bariatric surgery (BS) between June 2005 and June 2025, were propensity score matched (1:1) to cohorts treated with dipeptidyl peptidase-4 inhibitors (DPP-4i) using potential confounding factors. Using Cox regression analysis, we estimated hazard ratios (HRs) of composite and individual OAC: breast, colorectal, gallbladder, liver, multiple myeloma, oesophageal, ovarian, pancreatic, renal, gastric cardia, thyroid and uterine cancers. RESULTS: In 64,178 matched pairs (mean follow-up 911 days), semaglutide (vs. DPP-4i) was associated with lower rates of composite OAC (HR: 0.88; 95% CI: 0.82-0.95), colorectal (0.80; 0.67-0.97), liver (0.75; 0.60-0.95) and pancreatic (0.76; 0.60-0.96) cancers. In 19,682 matched pairs (mean follow-up 435 days), tirzepatide (vs. DPP-4i) was associated with a non-significant lower rate of composite OAC (0.84; 0.69-1.01) but a significant lower rate of ovarian cancer (0.31; 0.10-0.95). In 9642 matched pairs (mean follow-up 1746 days), BS (vs. DPP-4i) was associated with lower rates of composite OAC (0.85; 0.74-0.98), liver (0.56; 0.32-0.97) and uterine cancers (0.59; 0.38-0.90), and higher rates of gastric cardia cancer (10.54; 1.35-82.38) and oesophageal cancer (4.78; 1.04-21.87). CONCLUSIONS: Semaglutide and BS were associated with lower cancer rates in individuals with overweight/obesity and T2D, with non-significant lower rates also observed with tirzepatide. These findings suggest weight-loss interventions may contribute to cancer prevention in this population. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ipaye, Testimony AU - Ipaye T AUID- ORCID: 0009-0000-3190-4975 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - Leicester Cancer Research Centre, University of Leicester, Leicester, UK. FAU - Goldney, Jonathan AU - Goldney J AUID- ORCID: 0000-0001-8553-8296 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Wilkinson, Thomas J AU - Wilkinson TJ AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Yates, Thomas AU - Yates T AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Brown, Karen AU - Brown K AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Cancer Research Centre, University of Leicester, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - NIHR Leicester Biomedical Research Centre/ GR - 223512/Z/21/Z/Wellcome Trust Leicestershire Healthcare Inequalities Improvement Doctoral Training Programme/ PT - Journal Article PT - Observational Study DEP - 20250903 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/complications/therapy/epidemiology MH - Middle Aged MH - Retrospective Studies MH - *Obesity/complications/therapy MH - *Overweight/complications/therapy MH - Male MH - *Neoplasms/epidemiology/etiology/prevention & control MH - Aged MH - Adult MH - Glucagon-Like Peptides/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Bariatric Surgery MH - Weight Loss MH - *Weight Reduction Programs MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587238 OTO - NOTNLM OT - TriNetX OT - bariatric surgery OT - cancer OT - obesity OT - overweight OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight loss COIS- D.P. has received honoraria for lectures from Novo Nordisk, Eli Lilly, Boehringer Ingelheim and Johnson & Johnson; consultancy fees from Regeneron; and research grants from Novo Nordisk, the Novo Nordisk UK Research Foundation, the Academy of Medical Sciences/Diabetes UK, and the National Institute for Health and Care Research (NIHR). MJD has acted as a consultant/advisor and speaker for Eli Lilly, Novo Nordisk and Sanofi, has attended advisory boards for AbbVie, Amgen, AstraZeneca, Biomea Fusion, Carmot/Roche, Daewoong Pharmaceutical, Sanofi, Zealand Pharma, Regeneron, GSK and EktaH, and as a speaker for AstraZeneca, Boehringer Ingelheim and Zuellig Pharma. She has received grants from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. TJW has received consulting fees from Regeneron and Baxter Int. FZ has received consulting fees from Servier, Menarini and Daiichi Sankyo. TY has received investigated initiated funding from Astra Zeneca, has acted as a consultant for Regeneron, and has received contacted research funding from the Reinsurance Group of America. EDAT- 2025/09/04 06:37 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/04 01:03 PHST- 2025/08/15 00:00 [revised] PHST- 2025/05/12 00:00 [received] PHST- 2025/08/22 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/04 06:37 [pubmed] PHST- 2025/09/04 01:03 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70090 [pii] AID - 10.1111/dom.70090 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):6914-6926. doi: 10.1111/dom.70090. Epub 2025 Sep 3. PMID- 40900331 OWN - NLM STAT- MEDLINE DCOM- 20260212 LR - 20261009 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 399 IP - 2 DP - 2026 Jan TI - Mapping the global research landscape of tirzepatide: a bibliometric analysis of trends, collaborations, and emerging themes in obesity and diabetes managements. PG - 2577-2591 LID - 10.1007/s00210-025-04574-1 [doi] AB - Tirzepatide, a dual GIP/GLP-1 receptor agonist, shows promise in managing obesity and type 2 diabetes. This bibliometric analysis maps its research landscape, identifying trends, collaborations, and emerging themes to guide future investigations. A structured search of the Scopus database was performed using the keywords "tirzepatide" in titles or abstracts, limited to English-language original articles. A total of 446 documents were retrieved. Bibliometric analysis was conducted using VOSviewer (v1.6.19), Biblioshiny (Rstudio plugin), and CiteSpace (v6.2.R6) to visualize co-authorship, keyword co-occurrence, citation patterns, and thematic evolution. Tirzepatide publications peaked in 2024 (n = 163), with the USA leading (n = 243, 10,076 citations). Key authors included Urva, S. and Haupt, A. Three thematic clusters emerged: pharmacological mechanisms, clinical outcomes, and study design. Emerging topics included weight reduction, pharmacovigilance, and cost-effectiveness. Co-citation analysis identified four author clusters, with Frias J.P. (TLS = 13,605) most influential. Journals like Diabetes, Obesity and Metabolism dominated. Thematic evolution showed shifts toward real-world evidence and metabolic dysfunction-associated steatotic liver disease, reflecting broadening research scope. Tirzepatide research is growing globally with diverse collaborations, informing future therapeutic strategies and highlighting gaps in long-term safety, accessibility, and cost-effectiveness. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Taha, Manal Mohamed Elhassan AU - Taha MME AD - Health Research Centre, Jazan University, Jazan, Saudi Arabia. FAU - Abdelwahab, Siddig Ibrahim AU - Abdelwahab SI AD - Health Research Centre, Jazan University, Jazan, Saudi Arabia. sadiqa@jazanu.edu.sa. FAU - Oraibi, Omar AU - Oraibi O AD - Faculty of Medicine, Jazan University, Jazan, Saudi Arabia. FAU - Madkhali, Mohammed A AU - Madkhali MA AD - Faculty of Medicine, Jazan University, Jazan, Saudi Arabia. FAU - Alhazmi, Abdulhameed Albarraq AU - Alhazmi AA AD - University Hospital, Jazan University, Jazan, Saudi Arabia. FAU - Jeraiby, Mohammed AU - Jeraiby M AD - Department of Basic Medical Science, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia. FAU - Abdullah, Saleh M AU - Abdullah SM AD - Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia. FAU - Farasani, Abdullah AU - Farasani A AD - Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia. FAU - Moshi, Jobran M AU - Moshi JM AD - Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia. FAU - Khamjan, Nizar A AU - Khamjan NA AD - Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia. FAU - Alshahrani, Saeed AU - Alshahrani S AD - Department of Pharmacology and Toxicology, College of Pharmacy, Jazan, Saudi Arabia. FAU - Shubaily, Hussam M AU - Shubaily HM AD - Faculty of Medicine, Jazan University, Jazan, Saudi Arabia. FAU - Sahli, Khaled A AU - Sahli KA AD - Security Forces Hospitals Program, General Directorate of Medical Services, Ministry of Interior, Riyadh, Kingdom of Saudi Arabia. FAU - Qadri, Marwa AU - Qadri M AD - Department of Pharmacology and Toxicology, College of Pharmacy, Jazan, Saudi Arabia. FAU - Khardali, Amani AU - Khardali A AD - Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. AD - Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. LA - eng GR - 296/Jazan University/ PT - Journal Article DEP - 20250903 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Bibliometrics MH - *Obesity/drug therapy MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Biomedical Research/trends MH - Animals MH - Tirzepatide OTO - NOTNLM OT - Bibliometric analysis OT - GLP-1 receptor agonists OT - Obesity OT - Tirzepatide OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: None. Clinical trial number: Not applicable. Consent for publication: None. Competing interests: The authors declare no competing interests. EDAT- 2025/09/03 12:35 MHDA- 2026/02/12 12:50 CRDT- 2025/09/03 11:13 PHST- 2025/08/18 00:00 [received] PHST- 2025/08/20 00:00 [accepted] PHST- 2026/02/12 12:50 [medline] PHST- 2025/09/03 12:35 [pubmed] PHST- 2025/09/03 11:13 [entrez] AID - 10.1007/s00210-025-04574-1 [pii] AID - 10.1007/s00210-025-04574-1 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2026 Jan;399(2):2577-2591. doi: 10.1007/s00210-025-04574-1. Epub 2025 Sep 3. PMID- 40900212 OWN - NLM STAT- MEDLINE DCOM- 20260126 LR - 20261009 IS - 1563-258X (Electronic) IS - 0043-5341 (Linking) VI - 176 IP - 1-2 DP - 2026 Feb TI - Treatment outcomes and safety profile of SGLT2 inhibitors versus GLP-1 agonists in type 2 diabetes mellitus : Systematic review of real-world observational studies. PG - 45-59 LID - 10.1007/s10354-025-01108-5 [doi] AB - PURPOSE: Several pharmacotherapies are available to treat type 2 diabetes mellitus (T2DM) among which sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 (GLP-1) receptor agonists are significant. The current systematic review aims to critically evaluate various clinical outcomes and safety profile of SGLT2is in comparison to GLP‑1 receptor agonists for the management of T2DM utilizing real-world clinical data. METHODS: A total of 22,100 research articles were extracted from several electronic databases including EMBASE, PubMed, Clinicaltrials.gov, and Cochrane Library from January 2010 to September 2024. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to maintain consistency and transparency in research. To obtain insights from the real-world clinical data, observational studies were used for this review, excluding , randomized controlled trials. RESULTS: The pooled analysis showed that risk ratio (RR) of heart failure and MACE (major cardiovascular events) or revascularization, and odds ratio (OR) of renal outcomes were slightly higher among SGLT2is (experimental) as compared to GLP‑1 agonist (control). In addition, the pooled analysis of hypoglycemic events and all-cause mortalities favored SGLT2is as compared to GLP‑1 agonist. CONCLUSION: SGLT2is appear to be more effective in lowering hospitalization for heart failure; GLP‑1 medication appears to be safer and more successful in treating MACE and improving renal outcomes. Occurrence of hypoglycemic events and the rate of all-cause mortality were found to be low in the SGLT2is group, which supported the clinical implication of SGLT2is. CI - (c) 2025. Der/die Autor(en), exklusiv lizenziert an Springer-Verlag GmbH Austria, ein Teil von Springer Nature. FAU - Alam, Aftab AU - Alam A AUID- ORCID: 0000-0001-6733-8311 AD - Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia. FAU - Imran, Mohd AU - Imran M AUID- ORCID: 0000-0002-6064-1040 AD - Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha, Saudi Arabia. AD - Center for Health Research, Northern Border University, Arar, 73213, Saudi Arabia. FAU - Ur Rehman, Zia AU - Ur Rehman Z AUID- ORCID: 0000-0002-6540-7966 AD - Health Research Centre , Jazan University, 114, Jazan, Saudi Arabia, 45142. AD - Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy , Jazan University, 114, Jazan, Saudi Arabia, 45142. FAU - Sahoo, Biswa Mohan AU - Sahoo BM AUID- ORCID: 0000-0001-8822-0427 AD - School of Pharmacy and Life Sciences, Centurion University of Technology & Management, Jatni, Odisha, India. FAU - Mahapatra, Manoj Kumar AU - Mahapatra MK AD - Department of Pharmaceutical Chemistry, Kanak Manjari Institute of Pharmaceutical Sciences, 769015, Rourkela, Odisha, India. manojbit07@gmail.com. LA - eng PT - Journal Article PT - Systematic Review TT - Therapieergebnisse und Sicherheitsprofil von SGLT2-Inhibitoren versus GLP-1-Agonisten bei Diabetes mellitus Typ 2 : Systematische Ubersichtsarbeit zu Beobachtungsstudien aus der Praxis. DEP - 20250903 PL - Austria TA - Wien Med Wochenschr JT - Wiener medizinische Wochenschrift (1946) JID - 8708475 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Observational Studies as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - Cardiovascular outcomes OT - Glucagon-like peptide 1 agonists OT - Kidney function OT - Real-world observational studies OT - Sodium-glucose cotransporter 2 inhibitors COIS- Conflict of interest: A. Alam, M. Imran, Z. ur Rehman, B.M. Sahoo and M.K. Mahapatra declare that they have no competing interests. EDAT- 2025/09/03 12:34 MHDA- 2026/01/26 13:05 CRDT- 2025/09/03 11:05 PHST- 2025/04/24 00:00 [received] PHST- 2025/08/03 00:00 [accepted] PHST- 2026/01/26 13:05 [medline] PHST- 2025/09/03 12:34 [pubmed] PHST- 2025/09/03 11:05 [entrez] AID - 10.1007/s10354-025-01108-5 [pii] AID - 10.1007/s10354-025-01108-5 [doi] PST - ppublish SO - Wien Med Wochenschr. 2026 Feb;176(1-2):45-59. doi: 10.1007/s10354-025-01108-5. Epub 2025 Sep 3. PMID- 40900093 OWN - NLM STAT- MEDLINE DCOM- 20260702 LR - 20260702 IS - 1572-0241 (Electronic) IS - 0002-9270 (Linking) VI - 121 IP - 7 DP - 2026 Jul 1 TI - Gastrointestinal and Hepatobiliary Safety of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes. PG - 1762-1771 LID - 10.14309/ajg.0000000000003760 [doi] AB - INTRODUCTION: To evaluate the long-term gastrointestinal (GI) and hepatobiliary safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus, compared with other oral antidiabetic medications. METHODS: A retrospective cohort study using the TriNetX network was conducted between 2010 and 2020. After 1:1 propensity score matching, 230,415 patients were included in each group (GLP-1 RAs vs oral antidiabetes mellitus medications). Hazard ratios (HRs) for GI and hepatobiliary outcomes were assessed over 5 years. RESULTS: Among 230,415 matched patients per group, GLP-1 RA use was associated with a higher risk of gastroparesis (HR 1.591, P < 0.001) and intussusception (HR 1.383, P = 0.025) compared with oral antidiabetic therapy. There were no significant differences in acute pancreatitis, cholecystitis, or cholecystectomy rates between groups. Conversely, GLP-1 RA therapy was not associated with increased incidence of GI cancers. Lower hazard ratios were observed for pancreatic (HR 0.897, P = 0.038), gastric (HR 0.838, P = 0.034), esophageal (HR 0.741, P = 0.001), and colorectal cancer (HR 0.870, P = 0.001), although causality cannot be inferred. No significant differences were observed in biliary cancer or hepatocellular carcinoma. DISCUSSION: In this large real-world cohort study, GLP-1 RA therapy was not associated with increased risk of most serious GI or hepatobiliary outcomes compared with other oral diabetes medications. These findings support the overall GI and hepatobiliary safety of GLP-1 RAs in patients with type 2 diabetes, while underscoring the need for vigilance regarding gastroparesis and intussusception in susceptible individuals. Longer-term studies are warranted to fully evaluate cancer risk. CI - Copyright (c) 2025 by The American College of Gastroenterology. FAU - Niu, Chengu AU - Niu C AUID- ORCID: 0000-0001-5610-5897 AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Sun, Kefang AU - Sun K AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Zhang, Jing AU - Zhang J AD - Rainier Springs Behavioral Health Hospital, Vancouver, Washington, USA. FAU - Elkhapery, Ahmed AU - Elkhapery A AUID- ORCID: 0000-0003-0705-1137 AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Zhu, Kaiwen AU - Zhu K AUID- ORCID: 0000-0002-1734-2512 AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Malik, Sheza AU - Malik S AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Xue, Chao AU - Xue C AD - Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA. FAU - Okolo, Patrick I AU - Okolo PI AD - Division of Gastroenterology, Carillion Clinic, Roanoke, Virginia, USA. LA - eng PT - Journal Article DEP - 20250903 PL - United States TA - Am J Gastroenterol JT - The American journal of gastroenterology JID - 0421030 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - *Gastroparesis/chemically induced/epidemiology MH - Propensity Score OTO - NOTNLM OT - GLP-1 receptor agonists OT - TriNetX database OT - gastrointestinal OT - safety OT - type 2 diabetes EDAT- 2025/09/03 11:15 MHDA- 2026/07/02 12:33 CRDT- 2025/09/03 10:34 PHST- 2025/05/21 00:00 [received] PHST- 2025/08/19 00:00 [accepted] PHST- 2026/07/02 12:33 [medline] PHST- 2025/09/03 11:15 [pubmed] PHST- 2025/09/03 10:34 [entrez] AID - 00000434-990000000-01925 [pii] AID - 10.14309/ajg.0000000000003760 [doi] PST - ppublish SO - Am J Gastroenterol. 2026 Jul 1;121(7):1762-1771. doi: 10.14309/ajg.0000000000003760. Epub 2025 Sep 3. PMID- 40899869 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20260904 IS - 1558-9455 (Electronic) IS - 1558-9447 (Print) IS - 1558-9447 (Linking) VI - 21 IP - 6 DP - 2026 Jul TI - Glucagon-Like Peptide-1 Receptor Agonist Therapy Associated With Fewer Diagnoses of Carpal Tunnel Syndrome Within 2 Years of Treatment. PG - 936-943 LID - 10.1177/15589447251366676 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1) are approved for type 2 diabetes treatment. Given the link between diabetes-associated metabolic inflammation and increased carpal tunnel syndrome (CTS) risk, the aim of this study was to investigate development of CTS in diabetic patients who both were and were not taking GLP-1 therapy using a large claims database. METHODS: A retrospective cohort study used a national claims database to identify diabetic patients. Those prescribed GLP-1 therapy were matched to controls by age, sex, comorbidity index, tobacco use, and obesity. Multivariable logistic regression evaluated the 2-year CTS incidence, controlling for various health conditions and socioeconomic factors. Secondary analysis also evaluated the rate of carpal tunnel release (CTR) after being diagnosed with CTS. RESULTS: Glucagon-like peptide-1 therapy significantly reduced 2-year CTS diagnosis risk (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.46-0.52; P < .001). Independent risk factors for increased CTS incidence included chronic obstructive pulmonary disease, osteoarthritis, coronary artery disease, depression, hypothyroidism, and rheumatoid arthritis (RA). Of patients who developed CTS, GLP-1 therapy was associated with increased odds of undergoing CTR (OR 1.23; 95% CI: 1.08-1.41; P = .002). CONCLUSIONS: Glucagon-like peptide-1 therapy is associated with decreased CTS risk in diabetic patients-potentially due to improved metabolic health-and increased odds of undergoing CTR once diagnosed. Further research is needed to clarify GLP-1 therapy's role in reducing nervous system and musculoskeletal disease burden. FAU - Hiredesai, Annika N AU - Hiredesai AN AUID- ORCID: 0009-0009-0043-1189 AD - Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA. FAU - Holle, Alejandro M AU - Holle AM AUID- ORCID: 0009-0004-1936-9155 AD - Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA. FAU - Zhuang, Joyce AU - Zhuang J AD - Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA. FAU - Howlett, Carina P AU - Howlett CP AD - Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA. FAU - Lai, Cara H AU - Lai CH AD - Mayo Clinic, Phoenix, AZ, USA. FAU - Renfree, Kevin J AU - Renfree KJ AUID- ORCID: 0000-0001-7428-848X AD - Mayo Clinic, Phoenix, AZ, USA. FAU - Noland, Shelley S AU - Noland SS AUID- ORCID: 0000-0003-0459-1306 AD - Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article DEP - 20250903 PL - United States TA - Hand (N Y) JT - Hand (New York, N.Y.) JID - 101264149 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Carpal Tunnel Syndrome/epidemiology/prevention & control/diagnosis MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Risk Factors MH - Aged MH - Incidence MH - *Hypoglycemic Agents/therapeutic use MH - Osteoarthritis/epidemiology MH - Logistic Models MH - Arthritis, Rheumatoid/epidemiology MH - Pulmonary Disease, Chronic Obstructive/epidemiology PMC - PMC12408536 OTO - NOTNLM OT - GLP-1 OT - carpal tunnel release OT - carpal tunnel syndrome OT - diabetes OT - metabolic health COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/09/03 11:16 MHDA- 2026/06/18 06:31 PMCR- 2026/09/03 CRDT- 2025/09/03 09:13 PHST- 2026/06/18 06:31 [medline] PHST- 2025/09/03 11:16 [pubmed] PHST- 2025/09/03 09:13 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - 10.1177_15589447251366676 [pii] AID - 10.1177/15589447251366676 [doi] PST - ppublish SO - Hand (N Y). 2026 Jul;21(6):936-943. doi: 10.1177/15589447251366676. Epub 2025 Sep 3. PMID- 40897378 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260305 IS - 1365-2133 (Electronic) IS - 0007-0963 (Linking) VI - 194 IP - 1 DP - 2026 Jan 6 TI - Glucagon-like peptide-1 receptor agonists and reduced mortality, cardiovascular and psychiatric risks in patients with psoriasis: a large-scale cohort study. PG - 59-66 LID - 10.1093/bjd/ljaf346 [doi] AB - BACKGROUND: Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidities in patients with psoriasis. OBJECTIVES: To investigate all-cause mortality, cardiovascular, inflammatory and psychiatric outcomes, and adverse events in patients with psoriasis treated with GLP-1RAs. METHODS: This retrospective population-based cohort study used real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with a GLP-1RA during the follow-up period of 2 years were compared with those treated with other systemic antidiabetic or antiobesity drugs. After 1 : 1 propensity score matching for relevant risk factors, 3048 participants were included in each cohort. Primary outcomes included the risk of cardiometabolic, psychiatric and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and the results were further validated through two sensitivity analyses involving (i) later follow-up periods or (ii) the exclusion of patients with pustular psoriasis. RESULTS: In the matched cohorts of 3048 patients with psoriasis treated with a GLP-1RA [60.4% women, mean (SD) age 56.94 (12.02) years] vs. other antidiabetic and antiobesity drugs [61.9% women, mean (SD) age 56.42 (14.16) years], GLP-1RA treatment was associated with significantly decreased all-cause mortality [hazard ratio (HR) 0.219, 95% confidence interval (CI) 0.123-0.391; P < 0.001] and reduced risk of major adverse cardiac events (HR 0.561, 95% CI 0.442-0.714; P < 0.001). Additionally, lower risks for alcohol (HR 0.346, 95% CI 0.174-0.685; P = 0.009) and substance abuse (HR 0.510, 95% CI 0.350-0.743; P = 0.002) were found. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis than in those with obesity or diabetes without psoriasis. The findings were consistent across all sensitivity analyses. CONCLUSIONS: GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Olbrich, Henning AU - Olbrich H AUID- ORCID: 0000-0003-0863-7148 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Kridin, Khalaf AU - Kridin K AUID- ORCID: 0000-0001-9971-9151 AD - Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel. AD - Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. AD - Lubeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany. FAU - Zirpel, Henner AU - Zirpel H AUID- ORCID: 0000-0003-0053-4312 AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. FAU - Hernandez, Gema AU - Hernandez G AD - TriNetX, LLC, Cambridge, MA, USA. AD - Biomedical Informatics Group Artificial Intelligence Department, E.T.S.I. Informaticos, Universidad Politecnica de Madrid, Madrid, Spain. FAU - Sadik, Christian D AU - Sadik CD AUID- ORCID: 0000-0001-6701-048X AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Gaffal, Evelyn AU - Gaffal E AUID- ORCID: 0000-0002-4639-9841 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Thaci, Diamant AU - Thaci D AUID- ORCID: 0000-0001-8513-550X AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. FAU - Ludwig, Ralf J AU - Ludwig RJ AUID- ORCID: 0000-0002-1394-1737 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. AD - Lubeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany. AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. LA - eng GR - Cluster of Excellence 'Precision Medicine in Chronic Inflammation'/ GR - Deutsche Forschungsgemeinschaft/ GR - Schleswig-Holstein/ PT - Journal Article PL - England TA - Br J Dermatol JT - The British journal of dermatology JID - 0004041 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Br J Dermatol. 2026 Jan 6;194(1):5-6. doi: 10.1093/bjd/ljaf382. PMID: 41037492 MH - Humans MH - *Psoriasis/mortality/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Cardiovascular Diseases/prevention & control/mortality/epidemiology MH - *Obesity/drug therapy/mortality MH - Adult MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Glucagon-Like Peptides/therapeutic use MH - *Mental Disorders/prevention & control/epidemiology MH - Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Follow-Up Studies MH - Comorbidity MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OAB - Psoriasis is a common skin condition. It affects 2% to 3% of the world's population. People with psoriasis can have a higher risk of heart diseases and mental health conditions like depression. A new class of drugs called 'GLP-1RA' is being used to treat people with obesity and type 2 diabetes. These drugs have been effective in reducing risks of heart disease and suicidal thoughts. We are researchers from Germany, Israel and Spain. We used data from the USA to investigate whether patients with psoriasis could benefit from GLP-1RA treatment. We analysed electronic records collected by healthcare providers in the USA. Patients with psoriasis were selected. We then identified who was treated with GLP-1RA or with other drugs for diabetes and obesity. Next, we looked at how many of these patients developed heart, mental health and autoimmune conditions. Afterwards, we performed the same analysis with patients without psoriasis. We found that patients with psoriasis treated with GLP-1RA had a lower risk of dying. They also had lower risks of heart disease and alcohol or drug abuse. However, the risk was no different for unwanted drug effects or other autoimmune diseases. The risk reductions were higher than in people without psoriasis. Our study findings suggest that people with psoriasis could benefit from GLP-1RA treatment for obesity or type 2 diabetes. This could help lead clinicians to provide more treatment choices for people with psoriasis. OABL- eng EDAT- 2025/09/02 22:41 MHDA- 2026/01/06 19:17 CRDT- 2025/09/02 20:03 PHST- 2024/09/02 00:00 [received] PHST- 2025/07/22 00:00 [revised] PHST- 2025/08/27 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2025/09/02 22:41 [pubmed] PHST- 2025/09/02 20:03 [entrez] AID - 8246223 [pii] AID - 10.1093/bjd/ljaf346 [doi] PST - ppublish SO - Br J Dermatol. 2026 Jan 6;194(1):59-66. doi: 10.1093/bjd/ljaf346. PMID- 40892617 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 86 IP - 20 DP - 2025 Nov 18 TI - Sex Differences in Effectiveness of Semaglutide in Patients With Peripheral Artery Disease: The STRIDE Trial. PG - 1843-1857 LID - S0735-1097(25)07554-0 [pii] LID - 10.1016/j.jacc.2025.08.046 [doi] AB - BACKGROUND: Peripheral artery disease (PAD) is prevalent in women and men with type 2 diabetes (T2D). Sex-based differences exist in its epidemiology, clinical presentation, functional impact, outcomes, and potentially in responses to treatments. Recently, semaglutide 1.0 mg has been shown to improve functional outcomes and health-related quality of life in individuals with early symptomatic PAD and T2D in the STRIDE trial. OBJECTIVES: The objective of this study was to describe baseline characteristics, functional status, and therapeutic efficacy of once-weekly semaglutide 1.0 mg between females and males with PAD and T2D as a post hoc analysis from the STRIDE trial. METHODS: The primary endpoint in STRIDE was the ratio to baseline in maximum walking distance (MWD) at week 52 on a constant load treadmill. Confirmatory secondary endpoints included change in MWD at week 57, change in pain-free walking distance at week 52, and change in PAD-specific Vascular Quality of Life Questionnaire-6 total score from baseline to week 52. Herein, we report the outcomes analyzed by sex. RESULTS: Of 792 participants, 195 (24.6%) were female and 597 (75.4%) were male. Females were younger, had lower rates of smoking, lower prevalence of concomitant coronary artery disease and heart failure, and less frequent use of antiplatelet therapies compared with males. Geometric mean MWD at baseline was 187.3 m (coefficient of variation: 0.6) and 191.5 m (coefficient of variation: 0.6) in females and males, respectively. At week 52, there was a consistent improvement in MWD across sexes, which favored semaglutide treatment (P-interaction value = 0.65). At week 57, there was a consistent trend for improved MWD that favored semaglutide treatment for both females and males (P interaction = 0.53). Improvement in pain-free walking distance was consistent across sexes at week 52 in favor of semaglutide (P interaction = 0.80). Likewise, PAD-specific quality of life (assessed using Vascular Quality of Life Questionnaire-6) improvements with semaglutide in both sexes were consistent with the overall trial. CONCLUSIONS: In this post hoc analysis from STRIDE, semaglutide 1.0 mg exhibited consistent improvements in functional outcomes in people with early symptomatic PAD and T2D regardless of sex. Females with PAD demonstrated differences in baseline demographics and treatment patterns compared with males, highlighting the importance of sex-specific evaluation in PAD trials. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. Electronic address: subodh.verma@unityhealth.to. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Horsens Regional Hospital, Horsens, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute of Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Rasouli, Neda AU - Rasouli N AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA. FAU - Sourij, Harald AU - Sourij H AD - Cardiometabolic Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Thomas, Sebastian AU - Thomas S AD - Novo Nordisk GBS India, Bangalore, India. FAU - Norgaard, Sidse K AU - Norgaard SK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. Electronic address: marc.bonaca@cpcmed.org. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250831 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Peripheral Arterial Disease/drug therapy/epidemiology/physiopathology MH - Quality of Life MH - Sex Factors MH - Treatment Outcome MH - Walking/physiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - STRIDE OT - glucagon-like peptide-1 receptor agonist OT - peripheral artery disease OT - semaglutide OT - sex-based differences OT - type 2 diabetes COIS- Funding Support and Author Disclosures This work was supported by the trial sponsor; Novo Nordisk A/S, Denmark. Dr Verma has received payment or honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Heart Research Centre, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, Sanofi, and Sun Pharma; has served on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Sanofi. Dr Catarig is an employee of and owns shares in Novo Nordisk. Dr Houlind has received payment or honoraria, along with travel support, to give a presentation at a workshop organized by LeMaitre. Dr Ludvik has received consulting fees, payment, or honoraria from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has received travel support from Novo Nordisk, with unpaid roles as a National Leader for the Novo Nordisk ESSENCE trial; is a National Leader for the Eli Lilly Triumph-Outcome Study; and is an advisor for an advisory board for the Austrian Obesity Society. Dr Nordanstig has received payment or honoraria from Novo Nordisk; has received travel support from Philips Medical and Abbott; has served on advisory boards for AstraZeneca, Novo Nordisk, and iThera Medical; and has a research grant from the Swedish Heart and Lung Foundation 2021-26, with unpaid roles as President of the Swedish Society for Vascular Surgery and the Swedish Councillor for the European Society for Vascular Surgery 2020-23. Dr Rasouli has served on advisory boards for Eli Lilly and Novo Nordisk; and has received research grants from Eli Lilly, Novo Nordisk, and Soma Scan. Dr Sourij has received payment or honoraria from Amarin, Amgen, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, and Novo Nordisk; has received travel support from Boehringer Ingelheim, Daiichi-Sankyo, and Novo Nordisk; and has served on advisory boards for Amarin, Amgen, Daiichi-Sankyo, Novartis, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, with unpaid roles as a board member of the Austrian Diabetes Association. Dr Thomas is an employee and shareholder at Novo Nordisk. Dr Norgaard is an employee of Novo Nordisk. Dr Bonaca is the Executive Director of the Colorado Prevention Center, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant or consulting funding between August, 2021 and the present from: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, Array BioPharma, AstraZeneca and Affiliates, Atentiv, Audentes Therapeutics, Bayer and Affiliates, Bristol Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, Epizon Pharma, Esperion Therapeutics, Everly Well, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, Janssen and Affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Merck and Affiliates, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanofi-Aventis Group, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, Tourmaline, VarmX, and Virta Health Corporation. EDAT- 2025/09/02 22:21 MHDA- 2025/11/13 06:30 CRDT- 2025/09/02 12:57 PHST- 2025/07/07 00:00 [received] PHST- 2025/08/15 00:00 [revised] PHST- 2025/08/19 00:00 [accepted] PHST- 2025/11/13 06:30 [medline] PHST- 2025/09/02 22:21 [pubmed] PHST- 2025/09/02 12:57 [entrez] AID - S0735-1097(25)07554-0 [pii] AID - 10.1016/j.jacc.2025.08.046 [doi] PST - ppublish SO - J Am Coll Cardiol. 2025 Nov 18;86(20):1843-1857. doi: 10.1016/j.jacc.2025.08.046. Epub 2025 Aug 31. PMID- 40892610 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20251209 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 86 IP - 20 DP - 2025 Nov 18 TI - Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients. PG - 1805-1819 LID - S0735-1097(25)07492-3 [pii] LID - 10.1016/j.jacc.2025.08.027 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined. OBJECTIVES: Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods. METHODS: Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively. RESULTS: A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis, or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles. CONCLUSIONS: GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals. (PROSPERO [GLP-1 RAs Reduce Mortality and Cardiovascular Events Across the Spectrum of Treated Patients: A Systematic Review and Meta-Analysis]; CRD420251032222). CI - Copyright (c) 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Galli, Mattia AU - Galli M AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Cardiovascular Department, Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy. Electronic address: mattia.galli@uniroma1.it. FAU - Benenati, Stefano AU - Benenati S AD - Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, IRCCS Italian Cardiology Network, Genova, Italy. FAU - Laudani, Claudio AU - Laudani C AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Simeone, Beatrice AU - Simeone B AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Sarto, Gianmarco AU - Sarto G AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Ortega-Paz, Luis AU - Ortega-Paz L AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Rocco, Erica AU - Rocco E AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Bernardi, Marco AU - Bernardi M AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Spadafora, Luigi AU - Spadafora L AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - D'Amario, Domenico AU - D'Amario D AD - Department of Translational Medicine, Division of Cardiology, Universita del Piemonte Orientale, AOU Maggiore della Carita, Novara, Italy. FAU - Greco, Ernesto AU - Greco E AD - Department of Health and Life Sciences, European University of Rome, Rome, Italy. FAU - Frati, Giacomo AU - Frati G AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; IRCCS NeuroMed, Pozzilli, Italy. FAU - Federici, Massimo AU - Federici M AD - Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. FAU - Mehran, Roxana AU - Mehran R AD - Center for Interventional Cardiovascular Research & Clinical Trials, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Crea, Filippo AU - Crea F AD - Center of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy. FAU - Angiolillo, Dominick J AU - Angiolillo DJ AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Sciarretta, Sebastiano AU - Sciarretta S AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; IRCCS NeuroMed, Pozzilli, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250827 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic/methods OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular effects OT - efficacy OT - mortality OT - safety COIS- Funding Support and Author Disclosures Dr Galli has received consulting fees from Genomadix; is the principal investigator of the following active grant: Sapienza University of Rome (Grant protocol n. RG1241910F5A1A50); and is an associate editor at European Heart Journal. Dr Federici has received consulting fees or honoraria from Amgen, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Novo Nordisk, and Sanofi. Dr Mehran has received institutional research funding from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; has equity <1% in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (spouse); serves on scientific advisory board for the American Medical Association, American College of Cardiology (board of trustees member), Society for Cardiovascular Angiography and Interventions (Women in Innovations committee member), and an associate editor at JAMA; and is unpaid faculty of the Cardiovascular Research Foundation. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Sciarretta has received honoraria for speeches and/or advisory board participation from Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2025/09/02 22:22 MHDA- 2025/11/13 12:32 CRDT- 2025/09/02 12:57 PHST- 2025/07/23 00:00 [received] PHST- 2025/08/13 00:00 [revised] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/11/13 12:32 [medline] PHST- 2025/09/02 22:22 [pubmed] PHST- 2025/09/02 12:57 [entrez] AID - S0735-1097(25)07492-3 [pii] AID - 10.1016/j.jacc.2025.08.027 [doi] PST - ppublish SO - J Am Coll Cardiol. 2025 Nov 18;86(20):1805-1819. doi: 10.1016/j.jacc.2025.08.027. Epub 2025 Aug 27. PMID- 40892247 OWN - NLM STAT- MEDLINE DCOM- 20251223 LR - 20251226 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 62 IP - 12 DP - 2025 Dec TI - The impact of type 2 diabetes on aging: multidimensional approaches to preserve cognitive health. PG - 2223-2234 LID - 10.1007/s00592-025-02583-3 [doi] AB - The growing prevalence of type 2 diabetes (T2D) among older adults represents a major public health concern, given its association with accelerated cognitive decline and increased risk of neurodegenerative diseases. Several diabetes-related mechanisms, including chronic hyperglycaemia, oxidative stress, vascular dysfunction, and insulin resistance in the brain, negatively impact key cognitive domains, including memory and executive functions. These neuropathophysiological alterations are also linked to structural brain changes, contributing to vulnerability to dementia. This narrative review examines both established and emerging strategies aimed at counteracting the cognitive impact of T2D in aging populations. Traditional interventions, especially structured physical activity programs, have consistently demonstrated benefits for global cognitive functioning. In parallel, new pharmacological treatments, such as GLP-1 receptor agonists (e.g., semaglutide), not only improve glycemic control but may also exert neuroprotective effects. Multidomain approaches integrating metabolic management, nutritional optimization, physical exercise, and social engagement, such as those tested in the J-MIND-Diabetes study, have yielded promising outcomes in preserving cognitive functions. We argue that combining pharmacological and behavioral strategies holds significant potential for supporting cognitive health in elderly individuals with T2D. Such multimodal interventions may enhance resilience to cognitive decline, improve quality of life, and promote healthy brain aging in this at-risk population. CI - (c) 2025. The Author(s). FAU - Lucia, Stefania AU - Lucia S AUID- ORCID: 0000-0002-5033-2121 AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. slucia@sissa.it. FAU - Fornaro, Silvia AU - Fornaro S AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. FAU - Federici, Massimo AU - Federici M AD - Department of Systems Medicine, University of Roma Tor Vergata, 00133, Rome, Italy. FAU - Rumiati, Raffaella Ida AU - Rumiati RI AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. AD - Department of Systems Medicine, University of Roma Tor Vergata, 00133, Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250902 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy/psychology MH - *Aging/physiology/psychology MH - *Cognition/physiology MH - *Cognitive Dysfunction/prevention & control MH - Exercise MH - Aged MH - Brain PMC - PMC12727764 OTO - NOTNLM OT - Aging OT - Cognition OT - Physical activity OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of interest: The authors declare no conflicts of interest. EDAT- 2025/09/02 22:20 MHDA- 2025/12/23 12:48 PMCR- 2025/09/02 CRDT- 2025/09/02 11:14 PHST- 2025/07/11 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/12/23 12:48 [medline] PHST- 2025/09/02 22:20 [pubmed] PHST- 2025/09/02 11:14 [entrez] PHST- 2025/09/02 00:00 [pmc-release] AID - 10.1007/s00592-025-02583-3 [pii] AID - 2583 [pii] AID - 10.1007/s00592-025-02583-3 [doi] PST - ppublish SO - Acta Diabetol. 2025 Dec;62(12):2223-2234. doi: 10.1007/s00592-025-02583-3. Epub 2025 Sep 2. PMID- 40889707 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20260527 IS - 1665-2681 (Print) IS - 1665-2681 (Linking) VI - 30 IP - 2 DP - 2025 Jul-Dec TI - Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide. PG - 102107 LID - S1665-2681(25)00332-1 [pii] LID - 10.1016/j.aohep.2025.102107 [doi] AB - INTRODUCTION AND OBJECTIVES: Disruptions in one-carbon metabolism (OCM) have been linked to cardiometabolic diseases. We evaluated alterations in OCM metabolites and enzymes and the impact of semaglutide in MASLD. MATERIALS AND METHODS: Using targeted metabolomics and bulk-transcriptomics, we analyzed components of OCM in plasma samples and liver biopsies from MASLD patients (n = 100 with F0-F4 fibrosis, 51 % type 2 diabetes) and healthy controls (n = 50). Untargeted metabolomics and transcriptomics were used to analyze plasma and liver specimens from mice with diet-induced obesity and steatohepatitis (DIO-MASH) treated with vehicle or semaglutide compared with chow for 12 weeks. RESULTS: In patients with MASLD vs healthy controls, changes in the concentrations of folate and pyridoxal 5'-phosphate (vitamin B6), betaine, serine, and glycine suggested alteration to the activity of the transsulfuration pathway as well as the methionine and folate cycles. Increased concentrations of metabolites related to enhanced homocysteine conversion and elevated glutamate were also observed. These findings were supported by corresponding alterations in the activity of key enzymes. Similar patterns were identified in comparisons of patients with significant vs no/mild fibrosis and in DIO-MASH mice vs chow. Treatment with semaglutide led to reductions in body weight, hepatic inflammation, and fibrosis and largely reversed the metabolic and gene expression changes observed in DIO-MASH mice. CONCLUSIONS: MASLD may be linked to alterations in key metabolites and enzymes involved in OCM. The changes in humans were replicated in a MASLD mouse model, and reversal was found after treatment with semaglutide. CI - Copyright (c) 2025 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Werge, Mikkel Parsberg AU - Werge MP AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - McCann, Adrian AU - McCann A AD - Bevital AS, Bergen, Norway. FAU - Rashu, Elias Badal AU - Rashu EB AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Lam, Shi Min AU - Lam SM AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Hetland, Liv Eline AU - Hetland LE AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Thing, Mira AU - Thing M AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Nabilou, Puria AU - Nabilou P AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Junker, Anders Ellekaer AU - Junker AE AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Norlin, Jenny AU - Norlin J AD - Global Translation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Veidal, Sanne AU - Veidal S AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Holst, Dorte AU - Holst D AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Bugge, Anne AU - Bugge A AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Viuff, Birgitte Martine AU - Viuff BM AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Hvid, Henning AU - Hvid H AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Bendtsen, Kristian M AU - Bendtsen KM AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Mazzoni, Gianluca AU - Mazzoni G AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Harder, Lea Moerch AU - Harder LM AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Vyberg, Mogens AU - Vyberg M AD - Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark; Center for RNA medicine, Aalborg University, Campus Copenhagen, Denmark. FAU - Serizawa, Reza AU - Serizawa R AD - Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark. FAU - Bendtsen, Flemming AU - Bendtsen F AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Ueland, Per Magne AU - Ueland PM AD - Bevital AS, Bergen, Norway. FAU - Galsgaard, Elisabeth Douglas AU - Galsgaard ED AD - Global Translation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Wewer Albrechtsen, Nicolai J AU - Wewer Albrechtsen NJ AD - Clinical Proteomic Group, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Dept Clinical Biochemistry, Copenhagen University Hospital Bispebjerg and Frederiksberg, Denmark. FAU - Gluud, Lise Lotte AU - Gluud LL AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: lise.lotte.gluud.01@regionh.dk. LA - eng PT - Journal Article DEP - 20250830 PL - Mexico TA - Ann Hepatol JT - Annals of hepatology JID - 101155885 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Male MH - *Liver/metabolism/pathology/drug effects MH - Female MH - Metabolomics/methods MH - Middle Aged MH - Disease Models, Animal MH - Mice, Inbred C57BL MH - Case-Control Studies MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/genetics/blood MH - Mice MH - Liver Cirrhosis/metabolism MH - Diabetes Mellitus, Type 2/complications MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Biomarker OT - GAN DIONASH OT - Keywords: Non-alcoholic steatohepatitis OT - Metabolomics OT - OCM OT - RNAseq OT - Semaglutide OT - Transcriptomics OT - mRNA COIS- Declaration of interests Lise Lotte Gluud has received consulting fees and payment or honoraria for lectures, presentations or manuscript writing from: Boehringer Ingelheim, Novo Nordisk, Pfizer, Gilead, AstraZeneca, Norgine, Sobi, Becton Dickinson, and Alexion. Jenny Norlin, Sanne Veidal, Dorte Holst, Anne Bugge, Lea Morch Harder, Gianluca Mazzoni, Birgitte Martine Viuff, Henning Hvid, Kristian Moss Bendtsen and Elisabeth Douglas Galsgaard are employed at Novo Nordisk A/S. EDAT- 2025/09/02 00:44 MHDA- 2025/12/05 01:02 CRDT- 2025/09/01 19:14 PHST- 2025/01/02 00:00 [received] PHST- 2025/06/04 00:00 [revised] PHST- 2025/06/13 00:00 [accepted] PHST- 2025/12/05 01:02 [medline] PHST- 2025/09/02 00:44 [pubmed] PHST- 2025/09/01 19:14 [entrez] AID - S1665-2681(25)00332-1 [pii] AID - 10.1016/j.aohep.2025.102107 [doi] PST - ppublish SO - Ann Hepatol. 2025 Jul-Dec;30(2):102107. doi: 10.1016/j.aohep.2025.102107. Epub 2025 Aug 30. PMID- 40887719 OWN - NLM STAT- MEDLINE DCOM- 20250901 LR - 20250904 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 17 IP - 9 DP - 2025 Sep TI - Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials. PG - e70151 LID - 10.1111/1753-0407.70151 [doi] LID - e70151 AB - BACKGROUND: This meta-analysis aims to assess the association between exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the incidence of suicidal behavior in patients with type 2 diabetes mellitus (T2DM)/obesity. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov, was conducted from the inception of the databases. The risk ratio (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: This meta-analysis included data from 25 randomized controlled trials (RCTs). The results indicated no significant difference in the incidence of suicidal behavior between the GLP-1 RA exposure group and the control group (RR = 0.84, 95% CI: 0.54-1.32, p = 0.46, I(2) = 0%). Subgroup analysis showed no significant differences in the incidence of suicidal behavior among participants with T2DM (RR = 0.74), obesity (RR = 1.07), adolescents (RR = 0.91), and adults (RR = 0.84). Additionally, no significant differences were observed between the two groups in any type of suicidal behavior, including suicidal ideation (RR = 1.04), suicide attempts (RR = 0.68), depression-related suicides (RR = 0.65), and completed suicides (RR = 1.06). There were also no significant differences between the groups for any type of GLP-1 RA, including dulaglutide (RR = 0.46), exenatide (RR = 0.98), semaglutide (RR = 0.82), lixisenatide (RR = 1.25), and liraglutide (RR = 0.92). No significant differences were observed between the exposure group and control group according to different comparators, including placebo (RR = 0.91) and others (RR = 1.08). All subgroup analyses showed p-values greater than 0.05 (two-sided tests) and I(2) values of 0%. CONCLUSION: Our findings suggest that there is no significant association between GLP-1 RA exposure and suicidal behaviors in patients with T2DM or obesity. CI - (c) 2025 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Chen, Jingqi AU - Chen J AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhang, Qiufeng AU - Zhang Q AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Wu, Qingping AU - Wu Q AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhang, Xiaoming AU - Zhang X AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Xiang, Zhiyi AU - Xiang Z AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhu, Sidong AU - Zhu S AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Dai, Tianfu AU - Dai T AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Si, Yuexiu AU - Si Y AUID- ORCID: 0000-0002-3488-2860 AD - Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, China. LA - eng PT - Journal Article PT - Meta-Analysis PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy/psychology MH - Suicidal Ideation MH - *Suicide/psychology/statistics & numerical data MH - Liraglutide/therapeutic use MH - Adult MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives PMC - PMC12399406 OTO - NOTNLM OT - GLP-1 RAs OT - meta-analysis OT - obesity OT - suicidal behavior OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/09/02 04:46 MHDA- 2025/09/02 04:47 PMCR- 2025/08/31 CRDT- 2025/09/01 00:04 PHST- 2025/07/16 00:00 [revised] PHST- 2025/04/09 00:00 [received] PHST- 2025/07/31 00:00 [accepted] PHST- 2025/09/02 04:47 [medline] PHST- 2025/09/02 04:46 [pubmed] PHST- 2025/09/01 00:04 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - JDB70151 [pii] AID - 10.1111/1753-0407.70151 [doi] PST - ppublish SO - J Diabetes. 2025 Sep;17(9):e70151. doi: 10.1111/1753-0407.70151. PMID- 40887578 OWN - NLM STAT- MEDLINE DCOM- 20250901 LR - 20260918 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Aug 31 TI - SGLT2 inhibitors and GLP-1 receptor agonists: impact on mortality in diabetic patients with cardiovascular disease. PG - 353 LID - 10.1186/s12933-025-02874-7 [doi] LID - 353 AB - BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to reduce cardiovascular risk and mortality in patients with type 2 diabetes mellitus (T2D), yet remain underutilized in clinical practice. This study aimed to evaluate real-world treatment patterns and associated mortality outcomes among patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). METHODS: The CARdiovascular and DIABetes (CARDIAB) cohort included 138,397 patients with T2D and ASCVD. Patients were categorized into four treatment groups: (i) both SGLT2-I and GLP-1RA, (ii) SGLT2-I only, (iii) GLP-1RA only, and (iv) neither medication. The primary outcome was all-cause mortality. RESULTS: Of the 138,397 patients, 57% received neither SGLT2-I nor GLP-1RA, 17% received both, 20% received SGLT2-I only, and 6% received GLP-1RA only. Female sex, older age, non-coronary ASCVD, and absence of follow-up in specialized cardiology or diabetes clinics were associated with lower treatment rates. Compared to those receiving neither medication, all-cause mortality was significantly lower among patients treated with SGLT2-I only (HR 0.28, 95% CI 0.27-0.29), GLP-1RA only (HR 0.39, 95% CI 0.37-0.40) and both agents (HR 0.17, 95% CI 0.16-0.18). This association remained significant following a multivariate analysis. CONCLUSION: In patients with T2D and ASCVD, treatment with SGLT2-I and GLP-1RA, especially in combination, is associated with a substantial reduction in mortality. These findings highlight significant gaps in implementation and the urgent need to optimize use of evidence-based therapies in this high-risk population. CI - (c) 2025. The Author(s). FAU - Arow, Ziad AU - Arow Z AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Hornik-Lurie, Tzipi AU - Hornik-Lurie T AD - Meir Medical Center Research Institute, Kfar Saba, Israel. FAU - Hilu, Ranin AU - Hilu R AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Giladi, Ela AU - Giladi E AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Arnson, Yoav AU - Arnson Y AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Vaknin-Assa, Hana AU - Vaknin-Assa H AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Assali, Abid AU - Assali A AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Pereg, David AU - Pereg D AD - Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel. davidpe@tauex.tau.ac.il. AD - Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. davidpe@tauex.tau.ac.il. CN - CARDIAB research group LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250831 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - Middle Aged MH - Aged MH - Treatment Outcome MH - Risk Assessment MH - *Cardiovascular Diseases/mortality/diagnosis/prevention & control MH - Time Factors MH - *Incretins/therapeutic use/adverse effects MH - United States/epidemiology MH - Risk Factors MH - *Practice Patterns, Physicians'/trends MH - Drug Therapy, Combination MH - Cause of Death MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12400556 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists (GLP-1RA) OT - Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: The study was approved by the local institutional ethics committee in accordance with the principles of the Declaration of Helsinki. In line with Ministry of Health regulations, written informed consent was not required, as data were anonymized and collected retrospectively from electronic medical records without direct patient involvement. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/09/02 04:46 MHDA- 2025/09/02 04:47 PMCR- 2025/08/31 CRDT- 2025/08/31 23:23 PHST- 2025/06/20 00:00 [received] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/09/02 04:47 [medline] PHST- 2025/09/02 04:46 [pubmed] PHST- 2025/08/31 23:23 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - 10.1186/s12933-025-02874-7 [pii] AID - 2874 [pii] AID - 10.1186/s12933-025-02874-7 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Aug 31;24(1):353. doi: 10.1186/s12933-025-02874-7. PMID- 40886075 OWN - NLM STAT- MEDLINE DCOM- 20251014 LR - 20260223 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 334 IP - 14 DP - 2025 Oct 14 TI - Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. PG - 1255-1266 LID - 10.1001/jama.2025.14092 [doi] AB - IMPORTANCE: Heart failure with preserved ejection fraction (HFpEF) is a major cause of hospitalization, often occurring in patients with cardiometabolic comorbidities such as obesity and type 2 diabetes. Although early trials of semaglutide and tirzepatide have shown promising results in improving symptoms, those findings were based on few clinical events, leaving treatment recommendations uncertain. OBJECTIVE: To evaluate the effectiveness and safety of semaglutide and tirzepatide in patients with cardiometabolic HFpEF in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Five cohort studies using national US health care claims data from 2018 to 2024. Two cohort studies emulated the STEP-HFpEF DM (semaglutide) and SUMMIT (tirzepatide) trials to benchmark results. Eligibility criteria were then expanded to evaluate treatment effects in patients typically treated in clinical practice. Finally, a head-to-head comparison of tirzepatide and semaglutide was implemented. Follow-up was up to 52 weeks. EXPOSURES: New use of semaglutide, tirzepatide, or sitagliptin as a placebo proxy. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of hospitalization for heart failure or all-cause mortality. Negative control outcomes, secondary end points, subgroups, and sensitivity analyses were prespecified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting proportional hazards models with propensity score weighting to adjust for a comprehensive set of pretreatment patient characteristics. RESULTS: Benchmarking of the 2 trial emulations demonstrated high agreement on all prespecified metrics. In analyses using expanded eligibility criteria, 58 333 patients were included in the semaglutide vs sitagliptin cohort, 11 257 for tirzepatide vs sitagliptin, and 28 100 for tirzepatide vs semaglutide. Initiators of semaglutide (HR, 0.58 [95% CI, 0.51-0.65]) and tirzepatide (HR, 0.42 [95% CI, 0.31-0.57]) had substantially lower risk of the primary end point compared with sitagliptin. Tirzepatide had no meaningfully lowered risk compared with semaglutide (HR, 0.86 [95% CI, 0.70-1.06]). Negative controls, secondary end points, subgroups, and sensitivity analyses showed consistent results. No substantially increased risk was observed for select safety end points. CONCLUSIONS AND RELEVANCE: In patients with cardiometabolic HFpEF, semaglutide and tirzepatide showed more than 40% risk reduction for the composite of hospitalization for heart failure or all-cause mortality compared with a placebo proxy. Tirzepatide showed no meaningful benefit over semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT06914102, NCT06914154, NCT06914141. FAU - Kruger, Nils AU - Kruger N AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz- und Kreislauferkrankungen, Partner Site Munich Heart Alliance, Munich, Germany. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Fuse, Kenshiro AU - Fuse K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Matseyko, Sofiya AU - Matseyko S AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. FAU - Sreedhara, Sushama Kattinakere AU - Sreedhara SK AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Hahn, Georg AU - Hahn G AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Schunkert, Heribert AU - Schunkert H AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz- und Kreislauferkrankungen, Partner Site Munich Heart Alliance, Munich, Germany. FAU - Wang, Shirley V AU - Wang SV AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT06914154 SI - ClinicalTrials.gov/NCT06914141 SI - ClinicalTrials.gov/NCT06914102 GR - R01 HL141505/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Observational Study PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - TS63EW8X6F (Sitagliptin Phosphate) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1001/jama.2023.16674 CIN - doi: 10.1001/jama.2024.21051 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/drug therapy/etiology/mortality/physiopathology MH - Hospitalization/statistics & numerical data MH - Sitagliptin Phosphate/therapeutic use/adverse effects MH - Stroke Volume/physiology MH - *Tirzepatide/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Glucagon-Like Peptide 1/administration & dosage/adverse effects MH - Follow-Up Studies MH - Obesity/complications/drug therapy MH - Administrative Claims, Healthcare/statistics & numerical data MH - Semaglutide PMC - PMC12400167 MID - NIHMS2138072 COIS- Conflict of Interest Disclosures: Dr Schneeweiss reported personal fees from Aetion Inc, a software-enabled analytics company, and grants from Bayer, UCB, and Boehringer Ingelheim to Brigham and Women's Hospital outside the submitted work. Dr Schunkert reported personal fees from AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Pharmacosmos, Sanofi, Servier, Synlab, Amgen, and Amarin outside the submitted work. Dr Wang reported personal fees from MITRE, a federally funded research and development center for the Centers for Medicare & Medicaid Services and personal fees from Cytel Inc during the conduct of the study. No other disclosures were reported. EDAT- 2025/09/02 04:46 MHDA- 2025/10/14 12:29 PMCR- 2026/03/03 CRDT- 2025/08/31 04:33 PHST- 2025/10/14 12:29 [medline] PHST- 2025/09/02 04:46 [pubmed] PHST- 2025/08/31 04:33 [entrez] PHST- 2026/03/03 00:00 [pmc-release] AID - 2838293 [pii] AID - joi250060 [pii] AID - 10.1001/jama.2025.14092 [doi] PST - ppublish SO - JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092. PMID- 40889359 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 9 DP - 2025 Sep TI - In symptomatic peripheral artery disease with T2D, semaglutide increased maximum walking distance at 1 y. PG - JC100 LID - 10.7326/ANNALS-25-03196-JC [doi] AB - GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text]. FAU - Ades, Matthew AU - Ades M AD - McGill University, Montreal, Quebec, Canada (M.A.). FAU - Anand, Sonia S AU - Anand SS AUID- ORCID: 0000-0003-3692-7441 AD - McMaster University, Hamilton, Ontario, Canada (S.S.A.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20250902 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Peripheral Arterial Disease/drug therapy/physiopathology/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - *Walking MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/09/01 20:44 MHDA- 2025/09/16 18:31 CRDT- 2025/09/01 17:02 PHST- 2025/09/16 18:31 [medline] PHST- 2025/09/01 20:44 [pubmed] PHST- 2025/09/01 17:02 [entrez] AID - 10.7326/ANNALS-25-03196-JC [doi] PST - ppublish SO - Ann Intern Med. 2025 Sep;178(9):JC100. doi: 10.7326/ANNALS-25-03196-JC. Epub 2025 Sep 2. PMID- 40888243 OWN - NLM STAT- MEDLINE DCOM- 20251007 LR - 20260428 IS - 1326-5377 (Electronic) IS - 0025-729X (Print) IS - 0025-729X (Linking) VI - 223 IP - 7 DP - 2025 Oct 6 TI - Incidence of GLP-1 receptor agonist use by women of reproductive age attending general practices in Australia, 2011-2022: a retrospective open cohort study. PG - 365-371 LID - 10.5694/mja2.70026 [doi] AB - OBJECTIVE: To examine longitudinal changes in the initial prescribing of glucagon-like peptide 1 (GLP-1) receptor agonists for women of reproductive age in Australia; to determine whether contraception recommendations are being followed; and to estimate the frequency of pregnancy among women using GLP-1 receptor agonists. STUDY DESIGN: Retrospective open cohort study; analysis of MedicineInsight general practice data. SETTING, PARTICIPANTS: Women aged 18-49 years who visited participating general practices three or more times during the study period (1 January 2011 - 31 July 2022). MAIN OUTCOME MEASURES: Age-standardised incidence of initial GLP-1 receptor agonist prescribing, by year and type 2 diabetes status; proportion of women using highly effective contraception at the time of GLP-1 receptor agonist initiation (contraception overlap); age-standardised incidence of pregnancy within six months of the first prescribing of GLP-1 receptor agonists. RESULTS: Of 1 635 684 women aged 18-49 years, 18 010 (1.1%) were first prescribed GLP-1 receptor agonists during 2011-2022, of whom 3739 (20.8%) had type 2 diabetes. The age-standardised incidence of GLP-1 receptor agonist prescribing for women with type 2 diabetes increased from 13.0 per 1000 women in 2011 to 88.5 per 1000 women in 2022; for women without type 2 diabetes, it increased from 0 to 14.9 per 1000 women. Of the 6293 women first prescribed GLP-1 receptor agonists during 2022, 6954 (90.5%) did not have type 2 diabetes. Contraception overlap with first prescribing of GLP-1 receptor agonists was determined for 3825 women (21.2%). Pregnancies within six months of GLP-1 receptor agonist prescribing were documented for 232 of 10 781 women for whom at least six months of follow-up data were available. CONCLUSIONS: The prescribing of GLP-1 receptor agonists for women of reproductive age is increasing in Australia, and most prescriptions are for women not diagnosed with type 2 diabetes. Fewer than one in four women are using contraception at the time of treatment initiation, and a considerable number are pregnant within six months of the initial prescribing of GLP-1 receptor agonists. Further evidence and guidelines are needed to support the safe and effective use of GLP-1 receptor agonists by women of reproductive age. CI - (c) 2025 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd. FAU - Thapaliya, Kailash AU - Thapaliya K AUID- ORCID: 0000-0002-2897-6844 AD - Flinders University, Adelaide, SA. AD - South Australian Health and Medical Research Institute, Adelaide, SA. FAU - Sweeting, Arianne AU - Sweeting A AUID- ORCID: 0000-0001-6843-6247 AD - Royal Prince Alfred Hospital, Sydney, NSW. AD - The University of Sydney, Sydney, NSW. FAU - Black, Kirsten I AU - Black KI AD - The University of Sydney, Sydney, NSW. AD - Sydney Local Area Health District, Sydney, NSW. FAU - Poprzeczny, Amanda AU - Poprzeczny A AD - The University of Adelaide, Adelaide, SA. AD - Women's and Children's Hospital Adelaide, Adelaide, SA. FAU - Mazza, Danielle AU - Mazza D AUID- ORCID: 0000-0001-6158-7376 AD - Monash University, Melbourne, VIC. AD - SPHERE NHMRC Centre of Research Excellence, Monash University, Melbourne, VIC. FAU - Grzeskowiak, Luke E AU - Grzeskowiak LE AD - Flinders University, Adelaide, SA. AD - South Australian Health and Medical Research Institute, Adelaide, SA. AD - SA Pharmacy, SA Health, Adelaide, SA. LA - eng GR - CRF-210323/Channel 7 Children's Research Foundation/ GR - APP2024717/National Health and Medical Research Council/ PT - Journal Article DEP - 20250901 PL - Australia TA - Med J Aust JT - The Medical journal of Australia JID - 0400714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Med J Aust. 2026 Mar;224(3):e70163. doi: 10.5694/mja2.70163. PMID: 41845954 MH - Humans MH - Female MH - Adult MH - Retrospective Studies MH - Australia/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - General Practice/statistics & numerical data MH - Pregnancy MH - Adolescent MH - Young Adult MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Incidence MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12502889 OTO - NOTNLM OT - Contraception OT - Diabetes mellitus, type 2 OT - Pharmacoepidemiology OT - Reproduction COIS- No relevant disclosures. EDAT- 2025/09/01 08:44 MHDA- 2025/10/07 12:30 PMCR- 2025/10/07 CRDT- 2025/09/01 06:02 PHST- 2024/07/09 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/10/07 12:30 [medline] PHST- 2025/09/01 08:44 [pubmed] PHST- 2025/09/01 06:02 [entrez] PHST- 2025/10/07 00:00 [pmc-release] AID - MJA270026 [pii] AID - 10.5694/mja2.70026 [doi] PST - ppublish SO - Med J Aust. 2025 Oct 6;223(7):365-371. doi: 10.5694/mja2.70026. Epub 2025 Sep 1. PMID- 40887408 OWN - NLM STAT- MEDLINE DCOM- 20260506 LR - 20260506 IS - 1526-0550 (Electronic) IS - 1526-0542 (Linking) VI - 58 DP - 2026 Jun TI - Could Glucagon-Like Peptide-1 (GLP-1) receptor antagonists be used to treat obstructive sleep apnoea in children and adolescents with obesity? PG - 62-68 LID - S1526-0542(25)00077-6 [pii] LID - 10.1016/j.prrv.2025.08.001 [doi] AB - Obstructive sleep apnoea (OSA) and obesity may co-exist in children and adolescents. Childhood obesity tends to persist into adulthood. Sustained weight loss is recommended for obesity and OSA but may be very difficult to achieve and maintain in the real world. The need to provide effective and integrated solutions for the constellation of associated pro-inflammatory and mechanical complications of obesity including obstructive sleep apnoea, metabolic syndrome, and type 2 diabetes mellitus is obvious. Sleep laboratories cannot meet the demand for diagnostic polysomnograms and under resourced paediatric obesity clinics limit themselves to treating those with severe obesity. Importantly, readily accessible resources, such as community-based dietitians and other allied health professionals, are both scarce and overwhelmed by demands for their services. The result is that many families who need assistance, especially those with socio-economic disadvantage and those with neurodiverse children, are unable to access treatments in a timely and equitable manner. In adults, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been demonstrated to reduce body weight by up to 15 % in a 12-month period, improve glycaemic control, improve blood pressure and cardiovascular risk factors and significantly decrease the severity of obstructive sleep apnoea. As part of an integrated, multi-disciplinary approach, GLP-1 RA treatment in the medium to long term may be useful in those adolescents with severe obesity and OSA who are unable, unwilling or unsuitable for treatment with adenotonsillectomy or continuous positive airway pressure [CPAP]. Treatment benefits using GLP-1 RAs as adjunct therapy for OSA have been demonstrated in adults. The time has come to consider prioritising funded availability for adolescents with severe OSA and obesity in combination with support for behaviour change. CI - Crown Copyright (c) 2025. Published by Elsevier Ltd. All rights reserved. FAU - Silva, Dilan AU - Silva D AD - Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia. FAU - Baur, Louise AU - Baur L AD - Douglas Burrows Professor of Paediatrics & Child Health, Children's Hospital Westmead Clinical School, Sydney Medical School, University of Sydney, Camperdown, NSW 2006, Australia; Weight Management Service, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia. FAU - Fitzgerald, Dominic A AU - Fitzgerald DA AD - Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia. Electronic address: dominic.fitzgerald@health.nsw.gov.au. LA - eng PT - Journal Article PT - Review DEP - 20250815 PL - England TA - Paediatr Respir Rev JT - Paediatric respiratory reviews JID - 100898941 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sleep Apnea, Obstructive/drug therapy/complications MH - Child MH - Adolescent MH - *Pediatric Obesity/complications/drug therapy MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss OTO - NOTNLM OT - Apnoea hypopnea index (AHI) OT - Body mass index (BMI) OT - Childhood obesity OT - GLP-1 receptor agonist (GLP-1 RA) OT - Obstructive sleep apnoea (OSA) COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/01 00:45 MHDA- 2026/05/07 00:33 CRDT- 2025/08/31 21:55 PHST- 2025/08/14 00:00 [received] PHST- 2025/08/14 00:00 [accepted] PHST- 2026/05/07 00:33 [medline] PHST- 2025/09/01 00:45 [pubmed] PHST- 2025/08/31 21:55 [entrez] AID - S1526-0542(25)00077-6 [pii] AID - 10.1016/j.prrv.2025.08.001 [doi] PST - ppublish SO - Paediatr Respir Rev. 2026 Jun;58:62-68. doi: 10.1016/j.prrv.2025.08.001. Epub 2025 Aug 15. PMID- 40883386 OWN - NLM STAT- MEDLINE DCOM- 20250829 LR - 20250901 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Aug 29 TI - Effect of GLP-1RA on coronary progression and cardiovascular outcomes in type 2 diabetic patients after PCI: a prospective cohort study. PG - 31824 LID - 10.1038/s41598-025-17574-1 [doi] LID - 31824 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce incidence of cardiovascular events in type 2 diabetes (T2D) patients. Yet, the impact of GLP-1RAs on coronary lesion progression and cardiovascular outcomes after coronary stent implantation remains unclear. We aimed to investigate the effects of GLP-1RAs on coronary lesion progression and major adverse cardiovascular events (MACEs) after percutaneous coronary intervention (PCI). This prospective cohort study enrolled 1664 patients with T2D who underwent PCI from January 2020 to March 2024. Matched GLP-1RAs-treated and non-treated cohorts were formed using the propensity score matching method. The primary endpoint was the incidence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure). Secondary endpoints included in-stent restenosis and non-target lesion progression. Two 131-patient cohorts with balanced baseline characteristics were formed by propensity score matching. During the median follow-up period of 20 months (ranging from 6 to 48 months), the incidence of MACEs was significantly lower in the GLP-1RA group (7.63%)compared to the control group (19.85%) (HR 0.444; 95%CI, 0.215-0.918; P = 0.024). During a median follow-up period of 12 months, 79.39% (104/131) of patients in the control group and 82.44% (108/131) of patients in the GLP-1RA group successfully underwent coronary angiography follow-up. The incidence of in-stent restenosis was 2.78% (3/108) in the GLP-1RA group and 11.54% (12/104) in the control group (P = 0.028). Non-target lesion progression was found in 10.19% (11/108) patient of the GLP-1RA group and 22.12% (23/104) in the control group (P = 0.037). Notable disparities were observed between the two groups regarding improvements of BMI, SBP, HbA1c, LDL-C, CRP. GLP-1RAs significantly reduced the incidence of MACEs and coronary lesion progression in patients with T2D after coronary stent implantation. These findings suggest that GLP-1RAs may have beneficial effects on cardiovascular outcomes and coronary artery disease progression in this population. CI - (c) 2025. The Author(s). FAU - Zeng, Huasu AU - Zeng H AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Hu, Jingchao AU - Hu J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Zhuo, Yang AU - Zhuo Y AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. AD - Department of Cardiology, The First People's Hospital of the Lancang Lahu Autonomous County, Yunnan, People's Republic of China. FAU - Wang, Min AU - Wang M AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Gao, Lin AU - Gao L AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Tang, Zhengde AU - Tang Z AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Zhang, JunFeng AU - Zhang J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. FAU - Yin, Ping AU - Yin P AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. yin_ping@outlook.com. FAU - Gu, Jun AU - Gu J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. forrestgu@126.com. FAU - Wang, Changqian AU - Wang C AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China. wangcqdr@163.com. LA - eng GR - 202402AA310073/Science and Technology Planning Project of Yunnan Province of China/ GR - 82100462/National Natural Science Foundation of China/ GR - 202240149/Shanghai Municipal Health Commission/ GR - JYLJ202209/Clinical Research Program of Shanghai Ninth People's Hospital/ GR - SHDC12023123/the 15th Batch of Emerging Frontier Project Topics of Shanghai Shenkang/ PT - Journal Article DEP - 20250829 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Percutaneous Coronary Intervention/adverse effects MH - Middle Aged MH - Prospective Studies MH - Aged MH - Disease Progression MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Incidence MH - *Coronary Artery Disease PMC - PMC12397294 OTO - NOTNLM OT - Coronary lesion progression OT - GLP-1RAs OT - Major adverse cardiovascular events OT - Percutaneous coronary intervention OT - Type 2 diabetes COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/09/01 16:44 MHDA- 2025/09/01 16:45 PMCR- 2025/08/29 CRDT- 2025/08/29 23:25 PHST- 2025/04/09 00:00 [received] PHST- 2025/08/25 00:00 [accepted] PHST- 2025/09/01 16:45 [medline] PHST- 2025/09/01 16:44 [pubmed] PHST- 2025/08/29 23:25 [entrez] PHST- 2025/08/29 00:00 [pmc-release] AID - 10.1038/s41598-025-17574-1 [pii] AID - 17574 [pii] AID - 10.1038/s41598-025-17574-1 [doi] PST - epublish SO - Sci Rep. 2025 Aug 29;15(1):31824. doi: 10.1038/s41598-025-17574-1. PMID- 40886073 OWN - NLM STAT- MEDLINE DCOM- 20250922 LR - 20260611 IS - 2055-6845 (Electronic) IS - 2055-6837 (Print) VI - 11 IP - 6 DP - 2025 Sep 22 TI - Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis. PG - 552-561 LID - 10.1093/ehjcvp/pvaf037 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D), but heterogeneity exists across cardiovascular outcome trials (CVOTs). A comprehensive search of PubMed, EMBASE, and Cochrane Library was conducted through November 2024. Eligible CVOTs compared GLP-1 RAs with placebo in T2D patients. The primary outcome was MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I(2), tau(2), and R(2). Meta-regression analyses evaluated the influence of baseline covariates on cardiovascular benefits of GLP-1 RAs, contingent upon the detection of moderate to substantial heterogeneity (I(2) >/= 30%). Sensitivity analyses and GRADE assessments were also performed. Ten trials (67 769 patients; 34 536 receiving GLP-1 RAs) were analyzed. GLP-1 RAs significantly reduced MACE compared with placebo (OR = 0.87, 95% CI: 0.81-0.93, P < 0.001, I(2) = 48.4%). Cardiovascular death (OR = 0.86, 95% CI: 0.79-0.94, P < 0.001, I(2) = 22.6%) and all-cause mortality (OR = 0.87, 95% CI: 0.82-0.94, P < 0.001, I(2) = 17.7%) were also reduced. Meta-regression revealed a greater cardiovascular benefit in patients with higher baseline body mass index (BMI; logOR = -0.098 per kg/m(2), P = 0.006, R(2) = 99.98%) and older age (logOR = -0.033 per year, P = 0.023, R(2) = 75.47%). Sensitivity analyses confirmed the robustness of these findings, with consistent effect sizes and no single trial unduly influencing the results. The certainty of evidence was rated as high for all outcomes based on GRADE criteria. GLP-1 RAs significantly reduce MACE, cardiovascular death, and all-cause mortality in T2D patients. Higher baseline BMI and older age were associated with greater cardiovascular benefit. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Cardiology. FAU - Kalayci, Arzu AU - Kalayci A AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. AD - Baim Institute for Clinical Research, 930 Commonwealth Avenue, Suite 3, Boston, MA 02215, USA. FAU - Januzzi, James Louis AU - Januzzi JL AD - Baim Institute for Clinical Research, 930 Commonwealth Avenue, Suite 3, Boston, MA 02215, USA. AD - Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. FAU - Mitsunami, Makiko AU - Mitsunami M AD - Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. FAU - Tanboga, Ibrahim Halil AU - Tanboga IH AD - Department of Cardiology, Hisar Intercontinental Hospital, Nisantasi University, Yamanevler, Site Yolu Cd No:7, 34768 Umraniye, Istanbul, Turkey. FAU - Karabay, Can Yucel AU - Karabay CY AD - Department of Cardiology, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, Selimiye, Tibbiye Cd No:25, 34668 Uskudar, Istanbul, Turkey. FAU - Gibson, Charles Michael AU - Gibson CM AD - Baim Institute for Clinical Research, 930 Commonwealth Avenue, Suite 3, Boston, MA 02215, USA. AD - Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. LA - eng GR - T32 HL094301/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome PMC - PMC12450594 OTO - NOTNLM OT - Cardiovascular outcomes OT - Effect modification OT - GLP-1 receptor agonists OT - Meta-analysis OT - Meta-regression OT - Type 2 diabetes COIS- Conflict of interest: Dr. Januzzi has received research support from Abbott, Applied Therapeutics, AstraZeneca, HeartFlow, and Novartis; he has received consulting income from Abbott, Applied Therapeutics, AstraZeneca, Beckman, Bristol Myers Squibb, Boehringer Ingelheim, Intellia, Novartis, Pfizer, Merck, Roche Diagnostics, and Siemens; he participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Horizon, Johnson & Johnson, and Takeda and reports equity in Imbria Pharmaceuticals and Jana Care. Dr. Gibson has received research support from Johnson & Johnson and CSL Behring; and consulting support from AstraZeneca, CSL Behring, Johnson & Johnson, Janssen, and Bayer. All other authors declare no conflicts of interest. EDAT- 2025/08/31 08:44 MHDA- 2025/09/22 06:31 PMCR- 2025/08/31 CRDT- 2025/08/31 04:22 PHST- 2025/02/25 00:00 [received] PHST- 2025/04/23 00:00 [revised] PHST- 2025/05/12 00:00 [accepted] PHST- 2025/09/22 06:31 [medline] PHST- 2025/08/31 08:44 [pubmed] PHST- 2025/08/31 04:22 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - 8172530 [pii] AID - pvaf037 [pii] AID - 10.1093/ehjcvp/pvaf037 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2025 Sep 22;11(6):552-561. doi: 10.1093/ehjcvp/pvaf037. PMID- 40886061 OWN - NLM STAT- MEDLINE DCOM- 20260308 LR - 20260920 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 47 IP - 10 DP - 2026 Mar 9 TI - Semaglutide promotes bone marrow-derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial. PG - 1171-1182 LID - 10.1093/eurheartj/ehaf690 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major atherosclerotic cardiovascular events in individuals living with either diabetes or obesity. Since the turnover of vascular regenerative (VR) stem and progenitor cells has been demonstrated to modulate vessel repair and atherothrombotic risk, this study aimed to determine the effect of the GLP-1RA semaglutide on the levels of circulating VR cells. METHODS: SEMA-VR CardioLink-15 was a randomized translational trial of usual care vs semaglutide for 6 months in 46 participants with either type 2 diabetes and/or obesity plus atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors. Vascular regenerative cells were enumerated using multi-parametric flow cytometry for high aldehyde dehydrogenase activity (ALDHhi) and lineage-specific cell surface marker expression. The primary endpoint was the 6-month change in VR cell content. RESULTS: Compared with usual care (n = 24), semaglutide (n = 22) led to a greater increase in the number of VR cells [high aldehyde dehydrogenase 1A1 activity and low side scatter (ALDHhiSSClow): +0.8% vs +34.8%; P = .036], pan-haematopoietic myeloid progenitors (ALDHhiSSClowCD45+: +2.8% vs +40.1%; P = .017), and endothelial precursors (ALDHhiSSClowCD34+ CD133+ CD45-: -2.3% vs +66.2%; P = .037) from baseline. Semaglutide also decreased granulocyte precursors (ALDHhiSSChi: +0.3% vs -50.8%; P = .002), particularly those expressing the neutrophil activation marker CD66b and chemokine receptor CXCR2. Semaglutide down-regulated serum proteins over-represented in pro-inflammatory tumour necrosis factor and interleukin signalling pathways. CONCLUSIONS: In people living with either type 2 diabetes or obesity plus ASCVD risk, semaglutide increased circulating VR cell content while reducing pro-inflammatory granulocyte precursors and cytokine production. Collectively, these findings suggest that semaglutide may improve endogenous progenitor cell-mediated blood vessel repair processes. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Park, Brady AU - Park B AUID- ORCID: 0000-0001-6629-285X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Dennis, Fallon AU - Dennis F AUID- ORCID: 0009-0008-7645-7599 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - He, Arianna Z AU - He AZ AUID- ORCID: 0009-0002-5998-4983 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Krishnaraj, Aishwarya AU - Krishnaraj A AUID- ORCID: 0000-0003-3763-478X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Bakbak, Ehab AU - Bakbak E AUID- ORCID: 0000-0003-4687-6553 AD - Faculty of Medicine, University of Queensland, Brisbane, Australia. FAU - Dennis, Cole J AU - Dennis CJ AUID- ORCID: 0009-0000-1075-8139 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Pan, Yi AU - Pan Y AUID- ORCID: 0009-0003-3383-1943 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. FAU - Misner, Elizabeth AU - Misner E AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. FAU - Thayanithy, Veena AU - Thayanithy V AD - North York Diagnostic and Cardiac Centre, Toronto, ON, Canada. AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Lambotharan, Bhavaani AU - Lambotharan B AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Lambotharan, Vaasudevan AU - Lambotharan V AD - Legacy Medical Centre, Toronto, ON, Canada. AD - North West of England School of Foundation Training and Physician Associates, Manchester, United Kingdom. FAU - Lambotharan, Aruna AU - Lambotharan A AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Mazer, C David AU - Mazer CD AUID- ORCID: 0000-0003-2566-4308 AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Anesthesia, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada. AD - Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. AD - Department of Physiology, University of Toronto, Toronto, ON, Canada. FAU - Quan, Adrian AU - Quan A AUID- ORCID: 0000-0001-8008-028X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. FAU - Teoh, Hwee AU - Teoh H AUID- ORCID: 0000-0003-1036-4767 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Division of Endocrinology and Metabolism, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada. FAU - Hess, David A AU - Hess DA AUID- ORCID: 0000-0003-2186-3166 AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Physiology and Pharmacology, Western University, London, ON, Canada. AD - Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Surgery, University of Toronto, 149 College Street, Toronto M5T 1P5, ON, Canada. LA - eng GR - 186065/CAPMC/CIHR/Canada PT - Journal Article PT - Randomized Controlled Trial PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - doi: 10.1093/eurheartj/ehaf983 MH - Humans MH - Male MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Stem Cells/drug effects MH - Aged MH - *Atherosclerosis/prevention & control/drug therapy MH - Obesity/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Regeneration/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13016833 OTO - NOTNLM OT - Atherosclerosis OT - Cardiometabolic disease OT - GLP-1 receptor agonists OT - Obesity OT - Progenitor cell OT - Semaglutide EDAT- 2025/08/31 08:44 MHDA- 2026/03/09 00:36 PMCR- 2025/08/31 CRDT- 2025/08/31 02:23 PHST- 2025/07/06 00:00 [received] PHST- 2025/08/16 00:00 [revised] PHST- 2025/08/19 00:00 [accepted] PHST- 2026/03/09 00:36 [medline] PHST- 2025/08/31 08:44 [pubmed] PHST- 2025/08/31 02:23 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - 8243693 [pii] AID - ehaf690 [pii] AID - 10.1093/eurheartj/ehaf690 [doi] PST - ppublish SO - Eur Heart J. 2026 Mar 9;47(10):1171-1182. doi: 10.1093/eurheartj/ehaf690. PMID- 40875223 OWN - NLM STAT- MEDLINE DCOM- 20251016 LR - 20260909 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 10 DP - 2025 Oct 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Uveitis. PG - 823-832 LID - 10.1001/jamaophthalmol.2025.2822 [doi] AB - IMPORTANCE: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for glycemic control in diabetes, may possess anti-inflammatory properties. Understanding their potential protective role against uveitis could provide insights into novel therapeutic strategies. OBJECTIVE: To evaluate whether being prescribed a GLP-1RA is associated with a reduced risk of developing uveitis. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study using electronic health record (EHR) network data from 2006 to 2025. Propensity score matching was applied to control for demographics, smoking status, hypertension, body mass index, hemoglobin A1c, and diabetic retinopathy stage. Data from the US Collaborative Network of TriNetX, a large multicenter EHR platform, were used in this analysis. Included were patients with and without diabetes with prescriptions for GLP-1RAs, metformin, insulin, or sodium-glucose cotransporter 2 inhibitors (SGLT2is). The control groups consisted of patients without prescriptions for each medication. EXPOSURE: Use of GLP-1RAs, metformin, insulin, or SGLT2is, identified through prescription records. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of noninfectious uveitis, identified using International Classification of Diseases (ICD) encounter diagnosis codes. Risk ratios (RRs) with 95% CIs were calculated to assess the association between GLP-1RA use and uveitis risk. Analyses included risk of overall uveitis and subtypes such as chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis. RESULTS: A total of 516 052 patients were included in this study, 258 026 (mean [SD] age, 56.4 [13.7] years; 159 025 female [61.6%]) in the GLP-1RA group and 258 026 (mean [SD] age, 56.4 [14.0] years; 159 374 female [61.8%]) in the control group. The GLP-1RA cohort had a reduced risk of uveitis compared with controls (RR, 0.48; 95% CI, 0.46-0.51). This was consistent among those with type 2 diabetes (RR, 0.54; 95% CI, 0.51-0.58) and those without diabetes (RR, 0.52; 95% CI, 0.46-0.59). Compared with the cohorts taking metformin (RR, 0.58; 95% CI, 0.54-0.62) and insulin (RR, 0.57; 95% CI, 0.54-0.61), GLP-1RA prescriptions were associated with greater protection against uveitis. However, GLP-1RAs were associated with a slightly increased uveitis risk vs SGLT2is (RR, 1.17; 95% CI, 1.04-1.32). SGLT2i prescriptions were also associated with reduced uveitis risk compared with controls (RR, 0.52; 95% CI, 0.48-0.56). CONCLUSIONS AND RELEVANCE: This cohort study found that GLP-1RA prescriptions were associated with a lower risk of uveitis compared with controls. These findings suggest potential anti-inflammatory benefits beyond glycemic control, warranting further investigation into their role in ocular inflammatory diseases. FAU - Mohan, Nitesh AU - Mohan N AD - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. AD - Case Western Reserve University, Cleveland, Ohio. AD - Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. FAU - Srivastava, Sunil K AU - Srivastava SK AD - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Ophthalmology, MetroHealth Hospital, Cleveland, Ohio. FAU - Schulgit, Matthew J AU - Schulgit MJ AD - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. AD - Case Western Reserve University, Cleveland, Ohio. AD - Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. FAU - Nowacki, Amy S AU - Nowacki AS AD - Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio. FAU - Kaelber, David C AU - Kaelber DC AD - The Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio. AD - Department of Internal Medicine, Case Western Reserve University, Cleveland, Ohio. AD - Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio. AD - Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio. FAU - Sharma, Sumit AU - Sharma S AD - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. AD - Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio. LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - JAMA Ophthalmol. 2025 Oct 1;143(10):832-833. doi: 10.1001/jamaophthalmol.2025.2824. PMID: 40875214 MH - Humans MH - Female MH - Retrospective Studies MH - Male MH - *Uveitis/epidemiology/prevention & control MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Incidence MH - Aged MH - Risk Factors MH - United States/epidemiology MH - Electronic Health Records MH - Adult MH - Propensity Score MH - Metformin/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC12395358 COIS- Conflict of Interest Disclosures: Dr Srivastava reported receiving personal fees from Bausch, Zeiss, Novartis, AbbVie, and Jcyte and grants from Regeneron, Eyepoint, and Novartis outside the submitted work. Dr Kaelber reported receiving grants from National Institutes of Health National Center for Advancing Translational Sciences/Clinical and Translational Science Awards during the conduct of the study. Dr Sharma reported receiving personal fees from 4DMT, Alimera, AbbVie, Apellis, Astellas, Bausch and Lomb, Clearside, Eyepoint, Harrow, Genentech/Roche, Kodiak, Merck, Regeneron, Regenxbio, Ripple, Volk, and Zeiss and grants from Acelyrin, Gilead, Genentech/Roche, Santen, IONIS, and Kodiak outside the submitted work. No other disclosures were reported. EDAT- 2025/08/30 04:46 MHDA- 2025/10/16 12:31 PMCR- 2026/08/28 CRDT- 2025/08/28 11:33 PHST- 2025/10/16 12:31 [medline] PHST- 2025/08/30 04:46 [pubmed] PHST- 2025/08/28 11:33 [entrez] PHST- 2026/08/28 00:00 [pmc-release] AID - 2838119 [pii] AID - eoi250044 [pii] AID - 10.1001/jamaophthalmol.2025.2822 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Oct 1;143(10):823-832. doi: 10.1001/jamaophthalmol.2025.2822. PMID- 40870438 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 8 DP - 2025 Jul 31 TI - The Effectiveness of Semaglutide on a Composite Endpoint of Glycemic Control and Weight Reduction and Its Effect on Lipid Profile Among Obese Type 2 Diabetes Patients. LID - 10.3390/medicina61081393 [doi] LID - 1393 AB - Background and Objectives: Obesity and type 2 diabetes (T2D) are closely linked and associated with a higher risk of complications. This study aims to evaluate the effectiveness of once-weekly semaglutide in achieving a composite endpoint of A1C and weight reduction. Materials and Methods: This retrospective cohort study assessed the effectiveness of semaglutide in obese patients with T2D at a tertiary care hospital in Saudi Arabia. This study included patients who received semaglutide treatment for 12 months, and the endpoint was reducing A1C by >/= 1% and body weight by >/= 5% after 12 months of starting semaglutide. Secondary endpoints include predictors of achieving the composite endpoint and the effect on the lipid profile. Results: The present study enrolled 459 participants, with dyslipidemia and hypertension being the most common comorbidities. After 12 months of treatment with semaglutide, 42% of the patients achieved the composite endpoint. Semaglutide significantly reduced weight, BMI, A1C, FBG, total cholesterol, LDL, and triglycerides. The subgroup analysis showed that patients who achieved the composite endpoint were younger and had significantly lower use of insulin. Females in the study had significantly higher BMI, A1C, and HDL levels and lower levels of triglycerides compared to males. Multivariate analysis revealed that baseline BMI (aOR = 0.953; 95% CI: 0.915 to 0.992; p = 0.02), baseline A1C (aOR = 1.213; 95% CI: 1.062 to 1.385; p = 0.004), and receiving insulin (aOR = 0.02; 95% CI: 0.001 to 0.343; p = 0.007) were significant predictors of composite endpoint achievement. Conclusions: Semaglutide is a valuable option for the treatment of obese patients with T2D. This study found that semaglutide is effective in reducing weight and A1C and improving the lipid profile. The predictors of achievement of the composite endpoint were lower baseline BMI, higher baseline A1C, and insulin non-use. FAU - Alarfaj, Sumaiah J AU - Alarfaj SJ AUID- ORCID: 0000-0002-3144-8305 AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia. LA - eng PT - Journal Article DEP - 20250731 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Lipids) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - Saudi Arabia MH - *Glycemic Control/methods/standards/statistics & numerical data MH - *Weight Loss/drug effects MH - *Lipids/blood/analysis MH - Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged MH - Glycated Hemoglobin/analysis MH - Cohort Studies MH - Blood Glucose/analysis/drug effects MH - Body Mass Index MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12387961 OTO - NOTNLM OT - A1C OT - Saudi OT - composite OT - diabetes mellitus OT - effectiveness OT - glucagon-like peptide-1 receptor agonist OT - lipid profile OT - semaglutide OT - type 2 OT - weight reduction COIS- The author declares no conflicts of interest. EDAT- 2025/08/30 04:50 MHDA- 2025/08/30 04:51 PMCR- 2025/07/31 CRDT- 2025/08/28 01:15 PHST- 2025/07/03 00:00 [received] PHST- 2025/07/25 00:00 [revised] PHST- 2025/07/28 00:00 [accepted] PHST- 2025/08/30 04:51 [medline] PHST- 2025/08/30 04:50 [pubmed] PHST- 2025/08/28 01:15 [entrez] PHST- 2025/07/31 00:00 [pmc-release] AID - medicina61081393 [pii] AID - medicina-61-01393 [pii] AID - 10.3390/medicina61081393 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Jul 31;61(8):1393. doi: 10.3390/medicina61081393. PMID- 40870388 OWN - NLM STAT- MEDLINE DCOM- 20250902 LR - 20250902 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 8 DP - 2025 Jul 25 TI - Real-World Sex Differences in Response to Treatment with Glucagon-like Peptide-1 Receptor Agonists: Analysis of Single-Center Outpatient Case Series. LID - 10.3390/medicina61081343 [doi] LID - 1343 AB - Background and Objectives: Type 2 diabetes (T2D) is a global health burden with increasing prevalence, necessitating effective management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as beneficial therapies, promoting both glycemic control and weight loss, yet real-world data on sex differences in response are limited. This study aimed to investigate sex-based differences in glycemic and weight outcomes, as well as adverse effects, in T2D patients treated with GLP-1 RAs at a single diabetes center. Materials and Methods: In this retrospective analysis, 114 patients (58.8% men) with T2D who were initiated on GLP-1 RA therapy between 2015 and 2023 were evaluated. Data on HbA1c, BMI, and adverse events were collected at baseline and 3, 6, and 12 months post-treatment initiation. Results: Our findings indicated a statistically significant HbA1c reduction (from 8.6% at GLP-1 RA initiation to 6.9% at 12 months in men (p < 0.001) and from 8.4% at initiation to 7.0% at 12 months after GLP-1 RA initiation (p < 0.001) in women). By 12 months, a significantly greater proportion of women compared to men achieved >/= 5% (51.1% vs. 28.4%, p = 0.019) and >/=10% weight loss (29.8% vs. 9.0%, p = 0.006), with both differences reaching statistical significance. A statistically significant difference in weight loss in mean weight change and percent weight change in men vs. women was observed from month 6 of therapy. Conclusions: These findings underscore the effectiveness of GLP-1 RAs in improving glycemic control and weight loss in a real-world setting and suggest that women may experience greater weight reduction. Understanding these differences could inform personalized treatment strategies for optimized outcomes in T2D management. FAU - Inceu, Georgeta Victoria AU - Inceu GV AUID- ORCID: 0000-0002-1624-6916 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Craciun, Anca-Elena AU - Craciun AE AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. AD - 2nd Department, Faculty of Nursing and Health Sciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, 4 Louis Pasteur Street, 400349 Cluj-Napoca, Romania. FAU - Ciobanu, Dana Mihaela AU - Ciobanu DM AUID- ORCID: 0000-0003-3351-6110 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Berchisan, Antonia AU - Berchisan A AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Fodor, Adriana AU - Fodor A AUID- ORCID: 0000-0002-1124-6984 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Bala, Cornelia AU - Bala C AUID- ORCID: 0000-0001-6216-9088 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Roman, Gabriela AU - Roman G AUID- ORCID: 0000-0002-5981-5672 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. FAU - Rusu, Adriana AU - Rusu A AUID- ORCID: 0000-0003-0977-8874 AD - Department of Diabetes and Nutrition Diseases, "Iuliu Hatieganu" University of Medicine and Pharmacy, 2-4 Clinicilor St., 400006 Cluj-Napoca, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania. AD - 2nd Department, Faculty of Nursing and Health Sciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, 4 Louis Pasteur Street, 400349 Cluj-Napoca, Romania. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250725 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glycated Hemoglobin) SB - IM MH - *Diabetes Mellitus, Type 2/blood/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Sex Factors MH - Treatment Outcome MH - *Glycemic Control/methods/statistics & numerical data MH - Body Weight/drug effects MH - Retrospective Studies MH - Glycated Hemoglobin/analysis MH - *Weight Loss/drug effects MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged PMC - PMC12388165 OTO - NOTNLM OT - glucagon-like peptide-1 OT - glycemic control OT - sex differences OT - type 2 diabetes OT - weight management COIS- G.I. reports honoraria for lectures, advisory board participation, and other support from Novo Nordisk, Boehringer Ingelheim, Astra Zeneca, Eli Lilly, Servier, Viatris, Zentiva, Worwag Pharma, and Sanofi. A.R. declares support from Sanofi for meeting attendance. C.B. reports honoraria for lectures, advisory board participation, and other support and fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic, Sanofi, and Worwag. She is also the president of the Romanian Society for Diabetic Neuropathy (unpaid). D.M.C. reports honoraria for lectures and other support from Sanofi, AstraZeneca, Eli Lilly, Medtronic, and Novo Nordisk. C.B. reports honoraria for lectures, advisory boards, and other support and fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic, Sanofi, and Worwag. A.E.C. reports honoraria for lectures, advisory boards, and other support from Novo Nordisk, Servier, Boehringer Ingelheim, Medtronic, Eli Lilly, Viatris, AstraZeneca, Berlin Chemie Menarini, and Sanofi. G.R. reports honoraria for lectures, advisory boards, expert testimony, and other support from Eli Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Medtronic, and Sanofi. A.F. reports honoraria for lectures, advisory boards, and other support and fees from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, and Sanofi. A.B. has nothing to declare. EDAT- 2025/08/30 04:48 MHDA- 2025/08/30 04:49 PMCR- 2025/07/25 CRDT- 2025/08/28 01:15 PHST- 2025/06/24 00:00 [received] PHST- 2025/07/16 00:00 [revised] PHST- 2025/07/23 00:00 [accepted] PHST- 2025/08/30 04:49 [medline] PHST- 2025/08/30 04:48 [pubmed] PHST- 2025/08/28 01:15 [entrez] PHST- 2025/07/25 00:00 [pmc-release] AID - medicina61081343 [pii] AID - medicina-61-01343 [pii] AID - 10.3390/medicina61081343 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Jul 25;61(8):1343. doi: 10.3390/medicina61081343. PMID- 40849680 OWN - NLM STAT- MEDLINE DCOM- 20250824 LR - 20260127 IS - 1941-5923 (Electronic) IS - 1941-5923 (Linking) VI - 26 DP - 2025 Aug 24 TI - Semaglutide Overdose in a Diabetic Patient: Suicidal Behavior and Multiorgan Failure. PG - e947682 LID - 10.12659/AJCR.947682 [doi] LID - e947682 AB - BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity in recent years. Consequently, Semaglutide prescription rates have increased for both its indicated and off-label uses. A possible link between GLP-1 RAs and suicidal behavior has been proposed. CASE REPORT We describe a rare case of suicide-related behavior, adverse outcomes, and a self-injected Semaglutide overdose in a 67-year-old man with diabetes mellitus and overweight. The patient had been on a weekly 1-mg Semaglutide regimen for 1 year prior to hospitalization. He presented with multiorgan failure, hypoglycemia, cholestatic liver dysfunction, and 2 duodenal ulcers, and reported weakness, appetite loss, epigastric pain, severe diarrhea, and melena over 2 weeks, and syncope the day before admission. His clinical status improved gradually, including duodenal ulcers upon discharge. In further questioning, the patient recalled feeling moody and injecting his monthly Semaglutide prescription all at 1 time, 14 days before admission. The self-injection of an overdose 4 times greater than permitted may be considered suicidal behavior for 6 reasons: (1) Semaglutide treatment began more than 1 year before the event; (2) The patient was experienced in self-injecting; (3) A single injection is limited to the weekly recommended dose; (4) If multiple injections exceed the pre-filled monthly amount, an overdose might occur; (5) Semaglutide application by pen is very safe; and (6) He reported being dysphoric prior to the event. CONCLUSIONS Patients receiving GLP-1 Ras, such as Semaglutide, should be screened for common mental disorders in clinical practice. Also, we suggest multiorgan failure should be excluded in Semaglutide-treated patients with acute illness onset. FAU - Zamir, Doron AU - Zamir D AD - Department of Internal Medicine D, Barzilai University Medical Center, Ashkelon, Israel. AD - Faculty of Health Sciences, Ben-Gurion University of Negev, Beersheba, Israel. FAU - Ovadia, Yaniv S AU - Ovadia YS AD - Department of Internal Medicine D, Barzilai University Medical Center, Ashkelon, Israel. AD - Research and Development Authority, Barzilai University Medical Center, Ashkelon, Israel. FAU - Ben-Bassat, Ofer AU - Ben-Bassat O AD - Gastroenterology Institute, Barzilai University Medical Center, Ashkelon, Israel. FAU - Zamir, Mariana AU - Zamir M AD - Division of Dermatology, Sheba Medical Center, Tel Hashomer, Israel. FAU - Malnick, Stephen D H AU - Malnick SDH AD - Department of Internal Medicine C, Kaplan Medical Center, Rehovot, Israel. AD - Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng PT - Case Reports PT - Journal Article DEP - 20250824 PL - United States TA - Am J Case Rep JT - The American journal of case reports JID - 101489566 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Aged MH - *Glucagon-Like Peptides/adverse effects/poisoning/administration & dosage MH - *Drug Overdose MH - *Hypoglycemic Agents/poisoning/adverse effects MH - *Multiple Organ Failure/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Suicide, Attempted MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12396086 COIS- Conflict of interest: None declared EDAT- 2025/08/30 04:49 MHDA- 2025/08/30 04:50 PMCR- 2025/08/24 CRDT- 2025/08/24 01:23 PHST- 2025/08/30 04:50 [medline] PHST- 2025/08/30 04:49 [pubmed] PHST- 2025/08/24 01:23 [entrez] PHST- 2025/08/24 00:00 [pmc-release] AID - 947682 [pii] AID - 10.12659/AJCR.947682 [doi] PST - epublish SO - Am J Case Rep. 2025 Aug 24;26:e947682. doi: 10.12659/AJCR.947682. PMID- 40875227 OWN - NLM STAT- MEDLINE DCOM- 20260325 LR - 20260513 IS - 1529-4242 (Electronic) IS - 0032-1052 (Linking) VI - 157 IP - 4 DP - 2026 Apr 1 TI - Perioperative GLP-1 Receptor Agonist Use and Surgical Outcomes in Nonbariatric Abdominal Panniculectomy: A 10-Year Retrospective Analysis. PG - 645-655 LID - 10.1097/PRS.0000000000012405 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are increasingly used for treatment of patients with type 2 diabetes and obesity because of their metabolic benefits and potential wound-healing properties. However, their perioperative safety in acute surgical settings remains unclear. GLP-1 RAs may alter tissue quality and intensify GLP-1 RA-related side effects. This study was performed to examine postoperative complications and GLP-1 RA-associated adverse effects in nonbariatric patients undergoing panniculectomy. METHODS: The authors conducted a retrospective review of 373 patients who underwent panniculectomy from January of 2013 through January of 2023, including 81 GLP-1 RA users and 292 nonusers. Patients with previous bariatric surgery or concomitant hernia repair were excluded due to the added complexity of mesh placement and altered tissue planes, which could confound wound-healing outcomes. 1 All participants had at least 1 year of follow-up. Baseline demographics, nutritional markers, and GLP-1 RA therapy duration were recorded. Logistic regression was performed to adjust for confounders when comparing complications and adverse effects. RESULTS: GLP-1 RA users had higher rates of type 2 diabetes (55.6% versus 29.5% [ P = 0.01]), hypertension (69.1% versus 52.7% [ P = 0.04]), and chronic obstructive pulmonary disease (17.3% versus 6.5% [ P = 0.02]), along with elevated prealbumin levels (22.8 +/- 6.6 versus 20.4 +/- 7.7 mg/dL [ P = 0.030]). Analyses showed a greater incidence of delayed wound healing (18.5% versus 7.5% [ P = 0.0066]) but lower seroma rates (4.9% versus 14.0% [ P = 0.032]) in GLP-1 RA users. These differences persisted on multivariable regression. No significant differences were noted in infection, fat necrosis, hematoma, or GLP-1 RA-related gastrointestinal side effects. CONCLUSIONS: GLP-1 RAs demonstrate promise in chronic wound care. Their use was correlated with increased incidence of delayed wound healing but fewer seromas in acute surgical settings. Overall, these findings support their perioperative safety, but vigilant monitoring for potential wound-healing delays is advised. CI - Copyright (c) 2025 by the American Society of Plastic Surgeons. FAU - Koenig, Zachary A AU - Koenig ZA AD - From the Division of Plastic Surgery and. FAU - Rashid, Sydney AU - Rashid S AD - Department of Medical Education, West Virginia University School of Medicine. FAU - Hobbs, Gerlad R AU - Hobbs GR AD - Department of Medical Education, West Virginia University School of Medicine. FAU - Uygur, Halil Safak AU - Uygur HS AD - From the Division of Plastic Surgery and. LA - eng PT - Journal Article DEP - 20250826 PL - United States TA - Plast Reconstr Surg JT - Plastic and reconstructive surgery JID - 1306050 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - Middle Aged MH - *Abdominoplasty/methods/adverse effects MH - *Postoperative Complications/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult MH - Treatment Outcome MH - Follow-Up Studies MH - Perioperative Care/methods MH - Wound Healing/drug effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use EDAT- 2025/08/28 20:46 MHDA- 2026/03/25 19:36 CRDT- 2025/08/28 11:33 PHST- 2026/03/25 19:36 [medline] PHST- 2025/08/28 20:46 [pubmed] PHST- 2025/08/28 11:33 [entrez] AID - 00006534-202604000-00014 [pii] AID - 10.1097/PRS.0000000000012405 [doi] PST - ppublish SO - Plast Reconstr Surg. 2026 Apr 1;157(4):645-655. doi: 10.1097/PRS.0000000000012405. Epub 2025 Aug 26. PMID- 40875186 OWN - NLM STAT- MEDLINE DCOM- 20251101 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 11 DP - 2025 Nov TI - Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with Overweight or Obesity and Without Type 2 Diabetes (SHAPE). PG - 5468-5480 LID - 10.1007/s12325-025-03340-2 [doi] AB - INTRODUCTION: Semaglutide 2.4 mg injection (Wegovy((R))), a glucagon-like peptide-1 (GLP-1) receptor agonist, was approved by the US Food and Drug Administration for weight management in June 2021. Tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, was approved for type 2 diabetes mellitus (T2DM; Mounjaro((R))) in May 2022 and weight management (Zepbound((R))) in November 2023. Due to limited data on the long-term effectiveness of these medications, this study assessed real-world weight loss with semaglutide 2.4 mg or tirzepatide after 1 year in patients with overweight or obesity and without T2DM. METHODS: This retrospective cohort study included adults with overweight or obesity and >/= 1 pharmacy claim for semaglutide 2.4 mg or tirzepatide in the US Komodo Health database between June 4, 2021, and December 15, 2023. Patients had continuous enrollment for 1 year before (baseline period) and 1 year after (follow-up period) the index date (date of treatment initiation) and persistence on therapy (no gap of > 30 days' supply) during follow-up. Patients with T2DM at baseline were excluded. Weight change from index to 1 year was descriptively assessed. RESULTS: Overall, 9916 patients were included (semaglutide 2.4 mg, n = 6794; tirzepatide, n = 3122). Baseline characteristics were descriptively similar for semaglutide 2.4 mg and tirzepatide: mean age was 47.8 and 49.5 years, 79.8% and 77.9% were female, and mean index weight was 104.5 and 104.9 kg, respectively. After 1 year of follow-up, the mean weight loss from baseline with semaglutide 2.4 mg and tirzepatide was - 14.6 and - 17.2 kg, respectively, with percent weight loss of - 14.1% and - 16.5%. Most (83.5%) patients treated with semaglutide 2.4 mg reached the maximum dose (2.4 mg), while 25.9% of patients treated with tirzepatide reached the maximum dose (15 mg). CONCLUSION: Findings suggest semaglutide 2.4 mg and tirzepatide are used in descriptively similar populations and both resulted in clinically meaningful weight loss after 1 year of treatment. CI - (c) 2025. The Author(s). FAU - Ng, Carmen D AU - Ng CD AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. cevn@novonordisk.com. FAU - Divino, Victoria AU - Divino V AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Wang, Julia AU - Wang J AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Toliver, Joshua C AU - Toliver JC AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Buss, Marcio AU - Buss M AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. LA - eng PT - Journal Article DEP - 20250828 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Overweight/drug therapy MH - *Obesity/drug therapy MH - *Tirzepatide/therapeutic use/administration & dosage MH - Adult MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12579654 OAB - Obesity, a condition of higher than normal body fat, is common among adults. Obesity contributes to many health problems and higher medical costs compared with adults with normal weight. This study examined the weight loss of patients treated with two drugs recently approved by the US Food and Drug Administration for weight management: semaglutide and tirzepatide. Both drugs affect weight by impacting the glucagon-like peptide-1 system. The US Komodo Health database, which provides patient medical history for over 140 million US patients, including medical and pharmacy claims, clinical observations, and laboratory results, was used to examine data for adults with overweight or obesity who had at least one pharmacy claim for semaglutide or tirzepatide. Weight change 1 year after the start of treatment was measured. This study found that patients treated with semaglutide and tirzepatide had generally similar characteristics, such as age, gender, and starting weight before treatment. After 1 year of treatment, the average weight loss with semaglutide was -14.6 kg, or 14.1% of body weight; the average weight loss with tirzepatide was -17.2 kg, or 16.5% of body weight. Findings from this study suggest that semaglutide and tirzepatide are used for patients with similar characteristics and both led to meaningful weight loss after 1 year of treatment. Given the study size and patient information from the database, the results likely reflect outcomes for real-world patients taking semaglutide or tirzepatide for obesity management. OABL- eng OTO - NOTNLM OT - Clinical practice OT - Obesity OT - Overweight OT - Real-world evidence OT - Semaglutide OT - Tirzepatide OT - Weight loss OT - Weight management COIS- Declarations. Conflict of Interest: Carmen D. Ng, Victoria Divino, Julia Wang, Joshua C. Toliver, and Marcio Buss are employees and shareholders of Novo Nordisk Inc. Ethical Approval: This study was conducted in accordance with relevant guidelines and regulations, including the principals of the Declaration of Helsinki of 1964 and its later amendments. This study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data. The Department of Health and Human Services does not consider analysis of de-identified secondary data to meet the definition for human subject research. Therefore, this study was exempt from federal regulations covering human subject research and did not require institutional review board review. This is as per exemption (d)4 from 45 CFR 46.104. Novo Nordisk Inc. has a data access license to the Komodo Health database. EDAT- 2025/08/28 20:45 MHDA- 2025/11/01 21:22 PMCR- 2025/08/28 CRDT- 2025/08/28 11:24 PHST- 2025/06/18 00:00 [received] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/11/01 21:22 [medline] PHST- 2025/08/28 20:45 [pubmed] PHST- 2025/08/28 11:24 [entrez] PHST- 2025/08/28 00:00 [pmc-release] AID - 10.1007/s12325-025-03340-2 [pii] AID - 3340 [pii] AID - 10.1007/s12325-025-03340-2 [doi] PST - ppublish SO - Adv Ther. 2025 Nov;42(11):5468-5480. doi: 10.1007/s12325-025-03340-2. Epub 2025 Aug 28. PMID- 40874398 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Cardiovascular and kidney outcomes of GLP-1 receptor agonists in adults with obesity: A target trial emulation study. PG - 6527-6536 LID - 10.1111/dom.70054 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular and renal benefits in type 2 diabetes, but their real-world effects in individuals with obesity without diabetes are unclear. This study aimed to evaluate the cardiovascular and kidney outcomes of GLP-1RAs versus other anti-obesity medications (AOMs) in adults with obesity. MATERIALS AND METHODS: This target trial emulation used TriNetX electronic health records (July 2021-May 2025) to identify adults with obesity and no diabetes history who initiated GLP-1RAs (liraglutide, semaglutide, or tirzepatide) or other AOMs. Outcomes included major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), all-cause mortality, mental health conditions, and safety outcomes. Propensity score matching (1:1) balanced baseline characteristics; Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The study included 140 169 matched pairs of GLP-1RA and AOM initiators. Mean follow-up was 392 days for GLP-1RA users and 564 days for AOM users. Compared to AOMs, GLP-1RA use was associated with lower risks of MACE (HR, 0.76; 95% CI, 0.72-0.81), MAKE (HR, 0.64; 95% CI, 0.55-0.74), and all-cause mortality (HR, 0.49; 95% CI, 0.42-0.57). Mental health outcomes also improved, with reduced risks of depression (HR, 0.63), suicidal ideation/attempt (HR, 0.42), and substance use disorder (HR, 0.58). GLP-1RAs were not associated with increased risks of acute pancreatitis (HR, 1.17), hypoglycemia (HR, 1.08), or gastrointestinal symptoms (HR, 0.99). CONCLUSIONS: Among adults with obesity but without diabetes, GLP-1RA use was associated with reduced cardiovascular, kidney, mortality, and mental health risks compared to other AOMs. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhou, Ting AU - Zhou T AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Zhang, Dazheng AU - Zhang D AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Chen, Jiajie AU - Chen J AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AD - Pfizer Inc., New York City, New York, USA. FAU - Asch, David A AU - Asch DA AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Division of General Internal Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence-Based Practice (CEP), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Institute for Biomedical Informatics (IBI), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - U01TR003709/CL/CLC NIH HHS/United States GR - R01AG073435/CL/CLC NIH HHS/United States GR - R01DK128237/CL/CLC NIH HHS/United States GR - R21AI167418/CL/CLC NIH HHS/United States GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - RF1 AG077820/AG/NIA NIH HHS/United States GR - R01 LM013519/LM/NLM NIH HHS/United States GR - R01LM013519/CL/CLC NIH HHS/United States GR - R56AG074604/CL/CLC NIH HHS/United States GR - RF1AG077820/CL/CLC NIH HHS/United States GR - U24 MH136069/MH/NIMH NIH HHS/United States GR - R21 EY034179/EY/NEI NIH HHS/United States GR - R21 AI167418/AI/NIAID NIH HHS/United States GR - U01 TR003709/TR/NCATS NIH HHS/United States GR - R56 AG074604/AG/NIA NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - R21EY034179/CL/CLC NIH HHS/United States GR - U24MH136069/CL/CLC NIH HHS/United States PT - Journal Article DEP - 20250828 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - *Obesity/drug therapy/complications MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control/chemically induced MH - Adult MH - Liraglutide/therapeutic use MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney Diseases/epidemiology/chemically induced MH - Aged MH - Kidney/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12515787 OTO - NOTNLM OT - GLP-1 receptor agonists OT - anti-obesity medication OT - major adverse cardiovascular events OT - major adverse kidney events COIS- Dr. David A. Asch is a partner and part-owner of VAL Health and serves on the advisory boards of Thrive Global and Morpheus. Dr. Yong Chen (Pfizer, New York City, NY, USA) reported receiving personal fees from Merck & Co., Inc. and Pfizer Inc. outside the submitted work. All other authors declare no conflict of interest. EDAT- 2025/08/28 08:45 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/08/28 06:07 PHST- 2025/08/13 00:00 [revised] PHST- 2025/06/16 00:00 [received] PHST- 2025/08/14 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/28 08:45 [pubmed] PHST- 2025/08/28 06:07 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70054 [pii] AID - 10.1111/dom.70054 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6527-6536. doi: 10.1111/dom.70054. Epub 2025 Aug 28. PMID- 40866167 OWN - NLM STAT- MEDLINE DCOM- 20260410 LR - 20260410 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 34 IP - 10 DP - 2025 Oct TI - Implementation Barriers to Evidence-Based Cardiovascular-Kidney-Metabolic Syndrome Management. PG - 1060-1068 LID - S1443-9506(25)00461-5 [pii] LID - 10.1016/j.hlc.2025.05.095 [doi] AB - Cardiovascular-kidney-metabolic (CKM) syndrome is a newly defined health syndrome, encompassing the overlapping pathophysiology and risk factors of cardiovascular and kidney disease, obesity, and type 2 diabetes. It is the leading cause of morbidity and mortality worldwide, with an annual health cost of approximately AUD $24 billion in Australia alone. A disproportionate burden is observed among those with adverse social determinants of health. Despite compelling evidence demonstrating improved metabolic risk factors and reduced risk of kidney failure and cardiovascular events, uptake of traditional and novel cardio-kidney metabolic therapies, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists, remains low. This delay underscores many challenges to optimal CKM syndrome care, including system barriers such as public health policy, siloed health care, and inequitable access to pharmacotherapies; provider barriers, including lack of awareness and clinical inertia; and patient barriers such as social determinants of health. A global shift in the approach to healthcare that focuses on multidimensional, multidisciplinary care and provision of pharmacotherapies in patient groups most at risk is required to change the trajectory of this public health emergency. CI - Crown Copyright (c) 2025. Published by Elsevier B.V. All rights reserved. FAU - Davis, Gina AU - Davis G AD - Department of Nephrology, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Kim, Dana AU - Kim D AD - Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia. FAU - Jun, Min AU - Jun M AD - Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia. FAU - Kotwal, Sradha S AU - Kotwal SS AD - Department of Nephrology, Prince of Wales Hospital, Sydney, NSW, Australia; Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia. Electronic address: skotwal@georgeinstitute.org.au. LA - eng PT - Journal Article PT - Review DEP - 20250826 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Mineralocorticoid Receptor Antagonists) SB - IM MH - *Evidence-Based Medicine/methods/standards MH - Syndrome MH - *Cardiovascular Diseases/complications/drug therapy/metabolism MH - *Renal Insufficiency, Chronic/complications/drug therapy/metabolism MH - *Metabolic Syndrome/complications/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - *Obesity/complications/drug therapy/metabolism MH - Humans MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - Health Policy MH - Public Health/standards OTO - NOTNLM OT - Cardiovascular disease OT - Cardiovascular-kidney-metabolic syndrome OT - Chronic kidney disease OT - Metabolic syndrome OT - Social determinants of health COIS- Declaration of Competing Interests There are no conflicts of interest to disclose. EDAT- 2025/08/28 00:47 MHDA- 2025/10/09 00:31 CRDT- 2025/08/27 21:53 PHST- 2025/01/28 00:00 [received] PHST- 2025/05/25 00:00 [revised] PHST- 2025/05/26 00:00 [accepted] PHST- 2025/10/09 00:31 [medline] PHST- 2025/08/28 00:47 [pubmed] PHST- 2025/08/27 21:53 [entrez] AID - S1443-9506(25)00461-5 [pii] AID - 10.1016/j.hlc.2025.05.095 [doi] PST - ppublish SO - Heart Lung Circ. 2025 Oct;34(10):1060-1068. doi: 10.1016/j.hlc.2025.05.095. Epub 2025 Aug 26. PMID- 40865627 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260323 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 24 IP - 4 DP - 2026 Apr TI - Glucagon-like Peptide-1 Receptor Agonists Are Associated With a Lower Risk of Peptic Ulcer Disease: A Nationwide Cohort Study. PG - 974-985 LID - S1542-3565(25)00735-9 [pii] LID - 10.1016/j.cgh.2025.08.015 [doi] AB - BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for type 2 diabetes mellitus (T2DM) to improve glycemic control and lower cardiovascular risk. Although the impact of GLP-1RAs on gastrointestinal motility has been characterized, their association with mucosal damage, such as in peptic ulcer disease (PUD), has received little attention. METHODS: We conducted a nationwide retrospective study of adults with T2DM using the "All of Us" National Institutes of Health database, including a sub-group analysis of adults who were newly initiated on GLP-1RAs or insulin as second-line therapy. Our primary outcome was the odds of PUD diagnosis after time-dependent use of GLP-1RAs, adjusting for use of insulin, nonsteroidal anti-inflammatory drugs, steroids, and proton pump inhibitors and other confounders. In a subgroup analysis, we used a weighted, time-varying Cox proportional hazards model, while accounting for the competing risks of death and gastrectomy. RESULTS: A total of 66,102 participants with T2DM were identified and included in our primary analysis. After adjusting for possible confounders, GLP-1RAs were associated with significantly lower odds of PUD diagnosis (adjusted odds ratio 0.56; 95% confidence interval, 0.45-0.71; P < .001). Our subgroup included a total of 3313 patients (1270 new GLP-1RA users; 2043 new insulin users). In this analysis, switching to a GLP-1RA as second-line therapy was associated with a significantly lower hazard of PUD compared with switching to insulin (adjusted hazard ratio [HR], 0.44; 95% confidence interval, 0.30-0.63; P < .001). The model confirmed that active use of nonsteroidal anti-inflammatory drugs (HR, 2.39) and steroids (HR, 1.84) were also associated with increased likelihood of PUD. CONCLUSIONS: In this nationwide cohort study of patients with T2DM, GLP-1RA use was associated with 44% lower odds of PUD. In our propensity score-matched subgroup, switching to GLP-1RA as second-line therapy was associated with a 56% lower hazard of PUD vs insulin. These findings indicate an association between GLP-1RA use and reduced risk of PUD. CI - Copyright (c) 2026 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Seika, Philippa AU - Seika P AD - Department of Surgery, Campus Charite Mitte, Campus Virchow-Klinikum, Charite Universitatsmedizin, Berlin, Germany; Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Chang, Jocelyn AU - Chang J AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Hong, Su Min AU - Hong SM AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Ballou, Sarah AU - Ballou S AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Rangan, Vikram AU - Rangan V AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Ramprasad, Chethan AU - Ramprasad C AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Iturrino, Johanna AU - Iturrino J AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Denecke, Christian AU - Denecke C AD - Department of Surgery, Campus Charite Mitte, Campus Virchow-Klinikum, Charite Universitatsmedizin, Berlin, Germany. FAU - Lembo, Anthony AU - Lembo A AD - Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Nee, Judy AU - Nee J AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Kulkarni, Subhash AU - Kulkarni S AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts; Program in Neuroscience, Harvard Medical School, Boston, Massachusetts. FAU - Pasricha, Trisha AU - Pasricha T AD - Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts. Electronic address: tpasrich@bidmc.harvard.edu. LA - eng PT - Journal Article DEP - 20250825 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peptic Ulcer/epidemiology/prevention & control MH - Aged MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Risk Assessment OTO - NOTNLM OT - Glucagon- OT - Peptic Ulcer Disease OT - Type 2 Diabetes Mellitus OT - ike Peptide-1 Receptor Agonists EDAT- 2025/08/28 00:47 MHDA- 2026/03/23 06:32 CRDT- 2025/08/27 19:11 PHST- 2025/01/31 00:00 [received] PHST- 2025/08/07 00:00 [revised] PHST- 2025/08/13 00:00 [accepted] PHST- 2026/03/23 06:32 [medline] PHST- 2025/08/28 00:47 [pubmed] PHST- 2025/08/27 19:11 [entrez] AID - S1542-3565(25)00735-9 [pii] AID - 10.1016/j.cgh.2025.08.015 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2026 Apr;24(4):974-985. doi: 10.1016/j.cgh.2025.08.015. Epub 2025 Aug 25. PMID- 40865282 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260325 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 781 DP - 2025 Sep 25 TI - Computational assessment of the dimeric incretin GLP-1cpGLP-1 reveals the structural bases for its activity. PG - 152525 LID - S0006-291X(25)01240-9 [pii] LID - 10.1016/j.bbrc.2025.152525 [doi] AB - Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, leading to hyperglycemia. The glucagon-like peptide-1 receptor (GLP-1R), a class B1 G protein-coupled receptor (GPCR), plays a crucial role in glucose homeostasis by enhancing insulin secretion, inhibiting glucagon release, and promoting satiety. However, the short half-life of endogenous GLP-1 due to rapid enzymatic degradation has led to the development of GLP-1 receptor agonists (GLP-1RAs) with improved stability and efficacy. This study investigates GLP-1cpGLP-1, a dimeric GLP-1 analog active in vivo, incorporating a flexible C-peptide linker, designed to enhance receptor activation and prolong therapeutic effects. Using molecular dynamics simulations and structural modeling, we analyzed the interaction dynamics of GLP-1cpGLP-1 with GLP-1R, comparing its binding mode to native GLP-1. Our findings reveal that GLP-1cpGLP-1 maintains essential interactions required for receptor activation while introducing novel contacts at an allosteric site, suggesting a possible positive allosteric auto-modulation mechanism. These insights highlight GLP-1cpGLP-1's potential as an innovative GLP-1RA with enhanced pharmacokinetics and receptor engagement, paving the way for future incretin-based therapeutics in T2DM and obesity. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Mariam, Zamara AU - Mariam Z AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. FAU - Abolhasan, Mohammad Reza AU - Abolhasan MR AD - Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. FAU - Reynolds, Christopher A AU - Reynolds CA AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. FAU - Yousefi, Reza AU - Yousefi R AD - Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. FAU - Deganutti, Giuseppe AU - Deganutti G AD - Centre for Health and Life Sciences, Coventry University, Coventry, UK. Electronic address: ad5288@coventry.ac.uk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250820 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Glucagon-Like Peptide 1/chemistry/analogs & derivatives/metabolism MH - Molecular Dynamics Simulation MH - Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - *Incretins/chemistry/metabolism MH - Humans MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Protein Multimerization MH - Protein Binding OTO - NOTNLM OT - G protein-coupled receptor OT - Glucagon-like peptide-1 receptor OT - Incretin OT - Molecular dynamics simulations OT - Type 2 diabetes COIS- Declaration of competing interest None Declared. EDAT- 2025/08/28 00:47 MHDA- 2025/09/16 13:01 CRDT- 2025/08/27 18:06 PHST- 2025/06/25 00:00 [received] PHST- 2025/08/14 00:00 [revised] PHST- 2025/08/19 00:00 [accepted] PHST- 2025/09/16 13:01 [medline] PHST- 2025/08/28 00:47 [pubmed] PHST- 2025/08/27 18:06 [entrez] AID - S0006-291X(25)01240-9 [pii] AID - 10.1016/j.bbrc.2025.152525 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2025 Sep 25;781:152525. doi: 10.1016/j.bbrc.2025.152525. Epub 2025 Aug 20. PMID- 40859882 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Efficacy and safety benefits of HR17031, a fixed-ratio combination of INS068 and noiiglutide, versus its components alone in Chinese patients with type 2 diabetes uncontrolled on oral antidiabetic drug(s): A phase 2, multicentre, open-label, randomised, parallel three-arm, treat-to-target trial. PG - 6428-6439 LID - 10.1111/dom.70036 [doi] AB - AIMS: To assess the efficacy and safety of HR17031, a fixed-ratio combination of basal insulin analogue (INS068) and GLP-1 receptor agonist (noiiglutide), versus its components alone in patients with type 2 diabetes uncontrolled on metformin with or without a second oral antidiabetic drug. MATERIALS AND METHODS: This phase 2 multicentre trial randomised 455 patients with type 2 diabetes (HbA1c 7.5%-11.0% [58.0-97.0 mmol/mol]; previous metformin +/- another oral antidiabetic drug) 2:2:1 to HR17031 (n = 183), INS068 (n = 182) or noiiglutide (n = 90). The primary endpoint was HbA1c change from baseline to week 26. RESULTS: HR17031 achieved a greater reduction in HbA1c than INS068 and noiiglutide (-2.4% [-26 mmol/mol] vs. -1.5% [-16 mmol/mol] and -1.7% [-19 mmol/mol]), indicating superiority for HR17031 over both INS068 and noiiglutide (least-squares mean difference = -0.9% [-10 mmol/mol] and -0.7% [-7 mmol/mol], respectively; both p < 0.0001). More patients reached HbA1c target <7.0% (53 mmol/mol) and /=18 years were randomised to once-daily oral semaglutide 3, 7, or 14 mg, or placebo (PIONEER 11) or sitagliptin 100 mg (PIONEER 12). Changes from baseline in HbA(1c) and body weight at week 26 were analysed in subgroups according to the following baseline characteristics: age, HbA(1c), body mass index, duration of diabetes, and presence of gastrointestinal disease. Adverse events (AEs) by baseline subgroups were also assessed. RESULTS: In total, 390 (PIONEER 11) and 1084 (PIONEER 12) Chinese participants with type 2 diabetes were evaluated. Most baseline characteristics were similar across the two trials in the different subgroups. Overall, greater reductions in HbA(1c) and body weight were observed with oral semaglutide versus comparators across the subgroups. A significant difference was observed for change in HbA(1c) by baseline HbA(1c) subgroups (p(int) <0.05), with greater reductions observed in the subgroups with higher baseline HbA(1c). Most AEs were gastrointestinal-related and mild-to-moderate. CONCLUSIONS/INTERPRETATION: Oral semaglutide reduces HbA(1c) and body weight across a range of baseline subgroups in a Chinese population with type 2 diabetes without any unexpected additional safety concerns. These results support the use of oral semaglutide in a broad population in clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yuan, Guoyue AU - Yuan G AUID- ORCID: 0000-0003-0822-6066 AD - Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liu, Jun AU - Liu J AD - Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China. FAU - Zhang, Bingjie AU - Zhang B AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. LA - eng GR - N/A/Novo Nordisk Shanghai (Ltd)/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250822 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose MH - Body Weight/drug effects MH - China/epidemiology/ethnology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/administration & dosage MH - *Sitagliptin Phosphate/administration & dosage MH - Treatment Outcome MH - *East Asian People/statistics & numerical data MH - *Glucagon-Like Peptide 1/administration & dosage MH - Semaglutide PMC - PMC12515755 OTO - NOTNLM OT - GLP-1RA OT - HbA1c OT - body weight OT - oral semaglutide OT - safety OT - type 2 diabetes COIS- Linong Ji reports receiving consulting or lecture fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Innovent Biologics, Gan & Lee Pharmaceuticals, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare. Linong Ji is also the independent Director of Shanghai Benemae Pharmaceutical Corporation. Jun Liu and Guoyue Yuan declared no conflicts of interest. Bingjie Zhang, Wenyan Liu, and Zewei Shen are employees of Novo Nordisk and own stock in the company. EDAT- 2025/08/22 12:45 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/08/22 06:43 PHST- 2025/08/05 00:00 [revised] PHST- 2025/03/04 00:00 [received] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/22 12:45 [pubmed] PHST- 2025/08/22 06:43 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70031 [pii] AID - 10.1111/dom.70031 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6386-6394. doi: 10.1111/dom.70031. Epub 2025 Aug 22. PMID- 40842022 OWN - NLM STAT- MEDLINE DCOM- 20251216 LR - 20260630 IS - 2163-8306 (Electronic) IS - 2163-8306 (Linking) VI - 14 IP - 12 DP - 2025 Dec TI - A Combined Modeling Approach to Predict the Effect of Gastric Emptying Delay on the Pharmacokinetics of Small Molecules. PG - 2026-2039 LID - 10.1002/psp4.70101 [doi] AB - Dulaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, is approved for improving glycemic control and reducing cardiovascular risks in patients with type 2 diabetes mellitus (T2DM). This research investigates the effect of dulaglutide on gastric emptying and its impact on the pharmacokinetics (PK) of orally administered molecules utilizing a combination of population pharmacokinetic (PopPK) and physiologically based pharmacokinetic (PBPK) modeling approaches. In clinical studies, the gastric emptying delay (GED) was evaluated in healthy participants and patients with T2DM at various dose levels of dulaglutide. A PopPK model estimated the exposure-dependent delay in gastric emptying, which was then input into the orally administered small molecule PBPK models. These PBPK models, informed by internal clinical studies and publicly available data, quantified the effect of dulaglutide-induced GED on the area under the curve (AUC), maximum concentration (C(max)), and time to maximum concentration (t(max)) of the co-administered drugs. The modeling approach was verified for reproducing observed GED-mediated drug-drug interactions (DDIs) at low doses of dulaglutide and to predict DDIs at a 4.5 mg dulaglutide dose. The clinical studies demonstrated that the 1.5 mg dulaglutide dose has no clinically relevant effect on the pharmacokinetics of small molecules, and the modeling led to a similar conclusion at 4.5 mg dulaglutide. This work demonstrates that modeling approaches can be used to predict potential GLP-1-mediated DDIs related to gastric emptying delay, increasing the efficiency of the clinical pharmacology programs. CI - (c) 2025 Eli Lilly and Company. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Posada, Maria M AU - Posada MM AUID- ORCID: 0000-0003-4645-0763 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Schneck, Karen B AU - Schneck KB AUID- ORCID: 0000-0002-9229-4987 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Morse, Bridget L AU - Morse BL AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rougee, Luc R A AU - Rougee LRA AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Tham, Lai San AU - Tham LS AUID- ORCID: 0000-0002-1249-8526 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Lilly Centre for Clinical Pharmacology, Singapore, Singapore. FAU - Rehmel, Jessica F AU - Rehmel JF AUID- ORCID: 0009-0001-5049-1018 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thompson, Brian AU - Thompson B AUID- ORCID: 0000-0003-3055-9414 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Stamatis, Stephen D AU - Stamatis SD AUID- ORCID: 0000-0001-9919-2011 AD - Synthetic Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Hall, Stephen D AU - Hall SD AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Dickinson, Gemma L AU - Dickinson GL AUID- ORCID: 0009-0008-1808-6881 AD - Global PK/PD and Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250821 PL - United States TA - CPT Pharmacometrics Syst Pharmacol JT - CPT: pharmacometrics & systems pharmacology JID - 101580011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Gastric Emptying/drug effects MH - *Glucagon-Like Peptides/analogs & derivatives/pharmacokinetics/administration & dosage/pharmacology MH - *Models, Biological MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - *Immunoglobulin Fc Fragments/administration & dosage/pharmacology MH - *Recombinant Fusion Proteins/pharmacokinetics/administration & dosage/pharmacology MH - Adult MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/pharmacokinetics/administration & dosage MH - Area Under Curve MH - Administration, Oral MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12706417 OTO - NOTNLM OT - GLP1 receptor agonist OT - PBPK OT - drug-drug interactions OT - dulaglutide OT - gastric emptying delay COIS- All authors (M.M.P., K.B.S., B.L.M., B.T., J.F.R., L.R.A.R., L.S.T., S.D.H., S.D.S., and G.L.D.) are paid employees or retirees of Eli Lilly and Company and hold stock ownership in Eli Lilly and Company. EDAT- 2025/08/22 08:44 MHDA- 2025/12/16 06:29 PMCR- 2025/08/21 CRDT- 2025/08/22 00:32 PHST- 2025/07/21 00:00 [revised] PHST- 2025/04/14 00:00 [received] PHST- 2025/07/24 00:00 [accepted] PHST- 2025/12/16 06:29 [medline] PHST- 2025/08/22 08:44 [pubmed] PHST- 2025/08/22 00:32 [entrez] PHST- 2025/08/21 00:00 [pmc-release] AID - PSP470101 [pii] AID - 10.1002/psp4.70101 [doi] PST - ppublish SO - CPT Pharmacometrics Syst Pharmacol. 2025 Dec;14(12):2026-2039. doi: 10.1002/psp4.70101. Epub 2025 Aug 21. PMID- 40841345 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260903 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 Suppl 2 IP - Suppl 2 DP - 2026 Sep TI - Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes. PG - 75-87 LID - 10.1002/oby.24366 [doi] AB - OBJECTIVE: The real-world evidence on the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer risk remains limited and mixed. METHODS: In 2013-2020 national Medicare claims data, we included cancer-naive patients with type 2 diabetes (T2D). We identified those who initiated GLP-1 RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP4i) and conducted 1:1 propensity score matching for confounding adjustment. Cox proportional hazards models were used to estimate hazard ratios (HR) of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer). RESULTS: In the matched GLP-1RA versus SGLT2i cohort (n = 21,362 pairs), GLP-1RA users had similar overall cancer risk with SGLT2i users (HR, 1.03 [95% CI, 0.95-1.12]), but GLP-1RAs were associated with an increased kidney cancer risk (HR, 1.43 [1.06-1.92]). In the matched GLP-1RA versus DPP4i cohort (n = 20,962 pairs), the GLP-1RA versus DPP4i comparison showed no significant difference in overall cancer risk (HR, 0.96 [0.89-1.04]) but revealed a significantly elevated endometrial cancer risk (HR, 1.55 [1.01-2.37]). CONCLUSION: GLP-1RAs might be associated with an increased risk of certain cancer types. Future studies are needed to validate the potential tumorigenic risk associated with GLP1-RAs. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Lu, Ying AU - Lu Y AUID- ORCID: 0009-0007-0674-3015 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Dai, Hao AU - Dai H AD - Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. FAU - Tang, Huilin AU - Tang H AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Donahoo, William T AU - Donahoo WT AUID- ORCID: 0000-0002-2126-860X AD - Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - George, Thomas J AU - George TJ AD - Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Sun, Ramon C AU - Sun RC AD - Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA. AD - Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, Florida, USA. FAU - Jiang, Sizun AU - Jiang S AD - Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. AD - Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Pathology, Dana Farber Cancer Institute, Boston, Massachusetts, USA. FAU - Tan, Aik Choon AU - Tan AC AD - Department of Oncological Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. AD - Department of Biomedical Informatics, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. FAU - Guo, Yi AU - Guo Y AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Licht, Jonathan D AU - Licht JD AD - University of Florida Health Cancer Center, University of Florida Health, Gainesville, Florida, USA. FAU - Allen, John M AU - Allen JM AUID- ORCID: 0000-0002-0033-4508 AD - Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana, USA. FAU - Lee, Kelvin P AU - Lee KP AD - Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA. AD - Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. AD - Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA. AD - Regenstrief Institute, Indianapolis, Indiana, USA. LA - eng GR - R01 AG084236/AG/NIA NIH HHS/United States GR - U18 DP006512/DP/NCCDPHP CDC HHS/United States GR - U01 HS010465/HS/AHRQ HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States GR - R01 AG083039/AG/NIA NIH HHS/United States GR - R01 CA246418/CA/NCI NIH HHS/United States GR - U18DP006512/CC/CDC HHS/United States GR - R01CA246418/AG/NIA NIH HHS/United States GR - R01AG084236/AG/NIA NIH HHS/United States GR - R01AG083039/AG/NIA NIH HHS/United States GR - U18 HS025298/HS/AHRQ HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - U01 HS009949/HS/AHRQ HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States GR - R01AG083039/AG/NIA NIH HHS/United States GR - R01AG084236/AG/NIA NIH HHS/United States GR - R01CA246418/AG/NIA NIH HHS/United States GR - U18DP006512/JG/JG CDC HHS/United States PT - Journal Article DEP - 20250821 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Aged MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/epidemiology/etiology/chemically induced MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - United States/epidemiology MH - Aged, 80 and over MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Risk Factors MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Medicare MH - Proportional Hazards Models PMC - PMC12906048 MID - NIHMS2121454 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cancer OT - dipeptidyl peptidase-4 inhibitors OT - sodium-glucose cotransporter-2 inhibitors OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/08/22 00:44 MHDA- 2026/09/02 05:36 PMCR- 2026/09/02 CRDT- 2025/08/21 23:03 PHST- 2025/05/13 00:00 [revised] PHST- 2025/04/16 00:00 [received] PHST- 2025/05/15 00:00 [accepted] PHST- 2026/09/02 05:36 [medline] PHST- 2025/08/22 00:44 [pubmed] PHST- 2025/08/21 23:03 [entrez] PHST- 2026/09/02 00:00 [pmc-release] AID - OBY24366 [pii] AID - 10.1002/oby.24366 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Sep;34 Suppl 2(Suppl 2):75-87. doi: 10.1002/oby.24366. Epub 2025 Aug 21. PMID- 40833394 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20250825 IS - 1535-1386 (Electronic) IS - 0021-9355 (Print) IS - 0021-9355 (Linking) VI - 107 IP - 16 DP - 2025 Jul 10 TI - GLP-1 Receptor Agonists in Orthopaedic Surgery: Implications for Perioperative Care and Outcomes: An Orthopaedic Surgeon's Perspective. PG - 1879-1886 LID - 10.2106/JBJS.24.01287 [doi] AB - ➢ Glucagon-like peptide-1 (GLP-1) receptor agonists are a promising tool for preoperative weight loss in the patient who is undergoing orthopaedic surgery and has concomitant obesity and type-2 diabetes mellitus.➢ With regard to the perioperative management of GLP-1 receptor agonists for the orthopaedic surgeon, the American Society of Anesthesiologists (ASA) recommends withholding daily-dose GLP-1 therapy on the day of the elective surgical procedure and withholding weekly-dose therapy for the week prior to the procedure.➢ The ASA recommends postponing surgery or proceeding with "full stomach precautions" if the patient undergoing an orthopaedic procedure and taking GLP-1 therapy exhibits gastrointestinal symptoms on the day of the elective procedure.➢ In the trauma setting, patients taking GLP-1 therapy should proceed with the surgical procedure at the discretion of the surgeon with full stomach precautions or a preoperative point-of-care gastric ultrasound.➢ GLP-1 receptor agonists show the potential for disease modification in osteoarthritis and osteoporosis. CI - Copyright (c) 2025 The Author(s). Published by The Journal of Bone and Joint Surgery, Incorporated. FAU - Ramanathan, Rahul AU - Ramanathan R AUID- ORCID: 0000-0002-1093-3678 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Lee, Joon Y AU - Lee JY AUID- ORCID: 0000-0001-5884-0561 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Dalton, Jonathan F AU - Dalton JF AUID- ORCID: 0000-0002-7452-2712 AD - The Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Lin, Ryan T AU - Lin RT AUID- ORCID: 0000-0002-3683-4678 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Lee, Isaac AU - Lee I AUID- ORCID: 0009-0009-6074-4064 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Gonzalez, Christopher Jr AU - Gonzalez C Jr AUID- ORCID: 0000-0001-6227-8372 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Shaw, Jeremy D AU - Shaw JD AUID- ORCID: 0000-0002-7057-0047 AD - Intermountain Health, Salt Lake City, Utah. FAU - Schroeder, Gregory D AU - Schroeder GD AUID- ORCID: 0000-0002-8895-1964 AD - The Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Kepler, Christopher K AU - Kepler CK AUID- ORCID: 0000-0002-0996-4346 AD - The Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Spitnale, Michael AU - Spitnale M AUID- ORCID: 0000-0001-7955-3174 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. FAU - Vaccaro, Alexander R AU - Vaccaro AR AUID- ORCID: 0000-0002-8073-0796 AD - The Rothman Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Gabrielli, Alexandra S AU - Gabrielli AS AUID- ORCID: 0000-0003-2643-4387 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. AD - Tri Rivers Musculoskeletal Center, Pittsburgh, Pennsylvania. FAU - Wawrose, Richard A AU - Wawrose RA AUID- ORCID: 0009-0007-3189-8676 AD - Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. AD - The Orland Bethel Family MSK Research Center (BMRC), Pittsburgh, Pennsylvania. AD - Pittsburgh Orthopaedic Spine Research Group (POSR), Pittsburgh, Pennsylvania. LA - eng PT - Journal Article PT - Review DEP - 20250710 PL - United States TA - J Bone Joint Surg Am JT - The Journal of bone and joint surgery. American volume JID - 0014030 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Orthopedic Procedures MH - *Perioperative Care/methods MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Orthopedic Surgeons PMC - PMC12356572 COIS- Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I714). EDAT- 2025/08/22 16:44 MHDA- 2025/08/22 16:45 PMCR- 2025/08/15 CRDT- 2025/08/20 10:56 PHST- 2025/08/22 16:45 [medline] PHST- 2025/08/22 16:44 [pubmed] PHST- 2025/08/20 10:56 [entrez] PHST- 2025/08/15 00:00 [pmc-release] AID - 00004623-202508200-00017 [pii] AID - JBJS-D-24-01287 [pii] AID - 10.2106/JBJS.24.01287 [doi] PST - epublish SO - J Bone Joint Surg Am. 2025 Jul 10;107(16):1879-1886. doi: 10.2106/JBJS.24.01287. PMID- 40839017 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1861-0692 (Electronic) IS - 1861-0684 (Print) IS - 1861-0684 (Linking) VI - 115 IP - 8 DP - 2026 Aug TI - GLP-1 receptor agonists in atherosclerotic cardiovascular disease and diabetes mellitus or obesity: investigation of the potential role in a German inpatient dataset. PG - 1343-1350 LID - 10.1007/s00392-025-02735-z [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1 RA) reduce major adverse cardiovascular events in patients with diabetes mellitus and atherosclerotic cardiovascular disease (ASCVD) or increased cardiovascular risk. Recently, the GLP-1 RA semaglutide was reported to reduce cardiovascular events in ASCVD patients with overweight or obesity even in the absence of diabetes mellitus. Accordingly, this was included in the current European Society of Cardiology guidelines for secondary prevention. We aimed to assess the number of inpatients with ASCVD who could qualify for therapy with GLP-1 RA. METHODS: Using nationwide data from the Research Data Centre of the Federal Statistical Office of Germany, a random 10% sample of all adult inpatients in 2022 was analyzed. The proportions of ASCVD, obesity, and diabetes mellitus were examined. RESULTS: The 10% sample included 1,446,420 patients with a mean age of 63.16 years, 52.50% were female. ASCVD was present in 229,619 inpatients (15.87%), including those with coronary artery disease, history of myocardial infarction, peripheral vascular disease or stroke. Among ASCVD patients, 79,516 individuals (34.63% of ASCVD patients) also suffered from type 2 diabetes mellitus and 15,624 individuals were diagnosed with obesity. Approximately half of those (N = 7,256) had ASCVD and obesity without diabetes mellitus (3.16% of ASCVD patients). Overall, 37.79% of ASCVD patients also suffered from type 2 diabetes mellitus or obesity. CONCLUSION: In this data sampling of German inpatients, more than one-third of ASCVD patients may qualify for GLP-1 RA therapy due to concomitant diabetes mellitus or obesity. That corresponds to about 6% of inpatients in Germany. CI - (c) 2025. The Author(s). FAU - Oettinger, Vera AU - Oettinger V AUID- ORCID: 0000-0003-4460-2102 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. vera.oettinger@uniklinik-freiburg.de. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. vera.oettinger@uniklinik-freiburg.de. FAU - von Zur Muhlen, Constantin AU - von Zur Muhlen C AUID- ORCID: 0000-0003-2767-8009 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Kaier, Klaus AU - Kaier K AUID- ORCID: 0000-0003-0837-6945 AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. AD - Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany. FAU - Wolf, Dennis AU - Wolf D AUID- ORCID: 0000-0003-1525-4348 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Rilinger, Jonathan AU - Rilinger J AUID- ORCID: 0000-0001-9333-3629 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Maier, Alexander AU - Maier A AUID- ORCID: 0000-0003-0200-7495 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Jackel, Markus AU - Jackel M AUID- ORCID: 0000-0001-8638-5228 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Westermann, Dirk AU - Westermann D AUID- ORCID: 0000-0002-7542-1956 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Hilgendorf, Ingo AU - Hilgendorf I AUID- ORCID: 0000-0002-0024-1643 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Bockelmann, Dalibor AU - Bockelmann D AD - Medical Strategy Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. LA - eng PT - Journal Article DEP - 20250821 PL - Germany TA - Clin Res Cardiol JT - Clinical research in cardiology : official journal of the German Cardiac Society JID - 101264123 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Germany/epidemiology MH - Middle Aged MH - *Obesity/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Atherosclerosis/epidemiology/drug therapy MH - Aged MH - *Inpatients MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Adult PMC - PMC13346366 OTO - NOTNLM OT - ASCVD OT - Atherosclerotic cardiovascular disease OT - Diabetes mellitus OT - Electronic health records OT - GLP-1 receptor agonist OT - Obesity COIS- Declarations. Ethics approval and informed consent: The investigators in this study did not have direct access to individual patient data for this analysis. Access was granted by Destatis only for summarized results. Ethics committee approval and informed consent were therefore not required according to German law. Destatis anonymised all pooled results and any information that could potentially identify an individual patient or an individual center has been censored by Destatis to ensure privacy. Conflicts of interest: The authors declare that they have no conflict of interest. EDAT- 2025/08/21 12:47 MHDA- 2026/07/08 18:50 PMCR- 2025/08/21 CRDT- 2025/08/21 11:03 PHST- 2025/03/30 00:00 [received] PHST- 2025/08/01 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2025/08/21 12:47 [pubmed] PHST- 2025/08/21 11:03 [entrez] PHST- 2025/08/21 00:00 [pmc-release] AID - 10.1007/s00392-025-02735-z [pii] AID - 2735 [pii] AID - 10.1007/s00392-025-02735-z [doi] PST - ppublish SO - Clin Res Cardiol. 2026 Aug;115(8):1343-1350. doi: 10.1007/s00392-025-02735-z. Epub 2025 Aug 21. PMID- 40836732 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20250821 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 73 IP - 7 DP - 2025 Jul TI - MASLD Pharmacotherapy: Current Standards, Emerging Treatments, and Practical Guidance for Indian Physicians. PG - e45-e60 LID - 10.59556/japi.73.1058 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a significant public health issue worldwide, with a pronounced impact in India due to the escalating rates of obesity and type 2 diabetes mellitus (T2DM) driving its prevalence. This condition spans a range of hepatic disorders, from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), accompanied by differing levels of hepatic fibrosis, heightening the likelihood of progression to cirrhosis, liver cancer, and cardiovascular complications. While lifestyle modification remains the cornerstone of MASLD management, pharmacologic therapies are increasingly recognized as essential for patients with progressive disease or those at higher risk of complications. Recent insights into the pathogenesis of MASLD have led to the development of innovative therapies targeting key mechanisms such as hepatic steatosis, insulin resistance, inflammation, and hepatic fibrosis. Several pharmacological agents have shown encouraging results in clinical trials, including thyroid hormone receptor-beta agonist resmetirom, glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide, peroxisome proliferator-activated receptor (PPAR) agonists such as pioglitazone and saroglitazar, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and vitamin E. Furthermore, emerging therapies, including the dual incretin agonist tirzepatide and fibroblast growth factor (FGF) analogs, hold the potential to transform future treatment strategies. This review provides a comprehensive overview of current and evolving pharmacologic options for MASLD, with a focus on practical recommendations tailored for Indian physicians. A structured treatment algorithm for noncirrhotic MASLD (F0-F3 fibrosis) is presented, incorporating only drugs currently available in India and stratified based on diabetes status and hepatic fibrosis severity. Given India's vast and diverse patient population, ensuring access to cost-effective therapies remains a challenge, necessitating a pragmatic approach that balances efficacy, affordability, and real-world feasibility. This review serves as a practical clinical guide, equipping physicians with evidence-based recommendations to optimize MASLD management in routine practice. CI - (c) Journal of The Association of Physicians of India 2025. FAU - Kumar, Ashish AU - Kumar A AD - Professor, Department of Gastroenterology, Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Delhi, India, Corresponding Author, Orcid: https://orcid.org/0000-0001-6680-7227. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - India MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - Practice Guidelines as Topic MH - Hypoglycemic Agents/therapeutic use EDAT- 2025/08/21 06:28 MHDA- 2025/08/21 06:29 CRDT- 2025/08/21 03:33 PHST- 2025/08/21 06:29 [medline] PHST- 2025/08/21 06:28 [pubmed] PHST- 2025/08/21 03:33 [entrez] AID - 10.59556/japi.73.1058 [doi] PST - ppublish SO - J Assoc Physicians India. 2025 Jul;73(7):e45-e60. doi: 10.59556/japi.73.1058. PMID- 40836299 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20261012 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Aug 20 TI - Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis. PG - 343 LID - 10.1186/s12933-025-02892-5 [doi] LID - 343 AB - BACKGROUND: Patients with type 2 diabetes (T2D) and hypertension are at increased risk of adverse cardiovascular (CV) events. However, real-world evidence comparing the CV effectiveness and safety of major hypoglycemic drug classes remains limited in this population. This multicenter pooled analysis aims to directly compare the CV outcomes and safety profiles of these key agents in patients with T2D and hypertension. METHODS: We analyzed electronic health records from two databases in a cohort study of T2D patients with hypertension who had initiated metformin as first-line therapy. Propensity score matching (PSM) and Cox proportional hazards models were used to compare the risks of 3-/4-point major adverse cardiovascular events (MACE) and safety outcomes across drug classes added to metformin: insulin, sulfonylureas (SUs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP4is), glinides, acarbose, and sodium-glucose transporter 2 inhibitors (SGLT2is). RESULTS: Compared with insulin, GLP-1 RAs, DPP4is, and glinides were associated with a lower risk of 3-point MACE (HR: 0.48 [0.31-0.76], 0.70 [0.57-0.85], and 0.70 [0.52-0.94], respectively). SUs were associated with a higher risk of 3-point MACE compared with DPP4is (HR: 1.30 [1.06-1.59]). DPP4is, GLP-1 RAs, and glinides showed a lower risk of 3-point MACE compared with acarbose (HR: 0.62 [0.51-0.76], 0.47 [0.29-0.75], and 0.59 [0.43-0.81], respectively). Similar patterns were observed for 4-point MACE. For safety outcomes, DPP4is were associated with a reduced risk of chronic kidney disease, while insulin use was associated with reduced risks of inflammatory polyarthritis and insomnia. However, DPP4is were associated with higher risks of coronary atherosclerotic diseases and hypertensive heart disease. CONCLUSIONS: This study highlights the differential cardiovascular effectiveness and safety profiles of hypoglycemic therapies in real-world settings, providing valuable insights for optimizing T2D management, particularly in patients with comorbid hypertension. CI - (c) 2025. The Author(s). FAU - Wei, Zhiyuan AU - Wei Z AUID- ORCID: 0009-0000-9341-4111 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. AD - Institute of Medical Informatics and Management, Nanjing Medical University, Nanjing, 210029, Jiangsu, China. FAU - Xu, Wanqian AU - Xu W AUID- ORCID: 0009-0003-0111-2338 AD - General Practice Medical Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. FAU - Wang, Yu AU - Wang Y AUID- ORCID: 0000-0002-8059-8051 AD - Research Center for Scientific Data Hub , Zhejiang Lab , Hangzhou, 311100, Zhejiang, China. FAU - Tian, Yu AU - Tian Y AUID- ORCID: 0000-0002-6791-8217 AD - Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University , Hangzhou, 310027 , Zhejiang , China. FAU - Wang, Zhongmin AU - Wang Z AUID- ORCID: 0009-0000-7561-7775 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. AD - Medical Technology Administration Office, The First Affiliated Hospital with Nanjing Medical University , Nanjing, 210029, Jiangsu, China. FAU - Jing, Shenqi AU - Jing S AUID- ORCID: 0000-0002-8529-0566 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. AD - Department of Information , The First Affiliated Hospital with Nanjing Medical University , Nanjing, 210029 , Jiangsu , China. FAU - Liu, Weina AU - Liu W AUID- ORCID: 0000-0001-5377-9714 AD - Department of Nutrition and Food Hygiene, School of Public Health , Southeast University , Nanjing, 210009 , Jiangsu , China. FAU - Shen, Sipeng AU - Shen S AUID- ORCID: 0000-0003-0436-4736 AD - Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. FAU - Qin, Chenlong AU - Qin C AUID- ORCID: 0009-0009-0912-5639 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. AD - Institute of Medical Informatics and Management, Nanjing Medical University, Nanjing, 210029, Jiangsu, China. FAU - Zhang, Xin AU - Zhang X AUID- ORCID: 0000-0003-0047-3134 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. zx6800@njmu.edu.cn. AD - Department of Information , The First Affiliated Hospital with Nanjing Medical University , Nanjing, 210029 , Jiangsu , China. zx6800@njmu.edu.cn. FAU - Li, Jingsong AU - Li J AUID- ORCID: 0000-0002-1064-637X AD - Research Center for Scientific Data Hub , Zhejiang Lab , Hangzhou, 311100, Zhejiang, China. ljs@zju.edu.cn. AD - Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University , Hangzhou, 310027 , Zhejiang , China. ljs@zju.edu.cn. FAU - Liu, Yun AU - Liu Y AUID- ORCID: 0000-0002-6431-4469 AD - Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. liuyun@njmu.edu.cn. AD - Department of Geriatrics, Division of Geriatric Endocrinology , The First Affiliated Hospital with Nanjing Medical University , Nanjing, 210029, Jiangsu, China. liuyun@njmu.edu.cn. LA - eng GR - 82404291/National Natural Science Foundation of China (NSFC) Youth Science Fund/ GR - BK20241308/Basic Research Program of Jiangsu Province/ GR - 2024ZD0531800/National Science and Technology Major Project/ GR - 2023YFC3605800/National Key Research and Development Program of China/ GR - QY202403/Leading Major Projects in Basic Research at the Forefront of the Institute (China)/ GR - BK20243054/Major Special Projects of Jiangsu Provincial Department of Science and Technology (China)/ GR - BE2023781/Social Development Plan of Jiangsu Provincial Department of Science and Technology (China)/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250820 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Antihypertensive Agents) RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Antihypertensive Agents/therapeutic use/adverse effects MH - *Blood Glucose/drug effects/metabolism MH - *Cardiovascular Diseases/diagnosis/prevention & control/epidemiology MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Drug Therapy, Combination MH - Electronic Health Records MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Disease Risk Factors MH - *Hypertension/drug therapy/diagnosis/epidemiology/physiopathology/mortality MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Retrospective Studies MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome PMC - PMC12369064 OTO - NOTNLM OT - Cardiovascular safety OT - Hypertension OT - Major adverse cardiovascular events (MACE) OT - Real-world evidence OT - Retrospective study OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of Nanjing Medical University (2023(498)), with informed consent waived due to its retrospective nature. It adhered to the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Competing interests: The authors declare no competing interests. EDAT- 2025/08/21 06:28 MHDA- 2025/08/21 06:29 PMCR- 2025/08/20 CRDT- 2025/08/21 00:32 PHST- 2025/03/27 00:00 [received] PHST- 2025/07/30 00:00 [accepted] PHST- 2025/08/21 06:29 [medline] PHST- 2025/08/21 06:28 [pubmed] PHST- 2025/08/21 00:32 [entrez] PHST- 2025/08/20 00:00 [pmc-release] AID - 10.1186/s12933-025-02892-5 [pii] AID - 2892 [pii] AID - 10.1186/s12933-025-02892-5 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Aug 20;24(1):343. doi: 10.1186/s12933-025-02892-5. PMID- 40834980 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 6 DP - 2025 Nov TI - Are GLP-1 receptor agonists and diabetic retinopathy foes or friends? PG - 101696 LID - S1262-3636(25)00090-4 [pii] LID - 10.1016/j.diabet.2025.101696 [doi] AB - With the increasing number of patients with diabetes worldwide, the number of patients with diabetic retinopathy (DR) is also increasing, which affects the lives of patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are anti-diabetic drugs that mimic the action of endogenous glucagon-like peptide-1, which significantly improve glycemic control in patients with type 2 diabetes. GLP-1RAs can repair the blood-retinal barrier function by activating the GLP-1 receptor in retinal endothelial cells and nerve cells, inhibiting the RhoA/ROCK signaling pathway, up-regulating the tight junction protein occludin and ZO-1, and inhibiting the activation of microglia, reducing the release of pro-inflammatory factors, and reducing neuroinflammation and vascular leakage. However, some GLP-1RAs may increase the risk of DR, such as diabetic macular edema and proliferative DR, and may increase the risk of DR deterioration, especially during rapid glucose lowering. Although the new GLP-1/GIP dual-receptor agonists and GLP-1/GIP/glucagon tri-receptor agonists show comprehensive benefit potential by effectively improving body metabolism, the short-term negative effect of sudden blood glucose drop still needs to be paid attention to. For patients with moderate to severe DR, it is necessary to strengthen ophthalmic monitoring to avoid rapid blood glucose decline in the initial treatment. In the long-term treatment, metabolic benefits and retinal risks need to be weighed, and the patient's condition needs to be evaluated before treatment. Therefore, GLP-1RAs has a duality of "mechanism protection and clinical risk" on DR, and individualized treatment strategy should take into consideration drug characteristics, DR severity and glucose control. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Liu, Kai AU - Liu K AD - Department of Endocrinology, Harbin second hospital, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang Province 150086, China. FAU - Liu, Shu AU - Liu S AD - Health Management Centre, Fourth affiliated hospital of Harbin medical university, Harbin 150000, Heilongjiang, China. FAU - Wang, Dong AU - Wang D AD - Scientific Research Centre, Second affiliated hospital of Harbin medical university, Harbin 150000, China. FAU - Qiao, Hong AU - Qiao H AD - Department of Endocrinology, Harbin second hospital, No. 246, Xuefu Road, Nangang District, Harbin, Heilongjiang Province 150086, China. Electronic address: qiaohong@hrbmu.edu.cn. LA - eng PT - Journal Article PT - Review DEP - 20250818 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Diabetic retinopathy OT - GLP-1RAs OT - Inflammatory factor OT - Microvascular injury OT - Neuroinflammation OT - Oxidative stress COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2025/08/21 00:30 MHDA- 2025/11/22 00:28 CRDT- 2025/08/20 19:31 PHST- 2025/08/04 00:00 [received] PHST- 2025/08/06 00:00 [accepted] PHST- 2025/11/22 00:28 [medline] PHST- 2025/08/21 00:30 [pubmed] PHST- 2025/08/20 19:31 [entrez] AID - S1262-3636(25)00090-4 [pii] AID - 10.1016/j.diabet.2025.101696 [doi] PST - ppublish SO - Diabetes Metab. 2025 Nov;51(6):101696. doi: 10.1016/j.diabet.2025.101696. Epub 2025 Aug 18. PMID- 40834675 OWN - NLM STAT- MEDLINE DCOM- 20251128 LR - 20251128 IS - 1873-5800 (Electronic) IS - 0968-0160 (Linking) VI - 57 DP - 2025 Dec TI - GLP-1 agonists are protective against postoperative complications following total knee arthroplasty. PG - 77-83 LID - S0968-0160(25)00210-8 [pii] LID - 10.1016/j.knee.2025.08.007 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RAs) have gained prominence for managing type 2 diabetes mellitus and obesity. Their impact in orthopedic surgery, particularly total knee arthroplasty (TKA), remains underexplored. Thus, this study aimed to investigate the influence of GLP1RAs on 90-day medical complications and 2-year surgical outcomes following TKA. METHODS: A retrospective cohort analysis was performed using a national all-payer claims database. Patients who underwent primary TKA were stratified into two groups: patients who received a GLP1RA within 6 months prior to surgery (GLP-1 cohort) and patients who did not have a GLP1RA history. Outcomes included the incidence of 90-day readmission and medical complications, and 2-year surgical complications. Univariate and multivariable regression analysis was conducted to compare outcomes. RESULTS: Patients in the GLP-1 cohort exhibited a lower 90-day readmission rate (OR: 0.77; P < 0.001) and fewer medical complications such as arrhythmia (OR: 0.78), death (OR: 0.24), and deep vein thrombosis (OR: 0.70) compared to the control (P < 0.05 for all). However, they experienced a higher odds of acute renal failure (OR: 1.16; P = 0.001). No significant differences were observed in 2-year surgical outcomes. CONCLUSION: GLP1RAs use is associated with a reduced incidence of certain 90-day medical complications following TKA. We believe that this is likely due to their effects on weight loss and glycemic control. However, they are associated with an increased risk of acute renal failure. GLP1RAs do not appear to influence long-term surgical outcomes, suggesting their benefits are primarily confined to the early postoperative period. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Ranson, Rachel AU - Ranson R AD - Department of Orthopaedic Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: rachelannranson@gmail.com. FAU - Parel, Philip M AU - Parel PM AD - Department of Orthopaedic Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: pmparel208@gwmail.gwu.edu. FAU - Kirkland, Julia AU - Kirkland J AD - Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States. Electronic address: julia.kirkland@kansascity.edu. FAU - Durbin, Jackson W AU - Durbin JW AD - Department of Orthopaedic Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: jackson.durbin@gwmail.gwu.edu. FAU - Villa, Jordan C AU - Villa JC AD - Department of Orthopaedic Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. FAU - Sterling, Robert AU - Sterling R AD - Department of Orthopaedic Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: rsterling@mfa.gwu.edu. LA - eng PT - Journal Article DEP - 20250819 PL - Netherlands TA - Knee JT - The Knee JID - 9430798 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Knee/adverse effects MH - Male MH - Female MH - Retrospective Studies MH - *Postoperative Complications/prevention & control/epidemiology MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Patient Readmission/statistics & numerical data MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Complications OT - GLP-1 OT - Glucagon-like peptide-1 agonist OT - Revision OT - Total knee arthroplasty COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: "Dr. Robert Sterling reports a relationship with Journal of Arthroplasty that includes: board membership. Dr. Robert Sterling reports a relationship with Journal of Bone and Joint Surgery that includes: board membership. Dr. Robert Sterling reports a relationship with American Academy of Orthopedic Surgeons that includes: board membership. Dr. Robert Sterling reports a relationship with American Association of Hip and Knee Surgeons that includes: board membership. Dr. Robert Sterling reports a relationship with American Orthopedic Association that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.". EDAT- 2025/08/21 00:29 MHDA- 2025/11/29 02:21 CRDT- 2025/08/20 18:10 PHST- 2024/10/15 00:00 [received] PHST- 2025/06/03 00:00 [revised] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/11/29 02:21 [medline] PHST- 2025/08/21 00:29 [pubmed] PHST- 2025/08/20 18:10 [entrez] AID - S0968-0160(25)00210-8 [pii] AID - 10.1016/j.knee.2025.08.007 [doi] PST - ppublish SO - Knee. 2025 Dec;57:77-83. doi: 10.1016/j.knee.2025.08.007. Epub 2025 Aug 19. PMID- 40832978 OWN - NLM STAT- MEDLINE DCOM- 20251215 LR - 20251217 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 1 DP - 2026 Feb TI - Effect of Tirzepatide on the Risk of Developing Type 2 Diabetes Mellitus Among the People Living With Obesity or Overweight: A Systematic Review. PG - e70042 LID - 10.1111/cob.70042 [doi] AB - Tirzepatide provides superior efficacy in weight reduction and metabolic control compared to existing therapies. The present systematic review assessed the effect of Tirzepatide on the risk of developing type 2 diabetes mellitus (T2DM) among people living with obesity or overweight. Six major databases [MEDLINE (PubMed), ClinicalTrials.gov, EMBASE, Scopus, Web of Science and Cochrane Library] were searched for potential studies published till 10 July 2025. Two-stage dual screening with third-person adjudication was adopted for screening of studies. PROSPERO ID: CRD42024614466. RoB 2.0 and the Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials (RCTs) and cohort studies, respectively. Database search yielded 2601 studies, among which three studies were eligible (one RCT and two cohort studies) for systematic review. The hazard ratio (HR) for the new-onset diabetes at 12 months following the Tirzepatide intake was significantly lower than that of the Semaglutide group of patients (HR = 0.73, p < 0.001 [95% CI: 0.58-0.92]). The risk of the new-onset diabetes for 176 weeks (HR = 0.07, p < 0.001 [95% CI: < 0.01-0.1]) and 193 weeks (HR = 0.12, p < 0.001 [95% CI: 0.1-0.2]) following the Tirzepatide intake was significantly lower than that of the placebo group of patients. Tirzepatide might have significant efficacy in the prevention of T2DM in patients with obesity or overweight. CI - (c) 2025 World Obesity Federation. FAU - Pardeshi, Geeta AU - Pardeshi G AUID- ORCID: 0000-0001-6670-0235 AD - Department of Community Medicine, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, India. FAU - Kumbhar, Uddhav T AU - Kumbhar UT AUID- ORCID: 0000-0002-6735-0748 AD - Department of Community Medicine, KIMS, Karad, India. FAU - Kaviprawin, Mogan AU - Kaviprawin M AUID- ORCID: 0000-0002-1659-059X AD - South Asia Field Epidemiology and Technology Network, Inc., (SAFETYNET), Chennai, India. FAU - Debnath, Aninda AU - Debnath A AUID- ORCID: 0000-0002-2117-4195 AD - Department of Community Medicine, Maulana Azad Medical College, New Delhi, India. FAU - Dubey, Ashok Kumar AU - Dubey AK AUID- ORCID: 0000-0002-4246-8627 AD - Department of Pharmacology, AIIMS, Bilaspur, India. FAU - Deshmukh, Kalyani AU - Deshmukh K AUID- ORCID: 0009-0009-7125-4896 AD - Technical Resource Centre, Centre for Evidence based Guidelines, All India Institute of Medical Sciences, Nagpur, India. FAU - Goyal, Chanchal AU - Goyal C AUID- ORCID: 0009-0002-8484-1255 AD - Centre for Evidence based Guidelines, ICMR-DHR, New Delhi, India. FAU - Gandhi, Aravind P AU - Gandhi AP AUID- ORCID: 0000-0003-3898-5450 AD - Department of Community Medicine, All India Institute of Medical Sciences, Nagpur, India. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250820 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/prevention & control/etiology/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Tirzepatide/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Adult OTO - NOTNLM OT - Tirzepatide OT - glycemic control OT - obesity OT - type 2 diabetes mellitus OT - weight loss EDAT- 2025/08/20 12:31 MHDA- 2025/12/16 00:34 CRDT- 2025/08/20 07:43 PHST- 2025/07/21 00:00 [revised] PHST- 2025/04/06 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/12/16 00:34 [medline] PHST- 2025/08/20 12:31 [pubmed] PHST- 2025/08/20 07:43 [entrez] AID - 10.1111/cob.70042 [doi] PST - ppublish SO - Clin Obes. 2026 Feb;16(1):e70042. doi: 10.1111/cob.70042. Epub 2025 Aug 20. PMID- 40831316 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel GLP-1R/GIPR dual agonist, HISHS-2001. PG - 5938-5949 LID - 10.1111/dom.16652 [doi] AB - AIMS: The use of incretin analogues has emerged as an effective approach to achieve both enhanced insulin secretion and weight loss in Type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have shown particular promise. However, off-target effects remain a complication of using these agents, and modified versions with optimised pharmacological profiles and/or biased signalling are sought. MATERIALS AND METHODS: Ligand synthesis was achieved using standard solid-phase techniques. Assessments of GLP-1R-binding kinetics, G protein recruitment and receptor internalisation were performed using biochemical and imaging approaches. Insulin secretion was measured in purified mouse and human islets, and drug efficacy was assessed in hyperglycaemic db/db mice. RESULTS: We describe the synthesis and properties of a molecule which binds to both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors (GLP-1R and GIPR) to enhance insulin secretion. HISHS-2001 shows increased affinity at the GLP-1R, as well as a tendency towards reduced internalisation and recycling at this receptor versus FDA-approved dual GLP-1R/GIPR agonist tirzepatide. HISHS-2001 also displayed significantly greater bias towards cAMP generation versus beta-arrestin 2 recruitment compared to tirzepatide. In contrast, G(alpha)s recruitment was lower versus tirzepatide at the GLP-1R, but unchanged at the GIPR. Administered to obese hyperglycaemic db/db mice, HISHS-2001 increased circulating insulin whilst lowering body weight and HbA1c with similar efficacy to tirzepatide at substantially lower doses. CONCLUSION: HISHS-2001 represents a novel dual receptor agonist with a promising pharmacological profile and actions. Future clinical studies will be needed to assess the safety and efficacy of this molecule in humans. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Manchanda, Yusman AU - Manchanda Y AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Jones, Ben AU - Jones B AUID- ORCID: 0000-0003-0461-2584 AD - Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Carrat, Gaelle AU - Carrat G AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Ramchunder, Zenouska AU - Ramchunder Z AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Marchetti, Piero AU - Marchetti P AD - Department of Experimental and Clinical Medicine, Pancreatic Islets Laboratory, University of Pisa, Pisa, Italy. FAU - Leclerc, Isabelle AU - Leclerc I AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. AD - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM) et Faculte de Medecine, Universite de Montreal, Montreal, Quebec, Canada. FAU - Thennati, Rajamannar AU - Thennati R AD - Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India. FAU - Burade, Vinod AU - Burade V AD - Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India. FAU - Natarajan, Muthukumaran AU - Natarajan M AD - Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India. FAU - Shahi, Pradeep AU - Shahi P AD - Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India. FAU - Tomas, Alejandra AU - Tomas A AUID- ORCID: 0000-0002-2290-8453 AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Rutter, Guy A AU - Rutter GA AUID- ORCID: 0000-0001-6360-0343 AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. AD - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM) et Faculte de Medecine, Universite de Montreal, Montreal, Quebec, Canada. AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. AD - Research Institute of the McGill University Health Sciences Centre, Montreal, Quebec, Canada. LA - eng GR - R01DK135268/Division of Diabetes, Endocrinology, and Metabolic Diseases/ GR - WT212625/Z/18/Z/WT_/Wellcome Trust/United Kingdom GR - R01 DK135268/DK/NIDDK NIH HHS/United States GR - CRCHUM/ GR - 4-SRA-2023-1182-S-N/Breaktrough Type 1 Diabetes/ GR - JDRF 4-SRA-2023-1182-S-N/CIHR-JDRF Team/ GR - BDA 16/0005485/DUK_/Diabetes UK/United Kingdom GR - Sun Pharmaceutical Industries/ GR - 301619/Z/23/Z/WT_/Wellcome Trust/United Kingdom GR - CIHR-IRSC TDP-186358/Institute of Nutrition, Metabolism and Diabetes/ GR - Lilly Research Award Program/ GR - MR/X021467/1/MRC_/Medical Research Council/United Kingdom GR - CFI 42649/Canada Foundation for Innovation/ GR - Society for Endocrinology/ GR - MR/R022259/1/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article DEP - 20250820 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (GLP1R protein, human) SB - IM UOF - bioRxiv. 2025 Jan 17:2025.01.13.632834. doi: 10.1101/2025.01.13.632834. PMID: 39868265 MH - Animals MH - Humans MH - *Insulin Secretion/drug effects MH - Mice MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Receptors, Gastrointestinal Hormone/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Male MH - *Hypoglycemic Agents/pharmacology MH - Insulin/metabolism MH - Kinetics MH - Mice, Inbred C57BL MH - Islets of Langerhans/metabolism/drug effects MH - Protein Binding PMC - PMC12409219 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - beta cell function OT - insulin secretion COIS- Vinod Burade, Thennati Rajamannar, Muthukumaran Natarajan, and Pradeep Shahi are employees of Sun Pharmaceuticals, from whom Guy A. Rutter and Alejandra Tomas have received grant funding. EDAT- 2025/08/20 06:33 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/08/20 03:43 PHST- 2025/07/17 00:00 [revised] PHST- 2025/01/17 00:00 [received] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/08/20 06:33 [pubmed] PHST- 2025/08/20 03:43 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16652 [pii] AID - 10.1111/dom.16652 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5938-5949. doi: 10.1111/dom.16652. Epub 2025 Aug 20. PMID- 40829097 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 8 DP - 2025 Aug 1 TI - Trends in glucagon-like peptide 1 receptor agonist prescribing patterns. PG - e228-e234 LID - 10.37765/ajmc.2025.89778 [doi] AB - OBJECTIVE: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes. STUDY DESIGN: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other GLP-1 RAs and stratifying by diabetes and overweight/obesity indications. METHODS: The study included individuals 18 years or older with 12 months of continuous enrollment from 2018 to 2023, categorizing GLP-1 RA users into 4 groups based on diabetes and obesity/overweight diagnosis codes within a year of their index date. RESULTS: Prescribing of GLP-1 RA medications, particularly semaglutides, increased notably over the years, whereas dulaglutide, liraglutide, and exenatide use declined. When investigating possible premature prescribing by examining users with no diabetes indication, the number of prediabetes or abnormal glucose diagnoses increased slightly before the index GLP-1 RA prescribing index date. However, less than 9% received a diabetes or prediabetes diagnosis 30 days after starting a GLP-1 RA. CONCLUSIONS: From 2018 to 2023, GLP-1 RA prescribing increased significantly, with semaglutide approved for weight loss rising to 60% share in the nondiabetic obese/overweight group. Trends showed a notable rise in prescriptions for nondiabetic and obese/overweight patients. FAU - Ukhanova, Maria AU - Ukhanova M AD - UTHealth Houston School of Public Health, Center for Health Care Data, 1200 Pressler St, Houston, TX 77030. Email: maria.ukhanova.1@uth.tmc.edu. FAU - Wozny, Joseph S AU - Wozny JS FAU - Truong, Chau N AU - Truong CN FAU - Ghosh, Lopita AU - Ghosh L FAU - Krause, Trudy M AU - Krause TM LA - eng PT - Journal Article PT - Observational Study DEP - 20250801 PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Practice Patterns, Physicians'/trends/statistics & numerical data MH - Male MH - Female MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Obesity/drug therapy MH - United States MH - Aged MH - Adult MH - Liraglutide/therapeutic use MH - Exenatide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Overweight/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/08/19 18:30 MHDA- 2025/08/31 20:08 CRDT- 2025/08/19 16:03 PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/19 18:30 [pubmed] PHST- 2025/08/19 16:03 [entrez] AID - 89778 [pii] AID - 10.37765/ajmc.2025.89778 [doi] PST - epublish SO - Am J Manag Care. 2025 Aug 1;31(8):e228-e234. doi: 10.37765/ajmc.2025.89778. PMID- 40817831 OWN - NLM STAT- MEDLINE DCOM- 20251009 LR - 20251009 IS - 1945-7170 (Electronic) IS - 0013-7227 (Linking) VI - 166 IP - 11 DP - 2025 Oct 9 TI - Novel Dual and Triple Agonists Targeting GLP-1, GIP, Glucagon, and GDF15 for Type 2 Diabetes and Obesity Management. LID - bqaf130 [pii] LID - 10.1210/endocr/bqaf130 [doi] AB - The rising global incidence of type 2 diabetes mellitus and obesity underscores a critical public health challenge, with obesity serving as a primary contributor to insulin resistance. Current treatment modalities, including SGLT2 inhibitors and GLP-1 receptor agonists, have shown efficacy in glycemic control and weight management but remain insufficient for all patients. This review focuses on novel dual and triple agonists targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and growth differentiation factor 15 (GDF15) due to their emerging clinical importance and recent preclinical progress. Other peptide-based therapies, such as amylin analogs, are beyond the scope of this work and will be addressed in future reviews. Evidence suggests that these novel agents not only improve metabolic parameters but may also offer cardioprotective and anti-inflammatory benefits. While advancements in understanding their mechanisms of action are promising, the safety profiles of these treatments warrant careful evaluation due to potential adverse effects. This review aims to provide a comprehensive overview of the evolving landscape of antidiabetic pharmacotherapy, emphasizing the unique benefits and challenges of emerging agents to optimize clinical outcomes in type 2 diabetes mellitus management. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Zhang, Jiudan AU - Zhang J AUID- ORCID: 0009-0005-4430-9311 AD - Department of Endocrinology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. AD - Department of Endocrinology, Diabetes and Nutrition, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, Berlin 12203, Germany. FAU - Sanan, Shriya AU - Sanan S AD - Hindu Rao Hospital, New Delhi 110007, India. FAU - Csanalosi, Marta AU - Csanalosi M AD - Department of Endocrinology, Diabetes and Nutrition, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, Berlin 12203, Germany. FAU - Zheng, Chao AU - Zheng C AUID- ORCID: 0000-0002-2779-0255 AD - Department of Endocrinology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Pfeiffer, Andreas F H AU - Pfeiffer AFH AD - Department of Endocrinology, Diabetes and Nutrition, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, Berlin 12203, Germany. LA - eng GR - No. LTGY24H070003/Zhejiang Provincial Natural Science Foundation/ GR - No. 2024KY1199/Medical and Health Research Project of Zhejiang Province/ GR - No. 2024C03269/Zhejiang Province Science and Technology/ PT - Journal Article PT - Review PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Growth Differentiation Factor 15) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) RN - 0 (GDF15 protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Humans MH - *Growth Differentiation Factor 15/agonists MH - *Obesity/drug therapy/metabolism MH - *Gastric Inhibitory Polypeptide/agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon/agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1/GIP/GDF15/glucagon OT - dual/triple agonists OT - obesity OT - type 2 diabetes EDAT- 2025/08/16 12:31 MHDA- 2025/10/09 12:30 CRDT- 2025/08/16 07:32 PHST- 2025/06/21 00:00 [received] PHST- 2025/10/09 12:30 [medline] PHST- 2025/08/16 12:31 [pubmed] PHST- 2025/08/16 07:32 [entrez] AID - 8236487 [pii] AID - 10.1210/endocr/bqaf130 [doi] PST - ppublish SO - Endocrinology. 2025 Oct 9;166(11):bqaf130. doi: 10.1210/endocr/bqaf130. PMID- 40816736 OWN - NLM STAT- MEDLINE DCOM- 20251201 LR - 20260831 IS - 1499-2752 (Electronic) IS - 0315-162X (Linking) VI - 52 IP - Suppl 3 DP - 2025 Dec 1 TI - What Clinicians Need to Know About Glucagon-like Peptide 1 Agonists. PG - 52-54 LID - 10.3899/jrheum.2025-0531 [doi] AB - The interplay between metabolic health and autoimmune diseases such as psoriasis (PsO) and psoriatic arthritis (PsA) has garnered increasing attention. Obesity, a key feature of metabolic syndrome, exacerbates disease severity in these conditions, prompting the exploration of treatments addressing both the immune system and metabolism. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), primarily used for type 2 diabetes mellitus, have demonstrated benefits beyond glycemic control, including promoting weight loss, improving metabolic health, and potentially modulating immune responses. There is also a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist with similar and potentially superior capabilities; throughout this manuscript these will be collectively known as GLP-1RA. Recent studies also suggest that GLP-1RAs may help manage PsO and PsA in patients with obesity. These medications may offer dual benefits by reducing inflammation and addressing metabolic abnormalities like insulin resistance and hyperlipidemia. This article reports on a presentation given at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2024 annual meeting underscoring the potential of GLP-1RAs as a therapeutic option, particularly for obese patients with PsO and PsA. Although promising, the evidence supporting GLP-1RAs for treating PsO and PsA remains limited, necessitating further clinical research to evaluate their safety and efficacy. CI - Copyright (c) 2025 by The Journal of Rheumatology. FAU - da Silva, Dimitri Luz Felipe AU - da Silva DLF AUID- ORCID: 0000-0003-0869-9330 AD - D.L.F. da Silva, MD, MSc, University of Santo Amaro, Sao Paulo, Sao Paulo, Brazil; dimitriluz@hotmail.com. FAU - Singla, Shikha AU - Singla S AUID- ORCID: 0000-0002-5540-8850 AD - S. Singla, MD, Medical College of Wisconsin, Department of Rheumatology, Milwaukee, Wisconsin, USA. FAU - Mease, Philip J AU - Mease PJ AUID- ORCID: 0000-0002-6620-0457 AD - P.J. Mease, MD, Providence Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington, USA. LA - eng PT - Journal Article PT - Review DEP - 20251201 PL - Canada TA - J Rheumatol JT - The Journal of rheumatology JID - 7501984 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Arthritis, Psoriatic/drug therapy/complications MH - *Obesity/drug therapy/complications MH - *Psoriasis/drug therapy/complications MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/agonists OTO - NOTNLM OT - GRAPPA OT - glucagon-like peptide 1 receptor agonists OT - psoriasis OT - psoriatic arthritis EDAT- 2025/08/16 00:29 MHDA- 2025/12/02 01:00 CRDT- 2025/08/15 20:33 PHST- 2025/05/09 00:00 [accepted] PHST- 2025/12/02 01:00 [medline] PHST- 2025/08/16 00:29 [pubmed] PHST- 2025/08/15 20:33 [entrez] AID - jrheum.2025-0531 [pii] AID - 10.3899/jrheum.2025-0531 [doi] PST - epublish SO - J Rheumatol. 2025 Dec 1;52(Suppl 3):52-54. doi: 10.3899/jrheum.2025-0531. PMID- 40816061 OWN - NLM STAT- MEDLINE DCOM- 20250918 LR - 20260127 IS - 1532-866X (Electronic) IS - 0049-0172 (Linking) VI - 74 DP - 2025 Oct TI - Impact of oral semaglutide on serum urate levels in people with type 2 diabetes: A retrospective real-world analysis (URISEMA study). PG - 152807 LID - S0049-0172(25)00178-7 [pii] LID - 10.1016/j.semarthrit.2025.152807 [doi] AB - BACKGROUND: Evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on serum urate (SU) levels in people with type 2 diabetes (PWT2D) is limited. This study investigates the effect of oral semaglutide on SU levels. METHODS: Retrospective, observational study including PWT2D who were prescribed oral semaglutide. The primary endpoint was achieving SU levels below 6 mg/dL at 12 months of follow-up (FU). Secondly, we assessed baseline factors associated with achieving SU levels of <6 mg/dL and average reductions in SU levels. RESULTS: The study included 236 patients (median age 64 years, BMI 33.8 kg/m(2), HbA1c 7.6 %, 40.7 % women, 52.3 % on SGLT2 inhibitors). Baseline SU was 5.2 mg/dL, 66.1 % had SU levels <6 mg/dL, and 23.7 % had hyperuricemia. Under oral semaglutide, 70.7 % and 76 % showed SU <6 mg/dL at 6 and 12 months, respectively. After multivariate adjustment, only SU >/=7 mg/dL (OR 4.54, 95 %CI 1.08-19.25) and switching from a DPP-4 inhibitor (OR 6.53, 95 %CI 1.57-27.32) were associated with achieving the SU target. SU decreased by 0.1 mg/dL after 6 months (p = 0.52) and by 0.2 mg/dL (p = 0.01) at 12 months FU. Greater reductions were observed in those with baseline SU >6 mg/dL (0.6 mg/dL and 0.8 mg/dl, respectively; all p < 0.001). Changes in SU levels were independent of improved metabolic control, weight loss, or baseline use of GLP-1 RAs or SGLT2 inhibitors. CONCLUSION: Oral semaglutide in real-world settings showed a modest reduction in SU levels in PWT2D, particularly linked to baseline hyperuricemia (with notable reduction figures) and switching from DPP-4 inhibitors. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain; Department of Clinical Medicine. Miguel Hernandez University, Spain. Electronic address: omorenoperez@hotmail.es. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain; Health Science Faculty-HM Hospitals, Camilo Jose Cela University, Madrid, Spain; HM Hospitals Health Research Institute, Madrid, Spain. FAU - Carreno-Valdivia, Ruben AU - Carreno-Valdivia R AD - Medical School. Miguel Hernandez University, Spain. FAU - Rodriguez-Bedoya, Maria AU - Rodriguez-Bedoya M AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Roldan-Sanchez, Ada AU - Roldan-Sanchez A AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Andres, Mariano AU - Andres M AD - Department of Clinical Medicine. Miguel Hernandez University, Spain; Department of Rheumatology. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. LA - eng PT - Journal Article PT - Observational Study DEP - 20250807 PL - United States TA - Semin Arthritis Rheum JT - Seminars in arthritis and rheumatism JID - 1306053 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 268B43MJ25 (Uric Acid) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Uric Acid/blood MH - Administration, Oral MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Associated factors OT - Gout OT - Observational study OT - Oral semaglutide OT - Real-World data OT - Serum urate OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Oscar Moreno Perez reports financial support was provided by Eli Lilly and Company. Oscar Moreno Perez reports financial support was provided by Boehringer Ingelheim Corp USA. Oscar Moreno Perez reports financial support was provided by Bayer Corporation. Oscar Moreno Perez reports financial support was provided by AstraZeneca Pharmaceuticals LP. Oscar Moreno Perez reports financial support was provided by Novo Nordisk Inc. Mariano Andres reports financial support was provided by Sobi. Mariano Andres reports financial support was provided by Grunenthal Laboratories LLC. Oscar Moreno Perez reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Boehringer Ingelheim Corp USA that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Bayer Corporation that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Novo Nordisk Inc that includes: consulting or advisory, funding grants, and speaking and lecture fees. Mariano Andres reports a relationship with Sobi that includes: consulting or advisory. Mariano Andres reports a relationship with Grunenthal Laboratories LLC that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/08/16 00:29 MHDA- 2025/09/19 00:36 CRDT- 2025/08/15 18:12 PHST- 2025/06/03 00:00 [received] PHST- 2025/07/15 00:00 [revised] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/19 00:36 [medline] PHST- 2025/08/16 00:29 [pubmed] PHST- 2025/08/15 18:12 [entrez] AID - S0049-0172(25)00178-7 [pii] AID - 10.1016/j.semarthrit.2025.152807 [doi] PST - ppublish SO - Semin Arthritis Rheum. 2025 Oct;74:152807. doi: 10.1016/j.semarthrit.2025.152807. Epub 2025 Aug 7. PMID- 40815181 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260710 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 45 IP - 9 DP - 2025 Sep TI - Safety Choice Drivers of the Coming Treatment Options for Non-Cirrhotic Metabolic Steatohepatitis. PG - e70271 LID - 10.1111/liv.70271 [doi] AB - Metabolic dysfunction associated steatohepatitis (MASH), formerly known as NASH, represents one of the leading causes of chronic liver disease worldwide. Its high prevalence is driven by insulin resistance, obesity and type 2 diabetes (T2D) and is associated with cardiovascular disease. The main driver of liver damage is fat accumulation in hepatocytes leading to inflammation and fibrosis development. People with MASH and clinically significant fibrosis (stage F2/F3) are 'at risk' of progressing to cirrhosis and hepatocellular carcinoma and are considered in need of treatment. Metabolic drivers of MASH originating outside the liver, for example, from the adipose tissue and the gut, and genetic heterogeneity contribute to making the prevalent pathogenetic factor difficult to dissect at an individual level. In this scenario, the Food and Drug Administration's conditional approval of the liver-directed thyroid hormone receptor beta agonist Resmetirom as the first pharmacological treatment for MASH last March 2024 and the expected extension of the glucagon-like protein-1 receptor agonist Semaglutide indication from diabetes and obesity to MASH mark a key milestone. Both drugs are also under evaluation by the European Medicines Agency. The proven efficacy of these compounds in clinical trials needs to be balanced against safety profiles and patient preferences. To investigate future trajectories and possible uses as mono-therapy or in combination, we examined available results of clinical trials and real-life studies. Despite the need to await the final results of outcome studies to exclude any possible challenges for both compounds, safety profiles and external factors including reimbursement policies or supply limitations may currently guide the individual choice. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Mangia, Alessandra AU - Mangia A AUID- ORCID: 0000-0002-2600-3555 AD - Liver Unit, Fondazione IRCCS, "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy. FAU - Valenti, Luca V C AU - Valenti LVC AD - Biological Resource Center/Biobank, Fondazione "Ca Granda" IRCCS Ospedale Maggiore Policlinico, Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Propionates) RN - 0 (Chalcones) SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - Liver Cirrhosis/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/complications MH - Liver/pathology MH - Propionates MH - Chalcones OTO - NOTNLM OT - Efruxifermin OT - Lanifibranor OT - MASH/MASLD OT - Resmetirom OT - Semaglutide OT - Survodutide EDAT- 2025/08/15 12:35 MHDA- 2025/08/31 20:08 CRDT- 2025/08/15 09:18 PHST- 2025/07/21 00:00 [revised] PHST- 2025/06/21 00:00 [received] PHST- 2025/07/29 00:00 [accepted] PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/15 12:35 [pubmed] PHST- 2025/08/15 09:18 [entrez] AID - 10.1111/liv.70271 [doi] PST - ppublish SO - Liver Int. 2025 Sep;45(9):e70271. doi: 10.1111/liv.70271. PMID- 40814081 OWN - NLM STAT- MEDLINE DCOM- 20250910 LR - 20260814 IS - 0310-057X (Print) IS - 1448-0271 (Electronic) IS - 0310-057X (Linking) VI - 53 IP - 5 DP - 2025 Sep TI - 2025 ADS/ANZCA/GESA/NACOS clinical practice recommendations on the peri-procedural use of GLP-1/GIP receptor agonists. PG - 300-306 LID - 10.1177/0310057X251355288 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes and/or obesity. The physiological actions of endogenous GLP-1, and synthetic GLP-1RAs include inhibition of gastric emptying. This has peri-procedural implications due to the potential increased risk of retained gastric contents which may result in pulmonary aspiration. There is a need for local evidence-based guidelines to best manage patients on GLP-1RAs and dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor co-agonists (GLP-1/GIPRAs) presenting for surgical and medical procedures requiring sedation or anaesthesia. A panel of experts was formed to consider the peri-procedural implications of GLP-1RA and GLP-1/GIPRA use and establish best practice recommendations based on the current evidence.We recommend that all patients should be asked about glucagon-like peptide-1 receptor agonist (GLP-1RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor co-agonist (GLP-1/GIPRA) use prior to anaesthesia or sedation for surgical and endoscopic procedures and be informed of the benefits and risks. We also recommend that GLP-1RAs and GLP-1/GIPRAs be continued in the peri-procedural period. Preprocedural diet modification with a 24-h clear fluid diet, followed by standard 6-h fasting, should be recommended for all patients receiving GLP-1RAs or GLP-1/GIPRAs. In patients who have not completed or are unable to have a 24-h liquid diet, risk stratification using gastric ultrasound or minimally sedated gastroscopy to assess gastric contents is recommended, as is the use of intravenous erythromycin. We cannot currently recommend using the absence of gastrointestinal symptoms for risk stratification, nor can we recommend an adequate cessation period for GLP-1RAs and GLP-1/GIPRAs to ensure gastric emptying has returned to baseline levels. This clinical guideline, developed by multiple professional bodies, outlines current best practice recommendations for patients taking GLP-1RAs and combined GLP-1/GIPRAs who require general anaesthesia, sedation and/or endoscopic procedures. The guide provides a structure for Australian and New Zealand primary health practitioners, gastroenterologists, surgeons, endocrinologists, anaesthetists and perioperative physicians to support clinical decisions in these patients. FAU - Hocking, Samantha L AU - Hocking SL AD - Charles Perkins Centre, University of Sydney, Camperdown, Australia. AD - Faculty of Medicine and Health, University of Sydney, Camperdown, Australia. AD - Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, Australia. RINGGOLD: 2205 FAU - Scott, David A AU - Scott DA AD - Department of Critical Care, University of Melbourne, Melbourne, Australia. AD - Department of Anaesthesia and Acute Pain Medicine, St Vincent's Hospital, Melbourne, Australia. FAU - Remedios, Matthew L AU - Remedios ML AD - Department of Gastroenterology, Wesley Hospital, Brisbane, Australia. RINGGOLD: 60576 FAU - Horowitz, Michael AU - Horowitz M AD - Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia. RINGGOLD: 1066 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia. RINGGOLD: 1062 FAU - Story, David A AU - Story DA AUID- ORCID: 0000-0002-6479-1310 AD - Department of Critical Care, University of Melbourne, Melbourne, Australia. FAU - Greenfield, Jerry R AU - Greenfield JR AD - Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, Australia. AD - Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, Australia. RINGGOLD: 2785 AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia. RINGGOLD: 98994 FAU - Boussioutas, Alex AU - Boussioutas A AD - Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. AD - Department of Gastroenterology, The Alfred, Monash University, Melbourne, Australia. FAU - Devereaux, Benedict AU - Devereaux B AD - School of Medicine, The University of Queensland, Brisbane, Australia. RINGGOLD: 1974 AD - Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia. FAU - Andrikopoulos, Sofianos AU - Andrikopoulos S AD - Australian Diabetes Society, Sydney, Australia. FAU - Shaw, Jonathan E AU - Shaw JE AD - Baker Heart and Diabetes Institute, Melbourne, Australia. AD - School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Australia. FAU - Olesnicky, Benjamin L AU - Olesnicky BL AUID- ORCID: 0000-0002-2650-7593 AD - Faculty of Medicine and Health, University of Sydney, Camperdown, Australia. AD - Department of Anaesthesia, Pain, and Perioperative Medicine, Royal North Shore Hospital, St Leonards, Australia. LA - eng PT - Journal Article PT - Practice Guideline DEP - 20250814 PL - United States TA - Anaesth Intensive Care JT - Anaesthesia and intensive care JID - 0342017 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM CIN - Anaesth Intensive Care. 2026 Aug 14:310057X261460073. doi: 10.1177/0310057X261460073. PMID: 42598987 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Perioperative Care/methods MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC12420935 OTO - NOTNLM OT - Aspiration OT - diabetes OT - fasting OT - glucagon like peptide agonist OT - obesity OT - perioperative medicine OT - pharmacology COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/08/15 10:55 MHDA- 2025/09/10 12:32 PMCR- 2025/09/10 CRDT- 2025/08/15 01:02 PHST- 2025/09/10 12:32 [medline] PHST- 2025/08/15 10:55 [pubmed] PHST- 2025/08/15 01:02 [entrez] PHST- 2025/09/10 00:00 [pmc-release] AID - 10.1177_0310057X251355288 [pii] AID - 10.1177/0310057X251355288 [doi] PST - ppublish SO - Anaesth Intensive Care. 2025 Sep;53(5):300-306. doi: 10.1177/0310057X251355288. Epub 2025 Aug 14. PMID- 40813129 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260925 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 390 DP - 2025 Aug 14 TI - Cardiovascular, kidney related, and weight loss effects of therapeutics for type 2 diabetes: a living clinical practice guideline. PG - e082071 LID - 10.1136/bmj-2024-082071 [doi] LID - e082071 AB - CLINICAL QUESTION: What are the benefits and harms of medications for adults with type 2 diabetes at varied risks of cardiovascular and kidney related complications? CONTEXT: Emerging clinical trials of novel medications have demonstrated benefits on cardiovascular, kidney, and weight related outcomes in people with type 2 diabetes. Dynamically updated practice guidelines adhering to standards of trustworthiness are necessary in response to a rapidly evolving evidence base and the availability of multiple medication alternatives. This living practice guideline incorporates the latest available medications and evidence and provides recommendations stratified by risks of cardiovascular and kidney complications to inform diabetes management. RECOMMENDATIONS: The panel issued risk-stratified recommendations regarding four prioritised medications for adults with type 2 diabetes (SGLT-2 inhibitors, GLP-1 receptor agonists, finerenone and tirzepatide):* Lower risk (three or fewer cardiovascular risk factors without established cardiovascular disease (CVD) or chronic kidney disease (CKD)): weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists.* Moderate risk (more than three cardiovascular risk factors without established CVD or CKD; or established CVD and/or CKD at lower risk of complications): weak recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation against finerenone in adults with CKD.* Higher risk (established CVD and/or CKD at higher risk of complications, or established heart failure): strong recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation in favour of finerenone in adults with CKD.* Across risk strata: weak recommendation in favour of tirzepatide in adults with obesity. ABOUT THIS GUIDELINE AND HOW IT WAS CREATED: An international panel including two patient partners, clinicians, and methodologists produced these recommendations. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits, harms and burdens of treatment from an individual patient perspective. Recommendations were informed by a linked living systematic review and network meta-analysis evaluating relative benefits and harms updated to 31 July 2024; and by linked systematic reviews addressing risk prediction models and values and preferences of adults with type 2 diabetes. Candidate therapeutics are prioritised based on availability of sufficient randomised trial data, relevance to a global audience and likelihood of changing practice.This is the first version of the living guideline. The guideline is part of the BMJ Rapid Recommendations series. MAGICapp displays the most recent version of the guideline and full content including evidence summaries and decision aids; major updates will be published in The BMJ. We encourage re-use, adaptation and translation of these living guidelines, and recognise that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Agarwal, Arnav AU - Agarwal A AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - Division of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - Mustafa, Reem AU - Mustafa R AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas, KS, USA. FAU - Manja, Veena AU - Manja V AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of California Davis, CA, USA. FAU - Agoritsas, Thomas AU - Agoritsas T AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada per@magicevidence.org thomas@magicevidence.org. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Division of General Internal Medicine, Department of Medicine, Hopitaux Universitaire de Geneve and University of Geneva, Geneva, Switzerland. FAU - Macdonald, Helen AU - Macdonald H AD - The BMJ, BMA House, Tavistock Square, London, UK. FAU - Li, Sheyu AU - Li S AD - Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China. AD - Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Foroutan, Farid AU - Foroutan F AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Ted Rogers Center for Heart Research, Toronto, Ontario, Canada. FAU - Rayner, Daniel AU - Rayner D AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. FAU - Rodriguez-Gutierrez, Rene AU - Rodriguez-Gutierrez R AD - Endocrinology Division, Department of Internal Medicine, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico. AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Nuevo Leon, Mexico. AD - Knowledge and Evaluation Research Unit in Endocrinology, Mayo Clinic, Rochester, MN, USA. FAU - Asvold, Bjorn Olav AU - Asvold BO AD - Department of Endocrinology, Clinic of Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. AD - HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. FAU - Heen, Anja Fog AU - Heen AF AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Department of Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway. FAU - Gabi, Jenan AU - Gabi J AD - Palestine Diabetes Institute, Nablus, Palestine. FAU - Guo, Lixin AU - Guo L AD - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Hao, Qiukui AU - Hao Q AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - The Center of Gerontology and Geriatrics/National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. FAU - Jeppesen, Britta Tendel AU - Jeppesen BT AD - Future Evidence Foundation, Melbourne, Australia. FAU - Jha, Vivekanand AU - Jha V AD - George Institute for Global Health, New Delhi, India. AD - School of Public Health, Imperial College London, South Kensington Campus, London, UK. AD - Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India. FAU - Nagler, Evi AU - Nagler E AD - Department of Nephrology, Ghent University Hospital, Ghent, Belgium. FAU - Odom, Adrienne AU - Odom A AD - patient partner, USA. FAU - Rodondi, Nicolas AU - Rodondi N AD - Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. AD - Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Shetty, Sahana AU - Shetty S AD - Department of Endocrinology, Kasturba Medical College (KMC)- Manipal, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India. FAU - Vermandere, Mieke AU - Vermandere M AD - Solidaris, Brussels, Belgium. FAU - Wright, Robin AU - Wright R AD - patient partner, USA. FAU - Guyatt, Gordon AU - Guyatt G AD - Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada. AD - Division of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - Vandvik, Per Olav AU - Vandvik PO AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway per@magicevidence.org thomas@magicevidence.org. AD - Institute of Health and Society, University of Oslo Faculty of Medicine, Oslo, Norway. LA - eng PT - Journal Article PT - Practice Guideline DEP - 20250814 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Weight Loss/drug effects MH - *Cardiovascular Diseases/prevention & control/etiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/prevention & control/etiology PMC - PMC12355350 COIS- Competing interests: All authors have completed the BMJ Rapid Recommendations interest of disclosure form. The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions. MAGIC and The BMJ assessed declared interests from other co-authors of this publication and found no relevant conflicts of interests. EDAT- 2025/08/14 22:51 MHDA- 2025/08/31 20:08 PMCR- 2025/08/14 CRDT- 2025/08/14 21:53 PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/14 22:51 [pubmed] PHST- 2025/08/14 21:53 [entrez] PHST- 2025/08/14 00:00 [pmc-release] AID - bmj-2024-082071.R2 [pii] AID - agaa082071 [pii] AID - 10.1136/bmj-2024-082071 [doi] PST - epublish SO - BMJ. 2025 Aug 14;390:e082071. doi: 10.1136/bmj-2024-082071. PMID- 40813122 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260703 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 390 DP - 2025 Aug 14 TI - Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis. PG - e083039 LID - 10.1136/bmj-2024-083039 [doi] AB - OBJECTIVE: To provide up-to-date evidence on key benefits, harms, and uncertainties regarding medications for adults with type 2 diabetes. DESIGN: Living systematic review and network meta-analysis (NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches. Updates are planned at least two times a year. DATA SOURCES: Medline and Embase, searched up to 31 July 2024 for the current iteration. STUDY SELECTION: Randomised controlled trials of at least 24 weeks comparing one or more medications with standard treatment, placebo, or each other. RESULTS: The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease). The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval -9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty). Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/). Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty). CONCLUSIONS: This living systematic review provides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42022325948. A more detailed protocol is available at https://data.aliveevidence.org/records/q02rv-km486. READERS' NOTES: This article is the first version of a living systematic review. It is linked to a living BMJ Rapid Recommendation and other living clinical practice guidelines, presenting risk stratified recommendations for patients with type 2 diabetes at lower, moderate, and higher risk of cardiovascular and kidney complications. The latest evidence will be made available via the BMJ Rapid Recommendation and via an interactive GRADE evidence summary (MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/). Major updates will be published in The BMJ. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Nong, Kailei AU - Nong K AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - co-first authors who contribute equally to this study. FAU - Jeppesen, Britta Tendal AU - Jeppesen BT AD - Future Evidence Foundation, Melbourne, Australia. AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. AD - co-first authors who contribute equally to this study. FAU - Shi, Qingyang AU - Shi Q AD - Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands. AD - co-first authors who contribute equally to this study. FAU - Agoritsas, Thomas AU - Agoritsas T AD - Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada. AD - Division of General Internal Medicine, Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - Guyatt, Gordon H AU - Guyatt GH AD - Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - White, Heath AU - White H AD - Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. FAU - Gao, Yiyuan AU - Gao Y AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Agarwal, Arnav AU - Agarwal A AD - Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada. FAU - Macdonald, Helen AU - Macdonald H AD - BMJ Editorial Tavistock Square, London, UK. FAU - Zou, Xinyu AU - Zou X AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Millard, Tanya AU - Millard T AD - Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. AD - Australian Diabetes Society, Sydney, Australia. FAU - Schnell, Oliver AU - Schnell O AD - Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, RWTH Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Brosius, Frank C 3rd AU - Brosius FC 3rd AD - Division of Nephrology, University of Arizona College of Medicine Tucson, Tucson, AZ, USA. FAU - McDonald, Steve AU - McDonald S AD - Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. FAU - Quigley, Matthew AU - Quigley M AD - Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. FAU - Tian, Xin AU - Tian X AD - Healthcare Innovation Research Laboratory, Nursing Key Laboratory of Sichuan Province, National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China. FAU - Fan, Qinlin AU - Fan Q AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - White, Barbara AU - White B AD - Australian Diabetes Society, Sydney, Australia. FAU - Mao, Yunhe AU - Mao Y AD - Department of Orthopaedics, Orthopaedic Research Institute, West China Hospital, Sichuan University, Chengdu, China. FAU - Pan, Xiaohui AU - Pan X AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Liu, Changhai AU - Liu C AD - Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. AD - Division of Infectious Diseases, State Key Laboratory of Biotherapy and Centre of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China. FAU - Zhai, Chunjuan AU - Zhai C AD - Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China. FAU - Yuan, Chi AU - Yuan C AD - Department of Paediatric Surgery, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Qiang AU - Li Q AD - Department of Hypertension and Endocrinology, Daping Hospital, Centre for Hypertension and Metabolic Diseases, Army Medical University of PLA, Chongqing Institute of Hypertension, Chongqing, China lisheyu@gmail.com. FAU - An, Jing AU - An J AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Gan, Yu AU - Gan Y AD - Department of Anaesthesiology, Laboratory of Anaesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anaesthesiology, Frontiers Science Centre for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. FAU - Wang, Yanyan AU - Wang Y AD - Healthcare Innovation Research Laboratory, Nursing Key Laboratory of Sichuan Province, National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China. FAU - Jin, Yinghui AU - Jin Y AD - Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Sun, Feng AU - Sun F AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. FAU - Zhu, Zhiming AU - Zhu Z AD - Department of Hypertension and Endocrinology, Daping Hospital, Centre for Hypertension and Metabolic Diseases, Army Medical University of PLA, Chongqing Institute of Hypertension, Chongqing, China. FAU - Ryden, Lars AU - Ryden L AD - Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. FAU - Standl, Eberhard AU - Standl E AD - Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany. FAU - Turner, Tari AU - Turner T AD - Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. FAU - Vandvik, Per Olav AU - Vandvik PO AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Department of Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway. AD - co-senior authors of this study. FAU - Li, Sheyu AU - Li S AUID- ORCID: 0000-0003-0060-0287 AD - Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China lisheyu@gmail.com. AD - MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - co-senior authors of this study. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250814 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Randomized Controlled Trials as Topic MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the West China Hospital, Sichuan University for the submitted work; KNong, BTJeppesen, QShi, TAgoritsas, GGuyatt, HWhite, YGao, AAgarwal, HMacdonald, XZou, TMillard, SMcdonald, MQuigley, XTian, QFan, BWhite, YMao, XPan, CLiu, CZhai, CYuan, QLi, JAn, YGan, YWang, YJin, FSun, ZZhu, TTurner, and POVandvik: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. EStandl reported personal fees from Oxford Diabetes Trials Unit, Bayer, Berlin Chemie, Boehringer Ingelheim, Menarini, Merck Serono, EXCEMED, Novartis, Novo Nordisk, and Sanofi. LRyden reported grants or contracts from Swedish Heart Lung Foundation, Stockholm County Council, Erling Perssons Foundation and Boehringer-Ingelheim, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer AG, Boehringer Ingelheim, Novo Nordisk. FBrosiusIII reported grants or contracts from National Institutes of Health, and consulting fees from Gilead Sciences. OSchnell reported payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott Diagnostics, Lilly Deutschland, Boehringer Ingelheim, Bayer, Mannkind, and Lifescan and is a founder and CEO of Sciarc GmbH. NMarx reported grants or contracts from Boehringer Ingelheim, Merck, Novo Nordisk, Deutsche Forschungsgesellschaft (German Research Foundation; TRR 219), and consulting fees from Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, AstraZeneca. SLi received the funds from West China Hospital of Sichuan University, National Natural Science Foundation of China, and Sichuan Science and Technology Program. EDAT- 2025/08/14 22:50 MHDA- 2025/08/31 20:08 CRDT- 2025/08/14 21:52 PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/14 22:50 [pubmed] PHST- 2025/08/14 21:52 [entrez] AID - 10.1136/bmj-2024-083039 [doi] PST - epublish SO - BMJ. 2025 Aug 14;390:e083039. doi: 10.1136/bmj-2024-083039. PMID- 40812084 OWN - NLM STAT- MEDLINE DCOM- 20250903 LR - 20260730 IS - 1872-6976 (Electronic) IS - 0167-4943 (Linking) VI - 138 DP - 2025 Nov TI - Efficacy of GLP-1 receptor agonists among older adults: a meta-analysis of cardio-kidney outcome trials. PG - 105981 LID - S0167-4943(25)00238-9 [pii] LID - 10.1016/j.archger.2025.105981 [doi] AB - BACKGROUND: Older adults face high cardiovascular (CV) and kidney risk but may be underrepresented in randomized controlled trials (RCTs). While GLP-1RAs have been shown to provide CV and kidney benefits, estimates for efficacy and safety endpoints among older adults remain less certain. This meta-analysis assesses their impact on CV and kidney outcomes. METHODS: This systematic review and meta-analysis followed PRISMA guidelines. Outcomes included composite kidney outcome, 3-point major adverse cardiovascular events (3p-MACE), CV death, stroke, myocardial infarction (MI), and hospitalization for heart failure (HHF). Hazard ratios (HRs) were pooled using a random-effects model. Subgroup analysis was performed between older adults (>/=65 years) and younger adults (<65 years). RESULTS: Eleven RCTs with 85,373 participants were included, out of which 44,013 (51.6 %) were older adults. Among older adults, GLP-1RAs significantly reduced the composite kidney outcome by 22 % (HR: 0.78; 95 % CI: 0.70-0.87; p < 0.001), 3-p MACE by 15 % (HR: 0.85; 95 % CI: 0.78-0.94; p = 0.001), and CV death by 15 % (HR: 0.85; 95 % CI: 0.72-1.00; p = 0.05). Nonsignificant trends were observed for stroke (HR: 0.86; 95 % CI: 0.74-1.01; p = 0.06), MI (HR: 0.86; 95 % CI: 0.70-1.05; p = 0.14), and HHF (HR: 0.88; 95 % CI: 0.73-1.06; p = 0.17). These efficacy estimates among older adults were consistent with those among younger adults, with statistical evidence of heterogeneity (all p for interaction > 0.2). CONCLUSIONS: GLP-1RAs significantly reduce MACE, CV death, and kidney events in older adults, supporting their use in this population. While benefits on stroke, MI, and HHF were less conclusive, trends favor GLP-1RA use. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Waqas, Saad Ahmed AU - Waqas SA AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. Electronic address: ahsaad404@gmail.com. FAU - Ali, Dua AU - Ali D AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. Electronic address: dua.ali23@dmc.duhs.edu.pk. FAU - Afridi, Muhammad Khalid AU - Afridi MK AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Siddiqui, Hasan Fareed AU - Siddiqui HF AD - Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Nazir, Arif AU - Nazir A AD - Abode Care Partners, Associate Clinical Professor of Family and Geriatric Medicine (Gratis), University of Louisville School of Medicine, Louisville, USA. FAU - Greene, Stephen J AU - Greene SJ AD - Duke Clinical Research Institute, Durham, NC, USA; Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. FAU - Khan, Muhammad Shahzeb AU - Khan MS AD - Baylor College of Medicine, Temple, TX, USA; Baylor Scott and White Heart Hospital, Plano, TX, USA; Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, TX, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250808 PL - Netherlands TA - Arch Gerontol Geriatr JT - Archives of gerontology and geriatrics JID - 8214379 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Aged MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Failure MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP-1 receptor agonists OT - Kidney outcomes OT - Meta-analysis OT - Older adults COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/08/14 22:51 MHDA- 2025/09/04 00:35 CRDT- 2025/08/14 18:10 PHST- 2025/06/08 00:00 [received] PHST- 2025/07/17 00:00 [revised] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/04 00:35 [medline] PHST- 2025/08/14 22:51 [pubmed] PHST- 2025/08/14 18:10 [entrez] AID - S0167-4943(25)00238-9 [pii] AID - 10.1016/j.archger.2025.105981 [doi] PST - ppublish SO - Arch Gerontol Geriatr. 2025 Nov;138:105981. doi: 10.1016/j.archger.2025.105981. Epub 2025 Aug 8. PMID- 40808573 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Orforglipron, an oral non-peptide glucagon-like peptide-1 receptor agonist, improves markers of beta-cell function and insulin sensitivity in type 2 diabetes. PG - 6314-6322 LID - 10.1111/dom.70022 [doi] AB - AIMS: These participant-level exploratory analyses evaluated the effects of orforglipron, a once-daily, orally administered non-peptide glucagon-like peptide-1 receptor agonist, versus dulaglutide and placebo, on beta-cell function and insulin sensitivity biomarkers. MATERIALS AND METHODS: Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo. Treatment effects on beta-cell function and insulin sensitivity markers were assessed, including homeostatic model assessment indices of beta-cell function and insulin resistance (HOMA-B and HOMA-IR, respectively); fasting C-peptide, insulin, serum glucose, and glucagon; adiponectin; insulin-like growth factor binding protein 2; proinsulin; and the proinsulin/insulin ratio. RESULTS: Orforglipron doses of 12 mg and higher were associated with improved beta-cell function and insulin sensitivity. HOMA-B increased up to 123% (C-peptide) and 132% (insulin) with orforglipron doses of 12 mg and higher from baseline to week 4 before stabilising. HOMA-B increases were greater with all orforglipron doses than with dulaglutide. Additional beta-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide. HOMA-IR values decreased up to 16% (C-peptide) and 23% (insulin) with orforglipron by week 26. Reductions in HOMA-IR (insulin) were significant versus baseline only for the highest dose. IGFBP-2 and adiponectin, corollary biomarkers of insulin sensitivity, were generally improved with orforglipron. CONCLUSIONS: Increased HOMA-B and improved metabolic biomarkers suggest that treatment with the orally administered non-peptide GLP-1 receptor agonist orforglipron enhanced pancreatic beta-cell function and insulin sensitivity in patients with T2D. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas, Texas, USA. FAU - Robins, Deborah A AU - Robins DA AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Duffin, Kevin L AU - Duffin KL AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wilson, Jonathan M AU - Wilson JM AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Lin, Yanzhu AU - Lin Y AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Banerjee, Hiya AU - Banerjee H AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Eyde, Sarah AU - Eyde S AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kazda, Christof AU - Kazda C AUID- ORCID: 0000-0002-2538-2573 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Konig, Manige AU - Konig M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mather, Kieren J AU - Mather KJ AUID- ORCID: 0000-0001-8696-7500 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250814 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 0 (Insulin) RN - 0 (Adiponectin) RN - 0 (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Insulin Resistance MH - *Insulin-Secreting Cells/drug effects/metabolism/physiology MH - Male MH - Female MH - Middle Aged MH - Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Biomarkers/blood MH - Immunoglobulin Fc Fragments/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - C-Peptide/blood MH - Administration, Oral MH - Aged MH - Insulin/blood MH - Double-Blind Method MH - Adiponectin/blood MH - Adult MH - Oxadiazoles MH - Fluorine Compounds OTO - NOTNLM OT - GLP-1 OT - anti-diabetic drug OT - beta cell function OT - glycaemic control OT - insulin resistance OT - insulin secretion EDAT- 2025/08/14 06:28 MHDA- 2025/10/13 00:27 CRDT- 2025/08/14 04:03 PHST- 2025/07/28 00:00 [revised] PHST- 2025/05/16 00:00 [received] PHST- 2025/08/03 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/14 06:28 [pubmed] PHST- 2025/08/14 04:03 [entrez] AID - 10.1111/dom.70022 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6314-6322. doi: 10.1111/dom.70022. Epub 2025 Aug 14. PMID- 40803507 OWN - NLM STAT- MEDLINE DCOM- 20250905 LR - 20250905 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 227 DP - 2025 Sep TI - GLP-1 receptor agonists and risk of hepatocellular carcinoma and all-cause mortality in patients with MASLD and type 2 diabetes: a propensity score-matched population-based cohort study. PG - 112407 LID - S0168-8227(25)00421-8 [pii] LID - 10.1016/j.diabres.2025.112407 [doi] AB - BACKGROUND: Hepatocellular carcinoma (HCC) is increasingly driven by non-viral causes, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), which commonly coexists with type 2 diabetes mellitus (T2DM). Given the strong link between T2DM and HCC and the lack of approved pharmacologic preventive strategies, agents with dual metabolic and oncologic benefits are urgently needed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory, anti-fibrotic, and potential anti-tumor effects. METHODS: We conducted a multinational retrospective cohort study using the TriNetX global network to evaluate associations between GLP-1RA use and incident HCC in patients with MASLD and T2DM. Adults aged 18-90 years with both conditions were identified between 2005 and 2025. Primary outcome was incident HCC; secondary was all-cause mortality. Adjusted hazard ratios (aHRs) were estimated using Cox models. RESULTS: After matching, 152,329 patients were included in each group. GLP-1RA use was associated with lower risks of HCC (aHR, 0.64; 95% CI, 0.42-0.98) and all-cause mortality (aHR, 0.37; 95% CI, 0.36-0.38). Subgroup, sensitivity, and control analyses supported the robustness of findings. CONCLUSIONS: GLP-1RA use was associated with significantly reduced risks of HCC and death in patients with MASLD and T2DM, supporting its potential for HCC chemoprevention. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Ng, Hui-Ji AU - Ng HJ AD - Division of Thoracic Surgery, Department of Surgery, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Jao, An-Tzu AU - Jao AT AD - Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan; Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. FAU - Wu, Szu-Yuan AU - Wu SY AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: szuyuanwu5399@gmail.com. FAU - Soong, Ruey-Shyang AU - Soong RS AD - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan; Transplantation Center, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Organ Transplantation, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: kodlp62@gmail.com. LA - eng PT - Journal Article DEP - 20250811 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/epidemiology/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality/epidemiology MH - *Liver Neoplasms/epidemiology/mortality MH - Middle Aged MH - Male MH - Female MH - Aged MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged, 80 and over MH - Propensity Score MH - Adolescent MH - Young Adult MH - *Fatty Liver/complications/mortality/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Cohort Studies OTO - NOTNLM OT - Chemoprevention OT - GLP-1 receptor agonists OT - Hepatocellular carcinoma OT - MASLD OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/08/14 00:28 MHDA- 2025/09/06 00:34 CRDT- 2025/08/13 19:38 PHST- 2025/07/06 00:00 [received] PHST- 2025/07/30 00:00 [revised] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/06 00:34 [medline] PHST- 2025/08/14 00:28 [pubmed] PHST- 2025/08/13 19:38 [entrez] AID - S0168-8227(25)00421-8 [pii] AID - 10.1016/j.diabres.2025.112407 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Sep;227:112407. doi: 10.1016/j.diabres.2025.112407. Epub 2025 Aug 11. PMID- 40803202 OWN - NLM STAT- MEDLINE DCOM- 20250926 LR - 20260920 IS - 1521-0081 (Electronic) IS - 0031-6997 (Print) IS - 0031-6997 (Linking) VI - 77 IP - 5 DP - 2025 Sep TI - Modern antidiabetic therapy by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors against cardiovascular diseases. PG - 100082 LID - S0031-6997(25)07490-3 [pii] LID - 10.1016/j.pharmr.2025.100082 [doi] LID - 100082 AB - Diabetes and related metabolic diseases have a high prevalence with increasing incidence and create a significant socioeconomic burden by their contribution to global mortality and disability-adjusted life years. According to data from the Global Burden of Disease Study, high fasting plasma glucose and high total cholesterol rank third and fourth in the list of global health risk factors, just behind high blood pressure and smoking. Diabetes adversely affects endothelial and cardiac function, thereby contributing significantly to the development and progression of cardiovascular diseases, which represents the leading health risk factors and causes of death worldwide. Oxidative stress and inflammation play a key role in the pathophysiology underlying diabetes mellitus and the associated cardiometabolic complications, such as metabolic dysfunction-associated fatty liver disease, hypertension, atherosclerosis, myocardial ischemia/reperfusion, and heart failure. Here, we highlight the beneficial effects of the modern antidiabetic drug classes of dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors on overall and cardiovascular mortality of diabetic individuals, with particular emphasis on their effects on oxidative stress, inflammation, and endothelial dysfunction. We discuss the mechanisms of action and pleiotropic beneficial effects and compare them with standard diabetic and cardiovascular therapy. SIGNIFICANCE STATEMENT: Modern antidiabetic drugs confer organ protection that goes beyond simple glucose-lowering. SGLT2 inhibitors and incretin-based drugs possess direct reno-, vasculo-, and cardioprotective effects that are based on potent antioxidant and anti-inflammatory properties. Other pleiotropic effects comprise improved lipid handling and weight loss, prevention of thrombosis and ischemic heart damage, and beneficial regulation of nitric oxide signaling and epigenetic and microbiotic pathways. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Steven, Sebastian AU - Steven S AD - Department for Cardiology 1, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partnersite Rhine-Main, Mainz, Germany; Department of Cardiology, Goethe University Frankfurt, Germany. FAU - Kuntic, Marin AU - Kuntic M AD - Department for Cardiology 1, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partnersite Rhine-Main, Mainz, Germany. FAU - Munzel, Thomas AU - Munzel T AD - Department for Cardiology 1, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partnersite Rhine-Main, Mainz, Germany. FAU - Daiber, Andreas AU - Daiber A AD - Department for Cardiology 1, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partnersite Rhine-Main, Mainz, Germany. Electronic address: daiber@uni-mainz.de. LA - eng PT - Journal Article PT - Review DEP - 20250711 PL - Netherlands TA - Pharmacol Rev JT - Pharmacological reviews JID - 0421737 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy/metabolism MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Animals MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Oxidative Stress/drug effects PMC - PMC12799437 COIS- Conflicts of interest Andreas Daiber reports financial support provided by Mainz Heart Foundation. Thomas Munzel reports financial support provided by German Center for Cardiovascular Disease. Sebastian Steven reports financial support provided by Else Kroner-Fresenius Foundation. Andreas Daiber and Thomas Munzel received research grant support from Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim (more than 5 years ago). EDAT- 2025/08/14 00:28 MHDA- 2025/09/27 00:30 PMCR- 2025/07/10 CRDT- 2025/08/13 18:14 PHST- 2024/12/03 00:00 [received] PHST- 2025/07/01 00:00 [revised] PHST- 2025/07/05 00:00 [accepted] PHST- 2025/09/27 00:30 [medline] PHST- 2025/08/14 00:28 [pubmed] PHST- 2025/08/13 18:14 [entrez] PHST- 2025/07/10 00:00 [pmc-release] AID - S0031-6997(25)07490-3 [pii] AID - 100082 [pii] AID - 10.1016/j.pharmr.2025.100082 [doi] PST - ppublish SO - Pharmacol Rev. 2025 Sep;77(5):100082. doi: 10.1016/j.pharmr.2025.100082. Epub 2025 Jul 11. PMID- 40798976 OWN - NLM STAT- MEDLINE DCOM- 20260415 LR - 20260415 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 32 IP - 14 DP - 2026 TI - An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs. PG - 1095-1106 LID - 10.2174/0113816128375766250720234005 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity. METHODS: The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria. RESULTS: They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties. DISCUSSION: The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties. CONCLUSION: GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Zayed, Mohamed F AU - Zayed MF AUID- ORCID: 0000-0001-8683-5460 AD - Pharmaceutical Sciences Department, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Khayat, Nada O AU - Khayat NO AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alsibyani, Rawan W AU - Alsibyani RW AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alshami, Rahaf Z AU - Alshami RZ AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alsubahi, Ramzyah A AU - Alsubahi RA AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alamoudi, Mariam K AU - Alamoudi MK AD - Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/pharmacokinetics/chemistry/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Design MH - *Glucagon-Like Peptide 1 MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism OTO - NOTNLM OT - GLP-1 receptors agonists OT - glucagon OT - insulin OT - pharmacokinetic OT - physicochemical OT - type 2 diabetes mellitus EDAT- 2025/08/13 06:30 MHDA- 2026/04/15 06:29 CRDT- 2025/08/13 02:23 PHST- 2024/12/19 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2026/04/15 06:29 [medline] PHST- 2025/08/13 06:30 [pubmed] PHST- 2025/08/13 02:23 [entrez] AID - CPD-EPUB-150007 [pii] AID - 10.2174/0113816128375766250720234005 [doi] PST - ppublish SO - Curr Pharm Des. 2026;32(14):1095-1106. doi: 10.2174/0113816128375766250720234005. PMID- 40798974 OWN - NLM STAT- MEDLINE DCOM- 20260218 LR - 20260528 IS - 2212-4063 (Electronic) IS - 1871-529X (Linking) VI - 25 IP - 4 DP - 2025 TI - Oral Semaglutide: A Step Forward in Cardiovascular Risk Management for Type 2 Diabetes. PG - 227-230 LID - 10.2174/011871529X421551250801194823 [doi] AB - Recent cardiovascular outcome trials (CVOTs) have reshaped the therapeutic landscape of type 2 diabetes mellitus (T2DM), revealing that certain glucose-lowering agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer substantial cardiovascular benefits beyond glycemic control. Injectable GLP-1RAs, such as semaglutide and liraglutide, have been shown to reduce major adverse cardiovascular events (MACE), but barriers, including cost, access, and the burden of injections, persist. The SOUL trial marks a significant milestone by evaluating oral semaglutide in high-risk patients, demonstrating a 14% reduction in MACE versus placebo and reinforcing GLP-1RAs cardioprotective potential in an oral formulation. This advancement holds promise for patient populations underrepresented in prior trials. However, gastrointestinal side effects and strict dosing requirements challenge long-term adherence. While the findings suggest improved accessibility and real-world applicability, further comparative trials with injectables, extended follow-up, and cost-effectiveness studies are essential. As evidence evolves, oral GLP-1RAs may represent a more patient-centered approach to managing diabetes and cardiovascular risk. This perspective article aims to explore the implications of the SOUL trial, highlight ongoing challenges in adherence and implementation, and discuss the future role of oral GLP-1RAs in cardiovascular and diabetes care. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Luna-Ceron, Eder AU - Luna-Ceron E AUID- ORCID: 0000-0002-6484-4304 AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Kattamuri, Lakshmi AU - Kattamuri L AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Duvvuru, Sparsha Reddy AU - Duvvuru SR AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Mukherjee, Debabrata AU - Mukherjee D AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. AD - Cardiovascular Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Cardiovasc Hematol Disord Drug Targets JT - Cardiovascular & hematological disorders drug targets JID - 101269160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - Administration, Oral MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Disease Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - Oral semaglutide OT - SOUL trial OT - cardiovascular outcomes OT - medication adherence. OT - type 2 diabetes EDAT- 2025/08/13 06:30 MHDA- 2026/02/18 10:06 CRDT- 2025/08/13 02:23 PHST- 2025/06/10 00:00 [received] PHST- 2025/07/03 00:00 [revised] PHST- 2025/07/10 00:00 [accepted] PHST- 2026/02/18 10:06 [medline] PHST- 2025/08/13 06:30 [pubmed] PHST- 2025/08/13 02:23 [entrez] AID - CHDDT-EPUB-150002 [pii] AID - 10.2174/011871529X421551250801194823 [doi] PST - ppublish SO - Cardiovasc Hematol Disord Drug Targets. 2025;25(4):227-230. doi: 10.2174/011871529X421551250801194823. PMID- 40798873 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients-A systematic review and network meta-analysis. PG - 6254-6263 LID - 10.1111/dom.70010 [doi] AB - AIMS: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) is a common complication that increases the risk of cardiovascular (CV) events and kidney failure. Recent therapies, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase IV (DPP-4) inhibitors, show promise in improving outcomes. However, evidence of their comparative effectiveness in reducing CV and renal outcomes is scarce. MATERIALS AND METHODS: We searched electronic databases such as PubMed, Scopus, and clinical trial registries for randomized controlled trials (RCTs) published between 2014 and 2024. A network meta-analysis (NMA) was employed to evaluate the effectiveness of antidiabetic drugs on cardiorenal outcomes. Primary outcomes were (1) major adverse CV events (MACE), (2) composite renal outcomes, (3) all-cause mortality. Other outcomes included heart failure (HF), stroke, macroalbuminuria, and a decline in estimated glomerular filtration rate (eGFR) >40% or renal replacement therapy. RESULTS: Twenty-six studies with 143 296 participants with T2DM and CKD were included. SGLT2 inhibitors were highly effective in reducing the risk of renal outcomes such as composite events (P-score: 0.94), eGFR decline >40% or renal replacement therapy (0.99) and CV outcomes such as MACE (0.93) and HF (1.00) followed by GLP-1 RA. While GLP-1 RA was particularly effective in reducing the risk of MI (0.87), macroalbuminuria (0.86) and stroke (0.83) compared to SGLT2 inhibitors. Both SGLT2 inhibitors and GLP-1 receptor agonists are highly effective (0.83) in reducing all-cause mortality. DPP-4 inhibitors had limited benefits compared to SGLT2 inhibitors and GLP-1 RA. CONCLUSION: SGLT2 inhibitors followed by GLP-1 RA provide strong benefits for CV and kidney health in patients with T2DM and CKD. SGLT2 inhibitors demonstrate superior benefit over GLP-1 receptor agonists for HF and renal outcomes, highlighting their preferred role in these clinical scenarios. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Bramlage, Peter AU - Bramlage P AUID- ORCID: 0000-0003-4970-2110 AD - Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany. FAU - Vijayan, Anjaly AU - Vijayan A AUID- ORCID: 0009-0009-0915-427X AD - Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany. FAU - Varghese, Treesa P AU - Varghese TP AUID- ORCID: 0000-0002-8337-319X AD - Department of Pharmacy Practice, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, India. FAU - Melepurakkal Sadanandan, Deepthy AU - Melepurakkal Sadanandan D AD - Women's & Children's Health Research Unit, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, India. FAU - Lanzinger, Stefanie AU - Lanzinger S AUID- ORCID: 0000-0002-3789-6459 AD - Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. AD - German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. FAU - Rodriguez, Carmen Ferrero AU - Rodriguez CF AD - Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250812 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetic Nephropathies/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glomerular Filtration Rate/drug effects MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - antidiabetic drugs OT - cardiovascular outcomes OT - chronic kidney disease OT - meta-analysis OT - renal outcomes OT - systematic review OT - type 2 diabetes EDAT- 2025/08/13 06:30 MHDA- 2025/10/13 00:27 CRDT- 2025/08/13 01:33 PHST- 2025/07/15 00:00 [revised] PHST- 2025/04/10 00:00 [received] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/13 06:30 [pubmed] PHST- 2025/08/13 01:33 [entrez] AID - 10.1111/dom.70010 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6254-6263. doi: 10.1111/dom.70010. Epub 2025 Aug 12. PMID- 40796776 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20250826 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 16 IP - 1 DP - 2025 Aug 12 TI - A retrospective analysis of combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in patients with MASLD. PG - 7459 LID - 10.1038/s41467-025-62891-8 [doi] LID - 7459 AB - The impact of adding glucagon-like peptide-1 receptor agonists (GLP-1RAs) to sodium-glucose co-transporter-2 inhibitors (SGLT2is) for metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This retrospective study compared the effect of GLP-1RA plus SGLT2i versus SGLT2i alone for MASLD. Combination therapy was associated with a lower risk of primary composite outcomes of all-cause hospitalization, all-cause mortality, major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), and major adverse liver outcomes (MALO) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.84-0.91). Combination therapy also showed lower risks for all-cause hospitalization (HR, 0.86; 95% CI, 0.82-0.90), all-cause mortality (HR, 0.45; 95% CI, 0.38-0.53), MAKE (HR, 0.72; 95% CI, 0.60-0.89), and MALO (HR, 0.61; 95% CI, 0.53-0.69). In contrast, compared to GLP-1RA monotherapy, combination therapy did not confer additional benefit except for all-cause mortality. Overall, combination therapy with GLP-1RA plus SGLT2i was associated with better clinical outcomes of MASLD, compared to SGLT2i monotherapy. CI - (c) 2025. The Author(s). FAU - Wu, Jheng-Yan AU - Wu JY AUID- ORCID: 0000-0002-3290-1909 AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Hsu, Wan-Hsuan AU - Hsu WH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Chia-Chih AU - Kuo CC AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Tsai, Ya-Wen AU - Tsai YW AD - Division of Preventive Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Liu, Ting-Hui AU - Liu TH AD - Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Hung, Kuo-Chuan AU - Hung KC AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. FAU - Yu, Tsung AU - Yu T AD - Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. dtmed141@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. dtmed141@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250812 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects/administration & dosage MH - Retrospective Studies MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Middle Aged MH - Aged MH - Drug Therapy, Combination MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hospitalization/statistics & numerical data MH - Hypoglycemic Agents/therapeutic use PMC - PMC12343782 COIS- Competing interests: The authors declare no competing interests. EDAT- 2025/08/13 00:27 MHDA- 2025/08/31 20:07 PMCR- 2025/08/12 CRDT- 2025/08/12 23:30 PHST- 2024/11/25 00:00 [received] PHST- 2025/07/31 00:00 [accepted] PHST- 2025/08/31 20:07 [medline] PHST- 2025/08/13 00:27 [pubmed] PHST- 2025/08/12 23:30 [entrez] PHST- 2025/08/12 00:00 [pmc-release] AID - 10.1038/s41467-025-62891-8 [pii] AID - 62891 [pii] AID - 10.1038/s41467-025-62891-8 [doi] PST - epublish SO - Nat Commun. 2025 Aug 12;16(1):7459. doi: 10.1038/s41467-025-62891-8. PMID- 40796052 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 6 DP - 2025 Nov TI - Reduced risks of colorectal cancer with GLP-1RAs in type 2 diabetes: A nationwide cohort study using a target trial emulation framework. PG - 101695 LID - S1262-3636(25)00089-8 [pii] LID - 10.1016/j.diabet.2025.101695 [doi] AB - AIM: - Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer (CRC). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce CRC risk compared to insulin therapy; however, current evidence is controversial. We aimed to evaluate the association between CRC and the use of GLP-1RAs and long-acting insulins (LAIs). METHODS: - This target trial emulation employed nationwide data from a Taiwanese T2D cohort. We identified new GLP-1RA and LAI users from 2013 to 2021, and applied propensity score (PS) matching to ensure comparable baseline characteristics. The primary outcome was CRC. Follow-up lasted until outcome occurrence, death, or study end in 2022, whichever came first. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated to assess the association between treatment and outcomes. Sensitivity analyses-including stabilized inverse probability weighting, time-dependent survival analysis, E-values, and negative control outcome analyses-were conducted to test the robustness of findings. RESULTS: - We included 11,726 PS-matched pairs of GLP-1RA and LAI users and found no significant baseline disparities between cohorts. Compared to LAIs, GLP-1RAs were associated with significantly reduced CRC risk (HR [95 % CI]: 0.66 [0.48-0.92]), with the association limited to the rectum (HR: 0.53 [0.28-0.92]) but not observed in the right- or left-sided colon (right, HR: 0.69 [0.41-1.19]; left, HR: 0.77 [0.44-1.33]). These findings were consistent across sensitivity analyses and among patients with varying baseline characteristics. CONCLUSION: - Among patients with T2D requiring injectable glucose-lowering agents, GLP-1RA use, compared to LAIs, was associated with reduced CRC risk, particularly in the rectum. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Wu, Chih-Chien AU - Wu CC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Su, Chien-Chou AU - Su CC AD - Clinical Innovation and Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Chang, Yu-Ching AU - Chang YC AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lee, Pei-Ting AU - Lee PT AD - Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Su, Yi-Chia AU - Su YC AD - Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan. Electronic address: jia.love70@vghks.gov.tw. LA - eng GR - KSVGH114-124/Kaohsiung Veterans General Hospital/ PT - Journal Article DEP - 20250810 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Long-Acting) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Colorectal Neoplasms/epidemiology/prevention & control MH - Female MH - Male MH - Middle Aged MH - Taiwan/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Cohort Studies MH - *Insulin, Long-Acting/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Colorectal cancer risk OT - Glucagon-like peptide-1 receptor agonists OT - Glucose-lowering agents OT - Long-acting insulins OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no competing interests EDAT- 2025/08/13 00:27 MHDA- 2025/11/22 00:28 CRDT- 2025/08/12 19:26 PHST- 2025/06/16 00:00 [received] PHST- 2025/07/28 00:00 [revised] PHST- 2025/08/01 00:00 [accepted] PHST- 2025/11/22 00:28 [medline] PHST- 2025/08/13 00:27 [pubmed] PHST- 2025/08/12 19:26 [entrez] AID - S1262-3636(25)00089-8 [pii] AID - 10.1016/j.diabet.2025.101695 [doi] PST - ppublish SO - Diabetes Metab. 2025 Nov;51(6):101695. doi: 10.1016/j.diabet.2025.101695. Epub 2025 Aug 10. PMID- 40788647 OWN - NLM STAT- MEDLINE DCOM- 20250811 LR - 20260717 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 8 DP - 2025 Aug 1 TI - GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes. PG - e2526321 LID - 10.1001/jamanetworkopen.2025.26321 [doi] LID - e2526321 AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. OBJECTIVE: To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of adults (aged >/=18 years) with T2D and a recent hemoglobin A1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. EXPOSURES: At least 2 prescriptions of a GLP-1 RA given 6 months apart. MAIN OUTCOMES AND MEASURES: Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. RESULTS: After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D. FAU - Ramsey, David J AU - Ramsey DJ AD - Division of Ophthalmology, Department of Surgery, UMass Chan-Lahey School of Medicine, Burlington, Massachusetts. AD - Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts. AD - Department of Biomedical Sciences and Disease, New England College of Optometry, Boston, Massachusetts. FAU - Makwana, Bhargav AU - Makwana B AD - Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Dani, Sourbha S AU - Dani SS AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Patel, Manav AU - Patel M AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Panchal, Krisha AU - Panchal K AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Shah, Jui AU - Shah J AD - Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Khadke, Sumanth AU - Khadke S AD - Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Kumar, Ashish AU - Kumar A AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Patel, Tirth AU - Patel T AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Medicine, Saint Luke's Mid America Heart Institute and the University of Missouri, Kansas City. FAU - Fonarow, Gregg C AU - Fonarow GC AD - Division of Cardiology, Department of Medicine, Ronald Reagan-UCLA (University of California, Los Angeles) Medical Center, Los Angeles. FAU - Ramsey, Kathryn Moynihan AU - Ramsey KM AD - Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Nohria, Anju AU - Nohria A AD - Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts. FAU - Butler, Javed AU - Butler J AD - Department of Cardiovascular Medicine, Baylor Scott and White Research Institute, Dallas, Texas. AD - Department of Cardiovascular Medicine, University of Mississippi, Jackson. FAU - Ganatra, Sarju AU - Ganatra S AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.26336 MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Retrospective Studies MH - *Diabetic Retinopathy/epidemiology/chemically induced MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced PMC - PMC12340654 COIS- Conflict of Interest Disclosures: Dr D.J. Ramsey reported receiving personal fees from Regeneron Pharmaceuticals and Beaver-Visitec International Inc outside the submitted work. Dr Kosiborod reported receiving institutional support from grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; personal fees from AstraZeneca, Boehringer Ingelheim, Pfizer, 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, Bayer, Corcept Therapeutics, Cytokinetics, Dexom, Eli Lilly, Esperion Therapeutics, Imbria Therapeutics, Janssen, Lexicon Pharmaceuticals, Merck, NoroNordisk, Pharmacosmos, Regeneron Pharmaceuticals, Roche, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; stock options held in Artera Health and Saghmos Therapeutics; and salary from AstraZeneca Research and Development outside the submitted work. Dr Fonarow reported receiving personal fees from Abbot, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer outside the submitted work. Dr Nohria reported receiving personal fees from AstraZeneca and Takeda Oncology and grants from Bristol Myers Squibb outside the submitted work. Dr Butler reported receiving personal fees from Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Faraday, Idorsia, Impulse Dynamics, Imbria, Innolife, Intellia, Inventiva, Levator, Lexicon, Eli Lilly, Mankind, Medtronic, Merck, New Amsterdam, Novartis, NovoNordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron Pharmaceuticals, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, scPharmaceuticals, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromic, Vera, and Zoll outside the submitted work. No other disclosures were reported. EDAT- 2025/08/11 12:33 MHDA- 2025/08/11 12:34 PMCR- 2025/08/11 CRDT- 2025/08/11 11:42 PHST- 2025/08/11 12:34 [medline] PHST- 2025/08/11 12:33 [pubmed] PHST- 2025/08/11 11:42 [entrez] PHST- 2025/08/11 00:00 [pmc-release] AID - 2837378 [pii] AID - zoi250740 [pii] AID - 10.1001/jamanetworkopen.2025.26321 [doi] PST - epublish SO - JAMA Netw Open. 2025 Aug 1;8(8):e2526321. doi: 10.1001/jamanetworkopen.2025.26321. PMID- 40788646 OWN - NLM STAT- MEDLINE DCOM- 20250811 LR - 20260717 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 8 DP - 2025 Aug 1 TI - Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes. PG - e2526327 LID - 10.1001/jamanetworkopen.2025.26327 [doi] LID - e2526327 AB - IMPORTANCE: Semaglutide and tirzepatide, the new generation of glucagon-like peptide-1 receptor agonist used to treat type 2 diabetes and obesity, were recently reported to be associated with increased risk of nonarteritic anterior ischemic optic neuropathy (NAION). However, reported associations were inconsistent, and it remains unknown if semaglutide or tirzepatide is associated with other disorders of the optic nerve and visual pathways. OBJECTIVE: To examine associations of treatment with either semaglutide or tirzepatide with first-time diagnoses of optic nerve and visual pathway disorders in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study emulated target trials based on a nationwide, population-based database of US patient electronic health records from December 2017 to January 2023. Models were adjusted by propensity score matching. Eligible patients had type 2 diabetes and no prior diagnosis of eye disorders and were prescribed semaglutide, tirzepatide, or other antidiabetic medications. EXPOSURES: Prescription of semaglutide or tirzepatide vs other antidiabetic medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other glucagon-like peptide 1 receptor agonists). MAIN OUTCOMES AND MEASURES: First-time diagnoses of NAION and other optic nerve disorders during a 2-year follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: After propensity score matching among 1 511 637 eligible patients, the study population comprised 159 398 matched patients with type 2 diabetes (mean [SD] age, 56.5 [13.3] years; 83 123 women [52.15%]), including 79 699 patients in the semaglutide or tirzepatide group and 79 699 patients in the comparison group. During the 2-year follow-up, there were 35 patients (0.04%) with NAION in the semaglutide or tirzepatide group and 19 patients (0.02%) with NAION in the matched comparison group (hazard ratio, 1.76 [95% CI, 1.01-3.07]). There were 93 patients (0.12%) with other optic nerve disorders in the semaglutide or tirzepatide group and 54 patients (0.07%) with other optic nerve disorders in the matched comparison group (hazard ratio, 1.65 [95% CI, 1.18-2.31]). No association was found with other disorders of the optic nerve or visual pathways. CONCLUSIONS AND RELEVANCE: In this study of patients with type 2 diabetes who had no prior eye disorders, patients prescribed semaglutide or tirzepatide had an increased risk of NAION and other optic nerve disorders, although the overall risk was low. These findings highlight the need for close monitoring of these conditions. FAU - Wang, Lindsey AU - Wang L AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, North Bethesda, Maryland. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, MetroHealth System, Cleveland, Ohio. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.26336 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Cohort Studies MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12340659 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/08/11 12:33 MHDA- 2025/08/11 12:34 PMCR- 2025/08/11 CRDT- 2025/08/11 11:42 PHST- 2025/08/11 12:34 [medline] PHST- 2025/08/11 12:33 [pubmed] PHST- 2025/08/11 11:42 [entrez] PHST- 2025/08/11 00:00 [pmc-release] AID - 2837377 [pii] AID - zoi250741 [pii] AID - 10.1001/jamanetworkopen.2025.26327 [doi] PST - epublish SO - JAMA Netw Open. 2025 Aug 1;8(8):e2526327. doi: 10.1001/jamanetworkopen.2025.26327. PMID- 40788386 OWN - NLM STAT- MEDLINE DCOM- 20251009 LR - 20261009 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 81 IP - 11 DP - 2025 Nov TI - The correlation between novel antidiabetic agents utilization and hepatocellular carcinoma incidence in type 2 diabetes patients: a network meta-analysis. PG - 1643-1658 LID - 10.1007/s00228-025-03899-3 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of hepatocellular carcinoma (HCC). Research on the hepatoprotective effects of antidiabetic agents is ongoing. This study aimed to investigate the correlation between novel antidiabetic agents and HCC incidence in T2D patients through a network meta-analysis. METHODS: The study followed a predefined PROSPERO-registered protocol (CRD420251068833) and reported results per the PRISMA extension for network meta-analysis. Databases such as PubMed, Web of Science, Cochrane Library, Embase, and Medline were searched from their inception to June 6, 2025. Eligible studies involved patients aged >/= 18 with T2D, covering various antidiabetic drugs. Data extraction used standardized tables, with primary and secondary outcomes including HCC incidence, hepatic cirrhosis, hepatic metabolic dysfunction, and all-cause mortality. RESULTS: A total of 5,018 citations were retrieved, with 28 cohort studies involving 18,212,739 participants meeting the inclusion criteria. No inconsistency was found among outcome studies. SGLT-2 inhibitors (SGLT-2i) were most effective in reducing HCC incidence. In secondary outcome analysis, SGLT-2i and Glucagon-like peptide-1 receptor agonist (GLP-1 RA) were most effective for reducing hepatic cirrhosis incidence. For hepatic metabolic dysfunction, SGLT-2i, GLP-1 RA, and DPP4i ranked from most to least effective. For all-cause mortality, GLP-1 RA ranked highest. No publication bias was detected. CONCLUSION: This network meta-analysis indicates that SGLT-2i and GLP-1 RA may be preferred for T2D patients to reduce HCC incidence and other hepatic-related outcomes. Further research is needed to confirm these findings and explore the underlying mechanisms. SYSTEMATIC REVIEW REGISTRATION: CRD420251068833. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Lin, Junjie AU - Lin J AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Ren, Tianshu AU - Ren T AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Zhao, Qingchun AU - Zhao Q AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Tong, Qiang AU - Tong Q AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Liu, Jiahui AU - Liu J AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Kang, Ye AU - Kang Y AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. FAU - Yuan, Yuan AU - Yuan Y AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China. yuanyuan19871207@163.com. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250811 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - Eur J Clin Pharmacol. 2026 Jun 17;82(7):176. doi: 10.1007/s00228-026-04107-6. PMID: 42303900 MH - Humans MH - *Carcinoma, Hepatocellular/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - *Liver Neoplasms/epidemiology/prevention & control MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use OTO - NOTNLM OT - DPP4 inhibitors OT - GLP-1 receptor agonist OT - Hepatocellular Carcinoma OT - SGLT-2 inhibitors OT - Type 2 Diabetes COIS- Declarations. Competing interests: The authors declare no competing interests. Human ethics and consent to participate declarations: Not applicable. EDAT- 2025/08/11 12:32 MHDA- 2025/10/09 12:30 CRDT- 2025/08/11 11:12 PHST- 2025/06/18 00:00 [received] PHST- 2025/08/03 00:00 [accepted] PHST- 2025/10/09 12:30 [medline] PHST- 2025/08/11 12:32 [pubmed] PHST- 2025/08/11 11:12 [entrez] AID - 10.1007/s00228-025-03899-3 [pii] AID - 10.1007/s00228-025-03899-3 [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2025 Nov;81(11):1643-1658. doi: 10.1007/s00228-025-03899-3. Epub 2025 Aug 11. PMID- 40788007 OWN - NLM STAT- MEDLINE DCOM- 20251212 LR - 20260130 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 111 IP - 12 DP - 2025 Dec 1 TI - Association of semaglutide use with outcomes in chronic plantar heel pain: a prospective observational cohort and a pilot interventional study. PG - 9333-9341 LID - 10.1097/JS9.0000000000003156 [doi] AB - BACKGROUND: Whether patients with chronic plantar heel pain (PHP) can benefit from glucagon-like peptide-1 receptor agonists (GLP1-RAs) remained unclear. METHODS: This study included a prospective observational cohort and a pilot interventional component. In the observational arm, more than 3000 adults with chronic PHP (duration of symptoms >6 months) were recruited with at least 2-year follow-up from two medical centers. The primary endpoint was the change from baseline of Foot Health Status Questionnaire (FHSQ) pain subdomain at the last follow-up. Secondary endpoints included first-step pain, FHSQ function subdomain, the amount of NSAIDs consumption, number of injection therapies/extracorporeal shockwave therapy (ESWT) sessions/manual stretching, days of orthosis wearing and thickness of plantar fascia. As supporting evidence, a pilot interventional study was conducted in 30 patients with chronic PHP who received semaglutide, with outcomes assessed over 12 months using before-and-after evaluations of pain, function, and imaging. RESULTS: In the prospective observational cohort, 92 out of 2902 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss in the final analysis were identified. Change from baseline in FHSQ pain subdomain was significantly higher in semaglutide group compared with control group (adjusted mean difference, 14.86 [95% CI, 9.97 to 19.75], P < 0.001), favoring semaglutide. Similar results were observed from the analysis of FHSQ function subdomain, first-step pain and several therapeutic interventions (oral and topical NSAIDs, corticosteroid injection and orthosis wearing). For structural alterations, plantar fascia thickening velocity was significantly lower in the semaglutide group when compared with control group (-0.25 mm/year [-0.41 to -0.09], P = 0.002). For interventional use of semaglutide, improvements in all measured outcomes (FHSQ pain/function subscales, first-step pain and thickness of plantar fascia) were observed with all P values less than 0.001. In the interventional substudy, mean FHSQ pain scores improved from 28.09 +/- 10.34 at baseline to 60.28 +/- 21.34 at follow-up ( P < 0.001). FHSQ function subdomain scores increased from 27.23 +/- 17.44 to 80.71 +/- 19.55 ( P < 0.001). CONCLUSIONS: Semaglutide might be a potential therapeutic candidate for chronic PHP patients by improving patient-reported outcomes and plantar fascia thickening. Further randomized trial is warranted by our study to further evaluate the therapeutic effects of GLP-1RAs on chronic PHP. CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Yang, Fan AU - Yang F AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhou, Lenian AU - Zhou L AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhang, Jieyuan AU - Zhang J AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wang, Qiuke AU - Wang Q AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Cai, Qianying AU - Cai Q AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wang, Jiazheng AU - Wang J AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wu, Chenglin AU - Wu C AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Li, Xueqian AU - Li X AD - Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China. FAU - Zhang, Jinshan AU - Zhang J AD - Department of Orthopaedics, Jinjiang Municipal Hospital, Fujian, People's Republic of China. FAU - Zheng, Yongqiang AU - Zheng Y AD - Department of Orthopaedics, Jinjiang Municipal Hospital, Fujian, People's Republic of China. FAU - Ma, Xin AU - Ma X AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhu, Hongyi AU - Zhu H AUID- ORCID: 0000-0001-9643-0790 AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Shi, Zhongmin AU - Shi Z AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. LA - eng PT - Journal Article PT - Observational Study DEP - 20250808 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Pilot Projects MH - Male MH - Middle Aged MH - Prospective Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Aged MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Chronic Pain/drug therapy/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Fasciitis, Plantar/drug therapy MH - Heel MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Pain Measurement MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12695207 OTO - NOTNLM OT - GLP1-RA OT - obesity OT - plantar fasciitis OT - plantar heel pain OT - semaglutide OT - weight loss COIS- Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. The authors declare no competing interests. EDAT- 2025/08/11 12:33 MHDA- 2025/12/12 07:20 PMCR- 2025/12/10 CRDT- 2025/08/11 09:03 PHST- 2025/04/24 00:00 [received] PHST- 2025/07/20 00:00 [accepted] PHST- 2025/12/12 07:20 [medline] PHST- 2025/08/11 12:33 [pubmed] PHST- 2025/08/11 09:03 [entrez] PHST- 2025/12/10 00:00 [pmc-release] AID - 01279778-202512000-00044 [pii] AID - IJS-D-25-01986 [pii] AID - 10.1097/JS9.0000000000003156 [doi] PST - ppublish SO - Int J Surg. 2025 Dec 1;111(12):9333-9341. doi: 10.1097/JS9.0000000000003156. Epub 2025 Aug 8. PMID- 40787019 OWN - NLM STAT- MEDLINE DCOM- 20250811 LR - 20260127 IS - 0026-6620 (Print) IS - 0026-6620 (Linking) VI - 122 IP - 4 DP - 2025 Jul-Aug TI - Injections vs. Scalpels: Where Do Surgery and GLP-1's Align in Modern Obesity treatment? PG - 340-344 AB - Recent advancements in pharmacologic treatment of obesity and metabolic disease with nutrient-stimulated hormones (NuSH), particularly Semaglutide and Tirzepatide, have been revolutionary, showing weight reduction results comparable to some surgical options. This is especially promising as, despite the proven efficacy and safety of metabolic/bariatric surgery (MBS), its utilization has remained quite limited. This review article discusses the current literature on the comparative effectiveness of these two treatments and their impact on comorbidities such as type 2 diabetes mellitus (DM2) and cardiovascular disease. While weight reduction with these NewSH's (sic) appears similar to a sleeve gastrectomy, though significantly less than gastric bypass, MBS remains the gold standard treatment for patients with more severe obesity especially those with higher cardiometabolic disease burden. CI - Copyright 2025 by the Missouri State Medical Association. FAU - Lindquist, Matthew AU - Lindquist M AD - Owner and Founder of MoKan Weight Loss and Metabolic Health LLC, Prairie Village, Kansas, Missouri, USA. FAU - Varghese, Esther AU - Varghese E AD - Internal Medicine Resident at Thomas Hospital, Fairhope, Alabama, USA. FAU - Bassham, Cooper AU - Bassham C AD - Medical Student at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Mo Med JT - Missouri medicine JID - 0400744 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/surgery/drug therapy/therapy MH - *Bariatric Surgery/methods MH - *Glucagon-Like Peptide 1/therapeutic use/administration & dosage MH - Diabetes Mellitus, Type 2 MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Injections MH - Semaglutide PMC - PMC12331298 COIS- Disclosure: This manuscript is based on a lecture presented April 5, 2024, at the 2024 Missouri State Medical Association Annual Convention in St. Louis, Missouri. ML is a member of the Obesity Speaker's Bureau for Novo Nordisk and Eli Lilly. Artificial intelligence, language models, machine learning, or similar technologies were not used in the conceptualization, study, research, preparation, or writing of this manuscript. EDAT- 2025/08/11 17:20 MHDA- 2025/08/11 17:21 PMCR- 2025/07/01 CRDT- 2025/08/11 06:24 PHST- 2025/08/11 17:21 [medline] PHST- 2025/08/11 17:20 [pubmed] PHST- 2025/08/11 06:24 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - ms122_p0340 [pii] PST - ppublish SO - Mo Med. 2025 Jul-Aug;122(4):340-344. PMID- 40785519 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Effectiveness of GLP-1RA according to different type 2 diabetes phenotypes: A retrospective study. PG - 6210-6219 LID - 10.1111/dom.70005 [doi] AB - AIMS: Type 2 diabetes (T2D) is a heterogeneous disease, with varying pathogenetic mechanisms influencing treatment response. Glucagon-like peptide-1 receptor agonists (GLP-1RA) offer clear metabolic benefits in T2D, but interindividual variability in response is observed. This retrospective study investigated whether GLP-1RA effectiveness varies by T2D phenotypes (severe insulin-deficient diabetes [SIDD], severe insulin-resistant diabetes [SIRD], mild obesity-related diabetes [MOD], mild age-related diabetes [MARD]) and assessed predictors of HbA1c reduction. MATERIALS AND METHODS: Individuals attending the Endocrinology Unit at the University Hospital Policlinico Consorziale in Bari, Italy, between 01 January 2014, and 31 August 2024, were evaluated for participation. T2D phenotypes were assigned using the algorithm by Bello-Chavolla. The primary outcome was the difference in HbA1c change from baseline among phenotypes, and predictors were identified using SHAP and multivariable regression. Time to treatment failure (HbA1c >7.0%) was estimated with Kaplan-Meier analysis. RESULTS: Among 181 patients, SIDD individuals yielded a significantly greater HbA1c reduction (-2.6%[1.9]) versus other phenotypes (p < 0.0001). Baseline HbA1c was the strongest predictor of HbA1c reduction. SIDD was linked to faster treatment failure (HR 3.69, 95% CI 1.37-9.94;p < 0.01), but this effect disappeared after adjustment for baseline HbA1c. CONCLUSION: This study adds to the emerging evidence against the hard clustering approach to T2D phenotyping in terms of response to treatment and time to treatment failure, particularly with GLP-1RA. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Caruso, Irene AU - Caruso I AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Giordano, Fiorella AU - Giordano F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Matichecchia, Immacolata Ilaria AU - Matichecchia II AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Di Gioia, Ludovico AU - Di Gioia L AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Di Molfetta, Sergio AU - Di Molfetta S AUID- ORCID: 0000-0003-3454-7330 AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Cignarelli, Angelo AU - Cignarelli A AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Sorice, Gian Pio AU - Sorice GP AUID- ORCID: 0000-0001-9489-1534 AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Natalicchio, Annalisa AU - Natalicchio A AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Laviola, Luigi AU - Laviola L AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Giorgino, Francesco AU - Giorgino F AUID- ORCID: 0000-0001-7372-2678 AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. LA - eng GR - DM 1557 11.10.2022/NextGenerationEU/ PT - Journal Article DEP - 20250811 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Female MH - Male MH - Phenotype MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Treatment Outcome MH - Italy/epidemiology MH - Blood Glucose PMC - PMC12515759 OTO - NOTNLM OT - GLP-1 receptor agonists OT - phenotypes OT - type 2 diabetes COIS- Angelo Cignarelli has received speakers honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, Roche Diagnostics and Sanofi. Fiorella Giordano received speakers honoraria from Eli Lilly and Novo Nordisk. Francesco Giorgino has been on advisory boards, received consulting fees or speaker honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Lifescan, Medimmune, Merck Sharp & Dohme, Medtronic, Novo Nordisk, Roche Diabetes Care, Sanofi. Gian Pio Sorice has been on advisory boards, received consulting fees or speaker honoraria from Amgen, Amryt Pharma, Eli Lilly, Farmitalia, Novo Nordisk, Sanofi; Irene Caruso has received speaker fees or travel grants from Abbott, Guidotti SpA, Eli Lilly; Ludovico Di Gioia has been on advisory boards, received consulting fees or speaker honoraria from Abbott, Eli Lilly, Lusofarmaco, MOVI SpA, Novo Nordisk, Roche Diabetes Care, Sanofi, Theras. Luigi Laviola has been on advisory boards, received consulting fees or speaker honoraria from Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck Sharp & Dohme, Medtronic, Menarini, MOVI SpA, Mundipharma, Novo Nordisk, Roche Diabetes Care, Sanofi, Terumo. Sergio Di Molfetta has received speaker fees from Ascensia Diabetes Care, MOVI SpA, Roche Diabetes Care. EDAT- 2025/08/11 06:27 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/08/11 04:49 PHST- 2025/07/16 00:00 [revised] PHST- 2025/03/02 00:00 [received] PHST- 2025/07/26 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/11 06:27 [pubmed] PHST- 2025/08/11 04:49 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70005 [pii] AID - 10.1111/dom.70005 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6210-6219. doi: 10.1111/dom.70005. Epub 2025 Aug 11. PMID- 40784425 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20260711 IS - 1532-8406 (Electronic) IS - 0883-5403 (Linking) VI - 40 IP - 12 DP - 2025 Dec TI - As Few as Three Months of Preoperative Semaglutide Exposure Prior to Total Knee Arthroplasty Is Associated With Reduced Postoperative Adverse Events in Patients Who Have Type II Diabetes. PG - 3089-3096.e1 LID - S0883-5403(25)01008-3 [pii] LID - 10.1016/j.arth.2025.08.003 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been increasingly used for the management of type II diabetes mellitus (T2DM). Although recent literature suggests semaglutide may reduce postoperative total knee arthroplasty (TKA) complications, to our knowledge, the minimum duration of semaglutide exposure associated with superior outcomes has never been studied. METHODS: A retrospective cohort of patients with T2DM was identified from a national database and stratified into one of five mutually exclusive groups of semaglutide exposure before TKA: six to 12 months, three to six months, two to three months, one to two months, or less than one month. Each cohort was individually matched 1:4 with non-semaglutide T2DM TKA controls. The occurrence of 90-day severe adverse events including surgical site infection, sepsis, venous thromboembolism, cardiac events, pancreatitis, and minor adverse events (MAEs) including wound dehiscence, hematoma, transfusion, acute kidney injury, pneumonia, and urinary tract infection, was compared using multivariable logistic regression. RESULTS: After matching, patient cohorts with preoperative semaglutide exposure for six to 12 months, three to six months, two to three months, one to two months, and less than one month included 745, 451, 210, 113, and 91, respectively. Patients initiating semaglutide less than one month before TKA revealed lower odds of MAE (odds ratio 0.16, P < 0.001), with consistent reduction in MAE across all increased exposure durations (P < 0.001 for all). Reduced odds of severe adverse events were significant after a minimum of two to three months of preoperative exposure (odds ratio 0.25, P < 0.001). CONCLUSIONS: A 3-month period of preoperative semaglutide exposure before TKA appears to be sufficient to reduce both minor and severe postoperative adverse events. Although these observational findings cannot establish causation, they have major clinical implications and lay the foundation for prospective analysis aimed at optimizing preoperative care pathways. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Vasudevan, Rajiv S AU - Vasudevan RS AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Ansah-Twum, Jeremy K AU - Ansah-Twum JK AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Rubin, Lee E AU - Rubin LE AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250808 PL - United States TA - J Arthroplasty JT - The Journal of arthroplasty JID - 8703515 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Knee/adverse effects MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Retrospective Studies MH - Middle Aged MH - *Postoperative Complications/prevention & control/epidemiology/etiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Time Factors MH - Preoperative Care/methods MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - glucagon-like peptide-1 OT - preoperative optimization OT - semaglutide OT - total knee arthroplasty OT - type II diabetes EDAT- 2025/08/11 00:26 MHDA- 2025/11/20 00:30 CRDT- 2025/08/10 19:33 PHST- 2025/04/10 00:00 [received] PHST- 2025/08/01 00:00 [revised] PHST- 2025/08/03 00:00 [accepted] PHST- 2025/11/20 00:30 [medline] PHST- 2025/08/11 00:26 [pubmed] PHST- 2025/08/10 19:33 [entrez] AID - S0883-5403(25)01008-3 [pii] AID - 10.1016/j.arth.2025.08.003 [doi] PST - ppublish SO - J Arthroplasty. 2025 Dec;40(12):3089-3096.e1. doi: 10.1016/j.arth.2025.08.003. Epub 2025 Aug 8. PMID- 40783459 OWN - NLM STAT- MEDLINE DCOM- 20260216 LR - 20261009 IS - 1573-2568 (Electronic) IS - 0163-2116 (Linking) VI - 71 IP - 1 DP - 2026 Jan TI - Aspiration Risk During Endoscopic Procedures While on GLP-1 Agonist Therapy. PG - 211-220 LID - 10.1007/s10620-025-09307-1 [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) are increasingly prescribed for Type 2 diabetes and weight management. Given their effect on gastric emptying, concerns have emerged regarding aspiration risk during endoscopic procedures. While aspiration risk is recognized during esophagogastroduodenoscopy (EGD), data on GLP-1RA users-particularly those undergoing colonoscopy-are limited. This study evaluated aspiration risk in patients undergoing EGD versus colonoscopy while on GLP-1RA therapy. METHODS: We performed a retrospective cohort study of adult patients (18-70 years) who underwent EGD or colonoscopy at Baylor Scott & White Medical Center Temple from July 2017 to July 2024. Patients were stratified by GLP-1RA use. The primary outcome was aspiration-related diagnosis within 30 days, identified via ICD-10 codes. Chi-square testing and logistic regression were used to assess associations. RESULTS: Among 13,523 patients (7431 EGD; 6092 colonoscopy), 713 (5.3%) were GLP-1RA users. Aspiration events were more frequent following EGD than colonoscopy (adjusted OR = 2.36, P = 0.0200). No aspiration events occurred in GLP-1RA users. Multivariable analysis identified Black race as independently associated with increased aspiration risk (adjusted OR = 2.77, P = 0.0061), while higher BMI was associated with lower aspiration risk. GLP-1RA users had higher BMI and more frequent diabetes and gastroparesis, but no independent association with aspiration risk was observed. CONCLUSION: Aspiration risk was significantly higher with EGD than colonoscopy, but GLP-1RA use did not increase aspiration risk for either procedure. These findings suggest that routine GLP-1RA use may not be associated with increased aspiration risk in the outpatient setting. Prospective studies are needed to guide risk-based peri-procedural management. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Stryelkina, Maryana AU - Stryelkina M AD - Division of Internal Medicine, Department of Medicine, Baylor Scott & White Medical Center, Temple, TX, 76508, USA. FAU - Molina, Robert AU - Molina R AD - Division of Internal Medicine, Department of Medicine, Baylor Scott & White Medical Center, Temple, TX, 76508, USA. FAU - Janice, Thomas AU - Janice T AD - Division of Internal Medicine, Department of Medicine, Baylor Scott & White Medical Center, Temple, TX, 76508, USA. FAU - Ancha, Anupama AU - Ancha A AD - Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, 2401 S. 31st Street, Temple, TX, 76508, USA. FAU - Bejcek, Justin AU - Bejcek J AD - Department of Medical Education, Edward Via College of Osteopathic Medicine, Monroe, LA, 71203, USA. FAU - Ian, Fladie AU - Ian F AD - Division of Internal Medicine, Department of Medicine, Baylor Scott & White Medical Center, Temple, TX, 76508, USA. FAU - Mullarkey, Michael AU - Mullarkey M AD - Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, 2401 S. 31st Street, Temple, TX, 76508, USA. FAU - Johnson, Christopher AU - Johnson C AD - Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, 2401 S. 31st Street, Temple, TX, 76508, USA. Christopher.Johnson@BSWHealth.org. AD - School of Medicine, Baylor College of Medicine, Temple, TX, 76508, USA. Christopher.Johnson@BSWHealth.org. LA - eng PT - Journal Article DEP - 20250809 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Middle Aged MH - Female MH - Retrospective Studies MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Colonoscopy/adverse effects MH - *Endoscopy, Digestive System/adverse effects MH - Young Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Adolescent MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - *Respiratory Aspiration/epidemiology/etiology OTO - NOTNLM OT - Aspiration pneumonia OT - Colonoscopy OT - Delayed gastric emptying OT - EGD OT - GLP-1 receptor agonists COIS- Declarations. Conflict of interest: The authors declare no competing interests. Ethical Approval: Due to the retrospective nature of the study and use of anonymized data, the Baylor Scott & White Institutional Review Board committee approved a waiver of informed consent. Consent for Publication: Not applicable. EDAT- 2025/08/10 06:16 MHDA- 2026/02/16 12:30 CRDT- 2025/08/09 23:21 PHST- 2025/06/23 00:00 [received] PHST- 2025/07/29 00:00 [accepted] PHST- 2026/02/16 12:30 [medline] PHST- 2025/08/10 06:16 [pubmed] PHST- 2025/08/09 23:21 [entrez] AID - 10.1007/s10620-025-09307-1 [pii] AID - 10.1007/s10620-025-09307-1 [doi] PST - ppublish SO - Dig Dis Sci. 2026 Jan;71(1):211-220. doi: 10.1007/s10620-025-09307-1. Epub 2025 Aug 9. PMID- 40782670 OWN - NLM STAT- MEDLINE DCOM- 20250809 LR - 20260608 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 6 IP - 8 DP - 2025 Aug 8 TI - SOUL searching in GLP-1 therapy: Oral semaglutide confirms cardioprotection in type 2 diabetes. PG - 100774 LID - S2666-6340(25)00201-6 [pii] LID - 10.1016/j.medj.2025.100774 [doi] AB - Semaglutide's evolution from weekly injections to an SNAC-enabled tablet preserved its metabolic and cardiovascular efficacy. Large injectable CVOTs have demonstrated robust cardioprotection, and the SOUL trial now shows a 14% reduction in major adverse cardiovascular events with the oral formulation.(1) These data confirm formulation-independent benefit, positioning oral semaglutide as the only cardioprotective, non-injectable, GLP-1RA for high-risk type 2 diabetes. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Schwarz, Christine Rode AU - Schwarz CR AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. Electronic address: christine.rode.schwarz@regionh.dk. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Cardiotonic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Humans MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Cardiotonic Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests C.R.S. has served as a consultant to and/or received research support from Eli Lilly and Novo Nordisk. T.V. has served on scientific advisory panels, been part of speaker's bureaus, and served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Regor, Roche, Sanofi, Sun Pharmaceuticals, and Zealand Pharma. EDAT- 2025/08/10 06:16 MHDA- 2025/08/10 06:17 CRDT- 2025/08/09 18:17 PHST- 2025/06/17 00:00 [received] PHST- 2025/06/18 00:00 [revised] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/08/10 06:17 [medline] PHST- 2025/08/10 06:16 [pubmed] PHST- 2025/08/09 18:17 [entrez] AID - S2666-6340(25)00201-6 [pii] AID - 10.1016/j.medj.2025.100774 [doi] PST - ppublish SO - Med. 2025 Aug 8;6(8):100774. doi: 10.1016/j.medj.2025.100774. PMID- 40782266 OWN - NLM STAT- MEDLINE DCOM- 20250809 LR - 20260127 IS - 1432-0827 (Electronic) IS - 0171-967X (Linking) VI - 116 IP - 1 DP - 2025 Aug 9 TI - Effect of Oral Semaglutide on Volumetric BMD and Bone Microarchitecture in Overweight/Obese Individuals with Type 2 Diabetes. PG - 105 LID - 10.1007/s00223-025-01417-2 [doi] AB - Obesity, type 2 diabetes, and therapeutic weight loss are all associated with impaired bone quantity and microarchitecture. Glucagon-like peptide receptor analogs (GLP1RAs) have direct beneficial effects on bone microarchitecture, in preclinical settings. This study aimed to evaluate the net impact of GLP1RA on microarchitecture in overweight/obese type 2 diabetes individuals. It was an interventional, paired-sample cohort study with oral semaglutide in consecutive type 2 diabetes patients with overweight/obesity and metabolic-dysfunction associated steatotic liver disease. Oral semaglutide was initiated at 3 mg daily, with escalation to 14 mg at the end of 12 weeks. Bone turnover markers (P1NP, beta-CTX) were estimated by electrochemiluminescence and body composition by DXA. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed using HRpQCT (XtremeCT II, Scanco Medical). There were 36 patients (44% males) with a mean (+/- SD) age of 50.8 +/- 10.1 years, mean BMI of 34.3 +/- 6.2 kg/m(2) and median duration of diabetes being 7 (IQR 2-13) years. At 52 weeks, there was an increase in tibial total vBMD (317.4 +/- 47.4 vs. 331.6 +/- 52.7 mg HA/cm(3), p = 0.06) and cortical vBMD at both radius and tibia (trend towards significance). Trabecular vBMD and trabecular bone volume fraction at radius were also increased. Males showed significantly increased tibial total and cortical vBMD, and trabecular bone volume fraction, but there was no significant change in females. There were no significant differences in bone microarchitecture based on steatosis or fibrosis reduction. Oral semaglutide improves vBMD in overweight/obese type 2 diabetes, despite a significant reduction in body weight. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Das, Liza AU - Das L AUID- ORCID: 0000-0002-9701-9554 AD - Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. FAU - Bhadada, Sanjay Kumar AU - Bhadada SK AUID- ORCID: 0000-0002-0410-8778 AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. bhadadask@gmail.com. FAU - Arjunan, Durairaj AU - Arjunan D AUID- ORCID: 0000-0001-5110-334X AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. FAU - Duseja, Ajay AU - Duseja A AUID- ORCID: 0000-0003-3590-2664 AD - Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. LA - eng PT - Journal Article DEP - 20250809 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Bone Density/drug effects MH - Middle Aged MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - *Obesity/complications/drug therapy MH - Adult MH - *Overweight/complications/drug therapy MH - *Bone and Bones/drug effects MH - Hypoglycemic Agents/therapeutic use/pharmacology/administration & dosage MH - Administration, Oral MH - Cohort Studies MH - Bone Remodeling/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Bone microarchitecture OT - Glucagon-like peptide receptor analogs OT - HRpQCT OT - MASLD OT - Obesity OT - Semaglutide OT - Weight loss COIS- Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Research Involving Human Participants and/or Animals: The study was approved by the Institutional Ethics Committee (PGIMER IEC) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Informed Consent: Written, informed consent was obtained from all participants. EDAT- 2025/08/09 13:48 MHDA- 2025/08/09 13:49 CRDT- 2025/08/09 11:16 PHST- 2025/04/20 00:00 [received] PHST- 2025/07/22 00:00 [accepted] PHST- 2025/08/09 13:49 [medline] PHST- 2025/08/09 13:48 [pubmed] PHST- 2025/08/09 11:16 [entrez] AID - 10.1007/s00223-025-01417-2 [pii] AID - 10.1007/s00223-025-01417-2 [doi] PST - epublish SO - Calcif Tissue Int. 2025 Aug 9;116(1):105. doi: 10.1007/s00223-025-01417-2. PMID- 40782123 OWN - NLM STAT- MEDLINE DCOM- 20250922 LR - 20260127 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 34 IP - 9 DP - 2025 Sep TI - Tirzepatide for metabolic dysfunction-associated steatohepatitis: results from phase II clinical trials and perspectives. PG - 655-663 LID - 10.1080/13543784.2025.2546812 [doi] AB - INTRODUCTION: Tirzepatide is a once-weekly injectable dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. GIP and GLP-1 are incretins promoting insulin release from pancreatic beta-cells. Results from clinical trials have confirmed that tirzepatide exerts favorable effects on glucose metabolism and insulin resistance, reduces food intake and has been approved for the treatment of adults with type 2 diabetes, and who are overweight/obese or who have weight-related comorbidities. AREAS COVERED: Results from SYNERGY-NASH, a phase 2 study involving patients with biopsy-proven MASH and stage 2 or 3 fibrosis, have shown that tirzepatide achieved MASH resolution with no worsening of fibrosis in a significantly higher percentage of patients than placebo. Additionally, more patients in the tirzepatide group in comparison to placebo achieved a 1-stage or greater fibrosis improvement without worsening of MASH, but the study was not powered to detect this change, and noninvasive biomarkers of fibrosis were not significantly improved. EXPERT OPINION: While these results suggest a potential role for tirzepatide in MASH treatment given its ability to improve insulin sensitivity and reduce food intake, factors already shown to be beneficial in reducing livers steatosis and fibrosis, larger clinical trials are needed. FAU - Fiorucci, Stefano AU - Fiorucci S AD - Department of Medicine and Surgery, Section of Gastroenterology, University of Perugia, Perugia, Italy. FAU - Urbani, Ginevra AU - Urbani G AD - Department of Medicine and Surgery, Section of Gastroenterology, University of Perugia, Perugia, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250825 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - Insulin Resistance MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Clinical Trials, Phase II as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - *Non-alcoholic Fatty Liver Disease/drug therapy/physiopathology/pathology MH - Animals MH - Obesity/complications/drug therapy MH - Hypoglycemic Agents/pharmacology/administration & dosage MH - Adult MH - Gastric Inhibitory Polypeptide MH - Liver Cirrhosis/drug therapy/etiology/pathology MH - Receptors, Gastrointestinal Hormone OTO - NOTNLM OT - Dual incretin agonist OT - Glucagon-like peptide (GLP)-1 OT - Glucose-dependent insulinotropic polypeptide (GIP) OT - Liver fibrosis OT - Liver steatohepatitis OT - Obesity OT - Type 2 diabetes EDAT- 2025/08/09 13:48 MHDA- 2025/09/22 06:31 CRDT- 2025/08/09 10:53 PHST- 2025/09/22 06:31 [medline] PHST- 2025/08/09 13:48 [pubmed] PHST- 2025/08/09 10:53 [entrez] AID - 10.1080/13543784.2025.2546812 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2025 Sep;34(9):655-663. doi: 10.1080/13543784.2025.2546812. Epub 2025 Aug 25. PMID- 40780839 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20250813 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 4 DP - 2025 Aug 7 TI - Association between dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and COVID-19 infection and adverse outcomes: a cohort study. LID - 10.1136/bmjdrc-2024-004677 [doi] LID - e004677 AB - INTRODUCTION: People with type 2 diabetes (T2DM) have an elevated risk of adverse outcomes from COVID-19. Dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 receptor agonists (GLP1RAs) might have favorable effects on COVID-19 outcomes. RESEARCH DESIGN AND METHODS: We conducted a population-based cohort study in Ontario, Canada. We compared the risk of both COVID-19 infection as well as adverse outcomes between users of DPP4i or GLP1RA and users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or sulfonylureas (SUs). The study population was persons >/=66 years with T2DM taking metformin who had >/=1 COVID-19 PCR test between January 2020 and July 2021. We compared (1) COVID-19 infection and (2) adverse outcomes at 30 days among COVID-19 positive patients (major cardiovascular (CV) events, hospitalizations, intensive care unit admission, all-cause mortality, venous thromboembolism, mechanical ventilation). We reported weighted risk differences (RDs) and relative risks (RRs). RESULTS: There were 26,485 DPP4i/GLP1RA users (mean age 76, 47% female, 91% DPP4i users) and 14,487 SGLT2i/SU users (mean age 75, 39% female, 65% SGLT2i users). The weighted rate of COVID-19 infection in DPP4i/GLP1RA users was 10.3% compared with 10.4% among SGLT2i/SU users (weighted RD -0.06, 95% CI -0.79 to 0.66; RR 0.99, 95% CI 0.93 to 1.07). Among COVID-19 positive patients, the weighted RD for all-cause hospitalization for DPP4i/GLP1RA users versus SGLT2i/SU users was -6.72% (95% CI -3.02 to -10.4) and the adjusted weighted RR was 0.79 (95% CI 0.70 to 0.89). For major CV events, the weighted RD was -1.91% (95% CI -4.00 to 0.18) and RR 0.73 (95% CI 0.54 to 1.00). CONCLUSIONS: DPP4i/GLP1RA use was not associated with reduced risk of COVID-19 infection compared with SGLT2i/SU use. DPP4i/GLP1RA use was associated with reduced risk of 30-day hospitalization among COVID-19 positive older adults and a possible trend towards a lower associated risk of CV events. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Thompson, Wade AU - Thompson W AUID- ORCID: 0000-0002-8268-4092 AD - Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada. AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Women's College Research Institute, Toronto, Ontario, Canada. FAU - Yu, Bing AU - Yu B AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. FAU - Porter, Joan AU - Porter J AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. FAU - Fang, Jiming AU - Fang J AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. FAU - Ferreira-Legere, Laura E AU - Ferreira-Legere LE AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. FAU - Austin, Peter C AU - Austin PC AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Sunnybrook Research Institute, Toronto, Ontario, Canada. FAU - Jackevicius, Cynthia A AU - Jackevicius CA AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Western University of Health Sciences, Pomona, California, USA. FAU - Ross, Heather AU - Ross H AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. AD - Toronto General Hospital Research Institute, Toronto, Ontario, Canada. FAU - Lee, Douglas S AU - Lee DS AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Weisman, Alanna AU - Weisman A AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Farkouh, Michael E AU - Farkouh ME AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. AD - Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada. FAU - Gershon, Andrea S AU - Gershon AS AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Sunnybrook Research Institute, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Atzema, Clare L AU - Atzema CL AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Sunnybrook Research Institute, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Kwong, Jeffrey C AU - Kwong JC AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. AD - Department of Family & Community Medicine and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. AD - Public Health Ontario, Toronto, Ontario, Canada. AD - Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, Ontario, Canada. AD - University Health Network, Toronto, Ontario, Canada. FAU - Ha, Andrew AU - Ha A AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. AD - Toronto General Hospital Research Institute, Toronto, Ontario, Canada. FAU - Dzavik, Vladimir AU - Dzavik V AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. FAU - Udell, Jacob A AU - Udell JA AD - Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada jay.udell@utoronto.ca. AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. AD - Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. AD - Department of Medicine, Women's College Hospital, Toronto, Ontario, Canada. LA - eng PT - Journal Article DEP - 20250807 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *COVID-19/epidemiology/complications/mortality MH - Female MH - Male MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - SARS-CoV-2 MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Cohort Studies MH - Ontario/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Hospitalization/statistics & numerical data MH - Aged, 80 and over MH - Sulfonylurea Compounds/therapeutic use PMC - PMC12336545 OTO - NOTNLM OT - COVID-19 OT - Diabetes Mellitus, Type 2 OT - Pharmacoepidemiology COIS- Competing interests: JU has received speaker/consulting honoraria from Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis, Sanofi, and grant support to his institutions from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Novartis, Sanofi. DSL is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. MEF is the Peter Munk Chair in Multinational Clinical Trials at Peter Munk Cardiac Centre, University Health Network, University of Toronto. VD has received research grants from AstraZeneca. EDAT- 2025/08/09 13:49 MHDA- 2025/08/09 13:50 PMCR- 2025/08/07 CRDT- 2025/08/08 21:13 PHST- 2024/10/16 00:00 [received] PHST- 2025/06/26 00:00 [accepted] PHST- 2025/08/09 13:50 [medline] PHST- 2025/08/09 13:49 [pubmed] PHST- 2025/08/08 21:13 [entrez] PHST- 2025/08/07 00:00 [pmc-release] AID - 13/4/e004677 [pii] AID - bmjdrc-2024-004677 [pii] AID - 10.1136/bmjdrc-2024-004677 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Aug 7;13(4):e004677. doi: 10.1136/bmjdrc-2024-004677. PMID- 40779264 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20260717 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 8 DP - 2025 Aug 1 TI - Changes in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide. PG - e2526013 LID - 10.1001/jamanetworkopen.2025.26013 [doi] LID - e2526013 AB - IMPORTANCE: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored. OBJECTIVE: To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 23 522 adults (>/=18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System. EXPOSURE: The first prescription of semaglutide identified at the ingredient level, stratified by type 2 diabetes status. MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in weight (% baseline), blood pressure (BP), total cholesterol, and hemoglobin A1c. Secondary outcomes assessed health care expenditures using Medicare-based cost estimates. A staggered difference-in-differences design compared outcomes of patients after the first semaglutide prescription with those of patients who had not yet received their prescription during the same period. RESULTS: The study cohort included 23 522 patients (mean [SD] age at initiation of semaglutide, 56.2 [12.9] years; 66.7% female; 68.6% with diabetes). In the overall cohort, initiation of semaglutide was significantly associated with a -3.8% (95% CI, -3.9% to -3.7%) reduction in weight at 13 to 24 months, with a -5.1% (95% CI, -5.5% to -4.7%) reduction in weight among patients without diabetes. Significant reductions in diastolic BP (-1.5 mm Hg; 95% CI, -1.7 to -1.4 mm Hg), systolic BP (-1.1 mm Hg; 95% CI, -1.4 to -0.8 mm Hg), and total cholesterol (-12.8 mg/dL; 95% CI, -14.3 to -11.4 mg/dL) were also observed. Hemoglobin A1c reductions were greater among patients with diabetes (-0.3%; 95% CI, -0.3% to -0.2%) compared with patients without diabetes (-0.1%; 95% CI, -0.2% to -0.01%). Imputed health care expenditures, excluding the cost of semaglutide, increased by $80 per month (95% CI, $68-$92 per month) during the 13- to 24-month period, which was associated with inpatient stays shifting to more expensive circulatory and metabolic diagnoses. CONCLUSIONS AND RELEVANCE: In this cohort study of adults prescribed semaglutide, initiation was associated with reductions in weight and cardiovascular risk factors but increases in health care expenditures, excluding semaglutide costs. These findings suggest potential clinical benefits in routine practice, while highlighting the need to evaluate the long-term impact of semaglutide on economic outcomes. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Liu, Yuntian AU - Liu Y AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Totojani, Tedi AU - Totojani T AD - Yale School of Management, New Haven, Connecticut. FAU - Kim, Chungsoo AU - Kim C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. FAU - Khera, Rohan AU - Khera R AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. FAU - Xu, Hua AU - Xu H AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Brush, John E Jr AU - Brush JE Jr AD - Sentara Health Research Center, Sentara Health, Virginia Beach, Virginia. AD - Macon & Joan Brock Virginia Health Sciences at Old Dominion University, Norfolk, Virginia. FAU - Krumholz, Harlan M AU - Krumholz HM AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Abaluck, Jason AU - Abaluck J AD - Yale School of Management, New Haven, Connecticut. AD - National Bureau of Economic Research, New Haven, Connecticut. LA - eng GR - R01 HL169954/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural DEP - 20250801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Pressure/drug effects MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Glycated Hemoglobin/analysis MH - *Health Expenditures/statistics & numerical data MH - *Heart Disease Risk Factors MH - Retrospective Studies MH - United States MH - *Glucagon-Like Peptide-1 Receptor Agonists/economics/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12334959 COIS- Conflict of Interest Disclosures: Dr Lu reported receiving grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Sentara Research Foundation, and Novartis outside the submitted work. Dr Khera reported receiving grants from the National Heart, Lung, and Blood Institute, the Doris Duke Charitable Foundation, Bristol Myers Squibb (through Yale), Novo Nordisk (through Yale), and BridgeBio (through Yale); and being an academic cofounder of Ensight-AI and Evidence2Health outside the submitted work. Dr Krumholz reported receiving options from Element Science and Identifeye; receiving payments from F-Prime for advisory roles; being a co-founder of, and holding equity in, Hugo Health, Refactor Health, and ENSIGHT-AI; and being associated with research contracts through Yale University with Janssen, Kenvue, Novartis, and Pfizer. No other disclosures were reported. EDAT- 2025/08/08 12:29 MHDA- 2025/08/08 12:30 PMCR- 2025/08/08 CRDT- 2025/08/08 11:33 PHST- 2025/08/08 12:30 [medline] PHST- 2025/08/08 12:29 [pubmed] PHST- 2025/08/08 11:33 [entrez] PHST- 2025/08/08 00:00 [pmc-release] AID - 2837364 [pii] AID - zoi250733 [pii] AID - 10.1001/jamanetworkopen.2025.26013 [doi] PST - epublish SO - JAMA Netw Open. 2025 Aug 1;8(8):e2526013. doi: 10.1001/jamanetworkopen.2025.26013. PMID- 40774571 OWN - NLM STAT- MEDLINE DCOM- 20260205 LR - 20260205 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 10 IP - 2 DP - 2026 Feb TI - Risk of Sight-Threatening Diabetic Retinopathy with Glucagon-Like Peptide-1 Receptor Agonist Use in Routine Clinical Practice: Comparative Effectiveness of Semaglutide, Dulaglutide, Liraglutide, and Exenatide. PG - 142-151 LID - S2468-6530(25)00355-0 [pii] LID - 10.1016/j.oret.2025.07.019 [doi] AB - PURPOSE: To investigate whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents differ with respect to the risk of developing sight-threatening diabetic retinopathy complications in patients with type 2 diabetes at moderate cardiovascular risk. DESIGN: Retrospective observational study under the target trial emulation framework involving adult (>/=21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014 to December 31, 2022. The study population included adults with type 2 diabetes, moderate cardiovascular disease risk, no baseline advanced diabetic retinopathy, and minimum 1 year enrollment before GLP-1 RA treatment. METHODS: Because of differences in GLP-1 RA agent use over time, we performed both a 3-way comparison of patients initiating liraglutide, dulaglutide, or exenatide from January 1, 2015, to December 31, 2021, and a 2-way comparison of patients initiating semaglutide or dulaglutide between January 1, 2019, and December 31, 2021. We assessed differences in complications using inverse propensity score weighted Cox proportional hazards models. MAIN OUTCOME MEASURES: Treatment for diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). RESULTS: When comparing patients who initiated treatment with exenatide (n = 14 076, median follow-up 969 days; interquartile range [IQR] 578-1444) to those starting dulaglutide (n = 54 787, median follow-up 948 days; IQR 551-1457) or liraglutide (n = 25 562, median follow-up 1007 days; IQR 575-1494), no differences were found in the hazard (hazard ratio [HR]) of composite treatment for DME or PDR: exenatide versus dulaglutide (HR 0.90; 95% confidence interval (CI): 0.73-1.12), liraglutide versus dulaglutide (HR: 0.97; 95% CI: 0.79-1.19), or liraglutide versus exenatide (HR: 1.08; 95% CI: 0.83-1.38), nor were differences found in any comparisons for treatment of DME (HR: 0.93 [95% CI: 0.74-1.18]; HR 0.99 [95% CI: 0.79-1.24]; HR: 1.06 [95% CI: 0.80-1.40]) or PDR individually (HR: 1.16 [95% CI: 0.81-1.67]; HR: 1.05 [95% CI: 0.73-1.51]; HR: 0.91 [95% CI: 0.58-1.40). Likewise, when comparing patients initiating semaglutide (n = 30 911, median follow-up 625 days [IQR: 455-850]) versus dulaglutide (n = 32 844, median follow-up 639 days [IQR: 459-878]), the hazards for treatment of DME or PDR (HR: 0.88; 95% CI: 0.70-1.11), DME (HR: 0.89; 95% CI: 0.69-1.14), and PDR (HR: 0.70; 95% CI: 0.45-1.09) all found no difference between drugs. CONCLUSIONS: Despite the differences in systemic efficacy among the examined GLP-1 RAs, we identified no difference in the risk of sight-threatening diabetic retinopathy after initiation of different GLP-1 RA agents among adults with type 2 diabetes at moderate cardiovascular risk. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2025 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Barkmeier, Andrew J AU - Barkmeier AJ AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. Electronic address: barkmeier.andrew@mayo.edu. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Herrin, Jeph AU - Herrin J AD - Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. FAU - Ross, Joseph S AU - Ross JS AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairie, Minnesota; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; University of Maryland Institute for Health Computing, North Bethesda, Maryland. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250806 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetic Retinopathy/epidemiology/etiology/drug therapy/diagnosis MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Exenatide/therapeutic use MH - Retrospective Studies MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Liraglutide/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments MH - Middle Aged MH - Follow-Up Studies OTO - NOTNLM OT - Diabetic macular edema OT - Diabetic retinopathy OT - Glucagon-like protein-1 receptor agonist OT - Proliferative diabetic retinopathy OT - Semaglutide EDAT- 2025/08/08 00:28 MHDA- 2026/02/06 00:30 CRDT- 2025/08/07 19:50 PHST- 2025/02/27 00:00 [received] PHST- 2025/07/28 00:00 [revised] PHST- 2025/07/30 00:00 [accepted] PHST- 2026/02/06 00:30 [medline] PHST- 2025/08/08 00:28 [pubmed] PHST- 2025/08/07 19:50 [entrez] AID - S2468-6530(25)00355-0 [pii] AID - 10.1016/j.oret.2025.07.019 [doi] PST - ppublish SO - Ophthalmol Retina. 2026 Feb;10(2):142-151. doi: 10.1016/j.oret.2025.07.019. Epub 2025 Aug 6. PMID- 40762050 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Efficacy and safety of CT-868, a novel, fully biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in type 2 diabetes: A double-blind, randomized placebo controlled phase 2 trial. PG - 1673-1682 LID - 10.1111/dom.70006 [doi] AB - AIMS: To assess the glycaemic efficacy and safety of CT-868, a cAMP signal-biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in participants with type 2 diabetes (T2D). MATERIALS AND METHODS: This 26-week (W), phase 2, randomized, double-blind placebo-controlled trial enrolled adults with T2D, Body Mass Index >/=27 kg/m(2), and glycated haemoglobin (HbA1c) 7.0-10.0%. Participants were randomized (1:2:1) to once-daily CT-868 1.75 mg, 4.0 mg, or placebo. Due to COVID-19-related CT-868 supply constraints, some participants randomized to 4.0 mg received 3.25 mg maximum and were analysed as a separate dose arm. The primary endpoint was change from baseline in HbA1c at W26. Secondary endpoints included changes from baseline to W26 in fasting glucose, 7-point self-monitored blood glucose (SMBG), body weight, lipids and the occurrence of adverse events (AEs). RESULTS: Overall, 103 participants were enrolled (CT-868 1.75 mg, n = 26; 3.25 mg, n = 18; 4.0 mg, n = 32; placebo, n = 27). Clinically meaningful and statistically significant improvements in HbA1c were observed with CT-868 at W26 (-1.61 to -2.24%-points vs. placebo; all p < 0.001). Body weight was modestly reduced with CT-868 4.0 mg at W26 (-2.9% vs. placebo, p < 0.001). CT-868 improved fasting glucose, SMBG, and most lipid parameters vs. placebo. AEs were mostly mild/moderate. No participants experienced hypoglycaemia. CONCLUSIONS: CT-868 1.75 to 4.0 mg yielded robust, clinically meaningful decreases in HbA1c, supporting potent glycaemic-lowering effects and improved key lipid parameters in participants with overweight/obesity and T2D, despite modest weight loss. CT-868 was well tolerated, supporting future investigation of higher doses to maximize weight loss. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chakravarthy, Manu V AU - Chakravarthy MV AUID- ORCID: 0000-0002-3699-150X AD - Roche-Genentech, South San Francisco, California, USA. FAU - Elliott, Michael A AU - Elliott MA AUID- ORCID: 0009-0004-0744-5472 AD - Roche-Genentech, South San Francisco, California, USA. FAU - Acosta, Luis AU - Acosta L AUID- ORCID: 0009-0000-9439-2903 AD - Roche-Genentech, South San Francisco, California, USA. FAU - Sonnenberg, Gabriele E AU - Sonnenberg GE AUID- ORCID: 0000-0002-1320-3128 AD - Roche-Genentech, South San Francisco, California, USA. FAU - Bialonczyk, Damian AU - Bialonczyk D AUID- ORCID: 0000-0001-9369-8193 AD - Roche-Genentech, South San Francisco, California, USA. FAU - Wu, Jingtao AU - Wu J AUID- ORCID: 0009-0008-3080-7012 AD - Roche-Genentech, South San Francisco, California, USA. FAU - Arguelles-Tello, Federico A AU - Arguelles-Tello FA AUID- ORCID: 0000-0001-5393-872X AD - Avante-Sante Research Center, San Pedro Garza Garcia, Mexico. FAU - Garcia-Reza, Raymundo AU - Garcia-Reza R AUID- ORCID: 0000-0002-1463-3568 AD - Unidad Biomedica Avanzada Monterrey, Monterrey, Mexico. FAU - Gonzalez-Gonzalez, Jose Gerardo AU - Gonzalez-Gonzalez JG AUID- ORCID: 0000-0002-6609-9483 AD - Universidad Autonoma de Nuevo Leon, San Pedro Garza Garcia, Mexico. FAU - Hansen, Stig K AU - Hansen SK AUID- ORCID: 0009-0003-5437-2555 AD - Kimia Therapeutics, Berkeley, California, USA. FAU - Frias, Juan P AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - Charles R. Drew University of Medicine and Science, Los Angeles, California, USA. LA - eng GR - Carmot Therapeutics, Inc. (now Roche)/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20250805 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Male MH - Female MH - Middle Aged MH - Aged MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Blood Glucose/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Adult MH - *Receptors, Gastrointestinal Hormone/agonists PMC - PMC12890765 OTO - NOTNLM OT - glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist OT - glycaemic control OT - incretin OT - obesity OT - type 2 diabetes COIS- Manu V. Chakravarthy, Luis Acosta, Gabriele E. Sonnenberg, Damian Bialonczyk, and Jingtao Wu are full-time employees of Roche (previously Carmot Therapeutics) and may hold Roche stock and/or stock options. Michael A. Elliott is a former employee of Carmot Therapeutics (now Roche). Federico A. Arguelles-Tello, Raymundo Garcia-Reza, and Jose Gerardo Gonzalez-Gonzalez are employees of Avant-Sante, which has a consulting agreement with Carmot/Roche. Stig K. Hansen is a former employee of Carmot Therapeutics (now Roche) and a current employee of Kimia Therapeutics. Juan P. Frias is also an employee of Biomea Fusion Inc. and has a consulting agreement with Carmot/Roche. EDAT- 2025/08/05 06:28 MHDA- 2026/02/11 00:39 PMCR- 2026/02/11 CRDT- 2025/08/05 05:02 PHST- 2025/07/17 00:00 [revised] PHST- 2025/05/29 00:00 [received] PHST- 2025/07/25 00:00 [accepted] PHST- 2026/02/11 00:39 [medline] PHST- 2025/08/05 06:28 [pubmed] PHST- 2025/08/05 05:02 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - DOM70006 [pii] AID - 10.1111/dom.70006 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):1673-1682. doi: 10.1111/dom.70006. Epub 2025 Aug 5. PMID- 40760786 OWN - NLM STAT- MEDLINE DCOM- 20250919 LR - 20260701 IS - 1749-6632 (Electronic) IS - 0077-8923 (Linking) VI - 1551 IP - 1 DP - 2025 Sep TI - Generalizability of glucagon-like peptide 1 receptor agonist clinical trial results to product labeling and the real world. PG - 15-18 LID - 10.1111/nyas.70025 [doi] AB - "Generalizability" refers to when trial results are applied to populations that did not participate in the trial. It is important when pre-licensing trial results are used by regulators to authorize the use of a drug in different countries. To "generalize" the results, the trial sample must represent the population from which participants are drawn. They must also ensure that the trial will mimic usual clinical practice. Double-blind, placebo-controlled phase 3 trials are very different from usual practice. Investigators have flagged that samples from phase 3 trials of liraglutide, semaglutide, and tirzepatide excluded one-third of US adults without diabetes who were eligible for weight loss. The authors advised caution on "generalizing" the results to populations excluded from these trials. However, they erroneously used "generalizability" when referring to "representativeness." Similarly, in studies assessing whether real-world populations from China, the United Kingdom, the United States, and Spain were represented in cardiovascular outcomes phase 3 trials in type 2 diabetes with dulaglutide, exenatide, liraglutide, and semaglutide, the authors used "generalizability" in the texts of the articles. The enrolled trial samples were not representative of the real-world population: the term "generalizable" should not have been used. There is widespread confusion among investigators regarding the correct use of the term "generalizability." CI - (c) 2025 The New York Academy of Sciences. FAU - Dal-Re, Rafael AU - Dal-Re R AUID- ORCID: 0000-0002-0980-2486 AD - Epidemiology Unit, Health Research Institute-Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid, Madrid, Spain. LA - eng PT - Journal Article DEP - 20250804 PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Clinical Trials, Phase III as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Drug Labeling MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - PRECIS-2 OT - applicability OT - explanatory trials OT - pivotal trials OT - pragmatic trials OT - representativeness OT - semantics EDAT- 2025/08/05 06:28 MHDA- 2025/09/19 18:30 CRDT- 2025/08/05 01:32 PHST- 2025/09/19 18:30 [medline] PHST- 2025/08/05 06:28 [pubmed] PHST- 2025/08/05 01:32 [entrez] AID - 10.1111/nyas.70025 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2025 Sep;1551(1):15-18. doi: 10.1111/nyas.70025. Epub 2025 Aug 4. PMID- 40760383 OWN - NLM STAT- MEDLINE DCOM- 20260129 LR - 20260701 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 1 DP - 2026 Jan TI - Fill Patterns of Glucose-Lowering Drugs with Cardiovascular and Kidney Benefits in the Rural and Urban United States, 2012-2021. PG - 126-133 LID - 10.1007/s11606-025-09784-0 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular and kidney outcomes, but accessibility concerns persist. Whether access is worse in rural communities is unknown. OBJECTIVE: To examine fills of GLP1RA/SGLT2i by adults with type 2 diabetes in rural and urban US counties. DESIGN: Cross-sectional use claims from OptumLabs(R) Data Warehouse, 2012-2021. PATIENTS: Adults with type 2 diabetes. MAIN MEASURES: We examined rates and odds of fills of GLP1RA or SGLT2i, adjusting for time period, age, sex, presence of cardiorenal comorbidities (heart failure [HF], atherosclerotic cardiovascular disease [ASCVD], chronic kidney disease stages 3-4 [CKD]), and rurality. KEY RESULTS: The study included 2,579,577 adults with type 2 diabetes (mean age 63.9; 49.6% female). Compared to 2012-2015, fills of GLP1RA/SGLT2i increased in 2016-2018 (OR 2.49; 95% CI 2.47-2.52) and 2019-2021 (OR 4.35; 95% CI 4.30-4.39). By 2019-2021, the percentages of patients filling GLP1RA/SGLT2i in cities, small towns, and remote areas were 18.8%, 18.8%, and 17.4%, respectively. Small town residents had higher odds of fills than those in cities (OR 1.05; 95% CI 1.04-1.06). Older age was associated with lower fill rates; compared to 18-44 year olds, odds for those 45-64 years were OR 0.88 (95% CI 0.87-0.89), 65-74 years: OR 0.48 (95% CI 0.47-0.48), and >/= 75 years: OR 0.17 (95% CI 0.17-0.18). Men were less likely to fill GLP1RA/SGLT2i than women (OR 0.91; 95% CI 0.90-0.92). Presence of ASCVD and CKD were associated with greater odds of filling GLP1RA/SGLT2i (OR 1.03 [95% CI 1.01-1.05] and OR 1.12 [95% CI 1.10-1.14], respectively), while HF was associated with lower odds (OR 0.86 [95% CI 0.85-0.88]). CONCLUSIONS: GLP1RA and SGLT2i fills increased over time but remained low overall. They were filled more often by younger people, women, those with ASCVD or CKD (but not with HF), and in small towns. CI - (c) 2025. The Author(s). FAU - Steiger, Kyle AU - Steiger K AD - Internal Medicine Residency, Mayo Clinic, Rochester, MN, USA. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA. AD - OptumLabs, Eden Prairie, MN, USA. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA. FAU - McCoy, Rozalina G AU - McCoy RG AUID- ORCID: 0000-0002-2289-3183 AD - OptumLabs, Eden Prairie, MN, USA. Rozalina.McCoy@som.umaryland.edu. AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Baltimore, MD, 21201, USA. Rozalina.McCoy@som.umaryland.edu. AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA. Rozalina.McCoy@som.umaryland.edu. LA - eng GR - K23 DK114497/DK/NIDDK NIH HHS/United States GR - K23DK114497/DK/NIDDK NIH HHS/United States GR - K23DK114497/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250804 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - United States/epidemiology MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - *Rural Population/trends MH - *Hypoglycemic Agents/therapeutic use MH - *Urban Population/trends/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Cardiovascular Diseases/epidemiology/prevention & control PMC - PMC12855668 OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - Glucagon-like peptide OT - Heart failure OT - Sodium/glucose cotransporter-2 COIS- Declarations. Human Ethics and Consent to Participate: The study was exempt by Mayo Clinic from Institutional Review Board review as all data are de-identified. Informed consent does not apply. Conflict of Interest: No competing financial interests exist. In the last 36 months, Dr. McCoy has received support from NIDDK, National Institute on Aging of the NIH, the Patient Centered Outcomes Research Institute (PCORI), National Center for Advancing Translational Sciences (NCATS), and the American Diabetes Association for unrelated work. She served as a consultant to EmmiEducate(R) (Wolters Kluwer) and the Yale-New Haven Health System's Center For Outcomes Research and Evaluation and has received speaking honoraria and travel support from the American Diabetes Association. In the last 36 months, Dr. Herrin has received support from the National Institutes of Health, PCORI, the Agency for Healthcare Research and Quality, and the Centers for Medicare and Medicaid Services. Disclaimer: Study contents are the sole responsibility of the authors and do not necessarily represent the official views of NIH. EDAT- 2025/08/05 06:28 MHDA- 2026/01/29 19:11 PMCR- 2025/08/04 CRDT- 2025/08/05 00:37 PHST- 2025/03/13 00:00 [received] PHST- 2025/07/21 00:00 [accepted] PHST- 2026/01/29 19:11 [medline] PHST- 2025/08/05 06:28 [pubmed] PHST- 2025/08/05 00:37 [entrez] PHST- 2025/08/04 00:00 [pmc-release] AID - 10.1007/s11606-025-09784-0 [pii] AID - 9784 [pii] AID - 10.1007/s11606-025-09784-0 [doi] PST - ppublish SO - J Gen Intern Med. 2026 Jan;41(1):126-133. doi: 10.1007/s11606-025-09784-0. Epub 2025 Aug 4. PMID- 40759509 OWN - NLM STAT- MEDLINE DCOM- 20250804 LR - 20260127 IS - 1757-790X (Electronic) IS - 1757-790X (Linking) VI - 18 IP - 8 DP - 2025 Aug 4 TI - Neuropsychiatric side effects of semaglutide in patients with dementia. LID - e262743 [pii] LID - 10.1136/bcr-2024-262743 [doi] AB - An older woman with dementia and type 2 diabetes was started on semaglutide and subsequently developed severe psychological and physical symptoms, including apathy, significant weight loss and decreased appetite. These symptoms markedly improved after the medication was discontinued. This case underscores the importance of recognising potential psychiatric side effects of semaglutide, especially in older adults with cognitive impairment. The experience highlights the need for careful monitoring when prescribing semaglutide in this population and suggests that discontinuation should be considered if adverse symptoms arise. It also raises awareness about the limited safety data on semaglutide in older patients, emphasising the necessity of further research to understand its effects on this vulnerable group. CI - (c) BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Jamshed, Namirah AU - Jamshed N AUID- ORCID: 0000-0002-3471-703X AD - Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA namirah.jamshed@utsouthwestern.edu. FAU - Rehman, Syed Tabish AU - Rehman ST AUID- ORCID: 0000-0003-1532-5978 AD - The Aga Khan University, Karachi, Sindh, Pakistan. FAU - Khan, Noor AU - Khan N AD - Internal Medicine, UPMC, Pittsburgh, Pennsylvania, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20250804 PL - England TA - BMJ Case Rep JT - BMJ case reports JID - 101526291 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Apathy/drug effects MH - *Dementia/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Dementia, Alzheimer's type OT - Depressive disorder OT - Diabetes OT - Memory Disorders COIS- Competing interests: None declared. EDAT- 2025/08/05 00:29 MHDA- 2025/08/05 00:30 CRDT- 2025/08/04 21:24 PHST- 2025/08/05 00:30 [medline] PHST- 2025/08/05 00:29 [pubmed] PHST- 2025/08/04 21:24 [entrez] AID - 18/8/e262743 [pii] AID - 10.1136/bcr-2024-262743 [doi] PST - epublish SO - BMJ Case Rep. 2025 Aug 4;18(8):e262743. doi: 10.1136/bcr-2024-262743. PMID- 40758358 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20260806 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 185 IP - 10 DP - 2025 Oct 1 TI - Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. PG - 1206-1217 LID - 10.1001/jamainternmed.2025.3599 [doi] AB - IMPORTANCE: The efficacy and safety of oral semaglutide, 50 mg, in an East Asian population that also includes individuals with type 2 diabetes (T2D), who are prone to weight-related complications at lower body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) thresholds than other ethnic groups, is currently unknown. OBJECTIVE: To assess the efficacy and safety of once-daily oral semaglutide, 50 mg, for the treatment of overweight and obesity in East Asian individuals with or without T2D. DESIGN, SETTING, AND PARTICIPANTS: The OASIS 2 trial was a 68-week (plus 7 weeks of follow-up) multicenter, double-blind, placebo-controlled phase 3a randomized clinical trial conducted from November 2021 to September 2023 in Japan and South Korea. Adults with a BMI of 27.0 or greater with 2 or more related complications or a BMI of 35.0 or greater with 1 or more related complications were enrolled. Approximately 25% of participants were planned to have T2D at screening. Data were analyzed from March 2022 to July 2025. INTERVENTIONS: Participants were assigned 2:1 to once-daily oral semaglutide, 50 mg, or placebo, plus lifestyle recommendations, for 68 weeks. MAIN OUTCOMES AND MEASURES: The coprimary end points were percentage change in body weight from baseline and the proportion of participants who achieved 5% or greater body weight reductions. Changes in physical function, cardiometabolic risk factors, and safety were also evaluated. RESULTS: Overall, 201 participants (mean [SD] age, 49 [11] years; mean [SD] body weight, 91.9 [18.2] kg; 87 [43.3%] female; 51 [25.4%] with T2D) were randomized to semaglutide (n = 134) or placebo (n = 67). The mean (SEM) percentage change in body weight was -14.3% (0.8) with semaglutide vs -1.3% (1.1) with placebo (estimated treatment difference, -13.07 percentage points; 95% CI, -15.61 to -10.52; P < .001). More participants had 5% or greater body weight reductions with semaglutide vs placebo (107 of 127 [84.3%] vs 11 of 64 [17.2%]; odds ratio, 23.00; 95% CI, 10.28-51.42; P < .001). Gastrointestinal tract adverse events were reported by 85 of 134 participants (63.4%) with semaglutide and 23 of 66 with placebo (34.8%). Adverse events led to treatment discontinuation in 6 of 134 participants (4.5%) in the semaglutide arm. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among East Asian adults with overweight or obesity, with or without T2D, oral semaglutide, 50 mg, led to a superior and clinically meaningful reduction in body weight compared with placebo, with a safety profile consistent with the glucagon-like peptide-1 receptor agonist class. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05132088. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. FAU - Heftdal, Line Dam AU - Heftdal LD AD - Novo Nordisk, Soborg, Denmark. FAU - Ko, Hae-Jin AU - Ko HJ AD - Kyungpook National University School of Medicine, Kyungpook National University Hospital, Daegu, South Korea. FAU - Overvad, Maria AU - Overvad M AD - Novo Nordisk, Soborg, Denmark. FAU - Shimomura, Iichiro AU - Shimomura I AD - Graduate School of Medicine, Osaka University, Osaka, Japan. FAU - Thamattoor, Usha K AU - Thamattoor UK AD - Novo Nordisk, Bangalore, India. FAU - Kim, Kyoung-Kon AU - Kim KK AD - Gachon University College of Medicine, Gachon University Gil Medical Center, Incheon, South Korea. CN - OASIS 2 Investigators LA - eng SI - ClinicalTrials.gov/NCT05132088 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Intern Med. 2025 Oct 1;185(10):1217. doi: 10.1001/jamainternmed.2025.3618. PMID: 40758368 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Double-Blind Method MH - East Asian People MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Hypoglycemic Agents/administration & dosage MH - Japan/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Republic of Korea/epidemiology MH - Semaglutide MH - Treatment Outcome MH - Weight Loss/drug effects PMC - PMC12322823 COIS- Conflict of Interest Disclosures: Dr Kadowaki reported grants and personal fees from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co Ltd, Novo Nordisk Pharma Ltd, Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co Ltd, Sumitomo Pharma Co Ltd, Kyowa Kirin, Daiichi Sankyo, and Takeda Pharma; personal fees from MSD Corporation, Abbott Japan Ltd, Teijin Pharma Ltd, Ono Pharmaceutical Co Ltd, FUJIFILM Toyama Chemical Co Ltd, Medtronic Japan, and AstraZeneca outside the submitted work. Dr Heftdal reported nonfinancial support from OPEN Health Communications during the conduct of the study and is an employee and shareholder of Novo Nordisk outside the submitted work. Dr Ko reported grants from Novo Nordisk during the conduct of the study; grants from Boehringer Ingelheim, Huons, and Hanmi Pharma Korea; and personal fees from Novo Nordisk, Hanmi Pharma Korea, Amgen Korea, and Alvogen Korea outside the submitted work. Dr Overvad is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Shimomura reported grants from Eli Lilly Japan K.K., Teijin Pharma, Mochida Pharmaceutical, Kowa, Kyowa Kirin, Sumitomo Pharma, Rohto Pharmaceutical, Kobayashi Pharmaceutical, Nissin Foods Holdings, Cancerscan, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Osaka Central Hospital, Hakuhokai Central Hospital, Midori Health Care Center, Kyowakai Medical Corporation, Ono Medical Research Foundation, Suzuken Memorial Foundation, Manpei Suzuki Diabetes Foundation, and Japan Agency for Medical Research and Development; consulting fees from Merck Sharpe & Dohme K.K., Taisho Pharmaceutical, Nippon Boehringer Ingelheim, and Novo Nordisk Pharma; and personal fees from Arcray, Merck Sharpe & Dohme K.K., Astellas Pharma, AstraZeneca K.K., Abbott Japan, Ono Pharmaceutical, Otsuka Pharmaceutical, Kyorin Pharmaceutical, Johnson & Johnson K.K., Kyowa Kirin, Kowa, Sanofi, Sumitomo Pharma, Sanwa Kagaku Kenkyusho, Teijin Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Nipro Corporation, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim, Novartis Pharma K.K., Novo Nordisk Pharma, Mochida Pharmaceutical, Bayer Yakuhin, Pfizer Japan, and Lotte outside the submitted work; participates on the advisory board for AstraZeneca K.K., Novo Nordisk Pharma, Eli Lilly Japan K.K., Amgen, Shionogi & Co., Sumitomo Pharma, and Nissin Foods Holdings; and is an unpaid member of boards for the Japan Society for the Study of Obesity, Japan Endocrine Society, Japan Diabetes Society, Japanese Society for Treatment of Obesity, Japanese Society of Molecular Medicine, Japanese Society of Internal Medicine, Japan Atherosclerosis Society, Japan Society of Metabolism and Clinical Nutrition, and Japanese Society of Anti-Aging Medicine. Dr Thamattoor is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Kim reported grants from Novo Nordisk during the conduct of the study; grants from Hanmi Pharmaceutical, Alvogen Korea, Huons, Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and personal fees from Eli Lilly Korea, Novo Nordisk, Hanmi Pharmaceutical, Alvogen Korea, and Chong Kun Dang outside the submitted work. No other disclosures were reported. FIR - Kunishige, Hideyuki IR - Kunishige H FIR - Okude, Jun IR - Okude J FIR - Sato, Naoki IR - Sato N FIR - Takeda, Satoshi IR - Takeda S FIR - Uemura, Koji IR - Uemura K FIR - Osonoi, Takeshi IR - Osonoi T FIR - Isshiki, Satomi IR - Isshiki S FIR - Ito, Naoaki IR - Ito N FIR - Naito, Hitoshi IR - Naito H FIR - Oka, Norihiko IR - Oka N FIR - Hosoya, Mitsuru IR - Hosoya M FIR - Saito, Miyoko IR - Saito M FIR - Takizawa, Hiroki IR - Takizawa H FIR - Asano, Hiroshi IR - Asano H FIR - Shirabe, Shinichiro IR - Shirabe S FIR - Asakura, Taro IR - Asakura T FIR - Kaneshiro, Mizuki IR - Kaneshiro M FIR - Matsuura, Hitoshi IR - Matsuura H FIR - Ohira, Akeo IR - Ohira A FIR - Nakano, Saburo IR - Nakano S FIR - Mori, Yasumichi IR - Mori Y FIR - Matsumura, Kimio IR - Matsumura K FIR - Nagasawa, Kaoru IR - Nagasawa K FIR - Kadowaki, Takashi IR - Kadowaki T FIR - Uchida, Takayasu IR - Uchida T FIR - Kikuno, Shota IR - Kikuno S FIR - Suzuki, Yuya IR - Suzuki Y FIR - Kaneko, Shizuka IR - Kaneko S FIR - Onaka, Haruhiko IR - Onaka H FIR - Ueba, Yoko IR - Ueba Y FIR - Onda, Yoshiyuki IR - Onda Y FIR - Minami, Tomoko IR - Minami T FIR - Osugi, Tomoaki IR - Osugi T FIR - Tokumoto, Shinsuke IR - Tokumoto S FIR - Motohashi, Kazuya IR - Motohashi K FIR - Okada, Mutsumi IR - Okada M FIR - Machida, Nao IR - Machida N FIR - Kizawa, Shun IR - Kizawa S FIR - Nishizawa, Hitoshi IR - Nishizawa H FIR - Maeda, Norikazu IR - Maeda N FIR - Shimomura, Iichiro IR - Shimomura I FIR - Fujishima, Yuya IR - Fujishima Y FIR - Fukuda, Shiro IR - Fukuda S FIR - Nagashima, Hirotaka IR - Nagashima H FIR - Horie, Yoshimasa IR - Horie Y FIR - Ohyama, Takako IR - Ohyama T FIR - Yoshida, Kazu IR - Yoshida K FIR - Yamamoto, Asaji IR - Yamamoto A FIR - Kishi, Akiko IR - Kishi A FIR - Soeda, Koutarou IR - Soeda K FIR - Fujita, Hayato IR - Fujita H FIR - Tsuji, Aki IR - Tsuji A FIR - Takahashi, Yuichi IR - Takahashi Y FIR - Inoue, Satoshi IR - Inoue S FIR - Yagi, Michio IR - Yagi M FIR - Owada, Yasuko IR - Owada Y FIR - Kanada, Shigeto IR - Kanada S FIR - Furuie, Hidetoshi IR - Furuie H FIR - Suga, Yasuhiko IR - Suga Y FIR - Inomoto, Takuya IR - Inomoto T FIR - Yamaguchi, Daiki IR - Yamaguchi D FIR - Yoshida, Kayo IR - Yoshida K FIR - Yamahara, Kenichi IR - Yamahara K FIR - Nanto, Masanobu IR - Nanto M FIR - Kobayashi, Sumiko IR - Kobayashi S FIR - Soma, Yuko IR - Soma Y FIR - Matsuoka, Osamu IR - Matsuoka O FIR - Kawai, Makoto IR - Kawai M FIR - Kawai, Mie IR - Kawai M FIR - Ito, Miki IR - Ito M FIR - Yamaguchi, Izumi IR - Yamaguchi I FIR - Matsuda, Hideki IR - Matsuda H FIR - Otake, Sachiko IR - Otake S FIR - Sung, Eunju IR - Sung E FIR - Cho, InYoung IR - Cho I FIR - Yoon, HyunJung IR - Yoon H FIR - Kang, HyunJun IR - Kang H FIR - Kim, Kyoung-Kon IR - Kim KK FIR - Ko, Hae-Jin IR - Ko HJ FIR - Hong, Hee-Eun IR - Hong HE FIR - Kim, Ju Young IR - Kim JY FIR - Koo, Hyeyeon IR - Koo H FIR - Lee, Sumi IR - Lee S FIR - Cho, Eun-Byul IR - Cho EB FIR - Yoo, MunYoung IR - Yoo M EDAT- 2025/08/04 12:27 MHDA- 2025/10/06 12:31 PMCR- 2026/08/04 CRDT- 2025/08/04 11:34 PHST- 2025/10/06 12:31 [medline] PHST- 2025/08/04 12:27 [pubmed] PHST- 2025/08/04 11:34 [entrez] PHST- 2026/08/04 00:00 [pmc-release] AID - 2836932 [pii] AID - ioi250046 [pii] AID - 10.1001/jamainternmed.2025.3599 [doi] PST - ppublish SO - JAMA Intern Med. 2025 Oct 1;185(10):1206-1217. doi: 10.1001/jamainternmed.2025.3599. PMID- 40755395 OWN - NLM STAT- MEDLINE DCOM- 20260113 LR - 20260614 IS - 1945-7189 (Electronic) IS - 0163-769X (Linking) VI - 47 IP - 1 DP - 2026 Jan 13 TI - Innovative Molecules and Delivery Technologies Enabling the Future of GLP-1-based Therapies. PG - 1-23 LID - 10.1210/endrev/bnaf027 [doi] AB - The multiple physiological effects of gut hormones in different metabolic tissues make them attractive therapeutic targets for the treatment of metabolic diseases. Currently, only glucagon-like peptide-1 (GLP-1) receptor-based agonists and oral dipeptidyl peptidase-4 inhibitors are available on the market. Despite their positive clinical outcomes across a range of indications, these treatments present several clinical challenges, including high costs, the need for peptide injections, and requirements for repeated administration. These limitations have driven research into improved GLP-1-based therapies, such as oral small-molecule agonists and novel drug delivery strategies based on emerging GLP-1 medicines. This article describes the challenges in clinical application and development of GLP-1-based pharmacotherapies. We review the development of oral small-molecule agonists and various drug delivery technologies, including ultralong-acting injectable technologies, continuous-acting implantable pumps, smart-acting electronic devices, nutrient-induced cell therapies, and noninvasive delivery systems. We discuss the current state of research, challenges to overcome, and opportunities to improve patient compliance and clinical outcomes. Additionally, we explore how endocrinological effects and patient-oriented needs can guide the development of advanced GLP-1 medicines. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Xu, Yining AU - Xu Y AUID- ORCID: 0000-0001-6201-9338 AD - Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Department of Medicine and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada M5G 1X5. FAU - Traverso, Giovanni AU - Traverso G AUID- ORCID: 0000-0001-7851-4077 AD - Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. AD - Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. FAU - Beloqui, Ana AU - Beloqui A AUID- ORCID: 0000-0003-4221-3357 AD - Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Universite Catholique de Louvain, UCLouvain, Brussels 1200, Belgium. AD - WEL Research Institute, Wavre 1300, Belgium. LA - eng GR - National Nature Science Foundation of China/ GR - 82370860/General Program/ GR - 2024YFHZ0326/Department of Science and Technology of Sichuan Province/ GR - ZYYC25001/Project for Disciplines of Excellence/ GR - YJ202412/Fundamental Research Funds for the Central Universities/ GR - 192044/Sichuan University Interdisciplinary Innovation Fund/ GR - OG-3-24-5819-DD/Diabetes Canada-Canadian Cancer Society/ GR - Sinai Health Novo Nordisk Foundation/ GR - Novo Nordisk A/S/ GR - Massachusetts Institute of Technology/ GR - Brigham and Women's Hospital/ GR - D24AC00040-00/the Advanced Research Projects Agency for Health/ GR - WELBIO-CR-2022 S - 01/WEL Research Institute investigator/ GR - ERC_/European Research Council/International GR - 850997/European Union's Horizon 2020 research and innovation program/ GR - J.0009.22/European Union's Horizon 2020 research and innovation program/ PT - Journal Article PT - Review PL - United States TA - Endocr Rev JT - Endocrine reviews JID - 8006258 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/agonists/administration & dosage MH - *Drug Delivery Systems/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Animals OTO - NOTNLM OT - GIP OT - GLP-1 OT - diabetes OT - glucagon-like peptide 1 OT - innovative technologies OT - metabolic disorders OT - obesity OT - weight loss EDAT- 2025/08/04 06:27 MHDA- 2026/01/13 07:43 CRDT- 2025/08/04 05:33 PHST- 2025/03/14 00:00 [received] PHST- 2026/01/13 07:43 [medline] PHST- 2025/08/04 06:27 [pubmed] PHST- 2025/08/04 05:33 [entrez] AID - 8221663 [pii] AID - 10.1210/endrev/bnaf027 [doi] PST - ppublish SO - Endocr Rev. 2026 Jan 13;47(1):1-23. doi: 10.1210/endrev/bnaf027. PMID- 40755350 OWN - NLM STAT- MEDLINE DCOM- 20260206 LR - 20260206 IS - 1699-5848 (Electronic) IS - 0213-3911 (Linking) VI - 41 IP - 3 DP - 2026 Mar TI - The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review. PG - 371-381 LID - 10.14670/HH-18-967 [doi] AB - INTRODUCTION: For the last three decades, bariatric/metabolic surgeries have highlighted the relevance of certain gastrointestinal hormones in controlling and regulating glucose metabolism. The incretins have been a significant focus in developing therapies against Type 2 Diabetes Mellitus (T2DM). Glucagon-like peptide-1 (GLP-1) has been a primary focus in this field, leading to the development of analogues with high therapeutic potential and efficiency, such as semaglutide. However, recently another incretin, glucose-dependent insulinotropic polypeptide (GIP), has become a key target in T2DM drug development due to its complex pleiotropic effects, which include modulating insulin/glucagon secretion, acting on adipose tissue, and regulating appetite. The description of GIP properties as dual can be ambiguous, as this may refer either to its capacity to regulate both insulin and glucagon or to its distinct actions at the central versus peripheral level. Connecting this multifaceted activity was the rationale for developing combined GIP/GLP-1 analogues, like tirzepatide, and has culminated in triple-receptor agonists such as retratutide, which also engages the glucagon receptor (LY3437943). These multi-agonists potentially enhance the therapeutic potential of GLP-1 analogues. COMMENTARIES: This review covers GIP physiology, its role within the context of T2DM, and the properties of GIP analogues, which represent a new line of drugs against T2DM. This field includes not only GIP analogues, since some are dual or triple agonists that also target GLP-1. We aim to elucidate the future perspectives offered by the use of these drugs. CI - (c)The Author(s) 2025. Open Access. This article is licensed under a Creative Commons CC-BY International License. FAU - Almorza-Gomar, David AU - Almorza-Gomar D AD - Department of Operative Statistics and Research, University of Cadiz, Cadiz, Spain. FAU - Diaz-Gomez, Alfredo AU - Diaz-Gomez A AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - San Carlos Hospital, Andalusian Health System, Cadiz, Spain. FAU - Visiedo, Francisco AU - Visiedo F AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. FAU - Garcia-Ortiz, Jose-Carlos AU - Garcia-Ortiz JC AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Jerez University Hospital, University of Cadiz, Cadiz, Spain. FAU - Camacho-Ramirez, Alonso AU - Camacho-Ramirez A AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. AD - Surgery Service, Puerta del Mar University Hospital, University of Cadiz, Cadiz, Spain. FAU - Ribelles-Garcia, Antonio AU - Ribelles-Garcia A AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Social Sustainable Development Research Institute, University of Cadiz, Cadiz, Spain. FAU - Prada-Oliveira, Jose-Arturo AU - Prada-Oliveira JA AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. arturo.prada@uca.es. FAU - Perez-Arana, Gonzalo-Martin AU - Perez-Arana GM AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. gonzalo.perez@uca.es. LA - eng PT - Journal Article PT - Review DEP - 20250715 PL - Spain TA - Histol Histopathol JT - Histology and histopathology JID - 8609357 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Carbohydrate Metabolism/drug effects/physiology MH - Animals MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1/metabolism MH - Incretins/metabolism EDAT- 2025/08/04 06:27 MHDA- 2026/02/06 14:37 CRDT- 2025/08/04 05:13 PHST- 2026/02/06 14:37 [medline] PHST- 2025/08/04 06:27 [pubmed] PHST- 2025/08/04 05:13 [entrez] AID - HH-18-967 [pii] AID - 10.14670/HH-18-967 [doi] PST - ppublish SO - Histol Histopathol. 2026 Mar;41(3):371-381. doi: 10.14670/HH-18-967. Epub 2025 Jul 15. PMID- 40752805 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260821 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 440 DP - 2025 Dec 1 TI - Effects of oral semaglutide on cardiovascular outcomes: A systematic review and meta-analysis. PG - 133683 LID - S0167-5273(25)00726-0 [pii] LID - 10.1016/j.ijcard.2025.133683 [doi] AB - BACKGROUND: Cardiovascular disease remains a leading cause of morbidity and mortality in type 2 diabetic mellitus (T2DM) patients. While injectable GLP-1 RAs have demonstrated efficacy in reducing cardiovascular risk, an oral formulation of semaglutide was developed to improve accessibility and treatment adherence, however, its therapeutic potential has yet to be fully elucidated. This meta-analysis evaluates the efficacy of oral semaglutide on cardiovascular outcomes to better inform clinical decision-making. METHODS: A systematic search was conducted in major databases for randomized controlled trials (RCTs) up to May 2025, with a primary outcome of cardiovascular events, expanded outcomes included nonfatal stroke, death from cardiovascular cause, and nonfatal myocardial infarction, and the secondary outcome was all-cause mortality. Statistical analysis was performed using RStudio, with heterogeneity assessed via I(2) statistics. RESULTS: A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies. A significant difference was observed for cardiovascular events with a risk ratio (RR) of 0.86 (95 % CI: 0.78-0.95; p = 0.0029; I(2) = 0 %) and hazard ratio (HR) of 0.85 (95 % CI: 0.77-0.95), respectively. In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction. CONCLUSION: The meta-analysis revealed that oral semaglutide was cardioprotective in T2DM patients with consistent reductions in cardiovascular event risk. However, the lack of significance in the remaining outcomes underscores the need for further investigation. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Rebelo, Thiago Gorayeb AU - Rebelo TG AD - University of Ottawa, ON, Ottawa, Canada. Electronic address: thiagogrebelo@hotmail.com. FAU - de Araujo Paysano, Maria Lucia Brito AU - de Araujo Paysano MLB AD - Professor Rubem David Azulay Institute of Dermatology, RJ, Rio de Janeiro, Brazil. FAU - Matheus, Gustavo Tadeu Freitas Uchoa AU - Matheus GTFU AD - Federal University of Triangulo Mineiro, MG, Uberaba, Brazil. FAU - Ribeiro, Danilo Monteiro AU - Ribeiro DM AD - University Anhembi Morumbi, SP, Sao Paulo, Brazil. FAU - Said, Thomas Benevides AU - Said TB AD - Federal University of Amazonas, AM, Manaus, Brazil. FAU - Kelly, Francinny Alves AU - Kelly FA AD - Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250731 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage MH - *Cardiovascular Diseases/drug therapy/prevention & control/epidemiology/diagnosis MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Randomized Controlled Trials as Topic/methods MH - Hypoglycemic Agents/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP-1 receptor agonists OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2025/08/03 03:46 MHDA- 2025/09/01 00:44 CRDT- 2025/08/02 19:41 PHST- 2025/05/17 00:00 [received] PHST- 2025/07/24 00:00 [revised] PHST- 2025/07/30 00:00 [accepted] PHST- 2025/09/01 00:44 [medline] PHST- 2025/08/03 03:46 [pubmed] PHST- 2025/08/02 19:41 [entrez] AID - S0167-5273(25)00726-0 [pii] AID - 10.1016/j.ijcard.2025.133683 [doi] PST - ppublish SO - Int J Cardiol. 2025 Dec 1;440:133683. doi: 10.1016/j.ijcard.2025.133683. Epub 2025 Jul 31. PMID- 40751153 OWN - NLM STAT- MEDLINE DCOM- 20250802 LR - 20250805 IS - 1471-2474 (Electronic) IS - 1471-2474 (Linking) VI - 26 IP - 1 DP - 2025 Aug 1 TI - Differential effects of GLP-1 receptor agonists on diabetic osteopathy in type 2 diabetes: a patient-stratified network meta-analysis. PG - 742 LID - 10.1186/s12891-025-09022-y [doi] LID - 742 AB - INTRODUCTION: Diabetic osteopathy is a skeletal disorder that is characterized by increased fracture risk despite normal bone mineral density. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their effects on diabetic bone disease were not studied nor investigated sufficiently in previous studies in the literature. We conducted a network meta-analysis to evaluate the differential effects of GLP-1 RAs on bone health outcomes in patients with T2DM. METHODS: We performed a systematic review and network meta-analysis of randomized controlled trials evaluating GLP-1 RAs with bone-related outcomes in T2DM patients. Primary outcomes included changes in bone mineral density (BMD), bone turnover markers, and fracture incidence. RESULTS: A total of 33 randomized controlled trials (33,107 participants) were included. GLP-1 RAs demonstrated improvements in BMD at the lumbar spine (0.052 g/cm(2) [0.043-0.061]), total hip (0.047 g/cm(2) [0.037-0.057]), and femoral neck (0.072 g/cm(2) [0.060-0.084]), however BMD findings from studies less than 52 weeks require cautious interpretation per clinical densitometry standards. They reduced bone resorption (beta-CTX SMD -0.36 [-0.53, -0.20]) while increasing formation markers, possibly normalizing the uncoupled remodeling characteristic of diabetic osteopathy. Long-term treatment was associated with reduced fracture risk by 20% (RR 0.80 [0.65-0.94]). CONCLUSIONS: GLP-1 RAs may provide skeletal benefits in T2DM patients by addressing specific mechanisms underlying diabetic osteopathy. The skeletal effects appear to vary according to agent type, patient characteristics, and treatment duration, suggesting promising role for personalized approaches to therapy selection. When bone health is a concern, GLP-1 RAs may represent a beneficial therapeutic option that could simultaneously address both metabolic and skeletal outcomes in patients with T2DM, though further bone-specific studies is needed for newer agents. CI - (c) 2025. The Author(s). FAU - Alalwani, Yazan Jumah AU - Alalwani YJ AD - College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. FAU - Alshahrani, Ali Saad AU - Alshahrani AS AD - Department of Orthopedic Surgery, King Fahad University Hospital, Khobar, Saudi Arabia. FAU - Alsudays, Aseel Ibrahem AU - Alsudays AI AD - College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah, Saudi Arabia. FAU - Almutairi, Reema Nasser Awad AU - Almutairi RNA AD - College of Medicine, Taibah University, Madinah, Saudi Arabia. FAU - Arab, Rana Ali Hassan AU - Arab RAH AD - College of Medicine, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia. FAU - Alqahtani, Reema Safar Ali AU - Alqahtani RSA AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Alrefaei, Omar Saad AU - Alrefaei OS AD - College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. FAU - Alqahtani, Rana AU - Alqahtani R AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Ofaysan, Meshal Salman Bin AU - Ofaysan MSB AD - College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia. FAU - Azzam, Ahmed Y AU - Azzam AY AD - Director of Clinical Research and Clinical Artificial Intelligence, ASIDE Healthcare, Lewes, Delaware, USA. ahmedyazzam@gmail.com. FAU - Alomran, Ammar K AU - Alomran AK AD - Department of Orthopedic Surgery, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250801 PL - England TA - BMC Musculoskelet Disord JT - BMC musculoskeletal disorders JID - 100968565 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Bone Density/drug effects MH - Bone Remodeling/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Fractures, Bone/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Randomized Controlled Trials as Topic/methods MH - Treatment Outcome PMC - PMC12315457 OTO - NOTNLM OT - Bone health OT - Diabetic osteopathy OT - GLP-1 receptor agonists OT - Skeletal disorders OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Ethical approvals were waived for this study, since this study did not involve direct human patients' data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/08/02 10:43 MHDA- 2025/08/02 10:44 PMCR- 2025/08/01 CRDT- 2025/08/02 00:21 PHST- 2025/05/02 00:00 [received] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/08/02 10:44 [medline] PHST- 2025/08/02 10:43 [pubmed] PHST- 2025/08/02 00:21 [entrez] PHST- 2025/08/01 00:00 [pmc-release] AID - 10.1186/s12891-025-09022-y [pii] AID - 9022 [pii] AID - 10.1186/s12891-025-09022-y [doi] PST - epublish SO - BMC Musculoskelet Disord. 2025 Aug 1;26(1):742. doi: 10.1186/s12891-025-09022-y. PMID- 40750324 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20251001 IS - 1939-2869 (Electronic) IS - 0891-1150 (Linking) VI - 92 IP - 8 DP - 2025 Aug 1 TI - Glucagon-like peptide-1 receptor agonists and pancreatitis: A reconcilable divorce. PG - 483-489 LID - 10.3949/ccjm.92a.24113 [doi] AB - Early clinical trials suggested that patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists had a slightly increased risk of acute pancreatitis. Consequently, clinicians have avoided using GLP-1 receptor agonists in patients with a history of acute pancreatitis. However, recent large meta-analyses of clinical trial data do not support a class-wide risk. Denying these valuable therapeutic medications to patients with a history of pancreatitis seems unwarranted. CI - Copyright (c) 2025 The Cleveland Clinic Foundation. All Rights Reserved. FAU - Mehta, Adi E AU - Mehta AE AD - Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH mehtaae@ccf.org. FAU - Lomeli, Laura D AU - Lomeli LD AD - Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH; Osteopathic Medical Student Year 1, Ohio University Heritage College of Osteopathic Medicine, Cleveland Campus, Cleveland, OH. FAU - Pantalone, Kevin M AU - Pantalone KM AD - Director, Diabetes Initiatives, Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH. LA - eng PT - Journal Article PT - Review DEP - 20250801 PL - United States TA - Cleve Clin J Med JT - Cleveland Clinic journal of medicine JID - 8703441 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Cleve Clin J Med. 2025 Oct 1;92(10):593. PMID: 41033851 MH - Humans MH - *Pancreatitis/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy EDAT- 2025/08/02 10:42 MHDA- 2025/08/02 10:43 CRDT- 2025/08/01 21:42 PHST- 2025/08/02 10:43 [medline] PHST- 2025/08/02 10:42 [pubmed] PHST- 2025/08/01 21:42 [entrez] AID - 92/8/483 [pii] AID - 10.3949/ccjm.92a.24113 [doi] PST - epublish SO - Cleve Clin J Med. 2025 Aug 1;92(8):483-489. doi: 10.3949/ccjm.92a.24113. PMID- 40746012 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis. PG - 5498-5505 LID - 10.1111/dom.16592 [doi] AB - AIM: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist for type 2 diabetes, chronic weight management and obstructive sleep apnoea (in the US). To assess the contribution of weight loss (WL) to the observed glycaemic effect, we performed mediation analysis of three randomized, controlled, parallel, 4-arm SURPASS(S)-trials; 1, 2 and 5, for a total of 2831 participants. MATERIALS AND METHODS: WL dependent (WL-D) and WL independent (WL-IND) effects on comparator-adjusted glycated haemoglobin A1c (HbA1c) reduction at Week 40 were estimated using mediation analysis, adjusted for baseline HbA1c and study-specific stratification factors. RESULTS: The difference in mean HbA1c change from baseline at 40 weeks (total effect) between tirzepatide and the placebo group ranged from -20.0 to -14.6 mmol/mol, and that between tirzepatide and semaglutide (1 mg) ranged from -5.1 to -1.9 mmol/mol. In the placebo-controlled trials, 12%-27% of the difference in HbA1c change between tirzepatide dose arms and placebo was estimated as being mediated through WL when given as monotherapy (S1), and 25%-45% when on the background of insulin with or without metformin (S5). Compared with semaglutide, 54%-71% of the difference in HbA1c change between tirzepatide and semaglutide was estimated as being WL-D. CONCLUSION: The tirzepatide-induced HbA1c reductions from baseline, compared with placebo or semaglutide, were mediated through both WL-D and WL-IND effects. Estimated contributions of WL to the difference in glycaemic efficacy varied and were highest when tirzepatide was compared with semaglutide and less pronounced when compared with placebo. These results help to understand that other factors beyond weight reduction contribute to HbA1c reduction with tirzepatide. CI - (c) 2025 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Research, Steno Diabetes Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Malecki, Maciej T AU - Malecki MT AD - Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland. FAU - Sharma, Palash AU - Sharma P AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thieu, Vivian T AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Chivukula, Krishna Karthik AU - Chivukula KK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kiljanski, Jacek AU - Kiljanski J AUID- ORCID: 0000-0003-0354-0558 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article DEP - 20250731 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - *Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12409195 OTO - NOTNLM OT - HbA1c OT - SURPASS studies OT - mediation analysis OT - tirzepatide OT - weight loss OT - weight-loss dependent effects OT - weight-loss independent effects COIS- TV has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, Astra-Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals, and Zealand Pharma. MTM has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Abbott, AstraZeneca, Ascentia, Adamed, Bayer, Berlin-Chemie, Boehringer Ingelheim, Dexcom, Eli Lilly and Company, Krka, Medtronic, Merck, Novo Nordisk, Sanofi, and Servier. PS, VTT, KC, and JK are all employees and shareholders of Eli Lilly and Company. EDAT- 2025/08/01 06:28 MHDA- 2025/09/04 06:36 PMCR- 2025/09/04 CRDT- 2025/08/01 02:42 PHST- 2025/06/12 00:00 [revised] PHST- 2025/03/26 00:00 [received] PHST- 2025/06/24 00:00 [accepted] PHST- 2025/09/04 06:36 [medline] PHST- 2025/08/01 06:28 [pubmed] PHST- 2025/08/01 02:42 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16592 [pii] AID - 10.1111/dom.16592 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5498-5505. doi: 10.1111/dom.16592. Epub 2025 Jul 31. PMID- 40738102 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260609 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 6 IP - 9 DP - 2025 Sep 12 TI - Recognizing overweight and obesity as chronic diseases and acknowledging root causes. PG - 100782 LID - S2666-6340(25)00209-0 [pii] LID - 10.1016/j.medj.2025.100782 [doi] AB - As obesity increases in the global population, it is important to recognize that obesity is not a willpower failure but a chronic disease regulated by genetic, environmental, and hormonal control of energy balance. Obesity is also caused by social and political factors, including poor regulation of the food industry and lack of access to healthy, affordable foods. To de-stigmatize obesity, we need to understand and teach the pathophysiology of overweight and obesity in the same way we teach the pathophysiology of cardiovascular disease or type 2 diabetes. The controversy surrounding the need for new incretin-mimetic obesity medications illustrates the lack of understanding of obesity as a chronic disease. While we may not be able to change social conditions, modify genetic or environmental factors, or regulate the food industry, we can de-stigmatize obesity and overweight in our clinics and offer appropriate treatment. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Falahee, Bryn E AU - Falahee BE AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. FAU - Kim, Dong Wook AU - Kim DW AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. FAU - Apovian, Caroline M AU - Apovian CM AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: capovian@mgb.org. LA - eng PT - Journal Article PT - Review DEP - 20250729 PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 SB - IM MH - Humans MH - *Obesity/etiology/physiopathology/complications MH - Chronic Disease MH - *Overweight/physiopathology/etiology/complications MH - Diabetes Mellitus, Type 2/etiology MH - Cardiovascular Diseases/etiology OTO - NOTNLM OT - Obesity OT - Semaglutide OT - anti-obesity medications OT - chronic disease OT - food policy OT - hormonal control of metabolism OT - social determinants of health OT - tirzepatide COIS- Declaration of interests C.M.A. reports serving on advisory boards for Altimmune, Inc., BioAge, Bioinq, CinFina Pharma, Inc., Cowen and Company, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Gelesis, Srl., Lilly USA, LLC, L-Nutra, Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences, Inc., Riverview School, Roman Health, Vida Ventures, Inc., Veru, Inc., Wave Life Sciences, and Xeno Biosciences. EDAT- 2025/07/31 00:28 MHDA- 2025/09/16 13:02 CRDT- 2025/07/30 18:42 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/11 00:00 [revised] PHST- 2025/07/03 00:00 [accepted] PHST- 2025/09/16 13:02 [medline] PHST- 2025/07/31 00:28 [pubmed] PHST- 2025/07/30 18:42 [entrez] AID - S2666-6340(25)00209-0 [pii] AID - 10.1016/j.medj.2025.100782 [doi] PST - ppublish SO - Med. 2025 Sep 12;6(9):100782. doi: 10.1016/j.medj.2025.100782. Epub 2025 Jul 29. PMID- 40737110 OWN - NLM STAT- MEDLINE DCOM- 20250919 LR - 20251017 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 10 DP - 2025 Oct 1 TI - Risk of Phimosis Associated With SGLT2i Versus GLP-1RA: A Danish Cohort Study. PG - 1774-1782 LID - 10.2337/dc25-0693 [doi] AB - OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide 1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS: In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS: In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS: SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use. CI - (c) 2025 by the American Diabetes Association. FAU - Ljungberg, Christine AU - Ljungberg C AUID- ORCID: 0009-0004-7226-2488 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Norgaard, Mette AU - Norgaard M AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Vandenbroucke-Grauls, Christina AU - Vandenbroucke-Grauls C AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. AD - Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Amsterdam, the Netherlands. FAU - Jakobsen, Jakob Kristian AU - Jakobsen JK AD - Department of Urology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Charles, Morten Haaning AU - Charles MH AD - Department of Public Health, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Pottegard, Anton AU - Pottegard A AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark. FAU - Dalager-Pedersen, Michael AU - Dalager-Pedersen M AD - Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Sorensen, Henrik Toft AU - Sorensen HT AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Epidemiology, Center for Population Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Thomsen, Reimar Wernich AU - Thomsen RW AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. LA - eng GR - Aarhus University/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Denmark/epidemiology MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cohort Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Hypoglycemic Agents/therapeutic use/adverse effects EDAT- 2025/07/30 18:28 MHDA- 2025/09/19 18:30 CRDT- 2025/07/30 12:22 PHST- 2025/03/21 00:00 [received] PHST- 2025/07/03 00:00 [accepted] PHST- 2025/09/19 18:30 [medline] PHST- 2025/07/30 18:28 [pubmed] PHST- 2025/07/30 12:22 [entrez] AID - 163054 [pii] AID - 10.2337/dc25-0693 [doi] PST - ppublish SO - Diabetes Care. 2025 Oct 1;48(10):1774-1782. doi: 10.2337/dc25-0693. PMID- 40736924 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20251108 IS - 1534-6242 (Electronic) IS - 1523-3804 (Print) IS - 1523-3804 (Linking) VI - 27 IP - 1 DP - 2025 Jul 30 TI - The Expanding Scope of GLP-1 Receptor Agonists: Six Uses Beyond Diabetes. PG - 76 LID - 10.1007/s11883-025-01319-6 [doi] AB - PURPOSE OF REVIEW: This review summarizes recent advances in the clinical applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond their established role in glycemic control for type 2 diabetes (T2DM). RECENT FINDINGS: Originally developed for glycemic control in T2DM, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now being utilized for a range of additional diseases and conditions. Strong evidence supports their efficacy in inducing clinically meaningful weight loss in individuals with overweight or obesity. Further studies have demonstrated cardiovascular benefits, kidney-protective effects, and therapeutic potential in obesity-related conditions such as obstructive sleep apnea and metabolic-associated steatotic liver disease. Emerging data also suggest possible roles in treating substance use disorders, including alcohol and nicotine dependence, though findings remain preliminary and variable. Despite these promising developments, GLP-1RAs are associated with side effects and high costs, contributing to variability in patient access. The therapeutic scope of GLP-1 receptor agonists extends beyond diabetes to multiple other conditions. Broader adoption requires careful evaluation of safety, cost, and evidence for less-established indications. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Sheth, Kyle AU - Sheth K AD - School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Kim, Stephanie AU - Kim S AD - School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Porterfield, Laura AU - Porterfield L AD - Department of Family Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Virani, Salim S AU - Virani SS AD - Section of Cardiology, Department of Medicine, Aga Khan University, Karachi, Pakistan. AD - Department of Population Health, Aga Khan University, Nairobi, Kenya. FAU - Wadhwani, Shikha AU - Wadhwani S AD - Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA. FAU - Vaughan, Elizabeth M AU - Vaughan EM AD - Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA. emvaugha@utmb.edu. AD - Department of Medicine, Baylor College of Medicine, Houston, TX, USA. emvaugha@utmb.edu. LA - eng GR - R01 DK129474/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20250730 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12590185 MID - NIHMS2119904 OTO - NOTNLM OT - Chronic kidney disease OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse cardiovascular events OT - Metabolic dysfunction-associated steatotic liver disease OT - Obesity OT - Obstructive sleep apnea COIS- Declarations. Human and Animal Rights and Informed Consent: This article is a narrative review of previously published studies; therefore, ethical approval and informed consent were not required. Competing Interests: The authors declare no competing interests. Topical Collection on Coronary Heart Disease: The Section Editors for the Topical Collection Coronary Heart Disease are Salim Virani and Mahmoud Al-Rifai. Please note that Section Editor, Salim Virani was not involved in the editorial process of this article as he is a co-author. EDAT- 2025/07/30 12:30 MHDA- 2025/07/30 18:28 PMCR- 2025/11/06 CRDT- 2025/07/30 11:53 PHST- 2025/07/03 00:00 [accepted] PHST- 2025/07/30 18:28 [medline] PHST- 2025/07/30 12:30 [pubmed] PHST- 2025/07/30 11:53 [entrez] PHST- 2025/11/06 00:00 [pmc-release] AID - 10.1007/s11883-025-01319-6 [pii] AID - 10.1007/s11883-025-01319-6 [doi] PST - epublish SO - Curr Atheroscler Rep. 2025 Jul 30;27(1):76. doi: 10.1007/s11883-025-01319-6. PMID- 40735942 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Association of GLP1-receptor agonist use with liver disease progression, major cardiovascular events, and mortality in people with hepatic steatosis and diabetes. PG - 5971-5984 LID - 10.1111/dom.16657 [doi] AB - AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease in the United States. MASLD can progress to liver cirrhosis and is associated with an increased risk of major acute cardiovascular events (MACE). This study aimed to examine the association of glucagon-like peptide-1 receptor agonists (GLP1-RA) use with liver disease progression, MACE, and death from any cause among people with hepatic steatosis. MATERIALS AND METHODS: This retrospective cohort study using national data from the Department of Veteran Affairs included people with non-alcoholic hepatic steatosis who initiated either GLP1-RA or dipeptidyl-peptidase-4 inhibitor (DPP4i) between 1 October 2005 and 30 September 2021. Primary outcomes were: (1) liver disease progression and (2) MACE and death from any cause (MACE/death). GLP1-RA users and DPP4i users were propensity score matched on 73 baseline characteristics. RESULTS: We matched 58 157 pairs of GLP1-RA and DPP4i users. GLP1-RA users had less liver disease progression (6.1%) compared with DPP4i users (7.0%), odds ratio (OR): 0.86; 95% confidence interval (95% CI): 0.82-0.90 and a lower risk of MACE/death (11.1% vs. 14.7%, respectively), OR: 0.72; 95% CI: 0.70-0.75. The number needed to treat to prevent one additional liver disease progression and MACE/death was 109 and 27 people, respectively. CONCLUSIONS: Among people with diabetes and hepatic steatosis, GLP1-RA use was associated with a lower risk of liver disease progression and a lower risk of MACE/death compared to DPP4i use. In people with MASLD, a holistic approach that seeks to lower MACE/death, beyond lowering liver disease progression alone, should be prioritised. CI - Published 2025. This article is a U.S. Government work and is in the public domain in the USA. FAU - Al Ashi, Suleiman AU - Al Ashi S AD - Endocrinology, Diabetes, and Metabolism Fellowship, University of Central Florida HCA Healthcare GME, Greater Orlando, Florida, USA. AD - Section of Endocrinology, Orlando VA Medical Center, Orlando, Florida, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA. FAU - Shah, Raj AU - Shah R AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA. AD - Section of Gastroenterology and Hepatology, Orlando VA Healthcare System, Orlando, Florida, USA. AD - Gastroenterology Fellowship, University of Central Florida/HCA Florida Healthcare, Florida, USA. FAU - Iftikhar, Nofel AU - Iftikhar N AD - College of Liberal Arts and Sciences, University of Florida, Gainesville, Florida, USA. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology, UT Southwestern Medical Center, Dallas, Texas, USA. AD - Peter O'Donnell Jr School of Public, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Kinaan, Mustafa AU - Kinaan M AD - Endocrinology, Diabetes, and Metabolism Fellowship, University of Central Florida HCA Healthcare GME, Greater Orlando, Florida, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA. FAU - Mansi, Ishak A AU - Mansi IA AUID- ORCID: 0000-0001-6122-3716 AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA. AD - Education Service, Orlando VA Healthcare System, Orlando, Florida, USA. LA - eng PT - Journal Article DEP - 20250730 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Disease Progression MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Cardiovascular Diseases/mortality/epidemiology/etiology MH - *Non-alcoholic Fatty Liver Disease/mortality/drug therapy/complications/pathology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - United States/epidemiology OTO - NOTNLM OT - cardiovascular disease OT - diabetes complications OT - fatty liver disease OT - glucagon-like peptide-1 receptor agonists OT - liver cirrhosis OT - mortality EDAT- 2025/07/30 12:30 MHDA- 2025/09/04 06:37 CRDT- 2025/07/30 06:52 PHST- 2025/07/16 00:00 [revised] PHST- 2025/06/16 00:00 [received] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/30 12:30 [pubmed] PHST- 2025/07/30 06:52 [entrez] AID - 10.1111/dom.16657 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5971-5984. doi: 10.1111/dom.16657. Epub 2025 Jul 30. PMID- 40735916 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Glycemic therapies and the risk of gastrointestinal adverse events in veterans with type 2 diabetes. PG - 5865-5877 LID - 10.1111/dom.16642 [doi] AB - AIMS: To compare the risk of gastrointestinal adverse events in new users of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and insulin glargine. MATERIALS AND METHODS: We conducted an active comparator, new user design study in veterans with type 2 diabetes who initiated one of these drug classes between 1 January 2018 and 31 December 2021 (N = 141 080). Inverse probability weighted Cox regression models were used to relate drug class to outcomes of gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis and all-cause death. RESULTS: There were 19 765 (14.0%) veterans initiated on GLP-1RA, 75 058 (53.2%) on SGLT2i and 46 257 (32.8%) on insulin glargine. Compared to SGLT2i, GLP-1RA had a higher hazard of gastroparesis (HR 1.65, 95% CI 1.33-2.05) but a similar mortality hazard. Compared to insulin glargine, GLP-1RA had a higher hazard of gastroparesis (HR 1.24, 95% CI 1.02, 1.52), but a lower hazard of all-cause death (HR 0.62, 95% CI 0.58, 0.66). Compared to SGLT2i, insulin glargine had a higher hazard of gastroparesis (HR 1.29, 95% CI 1.07, 1.56), intestinal obstruction (HR 1.26, 95% CI 1.11, 1.43) and all-cause death (HR 1.58, 95% CI 1.50, 1.65). Risks of gallstones, acute cholecystitis and pancreatitis were similar across the classes. CONCLUSIONS: In patients with type 2 diabetes at risk for gastroparesis, SGLT2i might be the preferred agent. In patients for whom SGLT2i is not an option or another agent is needed, patients and providers might need to weigh the higher risk of death with insulin glargine against the higher risk of gastroparesis with GLP-1RA. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Sarwal, Amara AU - Sarwal A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Singh, Ravinder AU - Singh R AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Wei, Guo AU - Wei G AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Shen, Jincheng AU - Shen J AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Nevers, McKenna AU - Nevers M AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Informatics, Decision-Enhancement, and Analytic Sciences (IDEAS) Center of Innovation, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah, USA. FAU - Hartsell, Sydney E AU - Hartsell SE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Derington, Catherine G AU - Derington CG AD - Division of Cardiology, Department of Medicine, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Takyi, Augustine AU - Takyi A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Chakravartula, Akhil R AU - Chakravartula AR AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Katkam, Niharika AU - Katkam N AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Boucher, Robert E AU - Boucher RE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Drakos, Stavros G AU - Drakos SG AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Greene, Tom AU - Greene T AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Beddhu, Srinivasan AU - Beddhu S AUID- ORCID: 0000-0002-3312-315X AD - Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal & Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah, USA. LA - eng GR - UM1TR004409/TR/NCATS NIH HHS/United States GR - UL1 RR025764/RR/NCRR NIH HHS/United States GR - 8UL1TR000105/TR/NCATS NIH HHS/United States GR - UM1 TR004409/TR/NCATS NIH HHS/United States GR - 5UL1TR001067-05/TR/NCATS NIH HHS/United States GR - R01 AG074592/AG/NIA NIH HHS/United States GR - R01 DK128640/DK/NIDDK NIH HHS/United States GR - UL1 TR000105/TR/NCATS NIH HHS/United States GR - UL1RR025764/TR/NCATS NIH HHS/United States GR - Veterans Health Administration Office of Rural Health/ GR - UL1 TR001067/TR/NCATS NIH HHS/United States GR - T32 HL007576/HL/NHLBI NIH HHS/United States GR - T35 DK103596/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20250730 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Veterans/statistics & numerical data MH - Middle Aged MH - *Insulin Glargine/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Aged MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Risk Factors PMC - PMC12409243 OTO - NOTNLM OT - GLP-1 OT - SGLT2 inhibitor OT - antidiabetic drug OT - database research OT - insulin glargine COIS- SB received research support from Bayer, Novo Nordisk and Boehringer Ingelheim. SD is a consultant with Abbott and receives research support from Novartis. EDAT- 2025/07/30 12:30 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/07/30 06:24 PHST- 2025/07/07 00:00 [revised] PHST- 2025/03/19 00:00 [received] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/30 12:30 [pubmed] PHST- 2025/07/30 06:24 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16642 [pii] AID - 10.1111/dom.16642 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5865-5877. doi: 10.1111/dom.16642. Epub 2025 Jul 30. PMID- 40732973 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 17 IP - 14 DP - 2025 Jul 17 TI - Clinical Effectiveness of Oral Semaglutide in Women with Type 2 Diabetes: A Nationwide, Multicentre, Retrospective, Observational Study (Women_ENDO2S-RWD Substudy). LID - 10.3390/nu17142349 [doi] LID - 2349 AB - Background: Sex differences in type 2 diabetes (T2D) are a growing area of diabetes research. No data have been reported on sex differences with oral semaglutide (oSEMA) in a real-world setting. Methods: We included people with T2D who started treatment with oSEMA in routine clinical practice between November 2021 and November 2022, with at least one report of clinical follow-up (FU) data at 3 months. We evaluated in women with T2D (WWT2D) the clinical effectiveness of oSEMA and factors associated with clinical response and persistence. We also analyzed differences in baseline characteristics, clinical effectiveness, persistence rates and safety according to biological sex. Results: Of the 1018 subjects [median age: 63 years, body mass index (BMI): 33.8 kg/m(2), HbA1c: 7.8%], 469 were WWT2D. In WWT2D, oSEMA reduced HbA1c by 0.7% [-0.1 to -1.3] and 0.9% [-0.2 to -1.5] at the 6- and 12-month FU visits, while weight decreased by 4.6% [2.0 to 7.9] and 7.2% [2.5 to 10.9], respectively. Weight loss was >10% in 29.8% of WWT2D (95% CI 25.8 to 34.1); meanwhile, the combined endpoint (HbA1c decrease >/= 1% + weight reduction >/= 5%) was achieved in 23.5% (95% CI 19.8 to 27.5%) of WWT2D at the 12-month FU visit. Achievement of glycaemic targets was similar in women and men (59.3% vs. 61.1%). We found no sex differences in weight loss (6.9% vs. 6.8%), oSEMA maintenance dose, persistence rate (76.3% vs. 77.3%), or adverse events. Conclusions: oSEMA was effective and safe in WWT2D in a real-world setting, with nearly one-third of patients reporting weight loss >10% and more than two-thirds achieving HbA1c < 7%. oSEMA showed no sex bias in terms of effectiveness and safety. FAU - Reyes-Garcia, Rebeca AU - Reyes-Garcia R AUID- ORCID: 0000-0003-1729-4431 AD - Endocrinology Unit, University Hospital of Torrecardenas, 04009 Almeria, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable "CIBERFES", Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AUID- ORCID: 0000-0002-8670-6404 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, 03550 Elche, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AUID- ORCID: 0000-0002-6803-6988 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. FAU - Modrego-Pardo, Ines AU - Modrego-Pardo I AUID- ORCID: 0000-0003-3060-449X AD - Department of Endocrinology and Nutrition, Marina Baixa Hospital, 03570 Villajoyosa, Spain. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AUID- ORCID: 0000-0002-0178-0040 AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, 29010 Malaga, Spain. AD - Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain. FAU - Casado Cases, Carlos AU - Casado Cases C AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, 28040 Madrid, Spain. FAU - Arias Mendoza, Nieves AU - Arias Mendoza N AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, 03600 Alicante, Spain. FAU - Tejera-Perez, Cristina AU - Tejera-Perez C AUID- ORCID: 0000-0002-2987-5922 AD - Department of Endocrinology and Nutrition, University Hospital Complex of Ferrol, 15405 A Coruna, Spain. FAU - Cardenas-Salas, Jersy AU - Cardenas-Salas J AUID- ORCID: 0000-0002-2485-484X AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, 28040 Madrid, Spain. FAU - Martinez-Fuster, Sandra AU - Martinez-Fuster S AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, 03600 Alicante, Spain. FAU - Lardies-Sanchez, Beatriz AU - Lardies-Sanchez B AD - Department of Endocrinology and Nutrition, Obispo Polanco Hospital, 44002 Teruel, Spain. FAU - Marquez-Pardo, Rosa AU - Marquez-Pardo R AUID- ORCID: 0000-0002-4914-4131 AD - Department of Endocrinology and Nutrition, Hospital Juan Ramon Jimenez, 21005 Huelva, Spain. FAU - Pines, Pedro AU - Pines P AD - Department of Endocrinology and Nutrition, Albacete University Hospital Complex, 02006 Albacete, Spain. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AUID- ORCID: 0000-0002-7954-5753 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. AD - Health Science Faculty-HM Hospitals, Camilo Jose Cela University, 28692 Madrid, Spain. AD - HM Hospitals Health Research Institute, 28015 Madrid, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, 29010 Malaga, Spain. AD - Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas, Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - On Behalf Of The Seen Diabetes Area AU - On Behalf Of The Seen Diabetes Area LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250717 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Retrospective Studies MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Aged MH - Treatment Outcome MH - Blood Glucose/drug effects MH - Male MH - Sex Factors MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12300082 OTO - NOTNLM OT - GLP-1 Agonist OT - cardiovascular disease OT - effectiveness OT - real life OT - women COIS- R.R.-G. has received honoraria as speaker and consulting fees by from Eli Lilly, Astra Zeneca, Dexcom and Novo Nordisk; O.M.-P. has received honoraria as speaker and consulting fees by from Eli Lilly, Boehringer-Ingelheim, Astra Zeneca and Novo Nordisk; C.T.-P. received honoraria as speaker and consulting fees by NovoNordisk, Astra Zeneca, Eli Lilly, Boehringer-Ingelheim, Esteve, MSD and Abbott; J.C.F.-G. has received speaker honoraria from Novo Nordisk, Lilly, Boehringer-Ingelheim, Esteve, Menarini, and AstraZeneca; J.C.-S. has received speaker honoraria from Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Sanofi Aventis and AstraZeneca; B.L.-S. has received honoraria as a speaker by from Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Lilly, Merck Sharp & Dohme, Sanofi and Mundipharma; P.P. has received honoraria as a speaker by from Astra Zeneca, Boehringer-Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, and Sanofi; IM-P has received speaker honoraria from Novo Nordisk, Nestle and AstraZeneca; V.K.D.-G., N.A.M., S.M.-F., C.G.-M., C.C.C. and R.M.-P. have no conflicts of interest. EDAT- 2025/07/30 06:30 MHDA- 2025/07/30 06:31 PMCR- 2025/07/17 CRDT- 2025/07/30 01:13 PHST- 2025/06/05 00:00 [received] PHST- 2025/07/03 00:00 [revised] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/07/30 06:31 [medline] PHST- 2025/07/30 06:30 [pubmed] PHST- 2025/07/30 01:13 [entrez] PHST- 2025/07/17 00:00 [pmc-release] AID - nu17142349 [pii] AID - nutrients-17-02349 [pii] AID - 10.3390/nu17142349 [doi] PST - epublish SO - Nutrients. 2025 Jul 17;17(14):2349. doi: 10.3390/nu17142349. PMID- 40730031 OWN - NLM STAT- MEDLINE DCOM- 20251020 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 11 DP - 2025 Nov 1 TI - Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis. PG - 1878-1887 LID - 10.2337/dc25-0472 [doi] AB - OBJECTIVE: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use. RESEARCH DESIGN AND METHODS: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent >/=50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended. RESULTS: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile of semaglutide was comparable between subgroups. CONCLUSIONS: In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use. CI - (c) 2025 by the American Diabetes Association. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - University of Copenhagen, Copenhagen, Denmark. FAU - Bakris, George AU - Bakris G AD - University of Chicago Medicine, Chicago, IL. FAU - Perkovic, Vlado AU - Perkovic V AD - University of New South Wales, Sydney, Australia. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, FL. FAU - Tuttle, Katherine R AU - Tuttle KR AD - University of Washington, Seattle, WA. AD - Providence Inland Northwest Health, Spokane, WA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Palo Alto, CA. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Busch, Robert S AU - Busch RS AD - Albany Medical College, Albany, NY. FAU - Schmieder, Ronald E AU - Schmieder RE AD - University Hospital Erlangen, Erlangen, Germany. FAU - Gillard, Pieter AU - Gillard P AD - Department of Endocrinology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. FAU - Mann, Johannes F E AU - Mann JFE AD - University Hospital Erlangen, Erlangen, Germany. AD - KfH Kidney Centre, Munich, Germany. CN - FLOW Investigator Group LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Diabetes Care. 2025 Nov 1;48(11):1875-1877. doi: 10.2337/dci25-0088. PMID: 41115233 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - *Renal Insufficiency, Chronic/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - *Mineralocorticoid Receptor Antagonists/therapeutic use MH - Aged MH - Glomerular Filtration Rate/drug effects MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12583412 FIR - Porto, A IR - Porto A FIR - Oviedo, A IR - Oviedo A FIR - Elbert, A IR - Elbert A FIR - Gelersztein, E IR - Gelersztein E FIR - Chertkoff, A IR - Chertkoff A FIR - Wassermann, A IR - Wassermann A FIR - Quevedo, M A IR - Quevedo MA FIR - MacIsaac, R IR - MacIsaac R FIR - Roger, S IR - Roger S FIR - Phoon, R IR - Phoon R FIR - Kerr, P IR - Kerr P FIR - Ajani, A IR - Ajani A FIR - Tan, S J IR - Tan SJ FIR - Colquhoun, D IR - Colquhoun D FIR - Mather, A IR - Mather A FIR - Gillard, P IR - Gillard P FIR - De Block, C IR - De Block C FIR - Debroye, C IR - Debroye C FIR - Duyck, F IR - Duyck F FIR - Krzesinski, J M IR - Krzesinski JM FIR - Lapauw, B IR - Lapauw B FIR - Preumont, V IR - Preumont V FIR - Vercammen, C IR - Vercammen C FIR - Kamenov, Z IR - Kamenov Z FIR - Bobeva, R IR - Bobeva R FIR - Levterov, G IR - Levterov G FIR - Gerilovska, S IR - Gerilovska S FIR - Yabrudi, N IR - Yabrudi N FIR - Stoyanovska-Elencheva, B IR - Stoyanovska-Elencheva B FIR - Nikitov, Z IR - Nikitov Z FIR - Franco, D IR - Franco D FIR - Akerman Augusto, G IR - Akerman Augusto G FIR - Salles, J IR - Salles J FIR - Canani, L IR - Canani L FIR - Krakauer, M IR - Krakauer M FIR - Cerqueira, M J IR - Cerqueira MJ FIR - Riella, M IR - Riella M FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Ajala, B IR - Ajala B FIR - Aggarwal, N IR - Aggarwal N FIR - Dumas, R IR - Dumas R FIR - O'Keefe, D IR - O'Keefe D FIR - Peterson, S IR - Peterson S FIR - Tsoukas, G IR - Tsoukas G FIR - Tailor, C IR - Tailor C FIR - Tytus, R IR - Tytus R FIR - Akhras, R IR - Akhras R FIR - Khandwala, H IR - Khandwala H FIR - Steen, O IR - Steen O FIR - Carbonneau, D IR - Carbonneau D FIR - Cha, J IR - Cha J FIR - Steele, A IR - Steele A FIR - Bailey, G IR - Bailey G FIR - Berlingieri, J IR - Berlingieri J FIR - Dzongowski, P IR - Dzongowski P FIR - Cherney, D IR - Cherney D FIR - Elliott, T IR - Elliott T FIR - Kovacs, C IR - Kovacs C FIR - Hamet, P IR - Hamet P FIR - Perkins, B IR - Perkins B FIR - Tennankore, K IR - Tennankore K FIR - Gupta, A IR - Gupta A FIR - Ji, L IR - Ji L FIR - Li, Y IR - Li Y FIR - Yuan, G IR - Yuan G FIR - Dong, X IR - Dong X FIR - Cariou, B IR - Cariou B FIR - Clavel, S IR - Clavel S FIR - Marchand, L IR - Marchand L FIR - Reznik, Y IR - Reznik Y FIR - Moulin, P IR - Moulin P FIR - Legrand, E IR - Legrand E FIR - Benoit Tricaud, I IR - Benoit Tricaud I FIR - Gourdy, P IR - Gourdy P FIR - Zaoui, P IR - Zaoui P FIR - Monier, A IR - Monier A FIR - Kazes, I IR - Kazes I FIR - Dahl, D IR - Dahl D FIR - Esser, M IR - Esser M FIR - Kruger, T IR - Kruger T FIR - Rose, L IR - Rose L FIR - Schmieder, R IR - Schmieder R FIR - Segner, A IR - Segner A FIR - Lee-Barkey, Y H IR - Lee-Barkey YH FIR - Vidal, S IR - Vidal S FIR - Schurholz, T IR - Schurholz T FIR - Boletis, I IR - Boletis I FIR - Raptis, A IR - Raptis A FIR - Lanaras, L IR - Lanaras L FIR - Pagkalos, E IR - Pagkalos E FIR - Doupis, J IR - Doupis J FIR - Bekiari, E IR - Bekiari E FIR - Goumenos, D IR - Goumenos D FIR - Papadopoulou, D IR - Papadopoulou D FIR - Tziomalos, K IR - Tziomalos K FIR - Karousos, G IR - Karousos G FIR - Somali, M IR - Somali M FIR - Markou, A IR - Markou A FIR - Zografou, I IR - Zografou I FIR - Wittmann, I IR - Wittmann I FIR - Brasnyo, P IR - Brasnyo P FIR - Balla, J IR - Balla J FIR - Petro, G IR - Petro G FIR - Baranyai, M IR - Baranyai M FIR - Dudas, M IR - Dudas M FIR - Vangel, S IR - Vangel S FIR - Konyves, L IR - Konyves L FIR - Vasas, S IR - Vasas S FIR - Tanczer, T IR - Tanczer T FIR - Shah, M IR - Shah M FIR - Anil, B T IR - Anil BT FIR - Bhalla, A IR - Bhalla A FIR - Gireesh, M S IR - Gireesh MS FIR - Prasad, N IR - Prasad N FIR - Sahay, M IR - Sahay M FIR - Jamale, T IR - Jamale T FIR - Jain, M IR - Jain M FIR - Magdum, M IR - Magdum M FIR - Dewan, D IR - Dewan D FIR - Dinesh, K IR - Dinesh K FIR - Kumar, H IR - Kumar H FIR - Jayakumar, K IR - Jayakumar K FIR - Murthy, S IR - Murthy S FIR - Srikanth, K IR - Srikanth K FIR - Gupta, S IR - Gupta S FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Wainstein, J IR - Wainstein J FIR - Chernin, G IR - Chernin G FIR - Kenis, I IR - Kenis I FIR - Trevisan, R IR - Trevisan R FIR - Bosi, E IR - Bosi E FIR - Setola, E IR - Setola E FIR - Fiorina, P IR - Fiorina P FIR - Penno, G IR - Penno G FIR - Pugliese, G IR - Pugliese G FIR - Giordano, C IR - Giordano C FIR - Orsi, E IR - Orsi E FIR - Cavallo, M G IR - Cavallo MG FIR - Tsuchida, K IR - Tsuchida K FIR - Sasaki, T IR - Sasaki T FIR - Seino, H IR - Seino H FIR - Kawada, T IR - Kawada T FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Shimizu, Y IR - Shimizu Y FIR - Mitomo, S IR - Mitomo S FIR - Nakamura, C IR - Nakamura C FIR - Takai, K IR - Takai K FIR - Maeda, H IR - Maeda H FIR - Nishi, H IR - Nishi H FIR - Nishida, Y IR - Nishida Y FIR - Yamada, M IR - Yamada M FIR - Fukushima, Y IR - Fukushima Y FIR - Kato, M IR - Kato M FIR - Sugawara, M IR - Sugawara M FIR - Araki, H IR - Araki H FIR - Nakagawa, A IR - Nakagawa A FIR - Onaka, H IR - Onaka H FIR - Sueyoshi, A IR - Sueyoshi A FIR - Kidokoro, K IR - Kidokoro K FIR - Tanabe, M IR - Tanabe M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Hasumi, S IR - Hasumi S FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Aguilar Salinas, C IR - Aguilar Salinas C FIR - Morales de Teresa, M IR - Morales de Teresa M FIR - Violante Ortiz, R M IR - Violante Ortiz RM FIR - Correa Rotter, J IR - Correa Rotter J FIR - Irizar Santana, S IR - Irizar Santana S FIR - Lim, S K IR - Lim SK FIR - Yoon, C K IR - Yoon CK FIR - Tan, F IR - Tan F FIR - Goh, B L IR - Goh BL FIR - Loh, C L IR - Loh CL FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Bax, W A IR - Bax WA FIR - van Raalte, D IR - van Raalte D FIR - Luik, P T IR - Luik PT FIR - de Vries, P A M IR - de Vries PAM FIR - Dorresteijn, J IR - Dorresteijn J FIR - AlHakim, M IR - AlHakim M FIR - van Wissen, S IR - van Wissen S FIR - Kamphuisen, P IR - Kamphuisen P FIR - Verhave, J IR - Verhave J FIR - Gumprecht, J IR - Gumprecht J FIR - Majcher-Witczak, G IR - Majcher-Witczak G FIR - Mlodawska-Choluj, D IR - Mlodawska-Choluj D FIR - Stompor, T IR - Stompor T FIR - Ciechanowski, W K IR - Ciechanowski WK FIR - Malecki, R IR - Malecki R FIR - Wasilewska, K IR - Wasilewska K FIR - Shamkhalova, M IR - Shamkhalova M FIR - Ruyatkina, L IR - Ruyatkina L FIR - Vagapova, G IR - Vagapova G FIR - Sergeeva-Kondrachenko, M IR - Sergeeva-Kondrachenko M FIR - Kargina, L IR - Kargina L FIR - Peskov, A IR - Peskov A FIR - Zhdanova, E IR - Zhdanova E FIR - Lysenko, T IR - Lysenko T FIR - Frolova, E IR - Frolova E FIR - Mishchenko, O IR - Mishchenko O FIR - Belousova, L IR - Belousova L FIR - Astamirova, K IR - Astamirova K FIR - Antonova, E IR - Antonova E FIR - Pergaeva, Y IR - Pergaeva Y FIR - Palyutin, S IR - Palyutin S FIR - Krasnopeeva Kabachkova, A N IR - Krasnopeeva Kabachkova AN FIR - Tyugaeva, A IR - Tyugaeva A FIR - Krasilnikova, E IR - Krasilnikova E FIR - Romasheva, E IR - Romasheva E FIR - Sorokin, M IR - Sorokin M FIR - Martinka, E IR - Martinka E FIR - Ilavska, A IR - Ilavska A FIR - Tomasova, L IR - Tomasova L FIR - Porubska, K IR - Porubska K FIR - Skripova, D IR - Skripova D FIR - Buganova, I IR - Buganova I FIR - Rociakova, J IR - Rociakova J FIR - Rosenberger, J IR - Rosenberger J FIR - Pavelcikova, A IR - Pavelcikova A FIR - Smik, R IR - Smik R FIR - Gorriz, J IR - Gorriz J FIR - Castro, C IR - Castro C FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soler, M IR - Soler M FIR - Martins, J IR - Martins J FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Phornphutkul, M IR - Phornphutkul M FIR - Supasyndh, O IR - Supasyndh O FIR - Kiattisunthorn, K IR - Kiattisunthorn K FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Susantitaphong, P IR - Susantitaphong P FIR - Helvaci, O IR - Helvaci O FIR - Ates, K IR - Ates K FIR - Arikan, I IR - Arikan I FIR - Arici, M IR - Arici M FIR - Suleymanlar, G IR - Suleymanlar G FIR - Yazici, H IR - Yazici H FIR - Alisir Ecder, S IR - Alisir Ecder S FIR - Gungor, O IR - Gungor O FIR - Ok, E IR - Ok E FIR - Seyahi, N IR - Seyahi N FIR - Eren, N IR - Eren N FIR - Yenicerioglu, Y IR - Yenicerioglu Y FIR - Chabanna, O IR - Chabanna O FIR - Panina, S IR - Panina S FIR - Semenovykh, P IR - Semenovykh P FIR - Leonidova, V IR - Leonidova V FIR - Zinych, O IR - Zinych O FIR - Legun, O IR - Legun O FIR - Kaydashev, I IR - Kaydashev I FIR - Bellary, S IR - Bellary S FIR - Boyle, J IR - Boyle J FIR - Chen, M IR - Chen M FIR - Mcknight, J IR - Mcknight J FIR - Pearson, E IR - Pearson E FIR - Philip, S IR - Philip S FIR - Sharma, S IR - Sharma S FIR - Wakeling, J IR - Wakeling J FIR - Tindall, H IR - Tindall H FIR - Yousseif, A IR - Yousseif A FIR - Aw, T IR - Aw T FIR - Guerrero, A IR - Guerrero A FIR - Arif, A IR - Arif A FIR - Betts, J IR - Betts J FIR - Busch, R IR - Busch R FIR - Desouza, C IR - Desouza C FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Dukes, C IR - Dukes C FIR - Hammoud, J IR - Hammoud J FIR - Houser, P IR - Houser P FIR - Jackson, T IR - Jackson T FIR - Kayali, Z IR - Kayali Z FIR - Young, L IR - Young L FIR - Klein, E IR - Klein E FIR - Nicol, P IR - Nicol P FIR - Smith, S IR - Smith S FIR - Snyder, B IR - Snyder B FIR - Soroka, E IR - Soroka E FIR - Wysham, C IR - Wysham C FIR - Akyea-Djamson, A IR - Akyea-Djamson A FIR - Arauz-Pacheco, C IR - Arauz-Pacheco C FIR - Horeish, A IR - Horeish A FIR - Chang, A IR - Chang A FIR - Connery, L IR - Connery L FIR - Gandy, W IR - Gandy W FIR - Gilbert, M IR - Gilbert M FIR - Hernandez, G IR - Hernandez G FIR - Hewitt, M IR - Hewitt M FIR - Huffman, D IR - Huffman D FIR - Lovell, C IR - Lovell C FIR - Masani, N IR - Masani N FIR - McGill, J IR - McGill J FIR - Siddiqui, I IR - Siddiqui I FIR - Perez, R IR - Perez R FIR - Reed, J IR - Reed J FIR - Sivalingam, K IR - Sivalingam K FIR - London, J IR - London J FIR - Saha, S IR - Saha S FIR - Awad, A IR - Awad A FIR - Billings, L IR - Billings L FIR - Blaze, K IR - Blaze K FIR - Stricklin, D IR - Stricklin D FIR - Brinson, C IR - Brinson C FIR - Bornfreund, J IR - Bornfreund J FIR - McCall, N IR - McCall N FIR - Buynak, R IR - Buynak R FIR - Cannon, K IR - Cannon K FIR - Daboul, N IR - Daboul N FIR - Acosta, I IR - Acosta I FIR - Diaz, J IR - Diaz J FIR - Greenwood, G IR - Greenwood G FIR - Hart, T IR - Hart T FIR - Hasan, S IR - Hasan S FIR - Iranmanesh, A IR - Iranmanesh A FIR - Koilpillai, R IR - Koilpillai R FIR - Latif, K IR - Latif K FIR - Lawrence, M IR - Lawrence M FIR - Chen, C IR - Chen C FIR - Marar, I IR - Marar I FIR - East, C IR - East C FIR - Patel, R IR - Patel R FIR - Rovner, S IR - Rovner S FIR - Seco, G IR - Seco G FIR - Shaikh, Z IR - Shaikh Z FIR - Traylor, H IR - Traylor H FIR - Zieve, F IR - Zieve F FIR - Aroda, V IR - Aroda V FIR - Ahmed, A IR - Ahmed A FIR - Biscoveanu, M IR - Biscoveanu M FIR - Budoff, M IR - Budoff M FIR - ElShahawy, M IR - ElShahawy M FIR - Garza, J IR - Garza J FIR - Hanson, L IR - Hanson L FIR - Reddy, J IR - Reddy J FIR - Rodriguez, H IR - Rodriguez H FIR - Shrestha, A IR - Shrestha A FIR - Bernardo, M IR - Bernardo M FIR - Christensen, T IR - Christensen T FIR - Denker, P IR - Denker P FIR - Dua, S IR - Dua S FIR - El Shahawy, M IR - El Shahawy M FIR - Farias, A IR - Farias A FIR - Fernando, R IR - Fernando R FIR - Jamal, A IR - Jamal A FIR - Jardula, M IR - Jardula M FIR - Moustafa, M IR - Moustafa M FIR - Posada, J IR - Posada J FIR - Sanchez, W IR - Sanchez W FIR - Vega, D IR - Vega D FIR - Kumar, J IR - Kumar J FIR - Sultan, S IR - Sultan S FIR - Bansal, S IR - Bansal S FIR - Benjamin, S IR - Benjamin S FIR - Brusco, O IR - Brusco O FIR - Wayne, J IR - Wayne J FIR - Gaona, R IR - Gaona R FIR - Degani, O IR - Degani O FIR - Figueroa, C IR - Figueroa C FIR - Montero, M IR - Montero M FIR - Rasouli, N IR - Rasouli N FIR - Zemel, L IR - Zemel L FIR - Fadda, G IR - Fadda G FIR - Shlesinger, Y IR - Shlesinger Y FIR - Charytan, D IR - Charytan D FIR - Butuk, D IR - Butuk D FIR - Stringam, S IR - Stringam S FIR - Espinosa, V IR - Espinosa V FIR - Brandon, D IR - Brandon D FIR - Shea, H IR - Shea H FIR - Cheung, D IR - Cheung D FIR - Sanchez, Y IR - Sanchez Y FIR - Kudva, Y IR - Kudva Y FIR - Beddhu, S IR - Beddhu S FIR - Rayner, B IR - Rayner B FIR - Bhorat, Q IR - Bhorat Q FIR - Badat, A IR - Badat A FIR - Makan, H IR - Makan H FIR - Joshi, M IR - Joshi M FIR - Basson, M IR - Basson M FIR - Naidoo, V IR - Naidoo V FIR - Amod, A IR - Amod A EDAT- 2025/07/30 00:30 MHDA- 2025/10/20 18:29 PMCR- 2025/07/29 CRDT- 2025/07/29 18:23 PHST- 2025/02/26 00:00 [received] PHST- 2025/06/12 00:00 [accepted] PHST- 2025/10/20 18:29 [medline] PHST- 2025/07/30 00:30 [pubmed] PHST- 2025/07/29 18:23 [entrez] PHST- 2025/07/29 00:00 [pmc-release] AID - 163056 [pii] AID - 250472 [pii] AID - 10.2337/dc25-0472 [doi] PST - ppublish SO - Diabetes Care. 2025 Nov 1;48(11):1878-1887. doi: 10.2337/dc25-0472. PMID- 40726453 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Evaluating biased agonism of glucagon-like peptide-1 (GLP-1) receptors to improve cellular bioenergetics: A systematic review. PG - 6105-6115 LID - 10.1111/dom.16660 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective antidiabetic and anti-obesity agents. Recent development and optimisation of these agents includes biased agonism (selective activation of a downstream signalling pathway) of the GLP-1 receptor, which has demonstrated greater weight-lowering effects and improved insulin response in treated persons relative to other GLP-1 RAs. We aim to synthesise current literature reporting on the effects of biased GLP-1 RAs and compare their effects on cellular-level bioenergetics compared to non-biased GLP-1 RAs. A systematic search was conducted on PubMed, Ovid, and Scopus databases from inception to April 2025 for studies reporting on the effects of GLP-1 receptor biased agonists on cellular bioenergetics. Primary studies reporting on the effects of biased GLP-1 RAs on cellular signal transduction and bioenergetic outcomes were sought for inclusion. Current literature to date suggests that GLP-1 receptor biased agonism contributes to improved bioenergetic outcomes. Biased agonism of the GLP-1 receptor was associated with increased cAMP production and accumulation, increased ERK1/2 phosphorylation, and decreased GLP-1 receptor internalisation and recycling. In addition, improved glucose control and insulin response were observed. GLP-1 receptor biased agonism may be associated with greater weight-lowering and glucose-lowering effects as well as improved safety and tolerability. Notwithstanding, additional studies are needed to parse the contributory effects of GLP-1 receptor biased agonism compared to agonism of GIP and glucagon receptors on anti-obesity and glucose-lowering effects as well as tolerability. Moreover, their effects on other metabolic outcomes are future research vistas. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wong, Sabrina AU - Wong S AD - Brain and Cognition Discovery Foundation, Toronto, Canada. AD - Poul Hansen Family Centre for Depression, University Health Network, Toronto, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. FAU - Le, Gia Han AU - Le GH AD - Brain and Cognition Discovery Foundation, Toronto, Canada. AD - Poul Hansen Family Centre for Depression, University Health Network, Toronto, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Canada. FAU - Dri, Christine E AU - Dri CE AD - Brain and Cognition Discovery Foundation, Toronto, Canada. FAU - Teopiz, Kayla M AU - Teopiz KM AD - Brain and Cognition Discovery Foundation, Toronto, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Canada. FAU - McIntyre, Roger S AU - McIntyre RS AUID- ORCID: 0000-0003-4733-2523 AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Canada. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250729 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Energy Metabolism/drug effects MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Obesity/drug therapy/metabolism MH - Signal Transduction/drug effects PMC - PMC12515783 OTO - NOTNLM OT - GLP-1 OT - biased agonism OT - bioenergetics OT - glucagon-like peptide-1 OT - glutamate OT - metabolism COIS- Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Kayla M. Teopiz has received fees from Braxia Scientific Corp. Sabrina Wong, Gia Han Le, and Christine E. Dri declare no competing interests. EDAT- 2025/07/29 06:30 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/07/29 05:32 PHST- 2025/07/17 00:00 [revised] PHST- 2025/06/20 00:00 [received] PHST- 2025/07/22 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/07/29 06:30 [pubmed] PHST- 2025/07/29 05:32 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM16660 [pii] AID - 10.1111/dom.16660 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6105-6115. doi: 10.1111/dom.16660. Epub 2025 Jul 29. PMID- 40725024 OWN - NLM STAT- MEDLINE DCOM- 20250729 LR - 20250801 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 14 DP - 2025 Jul 15 TI - Molecular Insights into the Potential Cardiometabolic Effects of GLP-1 Receptor Analogs and DPP-4 Inhibitors. LID - 10.3390/ijms26146777 [doi] LID - 6777 AB - Cardiovascular diseases (CVDs) are the leading cause of global mortality, with type 2 diabetes mellitus (T2DM) and obesity significantly increasing the risk of CVD. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4is) have gained attention for their potential cardioprotective effects. Therefore, this review aims to explore the molecular mechanisms underlying the cardiovascular benefits of these agents. A literature review was conducted searching PubMed databases from 1990 to January 2025, including research on the effects of GLP-1 RA and DPP-4i on cardiovascular health, specifically concerning atherosclerosis, coronary artery disease, vascular health, cardiac arrhythmias, myocardial infarction (MI), and heart failure, with a focus on the biochemical and molecular effects of these drugs. We analyzed 131 scientific publications, which indicate that GLP-1 RA and DPP-4i significantly reduce cardiovascular risk and major adverse cardiovascular events (MACEs), including atherosclerosis, myocardial infarction, and cardiac arrhythmias. These clinical outcomes are attributed to the mitigation of oxidative stress, inflammation, and endothelial dysfunction as well as improvement in mitochondrial function and lipid metabolism. GLP-1 RAs offer substantial cardiovascular benefits, making them valuable in managing T2DM and reducing CVD risk. Their integration into treatment regimens for CVD can reduce hospitalization rates, improve quality of life, and extend life expectancy. DPP-4is, while beneficial, are less effective in cardiovascular protection. Further research is needed to optimize therapeutic strategies and broaden the clinical application of these agents in cardiometabolic care. FAU - Krol, Malgorzata AU - Krol M AUID- ORCID: 0009-0008-8658-4356 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Kupnicka, Patrycja AU - Kupnicka P AUID- ORCID: 0000-0002-0756-6483 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Zychowska, Justyna AU - Zychowska J AUID- ORCID: 0009-0007-3477-3430 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Kapczuk, Patrycja AU - Kapczuk P AUID- ORCID: 0000-0002-2766-7783 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Szucko-Kociuba, Izabela AU - Szucko-Kociuba I AUID- ORCID: 0000-0002-2974-1908 AD - Institute of Biology, University of Szczecin, 13 Waska, 71-415 Szczecin, Poland. FAU - Prajwos, Eryk AU - Prajwos E AUID- ORCID: 0009-0002-9827-7114 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Chlubek, Dariusz AU - Chlubek D AUID- ORCID: 0000-0003-4497-4395 AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72, 70-111 Szczecin, Poland. LA - eng GR - WM-130/S/2025/The statutory budget of the Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin/ PT - Journal Article PT - Review DEP - 20250715 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/drug therapy/metabolism/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12295648 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular diseases OT - diabetes OT - dipeptidyl peptidase-4 inhibitor OT - glucagon-like peptide-1 OT - inflammation OT - mitochondrial function OT - oxidative stress COIS- The authors declare no conflicts of interest. EDAT- 2025/07/29 06:30 MHDA- 2025/07/30 00:31 PMCR- 2025/07/15 CRDT- 2025/07/29 01:14 PHST- 2025/05/11 00:00 [received] PHST- 2025/07/10 00:00 [revised] PHST- 2025/07/12 00:00 [accepted] PHST- 2025/07/30 00:31 [medline] PHST- 2025/07/29 06:30 [pubmed] PHST- 2025/07/29 01:14 [entrez] PHST- 2025/07/15 00:00 [pmc-release] AID - ijms26146777 [pii] AID - ijms-26-06777 [pii] AID - 10.3390/ijms26146777 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jul 15;26(14):6777. doi: 10.3390/ijms26146777. PMID- 40719033 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 7 IP - Suppl 7 DP - 2025 Aug TI - Practical limitations of complex insulin therapies in type 2 diabetes: Focus on therapy simplification using fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist. PG - 42-54 LID - 10.1111/dom.16645 [doi] AB - Until recently, people with type 2 diabetes mellitus (PwT2DM) with poor glycaemic control on oral antidiabetic medication were initiated on insulin therapy. While insulin-based therapies have been efficient in reducing hyperglycaemia, they have also been linked with an increased risk of hypoglycaemia, increased treatment burden, and weight gain. The advent of novel classes of antidiabetic agents, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) presents a significant shift in the T2DM treatment algorithms. These medications are not only efficient in the reduction of glycaemia but are also able to reduce weight and have cardiovascular and renal benefits. PwT2DM on complex insulin regimens can now benefit from therapy simplification, taking advantage of once-daily fixed-ratio combinations (FRC) of basal insulin and glucagon-like peptide-1 receptor agonist. Current evidence suggests that this approach is equally efficient in terms of glycaemic control with the additional benefit of the reduction of body weight, total daily dose of insulin, and the number of insulin injections administered per day with no increase or reduction of hypoglycaemia. The primary aim of this review is to present the current evidence supporting the simplification of complex insulin regimens in PwT2DM with the two currently available FRCs on the market (insulin glargine 100 U/mL and GLP-1 RA lixisenatide [iGlarLixi] or insulin degludec and GLP-1 RA liraglutide [IDegLira]) and to provide a simple clinical practice-oriented algorithm for clinicians based on the currently available evidence. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Horvath, Ludek AU - Horvath L AUID- ORCID: 0000-0001-7873-0159 AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. FAU - Novodvorsky, Peter AU - Novodvorsky P AUID- ORCID: 0000-0002-3292-7586 AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. FAU - Haluzik, Martin AU - Haluzik M AUID- ORCID: 0000-0002-0201-6888 AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. AD - General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. LA - eng GR - European Union/ PT - Journal Article PT - Review DEP - 20250728 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Drug Combinations) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Insulin, Long-Acting) RN - 839I73S42A (Liraglutide) RN - 2ZM8CX04RZ (Insulin Glargine) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Combinations MH - *Insulin/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Blood Glucose/drug effects/metabolism MH - Hypoglycemia/chemically induced/prevention & control MH - Sodium-Glucose Transporter 2 Inhibitors MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Liraglutide/administration & dosage MH - Glycemic Control MH - Insulin Glargine/administration & dosage/therapeutic use PMC - PMC12308273 OTO - NOTNLM OT - GLP-1 analogue OT - IDegLira OT - basal insulin OT - fixed-ratio combination OT - glucose lowering medication OT - hypoglycaemia OT - iGlarLixi COIS- L.H. declares no relevant conflict of interest. P.N. has served on speaker panels for Sanofi, Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Astra Zeneca, Mundipharma, Berlin Chemie, Krka, Viatris, Novartis, Abbott, and Medtronic; on advisory panels for Sanofi, Novo Nordisk, and Boehringer-Ingelheim; received honoraria or consulting fees from Merck and Eli Lilly; and received travel grants from Sanofi, Novo Nordisk, Berlin Chemie, Boehringer-Ingelheim, and Eli Lilly. M.H. has served on an advisory panel for Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma; and has served as a consultant for Eli Lilly, Novo Nordisk, Sanofi, Astra Zeneca, Mundipharma; and has received research support from AstraZeneca, Eli Lilly, Bristol-Meyers Squibb; and has received honoraria or consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Berlin Chemie, Eli Lilly, Janssen, Johnson & Johnson, Zentiva, and Merck. EDAT- 2025/07/28 19:00 MHDA- 2025/07/30 06:30 PMCR- 2025/07/30 CRDT- 2025/07/28 06:03 PHST- 2025/07/14 00:00 [revised] PHST- 2025/05/01 00:00 [received] PHST- 2025/07/14 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/07/28 19:00 [pubmed] PHST- 2025/07/28 06:03 [entrez] PHST- 2025/07/30 00:00 [pmc-release] AID - DOM16645 [pii] AID - 10.1111/dom.16645 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27 Suppl 7(Suppl 7):42-54. doi: 10.1111/dom.16645. Epub 2025 Jul 28. PMID- 40712696 OWN - NLM STAT- MEDLINE DCOM- 20251126 LR - 20260127 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 49 IP - 7 DP - 2025 Oct TI - In the Eye of Controversy: A Deeper Look Into the Impact of Glucagon-like Peptide-1 Receptor Agonists on Diabetic Retinopathy and Nonarteritic Anterior Ischemic Optic Neuropathy. PG - 401-410 LID - S1499-2671(25)00149-2 [pii] LID - 10.1016/j.jcjd.2025.07.002 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP1-RAs), a relatively new class of drugs, are used widely in treating type 2 diabetes mellitus and obesity. Maintaining long-term glycemic management lowers the risk of development and progression of diabetic retinopathy. However, recent literature has raised concerns about transient worsening of the condition with use of GLP1-RAs. In this review we evaluate the association between GLP1-RAs and retinopathy in patients with diabetes mellitus. We also analyzed the available evidence on the potential association between semaglutide therapy and nonarteritic anterior ischemic optic neuropathy (NAION). Our review consists of relevant publications, including meta-analyses, randomized controlled trials, and post hoc analyses, and outcomes of in vitro and in vivo research. The article search was conducted using several databases, including the WorldCat Discovery service provided by the Al Maktoum Medical Library, PubMed, and Google Scholar. Preclinical studies hint at possible protective effects on the retina, but a more complex picture is presented by clinical evidence. Although there have been cases of retinopathy development after GLP1-RA use, this may be due to a swift reduction in glycated hemoglobin levels rather than the drug's mechanism of action itself. Evidence linking semaglutide to NAION remains inconclusive and limited by methodological constraints. Large-scale studies with robust design are warranted to elucidate the potential association and to guide clinical practice. CI - Copyright (c) 2025 Diabetes Canada. Published by Elsevier Inc. All rights reserved. FAU - Nadeem, Nadia AU - Nadeem N AD - Department of Internal Medicine, Rashid Hospital, Dubai Health, Dubai, United Arab Emirates. Electronic address: nadianadeem24@gmail.com. FAU - Al Issa, Raghad Mazin AU - Al Issa RM AD - Department of Internal Medicine, Rashid Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Shah, Asnin AU - Shah A AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Wardeh, Rahaf AU - Wardeh R AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Rashid, Fauzia AU - Rashid F AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Abdelgadir, Elamin Ibrahim AU - Abdelgadir EI AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Bashier, Alaaeldin AU - Bashier A AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. LA - eng PT - Journal Article PT - Review DEP - 20250723 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/drug therapy MH - *Diabetic Retinopathy/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP1-RA OT - GLP1RA OT - agonistes du recepteur du peptide 1 similaire au glucagon OT - controle glycemique OT - diabetic retinopathy OT - diabete sucre de type 2 OT - glucagon-like peptide-1 receptor agonists OT - glycemic management OT - neuropathie optique ischemique anterieure non arteritique OT - nonarteritic anterior ischemic optic neuropathy OT - retinopathie diabetique OT - type 2 diabetes mellitus EDAT- 2025/07/28 08:44 MHDA- 2025/11/27 00:27 CRDT- 2025/07/25 19:36 PHST- 2025/04/19 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/07/12 00:00 [accepted] PHST- 2025/11/27 00:27 [medline] PHST- 2025/07/28 08:44 [pubmed] PHST- 2025/07/25 19:36 [entrez] AID - S1499-2671(25)00149-2 [pii] AID - 10.1016/j.jcjd.2025.07.002 [doi] PST - ppublish SO - Can J Diabetes. 2025 Oct;49(7):401-410. doi: 10.1016/j.jcjd.2025.07.002. Epub 2025 Jul 23. PMID- 40712124 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20260131 IS - 1539-2864 (Electronic) IS - 0275-004X (Linking) VI - 45 IP - 12 DP - 2025 Dec 1 TI - IMPACT OF GLP-1 RECEPTOR AGONISTS FOR TYPE 2 DIABETES MELLITUS ON THE DEVELOPMENT AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION. PG - 2241-2251 LID - 10.1097/IAE.0000000000004616 [doi] AB - PURPOSE: To evaluate whether GLP-1 receptor agonist (GLP-1RA) therapy reduces the risk of age-related macular degeneration (AMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: A retrospective cohort study using a global health research network matched T2DM patients on GLP-1RA versus non-GLP-1RA therapy. AMD incidence was determined over the first 1 to 10 years of treatment. Patients with baseline early or intermediate nonexudative AMD were also matched and assessed for progression to advanced AMD. Measures of association analysis was used to calculate risk, risk difference, and risk ratio. RESULTS: Among 600,816 matched patients without a history of AMD, GLP-1RA users had a 15% relative risk reduction in incidence of nonexudative AMD (RR, 0.851; 95% CI, 0.801-0.905; P < 0.0001) versus those who received alternative therapy. These patients also had a 20% relative risk reduction in incidence of exudative AMD (RR, 0.80; 95% CI, 0.808-0.989; P < 0.0001). To assess progression, 4,450 patients with early or intermediate AMD were matched between the cohorts. GLP-1RA use was associated with 29% relative risk reduction in progression to advanced nonexudative AMD (RR, 0.715; 95% CI, 0.529-0.967; P = 0.028) and a 27% relative risk reduction in progression to exudative AMD (RR, 0.729; 95% CI, 0.601-0.883; P = 0.001). CONCLUSION: GLP-1RA use may reduce both the risk and progression of AMD and progression of early and intermediate AMD to advanced AMD in adults with T2DM. GLP-1RAs have been shown to promote neuronal survival and reduce inflammation, which may provide a pathophysiological explanation of the potential beneficial role of GLP-1RAs. FAU - McLaughlin, Samantha A AU - McLaughlin SA AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and. FAU - Davila, Natalia AU - Davila N AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and. AD - Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas. FAU - Shields, Chloe AU - Shields C AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and. FAU - Bineshfar, Niloufar AU - Bineshfar N AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and. FAU - Banaee, Touka AU - Banaee T AD - Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas. FAU - Williams, Basil K Jr AU - Williams BK Jr AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and. LA - eng GR - UL1 TR001439/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Retina JT - Retina (Philadelphia, Pa.) JID - 8309919 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Disease Progression MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - Middle Aged MH - *Macular Degeneration/epidemiology/prevention & control/etiology MH - Follow-Up Studies MH - Aged, 80 and over OTO - NOTNLM OT - age-related macular degeneration OT - cohort study OT - exudative AMD OT - glucagon-like peptide-1 receptor agonist OT - nonexudative AMD OT - type 2 diabetes mellitus EDAT- 2025/07/25 18:27 MHDA- 2025/11/14 12:32 CRDT- 2025/07/25 16:22 PHST- 2025/11/14 12:32 [medline] PHST- 2025/07/25 18:27 [pubmed] PHST- 2025/07/25 16:22 [entrez] AID - 00006982-990000000-01148 [pii] AID - 10.1097/IAE.0000000000004616 [doi] PST - ppublish SO - Retina. 2025 Dec 1;45(12):2241-2251. doi: 10.1097/IAE.0000000000004616. PMID- 40711887 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 10 DP - 2025 Oct TI - A multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice (PIONEER REAL Japan): Subgroup analyses. PG - 1794-1807 LID - 10.1111/jdi.70099 [doi] AB - AIMS: HbA(1c) and body weight were assessed across selected subgroups of adults with type 2 diabetes receiving oral semaglutide in clinical practice. METHODS: In this non-interventional study, changes in HbA(1c) and body weight to end of study (EoS) and safety were assessed by subgroup: baseline age, body mass index (BMI), type 2 diabetes duration, participants switching from dipeptidyl peptidase-4 inhibitors, and semaglutide dose at EoS. RESULTS: All subgroups experienced reductions in HbA(1c) and body weight. Younger participants had greater reductions in HbA(1c) than older participants (-0.9, -0.7, -0.7, and -0.5 percentage points for participants aged <55, >/=55-<65, >/=65-<75, and >/=75 years, respectively [P = 0.0467]). Shorter type 2 diabetes duration and lower EoS semaglutide dose were associated with greater HbA(1c) reductions (-0.8, -0.7, and -0.6 percentage points with 5-10 years' duration, respectively [P < 0.0001]; -1.2, -0.7, and -0.4 percentage points with 3, 7, and 14 mg, respectively [P < 0.0001]). Changes in HbA(1c) were not significantly different across other subgroups. Lower EoS semaglutide dose was associated with greater body weight reductions (-3.8, -2.9, and -2.8 kg with 3, 7, and 14 mg, respectively [P < 0.0001]); body weight reductions were not significantly different across other subgroups. Adverse events were similar between subgroups, except that older subgroups experienced more events. CONCLUSIONS: HbA(1c) and body weight decreased across all subgroups, providing insights into oral semaglutide use in clinical practice for individuals with different characteristics in the real-world setting. CI - (c) 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for One Medicine Innovative Translational Research, Gifu University Institute of Advanced Studies, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Kawanami, Daiji AU - Kawanami D AUID- ORCID: 0000-0002-8926-4701 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Amadid, Hanan AU - Amadid H AD - Clinical Development and Project Leadership, Novo Nordisk A/S, Soborg, Denmark. FAU - Braae, Uffe Christian AU - Braae UC AD - Real-World Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AD - Global Patient Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-2965-6906 AD - Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University, Tokyo, Japan. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study DEP - 20250725 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Aged MH - Glycated Hemoglobin/analysis MH - Prospective Studies MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Japan MH - Body Weight/drug effects MH - Adult MH - Blood Glucose/analysis MH - Prognosis MH - Follow-Up Studies MH - *Biomarkers/analysis MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People PMC - PMC12489328 OTO - NOTNLM OT - Oral semaglutide OT - Real-world study OT - Type 2 diabetes COIS- Daisuke Yabe: received consulting/lecture fees from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd, Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and research funding/grants from Arkray Inc., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., and Terumo Corporation. Professor Yabe is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Yoshiyuki Hamamoto: received consulting/lecture fees from Eli Lilly Japan K.K., Daiichi Sankyo, Mitsubishi Tanabe Pharma Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., MSD K.K., and Sumitomo Pharma Co., Ltd.; and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Dr. Hamamoto is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and grants from Bayer Yakuhin Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation, and Sumitomo Pharma Co., Ltd. Rimei Nishimura received consulting/lecture fees from Abbott Japan LLC, Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company Ltd., Medtronic Japan Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd., and Teijin Pharma Ltd.; and research funding/grants from Abbott Japan LLC, Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., and Taisho Pharmaceutical Co., Ltd. Yasuo Terauchi received consulting/lecture fees from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and grants from Nippon Boehringer Ingelheim Co., Ltd., and Sumitomo Pharma Co., Ltd. Hanan Amadid is employed by and a shareholder in Novo Nordisk. Uffe Christian Braae is employed by and a shareholder in Novo Nordisk. Atheline Major-Pedersen is employed by and a shareholder in Novo Nordisk. Ryo Suzuki received lecture fees from Astellas Pharma Inc., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd., Teijin Healthcare Ltd; and grants from Nippon Boehringer Ingelheim Co., Ltd. Approval of the research protocol: The protocol for this research project was approved by suitably constituted ethics committees or institutional review boards of the institutions, and it conforms to the provisions of the Declaration of Helsinki. Ethics committees, institutional review boards, and approval numbers have been previously described. Informed consent: All informed consent was obtained from the participants and/or their guardians. Registry and the registration no. of the study/trial: This study is registered with ClinicalTrials.gov (NCT04878393; first submitted May 5, 2021). Animal studies: N/A. EDAT- 2025/07/25 18:26 MHDA- 2025/10/02 06:28 PMCR- 2025/07/25 CRDT- 2025/07/25 12:42 PHST- 2025/05/19 00:00 [revised] PHST- 2025/02/11 00:00 [received] PHST- 2025/05/31 00:00 [accepted] PHST- 2025/10/02 06:28 [medline] PHST- 2025/07/25 18:26 [pubmed] PHST- 2025/07/25 12:42 [entrez] PHST- 2025/07/25 00:00 [pmc-release] AID - JDI70099 [pii] AID - 10.1111/jdi.70099 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Oct;16(10):1794-1807. doi: 10.1111/jdi.70099. Epub 2025 Jul 25. PMID- 40706779 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260529 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 219 DP - 2025 Sep TI - Sex differences in the weight response to GLP-1RA in people with type 2 diabetes. A long-term longitudinal real-world study. PG - 107866 LID - S1043-6618(25)00291-9 [pii] LID - 10.1016/j.phrs.2025.107866 [doi] AB - Sex differences may influence pathophysiology, treatment response, and outcomes of type 2 diabetes (T2D). We assessed whether sex affected clinical response to GLP-1 receptor agonists (GLP-1RA) in a large real-world cohort. Thus, we conducted a multicentre, retrospective, longitudinal study of 7847 individuals with T2D initiating GLP-1RA therapy across 18 Italian diabetes centres. Participants were stratified by self-reported sex. The primary outcome was change in body weight over time; secondary outcomes included changes in HbA1c, renal function, and lipid profile. Analyses were performed using a mixed model for repeated measures, adjusting for baseline imbalances. Participants were 60 % male, with similar age, diabetes duration, and HbA1c (mean 8.0 %). Females had higher BMI but fewer micro- and macrovascular complications. Over a median 4-year follow-up, females experienced significantly greater weight reduction than males (adjusted mean difference: -1.1 kg; p < 0.001), with more females achieving a weight loss of >/= 5 % (66.5 % vs. 58.0 %, p < 0.001) or >/= 10 % (40.0 % vs 30.7 %, p < 0.001). This sex difference in weight loss remained unchanged after progressive adjustment for variables that differed between males and females, across GLP-1RA molecules, and after accounting for weight-adjusted drug doses. Instead, HbA1c reductions were comparable between men and women (mean difference 0.4 mmol/mol; p = 0.21). In conclusion, in this real-world cohort, women achieved greater weight loss than men after GLP-1RA initiation, independently of dosing. These findings highlight sex as a potential predictor of GLP-1RA response and support individualized T2D management. Further investigation is needed to clarify the biological mechanisms underlying this sex-specific response. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Marassi, Marella AU - Marassi M AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Cignarella, Andrea AU - Cignarella A AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Russo, Giuseppina T AU - Russo GT AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Nollino, Laura AU - Nollino L AD - Endocrine, Metabolic and Nutrition Disease, AULSS 2 Marca Trevigiana, Treviso, Italy. FAU - Strazzabosco, Marco AU - Strazzabosco M AD - Diabetology and Metabolic Diseases Unit, S. Bortolo Hospital Vicenza, Italy. FAU - Marzullo, Paolo AU - Marzullo P AD - Department of Translational Medicine, Universita del Piemonte Orientale, Novara, Italy. FAU - Leonetti, Frida AU - Leonetti F AD - Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. FAU - Avogaro, Angelo AU - Avogaro A AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy; Endocrinology and Metabolism Unit, ASL, Pescara, Italy, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy; Veneto Institute of Molecular Medicine, Padua, Italy. Electronic address: gianpaolo.fadini@unipd.it. CN - GLIMPLES study investigators LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250722 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Longitudinal Studies MH - Retrospective Studies MH - Sex Factors MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - Adipose tissue OT - Incretins OT - Obesity OT - Observational OT - Sex and gender medicine COIS- Declaration of Competing Interest GTR is on the advisory board and does consultancy and lectures for Novo Nordisk, AstraZeneca, Sanofi, Boehringer, Lilly, Mundipharma, and Sankyo. AC received grants from AstraZeneca, Lilly, Novo-Nordisk. He also received speaker fees, and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dohme, Menarini, Novo-Nordisk, Sanofi, Sigma-Tau, Takeda. AA received research grants, lecture, or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boehringer-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. LN speaker fees for lectures and consultancy from AstraZeneca, Lilly, Guidotti, Novo Nordisk, Sanofi, EG Stada. GPF received fees for lectures, consultancy, or advisory board from AstraZeneca, Boehringer, Lilly, Guidotti, Novartis, Novo Nordisk, Sanofi. MM, ACi, MS, PM, FL have nothing to disclose EDAT- 2025/07/25 00:28 MHDA- 2025/09/01 00:44 CRDT- 2025/07/24 19:35 PHST- 2025/04/24 00:00 [received] PHST- 2025/06/22 00:00 [revised] PHST- 2025/07/16 00:00 [accepted] PHST- 2025/09/01 00:44 [medline] PHST- 2025/07/25 00:28 [pubmed] PHST- 2025/07/24 19:35 [entrez] AID - S1043-6618(25)00291-9 [pii] AID - 10.1016/j.phrs.2025.107866 [doi] PST - ppublish SO - Pharmacol Res. 2025 Sep;219:107866. doi: 10.1016/j.phrs.2025.107866. Epub 2025 Jul 22. PMID- 40706753 OWN - NLM STAT- MEDLINE DCOM- 20260108 LR - 20260108 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 1 DP - 2026 Jan TI - Implications of Glucagon-like Peptide-1 Receptor Agonists on Thyroid Function and Thyroid Nodules: A Drug Target Mendelian Randomization and Cohort Study. PG - 60-66 LID - S1530-891X(25)00971-1 [pii] LID - 10.1016/j.eprac.2025.07.013 [doi] AB - OBJECTIVES: Glucagon-like Peptide-1 receptor agonists (GLP-1RAs) are antidiabetic medications, with conflicting reports about their relationship with thyroid diseases. This study investigates their effects on thyroid function and nodules in patients with diabetes. METHODS: Mendelian randomization was conducted to examine the association between genetically proxied GLP-1RA activity and thyroid diseases. This was followed by a cohort study involving 169 patients with diabetes, who were divided into a control group (control group, W/O GLP-1 treatment) and a GLP-1RA treatment group (GLP-1RAs group) based on their medication usage. Patients' thyroid function tests, thyroid nodule diameters, and Thyroid Imaging Reporting and Data System classifications were compared at baseline and after 12 months of treatment. RESULTS: Through Mendelian randomization, GLP-1RAs decrease free thyroxine (fT4) levels within the normal range [odds ratio (95% CI) = 0.9948 (0.9936-0.9961), P < .001]. Cohort study showed that after treatment, the nodule diameter increased in both the control group (0.69 vs 0.77, P = .004) and the GLP-1 group (0.68 vs 0.71, P = .019). In the GLP-1 group, the Thyroid Imaging Reporting and Data System (2.60 vs 2.69, P = .007) levels increased, while the fT4 (1.26 vs 1.17, P = .005) levels decreased. However, linear regression did not show significant association between GLP-1 and post-treatment differences in thyroid function or thyroid nodule. CONCLUSIONS: GLP-1RAs treatment of 12 months in patients with diabetes is considered relatively safe regarding thyroid disease although there is a potential risk for decreasing of fT4 levels and nodule growth/progression, with no clear evidence of superiority over other antidiabetic treatments. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Zhang, Zhijun AU - Zhang Z AD - Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Yang, Jingyun AU - Yang J AD - Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Gao, Ling AU - Gao L AD - Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: ling.gao@whu.edu.cn. LA - eng PT - Journal Article DEP - 20250722 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - Q51BO43MG4 (Thyroxine) SB - IM MH - Humans MH - *Thyroid Nodule/epidemiology/chemically induced/genetics MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Thyroid Gland/drug effects/physiopathology MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Mendelian Randomization Analysis MH - Thyroid Function Tests MH - Adult MH - Aged MH - Thyroxine/blood OTO - NOTNLM OT - GLP-1 receptor agonists OT - Mendelian randomization OT - thyroid function OT - thyroid nodules OT - type 2 diabetes COIS- Disclosure The authors have no conflicts of interest to disclose. EDAT- 2025/07/25 00:28 MHDA- 2026/01/09 00:26 CRDT- 2025/07/24 19:35 PHST- 2025/01/21 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/07/16 00:00 [accepted] PHST- 2026/01/09 00:26 [medline] PHST- 2025/07/25 00:28 [pubmed] PHST- 2025/07/24 19:35 [entrez] AID - S1530-891X(25)00971-1 [pii] AID - 10.1016/j.eprac.2025.07.013 [doi] PST - ppublish SO - Endocr Pract. 2026 Jan;32(1):60-66. doi: 10.1016/j.eprac.2025.07.013. Epub 2025 Jul 22. PMID- 40704485 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6. PG - 5706-5715 LID - 10.1111/dom.16621 [doi] AB - AIMS: Cardiorenal effects of semaglutide in people with type 2 diabetes (T2D) at high cardiovascular (CV) risk were investigated. MATERIALS AND METHODS: Post hoc analyses of pooled SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) data assessed time to primary major adverse CV events (MACE; CV death, non-fatal myocardial infarction, or non-fatal stroke), expanded MACE (MACE + hospitalisation for unstable angina or heart failure), CV death, all-cause death, and new or worsening nephropathy. The impact of body weight (BW) changes on primary MACE risk was also evaluated. Participants were stratified by prior CV disease (CVD) status and baseline body mass index (BMI). RESULTS: Semaglutide significantly reduced the risk of primary and expanded MACE, with a nonsignificant risk reduction of CV and all-cause death versus placebo in the overall population; the effect was consistent across all subgroups (p(INT) >0.05 for all comparisons). Semaglutide consistently reduced nephropathy risk versus placebo in the SUSTAIN 6 population (HR [95% CI]: 0.64 [0.46; 0.88], p = 0.0054) and across all subgroups (p(INT) >0.05 for all comparisons). When accounting for BW changes, treatment effects on primary MACE risk in the overall population and by BMI subgroups remained similar compared with the results of the main analysis. CONCLUSIONS: Semaglutide treatment improved cardiorenal outcomes versus placebo in people with T2D, regardless of prior CVD and baseline BMI. This improvement was observed even when accounting for changes in BW, indicating direct effects of semaglutide on the cardiorenal system. This analysis supports the broad efficacy of semaglutide in a diverse T2D population. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zhou, Jingmin AU - Zhou J AUID- ORCID: 0000-0003-0195-2727 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Li, Yang AU - Li Y AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Ge, Junbo AU - Ge J AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. LA - eng GR - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250724 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12409197 OTO - NOTNLM OT - GLP-1 analogue OT - body composition OT - cardiovascular disease OT - diabetic nephropathy OT - semaglutide OT - type 2 diabetes COIS- Jingmin Zhou declares no conflicts of interest. Mansoor Husain has received research grants from AstraZeneca, Merck, and Novo Nordisk; consultancy fees for participation in advisory board meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Roche; speaker fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck, and Novo Nordisk; and holds two patents relating to glucagon-like peptides. Yang Li, Wenyan Liu, and Zewei Shen are employees of Novo Nordisk and own stocks in the company. Tina Vilsboll has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Mundipharma, Novo Nordisk, Roche, Sun Pharmaceuticals, and Zealand Pharma. Junbo Ge declares no conflicts of interest. EDAT- 2025/07/24 12:28 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/07/24 06:02 PHST- 2025/07/04 00:00 [revised] PHST- 2025/05/05 00:00 [received] PHST- 2025/07/07 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/24 12:28 [pubmed] PHST- 2025/07/24 06:02 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16621 [pii] AID - 10.1111/dom.16621 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5706-5715. doi: 10.1111/dom.16621. Epub 2025 Jul 24. PMID- 40701453 OWN - NLM STAT- MEDLINE DCOM- 20250910 LR - 20260617 IS - 1096-3650 (Electronic) IS - 1044-579X (Linking) VI - 115 DP - 2025 Oct TI - Cancer prevention and interception with antidiabetic and anti-obesity drugs: Current and future perspectives. PG - 40-52 LID - S1044-579X(25)00102-6 [pii] LID - 10.1016/j.semcancer.2025.07.008 [doi] AB - Obesity and type 2 diabetes are major risk factors for cardiovascular diseases and multiple malignancies, and epidemiology reveals an increasing burden of obesity-related cancers, in particular liver, pancreatic and endometrial. Obesity is also clearly associated with an increased risk of breast cancer, particularly in postmenopausal women. Chronic hyperinsulinemia, systemic inflammation, and metabolic dysregulation create a tumor-promoting environment, emphasizing the need for interventions that target metabolic health and can provide cancer prevention or interception. This review examines the potential cancer-preventive effects of antidiabetic and anti-obesity drugs, summarizing current preclinical and clinical evidence on their mechanisms and efficacy. Among these agents, metformin has been extensively studied, demonstrating anticancer properties through AMP-activated protein kinase activation, mammalian target of rapamycin inhibition, and reduced insulin-like growth factor 1 signaling. Glucagon-like peptide-1 receptor agonists, including semaglutide and tirzepatide, promote weight loss, insulin sensitivity, and anti-inflammatory effects, with emerging evidence suggesting direct tumor-suppressive actions. Sodium-glucose cotransporter 2 inhibitors modulate tumor metabolism by reducing glucose availability and mitigating systemic inflammation. Other agents, including dipeptidyl peptidase-4 inhibitors, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors, have shown mixed evidence regarding their potential anticancer effects, necessitating further investigation. While observational studies and meta-analyses suggest a potential reduction in cancer risk with certain antidiabetic and anti-obesity agents, randomized controlled trials specifically assessing cancer prevention are limited. Additionally, long-term safety concerns, including potential tumor-promoting effects in specific contexts, warrant further investigation. Future research should focus on large-scale clinical trials and mechanistic studies to validate the oncologic benefits and risks of these agents. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Albini, Adriana AU - Albini A AD - Scientific Directorate, European Institute of Oncology IEO, IRCCS, Milan, Italy. Electronic address: adriana.albini@ieo.it. FAU - Cantelmo, Anna Rita AU - Cantelmo AR AD - Universite de Lille, Inserm, CHU Lille, Institute Pasteur de Lille, U1011-EGID, Lille F-59000, France. FAU - Mortara, Lorenzo AU - Mortara L AD - Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Molecular Pathology, Biochemistry and Immunology, MultiMedica, IRCCS, Milan, Italy. FAU - Noonan, Douglas M AU - Noonan DM AD - Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Molecular Pathology, Biochemistry and Immunology, MultiMedica, IRCCS, Milan, Italy. FAU - Corso, Giovanni AU - Corso G AD - Division of Breast Surgery, European Institute of Oncology IEO, IRCCS, Milan, Italy; Department of Oncology and Hematology, University of Milano, Milan, Italy. Electronic address: giovanni.corso@ieo.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250721 PL - England TA - Semin Cancer Biol JT - Seminars in cancer biology JID - 9010218 RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Neoplasms/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Anti-Obesity Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/complications OTO - NOTNLM OT - Anti-obesity drugs OT - Antidiabetic drugs OT - Diabetes, Cancer, Prevention, Interception OT - Metabolic reprogramming OT - Obesity COIS- Declaration of Competing Interest Authors state no conflict of interest. EDAT- 2025/07/24 00:25 MHDA- 2025/09/11 00:28 CRDT- 2025/07/23 19:38 PHST- 2025/02/17 00:00 [received] PHST- 2025/07/15 00:00 [revised] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/09/11 00:28 [medline] PHST- 2025/07/24 00:25 [pubmed] PHST- 2025/07/23 19:38 [entrez] AID - S1044-579X(25)00102-6 [pii] AID - 10.1016/j.semcancer.2025.07.008 [doi] PST - ppublish SO - Semin Cancer Biol. 2025 Oct;115:40-52. doi: 10.1016/j.semcancer.2025.07.008. Epub 2025 Jul 21. PMID- 40701338 OWN - NLM STAT- MEDLINE DCOM- 20251005 LR - 20260603 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 10 DP - 2025 Oct TI - Comprehensive Access to Semaglutide: Clinical and Economic Implications for Medicare. PG - 1488-1496 LID - S1098-3015(25)02472-6 [pii] LID - 10.1016/j.jval.2025.07.007 [doi] AB - OBJECTIVES: The objective of this study was to estimate comprehensive value of semaglutide in the Medicare population for current and future FDA-approved indications. METHODS: We used data from government reports, published clinical studies, and real-world claims to model clinical outcomes and costs in patients with diabetes, overweight/obesity, and metabolic-associated steatohepatitis over a 10-year period (2026 to 2035). We estimated the financial impact to the Medicare program by comparing the impact of costs of averted clinical events and anticipated treatment costs under various treatment utilization and price assumptions with a scenario in which no patients were treated with semaglutide. We used estimates of the net price of semaglutide, an estimated negotiated price based on a 10% discount from net price starting in year 2, and accounted for patient out-of-pocket costs. RESULTS: Over the 10-year period, we estimated that broad access to semaglutide would result in 38 950 cardiovascular events avoided, and 6180 deaths avoided due to reduction in cardiovascular events and improvement in chronic kidney disease or metabolic-associated steatohepatitis progression. The net financial impact to Medicare was estimated to be savings of $715 million over 10 years. Alternative scenarios yielded net savings ranging from $1.04 billion to $412 million. A scenario that accounted for loss of exclusivity of semaglutide and other treatments produced 10-year cost savings to Medicare of approximately $1.71 billion. CONCLUSIONS: Availability of semaglutide in Medicare for all FDA-approved indications would have a substantial impact on health outcomes at net savings of between $1.04 billion and $412 million over 10 years. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Dayer, Victoria W AU - Dayer VW AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. Electronic address: vwinslow@uw.edu. FAU - Nourhussein, Iman AU - Nourhussein I AD - Curta, Inc., Seattle, WA, USA. FAU - Kasle, Adam AU - Kasle A AD - Curta, Inc., Seattle, WA, USA. FAU - Hansen, Ryan N AU - Hansen RN AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. FAU - Navas, Angelo AU - Navas A AD - UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. FAU - Sullivan, Sean D AU - Sullivan SD AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. LA - eng PT - Journal Article DEP - 20250721 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/economics/therapeutic use MH - *Medicare/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - Drug Costs MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Cost-Benefit Analysis MH - Aged MH - Obesity/drug therapy/economics MH - Male MH - Female MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - MASH OT - Medicare OT - diabetes OT - obesity OT - semaglutide COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/07/24 00:25 MHDA- 2025/10/06 00:27 CRDT- 2025/07/23 19:37 PHST- 2025/04/25 00:00 [received] PHST- 2025/07/11 00:00 [revised] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/10/06 00:27 [medline] PHST- 2025/07/24 00:25 [pubmed] PHST- 2025/07/23 19:37 [entrez] AID - S1098-3015(25)02472-6 [pii] AID - 10.1016/j.jval.2025.07.007 [doi] PST - ppublish SO - Value Health. 2025 Oct;28(10):1488-1496. doi: 10.1016/j.jval.2025.07.007. Epub 2025 Jul 21. PMID- 40700548 OWN - NLM STAT- MEDLINE DCOM- 20260512 LR - 20260512 IS - 1753-4887 (Electronic) IS - 0029-6643 (Linking) VI - 84 IP - 6 DP - 2026 Jun 1 TI - Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Obese or Diabetic Patients With Obstructive Sleep Apnea Syndrome: A Meta-Analysis. PG - 1099-1110 LID - 10.1093/nutrit/nuaf115 [doi] AB - CONTEXT: Results of previous studies have suggested that obstructive sleep apnea syndrome (OSAS), particularly when accompanied by obesity or diabetes, is linked to glucose metabolism disorders driven by abnormal glucagon-like peptide-1 (GLP-1) secretion. However, the efficacy of GLP-1 receptor agonists (RAs) in this population remains uncertain. OBJECTIVE: We conducted a meta-analysis to investigate the relationship between serum GLP-1 levels and OSAS, as well as the efficacy of GLP-1 RAs in treating OSAS. DATA SOURCES: The Cochrane, CINAHL, EMBASE, Google Scholar, PubMed, ScienceDirect, Web of Science, CNKI, and Wan Fang databases were searched from inception to October 1, 2024. DATA EXTRACTION: We extracted data from the included studies on serum GLP-1 levels and the apnea-hypopnea index (AHI), lowest SpO2 (LSpO2) levels, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), body weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). DATA ANALYSIS: A total of 10 studies (1313 participants) were included in this analysis, comprising 4 case-control studies examining the relationship between serum GLP-1 levels and OSAS and 6 randomized controlled trials investigating the efficacy of GLP-1 RAs in patients with diabetes or obesity complicated by OSAS. Meta-analysis results indicated that compared to the non-OSAS or mild-OSAS individuals, fasting serum GLP-1 levels (mean difference [MD], -1.86 ug/L; 95% CI, -3.58 to -0.13; P = .04; I2 = 72%), and 1-hour postprandial GLP-1 levels (MD, -7.76 microg/L; 95% CI, -9.43 to -6.08; P < .00001; I2 = 49%) were significantly lower in patients with OSAS. Treatment with GLP-1 RA significantly improved the AHI (MD, -16.11 events/h; 95% CI, -26.23 to -5.99; P = .002; I2 = 96%), as well as reducing blood pressure, BMI, and FBG (P <.05). CONCLUSIONS: In patients with OSAS, serum GLP-1 levels are lower than those of healthy individuals. GLP-1 RAs may significantly reduce AHI in patients with obesity or diabetes. However, given the substantial heterogeneity among studies, the results should be interpreted with caution. Systematic Review Registration: PROSPERO registration No. CRD42024599675. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Xu, Shan AU - Xu S AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang City, Jiangxi Province 330006, China. FAU - Li, Jin'e AU - Li J AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang City, Jiangxi Province 330006, China. FAU - Qiu, Jiajun AU - Qiu J AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. FAU - Zhang, Yuying AU - Zhang Y AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. FAU - Yang, Shiqi AU - Yang S AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. FAU - Liu, Jianping AU - Liu J AUID- ORCID: 0009-0008-0138-6845 AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. AD - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China. LA - eng GR - 82160162/National Natural Science Foundation of China/ GR - 81760150/National Natural Science Foundation of China/ GR - 20202ACBL206008/Key Project of Jiangxi Provincial Natural Science Foundation/ GR - 2022efyA04/Second Affiliated Hospital of Nanchang University/ GR - 2024SSY06231/Jiangxi Province Key Laboratory of Molecular Medicine/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Nutr Rev JT - Nutrition reviews JID - 0376405 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Sleep Apnea, Obstructive/drug therapy/complications/blood MH - *Obesity/complications/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Glucagon-Like Peptide 1/blood MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Randomized Controlled Trials as Topic MH - Treatment Outcome OTO - NOTNLM OT - AHI OT - GLP-1 OT - OSAS OT - diabetes OT - metabolic disorders OT - obesity EDAT- 2025/07/23 18:28 MHDA- 2026/05/12 06:35 CRDT- 2025/07/23 14:13 PHST- 2026/05/12 06:35 [medline] PHST- 2025/07/23 18:28 [pubmed] PHST- 2025/07/23 14:13 [entrez] AID - 8211140 [pii] AID - 10.1093/nutrit/nuaf115 [doi] PST - ppublish SO - Nutr Rev. 2026 Jun 1;84(6):1099-1110. doi: 10.1093/nutrit/nuaf115. PMID- 40698871 OWN - NLM STAT- MEDLINE DCOM- 20250723 LR - 20260622 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 5 DP - 2025 Jul TI - Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists Versus Other Glucose-Lowering Agents in People With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Data. PG - e70066 LID - 10.1002/dmrr.70066 [doi] LID - e70066 AB - AIMS: Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents. MATERIALS AND METHODS: We searched PubMed and Embase for observational cohort studies (April 2005-January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, >/= 40 or >/= 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models. RESULTS: Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49-78 years, 5%-64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05-1.20]), kidney-related hospitalizations (1.66 [1.01-2.73]), and >/= 40% reduction in eGFR (1.40 [1.27-1.53]), without evidence for differences in risks of >/= 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing >/= 50% eGFR reduction (0.84 [0.76-0.92]), kidney-related hospitalizations (0.73 [0.65-0.83]), and ESKD (0.70 [0.63-0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80-0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk. CONCLUSIONS: In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i. CI - (c) 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Fishkin, Alisa AU - Fishkin A AUID- ORCID: 0009-0003-4992-495X AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Rozenberg, Aliza AU - Rozenberg A AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Schechter, Meir AU - Schechter M AUID- ORCID: 0000-0002-5071-3143 AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. FAU - Sehtman-Shachar, Dvora R AU - Sehtman-Shachar DR AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Aharon-Hananel, Genya AU - Aharon-Hananel G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Leibowitz, Gil AU - Leibowitz G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Yanuv, Ilan AU - Yanuv I AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Regeneron Pharmaceuticals Inc., New York, New York, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetic Nephropathies/prevention & control MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Prognosis PMC - PMC12285216 OTO - NOTNLM OT - GLP-1 RA OT - kidney outcomes OT - meta-analysis OT - real world data OT - systematic review OT - type 2 diabetes COIS- A.F. and D.R.S. have no conflict of interest to declare. I.Y. and A.R. received hourly payments from AstraZeneca through Hadassah Medical Centre and from Novo Nordisk. M.S. reports travel support from Novo Nordisk and AstraZeneca through Hadassah Medical Centre and lecturing fees from AstraZeneca (2022). O.M. reports Advisory Board membership for Novo Nordisk, Eli Lilly, Sanofi, MerckSharp and Dohme, Boehringer Ingelheim, AstraZeneca and BOL Pharma, research grant support through Hadassah Hebrew University Hospital from Novo Nordisk and AstraZeneca, and Speaker's Bureau participation for AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp and Dohme, and Boehringer Ingelheim. From May 1st, 2023, Ofri Mosenzon has been an employee of Regeneron Pharmaceuticals Inc. G.A.H. reported previous Advisory Board: Sanofi and Eli Lilly. She is a current PI in several RCTs conducted by Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca and Bayer, including the Confidence study, through Hadassah Medical Centre. G.A.H. reports travel support from Novo Nordisk and Medetronic through Hadassah Medical Centre and AstraZeneca through Sheba medical centre. Speakers Bureau: AstraZeneca, Novo Nordisk, Eli Lilly and Sanofi. G.L. reports participation in previous Advisory Boards: Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp and Dohme, Boehringer Ingelheim, AstraZeneca and Medtronic. He reports travel support from Novo Nordisk, Boehringer Ingelheim and AstraZeneca through Hadassah Medical Centre. Speakers Bureau: AstraZeneca, Novo Nordisk, Eli Lilly, Boehringer Ingelheim. EDAT- 2025/07/23 12:30 MHDA- 2025/07/23 12:31 PMCR- 2025/07/23 CRDT- 2025/07/23 08:22 PHST- 2025/04/11 00:00 [revised] PHST- 2024/05/25 00:00 [received] PHST- 2025/06/08 00:00 [accepted] PHST- 2025/07/23 12:31 [medline] PHST- 2025/07/23 12:30 [pubmed] PHST- 2025/07/23 08:22 [entrez] PHST- 2025/07/23 00:00 [pmc-release] AID - DMRR70066 [pii] AID - 10.1002/dmrr.70066 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 Jul;41(5):e70066. doi: 10.1002/dmrr.70066. PMID- 40695708 OWN - NLM STAT- MEDLINE DCOM- 20250823 LR - 20250823 IS - 1424-3911 (Electronic) IS - 1424-3903 (Linking) VI - 25 IP - 5 DP - 2025 Aug TI - Predictors of acute pancreatitis in patients treated with GLP-1 receptor agonists for weight management. PG - 609-613 LID - S1424-3903(25)00144-9 [pii] LID - 10.1016/j.pan.2025.06.018 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely prescribed for treating obesity and Type 2 Diabetes (T2D). There have been concerns that GLP-1RA is associated with acute pancreatitis (AP), although the data are controversial. We aimed to identify factors that impact the risk of AP after initiation of GLP-1RA treatment for obesity. METHODS: We performed a retrospective case-control study including adults patients initiated on a GLP-1RA for obesity management to determine risk factors associated with AP in obese patients taking GLP-1RA. We identified patients initiated on GLP-1RA. A multivariable logistic regression model was used to identify predictors of AP with GLP-1RA use. RESULTS: There were 2245 patients, of which 49 (2.2 %) developed AP after starting a GLP-1RA. A history of gallstone disease (adjusted odds ratio (aOR), 2.9 [95 % CI, 1.6 to 5.3]), history of AP (aOR 4.8 [CI, 1.8 to 13.2]), CAD/PVD (aOR 2 [CI, 1.01 to 3.9]) and tobacco use (aOR 2.4 [CI, 1.2 to 4.7]) were associated with a higher risk of AP with GLP-1RA use. Compared to a BMI 40 were associated with a lower risk of AP with GLP-1RA therapy, (aOR 0.2 [CI, 0.06 to 0.6]) and (aOR 0.25 [CI, 0.09 to 0.68]), respectively. CONCLUSION: A history of gallstone disease, history of AP, CAD/PVD, and tobacco use were associated with AP after initiation of GLP-1RA for obesity treatment. A higher BMI appears to be protective against AP. Recognizing factors associated AP after GLP-1RA initiation can inform clinicians on risk stratification. CI - Copyright (c) 2025. Published by Elsevier B.V. FAU - Postlethwaite, Robert AU - Postlethwaite R AD - Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX, USA. FAU - Amin, Amin M AU - Amin AM AD - Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX, USA. FAU - Alsawas, Rand AU - Alsawas R AD - Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX, USA. FAU - Almandoz, Jaime P AU - Almandoz JP AD - Division of Endocrinology, University of Texas Southwestern, Dallas, TX, USA. FAU - Sawas, Tarek AU - Sawas T AD - Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX, USA. Electronic address: tarek.sawas@UTsouthwestern.edu. LA - eng PT - Journal Article DEP - 20250626 PL - Switzerland TA - Pancreatology JT - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JID - 100966936 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Pancreatitis/chemically induced/epidemiology MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Obesity/drug therapy/complications MH - Case-Control Studies MH - Adult MH - Risk Factors MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Acute Disease MH - Hypoglycemic Agents/adverse effects/therapeutic use OTO - NOTNLM OT - Acute pancreatitis OT - Glucagon-like peptide-1 receptor agonists OT - Obesity COIS- Declaration of competing interest Robert Postlethwaite, Amin M Amin, Rand Alsawas and Tarek Sawas: None. Jaime Almandoz: Paid consultant/advisor for Novo Nordisk and Eli Lilly and Company. EDAT- 2025/07/23 11:25 MHDA- 2025/08/31 20:05 CRDT- 2025/07/22 21:59 PHST- 2025/01/17 00:00 [received] PHST- 2025/06/22 00:00 [revised] PHST- 2025/06/26 00:00 [accepted] PHST- 2025/08/31 20:05 [medline] PHST- 2025/07/23 11:25 [pubmed] PHST- 2025/07/22 21:59 [entrez] AID - S1424-3903(25)00144-9 [pii] AID - 10.1016/j.pan.2025.06.018 [doi] PST - ppublish SO - Pancreatology. 2025 Aug;25(5):609-613. doi: 10.1016/j.pan.2025.06.018. Epub 2025 Jun 26. PMID- 40695613 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250731 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 4 DP - 2025 Jul 22 TI - Evaluating GLP-1 receptor agonists versus metformin as first-line therapy for reducing dementia risk in type 2 diabetes. LID - 10.1136/bmjdrc-2025-004902 [doi] LID - e004902 AB - INTRODUCTION: No direct comparisons have evaluated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus metformin as first-line antidiabetic therapy for preventing dementia in patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the comparative effectiveness of GLP-1 RAs and metformin in reducing dementia risk. RESEARCH DESIGN AND METHODS: This retrospective cohort study used data from a global health research network between 2004 and 2024. Patients with T2DM initiating GLP-1 RAs or metformin as first-line monotherapy were included. Propensity score matching was employed to balance baseline characteristics. Dementia incidence was analyzed using Cox proportional hazards models, with sensitivity analyses to confirm robustness. RESULTS: Among 87,229 matched patients per cohort, GLP-1 RA use was associated with a significantly lower risk of overall dementia (adjusted HR (AHR) 0.90; 95% CI 0.85 to 0.95), Alzheimer's disease (AD) (AHR 0.88; 95% CI 0.83 to 0.94), and non-vascular dementias (non-VaDs) (AHR 0.75; 95% CI 0.70 to 0.81) compared with metformin. No significant difference was observed for VaD. Subgroup analyses showed consistent benefit across age and sex, with the strongest effect among older adults and females. CONCLUSIONS: GLP-1 RAs were more effective than metformin in reducing the risk of dementia-especially AD and non-vascular types-highlighting their potential as a preferred first-line treatment in T2DM. Further randomized trials are warranted to validate these findings. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Sun, Mingyang AU - Sun M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China zhangjiq@zzu.edu.cn szuyuanwu5399@gmail.com mingyangsun1986@163.com. AD - Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China. FAU - Wang, Xiaoling AU - Wang X AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. FAU - Lu, Zhongyuan AU - Lu Z AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. FAU - Yang, Yitian AU - Yang Y AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Lv, Shuang AU - Lv S AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Miao, Mengrong AU - Miao M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. FAU - Wu, Szu Yuan AU - Wu SY AUID- ORCID: 0000-0001-5637-558X AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan zhangjiq@zzu.edu.cn szuyuanwu5399@gmail.com mingyangsun1986@163.com. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. AD - Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Division of Radiation Oncology, Lo-Hsu Medical Foundation,Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. FAU - Zhang, Jiaqiang AU - Zhang J AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China zhangjiq@zzu.edu.cn szuyuanwu5399@gmail.com mingyangsun1986@163.com. AD - Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250722 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Dementia/prevention & control/epidemiology/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Aged MH - Middle Aged MH - Risk Factors MH - Follow-Up Studies MH - Incidence MH - Aged, 80 and over PMC - PMC12306345 OTO - NOTNLM OT - Dementia OT - Diabetes Mellitus, Type 2 OT - Glucagon-Like Peptide 1 OT - Metformin COIS- Competing interests: None declared. EDAT- 2025/07/23 11:24 MHDA- 2025/07/23 11:25 PMCR- 2025/07/22 CRDT- 2025/07/22 21:42 PHST- 2025/01/13 00:00 [received] PHST- 2025/05/17 00:00 [accepted] PHST- 2025/07/23 11:25 [medline] PHST- 2025/07/23 11:24 [pubmed] PHST- 2025/07/22 21:42 [entrez] PHST- 2025/07/22 00:00 [pmc-release] AID - 13/4/e004902 [pii] AID - bmjdrc-2025-004902 [pii] AID - 10.1136/bmjdrc-2025-004902 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Jul 22;13(4):e004902. doi: 10.1136/bmjdrc-2025-004902. PMID- 40694751 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250722 IS - 1526-632X (Electronic) IS - 0028-3878 (Linking) VI - 105 IP - 3 DP - 2025 Aug 12 TI - GLP-1RA-Associated Diabetic Lumbosacral Radiculoplexus and Common Fibular Neuropathies: A Case-Control Evaluation. PG - e213916 LID - 10.1212/WNL.0000000000213916 [doi] AB - BACKGROUND AND OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to treat obesity and diabetes. Semaglutide, a GLP-1RA, is linked to nonarteritic ischemic optic neuropathy (NAION), macular edema, and retinopathy. Because diabetic lumbosacral radiculoplexus neuropathy (DLRPN) and common fibular neuropathy (CFN) are associated with weight loss, we examined whether GLP-1RA usage is linked to these neuropathies. METHODS: We conducted a retrospective case-controlled study from April 28, 2005 (the first GLP-1RA Food and Drug Administration approval), to December 25, 2024. Patients diagnosed with DLRPN or CFN were analyzed for GLP-1RA exposure and clinical characteristics. A control group, matched for age, sex, body mass index (BMI), and diabetes status, was used to assess for an association with GLP-1RA use. RESULTS: We identified 26 individuals who developed 27 DLRPN episodes, with median symptom onset 6 months (range 3-35 months) after GLP-1RA initiation. At onset, they had a median glycated hemoglobin A1c (HbA1c) reduction of 2.4% (range 1%-8.5%) and a BMI decrease of 4 units (range 1-15), reflecting a 13.9% (range 3.6%-28.5%) weight loss. Microvasculitis was present in 4 of 5 nerve biopsies. Among 77 individuals with CFN, 82 episodes developed, with a mean GLP-1RA duration of 15 months (range 1-112 months). In individuals with CFN, the median HbA1c reduction was 1.2% (range -0.4% to 5%) and the BMI decrease was 4 units (range 0-15), corresponding to a 15.7% (range 3.0%-37.0%) weight loss. Patients with DLRPN experienced greater HbA1c reductions than patients with CFN (2.4% vs 1.2%, p < 0.001). New NAION, macular edema, or retinopathy were not seen with episodes. Compared with controls, GLP-1RA users were 51% more likely to develop DLRPN (odds ratio [OR] 1.5, 95% CI 1.2-1.9, p = 0.0008) and 30% more likely to develop CFN (OR 1.3, 95% CI 1.0-1.5, p = 0.018). All episodes occurred after 2015, with 3 DLRPN events and 7 CFN events occurring between 2015 and 2019, rising to 24 and 70 cases in 2020-2024, reflecting increases of 700% and 900%. DISCUSSION: GLP-1RA use is associated with an increased likelihood of DLRPN and CFN. DLRPN and its associated nerve microvasculitis seem more strongly linked to metabolic changes, particularly significant HbA1c reductions, while CFN has compressive neuropathy characteristics and is more influenced by weight loss. FAU - Triplett, James D AU - Triplett JD AUID- ORCID: 0000-0001-9402-1248 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. FAU - Pinto, Marcus V AU - Pinto MV AUID- ORCID: 0000-0002-9890-6657 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Young, Nathan P AU - Young NP AUID- ORCID: 0000-0001-7788-6493 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Staff, Nathan P AU - Staff NP AUID- ORCID: 0000-0001-6760-3859 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Chinmay, Marathe S AU - Chinmay MS AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia. FAU - Horowitz, Michael AU - Horowitz M AUID- ORCID: 0000-0002-0942-0306 AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia. FAU - Aragon Pinto, Catarina AU - Aragon Pinto C AUID- ORCID: 0000-0003-2929-3313 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Laughlin, Ruple S AU - Laughlin RS AUID- ORCID: 0000-0002-1884-5824 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Shouman, Kamal AU - Shouman K AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Berini, Sarah E AU - Berini SE AUID- ORCID: 0009-0005-5988-4255 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Mauermann, Michelle L AU - Mauermann ML AUID- ORCID: 0000-0001-9619-7802 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Dubey, Divyanshu AU - Dubey D AUID- ORCID: 0000-0001-6865-9045 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and. FAU - Mandrekar, Jay AU - Mandrekar J AUID- ORCID: 0000-0002-9718-4082 AD - Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN. FAU - Dyck, P James B AU - Dyck PJB AUID- ORCID: 0000-0003-0212-8254 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Klein, Christopher J AU - Klein CJ AUID- ORCID: 0000-0002-4012-8856 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and. LA - eng PT - Journal Article DEP - 20250722 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Diabetic Neuropathies/chemically induced/epidemiology MH - Case-Control Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peroneal Neuropathies/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - *Radiculopathy/chemically induced MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy EDAT- 2025/07/23 11:24 MHDA- 2025/07/23 11:25 CRDT- 2025/07/22 16:03 PHST- 2025/07/23 11:25 [medline] PHST- 2025/07/23 11:24 [pubmed] PHST- 2025/07/22 16:03 [entrez] AID - 10.1212/WNL.0000000000213916 [doi] PST - ppublish SO - Neurology. 2025 Aug 12;105(3):e213916. doi: 10.1212/WNL.0000000000213916. Epub 2025 Jul 22. PMID- 40693572 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260512 IS - 1445-5994 (Electronic) IS - 1444-0903 (Print) IS - 1444-0903 (Linking) VI - 55 IP - 10 DP - 2025 Oct TI - Is semaglutide cost-effective at closing the gap for Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity without type 2 diabetes? PG - 1725-1732 LID - 10.1111/imj.70160 [doi] AB - BACKGROUND: Aboriginal and Torres Strait Islander Australians experience worse healthcare outcomes due to increased prevalence of cardiovascular disease (CVD). A large proportion of this is preventable if CVD risk factors, such as obesity, are effectively treated. In the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) trial, the use of semaglutide for patients with CVD and obesity without type 2 diabetes (T2D) significantly reduced the prevalence of CVD. AIM: To determine the cost-benefit to the Australian healthcare system of funding early-access semaglutide for treating Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D. METHODS: A Markov cohort state-transition model was annually cycled for 25 years. The population was Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D. They received either semaglutide or standard care. Transition probabilities, utilities, costs and discounting were literature-derived. The incremental cost-effectiveness ratio (ICER) was our primary outcome. Disability-adjusted life-years (DALYs) and fatal and non-fatal CVD events prevented were secondary outcomes. Sensitivity analysis for various scenarios was performed. RESULTS: In the estimated 13 650 Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D, semaglutide was modelled to prevent an additional 929 fatal CVD events, 13 480 non-fatal CVD events and 8628 DALYs over 25 years at an additional cost to the Australian government of $25 956 522/year (<0.2% of annual CVD expenditure). The ICER was $75 206/DALYs. CONCLUSION: A strategy of early-access funding and use of semaglutide for Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D may be cost-effective to the Australian healthcare system while closing the gap in healthcare disparities. CI - (c) 2025 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians. FAU - Hargovan, Satyen AU - Hargovan S AUID- ORCID: 0000-0002-5194-5317 AD - Department of Cardiology, The Prince Charles Hospital, Brisbane, Queensland, Australia. AD - College of Medicine, James Cook University, Townsville, Queensland, Australia. FAU - Hunt, Nadine AU - Hunt N AD - National Centre for Aboriginal and Torres Strait Islander Wellbeing Research and National Centre for Epidemiology and Population Health, College of Health and Medicine, The Australian National University, Canberra, Australian Capital Territory, Australia. FAU - Kostakis, Hara AU - Kostakis H AD - Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, University of London, London, UK. FAU - Chow, Clara K AU - Chow CK AD - Westmead Applied Research Centre, University of Sydney, Sydney, New South Wales, Australia. AD - Department of Cardiology, Westmead Hospital, Sydney, New South Wales, Australia. LA - eng PT - Journal Article DEP - 20250722 PL - Australia TA - Intern Med J JT - Internal medicine journal JID - 101092952 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - Australia/epidemiology MH - *Australian Aboriginal and Torres Strait Islander Peoples/statistics & numerical data MH - *Cardiovascular Diseases/economics/drug therapy/ethnology/epidemiology MH - Cohort Studies MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/economics/epidemiology/drug therapy/ethnology MH - Markov Chains MH - *Obesity/drug therapy/economics/ethnology/epidemiology MH - *Glucagon-Like Peptide 1/economics/therapeutic use MH - Semaglutide PMC - PMC12515466 OTO - NOTNLM OT - Aboriginal and Torres Strait Islander OT - cardiovascular disease OT - economic analysis OT - obesity OT - prevention OT - semaglutide EDAT- 2025/07/23 10:54 MHDA- 2025/10/12 12:31 PMCR- 2025/10/12 CRDT- 2025/07/22 07:22 PHST- 2025/03/19 00:00 [received] PHST- 2025/06/15 00:00 [accepted] PHST- 2025/10/12 12:31 [medline] PHST- 2025/07/23 10:54 [pubmed] PHST- 2025/07/22 07:22 [entrez] PHST- 2025/10/12 00:00 [pmc-release] AID - IMJ70160 [pii] AID - 10.1111/imj.70160 [doi] PST - ppublish SO - Intern Med J. 2025 Oct;55(10):1725-1732. doi: 10.1111/imj.70160. Epub 2025 Jul 22. PMID- 40692597 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250724 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice. PG - 1547920 LID - 10.3389/fendo.2025.1547920 [doi] LID - 1547920 AB - AIM: We investigated the impact of genetic polymorphisms in the GLP1R and SLC5A2 genes on the response to treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose co-transporter-2 (SLGT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice. METHODS: In our prospective interventional cohort open-label real-world genetic association study (DRKS-ID: DRKS00034478, https://drks.de/search/en/trial/DRKS00034478), we enrolled 161 clinically well-defined T2DM patients who received SGLT2 inhibitors and/or GLP-1R agonists alongside other medications for 3-6 months. The study's primary outcomes (HbA1c, body mass, and blood pressure) were measured before the treatment and at the follow-up at 3-6 months. GLP1R rs6923761, rs10305420, and SLC5A2 rs9934336 genotypes were determined by competitive allele-specific polymerase chain reaction. In patients receiving GLP-1R agonists, we analyzed the effect of GLP1R polymorphisms on the patients' response to treatment, while in patients receiving SGLT2 inhibitors, we analyzed the impact of the SLC5A2 polymorphism on the treatment effect. RESULTS: Treatment with prescribed antihyperglycemic drugs improved all primary outcomes (p < 0.050). The normal GLP1R rs6923761 G allele was associated with a greater reduction in HbA1c with GLP-1R agonists treatment than the polymorphic A allele in the dominant model (p = 0.029). CONCLUSIONS: The prevalent polymorphic A allele of GLP1R rs6923761 polymorphism was associated with the clinically relevant lower glycemic response to GLP-1R agonists. The described impact extends to everyday clinical practice, indicating that knowledge of these genetic polymorphisms could facilitate the development of targeted and personalized therapy in managing T2DM. CI - Copyright (c) 2025 Tonin, Goricar, Blagus, Janez, Dolzan and Klen. FAU - Tonin, Gasper AU - Tonin G AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Faculty of Arts, University of Ljubljana, Ljubljana, Slovenia. FAU - Goricar, Katja AU - Goricar K AD - Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Blagus, Tanja AU - Blagus T AD - Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AD - Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Division of Internal Medicine, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Dolzan, Vita AU - Dolzan V AD - Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Klen, Jasna AU - Klen J AD - Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Division of Surgery, Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia. LA - eng PT - Journal Article DEP - 20250707 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (SLC5A2 protein, human) RN - 0 (GLP1R protein, human) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Sodium-Glucose Transporter 2/genetics MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Aged MH - Prospective Studies MH - Blood Glucose MH - *Blood Pressure/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Polymorphism, Single Nucleotide MH - Hypoglycemic Agents/therapeutic use MH - Glycemic Control MH - Follow-Up Studies PMC - PMC12277154 OTO - NOTNLM OT - GLP-1RA OT - GLP1R OT - SGLT2 OT - SLC5A2 OT - everyday clinical practice OT - polymorphism OT - treatment response OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/07/22 06:26 MHDA- 2025/07/22 06:27 PMCR- 2025/07/07 CRDT- 2025/07/22 04:38 PHST- 2024/12/18 00:00 [received] PHST- 2025/06/20 00:00 [accepted] PHST- 2025/07/22 06:27 [medline] PHST- 2025/07/22 06:26 [pubmed] PHST- 2025/07/22 04:38 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - 10.3389/fendo.2025.1547920 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jul 7;16:1547920. doi: 10.3389/fendo.2025.1547920. eCollection 2025. PMID- 40692593 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250905 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists - a comprehensive review. PG - 1605746 LID - 10.3389/fendo.2025.1605746 [doi] LID - 1605746 AB - Cardiovascular and renal complications remain leading causes of morbidity and mortality among individuals with type 2 diabetes mellitus (T2DM). Since 2015, large-scale cardiovascular outcome trials (CVOTs) have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce the risk of major adverse cardiovascular events, cardiovascular mortality, and heart failure hospitalization in patients with T2DM and established cardiovascular disease or high-risk profiles. These findings-originating from landmark trials such as EMPA-REG OUTCOME, LEADER, and SUSTAIN-6-have led to substantial revisions in international guidelines from the European Society of Cardiology, American College of Cardiology, and American Heart Association, which now recommend the use of SGLT2i or GLP-1 RAs, often in conjunction with metformin. SGLT2i have shown robust effects in reducing heart failure hospitalization and slowing the progression of chronic kidney disease, while GLP-1 RAs have demonstrated superior efficacy in reducing atherothrombotic events, particularly non-fatal stroke. Additionally, emerging data supports the complementary use of both drug classes, revealing additive benefits on cardiovascular and renal outcomes without increased toxicity. This narrative review summarizes the mechanisms of action, clinical efficacy, safety profiles, and sex-specific outcomes associated with SGLT2i and GLP-1 RAs. It also highlights key evidence supporting their combined use and underscores their critical role in optimizing long-term outcomes in patients with T2DM and cardiovascular disease. CI - Copyright (c) 2025 Aristizabal-Colorado, Corredor-Rengifo, Sierra-Castillo, Lopez-Corredor, Vernaza-Trujillo, Weir-Restrepo, Izquierdo-Condoy, Ortiz-Prado, Rico-Fontalvo, Gomez-Mesa, Abreu-Lomba and Rivera-Martinez. FAU - Aristizabal-Colorado, David AU - Aristizabal-Colorado D AD - Internal Medicine Department, Universidad Libre, Cali, Colombia. AD - Grupo Interinstitucional de Medicina Interna (GIMI1), Universidad Libre, Cali, Colombia. FAU - Corredor-Rengifo, David AU - Corredor-Rengifo D AD - Internal Medicine Department, Universidad Libre, Cali, Colombia. AD - Grupo Interinstitucional de Medicina Interna (GIMI1), Universidad Libre, Cali, Colombia. FAU - Sierra-Castillo, Santiago AU - Sierra-Castillo S AD - Epidemiology Department, Universidad Centros de Estudios en Salud (CES), Medellin, Colombia. FAU - Lopez-Corredor, Carolina AU - Lopez-Corredor C AD - Medicine Program, Universidad Santiago de Cali, Cali, Colombia. FAU - Vernaza-Trujillo, David-Alexander AU - Vernaza-Trujillo DA AD - Grupo Interinstitucional de Medicina Interna (GIMI1), Universidad Libre, Cali, Colombia. FAU - Weir-Restrepo, Danilo AU - Weir-Restrepo D AD - Internal Medicine Department, Universidad Centros de Estudios en Salud (CES), Medellin, Colombia. FAU - Izquierdo-Condoy, Juan S AU - Izquierdo-Condoy JS AD - One Health Research Group, Universidad de las Americas, Quito, Ecuador. FAU - Ortiz-Prado, Esteban AU - Ortiz-Prado E AD - One Health Research Group, Universidad de las Americas, Quito, Ecuador. FAU - Rico-Fontalvo, Jorge AU - Rico-Fontalvo J AD - Department of Nephrology, Faculty of Medicine, Universidad Simon Bolivar, Barranquilla, Colombia. AD - Latin American Society of Nephrology and Arterial Hypertension (SLANH), Ciudad de Panama, Panama. FAU - Gomez-Mesa, Juan-Esteban AU - Gomez-Mesa JE AD - Cardiology Department, Fundacion Valle del Lili, Cali, Colombia. AD - Department of Health Sciences, Universidad Icesi, Cali, Colombia. FAU - Abreu-Lomba, Alin AU - Abreu-Lomba A AD - Endocrinology Department, Clinica Imbanaco, Cali, Colombia. FAU - Rivera-Martinez, Wilfredo-Antonio AU - Rivera-Martinez WA AD - Grupo Interinstitucional de Medicina Interna (GIMI1), Universidad Libre, Cali, Colombia. AD - Endocrinology Department, Universidad de Antioquia, Medellin, Colombia. LA - eng PT - Journal Article PT - Review DEP - 20250707 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Front Endocrinol (Lausanne). 2025 Aug 20;16:1663787. doi: 10.3389/fendo.2025.1663787. PMID: 40909226 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Cardiovascular Diseases/drug therapy/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12277171 OTO - NOTNLM OT - GLP-1 agonists OT - SGLT2 inhibitors OT - cardiovascular outcomes OT - combination therapy OT - heart failure OT - renal outcomes COIS- JR-F declares that he has received honoraria for lectures for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lilly, Sanofi, Novartis, Abbvie, Merck, and Bayer. He has participated in Advisory Board with AstraZeneca, Boehringer Ingelheim, Bayer, and Novo Nordisk. J-EG-M declares that he has received honoraria for lectures for AstraZeneca, Bayer, Boheringer Ingelheim, Merck, and Xinetixs Pharma. He has participated in Advisory Board with AstraZeneca, and Boheringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/07/22 06:26 MHDA- 2025/07/22 06:27 PMCR- 2025/07/07 CRDT- 2025/07/22 04:38 PHST- 2025/04/03 00:00 [received] PHST- 2025/06/20 00:00 [accepted] PHST- 2025/07/22 06:27 [medline] PHST- 2025/07/22 06:26 [pubmed] PHST- 2025/07/22 04:38 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - 10.3389/fendo.2025.1605746 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jul 7;16:1605746. doi: 10.3389/fendo.2025.1605746. eCollection 2025. PMID- 40690769 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 9 DP - 2025 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes : A Target Trial Emulation. PG - 1258-1267 LID - 10.7326/ANNALS-24-02648 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to decrease blood glucose levels, promote weight loss, and prevent cardiovascular events. However, evidence is limited regarding their effect on dementia, although emerging observational studies, some with serious methodological limitations, have suggested large reductions in dementia associated with GLP-1RAs that may not be entirely causally related. OBJECTIVE: To compare the effect of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is) as second-line therapy for type 2 diabetes on risk for dementia among older adults. DESIGN: Target trial emulation. SETTING: United States from January 2016 to December 2020. PARTICIPANTS: Medicare fee-for-service beneficiaries aged 66 years or older with diabetes who used metformin and did not have dementia at baseline and initiated GLP-1RAs or DPP4is between January 2017 and December 2018. MEASUREMENTS: Onset of dementia was defined as 1 year before the date of a new dementia diagnosis. Risks were calculated at 30 months in GLP-1RA and DPP4i groups matched in a 1:2 ratio on an estimated propensity score and compared via ratios and differences. RESULTS: Among 2418 patients initiating GLP-1RAs and 4836 matched patients initiating DPP4is, the mean age was 71 years, and 55% were female. Over a median follow-up of 1.9 years, the outcome occurred in 96 patients in the GLP-1RA group and 217 in the DPP4i group. The estimated risk difference at 30 months was -0.93 (95% CI, -2.33 to 0.23) percentage points, and the estimated risk ratio was 0.83 (95% CI, 0.61 to 1.05). The estimated risk ratios were 0.64 (95% CI, 0.46 to 0.93) and 1.22 (95% CI, 0.74 to 1.66) among those younger than 75 years and aged 75 years or older, respectively. LIMITATIONS: Potential residual confounding (no data on body mass index, glycemic control, or duration of diabetes), outcome misclassification, and short follow-up. CONCLUSION: Among older adults with diabetes, no clear evidence was found that the incidence of dementia differed overall between patients using GLP-1RAs versus DPP4is. Under conventional statistical criteria, an effect of GLP-1RAs between a 39% decrease and a 5% increase in risk for dementia was highly compatible with the data, although estimates differed by age. Randomized trials are needed to quantify the effect of GLP-1RAs on dementia. PRIMARY FUNDING SOURCE: Gregory Annenberg Weingarten, GRoW @ Annenberg. FAU - Inoue, Kosuke AU - Inoue K AUID- ORCID: 0000-0001-9614-8103 AD - Department of Social Epidemiology, Graduate School of Medicine, Kyoto University, and Hakubi Center, Kyoto University, Kyoto, Japan (K.I.). FAU - Saliba, Debra AU - Saliba D AD - U.S. Department of Veterans Affairs Greater Los Angeles Healthcare System (VAGLAS) Geriatrics Research, Education and Clinical Centers, Los Angeles, California; Borun Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; and RAND Corporation, Santa Monica, California (D.S.). FAU - Gotanda, Hiroshi AU - Gotanda H AD - Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California (H.G.). FAU - Moin, Tannaz AU - Moin T AUID- ORCID: 0000-0002-5035-6641 AD - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California (T.M.). FAU - Mangione, Carol M AU - Mangione CM AUID- ORCID: 0000-0002-9475-2275 AD - Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, and Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, California (C.M.M.). FAU - Klomhaus, Alexandra M AU - Klomhaus AM AUID- ORCID: 0000-0002-7676-3595 AD - UCLA Department of Medicine Statistics Core, Los Angeles, California (A.M.K.). FAU - Tsugawa, Yusuke AU - Tsugawa Y AUID- ORCID: 0000-0002-1937-4833 AD - Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA; Department of Health Policy and Management, UCLA Fielding School of Public Health; and UCLA Department of Medicine Statistics Core, Los Angeles, California (Y.T.). LA - eng PT - Journal Article DEP - 20250722 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dementia/epidemiology/prevention & control MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Incidence MH - United States/epidemiology MH - Aged, 80 and over MH - Medicare MH - Metformin/therapeutic use COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/07/21 18:31 MHDA- 2025/09/17 00:30 CRDT- 2025/07/21 17:03 PHST- 2025/09/17 00:30 [medline] PHST- 2025/07/21 18:31 [pubmed] PHST- 2025/07/21 17:03 [entrez] AID - 10.7326/ANNALS-24-02648 [doi] PST - ppublish SO - Ann Intern Med. 2025 Sep;178(9):1258-1267. doi: 10.7326/ANNALS-24-02648. Epub 2025 Jul 22. PMID- 40690352 OWN - NLM STAT- MEDLINE DCOM- 20251222 LR - 20260226 IS - 1529-4242 (Electronic) IS - 0032-1052 (Linking) VI - 157 IP - 1 DP - 2026 Jan 1 TI - Disruptions in Aesthetic Medicine: A Global Analysis of GLP-1 Agonists Using Punctuated Equilibrium Framework. PG - 84-102 LID - 10.1097/PRS.0000000000012307 [doi] AB - BACKGROUND: The adoption of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, has significantly improved obesity and type 2 diabetes management. However, their unintended side effects, particularly facial volume loss, termed "Ozempic face," have disrupted aesthetic medicine. This intersection between metabolic health and aesthetics raises ethical dilemmas and growing dependency on corrective interventions such as dermal fillers. METHODS: A mixed-methods approach was used, incorporating content analysis, social media sentiment analysis, and social network modeling. Data were collected from 15 peer-reviewed studies, clinical reports, and 3.79 million social media posts across global regions. Sentiment analysis identified public perceptions, whereas network analysis examined influencer dominance in promoting aesthetic solutions. RESULTS: Findings revealed a 40% increase in filler consultations attributed to GLP-1-related aesthetic concerns. Sentiment analysis showed that 72% of high-engagement content was driven by influencers normalizing fillers as necessary adjuncts to GLP-1 therapies. Ethical concerns were prominent, particularly in regions such as Asia and South America, where commercial narratives dominate. In contrast, North America and Europe demonstrated a more balanced approach, prioritizing informed patient care under regulatory frameworks. CONCLUSIONS: GLP-1 therapies represent a transformative shift in metabolic care but introduce significant aesthetic, ethical, and psychological challenges. Social media amplifies commercial influences, often at the cost of evidence-based practice. Regulatory reforms, longitudinal studies, and enhanced patient education are critical to navigating this evolving landscape and ensuring patient well-being. CI - Copyright (c) 2025 by the American Society of Plastic Surgeons. FAU - Rahman, Eqram AU - Rahman E AD - From the Research and Innovation Hub, Innovation Aesthetics. FAU - Webb, William Richard AU - Webb WR AD - From the Research and Innovation Hub, Innovation Aesthetics. FAU - Sadeghi-Esfahlani, Shabnam AU - Sadeghi-Esfahlani S AD - Medical Technology Research Centre, Anglia Ruskin University. FAU - Rao, Parinitha AU - Rao P AD - The Skin Address (aesthetic dermatology practice). FAU - Garcia, Patricia E AU - Garcia PE AD - private practice. FAU - Sayed, Karim AU - Sayed K AD - Nomi Oslo. FAU - Ioannidis, Sotirios AU - Ioannidis S AD - Plastic Surgery Clinic. FAU - Yu, Nanze AU - Yu N AD - Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College. FAU - Nassif, Alexander D AU - Nassif AD AD - Departamento de Pesquisa, Nucleo Nassif-Ensino Medico e Pesquisa. FAU - Goodman, Greg J AU - Goodman GJ AD - Monash University Australia. AD - Dermatology Institute of Victoria. FAU - Carruthers, Jean D A AU - Carruthers JDA AD - Department of Ophthalmology, University of British Columbia. LA - eng GR - DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250715 PL - United States TA - Plast Reconstr Surg JT - Plastic and reconstructive surgery JID - 1306050 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dermal Fillers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cosmetic Techniques/ethics/adverse effects MH - Social Media/statistics & numerical data MH - *Glucagon-Like Peptides/adverse effects MH - *Dermal Fillers/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Esthetics MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/21 18:31 MHDA- 2025/12/22 12:55 CRDT- 2025/07/21 12:23 PHST- 2025/12/22 12:55 [medline] PHST- 2025/07/21 18:31 [pubmed] PHST- 2025/07/21 12:23 [entrez] AID - 00006534-990000000-02701 [pii] AID - 10.1097/PRS.0000000000012307 [doi] PST - ppublish SO - Plast Reconstr Surg. 2026 Jan 1;157(1):84-102. doi: 10.1097/PRS.0000000000012307. Epub 2025 Jul 15. PMID- 40685589 OWN - NLM STAT- MEDLINE DCOM- 20251028 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 33 IP - 11 DP - 2025 Nov TI - Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. PG - 2046-2054 LID - 10.1002/oby.24360 [doi] AB - OBJECTIVE: To compare the efficacy and safety of GLP-1 receptor agonists (GLP-1RAs), dual agonists (GLP-1RAs/GIP or GCGR), and retatrutide (GLP-1/GIP/glucagon) for weight loss in adults with overweight or obesity. METHODS: We conducted a systematic review and Bayesian network meta-analysis (NMA) of 19 randomized controlled trials (RCTs) including 29,506 adults (BMI >/= 25 kg/m(2)), assessing liraglutide, semaglutide, survodutide, tirzepatide, retatrutide, and placebo. Outcomes included mean weight loss, achievement of >/= 5%, >/= 10%, and >/= 15% weight loss, waist circumference (WC), BMI, and adverse events (AEs) at >/= 36 weeks. Subgroup and meta-regression analyses evaluated the impact of diabetes status, sex, age, and BMI. RESULTS: Retatrutide and dual agonists achieved equivalent mean weight loss (-11.0 kg), surpassing GLP-1RAs (-9.0 kg), with retatrutide excelling at achieving >/= 15% weight loss (OR 54.6). Dual agonists and GLP-1RAs followed (OR 16.4 and 9.0, respectively). Retatrutide had the highest AE risk. Meta-regression showed type 2 diabetes mellitus (T2DM) reduced weight loss by 4.338 kg for GLP-1RAs and 5.016 kg for dual agonists, with enhanced outcomes in female-dominant or high-BMI cohorts. CONCLUSIONS: Retatrutide offers superior weight loss efficacy but with a higher AE risk. Dual agonists provide a favorable efficacy-safety balance. Personalized treatment selection based on patient characteristics is recommended. CI - (c) 2025 The Obesity Society. FAU - Sinha, Binayak AU - Sinha B AD - Department of Endocrinology, Manipal Hospital, Kolkata, India. FAU - Ghosal, Samit AU - Ghosal S AUID- ORCID: 0000-0002-4141-5187 AD - Department of Internal Medicine, Nightingale Hospital, Kolkata, India. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250720 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Fatty Acids) RN - 0 (Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (retatrutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Bayes Theorem MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Randomized Controlled Trials as Topic MH - Tirzepatide MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Fatty Acids MH - Peptides MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - adverse events OT - dual agonists OT - network meta-analysis OT - obesity OT - retatrutide OT - weight loss EDAT- 2025/07/21 06:30 MHDA- 2025/10/28 06:30 CRDT- 2025/07/21 00:43 PHST- 2025/05/14 00:00 [revised] PHST- 2025/03/30 00:00 [received] PHST- 2025/05/15 00:00 [accepted] PHST- 2025/10/28 06:30 [medline] PHST- 2025/07/21 06:30 [pubmed] PHST- 2025/07/21 00:43 [entrez] AID - 10.1002/oby.24360 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Nov;33(11):2046-2054. doi: 10.1002/oby.24360. Epub 2025 Jul 20. PMID- 40682632 OWN - NLM STAT- MEDLINE DCOM- 20251107 LR - 20251107 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 25 IP - 6 DP - 2025 Nov TI - Association of Glucagon-Like Peptide-1 Receptor Agonist with Incident Atrial Fibrillation. PG - 803-816 LID - 10.1007/s40256-025-00751-y [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing cardiovascular events in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies associated GLP-1RAs with arrhythmogenesis, other studies suggested a decreased association with atrial fibrillation (AF). OBJECTIVE: The aim was to compare the risk of incident AF after initiation of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is), as active comparators, in patients with DM. DESIGN: A retrospective propensity score-matched cohort study was conducted. SETTING: The national data of Veterans Health Administration during fiscal years 2006-2021 were used for the study. PATIENTS: Adults who initiated either GLP-1RA or DPP4i medications were included. MEASUREMENTS: The primary outcome was a composite outcome of AF (diagnosis of AF/flutter or undergoing an AF procedure). RESULTS: Out of 116,235 GLP-1RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics. The composite outcome of AF was similar in the GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (p > 0.05). Individuals achieving 5% weight loss from baseline body weight had significantly lower AF incidence (OR 0.83, 95% CI 0.78-0.89), whereas no significant differences were observed in those with no weight loss or weight gain (OR 1.05, 95% CI 0.97-1.12). CONCLUSIONS: GLP-1RA use was not associated with a decreased or increased risk of AF compared to DPP4i use. In subgroup analysis, lower AF risk was seen in GLP-1RA versus DPP4i users who achieved weight loss, which suggests weight loss as a potential modifier of response to GLP-1RAs. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Khalil, Suzan AU - Khalil S AD - University of Central Florida/HCA Florida Healthcare, Greater Orlando, FL, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA. FAU - Hicks, William AU - Hicks W AD - University of Central Florida/HCA Florida Healthcare, Greater Orlando, FL, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA. FAU - Burke, Floyd W AU - Burke FW AD - Medicine Service, Section of Cardiology, Orlando VA Healthcare System, Orlando, FL, USA. FAU - Mansi, Ishak A AU - Mansi IA AUID- ORCID: 0000-0001-6122-3716 AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA. Ishak.mansi@va.gov. AD - Education Services, Orlando VA Healthcare System, 13800 Veterans Way, Orlando, FL, 32827, USA. Ishak.mansi@va.gov. LA - eng PT - Journal Article DEP - 20250719 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Atrial Fibrillation/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - Propensity Score MH - *Diabetes Mellitus, Type 2/drug therapy MH - United States/epidemiology MH - Cohort Studies COIS- Declarations. Disclosures: The authors have no disclosures. Funding: No external funding was used in the preparation of this article. This material is the result of work supported with resources and the use of facilities at the Orlando VA Healthcare System (Orlando, Florida). This research was supported, in part or in whole, by HCA Healthcare and/or an HCA Healthcare affiliated entity. Conflict of interest: Suzan Khalil, William Hicks, Floyd W. Burke, and Ishak A. Mansi declare that they have no potential conflicts of interest that might be relevant to the contents of this article. Data availability statement: Data are stored in the VA Informatics and Computing Infrastructure (VINCI), the operational platform for health services research at the Veterans Healthcare Administration (VHA). VINCI acts as the data steward for VHA Data Systems. Data in VINCI cannot be copied, transferred, or printed. Access to data by other researchers is possible following VINCI protocols, as described in VINCI Central web site: http://vaww.vinci.med.va.gov/VinciCentral . Ethics approval and consent to participate: The Orlando VA institutional review board approved the study and waived participants informed consent since only preexisting deidentified data were analyzed. Code availability: Not applicable. Consent for publication: Not applicable. Author contributions: Study concept and design: IAM, SK, and FWB. Acquisition of data; statistical analysis: IAM. Interpretation of data: SK, WLH, FWB, and IAM. Drafting of the manuscript: SK and WLH. Critical revision of the manuscript for important intellectual content: IAM, FWB, and SK. Study supervision: IAM and FWB. Has full access to all the data and takes responsibility for its integrity and the data analysis: IAM. EDAT- 2025/07/20 04:00 MHDA- 2025/11/07 12:47 CRDT- 2025/07/19 11:05 PHST- 2025/07/06 00:00 [accepted] PHST- 2025/11/07 12:47 [medline] PHST- 2025/07/20 04:00 [pubmed] PHST- 2025/07/19 11:05 [entrez] AID - 10.1007/s40256-025-00751-y [pii] AID - 10.1007/s40256-025-00751-y [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2025 Nov;25(6):803-816. doi: 10.1007/s40256-025-00751-y. Epub 2025 Jul 19. PMID- 40679854 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260520 IS - 1520-4812 (Electronic) IS - 1043-1802 (Linking) VI - 36 IP - 8 DP - 2025 Aug 20 TI - Innovative Glucagon-like Peptide 1 Receptor Agonists: Exploring the Therapeutic Potential of Specific Modified Monomer, Dimer, and Tetramer in Type 2 Diabetes Treatment. PG - 1753-1766 LID - 10.1021/acs.bioconjchem.5c00261 [doi] AB - Modified glucagon-like peptide 1 (GLP-1) plays a crucial role in type 2 diabetes (T2D) treatment. The comparative hypoglycemic effect among fatty-acid-modified GLP-1 monomer G20, dimer 2G21, and tetramer 4G18 was evaluated in T2D mice. The polymers exhibited an opposite solubility with their monomers. After single administration, the oral glucose tolerance test results showed that the monomers, dimer, or tetramer, respectively, had 3-9, 21, or 35 days of hypoglycemic effect or plasma stability. G20 had a moderate hypoglycemic effect, and its peak effect occurred in week 1 as semaglutide. 2G21 showed a strongly hypoglycemic effect in week 1-10, and its peak effect occurred in week 4. 4G18 had a weak effect initially but rapidly strengthened in weeks 6-10 and reached its peak effect in week 10. After the 10 week interference, compared to the model control group, G20 (-19.7 or -4.3%), 2G21-L/M/H (-15.9/-34.3/-26.7% or -6.0/-34.4/-36.2%), and 4G18-L/M/H groups (-44.3/-49.8/-53.8% or -40.9/-50.6/-50.8%) significantly exhibited hypoglycemic effects in postprandial glucose or fasting plasma glucose changes. Insulin altered +4.1% (G20), -9.6/+10.0/+36.5% (2G21-L/M/H), and +38.5/+28.7/+84.8% (4G18-L/M/H). HbA(1c) or body weight reduced -11.9 or -0.18% (G20), -5.2/-15.2/-19.1% or +0.5/-4.7/-1.2% (2G21-L/M/H), and -5.8/-4.8/-5.4% or -2.9/-2.1/-3.1% (4G18-L/M/H), showing a dose-dependent reduction in 2G21, whereas the 4G18 had lower variations. 2G21 induced a hypoglycemic effect and diet stress, whereas 4G18 only did a hypoglycemic effect and showed a stronger protection to the model organs and more improvement in the nerve muscle than G20 or 2G21. The endogenous insulin release depends not only on the GLP-1 peptide dose but also on the peptide chain in the polymer skeleton. FAU - Du, Yan AU - Du Y AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Liu, Tao AU - Liu T AD - Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Li, Hua-Lin AU - Li HL AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Luo, Qun AU - Luo Q AD - Translational Medicine Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China. FAU - Guo, Xiao-Yuan AU - Guo XY AD - Department of Pathology, Sanya People's Hospital, Sanya, Hainan Province 572000, China. FAU - Wang, Jian-Yun AU - Wang JY AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Wang, Xin-Rui AU - Wang XR AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Zhou, Ya-Man AU - Zhou YM AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Pan, Ya-Wen AU - Pan YW AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Yu, Li-Cheng AU - Yu LC AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Tan, Hong-Mei AU - Tan HM AD - Department of Clinical Laboratories, Luopu Community Health Service Center, Guangzhou 511431, China. FAU - Hu, Ke-Sheng AU - Hu KS AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Tang, Song-Shan AU - Tang SS AUID- ORCID: 0009-0000-9991-8636 AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250718 PL - United States TA - Bioconjug Chem JT - Bioconjugate chemistry JID - 9010319 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/chemistry/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mice MH - Male MH - *Glucagon-Like Peptide 1/chemistry/therapeutic use MH - Blood Glucose/analysis MH - Glucose Tolerance Test MH - Diabetes Mellitus, Experimental/drug therapy MH - Mice, Inbred C57BL MH - Semaglutide EDAT- 2025/07/18 12:29 MHDA- 2025/08/20 06:31 CRDT- 2025/07/18 11:52 PHST- 2025/08/20 06:31 [medline] PHST- 2025/07/18 12:29 [pubmed] PHST- 2025/07/18 11:52 [entrez] AID - 10.1021/acs.bioconjchem.5c00261 [doi] PST - ppublish SO - Bioconjug Chem. 2025 Aug 20;36(8):1753-1766. doi: 10.1021/acs.bioconjchem.5c00261. Epub 2025 Jul 18. PMID- 40678871 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 7 IP - Suppl 7 DP - 2025 Aug TI - An overview of randomized clinical trials of fixed-ratio combinations of basal insulin plus GLP-1RA (injectable therapy): Lessons for advancing therapy in people with type 2 diabetes. PG - 14-25 LID - 10.1111/dom.16616 [doi] AB - Advancing therapy in T2DM with injectables, i.e., basal insulin (BI) and GLP-1 receptor agonists (GLP-1RAs) is recommended after the failure of oral glucose lowering agents (OGLAs), BI alone, or BI in combination with OGLAs, especially in persons with, or at high risk of atherosclerotic cardiovascular disease (ASCVD). BI and GLP-1RAs can be administered separately or as fixed-ratio combinations (FRCs) for daily use (degludec+liraglutide, IDegLira, glargine-100 + lixisenatide iGlarLixi) or weekly use (icodec+semaglutide, IcoSema). The currently available FRCs IDegLira and iGlarLixi differ in their respective BI as well as GLP-1RA components. Liraglutide predominantly stimulates glucose-dependent endogenous insulin secretion in response to nutrient challenges. In contrast, the rapid-acting lixisenatide primarily delays gastric emptying over a few hours post-dosing with little or no impact on insulin secretion. IDegLira in DUAL studies and iGlarLixi in LixiLan studies appear to have equivalent lowering effects on HbA1c, although IDegLira achieves a greater reduction in body weight. The weekly FRC IcoSema is superior to weekly insulin icodec (COMBINE 1), to semaglutide (COMBINE 2), and non-inferior to basal-bolus insulin therapy (COMBINE 3). Comparison of IcoSema with glargine-100 is ongoing (COMBINE 4). However, all FRCs are limited by the low GLP-1RA dose relative to the insulin delivered. Whenever higher GLP-1RA doses are required (i.e., in obese people), the option of separate dosing of BI and GLP-1RA with independent titration of each component should be considered. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bolli, Geremia B AU - Bolli GB AUID- ORCID: 0000-0003-4966-4003 AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Porcellati, Francesca AU - Porcellati F AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Lucidi, Paola AU - Lucidi P AD - Centro Diabetologia Asl 2 Umbria 'Centro Storico', Foligno, Italy. FAU - Fanelli, Carmine G AU - Fanelli CG AUID- ORCID: 0000-0003-4063-158X AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Perseghin, Gianluca AU - Perseghin G AD - Department of Medicine and Surgery, Universita degli Studi di Milano Bicocca & Policlinico, di Monza, Monza, Italy. FAU - Horowitz, Michael AU - Horowitz M AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia. FAU - Owens, David R AU - Owens DR AUID- ORCID: 0000-0003-1002-1238 AD - Cardiff University Medical School, Cardiff, UK. LA - eng GR - University of Perugia/ GR - 2022KZ4KMY/MUR -PRIN/ PT - Journal Article PT - Review DEP - 20250717 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Drug Combinations) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Insulin, Long-Acting) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptides) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (IDegLira) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Combinations MH - Insulin Glargine/administration & dosage MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Liraglutide/administration & dosage MH - Drug Therapy, Combination MH - Glucagon-Like Peptides/administration & dosage MH - Peptides/administration & dosage MH - *Insulin/administration & dosage MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide-2 Receptor MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12308269 OTO - NOTNLM OT - GLP-1RA OT - basal insulin OT - fixed-ratio combinations basal insulin GLP-1RAs OT - type 2 diabetes COIS- G.B.B. has received honoraria for lecturing from Sanofi. F.P. receives clinical trial funding, advisory board, and lecture fees from Abbott, AstraZeneca, Lilly, Novo Nordisk, Sanofi. P.L. and C.G.F. have no conflicts of interest. G.P. has received honoraria for lecturing and advisory boards for Amgen, Bruno Farmaceutici, EG, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Echosens, Lilly, Menarini Diag, Merck, Novartis, Novo Nordisk, Pfizer, PikDare, Roche Diag, Sanofi, Servier; clinical trial funding from Novartis, Novo Nordisk, Merck. M.H. and D.R.O. have received lecture fees from Bayer, Boehringer Ingelheim, Roche, and Sanofi. EDAT- 2025/07/18 06:25 MHDA- 2025/07/30 06:30 PMCR- 2025/07/30 CRDT- 2025/07/18 05:43 PHST- 2025/06/24 00:00 [revised] PHST- 2025/05/04 00:00 [received] PHST- 2025/07/04 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/07/18 06:25 [pubmed] PHST- 2025/07/18 05:43 [entrez] PHST- 2025/07/30 00:00 [pmc-release] AID - DOM16616 [pii] AID - 10.1111/dom.16616 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27 Suppl 7(Suppl 7):14-25. doi: 10.1111/dom.16616. Epub 2025 Jul 17. PMID- 40677091 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - Weight reduction over time in tirzepatide-treated participants by early weight loss response: Post hoc analysis in SURMOUNT-1. PG - 5064-5071 LID - 10.1111/dom.16554 [doi] AB - AIMS: The objective was to assess weight reduction at Weeks 24 and 72 in participants treated with tirzepatide based on weight reduction response after 12 weeks of treatment in the SURMOUNT-1 trial. MATERIALS AND METHODS: This post hoc analysis included participants treated with tirzepatide who received >/=75% of the assigned treatment doses and had weight measurements at Weeks 0, 12, 24 and 72. Participants were categorized based on the 12-week response to tirzepatide: late responders (<5% weight reduction at Week 12) or early responders (>/=5% weight reduction at Week 12). RESULTS: A total of 1545 participants were included in the analyses, with 278 (18%) categorized as late responders and 1267 (82%) categorized as early responders. At baseline, late responders compared to early responders were more likely to be male (45% vs. 30%) and had higher body weight (110.2 vs. 103.6 kg), body mass index (BMI) (39.1 vs. 37.7 kg/m(2)) and waist circumference (117.5 vs. 113.4 cm). At the end of dose titration, Week 24, 194 (70%) late responders achieved >/=5% body weight reduction. At Week 72, 250 (90%) late responders achieved >/=5% body weight reduction. The mean time to reach 5% weight reduction for late responders was 24.8 +/- 12.7 weeks. Higher doses of tirzepatide were associated with higher proportions of participants achieving various weight reduction thresholds at Weeks 24 and 72. CONCLUSIONS: Among late responders to tirzepatide, the vast majority (90%) achieved 5% or more weight reduction at Week 72. This finding suggests that extending treatment well beyond 12 weeks may allow additional patients to achieve clinically meaningful weight reduction. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04184622, available at http://www. CLINICALTRIALS: gov/. CI - (c) 2025 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ard, Jamy AU - Ard J AUID- ORCID: 0000-0002-1643-6795 AD - Departments of Epidemiology & Prevention and Internal Medicine Vice Dean for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. FAU - Lee, Clare J AU - Lee CJ AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Gudzune, Kimberly AU - Gudzune K AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Addison, Brandi AU - Addison B AD - South Texas Endocrinology & Metabolism Center, PLLC, Corpus Christi, Texas, USA. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Cao, Dachuang AU - Cao D AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mast, Casey J AU - Mast CJ AUID- ORCID: 0009-0009-6808-6297 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Stefanski, Adam AU - Stefanski A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Falcon, Beverly AU - Falcon B AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mojdami, Donna AU - Mojdami D AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng SI - ClinicalTrials.gov/NCT04184622 GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250717 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Obesity/drug therapy MH - Time Factors MH - Tirzepatide MH - Treatment Outcome MH - Waist Circumference MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects PMC - PMC12326891 OTO - NOTNLM OT - response OT - tirzepatide COIS- Jamy Ard received research support from Nestle Healthcare Nutrition, Eli Lilly and Company, Boehringer Ingelheim, Epitomee, Inc., UnitedHealth Group R&D, KVKTech, WW and Novo Nordisk and is a consultant for Nestle Healthcare Nutrition, Eli Lilly and Company, Optum Labs R&D, Novo Nordisk, Intuitive, Regeneron, Brightseed, Amplifier Therapeutics, Amgen and Ingredion. Dr. Ard is an advisory board member for Novo Nordisk, Nestle Healthcare Nutrition, Eli Lilly and Company, WW and Boehringer Ingelheim. He is a member of the International Food Information Council-Assembly, The Obesity Society-President 2024, American Diabetes Association, Society of Behavioural Medicine, Roundtable on Obesity Solutions, American Society for Nutrition and American Society for Nutrition Foundation-Board of Trustees Executive Committee. Kimberly Gudzune was an Associate Professor in the Department of Medicine at the Johns Hopkins University School of Medicine and engaged in this research as a private advisor and not in her capacity as a Johns Hopkins faculty member. She received no compensation for this work. She has received personal fees for participation on advisory boards for Eli Lilly and Company and Novo Nordisk and travel support from Eli Lilly and Company and Novo Nordisk. Her former institution (Johns Hopkins) received grant funding from Novo Nordisk. Since the initial conduct of this research, Dr. Gudzune reports being an employee of the American Board of Obesity Medicine Foundation. Brandi Addison is a speaker for Eli Lilly and Company, Novo Nordisk and Corcept Therapeutics and is an advisory board member for Eli Lilly and Company. She is a member of the American Association of Clinical Endocrinology and The Obesity Society. Ildiko Lingvay received research funding (paid to institution) and/or products from Novo Nordisk, Sanofi, Boehringer-Ingelheim, Dexcom and received research-related consulting fees (paid to institution) from Novo Nordisk. She received advisory/consulting fees and/or other support from: AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly and Company, Intercept, Janssen/J&J, Juvena, Keros Therapeutic, Inc., Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD and Zealand Pharma. Clare J. Lee, Dachuang Cao, Casey J. Mast, Adam Stefanski, Beverly Falcon and Donna Mojdami are employees and shareholders of Eli Lilly and Company. EDAT- 2025/07/18 06:26 MHDA- 2025/08/06 12:28 PMCR- 2025/08/06 CRDT- 2025/07/18 04:15 PHST- 2025/05/30 00:00 [revised] PHST- 2025/03/27 00:00 [received] PHST- 2025/06/09 00:00 [accepted] PHST- 2025/08/06 12:28 [medline] PHST- 2025/07/18 06:26 [pubmed] PHST- 2025/07/18 04:15 [entrez] PHST- 2025/08/06 00:00 [pmc-release] AID - DOM16554 [pii] AID - 10.1111/dom.16554 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):5064-5071. doi: 10.1111/dom.16554. Epub 2025 Jul 17. PMID- 40676725 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260127 IS - 2058-1742 (Electronic) IS - 2058-1742 (Linking) VI - 11 IP - 8 DP - 2025 Dec 19 TI - Cardiovascular outcomes and safety of semaglutide in non-overweight populations with type 2 diabetes: a comparison with dipeptidyl peptidase 4 inhibitors. PG - 1319-1328 LID - 10.1093/ehjqcco/qcaf065 [doi] AB - AIMS: The effects of semaglutide on non-overweight patients with type 2 diabetes (T2D) remain unclear. We retrospectively compared all-cause mortality, cardiovascular outcomes, and adverse events in patients with T2D with a body mass index (BMI) < 25 kg/m(2) who received semaglutide or dipeptidyl peptidase 4 (DPP-4) inhibitors. METHODS AND RESULTS: Based on the TriNetX database of electronic medical records between 2018 and 2020, we identified 340 721 patients with T2D with a BMI <25 kg/m(2). Of the 6789 patients who received semaglutide, 2454 who received DPP-4 inhibitors after diagnosis were excluded. Of the 41 141 patients who received DPP-4 inhibitors, 5252 patients who received GLP-1 receptor agonists after diagnosis were excluded. After propensity score matching, 4194 patients were included in each group. The primary outcome was the 3-year cumulative incidence of all-cause mortality; the secondary outcomes were acute myocardial infarction (AMI) and stroke. The adverse events included nausea, vomiting, diarrhoea, and hypoglycaemia. The semaglutide group had a significantly lower risk of all-cause mortality compared to the DPP-4 inhibitor group [6.1% vs. 10.7%, P < 0.001; hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.45-0.65]. Semaglutide was not associated with the incidence of AMI (6.1% vs. 7.1%, P = 0.173; HR 0.87, 95% CI 0.72-1.06) or stroke (8.4% vs. 7.7%, P = 0.220; HR 1.11, 95% CI 0.94-1.32). Adverse events, including nausea and vomiting, diarrhoea, and hypoglycaemia, were not significantly different between the groups. CONCLUSION: In patients with T2D and BMI <25 kg/m2, semaglutide was associated with a lower 3-year risk of all-cause mortality than DPP-4 inhibitors. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - England TA - Eur Heart J Qual Care Clin Outcomes JT - European heart journal. Quality of care & clinical outcomes JID - 101677796 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1487. doi: 10.1093/ehjqcco/qcaf082. PMID: 40796132 CIN - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1263-1264. doi: 10.1093/ehjqcco/qcaf116. PMID: 40991735 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - *Cardiovascular Diseases/epidemiology/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Follow-Up Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - Retrospective Studies MH - Survival Rate/trends MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse event OT - All-cause mortality OT - Dipeptidyl peptidase-4 inhibitor OT - Glucagon-like peptide-1 receptor agonist OT - Non-overweight OT - Type 2 diabetes COIS- Conflict of interest: None. EDAT- 2025/07/18 01:38 MHDA- 2025/12/19 01:45 CRDT- 2025/07/17 23:52 PHST- 2025/03/02 00:00 [received] PHST- 2025/05/08 00:00 [revised] PHST- 2025/07/13 00:00 [accepted] PHST- 2025/12/19 01:45 [medline] PHST- 2025/07/18 01:38 [pubmed] PHST- 2025/07/17 23:52 [entrez] AID - 8205756 [pii] AID - 10.1093/ehjqcco/qcaf065 [doi] PST - ppublish SO - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1319-1328. doi: 10.1093/ehjqcco/qcaf065. PMID- 40676576 OWN - NLM STAT- MEDLINE DCOM- 20250718 LR - 20260925 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 25 IP - 1 DP - 2025 Jul 17 TI - Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte's secretome. PG - 182 LID - 10.1186/s12902-025-01999-w [doi] LID - 182 AB - BACKGROUND: Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections. METHODS: 17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel. RESULTS: Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy. CONCLUSIONS: The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission. CI - (c) 2025. The Author(s). FAU - Agareva, Margarita AU - Agareva M AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. AD - Lomonosov Moscow State University, Moscow, 119991, Russia. FAU - Michurina, Svetlana AU - Michurina S AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Tomilova, Alina AU - Tomilova A AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Shestakova, Ekaterina AU - Shestakova E AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Voznesenskaya, Anastasia AU - Voznesenskaya A AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Sineokaya, Maria AU - Sineokaya M AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Zubkova, Ekaterina AU - Zubkova E AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Ratner, Elizaveta AU - Ratner E AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Stafeev, Iurii AU - Stafeev I AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. yuristafeev@gmail.com. FAU - Parfyonova, Yelena AU - Parfyonova Y AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. AD - Lomonosov Moscow State University, Moscow, 119991, Russia. FAU - Shestakova, Marina AU - Shestakova M AD - Lomonosov Moscow State University, Moscow, 119991, Russia. AD - Endocrinology Research Centre, Moscow, 117292, Russia. LA - eng GR - 22-15-00365-capital PE, Cyrillic/Russian Science Foundation/ PT - Journal Article DEP - 20250717 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Incretins) RN - 0 (Cytokines) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood/pathology MH - Male MH - Female MH - Middle Aged MH - *Incretins/therapeutic use MH - Bariatric Surgery MH - *Cytokines/blood/metabolism MH - *Adipocytes/metabolism/drug effects MH - *Secretome/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - *Glucagon-Like Peptides/therapeutic use MH - Insulin Resistance MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12269230 OTO - NOTNLM OT - Adipocytes OT - Adipose-derived stem cells OT - Cytokines OT - Plasma OT - Secretome OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: The study protocol is in compliance with Declaration of Helsinki and was approved by the local ethics committee of the Endocrinology Research Centre (Moscow, Russia) in the framework of prolonged project "Dynamics of hormonal-metabolic factors, markers of "metabolic memory" and phenotypic characteristics of mature and progenitor cells of adipose tissue against the background of postbariatric remission of type 2 diabetes mellitus" (protocol #13 from 13 July 2022). Written informed consent was obtained from each of the volunteers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Disclosure summary: Authors have nothing to disclose. EDAT- 2025/07/18 01:41 MHDA- 2025/07/18 06:25 PMCR- 2025/07/17 CRDT- 2025/07/17 23:45 PHST- 2025/04/07 00:00 [received] PHST- 2025/07/07 00:00 [accepted] PHST- 2025/07/18 06:25 [medline] PHST- 2025/07/18 01:41 [pubmed] PHST- 2025/07/17 23:45 [entrez] PHST- 2025/07/17 00:00 [pmc-release] AID - 10.1186/s12902-025-01999-w [pii] AID - 1999 [pii] AID - 10.1186/s12902-025-01999-w [doi] PST - epublish SO - BMC Endocr Disord. 2025 Jul 17;25(1):182. doi: 10.1186/s12902-025-01999-w. PMID- 40673973 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 9 DP - 2025 Sep 1 TI - Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open-Label Pilot Study Examining a 16-Week Flexible Titration Regimen Versus Label-Recommended 8-Week Semaglutide Titration Regimen. PG - 1607-1611 LID - 10.2337/dc25-0690 [doi] AB - OBJECTIVE: To determine whether a slower, flexible titration regimen of semaglutide would improve adherence and reduce gastrointestinal adverse events (GI-AEs) compared with the label-recommended regimen in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 104 patients with T2D were randomized to label-recommended titration (0.25 mg, 0.5 mg, 1 mg at 4-week intervals) or flexible titration (starting at 0.0675 mg [measured as five clicks made by the dose selector dial], with gradual increases by 0.0675 mg/week and delays for GI-AEs) for 26 weeks. RESULTS: While final doses were similar between groups, only 2% of patients in the flexible arm withdrew due to GI-AEs vs. 19% in the label arm (P = 0.005). The flexible arm reported less nausea (45.1% vs. 64.2%; P = 0.051) and asthenia (9.8% vs. 24.5%; P = 0.047), with fewer days experiencing nausea (2.88 vs. 6.3 days; P = 0.017). HbA1c and BMI changes were similar between groups. CONCLUSIONS: Slower, flexible titration improved adherence and reduced adverse events without compromising efficacy. CI - (c) 2025 by the American Diabetes Association. FAU - Eldor, Roy AU - Eldor R AUID- ORCID: 0000-0002-1151-1370 AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - The Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Avraham, Noa AU - Avraham N AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - The Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Rosenberg, Orit AU - Rosenberg O AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. FAU - Shpigelman, Miriam AU - Shpigelman M AD - Clalit Health Services, Dan-Petah Tikva District, Israel. FAU - Golan-Cohen, Avivit AU - Golan-Cohen A AD - Medical Division, Leumit Health Services, Tel-Aviv, Israel. AD - Department of Family Medicine, The Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AUID- ORCID: 0000-0003-1289-5633 AD - Division of Endocrinology, Diabetes and Metabolism, Gertner Institute, Sheba Medical Centre, Ramat Gan, Israel. AD - Epidemiology Department, Herczeg Institute on Aging, The Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. FAU - Merzon, Eugene AU - Merzon E AUID- ORCID: 0000-0001-5469-0236 AD - Medical Division, Leumit Health Services, Tel-Aviv, Israel. AD - Adelson School of Medicine, Ariel University, Ariel, Israel. FAU - Buch, Assaf AU - Buch A AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - Department of Nutritional Sciences, School of Health Sciences, Ariel University, Ariel, Israel. LA - eng PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Diabetes Care. 2026 Feb 1;49(2):361. doi: 10.2337/dc26-er02a. PMID: 41337783 MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Middle Aged MH - Pilot Projects MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Aged MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/17 12:30 MHDA- 2025/09/08 08:05 CRDT- 2025/07/17 11:13 PHST- 2025/03/21 00:00 [received] PHST- 2025/06/16 00:00 [accepted] PHST- 2025/09/08 08:05 [medline] PHST- 2025/07/17 12:30 [pubmed] PHST- 2025/07/17 11:13 [entrez] AID - 162990 [pii] AID - 10.2337/dc25-0690 [doi] PST - ppublish SO - Diabetes Care. 2025 Sep 1;48(9):1607-1611. doi: 10.2337/dc25-0690. PMID- 40673553 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260822 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 14 IP - 15 DP - 2025 Aug 5 TI - Heterogeneity of Cardiovascular Effects of Second-Line Glucose-Lowering Therapies in Adults With Type 2 Diabetes Across the Range of Moderate Baseline Cardiovascular Risk. PG - e040217 LID - 10.1161/JAHA.124.040217 [doi] LID - e040217 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have favorable cardiovascular outcomes compared with dipeptidyl peptidase-4 inhibitors (DPP4is) and sulfonylureas in adults with type 2 diabetes and high cardiovascular risk. How these benefits vary across lower levels of cardiovascular risk is unknown. METHODS: We used nationwide claims data to emulate a comparative effectiveness trial and examine the heterogeneity of treatment effects of GLP-1RAs, SGLT2is, DPP4is, and sulfonylureas on major adverse cardiovascular events (MACEs) among adults with type 2 diabetes and moderate cardiovascular risk (annualized MACE risk 1%-5%, estimated using the annualized claims-based MACE estimator). RESULTS: Among 386 276 included adults with type 2 diabetes, 25.2% had baseline ACME-predicted MACE risk >1% to 4% to /=1 prescription for an SGLT2 inhibitor or a GLP1-RA (assessed separately) compared to those without CKD during 2020-2021. We also assessed prescriptions in a sub-population of CKD patients who met trial inclusion criteria: SGLT2 inhibitor (estimated glomerular filtration rate [eGFR] >/=20 mL/min/1.73m(2) and urine albumin-creatinine ratio [UACR] >/=22.6 mg/mmol) and GLP1-RA (eGFR >/=50 to <75 mL/min/1.73m(2) and UACR >33.9 to <565 mg/mmol, or eGFR >/=25 to <50 mL/min/1.73m(2) and UACR >11.3 to <565 mg/mmol). RESULTS: Of 114 499 adults with T2DM, 36 840 (32.1%) also had CKD. SGLT2 inhibitors were prescribed in 13.6% of patients without CKD, 14.4% of patients with CKD and 17.8% of patients meeting the trial target population definition. Across these groups, GLP1-RA were prescribed in 8.8%, 10.1% and 11.3% of patients, respectively. More advanced CKD stage and severely increased albuminuria were associated with a lower likelihood of SGLT2 inhibitor or GLP1-RA being prescribed. CONCLUSION: We observed low rates of SGLT2 inhibitor and GLP1-RA prescriptions in patients with T2DM irrespective of CKD status. Strategies are needed to improve prescription rates, with a particular focus on patients with high kidney and cardiovascular risk. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wallace, Hannah AU - Wallace H AUID- ORCID: 0000-0002-2728-4299 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - Western Health, Melbourne, Victoria, Australia. AD - Faculty of Medicine and Health, University of Melbourne, Melbourne, Victoria, Australia. FAU - Wick, James AU - Wick J AD - Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. FAU - Neuen, Brendon L AU - Neuen BL AUID- ORCID: 0000-0001-9276-8380 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Buizen, Luke AU - Buizen L AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Badve, Sunil V AU - Badve SV AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Chalmers, John AU - Chalmers J AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - de Oliveira Costa, Juliana AU - de Oliveira Costa J AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Falster, Michael O AU - Falster MO AUID- ORCID: 0000-0001-6444-7272 AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Ha, Jeffrey T AU - Ha JT AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Jardine, Meg J AU - Jardine MJ AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Ketema, Daniel Bekele AU - Ketema DB AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Lin, Jialing AU - Lin J AUID- ORCID: 0000-0002-0643-9191 AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia. FAU - Nelson, Craig AU - Nelson C AD - Western Health, Melbourne, Victoria, Australia. AD - Faculty of Medicine and Health, University of Melbourne, Melbourne, Victoria, Australia. FAU - Pearson, Sallie-Anne AU - Pearson SA AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Peiris, David AU - Peiris D AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Rodgers, Anthony AU - Rodgers A AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Sasaki, Takaya AU - Sasaki T AUID- ORCID: 0000-0001-9525-2638 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Woodward, Mark AU - Woodward M AUID- ORCID: 0000-0001-9800-5296 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - International Centre for Future Health Systems, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Gallagher, Martin AU - Gallagher M AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - The George Institute for Global Health, School of Public Health, Imperial College London, London, UK. FAU - Kotwal, Sradha S AU - Kotwal SS AUID- ORCID: 0000-0002-3294-4087 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - School of Clinical Medicine, Faculty of Medicine and Health, UNSW, Sydney, New South Wales, Australia. FAU - Ronksley, Paul AU - Ronksley P AD - Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. FAU - Jun, Min AU - Jun M AUID- ORCID: 0000-0003-1460-7535 AD - The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. AD - School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia. LA - eng GR - University of New South Wales/ GR - Eli Lilly Australia/ GR - Boehringer Ingelheim/ PT - Journal Article DEP - 20250716 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Renal Insufficiency, Chronic/complications/epidemiology/drug therapy MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Australia/epidemiology MH - Retrospective Studies MH - Middle Aged MH - Primary Health Care/statistics & numerical data MH - Aged MH - Prevalence MH - *Drug Prescriptions/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Practice Patterns, Physicians'/statistics & numerical data MH - Diabetic Nephropathies/epidemiology MH - Glomerular Filtration Rate PMC - PMC12409226 OTO - NOTNLM OT - chronic kidney disease OT - glucagon-like peptide-1 receptor agonists OT - primary care OT - sodium-glucose co-transporter 2 inhibitors OT - type 2 diabetes mellitus COIS- MJ is responsible for research projects that have received research funding from Boehringer Ingelheim and Eli Lilly Alliance. SSK has received consulting fees from Amgen, Chinook/Novartis and Boehringer and Ingelheim. BLN has received fees for travel support, advisory boards, publication support, scientific presentations and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer and Ingelheim, CSL-Behring, CSL-Seqirus, HCP Live, Medscape, Menarini, Novo Nordisk, Travere Therapeutics and Cornerstone Medical Education. SVB has received research grants from the National Health and Medical Research Council of Australia, advisory board fees from Bayer, AstraZeneca, Novo Nordisk and Vifor Pharma; speaker's honouraria from Bayer, AstraZeneca, Vifor Pharma and Pfizer; and nonfinancial research support from Bayer, all fees paid to The George Institute for Global Health. JTH has recieved travel support from CSL-Seqirus. MJJ is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant; is responsible for research projects that have received funding from Amgen, Baxter, CSL, Dimerix, Lilly, Gambro and MSD; and has received fees for advisory, steering committee and/or scientific presentations from Akebia, Amgen, AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Cesas Linx, Chinook, CSL, Janssen, Medscape, MSD, Novo Nordisk, Occuryx, Roche and Vifor, with any consultancy, honouraria or travel support paid to her institution. EDAT- 2025/07/16 12:29 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/07/16 07:03 PHST- 2025/06/22 00:00 [revised] PHST- 2025/04/29 00:00 [received] PHST- 2025/06/30 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/16 12:29 [pubmed] PHST- 2025/07/16 07:03 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16608 [pii] AID - 10.1111/dom.16608 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5599-5611. doi: 10.1111/dom.16608. Epub 2025 Jul 16. PMID- 40667705 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Adherence to GLP-1 receptor agonists and SGLT2 inhibitors by out-of-pocket spending among Medicare beneficiaries with diabetes. PG - 5683-5693 LID - 10.1111/dom.16619 [doi] AB - AIMS: To assess associations between out-of-pocket (OOP) expenditures and adherence to glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) among low-income Medicare beneficiaries with diabetes. MATERIALS AND METHODS: We analysed Medicare Current Beneficiary Survey two-year longitudinal data (2016-2021) on beneficiaries with diabetes using GLP-1RAs (N = 168; weighted = 2 187 500) or SGLT2i (N = 139; weighted = 1 741 910) in year one (baseline). Among these, N = 97 (weighted = 1 117 637) GLP-1RA and N = 73 (weighted = 785 301) SGLT2i users had an income below 200% of the Federal Poverty Level (low-income). Survey-weighted generalized Poisson regression assessed the association between baseline cumulative OOP drug expenses and year two adherence, defined as proportion of days covered (PDC). We repeated analyses in participants with higher income and using dual (Medicare/Medicaid) enrolment as a proxy for full coverage in low income. RESULTS: Year-two PDC was 65.2% (95% CI: 57.9%-72.6%) for low-income GLP-1RA users and 65.4% (95% CI: 58.3%-72.5%) for low-income SGLT2i users. We did not observe a significant association between OOP costs (mean: $253; range: $0-$4699) and adherence in low-income GLP-1RA users. For low-income SGLT2i users, higher OOP costs (mean: $204; $0-$2649) were associated with lower adherence: adjusted adherence ratio 0.959 (95% CI: 0.932-0.987) per $100 increase. Dual Medicare-Medicaid coverage was associated with increased adherence: adjusted adherence ratio 1.580 (95% CI: 1.061-2.352). For high-income GLP-1RA users, higher OOP expenditures were associated with increased adherence in the highest income range. CONCLUSIONS: OOP costs for GLP-1RAs and SGLT2i are substantial, potentially posing a particular burden for low-income Medicare beneficiaries. Policy changes may reduce this burden, although adherence improvements appear limited to beneficiaries using SGLT2i. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Klepser, Nicklas S AU - Klepser NS AD - Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA. AD - Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Weber, Ellerie S AU - Weber ES AD - Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Li, Lihua AU - Li L AD - Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA. AD - Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Fleischmann, Kirsten E AU - Fleischmann KE AD - Department of Medicine, University of California, San Francisco, California, USA. AD - Division of Cardiology, University of California, San Francisco, California, USA. FAU - Masharani, Umesh AU - Masharani U AD - Department of Medicine, University of California, San Francisco, California, USA. FAU - Park, Meyeon AU - Park M AD - Department of Medicine, University of California, San Francisco, California, USA. AD - Division of Nephrology, University of California, San Francisco, California, USA. FAU - Max, Wendy B AU - Max WB AD - Institute for Health & Aging and Department of Social and Behavioral Sciences, University of California, San Francisco, California, USA. FAU - Yeboah, Joseph AU - Yeboah J AD - Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston Salem, North Carolina, USA. FAU - Hunink, M G Myriam AU - Hunink MGM AD - Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. AD - Department of Radiology, Erasmus MC, Rotterdam, The Netherlands. AD - Center for Health Decision Sciences, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. FAU - Ferket, Bart S AU - Ferket BS AUID- ORCID: 0000-0003-2754-545X AD - Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA. AD - Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA. LA - eng GR - R01 HL153456/HL/NHLBI NIH HHS/United States GR - R01HL153456/HL/NHLBI NIH HHS/United States GR - R01HL153456/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20250716 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - United States/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - Male MH - Female MH - Aged MH - *Medicare/statistics & numerical data/economics MH - *Health Expenditures/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Hypoglycemic Agents/therapeutic use/economics MH - Aged, 80 and over MH - Longitudinal Studies MH - *Diabetes Mellitus/drug therapy/economics MH - Poverty PMC - PMC12313199 MID - NIHMS2097638 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - health economics OT - real-world evidence OT - type 2 diabetes COIS- Conflict of Interest: M.G.M.H. receives royalties from Cambridge University Press for a textbook on medical decision making and reimbursement of expenses from the European Society of Radiology (ESR) for work on the ESR guidelines for imaging referrals. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/07/16 12:28 MHDA- 2025/09/04 06:37 PMCR- 2026/07/16 CRDT- 2025/07/16 07:03 PHST- 2025/07/07 00:00 [revised] PHST- 2025/04/03 00:00 [received] PHST- 2025/07/08 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/16 12:28 [pubmed] PHST- 2025/07/16 07:03 [entrez] PHST- 2026/07/16 00:00 [pmc-release] AID - 10.1111/dom.16619 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5683-5693. doi: 10.1111/dom.16619. Epub 2025 Jul 16. PMID- 40667672 OWN - NLM STAT- MEDLINE DCOM- 20260618 LR - 20260726 IS - 1558-9455 (Electronic) IS - 1558-9447 (Print) IS - 1558-9447 (Linking) VI - 21 IP - 6 DP - 2026 Jul TI - Glucagon-like Peptide-1 Receptor Agonist Therapy Is Associated With Fewer Medical Complications After Carpal Tunnel Release in Diabetic Patients. PG - 922-929 LID - 10.1177/15589447251350181 [doi] AB - BACKGROUND: Diabetic patients experience carpal tunnel syndrome (CTS) at high rates, have increased symptom severity, and experience prolonged recovery after carpal tunnel release (CTR). This study assessed the association of glucagon-like peptide-1 receptor agonist (GLP-1) therapy with postoperative outcomes after CTR in type II diabetic patients with CTS. METHODS: Using the PearlDiver database, 25 229 diabetic patients with CTS who underwent CTR and were prescribed GLP-1 therapy were identified and exact matched to 25 229 controls based on age, sex, Elixhauser comorbidity index, tobacco use, obesity, hypothyroidism, and body mass index where available. Demographic variables and comorbidities were compared between groups using Kruskal-Wallis analyses for continuous variables and chi-square tests for categorical variables. Bivariate logistic regression analysis was conducted for 90-day outcomes and 2-year CTR revision. RESULTS: Patients on GLP-1 therapy had decreased risk of 90-day medical complications (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.84-0.96) and hospital readmission (OR = 0.85; 95% CI, 0.77-0.94) of 0.5% and 0.4%, respectively, compared with controls. No significant differences were found in 90-day surgical complications or 2-year revision rates between cohorts. There were no cases of aspiration pneumonia. The GLP-1 cohort had increased odds of higher 90-day total costs of care (OR = 2.42; 95% CI, 1.88-3.15). CONCLUSIONS: GLP-1 therapy is associated with reduced risk of 90-day medical complications and hospital readmission following CTR in diabetic patients, suggesting these medications may optimize comorbidity profiles via glucose control preoperatively. Future studies may examine whether GLP-1 therapy is associated with minimum clinically important difference in patient-reported outcome measures for CTS in diabetic patients. FAU - Hiredesai, Annika N AU - Hiredesai AN AUID- ORCID: 0009-0009-0043-1189 AD - Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA. FAU - Howlett, Carina P AU - Howlett CP AD - Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA. FAU - Kisiel, Sara AU - Kisiel S AUID- ORCID: 0009-0006-2466-8509 AD - University of Arizona College of Medicine, Phoenix, USA. FAU - Unadkat, Krishna AU - Unadkat K AUID- ORCID: 0009-0000-6475-2832 AD - Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA. FAU - Verhey, Jens T AU - Verhey JT AD - Department of Orthopedic Surgery, Mayo Clinic, Phoenix, AZ, USA. FAU - Renfree, Kevin J AU - Renfree KJ AUID- ORCID: 0000-0001-7428-848X AD - Department of Orthopedic Surgery, Mayo Clinic, Phoenix, AZ, USA. FAU - Noland, Shelley S AU - Noland SS AD - Department of Orthopedic Surgery, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article DEP - 20250716 PL - United States TA - Hand (N Y) JT - Hand (New York, N.Y.) JID - 101264149 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Carpal Tunnel Syndrome/surgery/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Male MH - *Postoperative Complications/prevention & control/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Patient Readmission/statistics & numerical data MH - Reoperation/statistics & numerical data MH - Case-Control Studies MH - Logistic Models PMC - PMC12267201 OTO - NOTNLM OT - GLP1 OT - carpal tunnel release OT - carpal tunnel syndrome OT - diabetes OT - diagnosis OT - nerve OT - nerve compression OT - outcomes OT - research & health outcomes COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/07/16 12:30 MHDA- 2026/06/18 06:31 PMCR- 2026/07/16 CRDT- 2025/07/16 06:42 PHST- 2026/06/18 06:31 [medline] PHST- 2025/07/16 12:30 [pubmed] PHST- 2025/07/16 06:42 [entrez] PHST- 2026/07/16 00:00 [pmc-release] AID - 10.1177_15589447251350181 [pii] AID - 10.1177/15589447251350181 [doi] PST - ppublish SO - Hand (N Y). 2026 Jul;21(6):922-929. doi: 10.1177/15589447251350181. Epub 2025 Jul 16. PMID- 40665896 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260630 IS - 2163-8306 (Electronic) IS - 2163-8306 (Linking) VI - 14 IP - 9 DP - 2025 Sep TI - From In Vitro Efficacy to Long-Term HbA1c Response for GLP-1R/GlucagonR Agonism Using the 4GI-HbA1c Systems Model. PG - 1515-1525 LID - 10.1002/psp4.70074 [doi] AB - For the treatment of Type 2 Diabetes, high efficacy approaches such as Glucagon-like peptide 1 (GLP-1)-based therapies are recommended for glucose control. Prediction of the clinical outcome of these therapies on glucose and hemoglobin A1c (HbA1c), using early available pharmacokinetic and in vitro efficacy information, can be a valuable tool for compound selection and supporting drug development. Our previously developed glucose homeostasis model (the 4GI model) is a systems model that is able to quantify drug effects on glucose based on in vitro potency and PK information. In this research, the model was coupled to an existing integrated glucose-red blood cell-HbA1c (IGRH) model for predicting the effects of GLP-1 and GLP-1/glucagon (dual) receptor agonists, liraglutide and cotadutide, on glucose and HbA1c. The 4GI model was validated for predicting 24-h glucose (C(glc,av)) with minimal model calibration using short-term Ph2a continuous glucose monitoring (CGM) data. Subsequently, the predicted C(glc,av) served as input for the HbA1c model to assess the predictiveness of the combined 4GI-HbA1c model on HbA1c. The resulting combined model was used in cotadutide's clinical development by providing predictive insights into the 26 weeks glucose and HbA1c dynamics of the Ph2b study prior to its initiation. Retrospective analysis showed that the model adequately predicted the effect of cotadutide and liraglutide on fasting plasma glucose and HbA1c (Root Means Square Percent Error (RMSPE) 5.9% and 13%, respectively). This demonstrates the potential of the 4GI-HbA1c systems model as a valuable tool in supporting the clinical development of novel GLP-1 and/or glucagon agonists. CI - (c) 2025 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Bosch, Rolien AU - Bosch R AUID- ORCID: 0000-0002-6675-8303 AD - LAP&P Consultants, Leiden, the Netherlands. AD - Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. FAU - Petrone, Marcella AU - Petrone M AD - Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK. FAU - Arends, Rosalin AU - Arends R AD - AstraZeneca, Gaithersburg, Maryland, USA. FAU - Sijbrands, Eric J G AU - Sijbrands EJG AUID- ORCID: 0000-0001-8857-7389 AD - Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. FAU - Hoefman, Sven AU - Hoefman S AD - LAP&P Consultants, Leiden, the Netherlands. FAU - Snelder, Nelleke AU - Snelder N AUID- ORCID: 0000-0003-1302-678X AD - LAP&P Consultants, Leiden, the Netherlands. LA - eng SI - ClinicalTrials.gov/NCT03244800 PT - Journal Article DEP - 20250716 PL - United States TA - CPT Pharmacometrics Syst Pharmacol JT - CPT: pharmacometrics & systems pharmacology JID - 101580011 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Glucagon) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Glycated Hemoglobin/metabolism/analysis MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/pharmacology MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Models, Biological MH - *Hypoglycemic Agents/pharmacology/pharmacokinetics MH - *Receptors, Glucagon/agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12439278 OTO - NOTNLM OT - 4GI OT - GLP-1R agonists OT - QSP OT - cotadutide OT - diabetes OT - systems pharmacology COIS- Rolien Bosch, Sven Hoefman and Nelleke Snelder are consultants at LAP&P. Marcella Petrone is an AstraZeneca employee and shareholder. Rosalin Arends was an employee of MedImmune/AstraZeneca at the time of the conduct of this work. Rosalin Arends is currently an employee of MapLight Therapeutics Inc. All other authors declared no competing interests for this work. EDAT- 2025/07/16 06:25 MHDA- 2025/09/17 00:31 PMCR- 2025/07/16 CRDT- 2025/07/16 05:03 PHST- 2025/06/18 00:00 [revised] PHST- 2024/11/13 00:00 [received] PHST- 2025/06/20 00:00 [accepted] PHST- 2025/09/17 00:31 [medline] PHST- 2025/07/16 06:25 [pubmed] PHST- 2025/07/16 05:03 [entrez] PHST- 2025/07/16 00:00 [pmc-release] AID - PSP470074 [pii] AID - 10.1002/psp4.70074 [doi] PST - ppublish SO - CPT Pharmacometrics Syst Pharmacol. 2025 Sep;14(9):1515-1525. doi: 10.1002/psp4.70074. Epub 2025 Jul 16. PMID- 40665260 OWN - NLM STAT- MEDLINE DCOM- 20250716 LR - 20250721 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 25 IP - 1 DP - 2025 Jul 16 TI - The effects of non-insulin anti-diabetic medications on the diabetic microvascular complications: a systematic review and meta-analysis of randomized clinical trials. PG - 179 LID - 10.1186/s12902-025-01985-2 [doi] LID - 179 AB - INTRODUCTION: Although the onset and progression of diabetic microvascular complications are linked to glycemic control, various antihyperglycemic drugs with distinct treatment targets may positively impact microvascular lesions beyond their glucose-lowering effects. Therefore, this systematic review emphasizes the clinical therapeutic implications of non-insulin anti-diabetic medications for diabetic microvascular complications. METHODS: We retrieved published literature reporting randomized clinical trials (RCTs) on the effects of microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR), from authenticated clinical databases: PubMed, Excerpta Medica database (EMBASE), and Web of Science. We synthesized data, including the continuous variable indices: estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), and urinary albumin excretion rate (UAE). Indices measuring cardiovascular autonomic neuropathy (CAN), vibration detection threshold (VDT), and retinal nerve fiber thickness (RNFL) were used to calculate microvascular effects. We also synthesized dichotomous variable indices, including the risks for DR and DPN. RESULTS: According to our analyses, there was sparse evidence strongly supporting that metformin (MET), Sulfonylurea (SUs), Repaglinide (Repa), or alpha-Glucosidase inhibitors (alpha-GIs) could benefit diabetic microvascular complications when adopted as monotherapy. Regardless of the no change in eGFR, two trials reporting Thiazolidinediones (TZDs) significantly reduced the UACR, while other clinical trials reported an increase in VDT and improvement in DR. Sodium glucose co-transporter inhibitors (SGLT-2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) both showed protective effects in preventing eGFR decline, with only SGLT-2i demonstrating a significant reduction in UACR. A recent trial showed that Dipeptidyl Peptidase IV inhibitors (DPP-IVi) may potentially reduce the risk of DPN, while GLP-1RA did not prove to alter the measures of CAN and DPN. However, the SUSTAIN 6 trial revealed that Semaglutide may increase the risk of DR. CONCLUSION: Besides their anti-hyperglycemic properties, some currently reviewed medications may exhibit unique anti-microvascular abilities. Due to ambiguous and conflicting available results, more emerging or ongoing trials will address this issue and could benefit clinical strategies for personalized treatment practices. CLINICAL TRIAL NUMBER: Not applicable. CI - (c) 2025. The Author(s). FAU - Wen, Song AU - Wen S AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. 379295093@qq.com. AD - Fudan Zhangjiang Institute, Shanghai Pudong Hospital, Shanghai, China. 379295093@qq.com. FAU - Yuan, Yue AU - Yuan Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Li, Yanyan AU - Li Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Xu, Chenglin AU - Xu C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Chen, Lijiao AU - Chen L AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Ren, Yishu AU - Ren Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Wang, Congcong AU - Wang C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - He, Yanju AU - He Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Li, Xiucai AU - Li X AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Gong, Min AU - Gong M AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Yuan, Xinlu AU - Yuan X AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Xu, Dongxiang AU - Xu D AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Wang, Chaoxun AU - Wang C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Zhou, Ligang AU - Zhou L AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. zhouligang1n1@163.com. AD - Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai, 201399, China. zhouligang1n1@163.com. LA - eng GR - KP0202118/Fudan Zhangjiang Clinical Medicine Innovation Fund Project/ GR - YC-2023-0404/Integrated Traditional Chinese and Western Medicine/ GR - FD2023A227/Fudan Good Practice Program of Teaching and Learning/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250716 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetic Angiopathies/drug therapy MH - *Diabetic Nephropathies/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/drug therapy MH - *Diabetic Neuropathies/drug therapy PMC - PMC12265122 OTO - NOTNLM OT - Diabetic microvascular complication OT - Diabetic nephropathy OT - Diabetic neuropathy OT - Diabetic retinopathy OT - Non-insulin anti-diabetic medication COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/07/16 00:26 MHDA- 2025/07/16 06:25 PMCR- 2025/07/16 CRDT- 2025/07/15 23:49 PHST- 2025/04/07 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/16 06:25 [medline] PHST- 2025/07/16 00:26 [pubmed] PHST- 2025/07/15 23:49 [entrez] PHST- 2025/07/16 00:00 [pmc-release] AID - 10.1186/s12902-025-01985-2 [pii] AID - 1985 [pii] AID - 10.1186/s12902-025-01985-2 [doi] PST - epublish SO - BMC Endocr Disord. 2025 Jul 16;25(1):179. doi: 10.1186/s12902-025-01985-2. PMID- 40664497 OWN - NLM STAT- MEDLINE DCOM- 20260325 LR - 20260901 IS - 1468-201X (Electronic) IS - 1355-6037 (Linking) VI - 112 IP - 8 DP - 2026 Mar 25 TI - Managing glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in clinical practice. PG - 422-430 LID - 10.1136/heartjnl-2024-324847 [doi] AB - The obesity epidemic has significantly heightened the impact of cardiometabolic risk factors on the global burden of cardiovascular and kidney diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), originally developed for type 2 diabetes treatment, have demonstrated in randomised controlled trials their ability to reduce the risk of cardiovascular and kidney diseases. This has led to substantial improvements in patient outcomes. SGLT2i, in particular, are the first class of drugs proven to improve the prognosis of patients with heart failure with preserved ejection fraction, and evidence is accumulating to suggest that also GLP-1RA might be beneficial in these patients. Remarkably, the benefits of GLP-1RA and SGLT2i are independent of type 2 diabetes status or baseline renal function. The critical role of these drug classes in managing high cardiovascular risk patients is increasingly acknowledged in guidelines, which now advocate their use across broader clinical phenotypes. This review compiles evidence supporting the use of these drugs in various clinical scenarios, highlighting their impact on outcomes and identifying patient subgroups most likely to benefit from their prescription. Guideline recommendations are summarised at the conclusion of each section. In the conclusion, we highlight how these drugs have changed our approach to cardiometabolic diseases and emphasise the potential advantages achievable by using their reciprocal combination and combinations with other drugs representing the foundation of the guidelines-directed medical therapy. CI - (c) Author(s) (or their employer(s)) 2026. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Dalpiaz, Hermann AU - Dalpiaz H AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy. FAU - Masi, Stefano AU - Masi S AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Stefano.masi@unipi.it. FAU - Piludu, Sara AU - Piludu S AD - Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy. FAU - Agnoletti, Davide AU - Agnoletti D AD - Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. FAU - Piani, Federica AU - Piani F AD - Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. FAU - Fiorini, Giulia AU - Fiorini G AD - Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. FAU - Borghi, Claudio AU - Borghi C AUID- ORCID: 0000-0002-7591-3686 AD - Unit of Internal Medicine, Policlinico S Orsola, University of Bologna, Bologna, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260325 PL - England TA - Heart JT - Heart (British Cardiac Society) JID - 9602087 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use/adverse effects OTO - NOTNLM OT - Cardiovascular Diseases OT - Heart Failure OT - Pharmacology, Clinical OT - Risk Factors COIS- Competing interests: SM has received honoraria for lecturer, editing and consulting activity from Servier, which are out of the scope of the current manuscript. CB has received research grant support from Menarini Corporate and Novartis Pharma; has served as a consultant for Novartis Pharma, Alfasigma, Grunenthal, Menarini Corporate and Laboratoires Servier; and received lecturing fees from Laboratoires Servier, Takeda, Astellas, Teijin, Novartis Pharma, Berlin Chemie and Sanofi. EDAT- 2025/07/16 00:26 MHDA- 2026/03/26 01:03 CRDT- 2025/07/15 21:32 PHST- 2024/12/04 00:00 [received] PHST- 2025/05/27 00:00 [accepted] PHST- 2026/03/26 01:03 [medline] PHST- 2025/07/16 00:26 [pubmed] PHST- 2025/07/15 21:32 [entrez] AID - heartjnl-2024-324847 [pii] AID - 10.1136/heartjnl-2024-324847 [doi] PST - epublish SO - Heart. 2026 Mar 25;112(8):422-430. doi: 10.1136/heartjnl-2024-324847. PMID- 40663350 OWN - NLM STAT- MEDLINE DCOM- 20250715 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 7 DP - 2025 Jul 1 TI - Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. PG - e2521016 LID - 10.1001/jamanetworkopen.2025.21016 [doi] AB - IMPORTANCE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, provide cardiometabolic benefits to patients with type 2 diabetes and obesity, but their potential benefits in mitigating neurodegenerative and cerebrovascular diseases remain unclear. OBJECTIVE: To evaluate the association of semaglutide and tirzepatide with the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage, and all-cause mortality compared with other antidiabetic drugs in adults with type 2 diabetes and obesity. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed electronic health record-based data from the TriNetX US network (December 1, 2017, to June 30, 2024) in adults aged 40 years or older with type 2 diabetes and obesity initiating semaglutide, tirzepatide, or other antidiabetic drugs, excluding those with prior neurodegenerative or cerebrovascular diseases. Propensity score matching was used to balance the baseline characteristics. EXPOSURES: Patients treated with antidiabetic drugs were categorized as GLP-1RA (semaglutide or tirzepatide) or other antidiabetic drug (biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones, and alpha-glucosidase inhibitors) users. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of neurodegenerative diseases (dementia, Parkinson disease, and mild cognitive impairment) and cerebrovascular (stroke and intracerebral hemorrhage) diseases, while the secondary outcome was all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs. RESULTS: A total of 60 860 adults with type 2 diabetes and obesity were included, with 30 430 each in the GLP-1RA group (mean [SD] age, 57.9 [9.9] years; 50.2% female) and the other antidiabetic drug group (mean [SD] age, 58.0 [10.8] years; 51.4% female) after propensity score matching. During a 7-year follow-up, GLP-1RA users had a lower risk of dementia (HR, 0.63; 95% CI, 0.50-0.81), stroke (HR, 0.81; 95% CI, 0.70-0.93), and all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78), with no significant differences in the risk of Parkinson disease or intracerebral hemorrhage. Subgroup analyses revealed greater benefits in patients aged 60 years or older, women, and patients with a body mass index of 30 to 40. CONCLUSIONS AND RELEVANCE: In this cohort study, the use of GLP-1RAs semaglutide and tirzepatide was associated with a lower risk of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs beyond glycemic control, warranting further trials to confirm these outcomes. FAU - Lin, Huan-Tang AU - Lin HT AD - Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. FAU - Tsai, Yung-Fong AU - Tsai YF AD - Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Liao, Pei-Lun AU - Liao PL AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. AD - Institute of Medicine, Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Aged MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Stroke/epidemiology/chemically induced MH - *Neurodegenerative Diseases/epidemiology/chemically induced MH - Incidence MH - Parkinson Disease/epidemiology MH - Dementia/epidemiology MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/15 12:29 MHDA- 2025/07/15 12:30 CRDT- 2025/07/15 11:32 PHST- 2025/07/15 12:30 [medline] PHST- 2025/07/15 12:29 [pubmed] PHST- 2025/07/15 11:32 [entrez] AID - 2836412 [pii] AID - 10.1001/jamanetworkopen.2025.21016 [doi] PST - epublish SO - JAMA Netw Open. 2025 Jul 1;8(7):e2521016. doi: 10.1001/jamanetworkopen.2025.21016. PMID- 40660809 OWN - NLM STAT- MEDLINE DCOM- 20260507 LR - 20260507 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 33 IP - 1 DP - 2026 Jan 6 TI - Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities. PG - 8-18 LID - 10.1093/eurjpc/zwaf426 [doi] AB - Chronic kidney disease (CKD) is a complex and progressive condition ultimately leading to premature death. Diabetes is the leading cause of end-stage kidney disease worldwide. Up till 2024, international clinical guidelines have established three therapeutic pillars to delay CKD progression in people with type 2 diabetes (T2D): renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, and the non-steroidal mineralocorticoid receptor antagonist finerenone. With the recent results from the Evaluate Renal Function with Semaglutide Once Weekly study, the glucagon-like peptide-l receptor agonist (GLP-1 RA) class is now considered a new therapeutic pillar in reducing CKD complications in this patient population. In this expert opinion, we identify patient populations at risk of developing new onset or worsening pre-existing CKD to explore optimal therapeutic strategies, introducing GLP-1 RAs. We highlight the important challenges that remain in optimising, sequencing, and combining these four therapeutic pillars. Even though the conventional approach of combining the pillars has been based on the historical emergence of evidence, we discuss the factors that would influence physicians' decision for preferring one pillar over another, and for selecting a certain combination, whether performed simultaneously or sequentially. These factors include the grade of CKD and the level of albuminuria; diabetic control (glycaemia); comorbidities: atherosclerotic cardiovascular disease, heart failure, obesity; concomitant medications; biological variables: potassium serum levels. The efficacy and safety profiles of each pillar, as demonstrated in landmark trials that have clearly shown the nephroprotective effects, along with real-world data, should also be carefully considered when selecting the most appropriate therapeutic option. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Halimi, Jean-Michel AU - Halimi JM AUID- ORCID: 0000-0002-0723-7735 AD - Department of Nephrology-Hypertension, Renal Dialysis and Transplantation, CHRU de Tours, 2 Boulevard Tonnelle, Tours 37000, France. AD - INSERM UMR 1327, ISCHEMIA, University of Tours, Tours, France. AD - INI-CRCT, Tours, France. FAU - Fauchier, Laurent AU - Fauchier L AD - Department of Cardiology, Centre Hospitalier Regional Universitaire de Tours, Tours, France. FAU - Karras, Alexandre AU - Karras A AD - Department of Nephrology, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France. AD - Department of Medicine, Universite Paris Cite, Paris, France. FAU - Amouyal, Chloe AU - Amouyal C AD - Diabetology Department, Institute of Cardiometabolism and Nutrition (ICAN), Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris, Paris 75013, France. AD - Sorbonne Universite, INSERM, Nutriomic Team, Paris, France. FAU - Eladari, Dominique AU - Eladari D AD - Medecine de Precision des maladies Metaboliques et Renales, Service de Nephrologie, CHU Amiens-Picardie, Universite de Picardie Jules Verne, Amiens 80054, France. AD - Paris Cardiovascular Research Center (PARCC), INSERM U970, Paris F-75015, France. AD - FCRIN-INI-CRCT, Vandoeuvre-les-Nancy 54500, France. FAU - Rossignol, Patrick AU - Rossignol P AD - Universite de Lorraine, INSERM CIC-P 1433, CHRU de Nancy, INSERM U1116, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. AD - Department of Medical Specialties and Nephrology-Hemodialysis, Princess Grace Hospital, and Centre d'Hemodialyse Prive de Monaco, and M-CRIN, Monaco, Monaco. FAU - Choukroun, Gabriel AU - Choukroun G AD - Nephrology Dialysis Transplantation Department, CHU Amiens Picardie and Jules Verne University, Amiens 80000, France. FAU - Zaoui, Philippe AU - Zaoui P AD - Department of Medicine, Universite Grenoble Alpes, La Tronche 38700, France. FAU - Girerd, Nicolas AU - Girerd N AD - University of Lorraine, Center of Plurithematic Clinical Investigations 1433 and INSERM U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. FAU - Hadjadj, Samy AU - Hadjadj S AUID- ORCID: 0000-0001-7110-6994 AD - L'Institut du Thorax, Nantes University, CHU Nantes, CNRS, INSERM, Nantes, France. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Review PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - DE2O63YV8R (finerenone) RN - 0 (Naphthyridines) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Renal Insufficiency, Chronic/drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Renin-Angiotensin System/drug effects MH - Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Naphthyridines/pharmacology/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Humans MH - Diabetic Nephropathies/drug therapy MH - Treatment Outcome OTO - NOTNLM OT - Chronic kidney disease OT - GLP-1 RA OT - Non-steroidal mineralocorticoid receptor antagonists OT - Renin-angiotensin system inhibitors OT - Renoprotection OT - SGLT2 inhibitor OT - Type 2 diabetes COIS- Conflict of interest: J.-M.H. received fees for advisory boards or lectures from Alexion, Astra Zeneca, Bayer, Boehringer Ingelheim France, Novo Nordisk, Servier, and Vifor Fresenius Pharma. L.F. received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb-Pfizer, Boehringer Ingelheim, and Novo Nordisk; and lecture fees from AstraZeneca, Bristol Myers Squibb-Pfizer, Boehringer Ingelheim, Boston Scientific, Medtronic, Novo Nordisk, and Zoll Medical. A.K. received consultancy fees from GSK, Vifor, Novartis, and Otsuka; received honoraria from Pfizer, Astra-Zeneca, GSK, Novartis, Vifor, Otsuka, and Bohringer-Ingelheim; has an advisory or leadership role for Novartis, Vifor, and Otsuka; and Speakers Bureau for Otsuka, Vifor, Pfizer, Astra-Zeneca, and Boehringer-Ingelheim. C.A. received honoraria from Lilly, Sanofi, Novo Nordisk, Decom. D.E. received travel grant and honoraria from Alnylam and participated to the advisory board of Alnylam and Novo Nordisk. P.R. reports receiving personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius, Idorsia, Novo Nordisk, and Vifor. G.C. received honoraria for advisory board and participating symposia by Astellas Pharma, GSK, CSL, Vifor, and Novo Nordisk. P.Z. received honoraria and consulting fees from Novo Nordisk, Astra-Zeneca, Boehringer Lilly, and Bayer. N.G. received honoraria from AstraZeneca, Bayer, Boehringer, Lilly, Novartis, Novo Nordisk. S.H. received institutional research grants from Astra-Zeneca, Asten Sante, Air Liquide Health Science, Bayer, Boehringer Ingelheim, Eli Lilly, Homeperf, ISIS Diabete, LVL, Nestle Home Care, Novo Nordisk, Pierre Fabre, Sanofi, Valbiotis and Vitalaire and served as consultant and/or received honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Mundi-pharma, Novo Nordisk, Novartis, Sanofi, Servier and Valbiotis. EDAT- 2025/07/15 06:28 MHDA- 2026/01/06 19:17 CRDT- 2025/07/15 03:12 PHST- 2025/04/19 00:00 [received] PHST- 2025/06/13 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2025/07/15 06:28 [pubmed] PHST- 2025/07/15 03:12 [entrez] AID - 8201743 [pii] AID - 10.1093/eurjpc/zwaf426 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2026 Jan 6;33(1):8-18. doi: 10.1093/eurjpc/zwaf426. PMID- 40658955 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 9 DP - 2025 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk for Gastroesophageal Reflux Disease in Patients With Type 2 Diabetes : A Population-Based Cohort Study. PG - 1268-1278 LID - 10.7326/ANNALS-24-03420 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), medications used to treat type 2 diabetes and obesity, are associated with delayed gastric emptying, which is a risk factor for gastroesophageal reflux disease (GERD). However, evidence linking these drugs to GERD is limited. OBJECTIVE: To estimate the effect of GLP-1 RAs compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the risk for GERD and its complications among patients with type 2 diabetes. DESIGN: Active-comparator new-user cohort study emulating a target trial. SETTING: U.K. Clinical Practice Research Datalink. PARTICIPANTS: Adults aged 18 years or older with type 2 diabetes initiating GLP-1 RAs or SGLT-2 inhibitors between 1 January 2013 and 31 December 2021, with follow-up until 31 March 2022. MEASUREMENTS: The primary outcome was incident GERD, and the secondary outcome was its complications. Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification. RESULTS: The study included 24 708 new users of GLP-1 RAs and 89 096 new users of SGLT-2 inhibitors. Over a median follow-up of 3.0 years, the RRs were 1.27 (95% CI, 1.14 to 1.42) for GERD, with an RD of 0.7 per 100 patients, and 1.55 (95% CI, 1.12 to 2.29) for its complications, with an RD of 0.8 per 1000 patients, among GLP-1 RA users compared with SGLT-2 inhibitor users. LIMITATION: Residual confounding due to lack of information on dietary or lifestyle factors. CONCLUSION: The estimated effect of GLP-1 RAs compared with SGLT-2 inhibitors suggested a higher risk for GERD and its complications in patients with type 2 diabetes. Clinicians should be aware of this potential adverse effect to provide timely prevention and treatment strategies. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. FAU - Noh, Yunha AU - Noh Y AUID- ORCID: 0000-0002-3645-7358 AD - College of Pharmacy, Chonnam National University, Gwangju, South Korea (Y.N.). FAU - Yin, Hui AU - Yin H AUID- ORCID: 0000-0002-8313-6944 AD - Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada (H.Y.). FAU - Yu, Oriana H Y AU - Yu OHY AUID- ORCID: 0000-0003-4877-557X AD - Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada (O.H.Y.Y.). FAU - Bitton, Alain AU - Bitton A AD - Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada (A.B.). FAU - Azoulay, Laurent AU - Azoulay L AUID- ORCID: 0000-0001-5162-3556 AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University; Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital; and Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada (L.A.). LA - eng PT - Journal Article DEP - 20250715 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastroesophageal Reflux/chemically induced/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Risk Factors MH - Adult MH - Cohort Studies MH - Incidence COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/07/14 18:26 MHDA- 2025/09/17 00:31 CRDT- 2025/07/14 17:03 PHST- 2025/09/17 00:31 [medline] PHST- 2025/07/14 18:26 [pubmed] PHST- 2025/07/14 17:03 [entrez] AID - 10.7326/ANNALS-24-03420 [doi] PST - ppublish SO - Ann Intern Med. 2025 Sep;178(9):1268-1278. doi: 10.7326/ANNALS-24-03420. Epub 2025 Jul 15. PMID- 40657828 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260613 IS - 1878-7177 (Electronic) IS - 0003-3006 (Print) IS - 0003-3006 (Linking) VI - 72 IP - 1 DP - 2025 Mar 12 TI - Implications of GLP-1 Agonists on Office-Based Sedation and General Anesthesia for Dentistry. PG - 52-58 LID - 10.2344/anpr-72-1-ANPR_Agonists [doi] AB - Incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are produced in the gut and play critical roles linking the processes of eating and digestion with the release of insulin from the pancreas and glucose homeostasis. GLP-1 receptor agonist and combination GLP-1/GIP receptor agonist medications are exogenous incretins that mimic their endogenous counterparts, but their significantly longer half-lives allow them to be clinically useful for managing diabetes mellitus type 2 (DMT2) and obesity. Recently, their use for weight loss has grown exponentially, increasing the potential that a provider of sedation or general anesthesia for dentistry will encounter a patient taking a GLP-1 or GLP-1/GIP combination receptor agonist. One of the clinical effects produced by these medications is decreased gastric emptying which increases satiety and decreases oral intake. While these medications are effective in the management of DMT2 and obesity, delayed gastric emptying can cause concerns for sedation and general anesthesia providers. Retained gastric contents can increase risks for emesis and subsequent pulmonary aspiration in the perioperative period. In 2024, a multisociety guidance document was published to provide recommendations for the management of these patients in the perioperative period. Recommendations emphasized risk stratification of individual patients and weighing the risks vs the benefits of holding or continuing GLP-1 and GLP-1/GIP combination receptor agonist medications. The recommendations also suggested shared decision making between the sedation or general anesthesia provider, the prescribing physician, and the patient should be used when developing a plan regarding the preoperative use of these medications. FAU - McKenzie, Craig AU - McKenzie C FAU - DeBernardo, Alexander AU - DeBernardo A FAU - Schwartz, Paul AU - Schwartz P LA - eng PT - Journal Article PT - Review DEP - 20250312 PL - United States TA - Anesth Prog JT - Anesthesia progress JID - 0043533 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Anesthesia, General/methods/adverse effects MH - *Anesthesia, Dental/methods MH - *Procedural Sedation/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Gastric Emptying/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC11922517 OTO - NOTNLM OT - Diabetes mellitus type 2 OT - GIP receptor agonist OT - GLP-1 receptor agonist OT - Obesity OT - Semaglutide OT - Tirzepatide EDAT- 2025/07/14 12:29 MHDA- 2025/07/14 12:30 PMCR- 2025/09/01 CRDT- 2025/07/14 08:27 PHST- 2024/03/21 00:00 [received] PHST- 2025/01/14 00:00 [accepted] PHST- 2025/07/14 12:30 [medline] PHST- 2025/07/14 12:29 [pubmed] PHST- 2025/07/14 08:27 [entrez] PHST- 2025/09/01 00:00 [pmc-release] AID - anpr721ANPRAgonists [pii] AID - 10.2344/anpr-72-1-ANPR_Agonists [doi] PST - epublish SO - Anesth Prog. 2025 Mar 12;72(1):52-58. doi: 10.2344/anpr-72-1-ANPR_Agonists. PMID- 40652323 OWN - NLM STAT- MEDLINE DCOM- 20250713 LR - 20260127 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 53 IP - 7 DP - 2025 Jul TI - Association of semaglutide use with depressive symptoms and suicidal behavior in a patient with type 2 diabetes: A case report. PG - 3000605251349393 LID - 10.1177/03000605251349393 [doi] LID - 03000605251349393 AB - Semaglutide is a glucagon-like peptide-1 receptor agonist used in the treatment of type 2 diabetes mellitus and management of obesity. Associations of glucagon-like peptide-1 receptor agonist use with psychiatric adverse events and suicidal behavior have been reported. A man in his late 70s with type 2 diabetes and no history of psychiatric illness or cognitive deficits was admitted to our clinic after his first suicide attempt involving the impulsive ingestion of brush cleaner liquid. A month before his presentation, he reported restlessness and depressive mood without any apparent trigger. This period was consistent with the time of semaglutide introduction. His psychiatric symptoms improved after semaglutide discontinuation. This case report highlights the importance of regular monitoring of depression and anxiety symptoms and the possibility of suicidal ideation in individuals with type 2 diabetes treated with semaglutide. This may enable early detection and prevention of serious psychiatric adverse events. FAU - Stojkovska, Anisija AU - Stojkovska A AD - University Psychiatric Clinic Ljubljana, Slovenia. FAU - Rus Prelog, Polona AU - Rus Prelog P AD - University Psychiatric Clinic Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Slovenia. FAU - Kokalj Palandacic, Anja AU - Kokalj Palandacic A AUID- ORCID: 0000-0002-4539-0044 AD - University Psychiatric Clinic Ljubljana, Slovenia. LA - eng PT - Case Reports PT - Journal Article DEP - 20250712 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/complications MH - Male MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Depression/chemically induced MH - Aged MH - *Suicidal Ideation MH - Suicide, Attempted/psychology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12255853 OTO - NOTNLM OT - Semaglutide OT - adverse effect OT - case report OT - depression OT - pharmacovigilance OT - suicide behavior EDAT- 2025/07/13 06:27 MHDA- 2025/07/13 06:28 PMCR- 2025/07/12 CRDT- 2025/07/13 01:12 PHST- 2025/07/13 06:28 [medline] PHST- 2025/07/13 06:27 [pubmed] PHST- 2025/07/13 01:12 [entrez] PHST- 2025/07/12 00:00 [pmc-release] AID - 10.1177_03000605251349393 [pii] AID - 10.1177/03000605251349393 [doi] PST - ppublish SO - J Int Med Res. 2025 Jul;53(7):3000605251349393. doi: 10.1177/03000605251349393. Epub 2025 Jul 12. PMID- 40652242 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20260819 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Jul 12 TI - Glucagon-like peptide-1 receptor agonist in myocardial infarction and atherosclerotic cardiovascular disease risk reduction: a comprehensive meta-analysis of number needed to treat, efficacy and safety. PG - 285 LID - 10.1186/s12933-025-02840-3 [doi] LID - 285 AB - BACKGROUND: Glucagon like peptide-1 receptor agonist (GLP-1RA) use in individuals with high atherosclerotic cardiovascular disease (ASCVD) risk reduces major adverse cardiovascular events (MACE). However, its clinical impact, in terms of numbers needed to treat (NNT), efficacy and safety profile in reducing the risk of myocardial infarction (MI) and the individual ASCVD constituents remain unclear. METHODS: Electronic databases, Medline and Embase were reviewed for randomized trials from inception to 29 May 2025. Risk-reduction effect of GLP-1RA were pooled using pairwise meta-analysis with random-effects model. The primary outcome was MI, and secondary outcomes were the individual ASCVD constituents. RESULTS: 109,846 patients from 25 unique studies were included. Over a follow-up duration of 3.48 +/- 1.51 (1.55 to 5.47) years, GLP-1RA reduced the risk of total MI (RR: 0.86, p < 0.01), with numbers needed to benefit (NNTB) of 207 to prevent one event of MI. Higher body mass index was associated with greater MI risk reduction (beta: -0.09, p = 0.03) in GLP-1RA users. GLP-1RA reduced cardiovascular mortality (RR: 0.87, p < 0.01, NNTB 170), MACE (RR: 0.87, p < 0.01, NNTB 67) and stroke (RR: 0.88, p < 0.01, NNTB 335) compared to placebo. GLP-1RA commonly resulted in gastrointestinal side-effects amongst other systems (RR: 1.55, p < 0.01, NNTH 9). CONCLUSION: GLP-1RA reduced the risk of MI, stroke, cardiovascular mortality and MACE in a broad range of patients with and without T2DM and/or prior ASCVD, supporting its role in ASCVD prevention, especially in the cohort with high BMI. TRIAL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/7VXN5 ). CI - (c) 2025. The Author(s). FAU - Tang, Ansel Shao Pin AU - Tang ASP AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Hsu, Jovan Teng Yuan AU - Hsu JTY AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chong, Sheena Kar Shuan AU - Chong SKS AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Quek, Jingxuan AU - Quek J AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Shek, Genevieve AU - Shek G AD - Wallace Wurth, University of New South Wales, Sydney, NSW, Australia. FAU - Sulaimi, Farisah AU - Sulaimi F AD - Wallace Wurth, University of New South Wales, Sydney, NSW, Australia. FAU - Chan, Kai En AU - Chan KE AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Anand, Vickram Vijay AU - Anand VV AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. FAU - Chong, Bryan AU - Chong B AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Mehta, Anurag AU - Mehta A AD - Virginia Commonwealth University Health Pauley Heart Center, Division of Cardiology (A.M.), Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, USA. FAU - Toh, Sue-Anne AU - Toh SA AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Department of Medicine, National University Hospital, Singapore, Singapore. AD - NOVI Health, Singapore, Singapore. AD - Regional Health System Office, National University Health System, Singapore, Singapore. FAU - Muthiah, Mark AU - Muthiah M AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. AD - National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AD - Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, London, UK. AD - Obesity, Type 2 Diabetes and Immunometabolism Research Group, Department of Diabetes, Faculty of Cardiovascular Medicine & Sciences, School of Life Course Sciences, King's College London, London, UK. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland. AD - Diabetes Research Centre , Ulster University , UK, UK. FAU - Chan, Mark Yan-Yee AU - Chan MY AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore. FAU - Mamas, Mamas Andreas AU - Mamas MA AD - Keele Cardiac Research Group, Keele University, Stoke-on-Trent, UK. FAU - Chin, Yip Han AU - Chin YH AD - Ministry of Health Holdings, Ministry of Health, Singapore, Singapore. FAU - Chew, Nicholas W S AU - Chew NWS AUID- ORCID: 0000-0002-0640-0430 AD - NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Nicholas_WS_Chew@nuhs.edu.sg. AD - Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore. Nicholas_WS_Chew@nuhs.edu.sg. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20250712 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Myocardial Infarction/prevention & control/diagnosis/epidemiology/mortality MH - Treatment Outcome MH - Risk Assessment MH - *Atherosclerosis/diagnosis/prevention & control/mortality/epidemiology/drug therapy MH - Randomized Controlled Trials as Topic MH - *Incretins/adverse effects/therapeutic use MH - *Numbers Needed To Treat MH - Male MH - Female MH - Time Factors MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/epidemiology MH - Heart Disease Risk Factors MH - Protective Factors MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12255114 OTO - NOTNLM OT - Cardiovascular disease OT - Cardiovascular mortality OT - GLP-1 receptor agonist OT - GLP-1RA OT - Myocardial infarction OT - Numbers-needed-to-treat OT - Stroke COIS- Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The study was exempt from IRB review as no confidential information was involved. Consent for publication: Not applicable. All other authors of the manuscript do not have a conflict of interest to declare. Authorship statement: All authors approve the final version of the manuscript, including the authorship list and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Presentations: No part of this manuscript or its contents have been presented in any capacity outside of this manuscript as of the time of submission. Registration and protocol: This review was registered on the Open Science Framework (OSF) registries prior to conduction ( https://doi.org/10.17605/OSF.IO/7VXN5 ). Competing interests: Dr Nicholas Chew is supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National University of Singapore Yong Loo Lin School of Medicine's Academic Fellowship Scheme, and NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS). EDAT- 2025/07/13 03:40 MHDA- 2025/07/13 03:41 PMCR- 2025/07/12 CRDT- 2025/07/12 23:33 PHST- 2025/03/15 00:00 [received] PHST- 2025/06/24 00:00 [accepted] PHST- 2025/07/13 03:41 [medline] PHST- 2025/07/13 03:40 [pubmed] PHST- 2025/07/12 23:33 [entrez] PHST- 2025/07/12 00:00 [pmc-release] AID - 10.1186/s12933-025-02840-3 [pii] AID - 2840 [pii] AID - 10.1186/s12933-025-02840-3 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Jul 12;24(1):285. doi: 10.1186/s12933-025-02840-3. PMID- 40649923 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20250716 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 13 DP - 2025 Jun 26 TI - Structure-Based Discovery of Orthosteric Non-Peptide GLP-1R Agonists via Integrated Virtual Screening and Molecular Dynamics. LID - 10.3390/ijms26136131 [doi] LID - 6131 AB - The development of orally bioavailable non-peptidomimetic glucagon-like peptide-1 receptor agonists (GLP-1RAs) offers a promising therapeutic avenue for the treatment of type 2 diabetes mellitus (T2DM) and obesity. An extensive in silico approach combining structure-based drug design and ligand-based strategies together with pharmacokinetic properties and drug-likeness predictions is implemented to identify novel non-peptidic GLP-1RAs from the COCONUT and Marine Natural Products (CMNPD) libraries. More than 700,000 compounds were screened by shape-based similarity filtering in combination with precision docking against the orthosteric site of the GLP-1 receptor (PDB ID: 6X1A). The docked candidates were further assessed with the molecular mechanics MM-GBSA tool to check the binding affinities; the final list of candidates was validated by running a 500 ns long MD simulation. Twenty final hits were identified, ten from each database. The hits contained compounds with reported antidiabetic effects but with no evidence of GLP-1 agonist activity, including hits 1, 6, 7, and 10. These findings proposed a novel mechanism for these hits through GLP-1 activity and positioned the other hits as potential promising scaffolds. Among the studied compounds-especially hits 1, 5, and 9-possessed strong and stable interactions with critical amino acid residues such as TRP-203, PHE-381, and GLN-221 at the active site of the 6X1A-substrate along with favorable pharmacokinetic profiles. Moreover, the RMSF and RMSD plots further suggested the possibility of stable interactions. Specifically, hit 9 possessed the best docking score with a DeltaG_bind value of -102.78 kcal/mol, surpassing even the control compound in binding affinity. The ADMET profiling also showed desirable drug-likeness and pharmacokinetic characteristics for hit 9. The pipeline of computational integration underscores the potential of non-peptidic alternatives in natural product libraries to pursue GLP-1-mediated metabolic therapy into advanced preclinical validation. FAU - Alturki, Mansour S AU - Alturki MS AUID- ORCID: 0000-0001-7702-9379 AD - Department of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Alkhodier, Reem A AU - Alkhodier RA AUID- ORCID: 0000-0002-3946-6145 AD - Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia. FAU - Gomaa, Mohamed S AU - Gomaa MS AUID- ORCID: 0000-0003-2112-9092 AD - Department of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Hussein, Dania A AU - Hussein DA AD - Department of Pharmacology, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Tawfeeq, Nada AU - Tawfeeq N AUID- ORCID: 0000-0002-9178-9021 AD - Department of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Al Khzem, Abdulaziz H AU - Al Khzem AH AUID- ORCID: 0009-0004-0079-8646 AD - Department of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Pottoo, Faheem H AU - Pottoo FH AUID- ORCID: 0000-0003-2577-7505 AD - Department of Pharmacology, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Albugami, Shmoukh A AU - Albugami SA AUID- ORCID: 0009-0005-6095-8784 AD - College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. FAU - Aldawsari, Mohammed F AU - Aldawsari MF AUID- ORCID: 0000-0003-1298-4863 AD - Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia. FAU - Rants'o, Thankhoe A AU - Rants'o TA AUID- ORCID: 0000-0001-8585-0888 AD - Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA. AD - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. LA - eng PT - Journal Article DEP - 20250626 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Ligands) SB - IM MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Molecular Docking Simulation MH - *Molecular Dynamics Simulation MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/chemistry/metabolism MH - *Hypoglycemic Agents/chemistry/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Drug Discovery MH - Ligands MH - Protein Binding PMC - PMC12249819 OTO - NOTNLM OT - GLP-1R OT - chemical scaffolds OT - molecular dynamics OT - oral therapy OT - virtual screening COIS- The authors declare no conflicts of interest. EDAT- 2025/07/13 03:31 MHDA- 2025/07/13 03:32 PMCR- 2025/06/26 CRDT- 2025/07/12 01:21 PHST- 2025/05/23 00:00 [received] PHST- 2025/06/21 00:00 [revised] PHST- 2025/06/23 00:00 [accepted] PHST- 2025/07/13 03:32 [medline] PHST- 2025/07/13 03:31 [pubmed] PHST- 2025/07/12 01:21 [entrez] PHST- 2025/06/26 00:00 [pmc-release] AID - ijms26136131 [pii] AID - ijms-26-06131 [pii] AID - 10.3390/ijms26136131 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jun 26;26(13):6131. doi: 10.3390/ijms26136131. PMID- 40649730 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20250716 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 13 DP - 2025 Jun 20 TI - Diabetes Mellitus in Kidney Transplant Recipients and New Hypoglycemic Agent Options. LID - 10.3390/ijms26135952 [doi] LID - 5952 AB - Diabetes mellitus (DM) is frequent in kidney transplant recipients (KTRs), reducing graft and patient survival. In recent years, hypoglycemic agents have been approved for chronic kidney disease (CKD) patients, such as sodium glucose co-transporter type 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), such as finerenone. Several studies demonstrated the ability of these drugs to reduce cardiovascular (CV) events and kidney disease progression in diabetic CKD patients. In this review, we will describe their use in KTRs with type 2 DM or post-transplant diabetes mellitus (PTDM), focusing on the potential positive effects. In particular, we will report literature data from observational studies, meta-analyses, and clinical trials. Based on their mechanism of actions, these drugs may balance the negative effects of immunosuppressive therapy on metabolic balance, reducing the risk of PTDM and CV events, that remain the first cause of death in KTRs. Generally, SGLT2is and GLP1RAs appear to be safe and efficacious in KTRs, and no interaction with immunosuppressive drugs or an increased risk of rejection has been reported. Regarding finerenone, no literature data are available and only one clinical trial is ongoing. In conclusion, although the 2022 KDIGO guidelines recommend caution in KTRs, the last meeting in Vienna on PTDM encourages their use in this population. FAU - Bartoli, Giulia AU - Bartoli G AD - Nephrology and Dialysis Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy. FAU - Dello Strologo, Andrea AU - Dello Strologo A AD - Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. AD - Department of Nephrology and Dialysis, Azienda USL Roma 6, 00040 Albano Laziale, Italy. FAU - Arena, Maria AU - Arena M AD - Nephrology, Dialysis and Transplantation Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. FAU - Ceravolo, Maria Jose AU - Ceravolo MJ AD - Nephrology and Dialysis Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy. FAU - Mitterhofer, Anna Paola AU - Mitterhofer AP AUID- ORCID: 0000-0002-0132-386X AD - Nephrology and Dialysis Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy. AD - Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. FAU - Pesce, Francesco AU - Pesce F AUID- ORCID: 0000-0002-2882-4226 AD - Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. AD - Division of Renal Medicine, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy. FAU - Grandaliano, Giuseppe AU - Grandaliano G AD - Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy. AD - Nephrology, Dialysis and Transplantation Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250620 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Kidney Transplantation/adverse effects MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/etiology MH - Transplant Recipients MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Renal Insufficiency, Chronic PMC - PMC12250267 OTO - NOTNLM OT - chronic kidney disease OT - glucagon-like peptide-1 receptor agonists OT - hypoglycemic agent OT - kidney transplantation OT - nonsteroidal mineralocorticoid receptor antagonist OT - post-transplant diabetes mellitus OT - sodium glucose co-transporter type 2 inhibitors COIS- The authors declare no conflicts of interest. EDAT- 2025/07/13 03:32 MHDA- 2025/07/13 03:33 PMCR- 2025/06/20 CRDT- 2025/07/12 01:20 PHST- 2025/05/14 00:00 [received] PHST- 2025/06/14 00:00 [revised] PHST- 2025/06/18 00:00 [accepted] PHST- 2025/07/13 03:33 [medline] PHST- 2025/07/13 03:32 [pubmed] PHST- 2025/07/12 01:20 [entrez] PHST- 2025/06/20 00:00 [pmc-release] AID - ijms26135952 [pii] AID - ijms-26-05952 [pii] AID - 10.3390/ijms26135952 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jun 20;26(13):5952. doi: 10.3390/ijms26135952. PMID- 40649729 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 13 DP - 2025 Jun 20 TI - Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study. LID - 10.3390/ijms26135951 [doi] LID - 5951 AB - Recent studies have demonstrated the efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in enhancing glycemic control, regulating body weight, and modulating lipid metabolism. However, their effects on lipoprotein subfractions have not been clarified. The objective of this 52-week, single-center, randomized trial was to compare the effects of subcutaneous semaglutide administered once weekly and oral sitagliptin administered once daily on anthropometric measurements and lipoprotein subfractions measured by Lipoprint gelelectrophoresis in patients with type 2 diabetes mellitus (T2DM). A total of 34 obese individuals with T2DM were enrolled in the study and randomly assigned to receive semaglutide (n = 18) or sitagliptin (n = 16). Thirty-one age- and body weight-matched non-diabetic obese individuals served as controls. Semaglutide treatment resulted in significant reductions in body mass index (BMI), waist circumference, and Hb(A1c), along with improvements in lipid parameters, including reductions in LDL cholesterol and non-HDL cholesterol levels, and redistribution of LDL and HDL subfractions toward a less atherogenic profile. Conversely, sitagliptin elicited modest glycemic improvements without substantial alterations in lipid composition. Multivariate regression analysis demonstrated that fluctuations in lipoprotein subfractions were not influenced by changes in BMI or HbA1c. These results support the pleiotropic metabolic benefits of semaglutide and its potential role in managing the cardiometabolic risk of T2DM. FAU - Toth, Laszlo Imre AU - Toth LI AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harsanyi, Adrienn AU - Harsanyi A AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Csiha, Sara AU - Csiha S AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - Department of Clinical Basics, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Molnar, Agnes AU - Molnar A AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Lorincz, Hajnalka AU - Lorincz H AUID- ORCID: 0009-0000-5303-3082 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Nagy, Attila Csaba AU - Nagy AC AUID- ORCID: 0000-0002-0554-7350 AD - Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Paragh, Gyorgy AU - Paragh G AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harangi, Mariann AU - Harangi M AUID- ORCID: 0000-0001-9761-9595 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - ELKH-UD Vascular Pathophysiology Research Group 11003, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Sztanek, Ferenc AU - Sztanek F AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. LA - eng GR - K142273/National Research, Development and Innovation Office - NKFIH/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250620 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Lipids) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/pharmacology MH - Male MH - Female MH - Middle Aged MH - Sitagliptin Phosphate/therapeutic use/administration & dosage MH - Follow-Up Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/metabolism MH - Body Mass Index MH - *Lipids/blood MH - Lipid Metabolism/drug effects MH - Aged MH - Adult MH - Blood Glucose MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12250273 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiometabolic risk OT - lipoprotein subfractions OT - semaglutide OT - sitagliptin OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/07/13 03:37 MHDA- 2025/07/13 03:38 PMCR- 2025/06/20 CRDT- 2025/07/12 01:20 PHST- 2025/05/19 00:00 [received] PHST- 2025/06/16 00:00 [revised] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/13 03:38 [medline] PHST- 2025/07/13 03:37 [pubmed] PHST- 2025/07/12 01:20 [entrez] PHST- 2025/06/20 00:00 [pmc-release] AID - ijms26135951 [pii] AID - ijms-26-05951 [pii] AID - 10.3390/ijms26135951 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jun 20;26(13):5951. doi: 10.3390/ijms26135951. PMID- 40641020 OWN - NLM STAT- MEDLINE DCOM- 20260624 LR - 20260624 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 32 IP - 20 DP - 2026 TI - Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease. PG - 1567-1591 LID - 10.2174/0113816128378484250619080753 [doi] AB - Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus (T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-beta agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However, the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/ fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM, and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Muzurovic, Emir AU - Muzurovic E AUID- ORCID: 0000-0003-2022-3298 AD - Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica, Montenegro. AD - Faculty of Medicine, University of Montenegro, Podgorica, Montenegro. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic. AD - First Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic. FAU - Horvath, Ludek AU - Horvath L AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic. AD - First Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic. FAU - Vlacho, Bogdan AU - Vlacho B AD - DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. FAU - Mauricio, Didac AU - Mauricio D AD - DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. AD - Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Medicine, University of Vic - Central University of Catalonia, Vic, Spain. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Incretins) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - *Fatty Liver/drug therapy/metabolism MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Obesity/drug therapy/metabolism OTO - NOTNLM OT - Metabolic-dysfunction associated steatotic liver disease OT - incretin-based agents OT - metabolic dysfunction/associated steatohepatitis OT - pathophysiology. OT - semaglutide OT - survodutide OT - tirzepatide EDAT- 2025/07/11 06:27 MHDA- 2026/06/25 00:33 CRDT- 2025/07/11 00:23 PHST- 2025/01/03 00:00 [received] PHST- 2025/03/21 00:00 [revised] PHST- 2025/04/17 00:00 [accepted] PHST- 2026/06/25 00:33 [medline] PHST- 2025/07/11 06:27 [pubmed] PHST- 2025/07/11 00:23 [entrez] AID - CPD-EPUB-149297 [pii] AID - 10.2174/0113816128378484250619080753 [doi] PST - ppublish SO - Curr Pharm Des. 2026;32(20):1567-1591. doi: 10.2174/0113816128378484250619080753. PMID- 40637950 OWN - NLM STAT- MEDLINE DCOM- 20260316 LR - 20260926 IS - 1573-7241 (Electronic) IS - 0920-3206 (Print) IS - 0920-3206 (Linking) VI - 40 IP - 2 DP - 2026 Apr TI - GLP1-RA and SGLT2-i: Implementation and Insulin Deescalation Strategies. PG - 779-793 LID - 10.1007/s10557-025-07744-8 [doi] AB - PURPOSE OF REVIEW: This review will summarize the most contemporary trials for glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and present guidance on management and recommendations on adjunctive tapering of insulin in patients with insulin-dependent diabetes mellitus, which we term "de-insulinization." RECENT FINDINGS: GLP1-RA and SGLT2-i are the principal classes of diabetes medications evidencing cardiovascular benefit. However, there is limited consensus on how to effectively prescribe and maintain these medications for patients on other glucose-lowering therapy, especially insulin. Patients with type 2 diabetes and cardiovascular disease should be started on either a GLP-1RA, SGLT-i, or both in high-risk cases, while simultaneously tapering any prescribed insulin regimen. Initial selection and transition of therapy should be approached individually and systematically, with prioritization of patients with other comorbidities such as coronary artery disease, chronic kidney disease, and other diabetes complications. CI - (c) 2025. The Author(s). FAU - Palani, Arthi AU - Palani A AUID- ORCID: 0009-0009-7943-1527 AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. aap238@njms.rutgers.edu. FAU - Patel, Sagar AU - Patel S AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. FAU - Patel, Shriya AU - Patel S AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. FAU - Srivastava, Shivani AU - Srivastava S AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. FAU - Patel, Jay AU - Patel J AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. FAU - Salehin, Salman AU - Salehin S AD - Division of Cardiology, University of Texas Medical Branch, Galveston, TX, USA. FAU - Birnbaum, Yochai AU - Birnbaum Y AD - Section of Cardiology, Baylor College of Medicine, Houston, TX, USA. FAU - Allencherril, Joseph AU - Allencherril J AD - Division of Cardiology, University of Texas Medical Branch, Galveston, TX, USA. LA - eng PT - Journal Article PT - Review DEP - 20250710 PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Insulin/administration & dosage/adverse effects MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Blood Glucose/drug effects/metabolism MH - Cardiovascular Diseases/prevention & control/epidemiology MH - *Incretins/adverse effects/administration & dosage/therapeutic use MH - Treatment Outcome PMC - PMC12992454 OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes OT - GLP-1RA OT - Heart failure OT - Insulin de-escalation OT - Outcomes OT - SGLT2-i COIS- Declarations. Ethics Approval: This is a review article that does not require ethics approval as it solely analyzes previously published data. All sources adhere to ethical guidelines regarding data collection and publication. Consent to Participate: Not applicable. Consent for Publication: All authors have reviewed and approved the final manuscript for publication. No other participants were involved in the research process. Conflict of interest: The authors declare no competing interests. EDAT- 2025/07/10 12:31 MHDA- 2026/03/16 21:57 PMCR- 2025/07/10 CRDT- 2025/07/10 11:19 PHST- 2025/06/25 00:00 [accepted] PHST- 2026/03/16 21:57 [medline] PHST- 2025/07/10 12:31 [pubmed] PHST- 2025/07/10 11:19 [entrez] PHST- 2025/07/10 00:00 [pmc-release] AID - 10.1007/s10557-025-07744-8 [pii] AID - 7744 [pii] AID - 10.1007/s10557-025-07744-8 [doi] PST - ppublish SO - Cardiovasc Drugs Ther. 2026 Apr;40(2):779-793. doi: 10.1007/s10557-025-07744-8. Epub 2025 Jul 10. PMID- 40637847 OWN - NLM STAT- MEDLINE DCOM- 20250913 LR - 20250913 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 9 DP - 2025 Sep TI - Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study. PG - 2069-2076 LID - 10.1007/s00125-025-06466-8 [doi] AB - AIMS/HYPOTHESIS: Early worsening of diabetic retinopathy (EWDR) has been described during treatment with glucagon-like peptide-1 receptor agonists including subcutaneous semaglutide. Whether EWDR occurs after initiating treatment with the potent glucagon-like peptide 1 / gastric inhibitory polypeptide receptor agonist tirzepatide is unknown. METHODS: In this retrospective cohort study using real-world clinical data, we matched 3435 tirzepatide-exposed (>/=180 days treatment) individuals with type 2 diabetes 1:1 with 3434 tirzepatide-unexposed individuals for sex, diabetes duration, retinopathy status, HbA(1c), number of retinal screening episodes and use of glucose-lowering medications. New-onset diabetic retinopathy and retinopathy progression were explored using conditional logistic regression. RESULTS: Individuals included in the study had tight baseline glycaemic control (mean HbA(1c) 56.1 +/- 15.8 mmol/mol [7.28 +/- 1.43%]). New-onset proliferative diabetic retinopathy (PDR) (grade R3M0, R3M1) occurred in 1.1% of tirzepatide-exposed (n=33) and 0.5% of tirzepatide-unexposed (n=17) individuals. Tirzepatide was significantly associated with new-onset PDR in multivariate analysis after adjustment for established risk factors (OR 2.15 [95% CI 1.24, 3.74], p<0.01). However, tirzepatide was also associated with reduced odds of new onset of retinopathy (OR 0.73 [95% CI 0.62, 0.86], p<0.001) in individuals without diabetic retinopathy (R0M0) at initiation in multivariate analysis, and was not significantly associated with retinopathy progression in individuals with mild non-proliferative diabetic retinopathy (NPDR, grade R1M0 or R1M1). CONCLUSIONS/INTERPRETATION: Tirzepatide therapy resulted in significantly increased odds of incident PDR, particularly in individuals with mild NPDR with maculopathy (grade R1M1), or moderate-to-severe NPDR with or without maculopathy (grade R2M0, R2M1). The increase in odds of progression would justify specialist ophthalmologist referral by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. CI - (c) 2025. The Author(s). FAU - Buckley, Adam J AU - Buckley AJ AUID- ORCID: 0000-0001-7471-0273 AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. abuckley@icldc.ae. FAU - Tan, Garry D AU - Tan GD AD - OCDEM, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Garry.tan@ocdem.ox.ac.uk. AD - Oxford NIHR Biomedical Research Centre, Oxford, UK. Garry.tan@ocdem.ox.ac.uk. FAU - Gruszka-Goh, Marta AU - Gruszka-Goh M AD - Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK. FAU - Scanlon, Peter H AU - Scanlon PH AD - Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK. FAU - Ansari, Imran AU - Ansari I AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. FAU - Suliman, Sara G I AU - Suliman SGI AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article DEP - 20250710 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Disease Progression MH - Glycated Hemoglobin/metabolism MH - Cohort Studies MH - Tirzepatide PMC - PMC12361273 OTO - NOTNLM OT - GIP OT - GLP-1RA OT - Retinopathy OT - Tirzepatide OT - Type 2 diabetes COIS- Acknowledgements: The authors wish to acknowledge the contributions of A. Lari, A. Thampi, C. Suangco, J. Espinosa, J. Vasquez, M. Marquez, M. Jadoun, S. Cyriac and S. Alberto, retinal graders at ICLDC. GDT is supported by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data availability: Data that underlie the results reported in this article after de-identification (text, tables and figures) will be available. Data will be available for up to 5 years following publication for sharing with researchers who submit a study question which, in the opinion of the authors, can reasonably be addressed by the data. Enquiries should be directed to abuckley@icldc.ae. An institutional contract and data sharing agreement will be required. Funding: No external funding was received. Authors' relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AJB performed data collection and statistical analysis and wrote the first draft of the manuscript. GDT, MG-G, PHS, IA and SGIS contributed to study methodology and revised and edited the final draft of the manuscript. The manuscript was approved for submission by all authors. AJB had access to the data used in this project and is the guarantor. EDAT- 2025/07/10 12:30 MHDA- 2025/09/13 18:29 PMCR- 2025/07/10 CRDT- 2025/07/10 11:13 PHST- 2024/12/06 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/09/13 18:29 [medline] PHST- 2025/07/10 12:30 [pubmed] PHST- 2025/07/10 11:13 [entrez] PHST- 2025/07/10 00:00 [pmc-release] AID - 10.1007/s00125-025-06466-8 [pii] AID - 6466 [pii] AID - 10.1007/s00125-025-06466-8 [doi] PST - ppublish SO - Diabetologia. 2025 Sep;68(9):2069-2076. doi: 10.1007/s00125-025-06466-8. Epub 2025 Jul 10. PMID- 40637050 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 7 IP - Suppl 7 DP - 2025 Aug TI - What is the 'real-world' experience with fixed-ratio combination therapy (insulin + GLP-1 receptor agonist) in routine clinical practice? Take-home messages for clinicians regarding key outcomes. PG - 26-41 LID - 10.1111/dom.16593 [doi] AB - AIMS: The fixed-ratio combinations (FRCs) of a basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA), IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), offer a once-daily injectable treatment option for adults with type 2 diabetes (T2D), combining complementary mechanisms of action to target both fasting and postprandial hyperglycaemia. While randomized controlled trials have demonstrated their efficacy and safety, real-world evidence (RWE) provides important insights into their effectiveness, tolerability and use across routine clinical practice. MATERIALS AND METHODS: This is a narrative review of selected real-world studies assessing the FRCs IDegLira and iGlarLixi in adults with T2D. Studies assessing the use of FRCs to intensify and simplify therapy, as well as their use in special populations such as older adults were reviewed and are summarized. RESULTS: Among individuals inadequately controlled on oral antihyperglycaemic drugs (OADs), basal insulin +/- OADs, or GLP-1 RAs, initiation of FRC therapy consistently improved glycaemic outcomes, supported modest weight loss or stability, and was associated with a low risk of hypoglycaemia. FRCs have also been evaluated as a strategy for simplifying complex insulin regimens. Transitions from basal-bolus or premixed insulin to FRCs maintained or improved glycaemic control while reducing total daily insulin dose and injection burden. Evidence in special populations and clinical contexts further supports the utility of FRCs. In older adults, FRC use was associated with reductions in HbA1c and hypoglycaemia risk, along with improvements in treatment satisfaction and functional measures. During Ramadan fasting, iGlarLixi demonstrated favourable glycaemic control, low hypoglycaemia incidence, modest weight loss and high adherence. Studies assessing glycaemic control using continuous glucose monitoring showed improvements in time in range, reductions in time above range and stable time below range, indicating enhanced glycaemic stability without increased risk of hypoglycaemia. Two real-world head-to-head studies comparing IDegLira and iGlarLixi found both FRCs to be effective and well tolerated. IDegLira was associated with greater weight loss and lower insulin dose requirements, while iGlarLixi showed advantages in postprandial glucose control. Both agents demonstrated significant improvements in HbA1c and low rates of hypoglycaemia. CONCLUSIONS: Collectively, these real-world studies confirm that FRCs are effective, safe and patient-centred treatment options for adults with T2D. Their simplified dosing, metabolic benefits and favourable safety profiles support their use for both therapy intensification and de-intensification across a broad spectrum of clinical scenarios. These findings reinforce results from randomized controlled trials, providing further confidence in the role of FRCs in contemporary diabetes care. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Frias, Juan Pablo AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - Department of Medicine, Charles R Drew University of Medicine and Science, Los Angeles, California, USA. LA - eng PT - Journal Article PT - Review DEP - 20250710 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin, Long-Acting) RN - 0 (Drug Combinations) RN - 0 (IDegLira) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 839I73S42A (Liraglutide) RN - 0 (Blood Glucose) RN - 0 (Peptides) RN - 74O62BB01U (lixisenatide) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Drug Combinations MH - Insulin Glargine/administration & dosage/therapeutic use MH - Liraglutide/administration & dosage/therapeutic use MH - Treatment Outcome MH - Blood Glucose/drug effects MH - Peptides/administration & dosage/therapeutic use MH - Hypoglycemia/chemically induced/prevention & control MH - Glycated Hemoglobin MH - Drug Therapy, Combination MH - Glucagon-Like Peptide-2 Receptor PMC - PMC12308270 OTO - NOTNLM OT - GLP-1 analogue OT - fixed-ratio combination OT - iGlarLixi OT - insulin analogues OT - real-world evidence COIS- Dr. Frias is an employee of Biomea Fusion. He has previously served as a consultant and as a speaker for Novo Nordisk and Sanofi. EDAT- 2025/07/10 12:31 MHDA- 2025/07/30 06:30 PMCR- 2025/07/30 CRDT- 2025/07/10 06:22 PHST- 2025/06/16 00:00 [revised] PHST- 2025/05/14 00:00 [received] PHST- 2025/06/22 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/07/10 12:31 [pubmed] PHST- 2025/07/10 06:22 [entrez] PHST- 2025/07/30 00:00 [pmc-release] AID - DOM16593 [pii] AID - 10.1111/dom.16593 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27 Suppl 7(Suppl 7):26-41. doi: 10.1111/dom.16593. Epub 2025 Jul 10. PMID- 40633588 OWN - NLM STAT- MEDLINE DCOM- 20251211 LR - 20251211 IS - 1878-1632 (Electronic) IS - 1529-9430 (Linking) VI - 26 IP - 1 DP - 2026 Jan TI - Association between glucagon-like peptide-1 receptor agonists and nonfusion risk after single-level anterior cervical discectomy and fusion. PG - 158-162 LID - S1529-9430(25)00329-8 [pii] LID - 10.1016/j.spinee.2025.07.010 [doi] AB - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a common procedure for treating degenerative cervical spine diseases. Successful fusion is essential for spinal stability, while pseudarthrosis can lead to pain and revision surgery. Glucagon-like peptide-1 (GLP-1) drugs, used for type 2 diabetes (T2DM) and obesity, have demonstrated benefits in vascular and bone health. PURPOSE: This study investigates whether perioperative GLP-1 drug use affects fusion rates in T2DM patients undergoing single-level ACDF. DESIGN: Retrospective cohort study. PATIENT SAMPLE: T2DM patients undergoing single-level ACDF. OUTCOME MEASUREMENT: Risk of pseudarthrosis, identified using ICD-10 code M96.0, at 6 months, 1 year, and 2 years postoperatively. METHODS: A retrospective analysis was conducted using the TriNetX database, identifying T2DM patients who underwent single-level ACDF via CPT codes. Patients were categorized based on GLP-1 drug use within 6 months before or after surgery. A 1:1 propensity score matching (PSM) controlled for age, sex, race, and comorbidities. RESULTS: Before propensity score matching (PSM), 1,245 GLP-1 drug users and 13,519 nonusers were included. After matching, 1,242 patients remained in each group. At 6 months, the nonfusion rate was 7.9% in the GLP-1 drug group and 13.6% in the nonuser group (OR=0.55, 95% CI: 0.42-0.72, p<.001), indicating 45% lower odds of pseudarthrosis in GLP-1 drug users. This trend remained consistent at 1 year (8.8% vs 14.5%, OR=0.57, 95% CI: 0.44-0.74, p<.001) and 2 years postoperatively (10.0% vs 15.5%, OR=0.61, 95% CI: 0.48-0.78, p<.001), suggesting a sustained reduction in the risk of nonfusion with GLP-1 drug use. CONCLUSIONS: Perioperative GLP-1 drug use is associated with a lower risk of pseudarthrosis in T2DM patients undergoing ACDF. These findings suggest a potential role for GLP-1 drugs in improving spinal fusion outcomes. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Chang, Yu AU - Chang Y AD - Section of neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138 Sheng Li Road, North District, Tainan City 704, Taiwan. FAU - Chi, Kuan-Yu AU - Chi KY AD - Department of Medicine, Jacobi Medical Center, 1400 Pelham Parkway South, Bronx, NY 10461, USA. FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, 1400 Pelham Parkway South, Bronx, NY 10461, USA. FAU - Lin, Hong-Min AU - Lin HM AD - Department of Family Medicine, Chi-Mei Medical Center No. 901, Zhonghua Road, Yongkang District, Tainan City 710, Taiwan. Electronic address: hongml2828@gmail.com. LA - eng PT - Journal Article DEP - 20250707 PL - United States TA - Spine J JT - The spine journal : official journal of the North American Spine Society JID - 101130732 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Spinal Fusion/adverse effects/methods MH - Male MH - Female MH - *Diskectomy/adverse effects/methods MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cervical Vertebrae/surgery MH - Aged MH - *Pseudarthrosis/epidemiology/etiology MH - *Postoperative Complications/epidemiology OTO - NOTNLM OT - Anterior cervical discectomy and fusion OT - Cervical spine surgery OT - Glucagon-like peptide-1 receptor agonists OT - Non-fusion OT - Pseudoarthrosis OT - Type 2 Diabetes Mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/10 00:36 MHDA- 2025/12/12 03:28 CRDT- 2025/07/09 19:31 PHST- 2025/03/13 00:00 [received] PHST- 2025/05/19 00:00 [revised] PHST- 2025/07/04 00:00 [accepted] PHST- 2025/12/12 03:28 [medline] PHST- 2025/07/10 00:36 [pubmed] PHST- 2025/07/09 19:31 [entrez] AID - S1529-9430(25)00329-8 [pii] AID - 10.1016/j.spinee.2025.07.010 [doi] PST - ppublish SO - Spine J. 2026 Jan;26(1):158-162. doi: 10.1016/j.spinee.2025.07.010. Epub 2025 Jul 7. PMID- 40632592 OWN - NLM STAT- MEDLINE DCOM- 20251008 LR - 20260919 IS - 1460-2105 (Electronic) IS - 0027-8874 (Print) IS - 0027-8874 (Linking) VI - 117 IP - 10 DP - 2025 Oct 1 TI - Association between glucagon-like peptidase 1 receptor agonist and obesity-related cancer in overweight or obese patients with type 2 diabetes: a nationwide cohort study. PG - 2053-2061 LID - 10.1093/jnci/djaf163 [doi] AB - BACKGROUND: Evidence regarding the effect of glucagon-like peptide 1 receptor (GLP-1) agonist, when compared with other glucose-lowering drugs, on obesity-related cancer in overweight or obese patients with type 2 diabetes is limited. METHODS: Using Merative Marketscan research databases, we identified all overweight or obese patients with type 2 diabetes aged 20-79 years who received GLP-1 agonist or other glucose-lowering drugs in the United States between January 2016 and June 2021. The primary outcome was obesity-related cancer, defined as a component of 13 cancer types. RESULTS: Among 919 609 overweight or obese individuals with type 2 diabetes (mean [SD] age = 52.3 [10.9] years; female, 53.5%), 16 653 newly diagnosed with obesity-related cancer were recorded during the 2 086 526 person-years of follow-up. GLP-1 agonist users (vs other glucose-lowering drugs users) were associated with lower incidence (7.5 vs 8.1 per 1000 person-years) and risk of obesity-related cancer (adjusted hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.83 to 0.91). This statistically significant association was consistent when comparing GLP-1 agonist with metformin (adjusted HR = 0.90, 95% CI = 0.86 to 0.95), dipeptidyl peptidase-4 inhibitor (adjusted HR = 0.88, 95% CI = 0.84 to 0.93), thiazolidinediones (adjusted HR = 0.84, 95% CI = 0.71 to 0.99), sulfonylureas (adjusted HR = 0.81, 95% CI = 0.74 to 0.88), sodium-glucose transport protein 2 inhibitor (adjusted HR = 0.73, 95% CI = 0.66 to 0.80), and insulin (adjusted HR = 0.70, 95% CI = 0.65 to 0.76; all P < .05) and was strengthened with increasing weight (overweight, mild to moderate, and severe obesity: HR = 0.95, 95% CI = 0.81 to 1.10, vs HR = 0.90, 95% CI = 0.84 to 0.97, vs HR = 0.82, 95% CI = 0.77 to 0.88, respectively; Pinteraction = .032). CONCLUSIONS: In a nationwide US cohort of overweight or obese patients with type 2 diabetes, GLP-1 agonist, when compared with other glucose-lowering drugs, was associated with a lower risk of obesity-related cancer, with more pronounced risk reduction with increasing body weight. CI - (c) The Author(s) 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Mao, Xianhua AU - Mao X AUID- ORCID: 0000-0003-4050-4759 AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States. AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China. AD - Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Zhang, Xinrong AU - Zhang X AUID- ORCID: 0000-0002-8393-8904 AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States. FAU - Henry, Linda AU - Henry L AUID- ORCID: 0000-0002-7833-6124 AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States. FAU - Cheung, Ka Shing AU - Cheung KS AUID- ORCID: 0000-0002-4838-378X AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China. AD - Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Yuen, Man-Fung AU - Yuen MF AUID- ORCID: 0000-0001-7985-7725 AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China. AD - State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China. FAU - Cheung, Ramsey AU - Cheung R AUID- ORCID: 0000-0002-0211-7013 AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States. AD - Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, United States. FAU - Seto, Wai-Kay AU - Seto WK AUID- ORCID: 0000-0002-9012-313X AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China. AD - Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. AD - State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China. FAU - Nguyen, Mindie H AU - Nguyen MH AUID- ORCID: 0000-0002-6275-4989 AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States. AD - Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, United States. AD - Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, CA, United States. LA - eng GR - UL1 TR003142/TR/NCATS NIH HHS/United States GR - UL1TR003142/National Center for Advancing Translational Science Clinical and Translational Science/ GR - NH/NIH HHS/United States PT - Journal Article PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - J Natl Cancer Inst. 2025 Oct 1;117(10):1966-1969. doi: 10.1093/jnci/djaf212. PMID: 40901707 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Middle Aged MH - *Obesity/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/epidemiology/etiology MH - Adult MH - Male MH - Aged MH - *Overweight/complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Cohort Studies MH - Incidence MH - Young Adult PMC - PMC12593220 COIS- M.H.N. received research grants via Stanford University from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Institute of Health, Glycotest and personal fees from consulting/advisory board from Exelixis, Gilead, GSK. M.F.Y. received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche, and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. W.K.S. received speaker's fees and is an advisory board member of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science; received speaker's fees and received research funding from AstraZeneca, and is an advisory board member, received speaker's fees and researching funding from Gilead Sciences. The other authors have nothing to disclose. EDAT- 2025/07/09 18:26 MHDA- 2025/10/09 00:30 PMCR- 2026/07/09 CRDT- 2025/07/09 12:03 PHST- 2025/03/18 00:00 [received] PHST- 2025/05/28 00:00 [revised] PHST- 2025/06/16 00:00 [accepted] PHST- 2025/10/09 00:30 [medline] PHST- 2025/07/09 18:26 [pubmed] PHST- 2025/07/09 12:03 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 8195732 [pii] AID - djaf163 [pii] AID - 10.1093/jnci/djaf163 [doi] PST - ppublish SO - J Natl Cancer Inst. 2025 Oct 1;117(10):2053-2061. doi: 10.1093/jnci/djaf163. PMID- 40631457 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20250719 IS - 2233-6087 (Electronic) IS - 2233-6079 (Print) IS - 2233-6079 (Linking) VI - 49 IP - 4 DP - 2025 Jul TI - Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning. PG - 525-541 LID - 10.4093/dmj.2025.0242 [doi] AB - Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated considerable efficacy in the treatment of diabetes and obesity, it is essential to recognize that their use is associated with certain intrinsic risks that must not be disregarded. The incidence of adverse effects, particularly gastrointestinal complications, psychiatric disorders, and ocular problems, highlights the critical need for thorough patient assessment and continuous monitoring to ensure both the safety and effectiveness of treatment. Despite the possibility of adverse events, GLP-1 RAs continue to represent a crucial therapeutic modality for metabolic disturbances. This highlights the significance of ongoing research initiatives aimed at optimizing their safe utilization and refining current treatment protocols to improve patient outcomes. This review summarizes updated research findings regarding the adverse effects of GLP-1 RAs, their mechanisms of action, and guidelines for clinical application. FAU - Kim, Jung A AU - Kim JA AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. FAU - Yoo, Hye Jin AU - Yoo HJ AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Review DEP - 20250701 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Gastrointestinal Diseases/chemically induced MH - Obesity/drug therapy PMC - PMC12270588 OTO - NOTNLM OT - Biliary tract diseases OT - Drug-related side effects and adverse reactions OT - Eye diseases OT - Gastrointestinal diseases OT - Glucagon-like peptide-1 receptor agonists OT - Mental disorders OT - Pancreatic diseases COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2025/07/09 12:28 MHDA- 2025/07/09 12:29 PMCR- 2025/07/01 CRDT- 2025/07/09 06:03 PHST- 2025/03/24 00:00 [received] PHST- 2025/05/30 00:00 [accepted] PHST- 2025/07/09 12:29 [medline] PHST- 2025/07/09 12:28 [pubmed] PHST- 2025/07/09 06:03 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - dmj.2025.0242 [pii] AID - dmj-2025-0242 [pii] AID - 10.4093/dmj.2025.0242 [doi] PST - ppublish SO - Diabetes Metab J. 2025 Jul;49(4):525-541. doi: 10.4093/dmj.2025.0242. Epub 2025 Jul 1. PMID- 40631351 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 19 DP - 2025 TI - Semaglutide Therapy and Accelerated Sarcopenia in Older Adults with Type 2 Diabetes: A 24-Month Retrospective Cohort Study. PG - 5645-5652 LID - 10.2147/DDDT.S531778 [doi] AB - PURPOSE: This study aimed to investigate changes in muscle mass and strength among older adults with type 2 diabetes who were treated with Semaglutide. METHODS: This was a retrospective cohort study comparing elderly patients with type 2 diabetes receiving Semaglutide to a matched control group. Changes in muscle mass and function over 24 months were assessed. Muscle mass was measured using the appendicular skeletal muscle mass index (ASMI), while muscle function was evaluated through grip strength and gait speed measurements. Differences between the two groups and changes before and after treatment were analyzed using the t-test. Additionally, multivariable linear regression models were constructed to identify clinical predictors of accelerated muscle loss during Semaglutide treatment. RESULTS: The study involved 220 patients treated with Semaglutide and 212 control subjects. The prevalence of sarcopenia among participants was 27.7%. Semaglutide treatment significantly reduced both body mass index and muscle mass compared to controls. Notably, divergent patterns emerged in functional measures. Grip strength initially improved but then declined in men, while it continued to decrease in women. Gait speed significantly reduced in both genders. Multivariable analysis identified Semaglutide dosage, baseline ASMI, and gait speed as independent predictors of muscle loss. CONCLUSION: The use of Semaglutide is associated with muscle loss and functional decline in older adults with type 2 diabetes, particularly at higher doses. This effect is especially significant in patients with sarcopenia. Consequently, it is crucial to assess the risks and benefits for each elderly patient individually and to implement appropriate monitoring and interventions. The potential for nutritional supplementation and targeted exercise regimens to counteract semaglutide-associated muscle decline merits systematic investigation. CI - (c) 2025 Ren et al. FAU - Ren, Qingjuan AU - Ren Q AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. FAU - Zhi, Lei AU - Zhi L AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. FAU - Liu, Hongfang AU - Liu H AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. LA - eng PT - Journal Article DEP - 20250703 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sarcopenia/chemically induced MH - Retrospective Studies MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Cohort Studies MH - Hand Strength MH - Aged, 80 and over MH - Muscle, Skeletal/drug effects MH - Middle Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12235021 OTO - NOTNLM OT - mass strength OT - muscle mass OT - older adults OT - sarcopenia OT - semaglutide OT - type 2 diabetes COIS- The authors declare that they have no competing interests in this work. EDAT- 2025/07/09 06:27 MHDA- 2025/07/09 06:28 PMCR- 2025/07/03 CRDT- 2025/07/09 05:11 PHST- 2025/04/01 00:00 [received] PHST- 2025/06/25 00:00 [accepted] PHST- 2025/07/09 06:28 [medline] PHST- 2025/07/09 06:27 [pubmed] PHST- 2025/07/09 05:11 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 531778 [pii] AID - 10.2147/DDDT.S531778 [doi] PST - epublish SO - Drug Des Devel Ther. 2025 Jul 3;19:5645-5652. doi: 10.2147/DDDT.S531778. eCollection 2025. PMID- 40629903 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - Glucagon-like peptide-1 receptor agonist treatment associated weight fluctuation and influencing factors in patients with overweight or obesity. PG - 5042-5051 LID - 10.1111/dom.16552 [doi] AB - OBJECTIVE: To characterize the weight fluctuation and explore its influencing factors after glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment in patients with overweight or obesity. METHODS: This retrospective cohort study enrolled 679 patients with overweight or obesity who initiated GLP-1RA treatment between November 2022 and October 2024. The weight measurements were collected during in-person clinic visits by uniform weighing scales and documented in the electronic medical record (EMR). The weight fluctuation curves were stratified into three phenotypes (Successful Weight Reduction, Remaining Stable and Weight Regain) and went through intergroup analyses. Subsequently, the association between potential influencing factors and weight fluctuations were estimated by univariate and multivariate logistic regression, where the weight fluctuation phenotypes were dichotomized into a binary variable, classified as "successful weight reduction" or "unsuccessful weight reduction". Subgroup analyses were performed in participants with obesity, prediabetes, liraglutide users and semaglutide users. RESULTS: Patients with a longer duration of GLP-1RA treatment (OR = 1.014, 95% CI, 1.008-1.019) and higher HOMA-beta (Homeostasis Model Assessment of beta-Cell Function) levels (OR = 4.912, 95% CI, 1.480 to 16.034) were more likely to achieve successful weight reduction at follow-up of 12 months. Non-diabetic status (OR = 2.176, 95% CI, 1.242-3.812) and using semaglutide (OR = 2.138, 95% CI, 1.162-3.935) were associated with successful weight reduction at the follow-up of 6 months. Additionally, a higher percentage body fat (PBF) in both male (OR = 3.990, 95% CI, 1.118-14.246) and female (OR = 2.266, 95% CI, 1.179-4.354) was associated with successful weight reduction. The weight regain group had a higher baseline eGFR than other two groups at the 3-month follow-up especially in participants with prediabetes (p = 0.009). Moreover, the J-shaped associations of basal metabolic rate, skeletal muscle mass, abdominal and limb muscle mass with the probability of successful weight reduction within 6 months, and a positive non-linear association of serum creatinine with the probability of successful weight reduction within 12 months have been characterized. CONCLUSION: A longer duration of GLP-1RA treatment, using semaglutide, non-diabetic status and higher PBF might be associated with better weight reduction. Basal metabolic rate, skeletal muscle mass, muscle mass of abdomen and limbs, and serum creatinine were non-linearly associated with the probability of successful weight reduction. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Wang, Jingxuan AU - Wang J AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lin, Chu AU - Lin C AUID- ORCID: 0000-0002-2365-9831 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Cai, Xiaoling AU - Cai X AUID- ORCID: 0000-0002-7881-0543 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Yiran AU - Wang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wei, Tingyang AU - Wei T AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Yuan AU - Wang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Tie, Changjie AU - Tie C AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Yuteng AU - Yang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lv, Fang AU - Lv F AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Wenjia AU - Yang W AUID- ORCID: 0000-0003-0610-5121 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. LA - eng GR - 2023ZD0508200/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ GR - 2023ZD0508205/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ PT - Journal Article DEP - 20250709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Adult MH - *Weight Loss/drug effects MH - Liraglutide/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Weight Gain/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonist OT - obesity OT - type 2 diabetes OT - weight fluctuation EDAT- 2025/07/09 06:26 MHDA- 2025/08/06 12:29 CRDT- 2025/07/09 04:03 PHST- 2025/06/06 00:00 [revised] PHST- 2025/02/28 00:00 [received] PHST- 2025/06/10 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/07/09 06:26 [pubmed] PHST- 2025/07/09 04:03 [entrez] AID - 10.1111/dom.16552 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):5042-5051. doi: 10.1111/dom.16552. Epub 2025 Jul 9. PMID- 40628673 OWN - NLM STAT- MEDLINE DCOM- 20250708 LR - 20260127 IS - 2053-3624 (Print) IS - 2053-3624 (Electronic) IS - 2053-3624 (Linking) VI - 12 IP - 2 DP - 2025 Jul 8 TI - Effectiveness of semaglutide on survival outcomes in patients with type 2 diabetes and chronic kidney disease. LID - 10.1136/openhrt-2025-003382 [doi] LID - e003382 AB - BACKGROUND: Type 2 diabetes (T2D) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular events, including death and heart failure (HF). The FLOW trial demonstrated that semaglutide reduces all-cause death, cardiovascular events and HF risk in patients with T2D and CKD. Since there is a difference in patient characteristics between clinical trials and real-world data, this study aims to investigate the association of semaglutide and all-cause death, acute HF or cardiovascular outcomes in patients with T2D and CKD using the data platform. METHODS: This multicentre retrospective observational study using TriNetX, a global healthcare data platform. We identified 1 151 750 patients aged >/=18 years with T2D and CKD diagnosed before 31 December 2020. Among these, 14 511 patients initiated semaglutide and 69 700 initiated sitagliptin between 1 January 2018 and 31 December 2020. After propensity score matching, 13 703 patients were included in each group. The primary outcome was the 3-year incidence of all-cause death. Secondary outcomes included acute HF, acute myocardial infarction and stroke. RESULTS: The 3-year risk of all-cause death in the semaglutide group relative to the sitagliptin group was significantly lower (7.2% (943/13 703) vs 9.5% (1196/13 703); p<0.001; HR, 0.76; 95% CI, 0.70 to 0.83). Similarly, the semaglutide group was less likely to have acute HF (12.1% vs 13.1%; HR, 0.92; 95% CI, 0.86 to 0.98). However, the risks of acute myocardial infarction and stroke in the semaglutide group relative to the sitagliptin group were not significant (9.6% vs 9.5%; HR, 1.01; 95% CI, 0.93 to 1.09 in acute myocardial infarction, and 9.2% vs 9.0%; HR, 1.02; 95% CI, 0.94 to 1.10 in stroke). CONCLUSIONS: In patients with T2D and CKD, semaglutide was associated with a lower 3-year risk of all-cause death compared with sitagliptin. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan tkato75@kuhp.kyoto-u.ac.jp. AD - Department of clinical trial facilitation, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250708 PL - England TA - Open Heart JT - Open heart JID - 101631219 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications/diagnosis MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - Retrospective Studies MH - *Renal Insufficiency, Chronic/mortality/drug therapy/complications/diagnosis MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Cause of Death/trends MH - Survival Rate/trends MH - Risk Factors MH - Follow-Up Studies MH - Risk Assessment MH - Incidence MH - Time Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12243591 OTO - NOTNLM OT - Diabetes Mellitus OT - Pharmacology, Clinical OT - RISK FACTORS COIS- Competing interests: None declared. EDAT- 2025/07/09 00:27 MHDA- 2025/07/09 00:28 PMCR- 2025/07/08 CRDT- 2025/07/08 22:53 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/09 00:28 [medline] PHST- 2025/07/09 00:27 [pubmed] PHST- 2025/07/08 22:53 [entrez] PHST- 2025/07/08 00:00 [pmc-release] AID - openhrt-2025-003382 [pii] AID - 10.1136/openhrt-2025-003382 [doi] PST - epublish SO - Open Heart. 2025 Jul 8;12(2):e003382. doi: 10.1136/openhrt-2025-003382. PMID- 40628316 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 378 DP - 2025 Oct 1 TI - Characterization of 0839 - A tool compound for pre-clinical mode-of-action studies of amylin analogues such as cagrilintide. PG - 123845 LID - S0024-3205(25)00480-1 [pii] LID - 10.1016/j.lfs.2025.123845 [doi] AB - Cagrilintide (also known as 0833) is an amylin and calcitonin receptor agonist in clinical development for weight management and type-2-diabetes in a fixed-dose combination with semaglutide. Here, we introduce 0174-0839 (0839) as a tool compound for mouse and rat in vivo and in vitro studies of amylin analogues such as cagrilintide. Structurally, 0839 shares 95 % sequence homology with 0833 and contains an identical acylation sidechain. Acute administration of 0839 and 0833 to normal weight rats' dose-dependently reduced food intake to a similar degree. Sub-chronically, 0839 and 0833 had comparable small and transient reducing effects on food intake and body weight in DIO mice, with similar additional add-on effects on top of semaglutide. In DIO rats, sub-chronic administration of 0833 and 0839 profoundly reduced food intake and body weight, and both potentiated semaglutide's effects on food intake and body weight to an equal extended. Both compounds mainly reduced body weight by fat mass reduction and equally improved metabolic parameters. Notably, 0839 is available through Novo Nordisk Compound Sharing, enabling advancement of mode-of-action studies in mice and rats whilst usage of cagrilintide and other amylin analogues in clinical development are restricted due to pharmacovigilance rules. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gabery, Sanaz AU - Gabery S AD - Medical & Science, Clinical Drug Development, Novo Nordisk A/S, Denmark. FAU - Glendorf, Tine AU - Glendorf T AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Ballarin-Gonzalez, Borja AU - Ballarin-Gonzalez B AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Pedersen, Kent AU - Pedersen K AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Kruse, Thomas AU - Kruse T AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Raun, Kirsten AU - Raun K AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Kuhre, Rune Ehrenreich AU - Kuhre RE AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. Electronic address: RUKU@novonordisk.com. LA - eng PT - Journal Article DEP - 20250706 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Rats MH - *Islet Amyloid Polypeptide/pharmacology/chemistry MH - Mice MH - Male MH - Eating/drug effects MH - Body Weight/drug effects MH - Mice, Inbred C57BL MH - Rats, Sprague-Dawley MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptides/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Amylin OT - Cagrilintide OT - Diet-induced obese mice and rats OT - Obesity-treatment OT - Tool compound COIS- Declaration of competing interest Rune Ehrenreich Kuhre reports a relationship with Novo Nordisk that includes: employment. All authors of this manuscript are employed by Novo Nordisk If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/09 00:27 MHDA- 2025/08/31 20:04 CRDT- 2025/07/08 19:22 PHST- 2025/03/12 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/07/04 00:00 [accepted] PHST- 2025/08/31 20:04 [medline] PHST- 2025/07/09 00:27 [pubmed] PHST- 2025/07/08 19:22 [entrez] AID - S0024-3205(25)00480-1 [pii] AID - 10.1016/j.lfs.2025.123845 [doi] PST - ppublish SO - Life Sci. 2025 Oct 1;378:123845. doi: 10.1016/j.lfs.2025.123845. Epub 2025 Jul 6. PMID- 40627548 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260925 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 9 DP - 2025 Sep 1 TI - Changes in beta-Cell Function and Insulin Sensitivity During Treatment With Dapagliflozin Alone or in Combination With Exenatide in Type 2 Diabetes. PG - 1545-1552 LID - 10.2337/dc25-0490 [doi] AB - OBJECTIVE: To examine the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) alone or with glucagon-like peptide 1 receptor agonists (GLP-1RAs) on beta-cell function (BCF) in type 2 diabetes. The hypothesis was that an SGLT2i combined with a GLP-1RA provides superior improvement in BCF than either agent alone. RESEARCH DESIGN AND METHODS: Ninety patients underwent a 180-min oral glucose tolerance test (OGTT) 1) after one drug dose (acute study) (placebo [n = 15], dapagliflozin [n = 25], exenatide [n = 25], and dapagliflozin/exenatide [n = 25]) and 2) after 1 and 4 months of therapy. Corrected Matsuda index (cMI) for urinary glucose loss, insulin secretion, and BCF indices were calculated during OGTT. RESULTS: In the acute study, mean +/- SEM cMI in dapagliflozin (2.29 +/- 0.33), exenatide (2.03 +/- 0.12), and dapagliflozin/exenatide (2.36 +/- 0.14) was higher (P < 0.05) than placebo (1.63 +/- 0.36). After 1 and 4 months, cMI remained similarly elevated in exenatide and increased further (P < 0.001) in dapagliflozin and dapagliflozin/exenatide. In the acute study, insulin secretion in dapagliflozin was similar to placebo but higher (P < 0.001 vs. both) in exenatide and dapagliflozin/exenatide. After 1 and 4 months in exenatide and in dapagliflozin/exenatide, insulin secretion remained higher (P < 0.01 vs. both) than dapagliflozin. BCF index in the acute study was 0.40 +/- 0.04 in placebo, 62% higher (P < 0.05) in dapagliflozin (0.65 +/- 0.10), threefold higher in exenatide (1.17 +/- 0.22), and fourfold higher in dapagliflozin/exenatide (1.69 +/- 0.12) (all P < 0.001 vs. placebo). At 1 and 4 months, BCF rose further in dapagliflozin and exenatide but did not increase further in dapagliflozin/exenatide. CONCLUSIONS: Dapagliflozin and exenatide monotherapy cause sustained improvements in BCF and insulin sensitivity. Combination therapy with dapagliflozin plus exenatide markedly augmented both BCF and insulin sensitivity above that with either agent alone. CI - (c) 2025 by the American Diabetes Association. FAU - Triplitt, Curtis AU - Triplitt C AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Cersosimo, Eugenio AU - Cersosimo E AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Alatrach, Mariam AU - Alatrach M AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Adams, John AU - Adams J AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Hansis-Diarte, Andrea AU - Hansis-Diarte A AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Baskoy, Gozde AU - Baskoy G AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Gastaldelli, Amalia AU - Gastaldelli A AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - Chavez-Velazquez, Alberto AU - Chavez-Velazquez A AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. FAU - DeFronzo, Ralph A AU - DeFronzo RA AUID- ORCID: 0000-0002-8581-6273 AD - Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX. AD - Texas Diabetes Institute, University Health System, San Antonio, TX. LA - eng GR - R01 DK107680/DK/NIDDK NIH HHS/United States GR - RO1-DK107680-05/NIH/NIDDK/ GR - AstraZeneca Pharmaceuticals/ PT - Clinical Trial, Phase IV PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 1ULL0QJ8UC (dapagliflozin) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/metabolism/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology/metabolism MH - Drug Therapy, Combination MH - *Exenatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glucose Tolerance Test MH - Insulin/metabolism MH - *Insulin Resistance/physiology MH - *Insulin-Secreting Cells/drug effects/physiology/metabolism MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Benzhydryl Compounds MH - Glucosides PMC - PMC12368385 COIS- Duality of Interest. R.A.D. is a member of the advisory boards of AstraZeneca, and Novo Nordisk; is a member of the speakers bureau of Novo Nordisk, CORCEPT, and AstraZeneca; and has grant support from AstraZeneca and Boehringer-Ingelheim. E.C. has grant support from AstraZeneca. A.G. has received an honorarium from Novo Nordisk and is consultant for Boehringer Ingelheim, Eli Lilly, Gilead, Inventive, and Pfizer. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/07/08 18:26 MHDA- 2025/08/31 20:03 PMCR- 2026/09/01 CRDT- 2025/07/08 13:03 PHST- 2025/02/27 00:00 [received] PHST- 2025/06/02 00:00 [accepted] PHST- 2025/08/31 20:03 [medline] PHST- 2025/07/08 18:26 [pubmed] PHST- 2025/07/08 13:03 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - 162908 [pii] AID - 250490 [pii] AID - 10.2337/dc25-0490 [doi] PST - ppublish SO - Diabetes Care. 2025 Sep 1;48(9):1545-1552. doi: 10.2337/dc25-0490. PMID- 40620210 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Association of semaglutide with less limb events in people with type 2 diabetes and peripheral artery disease or foot ulcers: An observational study comparing matched cohorts. PG - 5506-5513 LID - 10.1111/dom.16594 [doi] AB - AIMS: To compare major limb events in individuals with type 2 diabetes who initiated either injective or oral semaglutide versus other glucose-lowering therapies (GLT) in a real-world setting. MATERIALS AND METHODS: This was a single-centre retrospective observational study on new users of diabetes medications. Participants had to have type 2 diabetes and a diagnosis of peripheral artery disease (PAD) or foot ulcers. Participant characteristics were assessed before and after propensity score matching. The primary outcome was major limb events (a composite of peripheral percutaneous transluminal angioplasty [PTA] or critical limb ischaemia [CLI]); secondary outcomes included singularly PTA, CLI, gangrene and lower extremity amputation (LEA). RESULTS: We analysed two matched groups of 167 participants each, who were predominantly males (57%), aged 61 years, with a 12-year duration of diabetes, a baseline HbA1c of 8.0% and body mass index (BMI) of 31 kg/m(2). During a median follow-up of 30.1 months, a primary-outcome event occurred in 72 of the participants (43.0%; incidence, 8.1 events per 100 person-years) in the semaglutide group, as compared with 93 of the participants (56.0%; incidence, 10.4 events per 100 person-years) in the GLT group (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.029). Among the secondary outcomes, LEA (both major and minor) was 50% lower (HR = 0.50; 95% CI, 0.30-0.83, p = 0.008) in the semaglutide group as compared with the other group. CONCLUSIONS: Among people with type 2 diabetes and PAD or foot ulcers, the use of semaglutide was associated with a significantly lower risk of major limb events than other GLTs. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Caruso, Paola AU - Caruso P AUID- ORCID: 0000-0002-4756-2022 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Angelino, Silvia AU - Angelino S AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Matrone, Rita AU - Matrone R AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AUID- ORCID: 0000-0003-2972-9551 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Longo, Miriam AU - Longo M AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy. FAU - Volatile, Alessandra AU - Volatile A AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Petrizzo, Michela AU - Petrizzo M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Pontillo, Alessandro AU - Pontillo A AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Caputo, Mariangela AU - Caputo M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Carbone, Carla AU - Carbone C AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Gicchino, Maurizio AU - Gicchino M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AUID- ORCID: 0000-0002-4748-321X AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250707 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Retrospective Studies MH - *Peripheral Arterial Disease/complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetic Foot/prevention & control/epidemiology/complications MH - Aged MH - Amputation, Surgical/statistics & numerical data MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - critical limb ischaemia OT - gangrene OT - lower limb amputations OT - peripheral artery disease OT - peripheral percutaneous transluminal angioplasty OT - real-world OT - semaglutide OT - type 2 diabetes EDAT- 2025/07/07 06:26 MHDA- 2025/09/04 06:37 CRDT- 2025/07/07 04:54 PHST- 2025/06/19 00:00 [revised] PHST- 2025/05/10 00:00 [received] PHST- 2025/06/25 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/07 06:26 [pubmed] PHST- 2025/07/07 04:54 [entrez] AID - 10.1111/dom.16594 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5506-5513. doi: 10.1111/dom.16594. Epub 2025 Jul 7. PMID- 40619508 OWN - NLM STAT- MEDLINE DCOM- 20250706 LR - 20260127 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Jul 6 TI - Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis. PG - 24103 LID - 10.1038/s41598-025-09807-0 [doi] LID - 24103 AB - To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with type 2 diabetes (T2DM). Electronic databases were searched from inception to 2nd October 2024 for randomised controlled trials comparing GLP-1RAs treating T2DM. Bayesian network meta-analyses were conducted to analyze metabolic and safety outcomes. 64 trials comprising of 25,572 participants were identified. Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05). All treatments showed no statistically significant differences in BMI, SBP, DBP, TC, HDL-C and LDL-C compared to placebo. Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo. GLP-1 RAs had higher risk of gastrointestinal symptoms. Semaglutide increased the risk of hypoglycemia compared to placebo while liraglutide reduced the risk of hypoglycemia compared to traditional antidiabetic drugs. GLP-1RAs improve glycaemic control, with tirzepatide, semaglutide and liraglutide exhibiting the most significant improvements. Tirzepatide is more suitable for treating T2DM with obesity. For individuals with normal weight, both semaglutide and liraglutide are generally more effective for treating T2DM. However, considering the potential for semaglutide to cause hypoglycemia, liraglutide may be the optimal choice for T2DM treatment to minimize the risk of hypoglycemia. CI - (c) 2025. The Author(s). FAU - Ren, Xiaoyu AU - Ren X AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. FAU - Hua, Honghao AU - Hua H AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Wu, Yuanqin AU - Wu Y AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Zhang, Wei AU - Zhang W AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. FAU - Long, Xianzhen AU - Long X AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Bai, Yana AU - Bai Y AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Cheng, Ning AU - Cheng N AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. 1184231755@qq.com. LA - eng GR - (NO. 81673248/National Natural Science Foundation of China/ GR - (NO. 81673248/National Natural Science Foundation of China/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250706 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Tirzepatide/therapeutic use/adverse effects MH - Treatment Outcome MH - Semaglutide PMC - PMC12230154 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Network meta-analysis OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/07/07 00:26 MHDA- 2025/07/07 00:27 PMCR- 2025/07/06 CRDT- 2025/07/06 23:28 PHST- 2025/01/18 00:00 [received] PHST- 2025/06/30 00:00 [accepted] PHST- 2025/07/07 00:27 [medline] PHST- 2025/07/07 00:26 [pubmed] PHST- 2025/07/06 23:28 [entrez] PHST- 2025/07/06 00:00 [pmc-release] AID - 10.1038/s41598-025-09807-0 [pii] AID - 9807 [pii] AID - 10.1038/s41598-025-09807-0 [doi] PST - epublish SO - Sci Rep. 2025 Jul 6;15(1):24103. doi: 10.1038/s41598-025-09807-0. PMID- 40617160 OWN - NLM STAT- MEDLINE DCOM- 20250727 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 51 DP - 2025 Aug TI - Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study. PG - 252-265 LID - S0261-5614(25)00165-7 [pii] LID - 10.1016/j.clnu.2025.06.011 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are crucial in managing type 2 diabetes mellitus (T2DM) and obesity. Agents like dulaglutide, semaglutide, and liraglutide mimic endogenous GLP-1, enhancing insulin secretion and promoting satiety. Beyond glycemic control, they offer cardioprotective and neuroprotective benefits. However, concerns about psychiatric adverse effects have emerged, necessitating a systematic assessment of their safety profile. MATERIAL & METHODS: This multinational pharmacovigilance study utilized VigiBase(R) data up to December 1, 2024, focusing on adverse drug reaction (ADR) reports for GLP-1 RAs. Psychiatric ADRs were classified using MedDRA terminology. Disproportionality analyses were conducted via logistic regression to calculate reporting adjusted Reporting Odds Ratios (aRORs) within reports involving antidiabetic or anti-obesity medications. A causal forest model assessed the individual treatment effect (ITE) of semaglutide on depression and suicidality reporting. RESULTS: Among 2,061,901 reports, 21,414 involved psychiatric ADRs for GLP-1 RAs. Significant signals were observed for anxiety (aROR: 1.26, 95%CI: 1.18-1.35), depressed mood disorders (aROR: 1.70, 95%CI: 1.57-1.84) and suicidality (aROR 1.45, 95%CI: 1.29-1.63) with semaglutide, and eating disorders with all three GLP-1 RAs (aRORs between 4.17 and 6.80). The causal forest model estimated an average treatment effect of 0.0046 for semaglutide on depression and suicidality reporting, with significant heterogeneity across regions and demographic groups. DISCUSSION: The study found no significant increase in overall psychiatric ADR reporting for GLP-1 RAs, except for eating disorders and depression/suicidality in semaglutide-treated patients. Sensitivity analyses before June 4, 2021, found no signals, aligning with RCT data. Post-marketing reports linked semaglutide to depression and suicidal ideation, prompting regulatory investigations. The causal forest model revealed significant heterogeneity in the psychiatric safety profile of semaglutide, with regional factors influencing ADR reporting. CONCLUSION: While GLP-1 RAs do not show a significant increase in overall psychiatric ADR reporting, findings suggest that clinicians should remain vigilant for potential depressive symptoms and suicidality, particularly in individuals with obesity treated with semaglutide since its approval for weight management. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Nishida, Kazuki AU - Nishida K AD - Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan. FAU - Chretien, Basile AU - Chretien B AD - Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; Neuropresage Team, Normandie University, UNICAEN, INSERM, UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen-Normandie (BB@C), GIP Cyceron, 14000, Caen, France. Electronic address: chretien.basile.jean.bernard.u4@s.mail.nagoya-u.ac.jp. FAU - Dolladille, Charles AU - Dolladille C AD - Department of Pharmacology, Caen Normandie University Hospital, Caen, France. FAU - Ebina, Takumi AU - Ebina T AD - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Aleksic, Branko AU - Aleksic B AD - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Cabe, Nicolas AU - Cabe N AD - Neuropresage Team, Normandie University, UNICAEN, INSERM, UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen-Normandie (BB@C), GIP Cyceron, 14000, Caen, France; Department of Addictology, Caen Normandie University Hospital, Caen, France. FAU - Savey, Veronique AU - Savey V AD - Department of Nutrition, Caen Normandie University Hospital, Caen, France. FAU - Onoue, Takeshi AU - Onoue T AD - Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Yatsuya, Hiroshi AU - Yatsuya H AD - Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan. LA - eng PT - Journal Article DEP - 20250623 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Liraglutide/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Recombinant Fusion Proteins/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Pharmacovigilance MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Mental Disorders/chemically induced MH - Adverse Drug Reaction Reporting Systems MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse effects OT - GLP-1 receptor agonists OT - Pharmacovigilance OT - Psychiatry OT - Psychology COIS- Conflict of interest All authors declare no conflicts of interest. EDAT- 2025/07/06 06:18 MHDA- 2025/07/28 08:45 CRDT- 2025/07/05 18:09 PHST- 2025/04/22 00:00 [received] PHST- 2025/06/05 00:00 [revised] PHST- 2025/06/15 00:00 [accepted] PHST- 2025/07/28 08:45 [medline] PHST- 2025/07/06 06:18 [pubmed] PHST- 2025/07/05 18:09 [entrez] AID - S0261-5614(25)00165-7 [pii] AID - 10.1016/j.clnu.2025.06.011 [doi] PST - ppublish SO - Clin Nutr. 2025 Aug;51:252-265. doi: 10.1016/j.clnu.2025.06.011. Epub 2025 Jun 23. PMID- 40615102 OWN - NLM STAT- MEDLINE DCOM- 20250805 LR - 20250805 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 1003 DP - 2025 Sep 15 TI - The effects of GLP-1 receptor agonists on body composition in patients with type 2 diabetes, overweight or obesity: A meta-analysis of randomized controlled trials. PG - 177885 LID - S0014-2999(25)00639-9 [pii] LID - 10.1016/j.ejphar.2025.177885 [doi] AB - AIM: The objective is to evaluate the impacts of glucagon-like peptide 1 receptor agonists on body composition among patients with type 2 diabetes, overweight or obesity. METHODS: We conducted an extensive search in the PubMed, Embase, and Cochrane Library databases, scanning the literature related to GLP-1RAs from the establishment of the databases to October 15, 2024, without language restrictions. Ignoring heterogeneity, a random effects model is adopted. I(2) is utilized to assess the heterogeneity among studies. The weighted mean difference and 95 % confidence interval are employed to evaluate the differences in outcomes. The Cochrane risk of bias assessment tool is applied to evaluate the quality of randomized controlled trials. Statistical analysis is conducted using Review Manager version 5.4. RESULTS: 36 randomized controlled trials were included, involving 2555 participants. The study demonstrated that GLP-1RAs conspicuously decreased fat-related outcomes, encompassing fat mass, body fat percentage, visceral fat area and subcutaneous fat area. When placebo was adopted as a control, GLP-1RAs decreased the lean mass. No significant discrepancies were detected when oral antidiabetic drugs, insulin, and lifestyle interventions were employed as controls. There was no disparity in the effect of GLP-1RAs on the lean mass percentage. CONCLUSION: This study indicates that the treatment of GLP-1RAs can decrease fat mass. Lean mass loss was observed in the majority of studies, and the effect is more prominent in overweight and obese patients as well as in those with long-term treatment. However, there was no disparity in the effect of GLP-1RAs on the lean mass percentage. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Lu, Jieying AU - Lu J AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Zou, Shen AU - Zou S AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Liu, Xinyi AU - Liu X AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Wong, Ting Yat Patrick AU - Wong TYP AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Zhang, Xiaomin AU - Zhang X AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Xu, Ka Shing AU - Xu KS AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. FAU - Zhao, Yanchen AU - Zhao Y AD - Guangdong Experimental High School, Guangzhou, Guangdong, China. FAU - Hong, Yuanjia AU - Hong Y AD - Department of Endocrinology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. FAU - Cen, Aiying AU - Cen A AD - Department of Endocrinology, the People's Hospital of Jiangmen, Jiangmen, Guangdong, China. FAU - Wang, Yingxue AU - Wang Y AD - Department of Endocrinology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. Electronic address: smeea@126.com. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250703 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy/physiopathology MH - *Overweight/drug therapy MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Body composition OT - Glucagon-like peptide-1 receptor agonists OT - Overweight/obesity OT - Type 2 diabetes mellitus COIS- Declaration of competing interest We have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/05 00:28 MHDA- 2025/08/05 06:28 CRDT- 2025/07/04 19:44 PHST- 2025/01/30 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2025/08/05 06:28 [medline] PHST- 2025/07/05 00:28 [pubmed] PHST- 2025/07/04 19:44 [entrez] AID - S0014-2999(25)00639-9 [pii] AID - 10.1016/j.ejphar.2025.177885 [doi] PST - ppublish SO - Eur J Pharmacol. 2025 Sep 15;1003:177885. doi: 10.1016/j.ejphar.2025.177885. Epub 2025 Jul 3. PMID- 40614622 OWN - NLM STAT- MEDLINE DCOM- 20250908 LR - 20260710 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 10 DP - 2025 Oct TI - Association of tirzepatide with erectile dysfunction in people with type 2 diabetes. PG - 109116 LID - S1056-8727(25)00169-2 [pii] LID - 10.1016/j.jdiacomp.2025.109116 [doi] AB - AIMS: To evaluate the association between tirzepatide and the risk of developing erectile dysfunction (ED) in men with type 2 diabetes (T2D), compared with sitagliptin, injectable semaglutide, and dulaglutide. METHODS: This retrospective cohort study used the TriNetX global health research network from May 13, 2022 to May 17, 2025. Male patients aged 18-70 with T2D and no prior ED were included. Three 1:1 propensity score-matched comparisons were conducted: tirzepatide vs. sitagliptin, injectable semaglutide, or dulaglutide. The outcome was a diagnosis of ED or prescription of a PDE-5 inhibitor. RESULTS: Tirzepatide was associated with a significantly reduced risk of ED across all comparisons. Risk ratios (RR) for the composite outcome of ED diagnosis or PDE-5 inhibitor use were: tirzepatide vs. sitagliptin: RR, 0.70 (95 % CI: 0.64,0.76); tirzepatide vs. injectable semaglutide: RR, 0.67 (95 % CI: 0.62,0.72); tirzepatide vs. dulaglutide: RR, 0.55 (95 % CI: 0.51,0.59). All comparisons were statistically significant (p < 0.001). CONCLUSIONS: Tirzepatide was associated with a lower risk of ED in men with T2D compared to sitagliptin, injectable semaglutide, and dulaglutide. Randomized trials are needed to confirm these findings and explore potential mechanisms. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Cowart, Kevin AU - Cowart K AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; Morsani College of Medicine, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; College of Public Health, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Electronic address: kcowart2@usf.edu. FAU - Murphy, Christopher AU - Murphy C AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA. FAU - Carris, Nicholas AU - Carris N AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; Morsani College of Medicine, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA. LA - eng PT - Journal Article DEP - 20250630 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Erectile Dysfunction/epidemiology/prevention & control/etiology MH - Retrospective Studies MH - Adult MH - Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Sitagliptin Phosphate/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Young Adult MH - Adolescent MH - Immunoglobulin Fc Fragments/therapeutic use MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Dulaglutide OT - Erectile dysfunction OT - Mens health OT - PDE-5 inhibitor OT - Semaglutide OT - Sitagliptin OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest KC has received research funding from Sanofi Winthrop Industrie and Abbott Diabetes Care. NC has received research funding from Sanofi Winthrop Industrie. CM declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/07/05 00:28 MHDA- 2025/09/09 00:33 CRDT- 2025/07/04 18:11 PHST- 2025/05/30 00:00 [received] PHST- 2025/06/25 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2025/09/09 00:33 [medline] PHST- 2025/07/05 00:28 [pubmed] PHST- 2025/07/04 18:11 [entrez] AID - S1056-8727(25)00169-2 [pii] AID - 10.1016/j.jdiacomp.2025.109116 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Oct;39(10):109116. doi: 10.1016/j.jdiacomp.2025.109116. Epub 2025 Jun 30. PMID- 40610294 OWN - NLM STAT- MEDLINE DCOM- 20250727 LR - 20260127 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 35 IP - 9 DP - 2025 Sep TI - Therapeutic tailored approach in patients with diabetes, cardiovascular and renal comorbidities: A cardiologist's view. PG - 104033 LID - S0939-4753(25)00187-5 [pii] LID - 10.1016/j.numecd.2025.104033 [doi] AB - AIMS: The aim of this narrative review is to explore the management of hypoglycemic drugs in patients with type 2 diabetes mellitus (T2DM) and cardiovascular (CV) or renal disease using the most recent strategies. DATA SYNTHESIS: Cardiovascular diseases (CVD) are the principal source of sickness and mortality in patients with T2DM. The importance of CVD risk factors among individuals with diabetes has been the object of recent investigation and several recommendations have been updated thanks to studies focused on CV outcomes. These trials showed CV and renal protection in recently introduced drug classes, like SGLT-2 (sodium-glucose cotransporter-2) inhibitors and GLP-1 RAs (glucagon-like peptide-1 receptor agonists). CONCLUSIONS: Lowering the likelihood of CV accidents becomes a crucial objective in addition to glucose management. A multimodal management is the priority to counteract micro- and macrovascular complications of T2DM and reduce associated morbidity and mortality in addiction to the control of the other CV risk factors. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Nardi, Ermanno AU - Nardi E AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Prastaro, Maria AU - Prastaro M AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Santoro, Ciro AU - Santoro C AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. Electronic address: ciro.santoro@unina.it. FAU - Gallo, Luca AU - Gallo L AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Simeoli, Luisa AU - Simeoli L AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Fontanarosa, Sara AU - Fontanarosa S AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Paolillo, Stefania AU - Paolillo S AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Gargiulo, Paola AU - Gargiulo P AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Esposito, Giovanni AU - Esposito G AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Filardi, Pasquale Perrone AU - Filardi PP AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250401 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/epidemiology/blood MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology/mortality MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - *Blood Glucose/metabolism/drug effects MH - Risk Assessment MH - *Cardiologists MH - Comorbidity MH - Heart Disease Risk Factors MH - *Diabetic Nephropathies/diagnosis/epidemiology/prevention & control/mortality MH - *Incretins/therapeutic use/adverse effects MH - Biomarkers/blood MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Clinical Decision-Making MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Cardiovascular disease OT - Chronic kidney disease OT - Diabetes OT - Heart failure COIS- Declaration of conflict interests The authors declare that they have no conflict of interest. EDAT- 2025/07/04 00:27 MHDA- 2025/07/28 08:45 CRDT- 2025/07/03 21:52 PHST- 2024/10/30 00:00 [received] PHST- 2025/03/23 00:00 [revised] PHST- 2025/03/29 00:00 [accepted] PHST- 2025/07/28 08:45 [medline] PHST- 2025/07/04 00:27 [pubmed] PHST- 2025/07/03 21:52 [entrez] AID - S0939-4753(25)00187-5 [pii] AID - 10.1016/j.numecd.2025.104033 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2025 Sep;35(9):104033. doi: 10.1016/j.numecd.2025.104033. Epub 2025 Apr 1. PMID- 40609682 OWN - NLM STAT- MEDLINE DCOM- 20250925 LR - 20261014 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 65 IP - 5 DP - 2025 Sep-Oct TI - New onset diabetic retinopathy with glucagon-like peptide-1 receptor agonists: A case report. PG - 102475 LID - S1544-3191(25)00154-2 [pii] LID - 10.1016/j.japh.2025.102475 [doi] AB - BACKGROUND: Diabetic retinopathy (DR) is a leading cause of acquired vision loss in middle-aged adults. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used in the management of type 2 diabetes (T2D). Emerging evidence has suggested a possible link between GLP-1 RAs and the acceleration of DR. However, the evidence on the association between GLP-1RA therapies and risk for DR has been mixed, and there is limited guidance on how to manage new onset or worsening DR for patients taking GLP-1RA therapy. The objective of this case report is to describe the clinical decision-making involved in the management of a patient with T2D who developed new-onset and worsening retinopathy following the initiation of several GLP-1RA therapies. CASE SUMMARY: A 43-year-old female with T2D and class II obesity was diagnosed with mild nonproliferative DR after taking various GLP1-RA therapy (ie, exenatide ER and dulaglutide) and maintaining glycemic control for 19 months. The patient was later transitioned to subcutaneous semaglutide for additional weight loss, and diabetic macular edema was detected in the right eye 2 months after. Due to a potentially lower risk of DR complications, treatment was promptly switched to oral semaglutide. The patient's eye exam revealed that her DR improved and diabetic macular edema had significantly resolved 8 months after switching therapy. PRACTICE IMPLICATIONS: This case highlights a progressive decline in retinal health despite well-controlled T2D and the possible contribution of GLP-1RA therapy to DR progression. Switching to GLP-1RA agents with potentially lower risk for DR, such as oral semaglutide, may be beneficial when patients develop DR on GLP1-RA therapy. Further studies that evaluate the risk of DR while using GLP-1RA therapy, as well as the risk across the GLP1-RA class, are needed. Additional guidance on managing possible new onset or worsening DR on GLP-1RA therapy is especially necessary. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ko, Jennifer AU - Ko J FAU - Jahromi, Yaseman AU - Jahromi Y LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250702 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/chemically induced/diagnosis MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Adult MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use/administration & dosage MH - Exenatide/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosure The authors declare no relevant conflicts of interest or financial relationships. EDAT- 2025/07/04 00:27 MHDA- 2025/09/26 00:30 CRDT- 2025/07/03 19:12 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2025/09/26 00:30 [medline] PHST- 2025/07/04 00:27 [pubmed] PHST- 2025/07/03 19:12 [entrez] AID - S1544-3191(25)00154-2 [pii] AID - 10.1016/j.japh.2025.102475 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2025 Sep-Oct;65(5):102475. doi: 10.1016/j.japh.2025.102475. Epub 2025 Jul 2. PMID- 40608828 OWN - NLM STAT- MEDLINE DCOM- 20250703 LR - 20260127 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 20 IP - 7 DP - 2025 TI - Semaglutide ameliorates diabetes-associated cognitive dysfunction in mouse model of type 2 diabetes. PG - e0326897 LID - 10.1371/journal.pone.0326897 [doi] LID - e0326897 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction, which significantly impacts the quality of life. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown potential neuroprotective effects. This study investigates the efficacy of semaglutide in ameliorating cognitive dysfunction in a mouse model of T2DM. METHODS: Male C57BL/6J mice were fed a high-fat diet for four weeks and received a single intraperitoneal injection of streptozotocin (150 mg/kg) to induce T2DM. All mice were divided into four groups: control, diabetes control (T2DM), semaglutide treatment (semaglutide, 0.1 mg/kg) and dapagliflozin treatment (dapagliflozin 1 mg/kg). Cognitive function was assessed using the Morris water maze (MWM) test. Histomorphological analysis of hippocampal tissues was performed using H&E and Nissl staining. Immunofluorescence was used to assess LRP1 expression and apoptosis. Biochemical analyses measured oxidative stress markers (SOD, MDA) and inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, CRP). RESULTS: Semaglutide treatment significantly reduced blood glucose levels in diabetic mice. In the MWM test, semaglutide-treated mice showed reduced escape latencies, indicating improved spatial learning and memory. Histomorphological analysis revealed preserved neuronal structure in the hippocampus with reduced neuronal damage and apoptosis in the semaglutide-treated group. Immunofluorescence showed increased LRP1 expression and decreased apoptosis. Biochemical analyses indicated that semaglutide reduced oxidative stress and inflammatory markers, further supporting its neuroprotective effects. CONCLUSIONS: Semaglutide effectively ameliorates cognitive dysfunction in T2DM mice, likely through mechanisms involving the reduction of oxidative stress, inflammation, and neuronal apoptosis. These findings suggest that semaglutide has potential as a therapeutic agent for managing diabetes-associated cognitive decline. Further research, including long-term studies and clinical trials, is necessary to validate these findings and explore the broader applicability of semaglutide in treating cognitive impairments in diabetic patients. CI - Copyright: (c) 2025 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Zhu, Yan AU - Zhu Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - He, Yi AU - He Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Yang, Hongyan AU - Yang H AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Gao, Yanbo AU - Gao Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Wang, Yan AU - Wang Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Liu, Peiqing AU - Liu P AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Zhang, Mengjuan AU - Zhang M AUID- ORCID: 0009-0007-7370-8113 AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. LA - eng PT - Journal Article DEP - 20250703 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Benzhydryl Compounds) RN - 0 (Neuroprotective Agents) RN - 0 (Blood Glucose) RN - 0 (Glucosides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Male MH - Mice MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Cognitive Dysfunction/drug therapy/etiology MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Experimental/complications/drug therapy MH - Oxidative Stress/drug effects MH - Disease Models, Animal MH - Hippocampus/drug effects/metabolism/pathology MH - Apoptosis/drug effects MH - Diet, High-Fat/adverse effects MH - Benzhydryl Compounds/pharmacology MH - Neuroprotective Agents/pharmacology MH - Blood Glucose MH - Glucosides/pharmacology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12225814 COIS- The authors have declared that no competing interests exist. EDAT- 2025/07/03 18:26 MHDA- 2025/07/03 18:27 PMCR- 2025/07/03 CRDT- 2025/07/03 13:53 PHST- 2024/11/03 00:00 [received] PHST- 2025/06/05 00:00 [accepted] PHST- 2025/07/03 18:27 [medline] PHST- 2025/07/03 18:26 [pubmed] PHST- 2025/07/03 13:53 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - PONE-D-24-42194 [pii] AID - 10.1371/journal.pone.0326897 [doi] PST - epublish SO - PLoS One. 2025 Jul 3;20(7):e0326897. doi: 10.1371/journal.pone.0326897. eCollection 2025. PMID- 40608494 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260917 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 40 IP - 11 DP - 2025 Oct 30 TI - Rationale, design and baseline characteristics of REMODEL, a mechanism-of-action trial with semaglutide in people with type 2 diabetes and chronic kidney disease. PG - 2182-2192 LID - 10.1093/ndt/gfaf114 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and kidney failure globally. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces the risk of major kidney, cardiovascular and mortality outcomes in people with T2D and CKD, but the mechanism of action remains unclear. METHODS: The REMODEL trial (NCT04865770) is a 52-week placebo-controlled, double-blind, parallel-group, randomized trial in adults with T2D and CKD. Inclusion criteria include haemoglobin A1c (HbA1c) /=30-/=20-<5000 mg/g. The co-primary outcomes were magnetic resonance imaging (MRI) based, including change in kidney oxygenation, perfusion and inflammation. Secondary outcomes include change from baseline in creatine clearance rate, urinary sodium excretion, albumin excretion rate and kidney fibrosis and blood flow parameters measured by MRI. A subgroup had kidney biopsies at baseline and at the end of the treatment for tissue-based interrogation, including single nucleus and spatial transcriptomics, pathology and advanced histological assessment. RESULTS: Across eight countries, 106 participants (n = 33, biopsy subgroup) were enrolled. The mean age was 65.3 years [standard deviation (SD) 9.9] at baseline with HbA1c of 7.1% (SD 0.9), creatinine-based eGFR of 51.1 ml/min/1.73 m2 (SD 10.4) and median UACR of 187.3 mg/g (interquartile range 60.5-546.4). Renin-angiotensin system inhibitor use was 98.1% and sodium-glucose co-transporter 2 inhibitor use was 38.7%. In the kidney biopsy subgroup, baseline characteristics were like those of the full population. Histological analysis of kidney tissues revealed 17 participants with primarily diabetic nephropathy, 6 participants with primarily vascular features, 9 with mixed diabetic nephropathy and vascular characteristics and 1 with membranous nephropathy. CONCLUSION: The REMODEL trial leverages multipronged approaches to investigate the kidney-specific effects and underlying mechanisms of semaglutide in a representative population of people with T2D and CKD, which supports the generalizability and clinical relevance of the findings. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bjornstad, Petter AU - Bjornstad P AD - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, and Division of Endocrinology, Department of Pediatrics, University of Washington, Seattle, WA, USA. AD - Division of Renal Diseases and Hypertension, Department of Medicine, Section of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Chacko, Milenta M AU - Chacko MM AD - Novo Nordisk GBS India, Bangalore, India. FAU - Gunnarsson, Thomas P AU - Gunnarsson TP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hodgin, Jeffrey B AU - Hodgin JB AD - Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, MI, USA. FAU - Kretzler, Matthias AU - Kretzler M AD - Department of Internal Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service of Nephrology, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. FAU - Schytz, Philip A AU - Schytz PA AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane WA, USA. AD - Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle, WA, USA. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - Novo Nordisk/ PT - Clinical Trial Protocol PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Follow-Up Studies MH - Glomerular Filtration Rate MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Prognosis MH - *Renal Insufficiency, Chronic/drug therapy/etiology/pathology MH - Clinical Trials, Phase III as Topic MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12559791 OTO - NOTNLM OT - functional magnetic resonance imaging OT - gene expression OT - incretin therapy OT - kidney OT - nutrient-stimulated hormone (NuSH) therapy COIS- D.Z.I.C. has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, AbbVie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK and Novo Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. N.B., T.P.G. and P.A.S. are employees and stockholders of Novo Nordisk A/S. P.B. is a consultant and advisory board or steering committee member for Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Horizon Pharma/Amgen; DMC chair for Bayer; and received research funding from Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Horizon Pharma/Amgen and Merck. MMC: Employee and Stockholder of Novo Nordisk A/S. J.B.H. is a consultant for Sygnamap. M.K. is a consultant or receives funding all via the University of Michigan from Boehringer Ingelheim, Certa, Travere, Maze Therapeutics, Roche, AstraZeneca, Novo Nordisk, Moderna, Chinook, Angion Pharmaceuticals, RenalytixAI, Lilly, Gilead, Sanofi, Regeneron, Janssen, Vera Therapeutics and Dimerix. M.P. has served on advisory boards for GSK, Boehringer Ingelheim, Baxter, Novo Nordisk and Bayer; was a speaker for AstraZeneca, Astellas, Vifor, Baxter and Braun and received investigator-initiated grant support from Nephrospec. K.T. has received investigator-initiated grant support from Travere and Bayer to Providence Inland Northwest Health outside of the submitted work and consultancy fees from AstraZeneca, Boehringer Ingelheim, Bayer, Lilly, Novo Nordisk, Travere and Pfizer. EDAT- 2025/07/03 18:27 MHDA- 2025/10/30 00:26 PMCR- 2025/07/03 CRDT- 2025/07/03 12:33 PHST- 2024/12/20 00:00 [received] PHST- 2025/10/30 00:26 [medline] PHST- 2025/07/03 18:27 [pubmed] PHST- 2025/07/03 12:33 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 8185402 [pii] AID - gfaf114 [pii] AID - 10.1093/ndt/gfaf114 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2025 Oct 30;40(11):2182-2192. doi: 10.1093/ndt/gfaf114. PMID- 40605133 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20260311 IS - 1728-7731 (Electronic) IS - 1726-4901 (Print) IS - 1726-4901 (Linking) VI - 88 IP - 8 DP - 2025 Aug 1 TI - Incretin-based therapy: An update focusing on the major revolution in cardiovascular-kidney-metabolic health. PG - 585-593 LID - 10.1097/JCMA.0000000000001263 [doi] AB - Type 2 diabetes mellitus and obesity have become the rising burden across various geographic and economic regions, and they are also the common causes of chronic kidney disease, which further contributes to the development and progression of cardiovascular disease. The recently proposed cardiovascular-kidney-metabolic syndrome-the new paradigm of recognizing excess or dysfunctional adipose tissue as the shared pathophysiology-has signaled the interconnection of type 2 diabetes mellitus, obesity, chronic kidney disease, and cardiovascular disease beyond the disturbance of glucose homeostasis, for which recently developed incretin-based therapy has offered an avenue of holistic management. Glucagon-like peptide-1 (GLP1) is one of the incretins and potentiates insulin secretion after food intake, additionally offering extra-pancreatic metabolic effects-reduced hepatic gluconeogenesis and steatosis, increased muscular glucose uptake, and increased lipolysis and glucose uptake in the adipose tissue. Seven different GLP1 receptor agonists have been licensed globally. For those with type 2 diabetes mellitus, GLP1 receptor agonists overall reduce major adverse cardiovascular events by 14% (hazard ratio 0.86, 95% confidence interval 0.80-0.93) and all-cause death by 18% (hazard ratio 0.82, 95% confidence interval 0.82-0.94), and semaglutide, a long-acting GLP1 receptor agonist for once weekly injection, reduces major renal events by 24% (hazard ratio 0.76, 95% confidence interval 0.66-0.88). For obese patients without diabetes mellitus, semaglutide results in a 12.4% (95% confidence interval -13.4 to -11.5) reduction in body weight and 20% lower in the risk of major adverse cardiovascular events (hazard ratio 0.80, 95% confidence interval 0.72-0.90), while the burden of heart failure can also be improved by 7.8 points (95% confidence interval 4.8-10.9) in those with heart failure with preserved ejection fraction and obesity. These findings highlight the transformative role of GLP1 receptor agonists in the management of cardiovascular-kidney-metabolic syndrome. We reviewed the updated clinical evidence of incretin-based therapy and summarized its outcome benefits. CI - Copyright (c) 2025, the Chinese Medical Association. FAU - Chiang, Chern-En AU - Chiang CE AUID- ORCID: 0000-0002-1151-1047 AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Wang, Kang-Ling AU - Wang KL AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Cheng, Hao-Min AU - Cheng HM AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. AD - Division of Faculty Development, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. FAU - Chao, Tze-Fan AU - Chao TF AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Sung, Shih-Hsien AU - Sung SH AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Review DEP - 20250703 PL - Netherlands TA - J Chin Med Assoc JT - Journal of the Chinese Medical Association : JCMA JID - 101174817 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/etiology/drug therapy/prevention & control MH - *Metabolic Syndrome/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12637135 OTO - NOTNLM OT - Cardiovascular-kidney OT - Glucagon-like peptide-1 OT - Incretin OT - Obesity OT - metabolic syndrome COIS- Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. EDAT- 2025/07/03 06:28 MHDA- 2025/08/08 06:29 PMCR- 2025/07/03 CRDT- 2025/07/03 00:50 PHST- 2025/08/08 06:29 [medline] PHST- 2025/07/03 06:28 [pubmed] PHST- 2025/07/03 00:50 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 02118582-990000000-00541 [pii] AID - JCMA-D-25-00164 [pii] AID - 10.1097/JCMA.0000000000001263 [doi] PST - ppublish SO - J Chin Med Assoc. 2025 Aug 1;88(8):585-593. doi: 10.1097/JCMA.0000000000001263. Epub 2025 Jul 3. PMID- 40602613 OWN - NLM STAT- MEDLINE DCOM- 20251025 LR - 20260730 IS - 1538-7836 (Electronic) IS - 1538-7836 (Linking) VI - 23 IP - 11 DP - 2025 Nov TI - Glucagon-like peptide 1 receptor agonists and risk of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials. PG - 3527-3539 LID - S1538-7836(25)00409-X [pii] LID - 10.1016/j.jtha.2025.06.020 [doi] AB - BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs). OBJECTIVES: To investigate the impact of GLP-1RAs on VTE risk using data from RCTs. METHODS: We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis, and VTE at other sites, and the secondary outcomes were the individual events. RESULTS: Twenty-seven RCTs with 84 003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (risk ratio [RR], 0.70; 95% CI, 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR, 0.60; 95% CI, 0.39-0.94). In contrast, there were no significant differences in the risk of deep vein thrombosis (RR, 1.21; 95% CI, 0.69-2.12) or VTE at other sites (RR, 0.56; 95% CI, 0.25-1.26). CONCLUSION: In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity. CI - Copyright (c) 2025 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved. FAU - Chiang, Cho-Han AU - Chiang CH AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, USA. FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut, USA. FAU - Yu, Chun-Chiao AU - Yu CC AD - School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - See, Xin Ya AU - See XY AD - Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York, USA. FAU - Wang, Tsu Hsien AU - Wang TH AD - Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, New York, USA. FAU - Xanthavanij, Nutchapon AU - Xanthavanij N AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, USA. FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. FAU - Lo, Shao-Wei AU - Lo SW AD - Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Chiang, Cho-Hung AU - Chiang CH AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Lake, Leslie AU - Lake L AD - National Blood Clot Alliance, Philadelphia, Pennsylvania, USA. FAU - Lauw, Mandy N AU - Lauw MN AD - Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Bauer, Kenneth A AU - Bauer KA AD - Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. FAU - Kazi, Dhruv S AU - Kazi DS AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. FAU - Patell, Rushad AU - Patell R AD - Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: rpatell@bidmc.harvard.edu. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250630 PL - England TA - J Thromb Haemost JT - Journal of thrombosis and haemostasis : JTH JID - 101170508 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/diagnosis/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Incidence MH - *Incretins/therapeutic use/adverse effects MH - *Obesity/drug therapy/epidemiology/complications MH - Pulmonary Embolism/epidemiology/prevention & control MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome MH - *Venous Thromboembolism/prevention & control/epidemiology/diagnosis MH - Venous Thrombosis/epidemiology/prevention & control OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonists OT - pulmonary embolism OT - venous thromboembolism COIS- Declaration of competing interests M.N.L. reports research support from LeoPharma, outside the scope of the submitted work. K.A.B. reports consulting fees from Sanofi, outside the submitted work. R.P. reports consulting fees from Merck Research and Sanofi, outside the submitted work. Other authors report no conflicts. EDAT- 2025/07/03 00:27 MHDA- 2025/10/26 00:31 CRDT- 2025/07/02 19:15 PHST- 2025/05/07 00:00 [received] PHST- 2025/06/11 00:00 [revised] PHST- 2025/06/21 00:00 [accepted] PHST- 2025/10/26 00:31 [medline] PHST- 2025/07/03 00:27 [pubmed] PHST- 2025/07/02 19:15 [entrez] AID - S1538-7836(25)00409-X [pii] AID - 10.1016/j.jtha.2025.06.020 [doi] PST - ppublish SO - J Thromb Haemost. 2025 Nov;23(11):3527-3539. doi: 10.1016/j.jtha.2025.06.020. Epub 2025 Jun 30. PMID- 40602532 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20250801 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 226 DP - 2025 Aug TI - Impact of SGLT2 inhibitors on kidney health and survival in patients with polycystic kidney disease and type 2 diabetes. PG - 112357 LID - S0168-8227(25)00371-7 [pii] LID - 10.1016/j.diabres.2025.112357 [doi] AB - AIMS: To evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on dialysis, cardiovascular, and mortality risks in patients with polycystic kidney disease (PKD) and type 2 diabetes (T2D). METHODS: Using a target trial emulation within the TriNetX U.S. network (2015-2022), we identified 31,070 patients with both PKD and T2D. Three emulated trials were constructed via propensity score matching: SGLT2i vs. non-users (n = 2640 pairs), SGLT2i vs. DPP-4 inhibitors (n = 2016), and SGLT2i vs. GLP-1 receptor agonists (n = 1870). Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: Compared with non-users, SGLT2i users had lower risks of dialysis (HR: 0.657), acute kidney injury (AKI; HR: 0.896), and mortality (HR: 0.840). Against DPP-4 inhibitors, SGLT2i use was associated with reduced risks of dialysis (HR: 0.458), AKI (HR: 0.835), and mortality (HR: 0.813). Compared with GLP-1 RAs, SGLT2i users had a lower dialysis risk (HR: 0.531). CONCLUSION: SGLT2i use was associated with reduced risks of dialysis, AKI, and mortality in patients with PKD and T2D. These findings highlight a potential renal and survival benefit in this high-risk group. However, results were derived using an emulation protocol and propensity score methods based on electronic health records. KEY POINT: SGLT2i users were associated with a lower risk of dialysis, acute kidney injury, and mortality than non-SGLT2i users. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, Gueishan District, Taoyuan, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Dong, Chen AU - Dong C AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address: s0901047@gm.csmu.edu.tw. FAU - Hwu, Chii-Min AU - Hwu CM AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming Chiao Tung University School of Medicine, Taipei, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan; Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan. Electronic address: cch@nhri.edu.tw. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address: jccwei@gmail.com. LA - eng PT - Journal Article DEP - 20250630 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Aged MH - *Polycystic Kidney Diseases/mortality/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Renal Dialysis/statistics & numerical data MH - *Kidney/drug effects MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Acute kidney injury OT - Dialysis OT - Mortality OT - Polycystic kidney disease OT - SGLT2i OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/03 00:27 MHDA- 2025/08/02 10:45 CRDT- 2025/07/02 19:13 PHST- 2025/05/27 00:00 [received] PHST- 2025/06/14 00:00 [revised] PHST- 2025/06/28 00:00 [accepted] PHST- 2025/08/02 10:45 [medline] PHST- 2025/07/03 00:27 [pubmed] PHST- 2025/07/02 19:13 [entrez] AID - S0168-8227(25)00371-7 [pii] AID - 10.1016/j.diabres.2025.112357 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Aug;226:112357. doi: 10.1016/j.diabres.2025.112357. Epub 2025 Jun 30. PMID- 40600464 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - The cost-utility and budget impact analyses of Tirzepatide versus once-weekly Semaglutide as add-on therapy to metformin in patients with type 2 diabetes mellitus in China. PG - 5269-5279 LID - 10.1111/dom.16580 [doi] AB - AIM: To evaluate the long-term economic implications and potential budgetary consequences for the national health insurance system (NHIS) of tirzepatide versus semaglutide as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The demographic and clinical efficacy data were derived from the SURPASS-2 trial. The cost-utility analysis was performed to estimate the cost-utility by UK Prospective Diabetes Study Outcomes Model Version 2.2 from the Chinese health care providers' perspective, incorporating costs and quality-adjusted life years (QALYs). Sensitivity analyses were employed to investigate the presence of uncertainty. The financial implications for the relevant budgetary authority over 5 years were estimated. RESULTS: In the long-term treatment simulation, tirzepatide 5 and 10 mg yielded incremental QALYs of 0.05 and 0.09, in comparison with semaglutide 1 mg, respectively. The associated incremental costs for these treatments were $23 563.42 and $47 583.74, respectively. Consequently, the incremental cost-utility ratios were calculated to be $445 125.24/QALY and $543 829.19/QALY, both of which exceeded the established threshold of $29 599.90/QALY. These base-case results were validated through robust sensitivity analyses. The budget impact analysis showed that such an expansion would incur an additional budgetary burden of approximately $80 million to $490 million for the NHIS over a simulated 5-year period. CONCLUSION: This dual analysis provides policymakers and payers with a comprehensive basis for decision-making. Tirzepatide offered substantial long-term health benefits, but they were not cost-effective compared with semaglutide 1 mg in T2DM patients inadequately controlled with metformin under China's health care providers' perspective. The entry of tirzepatide 5 mg into the NHIS may increase the financial burden of national medical insurance, but overall health care expenditures are expected to decrease, driven primarily by significantly reduced out-of-pocket expenses for patients. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Wang, Sihua AU - Wang S AUID- ORCID: 0000-0001-6550-5059 AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Fan, Duncong AU - Fan D AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Yao, Qinhong AU - Yao Q AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Sun, Xiaojie AU - Sun X AUID- ORCID: 0009-0003-7629-8296 AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. LA - eng GR - YS2024-3-010/Zhejiang Medical Association/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250702 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/economics/administration & dosage/therapeutic use MH - Cost-Benefit Analysis MH - *Metformin/economics/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - China/epidemiology MH - Quality-Adjusted Life Years MH - Drug Therapy, Combination/economics MH - Female MH - Male MH - Middle Aged MH - Budgets MH - Aged MH - Drug Administration Schedule MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - budget impact analysis OT - cost-utility analysis OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus EDAT- 2025/07/02 12:30 MHDA- 2025/08/06 12:29 CRDT- 2025/07/02 07:23 PHST- 2025/06/19 00:00 [revised] PHST- 2025/04/07 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/07/02 12:30 [pubmed] PHST- 2025/07/02 07:23 [entrez] AID - 10.1111/dom.16580 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):5269-5279. doi: 10.1111/dom.16580. Epub 2025 Jul 2. PMID- 40594279 OWN - NLM STAT- MEDLINE DCOM- 20250702 LR - 20260127 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Jul 1 TI - Comparative cardiovascular outcomes of semaglutide to dulaglutide in patients with type 2 diabetes. PG - 21333 LID - 10.1038/s41598-025-06245-w [doi] LID - 21333 AB - Type 2 diabetes significantly increases cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce major adverse cardiovascular events, heart failure hospitalizations, and death. However, the comparison among GLP-1 RAs on cardiovascular outcomes is limited. We compared all-cause death and cardiovascular events in patients using semaglutide or dulaglutide in patients with type 2 diabetes. This retrospective observational study used the TriNetX database of deidentified electronic medical records from January 1, 2018, to December 31, 2020. We identified 4,691,652 patients with type 2 diabetes, among whom 231,075 initiated semaglutide and 189,103 initiated dulaglutide. After propensity score matching, 171,105 patients were included in each group. The primary outcome measure was all-cause death during the 3-year follow-up period.; secondary outcomes were acute myocardial infarction, stroke, and acute heart failure.Over 3 years, the risk for all-cause death in patients who received semaglutide relative to those who received dulaglutide was significantly lower (4.2% vs. 5.6%, p < 0.001; hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.72-0.78). Similarly, patients who received semaglutide were less likely to have acute myocardial infarction (5.2% vs. 5.6%; HR, 0.94; 95% CI, 0.91-0.97; p < 0.001), stroke (5.8% vs. 6.4%; HR, 0.90; 95% CI, 0.87-0.93; p < 0.001), and acute heart failure (5.3% vs. 6.1%; HR, 0.88; 95% CI, 0.85-0.91; p < 0.001).In this multicenter, retrospective, observational study, semaglutide was associated with lower 3-year risks of all-cause death, acute myocardial infarction, stroke, and acute heart failure compared with dulaglutide in patients with type 2 diabetes. CI - (c) 2025. The Author(s). FAU - Kishimori, Takefumi AU - Kishimori T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. tkato75@kuhp.kyoto-u.ac.jp. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250701 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use MH - Middle Aged MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/etiology/mortality MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12217050 COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/07/02 06:28 MHDA- 2025/07/02 06:29 PMCR- 2025/07/01 CRDT- 2025/07/02 00:55 PHST- 2025/04/15 00:00 [received] PHST- 2025/06/06 00:00 [accepted] PHST- 2025/07/02 06:29 [medline] PHST- 2025/07/02 06:28 [pubmed] PHST- 2025/07/02 00:55 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - 10.1038/s41598-025-06245-w [pii] AID - 6245 [pii] AID - 10.1038/s41598-025-06245-w [doi] PST - epublish SO - Sci Rep. 2025 Jul 1;15(1):21333. doi: 10.1038/s41598-025-06245-w. PMID- 40592472 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20260925 IS - 2046-2441 (Electronic) IS - 2046-2441 (Linking) VI - 15 IP - 7 DP - 2025 Jan TI - GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity. PG - 240303 LID - 10.1098/rsob.240303 [doi] LID - 240303 AB - The discovery of glucagon-like peptide-1 (GLP-1) has revolutionized metabolism research in the context of obesity and type 2 diabetes mellitus (T2DM). For example, worldwide, more than 537 million adults are affected with T2DM, and more than 30.3 million people in the USA alone are suffering from T2DM. Obesity is one independent risk factor for T2DM; therefore, targeting obesity may lower the T2DM development risk. Hence, pharmaceutical companies have developed different GLP-1R agonists (GLP-1RAs) to target obesity and T2DM, which comprised multibillion-dollar businesses. However, metabolism and immune response are well-correlated processes that affect each other. For example, recent advances in metabolic processes governing the immune response have led to the evolution of immunometabolism, which can be divided into cellular, tissue and systemic immunometabolism. The current open-question article is intended to explore the impact of the GLP-1/GLP-1R axis on the immune response governed by the functioning of various immune cells and their interaction with the nervous system and microbiota axis that further depends on the gender and circadian clock of the host. Along with food/sugar ingestion, several other factors controlling the GLP-1 secretion and its immunomodulatory functions have been discussed to highlight the importance of the GLP-1/GLP-1R axis in immunoregulation. Therefore, understanding the GLP-1/GLP-1R axis/interaction at the immunological level will help to understand the adverse events associated with GLP-1RAs and their use as an immunomodulatory agent in acute and chronic inflammatory conditions depending on the gender and metabolic status of the host. FAU - Kumar, Vijay AU - Kumar V AUID- ORCID: 0000-0001-9741-3597 AD - Department of Surgery, Morehouse School of Medicine, Atlanta, GA, USA. LA - eng PT - Journal Article PT - Review DEP - 20250702 PL - England TA - Open Biol JT - Open biology JID - 101580419 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/metabolism/immunology/etiology/drug therapy MH - *Obesity/metabolism/immunology MH - *Glucagon-Like Peptide 1/metabolism MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - Signal Transduction MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Immunity PMC - PMC12212992 OTO - NOTNLM OT - GLP-1/GLP-1R axis OT - L cells OT - hypothalamus OT - immunity OT - intraepithelial lymphocytes OT - macrophages COIS- I declare I have no competing interests. EDAT- 2025/07/02 00:27 MHDA- 2025/07/02 00:28 PMCR- 2025/07/02 CRDT- 2025/07/01 19:13 PHST- 2025/07/02 00:28 [medline] PHST- 2025/07/02 00:27 [pubmed] PHST- 2025/07/01 19:13 [entrez] PHST- 2025/07/02 00:00 [pmc-release] AID - rsob240303 [pii] AID - 10.1098/rsob.240303 [doi] PST - ppublish SO - Open Biol. 2025 Jan;15(7):240303. doi: 10.1098/rsob.240303. Epub 2025 Jul 2. PMID- 40590655 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20260626 IS - 2325-6621 (Electronic) IS - 2325-6621 (Linking) VI - 22 IP - 7 DP - 2025 Jul TI - Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence. PG - 1042-1052 LID - 10.1513/AnnalsATS.202409-923OC [doi] AB - Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists (tirzepatide) are approved for treatment of type 2 diabetes (T2D) and obesity. Objective: To compare the relative efficacy of tirzepatide, liraglutide, and semaglutide in reducing major adverse cardiovascular events (MACEs) in patients with obstructive sleep apnea (OSA) and T2D. Methods: We performed a retrospective cohort analysis in a large global federated database of patients with OSA and T2D. Two cohorts were generated, both with a treatment arm of patients prescribed tirzepatide. Liraglutide and semaglutide-treated patients provided the reference arms in cohort 1 and cohort 2, respectively. Cohorts underwent propensity-score matching at a 1:1 ratio for confounders. We examined rates of incident MACEs (composite outcome and individual components) over an 18-month follow up, and performed stratified analyses by body mass index, age, sex, and ethnicity. Finally, we assessed incident OSA in a secondary analysis of patients with T2D treated with tirzepatide compared with liraglutide and semaglutide. Results: After matching, each treatment arm included 7,836 patients in cohort 1 and 7,394 patients in cohort 2. Tirzepatide reduced the risk of incident MACEs compared with liraglutide (hazard ratio, 0.58; 95% confidence interval, 0.51-0.66) and semaglutide (0.86; 0.74-0.99). Tirzepatide was more efficacious in younger, male patients of White ethnicity. Moreover, tirzepatide reduced incident OSA compared with liraglutide (0.89; 0.82-0.97) but not semaglutide (0.94; 0.86-1.02). Conclusions: In patients with OSA and T2D, tirzepatide is associated with a lower incidence of MACEs compared with liraglutide and semaglutide. More robust randomized, controlled evidence is needed for these drugs in patients who are at such high risk. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Heague, Megan AU - Heague M AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. FAU - Hernadez, Gema AU - Hernadez G AD - TriNetX LLC, Cambridge, Massachusetts. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Craig, Sonya AU - Craig S AD - Liverpool University Hospital National Health Service Foundation Trust, Liverpool, United Kingdom. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Ann Am Thorac Soc JT - Annals of the American Thoracic Society JID - 101600811 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Liraglutide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Sleep Apnea, Obstructive/complications/drug therapy MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Aged MH - *Tirzepatide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - major adverse cardiovascular events OT - obstructive sleep apnoea OT - tirzepatide OT - type 2 diabetes EDAT- 2025/07/01 21:14 MHDA- 2025/07/01 21:15 CRDT- 2025/07/01 09:43 PHST- 2025/07/01 21:15 [medline] PHST- 2025/07/01 21:14 [pubmed] PHST- 2025/07/01 09:43 [entrez] AID - 10.1513/AnnalsATS.202409-923OC [doi] PST - ppublish SO - Ann Am Thorac Soc. 2025 Jul;22(7):1042-1052. doi: 10.1513/AnnalsATS.202409-923OC. PMID- 40590228 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20260625 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 13 DP - 2025 Jul 1 TI - Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. LID - 10.1172/JCI186425 [doi] LID - e186425 AB - Metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of MASLD, is now a leading cause of chronic liver disease worldwide. Driven by obesity and type 2 diabetes, MASH significantly increases the risk of cirrhosis, hepatocellular carcinoma, and liver failure. While public health interventions remain essential, therapeutic strategies targeting metabolic dysfunction, inflammation, and fibrosis are urgently needed. This Review focuses on pharmacological treatments in advanced development, including incretin-based therapies (GLP-1, dual, and triple agonists), metabolic modulators (PPAR, FGF21, and THR-beta agonists), and novel agents such as fatty acid synthase inhibitors. Current regulatory approval is based on histological end points, with increasing interest in noninvasive biomarkers and personalized treatment approaches. Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. Genetic variants (e.g., PNPLA3 polymorphisms) and emerging molecular biomarkers may enhance stratification, while artificial intelligence is beginning to shape trial design and drug development. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics. FAU - Newsome, Philip N AU - Newsome PN AD - Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, United Kingdom. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, and. AD - Division of Epidemiology, Department of Family Medicine and Public Health, UCSD, La Jolla, California, USA. LA - eng GR - P30 DK120515/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250701 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Incretins) SB - IM MH - Humans MH - Animals MH - *Fatty Liver/drug therapy/metabolism/pathology MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Incretins/therapeutic use MH - Liver Cirrhosis/metabolism/drug therapy/pathology MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy PMC - PMC12208534 COIS- Conflict of interest: PNN discloses the following financial relationship(s) on behalf of the University of Birmingham within the past 24 months: grant/research support from Boehringer Ingelheim and Novo Nordisk and consulting fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Intercept, Madrigal, Novo Nordisk, Sagimet, and 89 Bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse Bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics. RL has stock options in Sagimet Biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. RL is Co-founder of LipoNexus Inc. EDAT- 2025/07/01 21:14 MHDA- 2025/07/01 21:15 PMCR- 2025/07/01 CRDT- 2025/07/01 06:03 PHST- 2025/07/01 21:15 [medline] PHST- 2025/07/01 21:14 [pubmed] PHST- 2025/07/01 06:03 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - 186425 [pii] AID - 10.1172/JCI186425 [doi] PST - epublish SO - J Clin Invest. 2025 Jul 1;135(13):e186425. doi: 10.1172/JCI186425. eCollection 2025 Jul 1. PMID- 40589512 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250702 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Case Report: long-term misdiagnosis and follow-up of a patient with HNF4A-MODY carrying a new de novo mutation. PG - 1509135 LID - 10.3389/fendo.2025.1509135 [doi] LID - 1509135 AB - BACKGROUND: HNF4A-MODY constitutes 5%-10% of MODY cases; however, treatment options remain unclearly recommended, and long-term follow-up of patients with HNF4A-MODY is lacking due to limited research. Here, we report a case carrying a new de novo variant of HNF4A. The patient had been using insulin for up to 25 years before genetic diagnosis. CASE DESCRIPTION: A 38-year-old man sought consultation due to an increased daily insulin requirement and inadequate glycemic control. At the age of 13, the patent's parents discovered that he had significantly elevated fasting blood glucose levels accompanied by weight loss. He was subsequently diagnosed with type 1 diabetes and began insulin therapy. At a routine follow-up at age 21, another physician observed that his pancreatic islet function remained preserved, with negative results for diabetes-related antibodies. Consequently, his diagnosis was revised to type 2 diabetes, and the antihyperglycemic therapy was added in metformin and acarbose. Before the current consultation, the patient's insulin dosage had gradually increased to 80 units per day; however, glycemic control remained unsatisfactory. Whole exome sequencing identified a heterozygous variant, c.272G > A (p.R91H), in exon 3 of the HNF4A gene (NM_175914.5) in the patient. The patient's treatment regimen was modified to include metformin at a dosage of 1.0 g twice daily, semaglutide at 0.5 mg once weekly, and insulin glargine was gradually discontinued. The patient achieved adequate glycemic control during follow-up. CONCLUSION: This case emphasizes that spontaneous HNF4A-MODY is prone to misdiagnosis and the prolonged rate of pancreatic function decline in HNF4A-MODY. Glycemic control and complication progression could be acceptable in HNF4A-MODY cases treated with long-time insulin, but risks of hypoglycemic events, obesity, and atherosclerosis remain. Switching to GLP1RA treatment in HNF4A-MODY still yields a good effect after a prolonged disease course. CI - Copyright (c) 2025 Luo, Li and Wang. FAU - Luo, Jing AU - Luo J AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. AD - Department of Endocrinology and Metabolism, Tieling Central Hospital, Tieling, China. FAU - Li, Ai AU - Li A AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. AD - Department of Endocrinology and Metabolism, Tieling Central Hospital, Tieling, China. FAU - Wang, Xiaoli AU - Wang X AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. LA - eng SI - figshare/10.6084/m9.figshare.29236490 PT - Case Reports PT - Journal Article DEP - 20250616 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hepatocyte Nuclear Factor 4) RN - 0 (HNF4A protein, human) SB - IM MH - Humans MH - *Hepatocyte Nuclear Factor 4/genetics MH - Adult MH - Male MH - *Diabetes Mellitus, Type 2/genetics/diagnosis/drug therapy MH - *Diagnostic Errors MH - *Mutation MH - Follow-Up Studies PMC - PMC12207682 OTO - NOTNLM OT - GLP1RA OT - HNF4A OT - case report OT - maturity-onset diabetes of the young OT - mutation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/07/01 09:30 MHDA- 2025/07/01 21:16 PMCR- 2025/06/16 CRDT- 2025/07/01 04:14 PHST- 2024/10/10 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/07/01 21:16 [medline] PHST- 2025/07/01 09:30 [pubmed] PHST- 2025/07/01 04:14 [entrez] PHST- 2025/06/16 00:00 [pmc-release] AID - 10.3389/fendo.2025.1509135 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jun 16;16:1509135. doi: 10.3389/fendo.2025.1509135. eCollection 2025. PMID- 40589143 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250703 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 34 IP - 7 DP - 2025 Jul TI - Prescribing Patterns of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Patients With T2DM and ASCVD in South Korea. PG - e70183 LID - 10.1002/pds.70183 [doi] LID - e70183 AB - BACKGROUND: Despite the cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), their utilization remains low globally. This study aimed to evaluate the utilization of SGLT2i and GLP1RA in patients with T2DM and ASCVD, as well as the factors associated with their use in South Korea. METHODS: We conducted a retrospective study using the National Patient Sample claims data from 2015 to 2020. Adults aged 20 years or older with confirmed diagnoses of both T2DM and ASCVD between March 1 and October 31 of each year were included. The utilization of SGLT2i and GLP1RA was assessed based on prescriptions filled within 60 days of the index date. Multivariable logistic regression was used to identify factors associated with their use. Annual trends in utilization were evaluated using the Cochran-Armitage trend test. RESULTS: In our study of 57 576 study population, the use of SGLT2i increased from 1.20% in 2015 to 10.51% by 2020. GLP1RA usage increased from 0% to 1.17% over the same period. Older age, chronic kidney disease (OR 0.52, 95% CI 0.41-0.66), and concurrent use of dipeptidyl peptidase 4 inhibitors (DPP4i) (OR 0.09, 95% CI 0.09-0.10) significantly reduced the likelihood of SGLT2i use. In contrast, factors such as comorbid dyslipidemia (OR 1.41, 95% CI 1.25-1.60), heart failure (OR 1.22, 95% CI 1.09-1.37), concurrent use of sulfonylurea (SU) (OR 1.30, 95% CI 1.20-1.40), and prescriptions from cardiologists (OR 1.22, 95% CI 1.07-1.40) were positively associated with higher SGLT2i usage. For GLP1RA, negative influences included older age, concurrent DPP4i use (OR 0.12, 95% CI 0.08-0.16), and non-endocrinologist prescription, whereas female sex (OR 1.35, 95% CI 1.06-1.73), dyslipidemia (OR 1.68, 95% CI 1.10-2.66), and the use of insulin (OR 3.71, 95% CI 2.83-4.85), or SU (OR 3.13, 95% CI 2.44-4.02) use were positive factors. CONCLUSIONS: Despite the known cardiovascular benefits and increasing utilization trends of SGLT2i and GLP1RA, our findings reveal that 88.35% of eligible patients with T2DM and ASCVD remained untreated with these agents as of 2020. This study suggests disparities in the use of these agents based on patients' characteristics and physician specialties. Further efforts to explore and address potential barriers to the use of these agents could enhance their clinical benefits by improving access for high-risk patients. CI - (c) 2025 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Eom, Yeong Rok AU - Eom YR AD - College of Pharmacy, Pusan National University, Busan, Republic of Korea. FAU - Joo, Hajung AU - Joo H AD - College of Pharmacy, Northeastern University, Boston, USA. FAU - Chae, Seung Eun AU - Chae SE AD - College of Pharmacy, Pusan National University, Busan, Republic of Korea. FAU - Je, Nam Kyung AU - Je NK AUID- ORCID: 0000-0002-0299-5131 AD - College of Pharmacy, Pusan National University, Busan, Republic of Korea. AD - Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea. LA - eng PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Male MH - Female MH - Republic of Korea/epidemiology MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Practice Patterns, Physicians'/statistics & numerical data/trends MH - Adult MH - *Atherosclerosis/drug therapy/epidemiology MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - Young Adult PMC - PMC12209748 OTO - NOTNLM OT - atherosclerotic cardiovascular disease OT - glucagon-like peptide-1 receptor agonists OT - sodium-glucose cotransporter 2 inhibitors OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/07/01 09:30 MHDA- 2025/07/01 09:31 PMCR- 2025/07/01 CRDT- 2025/07/01 02:32 PHST- 2025/05/10 00:00 [revised] PHST- 2024/02/04 00:00 [received] PHST- 2025/06/04 00:00 [accepted] PHST- 2025/07/01 09:31 [medline] PHST- 2025/07/01 09:30 [pubmed] PHST- 2025/07/01 02:32 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - PDS70183 [pii] AID - 10.1002/pds.70183 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2025 Jul;34(7):e70183. doi: 10.1002/pds.70183. PMID- 40588647 OWN - NLM STAT- MEDLINE DCOM- 20250830 LR - 20250902 IS - 1432-1041 (Electronic) IS - 0031-6970 (Print) IS - 0031-6970 (Linking) VI - 81 IP - 9 DP - 2025 Sep TI - Variation in uptake of sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor analogues in adults with type 2 diabetes at high cardiovascular risk. PG - 1315-1327 LID - 10.1007/s00228-025-03870-2 [doi] AB - PURPOSE: We quantified variation in the uptake of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor analogues (GLP-1RA) across sociodemographic, behavioural and clinical characteristics of people with type 2 diabetes (T2D) at high cardiovascular risk. METHODS: We used the 45 and Up Study survey data (2018-2020) linked to dispensing and service claims for 10,171 people with T2D (56% male, median age of 72 years, median diabetes duration of 11 years). We calculated the prevalence of GLP-1RA and SGLT2i use within 1 year and used logistic regressions to assess associations with each participant characteristic. RESULTS: We found that 2270 (22.3%) people with T2D used SGLT2i and 679 (6.7%) used GLP-1RA. Use of these medicines was higher in people diagnosed with diabetes for a longer period, a high number of comorbidities and survey year, decreased in older people, and varied by sex. After adjusting for these factors, utilisation of these medicines was lower among people who consume alcohol (versus non-drinkers) and higher among those with overweight or obesity. SGLT2i use was also higher in people who were less physically active or had established cardiovascular disease and lower in people with anxiety or depression. GLP-1RA use was higher among people with poorer health and lower in people born outside Australia/New Zealand. CONCLUSION: Prevalent use of SGLT2i and GLP-1RA was suboptimal and varied across clinical characteristics and behavioural risk factors. While some variation reflects complexities in prescribing for this older population, there remains opportunity for optimised prescribing within this high-risk population. CI - (c) 2025. The Author(s). FAU - de Oliveira Costa, Juliana AU - de Oliveira Costa J AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Room 209, Samuels Building (F25), Sydney, NSW, 2052, Australia. j.costa@unsw.edu.au. FAU - Lin, Jialing AU - Lin J AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Room 209, Samuels Building (F25), Sydney, NSW, 2052, Australia. FAU - Milder, Tamara Y AU - Milder TY AD - Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia. AD - Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia. AD - Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, NSW, Australia. FAU - Havard, Alys AU - Havard A AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Room 209, Samuels Building (F25), Sydney, NSW, 2052, Australia. AD - National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia. FAU - Greenfield, Jerry R AU - Greenfield JR AD - Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia. AD - Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, NSW, Australia. FAU - Day, Richard O AU - Day RO AD - Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, NSW, Australia. FAU - Neuen, Brendon L AU - Neuen BL AD - The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. AD - Department of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia. FAU - Gibson, Alice A AU - Gibson AA AD - Menzies Centre for Health Policy and Economics, School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. FAU - Morton, Jedidiah I AU - Morton JI AD - Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. FAU - Sacre, Julian W AU - Sacre JW AD - Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. FAU - Pearson, Sallie-Anne AU - Pearson SA AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Room 209, Samuels Building (F25), Sydney, NSW, 2052, Australia. FAU - Falster, Michael O AU - Falster MO AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Room 209, Samuels Building (F25), Sydney, NSW, 2052, Australia. LA - eng GR - 2002889; 1183273/National Health and Medical Research Council (NHMRC) Ideas Grant/ GR - 2026621; APP1173784/NHMRC Emerging Leader Investigator Grant/ GR - 2023HIG69/Ramaciotti Foundation/ GR - 1196900/NHMRC Centre of Research Excellence in Medicines Intelligence/ GR - 107048; 105609/National Heart Foundation of Australia/ PT - Journal Article DEP - 20250630 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Aged MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged, 80 and over MH - *Hypoglycemic Agents/therapeutic use MH - Heart Disease Risk Factors PMC - PMC12398476 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Pharmacoepidemiology OT - Sodium -glucose cotransporter 2 inhibitor OT - Type 2 diabetes COIS- Declarations. Conflict of interest: The authors declare no competing interests. Competing interests: The authors declare no competing interests. EDAT- 2025/07/01 09:25 MHDA- 2025/09/02 14:45 PMCR- 2025/06/30 CRDT- 2025/06/30 23:20 PHST- 2025/03/20 00:00 [received] PHST- 2025/06/17 00:00 [accepted] PHST- 2025/09/02 14:45 [medline] PHST- 2025/07/01 09:25 [pubmed] PHST- 2025/06/30 23:20 [entrez] PHST- 2025/06/30 00:00 [pmc-release] AID - 10.1007/s00228-025-03870-2 [pii] AID - 3870 [pii] AID - 10.1007/s00228-025-03870-2 [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2025 Sep;81(9):1315-1327. doi: 10.1007/s00228-025-03870-2. Epub 2025 Jun 30. PMID- 40587855 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 7 DP - 2025 Jul TI - In high-risk type 2 diabetes, adding oral semaglutide to standard care reduced MACE at a mean 48 mo. PG - JC80 LID - 10.7326/ANNALS-25-02173-JC [doi] AB - GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text] Nephrology: [Formula: see text]. FAU - Bandi, Satya Sai Sri AU - Bandi SSS AUID- ORCID: 0009-0003-3698-2309 AD - Mayo Clinic, Rochester, Minnesota, USA (S.S.B., V.M.M.). FAU - Montori, Victor M AU - Montori VM AUID- ORCID: 0000-0003-0595-2898 AD - Mayo Clinic, Rochester, Minnesota, USA (S.S.B., V.M.M.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20250701 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Administration, Oral MH - *Cardiovascular Diseases/prevention & control MH - Male MH - Female MH - Middle Aged MH - Aged MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/07/01 04:51 MHDA- 2025/07/14 18:27 CRDT- 2025/06/30 17:02 PHST- 2025/07/14 18:27 [medline] PHST- 2025/07/01 04:51 [pubmed] PHST- 2025/06/30 17:02 [entrez] AID - 10.7326/ANNALS-25-02173-JC [doi] PST - ppublish SO - Ann Intern Med. 2025 Jul;178(7):JC80. doi: 10.7326/ANNALS-25-02173-JC. Epub 2025 Jul 1. PMID- 40587132 OWN - NLM STAT- MEDLINE DCOM- 20250630 LR - 20260307 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 6 DP - 2025 Jun 2 TI - GLP-1 RA Use and Major Adverse Cardiovascular Events in Patients With Monoclonal Gammopathy of Undetermined Significance. PG - e2517541 LID - 10.1001/jamanetworkopen.2025.17541 [doi] LID - e2517541 AB - IMPORTANCE: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have demonstrated cardiorenal benefits in patients with type 2 diabetes, but their effectiveness in patients with MGUS remains unexplored. OBJECTIVE: To assess the effectiveness of GLP-1 RAs for primary prevention of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with MGUS and diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used a propensity score-matched analysis of data from the TriNetX Global Database, encompassing patients diagnosed with diabetes and MGUS between January 1, 2018, and January 13, 2023. Patients with prior heart failure (HF), ischemic heart disease, coronary revascularization, or stroke or transient ischemic attack before MGUS diagnosis were excluded. The cohort was divided into 2 groups: GLP-1 RA users and nonusers at baseline. After 1:1 propensity score matching, GLP-1 RA users and nonusers were compared up to 5 years from the MGUS diagnosis date. Data analyses were completed January 19, 2025. EXPOSURE: GLP-1 RA use within 1 year before MGUS diagnosis. MAIN OUTCOMES AND MEASURES: The primary end point was MACCE, defined as a composite of all-cause mortality, new-onset HF, acute coronary syndrome, and stroke or transient ischemic attack. Secondary end points included individual MACCE components, decompensated HF, and acute kidney injury or end-stage kidney disease. RESULTS: A total of 4871 patients with MGUS (mean [SD] age, 68.9 [10.1] years; 2366 [48.5%] male) were included (473 GLP-1 RA users and 4398 non-users). A total of 460 users were matched to 460 nonusers, with balanced characteristics (mean [SD] age, 65.0 [10.6] vs 65.1 [11.0] years; 229 [49.7%] male vs 234 [50.8%] male), including 14 patients (3.0%) vs 13 patients (2.8%) identifying as Asian, 8 (21.3%) vs 92 (20.0%) as Black or African American, 25 patients (5.4%) vs 20 patients (4.3%) as Hispanic or Latino, and 243 patients (52.8%) vs 250 patients (54.3%) as White. GLP-1 RA use was associated with a significantly lower risk of MACCE (hazard ratio [HR], 0.75; 95% CI, 0.60-0.93). Significant reductions were also observed in all-cause mortality (HR, 0.57; 95% CI, 0.37-0.87), new-onset HF (HR, 0.69; 95% CI, 0.54-0.90), decompensated HF (HR, 0.60; 95% CI, 0.43-0.84), and acute kidney injury or end-stage kidney disease (HR, 0.73; 95% CI, 0.57-0.92). CONCLUSIONS AND RELEVANCE: The findings of this cohort study of GLP-1 RA use vs no use in patients with MGUS and diabetes suggest the potential of GLP-1 RA for primary prevention of MACCE. These findings warrant further investigation in prospective randomized trials. FAU - Chi, Kuan-Yu AU - Chi KY AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Desphande, Shweta AU - Desphande S AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Lee, Pei-Lun AU - Lee PL AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Soni, Anushri AU - Soni A AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Gonzales-Uribe, Antony AU - Gonzales-Uribe A AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Lessa, Yasmin AU - Lessa Y AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Morgan, Ahmed Ashraf AU - Morgan AA AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Chang, Yu AU - Chang Y AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Yu-Shiuan AU - Lin YS AD - Department of Education, Center for Evidence-Based Medicine, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Akman, Zafer AU - Akman Z AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Nouri, Armin AU - Nouri A AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Rossi, Raiza AU - Rossi R AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Babapour, Golsa AU - Babapour G AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Varrias, Dimitrios AU - Varrias D AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Parker, Terri AU - Parker T AD - Department of Internal Medicine, Section of Hematology, Yale University School of Medicine and Yale Cancer Center, New Haven, Connecticut. FAU - Baldassarre, Lauren A AU - Baldassarre LA AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Jha, Alokkumar AU - Jha A AD - Weill Cornell Medicine, New York, New York. FAU - Muchtar, Eli AU - Muchtar E AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota. FAU - Hull, Sarah C AU - Hull SC AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Kwan, Jennifer M AU - Kwan JM AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Nanna, Michael G AU - Nanna MG AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. LA - eng GR - K76 AG088428/AG/NIA NIH HHS/United States GR - P30 AG021342/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20250602 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - Retrospective Studies MH - Middle Aged MH - *Monoclonal Gammopathy of Undetermined Significance/complications/drug therapy/epidemiology MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Propensity Score PMC - PMC12210086 COIS- Conflict of Interest Disclosures: Dr Nanna reported receiving personal fees from Merck, Novo Nordisk, and HeartFlow during the conduct of the study and receiving research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute, the Yale Claude D. Pepper Older Americans Independence Center, and the National Institute on Aging outside the submitted work. No other disclosures were reported. EDAT- 2025/07/01 04:46 MHDA- 2025/07/01 04:47 PMCR- 2025/06/30 CRDT- 2025/06/30 11:33 PHST- 2025/07/01 04:47 [medline] PHST- 2025/07/01 04:46 [pubmed] PHST- 2025/06/30 11:33 [entrez] PHST- 2025/06/30 00:00 [pmc-release] AID - 2835801 [pii] AID - zoi250553 [pii] AID - 10.1001/jamanetworkopen.2025.17541 [doi] PST - epublish SO - JAMA Netw Open. 2025 Jun 2;8(6):e2517541. doi: 10.1001/jamanetworkopen.2025.17541. PMID- 40587084 OWN - NLM STAT- MEDLINE DCOM- 20260520 LR - 20260520 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 2 DP - 2026 Jun TI - Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes. PG - 224-236 LID - 10.23736/S2724-6507.25.04306-4 [doi] AB - The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented. FAU - Li, Yushan AU - Li Y AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - He, Ziling AU - He Z AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - Li, Chunyan AU - Li C AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - Huang, Jing AU - Huang J AD - School of Basic Medical Science, Department of Parasitology, Central South University, Changsha, China. FAU - Yu, Zheng AU - Yu Z AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China - yuzheng@csu.edu.cn. LA - eng PT - Journal Article PT - Review DEP - 20250630 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology MH - Humans MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Gastrointestinal Microbiome/drug effects MH - Metformin/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2025/07/01 04:48 MHDA- 2026/05/20 06:32 CRDT- 2025/06/30 11:21 PHST- 2026/05/20 06:32 [medline] PHST- 2025/07/01 04:48 [pubmed] PHST- 2025/06/30 11:21 [entrez] AID - S2724-6507.25.04306-4 [pii] AID - 10.23736/S2724-6507.25.04306-4 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Jun;51(2):224-236. doi: 10.23736/S2724-6507.25.04306-4. Epub 2025 Jun 30. PMID- 40586870 OWN - NLM STAT- MEDLINE DCOM- 20251031 LR - 20251031 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 10 DP - 2025 Oct TI - New generation agents for glycemic control and diabetic retinopathy progression: what we need to know? PG - 1573-1583 LID - 10.1007/s00592-025-02552-w [doi] AB - AIMS: To report on the current evidence of early worsening of diabetic retinopathy (EWDR) in patients treated with new-generation antidiabetic agents, with a focus on glucagon-like peptide-1 receptor agonists (GLP1-RA). METHODS: A comprehensive analysis of current literature was conducted, with a focus on studies evaluating the impact of glycemic control strategies and GLP1-RA on DR progression. References from landmark studies and recent trials were analyzed. RESULTS: Intensive glycemic control, while effective in reducing long-term microvascular complications including DR, has been associated with EWDR, particularly in cases with rapid HbA1c reductions. Emerging evidence links novel antidiabetic agents, including GLP1-RA, with increased risk of EWDR, though different studies have conflicting results. However, the risk of EWDR seems not to be directly linked to retinal toxicity from specific antidiabetic agents, but more likely to the rapid glycemic improvement. Risk factors for EWDR in these patients include higher baseline HbA1c, rapid and significant reductions in HbA1c levels during the first months of treatment, longer duration of diabetes, and more advanced stages of DR at baseline, while mild or moderate non-proliferative DR seem not be at higher risk of DR progression. CONCLUSIONS: While new antidiabetic therapies offer significant benefits for diabetes management, clinicians must be cautious when implementing intensive glycemic control in patients at risk for EWDR. Individualized treatment plans and close monitoring are essential to mitigate risks and optimize outcomes for patients with DR. CI - (c) 2025. Associazione Medici Diabetologi / Association of Diabetologists (AMD), Societa Italiana di Diabetologia / Italian Society of Diabetology (SID). FAU - Vujosevic, Stela AU - Vujosevic S AUID- ORCID: 0000-0001-6773-9967 AD - Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via San Vittore 12, 20123, Milan, Italy. stela.vujosevic@unimi.it. AD - Eye Clinic, IRCCS MultiMedica, 20123, Milan, Italy. stela.vujosevic@unimi.it. FAU - Toma, Caterina AU - Toma C AUID- ORCID: 0000-0002-1505-6029 AD - Eye Clinic, University Hospital Maggiore della Carita, 28100, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale "Amedeo Avogadro", 28100, Novara, Italy. FAU - Ferrulli, Anna AU - Ferrulli A AUID- ORCID: 0000-0002-8518-5547 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20142, Milan, Italy. FAU - De Cilla, Stefano AU - De Cilla S AUID- ORCID: 0000-0002-0267-3650 AD - Eye Clinic, University Hospital Maggiore della Carita, 28100, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale "Amedeo Avogadro", 28100, Novara, Italy. FAU - Nucci, Paolo AU - Nucci P AUID- ORCID: 0000-0002-4036-703X AD - Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via San Vittore 12, 20123, Milan, Italy. FAU - Luzi, Livio AU - Luzi L AUID- ORCID: 0000-0003-3183-0552 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20142, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, 20123, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250630 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Disease Progression MH - *Glycemic Control/methods MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Early worsening of diabetic retinopathy OT - Glucagon-like peptide-1 receptor agonists OT - SUSTAIN-6 trial OT - Semaglutide COIS- Declarations. Conflict of interest: The Authors have no conflicts of interest to declare. EDAT- 2025/07/01 04:47 MHDA- 2025/10/31 18:28 CRDT- 2025/06/30 11:13 PHST- 2025/02/25 00:00 [received] PHST- 2025/06/09 00:00 [accepted] PHST- 2025/10/31 18:28 [medline] PHST- 2025/07/01 04:47 [pubmed] PHST- 2025/06/30 11:13 [entrez] AID - 10.1007/s00592-025-02552-w [pii] AID - 10.1007/s00592-025-02552-w [doi] PST - ppublish SO - Acta Diabetol. 2025 Oct;62(10):1573-1583. doi: 10.1007/s00592-025-02552-w. Epub 2025 Jun 30. PMID- 40582734 OWN - NLM STAT- MEDLINE DCOM- 20250629 LR - 20250629 IS - 1558-2264 (Electronic) IS - 0733-8651 (Linking) VI - 43 IP - 3 DP - 2025 Aug TI - Role of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in Management of Cardiovascular-Kidney-Metabolic (CKM) Conditions. PG - 415-432 LID - S0733-8651(24)00113-9 [pii] LID - 10.1016/j.ccl.2024.12.003 [doi] AB - Use of glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, initially developed as glucose-lowering therapies for the management of type 2 diabetes, continues to expand in parallel with our understanding of their beneficial effects on cardiovascular-kidney-metabolic conditions. Large clinical outcome trials have established GLP-1 receptor agonists as guideline-directed therapies to improve glycemia, achieve, and maintain weight management goals, and mitigate cardiovascular and kidney risk, with early evidence suggesting similar benefits with the dual GIP/GLP-1 receptor agonist tirzepatide. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Alicic, Radica Z AU - Alicic RZ AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: Radica.Alicic@providence.org. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, 412 E. Spokane Falls Boulevard, Spokane, WA 99210, USA. LA - eng PT - Journal Article PT - Review DEP - 20250502 PL - Netherlands TA - Cardiol Clin JT - Cardiology clinics JID - 8300331 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - *Glucagon-Like Peptide 1/agonists/therapeutic use MH - *Gastric Inhibitory Polypeptide/agonists/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular outcome trials OT - Dulaglutide OT - Exenatide OT - Incretin hormones OT - Liraglutide OT - Pathomechanisms OT - Semaglutide OT - Tirzepatide COIS- Disclosures R.Z. Alicic is supported by NIH, United States research grants OT2HL161847, OT2OD032581, U24TR001608 and CDC project numbers 75D301 to 21-P-12254 and 75D301 to 23-C-18264; and reports other support from Brigham Research Institute, United States, Travere Therapeutics, United States, the Doris Duke Charitable Foundation, United States, Bayer AG, Germany, AstraZeneca, United Kingdom, Novo Nordisk, Denmark, The George Institute for Global Health, Australia, CareDx, United States, and KBP BioSciences, and personal fees from Boehringer Ingelheim, Bayer Pharmaceuticals, and Eli Lilly. J.J. Neumiller is supported by a NIH research grant OT2OD032581 and reports personal fees and other support from American College of Clinical Pharmacy, United States, Bayer AG, Sanofi, United States, Novo Nordisk, Boehringer Ingelheim, United States, Eli Lilly, Proteomics International, and Dexcom, United States. EDAT- 2025/07/01 04:06 MHDA- 2025/07/01 04:07 CRDT- 2025/06/29 20:53 PHST- 2025/07/01 04:07 [medline] PHST- 2025/07/01 04:06 [pubmed] PHST- 2025/06/29 20:53 [entrez] AID - S0733-8651(24)00113-9 [pii] AID - 10.1016/j.ccl.2024.12.003 [doi] PST - ppublish SO - Cardiol Clin. 2025 Aug;43(3):415-432. doi: 10.1016/j.ccl.2024.12.003. Epub 2025 May 2. PMID- 40582069 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20260710 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 9 DP - 2025 Sep TI - Heterogeneity of treatment effects of glucose-lowering drug classes for type 2 diabetes: LEGEND-T2DM network real-world evidence. PG - 109114 LID - S1056-8727(25)00167-9 [pii] LID - 10.1016/j.jdiacomp.2025.109114 [doi] AB - AIMS: To assess heterogeneity of treatment effects (HTE) of glucose-lowering drug classes by clinical (cardiovascular [CV] risk, renal impairment) and demographic (age, sex) subgroups in adults with type 2 diabetes mellitus (T2D). METHODS: The LEGEND-T2DM network identified 4,746,939 adults with T2D on metformin monotherapy who initiated one of four glucose-lowering drug classes: glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylureas. HTE was assessed between glucose-lowering drug classes by clinical (low CV risk vs. higher CV risk; without renal impairment vs. renal impairment) and demographic (lower vs. middle vs. older age; male vs. female) subgroups. Outcomes included MACE (primary), acute myocardial infarction, stroke, sudden cardiac death and safety endpoints. RESULTS: Pairwise differences (n = 1115 tests) between adjusted hazard ratios (HRs) showed 49 nominally significant associations (p < 0.05) and one statistically significant difference after Bonferroni correction (p < 4.5 x 10(-5)). Among older subjects (vs. younger), those taking GLP-1 RA (vs. sulfonylureas) had statistically significant difference in risk of hypoglycemia (HRs: lower age, 0.53 +/- 0.14 vs. older age, 0.20 +/- 0.05, p < 0.001). CONCLUSIONS: HTE among glucose-lowering drug classes by clinical and demographic subgroups may provide guidance to generate hypothesis-testing studies to inform T2D treatment decisions. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Davila-Garcia, David M AU - Davila-Garcia DM AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, United States; Institute for Informatics, Data Science & Biostatistics, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States. Electronic address: davila-garcia@wustl.edu. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, United States. Electronic address: tf2428@cumc.columbia.edu. FAU - Pratt, Nicole AU - Pratt N AD - Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Adelaide, Australia. Electronic address: Nicole.Pratt@unisa.edu.au. FAU - Natarajan, Karthik AU - Natarajan K AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, United States. Electronic address: kn2174@cumc.columbia.edu. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, United States. Electronic address: hripcsak@columbia.edu. LA - eng PT - Journal Article DEP - 20250626 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology/blood MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use/classification MH - Middle Aged MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Metformin/therapeutic use MH - Adult MH - Cardiovascular Diseases/epidemiology/prevention & control MH - Blood Glucose/analysis MH - Treatment Effect Heterogeneity OTO - NOTNLM OT - Clinical epidemiology OT - Glucose-lowering drug classes OT - Heterogeneity of treatment effect OT - LEGEND-T2DM OT - Real-world evidence OT - Type 2 diabetes COIS- Declaration of competing interest David M. Davila-Garcia: none; Thomas Falconer: none; Nicole Pratt: none; Karthik Natarajan: none; George Hripcsak: research grants from the US National Institutes of Health; contracts from Janssen Research and Development. EDAT- 2025/07/01 04:06 MHDA- 2025/07/10 00:36 CRDT- 2025/06/29 18:02 PHST- 2025/05/23 00:00 [received] PHST- 2025/06/20 00:00 [revised] PHST- 2025/06/23 00:00 [accepted] PHST- 2025/07/10 00:36 [medline] PHST- 2025/07/01 04:06 [pubmed] PHST- 2025/06/29 18:02 [entrez] AID - S1056-8727(25)00167-9 [pii] AID - 10.1016/j.jdiacomp.2025.109114 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Sep;39(9):109114. doi: 10.1016/j.jdiacomp.2025.109114. Epub 2025 Jun 26. PMID- 40581158 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20250801 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 226 DP - 2025 Aug TI - Clinical outcomes in people with type 2 diabetes and acute kidney disease: combined SGLT2i and GLP-1RA therapy vs. monotherapy. PG - 112339 LID - S0168-8227(25)00353-5 [pii] LID - 10.1016/j.diabres.2025.112339 [doi] AB - AIMS: To evaluate the effectiveness of combined therapy of Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus monotherapy in patients with type 2 diabetes mellitus (T2DM) and acute kidney disease (AKD). METHODS: This cohort study used TriNetX from adults with T2DM and AKD, treated with either SGLT2i, GLP-1RAs, or both from 2012 to 2023. Outcomes were all-cause mortality, major adverse kidney events (MAKE), and major adverse cardiovascular events (MACE). RESULTS: Among 29,269 patients, 1,591 (5.4 %) received combined therapy, 6,327 in the SGLT2i group, and 5,968 in the GLP-1RAs group. The combined group had significantly lower risks of all-cause mortality compared to SGLT2i monotherapy (aHR = 0.53) and GLP-1RAs monotherapy (aHR = 0.43) after a mean follow-up of 2.4 years. The combined group showed lower risks of MAKE compared to SGLT2i monotherapy (aHR = 0.70) and GLP-1RAs monotherapy (aHR = 0.45) after a mean follow-up of 2.7 years. MACE risk was similar across groups. The combined group had a higher risk of hypoglycemia (aHR = 1.51), diabetic retinopathy (aHR = 1.59) compared to the SGLT2i monotherapy group. CONCLUSIONS: Combined SGLT2i and GLP-1RA therapy offers better survival and kidney protection but requires careful monitoring for hypoglycemia and retinopathy. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan. Electronic address: kwuilus0101@gmail.com. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan City 710402, Taiwan. Electronic address: 60028A@gmail.com. FAU - Lai, Hsuan-Wen AU - Lai HW AD - Taipei Medical University, No. 250, Wuxing St., Xinyi Dist., Taipei City 110301, Taiwan; Cathay General Hospital, No. 280, Sec. 4, Ren'ai Rd., Da'an Dist., Taipei City 106438, Taiwan. Electronic address: b101108006@tmu.edu.tw. FAU - Wu, Vin-Cent AU - Wu VC AD - Department of Internal Medicine, Primary Aldosteronism Center of National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100225, Taiwan; NSARF (National Taiwan University Hospital Study Group of ARF) and TAIPAI, (Taiwan Primary Aldosteronism Investigators), Taipei, Taiwan. Electronic address: q91421028@ntu.edu.tw. LA - eng PT - Journal Article DEP - 20250626 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Drug Therapy, Combination MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - *Acute Kidney Injury/drug therapy/complications MH - *Diabetic Nephropathies/drug therapy MH - Cohort Studies OTO - NOTNLM OT - Combination OT - Glucagon-Like Peptide-1 Receptor Agonists OT - Mortality OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/01 04:46 MHDA- 2025/08/02 10:42 CRDT- 2025/06/28 19:15 PHST- 2025/04/26 00:00 [received] PHST- 2025/06/18 00:00 [revised] PHST- 2025/06/22 00:00 [accepted] PHST- 2025/08/02 10:42 [medline] PHST- 2025/07/01 04:46 [pubmed] PHST- 2025/06/28 19:15 [entrez] AID - S0168-8227(25)00353-5 [pii] AID - 10.1016/j.diabres.2025.112339 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Aug;226:112339. doi: 10.1016/j.diabres.2025.112339. Epub 2025 Jun 26. PMID- 40577036 OWN - NLM STAT- MEDLINE DCOM- 20250627 LR - 20250702 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 31 IP - 7 DP - 2025 Jul TI - Health care resource utilization and costs in Medicare Advantage beneficiaries using glucagon-like peptide-1 receptor agonists vs sodium-glucose cotransporter-2 inhibitors. PG - 627-640 LID - 10.18553/jmcp.2025.31.7.627 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended as first-line therapy for glycemic management for adults with type 2 diabetes and specific comorbidities. It is unknown whether there are meaningful differences in how GLP-1 RA vs SGLT2i therapy may affect health care resource utilization and medical costs. OBJECTIVE: To compare health care resource utilization and costs in adults with type 2 diabetes newly initiating GLP-1 RA vs SGLT2i therapy. METHODS: We used the Humana Healthcare Research database and a retrospective cohort study design to identify patients with type 2 diabetes, enrolled in a Medicare Advantage Prescription Drug plan from January 1, 2018, to June 30, 2022. Eligible patients had at least 2 pharmacy claims for a GLP-1 RA or SGLT2i drug and had at least 12 months of continuous enrollment prior to and after the first prescription claim. Propensity score matching adjusted for population differences between GLP-1 RA and SGLT2i groups. Subgroup analyses included patients with baseline atherosclerotic cardiovascular disease and obesity. Main outcomes included inpatient stays, emergency department visits, and all-cause health care costs in the 12-month follow-up period. RESULTS: The 1:1 matched cohort consisted of 22,167 individuals each treated with SGLT2i or GLP-1 RA, had a mean age of 68.2 years, and was 52.2% female, 73.4% White, and 18.6% Black. There were no significant differences in all-cause or diabetes-related inpatient stays or emergency department visits between GLP-1 RA and SGLT2i users for overall and subgroup analyses. Compared with SGLT2i patients, those on GLP-1 RA had 3.1% (95% CI = 0.9%-5.3%) higher medical costs in the overall cohort but 2.9% (95% CI = -5.5% to -0.2%) lower medical costs in the obesity subgroup. Pharmacy costs for patients on GLP-1 RA were 6% to 9% higher for overall and subgroup analyses, resulting in 4% to 6% higher total health care costs for GLP-1 RA users relative to SGLT2i users. CONCLUSIONS: There were no significant differences in health care resource utilization in the overall cohort between patients taking GLP-1 RA vs those taking SGLT2i, and pharmacy and total health care costs were higher in the GLP-1 RA group. In the obesity subgroup, GLP-1 RA initiators had lower medical costs. FAU - Poonawalla, Insiya B AU - Poonawalla IB AD - Humana Healthcare Research, Humana Inc., Louisville, KY. FAU - Abdal, Petir AU - Abdal P AD - Humana Pharmacy Solutions, Humana Inc., Louisville, KY. FAU - Hayes, Mary AU - Hayes M AD - Humana Pharmacy Solutions, Humana Inc., Louisville, KY. FAU - John, Isha AU - John I AD - Humana Pharmacy Solutions, Humana Inc., Louisville, KY. FAU - Diaz, Monica AU - Diaz M AD - Humana Pharmacy Solutions, Humana Inc., Louisville, KY. FAU - Dixon, Suzanne AU - Dixon S AD - Humana Healthcare Research, Humana Inc., Louisville, KY. FAU - Bowe, Andy AU - Bowe A AD - Humana Healthcare Research, Humana Inc., Louisville, KY. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - United States MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Medicare Part C/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Patient Acceptance of Health Care/statistics & numerical data MH - *Health Care Costs/statistics & numerical data MH - Middle Aged MH - Aged, 80 and over MH - Cohort Studies PMC - PMC12204329 COIS- Humana Healthcare Research, Inc., funded the research and manuscript development. No external funds were used in the creation of this work. Dr Poonawalla, Ms Dixon, and Mr Bowe are salaried employees of Humana Healthcare Research, Inc. Drs Abdal, Hayes, John, and Diaz are salaried employees of Humana Inc., which offers Medicare Advantage health plans. Drs Poonawalla, Abdal, Hayes, John, and Diaz own Humana stock earned as part of their employment. EDAT- 2025/06/27 12:29 MHDA- 2025/06/27 12:30 PMCR- 2025/07/01 CRDT- 2025/06/27 11:43 PHST- 2025/06/27 12:30 [medline] PHST- 2025/06/27 12:29 [pubmed] PHST- 2025/06/27 11:43 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - 10.18553/jmcp.2025.31.7.627 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2025 Jul;31(7):627-640. doi: 10.18553/jmcp.2025.31.7.627. PMID- 40571427 OWN - NLM STAT- MEDLINE DCOM- 20250626 LR - 20260806 IS - 2755-9734 (Electronic) IS - 2755-9734 (Linking) VI - 28 IP - 1 DP - 2025 Jun 26 TI - Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study. LID - 10.1136/bmjment-2025-301635 [doi] LID - e301635 AB - BACKGROUND: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. METHODS: This was a multinational self-controlled case series analysis using Hong Kong's Clinical Data Analysis and Reporting System (2008-2023), Taiwan's National Health Insurance Research Database (2012-2020) and the UK's IQVIA Medical Research Database with The Health Improvement Network (2000-2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. RESULTS: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1-30, Days 31-90, Days 91-180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. CONCLUSIONS: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. Published by BMJ Group. FAU - Peng, Zi-Yang AU - Peng ZY AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. FAU - Yan, Vincent Ka Chun AU - Yan VKC AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Wong, Vincent Kai Chung AU - Wong VKC AD - Department of Pharmacy, Queen Mary Hospital, Hong Kong SAR, China. FAU - Wong, Ian Chi Kei AU - Wong ICK AUID- ORCID: 0000-0001-8242-0014 AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China. AD - Advanced Data Analytics for Medical Science (ADAMS) Limited, Hong Kong SAR, China. AD - Aston Pharmacy School, Aston University, Birmingham, UK. FAU - Chan, Esther Wai Yin AU - Chan EWY AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China. AD - Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. AD - Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China. FAU - Wan, Eric Yuk Fai AU - Wan EYF AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China huangtz@mail.ncku.edu.tw yfwan@hku.hk. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong SAR, China. AD - Advanced Data Analytics for Medical Science (ADAMS) Limited, Hong Kong SAR, China. AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Ou, Huang-Tz AU - Ou HT AUID- ORCID: 0000-0002-5475-7848 AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan huangtz@mail.ncku.edu.tw yfwan@hku.hk. AD - Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250626 PL - England TA - BMJ Ment Health JT - BMJ mental health JID - 9918521385306676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Suicide, Attempted/statistics & numerical data MH - *Self-Injurious Behavior/epidemiology/chemically induced MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Adult MH - Case-Control Studies MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Hong Kong/epidemiology MH - Taiwan/epidemiology MH - United Kingdom/epidemiology PMC - PMC12207151 OTO - NOTNLM OT - Suicide & self-harm COIS- Competing interests: None declared. EDAT- 2025/06/27 00:28 MHDA- 2025/06/27 00:29 PMCR- 2025/06/26 CRDT- 2025/06/26 21:43 PHST- 2025/02/21 00:00 [received] PHST- 2025/06/02 00:00 [accepted] PHST- 2025/06/27 00:29 [medline] PHST- 2025/06/27 00:28 [pubmed] PHST- 2025/06/26 21:43 [entrez] PHST- 2025/06/26 00:00 [pmc-release] AID - bmjment-2025-301635 [pii] AID - 10.1136/bmjment-2025-301635 [doi] PST - epublish SO - BMJ Ment Health. 2025 Jun 26;28(1):e301635. doi: 10.1136/bmjment-2025-301635. PMID- 40571191 OWN - NLM STAT- MEDLINE DCOM- 20250725 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 5 DP - 2025 Sep TI - GLP-1 receptor agonists, body composition, skeletal muscle and risk of sarcopaenia: from promising findings in animal models to debated concern in human studies. PG - 101681 LID - S1262-3636(25)00075-8 [pii] LID - 10.1016/j.diabet.2025.101681 [doi] AB - BACKGROUND: - Glucagon-like peptide-1 (GLP-1)-based therapies induce a clinically relevant weight loss, which is associated with overall better prognosis in people with type 2 diabetes and/or clinical obesity. However, a risk of excessive reduction in fat-free mass (FFM) and skeletal muscle mass (SSM), potentially leading to sarcopaenia in at-risk patients, is currently a matter of debate as this negative effect could minimize their benefit/risk balance. METHODS: - An extensive literature search to detect animal and human studies that investigated the effects of GLP-1-based therapies on changes in body composition (FFM and SMM), muscle strength, structure, and function. RESULTS: - Favourable effects on SMM, intramuscular lipid deposition, inflammation and mitochondrial health were consistently reported in different rodent models with GLP-based therapies. However, mixed results were reported in human studies, some reported an excessive FFM/SMM loss while others arguing for a protective effect against sarcopaenia (including less myosteatosis). This controversy may result from misinterpretation of SMM derived from FFM changes and a lack of studies that properly investigate SMM, muscle function and structure in humans. CONCLUSION: - Maximizing fat loss while preserving lean (muscle) tissue mass and function is a central goal of modern obesity pharmacological treatments. Currently, available data preclude to have a definite conclusion about positive/negative effects of GLP-1-based therapies on muscle. Further investigations using accurate methodologies to assess not only SMM but also muscle structure, function (strength) and performance are needed to better analyse the effects of GLP-1-based therapies, especially among individuals at higher risk of sarcopaenia, older patients and frail people. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium; Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. Electronic address: andre.scheen@chuliege.be. LA - eng PT - Journal Article PT - Review DEP - 20250624 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Body Composition/drug effects MH - Animals MH - *Muscle, Skeletal/drug effects MH - *Sarcopenia/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Disease Models, Animal OTO - NOTNLM OT - Body composition - GLP-1 receptor agonist - Muscle - Obesity - Sarcopenia - Weight loss OT - Replace Sarcopenia by Sarcopaenia COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/06/27 00:28 MHDA- 2025/07/28 08:44 CRDT- 2025/06/26 19:15 PHST- 2025/05/19 00:00 [received] PHST- 2025/06/06 00:00 [revised] PHST- 2025/06/11 00:00 [accepted] PHST- 2025/07/28 08:44 [medline] PHST- 2025/06/27 00:28 [pubmed] PHST- 2025/06/26 19:15 [entrez] AID - S1262-3636(25)00075-8 [pii] AID - 10.1016/j.diabet.2025.101681 [doi] PST - ppublish SO - Diabetes Metab. 2025 Sep;51(5):101681. doi: 10.1016/j.diabet.2025.101681. Epub 2025 Jun 24. PMID- 40570020 OWN - NLM STAT- MEDLINE DCOM- 20250626 LR - 20260923 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 20 IP - 6 DP - 2025 TI - Superior cardiovascular protection with GLP-1 RAs over SGLT2 inhibitors in DM and HFpEF: A propensity score matching study. PG - e0326534 LID - 10.1371/journal.pone.0326534 [doi] LID - e0326534 AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and diabetes mellitus (DM) are interrelated conditions associated with high morbidity and mortality. This study compared the cardiovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus sodium-glucose cotransporter-2 (SGLT2) inhibitors in this population. METHODS: This retrospective cohort study used data from the TriNetX database. It included 2,177 matched pairs of patients with HFpEF and DM treated with either GLP-1 RAs or SGLT2 inhibitors. Outcomes assessed over three years were a composite of all-cause mortality and progression to systolic heart failure, acute myocardial infarction, or stroke. RESULTS: GLP-1 RAs significantly reduced the risk of composite outcomes at one year (Hazard Ratio, HR 0.784; 95% CI, 0.658-0.934), two years (HR 0.813; 95% CI, 0.702-0.941), and three years (HR 0.825; 95% CI, 0.717-0.950). Specifically, GLP-1 RAs showed significantly reduced risks of progression to systolic heart failure (HR 0.60) and stroke (HR 0.75) compared to SGLT2 inhibitors. These protective effects were most pronounced in the first year and showed a slightly diminishing trend. While not statistically significant, GLP-1 RAs also exhibited a trend towards fewer myocardial infarctions (HR 0.83) and lower mortality rates (HR 0.83) than SGLT2 inhibitors. Subgroup analyses revealed more significant benefits in patients aged >/=60, women, Caucasians, those without moderate-to-severe chronic kidney disease or chronic ischemic heart disease, and those with better-controlled DM. CONCLUSIONS: Among HFpEF patients with DM, GLP-1 RAs demonstrated superior cardiovascular protective effects compared with SGLT2 inhibitors over a 3-year follow-up period. Further randomized trials are required to confirm these findings. CI - Copyright: (c) 2025 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Li, Allen Cheng-Wei AU - Li AC AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of General Medicine, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan. FAU - Lin, Yang-Chi AU - Lin YC AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AUID- ORCID: 0000-0002-0794-9388 AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Chen, Lung-Ching AU - Chen LC AD - School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. AD - Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Chua, Su-Kiat AU - Chua SK AUID- ORCID: 0000-0003-1893-6360 AD - School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. AD - Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250626 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Retrospective Studies MH - *Heart Failure/drug therapy/physiopathology/complications/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Propensity Score MH - Middle Aged MH - Stroke Volume/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged, 80 and over PMC - PMC12200838 COIS- The authors have declared that no competing interests exist. EDAT- 2025/06/26 18:39 MHDA- 2025/06/26 18:40 PMCR- 2025/06/26 CRDT- 2025/06/26 13:54 PHST- 2024/09/01 00:00 [received] PHST- 2025/06/01 00:00 [accepted] PHST- 2025/06/26 18:40 [medline] PHST- 2025/06/26 18:39 [pubmed] PHST- 2025/06/26 13:54 [entrez] PHST- 2025/06/26 00:00 [pmc-release] AID - PONE-D-24-35455 [pii] AID - 10.1371/journal.pone.0326534 [doi] PST - epublish SO - PLoS One. 2025 Jun 26;20(6):e0326534. doi: 10.1371/journal.pone.0326534. eCollection 2025. PMID- 40562309 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20260603 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 9 DP - 2025 Sep TI - Use and Potential Misuse of Glucagon-Like Peptide-1 Receptor Agonists in France: A Nationwide Cohort Study. PG - 1335-1343 LID - S1098-3015(25)02404-0 [pii] LID - 10.1016/j.jval.2025.06.001 [doi] AB - OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), introduced in France in 2008 for type 2 diabetes mellitus (T2DM), have been indicated in the treatment of obesity with comorbidities since 2021. Their sharply increasing use over the last years led to supply shortages. Additionally, misuse is suspected in participants searching for weight loss. Consequently, this study aimed to describe the use of GLP-1 RAs in France and evaluate its potential misuse. METHODS: Incident users of GLP-1 RAs between January 01, 2017 and June 30, 2023 were identified in the French national health database based on the following possible indications: T2DM, obesity, and absence of T2DM or obesity. Monthly trends in GLP-1 RA use by indications were analyzed. Profiles of incident users from January 01, 2017 to June 30, 2023 were described. RESULTS: As incident GLP-1 RA users increased (5117 in January 2017 to 15 193 in June 2023), the proportion of GLP-1 RA users without T2DM or obesity rose from approximately 2% in 2020 to >5% in May 2022. These latter users, predominantly women (68.7%) who are younger than T2DM users (48.9 vs 62.0 years), included 4683 individuals (2.2% of all users) without comorbidities associated with overweight. They used predominantly OZEMPIC(R) (semaglutide). The use of GLP-1 RAs by these users was marked by a high proportion of single dispensing. Their consumption was equivalent to the annual treatment for approximately 1700 patients with T2DM or obesity. CONCLUSIONS: GLP-1 RA use has risen sharply, particularly among individuals without T2DM or obesity. Potential misuse was identified in 2.2% of users. This misuse still warrants further monitoring because the risks are unclear. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - du Soulier, Nathan AU - du Soulier N AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France. Electronic address: nathan.du-soulier@u-bordeaux.fr. FAU - Pariente, Antoine AU - Pariente A AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. FAU - Bezin, Julien AU - Bezin J AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. FAU - Grenet, Guillaume AU - Grenet G AD - Department of Medical Pharmacotoxicology, Hospices Civils de Lyon, Lyon, France. FAU - Faillie, Jean-Luc AU - Faillie JL AD - Department of Medical Pharmacology and Toxicology, CHU Montpellier, Univ. Montpellier, Montpellier, France; IDESP INSERM, Montpellier, France. FAU - de Germay, Sibylle AU - de Germay S AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250623 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - France/epidemiology MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Obesity/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Cohort Studies MH - Adult MH - Databases, Factual OTO - NOTNLM OT - GLP-1 receptor agonist OT - diabetes OT - misuse OT - obesity OT - weight management COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/06/26 00:27 MHDA- 2025/08/31 20:02 CRDT- 2025/06/25 19:14 PHST- 2024/12/12 00:00 [received] PHST- 2025/06/05 00:00 [revised] PHST- 2025/06/06 00:00 [accepted] PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/26 00:27 [pubmed] PHST- 2025/06/25 19:14 [entrez] AID - S1098-3015(25)02404-0 [pii] AID - 10.1016/j.jval.2025.06.001 [doi] PST - ppublish SO - Value Health. 2025 Sep;28(9):1335-1343. doi: 10.1016/j.jval.2025.06.001. Epub 2025 Jun 23. PMID- 40560644 OWN - NLM STAT- MEDLINE DCOM- 20250919 LR - 20250924 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 10 DP - 2025 Oct 1 TI - Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study. PG - 1728-1736 LID - 10.2337/dc25-0292 [doi] AB - OBJECTIVE: To compare the risk of lower-extremity amputations (LEAs) between new users of glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter 2 inhibitors (SGLT2is). RESEARCH DESIGN AND METHODS: This retrospective cohort study used TriNetX, a federated electronic health records network, including adults with type 2 diabetes who initiated GLP-1RAs or SGLT2is between May 2013 and March 2025. Propensity score matching (1:1) was used to balance demographics, comorbidities, medications, and laboratory values. Major (above-ankle) amputation-free survival was evaluated using Kaplan-Meier curves, while risks of major and minor LEAs, diabetic foot ulcers (DFUs), and mortality were estimated using hazard ratios (HRs) with 95% CIs. RESULTS: The matched cohorts included 180,740 GLP-1RA and 180,740 SGLT2i recipients. At 3 years, the GLP-1RA cohort was associated with greater major amputation-free survival (99.69% vs. 99.64%, P = 0.001) compared with the SGLT2i cohort. Additionally, GLP-1RA treatment was associated with a lower risk of major LEAs (HR 0.77 [95% CI 0.66, 0.90]), minor LEAs (HR 0.73 [95% CI 0.63, 0.84]), DFUs (HR 0.92 [95% CI 0.87, 0.96]), and mortality (HR 0.66 [95% CI 0.63, 0.69]). Risk reduction for major LEAs remained significant in individuals with peripheral artery disease (HR 0.68 [95% CI 0.56, 0.82]) and DFUs (HR 0.70 [95% CI 0.58, 0.84]). CONCLUSIONS: GLP-1RA treatment was associated with greater major amputation-free survival compared with SGLT2i in people with type 2 diabetes, particularly in high-risk subgroups. Prospective studies are needed to confirm findings and inform selection of glucose-lowering therapies for people at risk for diabetes-related amputations. CI - (c) 2025 by the American Diabetes Association. FAU - Hong, Alexander T AU - Hong AT AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Luu, Ivan Y AU - Luu IY AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Lin, Forest AU - Lin F AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Shin, Laura AU - Shin L AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Hsu, Chiu-Hsieh AU - Hsu CH AD - Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ. FAU - Shih, Chia-Ding AU - Shih CD AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Armstrong, David G AU - Armstrong DG AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Tan, Tze-Woei AU - Tan TW AUID- ORCID: 0000-0002-6658-9482 AD - Keck School of Medicine, University of Southern California, Los Angeles, CA. LA - eng GR - K23 DK122126/DK/NIDDK NIH HHS/United States GR - R03 DK140420/DK/NIDDK NIH HHS/United States GR - 1K23DK122126/National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases/ GR - 1R03DK140420/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Diabetes Care. 2025 Oct 1;48(10):1713-1715. doi: 10.2337/dci25-0070. PMID: 40971644 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - *Amputation, Surgical/statistics & numerical data MH - Male MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Lower Extremity/surgery MH - *Hypoglycemic Agents/therapeutic use MH - Diabetic Foot/surgery PMC - PMC12451831 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2025/06/25 12:28 MHDA- 2025/09/19 18:31 PMCR- 2025/06/25 CRDT- 2025/06/25 11:53 PHST- 2025/02/05 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/09/19 18:31 [medline] PHST- 2025/06/25 12:28 [pubmed] PHST- 2025/06/25 11:53 [entrez] PHST- 2025/06/25 00:00 [pmc-release] AID - 160665 [pii] AID - 250292 [pii] AID - 10.2337/dc25-0292 [doi] PST - ppublish SO - Diabetes Care. 2025 Oct 1;48(10):1728-1736. doi: 10.2337/dc25-0292. PMID- 40560166 OWN - NLM STAT- MEDLINE DCOM- 20260130 LR - 20260201 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 2 DP - 2026 Jan 30 TI - GLP-1-based therapeutics for cardiorenal protection in metabolic diseases. PG - 207-219 LID - 10.1093/ndt/gfaf110 [doi] AB - Over the last decade, significant progress has been made in cardiorenal protection for metabolic diseases such as type 2 diabetes (T2D) and obesity. With an expanding range of pharmacological options and continuously evolving guidelines, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have garnered substantial clinical and societal attention for their role in T2D and weight management. GLP-1RAs have consistently demonstrated robust HbA1c- and body weight-reducing efficacy in clinical and real-world studies. In addition, mounting data established their cardiorenal benefits beyond glycaemic control in select high-risk populations. In T2D, GLP-1RAs have been shown to improve both hard cardiovascular and, more recently, relevant kidney outcomes. Meanwhile, in individuals with obesity but without T2D, semaglutide (at a higher dose than in T2D) reduces body weight by up to 15% and lowers the risk of major adverse cardiovascular events by 20%. The success of GLP-1-based therapy fuelled the development of new single molecules that combine GLP-1R agonism with activation of other entero-pancreatic hormone receptors [e.g. glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin] aiming to achieve complementary and potentially synergistic effects. These next-generation GLP-1-based therapeutics for metabolic diseases, either already available or approaching clinical approval, appear to enhance metabolic and weight-reducing efficacy compared with existing GLP-1RAs. An example is tirzepatide, a dual GLP-1/GIP receptor agonist, which has been approved for both T2D and obesity management, demonstrating up to 22.5% weight loss in phase 3 trials. This review explores the landscape of current and emerging GLP-1-based therapies, their efficacy in managing hyperglycaemia and body weight, recent evidence supporting their cardiorenal benefits and clinical implications of these advancements. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Apperloo, Ellen M AU - Apperloo EM AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. FAU - Muskiet, Marcel H A AU - Muskiet MHA AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. LA - eng PT - Journal Article PT - Review PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Metabolic Diseases/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Obesity/drug therapy PMC - PMC12855604 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - kidney disease OT - obesity OT - type 2 diabetes COIS- E.M.A. reports no conflicts of interest. H.J.L.H. reports funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Novo Nordisk (all to the University of Groningen); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, Dimerix, Lilly, Fresenius, Gilead, Janssen, Novo Nordisk, Novartis and Travere Therapeutics; payment of honoraria for lectures from AstraZeneca, Novo Nordisk and Bayer; support for travel to and attending the American Diabetes Association meeting and American Society of Nephrology meeting from AstraZeneca and Lilly (to H.J.L.H. and the University of Groningen); and receipt of the study drug from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Novo Nordisk. D.H.v.R. has acted as a consultant and received honoraria from Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, Sanofi and AstraZeneca and has received research operating funds from the Boehringer Ingelheim-Lilly Diabetes Alliance, AstraZeneca and Novo Nordisk. M.H.A.M. has served as a consultant or on the advisory board for AstraZeneca, Bayer, Boehringer Ingelheim, Lilly and Novo Nordisk. EDAT- 2025/06/25 12:27 MHDA- 2026/01/30 06:30 PMCR- 2025/06/25 CRDT- 2025/06/25 10:53 PHST- 2025/04/26 00:00 [received] PHST- 2026/01/30 06:30 [medline] PHST- 2025/06/25 12:27 [pubmed] PHST- 2025/06/25 10:53 [entrez] PHST- 2025/06/25 00:00 [pmc-release] AID - 8173760 [pii] AID - gfaf110 [pii] AID - 10.1093/ndt/gfaf110 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Jan 30;41(2):207-219. doi: 10.1093/ndt/gfaf110. PMID- 40556828 OWN - NLM STAT- MEDLINE DCOM- 20250625 LR - 20250630 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs. PG - 1562815 LID - 10.3389/fendo.2025.1562815 [doi] LID - 1562815 AB - OBJECTIVE: We aimed to evaluate and compare the efficacy and safety of three antidiabetic drug classes-SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas-in patients with type 2 diabetes mellitus (T2DM) complicated by heart failure (HF). We focused on their differential effects on both cardiovascular outcomes (e.g., heart failure biomarkers and cardiac function) and metabolic outcomes (e.g., glycemic control and body weight), aiming to determine whether the newer agents offer superior cardiometabolic benefits. A network meta-analysis was conducted to integrate available evidence and compare all interventions simultaneously. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and the Cochrane Library. encompassing all available records up to December 10, 2024. Fourteen RCTs were included. A Bayesian network meta-analysis was utilized to integrate direct and indirect evidence, facilitating a comparative ranking of various SGLT2 inhibitors-canagliflozin (CANA), ipragliflozin (IPRA), empagliflozin (EMPA), remogliflozin (REMO), licogliflozin (LICO), and dapagliflozin (DAPA)-as well as one GLP-1 receptor agonist-semaglutide (SEMA)-and a sulfonylurea-glimepiride (GLIM)-with respect to their efficacy and safety profiles. RESULTS: SEMA (SMD = -0.22, 95% CI: -1.31 to 0.87) demonstrated the most favorable outcome in reducing BNP levels. LICO (SMD = -0.91, 95% CI: -1.76 to -0.06) ranked highest for body weight reduction, indicating the greatest impact. GLIM (SMD = -0.64, 95% CI: -1.12 to -0.17) showed the strongest effect on lowering HbA1c, while DAPA (SMD = 0.34, 95% CI: -0.97 to 1.65) was the top-ranked agent for improving LVEF. Safety analysis indicated that LICO and IPRA had the lowest incidence of adverse events. GLIM was associated with an increased risk of hypoglycemia, whereas DAPA was linked to a higher risk of urinary tract infections. CONCLUSION: SEMA significantly improves both metabolic control and BNP levels, making it suitable for patients requiring comprehensive management of metabolic abnormalities and heart failure. LICO offers a distinct advantage in weight management, particularly benefiting individuals with obesity. DAPA demonstrates notable efficacy in optimizing HbA1c and LVEF, making it a preferred option for patients needing more intensive cardiac support. Despite its moderate efficacy, GLIM remains a viable choice for certain patients due to its favorable safety profile and cost-effectiveness. Collectively, these findings provide essential evidence-based insights to guide individualized therapeutic strategies in type 2 diabetes complicated by heart failure. CI - Copyright (c) 2025 Gao, Wei, Zou, Yu, Song, Li, Han and Liu. FAU - Gao, Huize AU - Gao H AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Wei, Qian AU - Wei Q AD - The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Zou, Anqi AU - Zou A AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Yu, Keying AU - Yu K AD - The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Song, Da AU - Song D AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Li, Jian AU - Li J AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Han, Huize AU - Han H AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Liu, Aidong AU - Liu A AD - The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250610 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Heart Failure/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Sulfonylurea Compounds/therapeutic use PMC - PMC12185272 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - efficacy and safety OT - network meta-analysis OT - type 2 diabetes with heart failure COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/25 06:25 MHDA- 2025/06/25 06:26 PMCR- 2025/06/10 CRDT- 2025/06/25 04:27 PHST- 2025/01/18 00:00 [received] PHST- 2025/05/23 00:00 [accepted] PHST- 2025/06/25 06:26 [medline] PHST- 2025/06/25 06:25 [pubmed] PHST- 2025/06/25 04:27 [entrez] PHST- 2025/06/10 00:00 [pmc-release] AID - 10.3389/fendo.2025.1562815 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jun 10;16:1562815. doi: 10.3389/fendo.2025.1562815. eCollection 2025. PMID- 40555920 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Tirzepatide and cardiometabolic parameters in obesity: Summary of current evidence. PG - 5386-5392 LID - 10.1111/dom.16549 [doi] AB - Globally, cardiovascular diseases (CVDs) account for around one-third of all deaths. Clinical trial evidence suggests that treatment of people with obesity or type 2 diabetes (T2D) and CVD with glucagon-like peptide-1 (GLP-1) receptor agonists reduces the risk of major adverse cardiovascular events, heart failure outcomes and all-cause mortality. Tirzepatide is a once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that has demonstrated dose-dependent efficacy in people with obesity, T2D or both, in terms of glycaemic control and bodyweight reduction in clinical trials. This narrative review summarizes the current evidence regarding the effects of tirzepatide treatment on cardiometabolic parameters, including lipid profile, blood pressure and markers of renal function. Additionally, it summarizes the reported impact of tirzepatide treatment on other relevant parameters, such as body composition, liver fat, progression to T2D among individuals with prediabetes, and incidence of heart failure events. Considering the changing landscape of clinical trial evidence of tirzepatide's effects, this review aims to compile the available evidence, which suggests a promising outlook for the cardiometabolic benefits of tirzepatide. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Garcia-Perez, Luis-Emilio AU - Garcia-Perez LE AUID- ORCID: 0000-0003-3840-787X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rodriguez, Angel AU - Rodriguez A AUID- ORCID: 0000-0001-8721-9539 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kapoor, Richa AU - Kapoor R AUID- ORCID: 0009-0007-7077-2072 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Stefanski, Adam AU - Stefanski A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Hankosky, Emily R AU - Hankosky ER AUID- ORCID: 0000-0001-9934-584X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Review DEP - 20250624 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Obesity/drug therapy/complications/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Tirzepatide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Gastric Inhibitory Polypeptide/therapeutic use PMC - PMC12409218 OTO - NOTNLM OT - cardiometabolic factors OT - cardiovascular disease OT - obesity OT - tirzepatide COIS- Naveed Sattar has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics and Sanofi and grant funding paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics. Luis-Emilio Garcia-Perez, Angel Rodriguez, Richa Kapoor, Adam Stefanski and Emily R. Hankosky are employees and stockholders of Eli Lilly and Company, IN, USA. EDAT- 2025/06/25 00:28 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/06/24 23:22 PHST- 2025/05/27 00:00 [revised] PHST- 2025/03/06 00:00 [received] PHST- 2025/06/06 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/06/25 00:28 [pubmed] PHST- 2025/06/24 23:22 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16549 [pii] AID - 10.1111/dom.16549 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5386-5392. doi: 10.1111/dom.16549. Epub 2025 Jun 24. PMID- 40555703 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - PIONEER REAL Spain: A multicentre, prospective, real-world study of oral semaglutide use in adults with type 2 diabetes. PG - 4812-4824 LID - 10.1111/dom.16523 [doi] AB - AIMS: This study evaluated clinical outcomes of oral semaglutide treatment in adults with type 2 diabetes (T2D) in a real-world setting in Spain as part of the 13-country PIONEER REAL programme. MATERIALS AND METHODS: This multicentre, prospective, non-interventional, single-arm study (NCT05443334) followed participants for 34-44 weeks. Participants were treated as part of routine clinical practice and were naive to injectable glucose-lowering medication. The primary endpoint was the change in glycated haemoglobin (HbA(1c)) from baseline to end of study (EOS). Secondary endpoints included changes in body weight, the proportion of participants with HbA(1c) <7% at EOS, and treatment satisfaction. Selected outcomes were stratified (post hoc) by sodium-glucose cotransporter-2 inhibitor (SGLT2i) co-use and T2D duration. RESULTS: While 430 participants completed the study, 392 were on treatment at EOS. Estimated change in HbA(1c) was -1.4%-points (95%CI -1.5, -1.3; p < 0.0001) and in body weight -6.8% (95%CI -7.4, -6.1; p < 0.0001). In participants using SGLT2is, change in HbA(1c) was -1.8%-points (95%CI -2.1, -1.6; p < 0.0001) versus -1.2%-points (95%CI -1.3, -1.1; p < 0.0001) in participants without SGLT2is. HbA(1c) change was -1.4%-points (95%CI -1.6, -1.3; p < 0.0001) in participants with T2D duration 5 years. At EOS, 77.4% of participants achieved an HbA(1c) level <7% and 33.3% had >/=1%-point reduction in HbA(1c) and >/=5% body weight reduction. Treatment satisfaction increased, and no new safety concerns were identified. CONCLUSIONS: Oral semaglutide treatment improved glycaemic control and reduced body weight in Spanish clinical practice. Early intervention and SGLT2i co-treatment were associated with more favourable outcomes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Delgado Alvarez, Elias AU - Delgado Alvarez E AUID- ORCID: 0000-0001-6114-9712 AD - Hospital Universitario Central de Asturias, Universidad de Oviedo, Instituto de Investigacion Sanitaria del Principado de Asturias, Oviedo, Spain. AD - Centro de Investigacion Biomedica en Red Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Morales Portillo, Cristobal AU - Morales Portillo C AUID- ORCID: 0000-0003-0348-826X AD - Hospital Vithas Sevilla, Servicio de Endocrinologia, Sevilla, Spain. FAU - Abreu Padin, Cristina AU - Abreu Padin C AUID- ORCID: 0000-0002-9238-443X AD - Complejo Asistencial de Segovia, Servicio de Endocrinologia, Segovia, Spain. FAU - Aliaga Verdugo, Alberto AU - Aliaga Verdugo A AUID- ORCID: 0000-0002-4717-4345 AD - Clinica Nuevas Tecnologias en Diabetes y Endocrinologia, Sevilla, Spain. FAU - Piera Carbonell, Ana AU - Piera Carbonell A AUID- ORCID: 0000-0003-3948-0833 AD - Naranco Health Center, Public Health Service of the Principality of Asturias (SESPA), Oviedo, Spain. AD - Department of Medicine, University of Oviedo, Oviedo, Spain. FAU - Cadenas Gonzalez, Aida AU - Cadenas Gonzalez A AUID- ORCID: 0000-0002-7657-433X AD - Hospital Universitario Galdakao - Usansolo, Bizkaia, Spain. FAU - Amor Valero, Jaime AU - Amor Valero J AUID- ORCID: 0000-0001-6186-0846 AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Gonzalez Lopez, Veronica AU - Gonzalez Lopez V AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Rasmussen, Christina Louise AU - Rasmussen CL AUID- ORCID: 0000-0003-3920-373X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Scheuer, Stine Hedegaard AU - Scheuer SH AUID- ORCID: 0000-0002-1244-9871 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bellido Guerrero, Diego AU - Bellido Guerrero D AUID- ORCID: 0000-0003-0631-2710 AD - Clinica de Endocrinologia y Nutricion Dr. Bellido, Ferrol, Spain. LA - eng SI - ClinicalTrials.gov/NCT05443334 GR - N/A (sponsor of the clinical study)/Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250624 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Glycated Hemoglobin/analysis MH - Prospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Spain/epidemiology MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12326947 OTO - NOTNLM OT - GLP-1 analogue OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes OT - weight control COIS- The authors disclose the following competing interests: Elias Delgado Alvarez has received unrestricted research support from AstraZeneca, Novo Nordisk, Sanofi, Pfizer, and Roche and has received consulting fees and/or honoraria for membership on advisory boards and speakers bureaus from AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, GlaxoSmithKline, Pfizer, Almirall, Novartis, Abbott Laboratories, Esteve, and Merck Sharp & Dohme. Cristobal Morales Portillo has collaborated on clinical studies with Novo Nordisk, Sanofi, AstraZeneca, Pfizer, Eli Lilly, Merck, Lexicon, Hanmi, Janssen, Boehringer Ingelheim, Takeda, Roche, and Theracos and has served on advisory boards for Novo Nordisk, Eli Lilly, MSD, Boehringer Ingelheim, AstraZeneca, Sanofi, and Abbot and has received speaker fees from Sanofi, Novo Nordisk, AstraZeneca, Roche, Eli Lilly, Boehringer Ingelheim, MSD, Ferrer, Janssen, and Abbot. Cristina Abreu Padin has received research support from Sanofi, Novo Nordisk, Boehringer Ingelheim and Eli Lilly and has acted as a speaker for Sanofi, Novo Nordisk, Boehringer Ingelheim, AstraZeneca and Bristol-Myers Squibb. Alberto Aliaga Verdugo has received research support from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Gan & Lee, Janssen, Kowa, Lexicon, MSD, Novo Nordisk, Pfizer, and Sanofi and has received honoraria for membership on advisory boards and speakers bureaus from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. Ana Piera Carbonell has received fees for participation in presentations, talks, courses, conferences, or publications from Novo Nordisk, Novartis, MSD, Ferrer, Bayer, Sanofi-Aventis, AstraZeneca, Esteve, Boehringer Ingelheim, and Mylan. Aida Cadenas Gonzalez has received support for training, research, or outreach from GSK, Boehringer Ingelheim, Menarini, Janssen, Novo Nordisk, Pfizer, Esteve, Sanofi, Eli Lilly, Viatris, Faes, Alter, AstraZeneca, MSD, Fresenius, Rovi, Mundipharma, Daiichi Sankyo, Novartis, and Amarin. Jaime Amor Valero is an employee of Novo Nordisk Pharma SA. Veronica Gonzalez Lopez is an employee of Novo Nordisk Pharma SA. Christina Louise Rasmussen is an employee of Novo Nordisk A/S. Stine Hedegaard Scheuer is an employee of Novo Nordisk A/S. Diego Bellido Guerrero has received unrestricted research support from Novo Nordisk, Sanofi, Pfizer, Nestle HC, Persan Pharma, Abbott Laboratories and Eli Lilly and has received consulting fees and/or honoraria for membership on advisory boards and speakers bureaus from Novo Nordisk, Sanofi, Abbott Laboratories, and Eli Lilly. EDAT- 2025/06/25 00:28 MHDA- 2025/08/06 12:29 PMCR- 2025/08/06 CRDT- 2025/06/24 23:03 PHST- 2025/05/22 00:00 [revised] PHST- 2025/04/08 00:00 [received] PHST- 2025/05/30 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/06/25 00:28 [pubmed] PHST- 2025/06/24 23:03 [entrez] PHST- 2025/08/06 00:00 [pmc-release] AID - DOM16523 [pii] AID - 10.1111/dom.16523 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):4812-4824. doi: 10.1111/dom.16523. Epub 2025 Jun 24. PMID- 40553729 OWN - NLM STAT- MEDLINE DCOM- 20250804 LR - 20260702 IS - 1538-9375 (Electronic) IS - 1525-8610 (Linking) VI - 26 IP - 8 DP - 2025 Aug TI - Pattern of Antidiabetic Drug Prescription in Older Persons With Type 2 Diabetes: Results From the German DPV Registry. PG - 105724 LID - S1525-8610(25)00241-5 [pii] LID - 10.1016/j.jamda.2025.105724 [doi] AB - OBJECTIVES: To explore prescription patterns of SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) in older adults with type 2 diabetes (T2DM), analyzing age and sex differences. DESIGN: Observational retrospective study. SETTING AND PARTICIPANTS: Data from 103,820 patients aged 60 to 90 years from 518 diabetes centers in Germany, collected between 2017 and 2022 via the DPV registry. METHODS: Patients with at least 3 months' T2DM diagnosis were included. Treatment trends were analyzed using regression models adjusted for age and sex. Repeated measures were aggregated annually. RESULTS: Between 2017 and 2022, SGLT2i use rose from 7.3% to 27.4% and GLP-1RA use from 3.4% to 13.8%. Metformin use increased, while sulfonylureas declined. SGLT2i use was lower in women across all age groups. GLP-1RAs use increased more in younger patients. CONCLUSIONS AND IMPLICATIONS: Newer antidiabetic drugs are increasingly prescribed in older adults, but notable disparities by age and gender persist. These findings suggest the need to address potential biases and barriers to optimize equitable care in geriatric diabetes management. CI - Copyright (c) 2025 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved. FAU - Zeyfang, Andrej AU - Zeyfang A AD - Department of Internal Medicine, Geriatric Medicine and Diabetology, Medius Klinik Ostfildern-Ruit, Ostfildern, Germany; Institute of Epidemiology and Medical Biometry, CAQM, Ulm University, Ulm, Germany. Electronic address: andrej.zeyfang@gmail.com. FAU - Golz, Stefan AU - Golz S AD - Amedes MVZ for Diabetology, Esslingen, Germany. FAU - Iraci, Federica AU - Iraci F AD - Department of Internal Medicine, Geriatric Medicine and Diabetology, Medius Klinik Ostfildern-Ruit, Ostfildern, Germany. FAU - Wagner, Christian AU - Wagner C AD - Specialist Practice for Diabetology, Surheim, Germany. FAU - Scheer, Christian AU - Scheer C AD - Department of Internal Medicine, Prenzlau Hospital, Prenzlau, Germany. FAU - Kubiak, Thomas AU - Kubiak T AD - Department of Health Psychology, Johannes Gutenberg University, Mainz, Germany. FAU - Bozkurt, Latife AU - Bozkurt L AD - Department of Medicine III and Karl Landsteiner Institute for Metabolic Diseases and Nephrology, Clinic Hietzing, Vienna Health Care Group, Vienna, Austria. FAU - Heni, Martin AU - Heni M AD - Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany; Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tubingen, Tubingen, Germany. FAU - Holl, Reinhard W AU - Holl RW AD - Institute of Epidemiology and Medical Biometry, CAQM, Ulm University, Ulm, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250628 PL - United States TA - J Am Med Dir Assoc JT - Journal of the American Medical Directors Association JID - 100893243 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Female MH - Male MH - Germany MH - *Hypoglycemic Agents/therapeutic use MH - Registries MH - Retrospective Studies MH - Aged, 80 and over MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RA (glucagon-like peptide-1 receptor agonists) OT - SGLT2i (sodium-glucose cotransporter-2 inhibitors) OT - cardiovascular/renal benefits OT - older adults OT - treatment patterns OT - type-2 diabetes COIS- Disclosure The authors declare that there are no conflicts of interest that have influenced the study design, data interpretation, or reporting of the findings. EDAT- 2025/06/24 18:30 MHDA- 2025/08/05 00:29 CRDT- 2025/06/24 13:02 PHST- 2024/10/09 00:00 [received] PHST- 2025/05/05 00:00 [revised] PHST- 2025/05/07 00:00 [accepted] PHST- 2025/08/05 00:29 [medline] PHST- 2025/06/24 18:30 [pubmed] PHST- 2025/06/24 13:02 [entrez] AID - S1525-8610(25)00241-5 [pii] AID - 10.1016/j.jamda.2025.105724 [doi] PST - ppublish SO - J Am Med Dir Assoc. 2025 Aug;26(8):105724. doi: 10.1016/j.jamda.2025.105724. Epub 2025 Jun 28. PMID- 40552638 OWN - NLM STAT- MEDLINE DCOM- 20250913 LR - 20260829 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 106 IP - 4 DP - 2025 Aug TI - Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study. PG - 1509-1522 LID - 10.1177/13872877251351329 [doi] AB - BACKGROUND: Almost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia. OBJECTIVE: We aim to investigate if semaglutide is associated with a decreased risk of dementia. METHODS: We conducted emulation target trials based on a nationwide population-based database of patient electronic health records (EHRs) in the US among 1,710,995 eligible patients with type 2 diabetes (T2D) comparing semaglutide with other antidiabetic medications. First-time diagnosis of Alzheimer's disease-related dementia (ADRD) including vascular dementia, frontotemporal dementia, Lewy body dementia and other dementias were examined using Cox proportional hazards and Kaplan-Meier survival analyses during a 3-year follow-up. Models were adjusted by propensity-score matching. RESULTS: We show that semaglutide was associated with a significantly reduced risk of overall ADRD incidence with a hazard ratio ranging from 0.54 (0.49-0.59) compared with insulin, 0.67 (0.61-0.74) compared with metformin, to 0.80 (0.72-0.89) compared with older generation glucagon-like peptide-1 agonists (GLP-1RAs). The association varied for specific dementia types, with significantly reduced risk of vascular dementia and no evidence of associations with frontotemporal and Lewy body dementias. CONCLUSIONS: These findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D. Future works are needed to establish the causal relationships through randomized clinical trials and to characterize the underlying mechanisms. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Qi, Xin AU - Qi X AD - Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Gurney, Mark AU - Gurney M AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Perry, George AU - Perry G AUID- ORCID: 0000-0002-6547-0172 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. AD - Department of Neuroscience, Development and Regenerative Biology, College of Sciences, The University of Texas at San Antonio, San Antonio, TX, USA. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, North Bethesda, MD, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AG076051/AG/NIA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - R01 AG074346/AG/NIA NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - R01 AG065240/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250624 PL - United States TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - *Alzheimer Disease/epidemiology/prevention & control MH - Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Aged, 80 and over MH - *Dementia/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12262134 MID - NIHMS2093772 OTO - NOTNLM OT - Alzheimer's disease related dementias OT - Alzheimer's disease OT - Lewy body dementia OT - dementia OT - frontotemporal dementia OT - semaglutide OT - target trial emulation OT - type 2 diabetes OT - vascular dementia COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: George Perry is an Editor-in-Chief of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/06/24 13:08 MHDA- 2025/09/13 12:30 PMCR- 2025/07/15 CRDT- 2025/06/24 07:13 PHST- 2025/09/13 12:30 [medline] PHST- 2025/06/24 13:08 [pubmed] PHST- 2025/06/24 07:13 [entrez] PHST- 2025/07/15 00:00 [pmc-release] AID - 10.1177/13872877251351329 [doi] PST - ppublish SO - J Alzheimers Dis. 2025 Aug;106(4):1509-1522. doi: 10.1177/13872877251351329. Epub 2025 Jun 24. PMID- 40550229 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20260919 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 406 IP - 10499 DP - 2025 Jul 12 TI - Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial. PG - 135-148 LID - S0140-6736(25)01176-6 [pii] LID - 10.1016/S0140-6736(25)01176-6 [doi] AB - BACKGROUND: GLP-1 receptor agonists and amylin receptor agonists have shown clinically relevant weight loss and glucose-lowering effects in people with overweight, obesity, and type 2 diabetes. Amycretin is a novel, single-molecule GLP-1 receptor and amylin receptor agonist. We aimed to investigate the safety, tolerability, pharmacokinetic properties, and pharmacodynamic effects of single ascending doses (part A) and multiple ascending doses (parts B and C/D) of amycretin in adult participants with overweight or obesity. METHODS: In this phase 1, first-in-human, randomised, double-blind, placebo-controlled multipart study, participants were recruited at a single clinical research unit in San Antonio (TX, USA). Eligible individuals were men or women (including women of childbearing potential) aged 18-55 years at the time of signing informed consent with a BMI of 25.0-34.9 kg/m(2) for parts A and B and a BMI of 27.0-39.9 kg/m(2) for part C/D. For part A, participants were randomly assigned across six treatment groups (single ascending doses of oral amycretin [1 mg, 3 mg, 6 mg, 12 mg, 18 mg (12 + 6 mg per adaptive study design), or 25 mg]) or placebo (6:2 to amycretin groups vs placebo). Part A consisted of a 28-day screening period, a 1-day (single dose) intervention period, and a 21-day follow-up period. In part B, participants were randomly assigned across three treatment groups (multiple ascending doses of oral amycretin [3 mg, 6 mg, or 12 mg once daily]) or placebo (9:3 to amycretin groups vs placebo). Part B consisted of a 28-day screening period, a 10-day intervention period, and a 21-day follow-up period. In part C/D, 60 participants were randomly assigned to one of three dose-escalation treatment groups (multiple ascending doses of oral amycretin in a fixed titration regimen for all participants [part C1: from 3 mg to 50 mg once daily; part C2: from 6 mg to 2 x 50 mg (two tablets in a single daily dose); and part D: from 3 mg to 2 x 25 mg (two tablets in a single daily dose)]), or placebo (16:4 to amycretin groups vs placebo). Part C/D consisted of a 4-week screening period, a 12-week intervention period, and a 3-week follow-up period. The primary endpoint was the number of treatment-emergent adverse events reported from before dosing on day 1 (baseline) until the end-of-study visit on day 22 (part A), day 31 (part B), or day 105 (part C/D). Supportive secondary pharmacokinetic endpoints for parts A-D were area under the amycretin plasma concentration-time curve and maximum plasma concentration. Exploratory pharmacodynamic endpoints in part C/D were change in bodyweight (%) and fasting plasma glucose (mmol/L) from before dosing on day 1 until day 85. The safety analysis set, comprising all participants who were exposed to treatment, was used to analyse the endpoints and assessments related to safety. The full analysis set, comprising all randomly assigned participants, was used to analyse endpoints related to pharmacokinetic and exploratory pharmacodynamic endpoints. This study is registered with ClinicalTrials.gov, NCT05369390. FINDINGS: Between May 11, 2022, and Jan 9, 2024, 144 participants were enrolled in the study (48 participants in part A, 36 participants in part B, and 60 participants in part C/D). Across parts A-D, there were 364 treatment-emergent adverse events in 89 (62%) of 144 participants, all of which were mild or moderate in severity and increased in frequency in a dose-dependent manner. The most common treatment-emergent adverse events were gastrointestinal in nature (180 [49%] of 364 events), observed in 72 (81%) of 89 participants who reported a treatment-emergent adverse event. No deaths were reported. Amycretin plasma concentrations were consistent with dose proportionality across all treatment groups. INTERPRETATION: In people with overweight or obesity, amycretin appeared safe and tolerable. Results from this first-in-human, phase 1 study support further investigation of the weight loss properties of amycretin. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Gasiorek, Agnes AU - Gasiorek A AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark. Electronic address: aggq@novonordisk.com. FAU - Heydorn, Arne AU - Heydorn A AD - Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Gabery, Sanaz AU - Gabery S AD - Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Hjerpsted, Julie B AU - Hjerpsted JB AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark. FAU - Kirkeby, Katrine AU - Kirkeby K AD - Novo Nordisk A/S, Alborg, Denmark. FAU - Kruse, Thomas AU - Kruse T AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark. FAU - Petersen, Signe B AU - Petersen SB AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark. FAU - Toubro, Soren AU - Toubro S AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark. FAU - Vegge, Andreas AU - Vegge A AD - Research and Early Development, Novo Nordisk A/S, Malov, Denmark; Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Key, Cassandra AU - Key C AD - San Antonio Clinical Research Unit, ICON, San Antonio, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT05369390 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250620 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Amylin Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Double-Blind Method MH - Adult MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Amylin Receptor Agonists MH - *Obesity/drug therapy MH - Young Adult MH - *Hypoglycemic Agents/pharmacokinetics/adverse effects/administration & dosage/pharmacology MH - Adolescent MH - *Overweight/drug therapy MH - Dose-Response Relationship, Drug MH - Diabetes Mellitus, Type 2/drug therapy COIS- Declaration of interests AG, AH, SG, JBH, KK, TK, SBP, ST, and AV are employees of and shareholders in Novo Nordisk A/S. CK is an employee of ICON (contract research organisation). ICON received funding from Novo Nordisk A/S for conducting the clinical study described in this manuscript, for which CK was the principal investigator. EDAT- 2025/06/24 11:08 MHDA- 2025/07/13 03:40 CRDT- 2025/06/23 18:52 PHST- 2025/01/14 00:00 [received] PHST- 2025/05/09 00:00 [revised] PHST- 2025/06/02 00:00 [accepted] PHST- 2025/07/13 03:40 [medline] PHST- 2025/06/24 11:08 [pubmed] PHST- 2025/06/23 18:52 [entrez] AID - S0140-6736(25)01176-6 [pii] AID - 10.1016/S0140-6736(25)01176-6 [doi] PST - ppublish SO - Lancet. 2025 Jul 12;406(10499):135-148. doi: 10.1016/S0140-6736(25)01176-6. Epub 2025 Jun 20. PMID- 40549942 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20260127 IS - 1940-5480 (Electronic) IS - 1067-151X (Linking) VI - 33 IP - 16 DP - 2025 Jun 17 TI - Reduced 90-Day Cardiovascular and Infectious Complications After Open Reduction Internal Fixation of Ankle Fractures in Type II Diabetic Patients Using Semaglutide Preoperatively. PG - e971-e978 LID - 10.5435/JAAOS-D-25-00439 [doi] AB - BACKGROUND: Patients with type II diabetes mellitus (T2DM) are known to have inferior postoperative outcomes after open reduction and internal fixation (ORIF) of ankle fractures. Semaglutide (the active agent in Ozempic) has encouragingly been associated with improved postoperative outcomes across multiple elective orthopaedic surgeries; however, this has not been assessed for patients with T2DM undergoing ankle fracture ORIF. METHODS: Adult patients with T2DM who underwent ankle fracture ORIF were identified from the 2010-Q1 2023 PearlDiver M170Ortho database. Exclusion criteria included the following: age younger than 18, high-energy injury mechanisms, concomitant tibial plafond fracture, other non-ankle traumatic injuries, neoplastic or infectious diagnoses within 30 days preoperatively, and those with <90 days of follow-up. Patients with T2DM who used semaglutide within 1 year before ankle fracture ORIF were identified and matched 1:1 with patients with T2DM who had not used semaglutide based on age, sex, Elixhauser Comorbidity Index, end-organ diabetes complications, obesity (body mass index <30 vs. >30), insulin use, metformin use, sodium-glucose cotransport-2 inhibitor use, and insurance plan. The odds of 90-day adverse events were compared by multivariable logistic regression controlling for age, sex, and Elixhauser Comorbidity Index. Bonferroni correction of P < 0.005 was used to reduce the risk of type I error. RESULTS: Among patients with T2DM undergoing ankle fracture ORIF, semaglutide use was noted for 2,700 patients (2.73%). After matching, there were 804 (+)semaglutide and 804 (-)semaglutide patients. On multivariable analysis, (+)semaglutide patients had significantly lower odds of 90-day deep vein thrombosis (odds ratio [OR] 0.24), myocardial infarction (OR 0.34), surgical site infection (OR 0.30), sepsis (OR 0.38), pneumonia (OR 0.27), urinary tract infection (OR 0.27), wound dehiscence (OR 0.31), and emergency department visit (OR 0.45; P < 0.001 for all). CONCLUSION: This study found reductions in 90-day cardiovascular and infectious complications after ORIF of ankle fractures for patients with T2DM using semaglutide preoperatively as part of their glycemic control regimen. LEVEL OF EVIDENCE: Level III. CI - Copyright (c) 2025 by the American Academy of Orthopaedic Surgeons. FAU - Seddio, Anthony E AU - Seddio AE AD - From the Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Vasudevan, Rajiv S AU - Vasudevan RS FAU - Jonnalagadda, Anshu AU - Jonnalagadda A FAU - Slevin, John P AU - Slevin JP FAU - Grauer, Jonathan N AU - Grauer JN AUID- ORCID: 0000-0002-2626-7278 FAU - Fram, Brianna R AU - Fram BR LA - eng PT - Journal Article DEP - 20250617 PL - United States TA - J Am Acad Orthop Surg JT - The Journal of the American Academy of Orthopaedic Surgeons JID - 9417468 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - *Ankle Fractures/surgery/complications MH - *Fracture Fixation, Internal/adverse effects/methods MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - *Postoperative Complications/prevention & control/epidemiology MH - *Surgical Wound Infection/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/06/24 11:03 MHDA- 2025/08/01 18:34 CRDT- 2025/06/23 15:13 PHST- 2025/04/06 00:00 [received] PHST- 2025/05/03 00:00 [accepted] PHST- 2025/08/01 18:34 [medline] PHST- 2025/06/24 11:03 [pubmed] PHST- 2025/06/23 15:13 [entrez] AID - 00124635-990000000-01352 [pii] AID - 10.5435/JAAOS-D-25-00439 [doi] PST - epublish SO - J Am Acad Orthop Surg. 2025 Jun 17;33(16):e971-e978. doi: 10.5435/JAAOS-D-25-00439. PMID- 40549887 OWN - NLM STAT- MEDLINE DCOM- 20250903 LR - 20251203 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 393 IP - 9 DP - 2025 Sep 4 TI - Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. PG - 843-857 LID - 10.1056/NEJMoa2504214 [doi] AB - BACKGROUND: Maridebart cafraglutide (known as MariTide) is a long-acting peptide-antibody conjugate that combines glucagon-like peptide-1 receptor agonism and glucose-dependent insulinotropic polypeptide receptor antagonism and that is intended for the treatment of obesity. METHODS: We conducted a phase 2, double-blind, randomized, placebo-controlled, dose-ranging trial that included 11 groups as two cohorts. Participants with obesity (obesity cohort) were randomly assigned in a 3:3:3:2:2:2:3 ratio to receive maridebart cafraglutide subcutaneously at a dose of 140, 280, or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with 4-week dose escalation; 420 mg every 4 weeks with 12-week dose escalation; or placebo. Participants with obesity with type 2 diabetes (obesity-diabetes cohort) were randomly assigned in a 1:1:1:1 ratio to receive maridebart cafraglutide at a dose of 140, 280, or 420 mg every 4 weeks (all without dose escalation) or placebo. The primary end point was the percent change in body weight from baseline to week 52. RESULTS: We enrolled 592 participants. In the obesity cohort (465 participants; female sex, 63%; mean age, 47.9 years; mean body-mass index [BMI, the weight in kilograms divided by the square of the height in meters], 37.9), the mean percent change in body weight from baseline to week 52 on the basis of the treatment policy estimand (intention-to-treat approach) ranged from -12.3% (95% confidence interval [CI], -15.0 to -9.7) to -16.2% (95% CI, -18.9 to -13.5) with maridebart cafraglutide, as compared with -2.5% (95% CI, -4.2 to -0.7) with placebo. In the obesity-diabetes cohort (127 participants; female sex, 42%; mean age, 55.1 years; mean BMI, 36.5), the mean percent change in body weight from baseline to week 52 on the basis of the treatment policy estimand ranged from -8.4% (95% CI, -11.0 to -5.7) to -12.3% (95% CI, -15.3 to -9.2) with maridebart cafraglutide, as compared with -1.7% (95% CI, -2.9 to -0.6) with placebo. The mean change in the glycated hemoglobin level on the basis of the treatment policy estimand in this cohort was -1.2 to -1.6 percentage points in the maridebart cafraglutide groups and 0.1 percentage points in the placebo group. Gastrointestinal adverse events were common with maridebart cafraglutide, although less frequent with dose escalation and a lower starting dose. No unexpected safety signals emerged. CONCLUSIONS: In this phase 2 trial, once-monthly maridebart cafraglutide resulted in substantial weight reduction in participants with obesity with or without type 2 diabetes. (Funded by Amgen; ClinicalTrials.gov number, NCT05669599.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - Jastreboff, Ania M AU - Jastreboff AM AUID- ORCID: 0000-0003-1446-0991 AD - Section of Endocrinology and Metabolism, Department of Medicine, Yale School of Medicine, New Haven, CT. AD - Section of Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, CT. AD - Yale Obesity Research Center (Y-Weight), Yale School of Medicine, New Haven, CT. FAU - Ryan, Donna H AU - Ryan DH AD - Pennington Biomedical Research Center, Baton Rouge, LA. FAU - Bays, Harold E AU - Bays HE AD - Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, Louisville, KY. FAU - Ebeling, Peter R AU - Ebeling PR AD - Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. FAU - Mackowski, Mia G AU - Mackowski MG AD - Amgen, Thousand Oaks, CA. FAU - Philipose, Nisha AU - Philipose N AD - Amgen, Thousand Oaks, CA. FAU - Ross, Leorah AU - Ross L AD - Amgen, Thousand Oaks, CA. FAU - Liu, Yimeng AU - Liu Y AD - Amgen, Thousand Oaks, CA. FAU - Burns, Cassandra E AU - Burns CE AD - Amgen, Thousand Oaks, CA. FAU - Abbasi, Siddique A AU - Abbasi SA AD - Amgen, Thousand Oaks, CA. FAU - Pannacciulli, Nicola AU - Pannacciulli N AD - Amgen, Thousand Oaks, CA. CN - MariTide Phase 2 Obesity Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT05669599 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250623 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoconjugates) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM CIN - N Engl J Med. 2025 Dec 4;393(22):2274. doi: 10.1056/NEJMc2514331. PMID: 41337722 CIN - N Engl J Med. 2025 Dec 4;393(22):2274-2275. doi: 10.1056/NEJMc2514331. PMID: 41337723 CIN - N Engl J Med. 2025 Dec 4;393(22):2275. doi: 10.1056/NEJMc2514331. PMID: 41337724 MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Injections, Subcutaneous MH - *Obesity/drug therapy/complications MH - *Weight Loss/drug effects MH - Immunoconjugates MH - Receptors, Gastrointestinal Hormone/antagonists & inhibitors MH - Glucagon-Like Peptide 1/administration & dosage/adverse effects/analogs & derivatives MH - Aged FIR - Polasek, Thomas IR - Polasek T FIR - Markovic, Tania IR - Markovic T FIR - Reutens, Anne IR - Reutens A FIR - MacIsaac, Richard IR - MacIsaac R FIR - Ekinci, Elif IR - Ekinci E FIR - Ebeling, Peter IR - Ebeling P FIR - Poirier, Paul IR - Poirier P FIR - Bergeron, Jean IR - Bergeron J FIR - Bajaj, Harpreet IR - Bajaj H FIR - Lau, David IR - Lau D FIR - Schlosser, Robert IR - Schlosser R FIR - Braunerova, Radka Taxova IR - Braunerova RT FIR - Haluzik, Martin IR - Haluzik M FIR - Matoulek, Martin IR - Matoulek M FIR - Blueher, Matthias IR - Blueher M FIR - Dahl, Dominik IR - Dahl D FIR - Mai, Knut IR - Mai K FIR - Luk, On Yan Andrea IR - Luk OYA FIR - Kesmarky, Gabor IR - Kesmarky G FIR - Kovacs, Melinda IR - Kovacs M FIR - Pall, Istvan IR - Pall I FIR - Toldy Schedel, Emil IR - Toldy Schedel E FIR - Hasumi, Sumiko IR - Hasumi S FIR - Ito, Kumie IR - Ito K FIR - Miyata, Toshio IR - Miyata T FIR - Hayashi, Makoto IR - Hayashi M FIR - Shiraiwa, Toshihiko IR - Shiraiwa T FIR - Niiya, Tetsuji IR - Niiya T FIR - Osonoi, Takeshi IR - Osonoi T FIR - Hashimoto, Toshihiko IR - Hashimoto T FIR - Tsuji, Hideyuki IR - Tsuji H FIR - Lukaszewicz, Monika IR - Lukaszewicz M FIR - Wyzgowski, Przemyslaw IR - Wyzgowski P FIR - Jozefowska, Malgorzata IR - Jozefowska M FIR - Baszczynski, Jakub IR - Baszczynski J FIR - Smolen, Agata IR - Smolen A FIR - Wasilewska, Marta IR - Wasilewska M FIR - Lim, Soo IR - Lim S FIR - Kim, Kyoung Kon IR - Kim KK FIR - Kang, Jae-Heon IR - Kang JH FIR - Oh, Sang Woo IR - Oh SW FIR - Tinahones Madueno, Francisco Jose IR - Tinahones Madueno FJ FIR - Lecube Torello, Albert IR - Lecube Torello A FIR - Morales Portillo, Cristobal Jesus IR - Morales Portillo CJ FIR - Soto Gonzalez, Alfonso IR - Soto Gonzalez A FIR - Huang, Kuo-Chin IR - Huang KC FIR - Lin, Wen-Yuan IR - Lin WY FIR - Yang, Yi-Ching IR - Yang YC FIR - Lin, Tsung-Hsien IR - Lin TH FIR - Neutel, Joel IR - Neutel J FIR - Christiansen, Mark IR - Christiansen M FIR - Kipnes, Mark IR - Kipnes M FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Rudraraju, Madhavi IR - Rudraraju M FIR - Bays, Harold IR - Bays H FIR - White, Alexander IR - White A FIR - Weinstock, Ruth IR - Weinstock R FIR - Defronzo, Ralph IR - Defronzo R FIR - Henry, Timothy IR - Henry T FIR - Pannain, Silvana IR - Pannain S FIR - Denham, Douglas IR - Denham D FIR - Fatakia, Adil IR - Fatakia A FIR - Kim, Kenneth IR - Kim K FIR - Smith, Timothy IR - Smith T FIR - Brown, Ingrid IR - Brown I FIR - Vutikullird, Apinya IR - Vutikullird A FIR - Trivedi, Rupal IR - Trivedi R FIR - Romero, Christopher IR - Romero C FIR - Swain, James IR - Swain J FIR - Uribe, Eduardo IR - Uribe E FIR - Steil, Kenneth IR - Steil K FIR - Hopland, Jeffrey IR - Hopland J FIR - Fanning, Martha Sue IR - Fanning MS FIR - Mauri, Monica IR - Mauri M FIR - Studdard, Harry Earl IR - Studdard HE FIR - Glover, Richard IR - Glover R FIR - Connery, Lisa IR - Connery L FIR - Lucas, Kathryn IR - Lucas K EDAT- 2025/06/24 11:05 MHDA- 2025/09/03 18:36 CRDT- 2025/06/23 14:53 PHST- 2025/09/03 18:36 [medline] PHST- 2025/06/24 11:05 [pubmed] PHST- 2025/06/23 14:53 [entrez] AID - 10.1056/NEJMoa2504214 [doi] PST - ppublish SO - N Engl J Med. 2025 Sep 4;393(9):843-857. doi: 10.1056/NEJMoa2504214. Epub 2025 Jun 23. PMID- 40544585 OWN - NLM STAT- MEDLINE DCOM- 20250724 LR - 20250724 IS - 1095-9157 (Electronic) IS - 0896-8411 (Linking) VI - 155 DP - 2025 Jul TI - Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study. PG - 103453 LID - S0896-8411(25)00098-8 [pii] LID - 10.1016/j.jaut.2025.103453 [doi] AB - INTRODUCTION: The therapeutic advantages of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in diabetes management have been demonstrated. However, their potential association with autoimmune diseases remains unknown. Using a comprehensive real-world dataset, this study compared GLP-1 RAs against dipeptidyl peptidase-4 inhibitors (DPP-4is) with respect to the incidence of autoimmune diseases. METHODS: This retrospective cohort study, with an active-comparator and new-user design, analyzed data from the TriNetX US Collaborative Network. We identified 4,841,560 patients aged over 18 years with type 2 diabetes from 1 January 2015 to 31 December 2022. Finally, 412,021 and 383,415 patients were included in the GLP-1 RAs and DPP-4is groups, respectively. Propensity score matching was used to balance baseline characteristics, and hazard ratios (HRs) were estimated with Cox regression models over an eight-year follow-up. RESULTS: After propensity score matching, each group included 290,770 patients. The analysis revealed that patients receiving GLP-1 RAs exhibited significantly higher risks of certain autoimmune conditions, including ulcerative colitis (HR, 1.11; 95 % CI, 1.04-1.19), rheumatoid arthritis (HR, 1.08; 95 % CI, 1.03-1.12), autoimmune thyroiditis (HR, 1.30; 95 % CI, 1.24-1.38), ankylosing spondylitis (HR, 1.30; 95 % CI, 1.13-1.51), and psoriasis (HR, 1.17; 95 % CI, 1.12-1.22), compared to those on DPP-4is. Moreover, sensitivity analyses consistently revealed a significant link between GLP-1 RAs use and autoimmune diseases. CONCLUSIONS: This study suggests that compared with DPP-4is, the use of GLP-1 RAs is linked to increased risks of certain autoimmune diseases. Careful monitoring might be required among patients on GLP-1 RAs. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Lee, Yun-Jui AU - Lee YJ AD - Division of General Medicine, Department of Medical Education, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Chen, Mon-Ting AU - Chen MT AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Liou, Hung-Hsiang AU - Liou HH AD - Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan. FAU - Li, Tzu-Hao AU - Li TH AD - Division of Rheumatology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. Electronic address: chaosmyth.tw@gmail.com. LA - eng PT - Journal Article DEP - 20250621 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Autoimmune Diseases/epidemiology/etiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Retrospective Studies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Aged MH - Adult MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence OTO - NOTNLM OT - Autoimmune diseases OT - Diabetes mellitus OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Real-world evidence EDAT- 2025/06/23 06:13 MHDA- 2025/07/25 00:28 CRDT- 2025/06/22 18:02 PHST- 2025/02/13 00:00 [received] PHST- 2025/06/14 00:00 [revised] PHST- 2025/06/15 00:00 [accepted] PHST- 2025/07/25 00:28 [medline] PHST- 2025/06/23 06:13 [pubmed] PHST- 2025/06/22 18:02 [entrez] AID - S0896-8411(25)00098-8 [pii] AID - 10.1016/j.jaut.2025.103453 [doi] PST - ppublish SO - J Autoimmun. 2025 Jul;155:103453. doi: 10.1016/j.jaut.2025.103453. Epub 2025 Jun 21. PMID- 40544435 OWN - NLM STAT- MEDLINE DCOM- 20250917 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 393 IP - 11 DP - 2025 Sep 18 TI - Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. PG - 1065-1076 LID - 10.1056/NEJMoa2505669 [doi] AB - BACKGROUND: Orforglipron is a small-molecule, nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist in clinical development for type 2 diabetes and weight management. Additional data on the efficacy and safety of orforglipron are needed. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks. Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0. The primary end point was the change from baseline to week 40 in the glycated hemoglobin level. A key secondary end point was the percent change in body weight from baseline to week 40. RESULTS: A total of 559 participants underwent randomization. The mean glycated hemoglobin level at baseline was 8.0%. At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo. All three doses of orforglipron were superior to placebo with respect to the primary end point; the estimated mean difference from placebo was -0.83 percentage points (95% confidence interval [CI], -1.10 to -0.56) with the 3-mg dose, -1.06 percentage points (95% CI, -1.33 to -0.79) with the 12-mg dose, and -1.07 percentage points (95% CI, -1.33 to -0.81) with the 36-mg dose (P<0.001 for all comparisons). The mean glycated hemoglobin level at week 40 was 6.5 to 6.7% with orforglipron. The percent change in body weight from baseline to week 40 was -4.5% with the 3-mg dose, -5.8% with the 12-mg dose, -7.6% with the 36-mg dose, and -1.7% with placebo. The most common adverse events were mild-to-moderate gastrointestinal events, most of which occurred during dose escalation. No episodes of severe hypoglycemia were reported. Permanent discontinuation of orforglipron or placebo due to adverse events occurred in 4.4 to 7.8% of participants receiving orforglipron and 1.4% of participants receiving placebo. CONCLUSIONS: In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks. (Supported by Eli Lilly; ACHIEVE-1 ClinicalTrials.gov number, NCT05971940.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research Center at Medical City Dallas, Dallas. FAU - Hsia, Stanley AU - Hsia S AD - Velocity Clinical Research, Huntington Park, CA. FAU - Nevarez Ruiz, Luis AU - Nevarez Ruiz L AD - Hospital Angeles Chihuahua, Chihuahua, Mexico. FAU - Eyde, Sarah AU - Eyde S AD - Eli Lilly, Indianapolis. FAU - Cox, David AU - Cox D AD - Eli Lilly, Indianapolis. FAU - Wu, Wen-Shuo AU - Wu WS AD - Eli Lilly, Indianapolis. FAU - Liu, Rong AU - Liu R AD - Eli Lilly, Indianapolis. FAU - Li, Jianghao AU - Li J AD - Eli Lilly, Indianapolis. FAU - Fernandez Lando, Laura AU - Fernandez Lando L AD - Eli Lilly, Indianapolis. FAU - Denning, Max AU - Denning M AD - Eli Lilly, Indianapolis. FAU - Ludwig, Lisa AU - Ludwig L AD - Eli Lilly, Indianapolis. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly, Indianapolis. CN - ACHIEVE-1 Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT05971940 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250621 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM CIN - N Engl J Med. 2025 Dec 4;393(22):2276. doi: 10.1056/NEJMc2515117. PMID: 41337725 CIN - N Engl J Med. 2025 Dec 4;393(22):2276. doi: 10.1056/NEJMc2515117. PMID: 41337726 CIN - N Engl J Med. 2025 Dec 4;393(22):2276-2277. doi: 10.1056/NEJMc2515117. PMID: 41337727 CIN - N Engl J Med. 2025 Dec 4;393(22):2277-2279. doi: 10.1056/NEJMc2515117. PMID: 41337728 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/blood/diet therapy/drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/adverse effects/methods MH - Hypoglycemia/blood/chemically induced/epidemiology MH - Oxadiazoles MH - Fluorine Compounds FIR - Tan, Huiwen IR - Tan H FIR - Gao, Jialin IR - Gao J FIR - Ma, Jianhua IR - Ma J FIR - Zhao, Dong IR - Zhao D FIR - Li, Shu IR - Li S FIR - Yuan, Guoyue IR - Yuan G FIR - Lu, Yibing IR - Lu Y FIR - Li, Qingju IR - Li Q FIR - Li, Xinyu IR - Li X FIR - Guo, Lixin IR - Guo L FIR - Jiang, Xiaozhen IR - Jiang X FIR - Li, Yufeng IR - Li Y FIR - Wang, Yihua IR - Wang Y FIR - Liu, Lan IR - Liu L FIR - Dong, Xiaolin IR - Dong X FIR - Cheng, Zhifeng IR - Cheng Z FIR - Selvan, Chitra IR - Selvan C FIR - Shah, Meenakshi IR - Shah M FIR - C, Ambrish IR - C A FIR - Chawla, Manoj IR - Chawla M FIR - Agarwal, Sanjay IR - Agarwal S FIR - Ghosh, Sujoy IR - Ghosh S FIR - Mohan, Viswanathan IR - Mohan V FIR - Narang, Udit IR - Narang U FIR - Paturi, Vishnupriya IR - Paturi V FIR - Nakamura, Udai IR - Nakamura U FIR - Fukushima, Yasushi IR - Fukushima Y FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Matsuoka, Osamu IR - Matsuoka O FIR - Abe, Katsushige IR - Abe K FIR - Asakura, Taro IR - Asakura T FIR - Hayashi, Tsutomu IR - Hayashi T FIR - Iwamoto, Masahiro IR - Iwamoto M FIR - Onishi, Yukiko IR - Onishi Y FIR - Inoue, Satoshi IR - Inoue S FIR - Morinaga, Hiroshi IR - Morinaga H FIR - Takahashi, Hideo IR - Takahashi H FIR - Tokuyama, Takahiko IR - Tokuyama T FIR - Hasegawa, Atsushi IR - Hasegawa A FIR - Ceballos, Rosa Luna IR - Ceballos RL FIR - Nevarez, Luis IR - Nevarez L FIR - Lopez, Agustin IR - Lopez A FIR - Pelayo Orozco, Emilia IR - Pelayo Orozco E FIR - Villagordoa Mesa, Juan IR - Villagordoa Mesa J FIR - Barrat Hernandez, Alejandro IR - Barrat Hernandez A FIR - Stobschinski de Alba, Carlos Alejandro IR - Stobschinski de Alba CA FIR - Vidrio, Maricela IR - Vidrio M FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Rocher, Maray IR - Rocher M FIR - Guzman, David IR - Guzman D FIR - Ghorbani, Elham IR - Ghorbani E FIR - Farley, Harlicia IR - Farley H FIR - Noveck, Robert IR - Noveck R FIR - Wallace-Wilding, Kellie IR - Wallace-Wilding K FIR - Karr, Aaron IR - Karr A FIR - Kleess, Lauren IR - Kleess L FIR - Mattar, Peter IR - Mattar P FIR - Connery, Lisa IR - Connery L FIR - Youga, Henry IR - Youga H FIR - Vega, Damaris IR - Vega D FIR - Hassan, Amir IR - Hassan A FIR - Schultz, James IR - Schultz J FIR - Kim, John IR - Kim J FIR - Finley, Jon IR - Finley J FIR - Zapata, Juan IR - Zapata J FIR - Navarro, Martha IR - Navarro M FIR - Gabra, Nashwa IR - Gabra N FIR - Hartley, Paul IR - Hartley P FIR - Packer, Flint IR - Packer F FIR - Mandry, Jose IR - Mandry J FIR - Patton, Walter IR - Patton W FIR - Purighalla, Raman IR - Purighalla R FIR - Condit, Jonathan IR - Condit J FIR - Martinez Rivera, Orvil IR - Martinez Rivera O FIR - Patel, Neel IR - Patel N FIR - Lender, Dan IR - Lender D FIR - Serje, Jorge IR - Serje J FIR - Hsia, Stanley IR - Hsia S FIR - Hill, John IR - Hill J FIR - Montano, Charles IR - Montano C FIR - Presswood, Claire IR - Presswood C FIR - Saad, Abdulhassan IR - Saad A FIR - Igbinadolor, Awawu IR - Igbinadolor A FIR - Al-Karadsheh, Amer IR - Al-Karadsheh A FIR - Blake, Dwight IR - Blake D FIR - Greatwood, Rachel IR - Greatwood R FIR - Kumar, Amrendra IR - Kumar A FIR - Hopson, Shannon IR - Hopson S EDAT- 2025/06/23 04:45 MHDA- 2025/09/17 18:31 CRDT- 2025/06/22 11:43 PHST- 2025/09/17 18:31 [medline] PHST- 2025/06/23 04:45 [pubmed] PHST- 2025/06/22 11:43 [entrez] AID - 10.1056/NEJMoa2505669 [doi] PST - ppublish SO - N Engl J Med. 2025 Sep 18;393(11):1065-1076. doi: 10.1056/NEJMoa2505669. Epub 2025 Jun 21. PMID- 40544432 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 393 IP - 7 DP - 2025 Aug 14 TI - Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. PG - 648-659 LID - 10.1056/NEJMoa2502082 [doi] AB - BACKGROUND: Cagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring. METHODS: In this phase 3a, double-blind, randomized, placebo-controlled trial conducted in 12 countries, we assigned adults with a body-mass index of 27 or more, a glycated hemoglobin level of 7 to 10%, and type 2 diabetes in a 3:1 ratio to receive once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, along with lifestyle intervention, for 68 weeks. The two primary end points were the percent change in body weight and the percentage of patients with a weight reduction of at least 5%. Additional end points were changes in glycemic measures and safety assessments. Effect estimates were calculated with the use of the treatment-policy estimand (consistent with the intention-to-treat principle). RESULTS: A total of 1206 patients underwent randomization to either the cagrilintide-semaglutide group (904 patients) or the placebo group (302 patients). The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001). More patients in the cagrilintide-semaglutide group than in the placebo group had a weight reduction of 5% or more (P<0.001); the same was true of reductions of at least 10%, 15%, and 20% (P<0.001 for the last comparison). The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group. Gastrointestinal adverse events were reported by 72.5% of the patients in the cagrilintide-semaglutide group and 34.4% in the placebo group, most of which were transient and mild or moderate in severity. CONCLUSIONS: Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. AD - NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom. FAU - Bajaj, Harpreet S AU - Bajaj HS AD - Endocrine and Metabolic Research, LMC Healthcare, Brampton, ON, Canada. FAU - Broholm, Christa AU - Broholm C AD - Novo Nordisk, Soborg, Denmark. FAU - Eliasen, Astrid AU - Eliasen A AD - Novo Nordisk, Soborg, Denmark. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, University College Dublin School of Medicine, Dublin. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine, Endocrinology Division, University of Texas Southwestern Medical Center, Dallas. AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas. FAU - Lyndgaard, Christian Boge AU - Lyndgaard CB AD - Novo Nordisk, Soborg, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic Calgary, Calgary, AB, Canada. CN - REDEFINE 2 Study Group LA - eng SI - ClinicalTrials.gov/NCT05394519 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250622 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Drug Combinations) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - AO43BIF1U8 (cagrilintide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Double-Blind Method MH - Glycated Hemoglobin/analysis MH - Hypoglycemia/blood/chemically induced/diagnosis MH - Life Style MH - *Obesity/blood/complications/drug therapy MH - *Overweight/blood/complications/drug therapy MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Islet Amyloid Polypeptide/administration & dosage/adverse effects MH - Drug Combinations MH - Treatment Outcome MH - Intention to Treat Analysis MH - Continuous Glucose Monitoring MH - Glucagon-Like Peptide 1 MH - Semaglutide FIR - Sourij, Harald IR - Sourij H FIR - Kautzky-Willer, Alexandra IR - Kautzky-Willer A FIR - Adlbrecht, Christopher IR - Adlbrecht C FIR - Ludvik, Bernhard IR - Ludvik B FIR - Clodi, Martin IR - Clodi M FIR - Fliesser-Gorzer, Evelyn IR - Fliesser-Gorzer E FIR - Ajala, Buki IR - Ajala B FIR - Akhras, Ronald IR - Akhras R FIR - Bajaj, Harpreet IR - Bajaj H FIR - Dzongowski, Peter IR - Dzongowski P FIR - Jones, Michael IR - Jones M FIR - Khandwala, Hasnain IR - Khandwala H FIR - Noronha, Luis IR - Noronha L FIR - O'Keefe, Dennis IR - O'Keefe D FIR - Pedersen, Sue IR - Pedersen S FIR - Sahyouni, Elie IR - Sahyouni E FIR - Tailor, Chetna IR - Tailor C FIR - Wharton, Sean IR - Wharton S FIR - Garg, Naveen IR - Garg N FIR - Dahl, Dominik IR - Dahl D FIR - Erlinger, Moritz Mauro IR - Erlinger MM FIR - Hagenow, Andreas IR - Hagenow A FIR - Rose, Ludger IR - Rose L FIR - Sauter, Joachim IR - Sauter J FIR - Zeller, Helga IR - Zeller H FIR - Stahl, Hans-Detlev IR - Stahl HD FIR - Vidal, Simon IR - Vidal S FIR - Segner, Alexander IR - Segner A FIR - Katona, Eva IR - Katona E FIR - Pall, Istvan IR - Pall I FIR - Szocs, Albert IR - Szocs A FIR - Barta, Gyorgy IR - Barta G FIR - Nadas, Judit IR - Nadas J FIR - Revesz, Katalin IR - Revesz K FIR - Valkusz, Zsuzsanna IR - Valkusz Z FIR - Lavanya, Alapati IR - Lavanya A FIR - Prakash, Anupam IR - Prakash A FIR - Selvan, Chitra IR - Selvan C FIR - R, Chandni IR - R C FIR - Gupta, Yashdeep IR - Gupta Y FIR - Kashiva, Reema IR - Kashiva R FIR - Jabbar, P K IR - Jabbar PK FIR - Lila, Anurag IR - Lila A FIR - V, Mohan IR - V M FIR - Gupta, Sunil IR - Gupta S FIR - Marwah, Tiven IR - Marwah T FIR - Gadve, Sharvil IR - Gadve S FIR - Bhadada, Sanjay IR - Bhadada S FIR - Chaudhury, Tirthankar IR - Chaudhury T FIR - Seshadri, Krishna G IR - Seshadri KG FIR - Sharma, Balram IR - Sharma B FIR - Bhagwat, Nikhil IR - Bhagwat N FIR - le Roux, Carel IR - le Roux C FIR - Byrne, Maria IR - Byrne M FIR - Dunne, Fidelma IR - Dunne F FIR - Phelan, Niamh IR - Phelan N FIR - Sreenan, Seamus IR - Sreenan S FIR - Tokuyama, Takahiko IR - Tokuyama T FIR - Tosaki, Takahiro IR - Tosaki T FIR - Nishizawa, Hitoshi IR - Nishizawa H FIR - Yoshimitsu, Yamasaki IR - Yoshimitsu Y FIR - Osonoi, Takeshi IR - Osonoi T FIR - Mohamed Shah, Fatimah Zaherah IR - Mohamed Shah FZ FIR - Tan, Florence IR - Tan F FIR - Lee, Siow Ping IR - Lee SP FIR - Fam, Tem Lom IR - Fam TL FIR - Karim, Nor Afidah IR - Karim NA FIR - Hussein, Zanariah IR - Hussein Z FIR - Mustafa, Norlaila IR - Mustafa N FIR - Lee, Li Yuan IR - Lee LY FIR - Abdullah Hashim, Suraya Hanim IR - Abdullah Hashim SH FIR - Sorobka, Barbara IR - Sorobka B FIR - Ostrowska, Lucyna IR - Ostrowska L FIR - Madej, Andrzej IR - Madej A FIR - Hoffmann, Michal IR - Hoffmann M FIR - Matyjaszek-Matuszek, Beata IR - Matyjaszek-Matuszek B FIR - Pankowska, Ewa IR - Pankowska E FIR - Poplawska-Kita, Anna IR - Poplawska-Kita A FIR - Jankowski, Piotr IR - Jankowski P FIR - Rucinski, Gabriel IR - Rucinski G FIR - Bogdanski, Pawel IR - Bogdanski P FIR - Palka, Katarzyna IR - Palka K FIR - Gierach, Marcin IR - Gierach M FIR - Kedzierska-Kapuza, Karolina IR - Kedzierska-Kapuza K FIR - Wosko, Edyta IR - Wosko E FIR - Sriphrapradang, Chutintorn IR - Sriphrapradang C FIR - Piyayotai, Dilok IR - Piyayotai D FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Pongchaiyakul, Chatlert IR - Pongchaiyakul C FIR - Boonchaya-Anant, Patchaya IR - Boonchaya-Anant P FIR - Sriwijitkamol, Apiradee IR - Sriwijitkamol A FIR - Bain, Stephen IR - Bain S FIR - Capehorn, Matt IR - Capehorn M FIR - Clark, Rebecca IR - Clark R FIR - Creely, Steven IR - Creely S FIR - Davies, Melanie IR - Davies M FIR - Wilson, Laurie IR - Wilson L FIR - Gunstone, Anthony IR - Gunstone A FIR - King, Rhodri IR - King R FIR - Krzeminski, Andre IR - Krzeminski A FIR - Nyekiova, Maria IR - Nyekiova M FIR - Paul, Carolyn IR - Paul C FIR - Paul, Neil IR - Paul N FIR - Philbey, Chris IR - Philbey C FIR - Russell, Georgina IR - Russell G FIR - Singh, Ivor IR - Singh I FIR - Strzelecka, Anna IR - Strzelecka A FIR - Wyatt, Nell IR - Wyatt N FIR - Donnell, Philip O IR - Donnell PO FIR - Al-Karadsheh, Amer IR - Al-Karadsheh A FIR - Bailey, Timothy IR - Bailey T FIR - Barranco-Santana, Elizabeth A IR - Barranco-Santana EA FIR - Bartilucci, Darlene IR - Bartilucci D FIR - Bays, Harold IR - Bays H FIR - Malaeb, Samar IR - Malaeb S FIR - Bhargava, Anuj IR - Bhargava A FIR - Biggs, William IR - Biggs W FIR - Blevins, Thomas IR - Blevins T FIR - Broker, Robert IR - Broker R FIR - Bressler, Peter IR - Bressler P FIR - Brian, Susan IR - Brian S FIR - Chaicha-Brom, Tira IR - Chaicha-Brom T FIR - Chang, Anna IR - Chang A FIR - Christiansen, Mark IR - Christiansen M FIR - Dunn, Leonard IR - Dunn L FIR - Guzman, David IR - Guzman D FIR - Gerety, Gregg IR - Gerety G FIR - Harris, Kathleen IR - Harris K FIR - Hewitt, Mitzie IR - Hewitt M FIR - Houser, Patricia IR - Houser P FIR - Jardula, Michael IR - Jardula M FIR - Klein, Eric IR - Klein E FIR - Morin, David IR - Morin D FIR - Murray, Alexander IR - Murray A FIR - Oliver, David IR - Oliver D FIR - Pratley, Richard IR - Pratley R FIR - Pullman, John IR - Pullman J FIR - Reed, John 3rd IR - Reed J 3rd FIR - Rosenblit, Paul IR - Rosenblit P FIR - Rosenstock, Julio IR - Rosenstock J FIR - Scott, John IR - Scott J FIR - Smith, Timothy IR - Smith T FIR - Snyder, Brian IR - Snyder B FIR - Sugimoto, Danny IR - Sugimoto D FIR - Sultan, Senan IR - Sultan S FIR - Welch, Michelle IR - Welch M FIR - Woolley, Joseph IR - Woolley J FIR - Lingvay, Ildiko IR - Lingvay I FIR - Pau, Cindy IR - Pau C FIR - Gilbert, John IR - Gilbert J FIR - Greenway, Frank IR - Greenway F FIR - Wayne, Jeffrey IR - Wayne J FIR - Block, Bradley IR - Block B FIR - Cruz, Humberto IR - Cruz H EDAT- 2025/06/23 04:45 MHDA- 2025/08/31 20:02 CRDT- 2025/06/22 11:43 PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/23 04:45 [pubmed] PHST- 2025/06/22 11:43 [entrez] AID - 10.1056/NEJMoa2502082 [doi] PST - ppublish SO - N Engl J Med. 2025 Aug 14;393(7):648-659. doi: 10.1056/NEJMoa2502082. Epub 2025 Jun 22. PMID- 40543068 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 9 DP - 2025 Sep 1 TI - Benefit of Semaglutide in Symptomatic Peripheral Artery Disease by Baseline Type 2 Diabetes Characteristics: Insights From STRIDE, a Randomized, Placebo-Controlled, Double-Blind Trial. PG - 1529-1535 LID - 10.2337/dc25-1082 [doi] AB - OBJECTIVE: The Semaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes (STRIDE) trial (NCT04560998) showed that once-weekly subcutaneous semaglutide 1.0 mg significantly improved functional outcomes, symptoms, and quality of life in individuals with symptomatic peripheral artery disease (PAD) and type 2 diabetes. Whether these benefits are consistent across diabetes-related characteristics remains unclear. RESEARCH DESIGN AND METHODS: The primary outcome was the ratio to baseline (ETR) in maximum walking distance (MWD), with pain-free walking distance (PFWD) as a key secondary end point. Both were measured at 52 weeks using a constant load treadmill. Subgroup analyses were performed by diabetes duration, BMI, HbA1c, and diabetes medications. A mixed model for repeated measurements was used, incorporating treatment, region, and subgroup as fixed factors, and baseline value as covariate, along with the treatment-by-subgroup interaction. RESULTS: Among 792 participants (median diabetes duration 12.2 years, HbA1c 7.1%, and BMI 28.7 kg/m2), 35.1% used sodium-glucose cotransporter 2 inhibitors and 31.7% used insulin. Semaglutide significantly improved MWD regardless of diabetes duration (ETR of 1.15 vs. 1.13 for <10 vs. >/=10 years, P = 0.80), BMI (1.12 vs. 1.16 for <30 vs. >/=30 kg/m2, P = 0.58), HbA1c (1.13 for <7% and >/=7%, P = 0.99), or medication use. Semaglutide also improved PFWD across subgroups (P > 0.1 for all interactions). BMI reduction correlated weakly with MWD improvements and was more pronounced in the control individuals with higher baseline BMI. Safety outcomes were consistent across subgroups. CONCLUSIONS: Semaglutide improved walking function in people with PAD and type 2 diabetes, including individuals without obesity and those with well-controlled HbA1c. Benefits were consistent across BMI and HbA1c categories, supporting effectiveness beyond weight or glycemic changes. CI - (c) 2025 by the American Diabetes Association. FAU - Rasouli, Neda AU - Rasouli N AUID- ORCID: 0000-0003-1269-3580 AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, and VA Eastern Colorado Health Care, Aurora, CO. FAU - Guder Arslan, Ecenur AU - Guder Arslan E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Department of Vascular Surgery, Lillebaelt Hospital, Kolding, Denmark. AD - Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute of Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Sourij, Harald AU - Sourij H AUID- ORCID: 0000-0003-3510-9594 AD - Cardiometabolic Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Thomas, Sebastian AU - Thomas S AD - Novo Nordisk GBS India, Bangalore, India. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, CO. LA - eng GR - Novo Nordisk A/S, Denmark/ PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - *Peripheral Arterial Disease/blood/drug therapy/etiology MH - Walking MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12368379 COIS- Duality of Interest. N.R. has received consultation fees and/or research funding from Novo Nordisk, Eli Lilly, Sanofi, and SomaLogic. E.G.A. is an employee at Novo Nordisk. A.-M.C. is an employee and shareholder at Novo Nordisk. K.H. has received fees for consulting from Novo Nordisk and LeMaitre and funding for research from the Novo Nordisk Foundation. B.L. has received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Madrigal, MSD, Novo Nordisk, and Sanofi, and has received honoraria as a consultant and speaker from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. H.S. has received consulting fees and speaker honoraria from Amgen, Amarin, Boehringer Ingelheim, Novo Nordisk, Novartis, Daiichi Sankyo, Eli Lilly, and Cancom, and has received research funding from Boehringer Ingelheim, Novo Nordisk, and Eli Lilly (paid to the Medical University of Graz, Austria). S.T. is an employee and shareholder at Novo Nordisk. S.V. reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Anthos, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S&L Solutions Event Management, and Sanofi. M.P.B. is the executive director of CPC, a nonprofit academic research organization affiliated with the University of Colorado that receives or has received research grant/consulting funding between August 2021 and the present from Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, ARCA Biopharma, Array BioPharma, AstraZeneca and affiliates, Atentiv, Audentes Therapeutics, Bayer and affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, Bristol-Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, EPG Communication Holdings, Epizon Pharma, Esperion Therapeutics, Everlywell, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, Heartflow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen and affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Medpace, Merck and affiliates, Nectero Medical, Novartis, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, PPD Development, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanifit Therapeutics, Sanofi-Aventis Groupe, Silence Therapeutics, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, Brigham & Women's Hospital, The Feinstein Institutes for Medical Research, Thrombosis Research Institute, VarmX, Virta Health, Worldwide Clinical Trials, WraSer Pharmaceuticals, and Yale Cardiovascular Research Group. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/06/21 20:44 MHDA- 2025/08/31 20:02 PMCR- 2025/06/21 CRDT- 2025/06/21 14:32 PHST- 2025/05/08 00:00 [received] PHST- 2025/05/30 00:00 [accepted] PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/21 20:44 [pubmed] PHST- 2025/06/21 14:32 [entrez] PHST- 2025/06/21 00:00 [pmc-release] AID - 160652 [pii] AID - 251082 [pii] AID - 10.2337/dc25-1082 [doi] PST - ppublish SO - Diabetes Care. 2025 Sep 1;48(9):1529-1535. doi: 10.2337/dc25-1082. PMID- 40538007 OWN - NLM STAT- MEDLINE DCOM- 20250901 LR - 20260127 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 40 IP - 9 DP - 2025 Sep TI - Mechanism of Semaglutide in MASLD Treatment: Where Is the Master Key? PG - 2163-2175 LID - 10.1111/jgh.17037 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is used for weight reduction and metabolic improvement. Semaglutide effectively improves MASH but not confers histological fibrosis resolution. The key question remains whether semaglutide exerts direct, independent effects in ameliorating MASH or if its benefits are merely secondary to improvements in weight, insulin resistance, and glycemic control. The exact mechanisms of action through which semaglutide or other GLP-1 RAs offer liver protection are not entirely clear. METHODS: A comprehensive search in PubMed and EMBASE was conducted using the keywords "Semaglutide and NAFLD/MASLD", "glucagon-like peptide-1 receptor agonist and MASLD/NALFD", and "Semaglutide and type II diabetes/obesity and hypertension". Relevant papers published before February, 2025, were included. RESULTS: Semaglutide modulates several lipid-associated molecular pathways through unknown mechanisms. Preclinical and clinical studies suggest that semaglutide acts by (i) reducing appetite and increasing satiety, thereby decreasing dietary intake and subsequent free fatty acid export to the liver; (ii) reducing insulin resistance and improving insulin sensitivity and adipose dysfunction; (iii) reducing de novo lipogenesis by downregulating ChREBP and SREBP-1c signaling, as well as the expression of lipid-synthesizing genes; (iv) reducing the weight of white and brown adipose tissue; and (v) reducing inflammation by decreasing pro-inflammatory markers in GLP-1-expressing macrophages and favorably altering the gut microbiota. CONCLUSION: While this review explores the potential mechanisms of semaglutide action, the lack of GLP-1 receptor expression in the livers of mice and humans suggests that these mechanisms are associated with indirect modulation. Consequently, further mechanistic studies are needed to elucidate these pathways. TRIAL REGISTRATION: NOT APPLICABLE. CI - (c) 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Ezhilarasan, Devaraj AU - Ezhilarasan D AUID- ORCID: 0000-0002-5068-2383 AD - Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India. LA - eng GR - Adhoc 2020-4160/Indian Council of Medical Research/ PT - Journal Article PT - Review DEP - 20250619 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Humans MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Animals MH - Insulin Resistance MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liver/metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Lipogenesis/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - MASH OT - fatty liver OT - fibrosis OT - glucagon-like peptide-1 OT - obesity OT - steatosis OT - type 2 diabetes EDAT- 2025/06/20 11:31 MHDA- 2025/09/01 16:44 CRDT- 2025/06/20 01:13 PHST- 2025/05/27 00:00 [revised] PHST- 2025/04/01 00:00 [received] PHST- 2025/06/08 00:00 [accepted] PHST- 2025/09/01 16:44 [medline] PHST- 2025/06/20 11:31 [pubmed] PHST- 2025/06/20 01:13 [entrez] AID - 10.1111/jgh.17037 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2025 Sep;40(9):2163-2175. doi: 10.1111/jgh.17037. Epub 2025 Jun 19. PMID- 40537987 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - Indirect comparative efficacy and safety of tirzepatide 10 and 15 mg versus semaglutide 2.4 mg for the management of obesity and overweight in patients with type 2 diabetes. PG - 4709-4719 LID - 10.1111/dom.16508 [doi] AB - AIMS: This indirect treatment comparison (ITC) compared the efficacy and safety of tirzepatide with semaglutide for managing obesity or overweight in participants with type 2 diabetes (T2D), informed by the pivotal trials SURMOUNT-2 and STEP 2. MATERIALS AND METHODS: Participants had body mass index (BMI) >/= 27 kg/m(2), with >/=1 unsuccessful prior dietary weight reduction effort and glycated haemoglobin (HbA1c) 7%-10% on stable therapy. A heterogeneity assessment confirmed that study and patient baseline characteristics were similar. Bucher ITCs compared tirzepatide 10 and 15 mg once-weekly (QW) to semaglutide 2.4 mg QW via placebo, all adjunct to a reduced-calorie diet and increased physical activity. RESULTS: Tirzepatide 10 and 15 mg were associated with statistically significant greater reductions in weight, BMI and HbA1c versus semaglutide. Tirzepatide 15 mg was associated with statistically significant greater odds versus semaglutide of >/=5% and >/=15% weight reduction and statistically significant improvements in several cardiometabolic risk factors, including waist circumference, fasting plasma glucose and triglycerides. Both tirzepatide doses showed non-significant trends of greater improvements in high-density lipoprotein, low-density lipoprotein, systolic blood pressure and diastolic blood pressure versus semaglutide as well as a generally comparable safety profile to semaglutide. CONCLUSIONS: In this ITC versus semaglutide 2.4 mg, tirzepatide 10 and 15 mg were associated with statistically significant greater weight, BMI and HbA1c reduction and tirzepatide 15 mg with statistically significant improvements in multiple cardiometabolic risk factors crucial in managing obesity or overweight among patients with T2D. Both tirzepatide doses also had a generally similar safety profile to semaglutide. PLAIN LANGUAGE SUMMARY: What is the context and purpose of this research study? Excess weight and type 2 diabetes (T2D) are strongly connected, where most patients with T2D have obesity or overweight. Weight management is crucial for improving T2D outcomes and preventing its progression. Weight management comprises behavioural interventions, psychological support, dietary changes and physical activity programmes. Medications may also be prescribed or surgical options may also be considered. Two such medications for weight management are tirzepatide (up to 15 mg) and semaglutide (up to 2.4 mg), which are injected subcutaneously once per week to help control appetite by prolonging patients' feeling of fullness. These medications are also used at different doses to treat T2D. Because there were no clinical trials directly comparing tirzepatide and semaglutide, particularly in patients with both T2D and either obesity or overweight, this study aimed to indirectly compare the effectiveness and safety of tirzepatide and semaglutide for weight management in patients with overweight or obesity and T2D. What was done? We indirectly compared the efficacy and safety of two doses of tirzepatide (10 and 15 mg per week) versus semaglutide 2.4 mg per week for weight management in adults with both T2D and either obesity or overweight. We used data from two large clinical trials, SURMOUNT-2 and STEP 2, which tested tirzepatide and semaglutide, respectively, against a placebo, all adjunct to diet and exercise. An indirect treatment comparison of tirzepatide and semaglutide was then possible via the placebo arm acting as the common comparator. The similarity of study design and patient populations in the two trials was evaluated and found to be sufficiently close to allow meaningful comparisons. Appropriate statistical methodology was used to facilitate comparisons of the two trials. What were the main results? Compared to semaglutide 2.4 mg, the higher dose of tirzepatide (15 mg) was associated with a statistically significant improvement in several outcomes such as weight reduction, glycaemic outcomes and triglycerides, while the lower dose of tirzepatide (10 mg) was associated with some statistically significant improvements (e.g., weight reduction and HbA1c) and had otherwise comparable outcomes to semaglutide. However, both doses of tirzepatide were associated with statistically significant greater reductions in glycated haemoglobin A1c (HbA1c) compared to semaglutide, which is a key target of T2D treatment. Both doses of tirzepatide had a generally similar safety profile compared to semaglutide. What is the originality and relevance of this study? Currently, there are no clinical trials that compare tirzepatide and semaglutide directly for the management of obesity and overweight in patients with T2D. Previous studies have compared tirzepatide and semaglutide results from different clinical trials for weight management in patients without T2D, not specifically focusing on patients with T2D. This is the first study to indirectly compare tirzepatide and semaglutide for weight management in people with T2D who also have obesity or overweight. The findings of this study suggest that higher doses of tirzepatide may be more effective than semaglutide for weight reduction and improving other health-related outcomes in these patients. CI - (c) 2025 Eli Lilly and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ciudin, Andreea AU - Ciudin A AD - Endocrinology and Nutrition, Vall d'Hebron University Hospital, Barcelona, Spain. FAU - Johansson, Erin AU - Johansson E AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Zimner-Rapuch, Sarah AU - Zimner-Rapuch S AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bertrand, Marine AU - Bertrand M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Curteis, Tristan AU - Curteis T AD - Costello Medical, Manchester, UK. FAU - Clark, Laura J AU - Clark LJ AD - Costello Medical, Manchester, UK. FAU - Fan, Ludi AU - Fan L AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Sapin, Helene AU - Sapin H AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bergmann, Jean-Francois AU - Bergmann JF AD - Department of Internal Medicine, Lariboisiere Hospital, AP-HP, University Paris-Cite, Paris, France. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250619 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Blood Glucose MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy/blood MH - Glycated Hemoglobin/analysis MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Tirzepatide/administration & dosage/adverse effects MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12326929 OTO - NOTNLM OT - GIP OT - GLP-1 OT - type 2 diabetes OT - weight management COIS- AC: Honoraria from AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk; Member of the DMC of Boehringer Ingelheim clinical trials-SYNCRONIZE program; EJ, SZR, GKD, MB, LF, HS: Employee and shareholder of Eli Lilly and Company; TC, LJC: Employees of Costello Medical, which received payment from Eli Lilly and Company for analytical services for this study; JFB: Received honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Gilead, GSK, IQVIA, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Takeda. EDAT- 2025/06/20 11:31 MHDA- 2025/08/06 12:30 PMCR- 2025/08/06 CRDT- 2025/06/20 01:03 PHST- 2025/05/13 00:00 [revised] PHST- 2025/01/31 00:00 [received] PHST- 2025/05/22 00:00 [accepted] PHST- 2025/08/06 12:30 [medline] PHST- 2025/06/20 11:31 [pubmed] PHST- 2025/06/20 01:03 [entrez] PHST- 2025/08/06 00:00 [pmc-release] AID - DOM16508 [pii] AID - 10.1111/dom.16508 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):4709-4719. doi: 10.1111/dom.16508. Epub 2025 Jun 19. PMID- 40532767 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20250801 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 226 DP - 2025 Aug TI - Comparative outcomes of adding SGLT2 inhibitors versus incretin-based therapies to insulin in type 2 diabetes. PG - 112328 LID - S0168-8227(25)00342-0 [pii] LID - 10.1016/j.diabres.2025.112328 [doi] AB - AIMS: To compare the risks of cardiovascular events and major microvascular complications associated with adding sodium-glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to insulin therapy in patients with type 2 diabetes (T2D). METHODS: Using Taiwan's National Health Insurance Research Database (2008-2021), we identified 20,655 propensity score-matched pairs of SGLT2 inhibitor and DPP-4 inhibitor users, and 10,445 matched pairs of SGLT2 inhibitor and GLP-1 RA users, all receiving concurrent insulin therapy. Cox proportional hazards models were applied to assess outcome risks. RESULTS: SGLT2 inhibitor use was associated with significantly lower risks of major microvascular complications compared to both DPP-4 inhibitors (adjusted hazard ratio [aHR] 0.37, 95% CI: 0.33-0.41) and GLP-1 RAs (aHR 0.57, 95% CI: 0.49-0.66). Compared with DPP-4 inhibitors, SGLT2 inhibitors also conferred a lower risk of major adverse cardiovascular events (aHR 0.57, 95% CI: 0.53-0.61) and all-cause mortality (aHR 0.42, 95% CI: 0.39-0.45). CONCLUSIONS: In patients with T2D on insulin, adding SGLT2 inhibitors was associated with lower risks of cardiovascular events, major microvascular complications, and mortality compared to DPP-4 inhibitors, and lower risk of major microvascular complications compared to GLP-1 RAs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan 33354, Taiwan. Electronic address: yenfushun@gmail.com. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung City 40201, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan. Electronic address: jccwei@gmail.com. FAU - Huang, Yu-Han AU - Huang YH AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: viyi98.cmuh@gmail.com. FAU - Li, Pei-Yun AU - Li PY AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: peiyun.cmuh1999@gmail.com. FAU - Tsai, Fuu-Jen AU - Tsai FJ AD - School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan; Division of Medical Genetics, China Medical University Children's Hospital, Taichung 40447, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. Electronic address: 000704@tool.caaumed.org.tw. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan; Department of Health Services Administration, China Medical University, Taichung 40402, Taiwan; Department of Family Medicine, Min-Sheng General Hospital, 168 ChingKuo Road, Taoyuan 33044, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan. Electronic address: cch@nhri.edu.tw. FAU - Hwu, Chii-Min AU - Hwu CM AD - Faculty of Medicine, National Yang-Ming Chiao Tung University School of Medicine, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road, Beitou District, Taipei 11217, Taiwan. Electronic address: chhwu@vghtpe.gov.tw. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250616 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - *Incretins/therapeutic use MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Insulin/therapeutic use MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Taiwan/epidemiology MH - Treatment Outcome MH - Drug Therapy, Combination MH - Cardiovascular Diseases/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - All-cause mortality OT - Amputation OT - Coronary artery disease OT - End-stage kidney disease OT - Heart failure OT - Sight-threatening retinopathy OT - Stroke COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/06/19 00:25 MHDA- 2025/08/02 10:45 CRDT- 2025/06/18 19:12 PHST- 2025/02/07 00:00 [received] PHST- 2025/06/03 00:00 [revised] PHST- 2025/06/13 00:00 [accepted] PHST- 2025/08/02 10:45 [medline] PHST- 2025/06/19 00:25 [pubmed] PHST- 2025/06/18 19:12 [entrez] AID - S0168-8227(25)00342-0 [pii] AID - 10.1016/j.diabres.2025.112328 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Aug;226:112328. doi: 10.1016/j.diabres.2025.112328. Epub 2025 Jun 16. PMID- 40526989 OWN - NLM STAT- MEDLINE DCOM- 20250825 LR - 20260902 IS - 1872-7123 (Electronic) IS - 0165-1781 (Linking) VI - 351 DP - 2025 Sep TI - Efficacy and safety of GLP1-ras compared to SGLT2is and DPP-4is in individuals with schizophrenia and diabetes: A Danish nationwide target-trial emulation study. PG - 116592 LID - S0165-1781(25)00240-9 [pii] LID - 10.1016/j.psychres.2025.116592 [doi] AB - OBJECTIVE: Previous studies have suggested that glucagon-like-peptide-1-receptor-agonists (GLP1-ras) may offer neuroprotective and cardiovascular benefits. However, concerns have been raised about potential adverse effects of GLP1-ras including depression and suicidal ideation. This target-trial-emulation study aims to examine the effects of GLP1-ras treatment on psychiatric hospital admission and all-cause mortality in individuals with schizophrenia. METHODS: We used the Danish nationwide registers to identify all individuals diagnosed with schizophrenia and who were treated with metformin (Glucophage). Among these, we identified those who initiated second-line treatment for type-2-diabetes with one of the following glucose-lowering drugs: GLP1-ras, sodium-glucose-cotransporter-2-inhibitors(SGLT2is), or dipeptidyl-peptidase-4-inhibitors(DPP-4is). We then compared the hazard rate ratios(HRR) for psychiatric admission and all-cause mortality between the different treatment arms using a Cox-proportional-hazards model, adjusting for covariates to minimize confounding. RESULTS: We included 354 individuals with schizophrenia(47 % female, mean age 43.8 years) and type-2-diabetes who initiated treatment with a second-line GLD. Of these, 71, 197, and 86 initiated treatment with GLP1-ras, DPP-4is, and SGLT2is respectively. We found no difference in the risk of psychiatric admission between the three treatment arms. In the fully adjusted model, treatment with DPP-4is and SGLT2is analysed as a compound exposure, was not associated with a significant reduced risk of psychiatric admission, with a HRR of 0.78(95 %-CI:0.38-1.59), when compared to GLP1-ras. Only 5 deaths occurred during follow-up, making a comparison of all-cause mortality between the treatment arms unfeasible. CONCLUSION: We observed no difference in the risk of psychiatric admission or all-cause mortality for individuals with schizophrenia treated with GLP1-ras compared to SGLT2is and DPP-4is. CI - Copyright (c) 2025. Published by Elsevier B.V. FAU - Jacobsen, Soren L AU - Jacobsen SL AD - Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: SOERJC@rm.dk. FAU - Kohler-Forsberg, Ole AU - Kohler-Forsberg O AD - Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Danielsen, Andreas Aalkjaer AU - Danielsen AA AD - Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Rohde, Christopher AU - Rohde C AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Affective Disorder, Aarhus University Hospital - Psychiatry, Aarhus, Denmark. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250609 PL - Ireland TA - Psychiatry Res JT - Psychiatry research JID - 7911385 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Schizophrenia/drug therapy/epidemiology/mortality MH - Denmark/epidemiology MH - Female MH - Male MH - Middle Aged MH - Adult MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Registries/statistics & numerical data MH - Aged OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Pharmacoepidemiology OT - Safety profile OT - Schizophrenia OT - Target trial emulation OT - Type 2 diabetes COIS- Declaration of competing interest CR received the 2020 Lundbeck Foundation Talent Prize. AAD has received a speaker honorarium from Otsuka Pharmaceutical. OKF received speaker fees from Lundbeck Pharma A/S and is a consultant for WCG. SLJ received the Lundbeckfonden Scholarshipstipendium in Psychiatry. EDAT- 2025/06/17 18:26 MHDA- 2025/08/31 20:01 CRDT- 2025/06/17 17:59 PHST- 2025/03/26 00:00 [received] PHST- 2025/06/03 00:00 [revised] PHST- 2025/06/08 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/17 18:26 [pubmed] PHST- 2025/06/17 17:59 [entrez] AID - S0165-1781(25)00240-9 [pii] AID - 10.1016/j.psychres.2025.116592 [doi] PST - ppublish SO - Psychiatry Res. 2025 Sep;351:116592. doi: 10.1016/j.psychres.2025.116592. Epub 2025 Jun 9. PMID- 40523289 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 7 DP - 2025 Jul TI - Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes : Two Target Trial Emulation Studies. PG - 930-939 LID - 10.7326/ANNALS-24-00775 [doi] AB - BACKGROUND: Reduction of premature death and adverse cardiovascular outcomes is a key goal in type 2 diabetes management. OBJECTIVE: To compare mortality and cardiovascular event risks in patients treated with semaglutide versus empagliflozin and, secondarily, dulaglutide versus empagliflozin. DESIGN: Target trial emulation studies from observational data comparing semaglutide- or dulaglutide-treated patients with propensity score-matched patients treated with empagliflozin. SETTING: Health care system of 703 academic and community clinical practices. PARTICIPANTS: Patients aged 45 years or older with type 2 diabetes treated from 1 January 2019 to 31 December 2024 with semaglutide, dulaglutide, or empagliflozin. INTERVENTION: Initial treatment with semaglutide, dulaglutide, or empagliflozin. At baseline, concomitant treatment with other diabetes medication was permitted, excluding other glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors. MEASUREMENTS: A composite of death, myocardial infarction (MI), or stroke was the primary outcome, and secondary composite outcomes included death or MI, MI or stroke, and individual cardiac events. RESULTS: Patients treated with semaglutide (n = 7899) versus empagliflozin (n = 7899) were followed for a median of 2.2 years; the respective rates of the composite of death, MI, or stroke were 3.7% versus 4.5% at 2 years and 5.9% versus 6.9% at 3 years. Corresponding incidence rates for the composite outcome were 20.99 versus 23.56 per 1000 person-years, with a hazard ratio (HR) of 0.89 (95% CI, 0.78 to 1.02). The HRs for the individual outcomes were 0.97 (CI, 0.81 to 1.15) for death, 0.85 (CI, 0.68 to 1.05) for MI, and 0.62 (CI, 0.43 to 0.89) for stroke. Risks for dulaglutide- and empagliflozin-treated patients were similar for the composite outcome (HR, 1.03 [CI, 0.90 to 1.16]) and for death, MI, and stroke separately. LIMITATION: Observational study design, lack of data on cause-specific mortality, and residual confounding. CONCLUSION: Semaglutide treatment seems to confer some advantage over empagliflozin. This advantage was not observed for dulaglutide. PRIMARY FUNDING SOURCE: American Heart Association. FAU - Saeed, Anum AU - Saeed A AUID- ORCID: 0000-0003-1783-678X AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Mulukutla, Suresh R AU - Mulukutla SR AD - School of Medicine, University of Pittsburgh; Heart and Vascular Institute, UPMC; and Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (S.R.M.). FAU - Thoma, Floyd AU - Thoma F AD - Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (F.T.). FAU - Lemon, Lara AU - Lemon L AUID- ORCID: 0000-0001-6806-7787 AD - Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (L.L., K.K.). FAU - Koczo, Agnes AU - Koczo A AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Reis, Steven AU - Reis S AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Marroquin, Oscar AU - Marroquin O AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Kip, Kevin AU - Kip K AD - Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (L.L., K.K.). LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250617 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucosides/therapeutic use/adverse effects MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Benzhydryl Compounds/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Cardiovascular Diseases/mortality/prevention & control MH - Myocardial Infarction/epidemiology MH - Propensity Score MH - Stroke/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/06/16 18:26 MHDA- 2025/07/14 18:27 CRDT- 2025/06/16 17:03 PHST- 2025/07/14 18:27 [medline] PHST- 2025/06/16 18:26 [pubmed] PHST- 2025/06/16 17:03 [entrez] AID - 10.7326/ANNALS-24-00775 [doi] PST - ppublish SO - Ann Intern Med. 2025 Jul;178(7):930-939. doi: 10.7326/ANNALS-24-00775. Epub 2025 Jun 17. PMID- 40519161 OWN - NLM STAT- MEDLINE DCOM- 20250616 LR - 20250618 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 12 DP - 2025 Jun 16 TI - Should GLP-1 receptor agonist therapy be used to treat obesity in Bardet-Biedl syndrome? LID - 10.1172/JCI191822 [doi] LID - e191822 AB - Bardet-Biedl syndrome (BBS) is a complex genetic condition that can affect multiple organ systems, frequently causing pigmentary retinopathy, renal abnormalities, polydactyly, and obesity. Metabolic disturbances including obesity, unsuppressed appetite, and an increased risk of type 2 diabetes (T2D) present clinical management challenges. In this issue of the JCI, Singh et al. present a mouse model of a specific BBS subtype with genetic deletion of the Bbs5 gene. The model recapitulates many of the clinical features observed in patients living with BBS5 and sheds light on adipocyte biology, as well as the hypothalamic mechanisms driving hunger- and food-seeking behaviors that fuel the adverse metabolic phenotype. Importantly, exogenous GLP-1 receptor agonist treatment suppressed both appetite and weight, opening opportunities for direct translation into the clinical setting. FAU - Tomlinson, Jeremy W AU - Tomlinson JW LA - eng PT - Comment PT - Journal Article DEP - 20250616 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM CON - Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl syndrome mouse model MH - *Bardet-Biedl Syndrome/drug therapy/genetics/metabolism/complications/pathology MH - Animals MH - *Obesity/drug therapy/genetics/metabolism/etiology MH - Humans MH - Mice MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/genetics/drug therapy/metabolism MH - Disease Models, Animal MH - Glucagon-Like Peptide-1 Receptor MH - Mice, Knockout PMC - PMC12165807 COIS- Conflict of interest: The author has declared that no conflict of interest exists. EDAT- 2025/06/16 12:27 MHDA- 2025/06/16 12:28 PMCR- 2025/06/16 CRDT- 2025/06/16 06:03 PHST- 2025/06/16 12:28 [medline] PHST- 2025/06/16 12:27 [pubmed] PHST- 2025/06/16 06:03 [entrez] PHST- 2025/06/16 00:00 [pmc-release] AID - 191822 [pii] AID - 10.1172/JCI191822 [doi] PST - epublish SO - J Clin Invest. 2025 Jun 16;135(12):e191822. doi: 10.1172/JCI191822. eCollection 2025 Jun 16. PMID- 40518344 OWN - NLM STAT- MEDLINE DCOM- 20250903 LR - 20260127 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 139 DP - 2025 Sep TI - Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study. PG - 106378 LID - S0953-6205(25)00236-5 [pii] LID - 10.1016/j.ejim.2025.06.007 [doi] AB - BACKGROUND: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. This work analyzes the efficacy of once-daily oral semaglutide in terms of health status and change in body weight in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. METHODS: This prospective, real-world study included patients treated with once-daily semaglutide (O-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was the heart failure status, defined as the >/=5 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 18 months. RESULTS: After a 1:1 propensity score matching, 202 patients were included in each group (mean age 77.8 years, mean body mass index 33.5, 59.2 % females). Patients in the O-Sema Group were more likely to have an improvement in heart failure health status from baseline to 18 months (OR:2.92; 95 %CI: 1.45-4.90; p < 0.01). The mean change in body weight was -9.5 +/- 3.2 kg in patients with oral semaglutide and -2.0 +/- 1.1 kg in control patients (p < 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and the body weight (r=-0.577, p < 0.01) and glycated hemoglobin (r=-0.499, p = 0.011). It had good tolerability and safety. CONCLUSIONS: Once-daily oral semaglutide was associated with an improvement in heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with preserved ejection fraction is needed. CI - Copyright (c) 2025 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Trenas, Alicia AU - Trenas A AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Bernal-Lopez, Maria-Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Lopez-Carmona, Maria-Dolores AU - Lopez-Carmona MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Gomez-Doblas, Juan J AU - Gomez-Doblas JJ AD - Servicio de Cardiologia, Hospital Universitario Virgen de la Victoria, Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. FAU - Martinez-Esteban, Maria-Dolores AU - Martinez-Esteban MD AD - Servicio de Nefrologia, Hospital Regional Universitario de Malaga, Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, RICORS2040 (RD21/0005/0012 and RD24/0004/0026), Malaga, Spain. FAU - Bouarich, Oumayma AU - Bouarich O AD - Servicio de Nefrologia, Hospital Regional Universitario de Malaga, Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, RICORS2040 (RD21/0005/0012 and RD24/0004/0026), Malaga, Spain. FAU - Garcia-Casares, Natalia AU - Garcia-Casares N AD - Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. FAU - Fernandez-Garcia, Diego AU - Fernandez-Garcia D AD - Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Endocrinologia y Nutricion. Hospital Universitario Virgen de la Victoria, Malaga, Spain. FAU - de Lucas, Maria-Dolores Garcia AU - de Lucas MG AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. Electronic address: ricardogomezhuelgas@hotmail.com. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. Electronic address: luismiguelpb1984@gmail.com. LA - eng PT - Journal Article DEP - 20250614 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Heart Failure/drug therapy/complications/physiopathology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/complications MH - Prospective Studies MH - Stroke Volume MH - Aged, 80 and over MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Propensity Score MH - Glycated Hemoglobin MH - Body Weight MH - Weight Loss MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Heart failure OT - Obesity OT - Preserved left ventricular ejection fraction OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. EDAT- 2025/06/16 00:26 MHDA- 2025/09/03 12:34 CRDT- 2025/06/15 21:52 PHST- 2025/03/09 00:00 [received] PHST- 2025/06/03 00:00 [revised] PHST- 2025/06/05 00:00 [accepted] PHST- 2025/09/03 12:34 [medline] PHST- 2025/06/16 00:26 [pubmed] PHST- 2025/06/15 21:52 [entrez] AID - S0953-6205(25)00236-5 [pii] AID - 10.1016/j.ejim.2025.06.007 [doi] PST - ppublish SO - Eur J Intern Med. 2025 Sep;139:106378. doi: 10.1016/j.ejim.2025.06.007. Epub 2025 Jun 14. PMID- 40515833 OWN - NLM STAT- MEDLINE DCOM- 20251025 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 398 IP - 11 DP - 2025 Nov TI - Progress and challenges in obesity pharmacotherapy: semaglutide as a milestone. PG - 15257-15267 LID - 10.1007/s00210-025-04319-0 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, have emerged as effective therapies for glycaemic control and weight reduction in type 2 diabetes and obesity. Both injectable and oral formulations have been investigated in large phase III clinical trials, with growing interest in their long-term efficacy and safety. To review and compare the efficacy, safety, and tolerability of injectable and oral semaglutide formulations, with a focus on their role in chronic weight and glycaemic management. A narrative review was conducted based on data from pivotal clinical trials and real-world studies. Efficacy outcomes included changes in body weight and glycated haemoglobin (HbA1c). Safety profiles, adverse events, and patient adherence factors were also assessed. Injectable semaglutide (2.4 mg weekly) showed a mean weight reduction of 14.9% over 68 weeks in the STEP 1 trial, compared to 15.1% with oral semaglutide (50 mg daily) in the OASIS 1 study. Both formulations demonstrated significant improvements in HbA1c and cardiometabolic parameters. A real-world study found comparable efficacy between formulations. Gastrointestinal adverse events were most common, while serious events were rare. Long-term use was essential for sustained weight loss, as discontinuation led to significant weight regain. No consistent associations with increased cancer or psychiatric adverse events were confirmed. Both oral and injectable semaglutide are effective and generally well-tolerated options for chronic management of type 2 diabetes and obesity. Treatment adherence, long-term safety, and cost considerations should guide therapeutic choices. Ongoing monitoring is warranted to optimize outcomes and minimize risks. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ferrara, Francesco AU - Ferrara F AD - Pharmaceutical Department, Asl Napoli 3 Sud, Dell' Amicizia Street 72, Nola, Naples, Italy. f.ferrara@aslnapoli3sud.it. FAU - Bazzani, Denise AU - Bazzani D AD - Pharmaceutical Department, ATS Val Padana via Dei Toscani 1, 46100, Mantua, Italy. FAU - Crivelli, Barbara AU - Crivelli B AD - Hospital Pharmacy, IRCCS Ospedale Galeazzi - Sant'Ambrogio, via Cristina Belgioioso 173, 20157, Milan, Italy. FAU - Danieli, Elisa AU - Danieli E AD - Hospital Pharmacy, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. FAU - Gazzola, Pietro AU - Gazzola P AD - Hospital Pharmacy, IRCCS Humanitas Research Hospital, Via Alessandro Manzoni, 56 , 20089, Rozzano, Milan, Italy. FAU - Guarnieri, Greta AU - Guarnieri G AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Handschin, Giulia AU - Handschin G AD - Hospital Pharmacy, ASST Papa Giovanni XXIII, piazza OMS, 1, 24127, Bergamo, Italy. FAU - Lauria, Claudia AU - Lauria C AD - Hospital Pharmacy, Istituto Nazionale Dei Tumori, Via Giacomo Venezian, 1, 20133, Milan, Italy. FAU - Marchetti, Carlotta AU - Marchetti C AD - Pharmaceutical Department, ATS Montagna, Via Nazario Sauro, 36/38, 23100, Sondrio, Italy. FAU - Sbraga, Emanuele AU - Sbraga E AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Zero, Carmen AU - Zero C AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Zovi, Andrea AU - Zovi A AD - Hospital Pharmacist, Ministry of Health, Viale Giorgio Ribotta 5, 00144, Rome, Italy. FAU - Langella, Roberto AU - Langella R AD - Italian Society of Hospital Pharmacy (SIFO), SIFO Secretariat of the Lombardy Region, Via Carlo Farini, 81, 20159, Milan, Italy. FAU - Parati, Chiara AU - Parati C AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250614 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/administration & dosage/adverse effects/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Market dynamics OT - Safety OT - Semaglutide, GLP-1RA OT - Treatment of obesity COIS- Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: The authors consent to the publication of the manuscript. Conflicts of interest: The authors declare no competing interests. Clinical trial number: Not applicable. Disclosure: AZ declares that the opinions expressed are of a personal nature and do not in any way commit the responsibility of the Administration to which him belongs. EDAT- 2025/06/14 17:09 MHDA- 2025/10/25 06:29 CRDT- 2025/06/14 11:16 PHST- 2025/04/16 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/10/25 06:29 [medline] PHST- 2025/06/14 17:09 [pubmed] PHST- 2025/06/14 11:16 [entrez] AID - 10.1007/s00210-025-04319-0 [pii] AID - 10.1007/s00210-025-04319-0 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Nov;398(11):15257-15267. doi: 10.1007/s00210-025-04319-0. Epub 2025 Jun 14. PMID- 40514652 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20260804 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Jun 13 TI - Interleukin-1beta in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes. PG - 247 LID - 10.1186/s12933-025-02706-8 [doi] LID - 247 AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1beta (IL-1beta), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOS) trial showed that the inhibition of the IL-1beta pathway was associated with a reduction of CV events in high-risk patients. The present study was designed to determine: (i) whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on MASLD extent and IL-1beta expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; (ii) whether baseline IL-1beta levels may predict the extent of weight loss and related metabolic changes. METHODS: Thirty-two obese subjects with prediabetes (n = 16) or newly diagnosed T2D (n = 16), were randomized to the glucagon-like peptide receptor agonist (GLP1-RA) liraglutide or lifestyle counselling until achieving a comparable weight loss. Visceral adipose tissue (VAT) and gene expression of IL-1beta in peripheral blood mononuclear cells were assessed by magnetic resonance and real time PCR, respectively. RESULTS: At baseline, IL-1beta was positively correlated to body mass index (BMI), fasting plasma glucose, HbA1c, VAT, MASLD extent, platelet count, chemerin and interleukin-1 receptor antagonist (IL1-RA). After achievement of the weight loss target in the two groups, a significant but comparable reduction of IL-1beta (p for difference = 0.56) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C reactive protein (CRP), BMI and MASLD. Furthermore, basal IL-1beta levels independently predicted the extent of MASLD decrease (p = 0.030); subjects in the highest tertile showed a median decrease of - 8.0 (95% CI - 12.3 to - 4.8) compared with - 23.0 (95% CI - 39.5 to - 16.3) in the lowest tertile. CONCLUSION: In patients with obesity with initial impairment of glucose metabolism successful weight loss is associated with a reduction of both IL-1beta levels and MASLD degree. Of interest, basal levels of IL-1beta predict the extent of MASLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1beta a level as a drug-response biomarker. CI - (c) 2025. The Author(s). FAU - Simeone, Paola Giustina AU - Simeone PG AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. FAU - Costantino, Sarah AU - Costantino S AD - Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. FAU - Liani, Rossella AU - Liani R AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. FAU - Tripaldi, Romina AU - Tripaldi R AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. FAU - Di Castelnuovo, Augusto AU - Di Castelnuovo A AD - Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, IS, Italy. FAU - Tartaro, Armando AU - Tartaro A AD - Department of Neuroscience & Imaging, University of Chieti, Chieti, Italy. FAU - Mengozzi, Alessandro AU - Mengozzi A AD - Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Cosentino, Francesco AU - Cosentino F AD - Cardiology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden. FAU - Cipollone, Francesco AU - Cipollone F AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. FAU - Paneni, Francesco AU - Paneni F AD - Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. FAU - Santilli, Francesca AU - Santilli F AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. francesca.santilli@unich.it. AD - Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy. francesca.santilli@unich.it. LA - eng GR - PRIN No. 2010JS3PMZ/Italian Ministry of University and Research/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250613 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 839I73S42A (Liraglutide) RN - 0 (Interleukin-1beta) RN - 0 (IL1B protein, human) RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/blood/diagnosis/therapy/drug therapy/physiopathology MH - *Obesity/blood/therapy/diagnosis/physiopathology/complications MH - Middle Aged MH - Female MH - *Liraglutide/therapeutic use MH - Treatment Outcome MH - *Leukocytes, Mononuclear/metabolism/drug effects/immunology MH - *Prediabetic State/blood/diagnosis/therapy MH - *Interleukin-1beta/blood MH - *Weight Loss/drug effects MH - Biomarkers/blood MH - Hypoglycemic Agents/therapeutic use MH - Adult MH - Time Factors MH - Incretins/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Risk Reduction Behavior MH - Blood Glucose/metabolism/drug effects PMC - PMC12164075 OTO - NOTNLM OT - Adipose tissue OT - Biomarker OT - Inflammation OT - Interleukin-1beta OT - Liver disease OT - MASLD OT - Obesity OT - Prediabetes OT - Type 2 diabetes OT - Weight-loss COIS- Declarations. Ethics approval and consent to participate: The trial was approved by the Italian Ethics Committee of the University of Chieti (Approval n. 10 (protocol 20131) 23.05.2013). Each patient provided written informed consent before participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/06/14 16:45 MHDA- 2025/06/14 16:46 PMCR- 2025/06/13 CRDT- 2025/06/13 23:24 PHST- 2025/02/07 00:00 [received] PHST- 2025/03/24 00:00 [accepted] PHST- 2025/06/14 16:46 [medline] PHST- 2025/06/14 16:45 [pubmed] PHST- 2025/06/13 23:24 [entrez] PHST- 2025/06/13 00:00 [pmc-release] AID - 10.1186/s12933-025-02706-8 [pii] AID - 2706 [pii] AID - 10.1186/s12933-025-02706-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Jun 13;24(1):247. doi: 10.1186/s12933-025-02706-8. PMID- 40514554 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20261010 IS - 2731-7099 (Electronic) IS - 2731-7080 (Linking) VI - 66 IP - 9 DP - 2025 Sep TI - [Weight reduction with incretin mimetics-Opportunities and risks]. PG - 979-985 LID - 10.1007/s00108-025-01918-0 [doi] AB - BACKGROUND: Obesity affects a growing number of people worldwide and is associated with severe metabolic, cardiovascular and oncological complications. Obesity not only represents an individual health burden but is also a socioeconomic challenge. With the incretin mimetics liraglutide, semaglutide and tirzepatide, a new class of drugs is now available that for the first time enables substantial and clinically relevant weight reduction. OBJECTIVE: The article sheds light on the efficacy, safety and prospects of obesity treatment based on glucagon-like peptide 1 (GLP-1). In addition to the results of key clinical trials, potential risks, limitations of use, typical side effects and drug interactions are discussed. Economic aspects are also explained. RESULTS: Clinical trials show an average weight reduction of 15-20%, with tirzepatide in particular being highly effective. Positive side effects of the treatment mainly concern metabolism (prediabetes and type 2 diabetes regression) and cardiovascular diseases. The main side effects are the frequently occurring gastrointestinal disorders, such as nausea and vomiting. The long-term safety of the substances has not yet been conclusively proven. High costs, limited access and the potential for abuse pose additional challenges. Combination preparations and orally available drugs are currently under development. CONCLUSION: Incretin mimetics represent a major advance in the treatment of obesity but require careful selection, close monitoring and long-term integration into lifestyle measures. CI - (c) 2025. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature. FAU - Zech, Thomas J AU - Zech TJ FAU - Kirchweger, Benjamin AU - Kirchweger B FAU - Furst, Robert AU - Furst R AD - Pharmazeutische Biologie, Department Pharmazie - Zentrum fur Pharmaforschung, Ludwig-Maximilians-Universitat Munchen, Butenandtstr. 5, 81377, Munchen, Deutschland. robert.fuerst@cup.lmu.de. LA - ger PT - English Abstract PT - Journal Article PT - Review TT - Gewichtsreduktion mit Inkretinmimetika - Chancen und Risiken. DEP - 20250613 PL - Germany TA - Inn Med (Heidelb) JT - Innere Medizin (Heidelberg, Germany) JID - 9918384885306676 RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Liraglutide/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/therapeutic use/analogs & derivatives/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Semaglutide OTO - NOTNLM OT - Cardiovascular diseases OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide 1 OT - Incretin mimetics/adverse effects OT - Obesity COIS- Einhaltung ethischer Richtlinien. Interessenkonflikt: T.J. Zech halt Aktien von Eli Lilly und Novo Nordisk. B. Kirchweger und R. Furst geben an, dass kein Interessenkonflikt besteht. Fur diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgefuhrt. Fur die aufgefuhrten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. EDAT- 2025/06/14 16:46 MHDA- 2025/08/31 20:01 CRDT- 2025/06/13 23:20 PHST- 2025/05/12 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/14 16:46 [pubmed] PHST- 2025/06/13 23:20 [entrez] AID - 10.1007/s00108-025-01918-0 [pii] AID - 10.1007/s00108-025-01918-0 [doi] PST - ppublish SO - Inn Med (Heidelb). 2025 Sep;66(9):979-985. doi: 10.1007/s00108-025-01918-0. Epub 2025 Jun 13. PMID- 40514456 OWN - NLM STAT- MEDLINE DCOM- 20250807 LR - 20261010 IS - 1615-6692 (Electronic) IS - 0340-9937 (Linking) VI - 50 IP - 4 DP - 2025 Aug TI - [Bariatric surgery versus GLP-1 and dual GIP/GLP-1 receptor agonists : Effects on weight, risk factors and prognosis]. PG - 253-259 LID - 10.1007/s00059-025-05319-9 [doi] AB - To overcome the increasing prevalence of obesity and associated secondary diseases, effective treatment strategies are required. While bariatric surgery (BS) is an established method for significant and sustainable weight reduction, drug treatment with glucagon-like peptide 1 (GLP-1), GLP‑1 receptor agonists (GLP‑1 RA) and dual glucose-dependent insulinotropic peptide (GIP)/GLP‑1 RA has gained increasing importance in recent years. This article highlights the effects of these both treatment approaches on body weight, cardiometabolic risk factors and long-term prognosis, particularly with respect to cardiovascular events and remission of type 2 diabetes. While BS shows more robust weight loss and greater improvement in metabolic parameters, GLP‑1 RA and dual GIP/GLP‑1 RA offer a conservative treatment alternative with a good safety profile. The choice of treatment should be individualized based on the patient risk profile and preferences. CI - (c) 2025. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature. FAU - Ordemann, Jurgen AU - Ordemann J AD - Berliner Adipositas Zentrum, Vivantes Berlin, Neue Bergstrasse 6, 13585, Berlin, Deutschland. juergen.ordemann@vivantes.de. FAU - Elbelt, Ulf AU - Elbelt U AD - Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik B, Universitatsklinikum Ruppin-Brandenburg, Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin, Deutschland. AD - MVZ Endokrinologikum Berlin, Berlin, Deutschland. LA - ger PT - Comparative Study PT - English Abstract PT - Journal Article PT - Review TT - Bariatrische Chirurgie im Vergleich zu GLP-1- und dualen GIP/GLP-1-Rezeptor-Agonisten : Effekt auf Gewicht, Risikofaktoren und Prognose. DEP - 20250613 PL - Germany TA - Herz JT - Herz JID - 7801231 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Bariatric Surgery/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2 MH - Prognosis MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Obesity/therapy MH - Risk Factors MH - *Glucagon-Like Peptide 1 MH - *Gastric Inhibitory Polypeptide MH - Evidence-Based Medicine OTO - NOTNLM OT - Bariatric surgery OT - Cardiovascular events OT - Drug therapy OT - Obesity OT - Weight loss COIS- Einhaltung ethischer Richtlinien. Interessenkonflikt: U. Elbelt hat Honorare fur Vortrage von NovoNordisk Pharma GmbH erhalten. J. Ordemann gibt an, dass kein Interessenkonflikt besteht. Fur diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgefuhrt. Fur die aufgefuhrten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. EDAT- 2025/06/14 16:45 MHDA- 2025/08/07 12:30 CRDT- 2025/06/13 23:19 PHST- 2025/05/07 00:00 [accepted] PHST- 2025/08/07 12:30 [medline] PHST- 2025/06/14 16:45 [pubmed] PHST- 2025/06/13 23:19 [entrez] AID - 10.1007/s00059-025-05319-9 [pii] AID - 10.1007/s00059-025-05319-9 [doi] PST - ppublish SO - Herz. 2025 Aug;50(4):253-259. doi: 10.1007/s00059-025-05319-9. Epub 2025 Jun 13. PMID- 40513367 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260428 IS - 1578-8989 (Electronic) IS - 0025-7753 (Linking) VI - 165 IP - 3 DP - 2025 Sep TI - GLP-1 agonists in glycemic and weight control of type 2 diabetes. New perspectives. PG - 107042 LID - S0025-7753(25)00270-2 [pii] LID - 10.1016/j.medcli.2025.107042 [doi] AB - Obesity and type 2 diabetes mellitus (DM2) are interrelated global problems affecting 988 and 537 million people, respectively, figures that are continuously increasing. Obesity is a key factor in DM2, as it intensifies insulin resistance and beta-cell dysfunction, accelerating disease progression. Weight loss improves glycemic control, reduces the occurrence of comorbidities and, in some cases, induces diabetes remission. In this regard, GLP-1 receptor agonists have revolutionized the treatment of DM2. Since the introduction of exenatide in 2005, more effective drugs have been developed that improve glycemic control, reduce weight, and decrease the occurrence of cardiovascular events. This article discusses the mechanisms of action and efficacy of these agents, highlighting recent advances such as polyagonists and oral formulations. CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Alonso, Silvia Patricia AU - Alonso SP AD - Endocrinologia y Nutricion, Hospital Universitario Costa del Sol, Marbella, Malaga, Espana. FAU - Valdes, Sergio AU - Valdes S AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Espana; Endocrinologia y Nutricion. Hospital Regional Universitario de Malaga/Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga-IBIMA, Malaga, Espana. Electronic address: sergio.valdes@hotmail.es. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Espana; Endocrinologia y Nutricion. Hospital Regional Universitario de Malaga/Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga-IBIMA, Malaga, Espana. LA - eng LA - spa GR - RHE-0038-2024/Junta de Andalucia/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review TT - Agonistas de GLP-1 en el control glucemico y ponderal de la diabetes tipo 2. Nuevas perspectivas. DEP - 20250612 PL - Spain TA - Med Clin (Barc) JT - Medicina clinica JID - 0376377 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Venoms) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Exenatide MH - *Obesity/complications/drug therapy MH - Weight Loss/drug effects MH - *Glycemic Control/methods MH - Peptides/therapeutic use/pharmacology MH - Liraglutide/therapeutic use MH - Venoms/therapeutic use/pharmacology MH - *Glucagon-Like Peptide 1/agonists OTO - NOTNLM OT - Diabetes tipo 2 y obesidad OT - GLP-1 OT - Type 2 diabetes and obesity EDAT- 2025/06/14 16:46 MHDA- 2025/09/01 00:45 CRDT- 2025/06/13 18:07 PHST- 2025/01/26 00:00 [received] PHST- 2025/04/06 00:00 [revised] PHST- 2025/04/09 00:00 [accepted] PHST- 2025/09/01 00:45 [medline] PHST- 2025/06/14 16:46 [pubmed] PHST- 2025/06/13 18:07 [entrez] AID - S0025-7753(25)00270-2 [pii] AID - 10.1016/j.medcli.2025.107042 [doi] PST - ppublish SO - Med Clin (Barc). 2025 Sep;165(3):107042. doi: 10.1016/j.medcli.2025.107042. Epub 2025 Jun 12. PMID- 40509955 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20251216 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 4 DP - 2025 Jul TI - Incidence of Glaucoma in Type 2 Diabetes Patients Treated With GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. PG - e70059 LID - 10.1002/edm2.70059 [doi] LID - e70059 AB - AIMS: Glaucoma, a leading cause of irreversible blindness, is particularly prevalent among individuals with Type 2 Diabetes Mellitus (T2DM), a known risk factor for the disease. This systematic review and meta-analysis aimed to evaluate the incidence of glaucoma in T2DM patients treated with Glucagon-Like Peptide 1 Receptor Agonists (GLP-1RAs) compared to those using other antihyperglycaemic agents. MATERIALS AND METHODS: A comprehensive search of literature was conducted using MEDLINE (PubMed), the Cochrane Library, Google Scholar, and Scopus up to September 14, 2024. Observational studies that reported the incidence of glaucoma among T2DM patients using GLP-1RAs versus other antihyperglycaemic drugs were included. Data analysis employed the random-effects model, presenting odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using I(2) statistics, and a sensitivity analysis was performed to test the result's robustness. RESULTS: Five observational studies involving 2,500,430 participants met the inclusion criteria. The meta-analysis indicated that GLP-1RA use was associated with a nonsignificant reduction in the incidence of glaucoma (OR: 0.78; 95% CI: 0.60 to 1.02; p = 0.01: I(2) = 88%). Sensitivity analysis by leave-one-out method showed a significant reduction of glaucoma in GLP-1 RA users. CONCLUSIONS: In conclusion, GLP-1RA usage in T2DM patients may be beneficial in lowering the risk of glaucoma under some circumstances. These results advocate for further clinical studies to confirm GLP-1RAs' protective ocular effects, potentially influencing future treatment guidelines and preventive care strategies for glaucoma patients. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Asif, Maheen AU - Asif M AUID- ORCID: 0009-0003-8086-000X AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Asif, Aliza AU - Asif A AD - Department of Endocrinolgy, King Edward Medical University, Lahore, Pakistan. FAU - Rahman, Ummi Aiman AU - Rahman UA AD - Department of Endocrinolgy, King Edward Medical University, Lahore, Pakistan. FAU - Farooqi, Hanzala Ahmed AU - Farooqi HA AD - Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan. FAU - Fatima, Oshaz AU - Fatima O AD - Department of Endocrinolgy, King Edward Medical University, Lahore, Pakistan. FAU - Ali, Waqar AU - Ali W AD - Department of Endocrinolgy, King Edward Medical University, Lahore, Pakistan. FAU - Jafar, Uzair AU - Jafar U AD - Department of Endocrinolgy, King Edward Medical University, Lahore, Pakistan. FAU - Jaber, Mohammed Hammad AU - Jaber MH AUID- ORCID: 0000-0002-1366-2375 AD - Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - *Glaucoma/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Observational Studies as Topic PMC - PMC12163345 OTO - NOTNLM OT - GLP-1RA OT - T2DM OT - glaucoma OT - meta analysis COIS- The authors declare no conflicts of interest. EDAT- 2025/06/13 06:34 MHDA- 2025/06/13 06:35 PMCR- 2025/06/13 CRDT- 2025/06/13 04:33 PHST- 2025/04/09 00:00 [revised] PHST- 2024/11/25 00:00 [received] PHST- 2025/05/11 00:00 [accepted] PHST- 2025/06/13 06:35 [medline] PHST- 2025/06/13 06:34 [pubmed] PHST- 2025/06/13 04:33 [entrez] PHST- 2025/06/13 00:00 [pmc-release] AID - EDM270059 [pii] AID - 10.1002/edm2.70059 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 Jul;8(4):e70059. doi: 10.1002/edm2.70059. PMID- 40505816 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20250801 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 226 DP - 2025 Aug TI - GLP-1 receptor agonists and hospitalization due to infections in patients with type 2 diabetes: A nationwide cohort study. PG - 112324 LID - S0168-8227(25)00338-9 [pii] LID - 10.1016/j.diabres.2025.112324 [doi] AB - AIMS: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) demonstrate pleiotropic effects, notably encompassing anti-inflammatory properties. We aim to compare the association of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is) with hospitalization due to various infectious diseases. METHODS: This population-based retrospective cohort study used data from the Taiwan National Health Insurance in 2016-2021. A total of 455,003 patients with type 2 diabetes were identified. We conducted a 1:1 propensity score-matched analysis of patients initiating GLP-1RA or DPP4i therapy. The outcomes assessed were hospitalizations due to various infections. RESULTS: In the matched cohort, we identified 17,706 GLP-1RA and 17,706 DPP4i initiators. GLP-1RA initiators exhibited a significantly lower risk of hospitalization due to lower respiratory tract infections (adjusted HR: 0.56; 95% CI, 0.49 to 0.65) and diabetic foot infections (adjusted HR: 0.77; CI, 0.65 to 0.91), but not intraabdominal (adjusted HR: 0.91; CI, 0.73 to 1.13) or reproductive and urinary tract infections (adjusted HR: 0.98; CI, 0.75 to 1.27) as compared with DPP4i initiators. CONCLUSION: Our study demonstrates that GLP-1RA administration offers advantages over DPP4is in reducing the incidence of severe lower respiratory tract infections and diabetic foot infections requiring hospitalization in individuals with type 2 diabetes. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Wang, Jiun-Ling AU - Wang JL AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan. FAU - Lee, Ching-Chi AU - Lee CC AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan. FAU - Ko, Wen-Chien AU - Ko WC AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan. FAU - Wu, Li-Chiu AU - Wu LC AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Chang, Chia-Hsuin AU - Chang CH AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: chiahsuin123@yahoo.com.tw. LA - eng PT - Journal Article DEP - 20250610 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - *Hospitalization/statistics & numerical data MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Taiwan/epidemiology MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies MH - *Infections/epidemiology MH - Adult OTO - NOTNLM OT - Diabetes mellitus OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Infection COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/06/13 00:27 MHDA- 2025/08/02 10:42 CRDT- 2025/06/12 19:37 PHST- 2025/03/21 00:00 [received] PHST- 2025/05/01 00:00 [revised] PHST- 2025/06/09 00:00 [accepted] PHST- 2025/08/02 10:42 [medline] PHST- 2025/06/13 00:27 [pubmed] PHST- 2025/06/12 19:37 [entrez] AID - S0168-8227(25)00338-9 [pii] AID - 10.1016/j.diabres.2025.112324 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Aug;226:112324. doi: 10.1016/j.diabres.2025.112324. Epub 2025 Jun 10. PMID- 40504374 OWN - NLM STAT- MEDLINE DCOM- 20251205 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 398 IP - 12 DP - 2025 Dec TI - Hemorrhoid risk among people with diabetes mellitus using glucose lowering agents. PG - 17479-17485 LID - 10.1007/s00210-025-04272-y [doi] AB - We investigated whether there is an association between using antidiabetic agents (ADAs) or insulin and hemorrhoid risk among people with diabetes mellitus (DM). We have essentially used a massive dataset to identify a statistical association between ADAs and hemorrhoidal disease. The hazard ratios (HRs) and 95% confidence intervals (CIs) for hemorrhoids were estimated using univariate and multivariate Cox proportional hazards models. Covariates used in the multivariate models included age, sex, comorbidities, and medications. A total of 126,897 patients who had DM between 2009 and 2016 were involved in this study. The joint effect analysis showed that anyone receiving medication therapy with dipeptidyl peptidase IV (DPP IV) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) can significantly lower the risk of hemorrhoid with the adjusted HR (aHR) of 0.64, 95% CI=0.62-0.67; aHR of 0.29, 95% CI=0.24-0.35; and aHR of 0.14, 95% CI=0.11-0.18, respectively. We found that SGLT2i is more potent for hemorrhoid prophylaxis in incidence rate among DM patients. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Hu, Wei-Syun AU - Hu WS AD - School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan. weisyunhu@gmail.com. AD - Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan. weisyunhu@gmail.com. FAU - Lin, Cheng-Li AU - Lin CL AD - Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250612 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - *Hemorrhoids/epidemiology/prevention & control MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Risk Factors MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Insulin/therapeutic use MH - *Diabetes Mellitus/drug therapy/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Antidiabetic agents OT - Diabetes mellitus OT - Hemorrhoid OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declarations. Disclaimer: The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. Human ethics: This study is in accordance with the Declaration of Helsinki. Ethical approval: This study was approved by the Research Ethics Committee of China Medical University and Hospital (CMUH110-REC1-038-CR-2)). Consent to participate: Not required. Consent for publication: Not required. Competing interests: The authors declare no competing interests. EDAT- 2025/06/12 12:31 MHDA- 2025/12/05 06:26 CRDT- 2025/06/12 11:13 PHST- 2024/11/27 00:00 [received] PHST- 2025/05/06 00:00 [accepted] PHST- 2025/12/05 06:26 [medline] PHST- 2025/06/12 12:31 [pubmed] PHST- 2025/06/12 11:13 [entrez] AID - 10.1007/s00210-025-04272-y [pii] AID - 10.1007/s00210-025-04272-y [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Dec;398(12):17479-17485. doi: 10.1007/s00210-025-04272-y. Epub 2025 Jun 12. PMID- 40501244 OWN - NLM STAT- MEDLINE DCOM- 20250612 LR - 20260127 IS - 3105-9686 (Electronic) IS - 1011-601X (Linking) VI - 38 IP - 2 DP - 2025 Mar-Apr TI - Effect of Semaglutide on C-peptide levels in patients with type 2 diabetes. PG - 457-461 AB - The study evaluated the effect of semaglutide treatment for type 2 diabetes mellitus (T2DM), specifically examining its effect on C-peptide levels. A total of 80 patients hospitalized for T2DM were included (January 2022-December 2023), and all patients had conventional treatment with oral metformin. Patients in the control group received subcutaneous insulin aspart, while patients in the observation group received subcutaneous semaglutide. Key variables, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PBG), and time to target blood glucose, were assessed at the baseline and again after three months. Serum endothelin-1 (ET-1), functional vasodilation (FMD), fasting C-peptide, fasting insulin (FINS), and the insulin resistance index (Homa-IR) were also measured. At the end of three months, the observation group had significantly lower 2h-PBG (9.01+/-0.53 mmol/L) and FBG (6.13+/-0.68 mmol/L) than the control group (P<0.05). Additionally, the time to target glucose was shorter in the observation group (3.88+/-0.69 vs. 5.73+/-1.01 days, P<0.05). The observation group also had lower ET-1, higher FMD, and increased Homa-IR (P<0.05). In conclusion, semaglutide optimizes glycemic control, lowers insulin resistance, and increases vasorelaxation function. Semaglutide has great potential as a therapeutic agent in T2DM. FAU - Fan, Pengxiang AU - Fan P AD - Department of Endocrinology, Tianshui Traditional Chinese Medicine Hospital, Tianshui, Gansu China. FAU - Ma, Xiaojun AU - Ma X AD - Department of Endocrinology, Tianshui Traditional Chinese Medicine Hospital, Tianshui, Gansu China. LA - eng PT - Journal Article PL - Pakistan TA - Pak J Pharm Sci JT - Pakistan journal of pharmaceutical sciences JID - 9426356 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (C-Peptide) RN - 0 (Endothelin-1) RN - 0 (Insulin) RN - 9100L32L2N (Metformin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Male MH - Female MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *C-Peptide/blood MH - Insulin Resistance MH - Aged MH - Endothelin-1/blood MH - Insulin/blood MH - Vasodilation/drug effects MH - Metformin/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/06/12 06:30 MHDA- 2025/06/12 06:31 CRDT- 2025/06/12 04:03 PHST- 2025/06/12 06:31 [medline] PHST- 2025/06/12 06:30 [pubmed] PHST- 2025/06/12 04:03 [entrez] PST - ppublish SO - Pak J Pharm Sci. 2025 Mar-Apr;38(2):457-461. PMID- 40500836 OWN - NLM STAT- MEDLINE DCOM- 20250611 LR - 20250611 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 75 IP - 5 DP - 2025 May TI - Choice of Insulin Coformulations: Biphasic Insulin Versus Insulin-GlP1RA. PG - 827-828 LID - 10.47391/JPMA.24-61 [doi] AB - This communication presents a pragmatic approachto describe the phenotypes which match with preferential usage of dual phase insulin or basal insulin+ glucagon-like peptide 1 receptor agonist (GLP1RA)coformulations. A comprehensive evaluation,including severity and style of glycaemia, clinical presentation, comorbidities, complications, and culinary preference, allows efficient choice of insulin formulation. This framework helps in initiation,intensification and interchange of injectable therapy,in an apt, and ept, manner. FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital, Karnal, India; University Centre for Research & Development, Chandigarh University, Mohali, India. FAU - Das, Sambit AU - Das S AD - Department of Endocrinology, Kalinga Institute of Medical Sciences, Bhubaneshwar, India. FAU - Bhattacharya, Saptarshi AU - Bhattacharya S AD - Department of Endocrinology, Apollo Indraprastha Hospitals, New Delhi, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India; Non-communicable disease unit, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53027-39-7 (Insulin, Isophane) RN - 0 (Drug Combinations) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Insulin/therapeutic use/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Insulin, Isophane/therapeutic use/administration & dosage MH - Drug Combinations MH - Blood Glucose/drug effects OTO - NOTNLM OT - BIAsp, GLP1RA, glargine, insulin, Biphasic insulin, IGlarLixi, lixisenatide, IDegAsp, LisproMix,IDegLira, person centred care, premixed insulin EDAT- 2025/06/12 00:38 MHDA- 2025/06/12 00:39 CRDT- 2025/06/11 23:38 PHST- 2025/06/12 00:39 [medline] PHST- 2025/06/12 00:38 [pubmed] PHST- 2025/06/11 23:38 [entrez] AID - xxx [pii] AID - 10.47391/JPMA.24-61 [doi] PST - ppublish SO - J Pak Med Assoc. 2025 May;75(5):827-828. doi: 10.47391/JPMA.24-61. PMID- 40499738 OWN - NLM STAT- MEDLINE DCOM- 20251022 LR - 20260610 IS - 1528-0012 (Electronic) IS - 0016-5085 (Linking) VI - 169 IP - 6 DP - 2025 Nov TI - Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. PG - 1268-1281 LID - S0016-5085(25)00845-5 [pii] LID - 10.1053/j.gastro.2025.06.003 [doi] AB - BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for glycemic control or weight management in patients with type 2 diabetes mellitus or overweight/obesity. However, there are concerns regarding their association with serious gastrointestinal adverse events, although findings have been inconsistent. METHODS: We systematically searched 5 databases for placebo-controlled randomized controlled trials assessing GLP-1RAs in patients with type 2 diabetes mellitus, overweight/obesity, or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease. We included trials that reported cholecystitis, cholelithiasis, cholangitis, cholestasis, pancreatitis, gastroesophageal reflux disease (GERD), gastritis, esophagitis, gastrointestinal ischemia, gastrointestinal hemorrhage, intestinal obstruction, paralytic ileus, gastrointestinal ulceration, gastrointestinal perforation, or gastroparesis. Meta-analyses were performed using a random-effects model, with subgroup analyses evaluating risks based on patient population, GLP-1RA vs dual-agonist formulation, weight-loss profile, dosing, and duration of action. RESULTS: We included 55 randomized controlled trials involving 106,395 participants. GLP-1RAs increased the risk of cholelithiasis (risk ratio [RR], 1.46; 95% CI, 1.09-1.97; 2 more cases per 1000) and probably increased the risk of GERD (RR, 2.19; 95% CI, 1.48-3.25; 4 more cases per 1000) compared with placebo. GLP-1RAs probably have little or no effect on the risk of other gastrointestinal or biliary events. Subgroup analyses showed that the increased risks of cholelithiasis and GERD were more pronounced in trials including individuals with overweight/obesity or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease, weight-loss-inducing GLP-1RAs, or high-dose formulations, although these subgroup effects were not statistically significant. CONCLUSIONS: GLP-1RAs are associated with an increased risk of cholelithiasis and GERD, but do not appear to increase the risk of other gastrointestinal or biliary adverse events. CI - Copyright (c) 2025 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Chiang, Cho-Hung AU - Chiang CH AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Jaroenlapnopparat, Aunchalee AU - Jaroenlapnopparat A AD - Digestive Health Institute, Orlando Health, Orlando, Florida. FAU - Colak, Sena Cakir AU - Colak SC AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts. FAU - Yu, Chun-Chiao AU - Yu CC AD - School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Xanthavanij, Nutchapon AU - Xanthavanij N AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts. FAU - Wang, Tsu-Hsien AU - Wang TH AD - Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, New York. FAU - See, Xin Ya AU - See XY AD - Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York. FAU - Lo, Shao-Wei AU - Lo SW AD - Harvard T.H. Chan School of Public Health, Boston, Massachusetts. FAU - Ko, Albert AU - Ko A AD - Harvard T.H. Chan School of Public Health, Boston, Massachusetts. FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut. FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. FAU - Hsia, Yuan Ping AU - Hsia YP AD - Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. Electronic address: yuangping1018@gmail.com. FAU - Chiang, Cho-Han AU - Chiang CH AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts. Electronic address: chiangchohan1129@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250609 PL - United States TA - Gastroenterology JT - Gastroenterology JID - 0374630 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Randomized Controlled Trials as Topic MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy MH - Risk Factors MH - Risk Assessment MH - *Incretins/adverse effects OTO - NOTNLM OT - Biliary Adverse Events OT - Gastrointestinal Adverse Events OT - Glucagon-Like Peptide-1 Receptor Agonists OT - Meta-Analysis OT - Randomized Controlled Trials EDAT- 2025/06/12 00:38 MHDA- 2025/10/23 00:26 CRDT- 2025/06/11 19:37 PHST- 2025/03/07 00:00 [received] PHST- 2025/06/01 00:00 [revised] PHST- 2025/06/02 00:00 [accepted] PHST- 2025/10/23 00:26 [medline] PHST- 2025/06/12 00:38 [pubmed] PHST- 2025/06/11 19:37 [entrez] AID - S0016-5085(25)00845-5 [pii] AID - 10.1053/j.gastro.2025.06.003 [doi] PST - ppublish SO - Gastroenterology. 2025 Nov;169(6):1268-1281. doi: 10.1053/j.gastro.2025.06.003. Epub 2025 Jun 9. PMID- 40499315 OWN - NLM STAT- MEDLINE DCOM- 20250717 LR - 20260127 IS - 1464-3391 (Electronic) IS - 0968-0896 (Linking) VI - 128 DP - 2025 Oct 1 TI - Design, synthesis, and biological evaluation of long-acting glucagon-like peptide-1 (GLP-1) conjugates modified with dual fatty acids and a proline-alanine-serine (PAS) polypeptide. PG - 118266 LID - S0968-0896(25)00207-X [pii] LID - 10.1016/j.bmc.2025.118266 [doi] AB - The increasing prevalence of type 2 diabetes presents a major global health challenge. Glucagon-like peptide-1 (GLP-1) receptor agonists offer glycemic control, weight loss, and cardiovascular benefits but are limited by rapid enzymatic degradation and short half-life. Semaglutide, modified with a C18 diacid, extends its half-life to one week. Building on this, we developed GLP-1 analogues incorporating a hydrophilic proline-alanine-serine (PAS) sequence, referred to as PAS100, which comprises 100 amino acids with repetitive Pro, Ala, and Ser residues, along with dual fatty acid modifications, to evaluate their long-term therapeutic effects on glycemic control and body weight regulation. Fifteen conjugates were synthesized, featuring dual fatty acid modifications at Lys(26) of Gly(8)-Arg(34)-GLP-1(7-37), with a PAS sequence at the C-terminus to mitigate lipidation-induced hydrophobicity. Seven exhibited enhanced GLP-1 receptor activation compared to their counterparts. Among them, B1, with two C14 monoacids and PAS100, exhibited approximately 3-fold increase in receptor activation compared to semaglutide. These seven conjugates were further evaluated in vivo, categorized into two groups based on their structural features, and compared with semaglutide for weight loss and blood glucose reduction in mice. Among these conjugates, compounds D1, D3, and D4 demonstrated glucose-lowering and weight-reducing effects comparable to semaglutide in vivo. Solubility measurements further confirmed that all d-series compounds displayed improved aqueous solubility, with D1 (bearing both a C14 monoacid and a C12 diacid and a PAS100) achieving the greatest enhancement, approximately two-fold higher than semaglutide. Surface plasmon resonance (SPR) analysis revealed that D1 exhibited a K(D) approximately three-fold lower than that of semaglutide, indicating an enhanced receptor-binding tendency. In conclusion, D1 emerges as a promising GLP-1 analogue with significant therapeutic potential for the treatment of type 2 diabetes. Moreover, the dual-fatty acid conjugation strategy combined with PASylation represents a versatile platform that may be extended to other lipidated peptide therapeutics. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Wang, Chengcheng AU - Wang C AD - Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 200240 Shanghai, China; National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China. FAU - Zhang, Jinhua AU - Zhang J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, 201203 Shanghai, China. FAU - Dong, Yuanzhen AU - Dong Y AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Xu, Jun AU - Xu J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Lu, Jianguang AU - Lu J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Ding, Chunyong AU - Ding C AD - Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 200240 Shanghai, China. Electronic address: chunding@sjtu.edu.cn. FAU - Cai, Zhengyan AU - Cai Z AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China. Electronic address: caizy2007@163.com. FAU - Feng, Jun AU - Feng J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. Electronic address: fengjdmr@163.com. LA - eng PT - Journal Article DEP - 20250606 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Fatty Acids) RN - 0 (Blood Glucose) RN - 9DLQ4CIU6V (Proline) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptide 1/chemistry/pharmacology/chemical synthesis MH - Animals MH - *Drug Design MH - *Hypoglycemic Agents/chemical synthesis/chemistry/pharmacology/therapeutic use MH - *Fatty Acids/chemistry MH - Mice MH - Humans MH - Structure-Activity Relationship MH - Diabetes Mellitus, Type 2/drug therapy MH - Blood Glucose MH - Molecular Structure MH - Male MH - Proline/chemistry MH - *Peptides/chemistry/pharmacology MH - Mice, Inbred C57BL MH - Semaglutide OTO - NOTNLM OT - Bioconjugates OT - Glucagon-like peptide-1 OT - Lipidation OT - Long-acting peptide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/06/12 00:38 MHDA- 2025/07/18 01:39 CRDT- 2025/06/11 18:14 PHST- 2025/03/02 00:00 [received] PHST- 2025/05/22 00:00 [revised] PHST- 2025/05/31 00:00 [accepted] PHST- 2025/07/18 01:39 [medline] PHST- 2025/06/12 00:38 [pubmed] PHST- 2025/06/11 18:14 [entrez] AID - S0968-0896(25)00207-X [pii] AID - 10.1016/j.bmc.2025.118266 [doi] PST - ppublish SO - Bioorg Med Chem. 2025 Oct 1;128:118266. doi: 10.1016/j.bmc.2025.118266. Epub 2025 Jun 6. PMID- 40498168 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20260419 IS - 1559-0100 (Electronic) IS - 1355-008X (Print) IS - 1355-008X (Linking) VI - 89 IP - 3 DP - 2025 Sep TI - GLP-1RA and the possible skin aging. PG - 680-685 LID - 10.1007/s12020-025-04293-w [doi] AB - "Ozempic face" and facial aging have been observed as side effects in many patients after glucagon like peptide 1 receptor agonists (GLP-1RA) therapy for type 2 diabetes mellitus (T2DM) and obesity. However, those medications can reduce systemic inflammation and possibly promote skin health. The rapid weight loss observed with GLP-1RA has been implicated in facial aging. However, recent evidence suggests further pathophysiological mechanisms for this side effect. The aim of this article is to review the literature and present available data on the possible mechanisms of GLP-1RA on skin aging. Indeed, GLP-1RA may affect other types of skin cells, which may accelerate the process of skin aging itself. More specifically, GLP-1RA can act on adipose-derived stem cells (ADSC) and fibroblasts, that present GLP-1R on their surface. Stimulation of the receptor reduces the ability of ADSC to produce protective cytokines. The absence of those cytokines promotes the production of reactive oxygen species (ROS) and causes oxidative damage on fibroblasts. GLP-1RA also reduce the glucose intake of the ADSC, leading to reduced production of ATP and apoptosis. Finally, the stimulation of GLP-1R on ADSCs reduces indirectly the production of estrogens from dermal white adipose tissues (DWAT), which reduces stimulation of fibroblasts to produce collagen. GLP-1RA can also affect the process of skin aging through interaction with advanced glycation end products (AGEs) and RAGE (receptors of AGEs) activation. In conclusion, many patients receiving GLP-1RA suffer from "Ozempic face" and facial aging. It seems that this complication is not exclusively related to decreased facial fat, but there are more aging mechanisms that have to be elucidated. CI - (c) 2025. The Author(s). FAU - Paschou, Ioanna A AU - Paschou IA AD - 1st Department of Dermatology and Venereology, "Andreas Sygros" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Sali, Evangelia AU - Sali E AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Paschou, Stavroula A AU - Paschou SA AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Tsamis, Konstantinos I AU - Tsamis KI AD - Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece. FAU - Peppa, Melpomeni AU - Peppa M AD - Endocrine Unit and Diabetes Center, Second Department of Internal Medicine, School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Psaltopoulou, Theodora AU - Psaltopoulou T AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Nicolaidou, Electra AU - Nicolaidou E AD - 1st Department of Dermatology and Venereology, "Andreas Sygros" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Stratigos, Alexander J AU - Stratigos AJ AD - 1st Department of Dermatology and Venereology, "Andreas Sygros" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. alstrat@med.uoa.gr. LA - eng PT - Journal Article PT - Review DEP - 20250611 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Skin Aging/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Animals PMC - PMC12370548 OTO - NOTNLM OT - AGEs OT - Aging OT - GLP-1RA OT - Obesity OT - Skin OT - Type 2 diabetes COIS- Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. EDAT- 2025/06/11 12:31 MHDA- 2025/08/31 20:01 PMCR- 2025/06/11 CRDT- 2025/06/11 11:05 PHST- 2025/03/01 00:00 [received] PHST- 2025/05/21 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/11 12:31 [pubmed] PHST- 2025/06/11 11:05 [entrez] PHST- 2025/06/11 00:00 [pmc-release] AID - 10.1007/s12020-025-04293-w [pii] AID - 4293 [pii] AID - 10.1007/s12020-025-04293-w [doi] PST - ppublish SO - Endocrine. 2025 Sep;89(3):680-685. doi: 10.1007/s12020-025-04293-w. Epub 2025 Jun 11. PMID- 40497353 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 7 IP - Suppl 7 DP - 2025 Aug TI - Current treatment guidelines and glycated haemoglobin goals for type 2 diabetes: Which patients are most likely to benefit from fixed-ratio basal insulin glucagon-like peptide-1 receptor agonist combinations? PG - 3-13 LID - 10.1111/dom.16502 [doi] AB - Basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are available in two fixed-ratio combinations (FRCs) for the treatment of type 2 diabetes (T2D), insulin degludec with liraglutide and insulin glargine with lixisenatide. FRCs offer a convenient strategy to administer basal insulin and a GLP-1 RA, taking advantage of complementary mechanisms in a single injection to minimize treatment burden and improve glycemic control while mitigating weight gain. For most, a glycated haemoglobin (HbA1c) goal for patients with T2D using a FRC would be <7%, though it can be adjusted based on patient-specific factors. An HbA1c goal of <6.5% is less likely to be appropriate for patients requiring basal insulin, which is included in the FRCs. Ideal candidates for FRCs are those (1) taking oral antihyperglycemic medications only with an HbA1c <10% and <2% away from goal, (2) those on basal insulin and above HbA1c goal, (3) those unwilling or unable to initiate or manage multiple daily injections (i.e., basal-bolus insulin therapy) and (4) those tolerating a GLP-1 RA who require basal insulin to achieve glycemic goals. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Cowart, Kevin AU - Cowart K AUID- ORCID: 0000-0002-6880-1600 AD - University of South Florida, Tampa, Florida, USA. FAU - Carris, Nicholas W AU - Carris NW AUID- ORCID: 0000-0001-8904-5034 AD - University of South Florida, Tampa, Florida, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20250611 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 54Q18076QB (insulin degludec) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Insulin, Long-Acting) RN - 839I73S42A (Liraglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Humans MH - Blood Glucose/metabolism/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Combinations MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycated Hemoglobin/analysis/metabolism MH - Glycemic Control MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Insulin Glargine/administration & dosage/therapeutic use MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Liraglutide/administration & dosage/therapeutic use MH - Peptides/administration & dosage/therapeutic use MH - Practice Guidelines as Topic MH - Glucagon-Like Peptide-2 Receptor PMC - PMC12308271 OTO - NOTNLM OT - GLP-1 analogue OT - basal insulin OT - glycaemic control OT - type 2 diabetes COIS- Dr. Carris and Dr. Cowart have received research funding [institution receives and manages funds] from Sanofi Winthrop Industrie. Dr. Cowart has received research funding from Abbott [institution receives and manages funds]. EDAT- 2025/06/11 12:30 MHDA- 2025/07/30 06:29 PMCR- 2025/07/30 CRDT- 2025/06/11 06:03 PHST- 2025/05/22 00:00 [revised] PHST- 2025/04/30 00:00 [received] PHST- 2025/05/28 00:00 [accepted] PHST- 2025/07/30 06:29 [medline] PHST- 2025/06/11 12:30 [pubmed] PHST- 2025/06/11 06:03 [entrez] PHST- 2025/07/30 00:00 [pmc-release] AID - DOM16502 [pii] AID - 10.1111/dom.16502 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27 Suppl 7(Suppl 7):3-13. doi: 10.1111/dom.16502. Epub 2025 Jun 11. PMID- 40496570 OWN - NLM STAT- MEDLINE DCOM- 20250611 LR - 20250612 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Glucagon-like peptide-1 receptor agonists in liver transplant recipients with diabetes: changes in glucose control and cardiometabolic risk factors. PG - 1586941 LID - 10.3389/fendo.2025.1586941 [doi] LID - 1586941 AB - INTRODUCTION: Data about efficacy and safety of GLP1 receptor agonists in liver-transplanted patients are lacking. METHODS: Among a population of liver-transplanted individuals with diabetes, we evaluated 68 patients before, 6, 12 and 18 months after starting a GLP1RA-based therapy, as add on to metformin or insulin. We assessed glycemic control, body weight and composition (with bio-impedance analysis), liver fibrosis and steatosis (with transient elastography). Amylase, lipase levels and concomitant therapies were recorded at basal and follow up evaluations. Patients had an e-mail contact to report any adverse events. RESULTS: We observed a significant decrease in fasting plasma glucose, HbA1c, weight, BMI, waist circumference. We demonstrated a reduction in total and LDL cholesterol. Liver stiffness decreased during the first 6 months. The rate of adverse events was low and the symptoms reported didn't require any medical measures: 26.9% reported mild nausea, only 3 patients (7.69%) discontinued the drug dose due to gastrointestinal intolerance. No pancreatitis episodes were detected, amylase and lipase levels didn't increase (despite concomitant calcineurin inhibitors). No adjustments in immunosuppressant therapy were reported. Among the 45 patients requiring insulin when a GLP1RA therapy was added on, 20 (33.2%) and 31 (45.5%) could suspend insulin therapy at, respectively, 6 and 18 months. DISCUSSION: In conclusion, GLP1RA-based therapy can be considered safe and effective in a short-term follow up in liver-transplanted patients. Further studies are needed to assess the effects of this drugs on long term complications, such as renal impairment, cardiovascular events and all-cause mortality. CI - Copyright (c) 2025 Grancini, Cogliati, Alicandro, Oliverio, Di Benedetto, Gaglio, Lampertico, Resi and Orsi. FAU - Grancini, Valeria AU - Grancini V AD - Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy. FAU - Cogliati, Irene AU - Cogliati I AD - Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy. FAU - Alicandro, Gianfranco AU - Alicandro G AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. AD - Mother and Child Department, Pediatric Cystic Fibrosis Center, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Oliverio, Andreina AU - Oliverio A AD - Nutrition Research and Metabolomics Unit, Department of Experimental Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Di Benedetto, Clara AU - Di Benedetto C AD - Division of Gastroenterology and Hepatology, Foundation Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Gaglio, Alessia AU - Gaglio A AD - Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy. FAU - Lampertico, Pietro AU - Lampertico P AD - Division of Gastroenterology and Hepatology, Foundation Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Resi, Veronica AU - Resi V AD - Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy. FAU - Orsi, Emanuela AU - Orsi E AD - Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy. LA - eng PT - Journal Article DEP - 20250527 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Liver Transplantation MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Cardiometabolic Risk Factors MH - *Blood Glucose/drug effects/metabolism MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Transplant Recipients MH - *Glycemic Control MH - Follow-Up Studies PMC - PMC12148859 OTO - NOTNLM OT - GLP1-RAs OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - liver transplantation OT - post transplant diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/11 11:29 MHDA- 2025/06/11 11:30 PMCR- 2025/05/27 CRDT- 2025/06/11 05:23 PHST- 2025/03/03 00:00 [received] PHST- 2025/04/28 00:00 [accepted] PHST- 2025/06/11 11:30 [medline] PHST- 2025/06/11 11:29 [pubmed] PHST- 2025/06/11 05:23 [entrez] PHST- 2025/05/27 00:00 [pmc-release] AID - 10.3389/fendo.2025.1586941 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 May 27;16:1586941. doi: 10.3389/fendo.2025.1586941. eCollection 2025. PMID- 40496556 OWN - NLM STAT- MEDLINE DCOM- 20250611 LR - 20250626 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - The potential biomarker value of soluble CD36 in the treatment of diabetic kidney disease: evidence from GLP-1 and insulin interventions. PG - 1605631 LID - 10.3389/fendo.2025.1605631 [doi] LID - 1605631 AB - BACKGROUND: Soluble CD36 (sCD36), the circulating form of the scavenger receptor CD36, plays a key role in lipid accumulation and inflammation during the progression of diabetic kidney disease (DKD), and has been proposed as a promising non-invasive biomarker. The renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) may involve modulation of sCD36. This study aimed to evaluate the impact of GLP-1RA and insulin treatment on sCD36 levels and their association with renal function in DKD patients. METHODS: This single-center, prospective observational cohort study enrolled 191 patients with type 2 diabetes and early-stage DKD, who were stratified into three groups based on treatment regimen: control group (n = 63), insulin group (n = 71), and GLP-1RA group (n = 57). All patients received standard care with metformin, with the insulin and GLP-1RA groups receiving additional respective treatments for 12 weeks. Clinical parameters including sCD36, urinary albumin-to-creatinine ratio (UACR), lipid profile, glycemic markers, and islet function indices were assessed at baseline and post-treatment. Intra- and inter-group comparisons were performed using paired tests and analysis of covariance. Generalized linear regression models were applied to assess the relationship between sCD36 and renal function. RESULTS: Baseline sCD36 and UACR levels were comparable across the three groups (P > 0.05). After 12 weeks, sCD36 levels significantly declined in the GLP-1RA group (median: 195.20 ng/mL, IQR: 160.45-314.75), compared to the insulin group (364.60 ng/mL, IQR: 279.10-394.10) and control group (386.10 ng/mL, IQR: 323.60-471.30) (P < 0.001). The GLP-1RA group also showed the most marked reduction in UACR (P < 0.001). Regression analysis demonstrated a significant positive association between sCD36 and UACR levels both before and after treatment (P < 0.001), and the change in sCD36 (DeltasCD36) was positively correlated with the improvement in UACR, suggesting a link to reduced renal lipotoxicity and inflammation. CONCLUSION: GLP-1RAs significantly reduce sCD36 and UACR levels in patients with early DKD, outperforming insulin in renoprotection. These findings raise the possibility that GLP-1RAs may exert renoprotective effects through modulation of CD36-related pathways, although direct mechanistic validation was not performed in this study.sCD36 may serve as a useful biomarker for monitoring DKD progression and therapeutic response, though further multicenter and long-term studies are needed to confirm its clinical utility. CI - Copyright (c) 2025 Li and Wang. FAU - Li, Wenxuan AU - Li W AD - Department of Endocrinology, The First Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Wang, Yangang AU - Wang Y AD - Department of Endocrinology, The First Affiliated Hospital of Qingdao University, Qingdao, China. LA - eng PT - Journal Article PT - Observational Study DEP - 20250527 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Biomarkers) RN - 0 (CD36 Antigens) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (CD36 protein, human) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Diabetic Nephropathies/drug therapy/blood MH - *Biomarkers/blood MH - Middle Aged MH - *CD36 Antigens/blood MH - *Insulin/therapeutic use MH - Prospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Aged MH - *Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult PMC - PMC12148844 OTO - NOTNLM OT - DKD OT - GLP-1RAs OT - biomarker OT - soluble CD36 OT - urinary albumin-to-creatinine ratio COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/11 11:29 MHDA- 2025/06/11 11:30 PMCR- 2025/05/27 CRDT- 2025/06/11 05:23 PHST- 2025/04/03 00:00 [received] PHST- 2025/04/28 00:00 [accepted] PHST- 2025/06/11 11:30 [medline] PHST- 2025/06/11 11:29 [pubmed] PHST- 2025/06/11 05:23 [entrez] PHST- 2025/05/27 00:00 [pmc-release] AID - 10.3389/fendo.2025.1605631 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 May 27;16:1605631. doi: 10.3389/fendo.2025.1605631. eCollection 2025. PMID- 40493797 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20250819 IS - 1473-6500 (Electronic) IS - 0952-7907 (Linking) VI - 38 IP - 4 DP - 2025 Aug 1 TI - Navigating the clinical benefits, risks, and emerging controversies with glucagon-like peptide-1 receptor agonists. PG - 533-539 LID - 10.1097/ACO.0000000000001522 [doi] AB - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the current clinical implications, benefits, and controversies surrounding the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This review discusses the potential risks associated with GLP-1 RA therapy, such as pulmonary aspirations, tachyphylaxis, and issues with drug efficacy over time.Furthermore, it examines the increasing ethical and medical concerns related to their off-label use, safety, and accessibility. RECENT FINDINGS: Recent studies highlight significant discrepancies in the recommendations provided by different medical societies on the perioperative management of GLP-1 RAs. In addition, insurance barriers exacerbate access issues, with substantial disparities in coverage for weight loss versus diabetes management. The rise of counterfeit GLP-1 RAs, unintentional overdoses, and the growing concern about long-term health impacts are also prominent challenges in the current landscape. SUMMARY: Despite increasing usage and the potential benefits of GLP-1 RAs, a lack of consensus on optimal perioperative management and long-term use, coupled with financial and regulatory barriers, creates significant challenges. Medical societies differ on key aspects such as fasting requirements and the risk of aspiration, and concerns about the safety of compounded and counterfeit products remain. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Sen, Sudipta AU - Sen S AD - Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas. FAU - Pai, Sher-Lu AU - Pai SL AD - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida. FAU - Harbell, Monica W AU - Harbell MW AD - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, Arizona, USA. LA - eng PT - Journal Article PT - Review DEP - 20250530 PL - United States TA - Curr Opin Anaesthesiol JT - Current opinion in anaesthesiology JID - 8813436 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Perioperative Care/methods/standards MH - Off-Label Use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Risk Assessment OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonist OT - perioperative outcomes OT - pulmonary aspiration OT - weight loss EDAT- 2025/06/10 18:27 MHDA- 2025/07/09 12:29 CRDT- 2025/06/10 14:54 PHST- 2025/07/09 12:29 [medline] PHST- 2025/06/10 18:27 [pubmed] PHST- 2025/06/10 14:54 [entrez] AID - 00001503-202508000-00032 [pii] AID - 10.1097/ACO.0000000000001522 [doi] PST - ppublish SO - Curr Opin Anaesthesiol. 2025 Aug 1;38(4):533-539. doi: 10.1097/ACO.0000000000001522. Epub 2025 May 30. PMID- 40491599 OWN - NLM STAT- MEDLINE DCOM- 20250610 LR - 20250611 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Case Report: Amelioration of severe metabolic dysfunction-associated steatohepatitis after switching from conventional GLP-1RAs to tirzepatide. PG - 1501984 LID - 10.3389/fendo.2025.1501984 [doi] LID - 1501984 AB - Metabolic dysfunction-associated steatohepatitis (MASH) has cardiometabolic risk factors, such as obesity and type 2 diabetes, and has been reported to have a potentially higher risk of mortality than conventional steatotic liver diseases. Liver fibrosis develops and can progress to cirrhosis and hepatocellular carcinoma. Although some antidiabetic agents have been reported to ameliorate the condition, no specific medical treatment has been developed to date. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) that has shown efficacy against MASH in some clinical trials. However, these trials were limited to those with mild-to-moderate fibrosis and their history of treatment was often unclear. Here, we report the case of a 50-year-old man with a 16-year history of diabetes. He demonstrated poor control of his diabetes with elevated liver enzymes. A liver biopsy was performed and he was diagnosed with steatohepatitis. Liraglutide was administered for 3 years but his liver function and glycemic control deteriorated gradually and a second liver biopsy was performed in 2023. The histological examination found cirrhosis and liraglutide was switched to tirzepatide. Over 6 months of administration of tirzepatide, the patient's glycated hemoglobin and elevated liver enzyme levels improved. A third biopsy was performed, which showed a marked improvement in histology, with the amelioration of liver fibrosis. A diagnosis of steatotic liver disease was made. Although some previous studies had demonstrated an amelioration of liver fibrosis and an improvement in the prognosis of patients following GLP-1RA treatment, effective medications for patients with severe fibrosis or who are refractory to treatment with GLP-1RAs has not been identified to date. We reported a case with severe MASH whose condition had ameliorated by switching from conventional GLP-1RAs to tirzepatide. CI - Copyright (c) 2025 Oe, Omori, Aimono, Furukawa, Kitakawa, Tateno, Sakai and Cho. FAU - Oe, Yuki AU - Oe Y AD - Department of Internal Medicine, Kushiro Red Cross Hospital, Kushiro, Japan. AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Omori, Takashi AU - Omori T AD - Department of Internal Medicine, Kushiro Red Cross Hospital, Kushiro, Japan. FAU - Aimono, Eriko AU - Aimono E AD - Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan. FAU - Furukawa, Shin AU - Furukawa S AD - Department of Internal Medicine, Kushiro Red Cross Hospital, Kushiro, Japan. FAU - Kitakawa, Hirohiko AU - Kitakawa H AD - Department of Internal Medicine, Kushiro Red Cross Hospital, Kushiro, Japan. FAU - Tateno, Masatoshi AU - Tateno M AD - Department of Pathology, Kushiro Red Cross Hospital, Kushiro, Japan. FAU - Sakai, Kiyoshi AU - Sakai K AD - Department of Internal Medicine, Kushiro Red Cross Hospital, Kushiro, Japan. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. AD - Clinical Research and Medical Innovation Center, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan. LA - eng PT - Case Reports PT - Journal Article DEP - 20250526 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Liraglutide/therapeutic use MH - *Fatty Liver/drug therapy/pathology/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liver Cirrhosis/drug therapy MH - Tirzepatide PMC - PMC12146166 OTO - NOTNLM OT - glucagon-like peptide 1 receptor OT - glucose-dependent insulinotropic polypeptide OT - metabolic dysfunction-associated steatohepatitis OT - obesity OT - type 2 diabetes COIS- YO has received honoraria for lectures from Novo Nordisk Pharma Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/10 06:28 MHDA- 2025/06/10 06:29 PMCR- 2025/05/26 CRDT- 2025/06/10 04:36 PHST- 2024/09/26 00:00 [received] PHST- 2025/04/25 00:00 [accepted] PHST- 2025/06/10 06:29 [medline] PHST- 2025/06/10 06:28 [pubmed] PHST- 2025/06/10 04:36 [entrez] PHST- 2025/05/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1501984 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 May 26;16:1501984. doi: 10.3389/fendo.2025.1501984. eCollection 2025. PMID- 40491239 OWN - NLM STAT- MEDLINE DCOM- 20250827 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 9 DP - 2025 Sep TI - Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. PG - 1657-1667 LID - 10.1002/oby.24331 [doi] AB - OBJECTIVE: The objective of this study was to characterize changes in body weight and glycated hemoglobin (in those with prediabetes at baseline) through 12 months by obesity pharmacotherapy discontinuation status. METHODS: This retrospective cohort study used electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who initiated injectable semaglutide or tirzepatide between 2021 and 2023. Treatment discontinuation was defined by a >90-day gap between exhaustion of previous supply and next dispense or end of study follow-up (December 2024) and was classified into early discontinuation (i.e., within 3 months of index date) and late discontinuation (i.e., within 3-12 months). RESULTS: We identified 7881 patients; 6109 received semaglutide, and 1772 received tirzepatide. A total of 80.8% had low maintenance dosages. Mean (SD) percentage weight reduction at 1 year was 8.7% (9.6%); and it was 3.6% (8.1%) with early discontinuation, 6.8% (9.1%) with late discontinuation, and 11.9% (9.2%) with non-discontinuation (p < 0.001). The mean (SD) absolute reduction in percent glycated hemoglobin at 1 year was 0.1 (0.4) with early discontinuation, 0.2 (0.4) with late discontinuation, and 0.4 (0.4) with non-discontinuation (p < 0.001). CONCLUSIONS: The average weight reduction in this cohort was lower than that observed in the main phase 3 trials, likely because of higher rates of discontinuation and lower maintenance dosages. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AUID- ORCID: 0000-0001-7137-9423 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Boyer, Christopher B AU - Boyer CB AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Griebeler, Marcio L AU - Griebeler ML AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Burguera, Bartolome AU - Burguera B AUID- ORCID: 0000-0001-9808-8327 AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - RPC8755/Cleveland Clinic Research Program Committees/ PT - Journal Article DEP - 20250610 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - Retrospective Studies MH - Female MH - Middle Aged MH - *Obesity/drug therapy MH - Glycated Hemoglobin/analysis MH - *Glycemic Control MH - Adult MH - Weight Loss/drug effects MH - *Tirzepatide/therapeutic use/administration & dosage MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2 MH - Ohio MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12381620 COIS- W. Scott Butsch reported advisory board fees from Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim, and Abbott Laboratories, as well as research funding from Eli Lilly and Company, outside the submitted work. Christopher B. Boyer reported consulting fees from Janssen Pharmaceuticals outside the submitted work. Marcio L. Griebeler reported research funding from Novo Nordisk A/S outside the submitted work. Michael B. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. The other authors declared no conflicts of interest. EDAT- 2025/06/10 06:28 MHDA- 2025/08/31 20:01 PMCR- 2025/08/27 CRDT- 2025/06/10 03:04 PHST- 2025/05/01 00:00 [revised] PHST- 2025/02/13 00:00 [received] PHST- 2025/05/02 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/10 06:28 [pubmed] PHST- 2025/06/10 03:04 [entrez] PHST- 2025/08/27 00:00 [pmc-release] AID - OBY24331 [pii] AID - 10.1002/oby.24331 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Sep;33(9):1657-1667. doi: 10.1002/oby.24331. Epub 2025 Jun 10. PMID- 40490579 OWN - NLM STAT- MEDLINE DCOM- 20250703 LR - 20261010 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 39 IP - 7 DP - 2025 Jul TI - Effects of preoperative glucagon-like peptide-1 receptor agonist therapy on weight loss following bariatric surgery. PG - 4545-4550 LID - 10.1007/s00464-025-11838-7 [doi] AB - INTRODUCTION: GLP-1 receptor agonists (GLP-1RAs) are increasingly prescribed for management of obesity and diabetes. In this context, we aim to determine the effect of preoperative GLP-1RA use on surgical outcomes and long-term weight loss following bariatric surgery. METHODS: We retrospectively identified diabetic patients undergoing primary bariatric surgery at an academic institution between 2014 and 2024. Patients on a GLP-1RA at the time of surgery were compared with GLP-1RA naive patients. Pearson's chi-squared and Fisher's exact tests were used where appropriate to compare the differences in baseline characteristics. A 1:1 nearest neighbor propensity match was used to assess the differences in postoperative outcomes. Mixed-effects models were created to account for repeated weight measures postoperatively with the interactions of GLP-1RA therapy on percent total body weight loss (%TBWL). These models were adjusted for procedure type, patient age, sex, and race. RESULTS: 323 patients met the inclusion criteria. 132 (40.9%) patients were on a GLP-1RA at the time of their procedure while 191 (59.1%) were not. On univariate comparison, GLP-1RA naive patients were less likely to have hyperlipidemia (57% v 69%, p = 0.03) and more likely to undergo RYGB than GLP-1RA patients (84.82% vs 62.88%, p < 0.001). There were no differences in any 30-day postoperative outcomes. GLP-1RA naive patients had better weight loss at one year postoperatively than GLP-1RA patients (TBWL 24.1% vs 20.5%, p = .003). As the follow-up period extended, the weight loss between the groups became more similar. At 5 years postoperatively, the GLP-1RA naive patients had 19.8% TBWL vs. 19.4% TBWL in the GLP-1RA group (p = 0.80). CONCLUSIONS: Preoperative GLP-1RA use is safe prior to bariatric surgery but is associated with inferior early postoperative weight loss in diabetic patients. GLP-1RA naive patients appear to experience greater weight recidivism when compared to patients on a GLP-1RA prior to surgery, resulting in comparable long-term weight loss. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Friesch, Mason AU - Friesch M AUID- ORCID: 0009-0000-9485-3386 AD - Stritch School of Medicine, Loyola University Chicago, 2160 S 1St Ave, Maywood, IL, USA. mfriesch@luc.edu. FAU - Fernando, Mitchel AU - Fernando M AD - Stritch School of Medicine, Loyola University Chicago, 2160 S 1St Ave, Maywood, IL, USA. FAU - Sheedy, Emma AU - Sheedy E AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. FAU - Helenowski, Irena AU - Helenowski I AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. FAU - Wool, Laura AU - Wool L AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. FAU - Edwards, Monica AU - Edwards M AD - Department of Medicine, Loyola University Medical Center, Maywood, IL, USA. FAU - Brown, Kevin AU - Brown K AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. FAU - Lau, James AU - Lau J AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. FAU - Cohn, Tyler AU - Cohn T AD - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA. LA - eng PT - Journal Article DEP - 20250609 PL - Germany TA - Surg Endosc JT - Surgical endoscopy JID - 8806653 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Weight Loss/drug effects MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Bariatric Surgery MH - Middle Aged MH - Adult MH - Treatment Outcome MH - *Preoperative Care/methods MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Obesity, Morbid/surgery/complications OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 agonists OT - Outcomes COIS- Declarations. Disclosures: Mr. Friesch, Mr. Fernando, Dr. Sheedy, Dr. Helenowski, Dr. Wool, Dr. Edwards, Dr. Brown, Dr. Lau, and Dr. Cohn have no conflict of interest. EDAT- 2025/06/10 00:30 MHDA- 2025/07/03 06:27 CRDT- 2025/06/09 23:18 PHST- 2025/03/15 00:00 [received] PHST- 2025/05/19 00:00 [accepted] PHST- 2025/07/03 06:27 [medline] PHST- 2025/06/10 00:30 [pubmed] PHST- 2025/06/09 23:18 [entrez] AID - 10.1007/s00464-025-11838-7 [pii] AID - 10.1007/s00464-025-11838-7 [doi] PST - ppublish SO - Surg Endosc. 2025 Jul;39(7):4545-4550. doi: 10.1007/s00464-025-11838-7. Epub 2025 Jun 9. PMID- 40490304 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20250624 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 19 IP - 24 DP - 2025 Jun 24 TI - Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics. PG - 22357-22375 LID - 10.1021/acsnano.5c05745 [doi] AB - Rational adjustment of surface physicochemical properties of inhalable nanocarriers significantly influences their in vivo fate during pulmonary delivery. Among these, surface hydrophilicity/hydrophobicity has been recognized as a critical factor in the transmucosal process. However, the impacts of surface hydrophilicity/hydrophobicity on the transcellular performance and ultimate therapeutic effects of pulmonary-delivered nanosystems still remain unelucidated. In this study, we developed a series of liposomes with varying surface hydrophilicity to investigate the effect of surface properties on both local and systemic drug delivery. Interestingly, low-hydrophilic liposomes exhibited enhanced systemic absorption, whereas high-hydrophilic liposomes demonstrated prolonged pulmonary residence after inhalation. To validate this principle, we applied two disease models. In a type II diabetes mellitus model, low hydrophilic liposomes loaded with GLP-1 receptor agonists (Liraglutide or Semaglutide) showed excellent systemic drug delivery and hypoglycemic effects. In an OVA-induced allergic asthma model, budesonide-loaded high hydrophilic liposomes significantly alleviated symptoms while reducing dosing frequency. Mechanistic studies further revealed that liposomes with lower surface hydrophilicity could enhance the transcellular transport efficiency of the drug through alveolar epithelial cells, while those with higher surface hydrophilicity prolonged the pulmonary residence of the drug by decreasing alveolar epithelium transportation and the avoidance of macrophage clearance. Lastly, we evaluated the biocompatibility of these liposomes following inhalation. Overall, tuning the surface hydrophilicity/hydrophobicity of inhalable nanocarriers to suit local or systemic delivery goals offers valuable insights for the rational design of advanced pulmonary delivery systems. FAU - Liu, Xi AU - Liu X AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Zhang, Lie AU - Zhang L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Li, Sa AU - Li S AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Xing, Liyun AU - Xing L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Ni, Mingjie AU - Ni M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Minyi AU - Huang M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Yuan AU - Huang Y AUID- ORCID: 0000-0003-3410-8602 AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. LA - eng PT - Journal Article DEP - 20250609 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Liposomes) RN - 0 (Anti-Asthmatic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 51333-22-3 (Budesonide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Hydrophobic and Hydrophilic Interactions MH - Administration, Inhalation MH - *Nanoparticles/chemistry MH - Mice MH - Liposomes/chemistry MH - *Asthma/drug therapy/chemically induced MH - *Anti-Asthmatic Agents/administration & dosage/chemistry/pharmacology/therapeutic use MH - Surface Properties MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/administration & dosage/chemistry/pharmacology/therapeutic use MH - Budesonide/administration & dosage/therapeutic use/chemistry MH - Drug Delivery Systems MH - Male MH - Hypoglycemic Agents/administration & dosage MH - Diabetes Mellitus, Experimental/drug therapy OTO - NOTNLM OT - GLP-1RAs OT - budesonide OT - inhalable liposome OT - pulmonary delivery OT - respiratory disease OT - surface hydrophilicity/hydrophobicity OT - systemic absorption EDAT- 2025/06/10 00:30 MHDA- 2025/06/24 13:16 CRDT- 2025/06/09 21:03 PHST- 2025/06/24 13:16 [medline] PHST- 2025/06/10 00:30 [pubmed] PHST- 2025/06/09 21:03 [entrez] AID - 10.1021/acsnano.5c05745 [doi] PST - ppublish SO - ACS Nano. 2025 Jun 24;19(24):22357-22375. doi: 10.1021/acsnano.5c05745. Epub 2025 Jun 9. PMID- 40490148 OWN - NLM STAT- MEDLINE DCOM- 20260222 LR - 20260222 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 24 IP - 3 DP - 2026 Mar TI - Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD. PG - 723-732.e10 LID - S1542-3565(25)00464-1 [pii] LID - 10.1016/j.cgh.2025.06.001 [doi] AB - BACKGROUND: We investigated the use of type 2 diabetes (T2D) medications, including pioglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, in individuals with T2D and metabolic dysfunction-associated steatotic liver disease (MASLD), and explored the effect of these medications on long-term risk of liver-related events (LREs) and progression of liver stiffness in a retrospective cohort study. METHODS: We enrolled 7867 individuals with T2D and MASLD from 16 tertiary referral centers between February 2004 and January 2023. We recorded the use of pioglitazone, GLP-1RAs, and SGLT-2 inhibitors and analyzed the effects of these antihyperglycemic medications on the risk of developing incident LREs and the progression of liver stiffness over a median of 5.1 years of follow-up. RESULTS: Pioglitazone, GLP-1RAs and SGLT-2 inhibitors were prescribed to 1238 (15.7%), 863 (11.0%), and 2386 (30.3%) individuals with T2D and MASLD, respectively. A significant increase in the utilization of GLP-1RAs and SGLT-2 inhibitors was observed from 2010-2017 to 2017-2023, with pioglitazone and SGLT-2 inhibitors being prescribed more frequently in Asian countries than in Western countries (pioglitazone: 17.9% vs 3.8%; SGLT-2 inhibitors: 34.4% vs 7.3%; P < .001). After propensity score matching, in competing risk models, SGLT-2 inhibitor use was significantly associated with a lower risk of developing both LREs (subdistribution hazard ratio, 0.23; 95% confidence interval, 0.08-0.69, P = .009) and liver stiffness progression (hazard ratio, 0.54; 95% confidence interval, 0.35-0.86, P = .008) after adjusting for potential confounders. CONCLUSIONS: SGLT-2 inhibitor use is more prevalent among Asian than Western individuals. SGLT-2 inhibitors are associated with a lower risk of LREs in individuals with T2D and MASLD. CI - Copyright (c) 2026 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Shi, Yu AU - Shi Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China. FAU - Kim, Seung Up AU - Kim SU AD - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Yip, Terry Cheuk-Fung AU - Yip TC AD - Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. FAU - Tsochatzis, Emmanuel AU - Tsochatzis E AD - University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom. FAU - Petta, Salvatore AU - Petta S AD - Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy. FAU - Nakajima, Atsushi AU - Nakajima A AD - Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Hagstrom, Hannes AU - Hagstrom H AD - Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden; Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden. FAU - Bugianesi, Elisabetta AU - Bugianesi E AD - Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Citta della Salute e della Scienza di Torino, University of Turin, Turin, Italy. FAU - Chan, Wah-Kheong AU - Chan WK AD - Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. FAU - Boursier, Jerome AU - Boursier J AD - Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France. FAU - George Goh, Boon-Bee AU - George Goh BB AD - Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore. FAU - Sanyal, Arun J AU - Sanyal AJ AD - Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia. FAU - Romero-Gomez, Manuel AU - Romero-Gomez M AD - Digestive Diseases Unit and CIBERehd, Virgen del Rocio University Hospital, Seville, Spain. FAU - Calleja, Jose Luis AU - Calleja JL AD - Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. FAU - de Ledinghen, Victor AU - de Ledinghen V AD - Echosens, Paris, France. FAU - Newsome, Philip Noel AU - Newsome PN AD - Institute of Hepatology, King's College Hospital, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. FAU - Fan, Jian-Gao AU - Fan JG AD - Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. FAU - Lai, Michelle AU - Lai M AD - Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. FAU - Castera, Laurent AU - Castera L AD - UMR1149 (CRI), INSERM, Universite Paris Cite, Paris, France; Service d'Hepatologie, Hopital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy, France. FAU - Fournier, Celine AU - Fournier C AD - Echosens, Paris, France. FAU - Lee, Hye Won AU - Lee HW AD - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Wong, Grace Lai-Hung AU - Wong GL AD - Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. FAU - Pennisi, Grazia AU - Pennisi G AD - Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy. FAU - Yoneda, Masato AU - Yoneda M AD - Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Shang, Ying AU - Shang Y AD - Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden. FAU - Armandi, Angelo AU - Armandi A AD - Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Citta della Salute e della Scienza di Torino, University of Turin, Turin, Italy. FAU - de Saint-Loup, Marc AU - de Saint-Loup M AD - Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France. FAU - Canivet, Clemence M AU - Canivet CM AD - Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France. FAU - Teh, Kevin Kim-Jun AU - Teh KK AD - Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore. FAU - Asgharpour, Amon AU - Asgharpour A AD - Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia. FAU - Gallego-Duran, Rocio AU - Gallego-Duran R AD - Digestive Diseases Unit and CIBERehd, Virgen del Rocio University Hospital, Seville, Spain. FAU - Llop, Elba AU - Llop E AD - Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. FAU - Lara-Romero, Carmen AU - Lara-Romero C AD - Digestive Diseases Unit and CIBERehd, Virgen del Rocio University Hospital, Seville, Spain. FAU - Chan, Mandy Sau-Wai AU - Chan MS AD - Echosens, Paris, France. FAU - Mahgoub, Sara AU - Mahgoub S AD - Institute of Hepatology, King's College Hospital, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. FAU - Lin, Huapeng AU - Lin H AD - Department of Gastroenterology and Hepatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Digestive Diseases Research and Clinical Translation, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Shanghai, China. FAU - Liu, Wen-Yue AU - Liu WY AD - Department of Endocrinology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Targher, Giovanni AU - Targher G AD - Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy. FAU - Byrne, Christopher D AU - Byrne CD AD - Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, University of Southampton, Southampton, United Kingdom. FAU - Wong, Vincent Wai-Sun AU - Wong VW AD - Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: wongv@cuhk.edu.hk. FAU - Zheng, Ming-Hua AU - Zheng MH AD - MAFLD Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. Electronic address: zhengmh@wmu.edu.cn. CN - VCTE-Prognosis Study Group LA - eng PT - Journal Article DEP - 20250607 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - X4OV71U42S (Pioglitazone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - Retrospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Pioglitazone/therapeutic use/adverse effects MH - *Fatty Liver/complications/epidemiology MH - Disease Progression MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Liver Fibrosis OT - Metabolic Dysfunction-Associated Steatotic Liver Disease OT - Outcome OT - Vibration-Controlled Transient Elastography FIR - Sanyal, Arun J IR - Sanyal AJ FIR - Nakajima, Atsushi IR - Nakajima A FIR - Bugianesi, Elisabetta IR - Bugianesi E FIR - Tsochatzis, Emmanuel IR - Tsochatzis E FIR - Goh, George Boon-Bee IR - Goh GB FIR - Hagstrom, Hannes IR - Hagstrom H FIR - Boursier, Jerome IR - Boursier J FIR - Calleja, Jose Luis IR - Calleja JL FIR - Romero-Gomez, Manuel IR - Romero-Gomez M FIR - Zheng, Ming-Hua IR - Zheng MH FIR - Newsome, Philip N IR - Newsome PN FIR - Petta, Salvatore IR - Petta S FIR - Kim, Seung Up IR - Kim SU FIR - de Ledinghen, Victor IR - de Ledinghen V FIR - Wong, Vincent Wai-Sun IR - Wong VW FIR - Chan, Wah-Kheong IR - Chan WK EDAT- 2025/06/10 00:30 MHDA- 2026/02/23 01:34 CRDT- 2025/06/09 19:35 PHST- 2025/01/18 00:00 [received] PHST- 2025/05/16 00:00 [revised] PHST- 2025/06/02 00:00 [accepted] PHST- 2026/02/23 01:34 [medline] PHST- 2025/06/10 00:30 [pubmed] PHST- 2025/06/09 19:35 [entrez] AID - S1542-3565(25)00464-1 [pii] AID - 10.1016/j.cgh.2025.06.001 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2026 Mar;24(3):723-732.e10. doi: 10.1016/j.cgh.2025.06.001. Epub 2025 Jun 7. PMID- 40489337 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 10 DP - 2025 Jul TI - External control arm with real world data to assess the effect of semaglutide on chronic kidney disease risk among patients with type 2 diabetes. PG - 1237-1243 LID - 10.1080/14656566.2025.2518329 [doi] AB - BACKGROUND: Clinical trials have shown semaglutide effective in mitigating risks associated with type 2 diabetes and chronic kidney disease. However, semaglutide's real-world effectiveness and long-term outcomes are not fully established. RESEARCH DESIGN & METHODS: Using 2019-2024 Kythera Labs data, an external control arm was created using criteria identified in the FLOW clinical trial. Primary outcomes were major kidney disease events (kidney failure onset and >/= 50% reduction in estimated glomerular filtration rate from baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes. RESULTS: The control arm (n = 896,257) was compared with the clinical trial cohort (n = 1,766). After propensity score matching on age, sex, socioeconomic status, and comorbidities, semaglutide treatment was associated with a 26% reduction in primary event risk compared with the comparator group (702 vs 1,068 events; HR: 0.74; 95% CI, 0.67-0.81), consistent with the 24% risk reduction observed in the clinical trial. CONCLUSION: Semaglutide treatment was linked to a significantly lower risk of clinically relevant renal outcomes. Our findings provide robust real-world evidence that supports the FLOW trial results regarding the renoprotective effects of semaglutide, highlighting its promise as an effective therapeutic option for managing renal complications. FAU - Baser, Onur AU - Baser O AD - Department of Economics, Bogazici Univerisity, Istanbul, Turkiye. AD - School of Public Health, City University of New York, New York, NY, USA. FAU - Lu, Yuanqing AU - Lu Y AD - Department of Outcomes Research, Columbia Data Analytics, New York, NY, USA. LA - eng PT - Journal Article DEP - 20250613 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/pharmacology MH - Female MH - Male MH - *Renal Insufficiency, Chronic/prevention & control/etiology/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology MH - Aged MH - Propensity Score MH - Glomerular Filtration Rate/drug effects MH - *Diabetic Nephropathies/prevention & control/etiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Semaglutide OT - chronic kidney disease OT - comparative effectiveness OT - observational study OT - real-world evidence OT - survival analysis OT - type 2 diabetes EDAT- 2025/06/09 18:28 MHDA- 2025/07/09 12:29 CRDT- 2025/06/09 12:42 PHST- 2025/07/09 12:29 [medline] PHST- 2025/06/09 18:28 [pubmed] PHST- 2025/06/09 12:42 [entrez] AID - 10.1080/14656566.2025.2518329 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jul;26(10):1237-1243. doi: 10.1080/14656566.2025.2518329. Epub 2025 Jun 13. PMID- 40482671 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260924 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 7 DP - 2025 Jul TI - Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial. PG - 568-579 LID - S2213-8587(25)00096-8 [pii] LID - 10.1016/S2213-8587(25)00096-8 [doi] AB - BACKGROUND: IcoSema is a once‑weekly combination therapy of basal insulin icodec (icodec) and semaglutide (a GLP‑1 analogue) currently in development. COMBINE 1 compared the efficacy and safety of IcoSema with once‑weekly icodec alone in adults with inadequately controlled type 2 diabetes on daily basal insulin therapy. METHODS: COMBINE 1, a 52‑week, open‑label, treat‑to‑target, randomised, phase 3a trial, was done at 192 outpatient clinics and hospital departments across 20 countries and regions. Individuals aged 18 years or older with a BMI of 40 kg/m(2) or less and type 2 diabetes (HbA(1c) 7.0-10.0% [53.0-85.8 mmol/mol]) treated with daily basal insulin with or without oral glucose‑lowering medications were randomly assigned (1:1) via a randomisation and trial supply management system to IcoSema (700 U/mL plus 2 mg/mL) or icodec (700 U/mL), both administered as subcutaneous injections on the same day each week, at any time of the day. There was no stratification based on participants' baseline characteristics. The primary endpoint was change in HbA(1c) from baseline to week 52, evaluated in the full analysis set (all randomly assigned participants). The trial is registered with ClinicalTrials.gov, NCT05352815, and has been completed. FINDINGS: Between June 1, 2022, and March 13, 2023, 1671 individuals were screened, of whom 1291 (mean age 60.6 years [SD 10.3]; 799 [62%] males and 492 [38%] females) were randomly assigned to IcoSema (n=646) or icodec (n=645). At week 52, from a baseline value of 8.22% (SD 0.83; 66.3 mmol/mol [9.1]), estimated mean change in HbA(1c) was -1.55 percentage points (SE 0.03; -16.9 mmol/mol [0.4]) with IcoSema and -0.89 percentage points (SE 0.03]; -9.7 mmol/mol [0.4]) with icodec (estimated treatment difference [ETD] -0.66 percentages points [95% CI -0.76 to -0.57]; -7.3 mmol/mol [-8.3 to -6.2]; p<0.0001; superiority confirmed). The rate of combined clinically significant or severe hypoglycaemia from baseline to week 57 was significantly lower with IcoSema than with icodec (0.14 vs 0.63 episodes per person‑year of exposure; estimated rate ratio 0.22 [95% CI 0.14 to 0.36]; p<0.0001; superiority confirmed). The most frequently reported adverse events were within the system organ class of gastrointestinal disorders in the IcoSema group (303 [47%] of 644 participants had 1033 events during the trial) and infections and infestations in the icodec group (275 [43%] of 644 participants had 466 events. 59 (9%) participants in the IcoSema group and 69 (11%) participants in the icodec group had a serious adverse event. No treatment-related deaths occurred. INTERPRETATION: In adults with inadequately controlled type 2 diabetes on daily basal insulin therapy, once‑weekly IcoSema showed superiority to once-weekly icodec alone in changes in HbA(1c) and in overall lower rate of combined clinically significant or severe hypoglycaemia. IcoSema might provide an option for insulin therapy intensification in adults with type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Chinese and Japanese translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Mathieu, Chantal AU - Mathieu C AD - Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Kim, Sin Gon AU - Kim SG AD - Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea. FAU - Larsen, Jonas Hughes AU - Larsen JH AD - Novo Nordisk, Aalborg, Denmark. FAU - Philis-Tsimikas, Athena AU - Philis-Tsimikas A AD - Scripps Whittier Diabetes Institute, San Diego, CA, USA. FAU - Ramachandran, Ambady AU - Ramachandran A AD - India Diabetes Research Foundation and Dr A Ramachandran's Diabetes Hospitals, Guindy, Chennai, India. FAU - Pagliaro Rocha, Thais M AU - Pagliaro Rocha TM AD - Novo Nordisk, Soborg, Denmark. FAU - Shankarappa, Vinay Babu AU - Shankarappa VB AD - Novo Nordisk, Soborg, Denmark. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. LA - eng SI - ClinicalTrials.gov/NCT05352815 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250604 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - *Glucagon-Like Peptides/administration & dosage MH - Adult MH - Drug Administration Schedule MH - *Insulin Glargine/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Blood Glucose MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests CM serves or has served on advisory panels for Abbott, Bayer, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Insulet, Medtronic, Novartis, Novo Nordisk, Roche, SAB Bio, Sanofi, and Vertex (financial compensation paid to institution); has received research support to institution from ActoBio Therapeutics, Medtronic, Novo Nordisk, and Sanofi; serves or has served on speaker bureaus for Abbott, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, Roche, Sanofi, and Vertex (financial compensation paid to institution); and is President of the European Association for the Study of Diabetes (EASD; all external support from EASD is to be found on www.easd.org) and Vice-President of the European Diabetes Forum. FG has received grants from Eli Lilly and Roche Diabetes Care; consulting fees from Eli Lilly and Novo Nordisk; support for attending meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, LifeScan, Merck Sharp & Dohme, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; serves or has served on advisory panels for AstraZeneca, Biomea, Boehringer Ingelheim, Eli Lilly, LifeScan, Merck Sharp & Dohme, MedImmune, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; has had unpaid leadership roles at EASD/EFSD, Societa Italiana di Endocrinologia (SIE), and FO.Ri.SIE; and has received support for medical writing and statistical analysis from AstraZeneca, Biomea, Eli Lilly, Novo Nordisk, and Sanofi Aventis. SGK has received consulting fees and honoraria from AstraZeneca, Boehringer Ingelheim, Celltrion, Eli Lilly, Novo Nordisk, and Sanofi; and grants for medical research from Abbott, AstraZeneca, Boehringer Ingelheim, Celltrion, and Viatris. JHL, TMPR, and VBS are employees of Novo Nordisk and hold stock options in Novo Nordisk. AP-T provides consultation and advisory services on behalf of her employer Scripps Health for Dexcom, Eli Lilly, Medtronic, and Novo Nordisk; has received honoraria and support for presentations and travel or attendance to meetings from Corcept, Dexcom, Eli Lilly, and Novo Nordisk; and participated on behalf of her employer Scripps Health on an advisory board for Medtronic. YT has received consulting or lecture fees from Astellas Pharma, AstraZeneca, Eli Lilly Japan, Kowa Company, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi, and Sumitomo Pharma; and grants from Nippon, Boehringer Ingelheim, and Sumitomo Pharma. LJ has received consulting fees or honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Innovent Biologics, MSD, Novo Nordisk, and Sanofi-Aventis; and has served on advisory panels for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi Aventis, Sibionics, and Sinocare. AR declares no competing interests. EDAT- 2025/06/08 03:37 MHDA- 2025/06/24 11:10 CRDT- 2025/06/07 18:52 PHST- 2024/12/06 00:00 [received] PHST- 2025/04/02 00:00 [revised] PHST- 2025/04/03 00:00 [accepted] PHST- 2025/06/24 11:10 [medline] PHST- 2025/06/08 03:37 [pubmed] PHST- 2025/06/07 18:52 [entrez] AID - S2213-8587(25)00096-8 [pii] AID - 10.1016/S2213-8587(25)00096-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Jul;13(7):568-579. doi: 10.1016/S2213-8587(25)00096-8. Epub 2025 Jun 4. PMID- 40482670 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260924 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 7 DP - 2025 Jul TI - Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. PG - 556-567 LID - S2213-8587(25)00052-X [pii] LID - 10.1016/S2213-8587(25)00052-X [doi] AB - BACKGROUND: IcoSema is a once-weekly combination therapy of basal insulin icodec (icodec) and semaglutide (a GLP-1 analogue) developed for the treatment of type 2 diabetes. We aimed to evaluate the efficacy and safety of IcoSema versus basal-bolus therapy (BBT) in adults with type 2 diabetes inadequately controlled on daily basal insulin. METHODS: COMBINE 3, a 52-week, open-label, treat-to-target, non-inferiority, randomised, phase 3a trial, was done across 109 outpatient clinics and hospital departments in 14 countries. Individuals aged 18 years or older with type 2 diabetes (HbA(1c) 7.0-10.0% [53.0-85.8 mmol/mol]) receiving daily basal insulin (20-80 U per day) were randomly assigned (1:1) to receive once-weekly IcoSema injection using a pen device or BBT (once-daily insulin glargine U100 with two to four daily insulin aspart injections) using an automated, interactive central web-response system. The primary endpoint was change in HbA(1c) from baseline to week 52, tested for non-inferiority (0.3 percentage-point margin). Confirmatory secondary endpoints were change in bodyweight from baseline to week 52; weekly total insulin dose during weeks 50-52; and combined clinically significant hypoglycaemic episodes (<3.0 mmol/L [<54 mg/dL], confirmed by blood glucose meter) or severe hypoglycaemic episodes (associated with severe cognitive impairment requiring external assistance for recovery) from baseline to week 57. The primary and confirmatory secondary endpoints were evaluated using the full analysis set (all randomly assigned participants). Descriptive statistics for safety endpoints were based on the safety analysis set (participants exposed to a trial product), with statistical analyses based on the full analysis set. This trial is registered with ClinicalTrials.gov (NCT05013229) and is complete. FINDINGS: Between Nov 30, 2021, and Sept 28, 2022, 844 participants were screened; 679 (mean age 59.6 years [SD 10.4]; 399 [59%] males and 280 [41%] females) were randomly assigned to IcoSema (n=340) or BBT (n=339). At week 52, estimated mean change in HbA(1c) was -1.47 percentage points (SE 0.05; -16.0 mmol/mol [0.6]) with IcoSema and -1.40 percentage points (0.06; -15.3 mmol/mol [0.7]) with BBT, confirming non-inferiority of IcoSema versus BBT (estimated treatment difference [ETD] -0.06 percentage points [95% CI -0.22 to 0.09; -0.70 mmol/mol [-2.39 to 0.99]; p<0.0001). Superiority was confirmed for IcoSema versus BBT for change in bodyweight from baseline to week 52 (ETD -6.72 kg [95% CI -7.58 to -5.86]; p<0.0001), weekly total insulin dose during weeks 50-52 (ETD -270 U [-303 to -236]; p<0.0001), and overall rate of clinically significant or severe hypoglycaemia from baseline to week 57 (0.21 vs 2.23 episodes per person-year of exposure; estimated rate ratio 0.12 [0.08 to 0.17]; p<0.0001). The most frequently reported adverse events during the trial were gastrointestinal disorders with IcoSema (148 [44%] of 340 participants had 443 events) and infections and infestations with BBT (116 [35%] of 328 participants had 193 events). INTERPRETATION: Once-weekly IcoSema achieved non-inferior HbA(1c) reduction and superiority in change in bodyweight, weekly total insulin dose, and hypoglycaemia rates versus daily BBT, suggesting that there is a potentially beneficial treatment intensification option for adults with type 2 diabetes. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Billings, Liana K AU - Billings LK AD - Department of Medicine, Endeavor Health/NorthShore Hospitals, and University of Chicago Pritzker School of Medicine, Skokie, IL, USA. Electronic address: lbillings@northshore.org. FAU - Andreozzi, Francesco AU - Andreozzi F AD - Department of Medical and Surgical Sciences and Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Frederiksen, Marie AU - Frederiksen M AD - Novo Nordisk, Soborg, Denmark. FAU - Gourdy, Pierre AU - Gourdy P AD - Department of Diabetology, Toulouse University Hospital, Toulouse, France; Institute of Metabolic and Cardiovascular Diseases, UMR1297 INSERM/UT3, Toulouse University, Toulouse, France. FAU - Gowda, Amoolya AU - Gowda A AD - Novo Nordisk, Soborg, Denmark. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Pletsch-Borba, Laura AU - Pletsch-Borba L AD - Novo Nordisk, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AD - Department of Diabetes, Metabolism, and Endocrinology, Tokyo Medical University, Tokyo, Japan. FAU - Unnikrishnan, A G AU - Unnikrishnan AG AD - Chellaram Diabetes Institute, Pune, Maharashtra, India. FAU - Vianna, Andre G D AU - Vianna AGD AD - Curitiba Diabetes Center, Department of Endocrine Diseases, Hospital Nossa Senhora das Gracas, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05013229 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250604 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - *Insulin/administration & dosage MH - *Insulin Glargine/administration & dosage MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Adult MH - *Glucagon-Like Peptides/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests LKB has received research support or consultant fees, or has served on advisory panels for Bayer, Dexcom, Endogenex, Eli Lilly, Novo Nordisk, Sanofi, Pfizer, and Xeris. FA has received consultant fees for Novo Nordisk. MF, AG, and LP-B are employees of Novo Nordisk and hold stock options. PG has received research support or consultant fees, or has served on advisory panels for Abbott, AbbVie, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Organon, Pfizer, and Sanofi. LJ has received research support or consultant fees, or has served on advisory panels for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare. RS has received research support or consultant fees, or has served on advisory panels for Astellas, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Sanofi, Sumitomo, and Teijin. AGU has received research support and served on advisory panels for Novo Nordisk and has received consulting fees for Abbott, Boehringer Ingelheim, and Novo Nordisk. AGDV has received research support or consultant fees or has served on advisory panels for Abbott Diabetes Care, AstraZeneca, Bayer, Eli Lilly, Eurofarma, Medtronic, Novo Nordisk, Roche Diabetes Care, and Servier. EDAT- 2025/06/08 03:37 MHDA- 2025/06/24 13:08 CRDT- 2025/06/07 18:52 PHST- 2024/10/11 00:00 [received] PHST- 2025/01/31 00:00 [revised] PHST- 2025/02/13 00:00 [accepted] PHST- 2025/06/24 13:08 [medline] PHST- 2025/06/08 03:37 [pubmed] PHST- 2025/06/07 18:52 [entrez] AID - S2213-8587(25)00052-X [pii] AID - 10.1016/S2213-8587(25)00052-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Jul;13(7):556-567. doi: 10.1016/S2213-8587(25)00052-X. Epub 2025 Jun 4. PMID- 40481909 OWN - NLM STAT- MEDLINE DCOM- 20250731 LR - 20250803 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 8 DP - 2025 Aug TI - An Overview of Currently Available Injectable Therapies in Diabetes: A Guide to Practitioners. PG - 3634-3656 LID - 10.1007/s12325-025-03250-3 [doi] AB - The management of diabetes has seen significant advancements with the introduction of various injectable therapies. Being a common chronic disorder, it is managed by doctors across all specialties worldwide. Despite the availability of new medications, healthcare professionals continue to face ambiguity due to differing terminologies and variations in regional practices. This review aims to elucidate the current therapeutic spectrum of injectable therapies in diabetes care, providing clarity on the types, mechanisms, and clinical implications of both insulin and non-insulin injections. An extensive review of existing literature was conducted, focusing on insulin injections (including short-acting, rapid-acting, ultra-rapid acting, intermediate-acting, long acting and ultra-long-acting types), non-insulin injections (such as glucagon-like peptide-1 [GLP-1] receptor agonists, dual GLP-1 and gastric inhibitory polypeptide [GIP] agonist, and amylin analogs) and co-formulations (long-acting insulin with GLP-1 or long-acting insulin with rapid acting insulin). We have included innovators and biosimilars in this review article for better understanding. Insulin therapies offer tailored glycemic control, while non-insulin injectables provide additional benefits in weight management and reduced hypoglycemia risk. This review serves as a comprehensive guide for healthcare providers worldwide to navigate the landscape of injectable treatment options in diabetes, with a focus on optimizing therapeutic outcomes through informed decision-making. CI - (c) 2025. The Author(s). FAU - Kesavadev, Jothydev AU - Kesavadev J AUID- ORCID: 0000-0001-6522-6391 AD - Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. jothydev@gmail.com. FAU - Basanth, Anjana AU - Basanth A AD - Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Shankar, Arun AU - Shankar A AD - Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Saboo, Banshi AU - Saboo B AD - Dia Care-Diabetes Care and Hormone Clinic, Diabetology, Ahmedabad, Gujarat, India. FAU - Mohan, Anjana Ranjit AU - Mohan AR AD - Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India. FAU - Joshi, Shashank AU - Joshi S AD - Joshi Clinic, Lilavati and Sir HN RF Hospitals, Mumbai, Maharashtra, India. FAU - Ghosh, Sujoy AU - Ghosh S AD - Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. FAU - Krishnan, Gopika AU - Krishnan G AD - Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Jothydev, Krishnadev AU - Jothydev K AD - Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Ashik, Asha AU - Ashik A AD - Dia Care-Diabetes Care and Hormone Clinic, Diabetology, Ahmedabad, Gujarat, India. AD - Jothydev's Diabetes and Research Centre, Kochi, Kerala, India. LA - eng PT - Journal Article PT - Review DEP - 20250607 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Insulin/administration & dosage/therapeutic use MH - Injections MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetes Mellitus/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 PMC - PMC12313841 OTO - NOTNLM OT - Amylin analogs OT - Clinical practice OT - Co-formulations OT - Diabetes management OT - GLP-1 receptor agonists OT - Injectable therapies OT - Insulin OT - Insulin analogs OT - Non-insulin injections COIS- Declarations. Conflict of Interest: The authors (Jothydev Kesavadev, Anjana Basanth, Arun Shankar, Banshi Saboo, Anjana Ranjit Mohan, Shashank Joshi, Sujoy Ghosh, Gopika Krishnan, Krishnadev Jothydev, Asha Ashik) declare that they have no conflicts of interest related to this manuscript. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2025/06/08 03:36 MHDA- 2025/07/31 18:28 PMCR- 2025/06/07 CRDT- 2025/06/07 11:06 PHST- 2025/02/08 00:00 [received] PHST- 2025/05/15 00:00 [accepted] PHST- 2025/07/31 18:28 [medline] PHST- 2025/06/08 03:36 [pubmed] PHST- 2025/06/07 11:06 [entrez] PHST- 2025/06/07 00:00 [pmc-release] AID - 10.1007/s12325-025-03250-3 [pii] AID - 3250 [pii] AID - 10.1007/s12325-025-03250-3 [doi] PST - ppublish SO - Adv Ther. 2025 Aug;42(8):3634-3656. doi: 10.1007/s12325-025-03250-3. Epub 2025 Jun 7. PMID- 40481813 OWN - NLM STAT- MEDLINE DCOM- 20250607 LR - 20260622 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 5 DP - 2025 Jul TI - Impact of Glucagon-Like Peptide-1 Receptor Agonists on the Dementia Incidence in Patients With Type 2 Diabetes Mellitus: A Population-Based Longitudinal Cohort Study. PG - e70058 LID - 10.1002/dmrr.70058 [doi] LID - e70058 AB - AIMS: Type 2 diabetes mellitus (T2DM) is recognized for increasing the risk of dementia; however, conclusive evidence supporting interventions to mitigate this risk remains elusive. This study endeavours to ascertain whether the glucagon-like peptide-1 receptor agonists (GLP-1RAs) correlate with reduced incidence of dementia. MATERIALS AND METHODS: The cohort comprised individuals initiating treatment with either GLP-1RAs or non-GLP-1RAs medications between 2013 and 2021. This study examined the association between GLP-1RAs and the risk of all-cause dementia. Propensity score-matched and Cox proportional hazard models were employed to calculate the adjusted hazard ratio (aHR) and confidence interval (CI) for the incidence of dementia. RESULTS: Among a cohort comprising 109,778 individuals, the use of GLP-1RA demonstrated a reduced risk of dementia compared with its non-use (aHR, 0.90; 95% CI, 0.83-0.97). Subgroup analyses stratified by different diabetic complications revealed significantly lower dementia incidence rates among GLP-1RAs users than among non-GLP-1RAs users. Individuals aged 0.05). CONCLUSION: In patients with T2DM, patients with treatment of GLP-1 RAs resulted in lower risks of osteoporosis than those without treatment of GLP-1 RAs. These findings support the potential bone-protective effects of GLP-1 RAs but further randomized controlled trials (RCTs) or large-scale database analyses are needed to confirm these observations and guide clinical recommendations. CI - Copyright (c) 2025 Chen, Lyu, Zhao, Han, Huang, Yang and Zhou. FAU - Chen, Ming AU - Chen M AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. FAU - Lyu, Yiming AU - Lyu Y AD - Medmotion Clinic, Shanghai, China. FAU - Zhao, Jingwei AU - Zhao J AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. FAU - Han, Xianwei AU - Han X AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. FAU - Huang, Tao AU - Huang T AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. FAU - Yang, Tongtao AU - Yang T AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. FAU - Zhou, Yong AU - Zhou Y AD - Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shanxi, China. LA - eng PT - Journal Article DEP - 20250521 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Osteoporosis/epidemiology/prevention & control/etiology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Incidence MH - China/epidemiology MH - Follow-Up Studies PMC - PMC12133453 OTO - NOTNLM OT - GLP-1 receptor agonists OT - bone metabolism OT - cohort study OT - electronic medical records OT - fracture risk OT - osteoporosis OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/05 06:27 MHDA- 2025/06/05 06:28 PMCR- 2025/05/21 CRDT- 2025/06/05 05:18 PHST- 2025/03/03 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2025/06/05 06:28 [medline] PHST- 2025/06/05 06:27 [pubmed] PHST- 2025/06/05 05:18 [entrez] PHST- 2025/05/21 00:00 [pmc-release] AID - 10.3389/fendo.2025.1586589 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 May 21;16:1586589. doi: 10.3389/fendo.2025.1586589. eCollection 2025. PMID- 40469023 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20250826 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 56 IP - 9 DP - 2025 Sep TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Nontraumatic Intracerebral Hemorrhage in Patients With Type 2 Diabetes. PG - 2761-2766 LID - 10.1161/STROKEAHA.125.050972 [doi] AB - BACKGROUND: GLP-1RAs (glucagon-like peptide-1 receptor agonists) have consistently demonstrated a protective effect against ischemic stroke. However, whether this benefit also extends to nontraumatic intracerebral hemorrhage (ICH) remains unknown. Given the blood pressure-lowering and anti-inflammatory properties of GLP-1RAs, we aimed to evaluate their potential impact on ICH risk in patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using global health care data from the TriNetX network. Patients with type 2 diabetes who used GLP-1RAs (n=326 777) were compared with those who did not (n=643 614). Propensity score matching (1:1) was performed to balance baseline characteristics, and follow-up was conducted for up to 4 years. The primary outcomes included all-cause mortality, ischemic stroke, and ICH (overall and by location). Hazard ratios and 95% CIs were calculated to assess the mean treatment effect in the treated group. RESULTS: After propensity score matching (resulting in 2 balanced groups of 255 460 individuals each), GLP-1RAs use was associated with a lower risk of ICH (hazard ratio, 0.743 [95% CI, 0.684-0.807]). The lower ICH risk associated with GLP-1RAs was observed across all ICH locations (all P230 million individuals globally. In the recent STRIDE trial, Bonaca et al.(1) demonstrated that semaglutide improved walking capacity and hemodynamic parameters and slowed PAD progression in patients with T2D. These results reveal an unanticipated vasculoprotective benefit of GLP-1RAs. CI - Published by Elsevier Inc. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. FAU - Hess, David A AU - Hess DA AD - Department of Physiology and Pharmacology, Western University, London, ON, Canada; Robarts Research Institute, London, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: dhess3@uwo.ca. LA - eng PT - Journal Article PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Peripheral Arterial Disease/drug therapy MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests S.V. reports receiving grants and/or research support and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Heart Research Center, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc., Sanofi, and Sun Pharma. EDAT- 2025/06/05 00:28 MHDA- 2025/06/05 00:29 CRDT- 2025/06/04 18:24 PHST- 2025/05/07 00:00 [received] PHST- 2025/05/08 00:00 [accepted] PHST- 2025/06/05 00:29 [medline] PHST- 2025/06/05 00:28 [pubmed] PHST- 2025/06/04 18:24 [entrez] AID - S1550-4131(25)00257-8 [pii] AID - 10.1016/j.cmet.2025.05.001 [doi] PST - ppublish SO - Cell Metab. 2025 Jun 3;37(6):1257-1259. doi: 10.1016/j.cmet.2025.05.001. PMID- 40466271 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260428 IS - 1578-8989 (Electronic) IS - 0025-7753 (Linking) VI - 165 IP - 3 DP - 2025 Sep TI - Efficacy of once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes. PG - 107019 LID - S0025-7753(25)00247-7 [pii] LID - 10.1016/j.medcli.2025.107019 [doi] AB - INTRODUCTION AND OBJECTIVES: There is still limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. We analyzed the efficacy in terms of health status, and the change in body weight of once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes. PATIENTS AND METHODS: This prospective, real-world study included patients with heart heart failure with preserved ejection fraction, obesity and type 2 diabetes treated with once-weekly 1.00mg semaglutide (Sema-Preserved Group) and patients not treated with glucagon-like peptide-1 receptor agonists (Control-Preserved Group). A 1:1 propensity score matching analysis was performed. The primary outcome was the heart failure status defined as the >/=5 point difference in the Spanish version of the Kansas City Cardiomyopathy Questionnaire total symptom score, and the change of body weight at 24 months. RESULTS: After matching, 203 patients were included in each group. A primary outcome event occurred in 123 patients (60.6%) in the Sema-Preserved Group and 36 (17.7%) in the Control-Preserved Group (odds ratio: 3.99; 95% confidence interval: 1.69-6.28; p<0.01), and the mean change in body weight was -12.9+/-4.2kg in patients with semaglutide and -2.5+/-1.1kg in control patients (p<0.01). There were also significant declines in the heart failure events, and in all-cause hospitalizations. CONCLUSIONS: Once-weekly 1.00mg semaglutide was associated with improved heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, obesity, and type 2 diabetes. Further research on glucagon-like peptide-1 receptor agonists in heart failure is needed. CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Bernal-Lopez, Maria-Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Trenas, Alicia AU - Trenas A AD - Servicio de Medicina Interna, Area Sanitaria Norte de Malaga, Hospital de Antequera, Antequera, Spain. FAU - Ricci, Michele AU - Ricci M AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Lopez-Carmona, Maria-Dolores AU - Lopez-Carmona MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Garcia de Lucas, Maria-Dolores AU - Garcia de Lucas MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: luismiguelpb1984@gmail.com. LA - eng LA - spa GR - CB06/03/0018/European Regional Development Fund (ERDF)/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250603 PL - Spain TA - Med Clin (Barc) JT - Medicina clinica JID - 0376377 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/drug therapy/complications/physiopathology MH - Male MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Prospective Studies MH - Middle Aged MH - *Obesity/complications MH - Stroke Volume MH - Treatment Outcome MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus tipo 2 OT - Fraccion de eyeccion ventricular izquierda preservada OT - Heart failure OT - Insuficiencia cardiaca OT - Obesidad OT - Obesity OT - Preserved left ventricular ejection fraction OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/06/05 00:28 MHDA- 2025/09/01 00:44 CRDT- 2025/06/04 18:15 PHST- 2024/11/24 00:00 [received] PHST- 2025/03/06 00:00 [revised] PHST- 2025/03/07 00:00 [accepted] PHST- 2025/09/01 00:44 [medline] PHST- 2025/06/05 00:28 [pubmed] PHST- 2025/06/04 18:15 [entrez] AID - S0025-7753(25)00247-7 [pii] AID - 10.1016/j.medcli.2025.107019 [doi] PST - ppublish SO - Med Clin (Barc). 2025 Sep;165(3):107019. doi: 10.1016/j.medcli.2025.107019. Epub 2025 Jun 3. PMID- 40465422 OWN - NLM STAT- MEDLINE DCOM- 20250721 LR - 20250725 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 8 DP - 2025 Aug 1 TI - Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study. PG - 1386-1394 LID - 10.2337/dc25-0154 [doi] AB - OBJECTIVE: To assess the association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and risk of incident thyroid tumors. RESEARCH DESIGN AND METHODS: The retrospective, active-comparator new-user cohort study used international administrative claims and electronic health record databases. Participants included patients with type 2 diabetes mellitus (T2DM) with prior metformin therapy initiating a GLP-1RA versus new users of sodium-glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP-4is), and sulfonylureas (SUs). The outcome was incident thyroid tumor and thyroid malignancy. Propensity score matching and stratification were used to adjust for confounders with an intention-to-treat and on-treatment strategy. Cox regression was used to estimate hazard ratios (HRs) pooled using a random-effects meta-analysis. Unmeasured confounding was evaluated using negative outcomes, with calibration of the HR. RESULTS: A total of 460,032 users of GLP-1RAs, 717,792 users of SGLT2is, 2,055,583 users of DPP-4is, and 1,119,868 users of SUs were included. Only U.S. cohorts passed study diagnostics. Thyroid tumor incidence ranged from 0.88 to 1.03 per 1,000 person-years in GLP-1RA cohorts. GLP-1RA exposure was not associated with an increased risk of thyroid tumors compared with SGLT2is, DPP-4is, or SUs (meta-analysis: GLP-1RA vs. SGLT2i HR range from 0.83 [95% CI 0.57-1.27] to 0.95 [0.85-1.06]; GLP-1RA vs. SU HR range from 0.95 [0.75-1.20] to 1.03 [0.87-1.23]; GLP-1RA vs. DPP-4i HR range from 0.78 [0.60-1.01] to 0.93 [0.83-1.04]). Analysis using thyroid malignancy and including a 1-year lag period produced similar conclusions. CONCLUSIONS: In patients with T2DM initiating second-line treatments, we observed no increased risk of thyroid tumors with GLP-1RA exposure. CI - (c) 2025 by the American Diabetes Association. FAU - Morales, Daniel R AU - Morales DR AUID- ORCID: 0000-0002-0063-8069 AD - Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, U.K. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan at Ann Arbor, Ann Arbor, MI. FAU - Viernes, Benjamin AU - Viernes B AD - Veterans Affairs Informatics and Computing Infrastructure Department of Veterans Affairs, Salt Lake City, UT. AD - Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT. FAU - DuVall, Scott L AU - DuVall SL AD - Veterans Affairs Informatics and Computing Infrastructure Department of Veterans Affairs, Salt Lake City, UT. AD - Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT. FAU - Matheny, Michael E AU - Matheny ME AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN. AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN. FAU - Simon, Katherine R AU - Simon KR AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN. AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY. FAU - Richter, Lauren R AU - Richter LR AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY. AD - Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY. FAU - Ostropolets, Anna AU - Ostropolets A AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY. FAU - Lau, Wallis C Y AU - Lau WCY AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China. AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, U.K. AD - Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, U.K. FAU - Man, Kenneth K C AU - Man KKC AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China. AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, U.K. AD - Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, U.K. FAU - Chattopadhyay, Shounak AU - Chattopadhyay S AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AUID- ORCID: 0000-0002-0210-655X AD - Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Minty, Evan AU - Minty E AD - Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD. FAU - Sun, Feng AU - Sun F AUID- ORCID: 0000-0003-4334-6805 AD - Department of Epidemiology and Biostatistics, Peking University, Beijing, China. FAU - Yin, Can AU - Yin C AD - DTA&AI, Real World Solutions, IQVIA, Durham, NC. FAU - Seager, Sarah L AU - Seager SL AD - DTA&AI, Real World Solutions, IQVIA, Durham, NC. FAU - Chai, Yi AU - Chai Y AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. FAU - Zhou, Jin J AU - Zhou JJ AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA. AD - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT. FAU - Reyes, Carlen AU - Reyes C AUID- ORCID: 0000-0001-8486-3265 AD - Real-World Epidemiology Research Group, Fundaci Institut Universitari per a la recerca a l'Atenci Primria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Pistillo, Andrea AU - Pistillo A AD - Real-World Epidemiology Research Group, Fundaci Institut Universitari per a la recerca a l'Atenci Primria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Duarte-Salles, Talita AU - Duarte-Salles T AD - Real-World Epidemiology Research Group, Fundaci Institut Universitari per a la recerca a l'Atenci Primria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Blacketer, Clair AU - Blacketer C AD - Observational Health Data Analytics, Janssen Research and Development, LLC, Titusville, NJ. FAU - Schuemie, Martijn J AU - Schuemie MJ AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA. AD - Epidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, NJ. FAU - Ryan, Patrick B AU - Ryan PB AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY. AD - Epidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, NJ. FAU - Krumholz, Harlan M AU - Krumholz HM AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT. AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, CT. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY. FAU - Khera, Rohan AU - Khera R AUID- ORCID: 0000-0001-9467-6199 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT. AD - Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, CT. FAU - Suchard, Marc A AU - Suchard MA AD - Veterans Affairs Informatics and Computing Infrastructure Department of Veterans Affairs, Salt Lake City, UT. AD - Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA. AD - Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. AD - Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. LA - eng GR - R01 HL169954/NH/NIH HHS/United States GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HG006139/HG/NHGRI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - K23 HL153775/NH/NIH HHS/United States GR - R01 LM006910/NH/NIH HHS/United States GR - K23 HL153775/HL/NHLBI NIH HHS/United States GR - R01 HG006139/NH/NIH HHS/United States GR - ORD 22-D4V/US Department of Veterans Affairs/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Thyroid Neoplasms/epidemiology/chemically induced MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC12281980 COIS- Duality of Interest. R.K. is an associate editor of the Journal of the American Medical Association and reported receiving support from the Doris Duke Charitable Foundation. He also receives research support through Yale from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is a coinventor of U.S. Provisional Patent Applications 63/619,241; 63/606,203; 63/177,117; 63/346,610; 63/428,569; and 63/484,426 unrelated to the current work. He is also a cofounder of Evidence2Health and Ensight-AI, both representing precision health platforms to improve evidence-based cardiovascular care. S.L.D. reports receiving grants from Alnylam Pharmaceuticals, Inc.; AstraZeneca Pharmaceuticals LP; Biodesix, Inc.; Celgene Corporation; Cerner Enviza; GSK PLC; Janssen Pharmaceuticals, Inc.; Novartis International AG; and Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. K.K.C.M. reported receiving support through a Maplethorpe Fellowship and the National Institute of Health Research, U.K.; European Commission Framework Horizon 2020; Hong Kong Research Grant Council; and Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work. In the past 3 years, H.M.K. received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a cofounder of Refactor Health and HugoHealth and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/06/04 18:30 MHDA- 2025/07/21 18:31 PMCR- 2025/06/04 CRDT- 2025/06/04 12:33 PHST- 2025/01/20 00:00 [received] PHST- 2025/05/01 00:00 [accepted] PHST- 2025/07/21 18:31 [medline] PHST- 2025/06/04 18:30 [pubmed] PHST- 2025/06/04 12:33 [entrez] PHST- 2025/06/04 00:00 [pmc-release] AID - 160553 [pii] AID - 250154 [pii] AID - 10.2337/dc25-0154 [doi] PST - ppublish SO - Diabetes Care. 2025 Aug 1;48(8):1386-1394. doi: 10.2337/dc25-0154. PMID- 40464480 OWN - NLM STAT- MEDLINE DCOM- 20250628 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 18 IP - 5 DP - 2025 May TI - COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes. PG - 259-262 LID - 10.1080/17512433.2025.2516784 [doi] AB - During treatment intensification of injectable therapies among persons with type 2 diabetes mellitus (T2DM) without evidence of severe insulin deficiency, a glucagon-like peptide-1 agonist (GLP-1 RA) is preferred to insulin. However, due to its progressive nature, many individuals over the course of disease will ultimately require insulin treatment. The use of fixed-ratio combination of basal insulin and GLP-1 RA represents a practical and convenient method for treatment intensification. It has been shown to be more efficacious in improving glycemic control, compared with GLP-1 RA or basal insulin alone, and similarly effective with lower insulin dose in reducing glycated hemoglobin (HbA(1c)) levels, along with less weight gain, and a lower risk of hypoglycemia compared with basal/bolus insulin therapy. The recently published COMBINE 2 trial reported that switching to weekly combination therapy of basal insulin icodec and semaglutide (IcoSema), compared with semaglutide, results in greater HbA(1c) reduction, similar risk of clinically significant or severe hypoglycemia and comparable gastrointestinal tolerability, but unfavorable weight change among individuals with T2DM inadequately controlled with GLP-1 RA therapy, with or without additional oral glucose-lowering drugs. IcoSema represents an effective, safe, and convenient therapeutic choice for treatment intensification in individuals with T2DM inadequately controlled with GLP-1 RA therapy. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20250609 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Hypoglycemic Agents/administration & dosage/adverse effects/pharmacology/therapeutic use MH - Insulin/administration & dosage/adverse effects MH - Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Drug Combinations MH - Hypoglycemia/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 agonist OT - IcoSema OT - icodec OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2025/06/04 12:29 MHDA- 2025/07/01 04:49 CRDT- 2025/06/04 08:43 PHST- 2025/07/01 04:49 [medline] PHST- 2025/06/04 12:29 [pubmed] PHST- 2025/06/04 08:43 [entrez] AID - 10.1080/17512433.2025.2516784 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2025 May;18(5):259-262. doi: 10.1080/17512433.2025.2516784. Epub 2025 Jun 9. PMID- 40464139 OWN - NLM STAT- MEDLINE DCOM- 20250604 LR - 20260924 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 17 IP - 6 DP - 2025 Jun TI - Trends in Pharmacological Treatment of Patients With New Onset Type 2 Diabetes: Usage Patterns in an Evolving Guideline Landscape. PG - e70108 LID - 10.1111/1753-0407.70108 [doi] LID - e70108 AB - AIMS: In patients with new onset type 2 diabetes, this study aimed to analyze glucose-lowering medication use patterns between 2014 and 2022. MATERIALS AND METHODS: This retrospective study included adults with incident type 2 diabetes in the University of California Health System between 2014 and 2022. We determined medications used within 1 year of diagnosis and evaluated statistical evidence of use pattern changes via Mann-Kendall trend tests. Four categories of high-risk patients requiring cardio-kidney-metabolic protection were also evaluated in stratified analyses based on 2024 ADA guidelines. RESULTS: Of 40 150 patients with incident type 2 diabetes, 38.5% initiated glucose-lowering medication within 1 year. Metformin remained the most used medication from 2014 to 2022. From 2014 to 2022, usage of GLP-1 receptor agonists and SGLT-2 inhibitors increased exponentially. GLP-1 receptor agonist use increased from below 2.5%-21%. While SGLT-2 inhibitor use increased from less than 2.5%-14%. This growth coincided with a decline in sulfonylurea usage. Among high-risk, insulin was most prevalent in those with heart failure or chronic kidney disease. However, usage of insulin declined overall in all groups. Utilization of SGLT-2 inhibitors was particularly high in patients with prior heart failure. CONCLUSIONS: In adults with new onset type 2 diabetes, GLP-1 receptor agonist and SGLT-2 inhibitor utilization has markedly increased, coordinating with evolving guidelines that emphasize cardiovascular and chronic kidney disease management. However, overall adoption rates of these medications remain low based on indicated populations. Sulfonylurea use declined while metformin remains the most frequently initiated treatment. CI - (c) 2025 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Hou, William AU - Hou W AD - Donald Bren School of Information and Computer Sciences, University of California, Irvine, California, USA. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Nephrology Division, University of Washington School of Medicine, Seattle, Washington, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA. FAU - Shen, Weining AU - Shen W AD - Department of Statistics, University of California, Irvine, California, USA. AD - Donald Bren School of Information and Computer Sciences, Irvine, California, USA. FAU - Reikes, Andrew AU - Reikes A AD - Divisions of General Internal Medicine and Endocrinology, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, USA. FAU - Watanabe, Jonathan H AU - Watanabe JH AUID- ORCID: 0000-0002-2543-5305 AD - Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, USA. LA - eng PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Female MH - Male MH - Middle Aged MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Practice Guidelines as Topic/standards MH - Metformin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians'/trends MH - Adult MH - Blood Glucose/analysis MH - Insulin/therapeutic use PMC - PMC12134773 OTO - NOTNLM OT - antidiabetic medications OT - cardiovascular disease OT - diabetes OT - guidelines OT - insulins OT - metformin OT - real-world data COIS- K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581, and CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Travere Therapeutics Inc., Bayer, and the Doris Duke Charitable Foundation. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Travere Therapeutics Inc., and Pfizer, and speaker fees from Novo Nordisk. W.H., W.S., and A.R. declare no conflicts of interest or financial relationships. J.H.W. has received funding support from the California Health Benefits Review Program and a UC Irvine Health Affairs Strategic Funding grant to examine incretin mimetic use. J.H.W. serves on the Forum on Drug, Discovery, Development, and Translation of the National Academies of Sciences, Engineering, and Medicine. EDAT- 2025/06/04 06:27 MHDA- 2025/06/04 06:28 PMCR- 2025/06/04 CRDT- 2025/06/04 05:43 PHST- 2024/11/23 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/06/04 06:28 [medline] PHST- 2025/06/04 06:27 [pubmed] PHST- 2025/06/04 05:43 [entrez] PHST- 2025/06/04 00:00 [pmc-release] AID - JDB70108 [pii] AID - 10.1111/1753-0407.70108 [doi] PST - ppublish SO - J Diabetes. 2025 Jun;17(6):e70108. doi: 10.1111/1753-0407.70108. PMID- 40450456 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20260127 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) VI - 72 IP - 6 DP - 2025 Jun-Jul TI - Real-world evaluation of the efficacy and safety of switching from weekly dulaglutide to weekly semaglutide: The SEMA-SWITCH study. PG - 501574 LID - S2530-0180(25)00075-7 [pii] LID - 10.1016/j.endien.2025.501574 [doi] AB - INTRODUCTION: Dulaglutide and semaglutide are once-weekly administered GLP-1 receptor agonists (GLP-1 RAs) indicated for the treatment of hyperglycemia in individuals with type 2 diabetes mellitus (T2DM) and obesity (BMI >/= 30 kg/m(2)). OBJECTIVE: To evaluate the efficacy and safety of switching from subcutaneous (SC) dulaglutide to SC semaglutide, in real-world conditions. MATERIALS AND METHODS: A total of 123 individuals with T2DM on SC dulaglutide, either as monotherapy or with other antihyperglycemic drugs, who switched to SC semaglutide were included. This switch was motivated by insufficient reduction in glycated hemoglobin (HbA1C), the need for greater weight loss, or gastrointestinal intolerance associated with dulaglutide. Changes with semaglutide in HbA1C and weight at 6, 12, 18, and 24 mo, as well as any changes in associated adverse effects. Data are expressed as mean +/- standard deviation. RESULTS: Previous treatment with dulaglutide (duration 16.9 +/- 13.8 mo) reduced HbA1c by 0.38% (p = 0.003 vs. baseline) and weight by -1.3 kg (p = 0.003 vs. baseline). After switching to semaglutide, an additional reduction in HbA1C levels was observed at 6, 12, 18, and 24 mo (-0.43%, p = 0.000; -0.54%, p = 0.000; -0.38%, p = 0.021; -0.12%, p = 0.622, respectively) and in weight at 6, 12, 18, and 24 mo (-2.7 kg, p = 0.000; -3.7 kg, p = 0.000; -5.4 kg, p = 0.001; -4.2 kg, p = 0.000, respectively) With no significant differences in the frequency of adverse effects after switching to semaglutide. CONCLUSIONS: In real-world conditions, switching dulaglutide to semaglutide in obese patients with T2DM is associated with an additional reduction in HbA1C and weight, without notable changes in the frequency of adverse effects. CI - Copyright (c) 2025 SEEN and SED. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Pardo Lozano, Felipe AU - Pardo Lozano F AD - Endocrinologia y Nutricion, Hospital Universitario La Plana, Castellon, Spain. Electronic address: feparloz@gmail.com. FAU - Rubio Marcos, Arantxa AU - Rubio Marcos A AD - Departamento de Endocrinologia y Nutricion, Hospital IMED Valencia, Valencia, Spain. FAU - Casan Fernandez, Rosa AU - Casan Fernandez R AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Bartual Rodrigo, Amparo AU - Bartual Rodrigo A AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Martinez-Hervas, Sergio AU - Martinez-Hervas S AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain; Instituto de Investigacion Sanitaria INCLIVA, Valencia, Spain; Departament de Medicina, Facultat de Medicina, Universitat de Valencia (UV), Valencia, Spain; CIBER de Diabetes y Enfermedades Metabolicas asociadas (CIBERDEM), Madrid, Spain. FAU - Ampudia-Blasco, Francisco Javier AU - Ampudia-Blasco FJ AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain; Instituto de Investigacion Sanitaria INCLIVA, Valencia, Spain; Departament de Medicina, Facultat de Medicina, Universitat de Valencia (UV), Valencia, Spain. LA - eng PT - Journal Article DEP - 20250530 PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Drug Administration Schedule MH - *Drug Substitution MH - Treatment Outcome MH - Obesity/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Injections, Subcutaneous MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Agonistas del receptor de GLP-1 OT - Diabetes tipo 2 OT - Dulaglutida OT - Dulaglutide OT - GLP-1 receptor agonists OT - Perdida de peso OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes OT - Weight loss COIS- Declaration of competing interest The authors Felipe Pardo Lozano, Arantxa Rubio Marcos, Rosa Casan Fernandez, Amparo Bartual Rodrigo, and Francisco Javier Ampudia-Blasco have participated in presentations on drugs for the treatment of diabetes and for weight loss in obesity. Dr. Sergio Martinez-Hervas has not collaborated with any laboratory that has products for the treatment of obesity. EDAT- 2025/06/04 19:07 MHDA- 2025/06/14 16:44 CRDT- 2025/06/01 01:49 PHST- 2024/10/06 00:00 [received] PHST- 2024/12/03 00:00 [revised] PHST- 2025/01/09 00:00 [accepted] PHST- 2025/06/14 16:44 [medline] PHST- 2025/06/04 19:07 [pubmed] PHST- 2025/06/01 01:49 [entrez] AID - S2530-0180(25)00075-7 [pii] AID - 10.1016/j.endien.2025.501574 [doi] PST - ppublish SO - Endocrinol Diabetes Nutr (Engl Ed). 2025 Jun-Jul;72(6):501574. doi: 10.1016/j.endien.2025.501574. Epub 2025 May 30. PMID- 40458885 OWN - NLM STAT- MEDLINE DCOM- 20250711 LR - 20260529 IS - 1744-8298 (Electronic) IS - 1479-6678 (Print) IS - 1479-6678 (Linking) VI - 21 IP - 9 DP - 2025 Jul TI - Semaglutide: a key medication for managing cardiovascular-kidney-metabolic syndrome. PG - 663-683 LID - 10.1080/14796678.2025.2511412 [doi] AB - Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; p = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; p = 0.002) with weekly 1.0 mg semaglutide in individuals with T2D with CKD. Beyond T2D, the SELECT trial highlighted semaglutide's efficacy in reducing MACE by 20% (HR 0.80; 95% CI: 0.72-0.90; p < 0.001) and slowing kidney function loss in overweight or obese individuals with preexisting CV disease using 2.4 mg weekly. Additionally, semaglutide alleviates heart failure symptoms and reduces hospitalizations in obese individuals regardless of T2D status. These findings underscore semaglutide's role in improving kidney, CV, and survival outcomes among high-risk patients. This review highlights the cardio-kidney-metabolic benefits of semaglutide in individuals with and without T2D to inform cardiologists about its potential to enhance patient care. FAU - MacIsaac, Richard J AU - MacIsaac RJ AUID- ORCID: 0000-0001-8058-6977 AD - Director of Endocrinology & Diabetes, St Vincent's Hospital Melbourne & Professorial Fellow University of Melbourne, Victoria, Australia. AD - Australian Centre For Accelerating Diabetes Innovations, University of Melbourne, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20250603 PL - England TA - Future Cardiol JT - Future cardiology JID - 101239345 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control/drug therapy/etiology MH - *Metabolic Syndrome/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12258229 OAB - Semaglutide, a medication in the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class, offers significant health benefits across cardiovascular (CV), kidney, and metabolic conditions, collectively known as cardiovascular-kidney-metabolic (CKM) syndrome. CKM syndrome encompasses interconnected issues such as obesity, type 2 diabetes (T2D), CV disease (CVD), and chronic kidney disease (CKD). These conditions are commonly seen together, increasing the risk of heart and kidney problems.Semaglutide has proven effective for weight loss, improved blood sugar control, and CV protection. Clinical trials have shown it reduces major heart events like heart attacks and strokes in individuals with and without diabetes. It also slows CKD progression and lowers hospitalization rates for heart failure, particularly in patients with obesity. Emerging evidence suggests semaglutide might have additional benefits, such as reducing inflammation, improving liver health, and lowering risks associated with atrial fibrillation and osteoarthritis.Semaglutide's real-world use supports clinical trial findings, demonstrating safety and effectiveness across diverse patient groups. Its safety profile is generally favorable, though gastrointestinal side effects can occur.By addressing multiple interconnected conditions, semaglutide is poised to transform care for patients at high risk of heart, kidney, and metabolic complications. Further research is exploring new dosing methods, combinations with other medications, and expanded use in non-diabetic populations to maximize its benefits. OABL- eng OTO - NOTNLM OT - Cardiovascular diseases OT - cardiovascular-kidney-metabolic syndrome OT - chronic kidney disease OT - diabetes, type 2 OT - glucagon-like peptide 1 receptor agonists OT - heart diseases OT - obesity OT - semaglutide COIS- R MacIsaac has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program and The National Health and Medical Research Council of Australia. He has also received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Merck Sharp & Dohme, Novartis and Boehringer Ingelheim. He is on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, Astra Zeneca, and Merck Shape and Dohme. Novo Nordisk, Sanofi, Boehringer Ingelheim and Astra Zeneca have supplied travel support. He has been a principal investigator for industry-sponsored clinical trials by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag and AbbVie. He was an investigator for the semaglutide trials SUSTAIN-6 and FLOW and was on the global expert panel for the FLOW trial. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Brad Dalton of medScript Communications provided medical writing and editorial support for this article, which Novo Nordisk funded. EDAT- 2025/06/03 06:27 MHDA- 2025/07/11 12:31 PMCR- 2025/06/03 CRDT- 2025/06/03 05:13 PHST- 2025/07/11 12:31 [medline] PHST- 2025/06/03 06:27 [pubmed] PHST- 2025/06/03 05:13 [entrez] PHST- 2025/06/03 00:00 [pmc-release] AID - 2511412 [pii] AID - 10.1080/14796678.2025.2511412 [doi] PST - ppublish SO - Future Cardiol. 2025 Jul;21(9):663-683. doi: 10.1080/14796678.2025.2511412. Epub 2025 Jun 3. PMID- 40448382 OWN - NLM STAT- MEDLINE DCOM- 20250531 LR - 20260925 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 21 IP - 6 DP - 2025 Jun TI - Heterogeneous treatment effects of GLP-1RAs and SGLT2is on risk of Alzheimer's disease and related dementia in patients with type 2 diabetes: Insights from a real-world target trial emulation. PG - e70313 LID - 10.1002/alz.70313 [doi] LID - e70313 AB - INTRODUCTION: This study assessed the heterogeneous treatment effects (HTEs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) on the risk of Alzheimer's disease and related dementias (ADRD). METHODS: This target trial emulation study included adults (>/= 50 years) with type 2 diabetes (T2D) and newly prescribed a GLP-1RA, SGLT2i, or other second-line glucose-lowering drugs (GLDs). A doubly robust learning approach was deployed to estimate the risk difference (RD) of ADRD and identify key subgroups. RESULTS: Both GLP-1RAs (RD, -1.5%) and SGLT2is (-1.7%) were associated with a reduced ADRD risk compared to other GLDs. Key subgroups were determined based on cardiovascular disease (CVD), cerebrovascular disease (CeVD), chronic kidney disease, and Hispanic ethnicity. Patients with CVD and CeVD had the greatest benefits from GLP-1RAs (-4.8%) and SGLT2is (-4.6%). No overall difference was observed between GLP-1RAs and SGLT2i. DISCUSSION: These findings suggest the importance of personalized treatment in diabetes management regarding ADRD risk. HIGHLIGHTS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with a decreased risk of Alzheimer's disease and related dementias (ADRD), while the protective association varied across subgroups defined by cardiovascular disease (CVD), cerebrovascular disease (CeVD), and chronic kidney disease (CKD). Similarly, sodium-glucose cotransporter-2 inhibitors (SGLT2is) were associated with a decreased risk of ADRD, with the protective association varying among subgroups defined by CVD, CeVD, and Hispanic ethnicity. There was no difference between GLP-1RAs and SGLT2is in the risk of ADRD. CI - (c) 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Tang, Huilin AU - Tang H AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Donahoo, William T AU - Donahoo WT AD - Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - DeKosky, Steven T AU - DeKosky ST AD - 1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA. AD - Department of Neurology and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Lee, Yao An AU - Lee YA AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Kotecha, Pareeta AU - Kotecha P AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Svensson, Mikael AU - Svensson M AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. LA - eng GR - R01AG076234/National Institutes of Health (NIH)/National Institute on Aging (NIA)/ GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - R01 AG076234/AG/NIA NIH HHS/United States GR - R01DK133465/NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ GR - R01 AG089445/AG/NIA NIH HHS/United States GR - R01AG089445/National Institutes of Health (NIH)/National Institute on Aging (NIA)/ GR - 2023PDVH1064032/The Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Predoctoral Fellowship/ PT - Journal Article PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Alzheimer Disease/epidemiology/prevention & control MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Dementia/epidemiology/prevention & control MH - Risk Factors MH - Treatment Effect Heterogeneity PMC - PMC12125485 OTO - NOTNLM OT - Alzheimer's disease and related dementias OT - GLP-1RAs OT - SGLT2is OT - type 2 diabetes COIS- The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information. EDAT- 2025/05/31 22:27 MHDA- 2025/05/31 22:28 PMCR- 2025/05/30 CRDT- 2025/05/31 02:53 PHST- 2025/04/28 00:00 [revised] PHST- 2024/12/09 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2025/05/31 22:28 [medline] PHST- 2025/05/31 22:27 [pubmed] PHST- 2025/05/31 02:53 [entrez] PHST- 2025/05/30 00:00 [pmc-release] AID - ALZ70313 [pii] AID - 10.1002/alz.70313 [doi] PST - ppublish SO - Alzheimers Dement. 2025 Jun;21(6):e70313. doi: 10.1002/alz.70313. PMID- 40447157 OWN - NLM STAT- MEDLINE DCOM- 20250719 LR - 20260127 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 388 DP - 2025 Nov 1 TI - Association of glucagon-like peptide-1 receptor agonists and seven common mental disorders: A drug target and mediation Mendelian randomization. PG - 119509 LID - S0165-0327(25)00951-6 [pii] LID - 10.1016/j.jad.2025.119509 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RA) have been associated with psychiatric symptoms; however, the causal relationships between GLP1RA and seven common mental disorders remain unknown. METHODS: Mendelian Randomization (MR) were employed to explore the causalities between GLP1RA and seven common mental disorders using genome-wide association study (GWAS) data from 3 million individuals. Type 2 diabetes, blood glucose levels, insulin levels, and appetite was used as positive control. Multiple validations were performed based on the Psychiatric Genomics Consortium (PGC), UK Biobank (UKB), and FinnGen databases. A two-step MR analysis was used to assess the mediating effects. Finally, a systematic review was conducted to validate the psychotropic side effects of GLP1RA. RESULTS: Positive control analysis indicated that the genetically predicted levels of GLP1R expression accurately reflect the physiological effects of GLP1RA, encompassing the reduction of blood glucose, fat reduction, endocrine regulation, and appetite suppression. GLP1RA reduced the risk of Major Depression Disorder (MDD) (OR = 0.6831 (0.6412-0.7277), FDR < 0.05), Bipolar Disorder (BID) (OR = 0.8019 (0.7504-0.857), FDR < 0.05), and Autism Spectrum Disorder (ASD) (OR = 0.7115 (0.6448-0.7852), FDR < 0.05). Meta results of MR support GLP1RA being a risk factor for Anorexia Nervosa (AN). The mediating MR results showed that serum glucagon and insulin levels were involved in the causal effects between GLP1R expression levels and AN (5.58 %) and BID (6.37 %) (P < 0.05). Finally, 16 observational studies were included in systematic review, most of which supported GLP1RA as a protective factor for MDD. CONCLUSIONS: Our study suggests that GLP1RA can reduce the risk of MDD, ASD, and BID. This study has significant implications for the safe application of GLP1RAs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Zhang, Zexin AU - Zhang Z AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Li, Shu AU - Li S AD - Xiamen University, School of Medicine, Xiamen, Fujian, China. FAU - Dai, Xinyue AU - Dai X AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Li, Cong AU - Li C AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Sun, Pengfei AU - Sun P AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Qu, Jianwen AU - Qu J AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Jiang, Haiyue AU - Jiang H AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: bjbjjhy@163.com. FAU - Pan, Bo AU - Pan B AD - Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: zbzbzhc@163.com. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250528 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Genome-Wide Association Study MH - *Mental Disorders/genetics MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Diabetes Mellitus, Type 2/genetics MH - Major Depressive Disorder/genetics OTO - NOTNLM OT - Depression OT - Glucagon-like peptide-1 receptor agonists OT - Mendelian randomization OT - Mental disorders OT - Side effects OT - Weight management COIS- Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors. All authors were not paid to write this article by a pharmaceutical company or other agency. EDAT- 2025/05/31 00:36 MHDA- 2025/07/19 16:45 CRDT- 2025/05/30 19:35 PHST- 2025/01/27 00:00 [received] PHST- 2025/05/24 00:00 [revised] PHST- 2025/05/26 00:00 [accepted] PHST- 2025/07/19 16:45 [medline] PHST- 2025/05/31 00:36 [pubmed] PHST- 2025/05/30 19:35 [entrez] AID - S0165-0327(25)00951-6 [pii] AID - 10.1016/j.jad.2025.119509 [doi] PST - ppublish SO - J Affect Disord. 2025 Nov 1;388:119509. doi: 10.1016/j.jad.2025.119509. Epub 2025 May 28. PMID- 40443145 OWN - NLM STAT- MEDLINE DCOM- 20250530 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 920 DP - 2025 May 28 TI - [Glucagon-like peptide 1 agonists : the fourth pillar of nephroprotection in type 2 diabetes]. PG - 1117-1120 LID - 10.53738/REVMED.2025.21.920.47251 [doi] AB - GLP1 agonists are the emerging fourth pillar of nephroprotection in type 2 diabetes (T2D), alongside renin-angiotensin system blockers, sodium-glucose cotransporter 2 inhibitors, and finerenone (a non-steroidal mineralocorticoid receptor antagonist). The FLOW study showed that semaglutide 1 mg weekly prescribed in T2D patients with moderate to severe renal disease resulted in a 24 % reduction in the risk of a major renal event (NNT: 20) after a median follow-up of 3.4 years and a 20 % reduction in the relative risk of all-cause mortality (NNT: 39). Tirzepatide (a dual GLP1-GIP agonist) shows promising potential, but further data are awaited. However, their use requires caution, especially with regard to gastrointestinal adverse effects and the risk of muscle loss. A multidisciplinary approach remains essential to optimize their efficacy and safety. FAU - Lamine, Faiza AU - Lamine F AUID- ORCID: 0000-0001-6299-714X AD - Unite d'endocrinologie-diabetologie, Service de medecine interne, Centre hospitalier de Rennaz, 1847 Rennaz. AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Chtioui, Haithem AU - Chtioui H AUID- ORCID: 0000-0003-3821-6942 AD - Service de pharmacologie medicale, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Zanchi, Anne AU - Zanchi A AUID- ORCID: 0000-0003-0987-9333 AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Service de nephrologie, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Agonistes du GLP-1: quatrieme pilier de la nephroprotection dans le diabete de type 2. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptides/therapeutic use MH - Semaglutide COIS- A. Zanchi a ete consultante pour les entreprises Lilly et Novo Nordisk. Les autres auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/05/30 07:41 MHDA- 2025/05/30 07:42 CRDT- 2025/05/30 02:53 PHST- 2025/05/30 07:42 [medline] PHST- 2025/05/30 07:41 [pubmed] PHST- 2025/05/30 02:53 [entrez] AID - RMS0920-004 [pii] AID - 10.53738/REVMED.2025.21.920.47251 [doi] PST - ppublish SO - Rev Med Suisse. 2025 May 28;21(920):1117-1120. doi: 10.53738/REVMED.2025.21.920.47251. PMID- 40443144 OWN - NLM STAT- MEDLINE DCOM- 20250530 LR - 20250530 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 920 DP - 2025 May 28 TI - [GLP-1 agonists : cardio-renal benefit in type 2 diabetic patient]. PG - 1112-1116 LID - 10.53738/REVMED.2025.21.920.47290 [doi] AB - GLP-1 analogs have revolutionized the management of type 2 diabetes, providing metabolic and cardiovascular benefits independent of glycemic control. In addition to promoting weight loss and improving endothelial function, they reduce the risk of major cardiovascular events and slow the progression of chronic kidney disease. Studies also highlight their potential in managing metabolic steatopathy and cognitive disorders. The combination of GLP-1 analogs and SGLT-2 inhibitors optimizes cardio-renal protection. A comprehensive approach combining pharmacological treatment and lifestyle modifications remains essential. FAU - Levy, Juliette AU - Levy J AUID- ORCID: 0000-0001-8128-6968 AD - Service de medecine interne generale, Departement de medecine, Hopitaux universitaires de Geneve, 1211 Geneve 14. FAU - Gariani, Karim AU - Gariani K AUID- ORCID: 0000-0001-8089-4785 AD - Service d'endocrinologie et diabetologie, Hopitaux universitaires de Geneve, 1211 Geneve 14. LA - fre PT - English Abstract PT - Journal Article TT - Analogues du GLP-1: benefice cardiorenal chez le patient diabetique de type 2. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Sodium-Glucose Transporter 2 Inhibitors MH - Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Renal Insufficiency, Chronic/prevention & control/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- J. Levy : n'a declare aucun conflit d'interets en relation avec cet article. K. Gariani declare des Advisory boards avec Lilly, Novo Nordisk et Bayer. EDAT- 2025/05/30 08:26 MHDA- 2025/05/30 08:27 CRDT- 2025/05/30 02:53 PHST- 2025/05/30 08:27 [medline] PHST- 2025/05/30 08:26 [pubmed] PHST- 2025/05/30 02:53 [entrez] AID - RMS0920-003 [pii] AID - 10.53738/REVMED.2025.21.920.47290 [doi] PST - ppublish SO - Rev Med Suisse. 2025 May 28;21(920):1112-1116. doi: 10.53738/REVMED.2025.21.920.47290. PMID- 40443143 OWN - NLM STAT- MEDLINE DCOM- 20250530 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 920 DP - 2025 May 28 TI - [Nutritional management of type 2 diabetes with GLP-1 and GLP-1/GIP agonists]. PG - 1106-1111 LID - 10.53738/REVMED.2025.21.920.47028 [doi] AB - In diabetic patients, treatment with GLP-1 (Glucagon-Like Peptide-1) and dual GLP-1/GIP (gastric inhibitory polypeptide) agonists, such as, respectively, semaglutide and tirzepatide, is effective in lowering blood sugar and reducing weight. However, their use requires dietary monitoring to prevent muscle loss which is often associated with rapid weight loss. The treatment should be accompanied by specific nutritional recommendations, including adequate hydration, quality carbohydrates, as well as a sufficient intake of high-quality proteins and fiber. Physical activity, particularly anaerobic and aerobic exercises, is strongly recommended to maintain muscle mass and support weight loss. Finally, special attention should be given to side effects such as nausea or constipation. FAU - Pabion, Celine AU - Pabion C AD - Dieteticienne diplomee HES, MSc, Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Pignolet-Marti, Anaelle AU - Pignolet-Marti A AD - Dieteticienne diplomee HES, Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Zanchi, Anne AU - Zanchi A AUID- ORCID: 0000-0003-0987-9333 AD - Service de nephrologie, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Borloz, Sylvie AU - Borloz S AUID- ORCID: 0000-0002-6199-1413 AD - Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Dieteticienne cheffe adjointe, MSc, Service d'endocrinologie, de diabetologie et metabolisme, nutrition clinique, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Prise en charge nutritionnelle du diabete de type 2 avec les agonistes GLP-1 et du GLP-1/GIP. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy/therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Gastric Inhibitory Polypeptide/agonists MH - Glucagon-Like Peptides/therapeutic use MH - Exercise MH - Weight Loss/drug effects MH - Blood Glucose/drug effects MH - Semaglutide COIS- Les auteures n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/05/30 08:04 MHDA- 2025/05/30 08:05 CRDT- 2025/05/30 02:53 PHST- 2025/05/30 08:05 [medline] PHST- 2025/05/30 08:04 [pubmed] PHST- 2025/05/30 02:53 [entrez] AID - RMS0920-002 [pii] AID - 10.53738/REVMED.2025.21.920.47028 [doi] PST - ppublish SO - Rev Med Suisse. 2025 May 28;21(920):1106-1111. doi: 10.53738/REVMED.2025.21.920.47028. PMID- 40439835 OWN - NLM STAT- MEDLINE DCOM- 20261012 LR - 20261014 IS - 1556-3308 (Electronic) IS - 1094-3412 (Linking) VI - 53 IP - 4 DP - 2026 Oct TI - Glucagon-Like Peptide-1 Use and Healthcare Resource Utilization for Depression and Anxiety Among Adults with Type 2 Diabetes: 2019 to 2023. PG - 622-638 LID - 10.1007/s11414-025-09950-6 [doi] AB - Mental health disorders, including depression and anxiety, are common comorbidities in individuals with type 2 diabetes mellitus (T2DM), contributing to increased healthcare resource utilization (HCRU) and the financial burden of the disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used for T2DM management, and emerging evidence suggests they may help alleviate mental health symptoms. This study examined the association between GLP-1RA (versus DPP-4 inhibitor [DPP-4i]) initiation and mental health-related HCRU in T2DM patients. Using data from the Komodo Healthcare Map, a national database of pharmacy and medical claims, this study conducted a retrospective cohort analysis with 774,968 adults who initiated GLP-1RAs or DPP-4i between January 2019 and March 2022. Patients were followed for 12 months, and mental health-related HCRU (emergency department, inpatient, outpatient hospital, and office visits) for depression and anxiety was assessed. A difference-in-differences analysis compared HCRU before and after medication initiation, adjusting for sociodemographic and clinical variables. GLP-1RA use was associated with significant reductions in outpatient hospital visits (IRR: 0.96; 95% CI: 0.95-0.98) for depression, and office visits for depression (IRR: 0.87; 95% CI: 0.82-0.92) and anxiety (IRR: 0.85; 95% CI: 0.81-0.90) compared to DPP-4i. However, no significant changes were observed in emergency or inpatient visits. Reductions were more pronounced with semaglutide, liraglutide, and dulaglutide. These findings suggest that GLP-1RAs may help reduce depression- and anxiety-related HCRU in patients with T2DM, indicating potential benefits beyond glycemic control. Further research is needed to explore long-term outcomes and the cost-effectiveness of GLP-1RAs for managing mental health comorbidities. CI - (c) 2025. National Council for Mental Wellbeing. FAU - Do, Duy AU - Do D AUID- ORCID: 0000-0001-9919-6848 AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. duy.do@evernorth.com. FAU - Lee, Tiffany AU - Lee T AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. FAU - Inneh, Angela AU - Inneh A AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. FAU - Patel, Urvashi AU - Patel U AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. LA - eng PT - Journal Article DEP - 20250529 PL - United States TA - J Behav Health Serv Res JT - The journal of behavioral health services & research JID - 9803531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Female MH - Retrospective Studies MH - Male MH - *Depression/drug therapy MH - Middle Aged MH - *Patient Acceptance of Health Care/statistics & numerical data MH - *Anxiety/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Semaglutide COIS- Declarations. Ethical approval and consent to participate: Not applicable. Reporting guidelines: This study was conducted in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational research. Conflict of interest: The authors declare no competing interests. EDAT- 2025/05/29 12:56 MHDA- 2026/10/12 17:30 CRDT- 2025/05/29 11:07 PHST- 2025/04/25 00:00 [accepted] PHST- 2026/10/12 17:30 [medline] PHST- 2025/05/29 12:56 [pubmed] PHST- 2025/05/29 11:07 [entrez] AID - 10.1007/s11414-025-09950-6 [pii] AID - 10.1007/s11414-025-09950-6 [doi] PST - ppublish SO - J Behav Health Serv Res. 2026 Oct;53(4):622-638. doi: 10.1007/s11414-025-09950-6. Epub 2025 May 29. PMID- 40437949 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials. PG - 4454-4468 LID - 10.1111/dom.16489 [doi] AB - AIMS: To assess if there is a difference in the oncogenic risk between GLP-1 RA and comparators in randomized controlled trials. MATERIALS AND METHODS: A meta-analysis of randomized controlled trials comparing GLP-1RA to any comparators for diabetes and/or obesity, lasting at least 52 weeks. The endpoints included the incidence of overall cancers and single malignancies. RESULTS: Fifty trials were included. GLP-1RA treatment was not associated with a significant difference in risk for overall cancer (MH-OR 1.05, 95% confidence interval [CI] [0.98, 1.13]). Uterine cancer was significantly reduced in the GLP-1RA arm in trials performed in subjects with obesity (MH-OR 0.24, 95% CI [0.06, 0.94]), but not in those aimed at diabetes treatment (MH-OR 0.92, [0.58, 1.47]). We detected an increase in the risk for thyroid cancer (MH-OR 1.55, [1.05, 2.27]), more evident in longer-term trials, and in the risk for colorectal cancer (MH-OR 1.27 [1.03, 1.57]), which, conversely, was significant only in shorter-term trials. No significant difference in the risk was detected for any other cancer. CONCLUSIONS: GLP-1 RA do not appear to produce an effect on most malignancies in clinical trials. A reduction of very close obesity-associated cancers seems possible, whereas a risk signal for thyroid cancer was observed, prompting the need for further specific studies. On the other hand, the small increase observed in colorectal cancer in shorter-term trials may be the effect of a disproportionate increase in diagnostic procedures in the GLP-1 RA arm, because of the suspicion raised by common side effects of GLP-1 RA. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Silverii, Giovanni Antonio AU - Silverii GA AUID- ORCID: 0000-0002-6695-3213 AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Marinelli, Christian AU - Marinelli C AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Bettarini, Costanza AU - Bettarini C AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Del Vescovo, Gloria Giovanna AU - Del Vescovo GG AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Monami, Matteo AU - Monami M AUID- ORCID: 0000-0001-9349-828X AD - Diabetology Unit, AOU Careggi, Florence, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AUID- ORCID: 0000-0001-9759-9408 AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250529 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Neoplasms/epidemiology/chemically induced MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Risk Factors MH - Colorectal Neoplasms/epidemiology/chemically induced MH - Incidence PMC - PMC12232360 OTO - NOTNLM OT - GLP-1 RA OT - cancer OT - dulaglutide OT - exenatide OT - glucagon-like peptide-1 receptor agonists OT - liraglutide OT - meta-analysis OT - obesity OT - semaglutide OT - type 2 diabetes mellitus COIS- GAS has received speaking or consultancy fees from Astra Zeneca, Eli-Lilly and Novo Nordisk, outside the submitted work. MM has received speaking fees from Astra Zeneca, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk and Sanofi, outside the submitted work. The unit directed by EM has received research grants from Abbott, Eli-Lilly and Novo Nordisk, outside the submitted work. EM has received consultancy fees or speaking fees from Astra Zeneca, Bayer, Boehringer-Ingelheim, Coresearch, Dexcom, Eli-Lilly, Molteni, Novo Nordisk, Pidkare and Sanofi, outside the submitted work. C.M., G.G.D.V. and C.B. do not have any competing interests to disclose. EDAT- 2025/05/29 06:26 MHDA- 2025/07/04 12:43 PMCR- 2025/07/07 CRDT- 2025/05/29 04:03 PHST- 2025/05/14 00:00 [revised] PHST- 2025/01/13 00:00 [received] PHST- 2025/05/14 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/29 06:26 [pubmed] PHST- 2025/05/29 04:03 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - DOM16489 [pii] AID - 10.1111/dom.16489 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4454-4468. doi: 10.1111/dom.16489. Epub 2025 May 29. PMID- 40437795 OWN - NLM STAT- MEDLINE DCOM- 20251112 LR - 20251211 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 40 IP - 5 DP - 2025 Oct TI - Current Status of Delay in Injectable Therapy among Type 2 Diabetes Mellitus Patients in South Korea: Multicenter Retrospective Study (2015-2021). PG - 727-736 LID - 10.3803/EnM.2024.2280 [doi] AB - BACKGRUOUND: We aimed to assess the therapeutic inertia associated with injectable therapies and the factors influencing glycemic control following these therapies in patients with type 2 diabetes mellitus (T2DM) in South Korea. METHODS: This multicenter, retrospective cohort study included 2,598 T2DM patients aged 20 to 75 years from 10 referral medical centers in South Korea. These patients had been treated with three or four oral antidiabetic drugs (OADs) and were subsequently initiated on insulin (n=1,942) or glucagon-like peptide-1 receptor agonists (GLP-1RAs, n=656) between January 2015 and December 2021. We analyzed the time to initiation of injectable therapy, changes in glycated hemoglobin (HbA1c), and associations between clinical factors and glycemic control. RESULTS: At the time of injectable therapy initiation, the mean HbA1c was 9.54%, with insulin users having a higher HbA1c level (9.79%) than GLP-1RA users (8.70%). The mean time from starting 3 or 4 OADs to initiating injectable therapy was 3.19 years: 53.5% of patients had started injectable therapy after 2 years, and 24.2% started after 5 years. Among insulin users, older age (P= 0.004), higher body mass index (P=0.035), and lower HbA1c levels at insulin initiation (P<0.001) were associated with better glycemic control. Among GLP-1RA users, only the HbA1c level at therapy initiation (P<0.001) was a significant factor. CONCLUSION: This study highlighted significant delays in initiating injectable therapies, particularly insulin, in T2DM patients in South Korea. Early initiation of injectable therapy may improve long-term glycemic control in these patients. FAU - Choi, Jong Han AU - Choi JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea. FAU - Moon, Min Kyong AU - Moon MK AD - Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. FAU - Kim, Hae Jin AU - Kim HJ AD - Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea. FAU - Lee, Kyung Ae AU - Lee KA AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea. FAU - Kim, Hyun Jin AU - Kim HJ AD - Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea. FAU - Ko, Jung Hae AU - Ko JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea. FAU - Yun, Jae-Seung AU - Yun JS AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Ko, Seung-Hyun AU - Ko SH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Chon, Suk AU - Chon S AD - Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea. FAU - Kim, Nam Hoon AU - Kim NH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. LA - eng GR - 2021F-8/Korean Diabetes Association/ PT - Journal Article PT - Multicenter Study DEP - 20250529 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - Retrospective Studies MH - Middle Aged MH - Male MH - Female MH - Republic of Korea/epidemiology MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Adult MH - *Insulin/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - *Time-to-Treatment/statistics & numerical data MH - Young Adult MH - Blood Glucose/analysis MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Follow-Up Studies MH - Injections MH - Glycemic Control/statistics & numerical data MH - Prognosis PMC - PMC12602008 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Glycemic control OT - Insulin OT - Treatment delay COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2025/05/29 06:26 MHDA- 2025/11/12 23:30 PMCR- 2025/10/01 CRDT- 2025/05/29 02:08 PHST- 2024/12/14 00:00 [received] PHST- 2025/03/12 00:00 [accepted] PHST- 2025/11/12 23:30 [medline] PHST- 2025/05/29 06:26 [pubmed] PHST- 2025/05/29 02:08 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - EnM.2024.2280 [pii] AID - enm-2024-2280 [pii] AID - 10.3803/EnM.2024.2280 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2025 Oct;40(5):727-736. doi: 10.3803/EnM.2024.2280. Epub 2025 May 29. PMID- 40436382 OWN - NLM STAT- MEDLINE DCOM- 20250528 LR - 20260512 IS - 1439-4413 (Electronic) IS - 0012-0472 (Linking) VI - 150 IP - 13 DP - 2025 Jun TI - [Risk Factor Management for Polyvascular Atherosclerosis]. PG - 747-753 LID - 10.1055/a-2362-4893 [doi] AB - Polyvascular atherosclerosis is characterized by atherosclerosis in several vascular territories, leading to an extremely high risk of myocardial infarction, ischemic stroke, and cardiovascular death. These patients derive a higher absolute risk reduction from preventive measures compared to individuals with monovascular atherosclerosis. The most important lifestyle factors are non-smoking and physical exercise. Pharmacological management includes lipid-lowering with an LDL-cholesterol target of <40mg/dl (1,0mmol/l) and blood-pressure control with a systolic target of 120mmHg. Diabetes type 2 in patients with polyvascular atherosclerosis should be treated with SGLT2-inhibitors and/or GLP1-receptor agonists. Patients with obesity and polyvascular disease should receive GLP1RA - regardless of the presence of diabetes. Thus, a comprehensive risk factor management in patients with polyvascular atherosclerosis is essential to improve long-term cardiovascular outcomes. CI - Thieme. All rights reserved. FAU - Reuser, Annika AU - Reuser A FAU - Laufs, Ulrich AU - Laufs U LA - ger PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review TT - Risikofaktor-Management bei polyvaskularer Atherosklerose. DEP - 20250528 PL - Germany TA - Dtsch Med Wochenschr JT - Deutsche medizinische Wochenschrift (1946) JID - 0006723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Atherosclerosis/prevention & control/therapy MH - Risk Factors MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Life Style MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use COIS- Annika Reuser gibt an, dass keine Interessenkonflikte bestehen. Prof. Ulrich Laufs erhielt in der Vergangenheit Honorare von Amgen, Daiichi Sankyo, Novartis und Sanofi. EDAT- 2025/05/29 00:27 MHDA- 2025/05/29 00:28 CRDT- 2025/05/28 19:53 PHST- 2025/05/29 00:28 [medline] PHST- 2025/05/29 00:27 [pubmed] PHST- 2025/05/28 19:53 [entrez] AID - 10.1055/a-2362-4893 [doi] PST - ppublish SO - Dtsch Med Wochenschr. 2025 Jun;150(13):747-753. doi: 10.1055/a-2362-4893. Epub 2025 May 28. PMID- 40434727 OWN - NLM STAT- MEDLINE DCOM- 20250718 LR - 20260127 IS - 1743-9159 (Electronic) IS - 1743-9159 (Linking) VI - 111 IP - 7 DP - 2025 Jul 1 TI - The impact of semaglutide on fusion rates following posterior lumbar fusion surgery in patients with type 2 diabetes. PG - 4898-4900 LID - 10.1097/JS9.0000000000002492 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used in managing type 2 diabetes mellitus (T2DM), has demonstrated cardiovascular and glycemic benefits. However, its influence on surgical outcomes, particularly spinal fusion, remains unclear. This study aims to evaluate the association between semaglutide use and pseudarthrosis rates following posterior lumbar fusion surgery in patients with T2DM. METHODS: Data were retrieved from the TriNetX Global Collaborative Network, which includes de-identified records from 117 healthcare systems. T2DM patients who underwent posterior lumbar fusion were identified using CPT codes, and semaglutide exposure was determined preoperatively. Patients were divided into semaglutide and non-semaglutide groups, with 1:1 propensity score matching applied. Pseudarthrosis was identified using ICD-10 code M96.0. RESULTS: After matching, baseline characteristics were well-balanced between groups with 884 patients in each group. Semaglutide users had significantly lower rates of pseudarthrosis at 6 months (8.0% vs. 13.1%, OR: 0.58; 95% CI: 0.42-0.79), 1 year (8.9% vs. 14.0%, OR: 0.60; 95% CI: 0.45-0.81), and two years (10.1% vs. 15.7%, OR: 0.60; 95% CI: 0.45-0.80) compared to non-users. CONCLUSIONS: Semaglutide use is associated with a reduced risk of pseudarthrosis following posterior lumbar fusion in patients with T2DM. Further studies are warranted to elucidate the mechanisms underlying this potential benefit and to assess its implications in broader patient populations. CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Chang, Yu AU - Chang Y AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Hong-Min AU - Lin HM AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. FAU - Chi, Kuan-Yu AU - Chi KY AD - Department of Family Medicine, Chi-Mei Medical Center, Tainan, Taiwan. FAU - Song, Junmin AU - Song J AD - Department of Family Medicine, Chi-Mei Medical Center, Tainan, Taiwan. FAU - Atwan, Hany AU - Atwan H AD - Faculty of Medicine, Assiut University, Assiut, Egypt. LA - eng PT - Journal Article DEP - 20250528 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Spinal Fusion/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Lumbar Vertebrae/surgery MH - Aged MH - *Pseudarthrosis/epidemiology/etiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - *Postoperative Complications/epidemiology/prevention & control MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - lumbar fusion surgery OT - pseudoarthrosis OT - semaglutide EDAT- 2025/05/28 12:28 MHDA- 2025/07/18 06:26 CRDT- 2025/05/28 11:23 PHST- 2025/04/22 00:00 [received] PHST- 2025/04/24 00:00 [accepted] PHST- 2025/07/18 06:26 [medline] PHST- 2025/05/28 12:28 [pubmed] PHST- 2025/05/28 11:23 [entrez] AID - 01279778-202507000-00069 [pii] AID - 10.1097/JS9.0000000000002492 [doi] PST - ppublish SO - Int J Surg. 2025 Jul 1;111(7):4898-4900. doi: 10.1097/JS9.0000000000002492. Epub 2025 May 28. PMID- 40434284 OWN - NLM STAT- MEDLINE DCOM- 20250528 LR - 20260821 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 18 IP - 6 DP - 2025 Jun TI - GLP-1 Agonists for Pediatric Psychopharmacology: Opportunities and Cautions. PG - e70262 LID - 10.1111/cts.70262 [doi] LID - e70262 AB - Glucagon-like peptide-1 agonists (GLP-1A) are increasingly prescribed to treat obesity and type 2 diabetes mellitus in children and adolescents. Emerging evidence suggesting neuropsychiatric effects presents an opportunity for pediatric psychopharmacology but requires careful consideration of potential adverse effects and risk of misuse. This perspective examines potential applications and cautions surrounding GLP-1As for pediatric mental health, particularly substance use, depression, and eating disorders, and advocates for research and clinical monitoring to ensure their safety and efficacy. CI - (c) 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Bartkoski, Michael AU - Bartkoski M AUID- ORCID: 0000-0001-8203-4121 AD - Division of Clinical Pharmacology, Toxicology, & Therapeutic Innovation, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA. AD - Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA. FAU - Poweleit, Ethan A AU - Poweleit EA AUID- ORCID: 0000-0001-6805-2243 AD - Division of Clinical Pharmacology, Toxicology, & Therapeutic Innovation, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA. FAU - Stancil, Stephani L AU - Stancil SL AUID- ORCID: 0000-0001-7308-3132 AD - Division of Clinical Pharmacology, Toxicology, & Therapeutic Innovation, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA. AD - Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA. AD - Department of Pediatrics, University of Missouri-Kansas City and University of Kansas Schools of Medicine, Kansas City, Missouri, USA. LA - eng GR - K23 MH130728/MH/NIMH NIH HHS/United States GR - T32 HD069038/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adolescent MH - Child MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Feeding and Eating Disorders/drug therapy/chemically induced MH - *Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Pediatric Obesity/drug therapy MH - Psychopharmacology/methods MH - Substance-Related Disorders PMC - PMC12117883 COIS- The authors declare no conflicts of interest. EDAT- 2025/05/28 12:27 MHDA- 2025/05/28 12:28 PMCR- 2025/05/28 CRDT- 2025/05/28 10:04 PHST- 2025/05/07 00:00 [revised] PHST- 2025/03/04 00:00 [received] PHST- 2025/05/12 00:00 [accepted] PHST- 2025/05/28 12:28 [medline] PHST- 2025/05/28 12:27 [pubmed] PHST- 2025/05/28 10:04 [entrez] PHST- 2025/05/28 00:00 [pmc-release] AID - CTS70262 [pii] AID - 10.1111/cts.70262 [doi] PST - ppublish SO - Clin Transl Sci. 2025 Jun;18(6):e70262. doi: 10.1111/cts.70262. PMID- 40424213 OWN - NLM STAT- MEDLINE DCOM- 20250725 LR - 20250725 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 31 DP - 2025 May 27 TI - Glucagon-Like Peptide-1 Receptor Agonists Lead to Gastrointestinal Benefits in Patients with Type 2 Diabetes: A Real-World Study. PG - e946935 LID - 10.12659/MSM.946935 [doi] LID - e946935 AB - BACKGROUND Glucagon-like peptide-1 receptor agonist (GLP1-RA) is a promising therapy for heart and kidney health in type 2 diabetes mellitus (T2DM). However, information on its GI benefits is limited. This study aimed to investigate the gastrointestinal (GI) outcomes of GLP1-RA use in patients with T2DM. MATERIAL AND METHODS This retrospective cohort study utilized the TriNetX Dataset with a new-user and active-comparator design. The study included 2 304 761 adult patients diagnosed with T2DM and an estimated glomerular filtration rate of >/=60 mL/min/1.73 m(2) from January 2019 to December 2022. To establish cohorts, we designated users of dipeptidyl peptidase-4 inhibitors (DPP4i) as the control group. Two cohorts were formed for analysis after propensity score matching by baseline characteristics, each comprising 127 216 patients - one using GLP1-RA and the other DPP4i. Cox proportional hazards regression models were used to evaluate GI outcomes over 4 years between groups. RESULTS After matching, the average age of the population was about 60 years, with approximately 55% male and 63% identifying as White people. GLP1-RA users demonstrated a lower risk of acute pancreatitis (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.83-0.97), liver failure (HR: 0.81, 95% CI: 0.75-0.88), peritonitis (HR: 0.85, 95% CI: 0.76-0.94), peptic ulcer (HR: 0.89, 95% CI: 0.84-0.94), and GI bleeding (HR: 0.95, 95% CI: 0.92-0.98) compared to DPP4i users, indicating significant GI-protective effects. Furthermore, the GI advantages of GLP14A over DPP4i were consistently observed across various propensity score matching models. CONCLUSIONS GLP1-RA treatment in T2DM has some GI advantages compared to DPP4, which should be considered when personalizing T2DM treatment. FAU - Hsu, Jung-Hui AU - Hsu JH AD - Division of Gastroenterology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Bai, Hsueh-Fen AU - Bai HF AD - Department of Intensive Care Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Chen, Mon-Ting AU - Chen MT AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. FAU - Wang, Jing-Tong AU - Wang JT AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Liu, Chieh-Yu AU - Liu CY AUID- ORCID: 0000-0003-3283-028X AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Tsai, Ming-Hsein AU - Tsai MH AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. LA - eng PT - Journal Article DEP - 20250527 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Protective Agents) SB - IM MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Gastrointestinal Tract/physiology MH - Treatment Outcome MH - Humans MH - Cohort Studies MH - Retrospective Studies MH - Male MH - Female MH - Adult MH - Middle Aged MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - *Protective Agents/therapeutic use MH - Digestive System Diseases/epidemiology/prevention & control PMC - PMC12125961 COIS- Conflict of interest: None declared EDAT- 2025/05/27 18:28 MHDA- 2025/05/27 18:29 PMCR- 2025/05/27 CRDT- 2025/05/27 13:23 PHST- 2025/05/27 18:29 [medline] PHST- 2025/05/27 18:28 [pubmed] PHST- 2025/05/27 13:23 [entrez] PHST- 2025/05/27 00:00 [pmc-release] AID - 946935 [pii] AID - 10.12659/MSM.946935 [doi] PST - epublish SO - Med Sci Monit. 2025 May 27;31:e946935. doi: 10.12659/MSM.946935. PMID- 40413013 OWN - NLM STAT- MEDLINE DCOM- 20250524 LR - 20250915 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) VI - 72 IP - 5 DP - 2025 May TI - Effect of glucagon-like peptide-1 receptor agonists on the risk of major adverse limb events in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials. PG - 501562 LID - S2530-0180(25)00058-7 [pii] LID - 10.1016/j.endien.2025.501562 [doi] AB - OBJECTIVE: To evaluate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the risk of major adverse limb events (MALE). METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials assessing the effects of GLP-1RAs therapy on peripheral arterial disease (PAD)-related outcomes in patients with type 2 diabetes mellitus (T2DM). This meta-analysis was performed according to PRISMA guidelines. The random-effects model was performed. RESULTS: A total of 6 randomized clinical trials were considered eligible for this systematic review. On the other hand, 4 clinical trials were included for the meta-analysis. A total of 15,427 subjects were allocated to the GLP-1RAs group, and 15,476 to the placebo group. Overall, this meta-analysis showed that the use of GLP-1RAs is associated with a lower risk of PAD-related events (OR, 0.78; 95%CI, 0.62-0.98, I(2)=39%) vs the placebo group. The analytical evaluation did not suggest publication bias, and the sensitivity analysis demonstrated that the result was robust. CONCLUSION: This meta-analysis demonstrated that the use of GLP-1RAs is associated with fewer PAD-related clinical events. Of note, despite the clinical significance of PAD, most analyzed studies did not specifically report on these events. Future studies should include PAD as a key endpoint. PROSPERO Registration: CRD42024565567. CI - Copyright (c) 2025 SEEN and SED. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Garagoli, Fernando AU - Garagoli F AD - Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Electronic address: fernando.garagoli@hospitalitaliano.org.ar. FAU - Masson, Walter AU - Masson W AD - Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. FAU - Barbagelata, Leandro AU - Barbagelata L AD - Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. FAU - Lobo, Martin AU - Lobo M AD - Cardiology Department, Hospital Militar Campo de Mayo, Buenos Aires, Argentina. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Peripheral Arterial Disease/prevention & control/etiology/epidemiology MH - *Diabetic Angiopathies/prevention & control/epidemiology OTO - NOTNLM OT - Agonistas del receptor del peptido similar al glucagon tipo 1 OT - Amputacion OT - Amputation OT - Diabetes mellitus OT - Enfermedad arterial periferica OT - Eventos adversos mayores en las extremidades OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse limb events OT - Peripheral arterial disease OT - Peripheral revascularization OT - Revascularizacion periferica EDAT- 2025/05/25 20:35 MHDA- 2025/05/25 20:36 CRDT- 2025/05/24 20:59 PHST- 2024/09/18 00:00 [received] PHST- 2024/11/29 00:00 [accepted] PHST- 2025/05/25 20:36 [medline] PHST- 2025/05/25 20:35 [pubmed] PHST- 2025/05/24 20:59 [entrez] AID - S2530-0180(25)00058-7 [pii] AID - 10.1016/j.endien.2025.501562 [doi] PST - ppublish SO - Endocrinol Diabetes Nutr (Engl Ed). 2025 May;72(5):501562. doi: 10.1016/j.endien.2025.501562. PMID- 40409279 OWN - NLM STAT- MEDLINE DCOM- 20250603 LR - 20260127 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 57 IP - 5 DP - 2025 May TI - Efficacy, Safety, and Future of GLP-1 Receptor Agonists: A Systematic Literature Review and Meta-Analysis. PG - 326-337 LID - 10.1055/a-2569-7315 [doi] AB - GLP-1 receptor agonists have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their comparative efficacy and broader applications remain subjects of ongoing research. The aim of the study was to evaluate and compare the efficacy, safety, and clinical applications of three GLP-1 receptor agonists - Semaglutide, Dulaglutide, and Exenatide - through systematic review and meta-analysis. A comprehensive search of PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science (2015-2023) identified 20 randomized controlled trials and observational studies. Primary outcomes included changes in HbA1c and body weight. Risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Semaglutide demonstrated superior efficacy with mean HbA1c reduction of 1.45% and weight loss of 1.44 kg. Dulaglutide showed consistent reductions in HbA1c (1.1%) and weight (1.2 kg). while Exenatide exhibited moderate effects. Meta-analysis revealed a significant pooled effect estimate favoring GLP-1 receptor agonists. with a mean HbA1c difference of -0.81 (95% CI: -0.92 to -0.70). Gastrointestinal side effects were most common, with Semaglutide showing the highest incidence. This meta-analysis establishes Semaglutide as the most effective GLP-1 receptor agonist for glycemic control and weight reduction, while Dulaglutide and Exenatide offer viable alternatives with fewer side effects. These findings support evidence-based decision-making in T2DM management and highlight the potential broader therapeutic applications of GLP-1 receptor agonists beyond diabetes care. CI - Thieme. All rights reserved. FAU - Katz, Griffin AU - Katz G AUID- ORCID: 0009-0005-4153-2913 AD - Edith Neumann School of Health and Human Services, Touro University California, Vallejo, United States. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250523 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Exenatide/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors declare that they have no conflict of interest. EDAT- 2025/05/24 00:46 MHDA- 2025/06/04 00:29 CRDT- 2025/05/23 18:42 PHST- 2025/06/04 00:29 [medline] PHST- 2025/05/24 00:46 [pubmed] PHST- 2025/05/23 18:42 [entrez] AID - 10.1055/a-2569-7315 [doi] PST - ppublish SO - Horm Metab Res. 2025 May;57(5):326-337. doi: 10.1055/a-2569-7315. Epub 2025 May 23. PMID- 40407287 OWN - NLM STAT- MEDLINE DCOM- 20250523 LR - 20250624 IS - 2245-1919 (Electronic) IS - 2245-1919 (Linking) VI - 72 IP - 5 DP - 2025 Apr 9 TI - Perioperative GLP1-RA management and risk of aspiration in patients with diabetes undergoing fast-track hip and knee arthroplasty. LID - A09240629 [pii] LID - 10.61409/A09240629 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Recently, concerns have been raised regarding perioperative GLP1-RA management due to delayed gastric emptying and the potential risk of pulmonary aspiration. However, since no prospective data are available on surgical patients, we aimed to investigate the risk of perioperative pulmonary aspiration in patients with T2D treated with a GLP1-RA undergoing fast-track hip and knee arthroplasty. METHODS: This was a prospective observational study within a multicentre fast-track hip and knee replacement collaboration in patients with T2D with receiving GLP-1 RA. Detailed data were collected from 1 October 2022 to 1 April 2024, including perioperative GLP1-RA management, type of anaesthesia, complications and postoperative length of stay (LOS). RESULTS: Among 426 patients with T2D, 19% had spinal anaesthesia without sedation, 53% had spinal anaesthesia with propofol sedation, and 26% had general anaesthesia. Data on perioperative management of GLP1-RAs were available in 93% of all patients, of whom 92% had continued their usual GLP1-RA regimen perioperatively, and the median LOS was one (IQR: 1-1) day. There were no cases with perioperative aspiration (0%; 95% confidence interval (CI): 0.0-0.9%) or LOS > 2 days (7%; 95% CI: 5-9%) potentially related to GLP1-RA-associated delayed gastric emptying. CONCLUSION: Our results support reconsidering the arguments for prolonged withholding of GLP1-RA treatment before surgery and suggest that it may be safe to continue GLP1-RA treatment up to the day of surgery in these patients. FUNDING: This study was supported financially by a grant from the NOVO NORDISK Foundation (grant number NNF21SA0073760). CLINICALTRIALS: gov (NCT05613439). CI - Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/. FAU - Mahmoud, Luma Issa AU - Mahmoud LI AD - Department of Anaesthesia and Intensive Care, Copenhagen University Hospital - Hvidovre Hospital. AD - Center for Fast-track Hip and Knee Replacement. FAU - Kehlet, Henrik AU - Kehlet H AD - Center for Fast-track Hip and Knee Replacement. AD - Section of Surgical Pathophysiology, Copenhagen University Hospital - Rigshospitalet. FAU - Madsbad, Sten AU - Madsbad S AD - The Department of Endocrinology, Copenhagen University Hospital - Hvidovre Hospital. FAU - Lindberg-Larsen, Martin AU - Lindberg-Larsen M AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Svendborg. FAU - Varnum, Claus AU - Varnum C AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery, Vejle Hospital, Lillebaelt Hospital. FAU - Jakobsen, Thomas AU - Jakobsen T AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery, Aalborg University Hospital. FAU - Andersen, Mikkel Rathsach AU - Andersen MR AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery, Copenhagen University Hospital - Herlev and Gentofte Hospital. FAU - Bieder, Manuel Josef AU - Bieder MJ AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery, Copenhagen University Hospital - Naestved, Slagelse and Ringsted Hospitals. FAU - Overgaard, Soren AU - Overgaard S AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery and Traumatology, Copenhagen University Hospital - Bispebjerg Hospital. AD - Department of Clinical Medicine, University of Copenhagen. FAU - Hansen, Torben Baek AU - Hansen TB AD - Center for Fast-track Hip and Knee Replacement. AD - University Clinic for Hand, Hip and Knee Surgery, Aarhus University Hospital - Hospital Unit West Jutland. FAU - Gromov, Kirill AU - Gromov K AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Orthopaedic Surgery, Copenhagen University Hospital - Hvidovre Hospital. FAU - Jorgensen, Christoffer Calov AU - Jorgensen CC AD - Center for Fast-track Hip and Knee Replacement. AD - Department of Anaesthesia, Copenhagen University Hospital - Hospital of Northern Zealand, Hillerod, Denmark. LA - eng SI - ClinicalTrials.gov/NCT05613439 PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250409 PL - Denmark TA - Dan Med J JT - Danish medical journal JID - 101576205 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - Prospective Studies MH - *Arthroplasty, Replacement, Knee/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Arthroplasty, Replacement, Hip/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Perioperative Care/methods MH - Length of Stay/statistics & numerical data MH - *Respiratory Aspiration/epidemiology/etiology MH - Postoperative Complications/epidemiology EDAT- 2025/05/23 12:30 MHDA- 2025/05/23 12:31 CRDT- 2025/05/23 08:43 PHST- 2025/05/23 12:31 [medline] PHST- 2025/05/23 12:30 [pubmed] PHST- 2025/05/23 08:43 [entrez] AID - A09240629 [pii] AID - 10.61409/A09240629 [doi] PST - epublish SO - Dan Med J. 2025 Apr 9;72(5):A09240629. doi: 10.61409/A09240629. PMID- 40404820 OWN - NLM STAT- MEDLINE DCOM- 20250710 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 8 DP - 2025 Aug TI - Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study. PG - 1666-1673 LID - 10.1007/s00125-025-06448-w [doi] AB - AIMS/HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice. METHODS: Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA(1c) and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA(1c) reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project. RESULTS: At 6 months' follow-up the median absolute HbA(1c) reduction was 5.3 mmol/mol (IQR 13.9, -1.0) (0.49% [1.27, -0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA(1c) (absolute reduction >/=5.5 mmol/mol [0.5%]) and body weight (relative reduction >/=5%). Men and those with a higher baseline HbA(1c) were more likely to show an HbA(1c) only response (36% of participants; both p<0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p<0.001). Higher baseline body weight and lower eGFR (both p<0.05) correlated with greater weight reduction, whereas lower baseline HbA(1c) and longer diabetes duration were linked to smaller HbA(1c) reductions (both p<0.001). CONCLUSIONS/INTERPRETATION: There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA(1c). Future studies should explore why some individuals achieve either weight loss or HbA(1c) reduction but not both. CI - (c) 2025. The Author(s). FAU - Heni, Martin AU - Heni M AUID- ORCID: 0000-0002-8462-3832 AD - Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. martin.heni@uniklinik-ulm.de. AD - Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tubingen, Tubingen, Germany. martin.heni@uniklinik-ulm.de. FAU - Fruhwald, Lisa AU - Fruhwald L AD - 5th Medical Department, Endocrinology, Rheumatology and Acute Geriatrics, Hospital Ottakring, Vienna, Austria. FAU - Karges, Wolfram AU - Karges W AD - Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany. FAU - Naudorf, Michael AU - Naudorf M AD - Diabetes Center Lindlar, Lindlar, Germany. FAU - Niemoller, Kathrin AU - Niemoller K AD - Knappschaftskrankenhaus Dortmund, Department of Internal Medicine V, Dortmund, Germany. FAU - Pagnia, Frank AU - Pagnia F AD - Specialised Diabetes Practice, Memmingen, Germany. FAU - Reindel, Jorg AU - Reindel J AD - Department of Diabetology, Metabolic Disorders and Nephrology, Hospital Karlsburg, Karlsburg, Germany. FAU - Seufert, Jochen AU - Seufert J AD - Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Ufer, Gisa AU - Ufer G AD - Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. FAU - Wagner, Christian AU - Wagner C AD - Specialised Diabetes Practice, Saaldorf-Surheim, Germany. FAU - Holl, Reinhard W AU - Holl RW AD - Institute of Epidemiology and Medical Biometry, CAQM, University of Ulm, Ulm, Germany. AD - German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany. FAU - Prinz, Nicole AU - Prinz N AUID- ORCID: 0000-0002-7570-9095 AD - Institute of Epidemiology and Medical Biometry, CAQM, University of Ulm, Ulm, Germany. AD - German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany. LA - eng GR - 875534/the Innovative Medicines Initiative 2 Joint Undertaking/ GR - 82DZD14E1G/German Center for Diabetes Research (DZD)/ GR - 1368-1711/Robert Koch Institut/ PT - Journal Article DEP - 20250522 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Aged MH - Registries MH - Immunoglobulin Fc Fragments/therapeutic use MH - Weight Loss/drug effects MH - Recombinant Fusion Proteins/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Body Weight/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12245949 OTO - NOTNLM OT - Body weight OT - GLP-1 receptor agonists OT - HbA1c OT - Heterogeneity OT - Real life COIS- Acknowledgements: Special thanks to A. Hungele and R. Ranz for support and development of the DPV documentation software (both clinical data managers, Ulm University). The authors further wish to express their special gratitude to all DPV centres participating in the initiative. Centres contributing data to the present analysis were Aachen - Innere RWTH, Aidlingen Praxisgemeinschaft, Asbach Kamillus-Klinik Innere, Augsburg IV, Medizinische Uni-Klinik, Bad Aibling Internist, Praxis, Bad Aibling Internistische Praxis-2, Bad Oeynhausen Herz-und Diabeteszentrum NRW, Bad Reichenhall Kreisklinik Innere Medizin, Bayreuth Innere Medizin, Berchtesgaden CJD, Bergen Gemeinschaftspraxis, Berlin DRK-Kliniken Mitte Innere, Berlin Endokrinologikum, Berlin Klinik St. Hedwig Innere, Berlin Oskar Zieten Krankenhaus Innere, Berlin Schlosspark-Klinik Innere, Berlin Vivantes Hellersdorf Innere, Bodnegg - MVZ Wollmarshohe, Bonn Schwerpunktpraxis, Bottrop Knappschaftskrankenhaus Innere, Bremen - Mitte Innere, Bremerhaven Kinderklinik, Castrop-Rauxel Rochus-Hospital, Chemnitz-Hartmannsdorf Innere Medizin - DIAKOMED-1, Coburg Innere Medizin, Coesfeld/Dulmen Innere Medizin, Darmstadt Innere Medizin, Deggendorf Gemeinschaftspraxis, Dortmund Johannes Hospital, Dortmund Knappschaftskrankenhaus Innere, Dortmund Medizinische Kliniken Nord, Dortmund-St. Josefshospital Innere, Dortmund-West Innere, Duisburg Homberg Helios Rhein-Ruhr Kliniken GmbH, Duisburg St. Anna Innere Helios Rhein-Ruhr Kliniken GmbH, Duisburg-Huckingen, Eckernforde Gemeinschaftspraxis, Eisleben Lutherstadt Helios-Klinik, Erlangen Uni Innere Medizin, Essen Diabetes-SPP, Essen Diabetes-Schwerpunktpraxis, Forchheim Diabeteszentrum SPP, Frankfurt Diabeteszentrum Rhein-Main-Erwachsenendiabetologie (Burgerhospital), Frankfurt Uni-Klinik Innere, Frankfurt-Sachsenhausen Innere, Frankfurt-Sachsenhausen Innere MVZ, Freiburg Uni Innere, Geislingen Klinik Helfenstein Innere, Giessen Evangelisches Krankenhaus Mittelhessen, Gottingen Uni Gastroenterologie, Gustrow Innere, Halberstadt Innere Medizin AMEOS Klinik, Hanau diabetolologische Schwerpunktpraxis, Heide Westkustenklinikum Innere Medizin, Heidelberg St. Josefskrankenhaus, Heidenheim Arztpraxis Allgemeinmedizin, Heilbronn Innere Klinik, Herford Innere Med I, Herne Evanangelisches Krankenhaus Innere, Hildesheim GmbH - Innere, Idar Oberstein Schwerpunktpraxis, Jena diabetologische Schwerpunktpraxis, Kamen Klinikum Westfalen Hellmig Krankenhaus, Kamen MKK - Medizinisches Kompetenzkollegium, Karlsburg Klinik fur Diabetes und Stoffwechsel, Karlsruhe Schwerpunktpraxis, Kirchheim-Nurtingen Innere, Koblenz Kemperhof 1. Medizinische Klinik, Konstanz Innere Klinik, Krefeld-Uerdingen St. Josef Innere, Landau Innere, Lilienthal Diabeteszentrum, Limburg Innere Medizin, Lindlar DM-Zentrum, Linz Krankenhaus Barmherzige Schwestern Kardiologie Abt. Int. II, Ludwigshafen diabetol. SPP, Luxembourg - Centre Hospitalier, Lubeck Uni-Klinik Innere Medizin, Lunen Klinik am Park, Magdeburg Stadtisches Klinikum Innere, Manderscheid Rathauspraxis, Marktredwitz Innere Medizin, Memmingen Internistische Praxis, Murnau am Staffelsee - diabetol. SPP, Muhlheim an der Ruhr Evang. Krankenhaus Medizinische Klinik, Munchen Diabetes-Zentrum Sud, Munchen Schwerpunktpraxis, Munster Herz Jesu Innere, Munster Ludgerus-Kliniken GmbH, Neunkirchen Innere Medizin, Neuwied Marienhaus Klinikum St. Elisabeth Innere, Oberndorf Gastroenterologische Praxis Schwerpunkt Diabetologie, Pirmasens Stadtisches Krankenhaus Innere, Prenzlau Krankenhaus Innere, Prien am Chiemsee Innere, Rosenheim Innere Medizin, Rosenheim Schwerpunktpraxis, Rottweil Gemeinschaftspraxis fur Innere Medizin, Saaldorf-Surheim Diabetespraxis, Schwerin Innere Medizin, Spaichingen Innere, Stuttgart Sana Klinik Bethesda, Tettnang Innere Medizin, Traunstein diabetologische Schwerpunktpraxis, Trostberg Innere, Ulm Schwerpunktpraxis Bahnhofsplatz, Ulm Uni Innere Medizin, Ulm Uni-Kinderklinik, Viersen internist. Praxis, Villingen-Schwenningen Schwarzwald-Baar-Klinikum Innere, Wangen Oberschwabenklinik Innere Medizin, Weisswasser Kreiskrankenhaus, Wernberg-Koblitz SPP, Wien Uni Innere Medizin III, Wittlich DSP, Worms Schwerpunktpraxis. Data availability: The data are not publicly available because they contain information that could compromise research participant privacy/consent. Funding: Open Access funding enabled and organized by Projekt DEAL. The DPV initiative is funded by the German Center for Diabetes Research (DZD, grant no. 82DZD14E1G), the Robert Koch Institute (RKI, grant no. 1368-1711) and the German Diabetes Association (DDG). In addition, this study is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project ( www.imisophia.eu ). SOPHIA has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement no. 875534. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and the T1D Exchange, JDRF and Obesity Action Coalition. This article reflects the authors' views and neither the IMI nor the European Union, EFPIA or any associated partners are responsible for any use that may be made of the information contained therein. Authors' relationships and activities: Outside the current work, MH reports lecture fees from Chiesi/Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk and Sanofi. He has also served on advisory boards for Chiesi/Amryt, Boehringer Ingelheim and Sanofi. He is also currently a board member of the German Diabetes Association (DDG). Outside the current work, MN reports lecture fees from AstraZeneca and Dexcom. He is a member of the scientific committee of the Arbeitsgemeinschaft Diabetes & Technologie of the German Diabetes Association (DDG). Outside the current work, JR reports lecture fees from AstraZeneca and Sanofi. Outside the current work, JS has received honoraria for talks and/or consultancy and/or research funding from Apitope, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, GI Dynamics, GlaxoSmithKline, Intarcia, Ipsen, Janssen, LifeScan, MedScape, MSD, Novartis, Novo Nordisk, OmniaMed, Pfizer, Roche, Sanofi, Servier, Takeda and Ypsomed. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: MH and NP designed/performed the analyses, discussed the findings and drafted the manuscript. LF, WK, MN, KN, FP, JR, JS, GU and CW were responsible for acquisition of the data and reviewed the manuscript critically for important intellectual content. RWH made substantial contributions to the initial conception of the work and reviewed the manuscript critically for important intellectual content. All authors approved the final version of the manuscript prior to submission. NP and RWH are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2025/05/23 00:27 MHDA- 2025/07/10 12:31 PMCR- 2025/05/22 CRDT- 2025/05/22 23:25 PHST- 2024/10/26 00:00 [received] PHST- 2025/03/25 00:00 [accepted] PHST- 2025/07/10 12:31 [medline] PHST- 2025/05/23 00:27 [pubmed] PHST- 2025/05/22 23:25 [entrez] PHST- 2025/05/22 00:00 [pmc-release] AID - 10.1007/s00125-025-06448-w [pii] AID - 6448 [pii] AID - 10.1007/s00125-025-06448-w [doi] PST - ppublish SO - Diabetologia. 2025 Aug;68(8):1666-1673. doi: 10.1007/s00125-025-06448-w. Epub 2025 May 22. PMID- 40401622 OWN - NLM STAT- MEDLINE DCOM- 20250603 LR - 20260708 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 14 IP - 11 DP - 2025 Jun 3 TI - Comparison of New-Onset Peripheral Artery Disease in Patients With Type 2 Diabetes Exposed to Sodium-Glucose Cotransporter-2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, or Glucagon-Like Peptide-1 Agonists: A Population-Based Cohort Study. PG - e034175 LID - 10.1161/JAHA.123.034175 [doi] LID - e034175 AB - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is), dipeptidyl peptidase-4 inhibitors (DPP4Is), and glucagon-like peptide-1 receptor agonists have been associated with improved cardiovascular outcomes and prognosis. The comparative risks of new-onset peripheral artery disease (PAD) between these medications remain unknown. This real-world study compared the risks of PAD in patients exposed to SGLT2I and DPP4I. METHODS AND RESULTS: This was a retrospective population-based cohort study of patients with type 2 diabetes on either an SGLT2I or a DPP4I between January 1, 2015, and December 31, 2015, using a territory-wide database from Hong Kong. The primary outcome was new-onset PAD. The secondary outcomes were cardiovascular hospitalization, cardiovascular death, and all-cause death. Propensity score matching (1:1 ratio) using the nearest neighbor search was performed. Multivariable Cox regression with time-weighted variables was used to identify significant associations. A 3-arm analysis including the glucagon-like peptide-1 receptor agonist cohort was conducted. This cohort included 75 470 patients with type 2 diabetes (median age, 62.3+/-12.8 years; 55.79% men). The SGLT2I and DPP4I groups consisted of 28 753 patients and 46 717 patients, respectively. After matching, 186 and 256 patients had PAD in the SGLT2I and DPP4I groups, respectively, over a median follow-up of 5.6 years. SGLT2I use was associated with lower risks of PAD (hazard ratio [HR], 0.79 [95% CI, 0.66-0.93]) compared with DPP4I use after adjusting for demographics, comorbidities, medications, renal function, and glycemic tests. The association remained consistent regardless of sex, age, and other metabolic diseases. In the 3-arm analysis, the risk of PAD was not statistically different between SGLT2Is and glucagon-like peptide-1 receptor agonists (HR, 1.18 [95% CI, 0.52-2.68]). The results remained consistent in the competing risk and the sensitivity analyses. CONCLUSIONS: SGLT2I use among patients with type 2 diabetes was associated with lower risks of new-onset PAD and PAD-related outcomes when compared with DPP4Is after adjustments. FAU - Chou, Oscar Hou-In AU - Chou OH AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. AD - Division of Clinical Pharmacology and Therapeutics, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China. FAU - Luo, Zhiyao AU - Luo Z AUID- ORCID: 0000-0003-0015-2023 AD - Institute of Biomedical Engineering, Department of Engineering Science University of Oxford Oxford UK. FAU - Chung, Cheuk To Skylar AU - Chung CTS AUID- ORCID: 0000-0002-0420-5359 AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. FAU - Chan, Jeffrey AU - Chan J AUID- ORCID: 0000-0003-0231-2393 AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. FAU - Li, Huixian AU - Li H AD - School of Life Sciences Chinese University of Hong Kong Hong Kong China. FAU - Lakhani, Ishan AU - Lakhani I AUID- ORCID: 0000-0001-7566-9700 AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. FAU - Lee, Sharen AU - Lee S AUID- ORCID: 0000-0002-2401-2837 AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. FAU - Lau, Dawnie Ho Hei AU - Lau DHH AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. FAU - Zhang, Qingpeng AU - Zhang Q AUID- ORCID: 0000-0002-6819-0686 AD - Musketeers Foundation Institute of Data Science and Department of Pharmacology and Pharmacy, LKS Faculty of Medicine The University of Hong Kong Hong Kong China. FAU - Liu, Tong AU - Liu T AUID- ORCID: 0000-0003-0482-0738 AD - Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China. FAU - Wong, Wing Tak AU - Wong WT AUID- ORCID: 0000-0002-4514-3780 AD - School of Life Sciences Chinese University of Hong Kong Hong Kong China. FAU - Cheung, Bernard Man Yung AU - Cheung BMY AUID- ORCID: 0000-0001-9106-7363 AD - Division of Clinical Pharmacology and Therapeutics, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China. FAU - Lip, Gregory Y H AU - Lip GYH AUID- ORCID: 0000-0002-7566-1626 AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital Liverpool UK. AD - Danish Center for Health Services Research, Department of Clinical Medicine Aalborg University Aalborg Denmark. FAU - Leung, Fung Ping AU - Leung FP AD - School of Life Sciences Chinese University of Hong Kong Hong Kong China. FAU - Tse, Gary AU - Tse G AUID- ORCID: 0000-0001-5510-1253 AD - Diabetes Research Unit Cardiovascular Analytics Group Hong Kong China. AD - School of Nursing and Health Sciences Hong Kong Metropolitan University Hong Kong China. FAU - Zhou, Jiandong AU - Zhou J AUID- ORCID: 0000-0003-3780-9033 AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China. AD - School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China. AD - Department of Pharmacology and Pharmacy The University of Hong Kong Hong Kong China. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250522 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - *Peripheral Arterial Disease/epidemiology/diagnosis MH - Aged MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Hong Kong/epidemiology MH - Risk Factors MH - Risk Assessment MH - Treatment Outcome MH - Time Factors MH - Incidence PMC - PMC12229098 OTO - NOTNLM OT - amputation OT - cardiovascular disease OT - dipeptidyl peptidase-4 inhibitors OT - glucagon-like peptide-1 receptor agonists OT - peripheral artery disease OT - sodium-glucose cotransporter-2 inhibitors COIS- None. EDAT- 2025/05/22 12:31 MHDA- 2025/06/03 12:31 PMCR- 2025/05/22 CRDT- 2025/05/22 06:43 PHST- 2025/06/03 12:31 [medline] PHST- 2025/05/22 12:31 [pubmed] PHST- 2025/05/22 06:43 [entrez] PHST- 2025/05/22 00:00 [pmc-release] AID - JAH310626 [pii] AID - 10.1161/JAHA.123.034175 [doi] PST - ppublish SO - J Am Heart Assoc. 2025 Jun 3;14(11):e034175. doi: 10.1161/JAHA.123.034175. Epub 2025 May 22. PMID- 40399267 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260307 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 16 IP - 1 DP - 2025 May 21 TI - GLP-1R/GCGR dual agonism dissipates hepatic steatosis to restore insulin sensitivity and rescue pancreatic beta-cell function in obese male mice. PG - 4714 LID - 10.1038/s41467-025-59773-4 [doi] LID - 4714 AB - An early driver of Type 2 diabetes mellitus (T2D) is ectopic fat accumulation, especially in the liver, that impairs insulin sensitivity. In T2D, GLP-1R/GCGR dual-agonists reduce glycaemia, body weight and hepatic steatosis. Here, we utilize cotadutide, a well characterized GLP-1R/GCGR dual-agonist, and demonstrate improvement of insulin sensitivity during hyperinsulinemic euglycemic clamp following sub-chronic dosing in male, diet-induced obese (DIO) mice. Phosphoproteomic analyses of insulin stimulated liver from cotadutide-treated mice identifies previously unknown and known phosphorylation sites on key insulin signaling proteins associated with improved insulin sensitivity. Cotadutide or GCGR mono-agonist treatment also increases brown adipose tissue (BAT) insulin-stimulated glucose uptake, while GLP-1R mono-agonist shows a weak effect. BAT from cotadutide-treated mice have induction of UCP-1 protein, increased mitochondrial area and a transcriptomic profile of increased fat oxidation and mitochondrial activity. Finally, the cotadutide-induced improvement in insulin sensitivity is associated with reduction of insulin secretion from isolated pancreatic islets indicating reduced insulin secretory demand. Here we show, GLP-1R/GCGR dual agonism provides multimodal efficacy to decrease hepatic steatosis and consequently improve insulin sensitivity, in concert with recovery of endogenous beta-cell function and reduced insulin demand. This substantiates GLP-1R/GCGR dual-agonism as a potentially effective T2D treatment. CI - (c) 2025. The Author(s). FAU - Laker, Rhianna C AU - Laker RC AUID- ORCID: 0000-0002-0507-7838 AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. rhianna.laker@astrazeneca.com. FAU - Egolf, Shaun AU - Egolf S AUID- ORCID: 0000-0001-5920-0144 AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Will, Sarah AU - Will S AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Lantier, Louise AU - Lantier L AUID- ORCID: 0000-0002-6620-4976 AD - Vanderbilt University Mouse Metabolic Phenotyping Center, Nashville, TN, USA. FAU - McGuinness, Owen P AU - McGuinness OP AUID- ORCID: 0000-0002-1778-3203 AD - Vanderbilt University Mouse Metabolic Phenotyping Center, Nashville, TN, USA. FAU - Brown, Charles AU - Brown C AD - Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, MD, USA. FAU - Bhagroo, Nicholas AU - Bhagroo N AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Oldham, Stephanie AU - Oldham S AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Kuszpit, Kyle AU - Kuszpit K AD - Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, MD, USA. FAU - Alfaro, Alex AU - Alfaro A AD - Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, MD, USA. FAU - Li, Xidan AU - Li X AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Kang, Taewook AU - Kang T AUID- ORCID: 0000-0003-3959-4777 AD - Department of Biochemistry and Molecular Biology, PR group, University of Southern Denmark, Odense, Denmark. FAU - Pellegrini, Giovanni AU - Pellegrini G AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Andreasson, Anne-Christine AU - Andreasson AC AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Kajani, Sarina AU - Kajani S AUID- ORCID: 0000-0003-2773-7195 AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Sitaula, Sadichha AU - Sitaula S AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. FAU - Larsen, Martin R AU - Larsen MR AUID- ORCID: 0000-0001-6203-0123 AD - Department of Biochemistry and Molecular Biology, PR group, University of Southern Denmark, Odense, Denmark. FAU - Rhodes, Christopher J AU - Rhodes CJ AUID- ORCID: 0000-0002-7450-1110 AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. christopher.rhodes@astrazeneca.com. LA - eng GR - P30 DK020593/DK/NIDDK NIH HHS/United States GR - S10 OD025199/OD/NIH HHS/United States GR - U2C DK135073/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20250521 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Insulin) RN - 0 (Glp1r protein, mouse) RN - 0 (Uncoupling Protein 1) SB - IM MH - Animals MH - Male MH - *Insulin Resistance MH - *Insulin-Secreting Cells/drug effects/metabolism MH - Mice MH - *Fatty Liver/drug therapy/metabolism MH - *Obesity/metabolism/drug therapy MH - Adipose Tissue, Brown/metabolism/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Mice, Obese MH - Insulin/metabolism MH - Liver/metabolism/drug effects/pathology MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Uncoupling Protein 1/metabolism MH - Glucose Clamp Technique PMC - PMC12095689 COIS- Competing interests: R.C.L., C.J.R., S.W., S.O., A.C.-A., S.K., S.E., N.B., and A.A. are current employees of AstraZeneca and may own stock in AstraZeneca. K.K., S.S., X.L., C.B., and G.P. are former employees and may also own stock in AstraZeneca. T.K. and M.R.L. have received research support from AstraZeneca. The remaining authors declare no competing interests. EDAT- 2025/05/22 00:28 MHDA- 2025/05/22 00:29 PMCR- 2025/05/21 CRDT- 2025/05/21 23:14 PHST- 2024/02/07 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2025/05/22 00:29 [medline] PHST- 2025/05/22 00:28 [pubmed] PHST- 2025/05/21 23:14 [entrez] PHST- 2025/05/21 00:00 [pmc-release] AID - 10.1038/s41467-025-59773-4 [pii] AID - 59773 [pii] AID - 10.1038/s41467-025-59773-4 [doi] PST - epublish SO - Nat Commun. 2025 May 21;16(1):4714. doi: 10.1038/s41467-025-59773-4. PMID- 40397216 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260924 IS - 1534-6293 (Electronic) IS - 1528-4042 (Print) IS - 1528-4042 (Linking) VI - 25 IP - 1 DP - 2025 May 21 TI - Emerging Treatments for Obesity: the Role of GLP1 Receptor Agonists on Stroke. PG - 36 LID - 10.1007/s11910-025-01423-9 [doi] LID - 36 AB - PURPOSE: Stroke is a leading cause of disability and mortality worldwide. It has been estimated that more than 90% of the risk of stroke is associated with modifiable factors, including diabetes, hypertension, obesity, and heart disease. Glucagon-like peptide 1 receptor agonists (GLP1RAs) have been shown to have a beneficial effect on these major risk factors. In this review, we discuss the evidence supporting the use of GLP1RAs on brain health, particularly in relation to stroke prevention. RECENT FINDINGS: The results of multiple randomized clinical trials demonstrate that, among patients with type 2 diabetes, GLP1RAs reduce body weight and improve glucose levels and lipid metabolism. In high-risk populations, GLP1RAs also reduce the risk of major adverse cardiovascular events, including all stroke and non-fatal stroke. Mechanistically, GLP1RAs have a beneficial effect on different stroke risk factors, support microvascular function, and reduce inflammation and oxidative stress. GLP1RAs are recommended for the primary prevention of stroke in patients with diabetes and elevated cardiovascular risk. CI - (c) 2025. The Author(s). FAU - Mariscal, Melissa AU - Mariscal M AD - Neurology and Rehabilitation, University of Illinois Chicago, 912 S Wood St, Chicago, IL, 60612, USA. mmaris3@uic.edu. FAU - Testai, Fernando D AU - Testai FD AD - Neurology and Rehabilitation, University of Illinois Chicago, 912 S Wood St, Chicago, IL, 60612, USA. LA - eng PT - Journal Article PT - Review DEP - 20250521 PL - United States TA - Curr Neurol Neurosci Rep JT - Current neurology and neuroscience reports JID - 100931790 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Stroke/prevention & control/drug therapy MH - *Obesity/drug therapy/complications MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12095380 OTO - NOTNLM OT - Cardiovascular disease OT - GLP-1 OT - GLP1RAs OT - Obesity OT - Stroke COIS- Declarations. Human and Animal Rights: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). Competing Interests: The authors declare no competing interests. EDAT- 2025/05/21 12:32 MHDA- 2025/05/21 18:29 PMCR- 2025/05/21 CRDT- 2025/05/21 11:18 PHST- 2025/05/01 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/05/21 12:32 [pubmed] PHST- 2025/05/21 11:18 [entrez] PHST- 2025/05/21 00:00 [pmc-release] AID - 10.1007/s11910-025-01423-9 [pii] AID - 1423 [pii] AID - 10.1007/s11910-025-01423-9 [doi] PST - epublish SO - Curr Neurol Neurosci Rep. 2025 May 21;25(1):36. doi: 10.1007/s11910-025-01423-9. PMID- 40394225 OWN - NLM STAT- MEDLINE DCOM- 20250618 LR - 20250618 IS - 2662-8465 (Electronic) IS - 2662-8465 (Linking) VI - 5 IP - 6 DP - 2025 Jun TI - Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice. PG - 1097-1113 LID - 10.1038/s43587-025-00869-3 [doi] AB - Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD model mice and negatively correlated with amyloid-beta (Abeta) load in patients with AD. Enhancing GLP-1 signaling through GLP-1RAs increased CaMKK2-AMPK signaling, which subsequently reduced BACE1-mediated cleavage of amyloid precursor protein (APP) and Abeta generation. GLP-1RAs also increased AMPK activity in microglia, inhibiting neuroinflammation and promoting Abeta phagocytosis. Consequently, GLP-1RAs inhibited plaque formation and improved memory deficits in AD model mice. Our findings indicate that AMPK activation mediates the effects of GLP-1RAs on AD, highlighting the therapeutic potential of GLP-1RAs for the treatment of AD. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Zhang, Yun AU - Zhang Y AUID- ORCID: 0009-0004-5878-6939 AD - Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. zhangyun_202104@163.com. AD - National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China. zhangyun_202104@163.com. FAU - Chen, Huaqiu AU - Chen H AD - National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Feng, Yijia AU - Feng Y AUID- ORCID: 0000-0002-7668-7350 AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Liu, Mingjing AU - Liu M AD - Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Lu, Zhi AU - Lu Z AD - Department of Nuclear Medicine, The First Affiliated Hospital, Dalian Medical University, Dalian, China. FAU - Hu, Bolang AU - Hu B AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Chen, Lifen AU - Chen L AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Zhang, Yang AU - Zhang Y AD - National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Liu, Jiawen AU - Liu J AD - National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Cai, Fang AU - Cai F AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Zhao, Yifan AU - Zhao Y AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Pan, Wenhao AU - Pan W AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Liao, Xinxin AU - Liao X AD - Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, China. FAU - Pan, Sipei AU - Pan S AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Bestard-Lorigados, Isabel AU - Bestard-Lorigados I AD - Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Wu, Yili AU - Wu Y AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. FAU - Song, Weihong AU - Song W AUID- ORCID: 0000-0001-9928-889X AD - The Second Affiliated Hospital and Yuying Children's Hospital, Zhejiang Key Laboratory of Alzheimer's Disease, Zhejiang Provincial Clinical Research Center for Mental Disorders, Wenzhou Medical University, Wenzhou, China. weihong@wmu.edu.cn. AD - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Center for Geriatric Medicine and Institute of Aging, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. weihong@wmu.edu.cn. AD - Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada. weihong@wmu.edu.cn. LA - eng GR - 82293642/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 82230043/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 82201576/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article DEP - 20250520 PL - United States TA - Nat Aging JT - Nature aging JID - 101773306 RN - 0 (Amyloid beta-Peptides) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase) RN - 0 (Amyloid beta-Protein Precursor) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 2.7.11.17 (Camkk2 protein, mouse) RN - EC 3.4.23.46 (Bace1 protein, mouse) SB - IM MH - Animals MH - *Alzheimer Disease/drug therapy/metabolism/pathology MH - Mice, Transgenic MH - Amyloid beta-Peptides/metabolism MH - *AMP-Activated Protein Kinases/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mice MH - Glucagon-Like Peptide 1/blood/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism MH - Disease Models, Animal MH - Humans MH - Signal Transduction/drug effects MH - Amyloid beta-Protein Precursor/metabolism MH - Phenotype MH - Microglia/metabolism/drug effects MH - Male MH - Amyloid Precursor Protein Secretases/metabolism MH - Aspartic Acid Endopeptidases/metabolism MH - Diabetes Mellitus, Type 2/drug therapy MH - Female COIS- Competing interests: The authors declare no competing interests. EDAT- 2025/05/21 00:30 MHDA- 2025/06/19 00:25 CRDT- 2025/05/20 23:28 PHST- 2024/10/12 00:00 [received] PHST- 2025/04/07 00:00 [accepted] PHST- 2025/06/19 00:25 [medline] PHST- 2025/05/21 00:30 [pubmed] PHST- 2025/05/20 23:28 [entrez] AID - 10.1038/s43587-025-00869-3 [pii] AID - 10.1038/s43587-025-00869-3 [doi] PST - ppublish SO - Nat Aging. 2025 Jun;5(6):1097-1113. doi: 10.1038/s43587-025-00869-3. Epub 2025 May 20. PMID- 40392993 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 6 DP - 2025 Jun 1 TI - Cost-effectiveness of Semaglutide Compared With Other Glucose-Lowering Medications in Treating Type 2 Diabetes: A Comprehensive Systematic Review and Meta-analysis. PG - 1032-1041 LID - 10.2337/dc24-2241 [doi] AB - BACKGROUND: Significant clinical efficacy has been shown for semaglutide in managing type 2 diabetes (T2D); however, its cost-effectiveness remains uncertain. PURPOSE: To systematically review existing evidence on cost-effectiveness of semaglutide versus other T2D medications. DATA SOURCES: PubMed, Embase, and the Cost-Effectiveness Analysis Registry (by 11 June 2024). STUDY SELECTION: A total of 45 articles (with 119 comparisons) from 2019 onward were included, representing Europe (n = 24), North America (n = 13), and Asia (all from China) (n = 8). DATA EXTRACTION: Study characteristics and model characteristics/inputs/results were extracted. Lifetime costs and quality-adjusted life-years were evaluated. Proportions for cost-effectiveness outcomes (dominant, cost-effective, not cost-effective) were calculated. Subgroup analyses by region, sponsor type, comparator type, and model assumptions were performed. In sensitivity analysis a standard willingness-to-pay threshold was applied. DATA SYNTHESIS: Of the articles included, 93.3% included adoption of a lifetime horizon and 84.4% a health care perspective and 68.9% were industry sponsored. For most studies reporting quality was high (86.7%). Overall, semaglutide was dominant/cost-effective in 73.9% of all comparisons. Notably, semaglutide was found to be dominant/cost-effective in all comparisons sponsored by Novo Nordisk versus in 50.0% of these funded by nonindustry sponsors and in none funded by other industry sponsors. Additionally, semaglutide was more cost-effective in high-income countries and in studies with adoption of a broader perspective, longer horizon, and lower discount rates. Results remained consistent with conversion with a common currency unit and willingness-to-pay threshold of US$50,000. LIMITATIONS: Less detailed demographic information for more granular analyses. CONCLUSIONS: Semaglutide is generally cost-effective compared with other glucose-lowering medications in evaluation against within-study willingness-to-pay thresholds; however, results varied by study sponsor type, region, and model assumptions, highlighting the need for transparent and context-sensitive economic evaluations. CI - (c) 2025 by the American Diabetes Association. FAU - Liu, Ziyun AU - Liu Z AUID- ORCID: 0009-0003-8364-3270 AD - Division of the Social Sciences, University of Chicago, Chicago, IL. FAU - Zeng, Baoqi AU - Zeng B AUID- ORCID: 0000-0003-4443-6183 AD - Central Laboratory, Peking University Binhai Hospital, Tianjin, China. AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. FAU - Sun, Feng AU - Sun F AUID- ORCID: 0000-0003-4334-6805 AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. AD - Key Laboratory of Epidemiology of Major Diseases, Peking University, Ministry of Health, Beijing, China. AD - Department of Ophthalmology, Peking University Third Hospital, Beijing, China. FAU - Xia, Qing AU - Xia Q AD - Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Cost-Benefit Analysis MH - *Hypoglycemic Agents/therapeutic use/economics MH - Quality-Adjusted Life Years MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12094200 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2025/05/20 18:29 MHDA- 2025/05/21 18:29 PMCR- 2025/05/20 CRDT- 2025/05/20 15:12 PHST- 2024/10/16 00:00 [received] PHST- 2025/03/01 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/05/20 18:29 [pubmed] PHST- 2025/05/20 15:12 [entrez] PHST- 2025/05/20 00:00 [pmc-release] AID - 158296 [pii] AID - dc242241 [pii] AID - 10.2337/dc24-2241 [doi] PST - ppublish SO - Diabetes Care. 2025 Jun 1;48(6):1032-1041. doi: 10.2337/dc24-2241. PMID- 40390279 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - Effects of GLP-1 receptor agonists on incidence and outcomes of ischemic stroke and myocardial infarction: A systematic review and meta-analysis. PG - 4387-4400 LID - 10.1111/dom.16476 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate cardiovascular benefits beyond glycemic control, but the benefits of protection across cerebrovascular and cardiovascular territories remain incompletely studied in the literature. We aim to evaluate whether GLP-1 RAs provide balanced protection against stroke and myocardial infarction (MI) and identify factors that modify this protection. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials comparing GLP-1 RAs with placebo that reported cerebrovascular and cardiovascular outcomes. We calculated hazard ratios (HRs) for stroke and MI and developed a novel Territorial Benefit Ratio (TBR = HR stroke/HR MI) to quantify relative cerebrovascular versus coronary protection. Meta-regression analyses identified factors modifying territorial protection. RESULTS: Eleven trials with 85 373 participants met inclusion criteria. GLP-1 RAs significantly reduced stroke (HR 0.88, 95% CI 0.80-0.96) and MI (HR 0.87, 95% CI 0.79-0.97), resulting in an overall balanced TBR of 1.01 (95% CI 0.89-1.15). Protection patterns varied significantly by patient subgroups: prior stroke history provided better stroke protection (HR 0.73, NNT 54), while prior MI history provided better MI protection (HR 0.79, NNT 55). MI protection emerged earlier within the first six months (HR 0.81), while stroke protection strengthened over time (over 24 months: HR 0.80). Renal dysfunction, atrial fibrillation, and hypertension shifted protection towards stroke, while dyslipidemia provided better MI protection. CONCLUSIONS: GLP-1 RAs demonstrate a protection-in-territory-at-risk pattern with important temporal findings and results translated. These findings support a personalised approach to GLP-1 RA therapy that considers patients' vascular history and risk profiles. The earlier emergence of MI protection and later strengthening of stroke protection deliver significant highlights for clinical expectations and treatment persistence. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Alammari, Nawal AU - Alammari N AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Alshehri, Atheel AU - Alshehri A AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Al Khalaf, Abdulhameed AU - Al Khalaf A AD - Department of Family Medicine, Al-Ahsa Health Cluster, Al-Ahsa, Saudi Arabia. FAU - Alamri, Rahaf Abdulaziz AU - Alamri RA AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Alhalal, Noor AU - Alhalal N AD - College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain. FAU - Sultan, Majd Abdullah AU - Sultan MA AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Ogran, Nesreen AU - Ogran N AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Aljohani, Razan Mubarak S AU - Aljohani RMS AD - College of Medicine, Al-Rayan Colleges, Madinah, Saudi Arabia. FAU - Alasmari, Sarah Mohammed Saad AU - Alasmari SMS AD - College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Alsharif, Sarah Badr AU - Alsharif SB AD - Department of Health Promotion and Health Education, College of Public Health and Health Informatics, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Al-Qahtani, Zainah AU - Al-Qahtani Z AD - Neurology Division, Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia. FAU - Azzam, Ahmed Y AU - Azzam AY AUID- ORCID: 0000-0002-4256-0159 AD - Medical Big Data Research Center, SNU Medical Research Center, Seoul National University (SNU), Seoul, South Korea. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250519 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Myocardial Infarction/epidemiology/prevention & control MH - *Ischemic Stroke/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 RA OT - cardiovascular disease OT - cerebrovascular disease OT - myocardial infarction OT - stroke EDAT- 2025/05/20 06:28 MHDA- 2025/07/04 12:43 CRDT- 2025/05/20 01:52 PHST- 2025/04/11 00:00 [received] PHST- 2025/05/08 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/20 06:28 [pubmed] PHST- 2025/05/20 01:52 [entrez] AID - 10.1111/dom.16476 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4387-4400. doi: 10.1111/dom.16476. Epub 2025 May 19. PMID- 40388980 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20260512 IS - 1439-4413 (Electronic) IS - 0012-0472 (Linking) VI - 150 IP - 12 DP - 2025 Jun TI - [GLP-1 agonists - new kid on the block in nephrology]. PG - 696-702 LID - 10.1055/a-2420-6176 [doi] AB - GLP-1 receptor agonists (GLP-1-RA) are emerging as promising agents beyond their established role in type 2 diabetes mellitus (T2DM) and obesity treatment, showing significant nephroprotective effects. The FLOW study demonstrated that semaglutide significantly slows the progression of chronic kidney disease (CKD) in T2DM patients. The nephroprotective mechanisms are multifactorial, including improved glycemic control, blood pressure reduction, antifibrotic, and anti-inflammatory effects. Early studies suggest that GLP-1-RA may also benefit patients without T2DM. Additionally, their combination with SGLT2 inhibitors is gaining relevance. Current evidence suggests that GLP-1-RA could play a key role in CKD management. Future studies will determine whether they can be established as a standard therapy to optimize care for high-risk patients. CI - Thieme. All rights reserved. FAU - Kraft, Leonie AU - Kraft L AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. FAU - Schanz, Moritz AU - Schanz M AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. FAU - Latus, Jorg AU - Latus J AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. LA - ger PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review TT - GLP-1-RA - "New kid on the block" in der Nephrologie? DEP - 20250519 PL - Germany TA - Dtsch Med Wochenschr JT - Deutsche medizinische Wochenschrift (1946) JID - 0006723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetic Nephropathies/drug therapy MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Leonie Kraft: Beratungsgremium: AstraZeneca Moritz Schanz: Vortragshonorare: AstraZeneca Jorg Latus: Beratungsgremien und Vortragshonorare von Boehringer Ingelheim, AstraZeneca, Lilly, Novo Nordisk EDAT- 2025/05/20 00:30 MHDA- 2025/05/20 00:31 CRDT- 2025/05/19 19:12 PHST- 2025/05/20 00:31 [medline] PHST- 2025/05/20 00:30 [pubmed] PHST- 2025/05/19 19:12 [entrez] AID - 10.1055/a-2420-6176 [doi] PST - ppublish SO - Dtsch Med Wochenschr. 2025 Jun;150(12):696-702. doi: 10.1055/a-2420-6176. Epub 2025 May 19. PMID- 40388382 OWN - NLM STAT- MEDLINE DCOM- 20250715 LR - 20260916 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 110 IP - 8 DP - 2025 Jul 15 TI - Novel Cardiometabolic Medications in the Cardiovascular-Kidney-Metabolic Syndrome Era. PG - 2105-2122 LID - 10.1210/clinem/dgaf295 [doi] AB - Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interplay of obesity, hypertension, hyperlipidemia, type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease, driving elevated morbidity and mortality. CKM syndrome encompasses a continuum of interrelated metabolic, renal, and cardiovascular dysfunctions attributed to obesity, impaired glucose regulation, and chronic inflammation. This review synthesizes recent literature on the efficacy of cardiorenal protective medications including sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in CKM syndrome management. Sodium-glucose cotransporter 2 inhibitor agents show promising outcomes, including reduced cardiovascular mortality, hospitalization for heart failure, and adverse kidney events across diverse patient populations, regardless of type 2 diabetes mellitus status. Similarly, glucagon-like peptide-1 receptor agonist agents demonstrate substantial benefits in weight loss, glycemic control, and reduced cardiovascular and kidney events. The review also highlights the necessity of equitable pharmacotherapy distribution to ensure that high-risk populations benefit from these advancements and the need for further precision-based therapeutic frameworks, policy innovations, and tailored interventions focused on CKM syndrome management. Finally, we discuss strategies for translating these findings into practice through an equity-focused lens to advance CKM health. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Pohlman, Neal AU - Pohlman N AD - Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. FAU - Patel, Prem N AU - Patel PN AD - Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. FAU - Essien, Utibe R AU - Essien UR AD - Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. FAU - Tang, Jasmyn J AU - Tang JJ AD - Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. FAU - Joseph, Joshua J AU - Joseph JJ AUID- ORCID: 0000-0001-9169-8261 AD - Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. AD - Division of Endocrinology, Diabetes and Metabolism, The Ohio State University College of Medicine, Columbus, OH 43210, USA. LA - eng GR - R01HS028822/American Heart Association/ GR - R01 HS028822/HS/AHRQ HHS/United States GR - 23SFRNPCS1067039/American Heart Association/ GR - R01DK132403/HS/AHRQ HHS/United States GR - R01 DK132403/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metabolic Syndrome/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardio-Renal Syndrome/drug therapy PMC - PMC12823194 MID - NIHMS2131510 OTO - NOTNLM OT - cardiovascular disease OT - cardiovascular-kidney-metabolic syndrome OT - kidney disease OT - obesity OT - type 2 diabetes mellitus EDAT- 2025/05/19 18:34 MHDA- 2025/07/15 12:30 PMCR- 2026/07/15 CRDT- 2025/05/19 13:24 PHST- 2024/11/22 00:00 [received] PHST- 2025/07/15 12:30 [medline] PHST- 2025/05/19 18:34 [pubmed] PHST- 2025/05/19 13:24 [entrez] PHST- 2026/07/15 00:00 [pmc-release] AID - 8137911 [pii] AID - 10.1210/clinem/dgaf295 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 Jul 15;110(8):2105-2122. doi: 10.1210/clinem/dgaf295. PMID- 40383371 OWN - NLM STAT- MEDLINE DCOM- 20250612 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 4 DP - 2025 Jul TI - What the diabetologist needs to know about the risk of non-arteritic anterior ischaemic optic neuropathy and GLP-1 receptor agonist use in patients with type 2 diabetes. PG - 101664 LID - S1262-3636(25)00058-8 [pii] LID - 10.1016/j.diabet.2025.101664 [doi] AB - AIM: Recent findings have raised concern about a potential association between semaglutide use and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare form of permanent vision loss. This report provides a critical analysis of the current knowledge of GLP-1 receptor agonist (RA) use and risk of NAION in patients with type 2 diabetes (T2D). METHODS: A literature search strategy was conducted for all English-language literature with a systematic review of key references up to April 2025. RESULTS: Across studies including patients with T2D, the relative increase in NAION risk associated with the use of a GLP-1 RA, mainly semaglutide, ranged from nonsignificant to fourfold, while the absolute number of affected patients remained low. Given the retrospective design of the main studies, no causal link could be established between the use of GLP-1RAs and NAION. Some mechanistic hypotheses have been put forward without any being formally demonstrated to date. The profound metabolic and haemodynamic changes induced by GLP-1RAs might be the trigger of NAION in predisposed patients with an optic "disc-at-risk", a potent anatomical risk factor easily detected by ocular examination. CONCLUSION: Pending studies clarifying this risk, these findings call for cautious use of GLP-1 RAs, particularly in patients with ocular risk factors. Given the widespread use of GLP-1RAs, clinicians should be aware of this potential risk, without overshadowing the remarkable benefit of GLP-1RAs in patients with type 2 diabetes. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Feldman-Billard, Sylvie AU - Feldman-Billard S AD - Centre d'Investigation Clinique 1423, INSERM, Hopital de la vision des 15-20, 28 rue de Charenton, Paris 75571, France. Electronic address: sfeldman@15-20.fr. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250516 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Disc-at-risk OT - GLP-1 receptor agonist OT - Non-arteritic anterior ischaemic optic neuropathy OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest Sylvie Feldman-Billard declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/05/19 00:37 MHDA- 2025/06/13 00:27 CRDT- 2025/05/18 19:36 PHST- 2025/04/14 00:00 [received] PHST- 2025/04/17 00:00 [revised] PHST- 2025/04/18 00:00 [accepted] PHST- 2025/06/13 00:27 [medline] PHST- 2025/05/19 00:37 [pubmed] PHST- 2025/05/18 19:36 [entrez] AID - S1262-3636(25)00058-8 [pii] AID - 10.1016/j.diabet.2025.101664 [doi] PST - ppublish SO - Diabetes Metab. 2025 Jul;51(4):101664. doi: 10.1016/j.diabet.2025.101664. Epub 2025 May 16. PMID- 40383360 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 277 DP - 2025 Sep TI - Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries. PG - 148-168 LID - S0002-9394(25)00239-9 [pii] LID - 10.1016/j.ajo.2025.05.007 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for type 2 diabetes and obesity; however, concerns about ophthalmic safety persist. This study examined associations between GLP-1 RAs and ocular adverse events (AEs). DESIGN: Global observational pharmacovigilance study. METHODS: We searched the US FAERS database (via OpenVigil 2.1) and WHO's VigiBase (via VigiAccess) for optic nerve and retinal AEs associated with semaglutide and tirzepatide, covering the period from their respective approval dates-December 2017 for semaglutide and May 2022 for tirzepatide-through September 2024. In FAERS, all other drugs were compared, while in VigiBase, metformin, empagliflozin, dulaglutide, and insulin served as controls. Disproportionality metrics included reporting odds ratios (RORs) with 95% confidence intervals. RESULTS: Semaglutide and tirzepatide accounted for 76 444 cases (0.59%) in FAERS (n = 12 936 341) and 118 639 cases (0.34%) in VigiBase (n > 35 000 000). Semaglutide showed significantly higher odds of ischemic optic neuropathy (ION) (FAERS: ROR = 11.12, 95% CI = 8.15-15.16; VigiBase: ROR = 68.58, 95% CI = 16.75-280.67), diabetic retinopathy (DR) (FAERS: ROR = 17.28, 95% CI = 13.62-21.91; VigiBase: ROR = 7.81, 95% CI = 5.60-10.90), as well as retinal/vitreous detachment, retinal/vitreous hemorrhage, and retinal tear (FAERS: ROR = 2.44-5.89, 95% CI = 1.70-8.97, all P < .001, IC(025) = 0.49, compared to all other drugs. VigiBase: ROR = 5.49-20.91, 95% CI = 2.71-90.11, all P /= 0.53, compared to metformin). Unique to VigiBase were macular edema (ROR = 3.87, 95% CI = 1.89-7.92), macular hole (ROR = 20.90, 95% CI = 2.65-165.01), and papilledema (ROR = 6.97, 95% CI = 2.53-19.17) (all P /= 0.27, compared to metformin). Sensitivity analyses using empagliflozin and dulaglutide revealed significant associations with ION and DR, while vitreous detachment and hemorrhage were significant when compared to dulaglutide. Additionally, when insulin was used as a comparator, semaglutide showed a higher ROR for ION (ROR = 9.84, 95% CI = 4.25-22.81, P < .0001, IC(025) = 0.42). However, tirzepatide was only significantly associated with DR in FAERS. CONCLUSIONS: Given the widespread use of semaglutide, its association with ocular AEs highlight the need for global pharmacovigilance and post-marketing surveillance. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Lakhani, Moiz AU - Lakhani M AD - From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa, Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Kwan, Angela T H AU - Kwan ATH AD - From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa, Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Mihalache, Andrew AU - Mihalache A AD - Temerty Faculty of Medicine (A.M., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Popovic, Marko M AU - Popovic MM AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Nanji, Keean AU - Nanji K AD - Department of Surgery (K.N., V.C.), Division of Ophthalmology, McMaster University, Hamilton, Ontario, Canada. FAU - Xie, Jim S AU - Xie JS AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Feo, Alessandro AU - Feo A AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA. FAU - Rabinovitch, David AU - Rabinovitch D AD - Faculty of Medicine (D.R.), Tel Aviv University, Tel Aviv, Israel. FAU - Shor, Reut AU - Shor R AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada. FAU - Sadda, SriniVas AU - Sadda S AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Doheny Eye Institute (S.S.), University of California - Los Angeles (UCLA), Pasadena, California, USA. FAU - Sarraf, David AU - Sarraf D AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Stein Eye Institute (D.S.), University of California - Los Angeles (UCLA), Los Angeles, California, USA. FAU - Hurley, Bernard AU - Hurley B AD - The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Margolin, Edward A AU - Margolin EA AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Kertes, Peter J AU - Kertes PJ AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; John and Liz Tory Eye Centre (P.J.K.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. FAU - Chaudhary, Varun AU - Chaudhary V AD - Department of Surgery (K.N., V.C.), Division of Ophthalmology, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods (V.C.), Evidence and Impact, McMaster University, Hamilton, Ontario, Canada. FAU - Muni, Rajeev H AU - Muni RH AD - Temerty Faculty of Medicine (A.M., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Kensington Eye Institute (R.H.M.), Kensington Vision and Research Centre, Toronto, Ontario, Canada. Electronic address: rajeev.muni@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250516 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - Male MH - Female MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Pharmacovigilance MH - *Retinal Diseases/chemically induced/epidemiology MH - Aged MH - Recombinant Fusion Proteins/adverse effects MH - *Optic Nerve Diseases/chemically induced/epidemiology MH - Databases, Factual MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/05/19 00:37 MHDA- 2025/09/08 07:58 CRDT- 2025/05/18 19:36 PHST- 2025/01/25 00:00 [received] PHST- 2025/04/25 00:00 [revised] PHST- 2025/05/08 00:00 [accepted] PHST- 2025/09/08 07:58 [medline] PHST- 2025/05/19 00:37 [pubmed] PHST- 2025/05/18 19:36 [entrez] AID - S0002-9394(25)00239-9 [pii] AID - 10.1016/j.ajo.2025.05.007 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Sep;277:148-168. doi: 10.1016/j.ajo.2025.05.007. Epub 2025 May 16. PMID- 40380806 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250701 IS - 1746-045X (Electronic) IS - 1746-0441 (Linking) VI - 20 IP - 7 DP - 2025 Jul TI - Animal models for development of anti-obesity drugs in the age of GLP-1 agents. PG - 913-925 LID - 10.1080/17460441.2025.2507766 [doi] AB - INTRODUCTION: Obesity is a major health crisis globally, with prevalence escalating significantly in recent decades. Obesity is not merely excessive weight but is associated with myriad health complications. Ensuring the translational effectiveness of pre-clinical obesity models is paramount, and the success of GLP-1 therapies has highlighted important benchmarks for guiding drug development. AREAS COVERED: The authors discuss the status of various animal models used for the development of anti-obesity drugs, with particular emphasis on rodent models and their validity of preclinical-to-clinical translation. They also highlight innovative animal model integration opportunities between obesity and other associated pathology. The article is based on literature searches using PubMed for content (up until February 2025). EXPERT OPINION: The effectiveness of GLP-1 therapies in treating type 2 diabetes and obesity presents an opportunity to evaluate the translational relevance of animal models of obesity. Due to their compelling safety profiles, GLP-1(s) are being tested in a wide range of obesity-associated diseases. Optimization of the mechanistic qualities in this drug class requires the incorporation of new endpoints beyond body weight, including lean mass preservation, cardiovascular health, and anti-inflammatory activities. Finally, we are compelled by the intersection of non-obesity disease models into an obesogenic framework to understand the combinatorial effects of obesity on these other disease indications, including heart failure, neurodegenerative diseases, and cancer. FAU - Culver, Alexander AU - Culver A AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. AD - Monument Biosciences, Indianapolis, IN, USA. FAU - Stayrook, Keith AU - Stayrook K AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. FAU - Comerota, Michele AU - Comerota M AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. FAU - Oblak, Adrian AU - Oblak A AD - Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Burris, Thomas AU - Burris T AD - College of Pharmacy, University of Florida, Gainesville, FL, USA. LA - eng PT - Journal Article PT - Review DEP - 20250521 PL - England TA - Expert Opin Drug Discov JT - Expert opinion on drug discovery JID - 101295755 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - *Obesity/drug therapy/physiopathology MH - Humans MH - *Anti-Obesity Agents/pharmacology/adverse effects MH - Disease Models, Animal MH - *Glucagon-Like Peptide 1/metabolism MH - Drug Development/methods MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - GLP-1 OT - Obesity OT - diabetes OT - drug discovery OT - mounjaro OT - ozempic OT - semaglutide OT - tirzepitide EDAT- 2025/05/17 17:01 MHDA- 2025/07/01 21:13 CRDT- 2025/05/17 04:12 PHST- 2025/07/01 21:13 [medline] PHST- 2025/05/17 17:01 [pubmed] PHST- 2025/05/17 04:12 [entrez] AID - 10.1080/17460441.2025.2507766 [doi] PST - ppublish SO - Expert Opin Drug Discov. 2025 Jul;20(7):913-925. doi: 10.1080/17460441.2025.2507766. Epub 2025 May 21. PMID- 40375735 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - Evaluating prediction of short-term tolerability of five type 2 diabetes drug classes using routine clinical features: UK population-based study. PG - 4320-4329 LID - 10.1111/dom.16470 [doi] AB - AIMS: A precision medicine approach in type 2 diabetes (T2D) needs to consider potential treatment risks alongside established benefits for glycaemic and cardiometabolic outcomes. Considering five major T2D drug classes, we aimed to describe variation in short-term discontinuation (a proxy of overall tolerability) by drug and patient routine clinical features and determine whether combining features in a model to predict drug class-specific tolerability has clinical utility. MATERIALS AND METHODS: UK routine clinical data (Clinical Practice Research Datalink, 2014-2020) of people with T2D initiating glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter-2 inhibitors (SGLT2i), thiazolidinediones (TZD) and sulfonylureas (SU) in primary care were studied. We first described the proportions of short-term (3-month) discontinuation by drug class across subgroups stratified by routine clinical features. We then assessed the performance of combining features to predict discontinuation by drug class using a flexible machine learning algorithm (a Bayesian Additive Regression Tree). RESULTS: Amongst 182 194 treatment initiations, discontinuation varied modestly by clinical features. Higher discontinuation on SGLT2i and GLP-1RA was seen for older patients and those with longer diabetes duration. For most other features, discontinuation differences were similar by drug class, with higher discontinuation for patients who had previously discontinued metformin, females and people of South-Asian and Black ethnicities. Lower discontinuation was seen for patients currently taking statins and blood pressure medication. The model combining all sociodemographic and clinical features had a low ability to predict discontinuation (AUC = 0.61). CONCLUSIONS: A model-based approach to predict drug-specific discontinuation for individual patients with T2D has low clinical utility. Instead of likely tolerability, prescribing decisions in T2D should focus on drug-specific side-effect risks and differences in the glycaemic and cardiometabolic benefits of available medication classes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Cardoso, Pedro AU - Cardoso P AUID- ORCID: 0000-0002-1014-9058 AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Young, Katie G AU - Young KG AUID- ORCID: 0000-0003-2570-3864 AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Hopkins, Rhian AU - Hopkins R AUID- ORCID: 0000-0001-6054-3582 AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Mateen, Bilal A AU - Mateen BA AUID- ORCID: 0000-0003-4423-6472 AD - Institute of Health Informatics, University College London, London, UK. FAU - Pearson, Ewan R AU - Pearson ER AUID- ORCID: 0000-0001-9237-8585 AD - Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. FAU - Hattersley, Andrew T AU - Hattersley AT AUID- ORCID: 0000-0001-5620-473X AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - McKinley, Trevelyan J AU - McKinley TJ AUID- ORCID: 0000-0002-9485-3236 AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Shields, Beverley M AU - Shields BM AUID- ORCID: 0000-0003-3785-327X AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Dennis, John M AU - Dennis JM AUID- ORCID: 0000-0002-7171-732X AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. CN - MASTERMIND consortium LA - eng GR - NIHR Exeter Clinical Research Facility/ GR - WT_/Wellcome Trust/United Kingdom GR - National Institute for Health and Care Research Exeter Biomedical Research Centre/ GR - 227 070/Z/23/Z/Wellcome Trust Early Career award/ GR - MR/N00633X/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20250516 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects/classification MH - Male MH - United Kingdom/epidemiology MH - Middle Aged MH - Aged MH - Sulfonylurea Compounds/therapeutic use/adverse effects MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Precision Medicine MH - Adult PMC - PMC12232322 OTO - NOTNLM OT - DPP4i OT - GLP-1RA OT - SGLT2i OT - SU OT - TZD OT - anti-hyperglycaemic treatment OT - clinical care OT - drug tolerability OT - precision medicine OT - treatment effect heterogeneity COIS- The authors declare no conflicts of interest. FIR - Hattersley, Andrew IR - Hattersley A FIR - Pearson, Ewan IR - Pearson E FIR - Jones, Angus IR - Jones A FIR - Shields, Beverley IR - Shields B FIR - Dennis, John IR - Dennis J FIR - Rodgers, Lauren IR - Rodgers L FIR - Henley, William IR - Henley W FIR - McDonald, Timothy IR - McDonald T FIR - Weedon, Michael IR - Weedon M FIR - Britten, Nicky IR - Britten N FIR - Angwin, Catherine IR - Angwin C FIR - Sattar, Naveed IR - Sattar N FIR - Lindsay, Robert IR - Lindsay R FIR - Jennison, Christopher IR - Jennison C FIR - Walker, Mark IR - Walker M FIR - Cruickshank, Kennedy IR - Cruickshank K FIR - Janmohamed, Salim IR - Janmohamed S FIR - Hyde, Christopher IR - Hyde C FIR - Holman, Rury IR - Holman R FIR - Farmer, Andrew IR - Farmer A FIR - Gray, Alastair IR - Gray A FIR - Gough, Stephen IR - Gough S FIR - Agbaje, Olorunsola IR - Agbaje O FIR - McKinley, Trevelyan IR - McKinley T FIR - Vollmer, Sebastian IR - Vollmer S FIR - Mateen, Bilal IR - Mateen B FIR - Hamilton, Prof William IR - Hamilton PW FIR - Young, Katie G IR - Young KG FIR - Cardoso, Pedro IR - Cardoso P FIR - Gudemann, Laura IR - Gudemann L EDAT- 2025/05/16 11:46 MHDA- 2025/07/04 12:43 PMCR- 2025/07/07 CRDT- 2025/05/16 03:23 PHST- 2025/04/23 00:00 [revised] PHST- 2025/03/11 00:00 [received] PHST- 2025/05/03 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/16 11:46 [pubmed] PHST- 2025/05/16 03:23 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - DOM16470 [pii] AID - 10.1111/dom.16470 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4320-4329. doi: 10.1111/dom.16470. Epub 2025 May 16. PMID- 40367988 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20250612 IS - 2233-6087 (Electronic) IS - 2233-6079 (Print) IS - 2233-6079 (Linking) VI - 49 IP - 3 DP - 2025 May TI - SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application. PG - 386-402 LID - 10.4093/dmj.2025.0220 [doi] AB - Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and significantly increases cardiovascular risk and mortality. Despite conventional therapies, including renin-angiotensin-aldosterone system inhibitors, substantial residual risk remains. The emergence of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has reshaped DKD management. Beyond glycemic control, these agents provide distinct and complementary cardiorenal benefits through mechanisms such as hemodynamic modulation, anti-inflammatory effects, and metabolic adaptations. Landmark trials, including CREDENCE, DAPA-CKD, EMPA-KIDNEY, and FLOW, have demonstrated their efficacy in preserving kidney function and reducing adverse outcomes. SGLT2 inhibitors appear more effective in mitigating glomerular hyperfiltration and lowering heart failure risk, whereas GLP-1 receptor agonists are particularly beneficial in reducing albuminuria and atherosclerotic cardiovascular events. Although indirect comparisons suggest that SGLT2 inhibitors may offer greater protection against kidney function decline, direct head-to-head trials are lacking. Combination therapy holds promise, however further studies are needed to define optimal treatment strategies. This review synthesizes current evidence, evaluates comparative effectiveness, and outlines future directions in DKD management, emphasizing precision medicine approaches to enhance clinical outcomes. The integration of these therapies represents a paradigm shift in diabetes care, expanding treatment options for people with diabetes mellitus at risk of kidney failure. FAU - Bae, Jae Hyun AU - Bae JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Review DEP - 20250501 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetic Nephropathies/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12086580 OTO - NOTNLM OT - Diabetes mellitus OT - Diabetic nephropathies OT - Glucagon-like peptide-1 receptor agonists OT - Renal insufficiency, chronic OT - Sodium-glucose transporter 2 inhibitors COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2025/05/15 00:36 MHDA- 2025/05/15 06:33 PMCR- 2025/05/01 CRDT- 2025/05/14 19:29 PHST- 2025/03/18 00:00 [received] PHST- 2025/04/23 00:00 [accepted] PHST- 2025/05/15 06:33 [medline] PHST- 2025/05/15 00:36 [pubmed] PHST- 2025/05/14 19:29 [entrez] PHST- 2025/05/01 00:00 [pmc-release] AID - dmj.2025.0220 [pii] AID - dmj-2025-0220 [pii] AID - 10.4093/dmj.2025.0220 [doi] PST - ppublish SO - Diabetes Metab J. 2025 May;49(3):386-402. doi: 10.4093/dmj.2025.0220. Epub 2025 May 1. PMID- 40366681 OWN - NLM STAT- MEDLINE DCOM- 20250702 LR - 20260515 IS - 2168-6238 (Electronic) IS - 2168-622X (Print) IS - 2168-622X (Linking) VI - 82 IP - 7 DP - 2025 Jul 1 TI - Glucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis. PG - 643-653 LID - 10.1001/jamapsychiatry.2025.0679 [doi] AB - IMPORTANCE: People with obesity and diabetes have poorer psychiatric and cognitive outcomes and lower quality of life (QOL) compared with those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity that may also influence psychiatric outcomes. OBJECTIVE: To conduct a meta-analysis of randomized placebo-controlled trials to evaluate psychiatric, cognitive, and QOL outcomes with GLP1-RA treatment. DATA SOURCES: MEDLINE, Embase, PsycINFO, and CENTRAL databases were searched from inception through June 24, 2024. STUDY SELECTION: Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with overweight/obesity and/or diabetes, reporting on psychiatric, cognition, or QOL outcomes, were included. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed in parallel by 2 reviewers. Random-effects meta-analysis was performed. Effect size measures were log risk ratios (log[RR]) and standardized mean differences (Hedges g). The quality of studies was appraised using the Cochrane risk-of-bias tool (RoB2). Certainty of evidence was assessed via GRADEpro. MAIN OUTCOMES AND MEASURES: Main outcomes were risk of psychiatric adverse events (serious and nonserious) and change in mental health symptom severity, health-related quality of life, and cognition. RESULTS: Eighty randomized clinical trials involving 107 860 patients were included in the meta-analysis. The mean (SD) age of participants across studies in the meta-analysis was 60.1 (7.1) years; 43 251 were female (40.1%) and 64 608 male (59.9%). GLP1-RA treatment was not associated with a significant difference in risk of serious psychiatric adverse events (log[RR] = -0.02; 95% CI, -0.20 to 0.17; P = .87) and nonserious psychiatric adverse events (log[RR] = -0.03; 95% CI, -0.21 to 0.16], P = .76), or depressive symptom change (g = 0.02; 95% CI, -0.51 to 0.55; P = .94), compared with placebo. GLP1-RA treatment was associated with improvements in restrained eating (g = 0.35; 95% CI, 0.13 to 0.57; P = .002) and emotional eating behavior (g = 0.32; 95% CI, 0.11 to 0.54; P = .003) and in mental health-related QOL (g = 0.15; 95% CI, 0.07 to 0.22; P < .001), physical health-related QOL (g = 0.20; 95% CI, 0.14 to 0.26; P < .001), diabetes-related QOL (g = 0.23; 95% CI, 0.15 to 0.32; P < .001), and weight-related QOL (g = 0.27; 95% CI, 0.18 to 0.35; P < .001) compared with placebo. CONCLUSIONS AND RELEVANCE: In patients with overweight/obesity and/or diabetes , GLP1-RA treatment is not associated with increased risk of psychiatric adverse events or worsening depressive symptoms relative to placebo and is associated with improvements in QOL, restrained eating, and emotional eating behavior. These findings provide reassurance regarding the psychiatric safety profile of GLP1-RAs and suggest that GLP1-RA treatment contributes to both physical and emotional well-being. FAU - Pierret, Aureliane C S AU - Pierret ACS AD - Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - Section of Endocrinology and Investigative Medicine, Imperial College London, London, United Kingdom. FAU - Mizuno, Yuya AU - Mizuno Y AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - South London and Maudsley NHS Foundation Trust, London, United Kingdom. AD - Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. FAU - Saunders, Pippa AU - Saunders P AD - Imperial College School of Medicine, London, United Kingdom. FAU - Lim, Eshaya AU - Lim E AD - Imperial College School of Medicine, London, United Kingdom. FAU - De Giorgi, Riccardo AU - De Giorgi R AD - Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom. AD - Oxford Health NHS Foundation Trust, Oxford, United Kingdom. FAU - Howes, Oliver D AU - Howes OD AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom. FAU - McCutcheon, Robert A AU - McCutcheon RA AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom. AD - Oxford Health NHS Foundation Trust, Oxford, United Kingdom. FAU - McGowan, Barbara AU - McGowan B AD - Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. AD - Diabetes, Endocrinology and Obesity Clinical Academic Group, King's Health Partners, London, United Kingdom. FAU - Sen Gupta, Piya AU - Sen Gupta P AD - Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. AD - Diabetes, Endocrinology and Obesity Clinical Academic Group, King's Health Partners, London, United Kingdom. FAU - Smith, Daniel AU - Smith D AD - Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. AD - Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom. FAU - Ismail, Khalida AU - Ismail K AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - Diabetes, Endocrinology and Obesity Clinical Academic Group, King's Health Partners, London, United Kingdom. FAU - Pillinger, Toby AU - Pillinger T AD - Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. AD - Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom. AD - Diabetes, Endocrinology and Obesity Clinical Academic Group, King's Health Partners, London, United Kingdom. AD - South London and Maudsley NHS Foundation Trust, London, United Kingdom. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - JAMA Psychiatry JT - JAMA psychiatry JID - 101589550 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Quality of Life MH - *Obesity/drug therapy/psychology MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/psychology PMC - PMC12079569 COIS- Conflict of Interest Disclosures: Dr Mizuno reported fellowship grants from Canon Foundation in Europe, consultant fees from WCG Clinical and Signant Health, and manuscript fees from Sumitomo Dainippon Pharma outside the submitted work. Dr Howes reported investigator-initiated research funding from and/or participated in advisory or speaker meetings organized by AbbVie, Alkermes, Angelini, Autifony, Biogen, Boehringer Ingelheim, Delix, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Janssen, Karuna, Lundbeck (where he was previously a part-time employee), Merck, Neumora, Neurocrine, Ontrack/Pangea, Otsuka, Sunovion, Teva, Recordati, Roche, ROVI Biotech, Viatris, and Mylan. Dr McCutcheon reported speaker/consultancy fees from Boehringer Ingelheim, Janssen, Karuna, Lundbeck, Newron, Otsuka, and Viatris and co-directing a company that designs digital resources to support treatment of mental ill health. Dr McGowan reported being a shareholder of Reset Health, receiving research grants from Novo Nordisk, and having received consultant fees for educational/advisory meetings from Novo Nordisk, Lilly, AstraZeneca, Janssen outside the submitted work. Dr Sen Gupta reported speaker fees/educational meeting support from Novo Nordisk outside the submitted work. Dr Ismail reported book royalties from Oxford University Press and her salary being funded in part by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC). Dr Pillinger reported receiving speaker/consultancy fees from Boehringer Ingelheim, Recordati, Lundbeck, Otsuka, Janssen, CNX Therapeutics, Sunovion, ROVI Biotech, Schwabe Pharma, and Lecturing Minds Stockholm AB; receiving book royalties from Wiley Blackwell; and co-directing a company that designs digital resources to support treatment of mental illness outside the submitted work. No other disclosures were reported. EDAT- 2025/05/14 12:40 MHDA- 2025/07/02 12:31 PMCR- 2026/05/14 CRDT- 2025/05/14 11:33 PHST- 2025/07/02 12:31 [medline] PHST- 2025/05/14 12:40 [pubmed] PHST- 2025/05/14 11:33 [entrez] PHST- 2026/05/14 00:00 [pmc-release] AID - 2833558 [pii] AID - yoi250018 [pii] AID - 10.1001/jamapsychiatry.2025.0679 [doi] PST - ppublish SO - JAMA Psychiatry. 2025 Jul 1;82(7):643-653. doi: 10.1001/jamapsychiatry.2025.0679. PMID- 40366278 OWN - NLM STAT- MEDLINE DCOM- 20250514 LR - 20250529 IS - 2639-8028 (Electronic) IS - 2639-8028 (Linking) VI - 7 IP - 5 DP - 2025 May 1 TI - Impact of Glucagon-Like Peptide-1 Receptor Agonist Exposure on Gastrointestinal Outcomes Among ICU Patients: A Multicenter Matched Cohort Study. PG - e1263 LID - 10.1097/CCE.0000000000001263 [doi] LID - e1263 AB - IMPORTANCE: Patients admitted to the ICU often experience gastrointestinal complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become increasingly prevalent in the treatment of type 2 diabetes mellitus and obesity, and there is evidence that their use may be associated with an increased risk of clinically significant gastrointestinal events. However, their impact on critically ill patients admitted to the medical ICU is unknown. OBJECTIVES: This study examined whether pre-ICU use of GLP-1RAs was associated with increased incidence of gastrointestinal complications and hospitalization outcomes. DESIGN, SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of critically ill patients admitted to academic and community hospitals of Mayo Clinic Health System from January 1, 2018, to December 31, 2023. Patients who were admitted to surgical ICUs and those who were exposed to GLP-1RA medications before but did not have an active prescription within 30 days of admission were excluded. Patients exposed to GLP-1RA were matched with those nonexposed in a 1:1 fashion based on demographic factors, factors affecting gastrointestinal motility, overall illness burden, and clinical acuity. MAIN OUTCOMES AND MEASURES: Outcomes of interest were the development of gastrointestinal dysfunction, ICU- and hospital-free days, and mortality. RESULTS: A total of 31,327 patients with diabetes or obesity were identified of whom these, 631 were exposed to GLP-1RA before admission. In the matched cohort of 1262 patients, baseline variables were evenly distributed between the two groups. There were no significant differences in the odds of developing nausea/vomiting, constipation, ileus, obstruction, impaction, or aspiration pneumonia between the GLP-1RA exposed and unexposed groups. Similarly, ICU and hospital mortality rates were comparable across the two groups. However, GLP-1RA exposed patients had significantly more hospital-free days compared with unexposed patients (estimate, 1.19; 95% CI, 0.38-2.0; p = 0.004). CONCLUSIONS AND RELEVANCE: GLP-1RA exposure was not associated with increased odds of clinically significant gastrointestinal complications in nonsurgical critically ill patients. Increased hospital-free days observed among GLP-1RA exposed patients requires further study. CI - Copyright (c) 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine. FAU - Gmehlin, Cameron G AU - Gmehlin CG AUID- ORCID: 0000-0003-0750-4781 AD - Department of Internal Medicine, Mayo Clinic, Rochester, MN. FAU - Nemet, Marko AU - Nemet M AD - Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. FAU - Rizwan, Zeeshan M AU - Rizwan ZM AD - Department of Pharmacy, Mayo Clinic, Rochester, MN. FAU - Ahmad, Sumera AU - Ahmad S AD - Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. FAU - Gajic, Ognjen AU - Gajic O AD - Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. FAU - Tekin, Aysun AU - Tekin A AD - Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250514 PL - United States TA - Crit Care Explor JT - Critical care explorations JID - 101746347 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Intensive Care Units/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastrointestinal Diseases/epidemiology/chemically induced MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Critical Illness/therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Cohort Studies PMC - PMC12080681 OTO - NOTNLM OT - critical care OT - gastrointestinal motility OT - gastrointestinal tract OT - gastrointestinal transit OT - glucagon-like peptide-1 receptor agonist COIS- The authors have disclosed that they do not have any potential conflicts of interest. EDAT- 2025/05/14 12:39 MHDA- 2025/05/14 12:40 PMCR- 2025/05/14 CRDT- 2025/05/14 10:13 PHST- 2025/05/14 12:40 [medline] PHST- 2025/05/14 12:39 [pubmed] PHST- 2025/05/14 10:13 [entrez] PHST- 2025/05/14 00:00 [pmc-release] AID - 02107256-202505000-00010 [pii] AID - CCE-D-25-00048 [pii] AID - 10.1097/CCE.0000000000001263 [doi] PST - epublish SO - Crit Care Explor. 2025 May 14;7(5):e1263. doi: 10.1097/CCE.0000000000001263. eCollection 2025 May 1. PMID- 40365883 OWN - NLM STAT- MEDLINE DCOM- 20250908 LR - 20260504 IS - 1897-4279 (Electronic) IS - 0022-9032 (Linking) VI - 83 IP - 7-8 DP - 2025 TI - SGLT2 inhibitors, GLP-1 receptor agonists, and their combination in diabetic cardiomyopathy: A prospective cohort study. PG - 814-822 LID - 10.33963/v.phj.106152 [doi] AB - BACKGROUND: The prevalence of diabetic cardiomyopathy (DiabCM) is increasing in parallel with diabetes mellitus, with no consensus on targeted treatment. AIMS: This study aims to investigate the cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) alone and combination on symptomatic DiabCM participants. MATERIAL AND METHODS: This was a single-center prospective cohort study focusing on patients with symptomatic DiabCM. The study comprised 587 participants: 154 in the SGLT2is group, 105 in the GLP-1RAs group, 93 in the SGLT2is combined with GLP-1RAs group (SGLT2is + GLP-1RAs), and 235 in the control group (without SGLT2is or GLP-1RAs). All participants were followed for 36 months. The primary outcome was a composite of all-cause death and hospitalization for heart failure. RESULTS: The incidence of endpoint event was lowest in the SGLT2is + GLP-1RAs group (23.7%), followed by the SGLT2is group (32.5%), GLP-1RAs group (39.0%), and control group (53.6%). Multivariable Cox regression analysis showed that SGLT2is (P <0.001), GLP-1RAs (P = 0.02) or SGLT2is + GLP-1RAs prescription (P <0.001) were independent protective factors for the occurrence of primary outcome. In subgroup analysis, SGLT2is or SGLT2is + GLP-1RAs treatment remained the independent factors for freedom from primary outcome in both heart failure with reduced ejection fraction + heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction patients. However, GLP-1RAs alone did not exert clinical benefits in subgroup analysis. CONCLUSIONS: SGLT2is and GLP-1RAs might reduce the incidence of all-cause mortality and heart failure hospitalization in patients with symptomatic DiabCM, and the combination of these two agents may further improve clinical outcomes. FAU - Zhang, Alian AU - Zhang A AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Yu, Jianying AU - Yu J AD - Shanghai Putuo Mental Health Center, Shanghai, China. FAU - Ke, Jiahan AU - Ke J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Yin, Ping AU - Yin P AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Zhang, Junfeng AU - Zhang J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Wang, Changqian AU - Wang C AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Tang, Zhengde AU - Tang Z AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. FAU - Gu, Jun AU - Gu J AD - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. gjforsub@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250514 PL - Poland TA - Kardiol Pol JT - Kardiologia polska JID - 0376352 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Prospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Diabetic Cardiomyopathies/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination OTO - NOTNLM OT - diabetic cardiomyopathy (DiabCM) OT - glucagon-like peptide-1 receptor agonists (GLP-1RAs) OT - heart failure OT - sodium-glucose cotransporter-2 inhibitors (SGLT2is) EDAT- 2025/05/14 12:39 MHDA- 2025/09/08 12:43 CRDT- 2025/05/14 06:53 PHST- 2025/05/07 00:00 [received] PHST- 2025/05/07 00:00 [accepted] PHST- 2025/09/08 12:43 [medline] PHST- 2025/05/14 12:39 [pubmed] PHST- 2025/05/14 06:53 [entrez] AID - VM/OJS/J/106152 [pii] AID - 10.33963/v.phj.106152 [doi] PST - ppublish SO - Kardiol Pol. 2025;83(7-8):814-822. doi: 10.33963/v.phj.106152. Epub 2025 May 14. PMID- 40364515 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260821 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - Glucagon-like peptide-1 receptor agonists and alcohol use disorders: An emerging unexpected beneficial effect. PG - 4083-4091 LID - 10.1111/dom.16453 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of people living with type 2 diabetes mellitus (T2DM) and/or obesity. Numerous concordant animal and human studies suggest that GLP-1RAs could reduce the risk of addiction, especially alcohol use disorders (AUD). This comprehensive review aims at summarising the known effects of GLP-1RAs on AUD. An extensive literature search detected clinical (either observational or controlled) studies that investigated the prevalence and severity of AUD in obese/T2DM patients treated with GLP-1RAs compared with a control group. In seven observational cohort studies (12 paired data for comparisons), the prevalence of AUD was reduced by 35% (hazard ratio 0.65; 95% confidence interval 0.56-0.74) with GLP-1RA therapy when compared to no-GLP-1 therapy. The protection by GLP-1RAs concerned both incidence and recurrence of AUD. These positive human findings confirm preclinical data in rodents and monkeys. Some genetic, experimental and functional neuroimaging human studies also supported a potential role of the GLP-1 system in the alcohol-related reward process. Only two randomised controlled trials are available yet with inconclusive results, but several are ongoing to confirm the protective effect of semaglutide on AUD. Different neuronal and psychological mechanisms involving the reward pathways are proposed to explain the favourable findings reported with GLP-1RAs. In conclusion, available data from observational cohort studies showed a concordant and significantly reduced risk of AUD and alcohol consumption habits with GLP-1RA therapy. However, further studies are required before considering any indication of GLP-1RAs for the prevention or management of AUD. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Scheen, Andre J AU - Scheen AJ AUID- ORCID: 0000-0001-9743-4371 AD - Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium. AD - Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. LA - eng PT - Journal Article PT - Review DEP - 20250513 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Animals MH - *Obesity/drug therapy/complications MH - *Alcoholism/prevention & control/epidemiology/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Observational Studies as Topic OTO - NOTNLM OT - GLP-1 receptor agonist OT - Semaglutide OT - addiction OT - alcohol OT - alcohol use disorder OT - obesity EDAT- 2025/05/14 11:42 MHDA- 2025/07/04 12:43 CRDT- 2025/05/14 01:33 PHST- 2025/04/29 00:00 [revised] PHST- 2025/03/03 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/14 11:42 [pubmed] PHST- 2025/05/14 01:33 [entrez] AID - 10.1111/dom.16453 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4083-4091. doi: 10.1111/dom.16453. Epub 2025 May 13. PMID- 40359784 OWN - NLM STAT- MEDLINE DCOM- 20250601 LR - 20260907 IS - 1872-7603 (Electronic) IS - 0165-0378 (Linking) VI - 169 DP - 2025 Jun TI - Immunological effects of GLP-1 analogs on female reproduction: Therapeutic perspectives for infertility and recurrent pregnancy loss. PG - 104538 LID - S0165-0378(25)00116-0 [pii] LID - 10.1016/j.jri.2025.104538 [doi] AB - This review evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating obesity-related infertility and recurrent pregnancy loss (RPL). Originally developed for managing type 2 diabetes mellitus (T2DM) and obesity, GLP-1RAs demonstrate potential in improving reproductive outcomes through their metabolic, vascular, and immunological effects. Obesity, a significant contributor to infertility and RPL, disrupts endocrine balance, promotes chronic inflammation, and impairs endometrial receptivity. GLP-1RAs alleviate these challenges by facilitating substantial weight loss, enhancing insulin sensitivity, and modulating immune responses. Research suggests that the immunological benefits of GLP-1RAs extend beyond their weight-loss effects. Key mechanisms associated with their impact on reproductive outcomes include macrophage polarization toward an anti-inflammatory phenotype, suppression of pro-inflammatory cytokine production, and restoration of maternal-fetal immune tolerance through increased regulatory T-cell activity. Emerging evidence highlights their role in enhancing vascularization and reducing oxidative stress at the maternal-fetal interface, critical processes for implantation and placental development. Despite these promising benefits, the use of GLP-1RAs during pregnancy remains contraindicated due to safety concerns. While they show promise in preconception protocols, further clinical trials are needed to establish their efficacy and safety in reproductive health. This review underscores the potential of GLP-1RAs as a multidimensional approach to managing infertility and RPL, particularly in obese women, and advocates for their integration into personalized therapeutic strategies to optimize reproductive outcomes. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Tavares, Ana Clara Muniz AU - Tavares ACM AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - Martins, Maria Yzadora Moura AU - Martins MYM AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - de Souza, Giselle Ferreira AU - de Souza GF AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - Lima, Eduarda Maia AU - Lima EM AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - Rocha, Camila Alves AU - Rocha CA AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - de Souza, Larissa Cruz AU - de Souza LC AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - Simoes, Julia Machado Luz AU - Simoes JML AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - de Araujo, Nicole Oliveira AU - de Araujo NO AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil. FAU - Cavalcante, Marcelo Borges AU - Cavalcante MB AD - Medical Course, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil; Graduate Program in Medical Sciences, Universidade de Fortaleza (UNIFOR), Fortaleza, CE 60.811-905, Brazil; CONCEPTUS - Reproductive Medicine, Fortaleza, CE 60.170-240, Brazil. Electronic address: marcelocavalcante.med@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20250508 PL - Ireland TA - J Reprod Immunol JT - Journal of reproductive immunology JID - 8001906 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Pregnancy MH - *Abortion, Habitual/immunology/drug therapy MH - *Obesity/immunology/drug therapy/complications MH - *Infertility, Female/drug therapy/immunology MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Reproduction/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/immunology OTO - NOTNLM OT - GLP-1 Analogs OT - Glucagon-like peptide-1 receptor agonists OT - Infertility OT - Obesity OT - Recurrent pregnancy loss OT - Reproductive immunology COIS- Declaration of Competing Interest The authors declare that there is no conflict of interest. EDAT- 2025/05/14 11:40 MHDA- 2025/06/04 22:06 CRDT- 2025/05/13 18:08 PHST- 2025/01/02 00:00 [received] PHST- 2025/03/16 00:00 [revised] PHST- 2025/05/05 00:00 [accepted] PHST- 2025/06/04 22:06 [medline] PHST- 2025/05/14 11:40 [pubmed] PHST- 2025/05/13 18:08 [entrez] AID - S0165-0378(25)00116-0 [pii] AID - 10.1016/j.jri.2025.104538 [doi] PST - ppublish SO - J Reprod Immunol. 2025 Jun;169:104538. doi: 10.1016/j.jri.2025.104538. Epub 2025 May 8. PMID- 40359555 OWN - NLM STAT- MEDLINE DCOM- 20250612 LR - 20250721 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 111 IP - 6 DP - 2025 Jun 1 TI - Glucagon-like-peptide-1 (GLP-1) receptor agonist use and the risk of pulmonary aspiration in patients undergoing surgery. PG - 4090-4093 LID - 10.1097/JS9.0000000000002425 [doi] AB - Glucagon-like-peptide-1 (GLP-1) receptor agonists are approved for the treatment of type II diabetes mellitus and obesity. These agents slow gastric emptying and may increase the risk of pulmonary aspiration, particularly in patients undergoing elective surgery. We used a claims database to examine the association between perioperative GLP-1 receptor agonist use and the risk of pulmonary aspiration. A total of 392 065 patients including 15 745 (4.0%) who used GLP-1 receptor agonist who underwent elective surgery were identified. The rate of pulmonary aspiration was 0.8% in those who received GLP-1 receptor agonists versus 0.7% in those who had not ( P = 0.61). After adjusting for other risk factors for aspiration, there was no association between GLP-1 agonist use and aspiration (OR = 1.07; 95% CI, 0.85-1.34). CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Wright, Jason D AU - Wright JD AUID- ORCID: 0000-0001-6390-825 AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York State, USA. AD - Herbert Irving Comprehensive Cancer Center, New York, New York State, USA. AD - New York-Presbyterian Hospital, New York, New York State, USA. FAU - Chen, Ling AU - Chen L AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York State, USA. FAU - Xu, Xiao AU - Xu X AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York State, USA. AD - Herbert Irving Comprehensive Cancer Center, New York, New York State, USA. FAU - Hur, Chin AU - Hur C AD - Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York State, USA. FAU - Matsuo, Koji AU - Matsuo K AD - Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California. FAU - Elkin, Elena B AU - Elkin EB AD - Herbert Irving Comprehensive Cancer Center, New York, New York State, USA. AD - Joseph L. Mailman School of Public Health, Columbia University, New York, New York, USA. FAU - Hershman, Dawn L AU - Hershman DL AD - Herbert Irving Comprehensive Cancer Center, New York, New York State, USA. AD - New York-Presbyterian Hospital, New York, New York State, USA. AD - Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York State, USA. AD - Joseph L. Mailman School of Public Health, Columbia University, New York, New York, USA. LA - eng GR - U01 CA265739/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20250512 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Elective Surgical Procedures/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Respiratory Aspiration/epidemiology/chemically induced MH - Retrospective Studies MH - Adult MH - *Postoperative Complications/epidemiology/chemically induced PMC - PMC12165584 OTO - NOTNLM OT - GLP-1 receptor agonist OT - aspiration OT - surgery COIS- Dr Wright has received royalties from UpToDate, honoraria from the American College of Obstetricians and Gynecologists, and research support from Merck. Dr. Xu has received honoraria from the American Association of Gynecologic Laparoscopists. Dr. Elkin has received research support from Pfizer. The other authors have no conflicts of interest. EDAT- 2025/05/13 18:41 MHDA- 2025/06/12 18:26 PMCR- 2025/06/13 CRDT- 2025/05/13 17:22 PHST- 2025/04/11 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/06/12 18:26 [medline] PHST- 2025/05/13 18:41 [pubmed] PHST- 2025/05/13 17:22 [entrez] PHST- 2025/06/13 00:00 [pmc-release] AID - 01279778-990000000-02297 [pii] AID - IJS-D-25-01780 [pii] AID - 10.1097/JS9.0000000000002425 [doi] PST - ppublish SO - Int J Surg. 2025 Jun 1;111(6):4090-4093. doi: 10.1097/JS9.0000000000002425. Epub 2025 May 12. PMID- 40359159 OWN - NLM STAT- MEDLINE DCOM- 20250929 LR - 20251025 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 40 IP - 10 DP - 2025 Sep 29 TI - How to individualize renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA. PG - 1977-1988 LID - 10.1093/ndt/gfaf069 [doi] AB - The interrelated pandemics of obesity and type 2 diabetes mellitus (T2DM) are fuelling an increase in the prevalence of chronic kidney disease (CKD), which amplifies the risk of cardiovascular events and may progress to end-stage kidney disease (ESKD). Treatment options for such patients have rapidly expanded over the past decade and continue to evolve. Herein, we primarily focus on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their role in the management of CKD in the setting of overweight/obesity and T2DM. Recommendations from the recent Kidney Disease: Improving Global Outcomes CKD guidelines are summarized and new evidence arising since publication of these guidelines is highlighted. We review clinical studies supporting the role of GLP-1RAs in patients with diabesity and CKD, including the FLOW trial, as well as exploring potential mechanisms of their nephroprotective effects. Their role in the management of patients with ESKD on maintenance dialysis and after kidney transplantation, while less evidence-based, is also discussed. The potential for other gut hormone-based therapies, including GLP-1/glucose-dependent insulinotropic polypeptide dual agonists (tirzepatide), triple agonists (incorporating glucagon agonism) and amylin analogues to improve cardiovascular and kidney outcomes in patients with CKD, is explored. We highlight the role of novel therapies distinct from the gut-kidney axis, including non-steroidal mineralocorticoid receptor antagonists (nsMRAs). We outline the potential for multitarget therapy incorporating renin-angiotensin-aldosterone system inhibitors, sodium-glucose co-transporter-2 inhibitors, incretin-based treatments and nsMRAs to improve cardiovascular and kidney outcomes in patients with overweight/obesity and T2DM. Current unknowns in the timing and sequence of multitarget therapy in patients with CKD are emphasized. Priority research questions for the future are highlighted throughout the review. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Morales, Enrique AU - Morales E AUID- ORCID: 0000-0002-5824-6973 AD - Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain. AD - Research Institute of University Hospital 12 de Octubre (imas12), Department of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Martin, William P AU - Martin WP AD - Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. FAU - Bevc, Sebastjan AU - Bevc S AD - Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia. AD - Medical Faculty, University of Maribor, Maribor, Slovenia. FAU - Jenssen, Trond G AU - Jenssen TG AD - Department of Transplantation Medicine, Section of Nephrology, Oslo University Hospital Rikshospitalet, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Miglinas, Marius AU - Miglinas M AD - Center of Nephrology, Santaros Klinikos, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. FAU - Trillini, Matias AU - Trillini M AD - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy. LA - eng GR - European Renal Association/ PT - Journal Article PT - Review PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/complications MH - *Renal Insufficiency, Chronic/prevention & control/etiology/complications/drug therapy MH - *Diabetes Mellitus, Type 2/complications MH - *Precision Medicine MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Prognosis MH - Diabesity PMC - PMC12548029 OTO - NOTNLM OT - CKD OT - incretin OT - obesity OT - renoprotective OT - type 2 diabetes COIS- T.G.J. has received speaker fees from Lilly and Novo Nordisk. The remaining authors declare no conflicts of interest. EDAT- 2025/05/13 18:39 MHDA- 2025/09/29 13:20 PMCR- 2025/05/13 CRDT- 2025/05/13 13:13 PHST- 2025/01/13 00:00 [received] PHST- 2025/09/29 13:20 [medline] PHST- 2025/05/13 18:39 [pubmed] PHST- 2025/05/13 13:13 [entrez] PHST- 2025/05/13 00:00 [pmc-release] AID - 8129710 [pii] AID - gfaf069 [pii] AID - 10.1093/ndt/gfaf069 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2025 Sep 29;40(10):1977-1988. doi: 10.1093/ndt/gfaf069. PMID- 40358690 OWN - NLM STAT- MEDLINE DCOM- 20260810 LR - 20261008 IS - 1861-0692 (Electronic) IS - 1861-0684 (Linking) VI - 115 IP - 9 DP - 2026 Sep TI - Impact of glp-1 receptor agonists on hospitalization for heart failure and all-cause death in patients with diabetes with and without heart failure: a real-world study. PG - 1512-1521 LID - 10.1007/s00392-025-02674-9 [doi] AB - OBJECTIVE: Evidence on the impact of GLP-1 RAs on HF hospitalization (HHF) and mortality has been inconsistent across clinical trials in patients with diabetes. We investigated the association between GLP-1 RAs and these outcomes in a real-world setting. METHODS: We selected individuals aged 45 years and older already treated with metformin living in Lombardy, Italy, and then split them into two groups if they initiated GLP-1 RAs or other antidiabetic drugs, between 2019 and 2021. A multivariable Cox proportional hazard regression model was performed to assess the association of GLP-1 RAs on HHF and all-cause death as hazard ratios (HRs) with 95% CI compared to the Other ADs group, stratifying by history of HF. The role of GLP-1 RAs was also investigated using the Inverse Probability Treatment Weighting (IPTW) and in the subgroup analyses. RESULTS: In total, 9795 patients in the GLP-1 RAs group (302 with HF; 9493 without) and 6018 in the Other ADs group (405 with HF; 5613 without) were included in the analysis. GLP-1 RAs use was significantly associated with a lower risk of HHF in patients with a history of HF (HR 0.65; CI 95% 0.426-0.987) and in those without (HR 0.52; CI 95% 0.371-0.733). A lower risk for all-cause death was also observed in GLP-1 RAs users (with HF: HR 0.45; CI 95% 0.320-0.638; without HF: HR 0.44; CI 95% 0.383-0.514). The results of the IPTW and subgroup analyses confirmed those of the main analysis. CONCLUSION: Our findings showed a benefit of GLP-1 RAs on HHF and all-cause death in patients with diabetes regardless of HF history. Although, our study presents several limitations, if confirmed through dedicated randomized trial, this could further expand the role of GLP-1RAs in cardiovascular prevention". CI - (c) 2025. Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ojeda-Fernandez, Luisa AU - Ojeda-Fernandez L AD - Laboratory of Cardiovascular Prevention, Department of Health Policy, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy. FAU - Torrigiani, Ginevra AU - Torrigiani G AD - Laboratory of Cardiovascular Prevention, Department of Health Policy, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy. AD - Department of Statistics and Quantitative Methods, Universita Degli Studi Di Milano-Bicocca, Milan, Italy. FAU - Molteni, Mauro AU - Molteni M AD - Internal Medicine, Tradate Hospital, Azienda Sociosanitaria Territoriale Dei Settelaghi, Tradate, VA, Italy. FAU - Fortino, Ida AU - Fortino I AD - Directorate General for Health, Lombardy Region, Milan, Italy. FAU - Cimminiello, Claudio AU - Cimminiello C AD - Arianna Foundation on Anticoagulation, Bologna, Italy. FAU - Baviera, Marta AU - Baviera M AD - Laboratory of Cardiovascular Prevention, Department of Health Policy, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy. marta.baviera@marionegri.it. LA - eng PT - Journal Article DEP - 20250513 PL - Germany TA - Clin Res Cardiol JT - Clinical research in cardiology : official journal of the German Cardiac Society JID - 101264123 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Heart Failure/mortality/complications MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Hospitalization/statistics & numerical data/trends MH - Cause of Death/trends MH - Middle Aged MH - Italy/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Risk Factors MH - Retrospective Studies MH - Follow-Up Studies OTO - NOTNLM OT - All-cause death OT - Antidiabetic drugs OT - Diabetes mellitus OT - GLP-1 receptor agonists OT - Heart failure COIS- Declarations. Conflict of interest: All authors declare no conflict of interest. EDAT- 2025/05/13 13:50 MHDA- 2026/08/10 12:37 CRDT- 2025/05/13 11:13 PHST- 2025/02/12 00:00 [received] PHST- 2025/05/02 00:00 [accepted] PHST- 2026/08/10 12:37 [medline] PHST- 2025/05/13 13:50 [pubmed] PHST- 2025/05/13 11:13 [entrez] AID - 10.1007/s00392-025-02674-9 [pii] AID - 10.1007/s00392-025-02674-9 [doi] PST - ppublish SO - Clin Res Cardiol. 2026 Sep;115(9):1512-1521. doi: 10.1007/s00392-025-02674-9. Epub 2025 May 13. PMID- 40358430 OWN - NLM STAT- MEDLINE DCOM- 20260130 LR - 20260326 IS - 1572-0241 (Electronic) IS - 0002-9270 (Linking) VI - 121 IP - 2 DP - 2026 Feb 1 TI - Glucagon-Like Peptide-1 Receptor Agonists Use Does Not Increase the Risk for Acute Pancreatitis and Is Associated With Lower Complications in Patients With Type 2 Diabetes Who Develop Acute Pancreatitis: A Multicenter Analysis. PG - 424-431 LID - 10.14309/ajg.0000000000003525 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) can lead to structural pancreatic changes potentially predisposing to acute pancreatitis (AP), increasing morbidity and mortality. Scarce data exist on the outcomes of AP in patients with T2DM who are taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The study aim was to evaluate AP outcome and all-cause mortality in patients with T2DM using GLP-1 RAs. METHODS: A retrospective cohort study was performed using population-based data from the TriNetX platform. Patients with T2DM receiving GLP-1 RAs drugs (semaglutide, liraglutide, dulaglutide, and tirzepatide) between January 1, 2015, and October 31, 2023, were included. This patient cohort was matched with patients with T2DM who did not receive GLP-1 RAs according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. To avoid confounding, etiologies of AP including alcohol-induced, trauma, biliary, class Ia drug-induced, hypertriglyceridemia, and postendoscopic retrograde cholangiopancreatography were excluded from both cohorts. Primary outcomes were risk of developing AP, need for parenteral nutrition, systemic complications (sepsis, systemic inflammatory response syndrome, shock, mechanical ventilation, acute kidney injury), and local pancreatic complications. The secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: A total of 740,370 patients with T2DM were identified with 29,423 on GLP-1 RAs; 20,459 of those 29,423 (mean [SD] age, 58.1 [11.9] years; 10,190 [49.85%] female) were matched with 20,459 individuals (mean [SD] age, 57.5 [13.9] years; 10,301 [50.35%] female) who did not take GLP-1 RAs. The GLP-1 RAs group had lower risk of complicated pancreatitis (HR 0.32; 95% confidence interval [CI] 0.14-0.74), parenteral nutrition needs (HR 0.28; 95% CI 0.09-0.83), sepsis (HR 0.71; 95% CI 0.59-0.84), acute kidney injury (HR 0.54; 95% CI 0.49-0.60), shock (HR 0.52; 95% CI 0.36-0.75), and mechanical ventilation support during admission (HR 0.23; 95% CI 0.16-0.33) compared with the non-GLP-1 RAs group. In addition, all-cause mortality was decreased in the GLP-1 agonist group compared with the non-GLP-1 agonist group (HR 0.45; 95% CI 0.41-0.49). Important to note that the GLP-1 RAs group had a tendency of lower risk of uncomplicated pancreatitis (HR 0.71; 95% CI 0.49-1.01) but without statistically significant result. No difference was found between the groups in risk of developing systemic inflammatory response syndrome if it occurs. DISCUSSION: GLP-1 RAs use does not increase AP risk is associated with lower complications in those who developed AP and linked with lower all-cause mortality in patients with T2DM. Prospective studies are needed to determine the mechanisms behind these findings. CI - Copyright (c) 2025 by The American College of Gastroenterology. FAU - Nieto, Luis M AU - Nieto LM AUID- ORCID: 0000-0001-6504-9348 AD - Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Martinez, John AU - Martinez J AD - Department of Medicine, Henry Ford Health, Grand Blanc, Michigan, USA. FAU - Narvaez, Sharon I AU - Narvaez SI AD - Department of Medicine, Piedmont Athens Regional Hospital, Athens, Georgia, USA. FAU - Ko, Donghyun AU - Ko D AUID- ORCID: 0000-0003-0592-490 AD - Department of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, Connecticut, USA. FAU - Kim, Do Han AU - Kim DH AUID- ORCID: 0000-0002-2815-1105 AD - Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Vega, Kenneth J AU - Vega KJ AUID- ORCID: 0000-0002-2432-6123 AD - Division of Gastroenterology and Hepatology, Prisma Health, Columbia, South Carolina, USA. FAU - Chawla, Saurabh AU - Chawla S AUID- ORCID: 0000-0001-6841-4929 AD - Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250513 PL - United States TA - Am J Gastroenterol JT - The American journal of gastroenterology JID - 0421030 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Pancreatitis/epidemiology/etiology MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Acute Disease MH - Risk Factors MH - Immunoglobulin Fc Fragments/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - acute pancreatitis OT - mortality OT - type 2 diabetes mellitus EDAT- 2025/05/13 13:50 MHDA- 2026/01/30 13:19 CRDT- 2025/05/13 09:52 PHST- 2025/02/05 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2026/01/30 13:19 [medline] PHST- 2025/05/13 13:50 [pubmed] PHST- 2025/05/13 09:52 [entrez] AID - 00000434-202602000-00027 [pii] AID - 10.14309/ajg.0000000000003525 [doi] PST - ppublish SO - Am J Gastroenterol. 2026 Feb 1;121(2):424-431. doi: 10.14309/ajg.0000000000003525. Epub 2025 May 13. PMID- 40349689 OWN - NLM STAT- MEDLINE DCOM- 20250618 LR - 20260720 IS - 1664-5502 (Electronic) IS - 1664-5502 (Linking) VI - 15 IP - 1 DP - 2025 TI - The Cardiac and Renal Safety of Semaglutide in Patients with Type 2 Diabetes: A Real-World Study Based on FAERS. PG - 413-422 LID - 10.1159/000546238 [doi] AB - BACKGROUND: Recently, a large clinical trial found that treatment with semaglutide significantly reduced the risk of renal damage and cardiovascular death in patients with type 2 diabetes (T2D). To validate these findings and ensure the suitability of the drug, it is necessary to address the renal and cardiac safety of semaglutide in patients with T2D through real-world safety evidence. METHODS: We examined post-marketing data on the use of semaglutide in patients with T2D using disproportionality analysis based on the FDA Adverse Event Reporting System database. We focused on the detection of positive signals for acute and chronic renal injury and cardiac adverse events associated with semaglutide therapy. RESULTS: A total of 2,380 patients were enrolled in semaglutide therapy in T2D patients with no renal or cardiac positive signals in four algorithmic thresholds, including disproportionality analysis. CONCLUSIONS: In the current study, we observed no significant cardiac or renal safety signals in patients with T2D treated with semaglutide. Our results provide further support for its use as initial and combination therapy in relevant populations. CI - (c) 2025 The Author(s). Published by S. Karger AG, Basel. FAU - Wang, Jingyu AU - Wang J AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Xie, Tong AU - Xie T AD - Renal Division, Peking University First Hospital, Beijing, China, xietong710@163.com. AD - Peking University Institute of Nephrology, Beijing, China, xietong710@163.com. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China, xietong710@163.com. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China, xietong710@163.com. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China, xietong710@163.com. FAU - Zhang, Yuemiao AU - Zhang Y AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhang, Hong AU - Zhang H AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250511 PL - Switzerland TA - Cardiorenal Med JT - Cardiorenal medicine JID - 101554863 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Female MH - Male MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Middle Aged MH - Aged MH - Product Surveillance, Postmarketing MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems MH - *Acute Kidney Injury/chemically induced/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse event OT - Cardiac disorders OT - Kidney injury OT - Pharmacovigilance OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/05/12 05:12 MHDA- 2025/06/19 00:25 CRDT- 2025/05/11 18:23 PHST- 2024/12/24 00:00 [received] PHST- 2025/04/30 00:00 [accepted] PHST- 2025/06/19 00:25 [medline] PHST- 2025/05/12 05:12 [pubmed] PHST- 2025/05/11 18:23 [entrez] AID - 000546238 [pii] AID - 10.1159/000546238 [doi] PST - ppublish SO - Cardiorenal Med. 2025;15(1):413-422. doi: 10.1159/000546238. Epub 2025 May 11. PMID- 40348599 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20250624 IS - 1600-0765 (Electronic) IS - 0022-3484 (Linking) VI - 60 IP - 5 DP - 2025 May TI - Glucagon-Like Peptide 1 Receptor Agonists (GLP-1RAs) Improve Periodontal and Peri-Implant Health in Type 2 Diabetes Mellitus. PG - 450-465 LID - 10.1111/jre.13410 [doi] AB - Type 2 diabetes mellitus (T2DM) affects millions globally and is strongly associated with oral health issues, particularly periodontitis. The bidirectional relationship between T2DM and periodontitis is well established, with poorly managed T2DM increasing the risk of inflammation, tissue damage, and dental implant failure. Advances in treatment, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), have led to better glycemic control and may reduce T2DM-related complications, highlighting their potential in addressing interconnected oral-systemic health challenges. This narrative review critically evaluates the literature on the impact of GLP-1RAs on periodontal and peri-implant health. 10 in vitro studies, nine preclinical animal studies, and one clinical study were explored to investigate their effects on periodontal regeneration, implant therapy, and related mechanisms. In vitro research revealed that GLP-1RAs, including exenatide and liraglutide, promoted osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through pathways such as the mitogen Wnt/beta-catenin and mitogen-activated protein kinase pathways, even in high glucose or inflammatory conditions. Synergistic effects with stromal cell-derived factor-1 further promoted PDLSC proliferation and bone regeneration. Animal studies demonstrated that GLP-1RAs mitigated periodontal inflammation, oxidative stress, and alveolar bone resorption while promoting bone remodeling and implant osseointegration, independently of glycemic control. Importantly, advanced delivery systems, such as exenatide-loaded chitosan-poly(lactic-coglycolic acid) microspheres, further increased peri-implant osseointegration in diabetic models. The sole clinical study, a retrospective cohort study, assessed peri-implant marginal bone loss in peri-implantitis patients treated with different hypoglycemic drugs. Results showed significantly less clinical and radiographic bone loss in the GLP-1RA group compared to insulin and metformin groups (p < 0.01). Overall, while GLP-1RAs have promising anti-inflammatory, osteoprotective, and pleiotropic properties, their role appears more aligned with preserving periodontal and peri-implant health in T2DM individuals than directly treating periodontitis or peri-implantitis. By delineating current evidence and research directions, this review calls for medical and dental professionals to collaborate in leveraging these novel treatment options in future studies to improve patient care and address the intricate challenges that diabetes presents to oral health. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Ahmad, Paras AU - Ahmad P AUID- ORCID: 0000-0001-7306-9795 AD - Department of Research, Advanced PRF Education, Florida, USA. FAU - Estrin, Nathan AU - Estrin N AD - Lake Erie College of Osteopathic Medicine School of Dental Medicine, Bradenton, Florida, USA. FAU - Farshidfar, Nima AU - Farshidfar N AUID- ORCID: 0000-0003-2944-5305 AD - Department of Periodontology, University of Bern, Bern, Switzerland. FAU - Zhang, Yufeng AU - Zhang Y AUID- ORCID: 0000-0001-8702-5291 AD - Department of Oral Implantology, University of Wuhan, Wuhan, China. FAU - Miron, Richard J AU - Miron RJ AUID- ORCID: 0000-0003-3290-3418 AD - Department of Periodontology, University of Bern, Bern, Switzerland. LA - eng PT - Journal Article PT - Review DEP - 20250509 PL - United States TA - J Periodontal Res JT - Journal of periodontal research JID - 0055107 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dental Implants) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Dental Implants MH - *Periodontitis/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Exenatide/pharmacology OTO - NOTNLM OT - Hypoglycemic agents OT - periodontitis OT - peri-implantitis EDAT- 2025/05/11 18:56 MHDA- 2025/06/24 18:30 CRDT- 2025/05/10 22:24 PHST- 2025/04/08 00:00 [revised] PHST- 2024/12/27 00:00 [received] PHST- 2025/04/08 00:00 [accepted] PHST- 2025/06/24 18:30 [medline] PHST- 2025/05/11 18:56 [pubmed] PHST- 2025/05/10 22:24 [entrez] AID - 10.1111/jre.13410 [doi] PST - ppublish SO - J Periodontal Res. 2025 May;60(5):450-465. doi: 10.1111/jre.13410. Epub 2025 May 9. PMID- 40347221 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20261010 IS - 1179-1942 (Electronic) IS - 0114-5916 (Linking) VI - 48 IP - 9 DP - 2025 Sep TI - Incretin-Based Drugs and the Incidence of Endometrial Cancer Among People with Type 2 Diabetes: Active Comparator New-User Design. PG - 1023-1033 LID - 10.1007/s40264-025-01551-8 [doi] AB - INTRODUCTION: The use of incretin-based drugs may be associated with a decreased risk of endometrial cancer among women with type 2 diabetes. METHODS: Using data from the UK Clinical Practice Research Datalink and linked databases, two new-user active comparator cohorts of women with type 2 diabetes who initiated glucagon-like peptide 1 receptor agonists (GLP-1 RAs) or sulfonylureas (cohort 1) and DPP-4 inhibitors or sulfonylureas (cohort 2) were assembled. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident endometrial cancer. RESULTS: Cohort 1 included 9239 new users of GLP-1 RAs and 80,086 new users of sulfonylureas. The GLP-1 RAs were not associated with a decreased risk of endometrial cancer when compared with sulfonylureas (HR: 1.11, 95% CI: 0.66-1.88). In a duration-response secondary analysis, use of GLP-1 RAs for more than two years was associated with an increased risk of endometrial cancer (HR: 2.47, 95% CI: 1.37-4.43) when compared to sulfonylureas When analysed by drug type, exenatide was associated with an elevated risk when compared to sulfonylureas (HR: 2.26, 95% CI:1.06-4.82). Cohort 2 included 42,486 new users of DPP-4 inhibitors and 79,353 new users of sulfonylureas. DPP-4 inhibitors were not associated with a decreased risk of endometrial cancer compared with sulfonylureas (HR: 1.00, 95% CI: 0.76-1.32). In a duration-response secondary analysis, use of DPP-4 inhibitors for more than two years was associated with an increased risk of endometrial cancer (HR: 1.63, 95% CI: 1.14-2.33) when compared to sulfonylureas. CONCLUSIONS: In this population-based study, the use of GLP-1 RAs and DPP-4 inhibitors was not associated with a decreased risk of endometrial cancer when compared with the use of sulfonylureas among women with type 2 diabetes. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Rothman, Sonny M AU - Rothman SM AUID- ORCID: 0000-0003-3126-639X AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, Quebec, H3T 1E2, Canada. AD - Department of Epidemiology, and Occupational Health, McGill University, BiostatisticsMontreal, QC, H3A 1G1, Canada. FAU - Yin, Hui AU - Yin H AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, Quebec, H3T 1E2, Canada. FAU - Yu, Oriana H Y AU - Yu OHY AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, Quebec, H3T 1E2, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada. AD - Division of Endocrinology and Metabolism, McGill University, Montreal, QC, H4A 3J1, Canada. FAU - Pollak, Michael AU - Pollak M AD - Division of Experimental Medicine, Lady Davis Institute of Medical Research, Jewish General Hospital, McGill University, Montreal, QC, H3T 1E2, Canada. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, H4A 3T2, Canada. FAU - Azoulay, Laurent AU - Azoulay L AUID- ORCID: 0000-0001-5162-3556 AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, Quebec, H3T 1E2, Canada. laurent.azoulay@mcgill.ca. AD - Department of Epidemiology, and Occupational Health, McGill University, BiostatisticsMontreal, QC, H3A 1G1, Canada. laurent.azoulay@mcgill.ca. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, H4A 3T2, Canada. laurent.azoulay@mcgill.ca. LA - eng GR - FDN-143328/CAPMC/CIHR/Canada GR - FDN-143328/CAPMC/CIHR/Canada PT - Journal Article DEP - 20250510 PL - New Zealand TA - Drug Saf JT - Drug safety JID - 9002928 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - *Endometrial Neoplasms/epidemiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Incretins/therapeutic use/adverse effects MH - Incidence MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sulfonylurea Compounds/therapeutic use/adverse effects MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - United Kingdom/epidemiology MH - Adult MH - Databases, Factual COIS- Declarations. Funding: This study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). The funding bodies had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Conflicts of Interest: L.A. received speaking and consulting fees from Pfizer, Roche and Boehringer Ingelheim for work unrelated to this project; other authors declare that they have no competing interests or relationships that could have appeared to influence the submitted work. L.A. is an editorial Board member of Drug Safety. L.A. was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. Ethics approval: The study protocol was approved by the Research Data Governance of the CPRD (Protocol 23_003631) and by the McGill University ethics committee. Consent to Publish: Not applicable. Consent to Participate: Not applicable. Data Availability: This study is based on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone. Because electronic health records are classified as "sensitive data" by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval through the individual constituent entities controlling access to the data. Specifically, the primary care data can be requested via application to the Clinical Practice Research Datalink ( https://www.cprd.com ). Code Availability: Codes may be made privately available upon reasonable request to the corresponding author. Author Contributions: S.R., L.A. and H.Y. were involved in the conception, design, conduct of study, analysis and interpretation of the results. O.Y. and M.P. were involved in the design, analysis, and interpretation of the results. S.R. wrote the manuscript. All authors edited, reviewed, approved the final version of the manuscript, and are accountable for its accuracy. L.A. acquired the data and supervised the study. EDAT- 2025/05/11 00:45 MHDA- 2025/08/08 12:30 CRDT- 2025/05/10 11:03 PHST- 2025/04/10 00:00 [accepted] PHST- 2025/08/08 12:30 [medline] PHST- 2025/05/11 00:45 [pubmed] PHST- 2025/05/10 11:03 [entrez] AID - 10.1007/s40264-025-01551-8 [pii] AID - 10.1007/s40264-025-01551-8 [doi] PST - ppublish SO - Drug Saf. 2025 Sep;48(9):1023-1033. doi: 10.1007/s40264-025-01551-8. Epub 2025 May 10. PMID- 40346323 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20261010 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 89 IP - 1 DP - 2025 Jul TI - Type 2 diabetic disease and current drug treatments: clinical and governance aspects. PG - 111-118 LID - 10.1007/s12020-025-04263-2 [doi] AB - AIMS: Type 2 diabetes mellitus (T2D) is recognized as one of the most pressing global health issues of our time. In Italy, its prevalence has grown significantly, currently affecting an estimated 4 million individuals. Moreover, it is believed that an additional 1 million people may be living with the condition without a formal diagnosis, underscoring the critical need for enhanced awareness, screening, and preventive measures. METHODS: All drug dispensing data for T2M in the year 2023 were extrapolated from an internal management system in order to evaluate the consumption and expenditure data for these drugs in an Italian regional setting. The classes sought involve new high-cost drugs: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors, Glucagon-like Peptide-1 (GLP1) Receptor Agonists, Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors. RESULT: A clear difference in the costs associated with each therapeutic class emerged, with important implications for the economic sustainability of the National Health Service (NHS). For the DPP4-inhibitor class, there was a value of total DDDs of 2,621,883, a total expenditure of euro2,744,960.13; for the SGLT2-inhibitor class, there was a consumption value of total DDDs of 4,467,797 and a total expenditure of euro6,702,941.75; GLP1- agonists, on the other hand, recorded a total DDD of 2,631,055.63, with an expenditure of euro7,539,247.97. CONCLUSIONS: The management of diabetic disease has seen a therapeutic evolution in recent years with increased effectiveness and rising costs of new drugs. For these reasons, it is of paramount importance that central governments adopt legislative measures to ensure greater therapeutic appropriateness that will ensure the sustainability of public health care. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ferrara, Francesco AU - Ferrara F AUID- ORCID: 0000-0001-9298-6783 AD - Hospital Pharmacist, Pharmacy Department, Naples, Italy. f.ferrara@aslnapoli3sud.it. FAU - Zovi, Andrea AU - Zovi A AUID- ORCID: 0000-0002-6528-2171 AD - Hospital Pharmacist, Ministry of Health, Rome, Italy. FAU - Langella, Roberto AU - Langella R AD - Italian Society of Hospital Pharmacy (SIFO), SIFO Secretariat of the Lombardy Region, Milan, Italy. FAU - Panico, Angela AU - Panico A AD - Specialist in hospital pharmacy, University of Naples Federico II, Napoli, Italy. FAU - Scognamiglio, Manlio AU - Scognamiglio M AD - Hospital Pharmacist Manager, Pharmaceutical department, Asl Salerno, Salerno, Italy. FAU - Trama, Ugo AU - Trama U AD - General Direction for Health Protection and Coordination of the Campania Regional Health System, Naples, Italy. FAU - Nava, Eduardo AU - Nava E AD - Director Pharmacy Department, Naples, Italy. LA - eng PT - Journal Article DEP - 20250509 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - Humans MH - *Hypoglycemic Agents/therapeutic use/economics MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/economics MH - Italy/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - Drug Costs MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Appropriateness OT - Chronic OT - Diabetic disease OT - Governance OT - Treatments COIS- Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Consent to publish: The authors consent to the publication of the manuscript. EDAT- 2025/05/10 00:47 MHDA- 2025/07/04 12:41 CRDT- 2025/05/09 23:27 PHST- 2025/01/16 00:00 [received] PHST- 2025/04/28 00:00 [accepted] PHST- 2025/07/04 12:41 [medline] PHST- 2025/05/10 00:47 [pubmed] PHST- 2025/05/09 23:27 [entrez] AID - 10.1007/s12020-025-04263-2 [pii] AID - 10.1007/s12020-025-04263-2 [doi] PST - ppublish SO - Endocrine. 2025 Jul;89(1):111-118. doi: 10.1007/s12020-025-04263-2. Epub 2025 May 9. PMID- 40345413 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260723 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 289 DP - 2025 Nov TI - Effect of once-weekly subcutaneous semaglutide on arterial inflammation in people with type 2 diabetes and cardiovascular disease using PET-MRI: Primary results of a randomized, double-blind, placebo-controlled trial. PG - 17-27 LID - S0002-8703(25)00156-5 [pii] LID - 10.1016/j.ahj.2025.05.001 [doi] AB - BACKGROUND: Semaglutide has demonstrated cardiovascular benefits in people with type 2 diabetes (T2D) with cardiovascular disease (CVD). Inflammation plays a well-documented role in atherosclerosis and glucagon-like peptide-1 receptor agonists, like semaglutide, have shown anti-inflammatory effects in animal and clinical studies. This trial investigated the effect of semaglutide on atherosclerotic inflammation in the carotid arteries using positron emission tomography (PET)-magnetic resonance imaging (MRI). METHODS: Patients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary and key secondary endpoints used PET-MRI with [(18)F]FDG and [(68)Ga]DOTATATE tracers to assess change from baseline to week 26 in plaque inflammation in the segments of the carotid arteries that were determined to be the most diseased and where plaque inflammation was quantified by the maximum target-to-background ratio (TBR(max)) of the tracers. Additional secondary endpoints assessed plaque morphology and burden using MRI at week 52, including total wall volume, lipid-rich necrotic core volume, and fibrous cap thickness. RESULTS: Of 101 patients, 87.1% were male, mean age was 66 years and they were well-treated according to guidelines. No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR(max) of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [(68)Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404). CONCLUSIONS: This trial explored the feasibility of following plaque inflammation with PET-MRI using [(18)F]FDG and [(68)Ga]DOTATATE. A significant effect of semaglutide versus placebo on carotid plaque inflammation could not be detected through the methodology used in this trial, likely due to minimal baseline inflammation. However, this does not exclude an effect of semaglutide on inflammation seen in previous preclinical and clinical studies. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04032197. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - James, Stefan AU - James S AD - Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: stefan.james@ucr.uu.se. FAU - Christoffersen, Andreas Dyreborg AU - Christoffersen AD AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hacker, Marcus AU - Hacker M AD - Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria. FAU - Jensen, Maria D Radu Juul AU - Jensen MDRJ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mellbin, Linda AU - Mellbin L AD - Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. FAU - Pieber, Thomas R AU - Pieber TR AD - Division for Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Ripa, Rasmus Sejersten AU - Ripa RS AD - Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen Denmark. FAU - Rossing, Peter AU - Rossing P AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen Denmark; Complications Research, Steno Diabetes Center, Copenhagen, Denmark. FAU - Svehlikova, Eva AU - Svehlikova E AD - Division for Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Kjaer, Andreas AU - Kjaer A AD - Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04032197 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250507 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Organometallic Compounds) RN - 0 (Radiopharmaceuticals) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Double-Blind Method MH - Drug Administration Schedule MH - Fluorodeoxyglucose F18 MH - *Glucagon-Like Peptides/administration & dosage MH - Injections, Subcutaneous MH - Magnetic Resonance Imaging/methods MH - Organometallic Compounds MH - Plaque, Atherosclerotic/drug therapy/diagnostic imaging MH - Positron-Emission Tomography/methods MH - Radiopharmaceuticals MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Conflict of interest SJ has received grants to his institution from Novo Nordisk, AstraZeneca, Amgen, Merck, and Novartis. ADC, J-PD and MDRJJ are employees and stockholders of Novo Nordisk A/S. MH has acted as consultant for ITM, Telix, Evomics and has received grants from Siemens Healthineers, Eli Lilly, Roche, Novartis, BMS, Ibsen, ITM, EZAG, Novo Nordisk, and has received payments for lectures from Siemens and Janssen. LM has received consulting and speaker fees for participation in advisory board, lectures and clinical trials supported and funded by Amgen, AstraZeneca, Bayer AG, Boehringer-Ingelheim, Janssen, Novartis, Novo Nordisk, and Sanofi, and received research grants from Amgen and Bayer AG. TRP has received research support from AstraZeneca, Novo Nordisk, and Sanofi and has served on advisory panels for Arecor Limited, Eli Lilly and Company, Novo Nordisk, and Roche Diabetes Care. RSR has received consultancy fees and holds stocks from Novo Nordisk A/S. PR has received grants to Steno Diabetes Center Copenhagen from AstraZeneca, Bayer AG, Lexicon, and Novo Nordisk and has received honoraria (paid to institution) from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Gilead, Sanofi. ES has no conflicts of interest. AK is a consultant for Novo Nordisk A/S and has received research funding from EU H2020, the Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, the Sygeforsikringen danmark, the Research Foundation of Rigshospitalet, the Danish National Research Foundation (grant 126) - PERSIMUNE, and Research Council for Independent Research. Andreas Kjaer is a Lundbeck Foundation Professor. EDAT- 2025/05/10 00:48 MHDA- 2025/07/30 06:30 CRDT- 2025/05/09 19:36 PHST- 2025/02/06 00:00 [received] PHST- 2025/05/02 00:00 [revised] PHST- 2025/05/03 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/05/10 00:48 [pubmed] PHST- 2025/05/09 19:36 [entrez] AID - S0002-8703(25)00156-5 [pii] AID - 10.1016/j.ahj.2025.05.001 [doi] PST - ppublish SO - Am Heart J. 2025 Nov;289:17-27. doi: 10.1016/j.ahj.2025.05.001. Epub 2025 May 7. PMID- 40344607 OWN - NLM STAT- MEDLINE DCOM- 20250827 LR - 20260127 IS - 1365-2125 (Electronic) IS - 0306-5251 (Linking) VI - 91 IP - 9 DP - 2025 Sep TI - Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus. PG - 2672-2683 LID - 10.1002/bcp.70093 [doi] AB - AIMS: Cotadutide is a dual glucagon-like peptide-1/glucagon receptor agonist. The objective of the analysis was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe the relationship between cotadutide exposure and response on urine albumin-to-creatinine ratio (UACR), urinary albumin (UALB), and body weight in participants with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) using data from a Phase2b study (NCT04515849). METHODS: A total of 247 participants with CKD and T2DM were randomized and titrated to either 100, 300 or 600 mug cotadutide, 1 mg semaglutide or placebo. UACR was measured biweekly from either morning void (Weeks 14 and 26) or spot urine (other visits). The analysis was implemented using a longitudinal non-linear mixed-effect model. The potential impact of covariates on efficacy in participants was quantified. RESULTS: PK/PD models were developed, and a significant relationship was identified between cotadutide exposure and PD biomarkers of UACR, UALB and body weight. The models described the data adequately; greater changes in PD responses were observed with higher cotadutide doses. Baseline mean blood pressure and baseline UALB were found to affect the reductions in UACR and UALB, respectively. Model-predicted relative change from placebo in UACR, UALB and body weight after 26 weeks of 600 mug cotadutide treatment were -45.6% (-52.4%, -38.7%), -47.2% (-56.0%, -39.9%) and -5.3% (-7.6%, -4.1%), respectively. CONCLUSIONS: This modelling assessment was successfully applied for cotadutide to understand the relationship between cotadutide dosing regimen and the response in UACR, UALB and body weight. These models have general application in analysing and interpreting data from CKD/diabetic kidney disease (DKD) studies. CI - (c) 2025 British Pharmacological Society. FAU - Yu, Hongtao AU - Yu H AUID- ORCID: 0000-0003-2278-4478 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parker, Victoria AU - Parker V AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Selvarajah, Viknesh AU - Selvarajah V AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Hansen, Lars AU - Hansen L AD - Early Clinical Development, R&D, AstraZeneca, Gaithersburg, UK. FAU - Robertson, Darren AU - Robertson D AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Hamren, Bengt AU - Hamren B AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. FAU - Khan, Anis AU - Khan A AUID- ORCID: 0000-0001-8262-3022 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parkinson, Joanna AU - Parkinson J AUID- ORCID: 0000-0003-4492-5243 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. LA - eng SI - ClinicalTrials.gov/NCT04515849 GR - AstraZeneca/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20250509 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - AYI8EX34EU (Creatinine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/urine MH - Male MH - Female MH - Middle Aged MH - *Renal Insufficiency, Chronic/drug therapy/complications/urine MH - *Models, Biological MH - *Hypoglycemic Agents/pharmacokinetics/pharmacology/administration & dosage MH - Aged MH - Double-Blind Method MH - Dose-Response Relationship, Drug MH - Albuminuria/urine MH - *Glucagon-Like Peptides/pharmacology/pharmacokinetics/administration & dosage MH - Adult MH - Body Weight/drug effects MH - Creatinine/urine MH - Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - modelling and simulation OT - pharmacokinetic-pharmacodynamic EDAT- 2025/05/09 18:31 MHDA- 2025/08/31 19:57 CRDT- 2025/05/09 16:24 PHST- 2025/04/15 00:00 [revised] PHST- 2024/11/13 00:00 [received] PHST- 2025/04/22 00:00 [accepted] PHST- 2025/08/31 19:57 [medline] PHST- 2025/05/09 18:31 [pubmed] PHST- 2025/05/09 16:24 [entrez] AID - 10.1002/bcp.70093 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2025 Sep;91(9):2672-2683. doi: 10.1002/bcp.70093. Epub 2025 May 9. PMID- 40342008 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260418 IS - 1559-0100 (Electronic) IS - 1355-008X (Print) IS - 1355-008X (Linking) VI - 89 IP - 1 DP - 2025 Jul TI - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) for the treatment of type 2 diabetes mellitus: friends or foes to bone health? a narrative review of clinical studies. PG - 30-38 LID - 10.1007/s12020-025-04253-4 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a relatively new class of drugs for treatment of Type 2 Diabetes mellitus (T2DM). They have proven to be excellent drugs not only for the results on glycemic control but also for weight loss, cardiovascular protection and several other potential metabolic effects. In contrast, the effects of GLP-1RAs drugs on bone metabolism and bone mineral density (BMD) remain less clearly defined. This narrative review aimed to explore the relationship between GLP-1RAs and bone in T2DM patients by reviewing clinical studies which assessed the effects of GLP-1RAs on BMD, markers of bone turnover and fragility fractures. In vitro and animal studies have demonstrated that GLP-1RAs treatment promotes bone formation and inhibits bone resorption. However, in humans, GLP-1RAs therapy has been shown to primarily stimulate bone resorption, as evidenced by a significant increase in type I collagen C-terminal cross-linked telopeptide levels, while promoting new bone formation to a lesser extent. Clinical studies indicate that GLP-1RAs therapy, in both diabetic and non-diabetic patients, results in a reduction in BMD, which is more pronounced at skeletal sites subjected to higher mechanical loading, such as the femur and tibia, and appears to correlate with the degree of weight loss. Furthermore, in the studies reviewed, parameters related to bone quality and strength, such as Trabecular bone score (TBS), microindentation, High-resolution peripheral Quantitative Computed Tomography (HR-pQCT), and Radiofrequency Echographic Multi Spectrometry (REMS) remain unaffected by GLP-1RAs. Additionally, the incidence of fragility fractures does not increase. CI - (c) 2025. The Author(s). FAU - Al Refaie, Antonella AU - Al Refaie A AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. AD - Division of Internal Medicine I, San Giuseppe Hospital, Empoli, Italy. FAU - Baldassini, Leonardo AU - Baldassini L AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Mondillo, Caterina AU - Mondillo C AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Gonnelli, Sara AU - Gonnelli S AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. AD - Department of Geriatrics, University Hospital of Nice, Nice, France. FAU - Ceccarelli, Elena AU - Ceccarelli E AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Tarquini, Roberto AU - Tarquini R AD - Division of Internal Medicine I, San Giuseppe Hospital, Empoli, Italy. FAU - Gonnelli, Stefano AU - Gonnelli S AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Gennari, Luigi AU - Gennari L AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Caffarelli, Carla AU - Caffarelli C AUID- ORCID: 0000-0003-4163-7289 AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. carla.caffarelli@unisi.it. LA - eng PT - Journal Article PT - Review DEP - 20250508 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Bone Density/drug effects MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Bone and Bones/drug effects/metabolism MH - Animals MH - Bone Remodeling/drug effects PMC - PMC12227486 OTO - NOTNLM OT - Bone mineral density (BMD) OT - Bone turnover markers (BTMs) OT - Fragility fractures OT - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) OT - Trabecular bone score (TBS) OT - Type 2 diabetes mellitus (T2DM) COIS- Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. EDAT- 2025/05/09 18:34 MHDA- 2025/07/04 12:44 PMCR- 2025/05/08 CRDT- 2025/05/09 12:19 PHST- 2025/01/04 00:00 [received] PHST- 2025/04/24 00:00 [accepted] PHST- 2025/07/04 12:44 [medline] PHST- 2025/05/09 18:34 [pubmed] PHST- 2025/05/09 12:19 [entrez] PHST- 2025/05/08 00:00 [pmc-release] AID - 10.1007/s12020-025-04253-4 [pii] AID - 4253 [pii] AID - 10.1007/s12020-025-04253-4 [doi] PST - ppublish SO - Endocrine. 2025 Jul;89(1):30-38. doi: 10.1007/s12020-025-04253-4. Epub 2025 May 8. PMID- 40340589 OWN - NLM STAT- MEDLINE DCOM- 20250626 LR - 20260307 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 9 DP - 2025 Jun TI - The contemporary landscape of cardiovascular optimization in type 2 diabetes: overcoming barriers to evidence-based use of newer antihyperglycemic agents. PG - 1009-1020 LID - 10.1080/14656566.2025.2504702 [doi] AB - INTRODUCTION: Cardiometabolic diseases, particularly type 2 diabetes (T2D) and cardiovascular disease (CVD), represent leading global health challenges with rising incidence and prevalence. Despite strong evidence supporting the benefits of sodium-glucose cotransporter inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in managing CVD risk in T2D, these therapies remain underutilized. AREAS COVERED: This review discusses the present state of SGLT2i and GLP-1 RA usage, emphasizing barriers to their adoption, including clinical inertia, high costs, and misconceptions about injectable therapies. The literature search was conducted using PubMed, UpToDate, major society journals, and clinical guidelines. Information was gathered from cohort studies, survey reports, randomized controlled trials, and meta-analyses that examine the effectiveness and challenges surrounding these treatments. EXPERT OPINION: Addressing the underuse of SGLT2i and GLP-1 RA requires a multifaceted approach. Key strategies include improving prescriber awareness, reducing out-of-pocket costs, fostering interdisciplinary collaboration, and leveraging digital health tools. Implementation science has shown promise in enhancing therapy uptake. Future efforts must integrate these therapies into value-based care models to ensure timely, equitable access, ultimately reducing cardiovascular (CV) morbidity and mortality in high-risk T2D populations. FAU - Malas, Kareem AU - Malas K AUID- ORCID: 0000-0002-1372-1355 AD - Department of Internal Medicine, University of Texas-Southwestern, Dallas, TX, USA. AD - Department of Internal Medicine, Parkland Health, Dallas, TX, USA. FAU - Kazmi, Salman AU - Kazmi S AD - Department of Internal Medicine, University of Texas-Southwestern, Dallas, TX, USA. AD - Department of Internal Medicine, Parkland Health, Dallas, TX, USA. AD - Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA. FAU - Kang, Yu Mi AU - Kang YM AD - Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA. FAU - McGuire, Darren K AU - McGuire DK AD - Department of Internal Medicine, University of Texas-Southwestern, Dallas, TX, USA. AD - Department of Internal Medicine, Parkland Health, Dallas, TX, USA. LA - eng GR - T32 DK007529/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20250513 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/economics MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - *Cardiovascular Diseases/prevention & control/etiology/epidemiology MH - *Hypoglycemic Agents/therapeutic use/economics/administration & dosage/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Evidence-Based Medicine OTO - NOTNLM OT - Cardiovascular disease OT - cardiometabolic disease OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - sodium-glucose cotransporter inhibitor EDAT- 2025/05/09 12:37 MHDA- 2025/06/26 12:29 CRDT- 2025/05/09 11:05 PHST- 2025/06/26 12:29 [medline] PHST- 2025/05/09 12:37 [pubmed] PHST- 2025/05/09 11:05 [entrez] AID - 10.1080/14656566.2025.2504702 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jun;26(9):1009-1020. doi: 10.1080/14656566.2025.2504702. Epub 2025 May 13. PMID- 40340524 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20250509 IS - 2168-6602 (Electronic) IS - 0890-1171 (Linking) VI - 39 IP - 5 DP - 2025 Jun TI - Glucagon-Like Peptide 1 Receptor Agonists and the Deepening Health Equity Divide in America. PG - 832-836 LID - 10.1177/08901171251335507b [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have changed the landscape of diabetes management, obesity treatment, and cardiometabolic health. As a result, GLP-1 utilization has increased significantly over the past few years. However, emerging evidence raises questions about the potential of these medications to widen existing health disparities. Cost, insurance status, and structural racism all are barriers to access, and these barriers hit hardest on underserved communities who are most in need of these drugs. This article discusses potential evidence of disparities in GLP=1 medication access, utilization, and availability, as well as potential solutions and frameworks that can be adopted with hopes of mitigating these disparities. FAU - Spinelli, Kateri J AU - Spinelli KJ AD - Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence Research Network, Portland, OR, USA. FAU - Oakes, Allison H AU - Oakes AH AD - Trilliant Health, Brentwood, TN, USA. LA - eng PT - Journal Article DEP - 20250508 PL - United States TA - Am J Health Promot JT - American journal of health promotion : AJHP JID - 8701680 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Health Equity MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States MH - *Healthcare Disparities MH - Health Services Accessibility MH - *Hypoglycemic Agents/therapeutic use/economics/supply & distribution MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - cardiovascular disease OT - diabetes mellitus OT - glucagon-like peptide 1 receptor agonists OT - health disparities OT - obesity OT - race & ethnicity COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/05/09 12:36 MHDA- 2025/05/09 12:37 CRDT- 2025/05/09 11:03 PHST- 2025/05/09 12:37 [medline] PHST- 2025/05/09 12:36 [pubmed] PHST- 2025/05/09 11:03 [entrez] AID - 10.1177/08901171251335507b [doi] PST - ppublish SO - Am J Health Promot. 2025 Jun;39(5):832-836. doi: 10.1177/08901171251335507b. Epub 2025 May 8. PMID- 40337971 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 2212-3911 (Electronic) IS - 1574-8863 (Linking) VI - 21 IP - 3 DP - 2026 TI - A Descriptive Analysis from VigiAccess on Drug-related Problems Associated with the Glucagon-like Peptide-1 Receptor Agonists. PG - e15748863367086 LID - 10.2174/0115748863367086250420011411 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely accepted for managing Type 2 Diabetes Mellitus. However, numerous drug-related problems (DRPs) have recently been reported about GLP-1 RAs. The present descriptive study aims to compile and report the DRPs of various GLP-1 RAs. METHODS: The DRPs reported for all the GLP-1 RAs, including exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and trazeptide, were extracted from the category of injury, poisoning, and procedural complications of VigiAccess. The Pharmaceutical Care Network Europe Association (PCNE) classification for drug-related problems (version 9.1) was used to categorize the DRPs into patient-related, healthcare practice-related, and patient- or healthcare practice- related. RESULTS: Overall, 315952 potential side effects (PSEs) were reported regarding GLP-1 RAs in VigiAccess under injury, poisoning, and procedural complications. Out of 315952 PSE reports, 84187 were DRPs of GLP-1 RAs. Among the patient-related DRPs, the administered incorrect dose (17797; 48.37%) was predominant, and most of the reports were documented for tirzepatide (9993; 23.82%). Off-label use (13600; 48.37%) was a predominant healthcare practicerelated DRP, most of which were from Tirzepatide (4945; 17.59%). DISCUSSION: The alarming DRP reports in this descriptive analysis regarding the dosing and offlabel use of GLP-1 Ras need further investigation to establish the contribution of underlying factors. CONCLUSION: Qualified healthcare practitioners must educate the patients administering the GLP- 1 RAs to minimize preventable DRPs. Also, careful and frequent monitoring of GLP-1 RAs improves therapeutic outcomes by ruling out DRPs. Healthcare practitioners should comply with approved therapeutic guidelines to enhance the treatment quality of GLP-1 RAs. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Amirthalingam, Palanisamy AU - Amirthalingam P AUID- ORCID: 0000-0002-5803-1227 AD - Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Drug Saf JT - Current drug safety JID - 101270895 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Adverse Drug Reaction Reporting Systems MH - Semaglutide MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology/diagnosis MH - Tirzepatide OTO - NOTNLM OT - Drug-related problems OT - VigiAccess OT - glucagon-like peptide-1 receptor agonists OT - off-label use OT - potential side effects OT - type-2 diabetes mellitus EDAT- 2025/05/08 12:24 MHDA- 2026/09/14 11:41 CRDT- 2025/05/08 07:23 PHST- 2024/10/27 00:00 [received] PHST- 2025/02/10 00:00 [revised] PHST- 2025/02/18 00:00 [accepted] PHST- 2026/09/14 11:41 [medline] PHST- 2025/05/08 12:24 [pubmed] PHST- 2025/05/08 07:23 [entrez] AID - CDS-EPUB-148210 [pii] AID - 10.2174/0115748863367086250420011411 [doi] PST - ppublish SO - Curr Drug Saf. 2026;21(3):e15748863367086. doi: 10.2174/0115748863367086250420011411. PMID- 40336001 OWN - NLM STAT- MEDLINE DCOM- 20250508 LR - 20250516 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 25 IP - 1 DP - 2025 May 7 TI - Influence of glucagon-like peptide-1 receptor agonists on renal parameters: a meta-analysis of randomized controlled trials. PG - 124 LID - 10.1186/s12902-025-01948-7 [doi] LID - 124 AB - AIMS: To verify the influence of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on renal function parameters in type 2 diabetes based on well-known randomized controlled trials (RCTs). METHODS: PubMed, Cochrane, Web of Science, Embase, and grey literature were searched for RCTs published until December 24, 2024. The quality of the RCTs was assessed using the Cochrane risk-of-bias tool. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated for continuous variables using meta-analysis. The primary outcomes were composite renal function parameters, including serum creatinine (Cr) levels, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), and urinary albumin-to-creatinine ratio (UACR). RESULTS: Pooled data from 24 studies revealed that GLP-1 RA positively influenced renal outcomes in the type 2 diabetes group to some extent compared with that in the control group. GLP- 1 RA decreased serum creatinine levels (WMD=-0.10, 95%CI -0.19 to -0.01, I(2) = 33%, P < 0.05), eGFR(WMD = 0.54, 95% CI 0.19 to 0.90, I(2) = 27%, P < 0.05), UAE (WMD=-11.92, 95% CI - 23.50 to - 0.33, I(2) = 0%, P < 0.05) and UACR (WMD: -1.01 mg/g, 95% CI:-1.68, -0.34, I(2) = 15%, P < 0.05) in the type 2 diabetes group. CONCLUSION: GLP-1 RA treatment significantly elevated eGFR, decreased the UACR, and positively influenced renal function outcomes in the type 2 diabetes group. CLINICAL TRIAL NUMBER: Not applicable. CI - (c) 2025. The Author(s). FAU - Li, Wenjing AU - Li W AD - Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. AD - Department of Cardiology, Binzhou People's Hospital, Binzhou, Shandong Province, 256600, China. FAU - Liang, Xiaoyan AU - Liang X AD - Department of Central Laboratory, Binzhou People's Hospital, Binzhou, Shandong, 256600, China. FAU - Sun, Na AU - Sun N AD - Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. FAU - Zhang, Daqing AU - Zhang D AD - Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. zhangdaqing2022@163.com. AD - Department of Cardiology, Shengjing Hospital of China Medical University, NO.36 Sanhao Street, Heping District, Shen Yang, Liaoning Province, 110004, China. zhangdaqing2022@163.com. LA - eng GR - SDYWZGKCJH2023026/Shandong Province Medical Workers Science and Technology Innovation Program/ GR - XJ2023006307/Scientific Research Foundation of Binzhou People's Hospital/ GR - 202301030188/Shandong Province Medical and Health Development Program/ PT - Journal Article PT - Meta-Analysis DEP - 20250507 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney/drug effects MH - *Diabetic Nephropathies PMC - PMC12056997 OTO - NOTNLM OT - Cr OT - GLP-1 RA OT - UACR OT - UAE OT - eGFR COIS- Declarations. Ethics approval and consent to participate: This is a systematic review and meta-analysis, ethics approval and consent to participate are not applicable. Consent for publication: Not applicable. This study does not involve human participants. Competing interests: The authors declare no competing interests. EDAT- 2025/05/08 00:24 MHDA- 2025/05/08 11:14 PMCR- 2025/05/07 CRDT- 2025/05/07 23:38 PHST- 2024/05/17 00:00 [received] PHST- 2025/04/28 00:00 [accepted] PHST- 2025/05/08 11:14 [medline] PHST- 2025/05/08 00:24 [pubmed] PHST- 2025/05/07 23:38 [entrez] PHST- 2025/05/07 00:00 [pmc-release] AID - 10.1186/s12902-025-01948-7 [pii] AID - 1948 [pii] AID - 10.1186/s12902-025-01948-7 [doi] PST - epublish SO - BMC Endocr Disord. 2025 May 7;25(1):124. doi: 10.1186/s12902-025-01948-7. PMID- 40331745 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250703 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 7 DP - 2025 Jul TI - Liver function effects of SGLT2 inhibitor and GLP-1 receptor agonist combination treatment in patients with type 2 diabetes (post hoc analysis of RECAP study). PG - 1243-1253 LID - 10.1111/jdi.70066 [doi] AB - AIM: The favor effect on liver disease by odium-glucose cotransporter inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP1Ra) was reported; however, the effect of the combination treatment of these drugs was not well known. METHODS: We retrospectively analyzed data for 643 patients with type 2 diabetes receiving SGLT2i + GLP1Ra combination treatment for at least 1 year (331 and 312 patients in the GLP1Ra- and SGLT2i-preceding groups, respectively). Propensity score (PS) matching was used to compare the effects of the preceding drugs on liver function. RESULTS: The mean AST and ALT values at baseline, at the initiation of combination treatment, and at final observation were 29.8 +/- 20.0 and 37.7 +/- 29.5, 28.7 +/- 17.3 and 35.3 +/- 6.0, 26.0 +/- 14.6 and 30.1 +/- 21.6 IU/L, respectively, indicative of significant improvements in liver function (P < 0.001). Conversely, significant progress in the fibrosis-4 (FIB-4) index category was observed even after the combination treatment (P = 0.03). Subgroup analysis revealed that a significant decrease in ALT was observed only in patients with a baseline ALT >/=30 IU/L after the combination treatment (P = 0.005). Improvement of the FIB-4 index category was observed in patients in the baseline FIB-4 index >/=2.6 group and in the 1.3 /=1.3. CI - (c) 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Tsuriya, Daisuke AU - Tsuriya D AD - Division of Endocrinology and Metabolism, 2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Kobayashi, Kazuo AU - Kobayashi K AUID- ORCID: 0000-0002-1284-9728 AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Takeshita, Kei AU - Takeshita K AD - Division of Endocrinology and Metabolism, 2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Hashimoto, Takuya AU - Hashimoto T AD - Division of Endocrinology and Metabolism, 2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Kimura, Moritsugu AU - Kimura M AD - Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. FAU - Muta, Yoshimi AU - Muta Y AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Yokomizo, Hisashi AU - Yokomizo H AUID- ORCID: 0000-0001-7759-2014 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Takashi, Yuichi AU - Takashi Y AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Tsukamoto, Shunichiro AU - Tsukamoto S AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Tamura, Kouichi AU - Tamura K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kanasaki, Keizo AU - Kanasaki K AUID- ORCID: 0000-0002-9563-502X AD - Department of Internal Medicine 1, Endocrinology and Metabolism, Shimane University Faculty of Medicine, The Center for Integrated Kidney Research and Advance, Faculty of Medicine, Shimane University, Izumo, Japan. FAU - Kawanami, Daiji AU - Kawanami D AUID- ORCID: 0000-0002-8926-4701 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Toyoda, Masao AU - Toyoda M AD - Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. LA - eng PT - Journal Article DEP - 20250507 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Drug Therapy, Combination MH - Aged MH - *Liver/drug effects/physiopathology MH - Liver Function Tests MH - *Hypoglycemic Agents/therapeutic use MH - Follow-Up Studies PMC - PMC12209503 OTO - NOTNLM OT - FIB-4 index OT - GLP-1 receptor agonist OT - Sodium-glucose cotransporter inhibitor COIS- Kazuo Kobayashi, Kei Takeshita, Takuya Hashimoto, Moritsugu Kimura, Yoshimi Muta, Hisashi Yokomizo, and Shunichiro Tsukamoto declare no conflict of interest. Keizo Kanasaki is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Keizo Kanasaki received lecture fees from Dainippon-Sumitomo Pharma, Astellas, Astra Zeneca, Ono, Otsuka, Taisho, Tanabe-Mitsubishi, Eli Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Bayer, Novartis, and Kowa and received research funding from Boehringer Ingelheim, Kowa, Mitsubishi Tanabe Pharma, and Bayer. Daisuke Tsuriya received lecture fees from Eli Lilly, Novo Nordisk, and Mitsubishi Tanabe. Yuichi Takashi received lecture fees from Kyowa Kirin. Kouichi Tamura has received honoraria/lecture fees from AstraZeneca, Novartis, Bayer, Otsuka Pharmaceutical, Boehringer Ingelheim, Fuji Pharma, Kyowa Kirin, Ono Pharmaceutical, Sanwa Kagaku, Mochida Pharmaceutical, Kowa, Eli Lilly, Novo Nordisk, commissioned clinical trials, contract research, and joint research funding: AstraZeneca, Bayer, Novartis, Chinook, Otsuka Medical Devices, Novo Nordisk, Terumo, Variatris, and Kowa, and scholarship donations: Otsuka Pharmaceutical, Bayer, Mochida Pharmaceutical, and Boehringer Ingelheim. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and grants from Bayer Yakuhin Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation, and Sumitomo Pharma Co., Ltd. Masao Toyoda received lecture fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sumitomo, and Mitsubishi Tanabe and received subsidies from Super Light Water, TAKAGI, Roche DC, and LifeScan. Approval of the research protocol: This study was approved by the Institutional Review Board for Clinical Research, Tokai University, Japan (approval on December 6, 2021). Informed consent: N/A. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2025/05/07 12:31 MHDA- 2025/07/01 09:30 PMCR- 2025/05/07 CRDT- 2025/05/07 08:34 PHST- 2025/03/12 00:00 [revised] PHST- 2024/12/24 00:00 [received] PHST- 2025/04/25 00:00 [accepted] PHST- 2025/07/01 09:30 [medline] PHST- 2025/05/07 12:31 [pubmed] PHST- 2025/05/07 08:34 [entrez] PHST- 2025/05/07 00:00 [pmc-release] AID - JDI70066 [pii] AID - 10.1111/jdi.70066 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Jul;16(7):1243-1253. doi: 10.1111/jdi.70066. Epub 2025 May 7. PMID- 40331425 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260821 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - Long-term delirium and survival outcomes in patients treated with GLP-1 receptor agonists versus metformin in type 2 diabetes: A population-based cohort study. PG - 3984-3996 LID - 10.1111/dom.16434 [doi] AB - AIM: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of delirium and mortality. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide metabolic and neuroprotective benefits, their long-term impact on delirium risk remains uncertain. This study compares GLP-1 RAs and metformin in relation to delirium and mortality in T2DM patients using real-world data. METHODS: A retrospective cohort study was conducted using the TriNetX global federated research network, which primarily comprises U.S.-based healthcare organisations (approximately 85%), with additional sites in Europe, Asia-Pacific and the Middle East. Adults (>/=18 years) with T2DM who initiated GLP-1 RAs or metformin were included. Propensity score matching (PSM) balances baseline characteristics. The primary outcome was incident delirium; the secondary outcome was all-cause mortality. Kaplan-Meier survival curves and time-dependent Cox models assessed associations. RESULTS: After 1:1 PSM (N = 63 096 per group), GLP-1 RAs showed no overall reduction in delirium risk (AHR: 0.98, 95% CI: 0.94-1.02, p = 0.3628). However, they were protective in the first 5 years (AHR: 0.89, 95% CI: 0.86-0.92, p < 0.0001) but increased delirium risk between 5 and 10 years (AHR: 1.15, 95% CI: 1.04-1.26, p = 0.0046). Subgroup analysis revealed lower delirium risk with GLP-1 RAs in middle-aged patients (40-79 years) and those with HbA1c <7.5%. Higher risk was observed in Asian and Native Hawaiian/Pacific Islander populations. However, these findings should be interpreted with caution due to the relatively small subgroup sizes and the limited representativeness of these groups within the predominantly U.S.-based database, in which Asian and Native Hawaiian/Pacific Islander patients together accounted for less than 5% of the overall cohort. Mortality risk was lower in absolute terms for GLP-1 RAs (6.28% vs. 9.95%) but higher in long-term hazard (AHR: 1.16, 95% CI: 1.12-1.21, p < 0.001). CONCLUSIONS: GLP-1 RA use was initially associated with a lower risk of delirium, but this association reversed over time. Subgroup variations suggest individualised treatment considerations. Metformin remains a preferred option given its stable cognitive and survival benefits. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Sun, Mingyang AU - Sun M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. FAU - Wang, Xiaoling AU - Wang X AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. AD - Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China. FAU - Lu, Zhongyuan AU - Lu Z AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. AD - Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China. FAU - Yang, Yitian AU - Yang Y AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. FAU - Lv, Shuang AU - Lv S AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. FAU - Miao, Mengrong AU - Miao M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. FAU - Wu, Szu-Yuan AU - Wu SY AUID- ORCID: 0000-0001-5637-558X AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan. AD - Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. AD - Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Division of Radiation Oncology, Department of Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. AD - Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. AD - Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Zhang, Jiaqiang AU - Zhang J AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250507 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Metformin/therapeutic use/adverse effects MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - *Delirium/epidemiology/mortality/chemically induced/etiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Adult MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor agonists OT - delirium OT - metformin OT - mortality OT - type 2 diabetes mellitus EDAT- 2025/05/07 12:31 MHDA- 2025/06/09 06:26 CRDT- 2025/05/07 06:33 PHST- 2025/04/19 00:00 [revised] PHST- 2025/02/26 00:00 [received] PHST- 2025/04/21 00:00 [accepted] PHST- 2025/06/09 06:26 [medline] PHST- 2025/05/07 12:31 [pubmed] PHST- 2025/05/07 06:33 [entrez] AID - 10.1111/dom.16434 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3984-3996. doi: 10.1111/dom.16434. Epub 2025 May 7. PMID- 40330819 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 19 DP - 2025 TI - A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist. PG - 3509-3537 LID - 10.2147/DDDT.S506957 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are peptide-derived analogs that were initially investigated to treat type 2 diabetes. Recently, a drug targeting the receptors of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (tirzepatide) has been introduced to the market, and its indications have expanded to include treating obesity. Here, we review the pharmacokinetics, pharmacokinetic drug-drug interactions (DDIs), and pharmacokinetic modeling approaches of four currently available GLP-1 RAs (exenatide, liraglutide, dulaglutide, and semaglutide) and tirzepatide. To address the extremely short half-life (2 min) of native human GLP-1, structural modifications have been applied to GLP-1 RAs and a dual GLP-1/GIP RA. These include amino acid sequence substitutions, fatty acid conjugation using a linker, and fusion with albumin or the IgG fragment crystallizable (Fc) region, resulting in minimal metabolism and renal excretion. Due to their diverse structures, the pharmacokinetic profiles vary, and a prolonged half-life may be associated with an increased risk of adverse events. Clinically significant drug-metabolizing enzyme- and transporter-mediated DDIs are yet to be reported. Mechanism-of-action-mediated DDIs are currently limited to those involving delayed gastric emptying, and most studies have found them to be clinically insignificant. However, significant changes in exposure were observed for oral contraceptives and levothyroxine following the administration of tirzepatide and oral semaglutide, respectively, indicating the need for close monitoring in these instances. Thirty models have been developed to predict pharmacokinetics and physiologically based pharmacokinetic modeling can be useful for assessing mechanism-of-action-mediated DDIs. Alterations in the volume of distribution and clearance resulting from other mechanisms of action (eg, reduced fat mass, changes in cytochrome P450 activity, and glomerular filtration rate) are key factors in determining pharmacokinetics. However, the DDIs mediated by these factors remain poorly understood and require further investigation to ensure that GLP-1 RAs can be safely used with concomitant medications. CI - (c) 2025 Min et al. FAU - Min, Jee Sun AU - Min JS AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Jo, Seong Jun AU - Jo SJ AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. AD - Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, 14214, USA. FAU - Lee, Sangyoung AU - Lee S AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Kim, Duk Yeon AU - Kim DY AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Kim, Da Hyun AU - Kim DH AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Lee, Chae Bin AU - Lee CB AUID- ORCID: 0000-0003-4551-9191 AD - Johns Hopkins Drug Discovery, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. FAU - Bae, Soo Kyung AU - Bae SK AUID- ORCID: 0000-0001-7258-7187 AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. LA - eng PT - Journal Article PT - Review DEP - 20250430 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Interactions MH - *Hypoglycemic Agents/pharmacokinetics MH - Glucagon-Like Peptides/pharmacokinetics/analogs & derivatives MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy MH - Receptors, Gastrointestinal Hormone PMC - PMC12052016 OTO - NOTNLM OT - GIP OT - GLP-1 OT - drug-drug interactions OT - pharmacokinetics OT - physiologically based pharmacokinetic model COIS- The authors report no conflicts of interest in this work. EDAT- 2025/05/07 06:28 MHDA- 2025/05/07 12:32 PMCR- 2025/04/30 CRDT- 2025/05/07 05:26 PHST- 2024/11/17 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/05/07 12:32 [medline] PHST- 2025/05/07 06:28 [pubmed] PHST- 2025/05/07 05:26 [entrez] PHST- 2025/04/30 00:00 [pmc-release] AID - 506957 [pii] AID - 10.2147/DDDT.S506957 [doi] PST - epublish SO - Drug Des Devel Ther. 2025 Apr 30;19:3509-3537. doi: 10.2147/DDDT.S506957. eCollection 2025. PMID- 40329607 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260821 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - Glucagon-like peptide 1 (GLP-1) receptor agonists' use during pregnancy: Safety data from regulatory clinical trials. PG - 4102-4108 LID - 10.1111/dom.16437 [doi] AB - AIMS: The prevalence of diabetes and obesity continues to rise in women of reproductive age, with significant implications for both mother and foetus. Glucagon-like peptide-1 receptor agonists are effective treatments of diabetes and obesity. However, no Glucagon-like peptide-1 receptor agonists are currently approved for use during pregnancy. We describe the outcomes of unplanned pregnancies during regulatory clinical trials of Glucagon-like peptide-1 receptor agonists submitted to the Food and Drug Administration and European Medicines Agency. MATERIALS AND METHODS: A search was conducted of the regulatory documentation published by the European Medicines Agency and the Food and Drug Administration on unplanned pregnancies during regulatory clinical trials of Glucagon-like peptide-1 receptor agonists. Clinical and Medical Reviews published by the Center for Drug Evaluation and Research at the Food and Drug Administration for every Glucagon-like peptide-1 receptor agonist prior to market authorisation were assessed to gather information on unplanned pregnancies that occurred while females were partaking in the clinical development programmes of such drugs. RESULTS: Evidence in women having planned pregnancies is lacking, and the only evidence thus far relies on pregnancies occurring inadvertently during Glucagon-like peptide-1 receptor agonist trials. The incidence of congenital abnormalities in humans appears relatively low following Glucagon-like peptide-1 receptor agonist use during pregnancy. CONCLUSIONS: Key knowledge gaps must be addressed before the introduction of the Glucagon-like peptide-1 receptor agonist class of drugs for pregnant women. Currently, Glucagon-like peptide-1 receptor agonists should be stopped as soon as the patient becomes aware of a pregnancy. The establishment of patient registries designed to capture data relating to cases of Glucagon-like peptide-1 receptor agonist exposure during pregnancy is a high priority, and where data already exist, the findings need to be published. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Parker, Claire H AU - Parker CH AUID- ORCID: 0009-0000-9597-6273 AD - Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA. FAU - Slattery, Craig AU - Slattery C AD - School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland. FAU - Brennan, Donal J AU - Brennan DJ AUID- ORCID: 0000-0002-6747-3342 AD - University College Dublin School of Medicine, Catherine McCauley Research Centre, Mater Misericoridiae University Hospital, Dublin, Ireland. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. LA - eng PT - Journal Article DEP - 20250506 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Female MH - Humans MH - Pregnancy MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy MH - *Pregnancy in Diabetics/drug therapy MH - Pregnancy Outcome PMC - PMC12232371 OTO - NOTNLM OT - GLP1-RA OT - GLP-1 OT - GLP-1 receptor agonists OT - foetal outcome OT - pregnancy OT - pregnancy risk COIS- CHP, CS and DJB have no conflicts of interest to declare. ClR reports grants from the EU Innovative Medicine Initiative, Irish Research Council, Science Foundation Ireland, Anabio and the Health Research Board. He serves on advisory boards and speakers panels of Novo Nordisk, Roche, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Gila, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, Keyron, AstraZeneca, Arrowhead Pharma, Amgen and Rhythm Pharma. ClR is the Chair of the Irish Society for Nutrition and Metabolism. ClR provides obesity clinical care in the My Best Weight clinic and Beyond BMI clinic and is a co-owner of these clinics. EDAT- 2025/05/07 06:27 MHDA- 2025/07/04 12:42 PMCR- 2025/07/07 CRDT- 2025/05/07 02:52 PHST- 2025/04/19 00:00 [revised] PHST- 2025/03/12 00:00 [received] PHST- 2025/04/22 00:00 [accepted] PHST- 2025/07/04 12:42 [medline] PHST- 2025/05/07 06:27 [pubmed] PHST- 2025/05/07 02:52 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - DOM16437 [pii] AID - 10.1111/dom.16437 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4102-4108. doi: 10.1111/dom.16437. Epub 2025 May 6. PMID- 40327845 OWN - NLM STAT- MEDLINE DCOM- 20251001 LR - 20260917 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 36 IP - 10 DP - 2025 Oct 1 TI - Rapid and Simultaneous Initiation of Guideline-Directed Kidney Therapies in Patients with CKD and Type 2 Diabetes. PG - 2061-2076 LID - 10.1681/ASN.0000000752 [doi] AB - The global incidence of CKD continues to rise, with type 2 diabetes as a major contributor. At any stage of CKD, patients with concurrent CKD and type 2 diabetes are at heightened cardiovascular risk and have a greater likelihood of dying from cardiovascular causes than progressing to kidney failure. Consequently, the use of "four pillars" of CKD therapy, including renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitor, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, has been advocated to reduce cardiovascular-kidney risk. Although these therapies can mitigate cardiovascular and kidney events when used individually, the residual risks of these events remain high across major clinical trials testing these therapies separately as well as in real-world clinical settings. This raises the question about when to optimally initiate these therapies, including strategies that start these agents in rapid sequence, or even simultaneously, to reduce long-term risk, thereby mirroring best practices with rapid titration schedules in patients with heart failure. However, initiating all four therapies simultaneously in the setting of CKD has not yet been tested due to lack of data on safety and tolerability in this high-risk population. Data regarding the safety profile of rapid sequence initiation remain limited. Therefore, our aim was to review the existing evidence on the safety profiles of guideline-recommended therapies and discuss the challenges associated with rapid sequence initiation of these treatments in patients with CKD. CI - Copyright (c) 2025 by the American Society of Nephrology. FAU - Rashid, Ahmed Mustafa AU - Rashid AM AD - Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas. FAU - Khan, Muhammad Shahzeb AU - Khan MS AD - Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas. AD - Baylor Scott and White: The Heart Hospital Plano, Plano, Texas. AD - Department of Medicine, Baylor College of Medicine, Temple, Texas. FAU - Cherney, David Z I AU - Cherney DZI AD - Division of Nephrology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada. FAU - Mehta, Ankit AU - Mehta A AD - Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas. FAU - Rangaswami, Janani AU - Rangaswami J AD - Department of Medicine, Veterans Affairs Medical Center, Washington, DC. AD - Division of Nephrology, George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Shafi, Tariq AU - Shafi T AUID- ORCID: 0000-0002-7222-4666 AD - Division of Nephrology, Baylor Scott and White Health, Temple, Texas. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas. AD - Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. LA - eng PT - Journal Article PT - Review DEP - 20250506 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - doi: 10.1681/ASN.0000000808 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Practice Guidelines as Topic MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Nephropathies/drug therapy MH - Cardiovascular Diseases/prevention & control PMC - PMC12499624 OTO - NOTNLM OT - CKD COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F222. EDAT- 2025/05/06 18:29 MHDA- 2025/10/01 18:28 PMCR- 2025/10/01 CRDT- 2025/05/06 16:23 PHST- 2025/10/01 18:28 [medline] PHST- 2025/05/06 18:29 [pubmed] PHST- 2025/05/06 16:23 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 00001751-202510000-00019 [pii] AID - JASN-2025-000020 [pii] AID - 10.1681/ASN.0000000752 [doi] PST - ppublish SO - J Am Soc Nephrol. 2025 Oct 1;36(10):2061-2076. doi: 10.1681/ASN.0000000752. Epub 2025 May 6. PMID- 40321113 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison. PG - 3757-3765 LID - 10.1111/dom.16401 [doi] AB - AIMS: Tirzepatide and semaglutide demonstrated clinically meaningful weight reduction in people with obesity or overweight and type 2 diabetes (T2D) in SURMOUNT-2 and STEP 2 clinical trials, respectively. In the absence of head-to-head trials, this study compared the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Mean percent change in weight from baseline, weight reduction >/=5% and mean change in glycated haemoglobin (HbA1c [%]) were compared between tirzepatide 10/15 mg (week 72, SURMOUNT-2) and semaglutide 2.4 mg (week 68, STEP 2) applying the Bucher method to the efficacy estimand. Sensitivity analyses included the use of matching-adjusted indirect comparison, treatment regimen estimand and comparing study outcomes at 68 weeks. RESULTS: Tirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01). Tirzepatide 15 mg had significantly higher odds of achieving >/=5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide. Sensitivity analyses were generally consistent with the primary analysis, exceptions including when power was reduced in the matching-adjusted indirect comparison analyses and in the categorical weight reduction outcome. CONCLUSIONS: This analysis suggested greater reductions in bodyweight and HbA1c (%) levels associated with tirzepatide 10 and 15 mg than with semaglutide 2.4 mg in people with obesity or overweight and T2D. CI - (c) 2025 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hankosky, Emily R AU - Hankosky ER AUID- ORCID: 0000-0001-9934-584X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - He, Xuanyao AU - He X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Malik, Raleigh AU - Malik R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Fraseur Brumm, Julia AU - Fraseur Brumm J AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wang, Fangyu AU - Wang F AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Niemeyer, Anthony AU - Niemeyer A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Zhang, Xiaotian M AU - Zhang XM AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - Eli Lilly and Company/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250505 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Overweight/drug therapy/complications MH - Glycated Hemoglobin/analysis MH - Weight Loss/drug effects MH - *Tirzepatide/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Treatment Outcome MH - Adult MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12146454 OTO - NOTNLM OT - indirect treatment comparison OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight reduction COIS- Emily R. Hankosky, Xuanyao He, Julia Fraseur Brumm, Fangyu Wang, Anthony Niemeyer and Xiaotian Michelle Zhang are employees and stockholders of Eli Lilly and Company, Indianapolis, United States. Raleigh Malik was an employee of Eli Lilly and Company at the time of the study. W. Timothy Garvey has served as a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Carmot/Roche, Regeneron and Merck, and as a site principal investigator for multi-centred clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens and Pfizer. EDAT- 2025/05/05 06:27 MHDA- 2025/06/09 06:26 PMCR- 2025/06/09 CRDT- 2025/05/05 04:53 PHST- 2025/03/18 00:00 [revised] PHST- 2025/01/03 00:00 [received] PHST- 2025/03/28 00:00 [accepted] PHST- 2025/06/09 06:26 [medline] PHST- 2025/05/05 06:27 [pubmed] PHST- 2025/05/05 04:53 [entrez] PHST- 2025/06/09 00:00 [pmc-release] AID - DOM16401 [pii] AID - 10.1111/dom.16401 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3757-3765. doi: 10.1111/dom.16401. Epub 2025 May 5. PMID- 40316896 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260615 IS - 2731-4553 (Electronic) IS - 2731-4553 (Linking) VI - 26 IP - 1 DP - 2025 May 2 TI - Barriers in prescribing antidiabetic medications with cardiovascular benefits: practice, experience, and attitudes of GPs in Croatia. PG - 143 LID - 10.1186/s12875-025-02837-7 [doi] LID - 143 AB - BACKGROUND: The treatment approaches of type 2 diabetes (T2D) are being transformed, due to the availability of novel antidiabetic medications, sodium-glucose co-transporter 2 inhibitors (SGLT2ins), and glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Despite their proven beneficial effects, recent research points to their insufficient prescription. This study aimed to reveal the prescription rates of SGLT2ins and GLP-1 RAs among general practitioners (GPs) in Croatia and to examine factors associated with their low self-confidence in prescribing them. METHODS: A self-designed survey questionnaire was used and delivered to the GPs' e-mail addresses in digital format. The data on the number of individuals diagnosed with T2D and prescribed new antidiabetic medications were checked by the respondents in their electronic database. Factors associated with lower GPs; self-confidence in prescribing SGLT2ins and GLP-1 RAs were assessed by bivariate and multivariate logistic regression analyses. RESULTS: The study included 168 GPs (66.1% women; 49.4% specialists in family medicine) and a cohort of 23,036 individuals with T2D. The prescription rates of SGLT2ins and GLP-1 RAs were 21.0% and 14.4%, respectively. Specialists stated a higher level of self-confidence in prescribing these medications, compared to other respondents. In the multivariate models, a factor that was shown to reduce the likelihood of low GPs; self-confidence in prescribing SGLT2ins was "familiarity with the side effects of these medications" (OR = 0.03), while factors that increased this likelihood were: "being familiar with GLP-1 RAs; side effects" (OR = 4.8), "an insufficient knowledge and experience of GPs in adjusting two target outcome measures to the same patient" (OR = 2.2), and "the GPs; assumption that the new guidelines; protocol which separates two target outcome measures is useful only in some cases but not in all" (OR = 5.4). Regarding GLP-1 RAs, only one factor - "familiarity of GPs with GLP-1 RAs side effects", was shown to reduce the probability of GPs; low self-confidence in prescribing this group of medications (OR = 0.27). CONCLUSION: It is of the utmost importance to identify barriers the GPs face when prescribing these medications, as well as to suggest potential strategies to optimize their prescription. CI - (c) 2025. The Author(s). FAU - Kurevija, Tomislav AU - Kurevija T AD - Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia. AD - Health Center of Osijek-Baranja County, Osijek, Croatia. FAU - Sojat, Dunja AU - Sojat D AD - Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia. AD - Health Center of Osijek-Baranja County, Osijek, Croatia. FAU - Bilic-Curcic, Ines AU - Bilic-Curcic I AD - Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia. AD - University Hospital Center Osijek, Osijek, Croatia. FAU - Canecki-Varzic, Silvija AU - Canecki-Varzic S AD - Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia. AD - University Hospital Center Osijek, Osijek, Croatia. FAU - Trtica-Majnaric, Ljiljana AU - Trtica-Majnaric L AD - Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia. ljiljana.majnaric@gmail.com. LA - eng PT - Journal Article DEP - 20250502 PL - England TA - BMC Prim Care JT - BMC primary care JID - 9918300889006676 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Croatia MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *General Practitioners/psychology/statistics & numerical data MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Attitude of Health Personnel MH - Surveys and Questionnaires MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12046718 OTO - NOTNLM OT - Cardiovascular risk OT - GLP-1 RAs OT - Prescribing barriers OT - Prescribing rates OT - SGLT2ins OT - Therapeutic inertia OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Faculty of Medicine, the Josip Juraj Strossmayer University of Osijek (No. 641-01/24-01/04), dated March 5, 2024. Each respondent who participated in the research completed an informed consent form in which they were informed of the conditions of participation and the reasons and method of conducting the research. Consent for publication: All respondents were asked for their consent to use the data obtained by the survey for publication. Competing interests: The authors declare no competing interests. EDAT- 2025/05/03 00:37 MHDA- 2025/05/03 22:25 PMCR- 2025/05/02 CRDT- 2025/05/02 23:33 PHST- 2024/12/10 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/05/03 22:25 [medline] PHST- 2025/05/03 00:37 [pubmed] PHST- 2025/05/02 23:33 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - 10.1186/s12875-025-02837-7 [pii] AID - 2837 [pii] AID - 10.1186/s12875-025-02837-7 [doi] PST - epublish SO - BMC Prim Care. 2025 May 2;26(1):143. doi: 10.1186/s12875-025-02837-7. PMID- 40316732 OWN - NLM STAT- MEDLINE DCOM- 20250710 LR - 20250713 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 8 DP - 2025 Aug TI - Treatment discontinuation among users of GLP-1 receptor agonists and SGLT2 inhibitors in a national population of individuals with type 2 diabetes. PG - 1680-1695 LID - 10.1007/s00125-025-06439-x [doi] AB - AIMS/HYPOTHESIS: Our aim was to assess treatment discontinuation, reinitiation and switching between drugs within the same drug class for glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors in individuals with type 2 diabetes. METHODS: We used data from nationwide registers in Sweden to perform separate analyses for all patients with type 2 diabetes who filled a first prescription of a GLP-1 receptor agonist or an SGLT2 inhibitor between 2017 and 2021. Patients were considered to be on treatment for the period during which prescriptions were refilled before the estimated end date of the most recent prescription, including a 90-day grace period, i.e. the time allowed between and after prescriptions before treatment is considered as discontinued. We used the Aalen-Johansen estimator to estimate cumulative incidences of discontinuation and reinitiation, and Fine-Gray sub-distribution hazard models to assess the association of clinical variables with the risk of discontinuation. RESULTS: Among 73,895 new users of GLP-1 receptor agonists, the cumulative incidence of treatment discontinuation was 23.6% at 1 year and 38.5% at 3 years. Among patients who discontinued, the cumulative incidence of treatment reinitiation was 41.1% at 1 year and 57.4% at 3 years after discontinuation. Among 113,207 new users of SGLT2 inhibitors, the cumulative incidence of treatment discontinuation was 27.9% at 1 year and 45.9% at 3 years, with a cumulative incidence of reinitiation of 40.4% at 1 year and 55.7% at 3 years after discontinuation. When varying the grace period between 60 days and 365 days, treatment discontinuation rates at 3 years ranged from 23.3% to 43.6% among GLP-1 receptor agonist users and from 28.8% to 50.6% among SGLT2 inhibitor users. The proportion of patients who had ongoing treatment, regardless of previous discontinuation episodes, ranged between approximately 70% and 80% for both drugs during a 1-5 year period after treatment initiation across analyses using various grace periods. In terms of switching, 22.9% of the GLP-1 receptor agonist users and 2.1% of the SGLT2 inhibitor users switched between drugs within the same drug class. Patient characteristics associated with treatment discontinuation were similar for GLP-1 receptor agonists and SGLT2 inhibitors, although the association between higher BMI and a lower likelihood of treatment discontinuation was stronger for GLP-1 receptor agonists. CONCLUSIONS/INTERPRETATION: Approximately half of type 2 diabetes patients who had started using GLP-1 receptor agonists or SGLT2 inhibitors had discontinued treatment within 5 years of follow-up. However, more than half of those who discontinued treatment subsequently reinitiated treatment, such that the proportion with ongoing treatment was approximately 70-80% for both drugs during a 1-5 year period after treatment initiation. This suggests that the proportion of patients with long-term use of the medications is larger than indicated by analyses focusing on treatment discontinuation. Patient characteristics associated with treatment discontinuation were similar for GLP-1 receptor agonists and SGLT2 inhibitors. CI - (c) 2025. The Author(s). FAU - Lim, Carl-Emil AU - Lim CE AUID- ORCID: 0000-0003-0501-9678 AD - Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. carlemil.lim@ki.se. FAU - Pasternak, Bjorn AU - Pasternak B AD - Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Eliasson, Bjorn AU - Eliasson B AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Ueda, Peter AU - Ueda P AD - Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Journal Article DEP - 20250502 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Sweden/epidemiology MH - Registries PMC - PMC12246030 OTO - NOTNLM OT - Adherence OT - Discontinuation OT - Drug switching OT - GLP-1 receptor agonists OT - Persistence OT - Proportion of patients covered OT - Reinitiation OT - SGLT2 inhibitors OT - Type 2 diabetes COIS- Acknowledgements: Some of the data were presented as an abstract at the EASD meeting in 2024. Data availability: The data analysed in this study are based on Swedish nationwide registers. Individual-level data in the registers can only be accessed through secure servers, and only export of aggregated data, as presented in research articles, is allowed according to Swedish law. Permission to access data can be made only after fulfilling specific requirements to safeguard the anonymity of the study participants. For these reasons, data cannot be made generally available. Funding: Open access funding provided by Karolinska Institute. PU was supported by a grant from the Strategic Research Area Epidemiology programme and a Faculty Funded Career Position at Karolinska Institutet. BP was supported by a consolidator investigator grant from Karolinska Institutet. The study was conducted with research grant support from the Swedish Heart-Lung Foundation, the Swedish Research Council and ALF Region Stockholm. Authors' relationships and activities: BE reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi outside the scope of the submitted work. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: C-EL and PU had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. C-EL, BP and PU designed the study. C-EL and PU drafted the manuscript. C-EL performed the statistical analysis. All authors contributed to the acquisition, analysis and interpretation of data, and to critical revision of the manuscript for important intellectual content. PU and BP obtained funding and supervised the study. All authors read and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. EDAT- 2025/05/03 00:37 MHDA- 2025/07/10 12:31 PMCR- 2025/05/02 CRDT- 2025/05/02 23:25 PHST- 2024/10/15 00:00 [received] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/07/10 12:31 [medline] PHST- 2025/05/03 00:37 [pubmed] PHST- 2025/05/02 23:25 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - 10.1007/s00125-025-06439-x [pii] AID - 6439 [pii] AID - 10.1007/s00125-025-06439-x [doi] PST - ppublish SO - Diabetologia. 2025 Aug;68(8):1680-1695. doi: 10.1007/s00125-025-06439-x. Epub 2025 May 2. PMID- 40311668 OWN - NLM STAT- MEDLINE DCOM- 20250822 LR - 20250822 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) VI - 86 IP - 3 DP - 2025 Sep TI - Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists and Sodium/Glucose Cotransporter 2 Inhibitors in Preventing Chronic Kidney Failure and Mortality in Patients With Type 2 Diabetes and CKD. PG - 301-313.e1 LID - S0272-6386(25)00831-5 [pii] LID - 10.1053/j.ajkd.2025.03.016 [doi] AB - RATIONALE & OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular, kidney, and survival outcomes in patients with type 2 diabetes; however, the comparative effectiveness of these drugs in a real-world setting remains unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 79,047 patients with type 2 diabetes and an estimated glomerular filtration rate<60mL/min/1.73m(2) in the Taiwan National Health Insurance Research Database between 2016 and 2021. EXPOSURE: Treatment with GLP-1RAs or SGLT2 inhibitors. OUTCOME: Initiation of kidney replacement therapy (KRT) and all-cause mortality. ANALYTIC APPROACH: Propensity score matching was performed to balance baseline characteristics between the groups. Cox proportional hazards models were used to estimate HRs and 95% CIs for each outcome using an intention-to-treat approach. RESULTS: 14,182 (7,091 initiating GLP-1RAs and 7,091 initiating SGLT2 inhibitors) individuals among the original cohort of 79,047 were included in the propensity score-matched analysis. With a median follow-up duration of 2.5 years, people initiating GLP-1RAs had a higher risk of requiring KRT than those initiating SGLT2 inhibitors (HR, 1.39; 95% CI, 1.19-1.63). Although tests of interaction did not have statistically significant findings, stratified analyses suggested possibly greater differences between the 2 drugs among patients with an estimated glomerular filtration rate<45mL/min/1.73m(2) or a urine albumin-creatinine ratio>300mg/g. Overall mortality did not differ between treatment groups. LIMITATIONS: Nonrandomized treatment selection. CONCLUSIONS: Patients receiving SGLT2 inhibitors exhibited lower rates of progression to KRT than those receiving GLP-1RAs. These findings may inform the choice of these therapies in the setting of chronic kidney disease and type 2 diabetes. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease is a major complication of type 2 diabetes that often leads to kidney failure and increased mortality. This study aimed to compare the effectiveness of 2 drug classes, glucagon-like peptide-1 receptor agonists and sodium/glucose cotransporter 2 inhibitors, in preventing kidney failure and death in patients with type 2 diabetes and chronic kidney disease. Using a nationwide health database in Taiwan, we applied rigorous statistical methods to balance differences between treatment groups and analyze outcomes. Our findings demonstrated that sodium/glucose cotransporter 2 inhibitors might be more effective than glucagon-like peptide-1 receptor agonists in reducing the risk of kidney failure, and possibly even more so in patients with advanced kidney disease. These results may inform the choice of these agents in the setting of chronic kidney disease and diabetes. CI - Copyright (c) 2025 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. FAU - Lee, Yen-Chieh AU - Lee YC AD - Department of Family and Community Medicine, Cathay General Hospital, National Taiwan University, Taipei, Taiwan. FAU - Wu, Li-Chiu AU - Wu LC AD - Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan; Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Chang, Chia-Hsuin AU - Chang CH AD - Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan; Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: chiahsuin123@yahoo.com.tw. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250429 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Kidney Failure, Chronic/prevention & control/mortality/etiology MH - *Renal Insufficiency, Chronic/mortality/complications/drug therapy MH - Taiwan/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glomerular Filtration Rate MH - *Diabetic Nephropathies MH - Cohort Studies OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitors OT - chronic kidney failure OT - cohort analysis OT - comparative effectiveness OT - kidney replacement therapy OT - mortality EDAT- 2025/05/02 00:27 MHDA- 2025/08/31 19:57 CRDT- 2025/05/01 19:30 PHST- 2024/09/20 00:00 [received] PHST- 2025/02/13 00:00 [revised] PHST- 2025/03/02 00:00 [accepted] PHST- 2025/08/31 19:57 [medline] PHST- 2025/05/02 00:27 [pubmed] PHST- 2025/05/01 19:30 [entrez] AID - S0272-6386(25)00831-5 [pii] AID - 10.1053/j.ajkd.2025.03.016 [doi] PST - ppublish SO - Am J Kidney Dis. 2025 Sep;86(3):301-313.e1. doi: 10.1053/j.ajkd.2025.03.016. Epub 2025 Apr 29. PMID- 40309769 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 9 DP - 2025 May 1 TI - GLP-1 receptor agonists for the treatment of alcohol use disorder. LID - 10.1172/JCI192414 [doi] LID - e192414 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are widely used in the treatment of metabolic disorders, including type 2 diabetes (T2D) and obesity. These medications primarily function by enhancing insulin secretion; however, emerging evidence suggests that the effects extend beyond metabolic regulation. In this issue of the JCI, Farokhnia et al. evaluated the effects of GLP-1RAs alongside another T2D treatment, dipeptidyl peptidase-4 inhibitors (DPP-4Is), on alcohol consumption in humans and preclinical models. In humans, GLP1-RAs, but not DPP-4Is, were associated with reductions in alcohol consumption. Similarly, DPP-4 inhibition had no effect on alcohol intake in rodents. These findings invite further exploration of the mechanisms by which GLP-1RAs reduce alcohol consumption and redefine our pharmacotherapy approach to alcohol use disorder (AUD) by opening the possibility for application as an early harm-reduction tool. FAU - Petrie, Gavin N AU - Petrie GN AD - Department of Psychiatry. AD - Mathison Centre for Mental Health Education and Research, and. AD - Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. FAU - Mayo, Leah M AU - Mayo LM AD - Department of Psychiatry. AD - Mathison Centre for Mental Health Education and Research, and. AD - Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. LA - eng PT - Comment PT - Journal Article DEP - 20250501 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM CON - Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Alcoholism/drug therapy/metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptides/therapeutic use MH - Mice MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12043078 COIS- Conflict of interest: The authors have declared that no conflict of interest exists. EDAT- 2025/05/01 12:29 MHDA- 2025/05/01 12:30 PMCR- 2025/05/01 CRDT- 2025/05/01 06:03 PHST- 2025/05/01 12:30 [medline] PHST- 2025/05/01 12:29 [pubmed] PHST- 2025/05/01 06:03 [entrez] PHST- 2025/05/01 00:00 [pmc-release] AID - 192414 [pii] AID - 10.1172/JCI192414 [doi] PST - epublish SO - J Clin Invest. 2025 May 1;135(9):e192414. doi: 10.1172/JCI192414. eCollection 2025 May 1. PMID- 40306364 OWN - NLM STAT- MEDLINE DCOM- 20250727 LR - 20250727 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 31 IP - 8 DP - 2025 Aug TI - Glucagon-like Peptide-1 Receptor Agonists Are Associated With Improved Survival and Reduced Liver-Related Events in Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Liver Disease: A Large Real-World Retrospective Study. PG - 1025-1032 LID - S1530-891X(25)00136-3 [pii] LID - 10.1016/j.eprac.2025.04.017 [doi] AB - OBJECTIVES: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or pioglitazone (PGZ) are associated with improved survival, reduced liver-related outcomes (LROs), and better metabolic outcomes in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD) or steatohepatitis (MASH). METHODS: We used the TriNetX platform to identify adults with T2DM and MASLD/MASH from 2006 onward (n = 558 075) using Internation Classification of Diseases codes. Patients with confounding liver diseases, overlapping study medications, or bariatric surgery were excluded. Three exclusive cohorts-GLP-1 RA, PGZ, and other antidiabetic agents (controls)-were formed. After 1:1 propensity score matching, time-to-event analyses were performed using Cox proportional hazards models and Kaplan-Meier methods. RESULTS: Among matched groups, GLP-1 RAs (n = 17 465) were associated with a 40.9% reduction in all-cause mortality versus controls (hazard ratio [HR] 0.59; P < .0001) and significantly lower rates of LRO (HR 0.77) and liver transplantation (HR 0.33). In contrast, PGZ (n = 1803) showed reduced LRO rates (HR 0.68) but not mortality. In cirrhotic patients, GLP-1 RA was linked to fewer transplant events but did not significantly reduce mortality. GLP-1 RA therapy noted greater reductions in body mass index and hemoglobin A1c relative to controls. CONCLUSIONS: In this large real-world cohort, GLP-1 RA use was associated with improved survival and hepatic outcomes in T2DM patients with MASLD/MASH, particularly among those without established cirrhosis. PGZ exhibited hepatic benefits. These findings highlight the potential importance of further prospective studies to evaluate early GLP-1 RA therapy in this high-risk diabetic population with MASLD/MASH. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Liu, Benjamin D AU - Liu BD AD - Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio. FAU - Aly, Mohammed AU - Aly M AD - Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. FAU - Hsin-Ti Lin, Cindy AU - Hsin-Ti Lin C AD - Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio. FAU - Panesar, Noordeep AU - Panesar N AD - Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio. FAU - Hill, Hannah AU - Hill H AD - Population Health and Equity Research Institute, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio. FAU - Qureshi, Kamran AU - Qureshi K AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri. Electronic address: kamran.qureshi@slu.edu. LA - eng PT - Journal Article DEP - 20250428 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Pioglitazone/therapeutic use MH - *Liver Diseases/mortality/etiology/drug therapy MH - Adult OTO - NOTNLM OT - GLP-1 receptor agonist OT - metabolic dysfunction-associated liver disease (MASLD) OT - metabolic dysfunction-associated steatohepatitis (MASH) OT - pioglitazone OT - real-world study OT - type 2 diabetes mellitus COIS- Disclosure Kamran Qureshi declares honoraria received from Gilead Sciences, Intercept Pharmaceuticals, Salix Pharmaceuticals, Madrigal Pharmaceuticals, and Phathom Pharmaceuticals for speaking engagements, which are unrelated to the submitted work. EDAT- 2025/05/01 00:27 MHDA- 2025/07/28 08:45 CRDT- 2025/04/30 19:31 PHST- 2025/01/26 00:00 [received] PHST- 2025/03/24 00:00 [revised] PHST- 2025/04/22 00:00 [accepted] PHST- 2025/07/28 08:45 [medline] PHST- 2025/05/01 00:27 [pubmed] PHST- 2025/04/30 19:31 [entrez] AID - S1530-891X(25)00136-3 [pii] AID - 10.1016/j.eprac.2025.04.017 [doi] PST - ppublish SO - Endocr Pract. 2025 Aug;31(8):1025-1032. doi: 10.1016/j.eprac.2025.04.017. Epub 2025 Apr 28. PMID- 40305684 OWN - NLM STAT- MEDLINE DCOM- 20250627 LR - 20250707 IS - 1538-6724 (Electronic) IS - 0031-9023 (Print) IS - 0031-9023 (Linking) VI - 105 IP - 6 DP - 2025 Jun 2 TI - Transforming Care: Implications of Glucagon Like Peptide-1 Receptor Agonists on Physical Therapist Practice. LID - 10.1093/ptj/pzaf061 [doi] LID - pzaf061 AB - The goal of this perspective is to bring awareness to the prevalence of glucagon-like peptide 1 receptor agonist (GLP-1 agonist) use, medication side effects, intervention considerations, and the role of the physical therapist in supporting their patients in their health journey when taking these medications. Management of obesity and diabetes is undergoing significant change with the increasing prevalence of GLP-1 agonist medications. This class of medications, which 1-in-8 adults in the United States report having taken, is becoming a critical component of obesity management, affecting the physiology and psychology of weight loss in novel ways. Due to the prevalence of musculoskeletal conditions in patients with diabetes and obesity, physical therapists can play a crucial role in the comprehensive care of patients on GLP-1 agonist therapy. This perspective explores the practice implications for managing patients living with obesity and/or diabetes who are taking GLP-1 agonists by describing the impact of GLP-1 agonists; the challenges of GLP-1 agonist use; and the considerations for recommending physical activity to patients using these medications. Physical therapists are well equipped to assist this population of patients by implementing strategies that enhance mobility, alleviate pain, prevent injury, mitigate lean muscle mass loss, and promote metabolic health, while adapting to the evolution of health and function patients experience while on GLP-1 agonist medications. As use of these drugs is expected to expand to other health conditions, there is a pressing need for physical therapists to adapt their practices to support the long-term health goals of their patients and ensure optimal patient outcomes. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the American Physical Therapy Association. FAU - Mulcahy, Julie AU - Mulcahy J AUID- ORCID: 0009-0009-2618-0971 AD - Clinical MSK, Omada Health, San Francisco, CA, United States. FAU - DeLaRosby, Anna AU - DeLaRosby A AUID- ORCID: 0009-0003-9040-0015 AD - Physera Physical Therapy Group, San Mateo, CA, United States. FAU - Norwood, Todd AU - Norwood T AUID- ORCID: 0000-0001-7231-3055 AD - Clinical MSK, Omada Health, San Francisco, CA, United States. LA - eng PT - Journal Article PT - Review PL - United States TA - Phys Ther JT - Physical therapy JID - 0022623 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Physical Therapists MH - *Physical Therapy Modalities MH - Diabetes Mellitus/drug therapy PMC - PMC12203058 OTO - NOTNLM OT - Cardiovascular Diseases OT - Diabetes Mellitus OT - GLP-1 OT - Medication Side Effects OT - Obesity OT - Patient Care OT - Pharmacology OT - Physical Therapists OT - Resistance Training OT - Weight Loss EDAT- 2025/04/30 18:30 MHDA- 2025/06/27 12:30 PMCR- 2025/04/30 CRDT- 2025/04/30 15:43 PHST- 2024/09/06 00:00 [received] PHST- 2025/02/27 00:00 [revised] PHST- 2025/03/14 00:00 [accepted] PHST- 2025/06/27 12:30 [medline] PHST- 2025/04/30 18:30 [pubmed] PHST- 2025/04/30 15:43 [entrez] PHST- 2025/04/30 00:00 [pmc-release] AID - 8123337 [pii] AID - pzaf061 [pii] AID - 10.1093/ptj/pzaf061 [doi] PST - ppublish SO - Phys Ther. 2025 Jun 2;105(6):pzaf061. doi: 10.1093/ptj/pzaf061. PMID- 40301134 OWN - NLM STAT- MEDLINE DCOM- 20260222 LR - 20261009 IS - 1573-501X (Electronic) IS - 1381-1991 (Linking) VI - 30 IP - 1 DP - 2026 Feb TI - GLP-1R agonists: recent advances, current gaps, and future challenges. PG - 101-112 LID - 10.1007/s11030-025-11195-6 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) emerged as a promising class of drugs and have been shown to be effective as a key regulator in managing glucose metabolism-associated diseases such as type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), cardiovascular effects, nephrological complications, diabetes, non-alcoholic fatty liver (NAFLD), as well as to control obesity. A few drugs included in GLP-1RA class are liraglutide, exenatide, and semaglutide. Most recent drug that is available in both oral and subcutaneous forms is semaglutide. Available, withdrawn, and investigational GLP-RAs are listed in this paper. This review article will also explore common side effects and safety profiles of both long-acting and short-acting GLP-1 RAs. Additionally, it will highlight the recent advances and ongoing challenges in the field of drug discovery related to GLP-1 receptor agonists. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Saran, Anukriti AU - Saran A AD - Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. anukritisaransingh@gmail.com. FAU - Raisinghani, Riya AU - Raisinghani R AD - Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. FAU - Paliwal, Sarvesh AU - Paliwal S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. FAU - Sharma, Swapnil AU - Sharma S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. LA - eng PT - Journal Article PT - Review DEP - 20250429 PL - Netherlands TA - Mol Divers JT - Molecular diversity JID - 9516534 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Liraglutide/therapeutic use OTO - NOTNLM OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 receptor OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declared that they have no conflict of interest. Ethical approval: As this submission is a review article ,it does not involve humans and animals, and no ethical approval was required for this publication. EDAT- 2025/04/30 00:31 MHDA- 2026/02/22 15:52 CRDT- 2025/04/29 23:13 PHST- 2025/02/06 00:00 [received] PHST- 2025/04/11 00:00 [accepted] PHST- 2026/02/22 15:52 [medline] PHST- 2025/04/30 00:31 [pubmed] PHST- 2025/04/29 23:13 [entrez] AID - 10.1007/s11030-025-11195-6 [pii] AID - 10.1007/s11030-025-11195-6 [doi] PST - ppublish SO - Mol Divers. 2026 Feb;30(1):101-112. doi: 10.1007/s11030-025-11195-6. Epub 2025 Apr 29. PMID- 40301081 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20250512 IS - 1881-784X (Electronic) IS - 1881-7831 (Linking) VI - 19 IP - 2 DP - 2025 May 9 TI - Effects of patient age on the therapeutic effects of GIP/GLP-1 receptor agonists (tirzepatide). PG - 133-135 LID - 10.5582/ddt.2025.01012 [doi] AB - Glucagon-like peptide-1 receptor agonist (GLP-1RA) has attracted attention owing to its hypoglycemic and weight-loss effects, and various dosage forms are available in the market. Recently, glucose-dependent insulin secretion-stimulating polypeptide (GIP), an incretin hormone in the same family as GLP-1, has attracted attention, and tirzepatide, a GIP/GLP-1RA, has been launched. Given the short duration of tirzepatide on the market and the fact that its therapeutic effects in patients of different ages have not been reported, we conducted this study. HbA1c improved significantly in patients aged >/= 65 years, whereas HbA1c, weight, and LDL cholesterol also improved significantly in patients aged 5% weight loss correlated with higher baseline levels of miR-15a-5p. Preclinical findings suggested GLP-1RA monotherapy increased cardiovascular action via non-exosomal miR-29b-3p, miR-34a-5p, miR-26a-5p, miR-181a-5p, and miR-93-5p. Silencing non-exosomal miR-204, miR-375, or miR-139-5p augmented exendin-4/liraglutide monotherapy-induced glucose-stimulated insulin secretion. Interestingly, GLP-1RA monotherapy reduced hepatic lipid accumulation in T2DM models with comorbid NAFLD via ABHD6 mRNA modulation by non-exosomal miR-5120. No clinical studies reported exosomal miRNAs, but a preclinical study linked GLP-1RA-induced exosomal let-7c-2-3p/miR-322-3p to bone protection in estrogen-deficient T2DM models. CONCLUSION: GLP-1RAs, both as first-line and second-line therapies, are beneficial for T2DM complicated by obesity, NAFLD, cardio-metabolic disease, and postmenopausal osteoporosis. Longitudinal trials that incorporate innovative multi-omics approaches are essential for distinguishing their miRNA expression pattern from other anti-diabetics. CI - (c) 2025. The Author(s). FAU - Yu, Haifeng AU - Yu H AD - Hubei Key Laboratory of Diabetes and Angiopathy, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, Hubei Province, China. FAU - Davoudi, Maryam AU - Davoudi M AD - Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. FAU - Sadegh-Nejadi, Sahar AU - Sadegh-Nejadi S AD - Department of Clinical Laboratory, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Miao, Xiaolei AU - Miao X AD - Hubei Key Laboratory of Diabetes and Angiopathy, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, Hubei Province, China. 345701500@qq.com. FAU - Bagherieh, Molood AU - Bagherieh M AD - Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran. Baqeriyeh@gmail.com. FAU - Afrisham, Reza AU - Afrisham R AUID- ORCID: 0000-0001-8064-118X AD - Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. rafrisham@sina.tums.ac.ir. LA - eng GR - Q201810/Department of Science and Technology, Hubei Provincial People's Government/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20250425 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9100L32L2N (Metformin) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - Drug Therapy, Combination MH - *Exosomes/drug effects/genetics/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Metformin/therapeutic use MH - *MicroRNAs/drug effects/genetics/metabolism PMC - PMC12032824 OTO - NOTNLM OT - Drug therapy, combination OT - Exosomes OT - Glucagon-like peptide-1 receptor agonists OT - MicroRNAs OT - Monotherapy OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Not Applicable. Consent of publication: Not Applicable. Competing interests: The authors have no conflict of interest. Disclosure: Declaration of AI-assisted technologies in the writing process: during the preparation of this review, the authors used ChatGPT to check the grammar and improve readability. After using the tools, we reviewed and edited the content as needed and took full responsibility for the content presented in the publication. EDAT- 2025/04/26 16:15 MHDA- 2025/04/26 16:16 PMCR- 2025/04/25 CRDT- 2025/04/25 23:45 PHST- 2025/01/13 00:00 [received] PHST- 2025/04/06 00:00 [accepted] PHST- 2025/04/26 16:16 [medline] PHST- 2025/04/26 16:15 [pubmed] PHST- 2025/04/25 23:45 [entrez] PHST- 2025/04/25 00:00 [pmc-release] AID - 10.1186/s12967-025-06461-y [pii] AID - 6461 [pii] AID - 10.1186/s12967-025-06461-y [doi] PST - epublish SO - J Transl Med. 2025 Apr 25;23(1):477. doi: 10.1186/s12967-025-06461-y. PMID- 40281304 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20260311 IS - 1474-1784 (Electronic) IS - 1474-1776 (Linking) VI - 24 IP - 8 DP - 2025 Aug TI - GLP-1-based therapies for diabetes, obesity and beyond. PG - 631-650 LID - 10.1038/s41573-025-01183-8 [doi] AB - Glucagon-like peptide 1 (GLP-1)-based therapies, such as semaglutide and tirzepatide, represent highly effective treatment options for people with type 2 diabetes and obesity, enabling effective control of glucose and weight loss, while reducing cardiovascular and renal morbidity and mortality. The success of these medicines has spurred development of next-generation GLP-1-based drugs, promising greater weight loss, improved tolerability and additional options for the route and frequency of dosing. This Review profiles established and emerging GLP-1-based medicines, discussing optimization of pharmacokinetics and tolerability, engagement of new therapeutically useful pathways and safety aspects. Structurally unique GLP-1-based medicines that achieve substantially greater and rapid weight loss may impact musculoskeletal health, providing a rationale for therapeutics that more selectively target adipose tissue loss while preserving muscle mass and strength. Ongoing clinical trials in peripheral vascular disease, neuropsychiatric and substance use disorders, metabolic liver disease, arthritis, hypertension and neurodegenerative disorders may broaden indications for GLP-1-based therapeutics. CI - (c) 2025. Springer Nature Limited. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Department of Medicine and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. drucker@lunenfeld.ca. LA - eng PT - Journal Article PT - Review DEP - 20250425 PL - England TA - Nat Rev Drug Discov JT - Nature reviews. Drug discovery JID - 101124171 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Nat Rev Drug Discov. 2025 Jul;24(7):570. doi: 10.1038/s41573-025-01231-3. PMID: 40437221 MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Glucagon-Like Peptide 1/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Animals MH - Weight Loss/drug effects MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Semaglutide COIS- Competing interests: D.J.D. has received consulting fees from Amgen, AstraZeneca Inc., Insulet, Kallyope and Pfizer Inc. and speaking fees from Boehringer Ingelheim and Novo Nordisk Inc. Mount Sinai Hospital has received investigator-initiated grant support from Amgen, Eli Lilly Inc., Novo Nordisk, Pfizer and Zealand Pharmaceuticals Inc. to support preclinical studies in the Drucker laboratory. EDAT- 2025/04/26 16:17 MHDA- 2025/08/02 10:43 CRDT- 2025/04/25 23:33 PHST- 2025/03/13 00:00 [accepted] PHST- 2025/08/02 10:43 [medline] PHST- 2025/04/26 16:17 [pubmed] PHST- 2025/04/25 23:33 [entrez] AID - 10.1038/s41573-025-01183-8 [pii] AID - 10.1038/s41573-025-01183-8 [doi] PST - ppublish SO - Nat Rev Drug Discov. 2025 Aug;24(8):631-650. doi: 10.1038/s41573-025-01183-8. Epub 2025 Apr 25. PMID- 40280862 OWN - NLM STAT- MEDLINE DCOM- 20250603 LR - 20250604 IS - 1879-3061 (Electronic) IS - 1043-2760 (Linking) VI - 36 IP - 6 DP - 2025 Jun TI - Promising results but caution needed in GLP-1RA large scale epidemiology. PG - 504-506 LID - S1043-2760(25)00075-X [pii] LID - 10.1016/j.tem.2025.03.015 [doi] AB - Investigating the association between glucagon-like peptide 1 receptor agonists (GLP1-RAs) and incident disease across 175 health outcomes in US Veterans with diabetes, Xie et al. recently reported lower risk for cardiokidney disease and substance use disorders, but higher risk for pancreatitis, gastrointestinal disorders, and arthritis. However, many apparent novel findings need testing or validation in randomized trials. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Deo, Salil V AU - Deo SV AD - Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Case School of Medicine, Case Western Reserve University, Cleveland, OH, USA; School of Health and Wellbeing, University of Glasgow, Glasgow, UK. Electronic address: svd14@case.edu. FAU - Sattar, Naveed A AU - Sattar NA AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk. LA - eng PT - Journal Article DEP - 20250424 PL - United States TA - Trends Endocrinol Metab JT - Trends in endocrinology and metabolism: TEM JID - 9001516 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - cardiometabolic disease OT - cardiovascular outcome trials OT - glucagon-like peptide 1 receptor agonist OT - obesity OT - real-world evidence COIS- Declaration of interest N.A.S. reports personal fees from Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi; and grant funding paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics, outside the submitted work. S.V.D. receives research support from Johnson and Johnson outside the submitted work. EDAT- 2025/04/26 16:14 MHDA- 2025/06/04 00:29 CRDT- 2025/04/25 22:03 PHST- 2025/03/12 00:00 [received] PHST- 2025/03/28 00:00 [revised] PHST- 2025/03/31 00:00 [accepted] PHST- 2025/06/04 00:29 [medline] PHST- 2025/04/26 16:14 [pubmed] PHST- 2025/04/25 22:03 [entrez] AID - S1043-2760(25)00075-X [pii] AID - 10.1016/j.tem.2025.03.015 [doi] PST - ppublish SO - Trends Endocrinol Metab. 2025 Jun;36(6):504-506. doi: 10.1016/j.tem.2025.03.015. Epub 2025 Apr 24. PMID- 40279144 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 6 DP - 2025 Jun 1 TI - High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial. PG - 905-913 LID - 10.2337/dc24-2425 [doi] AB - OBJECTIVE: Studies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg/week) in people with type 2 diabetes and overweight or obesity. RESEARCH DESIGN AND METHODS: In this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI >/=27 kg/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.c.) or placebo for 40 weeks. Doses were escalated every 4 weeks, followed by a maintenance period. Dose modifications were not allowed. Primary and secondary efficacy end points included change from baseline to week 40 in HbA1c and body weight, respectively. RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand. Dose-response modeling confirmed these findings. Treatment-emergent adverse events (AEs) and treatment discontinuations due to AEs, primarily gastrointestinal, were more frequent in the semaglutide 8 and 16 mg groups than in the 2 mg group. No severe hypoglycemic episodes were reported. CONCLUSIONS: Higher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway. CI - (c) 2025 by the American Diabetes Association. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Jorgensen, Nils B AU - Jorgensen NB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kumar, Bharath AU - Kumar B AD - Biostatistics, Novo Nordisk Service Centre India Private Ltd., Bangalore, India. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Laulund, Anne Sofie AU - Laulund AS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. CN - trial investigators LA - eng GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - UM1 TR004406/TR/NCATS NIH HHS/United States GR - Novo Nordisk/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Female MH - Male MH - *Obesity/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Overweight/drug therapy MH - Aged MH - Glycated Hemoglobin/metabolism MH - Adult MH - Metformin/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12094194 COIS- Funding and Duality of Interest. The trial was funded by Novo Nordisk A/S. Representatives of the sponsor (Novo Nordisk A/S) were involved in the study design; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript; those who meet authorship criteria are included in the author group, and other contributors are acknowledged. A medical writer (employed by the sponsor) assisted with editing the manuscript, under the direction of the authors. As noted below, all authors received some form of compensation from Novo Nordisk A/S during the design and execution phases of the trial. N.B.J. and A.S.L. are employees of Novo Nordisk A/S, and B.K. is an employee at Novo Nordisk Service Centre India Private Ltd. N.B.J. is a stockholder of Novo Nordisk A/S and Eli Lilly. A.S.L. is a stockholder of Novo Nordisk A/S. J.B.B. was supported by grants from the National Institutes of Health (National Center for Advancing Translational Sciences Clinical and Translational Science Award UM1TR004406 and National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center Award P30DK124723). V.R.A. reports institutional contracts with or grants from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Fractyl Health, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, and Servier and consultant contracts with Fractyl Health, Mediflix, Novo Nordisk, Pfizer, and Sanofi. J.B.B. reports that fees for contracted activities are paid to the University of North Carolina at Chapel Hill by Novo Nordisk for efforts of J.B.B. as an investigator, consultant, and expert witness; reports grant support from Bayer, Boehringer Ingelheim, Carmot Therapeutics, Corcept Therapeutics, Dexcom, Eli Lilly, Fractyl Health, Insulet, MannKind, and vTv Therapeutics; reports consulting fees from Alkahest, Altimmune, American Diabetes Association, Anji Pharmaceuticals, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Mediflix, Medscape, Medtronic MiniMed, Mellitus Health, Metsera, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Tandem Diabetes Care, Terns Pharmaceuticals, and Vertex Pharmaceuticals; reports payment for presentations from Boehringer Ingelheim; reports payment for expert testimony from Medtronic MiniMed; reports stock options from Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Praetego, and Stability Health; and reports serving on the scientific advisory board for Dasman Diabetes Center, Kuwait City, Kuwait. I.L. received research funding (paid to institution) from Novo Nordisk, Sanofi, and Boehringer Ingelheim; received research-related consulting fees (paid to institution) from Novo Nordisk; and received advisory/consulting fees and/or other support from AbbVie, Altimmune, AstraZeneca, Bayer, Betagenon AB, BIOIO, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Cytoki Pharma, Eli Lilly, Intercept, Janssen/Johnson & Johnson, Juvena Therapeutics, Keros Therapeutics, Mediflix, Merck, Metsera, Novo Nordisk, PharmaVentures, Pfizer, Regeneron Pharmaceuticals, Sanofi, Shionogi, Structure Therapeutics, Target RWE, Terns Pharmaceuticals, The Comm Group, WebMD, and Zealand Pharma. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/04/25 13:47 MHDA- 2025/05/21 18:29 PMCR- 2025/04/25 CRDT- 2025/04/25 11:42 PHST- 2024/11/05 00:00 [received] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/04/25 13:47 [pubmed] PHST- 2025/04/25 11:42 [entrez] PHST- 2025/04/25 00:00 [pmc-release] AID - 158206 [pii] AID - dc242425 [pii] AID - 10.2337/dc24-2425 [doi] PST - ppublish SO - Diabetes Care. 2025 Jun 1;48(6):905-913. doi: 10.2337/dc24-2425. PMID- 40277315 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260918 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 4 DP - 2025 May TI - Long-Term Effectiveness of Once-Weekly Semaglutide in Patients With Type 2 Diabetes Previously Treated With Insulin. A Multicentre Real-World Study. PG - e70045 LID - 10.1002/dmrr.70045 [doi] LID - e70045 AB - BACKGROUND: The introduction of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has provided new avenues for managing type 2 diabetes (T2D), aiming to achieve optimal glycaemic control while minimising treatment burden. We conducted a multicentre retrospective real-world study to assess the effectiveness of semaglutide once-weekly (OW) in patients previously treated with insulin. METHODS: We included individuals with T2D who were on insulin (basal and/or bolus) and initiated OW semaglutide at 18 specialist care centres. We collected retrospective data on baseline clinical characteristics and updated values of HbA1c and body weight. The primary outcome was the change in HbA1c analysed using the mixed model for repeated measures. Secondary outcomes included the changes in body weight, insulin discontinuation and the change in insulin doses. RESULTS: The study included 674 individuals. At baseline, participants were 61.7 years old, with a mean diabetes duration of 11.5 years and an HbA1c of 8.2%. During a median follow-up of 18 months, OW semaglutide initiation led to a significant reduction in HbA1c (-0.9%) and body weight (-4.3 kg), with 60% of patients achieving HbA1c < 7%. 32.8% of patients discontinued insulin therapy, 72.5% of whom achieved an HbA1c < 7%. Among patients on basal-bolus insulin, 75% completely discontinued bolus, 62% of whom achieved an HbA1c < 7%. Predictors of insulin discontinuation included shorter diabetes duration, lower baseline HbA1c, and lower insulin doses. Among patients who remained on insulin, initiation of OW semaglutide was associated with a decrease in total daily insulin requirement. CONCLUSION: Our study highlights OW semaglutide as a valuable addition to a T2D regimen based on insulin, offering effective glycaemic and weight control with the potential for insulin deintensification or discontinuation. CI - (c) 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Bonora, Benedetta Maria AU - Bonora BM AUID- ORCID: 0000-0002-6770-2723 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Giaccari, Andrea AU - Giaccari A AUID- ORCID: 0000-0002-7462-7792 AD - Endocrine and Metabolic Center, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Consoli, Agostino AU - Consoli A AUID- ORCID: 0000-0002-1885-451X AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy. AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Broglio, Fabio AU - Broglio F AD - Division of Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. CN - GLIMPLES Study Investigators LA - eng GR - Societa italiana di diabetologia/ PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Biomarkers/analysis MH - Blood Glucose/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/pathology MH - Drug Administration Schedule MH - Follow-Up Studies MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Insulin/therapeutic use MH - Prognosis MH - Retrospective Studies MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12023824 OTO - NOTNLM OT - body weight OT - glucose control OT - real-world effectiveness OT - retrospective study OT - semaglutide OT - type 2 diabetes COIS- B.M.B. received lecture or advisory board fees from AstraZeneca, Boehringer-Ingelheim, Lilly, MSD, Sanofi, Servier and Novo-Nordisk. A.G. has received lecture fees from AstraZeneca, Lilly and Novo Nordisk. A.C. received grants from AstraZeneca, Lilly, Novo-Nordisk. He also received speaker fees, and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dhome, Menarini, Novo-Nordisk, Sanofi, Sigma-Tau and Takeda. F.B. received lecture fees from Lilly and Novo-Nordisk. A.A. received research grants and lecture or advisory board fees from MSD, AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier and Takeda. G.P.F. received advisory board grants, honoraria or lecture fees from Abbott, AstraZeneca, Boehringer, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier and Takeda. EDAT- 2025/04/25 13:45 MHDA- 2025/04/25 13:46 PMCR- 2025/04/25 CRDT- 2025/04/25 08:33 PHST- 2025/02/10 00:00 [revised] PHST- 2024/06/11 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2025/04/25 13:46 [medline] PHST- 2025/04/25 13:45 [pubmed] PHST- 2025/04/25 08:33 [entrez] PHST- 2025/04/25 00:00 [pmc-release] AID - DMRR70045 [pii] AID - 10.1002/dmrr.70045 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 May;41(4):e70045. doi: 10.1002/dmrr.70045. PMID- 40275332 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260802 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Apr 24 TI - Real-world effectiveness of adding newer generation GLP-1RA to SGLT2i in type 2 diabetes. PG - 177 LID - 10.1186/s12933-025-02737-1 [doi] LID - 177 AB - BACKGROUND: Guidelines recommend combination therapy with glucagonlike peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) for cardiorenal risk reduction in people with type 2 diabetes (T2D); however, there is limited real-world evidence on the long-term effects of combination therapy on cardiometabolic and renal outcomes. The objective of this study was to assess cardiovascular (CV), metabolic, and renal effects of combination therapy with newer generation GLP-1RA (including once-weekly GLP-1RAs, once-daily oral semaglutide, and dual GLP-1/glucose-dependent insulinotropic polypeptide [GIP] agonists) and SGLT2i compared with SGLT2i alone. METHODS: This retrospective cohort study included data on US adults with T2D receiving SGLT2i from Komodo's Healthcare Map from January 1, 2017, to June 30, 2023. The study included 100,455 people in the combination GLP-1RA and SGLT2i group and 339,540 people in the comparison SGLT2i group across 3 cohorts: T2D with atherosclerotic cardiovascular disease (ASCVD), T2D, and T2D with chronic kidney disease (CKD). Entropy balancing was used to balance patient characteristics. Time to first event of ischemic stroke, myocardial infarction (MI), 3-point major adverse cardiovascular event (MACE), and 5-point MACE in T2D with ASCVD cohort were measured. In the T2D cohort, follow-up and change in glycated hemoglobin (HbA(1c)) and weight, odds of achieving HbA(1c) < 7% and HbA(1c) < 8%, and odds of achieving 5%, 10%, and 15% decrease in weight were also measured. RESULTS: The combination and comparison groups included 34,690 and 130,220 people, respectively, in the T2D with ASCVD cohort; 8,220 and 22,891 people, respectively, in the T2D cohort; and 8,783 and 35,532 people, respectively, in the T2D with CKD cohort. Compared with SGLT2i alone, combination therapy was significantly associated with 42% lower risk of ischemic stroke, 37% lower risk of MI, 46% lower risk of 3-point MACE, and 45% lower risk of 5-point MACE among people with T2D and ASCVD. Among the individual GLP-1RAs assessed, the largest reductions in CV risk, HbA(1c), and weight outcomes were observed with combination therapy with SGLT2i and once weekly semaglutide for T2D. CONCLUSIONS: Combination of SGLT2i and GLP-1RA achieved significantly better cardiometabolic outcomes compared with SGLT2i alone; this supports the hypothesis that the cardioprotective benefits of GLP-1RA and SGLT2i may be additive. CI - (c) 2025. The Author(s). FAU - Chaiyakunapruk, Nathorn AU - Chaiyakunapruk N AD - Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA. AD - IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, 507-2300 Eglinton Avenue West, Mississauga, ON, L5M 2V8, Canada. Alice.Cheng@unityhealth.to. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250424 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology/mortality MH - Retrospective Studies MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use/administration & dosage MH - Treatment Outcome MH - Middle Aged MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - *Incretins/adverse effects/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - *Blood Glucose/metabolism/drug effects MH - Biomarkers/blood MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology MH - United States/epidemiology MH - Risk Assessment MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12023599 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Chronic kidney disease OT - Combination therapy OT - Glucagonlike peptide-1 receptor agonist OT - Major adverse cardiovascular event OT - Sodium-glucose cotransporter 2 inhibitor OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: NC has nothing to disclose. XT, YL, MG, and LX are employees of Novo Nordisk Inc. AYYC received consulting/speaking honoraria from Abbott, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, GSK, HLS Therapeutics, Insulet, Janssen, Medtronic, Novo Nordisk, Pfizer, Sanofi, and Vertex. EDAT- 2025/04/25 01:21 MHDA- 2025/04/25 13:45 PMCR- 2025/04/24 CRDT- 2025/04/24 23:50 PHST- 2025/02/03 00:00 [received] PHST- 2025/04/09 00:00 [accepted] PHST- 2025/04/25 13:45 [medline] PHST- 2025/04/25 01:21 [pubmed] PHST- 2025/04/24 23:50 [entrez] PHST- 2025/04/24 00:00 [pmc-release] AID - 10.1186/s12933-025-02737-1 [pii] AID - 2737 [pii] AID - 10.1186/s12933-025-02737-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Apr 24;24(1):177. doi: 10.1186/s12933-025-02737-1. PMID- 40274278 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20250731 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 2 DP - 2025 Apr 23 TI - GLP-1 RA and dual GIP/GLP-1 RA treatment in MODY: a descriptive case series. LID - 10.1136/bmjdrc-2024-004885 [doi] LID - e004885 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dual glucose insulinotropic polypeptide (GIP)/GLP-1 RA are widely prescribed, but their effectiveness in different subtypes of maturity-onset diabetes of the young (MODY) is unknown. RESEARCH DESIGN AND METHODS: We present a descriptive case series of individuals from two MODY cohorts who used GLP-1 RA or dual GIP/GLP-1 RA. Paired t tests were used to compare HbA1c, body mass index (BMI), and sulfonylurea (SU) dose before and after GLP-1 RA or dual GIP/GLP-1 RA therapy. RESULTS: 10 individuals (4 hepatocyte nuclear factor-1alpha (HNF1A)-MODY, 4 hepatocyte nuclear factor-4alpha (HNF4A)-MODY, 1 ATP-binding cassette transporter subfamily C member 8 (ABCC8)-MODY, 1 hepatocyte nuclear factor-1beta (HNF1B)-MODY) were identified who used GLP-1 RA or dual GIP/GLP-1 RA. In patients with HNF1A-MODY and HNF4A-MODY, GLP-1 RA reduced HbA1c by 1.3% (p=0.010), BMI by 2.90 kg/m(2) (p=0.008), and total daily dose of SU by 66.6% (p=0.005). Dual GIP/GLP-1 RA treatment led to a non-statistically significant decrease in HbA1c of 1.8% (p=0.104), a statistically significant reduction in BMI of 8.73 kg/m(2) (p=0.010), and all patients discontinued SU (n=2) and one discontinued insulin. In patients with ABCC8-MODY and HNF1B-MODY, GLP-1 RA reduced HbA1c by 1.2% and 1.8%, BMI by 1.1 kg/m(2) and 1.2 kg/m(2), and the patients no longer required treatment with SU or insulin, respectively. CONCLUSIONS: GLP-1 RA and dual GIP/GLP-1 RA lowered HbA1c, BMI, and SU dose in patients with MODY. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Mehdi, Alina Z AU - Mehdi AZ AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Deng, Lily AU - Deng L AD - Division of Endocrinology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. FAU - Chase, Colby L AU - Chase CL AD - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Foss-Freitas, Maria Cristina AU - Foss-Freitas MC AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Gregg, Brigid AU - Gregg B AD - Department of Pediatrics, Division of Pediatric Endocrinology, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Naylor, Rochelle N AU - Naylor RN AD - Department of Pediatrics and Medicine, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, Illinois, USA. FAU - Oral, Elif A AU - Oral EA AUID- ORCID: 0000-0002-9171-1144 AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Herman, William H AU - Herman WH AUID- ORCID: 0000-0002-0502-674X AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Krishnamurthy, Mansa AU - Krishnamurthy M AUID- ORCID: 0000-0001-8178-0886 AD - Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. AD - Cincinnati Children's Hospital Medical Center. FAU - Broome, David T AU - Broome DT AUID- ORCID: 0000-0002-4964-7716 AD - Department of Metabolism, Endocrinology and Diabetes (MEND), University of Michigan Michigan Medicine, Ann Arbor, Michigan, USA broomeda@med.umich.edu. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20250423 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Sulfonylurea Compounds) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - Mason-Type Diabetes SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/pathology MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - Middle Aged MH - Body Mass Index MH - Sulfonylurea Compounds/therapeutic use MH - Biomarkers/analysis MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1 MH - Follow-Up Studies MH - Prognosis PMC - PMC12020758 OTO - NOTNLM OT - Diabetes Mellitus, Experimental OT - Genetics OT - Glucagon-Like Peptide 1 OT - Glycated Hemoglobin A COIS- Competing interests: DTB, MFdF, EAO and BEG receive grant support from the Caswell Diabetes Institute and from the National Institutes of Health (grant U54DK118612-04). EAO and MFdF are funded by the National Institutes of Health (grant R01DK125513). Duality of Interest. DTB is a research investigator for Fractyl Health Laboratories, Sanofi, the Type 1 Diabetes Exchange (T1DX-QI), and Rhythm Pharmaceuticals. MFdF is an advisory board member for PTC Pharmaceuticals and was a scientific presenter in a symposium funded by Amryt Pharmaceuticals. EAO has received grant support from Aegerion Pharmaceuticals (manufacturer of metreleptin), Akcea Therapeutics, Ionis Pharmaceuticals, Gemphire Therapeutics, Novo Nordisk, Rhythm Pharmaceuticals, Fractyl Health Laboratories and GI Dynamics. EAO has served as an advisor and/or a consultant to Aegerion Pharmaceuticals, Akcea Therapeutics, Ionis Pharmaceuticals, and Regeneron. EAO has royalty rights from the use of metreleptin in lipodystrophy. WHH is on data safety and monitoring boards for Merck Sharp & Dohme and Rivus Pharmaceuticals. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/04/25 01:20 MHDA- 2025/04/25 17:04 PMCR- 2025/04/23 CRDT- 2025/04/24 20:33 PHST- 2025/01/02 00:00 [received] PHST- 2025/04/07 00:00 [accepted] PHST- 2025/04/25 17:04 [medline] PHST- 2025/04/25 01:20 [pubmed] PHST- 2025/04/24 20:33 [entrez] PHST- 2025/04/23 00:00 [pmc-release] AID - 13/2/e004885 [pii] AID - bmjdrc-2024-004885 [pii] AID - 10.1136/bmjdrc-2024-004885 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Apr 23;13(2):e004885. doi: 10.1136/bmjdrc-2024-004885. PMID- 40269414 OWN - NLM STAT- MEDLINE DCOM- 20250424 LR - 20260512 IS - 1538-7488 (Electronic) IS - 0002-936X (Linking) VI - 125 IP - 5 DP - 2025 May 1 TI - GLP-1 Receptor Agonists Show Promise Beyond Diabetes and Weight Loss. PG - 16 LID - 10.1097/AJN.0000000000000074b [doi] AB - Researchers see benefits for addiction and obesity-related disorders. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Roush, Karen AU - Roush K LA - eng PT - Journal Article DEP - 20250424 PL - United States TA - Am J Nurs JT - The American journal of nursing JID - 0372646 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use EDAT- 2025/04/24 06:27 MHDA- 2025/04/24 12:29 CRDT- 2025/04/24 00:15 PHST- 2025/04/24 12:29 [medline] PHST- 2025/04/24 06:27 [pubmed] PHST- 2025/04/24 00:15 [entrez] AID - 00000446-202505000-00008 [pii] AID - 10.1097/AJN.0000000000000074b [doi] PST - ppublish SO - Am J Nurs. 2025 May 1;125(5):16. doi: 10.1097/AJN.0000000000000074b. Epub 2025 Apr 24. PMID- 40268291 OWN - NLM STAT- MEDLINE DCOM- 20250715 LR - 20260424 IS - 2287-285X (Electronic) IS - 2287-2728 (Print) IS - 2287-2728 (Linking) VI - 31 IP - 3 DP - 2025 Jul TI - Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study. PG - 1084-1099 LID - 10.3350/cmh.2024.1096 [doi] AB - BACKGROUND/AIMS: Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes. METHODS: Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative Marketscan(R) Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39-0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86-0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86-0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64-0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77-0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60-0.77. CONCLUSION: In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications. FAU - Mao, Xianhua AU - Mao X AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong. FAU - Zhang, Xinrong AU - Zhang X AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. FAU - Lai, Rongtao AU - Lai R AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. AD - Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Cheung, Ka-Shing AU - Cheung KS AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong. FAU - Yuen, Man-Fung AU - Yuen MF AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong. AD - State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong. FAU - Cheung, Ramsey AU - Cheung R AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. AD - Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA. FAU - Seto, Wai-Kay AU - Seto WK AD - Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong. AD - State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong. AD - Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Nguyen, Mindie H AU - Nguyen MH AD - Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. AD - Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA. LA - eng GR - UL1 TR003142/TR/NCATS NIH HHS/United States GR - UL-1TR003142/National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award/ GR - University of Hong Kong/ GR - Internal Stanford/ PT - Journal Article DEP - 20250423 PL - Korea (South) TA - Clin Mol Hepatol JT - Clinical and molecular hepatology JID - 101586730 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM CIN - Clin Mol Hepatol. 2026 Mar;32(2):e163-e164. doi: 10.3350/cmh.2025.0583. PMID: 40485099 CIN - Clin Mol Hepatol. 2026 Apr;32(2):924-927. doi: 10.3350/cmh.2025.0628. PMID: 40551542 CIN - Clin Mol Hepatol. 2026 Apr;32(2):e165-e166. doi: 10.3350/cmh.2025.0620. PMID: 40690958 CIN - Clin Mol Hepatol. 2026 Apr;32(2):e167-e169. doi: 10.3350/cmh.2025.0676. PMID: 40825722 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Liver Neoplasms/epidemiology/prevention & control/etiology MH - Aged MH - Carcinoma, Hepatocellular/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - *Fatty Liver/complications/drug therapy MH - Liver Cirrhosis/epidemiology MH - Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - Adult MH - Renal Insufficiency, Chronic/epidemiology MH - Incidence MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC12260620 OTO - NOTNLM OT - Cardiovascular disease OT - Fatty liver OT - Liver cancer OT - Metabolic dysfunction-associated steatotic liver disease OT - Non-alcoholic fatty liver disease COIS- Conflicts of Interest MHN received research grants via Stanford University from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest and personal fees from consulting/advisory board from Intercept, Exact Science, Gilead, GSK. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche, and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. WKS received speaker's fees and is an advisory board member of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, received speaker's fees and received research funding from AstraZeneca, and is an advisory board member, received speaker's fees and researching funding from Gilead Sciences. The other authors have nothing to disclose. EDAT- 2025/04/24 00:27 MHDA- 2025/07/15 06:27 PMCR- 2025/07/01 CRDT- 2025/04/23 19:58 PHST- 2024/12/05 00:00 [received] PHST- 2025/04/21 00:00 [accepted] PHST- 2025/07/15 06:27 [medline] PHST- 2025/04/24 00:27 [pubmed] PHST- 2025/04/23 19:58 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - cmh.2024.1096 [pii] AID - cmh-2024-1096 [pii] AID - 10.3350/cmh.2024.1096 [doi] PST - ppublish SO - Clin Mol Hepatol. 2025 Jul;31(3):1084-1099. doi: 10.3350/cmh.2024.1096. Epub 2025 Apr 23. PMID- 40265328 OWN - NLM STAT- MEDLINE DCOM- 20250724 LR - 20250729 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 15 IP - 4 DP - 2025 Aug TI - Effect of glucagon-like peptide 1 receptor agonists on systolic blood pressure in patients with obesity, with or without diabetes: A systematic review and network meta-analysis. PG - e70012 LID - 10.1111/cob.70012 [doi] LID - e70012 AB - The effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on systolic blood pressure (SBP) in patients with obesity with or without diabetes remains unclear. The aim was to compare the effect of different drug-dose combinations of GLP-1RAs on SBP. The secondary aim was to assess whether changes in SBP with GLP-1RAs are associated with weight change. MEDLINE and Cochrane were searched until January 2022 for randomized control trials (RCTs) on patients with obesity, evaluating the impact of semaglutide, liraglutide, efpeglenatide, or exenatide on SBP. Separate analyses were done for trials with and without diabetes. Multivariate meta-regression assessed if SBP changes with GLP-1RA varied based on weight change or follow-up duration. Thirty-five RCTs were included. Follow-up duration ranged from 12 to 68 weeks for T2DM and 12-56 weeks for non-T2DM patients. GLP-1RAs significantly lowered SBP for all patients (MD = -3.14 [-3.60; -2.68]). Subgroup analysis showed a significantly greater difference in SBP reduction for patients without diabetes (-3.80 [-4.24; -3.37]) when compared with patients with diabetes (-2.13 [-3.27; -1.00]). Among patients with diabetes, liraglutide < 2 mg OD showed the greatest reduction in SBP (-3.78 [-6.27; -1.28]), while efpeglenatide /=0.5 and <0.8), and an increase in the number of persons with no T2D medications other than insulin between periods (SMD >0.8). In the GLP-1RA cohorts, there was a medium decrease in persons using insulin. CONCLUSIONS: With the introduction of new treatments and emerging evidence supporting cardio-renal protective effects in people with CKD and T2D, notable changes in baseline treatment were observed in the medication-initiator cohort characteristics. These findings suggest the earlier use of cardio-renal protective medications in the course of T2D. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yano, Yuichiro AU - Yano Y AD - NCD Epidemiology Research Center, Shiga University of Medical Science, Otsu, Japan. AD - Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan. AD - AI Incubation Farm, Juntendo University, Tokyo, Japan. FAU - Okami, Suguru AU - Okami S AUID- ORCID: 0000-0003-4402-0209 AD - Medical Affairs and Pharmacovigilance, Bayer Yakuhin Ltd, Osaka, Japan. FAU - Kanegae, Hiroshi AU - Kanegae H AD - Genki Plaza Medical Centre for Health Care, Tokyo, Japan. FAU - Oberprieler, Nikolaus G AU - Oberprieler NG AD - Integrated Evidence Generation and Business Innovation, Bayer AG, Berlin, Germany. FAU - Johannes, Catherine AU - Johannes C AD - RTI Health Solutions, Waltham, Massachusetts, USA. FAU - Yamashita, Satoshi AU - Yamashita S AD - Medical Affairs and Pharmacovigilance, Bayer Yakuhin Ltd, Osaka, Japan. FAU - Yoshikawa-Ryan, Kanae AU - Yoshikawa-Ryan K AD - Medical Affairs and Pharmacovigilance, Bayer Yakuhin Ltd, Osaka, Japan. FAU - Kovesdy, Csaba P AU - Kovesdy CP AD - Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Vizcaya, David AU - Vizcaya D AD - Integrated Evidence Generation and Business Innovation, Bayer AG, Berlin, Germany. FAU - Kashihara, Naoki AU - Kashihara N AD - Kawasaki Geriatric Medical Center, Okayama, Japan. LA - eng GR - Bayer/ PT - Journal Article DEP - 20250421 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Female MH - *Renal Insufficiency, Chronic/drug therapy/complications/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Japan/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies PMC - PMC12146464 OTO - NOTNLM OT - chronic kidney disease OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - real-world OT - sodium-glucose cotransporter-2 inhibitor OT - treatment pattern COIS- S.O., N.G.O., K.Y.-R. and S.Y. are employees of Bayer. D.V. was an employee of Bayer when this research was conducted and is now an employee of Alexion Pharma S.L., Barcelona, Spain. Y.Y. reports consultancy for Bayer. H.K. reports no competing interests in conducting this study. C.J. is an employee of RTI Health Solutions, which received research funding for this study from Bayer. C.P.K. received consulting fees from Abbott, Akebia, AstraZeneca, Bayer, Boehringer Ingelheim, Cara Therapeutics, CSL Behring, CSL Vifor, GSK, Pharmacosmos, ProKidney, Renibus and Takeda. N.K. reports research grants from Daiichi Sankyo, AstraZeneca and Bayer. EDAT- 2025/04/22 06:26 MHDA- 2025/06/09 06:26 PMCR- 2025/06/09 CRDT- 2025/04/22 00:42 PHST- 2025/03/27 00:00 [revised] PHST- 2025/02/10 00:00 [received] PHST- 2025/03/30 00:00 [accepted] PHST- 2025/06/09 06:26 [medline] PHST- 2025/04/22 06:26 [pubmed] PHST- 2025/04/22 00:42 [entrez] PHST- 2025/06/09 00:00 [pmc-release] AID - DOM16394 [pii] AID - 10.1111/dom.16394 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3714-3724. doi: 10.1111/dom.16394. Epub 2025 Apr 21. PMID- 40259185 OWN - NLM STAT- MEDLINE DCOM- 20260509 LR - 20261010 IS - 2196-8837 (Electronic) IS - 2196-8837 (Linking) VI - 13 IP - 3 DP - 2026 Jun TI - Evidence-Based Practice in Prescribing SGLT2i and GLP-1 RA Across Ethnic and Racial Groups: a Systematic Review and Meta-analysis of Observational Studies. PG - 2197-2212 LID - 10.1007/s40615-025-02410-z [doi] AB - BACKGROUND: The newer classes of anti-diabetes medications have additional cardiovascular and renal effects, and restricted access would contribute to diabetes-related healthcare disparities. Hence, a systematic review, and meta-analysis, was undertaken to determine the existence of racial and ethnic disparities in the uptake of SGLT2i or GLP-1 RA. METHODS: The search was performed using Scopus, Cochrane Central Registry of Controlled Trials, PubMed, and Web of Science databases. Eligibility to include the studies was assessed independently, and this review included observational studies. The necessary information was extracted using the Cochrane-modified data extraction form. The quality of the studies was assessed using the Newcastle-Ottawa scale. RevMan v5.4.1 was used to conduct the analysis. The certainty of the evidence was measured with GradePro. RESULTS: The likelihood of prescription fills with SGLT2i and GLP-1 RA was lower among the Black population, with odds ratios (OR) of 0.81 (95% CI 0.75-0.88, p < 0.0001) for SGLT2i and 0.78 (95% CI 0.70-0.87, p < 0.0001) for GLP-1 RA when compared to White population. Additionally, Asian individuals and those classified under "Other" populations had a significant reduction in GLP-1 RA prescription fills, with odds ratios of 0.61 (95% CI 0.43-0.86) and 0.73 (95% CI 0.60-0.89), respectively. However, there was no significant difference in SGLT2i prescription fills among the Asian individuals (p = 0.56) or those in the "Other" population category (p = 0.51). CONCLUSIONS: The extent of evidence-based practice in prescribing SGLT2i was significantly low among the Black population compared to patients who are Whites. The number of prescriptions filled by GLP-1 RA was significantly low among the Asian population, the Black population, and other populations. Thus, policymakers and clinicians must take the necessary initiatives to achieve pharmacoequity in managing T2DM with co-morbidity conditions. CI - (c) 2025. W. Montague Cobb-NMA Health Institute. FAU - Ananthesh, L AU - Ananthesh L AD - Nitte (Deemed to be University) NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmacy Practice, Mangalore, India. FAU - Cutinha, Rasheal Maria AU - Cutinha RM AD - Nitte (Deemed to be University) NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmacy Practice, Mangalore, India. FAU - Basutkar, Roopa Satyanarayan AU - Basutkar RS AUID- ORCID: 0000-0001-8034-8100 AD - Nitte (Deemed to be University) NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmacy Practice, Mangalore, India. roopasatyanarayan@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250421 PL - Switzerland TA - J Racial Ethn Health Disparities JT - Journal of racial and ethnic health disparities JID - 101628476 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Observational Studies as Topic MH - *Ethnicity/statistics & numerical data MH - *Evidence-Based Practice MH - *Racial Groups/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - *Healthcare Disparities/ethnology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians'/statistics & numerical data OTO - NOTNLM OT - Diabetes mellitus OT - Disparities OT - Ethnicity OT - GLP-1 RA OT - Racial OT - SGLT2i OT - T2DM COIS- Declarations. Competing Interests: The authors declare no competing interests. EDAT- 2025/04/22 00:26 MHDA- 2026/05/10 05:19 CRDT- 2025/04/21 23:31 PHST- 2024/06/03 00:00 [received] PHST- 2025/03/24 00:00 [accepted] PHST- 2025/03/22 00:00 [revised] PHST- 2026/05/10 05:19 [medline] PHST- 2025/04/22 00:26 [pubmed] PHST- 2025/04/21 23:31 [entrez] AID - 10.1007/s40615-025-02410-z [pii] AID - 10.1007/s40615-025-02410-z [doi] PST - ppublish SO - J Racial Ethn Health Disparities. 2026 Jun;13(3):2197-2212. doi: 10.1007/s40615-025-02410-z. Epub 2025 Apr 21. PMID- 40258281 OWN - NLM STAT- MEDLINE DCOM- 20250616 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 6 DP - 2025 Jun TI - Availability of Cardioprotective Medications for Type 2 Diabetes in the Medicaid Program. PG - 808-818 LID - 10.7326/ANNALS-24-01449 [doi] AB - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the only type 2 diabetes medications that reduce cardiovascular disease and death, yet their availability in Medicaid is unclear. OBJECTIVE: To assess the unrestricted availability of SGLT2is and GLP-1 RAs, using dipeptidyl peptidase-4 inhibitors (DPP4is) as a benchmark. DESIGN: National cross-sectional study using publicly available data. SETTING: All 50 state Medicaid fee-for-service (FFS) plans and 273 nonelderly adult managed care organization (MCO) plans with comprehensive coverage in March 2024. PARTICIPANTS: Medicaid plans and enrollees with diabetes in those plans as of March 2024. MEASUREMENTS: Unrestricted availability was defined as having at least 1 medication in each class listed on the preferred drug list without prior authorization or step therapy. RESULTS: Of 50 FFS plans (including Washington, DC, and excluding 1 state, which had 5 MCO plans), 40 (80%) had unrestricted availability of SGLT2is, 30 (60%) of GLP-1 RAs, 41 (82%) of either, 29 (58%) of both, and 42 (84%) of DPP4is. Among 273 MCO plans (39 states; median, 6 plans [range, 2 to 24 plans]), 182 (67%) had availability of SGLT2is, 131 (48%) of GLP-1 RAs, 184 (67%) of either, 129 (47%) of both, and 204 (75%) of DPP4is. The proportion of MCO enrollees with availability varied markedly among states (SGLT2i range, 24% to 100%; GLP-1 RA range, 0% to 99%; DPP4i range, 41% to 100%). Primarily because of more MCO restrictions, 1.7 million enrollees (lower to upper bound, 1.33 million to 2.17 million enrollees; 25%) had restricted SGLT2i availability, 2.72 million (lower to upper bound, 2.12 million to 3.45 million; 40%) had restricted GLP-1 RA availability, and 1.5 million (lower to upper bound, 1.17 million to 1.90 million; 22%) had restricted DPP4i availability. Availability increased from 2020 to 2024, especially in FFS, but MCO GLP-1 RA availability has plateaued at below 60% since 2022. Tirzepatide was almost entirely restricted. LIMITATIONS: Diabetes enrollment was estimated using plan size and state and national prevalence data. The appropriateness of prior authorization restrictions was unknown. CONCLUSION: Many Medicaid enrollees have restricted access to cardioprotective medications, particularly in MCO plans for GLP-1 RA medications, with substantial state variation. Formulary coverage is a potential lever to increase availability of these medications while balancing pharmaceutical costs. PRIMARY FUNDING SOURCE: University of California, San Francisco, Action Research Center for Health Equity. FAU - Makam, Anil N AU - Makam AN AUID- ORCID: 0000-0001-7072-9946 AD - Division of Hospital Medicine, UCSF at San Francisco General Hospital; UCSF Philip R. Lee Institute for Health Policy Studies; and UCSF Action Research Center for Health Equity, San Francisco, California (A.N.M.). FAU - Bailey, Logan AU - Bailey L AD - School of Medicine, UCSF, San Francisco, and Departments of Graduate Medical Education and Emergency Medicine, Sutter Roseville Medical Center, Roseville, California (L.B.). FAU - Anderson, Nigel AU - Anderson N AD - School of Medicine, UCSF, San Francisco, California (N.A.). FAU - Bellitti, Kathy AU - Bellitti K AD - Fingertip Formulary, Clarivate Analytics, Chandler, Arizona (K.B.). FAU - Skinner, Sasha AU - Skinner S AD - Division of Hospital Medicine, UCSF at San Francisco General Hospital, San Francisco, California (S.S.). FAU - Nguyen, Oanh Kieu AU - Nguyen OK AD - Division of Hospital Medicine, UCSF at San Francisco General Hospital; UCSF Philip R. Lee Institute for Health Policy Studies; UCSF Action Research Center for Health Equity; and Chan Zuckerberg Biohub, San Francisco, California (O.K.N.). LA - eng PT - Journal Article DEP - 20250422 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Cardiotonic Agents) SB - IM MH - Humans MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Medicaid MH - Cross-Sectional Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/supply & distribution MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/supply & distribution MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/supply & distribution MH - *Cardiotonic Agents/therapeutic use/supply & distribution MH - Managed Care Programs MH - *Health Services Accessibility/statistics & numerical data MH - Fee-for-Service Plans MH - Cardiovascular Diseases/prevention & control MH - Adult COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/04/21 18:27 MHDA- 2025/06/16 18:25 CRDT- 2025/04/21 17:03 PHST- 2025/06/16 18:25 [medline] PHST- 2025/04/21 18:27 [pubmed] PHST- 2025/04/21 17:03 [entrez] AID - 10.7326/ANNALS-24-01449 [doi] PST - ppublish SO - Ann Intern Med. 2025 Jun;178(6):808-818. doi: 10.7326/ANNALS-24-01449. Epub 2025 Apr 22. PMID- 40257422 OWN - NLM STAT- MEDLINE DCOM- 20250421 LR - 20260707 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 45 IP - 5 DP - 2025 May TI - Comparative Hepatic Outcomes of SGLT2i or DPP4i Compared to GLP-1RA in CHB and T2DM Patients. PG - e70060 LID - 10.1111/liv.70060 [doi] AB - BACKGROUND: The prevalence of diabetes is increasing among chronic hepatitis B (CHB) patients. However, the relative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) or dipeptidyl peptidase-4 inhibitors (DPP4i), compared with glucagon-like peptide-1 receptor agonists (GLP-1RA), among such at-risk populations remains unclear in terms of reducing liver-related events (LRE). METHODS: Using a nationwide database (2019-2022), we identified CHB patients with diabetes (age >/= 40) and established two new-user cohorts: SGLT2i vs. GLP-1RA and DPP4i vs. GLP-1RA. LREs included hepatocellular carcinoma, cirrhosis, liver transplantation and liver-related mortality. For appropriate balancing, propensity score matching (PSM) was performed for each cohort. Multivariate Cox regression models were used to estimate LRE risk with adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Propensity score matching provided two separate cohorts: (1) SGLT2i (n = 2297) vs. GLP-1RA (n = 461) and (2) DPP4i (n = 803) vs. GLP-1RA (n = 165) users. The LREs risk was similar across each comparison, with aHRs of 0.82 (95% CI 0.49-1.37) for GLP-1RA (vs. SGLT2i) and 0.93 (95% CI 0.41-2.07) for GLP-1RA (vs. DPP4i), indicating no significant differences. Subgroup analyses showed a trend favouring GLP-1RA over SGLT2i in females, obese individuals, antiviral therapy (AVT) users, those with diabetes complications, longer diabetes duration and physically active individuals. Compared with DPP4i, the trend was observed in AVT users and those with a shorter diabetes duration, though none were statistically significant. CONCLUSION: Overall LRE risk was comparable between SGLT2i or DPP4i vs. GLP-1RA users. Further prospective studies are required to identify who can benefit from specific medication. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Yun, Byungyoon AU - Yun B AD - Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea. AD - The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Korea. AD - The Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul, Korea. FAU - Oh, Juyeon AU - Oh J AD - Department of Public Health, Graduate School, Yonsei University, Seoul, Korea. FAU - Park, Heejoo AU - Park H AD - Department of Public Health, Graduate School, Yonsei University, Seoul, Korea. FAU - Lee, Jian AU - Lee J AD - Department of Public Health, Graduate School, Yonsei University, Seoul, Korea. FAU - Kim, Beom Kyung AU - Kim BK AUID- ORCID: 0000-0002-5363-2496 AD - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. AD - Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. AD - Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea. FAU - Yoon, Jin-Ha AU - Yoon JH AD - Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea. AD - The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Korea. AD - The Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul, Korea. LA - eng GR - National Research Foundation of Korea/ GR - the National Research Foundation of Korea/ GR - RS-2024-00455210/the Korea Government (MSIT)/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hepatitis B, Chronic/complications/drug therapy MH - Propensity Score MH - Aged MH - Adult MH - Liver Cirrhosis/epidemiology MH - Liver Transplantation/statistics & numerical data MH - Liver Neoplasms/epidemiology MH - Carcinoma, Hepatocellular/epidemiology OTO - NOTNLM OT - liver-related events OT - nationwide study OT - new user cohort OT - oral antidiabetic drugs OT - propensity score matching EDAT- 2025/04/21 12:28 MHDA- 2025/04/21 12:29 CRDT- 2025/04/21 10:33 PHST- 2025/02/07 00:00 [revised] PHST- 2024/10/23 00:00 [received] PHST- 2025/02/27 00:00 [accepted] PHST- 2025/04/21 12:29 [medline] PHST- 2025/04/21 12:28 [pubmed] PHST- 2025/04/21 10:33 [entrez] AID - 10.1111/liv.70060 [doi] PST - ppublish SO - Liver Int. 2025 May;45(5):e70060. doi: 10.1111/liv.70060. PMID- 40257122 OWN - NLM STAT- MEDLINE DCOM- 20250508 LR - 20250512 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 68 IP - 9 DP - 2025 May 8 TI - Discovery and Evaluation of DA-302168S as an Efficacious Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist. PG - 9555-9583 LID - 10.1021/acs.jmedchem.5c00242 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) holds pivotal importance as a therapeutic target for type 2 diabetes (T2D) and obesity. Several oral small-molecule agonists targeting GLP-1R have been developed to date. Nevertheless, these agonists suffer from several limitations, including low potency, poor pharmacokinetics, and unfavorable safety profiles. Here, we report the discovery of compound 29 (DA-302168S), which exhibits higher potency both in vitro/in vivo while mitigating the risk of drug-drug interaction compared to other reported candidate compounds. Preclinical studies show full efficacy in cAMP activation, glucose reduction, and appetite suppression. Safety assessments reveal minimal risks with hERG IC(50) > 30 muM and no significant off-target toxicity. Its favorable pharmacokinetics support once-daily oral dosing, improving patient compliance. These findings suggest that compound 29 offers a promising therapeutic option for the management of T2D and obesity. Notably, it has successfully completed phase I clinical trials and is currently undergoing phase II clinical trials. FAU - Dong, Guangxin AU - Dong G AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Ye, Qijun AU - Ye Q AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Li, Wenwen AU - Li W AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Zhang, Shaofeng AU - Zhang S AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Yang, Zhenyu AU - Yang Z AUID- ORCID: 0000-0002-0633-8710 AD - West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Zhang, Rui AU - Zhang R AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Deng, Ta AU - Deng T AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Li, Haiyan AU - Li H AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Zhang, Yong AU - Zhang Y AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Zhang, Xiaojie AU - Zhang X AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - He, Shucheng AU - He S AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Zhou, Daoheng AU - Zhou D AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Zhang, Juan AU - Zhang J AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - He, Peng AU - He P AUID- ORCID: 0009-0008-3190-1908 AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Yu, Zhou AU - Yu Z AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. FAU - Li, Yi AU - Li Y AD - Chengdu DIAO Pharmaceutical Group Co., Ltd., Chengdu 610041, China. LA - eng PT - Journal Article DEP - 20250421 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - E0399OZS9N (Cyclic AMP) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Administration, Oral MH - Structure-Activity Relationship MH - Male MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/pharmacology/pharmacokinetics/chemistry/administration & dosage MH - *Drug Discovery MH - Mice MH - Rats MH - Diabetes Mellitus, Type 2/drug therapy MH - Cyclic AMP/metabolism MH - Cricetulus MH - CHO Cells EDAT- 2025/04/21 12:28 MHDA- 2025/05/08 12:24 CRDT- 2025/04/21 08:03 PHST- 2025/05/08 12:24 [medline] PHST- 2025/04/21 12:28 [pubmed] PHST- 2025/04/21 08:03 [entrez] AID - 10.1021/acs.jmedchem.5c00242 [doi] PST - ppublish SO - J Med Chem. 2025 May 8;68(9):9555-9583. doi: 10.1021/acs.jmedchem.5c00242. Epub 2025 Apr 21. PMID- 40253725 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260722 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 6 DP - 2025 Jun TI - The effects of SGLT2 inhibitors and GLP-1 receptor agonists on the triglyceride to HDL cholesterol ratio and the triglyceride-glucose index in patients with type 2 diabetes. PG - 109044 LID - S1056-8727(25)00097-2 [pii] LID - 10.1016/j.jdiacomp.2025.109044 [doi] AB - We analyzed the medical records of 100 patients with type 2 diabetes to evaluate the effects of new antidiabetic drugs on the TG/HDL-C ratio and the TG-glucose index. We found that GLP-1 RA treatment significantly improved both markers, while SGLT2 inhibitors led to significant reductions only in the latter. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Voziki, Dimitra AU - Voziki D AD - Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Internal Medicine and Diabetes Clinic, "G. Gennimatas" General Hospital, Thessaloniki, Greece. FAU - Dimakopoulos, Georgios AU - Dimakopoulos G AD - BIOSTATS, Epirus Science and Technology Park Campus, University of Ioannina, Ioannina, Greece. FAU - Stergiou, Ioannis AU - Stergiou I AD - Department of Internal Medicine and Diabetes Clinic, "G. Gennimatas" General Hospital, Thessaloniki, Greece. FAU - Zografou, Ioanna AU - Zografou I AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Rizzo, Manfredi AU - Rizzo M AD - School of Medicine, Promise Department, University of Palermo, Italy; Ras Al Khaimah Medical and Health Sciences University, RAK, United Arab Emirates. FAU - Liberopoulos, Evangelos N AU - Liberopoulos EN AD - First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Kotsa, Kalliopi AU - Kotsa K AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: thkoyfak@auth.gr. LA - eng PT - Journal Article DEP - 20250418 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Triglycerides) RN - 0 (Cholesterol, HDL) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Triglycerides/blood MH - *Cholesterol, HDL/blood MH - Blood Glucose/analysis/drug effects/metabolism MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies OTO - NOTNLM OT - Cardiovascular risk OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - TG/HDL-C ratio OT - TyG index COIS- Declaration of competing interest Manfredi Rizzo is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for this journal and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IS has received honoraria for lectures/advisory boards and research support from Astra Zeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi-Aventis, Menarini, Innovis, Abbot and Novo Nordisk. MR has given lectures, received honoraria and research support and participated in conferences, advisory boards and clinical trials sponsored by many pharmaceutical companies, including Amgen, Astra Zeneca, Biodexa, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mylan, Merck Sharp & Dohme, Novo Nordisk, Novartis, Roche, Sanofi and Servier. ENL has participated in educational, research, and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, and Servier.; KK has received honoraria for lectures/advisory boards and research support from Astra Zeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi-Aventis, ELPEN, MSD and Novo Nordisk. TK has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Menarini, Pharmaserve Lilly and Novo Nordisk, for advisory boards from Novo Nordisk and Boehringer Ingelheim, and has participated in sponsored studies by Eli-Lilly, AstraZeneca and Novo Nordisk. Other authors report no conflict of interest. EDAT- 2025/04/20 18:28 MHDA- 2025/05/01 06:27 CRDT- 2025/04/20 18:00 PHST- 2025/03/25 00:00 [received] PHST- 2025/04/17 00:00 [accepted] PHST- 2025/05/01 06:27 [medline] PHST- 2025/04/20 18:28 [pubmed] PHST- 2025/04/20 18:00 [entrez] AID - S1056-8727(25)00097-2 [pii] AID - 10.1016/j.jdiacomp.2025.109044 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Jun;39(6):109044. doi: 10.1016/j.jdiacomp.2025.109044. Epub 2025 Apr 18. PMID- 40251273 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20260925 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 31 IP - 7 DP - 2025 Jul TI - Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery. PG - 2269-2276 LID - 10.1038/s41591-025-03645-3 [doi] AB - Obesity is a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP1-RA) and bariatric surgery (BS) are effective weight loss interventions; however, the genetic factors influencing treatment response remain largely unexplored. Moreover, most previous studies have focused on race and ethnicity rather than genetic ancestry. Here we analyzed 10,960 individuals from 9 multiancestry biobank studies across 6 countries to assess the impact of known genetic factors on weight loss. Between 6 and 12 months, GLP1-RA users had an average weight change of -3.93% or -6.00%, depending on the outcome definition, with modest ancestry-based differences. BS patients experienced -21.17% weight change between 6 and 48 months. We found no significant associations between GLP1-RA-induced weight loss and polygenic scores for body mass index or type 2 diabetes, nor with missense variants in GLP1R. A higher body mass index polygenic score was modestly linked to lower weight loss after BS (+0.7% per s.d., P = 1.24 x 10(-4)), but the effect attenuated in sensitivity analyses. Our findings suggest known genetic factors have limited impact on GLP1-RA effectiveness with respect to weight change and confirm treatment efficacy across ancestry groups. CI - (c) 2025. The Author(s). FAU - German, Jakob AU - German J AUID- ORCID: 0009-0002-1257-7782 AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Eric and Wendy Schmidt Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Cordioli, Mattia AU - Cordioli M AUID- ORCID: 0000-0002-4872-0520 AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Tozzo, Veronica AU - Tozzo V AD - Department of Computational Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. FAU - Urbut, Sarah AU - Urbut S AUID- ORCID: 0000-0002-1135-9647 AD - Division of Cardiovascular Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. FAU - Arumae, Kadri AU - Arumae K AD - Institute of Psychology, University of Tartu, Tartu, Estonia. FAU - Smit, Roelof A J AU - Smit RAJ AD - The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. AD - Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Lee, Jiwoo AU - Lee J AUID- ORCID: 0000-0003-0555-585X AD - Broad Institute of MIT and Harvard, Cambridge, MA, USA. AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Li, Josephine H AU - Li JH AUID- ORCID: 0000-0003-2314-0914 AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. AD - Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Janucik, Adrian AU - Janucik A AD - Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. AD - Center for Digital Medicine, Medical University of Bialystok, Bialystok, Poland. FAU - Ding, Yi AU - Ding Y AD - Department of Computational Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. FAU - Akinkuolie, Akintunde AU - Akinkuolie A AD - Department of Computational Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. FAU - Heyne, Henrike O AU - Heyne HO AD - Hasso Plattner Institute, University of Potsdam, Potsdam, Germany. AD - Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Eoli, Andrea AU - Eoli A AUID- ORCID: 0000-0002-6505-3117 AD - Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Saad, Chadi AU - Saad C AD - Qatar Genome Program, Qatar Precision Health Institute, Qatar Foundation, Doha, Qatar. FAU - Al-Sarraj, Yasser AU - Al-Sarraj Y AD - Qatar Genome Program, Qatar Precision Health Institute, Qatar Foundation, Doha, Qatar. FAU - Abdel-Latif, Rania AU - Abdel-Latif R AD - Qatar Genome Program, Qatar Precision Health Institute, Qatar Foundation, Doha, Qatar. FAU - Mohammed, Shaban AU - Mohammed S AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Hail, Moza Al AU - Hail MA AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Barry, Alexandra AU - Barry A AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. AD - Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Wang, Zhe AU - Wang Z AUID- ORCID: 0000-0002-8046-4969 AD - The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Cajuso, Tatiana AU - Cajuso T AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. FAU - Corbetta, Andrea AU - Corbetta A AUID- ORCID: 0009-0001-8006-1211 AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Health Data Science Centre, Human Technopole, Milan, Italy. AD - MOX - Laboratory for Modeling and Scientific Computing, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Natarajan, Pradeep AU - Natarajan P AUID- ORCID: 0000-0001-8402-7435 AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. AD - Personalized Medicine, Mass General Brigham, Boston, MA, USA. AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. FAU - Ripatti, Samuli AU - Ripatti S AUID- ORCID: 0000-0002-0504-1202 AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. AD - Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. AD - Department of Public Health, Clinicum, University of Helsinki, Helsinki, Finland. AD - Analytic & Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Philippakis, Anthony AU - Philippakis A AD - Eric and Wendy Schmidt Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA. AD - Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Szczerbinski, Lukasz AU - Szczerbinski L AUID- ORCID: 0000-0002-6201-0605 AD - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. AD - Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. AD - Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland. AD - Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland. FAU - Pasaniuc, Bogdan AU - Pasaniuc B AD - Department of Computational Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. AD - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA. AD - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. AD - Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. AD - Institute of Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Kutalik, Zoltan AU - Kutalik Z AUID- ORCID: 0000-0001-8285-7523 AD - University Center for Primary Care and Public Health, Lausanne, Switzerland. AD - Department of Computational Biology, University of Lausanne, Lausanne, Switzerland. AD - Swiss Institute of Bioinformatics, Lausanne, Switzerland. FAU - Mbarek, Hamdi AU - Mbarek H AUID- ORCID: 0000-0002-1108-0371 AD - Qatar Genome Program, Qatar Precision Health Institute, Qatar Foundation, Doha, Qatar. FAU - Loos, Ruth J F AU - Loos RJF AUID- ORCID: 0000-0002-8532-5087 AD - The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. AD - Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Vainik, Uku AU - Vainik U AD - Institute of Psychology, University of Tartu, Tartu, Estonia. AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. AD - Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. FAU - Ganna, Andrea AU - Ganna A AUID- ORCID: 0000-0002-8147-240X AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. andrea.ganna@helsinki.fi. AD - Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. andrea.ganna@helsinki.fi. LA - eng GR - 101117251/EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ GR - R01 MH115676/MH/NIMH NIH HHS/United States GR - PSG759/Eesti Teadusagentuur (Estonian Research Council)/ GR - R01 HG009120/HG/NHGRI NIH HHS/United States GR - Eric and Wendy Schmidt Center Fellowship/Broad Institute/ GR - U01 HG011715/HG/NHGRI NIH HHS/United States GR - UL1 TR001881/TR/NCATS NIH HHS/United States GR - K23 DK131345/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20250418 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM UOF - medRxiv. 2025 Jan 08:2024.09.11.24313458. doi: 10.1101/2024.09.11.24313458. PMID: 39314946 MH - Humans MH - *Bariatric Surgery MH - *Weight Loss/genetics/drug effects MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/genetics MH - Body Mass Index MH - *Obesity/genetics/surgery/drug therapy MH - Diabetes Mellitus, Type 2/genetics/surgery MH - Adult MH - Glucagon-Like Peptide 1 MH - Treatment Outcome PMC - PMC12283387 COIS- Competing interests: A.G. is the founder of Real World Genetics OY. P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck and Novartis; scientific advisory board membership of Esperion Therapeutics, Preciseli, TenSixteen Bio and Tourmaline Bio; scientific co-founder of TenSixteen Bio; equity in MyOme, Preciseli and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. A.P. is an employee of Alphabet Corporation. He has previously received research support from Microsoft, Alphabet, Intel, IBM and Bayer. EDAT- 2025/04/19 00:56 MHDA- 2025/07/23 11:25 PMCR- 2025/04/18 CRDT- 2025/04/18 23:19 PHST- 2024/09/03 00:00 [received] PHST- 2025/03/07 00:00 [accepted] PHST- 2025/07/23 11:25 [medline] PHST- 2025/04/19 00:56 [pubmed] PHST- 2025/04/18 23:19 [entrez] PHST- 2025/04/18 00:00 [pmc-release] AID - 10.1038/s41591-025-03645-3 [pii] AID - 3645 [pii] AID - 10.1038/s41591-025-03645-3 [doi] PST - ppublish SO - Nat Med. 2025 Jul;31(7):2269-2276. doi: 10.1038/s41591-025-03645-3. Epub 2025 Apr 18. PMID- 40245017 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20250419 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 22 IP - 4 DP - 2025 Apr TI - Reduced insulin use and diabetes complications upon introduction of SGLT-2 inhibitors and GLP1-receptor agonists in low- and middle-income countries: A microsimulation. PG - e1004559 LID - 10.1371/journal.pmed.1004559 [doi] LID - e1004559 AB - BACKGROUND: Diabetes mellitus, particularly type 2 diabetes, is a growing health concern in low- and middle-income countries (LMICs). The potential impact of newer diabetes medications, such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, on insulin dosage and health outcomes in these settings is not well understood. METHODS AND FINDINGS: We developed a microsimulation model to estimate the impact of treating patients with type 2 diabetes who use insulin with GLP-1 receptor agonists or SGLT-2 inhibitors in LMICs. The model utilized data from the Global Health and Population Project on Access to Care for Cardiometabolic Diseases (HPACC) dataset, encompassing surveys from 79 countries and clinical trial data to estimate insulin dose reduction. We incorporated weight-based insulin dosing formulas and hazard ratios for severe hypoglycemia, cardiovascular and renal outcomes, side effects of new therapies, and mortality. The primary outcome was the change in insulin dosage, and secondary outcomes were disability-adjusted life years (DALYs) lost per 1,000 person-years by diabetes complication (micro- and macro-vascular). Our results indicate that the addition of GLP-1 receptor agonists or SGLT-2 inhibitors could reduce insulin dosage by 8.2 IU/day (IQR: 6.9, 9.5) and 5.3 IU/day (IQR: 4.5, 6.2), respectively. The median DALYs lost per 1,000 person-years decreased from 2.20 (IQR: 1.49, 4.02) to 1.01 (IQR: 0.61, 1.86) with GLP-1 receptor agonists and 1.25 (IQR: 0.81, 2.29) with SGLT-2 inhibitors. Primary benefits arose from weight loss, decreased cardiorenal disease, and decreased mortality, with smaller DALY benefits from the prevention of severe hypoglycemia. Key limitations include the inability to differentiate between type 1 and type 2 diabetes in some datasets and reliance on assumptions from clinical trials conducted primarily in high-income countries. CONCLUSIONS: The introduction of GLP-1 receptor agonists and SGLT-2 inhibitors for managing type 2 diabetes in LMICs could significantly reduce insulin dosage and associated health risks, leading to improved outcomes and reduced disability. These findings suggest that expanding access to these newer diabetes medications in LMICs could have substantial public health benefits. CI - Copyright: (c) 2025 Global Health & Population Project on Access to Care for Cardiometabolic Diseases (HPACC). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. CN - Global Health & Population Project on Access to Care for Cardiometabolic Diseases (HPACC) LA - eng PT - Journal Article DEP - 20250417 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Insulin/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Developing Countries MH - Male MH - Female MH - *Diabetes Complications/epidemiology MH - Middle Aged PMC - PMC12005516 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: SB and DF are Academic Editors on PLOS Medicine's editorial board. TB is the academic Editor-in-Chief of PLOS Medicine. EDAT- 2025/04/17 18:24 MHDA- 2025/04/17 18:25 PMCR- 2025/04/17 CRDT- 2025/04/17 13:36 PHST- 2024/08/13 00:00 [received] PHST- 2025/02/11 00:00 [accepted] PHST- 2025/04/17 18:25 [medline] PHST- 2025/04/17 18:24 [pubmed] PHST- 2025/04/17 13:36 [entrez] PHST- 2025/04/17 00:00 [pmc-release] AID - PMEDICINE-D-24-02659 [pii] AID - 10.1371/journal.pmed.1004559 [doi] PST - epublish SO - PLoS Med. 2025 Apr 17;22(4):e1004559. doi: 10.1371/journal.pmed.1004559. eCollection 2025 Apr. PMID- 40243679 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20250423 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 7 DP - 2025 Mar 26 TI - GLP-1 Receptor Agonists and Myocardial Perfusion: Bridging Mechanisms to Clinical Outcomes. LID - 10.3390/ijms26073050 [doi] LID - 3050 AB - Coronary microvascular dysfunction (CMD) is a key contributor to myocardial ischemia and adverse cardiovascular outcomes, particularly in individuals with metabolic disorders such as type 2 diabetes (T2D). While conventional therapies primarily target epicardial coronary disease, effective treatments for CMD remain limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as promising agents with cardiovascular benefits extending beyond glycemic control. Preclinical and clinical evidence suggests that GLP-1R activation enhances coronary microvascular function through mechanisms including improved endothelial function, increased nitric oxide bioavailability, attenuation of oxidative stress, and reduced vascular inflammation. Moreover, GLP-1R agonists have been shown to improve myocardial blood flow, myocardial perfusion reserve, and coronary endothelial function, particularly in high-risk populations. Despite these promising findings, inconsistencies remain across studies due to variability in patient populations, study designs, and imaging methodologies. This review summarizes current evidence on the role of GLP-1R agonists in myocardial perfusion, bridging mechanistic insights with clinical outcomes. Further large-scale, well-designed trials are needed to clarify their long-term impact on coronary microcirculation and explore their potential as targeted therapies for CMD. FAU - Karakasis, Paschalis AU - Karakasis P AUID- ORCID: 0000-0002-3561-5713 AD - Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece. FAU - Patoulias, Dimitrios AU - Patoulias D AUID- ORCID: 0000-0002-6899-684X AD - Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54124 Thessaloniki, Greece. FAU - Theofilis, Panagiotis AU - Theofilis P AUID- ORCID: 0000-0001-9260-6306 AD - First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece. FAU - Pamporis, Konstantinos AU - Pamporis K AUID- ORCID: 0000-0001-5411-6461 AD - First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece. FAU - Sagris, Marios AU - Sagris M AUID- ORCID: 0000-0002-3473-1368 AD - First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece. FAU - Vlachakis, Panayotis K AU - Vlachakis PK AUID- ORCID: 0000-0003-0736-4942 AD - First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54124 Thessaloniki, Greece. FAU - Antoniadis, Antonios P AU - Antoniadis AP AUID- ORCID: 0000-0002-6604-5581 AD - Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece. FAU - Fragakis, Nikolaos AU - Fragakis N AUID- ORCID: 0000-0002-7158-4950 AD - Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20250326 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Coronary Circulation/drug effects MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Myocardial Ischemia/drug therapy/metabolism MH - Microcirculation/drug effects PMC - PMC11988964 OTO - NOTNLM OT - GLP-1RAs OT - diabetes OT - glucagon-like peptide-1 receptor agonists OT - microvascular dysfunction OT - myocardial perfusion OT - obesity COIS- The authors declare no conflicts of interest. EDAT- 2025/04/17 12:27 MHDA- 2025/04/17 12:28 PMCR- 2025/03/26 CRDT- 2025/04/17 10:04 PHST- 2025/03/10 00:00 [received] PHST- 2025/03/21 00:00 [revised] PHST- 2025/03/24 00:00 [accepted] PHST- 2025/04/17 12:28 [medline] PHST- 2025/04/17 12:27 [pubmed] PHST- 2025/04/17 10:04 [entrez] PHST- 2025/03/26 00:00 [pmc-release] AID - ijms26073050 [pii] AID - ijms-26-03050 [pii] AID - 10.3390/ijms26073050 [doi] PST - epublish SO - Int J Mol Sci. 2025 Mar 26;26(7):3050. doi: 10.3390/ijms26073050. PMID- 40243535 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 7 DP - 2025 Mar 25 TI - Carnitine Deficiency Caused by Salcaprozic Acid Sodium Contained in Oral Semaglutide in a Patient with Multiple Acyl-CoA Dehydrogenase Deficiency. LID - 10.3390/ijms26072962 [doi] LID - 2962 AB - Carnitine plays an essential role in maintaining energy homeostasis and metabolic flexibility. Various medications, such as pivalate-conjugated antibiotics, valproic acid, and anticancer agents, can induce carnitine deficiency, inhibit the utilization of fatty acid, and contribute to the development of hypoglycemia. No studies have linked oral semaglutide to carnitine deficiency. Herein, we report the case of a 34-year-old male patient with multiple acyl-CoA dehydrogenase deficiency who developed carnitine deficiency attributable to salcaprozic acid sodium (SNAC) in oral semaglutide. The patient was diagnosed with type 2 diabetes mellitus at 32 years of age and was treated with semaglutide injections. Hypoglycemic symptoms appeared after switching to oral semaglutide, and the mean levels of blood-free carnitine significantly decreased. Liquid chromatography-tandem mass spectrometry analysis revealed a peak corresponding to the SNAC-carnitine complex (m/z 423.24) in the urine exclusively during the oral administration of semaglutide. The MS/MS spectra at m/z 423.24 contained peaks consistent with those of the SNAC and carnitine product ions. Our results suggest that through complexation with carnitine, SNAC may induce carnitine deficiency. Healthcare providers should monitor for carnitine deficiency when administering SNAC-containing medications to at-risk individuals. Furthermore, this case can raise more significant concerns about the potential impact of pharmaceutical excipients like SNAC on metabolic pathways. FAU - Mikami-Saito, Yasuko AU - Mikami-Saito Y AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Maekawa, Masamitsu AU - Maekawa M AUID- ORCID: 0000-0001-6723-0298 AD - Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. AD - Graduate School of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Watanabe, Masahiro AU - Watanabe M AD - Graduate School of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Hosaka, Shinichiro AU - Hosaka S AD - Department of Diabetes, Metabolism and Endocrinology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. FAU - Takahashi, Kei AU - Takahashi K AUID- ORCID: 0000-0001-9167-2336 AD - Department of Diabetes, Metabolism and Endocrinology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. FAU - Totsune, Eriko AU - Totsune E AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Arai-Ichinoi, Natsuko AU - Arai-Ichinoi N AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Kikuchi, Atsuo AU - Kikuchi A AUID- ORCID: 0000-0003-1002-8739 AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Kure, Shigeo AU - Kure S AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. FAU - Katagiri, Hideki AU - Katagiri H AD - Department of Diabetes, Metabolism and Endocrinology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. FAU - Wada, Yoichi AU - Wada Y AD - Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. LA - eng PT - Case Reports PT - Journal Article DEP - 20250325 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - S7UI8SM58A (Carnitine) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Carnitine/deficiency MH - Male MH - Adult MH - *Multiple Acyl Coenzyme A Dehydrogenase Deficiency/drug therapy/complications/metabolism MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/chemistry MH - Administration, Oral MH - Diabetes Mellitus, Type 2/drug therapy MH - Tandem Mass Spectrometry MH - Hypoglycemia/chemically induced MH - *Muscular Diseases/chemically induced MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11989126 OTO - NOTNLM OT - carnitine deficiency OT - multiple acyl-CoA dehydrogenase deficiency OT - oral semaglutide OT - salcaprozic acid sodium OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/04/17 12:26 MHDA- 2025/04/17 12:27 PMCR- 2025/03/25 CRDT- 2025/04/17 09:52 PHST- 2025/01/23 00:00 [received] PHST- 2025/03/19 00:00 [revised] PHST- 2025/03/21 00:00 [accepted] PHST- 2025/04/17 12:27 [medline] PHST- 2025/04/17 12:26 [pubmed] PHST- 2025/04/17 09:52 [entrez] PHST- 2025/03/25 00:00 [pmc-release] AID - ijms26072962 [pii] AID - ijms-26-02962 [pii] AID - 10.3390/ijms26072962 [doi] PST - epublish SO - Int J Mol Sci. 2025 Mar 25;26(7):2962. doi: 10.3390/ijms26072962. PMID- 40240532 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20261010 IS - 1476-5489 (Electronic) IS - 0955-9930 (Linking) VI - 37 IP - 8 DP - 2025 Aug TI - Male sexual dysfunction associated with GLP-1 receptor agonists: a cross-sectional analysis of FAERS data. PG - 661-667 LID - 10.1038/s41443-025-01061-2 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists, widely prescribed for type 2 diabetes and weight management, are known for their metabolic benefits but may have unrecognized side effects. This study investigates the association between GLP-1 receptor agonists and male sexual dysfunction using data from the FDA Adverse Event Reporting System (FAERS). Reports from Q4 2003 to Q1 2024 were analyzed using the OpenVigil 2.1 platform to identify male patients experiencing orgasmic dysfunction, erectile dysfunction, or decreased libido linked to GLP-1 receptor agonists (tirzepatide, semaglutide, dulaglutide, exenatide, lixisenatide, and liraglutide). After cleaning duplicate entries, disproportionality measures (reporting odds ratio (ROR), proportional reporting ratio (PRR), and relative reporting ratio (RRR)) were calculated, with Evans' criteria applied to assess signal significance. Among 182 cases identified, patients were predominantly aged 40-60 years, with exenatide accounting for 24.2% of reports, followed by semaglutide (21.4%). Diabetes was the most common indication (43.9%). Despite statistically significant chi-squared values (P < 0.0001), low ROR (0.41, 95% Confidence interval (CI): 0.36-0.48), PRR (0.41, 95% CI: 0.36-0.48), and RRR (0.42, 95% CI: 0.36-0.48) suggest a weak association. These findings underscore the need for monitoring as GLP-1 use expands, though overall patient risk remains low. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Pourabhari Langroudi, Ashkan AU - Pourabhari Langroudi A AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Chen, Abby L AU - Chen AL AUID- ORCID: 0000-0002-4985-2787 AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Basran, Satvir AU - Basran S AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Sommer, Elijah R AU - Sommer ER AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Stinson, James AU - Stinson J AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Cheng, Yu-Sheng AU - Cheng YS AUID- ORCID: 0000-0002-3981-8657 AD - Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Del Giuduce, Francesco AU - Del Giuduce F AD - Department of Maternal Infant and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy. FAU - Scott, Michael AU - Scott M AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. FAU - Eisenberg, Michael L AU - Eisenberg ML AUID- ORCID: 0000-0001-5482-0141 AD - Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA. eisenberg@stanford.edu. LA - eng PT - Journal Article DEP - 20250416 PL - England TA - Int J Impot Res JT - International journal of impotence research JID - 9007383 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Cross-Sectional Studies MH - Adult MH - Exenatide/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Adverse Drug Reaction Reporting Systems MH - Aged MH - Erectile Dysfunction/chemically induced MH - *Sexual Dysfunction, Physiological/chemically induced MH - United States/epidemiology MH - Liraglutide/adverse effects MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with relevant guidelines and regulations. This study utilized publicly available, de-identified data from the FDA Adverse Event Reporting System (FAERS), and therefore did not involve direct interaction with human participants or identifiable private information. As such, the Stanford University School of Medicine Institutional Review Board determined that the study was exempt from review (IRB exemption granted; no reference number applicable for de-identified dataset studies). Because the research did not involve the collection of identifiable human data or images, informed consent to participate and consent for publication were not required. EDAT- 2025/04/17 00:24 MHDA- 2025/09/08 07:55 CRDT- 2025/04/16 23:25 PHST- 2024/08/06 00:00 [received] PHST- 2025/03/27 00:00 [accepted] PHST- 2025/03/17 00:00 [revised] PHST- 2025/09/08 07:55 [medline] PHST- 2025/04/17 00:24 [pubmed] PHST- 2025/04/16 23:25 [entrez] AID - 10.1038/s41443-025-01061-2 [pii] AID - 10.1038/s41443-025-01061-2 [doi] PST - ppublish SO - Int J Impot Res. 2025 Aug;37(8):661-667. doi: 10.1038/s41443-025-01061-2. Epub 2025 Apr 16. PMID- 40239470 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260722 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 6 DP - 2025 Jun TI - Semaglutide, central retinal thickness and continuous glucose monitoring in persons with type 2 diabetes: A post-hoc analysis from a randomised trial. PG - 109039 LID - S1056-8727(25)00092-3 [pii] LID - 10.1016/j.jdiacomp.2025.109039 [doi] AB - AIMS: Glycemic control is important for preventing diabetic retinopathy (DR), but rapid improvements could deteriorate the disease. In some, but not all studies, semaglutide is speculated to worsen DR, but the mechanism is unknown. Central retinal thickness (CRT) is an early marker of DR. Therefore, the objective was to investigate whether increased Time in Range (TIR (3.9-10.0 mmol/L)), was associated with reduced CRT in persons treated with semaglutide. METHODS: Forty participants with type 2 diabetes were included in this post-hoc analysis of a 32-week randomised, placebo-controlled, partly open-label trial investigating the separate and combined effects of semaglutide and empagliflozin on target organ damage in 120 participants with type 2 diabetes. Individuals were randomised into four groups: i) semaglutide, ii) empagliflozin, iii) the combination or iv) placebo, n = 30 for each group). In the present study, 10 participants from each of the 4 arms participated. TIR was assessed using Continuous Glucose Measurement for 7-8 days and CRT was assessed using ocular coherence tomography. RESULTS: In the 10 individuals treated with semaglutide, CRT increased ~1 % (3.76 mum, 95%CI [-0.32; 7.85], p = 0.065) compared to placebo. This was attenuated with adjustment for TIR (p = 0.21). Independently of the four interventions, increased TIR remained associated with increased CRT (0.07 mum, 95%CI[0.03; 0.12]mum, p = 0.002). CONCLUSION: Semaglutide treatment did not impact CRT beyond what could be explained by changes in glycaemia. Across all interventions, increased TIR was associated with increases in CRT, thus supporting the link between rapid improved glycemia and DR. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. Electronic address: soegul@rm.dk. FAU - Vernstrom, Liv AU - Vernstrom L AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Sorensen, Steffen Skovgaard AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Funck, Kristian Lokke AU - Funck KL AD - Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Petersen, Line AU - Petersen L AD - Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Bek, Toke AU - Bek T AD - Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark; Diagnostic Centre, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20250410 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Benzhydryl Compounds) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - *Diabetic Retinopathy/prevention & control MH - *Retina/drug effects/pathology/diagnostic imaging MH - Blood Glucose/analysis/drug effects MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Blood Glucose Self-Monitoring MH - Tomography, Optical Coherence MH - Benzhydryl Compounds/therapeutic use MH - Continuous Glucose Monitoring MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Continuous glucose monitoring OT - Diabetic retinopathy OT - Glucagon-like peptide 1 receptor agonist OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Esben Laugesen reports financial support was provided by Novo Nordisk Foundation. Soeren Gullaksen reports financial support was provided by Danish Medical Association Research Fund. Liv Vernstroem reports financial support was provided by Aarhus University. Steffen Skovgaard Soerensen reports financial support was provided by Independent Research Fund Denmark. Per Loegstrup Poulsen reports financial support was provided by Novo Nordisk Foundation. Per Loegstrup Poulsen reports a relationship with AstraZeneca that includes: board membership and funding grants. Per Loegstrup Poulsen reports a relationship with Bayer AG that includes: board membership. Per Loegstrup Poulsen reports a relationship with Novo Nordisk that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/04/17 00:24 MHDA- 2025/05/01 06:28 CRDT- 2025/04/16 18:09 PHST- 2025/01/15 00:00 [received] PHST- 2025/03/25 00:00 [revised] PHST- 2025/04/07 00:00 [accepted] PHST- 2025/05/01 06:28 [medline] PHST- 2025/04/17 00:24 [pubmed] PHST- 2025/04/16 18:09 [entrez] AID - S1056-8727(25)00092-3 [pii] AID - 10.1016/j.jdiacomp.2025.109039 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Jun;39(6):109039. doi: 10.1016/j.jdiacomp.2025.109039. Epub 2025 Apr 10. PMID- 40237224 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20260924 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 4 IP - 4 DP - 2025 Apr 16 TI - Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors combination therapy for adults with type 2 diabetes mellitus: a network meta-analysis. PG - CD015952 LID - 10.1002/14651858.CD015952 [doi] LID - CD015952 AB - This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To evaluate the relative benefits and harms of therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), and their combination in adults with type 2 diabetes mellitus. Secondary objectives To determine the relative rankings of GLP-1RA, SGLT2i, and their combination, according to their comparative efficacy for the critical outcomes identified in this review through a network meta-analysis. CI - Copyright (c) 2025 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration. FAU - Osman, Alaa Am AU - Osman AA AD - Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Gezira, Wad Madani, Sudan. AD - Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary. FAU - Tayeb, Bizhar Ahmed AU - Tayeb BA AD - Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary. FAU - Metzendorf, Maria-Inti AU - Metzendorf MI AD - Institute of General Practice, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany. FAU - Bongaerts, Brenda AU - Bongaerts B AD - Institute of General Practice, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany. FAU - Mohammed, Neven AU - Mohammed N AD - Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Gezira, Wad Madani, Sudan. FAU - Njangiru, Isaac K AU - Njangiru IK AD - Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary. AD - Laikipia University, Nyahururu, Kenya. FAU - Franco, Juan Va AU - Franco JV AD - Institute of General Practice, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany. LA - eng PT - Journal Article DEP - 20250416 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Therapy, Combination/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Network Meta-Analysis as Topic MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Systematic Reviews as Topic PMC - PMC12001318 COIS- AO: none known BT: none known MM: none known BB: none known NM: none known IN: none known JF: none known Three authors are editorial members of Cochrane Metabolic and Endocrine Disorders: MM (Information Specialist), BB (Co-ordinating Editor), and JF (Managing Editor). JF is also the Contact Editor for Cochrane Urology. These authors were not involved in the editorial process for this protocol. EDAT- 2025/04/16 14:34 MHDA- 2025/04/16 14:35 PMCR- 2025/04/16 CRDT- 2025/04/16 07:14 PHST- 2025/04/16 14:35 [medline] PHST- 2025/04/16 14:34 [pubmed] PHST- 2025/04/16 07:14 [entrez] PHST- 2025/04/16 00:00 [pmc-release] AID - CD015952 [pii] AID - 10.1002/14651858.CD015952 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015952. doi: 10.1002/14651858.CD015952. PMID- 40232990 OWN - NLM STAT- MEDLINE DCOM- 20260427 LR - 20260427 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 39 IP - 3 DP - 2026 Jun TI - Asymptomatic Subcutaneous Semaglutide Overdose: A Case Report and Literature Review. PG - 219-224 LID - 10.1177/08971900251335111 [doi] AB - Semaglutide is a glucagon-like-peptide-1 receptor agonist (GLP-1 RA) that is approved for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Common adverse drug reactions (ADR) of semaglutide include nausea, vomiting, abdominal pain, constipation, and diarrhea, which are often dose-dependent in nature. Select ADRs that are less common, but may result in more significant concerns, include development of acute pancreatitis, gallbladder and biliary tract diseases, acute kidney injury, and ileus. Limited clinical literature exists at present regarding management of GLP-1 RA overdose, particularly for subcutaneous semaglutide. This report describes an 80-year-old male with T2DM and mild cognitive impairment who self-administered subcutaneous semaglutide 1 mg daily over the span of 7 days. The patient denied any ADRs, including those related to gastrointestinal upset or hypoglycemia. Blood glucose readings from the patient's glucometer ranged from 100 - 180 mg/dL. The patient declined to present for medical evaluation until 5 weeks after the overdose incident. No clinically significant changes were noted in his renal function, hepatic function, nor his pancreatic enzymes upon laboratory follow-up. Published reports concerning GLP-1 RA overdoses describe mixed presentation of patients following such events. Treatments detailed in the case reports included primarily supportive care measures. Based on the mechanism of action of GLP-1 RAs, and those case reports detailed, we recommend close monitoring and supportive care in the form of providing antiemetics, correcting fluid and electrolyte imbalances from gastrointestinal losses, and monitoring for hypoglycemia in the event of an overdose. FAU - Diec, Courtney B AU - Diec CB AD - Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, KS, USA. FAU - Cook, Elizabeth A AU - Cook EA AUID- ORCID: 0000-0002-3496-9587 AD - Department of Pharmacy - Clinical Services, Robert J. Dole Veterans Affairs Medical Center, Wichita, KS, USA. RINGGOLD: 20017 FAU - Nguyen, Nguyet T AU - Nguyen NT AD - Department of Pharmacy - Clinical Services, Robert J. Dole Veterans Affairs Medical Center, Wichita, KS, USA. RINGGOLD: 20017 LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20250415 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Drug Overdose/diagnosis MH - Aged, 80 and over MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Injections, Subcutaneous MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - drug overdose OT - glucagon-like-peptide-1 receptor agonist OT - semaglutide COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/04/15 18:24 MHDA- 2026/04/27 06:32 CRDT- 2025/04/15 13:03 PHST- 2026/04/27 06:32 [medline] PHST- 2025/04/15 18:24 [pubmed] PHST- 2025/04/15 13:03 [entrez] AID - 10.1177/08971900251335111 [doi] PST - ppublish SO - J Pharm Pract. 2026 Jun;39(3):219-224. doi: 10.1177/08971900251335111. Epub 2025 Apr 15. PMID- 40230336 OWN - NLM STAT- MEDLINE DCOM- 20250415 LR - 20260318 IS - 1399-0012 (Electronic) IS - 0902-0063 (Linking) VI - 39 IP - 4 DP - 2025 Apr TI - Efficacy, Tolerability, and Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP1-RA) in Kidney Transplant Recipients With Diabetes. PG - e70144 LID - 10.1111/ctr.70144 [doi] AB - INTRODUCTION: Uncontrolled diabetes after solid-organ transplantation has been associated with weight gain, high cardiovascular mortality, and transplant rejection. The current standard of care for uncontrolled diabetes after KT is insulin. Recently GLP1-RA have been proposed as an adjuvant medication for those with obesity, but there are concerns for side effects and safety. METHODS: Adults (n = 50) with diabetes who underwent KT from at a single academic medical center were included. This is a retrospective study of 25 recipients on insulin +/- oral antidiabetic medications who initiated GLP1-RA, and 25 recipients on insulin +/- oral agents. Metabolic issues and safety were evaluated before starting GLP1RA, and 6 and 12 months after. The linear mixed effects model was used to evaluate the mean difference in the change in the outcome between the two groups. RESULTS: KT participants were on average 56 years of age, 64% male, with T2D. The primary outcome of change in weight 12 months after initiation of GLP1-RA on an average was -10.1 pounds in the GLP1-RA group, compared to +6.0 pounds in the non-GLP1-RA group (p < 0.01), the change in BMI 12 months after initiation of GLP1-RA on an average was -1.7 kg/m(2) in the GLP1-RA group compared to +1.1 kg/m(2) in the non-GLP1-RA group (p < 0.01), and the change in creatinine 12 months after starting GLP1-RA was on average -0.2 mg/dL in the GLP1-RA group and on average +0.3 mg/dL in the non-GLP1-RA group (p < 0.01). The change in proteinuria 12 months after starting GLP1-RA was on average -128.4 in the GLP1-RA and on average +15.4 mg/dL in the controls (p < 0.01). The rate of GLP1-RA discontinuation was 0%. CONCLUSIONS: Well-selected post-kidney transplant participants demonstrated good tolerance for GLP-1RA. Participants who took GLP1-RA had better glycemic control, more weight loss, a decrease in daily insulin requirements, better preservation of kidney function, and reduced proteinuria 12 months after initiation of GLP1-RA compared to those who did not. GLP1-RA did not alter tacrolimus levels or doses. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Zelada, Henry AU - Zelada H AUID- ORCID: 0000-0002-8159-0625 AD - Division of Endocrinology Diabetes and Metabolism, David Geffen School of Medicine, University of California, Los Angeles, California, USA. FAU - Campana, Mario AU - Campana M AD - Division of Endocrinology Diabetes and Metabolism, Rush University Medical Center, Chicago, Illinois, USA. FAU - Kawai, Kosuke AU - Kawai K AD - Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, California, USA. FAU - Redden, David AU - Redden D AD - Division of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Agarwal, Gaurav AU - Agarwal G AD - Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA. FAU - Gutierrez, Orlando M AU - Gutierrez OM AD - Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA. FAU - Kumar, Vineeta AU - Kumar V AD - Division of Nephrology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA. LA - eng GR - P30 DK079626/DK/NIDDK NIH HHS/United States GR - UCLA Clinical and Translational Science Institute (NIH/NCATS UL1 TR001881)/ PT - Journal Article PL - Denmark TA - Clin Transplant JT - Clinical transplantation JID - 8710240 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Male MH - Female MH - *Kidney Transplantation/adverse effects MH - Middle Aged MH - Retrospective Studies MH - Follow-Up Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prognosis MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Graft Survival/drug effects MH - Kidney Function Tests MH - Risk Factors MH - Transplant Recipients MH - Adult MH - Glomerular Filtration Rate MH - *Graft Rejection/etiology/pathology MH - *Postoperative Complications/drug therapy MH - Blood Glucose MH - Biomarkers/analysis MH - *Kidney Failure, Chronic/surgery OTO - NOTNLM OT - diabetes OT - kidney (allograft) function OT - posttransplant EDAT- 2025/04/15 06:24 MHDA- 2025/04/15 06:25 CRDT- 2025/04/15 04:33 PHST- 2025/03/05 00:00 [revised] PHST- 2024/10/22 00:00 [received] PHST- 2025/03/19 00:00 [accepted] PHST- 2025/04/15 06:25 [medline] PHST- 2025/04/15 06:24 [pubmed] PHST- 2025/04/15 04:33 [entrez] AID - 10.1111/ctr.70144 [doi] PST - ppublish SO - Clin Transplant. 2025 Apr;39(4):e70144. doi: 10.1111/ctr.70144. PMID- 40230207 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - The effect of GLP-1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta-analysis. PG - 3607-3626 LID - 10.1111/dom.16366 [doi] AB - AIM: To investigate whether the antidiabetic agent glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can exert anti-inflammatory effects while lowering blood glucose, we performed a meta-analysis and systematic review. METHODS: We searched 4 online databases (Medline, Embase, Cochrane Library and the Web of Science) for randomised controlled trials (RCTs) that examined changes after GLP-1RAs intervention in commonly accepted biomarkers of inflammation: C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1(MCP-1) and advanced glycation end products (AGEs). RESULTS: This meta-analysis included 52 eligible RCTs (n = 4734) with a median follow-up of 24 weeks, a mean age of 54.13 years, 44.46% females, body mass index (BMI) 29.80 kg/m(2), glycated haemoglobin (HbA1c) 8.28% and diabetes duration 7.27 years. GLP-1 RAs treatment, compared to placebo or conventional diabetes therapies (including oral medicine and insulin), resulted in significant reductions in CRP, TNF-alpha, IL-6, IL-1beta and leptin (standard mean difference [SMD] -0.63 [-1.03, -0.23]; SMD -0.92 [-1.57, -0.27]; SMD -0.76 [-1.32, -0.20], SMD -3.89 [-6.56, -1.22], SMD -0.67 [-1.09, -0.26], respectively), as well as significant increases in adiponectin (SMD 0.69 [0.19, 1.19]). CONCLUSIONS: Our meta-analysis demonstrates that GLP-1 RAs exert significant anti-inflammatory effects in patients with T2DM. Our findings provide important insights that may guide the therapeutic application of GLP-1 RAs and inform the development of related therapies. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Ren, Yifan AU - Ren Y AUID- ORCID: 0009-0006-3295-5049 AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Chen, Yuzhang AU - Chen Y AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Zheng, Wenbin AU - Zheng W AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Kong, Wen AU - Kong W AUID- ORCID: 0000-0002-9275-8809 AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Liao, Yunfei AU - Liao Y AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Zhang, Jiaoyue AU - Zhang J AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Wang, Meng AU - Wang M AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. FAU - Zeng, Tianshu AU - Zeng T AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China. AD - Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China. LA - eng GR - 81974107/National Natural Science Foundation of China/ GR - 82270909/National Natural Science Foundation of China/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250415 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Biomarkers/blood MH - *Hypoglycemic Agents/therapeutic use MH - *Inflammation/blood/drug therapy MH - Randomized Controlled Trials as Topic MH - C-Reactive Protein/metabolism MH - Female OTO - NOTNLM OT - CRP OT - GLP-1 RAs OT - IL-6 OT - glucagon-like peptide-1 receptor agonists OT - inflammation OT - meta-analysis EDAT- 2025/04/15 06:24 MHDA- 2025/06/09 06:26 CRDT- 2025/04/15 03:13 PHST- 2025/03/11 00:00 [revised] PHST- 2024/09/06 00:00 [received] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/06/09 06:26 [medline] PHST- 2025/04/15 06:24 [pubmed] PHST- 2025/04/15 03:13 [entrez] AID - 10.1111/dom.16366 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3607-3626. doi: 10.1111/dom.16366. Epub 2025 Apr 15. PMID- 40230199 OWN - NLM STAT- MEDLINE DCOM- 20250415 LR - 20250418 IS - 1525-6049 (Electronic) IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 47 IP - 1 DP - 2025 Dec TI - Glucagon-like peptide-1 receptor agonists, inflammation, and kidney diseases: evidence from Mendelian randomization. PG - 2478488 LID - 10.1080/0886022X.2025.2478488 [doi] LID - 2478488 AB - OBJECTIVE: It has been proved that glucagon-like peptide-1 receptor (GLP1R) agonists have positive effects on renal outcomes in diabetic patients. However, it remains unknown whether GLP1R agonists could provide similar protection against other kidney diseases. METHODS: We performed two-sample Mendelian randomization (MR) analyses to determine the causal effects of GLP1R agonists on multiple kidney diseases. Exposure to GLP1R agonist was proxied by the available cis-eQTLs for GLP1R. Primary outcomes included the risk assessment for diabetic nephropathy, IgA nephropathy, membranous nephropathy, nephrotic syndrome, chronic kidney disease, acute glomerulonephritis, chronic glomerulonephritis and calculus of kidney/ureter. Type 2 diabetes and body mass index were used as positive control. Two-stage network MR analyses were conducted to assess the mediation effect of inflammatory proteins on the relationships between GLP1R agonists and kidney diseases. RESULTS: After meta-analyses of both discovery and validation cohorts, genetically proxied GLP1R agonist was found to significantly associated with a decreased risk of diabetic nephropathy (OR = 0.72, 95%CI = 0.54-0.97, p = 0.031) and IgA nephropathy (OR = 0.58, 95%CI = 0.36-0.94, p = 0.027). Two-stage network MR revealed that there was an indirect effect of GLP1R agonist on IgA nephropathy through signaling lymphocytic activation molecule family member 1 (SLAMF1), with a mediated proportion of 34.27% (95% CI, 1.47-67.03%, p = 0.041) of the total effect. CONCLUSIONS: The findings of current study presented genetic proof for the potential protective effects of GLP1R agonists in the development of diabetic nephropathy and IgA nephropathy, offering a novel sight for future mechanistic and clinical applications. FAU - Yao, Yu-Xuan AU - Yao YX AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Tang, Chen AU - Tang C AUID- ORCID: 0000-0002-7225-9105 AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Si, Feng-Lei AU - Si FL AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Lv, Ji-Cheng AU - Lv JC AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Shi, Su-Fang AU - Shi SF AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhou, Xu-Jie AU - Zhou XJ AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Liu, Li-Jun AU - Liu LJ AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhang, Hong AU - Zhang H AD - Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China. AD - Ministry of Education, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250415 PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/complications MH - *Diabetic Nephropathies/genetics/prevention & control MH - Glucagon-Like Peptide-1 Receptor/genetics MH - *Inflammation/genetics MH - *Kidney Diseases/genetics/prevention & control MH - Risk Assessment PMC - PMC12001840 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - IgA nephropathy OT - Mendelian randomization OT - chronic kidney disease OT - diabetic nephropathy COIS- No potential conflict of interest was reported by the author(s). EDAT- 2025/04/15 06:24 MHDA- 2025/04/15 06:25 PMCR- 2025/04/15 CRDT- 2025/04/15 03:13 PHST- 2025/04/15 06:25 [medline] PHST- 2025/04/15 06:24 [pubmed] PHST- 2025/04/15 03:13 [entrez] PHST- 2025/04/15 00:00 [pmc-release] AID - 2478488 [pii] AID - 10.1080/0886022X.2025.2478488 [doi] PST - ppublish SO - Ren Fail. 2025 Dec;47(1):2478488. doi: 10.1080/0886022X.2025.2478488. Epub 2025 Apr 15. PMID- 40228298 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 178 IP - 5 DP - 2025 May TI - Trends in Utilization of Glucose- and Weight-Lowering Medications After Tirzepatide Approval in the United States : A Population-Based Cohort Study. PG - 620-633 LID - 10.7326/ANNALS-24-02870 [doi] AB - BACKGROUND: Recent trends in use of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist (RA), versus other glucose-lowering medications (GLMs) and weight-lowering medications (WLMs) remain unexplored. OBJECTIVE: To describe trends in insurance claims for GLMs and WLMs after tirzepatide approval. DESIGN: Population-based cohort study. SETTING: Claims data from a large U.S. commercial database (January 2021 to December 2023). PARTICIPANTS: Adults (aged >/=18 years) with type 2 diabetes (T2D) and without diabetes with dispensations for GLMs and WLMs. Any use was defined as medication dispensation regardless of prior use. Incident use was defined as dispensation without use in the preceding year. MEASUREMENTS: Monthly trends in medication dispensations before and after tirzepatide market entry. Tirzepatide uptake was additionally compared with initial postapproval uptake of other GLMs and WLMs. RESULTS: Tirzepatide dispensations increased markedly among adults with T2D prescribed GLMs, reaching 12.3% of all GLM dispensations by December 2023. Similar patterns were observed for sodium-glucose cotransporter-2 inhibitors (14.5% to 24.4%) and GLP-1 RAs (19.5% to 28.5%). Dispensations of other GLMs, including metformin, declined. Among adults without diabetes but prescribed WLMs, tirzepatide (0.0% to 40.6%) and semaglutide (2.4 mg) (0.0% to 32.2%) dispensations increased sharply, but semaglutide (2.0 mg) was the most frequently dispensed WLM, increasing from 37.8% to 45.7%. Dispensations of other WLMs declined. Similar trends were observed among incident users. Tirzepatide uptake was more rapid and sustained compared with initial postapproval periods for other medications. LIMITATION: Generalizability to U.S. adults without commercial health insurance is uncertain. CONCLUSION: These findings highlight the sharp uptake of tirzepatide after U.S. market entry and enhance understanding of the rapidly shifting landscape of prescribing patterns for GLMs and WLMs. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases. FAU - Ostrominski, John W AU - Ostrominski JW AUID- ORCID: 0000-0002-2866-9414 AD - Cardiovascular Division, Division of Endocrinology, Diabetes and Hypertension, and Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.W.O.). FAU - Ortega-Montiel, Janinne AU - Ortega-Montiel J AUID- ORCID: 0000-0001-8196-6648 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Alix, Caroline AU - Alix C AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - DiCesare, Elyse AU - DiCesare E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Cromer, Sara J AU - Cromer SJ AUID- ORCID: 0000-0002-4924-2049 AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.J.C., D.J.W.). FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.J.C., D.J.W.). FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics and Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.M.P.). FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250415 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Male MH - Female MH - *Tirzepatide/therapeutic use MH - Adult MH - Aged MH - Cohort Studies MH - *Drug Utilization/trends MH - Drug Approval PMC - PMC12718076 MID - NIHMS2124627 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/04/14 18:24 MHDA- 2025/05/19 18:34 PMCR- 2025/12/20 CRDT- 2025/04/14 17:02 PHST- 2025/05/19 18:34 [medline] PHST- 2025/04/14 18:24 [pubmed] PHST- 2025/04/14 17:02 [entrez] PHST- 2025/12/20 00:00 [pmc-release] AID - 10.7326/ANNALS-24-02870 [doi] PST - ppublish SO - Ann Intern Med. 2025 May;178(5):620-633. doi: 10.7326/ANNALS-24-02870. Epub 2025 Apr 15. PMID- 40227520 OWN - NLM STAT- MEDLINE DCOM- 20251125 LR - 20261010 IS - 1573-6709 (Electronic) IS - 0033-2720 (Linking) VI - 96 IP - 4 DP - 2025 Dec TI - Semaglutide Plus Metformin Versus Metformin Alone For Antipsychotic-Induced Weight Gain In Patients With Type 2 Diabetes Mellitus. PG - 819-827 LID - 10.1007/s11126-025-10137-7 [doi] AB - To determine whether combination therapy (semaglutide + metformin) is more efficacious than monotherapy (metformin alone) in reducing the risk of antipsychotic-induced weight gain (AIWG) in patients with Type 2 Diabetes Mellitus (T2DM). This was a single-center, retrospective study evaluating patients >/= 18 years of age receiving care at Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) from January 2021 to December 2022. Subjects were identified by use of antipsychotic (quetiapine, risperidone, paliperidone, olanzapine, clozapine) with concomitant use of monotherapy or combination therapy. Key exclusion criteria included other medications impacting weight, unstable medical illness, active substance use disorder, and dual antipsychotic use. The primary endpoint was defined as weight loss >/= 5% from baseline. Secondary outcomes included BMI % difference and HbA1c difference from baseline. Data was analyzed using descriptive statistics. 31 patients were evaluated in each group for the final analysis. 38.7% (12/31) of patients in the monotherapy group achieved the primary outcome of weight loss >/= 5% from baseline vs. 61.29% (19/31) in the combination group (p = 0.04). For secondary outcomes, the BMI % difference from baseline in the monotherapy group was -3.88% vs. -5.58% in the combination group (p = 0.129). The monotherapy group had a difference in HbA1c % from baseline of 0.14% vs -0.9% in the combination group (p = 0.007). Among T2DM patients on antipsychotics, more patients in the combination group achieved weight loss >/= 5% within the study period compared to metformin monotherapy. Future research should account for non-diabetic patients, assess lifestyle factors, and exclude other psychotropic medications that may affect weight. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Vu, Catherine AU - Vu C AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. cthrnvu@gmail.com. FAU - Thai, Raymond AU - Thai R AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. FAU - Dike, Dozie AU - Dike D AD - Psychiatry & Behavioral Sciences Department, Baylor College of Medicine, Houston, TX, USA. FAU - Sydner, Bria AU - Sydner B AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250414 PL - United States TA - Psychiatr Q JT - The Psychiatric quarterly JID - 0376465 RN - 9100L32L2N (Metformin) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Metformin/pharmacology/administration & dosage MH - *Antipsychotic Agents/adverse effects MH - Male MH - Middle Aged MH - Female MH - *Weight Gain/drug effects MH - Retrospective Studies MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/pharmacology/administration & dosage MH - Aged MH - *Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Antipsychotics OT - Diabetes OT - Metformin OT - Semaglutide OT - Veterans OT - Weight gain COIS- Declarations. All authors of this article do not have any financial or non-financial interests directly or indirectly related to the work submitted. Human Ethics and Consent to Participate: This study was approved by the Baylor College of Medicine Institutional Review Board (IRB) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. EDAT- 2025/04/14 12:25 MHDA- 2025/11/25 13:55 CRDT- 2025/04/14 11:18 PHST- 2025/03/18 00:00 [accepted] PHST- 2025/11/25 13:55 [medline] PHST- 2025/04/14 12:25 [pubmed] PHST- 2025/04/14 11:18 [entrez] AID - 10.1007/s11126-025-10137-7 [pii] AID - 10.1007/s11126-025-10137-7 [doi] PST - ppublish SO - Psychiatr Q. 2025 Dec;96(4):819-827. doi: 10.1007/s11126-025-10137-7. Epub 2025 Apr 14. PMID- 40227398 OWN - NLM STAT- MEDLINE DCOM- 20250414 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 4 DP - 2025 Apr TI - Combined effect of continuous glucose monitoring and semaglutide: analysis of administrative claims. PG - 183-188 LID - 10.37765/ajmc.2025.89719 [doi] AB - OBJECTIVES: This study evaluated whether the combined use of continuous glucose monitoring (CGM) and semaglutide, a glucagon-like peptide-1 receptor agonist, was associated with larger hemoglobin A1c (HbA1c) improvements compared with use of semaglutide alone. STUDY DESIGN: Using US health care claims data from the Optum Clinformatics database, this retrospective analysis identified adults with type 2 diabetes (T2D) using semaglutide. METHODS: The CGM cohort had at least 1 CGM-related claim between January 1, 2019, and September 30, 2022. Random index dates were used in the control (non-CGM) cohort. At least 1 laboratory HbA1c value was required during baseline and follow-up periods. Outcomes included change in HbA1c and the proportion of people who reached American Diabetes Association (ADA) or Healthcare Effectiveness Data and Information Set (HEDIS) HbA1c targets of less than 7.0% or less than 8.0%, respectively. RESULTS: A total of 21,247 people with T2D were identified, with 18,488 in the control group and 2759 using CGM. Overall, a significantly greater reduction in HbA1c was observed in the CGM cohort compared with the control group (difference-in-differences, -0.55%; 95% CI, -0.64% to -0.47%; P < .0001). Among CGM users, the proportion meeting the ADA target of HbA1c less than 7.0% nearly doubled, and the proportion achieving the HEDIS target of HbA1c less than 8.0% increased by more than 50%. CONCLUSIONS: The results suggest that CGM provides an additive benefit to semaglutide, leading to greater decreases in HbA1c. Expanded use of these complementary therapies in the primary care setting could enable more people with T2D to achieve their glycemic goals. FAU - Nemlekar, Poorva M AU - Nemlekar PM FAU - Hannah, Katia L AU - Hannah KL FAU - Green, Courtney R AU - Green CR FAU - Grace, Thomas AU - Grace T FAU - Lynch, Peter M AU - Lynch PM FAU - Castle, Jessica R AU - Castle JR FAU - Norman, Gregory J AU - Norman GJ AD - Dexcom, Inc, 6340 Sequence Dr, San Diego, CA 92121. Email: greg.norman@dexcom.com. LA - eng PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Glycated Hemoglobin/analysis MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Blood Glucose Self-Monitoring/methods MH - Aged MH - Blood Glucose/analysis MH - United States MH - Adult MH - Continuous Glucose Monitoring MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/04/14 12:25 MHDA- 2025/04/14 12:26 CRDT- 2025/04/14 11:12 PHST- 2025/04/14 12:26 [medline] PHST- 2025/04/14 12:25 [pubmed] PHST- 2025/04/14 11:12 [entrez] AID - 89719 [pii] AID - 10.37765/ajmc.2025.89719 [doi] PST - ppublish SO - Am J Manag Care. 2025 Apr;31(4):183-188. doi: 10.37765/ajmc.2025.89719. PMID- 40227008 OWN - NLM STAT- MEDLINE DCOM- 20250414 LR - 20260710 IS - 1369-7625 (Electronic) IS - 1369-6513 (Print) IS - 1369-6513 (Linking) VI - 28 IP - 2 DP - 2025 Apr TI - What Are the Experiences, Views and Perceptions of Patients, Carers and Clinicians of Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs)? A Scoping Review. PG - e70251 LID - 10.1111/hex.70251 [doi] LID - e70251 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a pharmacological treatment option for both diabetes and weight loss. Qualitative evidence is vital in providing greater understanding of patients, practitioners and carers experience of taking or delivering GLP-1 RAs. This evidence can inform the current or future configuration and delivery of services. We conducted a scoping review to better understand the quantity, nature and key characteristics of qualitative primary evidence which explores the experiences, views and perceptions of patients, carers and clinicians regarding the use of GLP-1 RAs. METHODS: Four bibliographic databases were searched on 10 July 2024: MEDLINE, APA PsycInfo via Ovid, CINAHL Ultimate via EBSCOhost, ProQuest Dissertations and Theses Global via ProQuest. We also searched Google Scholar, two clinical trials registries, the pre-print server medRxiv and conducted citation searches. We sought qualitative research about the experiences of patients, carers and practitioners about any aspect of taking or prescribing GLP-1RAs, for any indication. Study selection and data extraction were performed by two independent reviewers. The included studies were collated, and their characteristics were described. RESULTS: After de-duplication 1545 titles and abstracts were screened for relevance, with 77 full-text articles assessed for eligibility, resulting in 25 included studies. More studies were focused on type 2 diabetes (n = 12) than weight loss (n = 9) or any indication (n = 4). The experiences of carers were not represented. No one area of experience (e.g. different indications or viewpoints) was well represented, either due to the absence or narrow focus of studies or lack of an in-depth analytical approach. CONCLUSION: Whilst primary qualitative evidence exploring patient and clinician experience of GLP-1 RAs was identified in this scoping review, the findings highlight a need for more robust qualitative research to be conducted across all user groups, in particular involving carers, and especially for the indication of weight loss within service settings. This evidence gap needs to be urgently addressed to ensure GLP-1 RAs are appropriately prescribed and patients and carers receive support from services suited to their needs. PATIENT OR PUBLIC CONTRIBUTION: Seventeen public collaborators contributed to the search by suggesting additional search terms, helping define the population for inclusion and contributing to protocol development. Their thoughts on the findings of the review helped form the basis for the discussion of this paper. CI - (c) 2025 The Author(s). Health Expectations published by John Wiley & Sons Ltd. FAU - Febrey, Sam AU - Febrey S AUID- ORCID: 0000-0002-4944-664X AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Nunns, Michael AU - Nunns M AUID- ORCID: 0000-0001-5500-0911 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Buckland, Jill AU - Buckland J AUID- ORCID: 0009-0009-1533-6862 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Abbott, Rebecca AU - Abbott R AUID- ORCID: 0000-0003-4165-4484 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. AD - NIHR Applied Research Collaboration South West Peninsula (PenARC), University of Exeter Medical School, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Bethel, Alison AU - Bethel A AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. AD - NIHR Applied Research Collaboration South West Peninsula (PenARC), University of Exeter Medical School, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Whear, Rebecca AU - Whear R AUID- ORCID: 0000-0002-8379-8198 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. AD - NIHR Applied Research Collaboration South West Peninsula (PenARC), University of Exeter Medical School, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Boddy, Kate AU - Boddy K AUID- ORCID: 0000-0001-9135-5488 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Melendez-Torres, G J AU - Melendez-Torres GJ AUID- ORCID: 0000-0002-9823-4790 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Coon, Jo Thompson AU - Coon JT AUID- ORCID: 0000-0002-5161-0234 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. AD - NIHR Applied Research Collaboration South West Peninsula (PenARC), University of Exeter Medical School, University of Exeter, St Lukes Campus, Exeter, Devon, UK. FAU - Shaw, Liz AU - Shaw L AUID- ORCID: 0000-0002-6092-5019 AD - Isca Evidence, University of Exeter Medical School, Faculty of Health & Life Sciences, University of Exeter, St Lukes Campus, Exeter, Devon, UK. LA - eng GR - This study was supported NIHR Evidence Synthesis Programme (NIHR153420)./ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Scoping Review PL - England TA - Health Expect JT - Health expectations : an international journal of public participation in health care and health policy JID - 9815926 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Attitude of Health Personnel MH - *Caregivers/psychology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Patients/psychology MH - Qualitative Research PMC - PMC11995417 OTO - NOTNLM OT - diabetes OT - glucagon-Like peptide 1 receptor agonists (GLP-1 RAs) OT - obesity OT - qualitative OT - scoping review OT - weight loss COIS- Fifteen of the 25 studies reported on conflict of interest [16, 19, 20, 22, 24, 25, 26, 29, 31, 33, 35, 37, 38, 39, 40] and out of these eleven declared some form of conflict [16, 19, 20, 24, 26, 29, 33, 35, 37, 38, 39]. Details of funding sources were reported in 20 studies [16, 17, 18, 19, 20, 21, 22, 24, 25, 26, 28, 29, 31, 33, 34, 35, 36, 38, 39, 40] and seven of these were partially or fully funded by a pharmaceutical company [16, 18, 21, 24, 33, 35, 38]. Ten studies did not include any conflict-of-interest statement [15, 16, 19, 21, 25, 26, 28, 30, 32, 34]. The authors declare no conflicts of interest. EDAT- 2025/04/14 12:25 MHDA- 2025/04/14 12:26 PMCR- 2025/04/14 CRDT- 2025/04/14 08:43 PHST- 2025/03/18 00:00 [revised] PHST- 2024/10/22 00:00 [received] PHST- 2025/03/22 00:00 [accepted] PHST- 2025/04/14 12:26 [medline] PHST- 2025/04/14 12:25 [pubmed] PHST- 2025/04/14 08:43 [entrez] PHST- 2025/04/14 00:00 [pmc-release] AID - HEX70251 [pii] AID - 10.1111/hex.70251 [doi] PST - ppublish SO - Health Expect. 2025 Apr;28(2):e70251. doi: 10.1111/hex.70251. PMID- 40223043 OWN - NLM STAT- MEDLINE DCOM- 20250522 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 85 IP - 6 DP - 2025 Jun TI - Association of Glucagon-Like Peptide-1 Receptor Agonist with Progression to Liver Cirrhosis and Alcohol-Related Admissions in Patients with Alcohol Use Disorder and Diabetes: A Retrospective Cohort Study. PG - 813-825 LID - 10.1007/s40265-025-02177-x [doi] AB - AIM: In recent years, use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased due to their beneficial effects on weight loss and cardiovascular outcomes. Lately, some animal studies and observational data suggested that GLP-1RA may be useful in the treatment of alcohol use disorder (AUD). We aim to compare the risk of progression to liver cirrhosis and alcohol-related hospital admission after initiation of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4i), as the active comparator, in patients with type 2 diabetes mellitus and AUD. METHODS: We conducted a retrospective propensity score-matched cohort study, utilizing new-user and active comparator design. The study used data from the Veterans Health Administration during fiscal years 2006 to 2021 encompassing adults with AUD who initiated either GLP-1RA or DPP4i prescriptions. Our two co-primary outcomes were progression to cirrhosis (compensated and decompensated cirrhosis) and alcohol-related hospital admission. RESULTS: The eligible cohort included 9965 GLP-1RA users and 19,688 DPP4i users. After propensity score matching, 7302 pairs were matched on 79 characteristics without residual imbalances. In the propensity score-matched cohort, progression to cirrhosis occurred in 6.6% of GLP-1RA users and 6.0% DPP4i users; odds ratio (OR): 1.1, 95% confidence interval (95% CI): 0.97-1.26. Alcohol-related hospital admission occurred in 1.4% of GLP-1RA users and in 1.7% of DPP4i users (OR: 0.85; 95% CI: 0.65-1.11). CONCLUSIONS: Use of GLP-1RA in patients with AUD was not associated with beneficial effect on progression to cirrhosis or alcohol-related hospital admission. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Al-Moussally, Feras AU - Al-Moussally F AUID- ORCID: 0009-0005-2751-3783 AD - Internal Medicine Residency, University of Central Florida HCA Healthcare GME, Greater Orlando, FL, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, 32827, USA. FAU - Khan, Saud AU - Khan S AD - Internal Medicine Residency, University of Central Florida HCA Healthcare GME, Greater Orlando, FL, USA. AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, 32827, USA. FAU - Katukuri, Vinay AU - Katukuri V AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, 32827, USA. AD - HCA Florida Osceola Hospital, Kissimmee, FL, USA. FAU - Kinaan, Mustafa AU - Kinaan M AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, 32827, USA. AD - Endocrinology, Diabetes, and Metabolism Fellowship, University of Central Florida HCA Healthcare GME, Greater Orlando, FL, USA. FAU - Mansi, Ishak A AU - Mansi IA AD - Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, 32827, USA. Ishak.mansi@va.gov. AD - Education Service, Orlando VA Healthcare System, 13800 Veterans Way, Orlando, FL, 32827, USA. Ishak.mansi@va.gov. LA - eng PT - Journal Article DEP - 20250413 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Liver Cirrhosis MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Disease Progression MH - *Alcoholism/drug therapy/complications MH - Hospitalization/statistics & numerical data MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Propensity Score MH - Cohort Studies MH - Adult MH - *Alcohol-Related Disorders/drug therapy COIS- Declarations. Funding: Resources of the Orlando VA Medical Center were used to conduct the study. This work was supported, in part or in whole, by HCA Healthcare and/or an HCA Healthcare affiliated entity. Role of Sponsor: None. Conflict of Interest/Disclosure: The authors declare that they do not have a financial conflict of interest related to this work. Disclaimer: The views expressed herein are those of the authors and do not reflect the official policy or position of the Veterans Health Administration, or the US Government or any of its affiliated entities. Some of the authors are employees of the US government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Data Availability Statement: Data are stored in the VA Informatics and Computing Infrastructure (VINCI), the operational platform for health services research at the Veterans Healthcare Administration (VHA). VINCI acts as data steward for VHA Data Systems. Data in VINCI cannot be copied, transferred, or printed. Access to data by other researchers is possible following VINCI protocols, as described in the VINCI Central website: http://vaww.vinci.med.va.gov/VinciCentral . Ethics Approval: The Orlando VA institutional review board approved the study. Consent to Participate: The Orlando VA institutional review board waived the need for participants' informed consent since only preexisting deidentified data were used. Consent for Publication: Not applicable. Author Contributions: FA: study concept and design, interpretation of data, and drafting of the manuscript. SK: study concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. VK: study concept and design, interpretation of data, and critical revision of the manuscript for important intellectual content. MK: study concept and design, interpretation of data, critical revision of the manuscript for important intellectual content, and study supervision. IM: study concept and design, acquisition of data along with statistical analysis, interpretation of data, critical revision of the manuscript for important intellectual content, and study supervision. Code Availability: Not applicable. EDAT- 2025/04/14 00:25 MHDA- 2025/05/23 00:27 CRDT- 2025/04/13 23:08 PHST- 2025/03/17 00:00 [accepted] PHST- 2025/05/23 00:27 [medline] PHST- 2025/04/14 00:25 [pubmed] PHST- 2025/04/13 23:08 [entrez] AID - 10.1007/s40265-025-02177-x [pii] AID - 10.1007/s40265-025-02177-x [doi] PST - ppublish SO - Drugs. 2025 Jun;85(6):813-825. doi: 10.1007/s40265-025-02177-x. Epub 2025 Apr 13. PMID- 40221226 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20250811 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 46 IP - 5 DP - 2025 May TI - Structural pharmacology and mechanisms of GLP-1R signaling. PG - 422-436 LID - S0165-6147(25)00043-4 [pii] LID - 10.1016/j.tips.2025.03.003 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R), a class B1 G protein-coupled receptor, plays critical roles in glucose homeostasis. Recent structural pharmacology studies using cryogenic electron microscopy, X-ray crystallography, mass spectrometry, and functional analyses, have provided valuable insights into its activation by endogenous hormones and mono- or dual agonists like semaglutide and tirzepatide, highly effective in treating type 2 diabetes and obesity. They highlight significant conformational changes in the extracellular and transmembrane domains of GLP-1R that drive receptor activation and downstream signal transduction. Additionally, allosteric modulators, supported by emerging structural information, show great promises as an alternative strategy. Future research investigating unexplored effector interactions, biased signaling, weight rebound mechanisms, and personalized therapy strategies will be critical for developing better therapeutic agents targeting GLP-1R. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Zhou, Qingtong AU - Zhou Q AD - Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China. FAU - Zhao, Fenghui AU - Zhao F AD - The National Center for Drug Screening, Shanghai 201203, China. FAU - Zhang, Yao AU - Zhang Y AD - Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. FAU - Yang, Dehua AU - Yang D AD - Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China; The National Center for Drug Screening, Shanghai 201203, China. FAU - Wang, Ming-Wei AU - Wang MW AD - Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China; Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 570228, China; Department of Chemistry, School of Science, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: mwwang@simm.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250411 PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - Signal Transduction/drug effects MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Hypoglycemic Agents/pharmacology OTO - NOTNLM OT - GLP-1R OT - GLP-1RA OT - allosteric modulation OT - conformational dynamics OT - diabetes OT - obesity OT - structural pharmacology COIS- Declaration of interests The authors declare no competing conflict of interest. EDAT- 2025/04/13 00:44 MHDA- 2025/05/04 15:35 CRDT- 2025/04/12 21:56 PHST- 2025/02/11 00:00 [received] PHST- 2025/03/13 00:00 [revised] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/05/04 15:35 [medline] PHST- 2025/04/13 00:44 [pubmed] PHST- 2025/04/12 21:56 [entrez] AID - S0165-6147(25)00043-4 [pii] AID - 10.1016/j.tips.2025.03.003 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2025 May;46(5):422-436. doi: 10.1016/j.tips.2025.03.003. Epub 2025 Apr 11. PMID- 40221023 OWN - NLM STAT- MEDLINE DCOM- 20250929 LR - 20260122 IS - 0210-5705 (Print) IS - 0210-5705 (Linking) VI - 48 IP - 8 DP - 2025 Oct TI - Multidisciplinary clinical practice guideline on the management of metabolic hepatic steatosis. PG - 502442 LID - S0210-5705(25)00118-9 [pii] LID - 10.1016/j.gastrohep.2025.502442 [doi] AB - Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan(R) for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1). CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Romero-Gomez, Manuel AU - Romero-Gomez M AD - UGC Aparato Digestivo, Hospital Universitario Virgen del Rocio, Sevilla, Espana; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Espana; Instituto de Biomedicina de Sevilla (HUVR/CSIC/US), Departamento de Medicina, Universidad de Sevilla, Sevilla, Espana; Asociacion Espanola para el Estudio del Higado, Espana. Electronic address: mromerogomez@us.es. FAU - Escalada, Javier AU - Escalada J AD - Sociedad Espanola de Endocrinologia y Nutricion. Clinica Universidad de Navarra, Pamplona, Espana; Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Espana; Instituto de Investigacion en la Salud de Navarra (IdiSNA), Pamplona, Espana. Electronic address: fjavier.escalada@gmail.com. FAU - Noguerol, Mar AU - Noguerol M AD - Centro de Salud Universitario Cuzco de Fuenlabrada, Madrid, Espana; Sociedad Espanola de Medicina de Familia y Comunitaria, Madrid, Espana. FAU - Perez, Antonio AU - Perez A AD - Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; CIBER de Diabetes y Enfermedades Metabolicas (CIBERDEM), Madrid, Espana; Sociedad Espanola de Diabetes, Madrid, Espana. FAU - Carretero, Juana AU - Carretero J AD - Hospital Universitario de Badajoz, Badajoz, Espana; Sociedad Espanola de Medicina Interna (SEMI), Madrid, Espana. FAU - Crespo, Javier AU - Crespo J AD - Hospital Universitario Marques de Valdecilla, Santander, Espana; Sociedad Espanola de Patologia Digestiva, Madrid, Espana; Grupo de Investigacion Clinica y Traslacional en Enfermedades Digestivas, Santander, Espana; Instituto de Investigacion Valdecilla (IDIVAL), Santander, Espana. FAU - Mascort, Juan J AU - Mascort JJ AD - Sociedad Espanola de Medicina de Familia y Comunitaria, Madrid, Espana; Centro de Salud Florida Sud, Institut Catala de la Salut, Hospitalet de Llobregat, Espana. FAU - Aguilar, Ignacio AU - Aguilar I AD - Centro de Salud Roquetas Norte, Roquetas de Mar, Almeria, Espana. FAU - Tinahones, Francisco AU - Tinahones F AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Espana; Departamento de Endocrinologia y Nutricion, Hospital Virgen de la Victoria, Malaga, Espana; Sociedad Espanola de Obesidad, Madrid, Espana; Instituto de Investigacion Biomedica de Malaga (IBIMA)-Plataforma Bionard, Universidad de Malaga, Malaga, Espana. FAU - Canones, Pedro AU - Canones P AD - Sociedad Espanola de Medicos Generales y de Familia, Madrid, Espana. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Sociedad Espanola de Medicina Interna (SEMI), Madrid, Espana; Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Malaga, Espana; Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Espana. FAU - de Luis, Daniel AU - de Luis D AD - Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valladolid, Valladolid, Espana; Centro de Investigacion de Endocrinologia y Nutricion, Universidad de Valladolid, Valladolid, Espana. FAU - Genua Trullos, Idoia AU - Genua Trullos I AD - Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; Sociedad Espanola de Diabetes, Madrid, Espana. FAU - Aller, Rocio AU - Aller R AD - Asociacion Espanola para el Estudio del Higado, Espana; Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; Sociedad Espanola de Diabetes, Madrid, Espana; Servicio de Aparato Digestivo, Hospital Clinico Universitario de Valladolid, Universidad de Valladolid, Valladolid, Espana; Ciber Enfermedades infecciosas (CIBERINFEC), Madrid, Espana. FAU - Rubio, Miguel A AU - Rubio MA AD - Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; Hospital Clinico San Carlos, Madrid, Espana. LA - eng LA - spa PT - Journal Article PT - Practice Guideline TT - Guia de practica clinica multidisciplinar de manejo de la esteatosis hepatica metabolica. DEP - 20250411 PL - Spain TA - Gastroenterol Hepatol JT - Gastroenterologia y hepatologia JID - 8406671 SB - IM EIN - Gastroenterol Hepatol. 2026 Jan 21:502639. doi: 10.1016/j.gastrohep.2025.502639. PMID: 41571546 MH - Humans MH - *Fatty Liver/therapy/diagnosis MH - *Non-alcoholic Fatty Liver Disease/therapy/diagnosis MH - Liver Cirrhosis/etiology MH - Risk Factors MH - Diabetes Mellitus, Type 2/complications MH - Delphi Technique MH - Patient Care Team OTO - NOTNLM OT - Derivacion OT - Deteccion OT - Detection OT - Esteatohepatitis OT - Esteatosis hepatica metabolica OT - Fibrosis OT - Metabolic hepatic steatosis OT - Referral OT - Steatohepatitis EDAT- 2025/04/13 00:44 MHDA- 2025/09/30 05:17 CRDT- 2025/04/12 19:36 PHST- 2025/02/25 00:00 [received] PHST- 2025/03/26 00:00 [revised] PHST- 2025/03/31 00:00 [accepted] PHST- 2025/09/30 05:17 [medline] PHST- 2025/04/13 00:44 [pubmed] PHST- 2025/04/12 19:36 [entrez] AID - S0210-5705(25)00118-9 [pii] AID - 10.1016/j.gastrohep.2025.502442 [doi] PST - ppublish SO - Gastroenterol Hepatol. 2025 Oct;48(8):502442. doi: 10.1016/j.gastrohep.2025.502442. Epub 2025 Apr 11. PMID- 40220796 OWN - NLM STAT- MEDLINE DCOM- 20250421 LR - 20250421 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 223 DP - 2025 May TI - Persistence with once-weekly glucagon-like peptide 1 receptor agonist therapy decreases the risk of major adverse cardiovascular events: A retrospective analysis of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. PG - 112162 LID - S0168-8227(25)00176-7 [pii] LID - 10.1016/j.diabres.2025.112162 [doi] AB - AIMS: To assess the association between remaining persistent with once-weekly glucagon-like peptide-1 receptor agonists (OW GLP-1 RAs) and the risk of major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). METHODS: We used the Optum Research Database to identify patients who initiated OW GLP-1 RAs between 1/1/2018-11/30/2022. Patients were classified as persistent or non-persistent depending on whether there was a >/= 60-day gap in medication supply after they continuously used the medication for the first three months. Adjusted time-varying Cox proportional hazards models assessed the associations between persistence status and risks of 2-point MACE, stroke, and myocardial infarction (MI). RESULTS: Persistent (n = 18,849) and non-persistent (n = 10,667) patients were followed for an average of 418 and 741 days, respectively. Mean (SD) persistence was 418 (339), and 288 (234) days for persistent and non-persistent patients, respectively. Remaining persistent was associated with significantly lower risks of 2-point MACE, stroke, and MI (all p < 0.001). The corresponding HRs (95 %CI) were 0.696 (0.626-0.774), 0.668 (0.573-0.777), and 0.710 (0.621-0.813). CONCLUSIONS: Persistence with OW GLP-1 RA therapy was associated with significantly lower MACE risk among patients with T2DM and ASCVD in a real-world setting. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. Electronic address: tydz@novonordisk.com. FAU - Zhu, Yong AU - Zhu Y AD - Optum, Eden Prairie, MN, USA. Electronic address: yong_zhu@optum.com. FAU - Gronroos, Noelle N AU - Gronroos NN AD - Optum, Eden Prairie, MN, USA. Electronic address: noelle.gronroos@optum.com. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. Electronic address: wlsx@novonordisk.com. FAU - Sargent, Andrew AU - Sargent A AD - Optum, Eden Prairie, MN, USA. Electronic address: andrew.sargent@optum.com. FAU - Gamble, Cory AU - Gamble C AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. Electronic address: cyga@novonordisk.com. FAU - Billings, Liana K AU - Billings LK AD - Endeavor Health (NorthShore Hospitals), Skokie, IL, USA. Electronic address: lbillings@northshore.org. LA - eng PT - Journal Article DEP - 20250410 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Atherosclerosis/epidemiology/complications MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Drug Administration Schedule OTO - NOTNLM OT - Cardiovascular Disease OT - Diabetes Mellitus, Type 2 OT - GLP-1 Receptor Agonists OT - Major Adverse Cardiac Events OT - Medication Persistence COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TJD is an employee and shareholder of Novo Nordisk, Inc. YZ is an employee of Optum, a business unit from UnitedHealth Group, and shareholder of UnitedHealth Group. NNG is an employee of Optum, a business unit from UnitedHealth Group, and shareholder of UnitedHealth Group. LX is an employee and shareholder of Novo Nordisk, Inc. AS is an employee of Optum, a business unit from UnitedHealth Group, and shareholder of UnitedHealth Group. CG is an employee and shareholder of Novo Nordisk, Inc. LKB has received consulting fees from Novo Nordisk, Endogenex, Sanofi, Dexcom, Eli Lilly, Bayer, Xeris, and Pfizer. EDAT- 2025/04/13 00:45 MHDA- 2025/04/22 00:26 CRDT- 2025/04/12 19:32 PHST- 2024/12/12 00:00 [received] PHST- 2025/03/12 00:00 [revised] PHST- 2025/04/06 00:00 [accepted] PHST- 2025/04/22 00:26 [medline] PHST- 2025/04/13 00:45 [pubmed] PHST- 2025/04/12 19:32 [entrez] AID - S0168-8227(25)00176-7 [pii] AID - 10.1016/j.diabres.2025.112162 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 May;223:112162. doi: 10.1016/j.diabres.2025.112162. Epub 2025 Apr 10. PMID- 40220748 OWN - NLM STAT- MEDLINE DCOM- 20250412 LR - 20260607 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 6 IP - 4 DP - 2025 Apr 11 TI - GLP-1 agonists to slow down Parkinson's progression? The quest continues. PG - 100645 LID - S2666-6340(25)00072-8 [pii] LID - 10.1016/j.medj.2025.100645 [doi] AB - A much-anticipated phase 3 clinical trial (EXENATIDE-PD3) tested whether exenatide, a GLP-1 receptor agonist used to treat type 2 diabetes, might be neuroprotective in persons with Parkinson's disease.(1) There was no difference between exenatide and matched placebo for the primary outcome or any secondary or exploratory outcomes. We discuss the implications for future attempts to modify the course of Parkinson's disease. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Bloem, Bastiaan R AU - Bloem BR AD - Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Centre of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands. Electronic address: bas.bloem@radboudumc.nl. FAU - Macklin, Eric A AU - Macklin EA AD - Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. FAU - Schwarzschild, Michael A AU - Schwarzschild MA AD - Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Venoms) RN - 0 (Peptides) RN - 0 (Neuroprotective Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Parkinson Disease/drug therapy MH - Exenatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Disease Progression MH - *Venoms/therapeutic use MH - *Peptides/therapeutic use MH - *Neuroprotective Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Clinical Trials, Phase III as Topic COIS- Declaration of interests B.R.B. serves as the co-editor-in-chief for the Journal of Parkinson's Disease; serves on the editorial boards of Practical Neurology and Digital Biomarkers; has received fees from serving on the scientific advisory board for the Critical Path Institute, Gyenno Science, MedRhythms, UCB, Kyowa Kirin, and Zambon (paid to the Institute); has received fees for speaking at conferences from AbbVie, Bial, Biogen, GE Healthcare, Oruen, Roche, UCB, and Zambon (paid to the Institute); and has received research support from Biogen, Cure Parkinson's, Davis Phinney Foundation, Edmond J. Safra Foundation, Fred Foundation, Gatsby Foundation, Hersenstichting Nederland, Horizon 2020, IRLAB Therapeutics, Maag Lever Darm Stichting, Michael J. Fox Foundation, Ministry of Agriculture, Ministry of Economic Affairs & Climate Policy, Ministry of Health, Welfare and Sport, Netherlands Organization for Scientific Research (ZonMw), Not Impossible, Parkinson Vereniging, Parkinson's Foundation, Parkinson's UK, Stichting Alkemade-Keuls, Stichting Parkinson NL, Stichting Woelse Waard, Topsector Life Sciences and Health, UCB, Verily Life Sciences, Roche, and Zambon. E.A.M. received research support via his institution from AI Therapeutics, Alector, Biohaven, Calico Therapeutics, Clene Nanomedicine, Denali Therapeutics, ITB-Med, Janssen, Lilly, Mitubishi Tanabe Pharma America, PharmAust, Prilenia Therapeutics, Revalesio, Seelos Therapeutics, UCB/Ra Pharma, and Woolsey; served on advisory boards for Annexon, Bial Biotech, Chase Therapeutics, HillHurst, and Merck; served on Steering Committees for Biogen and UCB; and served on DSMBs for Argenx, NeuroSense, Novartis, and Sanofi. M.A.S. in the past 3 years has served on clinical trial steering committees funded by Biogen (LUMA/LIGHTHOUSE) via the Parkinson Study Group (PSG), UCB (ORCHESTRA) via the PSG, Northwestern Univ. (SPARX3), Parkinson's Foundation (PD-GENEration), Sutter Health (TOPAZ), Farmer Family Foundation (LoCaMoTE-PD) via Massachusetts General Hospital (MGH), and X-linked Dystonia Parkinsonism Collaborative Center (via MGH); has received research grant support from the US National Institutes of Health (NIH), US Department of Defense, Michael J. Fox Foundation, and Cure Parkinson's; and has received educational grant funding from the US Food and Drug Administration, NIH, Sergey Brin Family Foundation, Parkinson's Foundation, Parkinson's UK, APDA, Parkinson Canada, Like Minds, Roche, Cerevel, Biogen, Sanofi, and UCB/Novartis. B.R.B., E.A.M., and M.A.S. do not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of their clinical or research activities. EDAT- 2025/04/13 00:44 MHDA- 2025/04/13 00:45 CRDT- 2025/04/12 18:16 PHST- 2025/03/02 00:00 [received] PHST- 2025/03/05 00:00 [revised] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/04/13 00:45 [medline] PHST- 2025/04/13 00:44 [pubmed] PHST- 2025/04/12 18:16 [entrez] AID - S2666-6340(25)00072-8 [pii] AID - 10.1016/j.medj.2025.100645 [doi] PST - ppublish SO - Med. 2025 Apr 11;6(4):100645. doi: 10.1016/j.medj.2025.100645. PMID- 40212008 OWN - NLM STAT- MEDLINE DCOM- 20250608 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials. PG - 3736-3746 LID - 10.1111/dom.16398 [doi] AB - AIMS: This study compares the therapeutic efficacy, gastrointestinal (GI) adverse event (AE) rates and the relationship between the therapeutic efficacy and GI AEs in randomized, placebo-controlled clinical trials (RCTs) of GLP-1 RAs and the dual GLP-1/GIP agonist tirzepatide. MATERIALS AND METHODS: A systematic PubMed search identified 38 phase 3 or 4 placebo-controlled RCTs of exenatide (b.i.d. and q.w.), lixisenatide, liraglutide, dulaglutide, albiglutide, semaglutide (s.c. and oral) and tirzepatide with a total of 16 660 individuals with type 2 diabetes (T2D) across 104 study arms. Changes in HbA1c, fasting plasma glucose and body weight and the proportion of GI AEs (nausea, vomiting or diarrhoea) were calculated by agent, preparation and dose. The correlation between odds ratios (ORs) for GI AEs and the magnitude of therapeutic efficacy was assessed in a linear regression analysis. RESULTS: Baseline characteristics were similar across studies: mean age 57 +/- 10 years, diabetes duration 8 +/- 6 years, body mass index (BMI) 31.9 +/- 5.8 kg/m(2) and HbA1c 8.2% +/- 0.9%. HbA1c reductions ranged from -0.63% +/- 0.03% (lixisenatide, 20 mug q.d.) to -1.79% +/- 0.09% (tirzepatide, 15 mg q.w.; p < 0.0001). Weight reductions ranged from -0.75 +/- 0.10 kg to -9.65 +/- 0.56 kg. Despite the high variability in therapeutic efficacy, ORs for GI AEs were similar across compounds/preparations. CONCLUSIONS: The magnitude of efficacy for intended therapeutic actions (HbA1c and body weight reduction) varied widely between incretin mimetic glucose-lowering agents. However, larger therapeutic efficacy was not systematically associated with higher GI AE or drug discontinuation rates, indicating better tolerability of the more effective agents/preparations. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - Division of Endocrinology, Diabetes and Hypertension and TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Punov, Viktoria AU - Punov V AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. LA - eng GR - T32 DK007529/DK/NIDDK NIH HHS/United States GR - 5T32DK007529/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250411 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - 0 (hemoglobin A1c protein, human) RN - 74O62BB01U (lixisenatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Incretins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Exenatide/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism/analysis MH - Middle Aged MH - Treatment Outcome MH - Tirzepatide MH - Blood Glucose/drug effects/metabolism MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Peptides/therapeutic use/adverse effects MH - Male MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Female MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Clinical Trials, Phase III as Topic MH - Vomiting/chemically induced MH - Nausea/chemically induced MH - Diarrhea/chemically induced MH - Glucagon-Like Peptide-2 Receptor MH - Semaglutide PMC - PMC12146062 MID - NIHMS2070980 OTO - NOTNLM OT - GLP-1 analogue OT - incretin therapy OT - systematic review OT - type 2 diabetes OT - weight management COIS- YMK and VP have nothing to disclose. SL is an advisory board member for Novo Nordisk and AstraZeneca and has served on the speakers' bureau of Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and MSD. He has received research funding from CKD and Daewoong Pharma. MAN has been member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co., Medtronic, Merck, Sharp & Dohme, Novo Nordisk, Pfizer, Regor, Sun Pharma and Structure Therapeutics (ShouTi, Gasherbrum). He has received grant support from Merck, Sharp & Dohme. He has also served on the speakers' bureau of Eli Lilly & Co., Menarini/Berlin Chemie, Merck, Sharp & Dohme, Medscape, Medical Learning Institute and Novo Nordisk. SL is an advisory board member for Novo Nordisk and AstraZeneca and has served on the speakers' bureau of Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and MSD. He has received research funding from Chong Kun Dang and Daewoong Pharma. EDAT- 2025/04/11 06:25 MHDA- 2025/06/09 00:28 PMCR- 2025/06/09 CRDT- 2025/04/11 05:24 PHST- 2025/03/26 00:00 [revised] PHST- 2025/02/25 00:00 [received] PHST- 2025/03/28 00:00 [accepted] PHST- 2025/06/09 00:28 [medline] PHST- 2025/04/11 06:25 [pubmed] PHST- 2025/04/11 05:24 [entrez] PHST- 2025/06/09 00:00 [pmc-release] AID - DOM16398 [pii] AID - 10.1111/dom.16398 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3736-3746. doi: 10.1111/dom.16398. Epub 2025 Apr 11. PMID- 40210807 OWN - NLM STAT- MEDLINE DCOM- 20250410 LR - 20250413 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 14 IP - 1 DP - 2025 Apr 11 TI - Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data. PG - 34 LID - 10.1007/s13679-025-00623-1 [doi] LID - 34 AB - PURPOSE OF REVIEW: The development of long-acting incretin receptor agonists represents a significant advance in the fight against the concurrent epidemics of type 2 diabetes mellitus (T2DM) and obesity. The aim of the present review is to examine the cellular processes underlying the actions of these new, highly significant classes of peptide receptor agonists. We further explore the potential actions of multi-agonist drugs as well as the mechanisms through which gut-brain communication can be used to achieve long-term weight loss without negative side effects. RECENT FINDINGS: Several unimolecular dual-receptor agonists have shown promising clinical efficacy studies when used alone or in conjunction with approved glucose-lowering medications. We also describe the development of incretin-based pharmacotherapy, starting with exendin- 4 and ending with the identification of multi-incretin hormone receptor agonists, which appear to be the next major step in the fight against T2DM and obesity. We discuss the multi-agonists currently in clinical trials and how each new generation of these drugs improves their effectiveness. Since most glucose-dependent insulinotropic polypeptide (GIP) receptor: glucagon-like peptide- 1 receptor (GLP- 1) receptor: glucagon receptor triagonists compete in efficacy with bariatric surgery, the success of these agents in preclinical models and clinical trials suggests a bright future for multi-agonists in the treatment of metabolic diseases. To fully understand how these treatments affect body weight, further research is needed. CI - (c) 2025. The Author(s). FAU - Anastasiou, Ioanna Alpha AU - Anastasiou IAlpha AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece. AD - Department of Pharmacology, National and Kapodistrian University of Athens, 11527, Athens, Greece. FAU - Argyrakopoulou, Georgia AU - Argyrakopoulou G AD - Diabetes and Obesity Unit, Athens Medical Center, 15125, Athens, Greece. FAU - Dalamaga, Maria AU - Dalamaga M AD - Department of Biological Chemistry, National and Kapodistrian University of Athens, 11527, Athens, Greece. FAU - Kokkinos, Alexander AU - Kokkinos A AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece. akokkinos@med.uoa.gr. LA - eng PT - Journal Article PT - Review DEP - 20250411 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Incretins/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Receptors, Gastrointestinal Hormone/agonists PMC - PMC11985575 OTO - NOTNLM OT - Glucagon OT - Glucagon-like peptide-1 receptor agonist OT - Glucose-dependent insulinotropic peptide receptor OT - Incretin OT - Obesity OT - Type 2 diabetes mellitus COIS- Compliance with Ethical Standards. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of Interest: The authors declare no competing interests. EDAT- 2025/04/11 00:33 MHDA- 2025/04/11 00:34 PMCR- 2025/04/11 CRDT- 2025/04/10 23:32 PHST- 2025/03/21 00:00 [accepted] PHST- 2025/04/11 00:34 [medline] PHST- 2025/04/11 00:33 [pubmed] PHST- 2025/04/10 23:32 [entrez] PHST- 2025/04/11 00:00 [pmc-release] AID - 10.1007/s13679-025-00623-1 [pii] AID - 623 [pii] AID - 10.1007/s13679-025-00623-1 [doi] PST - epublish SO - Curr Obes Rep. 2025 Apr 11;14(1):34. doi: 10.1007/s13679-025-00623-1. PMID- 40210453 OWN - NLM STAT- MEDLINE DCOM- 20250825 LR - 20260925 IS - 1468-330X (Electronic) IS - 0022-3050 (Print) IS - 0022-3050 (Linking) VI - 96 IP - 9 DP - 2025 Aug 14 TI - Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders. PG - 870-883 LID - 10.1136/jnnp-2024-335593 [doi] LID - e335593 AB - Disease-modifying treatments for major neurocognitive disorders, including Alzheimer's disease, Parkinson's disease and other cognitive deficits, are among the main unmet needs in modern medicine. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently licensed for the treatment of type 2 diabetes mellitus and obesity, offer a novel, multilayered mechanism for intervention in neurodegeneration through intermediate, aetiology-agnostic pathways, likely involving metabolic, inflammatory and several other relevant neurobiological processes. In vitro and animal studies have revealed promising signals of neuroprotection, with preliminary supportive evidence emerging from recent pharmacoepidemiological investigations and clinical trials. In this article, we comprehensively review studies that investigate the impact of GLP-1RAs on the various aetiologies of cognitive impairment and dementia syndromes. Focusing on evidence from human studies, we highlight how brain energy homeostasis, neurogenesis, synaptic functioning, neuroinflammation and other cellular stress responses, pathological protein aggregates, proteostasis, cerebrovascular system and blood-brain barrier dynamics may underlie GLP-1RA putative neuroprotective effects. We then report and appraise evidence from clinical studies, including observational investigations, clinical trials and pooled analyses. Finally, we discuss current challenges and perspectives ahead for research and clinical implementation of GLP-1RAs for the care of people with major neurocognitive disorders, including their individual brain penetrance potential, the need for response biomarkers and disease stage-based indications, their possible non-specific effects on brain health, their profile in terms of adverse events and other unwanted effects, the lack of long-term data for efficacy and safety, and issues surrounding cost and availability of treatment. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. FAU - De Giorgi, Riccardo AU - De Giorgi R AD - Department of Psychiatry, University of Oxford, Oxford, UK. AD - Oxford Health NHS Foundation Trust, Oxford, UK. FAU - Ghenciulescu, Ana AU - Ghenciulescu A AD - Department of Psychiatry, University of Oxford, Oxford, UK. FAU - Yotter, Courtney AU - Yotter C AD - Department of Psychiatry, University of Oxford, Oxford, UK. FAU - Taquet, Maxime AU - Taquet M AD - Department of Psychiatry, University of Oxford, Oxford, UK. FAU - Koychev, Ivan AU - Koychev I AUID- ORCID: 0000-0001-6813-8493 AD - Department of Psychiatry, University of Oxford, Oxford, UK ivan.koychev@psych.ox.ac.uk. AD - Division of Brain Sciences, Imperial College London, London, UK. LA - eng PT - Journal Article PT - Review DEP - 20250814 PL - England TA - J Neurol Neurosurg Psychiatry JT - Journal of neurology, neurosurgery, and psychiatry JID - 2985191R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Neuroprotective Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neurocognitive Disorders/drug therapy MH - *Neuroprotective Agents/therapeutic use MH - Animals MH - Cognitive Dysfunction/drug therapy MH - Brain/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Alzheimer Disease/drug therapy PMC - PMC12418562 OTO - NOTNLM OT - ALZHEIMER'S DISEASE OT - DEMENTIA OT - PARKINSON'S DISEASE COIS- Competing interests: RDG and IK are supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (NIHR203316). IK declares additional funding for this work through the UKRI Medical Research Council (MRC) (MR/T033371/1) and NIHR Development and Skills Enhancement Award (NIHR301616). IK is also in receipt of grant funding from Novo Nordisk for an investigator-initiated study of semaglutide in Alzheimer's disease; he is paid a medical advisor for digital healthcare companies in the dementia space (Five Lives SAS, Cognetivity Ltd, Cognes Ltd). EDAT- 2025/04/11 00:32 MHDA- 2025/08/31 19:54 PMCR- 2025/09/09 CRDT- 2025/04/10 21:33 PHST- 2025/02/15 00:00 [received] PHST- 2025/03/21 00:00 [accepted] PHST- 2025/08/31 19:54 [medline] PHST- 2025/04/11 00:32 [pubmed] PHST- 2025/04/10 21:33 [entrez] PHST- 2025/09/09 00:00 [pmc-release] AID - jnnp-2024-335593 [pii] AID - 10.1136/jnnp-2024-335593 [doi] PST - epublish SO - J Neurol Neurosurg Psychiatry. 2025 Aug 14;96(9):870-883. doi: 10.1136/jnnp-2024-335593. PMID- 40207412 OWN - NLM STAT- MEDLINE DCOM- 20250410 LR - 20260519 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 21 IP - 4 DP - 2025 Apr TI - Glycated hemoglobin and body mass index as mediators of GLP-1RAs and Alzheimer's disease and related dementias in patients with type 2 diabetes. PG - e70161 LID - 10.1002/alz.70161 [doi] LID - e70161 AB - INTRODUCTION: Whether reductions in glycated hemoglobin (HbA1c) levels and body mass index (BMI) mediate the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and Alzheimer's disease and related dementias (ADRD) risk is unknown. METHODS: This cohort study included 22,908 patients aged >/= 50 years with type 2 diabetes (T2D) newly prescribed GLP-1RA or other second-line glucose-lowering drugs (GLDs). Causal mediation analysis was used to estimate to what extent the effect of GLP-1RAs on ADRD risk was attributable to lowering HbA1c or BMI. RESULTS: Compared to other GLD users, GLP-1RA users had significant reductions in HbA1c levels by 0.16% and BMI by 0.23 kg/m(2), along with a 26% lower ADRD risk. The direct protective effect of GLP-1RAs on ADRD risk persisted even after accounting for HbA1c and BMI reductions, with minimal mediation effects observed through these factors. DISCUSSION: GLP-1RAs reduce ADRD risk, largely independent of their effects on HbA1c and BMI. HIGHLIGHTS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with reductions in glycated hemoglobin (HbA1c) and body mass index (BMI) compared to other second-line glucose-lowering drugs(GLDs). GLP-1RA users were associated with a 26% lower risk of Alzheimer's disease and related dementias (ADRD) than other GLD users. The protective effect of GLP-1RAs against ADRD in adults with type 2 diabetes (T2D) is largely independent of their effects on HbA1c and BMI. CI - (c) 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Tang, Huilin AU - Tang H AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Donahoo, William T AU - Donahoo WT AD - Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - DeKosky, Steven T AU - DeKosky ST AD - Department of Neurology and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA. AD - Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA. FAU - Lee, Yao An AU - Lee YA AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Svensson, Mikael AU - Svensson M AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. LA - eng GR - R01AG076234/AG/NIA NIH HHS/United States GR - R01AG089445/AG/NIA NIH HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - R01 AG076234/AG/NIA NIH HHS/United States GR - NH/NIH HHS/United States GR - R01 AG089445/AG/NIA NIH HHS/United States GR - 2023PDVH1064032/Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Predoctoral Fellowship/ PT - Journal Article PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glycated Hemoglobin/metabolism MH - *Body Mass Index MH - Male MH - Female MH - *Alzheimer Disease/epidemiology MH - Aged MH - Middle Aged MH - *Dementia/epidemiology MH - Cohort Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use PMC - PMC11982930 OTO - NOTNLM OT - Alzheimer's disease and related dementias OT - GLP-1RAs OT - body mass index OT - causal mediation analysis OT - glycated hemoglobin OT - type 2 diabetes COIS- All authors declare no conflict of interest. Author disclosures are available in the supporting information. EDAT- 2025/04/10 06:25 MHDA- 2025/04/10 06:26 PMCR- 2025/04/10 CRDT- 2025/04/10 05:24 PHST- 2025/03/08 00:00 [revised] PHST- 2024/12/22 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2025/04/10 06:26 [medline] PHST- 2025/04/10 06:25 [pubmed] PHST- 2025/04/10 05:24 [entrez] PHST- 2025/04/10 00:00 [pmc-release] AID - ALZ70161 [pii] AID - 10.1002/alz.70161 [doi] PST - ppublish SO - Alzheimers Dement. 2025 Apr;21(4):e70161. doi: 10.1002/alz.70161. PMID- 40202527 OWN - NLM STAT- MEDLINE DCOM- 20250721 LR - 20260813 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 8 DP - 2025 Aug 1 TI - Association of Patient Cost Sharing With Adherence to GLP-1RA and Adverse Health Outcomes. PG - 1329-1336 LID - 10.2337/dc24-2746 [doi] AB - OBJECTIVE: To examine the associations between patient out-of-pocket (OOP) costs and nonadherence to glucagon-like peptide 1 receptor agonists (GLP-1RA), and the consequent impact on adverse outcomes, including hospitalizations and emergency department (ED) visits. RESEARCH DESIGN AND METHODS: This retrospective cohort study used MarketScan Commercial data (2016-2021). The cohort included nonpregnant adults aged 18-64 years with type 2 diabetes who initiated GLP-1RA therapy. Participants were continuously enrolled in the same private insurance plan for 6 months before the prescription date and 1 year thereafter. Exposures included average first 30-day OOP costs for GLP-1RA, categorized into quartiles (lowest [Q1] to highest [Q4]). Primary outcomes were the annual proportion of days covered (PDC) for GLP-1RA and nonadherence, defined as PDC <0.8. Secondary outcomes included diabetes-related and all-cause hospitalizations and ED visits 1 year after GLP-1RA initiation. RESULTS: Among 61,907 adults who initiated GLP-1RA, higher 30-day OOP costs were associated with decreased adherence. Patients in the highest OOP cost quartile (Q4: $80-$3,375) had significantly higher odds of nonadherence (odds ratio [OR] 1.25; 95% CI 1.19-1.31) compared with those in Q1 ($0-$21). Nonadherence was linked to increased incidence rates of diabetes-related hospitalizations or ED visits (incidence rate ratio [IRR] 1.86; 95% CI 1.43-2.42), cumulative length of hospitalization (IRR 1.56; 95% CI 1.41-1.72), all-cause ED visits (IRR 1.38; 95% CI 1.32-1.45), and increased ED-related costs ($69.81, 95% CI $53.54-$86.08). CONCLUSIONS: Higher OOP costs for GLP-1RA were associated with reduced adherence and increased rates of adverse outcomes among patients with type 2 diabetes. CI - (c) 2025 by the American Diabetes Association. FAU - Zhang, Donglan AU - Zhang D AUID- ORCID: 0000-0001-5225-4721 AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. AD - Department of Population Health, New York University Grossman School of Medicine, New York, NY. FAU - Gencerliler, Nihan AU - Gencerliler N AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. FAU - Mukhopadhyay, Amrita AU - Mukhopadhyay A AD - Leon H. Charney Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY. AD - Department of Surgery, New York University Grossman School of Medicine, New York, NY. FAU - Blecker, Saul AU - Blecker S AD - Department of Population Health, New York University Grossman School of Medicine, New York, NY. AD - Department of Surgery, New York University Grossman School of Medicine, New York, NY. FAU - Grams, Morgan E AU - Grams ME AUID- ORCID: 0000-0002-4430-6023 AD - Department of Population Health, New York University Grossman School of Medicine, New York, NY. AD - Department of Surgery, New York University Grossman School of Medicine, New York, NY. FAU - Wright, Davene R AU - Wright DR AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Healthcare Institute, Boston, MA. FAU - Wang, Vivian Hsing-Chun AU - Wang VH AUID- ORCID: 0000-0002-5638-204X AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. FAU - Rajan, Anand AU - Rajan A AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. FAU - Butt, Eisha AU - Butt E AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. FAU - Shin, Jung-Im AU - Shin JI AUID- ORCID: 0000-0003-0374-6927 AD - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. FAU - Xu, Yunwen AU - Xu Y AUID- ORCID: 0000-0002-5946-2272 AD - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. FAU - Chhabra, Karan R AU - Chhabra KR AD - Department of Population Health, New York University Grossman School of Medicine, New York, NY. AD - Department of Surgery, New York University Grossman School of Medicine, New York, NY. AD - New York City Health and Hospitals/Bellevue, New York, NY. FAU - Divers, Jasmin AU - Divers J AD - Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY. AD - Department of Population Health, New York University Grossman School of Medicine, New York, NY. LA - eng GR - K23 HL171636/HL/NHLBI NIH HHS/United States GR - R01 DK139324/DK/NIDDK NIH HHS/United States GR - R01 MD013886/MD/NIMHD NIH HHS/United States GR - Doucette Innovation Fund/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Diabetes Care. 2025 Aug 1;48(8):1309-1311. doi: 10.2337/dci25-0030. PMID: 40690652 MH - Humans MH - Adult MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Adolescent MH - Young Adult MH - *Hypoglycemic Agents/therapeutic use/economics MH - *Cost Sharing MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Hospitalization/statistics & numerical data MH - Emergency Service, Hospital/statistics & numerical data PMC - PMC13053885 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2025/04/09 12:29 MHDA- 2025/07/21 18:31 PMCR- 2025/04/09 CRDT- 2025/04/09 11:03 PHST- 2024/12/10 00:00 [received] PHST- 2025/03/03 00:00 [accepted] PHST- 2025/07/21 18:31 [medline] PHST- 2025/04/09 12:29 [pubmed] PHST- 2025/04/09 11:03 [entrez] PHST- 2025/04/09 00:00 [pmc-release] AID - 158094 [pii] AID - 242746 [pii] AID - 10.2337/dc24-2746 [doi] PST - ppublish SO - Diabetes Care. 2025 Aug 1;48(8):1329-1336. doi: 10.2337/dc24-2746. PMID- 40199481 OWN - NLM STAT- MEDLINE DCOM- 20251117 LR - 20251117 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 110 IP - 12 DP - 2025 Nov 18 TI - Treatment Intensification Strategies and Metabolic Outcomes in Individuals With Type 2 Diabetes on GLP-1 RA Therapy. PG - e4101-e4110 LID - 10.1210/clinem/dgaf229 [doi] AB - CONTEXT: Despite the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), many patients with type 2 diabetes (T2D) require additional therapy to achieve glycated hemoglobin (HbA1c) targets. Few studies have explored real-world outcomes following GLP-1 RA failure. OBJECTIVE: This analysis evaluates different intensification approaches, timing, and outcomes in patients with T2D on GLP-1 RAs. METHODS: This retrospective cohort study was based on the AMD Annals database. From 191 041 patients on GLP-1 RAs between 2010 and 2022, individuals receiving a first therapeutic intensification were selected. Patients were stratified by intensification strategy; baseline characteristics were compared alongside HbA1c and weight changes at 6 and 12 months. RESULTS: Among the 37 198 intensified patients, the majority received oral antihyperglycemic drugs (OADs), particularly those with higher body mass index, lower HbA1c, and shorter disease duration. Basal insulin (BI) was mainly added in those with higher HbA1c (8.9%) and longer diabetes. Intensification with BI or switch to fixed ratio combinations (FRCs) yielded the greatest HbA1c reduction (-0.92 and -0.85%; P < .001) and weight neutrality, whereas OADs led to a higher target achievement rate (36% with HbA1c < 7%) and persistent weight loss. Switching to BB was reserved for more complicated patients and it was associated with weight gain (+2.9 kg; P < .001) and lower target achievement rate (16.8% HbA1c < 7%). Suboptimal insulin titration was observed across all strategies. CONCLUSION: Adding OADs or BI/FRCs to GLP-1 RAs are optimal intensification strategies to provide glycemic control while avoiding weight gain. Target achievement rates are poor in individuals switched to insulin therapy. Therapeutic inertia remains a critical issue in clinical practice. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Falcetta, Pierpaolo AU - Falcetta P AUID- ORCID: 0000-0002-3182-0453 AD - Diabetes Unit, Azienda USL Toscana Centro, 50053 Empoli, Italy. FAU - Zilich, Rita AU - Zilich R AD - Mix-X Partner, 20122 Milan, Italy. FAU - Baccetti, Fabio AU - Baccetti F AD - Diabetes Unit, ASL Toscana Nord-Ovest, 54100 Massa-Carrara, Italy. FAU - Baronti, Walter AU - Baronti W AD - Diabetes Unit, ASL Toscana Sud-Est, 58100 Grosseto, Italy. FAU - Masi, Davide AU - Masi D AUID- ORCID: 0000-0003-0820-633X AD - Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy. FAU - Morviducci, Lelio AU - Morviducci L AD - Diabetology and Nutrition Unit, Department of Medical Specialities, ASL 1, S. Spirito Hospital, 00193 Rome, Italy. FAU - Musacchio, Nicoletta AU - Musacchio N AD - Associazione Medici Diabetologi, 20156 Milano, Italy. FAU - Muselli, Marco AU - Muselli M AD - Rulex Innovation Labs, Rulex Inc, 16122 Genoa, Italy. FAU - Ozzello, Alessandro AU - Ozzello A AD - AI-AMD National Group, 10190 Bruino, Italy. FAU - Rossi, Antonio AU - Rossi A AUID- ORCID: 0000-0002-8660-2146 AD - I.R.C.C.S. Ospedale Galeazzi-Sant'Ambrogio, 20149 Milan, Italy. AD - Department of Biomedical and Clinical Sciences, University of Milan, 20122 Milan, Italy. FAU - Salomone, Enrica AU - Salomone E AD - Diabetology and Nutrition Unit, Department of Medical Specialities, ASL 1, S. Spirito Hospital, 00193 Rome, Italy. FAU - Verda, Damiano AU - Verda D AD - Rulex Innovation Labs, Rulex Inc, 16122 Genoa, Italy. FAU - Vezenkova, Maria AU - Vezenkova M AD - Deimos Engineering srl, 33100 Udine, Italy. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy. FAU - Ponzani, Paola AU - Ponzani P AD - Metabolism and Diabetes Unit, 16043 Chiavari, Italy. LA - eng GR - Sanofi/ PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Treatment Outcome MH - Blood Glucose/analysis MH - Drug Therapy, Combination OTO - NOTNLM OT - GLP-1 RA OT - HbA1c OT - intensification OT - type 2 diabetes EDAT- 2025/04/09 10:12 MHDA- 2025/11/18 00:28 CRDT- 2025/04/08 20:02 PHST- 2024/12/19 00:00 [received] PHST- 2025/11/18 00:28 [medline] PHST- 2025/04/09 10:12 [pubmed] PHST- 2025/04/08 20:02 [entrez] AID - 8108462 [pii] AID - 10.1210/clinem/dgaf229 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 Nov 18;110(12):e4101-e4110. doi: 10.1210/clinem/dgaf229. PMID- 40197714 OWN - NLM STAT- MEDLINE DCOM- 20250611 LR - 20260127 IS - 1535-2900 (Electronic) IS - 1079-2082 (Linking) VI - 82 IP - 12 DP - 2025 Jun 11 TI - On the front lines of cardiovascular-kidney-metabolic syndrome: Review of GLP-1 and Dual GLP-1/GIP receptor agonists in CV and kidney health. PG - 693-709 LID - 10.1093/ajhp/zxaf053 [doi] AB - PURPOSE: The purpose of this review is to highlight the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (GLP-1/GIP RAs) in managing cardiovascular-kidney-metabolic (CKM) syndrome, focusing on their cardiovascular (CV) and kidney-protective effects beyond glycemic control. SUMMARY: In multiple randomized controlled trials, GLP-1 RAs were demonstrated to confer significant benefits in reducing CV events and preserving kidney function in patients with preexisting atherosclerotic cardiovascular disease (ASCVD) and those at high CV risk. Current guidelines, including those from the Kidney Disease: Improving Global Outcomes (KDIGO) initiative and the American Diabetes Association (ADA), underscore the therapeutic potential of these agents for managing chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and metabolic syndrome. Additionally, emerging data suggests their utility beyond T2DM. This review summarizes the evidence supporting these guidelines, along with newer findings not yet fully integrated into clinical practice. It also examines the role of pharmacists and multidisciplinary teams, safety considerations, and practical strategies for managing common adverse effects. CONCLUSION: The integration of GLP-1 RAs and dual GLP-1/GIP RAs into clinical practice offers substantial benefits for patients, both with and without diabetes. Pharmacists play a pivotal role in recommending evidence-based treatments for those at high CV and kidney risk, educating patients, addressing social determinants of health, and bridging gaps across multidisciplinary care teams. CI - (c) American Society of Health-System Pharmacists 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Salama, Lavinia AU - Salama L AD - School of Pharmacy, University of Wyoming, Laramie, WY. AD - University of Wyoming Family Medicine Residency at Cheyenne, Cheyenne, WY, USA. FAU - Sinn, Levi AU - Sinn L AD - School of Pharmacy, University of Wyoming, Laramie, WY, USA. LA - eng PT - Journal Article PT - Review PL - England TA - Am J Health Syst Pharm JT - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JID - 9503023 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Metabolic Syndrome/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Randomized Controlled Trials as Topic/methods MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Renal Insufficiency, Chronic/drug therapy MH - Receptors, Gastrointestinal Hormone OTO - NOTNLM OT - cardiovascular-kidney protection OT - cardiovascular-kidney-metabolic syndrome OT - chronic kidney disease OT - dual glucagon-like peptide-1/gastric inhibitory polypeptide receptor agonists OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus EDAT- 2025/04/08 13:56 MHDA- 2025/06/12 00:38 CRDT- 2025/04/08 11:03 PHST- 2025/06/12 00:38 [medline] PHST- 2025/04/08 13:56 [pubmed] PHST- 2025/04/08 11:03 [entrez] AID - 8108095 [pii] AID - 10.1093/ajhp/zxaf053 [doi] PST - ppublish SO - Am J Health Syst Pharm. 2025 Jun 11;82(12):693-709. doi: 10.1093/ajhp/zxaf053. PMID- 40196945 OWN - NLM STAT- MEDLINE DCOM- 20250408 LR - 20250409 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 24 IP - 4 DP - 2025 Apr 1 TI - A Retrospective Comparative Analysis of Cutaneous Adverse Reactions in GLP-1 Agonist Therapies. PG - 413-415 LID - 10.36849/JDD.8605 [doi] AB - Glucagon-like peptide-1 (GLP-1) agonists are used to treat type 2 diabetes mellitus (T2DM) and have recently gained approval and popularity for treating obesity and weight loss. There is a lack of data evaluating the types of reactions associated with this medication class, and this study aimed to characterize the types of cutaneous reactions seen across different GLP-1 agonists, and whether differences exist in reactions based on the reason for medication use. Through a retrospective review of cutaneous adverse events associated with semaglutide, dulaglutide, tirzepatide, lixisenatide, liraglutide, and exenatide in the FDA Adverse Event Reporting System, it was found that the 5 most common cutaneous reactions associated with GLP-1 agonists were eczematous, pruritus, drug eruptions, hyperhidrosis, and alopecia. Life-threatening cutaneous adverse events accounted for 2.17% of all cutaneous reactions, with no statistically significant differences observed between drug types. It was also found that GLP-1 agonist use for T2DM exhibited significantly higher rates of alopecia (P=0.000) and hyperhidrosis (P=0.000) in comparison to use for weight management. J Drugs Dermatol. 2025;24(4):413-415. doi:10.36849/JDD.8605. FAU - Daniel, Sophia AU - Daniel S FAU - Waggett, Stephanie AU - Waggett S FAU - Lyles, Elliott AU - Lyles E FAU - Sagut, Pelin AU - Sagut P FAU - Shamaei Zadeh, Parisa AU - Shamaei Zadeh P FAU - Marcelletti, Anthony AU - Marcelletti A FAU - Stegura, Carol AU - Stegura C FAU - Wine Lee, Lara AU - Wine Lee L LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Drug Eruptions/etiology/epidemiology/diagnosis MH - Male MH - Female MH - *Glucagon-Like Peptide 1/agonists MH - Middle Aged MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Liraglutide/adverse effects MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Exenatide/adverse effects MH - Aged EDAT- 2025/04/08 13:55 MHDA- 2025/04/08 13:56 CRDT- 2025/04/08 09:58 PHST- 2025/04/08 13:56 [medline] PHST- 2025/04/08 13:55 [pubmed] PHST- 2025/04/08 09:58 [entrez] AID - S1545961625P8605X [pii] AID - 10.36849/JDD.8605 [doi] PST - ppublish SO - J Drugs Dermatol. 2025 Apr 1;24(4):413-415. doi: 10.36849/JDD.8605. PMID- 40196933 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 2 IP - Suppl 2 DP - 2025 Apr TI - Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. PG - 66-88 LID - 10.1111/dom.16364 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as key agents for weight management, based on their marked efficacy as observed in randomized controlled trials. While still limited, real-world studies on GLP-1RA use in populations with obesity are increasingly available. This narrative review discusses contemporary real-world evidence demonstrating the utilization, clinical and comparative effectiveness, and adverse effects of the currently approved GLP-1RA-based weight-loss therapies, that is, liraglutide, semaglutide and tirzepatide. The observed weight reduction in clinical practice overall tends to be lower than in randomized controlled trials; however, outcomes approach those seen in trials when focusing on highly adherent patients. Real-world studies demonstrate high discontinuation rates of GLP-1RAs (20%-50%) within the first year, and the use of much lower doses than those evaluated in clinical trials. Evidence from observational studies within type 2 diabetes or obesity populations suggests frequent gastrointestinal disturbances in GLP-1RA users, as also observed in trials, but no clear increase in risks of severe events like pancreatitis or pancreatic cancer, thyroid disorders, or depression and self-harm. Further evidence is needed to understand possible real-world associations of GLP-1RAs with eye disease and other rare outcomes. We provide 10 areas of particular importance for further research on GLP-1RA within the real-world space, including improved understanding of the exact drivers of early discontinuation and suboptimal dosing, studies of the effects of stopping GLP-1RA treatment, and investigations of clinical and cost-effectiveness for hard clinical outcomes in real-world settings, including not only cardio-reno-metabolic outcomes but also obesity-induced diseases like neuropsychiatric disease, cancer, musculoskeletal disease, and infections. PLAIN LANGUAGE SUMMARY: Recent advancements in weight-loss medications have sparked a lot of interest. The so-called GLP-1 receptor agonist medications (GLP-1RAs) have gained a lot of attention, because they have shown to be very effective, leading to significant weight loss in patients participating in clinical trials. GLP-1RAs, like liraglutide, semaglutide, and tirzepatide, help manage weight by mimicking hormones that control blood sugar and appetite. However, how these medications perform in real life can be different from the controlled settings of clinical trials, in which patients are carefully selected and their treatment plans closely followed. This literature review looks at how these medications are used and their effectiveness and safety in real-world settings. In real-life practice, GLP-1RAs are often less effective than in clinical trial conditions. This is usually because patients don't follow their medication plans as strictly as in trials. Real-world data shows that many patients use lower doses and do not stick to their treatment as strictly as participants in a controlled trial might, leading to less weight loss. However, those who do follow their plans closely can achieve results similar to those in trials. A major issue with GLP-1RAs is that many patients stop using them within the first year due to side effects or high costs of the medications, especially if not covered by insurance. Common side effects include nausea and digestive problems, which are the main reasons patients stop taking these treatments. These side effects are often manageable and decrease over time, and this reviews found no strong real-world evidence that GLP-1RAs cause severe side effects in many users. Despite these challenges, when GLP-1RAs are used effectively and consistently, they show substantial benefits in weight loss, most so the newest medications semaglutide and tirzepatide. These medications are also likely to help manage and prevent weight-related health conditions like type 2 diabetes and cardiovascular disease, but evidence for these beneficial outcomes is still scarce in real-world settings. The review emphasizes the need for more research to understand why many patients stop using these medications and how to improve dosing. It also calls for studies on the long-term effects of these therapies on various health outcomes, including mental health, cardiometabolic health, cancer, and rare conditions like eye diseases. Overall, while GLP-1RAs are a valuable tool for weight management, their real-world use requires careful consideration of individual patient factors, such as the ability to stick to treatment plans, manage side effects, and afford the medications. Further research will help make these treatments more effective for a wider range of people that need them. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Thomsen, Reimar W AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Mailhac, Aurelie AU - Mailhac A AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Lohde, Julie B AU - Lohde JB AD - Department of Biomedicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus, Denmark. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Department of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Review DEP - 20250408 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Liraglutide/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use/adverse effects/analogs & derivatives MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Tirzepatide/therapeutic use MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12000858 OTO - NOTNLM OT - drug safety OT - drug utilization OT - epidemiology OT - glucagon-like peptide-1 receptor agonists OT - medications for obesity OT - real-world evidence OT - treatment adherence OT - treatment outcomes OT - weight loss COIS- Anton Pottegard reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma(all regulator-mandated phase IV-studies), and an unrestricted research grant from Novo Nordisk, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. Reimar W. Thomsen reports that he has given single scientific presentations on medical research (both with and without financial compensation) for companies, including Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi. The Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the current study. Julie B. Lohdes PhD project is financed by the Novo Nordisk Foundation. Aurelie Mailhac reports no conflicts of interest. EDAT- 2025/04/08 06:24 MHDA- 2025/04/16 06:19 PMCR- 2025/04/16 CRDT- 2025/04/08 05:02 PHST- 2025/03/05 00:00 [revised] PHST- 2025/01/28 00:00 [received] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/04/16 06:19 [medline] PHST- 2025/04/08 06:24 [pubmed] PHST- 2025/04/08 05:02 [entrez] PHST- 2025/04/16 00:00 [pmc-release] AID - DOM16364 [pii] AID - 10.1111/dom.16364 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27 Suppl 2(Suppl 2):66-88. doi: 10.1111/dom.16364. Epub 2025 Apr 8. PMID- 40193407 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20250729 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 22 IP - 4 DP - 2025 Apr TI - Frailty in randomized controlled trials of glucose-lowering therapies for type 2 diabetes: An individual participant data meta-analysis of frailty prevalence, treatment efficacy, and adverse events. PG - e1004553 LID - 10.1371/journal.pmed.1004553 [doi] LID - e1004553 AB - BACKGROUND: The representation of frailty in type 2 diabetes trials is unclear. This study used individual participant data from trials of newer glucose-lowering therapies to quantify frailty and assess the association between frailty and efficacy and adverse events. METHODS AND FINDINGS: We analysed IPD from 34 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DDP4) inhibitors. Frailty was quantified using a cumulative deficit frailty index (FI). For each trial, we quantified the distribution of frailty; assessed interactions between frailty and treatment efficacy (HbA1c and major adverse cardiovascular events [MACE], pooled using random-effects network meta-analysis); and associations between frailty and withdrawal, adverse events, and hypoglycaemic episodes. Trial participants numbered 25,208. Mean age across the included trials ranged from 53.8 to 74.2 years. Using a cut-off of FI > 0.2 to indicate frailty, median prevalence was 9.5% (IQR 2.4%-15.4%). Applying a higher threshold of FI > 0.3, median prevalence was 0.5% (IQR 0.1%-1.5%). Prevalence was higher in trials of older people and people with renal impairment however, even in these higher risk populations, people with FI > 0.4 were generally absent. For SGLT2 inhibitors and GLP1 receptor agonists, there was a small attenuation in efficacy on HbA1c with increasing frailty (0.08%-point and 0.14%-point smaller reduction, respectively, per 0.1-point increase in FI), below the level of clinical significance. Findings for the effect of treatment on MACE (and whether this varied by frailty) had high uncertainty, with few events occurring in trial follow-up. A 0.1-point increase in the FI was associated with more all-cause adverse events regardless of treatment allocation (incidence rate ratio, IRR 1.44, 95% CI 1.35-1.54, p < 0.0001), adverse events judged to the possibly or probably related to treatment (1.36, 1.23, to 1.49, p < 0.0001), serious adverse events (2.09, 1.85, to 2.36, p < 0.0001), hypoglycaemia (1.21, 1.06, to 1.38, p = 0.012), baseline risk of MACE (hazard ratio 3.01, 2.48, to 3.67, p < 0.0001) and with withdrawal from the trial (odds ratio 1.41, 1.27, to 1.57, p < 0.0001). The main limitation was that the large cardiovascular outcome trials did not include data on functional status and so we were unable to assess frailty in these larger trials. CONCLUSIONS: Frailty was uncommon in these trials, and participants with a high degree of frailty were rarely included. Frailty is associated very modest attenuation of treatment efficacy for glycaemic outcomes and with greater incidence of both adverse events and MACE independent of treatment allocation. While these findings are compatible with calls to relax HbA1c-based targets in people living with frailty, they also highlight the need for inclusion of people living with frailty in trials. This would require changes to trial processes to facilitate the explicit assessment of frailty and support the participation of people living with frailty. Such changes are important as the absolute balance of risks and benefits remains uncertain among those with higher degrees of frailty, who are largely excluded from trials. CI - Copyright: (c) 2025 Wightman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Wightman, Heather AU - Wightman H AUID- ORCID: 0009-0009-3625-0945 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. FAU - Butterly, Elaine AU - Butterly E AUID- ORCID: 0000-0001-9410-0237 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. FAU - Wei, Lili AU - Wei L AUID- ORCID: 0000-0002-3255-3449 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. FAU - McChrystal, Ryan AU - McChrystal R AUID- ORCID: 0000-0003-1513-6966 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. FAU - Adler, Amanda AU - Adler A AD - Diabetes Trials Unit, University of Oxford, Oxford, United Kingdom. FAU - Phillippo, David AU - Phillippo D AUID- ORCID: 0000-0003-2672-7841 AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Dias, Sofia AU - Dias S AUID- ORCID: 0000-0002-2172-0221 AD - Centre for Reviews and Dissemination, University of York, York, United Kingdom. FAU - Welton, Nicky AU - Welton N AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Clegg, Andrew AU - Clegg A AD - Academic Unit for Ageing and Stroke Research, Bradford Teaching Hospitals NHS Foundation Trust, University of Leeds, Bradford, United Kingdom. FAU - Witham, Miles AU - Witham M AUID- ORCID: 0000-0002-1967-0990 AD - AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Leeds, United Kingdom. AD - NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne NHS Foundation Trust, Cumbria Northumberland Tyne and Wear NHS Foundation Trust and Newcastle University, Newcastle, United Kingdom. FAU - Rockwood, Kenneth AU - Rockwood K AUID- ORCID: 0000-0002-6674-995X AD - Division of Geriatric Medicine, Dalhousie University and Nova Scotia Health, Halifax, Nova Scotia, Canada. FAU - McAllister, David A AU - McAllister DA AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. FAU - Hanlon, Peter AU - Hanlon P AUID- ORCID: 0000-0002-5828-3934 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20250407 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - *Frailty/epidemiology MH - Randomized Controlled Trials as Topic MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Prevalence MH - Middle Aged MH - Treatment Outcome MH - Male MH - Female MH - *Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/metabolism PMC - PMC12052138 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: AC is part-funded by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration Yorkshire & Humber, the NIHR Leeds Biomedical Research Centre, and Health Data Research UK, an initiative funded by UK Research and Innovation Councils, NIHR, and the UK devolved administrations and leading medical research charities. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. NS declares grant funding from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics; consulting fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; payment for lectures or presentations from Abbott Laboratories, AbbVie, AstraZeneca, Boeringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi. All work was unrelated to this manuscript. MW declares grant funding from the National Institute for Health and Care Research, Medical Research Council and Biotechnology, and Biological Sciences Research Council. AA declares salary support from the National Institute for Health and Care Research Biomedical Research Centre (Oxford). DP declares consultancy fees from Bayer, AstraZeneca, and Bristol Myres Squibb. All work was unrelated to this manuscript. KR reports grants from Nova Scotia Health Research Fund, during the conduct of the study; personal fees from Ardea Outcomes , personal fees from Chinese Medical Association, personal fees from Wake Forest University Medical School Centre, personal fees from University of Nebraska - Omaha, personal fees from Australie New Zealand Society of Geriatric Medicine, personal fees from Atria Institute, personal fees from Fraser Health Authority, personal fees from McMster University, personal fees from EpiPharma Inc., outside the submitted work; in addition, Dr Rockwood has a patent Clinical Frailty Scale licensed to Enanta Pharmaceuticals, Inc., a patent Clinical Frailty Scale licensed to Synairgen Research Ltd, a patent Clinical Frailty Scale licensed to Faraday Pharmaceuticals, Inc., a patent Clinical Frailty Scale licensed to KCR S.A., a patent Clinical Frailty Scale licensed to Icosavax, Inc., a patent Pictorial Fit-Frail Scale licensed to Congenica, a patent Clinical Frailty Scale licensed to BioAge Labs Inc., a patent Clinical Frailty Scale licensed to Biotest AG, a patent Clinical Frailty Scale licensed to Qu Biologics Inc., a patent Clinical Frailty Scale licensed to AstraZeneca UK Limited, a patent Clinical Frailty Scale licensed to Cellcolabs AB, a patent Clinical Frailty Scale licensed to Pfizer Inc., a patent Clinical Frailty Scale licensed to W.L. Gore Associates Inc., a patent Clinical Frailty Scale pending to Cook Research Incorporated, a patent Clinical Frailty Scale pending to Rebibus Therapeutics Inc., and as part of Ardea Outcomes Inc. has a pending patent for Electronic Goal Attainment Scaling. Use of both the CFS and PFFS is free for education, research, and non-profit health care with completion of a permission agreement stipulating users will not change, charge for or commercialize the scales. For-profit entities (including pharma) pay a licensing fee, 15% of which is retained by the Dalhousie University Office of Commercialization and Innovation Engagement. After taxes, the remainder of the license fees is donated to the Dalhousie Medical Research Foundation. In addition to academic and hospital appointments, KR is co-founder of Ardea Outcomes (DGI Clinical until 2021), which in the past 3 years has had contracts with pharma and device manufacturers (Danone, Hollister, INmune, Novartis, Takeda) on individualized outcome measurement. EDAT- 2025/04/07 18:24 MHDA- 2025/05/05 18:35 PMCR- 2025/04/07 CRDT- 2025/04/07 13:43 PHST- 2024/09/12 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2025/05/05 00:00 [revised] PHST- 2025/05/05 18:35 [medline] PHST- 2025/04/07 18:24 [pubmed] PHST- 2025/04/07 13:43 [entrez] PHST- 2025/04/07 00:00 [pmc-release] AID - PMEDICINE-D-24-03055 [pii] AID - 10.1371/journal.pmed.1004553 [doi] PST - epublish SO - PLoS Med. 2025 Apr 7;22(4):e1004553. doi: 10.1371/journal.pmed.1004553. eCollection 2025 Apr. PMID- 40193122 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260211 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 82 IP - 5 DP - 2025 May 1 TI - Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis. PG - 450-460 LID - 10.1001/jamaneurol.2025.0360 [doi] AB - IMPORTANCE: Although diabetes is a risk factor for dementia, the effect of glucose-lowering therapy for prevention of incident dementia is uncertain. OBJECTIVE: To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes. DATA SOURCES: The PubMed and Embase databases were searched for studies published from inception of the database to July 11, 2024. STUDY SELECTION: Randomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores. Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials. Inclusion criteria were assessed independently and inconsistencies were resolved by consensus. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models were used to estimate a pooled treatment effect. MAIN OUTCOMES AND MEASURES: The primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia, and change in cognitive scores. RESULTS: Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04). CONCLUSIONS AND RELEVANCE: While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia. FAU - Seminer, Allie AU - Seminer A AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. FAU - Mulihano, Alfredi AU - Mulihano A AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. FAU - O'Brien, Clare AU - O'Brien C AD - University Hospital Galway, Galway, Ireland. FAU - Krewer, Finn AU - Krewer F AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. FAU - Costello, Maria AU - Costello M AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. AD - University Hospital Galway, Galway, Ireland. FAU - Judge, Conor AU - Judge C AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. AD - University Hospital Galway, Galway, Ireland. FAU - O'Donnell, Martin AU - O'Donnell M AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. AD - University Hospital Galway, Galway, Ireland. FAU - Reddin, Catriona AU - Reddin C AD - HRB Clinical Research Facility, University of Galway, Galway, Ireland. AD - University Hospital Galway, Galway, Ireland. AD - Wellcome Trust-HRB, Irish Clinical Academic Training, Dublin, Ireland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Cardiotonic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - X4OV71U42S (Pioglitazone) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - JAMA Neurol. 2025 May 1;82(5):437-438. doi: 10.1001/jamaneurol.2025.0237. PMID: 40193095 MH - Humans MH - *Cardiotonic Agents/therapeutic use MH - Cognitive Dysfunction/prevention & control MH - *Dementia/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Metformin/therapeutic use MH - Pioglitazone/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC11976645 COIS- Conflict of Interest Disclosures: Dr Krewer reported receiving grants from the Health Research Board (HRB; SDAP2023.036) outside the submitted work. Dr Reddin reported receiving grants from the Irish Clinical Academic Training Programme, Wellcome Trust, HRB (203930/B/16/Z), Health Service Executive, National Doctors Training and Planning, and Health and Social Care, Research and Development Division, Northern Ireland outside the submitted work. No other disclosures were reported. EDAT- 2025/04/07 13:17 MHDA- 2025/05/12 12:33 PMCR- 2025/04/07 CRDT- 2025/04/07 11:34 PHST- 2025/05/12 12:33 [medline] PHST- 2025/04/07 13:17 [pubmed] PHST- 2025/04/07 11:34 [entrez] PHST- 2025/04/07 00:00 [pmc-release] AID - 2831975 [pii] AID - noi250011 [pii] AID - 10.1001/jamaneurol.2025.0360 [doi] PST - ppublish SO - JAMA Neurol. 2025 May 1;82(5):450-460. doi: 10.1001/jamaneurol.2025.0360. PMID- 40193118 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260408 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 82 IP - 5 DP - 2025 May 1 TI - GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias. PG - 439-449 LID - 10.1001/jamaneurol.2025.0353 [doi] AB - IMPORTANCE: The association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) and risk of Alzheimer disease and related dementias (ADRD) remains to be confirmed. OBJECTIVE: To assess the risk of ADRD associated with GLP-1RAs and SGLT2is in people with type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS: This target trial emulation study used electronic health record data from OneFlorida+ Clinical Research Consortium from January 2014 to June 2023. Patients were 50 years or older with T2D and no prior diagnosis of ADRD or antidementia treatment. Among the 396 963 eligible patients with T2D, 33 858 were included in the GLP-1RA vs other glucose-lowering drug (GLD) cohort, 34 185 in the SGLT2i vs other GLD cohort, and 24 117 in the GLP-1RA vs SGLT2i cohort. EXPOSURES: Initiation of treatment with a GLP-1RA, SGLT2i, or other second-line GLD. MAIN OUTCOMES AND MEASURES: ADRD was identified using clinical diagnosis codes. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazard regression models with inverse probability of treatment weighting (IPTW) to adjust for potential confounders. RESULTS: This study included 33 858 patients in the GLP-1RA vs other GLD cohort (mean age, 65 years; 53.1% female), 34 185 patients in the SGLT2i vs other GLD cohort (mean age, 65.8 years; 49.3% female), and 24 117 patients in the GLP-1RA vs SGLT2i cohort (mean age, 63.8 years; 51.7% female). In IPTW-weighted cohorts, the incidence rate of ADRD was lower in GLP-1RA initiators compared with other GLD initiators (rate difference [RD], -2.26 per 1000 person-years [95% CI, -2.88 to -1.64]), yielding an HR of 0.67 (95% CI, 0.47-0.96). SGLT2i initiators had a lower incidence than other GLD initiators (RD, -3.05 per 1000 person-years [95% CI, -3.68 to -2.42]), yielding an HR of 0.57 (95% CI, 0.43-0.75). There was no difference between GLP-1RAs and SGLT2is, with an RD of -0.09 per 1000 person-years (95% CI, -0.80 to 0.63) and an HR of 0.97 (95% CI, 0.72-1.32). CONCLUSION AND RELEVANCE: In people with T2D, both GLP-1RAs and SGLT2is were statistically significantly associated with decreased risk of ADRD compared with other GLDs, and no difference was observed between both drugs. FAU - Tang, Huilin AU - Tang H AD - Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville. FAU - Donahoo, William T AU - Donahoo WT AD - Department of Medicine, College of Medicine, University of Florida, Gainesville. FAU - DeKosky, Steven T AU - DeKosky ST AD - Department of Neurology and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville. AD - 1Florida Alzheimer's Disease Research Center, University of Florida, Gainesville. FAU - Lee, Yao An AU - Lee YA AD - Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville. FAU - Kotecha, Pareeta AU - Kotecha P AD - Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville. FAU - Svensson, Mikael AU - Svensson M AD - Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - JAMA Neurol. 2025 May 1;82(5):437-438. doi: 10.1001/jamaneurol.2025.0237. PMID: 40193095 MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Male MH - Female MH - Aged MH - *Alzheimer Disease/epidemiology/chemically induced MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Dementia/epidemiology/chemically induced MH - Aged, 80 and over MH - Cohort Studies PMC - PMC11976648 COIS- Conflict of Interest Disclosures: Dr Tang reported receiving grants from Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation during the conduct of the study. Dr DeKosky reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study; personal fees from Acumen Pharmaceuticals, Biogen, and Vaccinex for serving as the data and safety monitoring board chair; Cognition Therapeutics for serving on the medical advisory board; Neurotherapeutics for serving as an associate editor; UpToDate for serving as a section editor for dementia; and consulting fees from Eisai, Lilly, Nido Biosciences, and Prevail Therapeutics outside the submitted work. Dr Kotecha reported receiving personal fees from Takeda Pharmaceuticals for serving as an intern in 2023 and Novo Nordisk for serving as a regulatory medical writer from 2021 to 2022 outside the submitted work. No other disclosures were reported. EDAT- 2025/04/07 13:16 MHDA- 2025/05/12 12:33 PMCR- 2026/04/07 CRDT- 2025/04/07 11:34 PHST- 2025/05/12 12:33 [medline] PHST- 2025/04/07 13:16 [pubmed] PHST- 2025/04/07 11:34 [entrez] PHST- 2026/04/07 00:00 [pmc-release] AID - 2831976 [pii] AID - noi250010 [pii] AID - 10.1001/jamaneurol.2025.0353 [doi] PST - ppublish SO - JAMA Neurol. 2025 May 1;82(5):439-449. doi: 10.1001/jamaneurol.2025.0353. PMID- 40189538 OWN - NLM STAT- MEDLINE DCOM- 20250516 LR - 20260127 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 23 IP - 1 DP - 2025 Apr 7 TI - Increased vision impairment reports linked to semaglutide: analysis of FDA adverse event data. PG - 203 LID - 10.1186/s12916-025-04031-z [doi] LID - 203 AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist widely prescribed for type 2 diabetes and obesity, has recently raised concerns about its ocular safety. This study aimed to investigate the association between semaglutide use and vision impairment using data from the FDA Adverse Event Reporting System (FAERS). METHODS: We conducted an analysis of FAERS data, comparing reports of vision impairment associated with semaglutide to those associated with other antidiabetic and weight loss medications. The main outcome measure was the reporting odds ratio (rOR) for vision impairment linked to semaglutide use compared to other medications. RESULTS: Semaglutide showed significantly higher reporting of vision impairment compared to other GLP-1 receptor agonists (rOR 1.95, 95% CI 1.75-2.17, p < 0.0001), DPP-4 inhibitors (rOR 2.46, 95% CI 2.12-2.86, p < 0.0001), SGLT2 inhibitors (rOR 3.89, 95% CI 3.35-4.51, p < 0.0001), and metformin (rOR 2.23, 95% CI 1.90-2.62, p < 0.0001). Similar findings were observed when compared to phentermine (rOR 1.57, 95% CI 1.07-2.31, p = 0.026) and orlistat (rOR 3.77, 95% CI 2.96-4.81, p < 0.0001). Topiramate was the sole exception, showing higher vision impairment reporting than semaglutide (rOR 0.30, 95% CI 0.20-0.45, p < 0.0001). CONCLUSIONS: These findings suggest a potentially elevated risk of vision impairment with semaglutide use compared to other diabetes and weight loss medications, warranting further investigation and vigilant post-marketing surveillance. Future studies should assess the clinical impact of this potential increased risk on an absolute scale to better inform treatment decisions. CI - (c) 2025. The Author(s). FAU - Massy, Marine AU - Massy M AUID- ORCID: 0009-0006-4282-8609 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. AD - Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. AD - Department of Biomedical Research, University of Bern, Bern, Switzerland. FAU - Marti, Stefanie AU - Marti S AUID- ORCID: 0000-0001-8237-6965 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. FAU - Hammer, Helly AU - Hammer H AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. FAU - Hoepner, Robert AU - Hoepner R AUID- ORCID: 0000-0002-0115-7021 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. robert.hoepner@insel.ch. LA - eng PT - Journal Article DEP - 20250407 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States/epidemiology MH - *Glucagon-Like Peptides/adverse effects MH - United States Food and Drug Administration MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Vision Disorders/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Female MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11974072 OTO - NOTNLM OT - Diabetes OT - Obesity OT - Semaglutide OT - Vision impairment COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Massy M reports no competing interests. Marti S reports no competing interests. Hammer H received research support and travel grants within the last 5 years from Biogen, Merck, Roche & Bristol Myers Squibb, Teva, Johnson&Johnson, Novartis. All not related to that work. Hoepner R received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Janssen, Bristol-Myers Squibb, Teva/Mepha and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, Chiesi, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society, the SITEM Insel Support Fund and is a member of the Advisory Board of the Swiss and International MS Society. He also serves as deputy editor in chief for Journal of Central Nervous System disease and is part of the ECTRIMS Young Investigator Committee. EDAT- 2025/04/07 02:02 MHDA- 2025/04/07 02:03 PMCR- 2025/04/07 CRDT- 2025/04/06 23:14 PHST- 2024/08/22 00:00 [received] PHST- 2025/03/21 00:00 [accepted] PHST- 2025/04/07 02:03 [medline] PHST- 2025/04/07 02:02 [pubmed] PHST- 2025/04/06 23:14 [entrez] PHST- 2025/04/07 00:00 [pmc-release] AID - 10.1186/s12916-025-04031-z [pii] AID - 4031 [pii] AID - 10.1186/s12916-025-04031-z [doi] PST - epublish SO - BMC Med. 2025 Apr 7;23(1):203. doi: 10.1186/s12916-025-04031-z. PMID- 40187657 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260812 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 431 DP - 2025 Jul 15 TI - Combination treatment of SGLT2i and GLP-1RA associated with improved cardiovascular outcomes in type 2 diabetes patients with acute coronary syndrome: A propensity score-matched cohort study. PG - 133229 LID - S0167-5273(25)00272-4 [pii] LID - 10.1016/j.ijcard.2025.133229 [doi] AB - BACKGROUND: Few studies have investigated the effect of the combined use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) on the cardiovascular (CV) composite outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS). METHODS: We retrospectively collected the data of 1325 T2D patients treated with SGLT2i for more than 3 months before ACS admission at Civil Aviation General Hospital. According to the initiative GLP-1RA use after admission, patients were divided into a combination group (SGLT2i and GLP-1RA) or a SGLT2i group. The primary CV composite outcomes were defined as the first occurrence of major adverse cardiovascular events (MACE) with 1-year, encompassing all cause death, CV death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission. Propensity score-matched (PSM) was used to control the confounding factors. RESULTS: After matching, 208 pairs were finally included. Compared with the SGLT2i group, the combination group demonstrated a 31.0 % reduced risk of MACE (HR = 0.690, 95 %CI: 0.488-0.976), attributed primarily to a substantial 22.9 % (HR = 0.771, 95 %CI: 0.599-0.992) reduction in all-cause mortality and a 36.3 % reduction in non-fatal stroke (HR = 0.637, 95 %CI: 0.413-0.982). Subgroup analyses indicated consistent CV benefits across different subgroups (P interaction values >0.05). CONCLUSIONS: The combined use of SGLT2i and GLP-1RA was associated with a significantly decreased risk of MACE primarily driven by the lowering risks of all-cause mortality and nonfatal stroke in T2D patients with ACS, compared with SGLT2i use alone. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Liu, Tao AU - Liu T AD - Department of Coronary Heart Disease, Civil Aviation General Hospital, No. 1 Gaojingjia Road, Chaoyang District, Beijing, China. FAU - Fan, Zeyuan AU - Fan Z AD - Department of Coronary Heart Disease, Civil Aviation General Hospital, No. 1 Gaojingjia Road, Chaoyang District, Beijing, China. Electronic address: fanzy_mhzyy@163.com. FAU - Li, Yuntao AU - Li Y AD - Department of Coronary Heart Disease, Civil Aviation General Hospital, No. 1 Gaojingjia Road, Chaoyang District, Beijing, China. FAU - Xiao, Bing AU - Xiao B AD - Department of Coronary Heart Disease, Civil Aviation General Hospital, No. 1 Gaojingjia Road, Chaoyang District, Beijing, China. FAU - He, Chang AU - He C AD - Department of Coronary Heart Disease, Civil Aviation General Hospital, No. 1 Gaojingjia Road, Chaoyang District, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250403 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/complications MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage MH - Retrospective Studies MH - *Acute Coronary Syndrome/drug therapy/epidemiology/diagnosis MH - *Propensity Score MH - Aged MH - Middle Aged MH - Treatment Outcome MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies MH - Follow-Up Studies OTO - NOTNLM OT - Acute coronary syndrome OT - Glucagon-like peptide 1 receptor agonist OT - Major adverse cardiovascular events OT - Propensity score-matched OT - Sodium-glucose cotransporter-2 inhibitor OT - Type 2 diabetes COIS- Declaration of competing interest The authors disclose no conflict of interest related to the writing, analysis, or publication of this paper. EDAT- 2025/04/06 04:44 MHDA- 2025/04/27 13:08 CRDT- 2025/04/05 19:36 PHST- 2025/02/08 00:00 [received] PHST- 2025/03/22 00:00 [revised] PHST- 2025/04/01 00:00 [accepted] PHST- 2025/04/27 13:08 [medline] PHST- 2025/04/06 04:44 [pubmed] PHST- 2025/04/05 19:36 [entrez] AID - S0167-5273(25)00272-4 [pii] AID - 10.1016/j.ijcard.2025.133229 [doi] PST - ppublish SO - Int J Cardiol. 2025 Jul 15;431:133229. doi: 10.1016/j.ijcard.2025.133229. Epub 2025 Apr 3. PMID- 40184508 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20260620 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 3 DP - 2025 May TI - Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies. PG - e70045 LID - 10.1002/edm2.70045 [doi] LID - e70045 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an efficacious treatment for type 2 diabetes mellitus (T2DM) and have demonstrated substantial weight loss effects. This systematic review compares two prevalent GLP-1RAs, tirzepatide and semaglutide, with their weight loss effects and rates of adverse events (AEs). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase and Cochrane Library for direct comparative studies between tirzepatide and semaglutide. A meta-analysis was conducted via a random-effects model to analyse the differences in weight loss outcomes between study cohorts. RESULTS: Four studies, with 28,827 patients (14,870 tirzepatide/13,928 semaglutide), mean age of 55.7 years (52.0 to 63.7) and mean follow-up of 35.9 weeks (23.6 to 44.6), were included in this study. Mean weight change across four studies for tirzepatide and semaglutide was -11.4% (-15.3% to -8.27%) and -7.3% (-8.3% to -6.08%), respectively. The meta-analysis supports these findings with a mean difference of -4.84 kg (95% CI: -6.21 to -3.47), favouring tirzepatide. The most common AEs were minor and moderate-severity gastrointestinal (GI) AEs. CONCLUSION: Current literature supports tirzepatide demonstrating a higher impact on weight loss than semaglutide, with both demonstrating high rates of minimal- to moderate-severity AEs. Further research with comparative head-to-head trials will better elucidate these weight loss effects and safety profiles. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Syed, Burhaan AU - Syed B AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Akhtar, Muzammil AU - Akhtar M AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Adam AU - Razick A AD - University of California, Los Angeles, Los Angeles, California, USA. FAU - Puglisi, Jose AU - Puglisi J AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - California Northstate University College of Medicine, Elk Grove, California, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11970626 OTO - NOTNLM OT - diabetes OT - meta-analysis OT - semaglutide OT - tirzepatide OT - weight loss COIS- The authors declare no conflicts of interest. EDAT- 2025/04/04 18:25 MHDA- 2025/04/04 18:26 PMCR- 2025/04/04 CRDT- 2025/04/04 15:02 PHST- 2025/02/15 00:00 [revised] PHST- 2024/10/24 00:00 [received] PHST- 2025/03/06 00:00 [accepted] PHST- 2025/04/04 18:26 [medline] PHST- 2025/04/04 18:25 [pubmed] PHST- 2025/04/04 15:02 [entrez] PHST- 2025/04/04 00:00 [pmc-release] AID - EDM270045 [pii] AID - 10.1002/edm2.70045 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 May;8(3):e70045. doi: 10.1002/edm2.70045. PMID- 40183412 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Population-level impact of semaglutide 2.4 mg in patients with obesity or overweight and cardiovascular disease: A modelling study based on the SELECT trial. PG - 3442-3452 LID - 10.1111/dom.16370 [doi] AB - AIM: To estimate the impact of semaglutide 2.4 mg treatment on the risk of major adverse cardiovascular events (MACE) in adults with overweight/obesity in the United States based on the SELECT trial of patients with atherosclerotic cardiovascular disease. MATERIALS AND METHODS: Using 2023 census projections and National Health and Nutrition Examination Survey data, we developed Markov population-based predictive models for US adults meeting SELECT inclusion criteria and, separately, for adults eligible for semaglutide 2.4 mg for its MACE risk reduction indication. The 10-year rate of recurrent MACE and deaths was estimated based on the Secondary Manifestations of ARTerial disease 2 risk calculator and estimated semaglutide 2.4 mg treatment effect as per the SELECT MACE hazard ratio. RESULTS: Of 6 164 019 US adults meeting the SELECT criteria, 2 523 218 (40.9%) are estimated to have >/=1 new MACE in the next 10 years with no additional intervention. Semaglutide 2.4 mg may prevent 496 400 events, a 16% relative reduction. An estimated 2 103 630 deaths are predicted over the next 10 years, of which 332 597 deaths (any cause, 16% relative reduction) could be avoided with semaglutide 2.4 mg. Among the estimated 22 653 158 meeting the MACE risk reduction FDA label criteria, 42.7% could experience >/=1 new MACE; treatment could prevent 1 934 493 MACE and 1 231 295 deaths (16% relative reduction for both). CONCLUSION: Four in 10 individuals in the United States meeting the SELECT criteria are estimated to experience a recurrent CV event without additional intervention. Semaglutide 2.4 mg can potentially prevent between half a million and up to 2 million MACE over the next 10 years in the population meeting SELECT and MACE risk reduction eligibility. PLAIN LANGUAGE SUMMARY: What is the context and purpose of this research study? More than 7 in 10 US adults have overweight or obesity, which increases the risk of heart disease. Semaglutide is a medication used to treat type 2 diabetes and obesity. A clinical study called SELECT found that semaglutide reduces the risk of heart attack, stroke, or death by 20% in adults with overweight or obesity and heart disease. What was done? Our research estimated how many people in the United States would meet the criteria for participation in SELECT, how many heart disease events they might have with regular medical care over the next 10 years, and how many could be avoided with semaglutide 2.4 mg treatment in addition to regular medical care. We also estimated how many people would still be alive if they were treated with semaglutide. We estimated the same information for all people eligible for treatment with semaglutide based on the US Food and Drug Administration (FDA) indication of semaglutide 2.4 mg in patients with heart disease. These estimations were based on a large survey of US adults. What were the main results? We found that over 6 million people would meet the SELECT study criteria. Of these, 41% are estimated to have at least 1 new heart disease event in the next 10 years. If treated with semaglutide 2.4 mg, nearly 500 000 heart disease events and more than 300 000 deaths could be avoided. More than 22 million adults would qualify for semaglutide 2.4 mg, according to the FDA indication. If all of these people were treated with semaglutide 2.4 mg, nearly 2 million heart disease events and more than 1 million deaths might be prevented. What is the originality and relevance of this study? Treatment with semaglutide 2.4 mg can reduce the risk of new heart disease events and death in patients with existing heart disease, showing a substantial impact of semaglutide treatment in a real-world setting in the United States. Our study used different analyses to add to the existing research about reducing the risk of heart disease in people with overweight or obesity. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Doan, Quan V AU - Doan QV AUID- ORCID: 0000-0003-1170-1120 AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Fabricatore, Anthony AU - Fabricatore A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Faurby, Mads AU - Faurby M AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Henry, Alasdair D AU - Henry AD AUID- ORCID: 0009-0006-2122-8620 AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Houshmand-Oeregaard, Azadeh AU - Houshmand-Oeregaard A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Levine, Alina AU - Levine A AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Navar, Ann Marie AU - Navar AM AUID- ORCID: 0000-0002-6197-9860 AD - Departments of Internal Medicine and Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Scassellati Sforzolini, Thomas AU - Scassellati Sforzolini T AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Toliver, Joshua C AU - Toliver JC AUID- ORCID: 0000-0002-9159-2587 AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. LA - eng GR - K76 AG088428/AG/NIA NIH HHS/United States GR - P30 AG021342/AG/NIA NIH HHS/United States GR - Novo Nordisk/ PT - Journal Article DEP - 20250404 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology/complications/mortality MH - *Obesity/complications/drug therapy MH - Adult MH - *Overweight/complications/drug therapy MH - United States/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Markov Chains MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046440 OTO - NOTNLM OT - United States OT - cardiovascular disease OT - cardiovascular risk OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - overweight OT - semaglutide COIS- MGN is a consultant for Merck, Novo Nordisk and HeartFlow, Inc. He reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute and the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342). AMN reports funding for research to her institution from Esperion and Amgen, and honoraria and consulting fees from Amgen, Eli Lilly, Esperion, Janssen, Merck, NewAmsterdam, Novo Nordisk, Novartis, Pfizer and Silence Therapeutics. Her spouse receives research funding to his institution from Amgen and Esperion, and consulting from Janssen and Amgen. MF, JCT, AF, ASH are employees and shareholders of Novo Nordisk Inc. ADH, TSS and AL are employed by Genesis Research Group, a consulting company that received funding from Novo Nordisk to carry out this research. QVD was employed by Genesis Research Group at the time the research was conducted. EDAT- 2025/04/04 12:29 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/04/04 07:42 PHST- 2025/03/14 00:00 [revised] PHST- 2024/12/12 00:00 [received] PHST- 2025/03/14 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/04/04 12:29 [pubmed] PHST- 2025/04/04 07:42 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16370 [pii] AID - 10.1111/dom.16370 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3442-3452. doi: 10.1111/dom.16370. Epub 2025 Apr 4. PMID- 40183385 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260127 IS - 1724-6016 (Electronic) IS - 1120-6721 (Linking) VI - 35 IP - 4 DP - 2025 Jul TI - Non arteritic ischemic optic neuropathy in a patient taking semaglutide: Is there a relation? A case report and a review of the literature. PG - NP10-NP15 LID - 10.1177/11206721251331655 [doi] AB - IntroductionThe glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as Semaglutide, have revolutionized the treatment of type 2 diabetes mellitus and obesity.Case desciptionThe aim of the present study was to report a case of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) occurring in a diabetic patient taking Semaglutide and to review the literature in order to find a possible relation between the ophthalmological event and the drug intake.DiscussionAlthough the clinical trials of Semaglutide did not report any significant increase in the risk of NAION, a recent retrospective cohort study suggested a possible association between NAION and GLP-1 RAs. After this publication, the association between NAION and Semaglutide became an hot topic and several studies were published, presenting conflicting results.Conclusion and ImportanceAlbeit the association between the use of GLP-1 RAs and NAION, to date, remain controversial, clinicians and ophthalmologists should be aware of such possible association to analyze for each patient the risk-benefit ratio. FAU - Maceroni, Martina AU - Maceroni M AUID- ORCID: 0000-0002-3754-7486 AD - Istituto di Oftalmologia, Universita Cattolica del Sacro Cuore, 00168 Roma, Italia. RINGGOLD: 96983 AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Sasso, Paola AU - Sasso P AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Giarletti, Matteo AU - Giarletti M AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Bruno, Valentina AU - Bruno V AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Minnella, Angelo Maria AU - Minnella AM AD - Istituto di Oftalmologia, Universita Cattolica del Sacro Cuore, 00168 Roma, Italia. RINGGOLD: 96983 AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20250404 PL - United States TA - Eur J Ophthalmol JT - European journal of ophthalmology JID - 9110772 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - Visual Acuity MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) OT - case report NAION OT - non-artehritic anterior ischemic optic neuropathy (NAION) OT - semaglutide COIS- Conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/04/04 12:30 MHDA- 2025/06/24 13:14 CRDT- 2025/04/04 07:33 PHST- 2025/06/24 13:14 [medline] PHST- 2025/04/04 12:30 [pubmed] PHST- 2025/04/04 07:33 [entrez] AID - 10.1177/11206721251331655 [doi] PST - ppublish SO - Eur J Ophthalmol. 2025 Jul;35(4):NP10-NP15. doi: 10.1177/11206721251331655. Epub 2025 Apr 4. PMID- 40182628 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20250604 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists. PG - 1532587 LID - 10.3389/fendo.2025.1532587 [doi] LID - 1532587 AB - OBJECTIVE: To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) treatment and the risk of esophageal cancer in adults with type 2 diabetes mellitus (T2DM) or obesity through a comprehensive meta-analysis. METHODS: A systematic computerized searches and collection of eligible randomized controlled trials (RCTs) was performed to compare the risk of esophageal cancer between GLP-1 RA and control agents. The bias risks and quality of the studies were evaluated, and a meta-analysis was conducted using Stata 18.0 and R 4.0.2 statistical software. RESULTS: The meta-analysis included data from six studies involving 13,391 participants. The pooled relative risk (RR) of esophageal cancer in patients using GLP-1 RAs compared to control agents was 0.46 (95% CI 0.13-1.59; p=0.725; I(2)=0%). Subgroup analyses stratified by age groups, intervention durations, BMI categories, and indications for T2DM or obesity treatment more often indicated no association between GLP-1 RAs use and increased risk of esophageal cancer. CONCLUSIONS: GLP-1 RAs did not increase the incidence of esophageal neoplasms, and there were not probably significant within-class differences in T2DM or obesity treatment. This finding supports the safety of GLP-1 RAs as a therapeutic option for the clinical management of T2DM. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024543945. CI - Copyright (c) 2025 Wu, Zeng, Liu, Teng, Zhou, Guo, Jiang and Xu. FAU - Wu, Qi AU - Wu Q AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. FAU - Zeng, Yan AU - Zeng Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. FAU - Liu, Yong AU - Liu Y AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Department of Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Intensive Care Unit, Wangcang People's Hospital, Guangyuan, China. FAU - Teng, Fangyuan AU - Teng F AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Zhou, Tiejun AU - Zhou T AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China. FAU - Guo, Man AU - Guo M AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Jiang, Zongzhe AU - Jiang Z AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Xu, Yong AU - Xu Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250320 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Esophageal Neoplasms/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy/complications MH - Risk Factors MH - Randomized Controlled Trials as Topic PMC - PMC11966957 OTO - NOTNLM OT - esophageal cancer OT - glucagon-like peptide-1 receptor agonist OT - meta-analysis OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/04/04 06:26 MHDA- 2025/04/04 06:27 PMCR- 2025/01/01 CRDT- 2025/04/04 05:13 PHST- 2024/11/26 00:00 [received] PHST- 2025/02/28 00:00 [accepted] PHST- 2025/04/04 06:27 [medline] PHST- 2025/04/04 06:26 [pubmed] PHST- 2025/04/04 05:13 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1532587 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Mar 20;16:1532587. doi: 10.3389/fendo.2025.1532587. eCollection 2025. PMID- 40181696 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Association of tirzepatide with glycaemic control and weight loss in a real world cohort of patients with type 2 diabetes from the United States. PG - 3453-3463 LID - 10.1111/dom.16372 [doi] AB - AIMS: The goal of this observational, single-cohort, pre-post study was to describe the association of tirzepatide with glycaemic control and weight loss in patients with type 2 diabetes (T2D) in a US commercially insured population. MATERIALS AND METHODS: Using the Healthcare Integrated Research Database (HIRD(R)), members >/=18 years, diagnosed with T2D, initiating tirzepatide between 13 May 2022 and 31 January 2023, with >/=1 glycated haemoglobin (HbA1c) result around the index date and the end of the 6-month follow-up period were identified. Baseline demographics and antihyperglycaemic medication use and key outcomes (HbA1c and weight) at 6-month follow-up were assessed overall and in subgroups stratified by baseline glucagon-like peptide-1 (GLP-1) receptor agonist (RA) use and HbA1c (<7% and >/=7%) level. RESULTS: The cohort of 2247 identified patients was primarily non-Hispanic White, female (58%), 54 years old, 54% had GLP-1 RA at baseline, 59% had an HbA1c >/=7% at baseline and 61% had overweight/obesity. At 6-month follow-up, a majority of the cohort (69%) had an HbA1c <7%, which was higher (77%) in the GLP-1 RA naive subgroup. Mean change in weight was: -6.3 kg for the overall cohort; -7.1 kg in patients with baseline HbA1c <7%; and -8.1 kg in the GLP-1 RA naive subgroup. CONCLUSION: In this observational, single-cohort study, at 6-month follow-up, patients with T2D initiating tirzepatide showed HbA1c and weight reductions; more pronounced HbA1c reductions occurred in GLP-1 RA naive patients or those with baseline HbA1c >/=7%, while more weight loss was observed among GLP-1 RA naive patients or those with baseline HbA1c <7%. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Mody, Reema AU - Mody R AUID- ORCID: 0000-0002-3442-1714 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Desai, Karishma AU - Desai K AUID- ORCID: 0000-0001-6108-4154 AD - Carelon Research, Wilmington, Delaware, USA. FAU - Teng, Chia-Chen AU - Teng CC AD - Carelon Research, Wilmington, Delaware, USA. FAU - Reznor, Gally AU - Reznor G AD - Carelon Research, Wilmington, Delaware, USA. FAU - Stockbower, Grace AU - Stockbower G AD - Carelon Research, Wilmington, Delaware, USA. FAU - Grabner, Michael AU - Grabner M AUID- ORCID: 0000-0002-6521-1007 AD - Carelon Research, Wilmington, Delaware, USA. FAU - Benneyworth, Brian D AU - Benneyworth BD AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Observational Study DEP - 20250404 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - United States/epidemiology MH - *Glycemic Control/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/analysis MH - Adult MH - *Tirzepatide/therapeutic use MH - Aged MH - Blood Glucose/drug effects MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GIP OT - GLP-1 OT - effectiveness OT - observational study OT - real-world evidence OT - type 2 diabetes EDAT- 2025/04/04 06:26 MHDA- 2025/05/03 22:25 CRDT- 2025/04/04 03:43 PHST- 2025/03/18 00:00 [revised] PHST- 2024/10/24 00:00 [received] PHST- 2025/03/18 00:00 [accepted] PHST- 2025/05/03 22:25 [medline] PHST- 2025/04/04 06:26 [pubmed] PHST- 2025/04/04 03:43 [entrez] AID - 10.1111/dom.16372 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3453-3463. doi: 10.1111/dom.16372. Epub 2025 Apr 4. PMID- 40181368 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20250728 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 23 IP - 1 DP - 2025 Apr 3 TI - Glucagon-like Peptide-1 receptor agonists for obstructive sleep apnea in patients with obesity and type 2 diabetes mellitus: a systematic review and meta-analysis. PG - 389 LID - 10.1186/s12967-025-06302-y [doi] LID - 389 AB - The systematic review was registered on the PROSPERO website (CRD42024558287). Our objective is to systematically summarise the clinical evidence of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for obstructive sleep apnea (OSA) in patients with Obesity or/and type 2 Diabetes Mellitus (T2DM). This analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. 10 databases and registers Web of Science, Scopus, PubMed, APA PsycInfo, Embase, Ovid, Cochrane Library, CINAHL, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) were retrieved from the establishment to July 14, 2024 for related randomized controlled trials (RCT) and non-RCTs. Data were extracted by two investigators separately, and only the RCTs were included in the quantitative synthesis. The outcome was operated by Review Manager 5.4 and Stata 15.0. Ten studies containing eight RCTs and two non-RCTs were included. The efficacy of the GLP-1 RA group in reducing apnea-hypopnea index (AHI) was superior to that of the control group in patients with T2DM (MD = -5.68, 95%CI [-7.97, -3.38], P < 0.00001, I(2) = 0%). GLP-1 RAs also possessed a tendency to reduce AHI in patients with obesity but more evidence is needed to support the findings due to the inconsistency. In consideration of the enhanced metabolic parameters observed with GLP-1 RAs, they may be recommended as useful hypoglycaemic medication for the management of T2DM with OSA. Patients with obesity and OSA may consider GLP-1 RA as a potential treatment option if the adverse events are deemed tolerable. CI - (c) 2025. The Author(s). FAU - Yang, Ruifeng AU - Yang R AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhang, Lindong AU - Zhang L AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Guo, Jiangfan AU - Guo J AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. AD - The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China. FAU - Wang, Ning AU - Wang N AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhang, Qiue AU - Zhang Q AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Qi, Zhiwei AU - Qi Z AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Wu, Lili AU - Wu L AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. FAU - Qin, Lingling AU - Qin L AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. AD - Department of Science and Technology, Beijing University of Chinese Medicine, Beijing, China. FAU - Liu, Tonghua AU - Liu T AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China. thliu@vip.163.com. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, China. thliu@vip.163.com. LA - eng GR - 2015B01022/International Cooperation Research Center for the Prevention and Treatment of Diabetes by Traditional Chinese Medicine/ GR - 90020165120003/Traditional Chinese Medicine intervention of metabolic diseases research project/ GR - 2024-JYB-KYPT-002/Key Laboratory Health Cultivation of the Ministry of Education Preservation/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250403 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Sleep Apnea, Obstructive/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications/drug therapy MH - Publication Bias MH - Randomized Controlled Trials as Topic PMC - PMC11967144 OTO - NOTNLM OT - Glucagon-like Peptide-1 receptor agonists OT - Obesity OT - Obstructive sleep apnea OT - Sleep-disordered breathing parameters OT - Type 2 diabetes mellitus COIS- Declarations. Ethical statement: Not applicable. Conflict of interest: The named authors have no conflicts of interest, financial or otherwise. EDAT- 2025/04/04 06:25 MHDA- 2025/04/04 06:26 PMCR- 2025/04/03 CRDT- 2025/04/04 00:57 PHST- 2024/12/31 00:00 [received] PHST- 2025/02/23 00:00 [accepted] PHST- 2025/04/04 06:26 [medline] PHST- 2025/04/04 06:25 [pubmed] PHST- 2025/04/04 00:57 [entrez] PHST- 2025/04/03 00:00 [pmc-release] AID - 10.1186/s12967-025-06302-y [pii] AID - 6302 [pii] AID - 10.1186/s12967-025-06302-y [doi] PST - epublish SO - J Transl Med. 2025 Apr 3;23(1):389. doi: 10.1186/s12967-025-06302-y. PMID- 40181228 OWN - NLM STAT- MEDLINE DCOM- 20250604 LR - 20260620 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 26 IP - 7 DP - 2025 Jul TI - How do glucagon-like Peptide-1 receptor agonists affect measures of muscle mass in individuals with, and without, type 2 diabetes: A systematic review and meta-analysis. PG - e13916 LID - 10.1111/obr.13916 [doi] LID - e13916 AB - Glucagon-like peptide-1 receptor agonists (GLP1RAs) are used for the management of type 2 diabetes (T2DM) and obesity. GLP1RAs induce significant weight loss but concerns have been raised regarding the associated effects on muscle mass (MM). We therefore conducted a systematic review and meta-analysis assessing the effects of GLP1RAs on various measures of MM in individuals living with overweight or obesity, with and without T2DM. Comprehensive search of Medline, Pubmed, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. Studies involving cohorts with a mean age over 40 years and a mean body mass index over 25 kg.m(-2) were included. The primary outcome was any measure used to estimate MM, whilst fat mass (FM) and total body weight were included as secondary outcomes. Thirty-eight publications, involving 1735 participants, were included in the review. Separate meta-analyses were performed for studies involving participants with T2DM and individuals without T2DM (non-DM). In individuals with T2DM, GLP1RAs induced a non-significant mean reduction in MM measures (-0.74 kg, 95% CI: -1.61, 0.14, p = 0.10), despite significantly reducing FM (-3.18 kg, 95% CI: -4.09, -2.28, p < 0.0001). In the non-DM analysis, a significant mean reduction in MM measures was observed (-1.41 kg, 95% CI: -2.12, -0.71, p = 0.0001), however, this was significantly less than the reduction in FM (-6.02 kg, 95% CI: -7.53, -4.50, p < 0.0001). In both populations, the reduction in measures of MM accounted for less than 20% of the total weight reduction. These findings provide some clarity to clinicians that use GLP1RAs to manage individuals with T2DM and/or obesity, however, further more detailed analysis of the impact of these medications on functional skeletal muscle is required. CI - (c) 2025 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Anyiam, Oluwaseun AU - Anyiam O AUID- ORCID: 0000-0003-2425-2299 AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, UK. AD - Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK. FAU - Ardavani, Arash AU - Ardavani A AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, UK. AD - Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK. FAU - Rashid, Rushdina Sofia Abdul AU - Rashid RSA AD - Department of Endocrinology and Diabetes, United Lincolnshire Hospitals NHS Trust, Lincoln, UK. FAU - Panesar, Avinash AU - Panesar A AD - Derbyshire Healthcare NHS Foundation Trust, Derby, UK. FAU - Idris, Iskandar AU - Idris I AUID- ORCID: 0000-0002-7548-8288 AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, UK. AD - Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250403 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Muscle, Skeletal/drug effects MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - Weight Loss/drug effects PMC - PMC12137041 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - muscle mass OT - obesity OT - type 2 diabetes COIS- The authors have no conflicts of interest to disclose in relation to this work. EDAT- 2025/04/04 06:26 MHDA- 2025/06/05 00:28 PMCR- 2025/06/05 CRDT- 2025/04/04 00:32 PHST- 2025/01/16 00:00 [revised] PHST- 2024/06/27 00:00 [received] PHST- 2025/02/07 00:00 [accepted] PHST- 2025/06/05 00:28 [medline] PHST- 2025/04/04 06:26 [pubmed] PHST- 2025/04/04 00:32 [entrez] PHST- 2025/06/05 00:00 [pmc-release] AID - OBR13916 [pii] AID - 10.1111/obr.13916 [doi] PST - ppublish SO - Obes Rev. 2025 Jul;26(7):e13916. doi: 10.1111/obr.13916. Epub 2025 Apr 3. PMID- 40175127 OWN - NLM STAT- MEDLINE DCOM- 20250702 LR - 20250717 IS - 1348-4540 (Electronic) IS - 0918-8959 (Print) IS - 0918-8959 (Linking) VI - 72 IP - 7 DP - 2025 Jul 1 TI - Physiology and clinical applications of GIP. PG - 751-764 LID - 10.1507/endocrj.EJ25-0087 [doi] AB - Glucose-dependent insulinotropic polypeptide (GIP) is secreted by enteroendocrine K cells, primarily located in the upper small intestine, in response to food intake and plays a significant role in the postprandial regulation of nutrient metabolism. Although the importance of GIP in metabolic regulation has long been recognized, progress in developing GIP as a therapeutic target has been limited. However, the GIP/GIP receptor (GIPR) axis has garnered increasing attention in recent years. Emerging evidence suggests that dual GIP/GLP-1 receptor agonists and triple GIP/GLP-1/glucagon receptor agonists provide beneficial metabolic effects in individuals with type 2 diabetes and obesity. In this review, we outline the physiological roles of GIP, detailing the mechanisms of GIP secretion from K cells in response to macronutrients, its actions on key target organs involved in metabolic regulation, and ongoing developments in its therapeutic applications. FAU - Yamane, Shunsuke AU - Yamane S AD - Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. FAU - Harada, Norio AU - Harada N AUID- ORCID: 0000-0001-8720-1013 AD - Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. AD - Department of Endocrinology and Metabolism, School of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Inagaki, Nobuya AU - Inagaki N AUID- ORCID: 0000-0001-8261-2593 AD - Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. AD - Medical Research Institute KITANO HOSPITAL, P.I.I.F. Tazuke-Kofukai, Osaka 530-8480, Japan. LA - eng PT - Journal Article PT - Review DEP - 20250403 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/physiology/metabolism/therapeutic use/pharmacology MH - Receptors, Gastrointestinal Hormone/agonists/metabolism MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Animals MH - Obesity/metabolism/drug therapy MH - *Enteroendocrine Cells/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12260194 OTO - NOTNLM OT - Diabetes OT - Glucose-dependent insulinotropic polypeptide (GIP) OT - Incretin OT - Obesity COIS- N.I. received clinical commissioned/joint research grant from asken, scholarship grant from Sumitomo Pharma, Mitsubishi Tanabe Pharma and Nippon Boehringer Ingelheim, and honoraria for lectures from Novo Nordisk Pharma, Sumitomo Pharma, Eli Lilly Japan and Mitsubishi Tanabe Pharma. N.H. received honoraria for lectures from Novo Nordisk Pharma, Mitsubishi Tanabe Pharma. S.Y. has no conflict of interest. EDAT- 2025/04/03 00:25 MHDA- 2025/07/03 00:27 PMCR- 2025/04/03 CRDT- 2025/04/02 21:33 PHST- 2025/07/03 00:27 [medline] PHST- 2025/04/03 00:25 [pubmed] PHST- 2025/04/02 21:33 [entrez] PHST- 2025/04/03 00:00 [pmc-release] AID - 10.1507/endocrj.EJ25-0087 [doi] PST - ppublish SO - Endocr J. 2025 Jul 1;72(7):751-764. doi: 10.1507/endocrj.EJ25-0087. Epub 2025 Apr 3. PMID- 40174283 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20250507 IS - 1095-9157 (Electronic) IS - 0896-8411 (Linking) VI - 153 DP - 2025 May TI - Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases. PG - 103414 LID - S0896-8411(25)00059-9 [pii] LID - 10.1016/j.jaut.2025.103414 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging with therapeutic agents for the treatment of two of the most prevalent metabolic disorders: diabetes and obesity. However, the causal relationship between GLP-1R agonists and autoimmune diseases is still unclear. METHODS: The available cis-eQTLs for drug target genes (GLP-1Rs) were used as proxies for exposure to GLP-1R agonists. Obesity and type 2 diabetes mellitus (T2DM) were used as positive controls to ensure the reliability of the genetic instrument. Mendelian randomization (MR) was performed to reveal the causal association of genetic proxy GLP-1R agonists with 18 autoimmune diseases from the IEU OpenGwas database and FinnGen database. Finally, the results of the two databases were analyzed via meta-analysis. RESULTS: A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instruments. Positive control analysis revealed that GLP-1R agonists were significantly associated with obesity (OR = 0.826, p = 0.021) and T2DM (OR = 0.886, p < 0.001), which is consistent with the meta-analysis. MR analysis revealed that increased expression of the GLP-1R gene has a significant protective effect on type 1 diabetes mellitus (T1DM), hypothyroidism, primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the MR analysis suggested that increased expression of GLP-1R agonists may increase the risk of Graves' disease (GD), ulcerative colitis (UC) and psoriasis. Our findings were consistent with those of the meta-analysis. CONCLUSIONS: This study provides new insights into potential adjuvant treatments for autoimmune diseases from the perspective of genetic variation and provides evidence for the safety of GLP-1R agonists. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Yang, Yuanyuan AU - Yang Y AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Liu, Wencong AU - Liu W AD - Department of Ultrasonics, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Zhang, Zechang AU - Zhang Z AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Zhang, Yujia AU - Zhang Y AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Wang, Xuebin AU - Wang X AD - College of Basic Medicine, Hebei Medical University, Shijiazhuang, China. FAU - Wang, Jing AU - Wang J AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Cai, Huaifang AU - Cai H AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Liu, Yichan AU - Liu Y AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Meng, Ran AU - Meng R AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Fu, Yuqi AU - Fu Y AD - School of Public Health, Hebei Medical University, Shijiazhuang, China. FAU - Luo, Hongmin AU - Luo H AD - Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, China. Electronic address: hongye-20@163.com. FAU - Yang, Lei AU - Yang L AD - Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, China. Electronic address: yanglei1127@hebmu.edu.cn. FAU - Liu, Wenxuan AU - Liu W AD - Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, China. Electronic address: 18300888@hebmu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250401 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Autoimmune Diseases/drug therapy/genetics/etiology MH - Polymorphism, Single Nucleotide MH - Diabetes Mellitus, Type 2/drug therapy/genetics MH - Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Obesity/drug therapy/genetics MH - Genetic Predisposition to Disease OTO - NOTNLM OT - Autoimmune diseases OT - Drug target OT - GLP-1R agonists OT - Mendelian randomization COIS- Declaration of competing interest No potential conflicts of interest relevant to this article were reported. EDAT- 2025/04/03 00:25 MHDA- 2025/05/05 06:27 CRDT- 2025/04/02 18:01 PHST- 2024/12/10 00:00 [received] PHST- 2025/03/20 00:00 [revised] PHST- 2025/03/27 00:00 [accepted] PHST- 2025/05/05 06:27 [medline] PHST- 2025/04/03 00:25 [pubmed] PHST- 2025/04/02 18:01 [entrez] AID - S0896-8411(25)00059-9 [pii] AID - 10.1016/j.jaut.2025.103414 [doi] PST - ppublish SO - J Autoimmun. 2025 May;153:103414. doi: 10.1016/j.jaut.2025.103414. Epub 2025 Apr 1. PMID- 40173095 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20250521 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 6 DP - 2025 Jun 1 TI - Risk of Urogenital Infections in People With Type 2 Diabetes Initiating SGLT2is Versus GLP-1RAs in Routine Clinical Care: A Danish Cohort Study. PG - 945-954 LID - 10.2337/dc24-2169 [doi] AB - OBJECTIVE: Anticipated risks of urinary tract infections (UTI) and genital tract infections (GTI) associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) may prevent their use in clinical practice. We investigated whether initiation of SGLT2is, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs), was associated with an elevated risk of UTI and GTI in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this cohort study emulating a target trial, we included all adult metformin users initiating SGLT2is or GLP-1RAs in Denmark in 2016-2021 and used inverse-probability of treatment (IPT) weighting to balance potential confounders. We estimated IPT-weighted risk and risk ratios of community- or hospital-treated UTI and GTI, performing both intention-to-treat and on-treatment analyses. RESULTS: This study included 52,414 SGLT2i initiators and 27,023 GLP-1RA initiators with a median follow-up of 2.9 to 3.9 years. The estimated risks of UTI within the first year were nearly identical: 10.0% for SGLT2is and 10.2% for GLP-1RAs in intention-to-treat analyses corresponding to a risk ratio of 0.98 (95% CI 0.94, 1.03). For GTI, the 1-year risks were elevated under SGLT2i therapy at 2.0% vs. 0.7% (risk ratio 2.95 [95% CI 2.52, 3.44]). During the 5-year follow-up, the relative UTI risk remained almost constant (0.96 [95% CI 0.94, 0.99]) whereas the GTI risk ratio with SGLT2is decreased to 1.64 (95% CI 1.49, 1.80). CONCLUSIONS: In routine clinical care, SGLT2i initiation is not associated with increased risk of UTI compared with GLP-1RA initiation. However, early GTI risk is up to threefold larger in SGLT2i users. CI - (c) 2025 by the American Diabetes Association. FAU - Ljungberg, Christine AU - Ljungberg C AUID- ORCID: 0009-0004-7226-2488 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Kristensen, Frederik Pagh Bredahl AU - Kristensen FPB AUID- ORCID: 0000-0001-5311-8924 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Dalager-Pedersen, Michael AU - Dalager-Pedersen M AD - Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Vandenbroucke-Grauls, Christina AU - Vandenbroucke-Grauls C AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. AD - Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Amsterdam, the Netherlands. FAU - Sorensen, Henrik Toft AU - Sorensen HT AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Norgaard, Mette AU - Norgaard M AUID- ORCID: 0000-0001-6110-5891 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Thomsen, Reimar Wernich AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. LA - eng PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Denmark/epidemiology MH - Female MH - Male MH - Middle Aged MH - *Urinary Tract Infections/epidemiology/chemically induced MH - Cohort Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Reproductive Tract Infections/epidemiology MH - Adult EDAT- 2025/04/02 18:24 MHDA- 2025/05/21 18:29 CRDT- 2025/04/02 13:13 PHST- 2024/10/03 00:00 [received] PHST- 2025/03/09 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/04/02 18:24 [pubmed] PHST- 2025/04/02 13:13 [entrez] AID - 158055 [pii] AID - 10.2337/dc24-2169 [doi] PST - ppublish SO - Diabetes Care. 2025 Jun 1;48(6):945-954. doi: 10.2337/dc24-2169. PMID- 40169145 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 405 IP - 10489 DP - 2025 May 3 TI - Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. PG - 1580-1593 LID - S0140-6736(25)00509-4 [pii] LID - 10.1016/S0140-6736(25)00509-4 [doi] AB - BACKGROUND: Peripheral artery disease is a highly morbid type of atherosclerotic vascular disease involving the legs and is estimated to affect over 230 million individuals globally. Few therapies improve functional capacity and health-related quality of life in people with lower limb peripheral artery disease. We aimed to evaluate whether semaglutide improves function as measured by walking ability as well as symptoms, quality of life, and outcomes in people with peripheral artery disease and type 2 diabetes. METHODS: STRIDE was a double-blind, randomised, placebo-controlled trial done at 112 outpatient clinical trial sites in 20 countries in North America, Asia, and Europe. Participants were aged 18 years and older, with type 2 diabetes and peripheral artery disease with intermittent claudication (Fontaine stage IIa, able to walk >200 m) and an ankle-brachial index of less than or equal to 0.90 or toe-brachial index of less than or equal to 0.70. Participants were randomly assigned (1:1) using an interactive web response system to receive subcutaneous semaglutide 1.0 mg once per week for 52 weeks or placebo. The primary endpoint was the ratio to baseline of the maximum walking distance at week 52 measured on a constant load treadmill in the full analysis set. Safety was evaluated in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT04560998 and is now completed. FINDINGS: From Oct 1, 2020, to July 12, 2024, 1363 patients were screened for eligibility, of whom 792 were randomly assigned to semaglutide (n=396) or placebo (n=396). 195 (25%) participants were female and 597 (75%) were male. Median age was 68.0 years (IQR 61.0-73.0). The estimated median ratio to baseline in maximum walking distance at week 52 was significantly greater in the semaglutide group than the placebo group (1.21 [IQR 0.95-1.55] vs 1.08 [0.86-1.36]; estimated treatment ratio 1.13 [95% CI 1.06-1.21]; p=0.0004). Six serious adverse events in five (1%) participants in the semaglutide group and nine serious adverse events in six (2%) participants in the placebo group were possibly or probably treatment related, with the most frequent being serious gastrointestinal events (two events reports by two [1%] in the semaglutide group and five events reported by three [1%] in the placebo group). There were no treatment-related deaths. INTERPRETATION: Semaglutide increased walking distance in patients with symptomatic peripheral artery disease and type 2 diabetes. Research implications include the need for future studies to further elucidate mechanisms of benefit and to assess the efficacy and safety in patients with peripheral artery disease who do not have type 2 diabetes. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: marc.bonaca@cpcmed.org. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Department of Vascular Surgery, Lillebaelt Hospital, Kolding, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Ramesh, Chethana Kalmady AU - Ramesh CK AD - Novo Nordisk India, Bangalore, India. FAU - Rasouli, Neda AU - Rasouli N AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. FAU - Sourij, Harald AU - Sourij H AD - Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Videmark, Alex AU - Videmark A AD - Novo Nordisk, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. CN - STRIDE Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT04560998 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250329 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2025 May 3;405(10489):1556-1557. doi: 10.1016/S0140-6736(25)00574-4. PMID: 40169146 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Ankle Brachial Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - Double-Blind Method MH - Intermittent Claudication/drug therapy/etiology MH - *Peripheral Arterial Disease/drug therapy/complications/physiopathology MH - Quality of Life MH - Treatment Outcome MH - *Walking MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests MPB is the Executive Director of the Colorado Prevention Center, a non-profit academic research organisation affiliated with the University of Colorado, that receives or has received research grant or consulting funding between August, 2021 and the present from: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, Array BioPharma, AstraZeneca and Affiliates, Atentiv, Audentes Therapeutics, Bayer and Affiliates, Bristol Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, Epizon Pharma, Esperion Therapeutics, Everly Well, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, Janssen and Affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Merck and Affiliates, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanofi-Aventis Group, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, VarmX, and Virta Health Corporation. A-MC is an employee of and owns shares in Novo Nordisk. KH has received payment or honoraria, along with travel support, to give a presentation at a workshop organised by LeMaitre. BL has received consulting fees, payment, or honoraria from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has received travel support from Novo Nordisk, with unpaid roles as a National Leader for the Novo Nordisk ESSENCE trial, a National Leader for the Eli Lilly Triumph-Outcome Study, and an advisor for an advisory board for the Austrian Obesity Society. JN has received payment or honoraria from Novo Nordisk; has received travel support from Philips Medical and Abbott; has served on advisory boards for AstraZeneca, Novo Nordisk, and iThera Medical; and has a research grant from the Swedish Heart and Lung Foundation 2021-26, with unpaid roles as President of the Swedish Society for Vascular Surgery and the Swedish Councillor for the European Society for Vascular Surgery 2020-23. CKR is an employee of and owns shares in Novo Nordisk. NR has served on advisory boards for Eli Lilly and Novo Nordisk, and has received research grants from Eli Lilly, Novo Nordisk, and Soma Scan. HS has received payment or honoraria from Amarin, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, and Novo Nordisk; has received travel support from Boehringer Ingelheim, Daiichi Sankyo, and Novo Nordisk; and has served on advisory boards for Eli Lilly and Novo Nordisk, with unpaid roles as a board member of the Austrian Diabetes Association. AV is an employee of Novo Nordisk. SV has received payment or honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, Sanofi, and Sun Pharmaceuticals; has served on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Sanofi. EDAT- 2025/04/02 00:25 MHDA- 2025/05/04 15:35 CRDT- 2025/04/01 19:53 PHST- 2025/02/27 00:00 [received] PHST- 2025/03/13 00:00 [revised] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/05/04 15:35 [medline] PHST- 2025/04/02 00:25 [pubmed] PHST- 2025/04/01 19:53 [entrez] AID - S0140-6736(25)00509-4 [pii] AID - 10.1016/S0140-6736(25)00509-4 [doi] PST - ppublish SO - Lancet. 2025 May 3;405(10489):1580-1593. doi: 10.1016/S0140-6736(25)00509-4. Epub 2025 Mar 29. PMID- 40164842 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20261010 IS - 2731-6866 (Electronic) IS - 2731-6858 (Linking) VI - 74 IP - 6 DP - 2025 Jun TI - [Effects of "new" antidiabetic drugs on management of anesthesia]. PG - 341-349 LID - 10.1007/s00101-025-01521-w [doi] AB - Around 9 million people live with diabetes mellitus (DM) in Germany. Around 500,000 new cases are documented every year. In addition, it must be assumed that there are at least 2 million unreported cases. The proportion of patients with type 2 DM is by far the highest and it is currently estimated that around 340,000 adults and 32,000 children are affected by type 1 DM [1]. People with diabetes have an increased mortality rate; however, this has decreased in recent years, particularly due to a reduction in cardiovascular mortality. "New" antidiabetic drugs have certainly played a relevant role in this. Various studies have shown that sodium-glucose Cotransporter 2 inhibitors (SGLT2 inhibitors) in particular but also glucagon-like peptide‑1 receptor agonists (GLP1-RA), have a significant benefit in patients with heart failure [2-5]. Surprisingly, this effect was also detectable in patients without DM [6]. Thus, the group of people who are treated with an SGLT2 inhibitor or a GLP1-RA has been expanded to include people who suffer from heart failure not associated with diabetes. This applies both to patients with reduced left ventricular systolic function (heart failure with reduced ejection fraction, HFrEF) and with preserved or mildly reduced systolic function (heart failure with preserved/mildly reduced ejection fraction, HFpEF/HFmrEF) [7]. In Germany heart failure is the most common diagnosis for hospitalization (40.6 cases/10,000 insurance years) and diseases of the cardiovascular system are the most common cause of death [8]. The increased risk of morbidity and mortality is also reflected in the perioperative setting.In addition to the risks posed by DM itself or associated diseases, the treatment with antidiabetic drugs can also lead to perioperative complications. This article focuses on the drug-related risks of the "new" antidiabetic drugs and draws conclusions regarding the management of anesthesia. The potentially life-threatening euglycemic diabetic ketoacidosis (eDKA) can be a perioperative side effect of SGLT2 inhibitors; however, the diagnosis is associated with hurdles. The GLP1-RAs are also increasingly being prescribed as they reduce cardiovascular risk and make weight loss much easier. GLP1-RAs delay gastric emptying, which potentially results in an increased risk of aspiration. In particular, if other risk factors for aspiration exist, patients should not be considered fasting, if the recommended break in GLP1‑RA intake has not been followed. CI - (c) 2025. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature. FAU - Rupprecht, Bernd AU - Rupprecht B AD - Klinik fur Anasthesiologie und Operative Intensivmedizin, Universitatsklinikum Augsburg, Stenglinstrasse 2, 86156, Augsburg, Deutschland. bernd.rupprecht@uk-augsburg.de. FAU - Dumps, Christian AU - Dumps C AD - Klinik fur Anasthesiologie und Operative Intensivmedizin, Universitatsklinikum Augsburg, Stenglinstrasse 2, 86156, Augsburg, Deutschland. LA - ger PT - English Abstract PT - Journal Article PT - Review TT - Auswirkungen "neuer" Antidiabetika auf das Anasthesiemanagement. DEP - 20250331 PL - Germany TA - Anaesthesiologie JT - Die Anaesthesiologie JID - 9918384886806676 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Anesthesia/methods MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Germany/epidemiology MH - Heart Failure OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Euglycemic diabetic ketoacidosis OT - Glucagon-like peptide‑1 receptor agonist OT - Perioperative management OT - Sodium-glucose Cotransporter 2 inhibitor COIS- Einhaltung ethischer Richtlinien. Interessenkonflikt: B. Rupprecht und C. Dumps geben an, dass kein Interessenkonflikt besteht. Fur diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgefuhrt. Fur die aufgefuhrten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. EDAT- 2025/04/01 00:27 MHDA- 2025/06/13 12:32 CRDT- 2025/03/31 23:29 PHST- 2025/02/13 00:00 [accepted] PHST- 2025/06/13 12:32 [medline] PHST- 2025/04/01 00:27 [pubmed] PHST- 2025/03/31 23:29 [entrez] AID - 10.1007/s00101-025-01521-w [pii] AID - 10.1007/s00101-025-01521-w [doi] PST - ppublish SO - Anaesthesiologie. 2025 Jun;74(6):341-349. doi: 10.1007/s00101-025-01521-w. Epub 2025 Mar 31. PMID- 40163884 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20260813 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 178 IP - 5_Supplement DP - 2025 May TI - Endocrinology: What You May Have Missed in 2024. PG - S20-S38 LID - 10.7326/ANNALS-25-00990 [doi] AB - During 2024, there were many practice-changing innovations in the field of endocrinology, particularly related to the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs). From the substantial new evidence published in 2024, 10 studies are highlighted that offer critical information for clinicians who manage or comanage patients with endocrine disorders including prediabetes, diabetes, obesity, and hyperparathyroidism. Two of the 10 articles are focused on use of GLP-1RAs in multiple clinical settings not studied in the original GLP-1RA trials, including after bariatric surgery and before endoscopy. Two additional studies focused on GLP-1RA explore the risk for thyroid cancer in patients prescribed GLP-1RA and the effect of a GLP-1RA on chronic kidney disease in patients with type 2 diabetes. Three articles investigate opportunities for deintensification of insulin frequency or an alternate method of insulin delivery in patients with type 2 diabetes. One article explores the cardiometabolic effects of intermittent fasting in persons with prediabetes and type 2 diabetes. The last 2 articles explore the incidence of diabetes after SARS-CoV-2 infection and the skeletal effects of parathyroidectomy as a treatment of hyperparathyroidism. The results of each study have a direct effect on the delivery of care for patients with prediabetes, type 2 diabetes, and hyperparathyroidism. FAU - Aman, Mohamed AU - Aman M AD - McMaster University, Hamilton, Ontario, Canada (M.A.). FAU - Jeevananthan, Athavi AU - Jeevananthan A AD - Duke University, Durham, North Carolina (A.J., M.M.-C., N.N., B.C.B.). FAU - Martinez-Cruz, Maria AU - Martinez-Cruz M AD - Duke University, Durham, North Carolina (A.J., M.M.-C., N.N., B.C.B.). FAU - Namasingh, Neesha AU - Namasingh N AD - Duke University, Durham, North Carolina (A.J., M.M.-C., N.N., B.C.B.). FAU - Batch, Bryan C AU - Batch BC AD - Duke University, Durham, North Carolina (A.J., M.M.-C., N.N., B.C.B.). LA - eng GR - T32 DK007012/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20250401 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - COVID-19/complications MH - Diabetes Mellitus, Type 2/drug therapy MH - *Endocrinology/trends MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prediabetic State/drug therapy MH - *Endocrine System Diseases/drug therapy/therapy MH - Hyperparathyroidism/drug therapy PMC - PMC13322357 MID - NIHMS2178664 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/03/31 21:17 MHDA- 2025/05/19 18:34 PMCR- 2026/07/01 CRDT- 2025/03/31 17:03 PHST- 2025/05/19 18:34 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 17:03 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 10.7326/ANNALS-25-00990 [doi] PST - ppublish SO - Ann Intern Med. 2025 May;178(5_Supplement):S20-S38. doi: 10.7326/ANNALS-25-00990. Epub 2025 Apr 1. PMID- 40163257 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20261010 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 30 IP - 4 DP - 2025 Jul TI - Semaglutide in heart failure and atherosclerotic cardiovascular disease: the current state-of-the-art. PG - 801-816 LID - 10.1007/s10741-025-10506-1 [doi] AB - Cardiovascular disease mortality rates, which had steadily declined over decades, are now plateauing or reversing due to the global rise in type 2 diabetes mellitus (T2DM) and obesity. These cardiometabolic conditions contribute significantly to atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease. Among emerging pharmacological treatments, glucagon-like peptide-1 receptor agonists, particularly semaglutide, have shown benefits beyond diabetes and obesity management, including cardioprotective and renoprotective effects. This state-of-the-art review comprehensively analyzes current evidence from clinical trials, identifies critical insights, and outlines research directions regarding semaglutide use in HF, ASCVD, and diabetic nephropathy. In ASCVD, semaglutide has demonstrated significant reductions in major adverse cardiovascular events, supported by findings from meta-analyses of trials in patients with T2DM and the SELECT trial for patients without T2DM. In a prespecified analysis of the SELECT trial, semaglutide demonstrated significant reductions in cardiovascular mortality and HF hospitalizations for patients with HF and ASCVD. In HF with preserved ejection fraction and mildly reduced ejection fraction, semaglutide improved symptoms, physical function, natriuretic peptide levels, echocardiographic parameters, and HF hospitalizations, as shown in the STEP-HFpEF program and a pooled analysis of trials. Furthermore, evidence from the FLOW trial underscores semaglutide's renal and cardiovascular benefits in diabetic nephropathy, irrespective of body mass index. While these findings suggest semaglutide's efficacy in cardiorenal diseases, gaps in evidence remain, including the need for event-driven trials in HF populations without ASCVD and irrespective of obesity. Future research should address these gaps, which could potentially update guideline recommendations. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Theodorakis, Nikolaos AU - Theodorakis N AD - Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. m.nikolaou@flemig-hospital.gr. AD - School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527, Athens, Greece. m.nikolaou@flemig-hospital.gr. FAU - Kreouzi, Magdalini AU - Kreouzi M AD - Department of Internal Medicine, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. FAU - Nikolaou, Maria AU - Nikolaou M AD - Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. LA - eng PT - Journal Article PT - Review DEP - 20250331 PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Heart Failure/drug therapy/physiopathology MH - *Atherosclerosis/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Coronary artery disease OT - Diabetic nephropathy OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure OT - Semaglutide COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/03/31 21:17 MHDA- 2025/06/13 12:32 CRDT- 2025/03/31 11:56 PHST- 2025/03/06 00:00 [accepted] PHST- 2025/06/13 12:32 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 11:56 [entrez] AID - 10.1007/s10741-025-10506-1 [pii] AID - 10.1007/s10741-025-10506-1 [doi] PST - ppublish SO - Heart Fail Rev. 2025 Jul;30(4):801-816. doi: 10.1007/s10741-025-10506-1. Epub 2025 Mar 31. PMID- 40163115 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20250804 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 3 DP - 2025 Mar 3 TI - Combination of Glucagon-Like Peptide 1 Receptor Agonist and Thiazolidinedione for Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes. PG - e252577 LID - 10.1001/jamanetworkopen.2025.2577 [doi] LID - e252577 AB - IMPORTANCE: Combination therapy has emerged as a critical area of interest in managing diabetes; however, the association of combination therapy with a glucagon-like peptide 1 receptor agonist (GLP-1RA) and thiazolidinedione and the risk of diabetes-related complications remains incompletely understood. OBJECTIVE: To compare the hazards of cardiovascular-related morbidities and mortality among patients with type 2 diabetes receiving combination therapy with a GLP-1RA plus thiazolidinedione, those receiving monotherapy with a GLP-1RA or thiazolidinedione, and nonusers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used nationwide data obtained from Taiwan's National Health Insurance Research Database. Patients older than 20 years with type 2 diabetes who received a GLP-1RA or thiazolidinedione between January 1, 2011, and December 31, 2020, were enrolled. The data analysis was performed from May 1 to May 22, 2024. MAIN OUTCOMES AND MEASURES: This study investigated the hazards of all-cause mortality, major adverse cardiovascular events, cardiovascular mortality, cardiovascular complications, and hypoglycemia in GLP-1RA and thiazolidinedione combination or monotherapy users compared with nonusers. RESULTS: A total of 110 411 patients were enrolled (mean [SD] age, 58.3 [11.9] years; 45.5% female; 47 526 GLP-1RA users, 32 203 thiazolidinedione users, and 30 682 GLP-1RA plus thiazolidinedione users), along with a propensity score-matched group of patients who did not use a GLP-1RA or thiazolidinedione, for a total cohort size of 220 822. Patients receiving GLP-1RA and thiazolidinedione dual therapy had significantly lower risk of all-cause mortality (adjusted hazard ratio [AHR], 0.20; 95% CI, 0.19-0.21; P < .001), major adverse cardiovascular events (AHR, 0.85; 95% CI, 0.82-0.89; P < .001), and cardiovascular mortality (AHR, 0.20; 95% CI, 0.18-0.23; P < .001) than those who did not receive a GLP-1RA or thiazolidinedione. However, a higher risk of hypoglycemia was seen in those receiving combination therapy (AHR, 1.61; 95% CI, 1.43-1.82; P < .001) and those receiving thiazolidinedione monotherapy (AHR, 1.69; 95% CI, 1.51-1.90; P < .001) compared with nonuse. This risk was mitigated with prolonged use. Thiazolidinedione monotherapy users had a significantly higher risk of all-cause mortality (AHR, 1.29; 95% CI, 1.24-1.34; P < .001) and cardiovascular mortality (AHR, 1.28; 95% CI, 1.13-1.45; P < .001) than GLP-1RA monotherapy users. Several sensitivity analyses further supported the robustness of these findings. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with type 2 diabetes, combination therapy with a GLP-1RA plus thiazolidinedione was associated with significantly lower hazards of mortality and cardiovascular complications compared with nonuse. The findings suggest that GLP-1RAs may mitigate the adverse cardiovascular effects of thiazolidinedione. FAU - Li, Jing-Xing AU - Li JX AD - Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Hsu, Tzu-Ju AU - Hsu TJ AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Lin, Heng-Jun AU - Lin HJ AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Hsu, Shu-Bai AU - Hsu SB AD - Department of Nursing, China Medical University Hospital, Taichung, Taiwan. FAU - Lu, Chiung-Ray AU - Lu CR AD - School of Medicine, China Medical University, Taichung, Taiwan. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Chung, Wei-Hsin AU - Chung WH AD - Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Liang, Shinn-Jye AU - Liang SJ AD - Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. AD - School of Chinese Medicine, China Medical University, Taichung, Taiwan. FAU - Tsai, Fuu-Jen AU - Tsai FJ AD - School of Chinese Medicine, China Medical University, Taichung, Taiwan. AD - Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. AD - Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan. AD - Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. FAU - Chang, Kuan-Cheng AU - Chang KC AD - Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. AD - Cardiovascular Research Laboratory, China Medical University Hospital, Taichung, Taiwan. AD - Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250303 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Thiazolidinediones) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - JAMA Netw Open. 2025 Jun 2;8(6):e2519672. doi: 10.1001/jamanetworkopen.2025.19672. PMID: 40459899 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Thiazolidinediones/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/mortality/epidemiology MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Taiwan/epidemiology PMC - PMC11959443 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/03/31 21:17 MHDA- 2025/03/31 21:18 PMCR- 2025/03/31 CRDT- 2025/03/31 11:52 PHST- 2025/03/31 21:18 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 11:52 [entrez] PHST- 2025/03/31 00:00 [pmc-release] AID - 2831946 [pii] AID - zoi250145 [pii] AID - 10.1001/jamanetworkopen.2025.2577 [doi] PST - epublish SO - JAMA Netw Open. 2025 Mar 3;8(3):e252577. doi: 10.1001/jamanetworkopen.2025.2577. PMID- 40162642 OWN - NLM STAT- MEDLINE DCOM- 20250528 LR - 20260202 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 392 IP - 20 DP - 2025 May 29 TI - Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. PG - 2001-2012 LID - 10.1056/NEJMoa2501006 [doi] AB - BACKGROUND: The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high cardiovascular risk. An assessment of the cardiovascular efficacy of oral semaglutide in persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both is needed. METHODS: In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years of age or older, had type 2 diabetes with a glycated hemoglobin level of 6.5 to 10.0%, and had known atherosclerotic cardiovascular disease, chronic kidney disease, or both to receive either once-daily oral semaglutide (maximal dose, 14 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke), assessed in a time-to-first-event analysis. The confirmatory secondary outcomes included major kidney disease events (a five-point composite outcome). RESULTS: Among the 9650 participants who had undergone randomization, the mean (+/-SD) follow-up was 47.5+/-10.9 months, and the median follow-up was 49.5 months. A primary-outcome event occurred in 579 of the 4825 participants (12.0%; incidence, 3.1 events per 100 person-years) in the oral semaglutide group, as compared with 668 of the 4825 participants (13.8%; incidence, 3.7 events per 100 person-years) in the placebo group (hazard ratio, 0.86; 95% confidence interval, 0.77 to 0.96; P = 0.006). The results for the confirmatory secondary outcomes did not differ significantly between the two groups. The incidence of serious adverse events was 47.9% in the oral semaglutide group and 50.3% in the placebo group; the incidence of gastrointestinal disorders was 5.0% and 4.4%, respectively. CONCLUSIONS: Among persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both, the use of oral semaglutide was associated with a significantly lower risk of major adverse cardiovascular events than placebo, without an increase in the incidence of serious adverse events. (Funded by Novo Nordisk; SOUL ClinicalTrials.gov number, NCT03914326.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - McGuire, Darren K AU - McGuire DK AD - University of Texas Southwestern Medical Center, Dallas. AD - Parkland Health System, Dallas. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, NS, Canada. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland. FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk, Soborg, Denmark. FAU - Ripa, Maria Sejersten AU - Ripa MS AD - Novo Nordisk, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk, Soborg, Denmark. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - Novo Nordisk, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, United Kingdom. FAU - Cavender, Matthew A AU - Cavender MA AUID- ORCID: 0000-0002-4466-4760 AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Gislum, Mette AU - Gislum M AD - Novo Nordisk, Soborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - n/a/Novo Nordisk/ PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250329 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - N Engl J Med. 2025 Aug 14;393(7):724-725. doi: 10.1056/NEJMc2508958. PMID: 40802952 CIN - N Engl J Med. 2025 Aug 14;393(7):725. doi: 10.1056/NEJMc2508958. PMID: 40802953 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Atherosclerosis/complications/drug therapy MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide FIR - Perez Manghi, F IR - Perez Manghi F FIR - Pozzi, J M IR - Pozzi JM FIR - Lorenzatti, A J IR - Lorenzatti AJ FIR - Visco, V E IR - Visco VE FIR - Piskorz, D IR - Piskorz D FIR - Nardone, L IR - Nardone L FIR - Chahin, M I IR - Chahin MI FIR - Bustamante Labarta, M IR - Bustamante Labarta M FIR - Luquez, C IR - Luquez C FIR - MacKinnon, I J IR - MacKinnon IJ FIR - Pieber, T IR - Pieber T FIR - Prager, R IR - Prager R FIR - Fliesser-Gorzer, E IR - Fliesser-Gorzer E FIR - Ebenbichler, C IR - Ebenbichler C FIR - Fasching, P IR - Fasching P FIR - Mathieu, C IR - Mathieu C FIR - De Block, C IR - De Block C FIR - Duyck, F IR - Duyck F FIR - Heyns, E IR - Heyns E FIR - Lapauw, B IR - Lapauw B FIR - Vercammen, C IR - Vercammen C FIR - Turatti, L A A IR - Turatti LAA FIR - Franco, D R IR - Franco DR FIR - Rea, R R IR - Rea RR FIR - Kurtz Lisboa, H R IR - Kurtz Lisboa HR FIR - Salles, J E IR - Salles JE FIR - Saraiva, J F K IR - Saraiva JFK FIR - Fonseca, A G T IR - Fonseca AGT FIR - Vidotti, M H IR - Vidotti MH FIR - Leite, S O IR - Leite SO FIR - Aggarwal, N IR - Aggarwal N FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Noronha, L IR - Noronha L FIR - Pedersen, S IR - Pedersen S FIR - Peterson, S IR - Peterson S FIR - Tellier, G IR - Tellier G FIR - Weisnagel, J IR - Weisnagel J FIR - Beca, S IR - Beca S FIR - Alasaad, H IR - Alasaad H FIR - Punthakee, Z IR - Punthakee Z FIR - Mancini, J G B IR - Mancini JGB FIR - Tytus, R IR - Tytus R FIR - Ransom, T P P IR - Ransom TPP FIR - Connelly, K IR - Connelly K FIR - Husain, M IR - Husain M FIR - Tsoukas, M IR - Tsoukas M FIR - Ji, L IR - Ji L FIR - Liu, J IR - Liu J FIR - Yuan, G IR - Yuan G FIR - Ye, X IR - Ye X FIR - Dong, X IR - Dong X FIR - Bian, F IR - Bian F FIR - Angelo, A A IR - Angelo AA FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Hernandez Erazo, I D IR - Hernandez Erazo ID FIR - Hernandez Ruiz, E A IR - Hernandez Ruiz EA FIR - Gomez Mesa, J E IR - Gomez Mesa JE FIR - Canecki Varzic, S IR - Canecki Varzic S FIR - Vucak Loncar, J IR - Vucak Loncar J FIR - Simegi-Djekic, V IR - Simegi-Djekic V FIR - Ticinovic Kurir, T IR - Ticinovic Kurir T FIR - Tusek, S IR - Tusek S FIR - Rahelic, D IR - Rahelic D FIR - Marusic, S IR - Marusic S FIR - Kruljac, I IR - Kruljac I FIR - Fabris Vitkovic, D IR - Fabris Vitkovic D FIR - Oznerova, M IR - Oznerova M FIR - Vrkoc, J IR - Vrkoc J FIR - Dolezalova, B IR - Dolezalova B FIR - Haluzik, M IR - Haluzik M FIR - Jankovec, Z IR - Jankovec Z FIR - Olsovsky, J IR - Olsovsky J FIR - Zemanova, J IR - Zemanova J FIR - Kyselova, P IR - Kyselova P FIR - Smahelova, A IR - Smahelova A FIR - Gregersen, S IR - Gregersen S FIR - Olsen, A-M Z IR - Olsen AZ FIR - Mikkelsen, D IR - Mikkelsen D FIR - Egstrup, K IR - Egstrup K FIR - Pedersen-Bjergaard, U IR - Pedersen-Bjergaard U FIR - Potier, L IR - Potier L FIR - Borot, S IR - Borot S FIR - Gaborit, B IR - Gaborit B FIR - Monier, A IR - Monier A FIR - Pradignac, A IR - Pradignac A FIR - Verges, B IR - Verges B FIR - Larroumet, A IR - Larroumet A FIR - Thuan, J-F IR - Thuan JF FIR - Birkenfeld, A IR - Birkenfeld A FIR - Kellerer, M IR - Kellerer M FIR - Ludemann, J IR - Ludemann J FIR - Esser, M IR - Esser M FIR - Kahrmann, G IR - Kahrmann G FIR - Kempe, H-P IR - Kempe HP FIR - Koch, T IR - Koch T FIR - Axthelm, C IR - Axthelm C FIR - Paschen, B IR - Paschen B FIR - Rose, L IR - Rose L FIR - Schaum, T IR - Schaum T FIR - Schulze, J IR - Schulze J FIR - Staudenmeyer, A IR - Staudenmeyer A FIR - Wenzl-Bauer, V IR - Wenzl-Bauer V FIR - Ma, R C W IR - Ma RCW FIR - Thomas, N IR - Thomas N FIR - Reddy, V S IR - Reddy VS FIR - Rao, P V IR - Rao PV FIR - Sahay, R IR - Sahay R FIR - Singh, J IR - Singh J FIR - Prakash, A IR - Prakash A FIR - Tandon, N IR - Tandon N FIR - Marwah, T IR - Marwah T FIR - Chaudhury, T IR - Chaudhury T FIR - Ghosh, S IR - Ghosh S FIR - Kanungo, A K IR - Kanungo AK FIR - Mittal, N IR - Mittal N FIR - Jacob, J J IR - Jacob JJ FIR - Chadha, M IR - Chadha M FIR - Chawla, M IR - Chawla M FIR - Bhagwat, N M IR - Bhagwat NM FIR - Jain, S M IR - Jain SM FIR - Thulaseedharan, N K IR - Thulaseedharan NK FIR - Girithara, G IR - Girithara G FIR - Desai, A IR - Desai A FIR - Sharma, S K IR - Sharma SK FIR - Murthy, S IR - Murthy S FIR - Sethi, B K IR - Sethi BK FIR - Kadam, Y IR - Kadam Y FIR - Kesavadev, J IR - Kesavadev J FIR - Daxini, B IR - Daxini B FIR - Chawla, R IR - Chawla R FIR - Gopalakrishnan, U A IR - Gopalakrishnan UA FIR - Baruah, M P IR - Baruah MP FIR - Reddy, S P IR - Reddy SP FIR - Suryanarayana, K M IR - Suryanarayana KM FIR - Singh, K P IR - Singh KP FIR - Saboo, B IR - Saboo B FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Hochberg, I IR - Hochberg I FIR - Sofer, Y IR - Sofer Y FIR - Tirosh, A IR - Tirosh A FIR - Shimon, I IR - Shimon I FIR - Vishlitzky, V IR - Vishlitzky V FIR - Bashkin, A IR - Bashkin A FIR - Tsur, A IR - Tsur A FIR - Shechter, M IR - Shechter M FIR - Andreozzi, F IR - Andreozzi F FIR - Setola, E IR - Setola E FIR - Consoli, A IR - Consoli A FIR - Lupoli, R IR - Lupoli R FIR - Genovese, S IR - Genovese S FIR - Maranghi, M IR - Maranghi M FIR - Lauro, D IR - Lauro D FIR - Citarrella, R IR - Citarrella R FIR - Fadini, G P IR - Fadini GP FIR - Murdolo, G IR - Murdolo G FIR - Di Carlo, A IR - Di Carlo A FIR - Giorgino, F IR - Giorgino F FIR - Buscemi, S IR - Buscemi S FIR - Hanaoka, K IR - Hanaoka K FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Ezaki, H IR - Ezaki H FIR - Yuki, H IR - Yuki H FIR - Kiyosue, A IR - Kiyosue A FIR - Hata, Y IR - Hata Y FIR - Sugawara, M IR - Sugawara M FIR - Domae, H IR - Domae H FIR - Iwata, H IR - Iwata H FIR - Nishida, Y IR - Nishida Y FIR - Igarashi, M IR - Igarashi M FIR - Fujino, S IR - Fujino S FIR - Oiwa, A IR - Oiwa A FIR - Oh, F IR - Oh F FIR - Sueyoshi, A IR - Sueyoshi A FIR - Murakami, T IR - Murakami T FIR - Tanaka, M IR - Tanaka M FIR - Idogaki, A IR - Idogaki A FIR - Onaka, H IR - Onaka H FIR - Mizote, I IR - Mizote I FIR - Doi, M IR - Doi M FIR - Ebisui, O IR - Ebisui O FIR - Tanabe, M IR - Tanabe M FIR - Natsuaki, M IR - Natsuaki M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Wan Mohamed, W M I IR - Wan Mohamed WMI FIR - Yahaya, N IR - Yahaya N FIR - Ratnasingam, J IR - Ratnasingam J FIR - Ong, T K IR - Ong TK FIR - Mohamad, M IR - Mohamad M FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Abdul Ghani, R IR - Abdul Ghani R FIR - Adam, N L IR - Adam NL FIR - Fam, T L IR - Fam TL FIR - Tan, F H S IR - Tan FHS FIR - Morales Villegas, E C IR - Morales Villegas EC FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Espinoza Peralta, D IR - Espinoza Peralta D FIR - Medina Pech, C E IR - Medina Pech CE FIR - Arechavaleta-Granell, M IR - Arechavaleta-Granell M FIR - Garcia Ulloa, A C IR - Garcia Ulloa AC FIR - Laviada Molina, H A IR - Laviada Molina HA FIR - Banda Elizondo, R G IR - Banda Elizondo RG FIR - Garza Ruiz, J A IR - Garza Ruiz JA FIR - Garcia Cantu, E A IR - Garcia Cantu EA FIR - van Bemmel, T IR - van Bemmel T FIR - de Valk, H W IR - de Valk HW FIR - Kooy, A IR - Kooy A FIR - Lieverse, L IR - Lieverse L FIR - Landewe-Cleuren, S A N T IR - Landewe-Cleuren SANT FIR - Hoogenberg, K IR - Hoogenberg K FIR - van Raalte, D IR - van Raalte D FIR - Jebbink, M IR - Jebbink M FIR - Oldenburg-Ligtenberg, C IR - Oldenburg-Ligtenberg C FIR - Abbink-Zandbergen, E IR - Abbink-Zandbergen E FIR - Mihai, B IR - Mihai B FIR - Crisan, C IR - Crisan C FIR - Filip, I IR - Filip I FIR - Busegeanu, M M IR - Busegeanu MM FIR - Roman, G IR - Roman G FIR - Mot, A C IR - Mot AC FIR - Nicoara, A IR - Nicoara A FIR - Anghel, V IR - Anghel V FIR - Pletea, N N IR - Pletea NN FIR - Suciu, M IR - Suciu M FIR - Strajer, D IR - Strajer D FIR - Cernea, S IR - Cernea S FIR - Zilov, A IR - Zilov A FIR - Kobalava, Z IR - Kobalava Z FIR - Ruyatkina, L A IR - Ruyatkina LA FIR - Suplotova, L A IR - Suplotova LA FIR - Sergeeva-Kondrachenko, M Y IR - Sergeeva-Kondrachenko MY FIR - Yanovskaya, M E IR - Yanovskaya ME FIR - Kargina, L IR - Kargina L FIR - Ignatyeva, A IR - Ignatyeva A FIR - Astamirova, K IR - Astamirova K FIR - Zalevskaya, A IR - Zalevskaya A FIR - Zagrebelnaya, O IR - Zagrebelnaya O FIR - Frolova, E V IR - Frolova EV FIR - Peskov, A B IR - Peskov AB FIR - Mishchenko, O IR - Mishchenko O FIR - Otroshchenko, O IR - Otroshchenko O FIR - Gaysina, L IR - Gaysina L FIR - Shabelnikova, O Y IR - Shabelnikova OY FIR - Saprina, T V IR - Saprina TV FIR - Lysenko, T A IR - Lysenko TA FIR - Kunitsyna, M IR - Kunitsyna M FIR - Zyangirova, S T IR - Zyangirova ST FIR - Lalic, N IR - Lalic N FIR - Lalic, K IR - Lalic K FIR - Beljic Zivkovic, T IR - Beljic Zivkovic T FIR - Kikovic, S IR - Kikovic S FIR - Djukic, A IR - Djukic A FIR - Pesic, M IR - Pesic M FIR - Dimic, D IR - Dimic D FIR - Stokic, E IR - Stokic E FIR - Mitrovic, M IR - Mitrovic M FIR - Polovina, S IR - Polovina S FIR - Djordjevic, M IR - Djordjevic M FIR - Sosovec, D IR - Sosovec D FIR - Pella, D IR - Pella D FIR - Donicova, V IR - Donicova V FIR - Hanackova Prasekova, S IR - Hanackova Prasekova S FIR - Koleny, D IR - Koleny D FIR - Culak, J IR - Culak J FIR - Cerna, K IR - Cerna K FIR - Hundza, V IR - Hundza V FIR - Gmitrov, J IR - Gmitrov J FIR - Lacka, J IR - Lacka J FIR - Plasil, R IR - Plasil R FIR - Amod, A IR - Amod A FIR - Bacus, H B IR - Bacus HB FIR - Bhorat, Q E IR - Bhorat QE FIR - Joshi, P IR - Joshi P FIR - Lakha, D R IR - Lakha DR FIR - Makan, V IR - Makan V FIR - Ntusi, N IR - Ntusi N FIR - Padayachee, T IR - Padayachee T FIR - Seeber, M E IR - Seeber ME FIR - Pillay, D IR - Pillay D FIR - Joshi, M IR - Joshi M FIR - Mayet, L IR - Mayet L FIR - Lee, J IR - Lee J FIR - Kim, S G IR - Kim SG FIR - Min, K W IR - Min KW FIR - Kang, E S IR - Kang ES FIR - Lee, W J IR - Lee WJ FIR - Choi, S H IR - Choi SH FIR - Lee, C B IR - Lee CB FIR - Lopez Suarez, A IR - Lopez Suarez A FIR - Garcia Ordonez, M A IR - Garcia Ordonez MA FIR - Garcia Quintana, A IR - Garcia Quintana A FIR - Mazon Ramos, P IR - Mazon Ramos P FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soto Gonzalez, A IR - Soto Gonzalez A FIR - Jodar, E IR - Jodar E FIR - Delgado Lista, J IR - Delgado Lista J FIR - Morales Portillo, C IR - Morales Portillo C FIR - Montalban Carrasco, C IR - Montalban Carrasco C FIR - Gorgojo Martinez, J J IR - Gorgojo Martinez JJ FIR - Tinahones, F IR - Tinahones F FIR - Tu, S-T IR - Tu ST FIR - Huang, C-N IR - Huang CN FIR - Chen, S-T IR - Chen ST FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Buranapin, S IR - Buranapin S FIR - Suwanagool, A IR - Suwanagool A FIR - Tantiwong, P IR - Tantiwong P FIR - Boonyavarakul, A IR - Boonyavarakul A FIR - Benjachareonwong, S IR - Benjachareonwong S FIR - Leelawattana, R IR - Leelawattana R FIR - Vathesatogkit, P IR - Vathesatogkit P FIR - Deerochanawong, C IR - Deerochanawong C FIR - Sonmez, Y A IR - Sonmez YA FIR - Oguz, A IR - Oguz A FIR - Tabak, O IR - Tabak O FIR - Kocak, M IR - Kocak M FIR - Sariakcali, B IR - Sariakcali B FIR - Bayram, F IR - Bayram F FIR - Guclu, M IR - Guclu M FIR - Gurkan, E IR - Gurkan E FIR - Kebapci, N IR - Kebapci N FIR - Comlekci, A IR - Comlekci A FIR - Acibucu, F IR - Acibucu F FIR - Ahbab, S IR - Ahbab S FIR - Bilen, H IR - Bilen H FIR - Mankovskyy, B IR - Mankovskyy B FIR - Urbanovych, A IR - Urbanovych A FIR - Kuskalo, P IR - Kuskalo P FIR - Bondarets, I IR - Bondarets I FIR - Petrosyan, O IR - Petrosyan O FIR - Pashkovska, N IR - Pashkovska N FIR - Oleksyk, O IR - Oleksyk O FIR - Kaydashev, I IR - Kaydashev I FIR - Maliar, K IR - Maliar K FIR - Myshanych, G IR - Myshanych G FIR - Bain, S C IR - Bain SC FIR - Black, D IR - Black D FIR - Johnston, P IR - Johnston P FIR - Dang, C IR - Dang C FIR - Dhatariya, K IR - Dhatariya K FIR - English, P IR - English P FIR - Field, B IR - Field B FIR - Grimmer, P IR - Grimmer P FIR - Gunstone, A IR - Gunstone A FIR - Ray, S IR - Ray S FIR - Tatovic, D IR - Tatovic D FIR - Kernohan, A IR - Kernohan A FIR - Lindsay, R IR - Lindsay R FIR - Mcknight, J A IR - Mcknight JA FIR - Park, A IR - Park A FIR - Patel, D IR - Patel D FIR - Philip, S IR - Philip S FIR - Randeva, H IR - Randeva H FIR - Sathyapalan, T IR - Sathyapalan T FIR - Turner, W IR - Turner W FIR - Wyatt, N IR - Wyatt N FIR - Allison, D C IR - Allison DC FIR - Awasty, V IR - Awasty V FIR - Ayele, E IR - Ayele E FIR - Bajaj, C IR - Bajaj C FIR - Budoff, M J IR - Budoff MJ FIR - Busch, R IR - Busch R FIR - Buse, J B IR - Buse JB FIR - Casaubon, L IR - Casaubon L FIR - Austin, P A IR - Austin PA FIR - Chaidarun, S S IR - Chaidarun SS FIR - Chochinov, R H IR - Chochinov RH FIR - Chu, J W IR - Chu JW FIR - Daboul, N Y IR - Daboul NY FIR - Dang, A H IR - Dang AH FIR - Desouza, C V IR - Desouza CV FIR - Everhart, B G IR - Everhart BG FIR - Arambasick, J IR - Arambasick J FIR - Fink, R I IR - Fink RI FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Fogarty, C M IR - Fogarty CM FIR - Gilbert, M P IR - Gilbert MP FIR - Johnson, D M IR - Johnson DM FIR - Krishnasamy, S S IR - Krishnasamy SS FIR - Lane, W S IR - Lane WS FIR - Nakhle, S N IR - Nakhle SN FIR - Levenson, D IR - Levenson D FIR - O'Donnell, P IR - O'Donnell P FIR - Weiss, D IR - Weiss D FIR - Risser, J A IR - Risser JA FIR - Wierum, C IR - Wierum C FIR - Sivalingam, K IR - Sivalingam K FIR - Gupta, D IR - Gupta D FIR - Philis-Tsimikas, A IR - Philis-Tsimikas A FIR - Pratley, R E IR - Pratley RE FIR - Mirza, L IR - Mirza L FIR - Snyder, B IR - Snyder B FIR - Rasouli, N IR - Rasouli N FIR - Porter, J IR - Porter J FIR - Ledesma, G N IR - Ledesma GN FIR - Powell, T IR - Powell T FIR - Tandron, I J IR - Tandron IJ FIR - Lingvay, I IR - Lingvay I FIR - Reed Iii, J C H IR - Reed Iii JCH FIR - Patel, M B IR - Patel MB FIR - Lovre, D IR - Lovre D FIR - Chaicha-Brom, T IR - Chaicha-Brom T FIR - Jantzi, C IR - Jantzi C FIR - Brautigam, D IR - Brautigam D FIR - Bao, S IR - Bao S FIR - Mbogua, C N IR - Mbogua CN FIR - Zemel, L R IR - Zemel LR FIR - Hasan, S IR - Hasan S FIR - Rosenstock, J IR - Rosenstock J FIR - Tran, H IR - Tran H FIR - Poremba, J IR - Poremba J FIR - Baker, C IR - Baker C FIR - Prier, K IR - Prier K FIR - Chilka, S IR - Chilka S FIR - Agaiby, J M IR - Agaiby JM FIR - Condit, J IR - Condit J FIR - Eagerton, D C IR - Eagerton DC FIR - Huffman, D IR - Huffman D FIR - Cornett, G M IR - Cornett GM FIR - Traylor, H IR - Traylor H FIR - Brinson, C IR - Brinson C FIR - Bays, H E IR - Bays HE FIR - Jerkins, T IR - Jerkins T FIR - Nicol, P R IR - Nicol PR FIR - Siddiqui, I A IR - Siddiqui IA FIR - Hewitt, M IR - Hewitt M FIR - Odugbesan, A O IR - Odugbesan AO FIR - Lillestol, M J IR - Lillestol MJ FIR - Thrasher, J R IR - Thrasher JR FIR - Gandy, W H Jr IR - Gandy WH Jr FIR - Pant, N IR - Pant N FIR - Nagelberg, S IR - Nagelberg S FIR - Cannon, K IR - Cannon K FIR - Anderson, M W IR - Anderson MW FIR - Bhargava, A IR - Bhargava A FIR - Doshi, A IR - Doshi A FIR - Jardula, M F IR - Jardula MF FIR - Montero, M IR - Montero M FIR - Purighalla, R S IR - Purighalla RS FIR - Warren, M L IR - Warren ML FIR - Harris, K IR - Harris K FIR - Jackson, R A IR - Jackson RA FIR - Khaira, A S IR - Khaira AS FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Gagianas, P J IR - Gagianas PJ FIR - Pantalone, K IR - Pantalone K FIR - Murray, A V IR - Murray AV FIR - McGuire, Darren K IR - McGuire DK FIR - Buse, John B IR - Buse JB FIR - Deanfield, John IR - Deanfield J FIR - Mann, Johannes F E IR - Mann JFE FIR - Poulter, Neil IR - Poulter N FIR - Marx, Nikolaus IR - Marx N FIR - Pop-Busui, Rodica IR - Pop-Busui R FIR - Emerson, Scott IR - Emerson S FIR - Mulvagh, Sharon L IR - Mulvagh SL FIR - Inzucchi, Silvio E IR - Inzucchi SE FIR - Brown-Frandsen, Kirstine IR - Brown-Frandsen K FIR - Hovingh, G Kees IR - Hovingh GK FIR - Engelmann, Mads D IR - Engelmann MD FIR - Billeskov Schelde, Peter IR - Billeskov Schelde P FIR - Rasmussen, Mads Frederik IR - Rasmussen MF FIR - Bain, Stephen C IR - Bain SC FIR - Cavender, Matthew A IR - Cavender MA FIR - Jhund Singh, Pardeep IR - Jhund Singh P FIR - Lorenzatti, Alberto IR - Lorenzatti A FIR - Pieber, Thomas IR - Pieber T FIR - Mathieu, Chantal IR - Mathieu C FIR - Kerr Saraiva, Jose Francisco IR - Kerr Saraiva JF FIR - Rea, Rosangela IR - Rea R FIR - Bajaj, Harpreet IR - Bajaj H FIR - Connelly, Kim IR - Connelly K FIR - Ji, Linong IR - Ji L FIR - Sanchez Garcia, Robinson IR - Sanchez Garcia R FIR - Canecki-Varzic, Silvija IR - Canecki-Varzic S FIR - Haluzik, Martin IR - Haluzik M FIR - Gregersen, Soren IR - Gregersen S FIR - Kellerer, Monika IR - Kellerer M FIR - Birkenfeld, Andreas IR - Birkenfeld A FIR - Chow, Francis Chun Chung IR - Chow FCC FIR - Mohan, V IR - Mohan V FIR - Nadu, Tamil IR - Nadu T FIR - Shechter, Michael IR - Shechter M FIR - Consoli, Agostino IR - Consoli A FIR - Watada, Hirotaka IR - Watada H FIR - Abdul Ghani, Rohana IR - Abdul Ghani R FIR - Arechavaleta Granell, Rosario IR - Arechavaleta Granell R FIR - van Bemmel, Thomas IR - van Bemmel T FIR - Roman, Gabriela IR - Roman G FIR - Zilov, Alexey IR - Zilov A FIR - Kobalava, Zhanna IR - Kobalava Z FIR - Lalic, Nebojsa IR - Lalic N FIR - Cerna, Katarina IR - Cerna K FIR - Amod, Aslam IR - Amod A FIR - Kim, Sin Gon IR - Kim SG FIR - Gorgojo Martinez, Juan Jose IR - Gorgojo Martinez JJ FIR - Mazon Ramos, Pilar IR - Mazon Ramos P FIR - Tu, Shih-Te IR - Tu ST FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Oguz, Aytekin IR - Oguz A FIR - Mankovskyy, Boris IR - Mankovskyy B FIR - DeSouza, Cyrus IR - DeSouza C FIR - Allison, Dale IR - Allison D FIR - de Lemos, James A IR - de Lemos JA FIR - Saver, Jeffrey L IR - Saver JL FIR - Wexler, Deborah J IR - Wexler DJ FIR - Fried, Linda IR - Fried L FIR - Floege, Jurgen IR - Floege J FIR - Goodman, Shaun IR - Goodman S FIR - Ferris, Frederick L 3rd IR - Ferris FL 3rd FIR - Gillen, Daniel L IR - Gillen DL FIR - Nuno, Michelle IR - Nuno M FIR - Roe, Matthew T IR - Roe MT FIR - Wiviott, Stephen IR - Wiviott S FIR - Ducrocq, Gregory IR - Ducrocq G FIR - Povsic, Thomas IR - Povsic T FIR - Rodriguez, Fatima IR - Rodriguez F FIR - Mehta, Rajendra IR - Mehta R FIR - Kong, David IR - Kong D FIR - Kontos, Christopher IR - Kontos C FIR - Phillips, Lawrence IR - Phillips L FIR - Leonardi, Sergio IR - Leonardi S FIR - Becker, Kyra J IR - Becker KJ FIR - Jordan, J Dedrick IR - Jordan JD FIR - Sung, Gene IR - Sung G FIR - Dombrowski, Keith IR - Dombrowski K FIR - Fisher, Deborah IR - Fisher D FIR - Gellad, Ziad IR - Gellad Z FIR - Wilder, Julius IR - Wilder J FIR - Leiman, David IR - Leiman D FIR - Dwyer, Jamie IR - Dwyer J FIR - Middleton, John IR - Middleton J FIR - Umanath, Kausik IR - Umanath K FIR - Chang, Tara IR - Chang T FIR - Diamond, Matthew J IR - Diamond MJ EDAT- 2025/03/31 21:17 MHDA- 2025/05/28 18:27 CRDT- 2025/03/31 07:53 PHST- 2025/05/28 18:27 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 07:53 [entrez] AID - 10.1056/NEJMoa2501006 [doi] PST - ppublish SO - N Engl J Med. 2025 May 29;392(20):2001-2012. doi: 10.1056/NEJMoa2501006. Epub 2025 Mar 29. PMID- 40156846 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 5 DP - 2025 May 1 TI - Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials. PG - 846-859 LID - 10.2337/dc25-0241 [doi] AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D), although whether benefits extend to both subcutaneous and oral formulations remains unclear. PURPOSE: In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinetics sufficient to provide 24-h activity) GLP-1RA in T2D. DATA SOURCES: A systematic review of PubMed was conducted (to 7 February 2025). STUDY SELECTION: Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with >/=500 individuals with T2D were included. DATA EXTRACTION: A random-effects model was used to estimate hazard ratios (HRs) for MACE, its components, all-cause mortality, hospitalization for heart failure (HHF), a composite kidney outcome (kidney failure [kidney replacement therapy or persistent estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2], sustained >/=50% eGFR decline or nearest equivalent, or kidney-related death), worsening kidney function, and safety outcomes. DATA SYNTHESIS: Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%). A consistent 14% reduction was seen for all MACE components. There was no significant heterogeneity by GLP-1RA administration route (subcutaneous vs. oral). There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events. LIMITATIONS: Trial-level meta-analyses preclude detailed subgroup analyses and may introduce ecological bias. CONCLUSIONS: As a group, long-acting GLP-1RA, including both injectable and oral formulations, reduce incidence of MACE, HHF, and kidney events and all-cause mortality in T2D. CI - (c) 2025 by the American Diabetes Association. FAU - Lee, Matthew M Y AU - Lee MMY AUID- ORCID: 0000-0001-9213-2067 AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Pop-Busui, Rodica AU - Pop-Busui R AUID- ORCID: 0000-0002-2042-1350 AD - Department of Medicine, Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, OR. FAU - Deanfield, John AU - Deanfield J AUID- ORCID: 0000-0001-8806-6052 AD - Institute of Cardiovascular Sciences, University College London, London, U.K. FAU - Emerson, Scott S AU - Emerson SS AUID- ORCID: 0000-0002-2695-0165 AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Inzucchi, Silvio E AU - Inzucchi SE AUID- ORCID: 0000-0003-1254-6636 AD - Section of Endocrinology, Yale School of Medicine, New Haven, CT. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University, Erlangen, Germany. FAU - Marx, Nikolaus AU - Marx N AUID- ORCID: 0000-0001-6141-634X AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AUID- ORCID: 0000-0002-7377-4053 AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Poulter, Neil R AU - Poulter NR AUID- ORCID: 0000-0002-6292-997X AD - Imperial Clinical Trials Unit, Imperial College London, London, U.K. FAU - Badve, Sunil V AU - Badve SV AUID- ORCID: 0000-0003-2269-312X AD - St George Hospital, Sydney, New South Wales, Australia. AD - Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL. FAU - Perkovic, Vlado AU - Perkovic V AUID- ORCID: 0000-0002-4257-7620 AD - Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - University of North Carolina School of Medicine, Chapel Hill, NC. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - University of Texas Southwestern Medical Center and Parkland Health, Dallas, TX. CN - SOUL Trial Investigators LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/mortality/epidemiology MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptides/therapeutic use MH - Administration, Oral MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/30 23:01 MHDA- 2025/04/25 06:28 CRDT- 2025/03/29 14:32 PHST- 2025/01/29 00:00 [received] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/04/25 06:28 [medline] PHST- 2025/03/30 23:01 [pubmed] PHST- 2025/03/29 14:32 [entrez] AID - 158048 [pii] AID - 10.2337/dc25-0241 [doi] PST - ppublish SO - Diabetes Care. 2025 May 1;48(5):846-859. doi: 10.2337/dc25-0241. PMID- 40156843 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260307 IS - 1524-4539 (Electronic) IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 151 IP - 23 DP - 2025 Jun 10 TI - Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial. PG - 1639-1650 LID - 10.1161/CIRCULATIONAHA.125.074545 [doi] AB - BACKGROUND: Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes. METHODS: The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events. RESULTS: Over a mean follow-up of 47.5+/-10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95; P-interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar. CONCLUSIONS: Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326. FAU - Marx, Nikolaus AU - Marx N AUID- ORCID: 0000-0001-6141-634X AD - Department of Internal Medicine I, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Germany (N.M.). FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, United Kingdom (J.E.D.). FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany (J.F.E.M.). AD - Friedrich Alexander University of Erlangen, Germany (J.F.E.M.). FAU - Arechavaleta, Rosario AU - Arechavaleta R AD - Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico (R.A.). FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - School of Medicine, Swansea University, United Kingdom (S.C.B.). FAU - Bajaj, Harpreet S AU - Bajaj HS AUID- ORCID: 0000-0002-1461-1465 AD - LMC Diabetes and Endocrinology, Brampton, Canada (H.S.B.). FAU - Bayer Tanggaard, Katrine AU - Bayer Tanggaard K AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AUID- ORCID: 0000-0003-1407-9023 AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Germany (A.L.B.). AD - Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, German Center for Diabetes Research (A.L.B.). FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - University of North Carolina School of Medicine, Chapel Hill (J.B.B.). FAU - Davicevic-Elez, Zaklina AU - Davicevic-Elez Z AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Desouza, Cyrus AU - Desouza C AUID- ORCID: 0000-0001-6660-0568 AD - Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha (C.D.). FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle (S.S.E.). FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Inzucchi, Silvio E AU - Inzucchi SE AUID- ORCID: 0000-0003-1254-6636 AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.). FAU - Jhund, Pardeep S AU - Jhund PS AUID- ORCID: 0000-0003-4306-5317 AD - British Heart Foundation, Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom (P.S.J.). FAU - Mulvagh, Sharon L AU - Mulvagh SL AUID- ORCID: 0000-0002-7377-4053 AD - Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada (S.L.M.). FAU - Pop-Busui, Rodica AU - Pop-Busui R AUID- ORCID: 0000-0002-2042-1350 AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland (R.P.-B.). FAU - Poulter, Neil R AU - Poulter NR AUID- ORCID: 0000-0002-6292-997X AD - Imperial Clinical Trials Unit, Imperial College London, United Kingdom (N.R.P.). FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Tu, Shih-Te AU - Tu ST AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan (S.-T.T.). FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas (D.K.M.). CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - P30 DK045735/DK/NIDDK NIH HHS/United States GR - U01 DK119083/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250329 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Cardiovascular Diseases/mortality/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12144549 OTO - NOTNLM OT - cardiovascular diseases OT - cardiovascular system OT - diabetes mellitus, type 2 OT - glucagon-like peptide-1 receptor agonists OT - renal insufficiency, chronic OT - semaglutide OT - sodium-glucose transporter 2 inhibitors COIS- Dr Marx is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TRR 219; project ID, 322900939 [M03, M05]); has given lectures for Bayer, Boehringer Ingelheim, Sanofi-Aventis, MSD, BMS, AstraZeneca, Lilly, and Novo Nordisk; has received unrestricted research grants from Boehringer Ingelheim; and has served as an advisor for Bayer, Boehringer Ingelheim, Sanofi-Aventis, MSD, BMS, AstraZeneca, and Novo Nordisk. In addition, Dr Marx served in trial leadership for Boehringer Ingelheim and Novo Nordisk. Dr Marx declines all personal compensation from pharma or device companies. Dr Deanfield reports grants or contracts from 2022 to 2025 from Alzheimer's Research UK and from 2019 to 2022 from the British Heart Foundation. He received consulting fees/honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. Dr Mann reports grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; and honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim. He is an author for UpToDate and has a leadership role in the KDIGO group. Dr Arechavaleta has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi. She has received advisory board fees and honoraria for clinical trials from Novo Nordisk and Eli Lilly. Dr Bain reports grants and honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Menarini, and Novo Nordisk. He has provided expert advice to the All-Wales Medicines Strategy Group and the National Institute for Health and Care Excellence (United Kingdom). Dr Bajaj reports trial fees paid to his institution by Abbott, Amgen, Anji Pharmaceuticals, Arrowhead Pharmaceuticals, AstraZeneca, Biomea, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Novartis, Novo Nordisk, and Pfizer. Dr Tanggaard is an employee at Novo Nordisk. Dr Birkenfeld is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; GRK2816; BI1292/12-1; 10-1; 9-1) and the German Federal Ministry for Education and Research (01GI0925) through the German Center for Diabetes Research (DZD e.V.). Dr Birkenfeld has given lectures for Novo Nordisk and Daiichi Sankyo, has received unrestricted research grants from Boehringer Ingelheim and AstraZeneca, and has served as an advisor for Bayer and Novo Nordisk. In addition, Dr Birkenfeld served in trial leadership for Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. Dr Birkenfeld declines all personal compensation from pharma or device companies. Dr Buse reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns Inc, Vertex, and Zealand; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. Dr Davicevic-Elez is an employee of and holds shares in Novo Nordisk. Dr Desouza reports Novo Nordisk research grants (payments to institution) and has personally received consulting fees from Eli Lilly and consulting fees and support for attending meetings or travel from Novo Nordisk. Dr Emerson declares consulting fees from Novo Nordisk for steering committee participation and from Boehringer Ingelheim for consulting regarding veterinary congestive heart failure; received support for attending meetings or travel from Novo Nordisk for attendance at steering committee and scientific meetings; and declares participation on an advisory board for Novo Nordisk, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GlaxoSmithKline, Lilly, Novartis, Bristol Myers, and Sanofi. Dr Engelmann is a full-time employee of Novo Nordisk and has stocks in the company. Dr Hovingh has received funding from the Klinkerpadfonds, paid to his former academic institute (Amsterdam UMC, The Netherlands). He is also an employee and shareholder of Novo Nordisk. Dr Inzucchi has served as a consultant or on advisory boards for Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, and Bayer. He has given lectures sponsored by AstraZeneca and Boehringer Ingelheim/Lilly. He declares royalties from McGraw Hill and Wolters Kluwer Health and support for attending meetings or travel from Novo Nordisk, AstraZeneca, Boehringer Ingelheim/Lilly, and Bayer. Dr Jhund reports speaker fees from AstraZeneca, Novartis, and ProAdWise Communications; advisory board fees from AstraZeneca; research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics. Dr Jhund reports other financial interests, including as Director of GCTP Ltd. His employer, the University of Glasgow, has been remunerated for his time working on clinical trials by AstraZeneca, Novartis, Novo Nordisk, and Bayer AG. Dr Mulvagh has served as a consultant or on advisory boards for Novo Nordisk and Merck. Dr Pop-Busui received research grant support to her institutions from NIDDK, Breakthrough T1D (formerly JDRF), Bayer, Lexicon Pharmaceuticals, and Novo Nordisk, and consulting fees from Averitas Pharma, Biogen, Lexicon Pharmaceuticals, Nevro Inc, Novo Nordisk, and Roche Diagnostic; received support for attending meetings or travel from Roche; participated on an advisory board for Biogen/Reata; and is a member of the board of directors of the American Diabetes Association. Dr Poulter received financial support from several pharmaceutical companies that manufacture blood pressure-lowering, lipid-lowering, and glucose-lowering agents for consultancy fees, research projects, and staff and for arranging and speaking at educational meetings including Servier, Pfizer, AstraZeneca, Amgen, Sanofi, and Novo Nordisk. He holds no stocks or shares in any such companies. Dr Rasmussen is an employee and shareholder in Novo Nordisk. Dr Tu has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr McGuire has received consulting fees from Novo Nordisk, AstraZeneca, Pfizer, Altimmune, Ventyx Pharmaceuticals, Bayer, Lexicon, Applied Therapeutics, Intercept Pharmaceuticals, Esperion, Lilly USA, Boehringer Ingelheim, New Amsterdam, CSL Behring, Amgen, Neurotronics, Metsera, Kailera, and Alveus Pharma. EDAT- 2025/03/30 23:01 MHDA- 2025/06/09 18:28 PMCR- 2025/06/07 CRDT- 2025/03/29 14:32 PHST- 2025/06/09 18:28 [medline] PHST- 2025/03/30 23:01 [pubmed] PHST- 2025/03/29 14:32 [entrez] PHST- 2025/06/07 00:00 [pmc-release] AID - CIRCULATIONAHA-2025-074545 [pii] AID - 10.1161/CIRCULATIONAHA.125.074545 [doi] PST - ppublish SO - Circulation. 2025 Jun 10;151(23):1639-1650. doi: 10.1161/CIRCULATIONAHA.125.074545. Epub 2025 Mar 29. PMID- 40150960 OWN - NLM STAT- MEDLINE DCOM- 20250603 LR - 20250603 IS - 2191-0286 (Electronic) IS - 0792-6855 (Linking) VI - 36 IP - 2-3 DP - 2025 Mar 1 TI - Incretin-based therapies: advancements, challenges, and future directions in type 2 diabetes management. PG - 95-111 LID - 10.1515/jbcpp-2025-0031 [doi] AB - Incretin-based medicines have considerably impacted the treatment of type 2 diabetes mellitus (T2DM), providing considerable advantages in glycemic regulation, weight control, and cardiovascular results. This narrative review examines progress in incretin medicines, encompassing glucagon-like peptide-1 (GLP-1) receptor agonists, dual-receptor, and triple-receptor agonists, while emphasizing their therapeutic advantages, obstacles, and prospective developments. The examined articles were sourced from databases including PubMed and Google Scholar, concentrating on publications predominantly from 2010 to 2024. Selective foundational papers released before this timeline were incorporated to furnish critical historical context about incretin processes and their discovery. Incretin-based medicines, despite their therapeutic efficacy, encounter hurdles including elevated treatment costs, patient compliance difficulties, and variability in response attributable to genetic and physiological variables. Moreover, there are still deficiencies in comprehending the long-term cardiovascular safety and cancer risks linked to these medicines. Emerging dual- and triple-receptor agonists demonstrate potential in overcoming the shortcomings of conventional GLP-1 receptor agonists, providing enhanced metabolic results and broader uses in intricate disease profiles. Future research must concentrate on economic obstacles, streamlined regimens, customized medicine, the integration of artificial intelligence, patient stratification, as well as the safety and efficacy of incretin-based medicines for holistic management of T2DM. CI - (c) 2025 Walter de Gruyter GmbH, Berlin/Boston. FAU - Alluri, Amruth A AU - Alluri AA AUID- ORCID: 0009-0000-1618-0606 AD - Internal Medicine, American University of the Caribbean School of Medicine, Cupecoy, Netherlands. FAU - Guntupalli, Yashaswi AU - Guntupalli Y AUID- ORCID: 0009-0005-0793-672X AD - Internal Medicine, 28660 Sri Venkateswara Institute of Medical Sciences , Tirupati, Andhra Pradesh, India. FAU - Suvarna, Shruti Suresh AU - Suvarna SS AD - Internal Medicine, American University of Barbados, Wildey, Barbados. FAU - Prystupa, Yuliya AU - Prystupa Y AD - Internal Medicine, Danbury Hospital, Danbury, USA. FAU - Khetan, Shrishti Prakash AU - Khetan SP AD - Internal Medicine, American University of Barbados, Wildey, Barbados. FAU - Vejandla, Bharath AU - Vejandla B AD - Internal Medicine, All American Institute of Medical Science, Black River, Jamaica. FAU - Babu Swathi, Naraginti Lenin AU - Babu Swathi NL AUID- ORCID: 0000-0002-3695-0732 AD - Jawaharlal Nehru Technological University, Anantapur, Andhra Pradesh, India. LA - eng PT - Journal Article PT - Review DEP - 20250331 PL - Germany TA - J Basic Clin Physiol Pharmacol JT - Journal of basic and clinical physiology and pharmacology JID - 9101750 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Incretins/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism OTO - NOTNLM OT - dual-receptor agonists OT - glp-1 receptor agonists OT - incretin-based therapies OT - obesity management OT - triple-receptor agonists OT - type 2 diabetes mellitus EDAT- 2025/03/28 06:25 MHDA- 2025/06/03 12:31 CRDT- 2025/03/28 02:43 PHST- 2025/02/17 00:00 [received] PHST- 2025/03/10 00:00 [accepted] PHST- 2025/06/03 12:31 [medline] PHST- 2025/03/28 06:25 [pubmed] PHST- 2025/03/28 02:43 [entrez] AID - jbcpp-2025-0031 [pii] AID - 10.1515/jbcpp-2025-0031 [doi] PST - epublish SO - J Basic Clin Physiol Pharmacol. 2025 Mar 31;36(2-3):95-111. doi: 10.1515/jbcpp-2025-0031. eCollection 2025 Mar 1. PMID- 40146102 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 5 DP - 2025 May 1 TI - Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes. PG - 400-407 LID - 10.1001/jamaophthalmol.2025.0349 [doi] AB - IMPORTANCE: Recent studies have suggested an association between nonarteritic anterior ischemic optic neuropathy (NAION) with semaglutide usage. However, the limitations of those analyses warrant further investigation, given the frequency of use of these medications in people with and without diabetes. OBJECTIVE: To investigate the association between semaglutide use and the risk of NAION among patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the TriNetX database between October 1, 2019, and December 31, 2023, to identify patients with diabetes with no history of NAION who were prescribed semaglutide. The semaglutide cohort was compared with a control group of randomly selected patients with diabetes who were prescribed non-glucagonlike peptide 1 (non-GLP-1) receptor agonist (RA) antidiabetic medications. The data analysis for this study was performed on September 1, 2024. EXPOSURES: Semaglutide history, identified using diagnostic codes. MAIN OUTCOMES AND MEASURES: Cumulative incidence and (HR) hazard ratio of NAION. RESULTS: A total of 3 344 205 patients with diabetes were included in this study. Regarding the diabetes cohort, a total of 174 584 patients with diabetes who received semaglutide (mean [SD] age, 58.3 [12.5] years; 90 427 female [51.8%]; 71 739 male [41.1%]) and 174 584 patients with diabetes who received non-GLP-1 RA medications (mean [SD] age, 58.2 [14.3] years; 90 475 female [51.82%]; 71 989 male [41.24%]) were recruited. Patients with diabetes taking semaglutide exhibited an absence of NAION risk at the 1-month (HR, 2.99; 95% CI, 0.31-28.75), 3-month (HR, 1.33; 95% CI, 0.30-5.93), 6-month (HR, 1.79; 95% CI, 0.60-5.35), and 1-year (HR, 1.94; 95% CI: 0.93-4.02) time points after the index date. However, those taking semaglutide were found to have an increased risk for NAION at the 2-year (HR, 2.39; 95% CI, 1.37-4.18), 3-year (HR, 2.44; 95% CI, 1.44-4.12), and 4-year (HR, 2.05; 95% CI, 1.26-3.34) time points from the index date. Increased risk for NAION was also noted in patients with diabetes and concomitant hypertension who were taking semaglutide (HR, 2.42; 95% CI, 1.19-4.92). An increased NAION risk was also observed among patients with diabetes who had a history of Ozempic (Novo Nordisk) use or stand-alone Ozempic (Novo Nordisk) prescription history. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that semaglutide use was associated with an increased risk of NAION in patients with diabetes. However, the study's retrospective design presents limitations, as it can only infer associations rather than establish causality; further studies are needed. FAU - Hsu, Alan Y AU - Hsu AY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. FAU - Kuo, Hou-Ting AU - Kuo HT AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - Department of General Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Wang, Yu-Hsun AU - Wang YH AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Lin, Chun-Ju AU - Lin CJ AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Shao, Yi-Ching AU - Shao YC AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan. FAU - Chiang, Chun-Chi AU - Chiang CC AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Hsia, Ning-Yi AU - Hsia NY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Lai, Chun-Ting AU - Lai CT AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Tseng, Hsin AU - Tseng H AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. FAU - Wu, Bing-Qi AU - Wu BQ AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - Department of General Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Chen, Huan-Sheng AU - Chen HS AD - An-Shin Dialysis Center, Excelsior Renal Service Co Ltd, Taiwan Branch, Taichung, Taiwan. FAU - Tsai, Yi-Yu AU - Tsai YY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Hsu, Min-Yen AU - Hsu MY AD - Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. AD - Office of Research and Development, Asia University, Taichung, Taiwan. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 May 1;143(5):408-409. doi: 10.1001/jamaophthalmol.2025.0350. PMID: 40146117 MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Female MH - Male MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - Aged MH - Risk Factors MH - Retrospective Studies MH - *Diabetes Mellitus/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Databases, Factual MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11950975 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/03/27 13:16 MHDA- 2025/05/15 12:36 PMCR- 2026/03/27 CRDT- 2025/03/27 11:32 PHST- 2025/05/15 12:36 [medline] PHST- 2025/03/27 13:16 [pubmed] PHST- 2025/03/27 11:32 [entrez] PHST- 2026/03/27 00:00 [pmc-release] AID - 2831924 [pii] AID - eoi250007 [pii] AID - 10.1001/jamaophthalmol.2025.0349 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 May 1;143(5):400-407. doi: 10.1001/jamaophthalmol.2025.0349. PMID- 40145463 OWN - NLM STAT- MEDLINE DCOM- 20250703 LR - 20250728 IS - 0310-057X (Print) IS - 0310-057X (Linking) VI - 53 IP - 4 DP - 2025 Jul TI - A case series of incidents reported to webAIRS relating to glucagon-like peptide 1 agonist use. PG - 220-230 LID - 10.1177/0310057X241311597 [doi] AB - The increasing prescription of glucagon-like peptide 1 (GLP-1) agonists presents a peri-operative challenge for anaesthetists. These drugs delay gastric emptying, potentially increasing pulmonary aspiration risk. Despite recent recommendations from the Australian and New Zealand College of Anaesthetists, Australian Society of Anaesthetists, and American Society of Anesthesiologists, there remain no formalised guidelines regarding preoperative optimisation for patients taking GLP-1 agonists. Given the current lack of evidence, we present a case series of incidents involving patients treated with GLP-1 agonists reported to webAIRS, a web-based anaesthetic incident reporting system in Australia and New Zealand. Among 11,700 reports from July 2009 to April 2024, 13 incidents related to GLP-1 agonist use were identified, including seven cases concerning aspiration. Patient factors potentially contributing to increased aspiration risks in these incidents included a higher body mass index, type 2 diabetes mellitus, gastro-oesophageal reflux disease, emergency case, and time from GLP-1 agonist cessation. Most incidents involved a rapid sequence induction for general anaesthesia with no cases utilising gastric ultrasound, preoperative nasogastric tube insertion, or intravenous erythromycin use. This case series highlights the potential concerns relating to GLP-1 treatment in the perioperative setting. Interdisciplinary collaboration and communication between anaesthetists, surgeons, general practitioners and endocrinologists are required to further investigate and establish preoperative guidelines for safe GLP-1 agonist use. Specifically, consideration in determining actual gastric contents of each patient despite generic fasting guidelines is needed. Early preoperative risk stratification should also improve patient safety and outcomes. FAU - Lam, Clayton Yx AU - Lam CY AUID- ORCID: 0000-0002-4668-7907 AD - Flinders Medical Centre, Department of Anaesthesia and Pain Medicine, Adelaide, Australia. AD - Flinders University College of Medicine and Public Health, Adelaide, Australia. FAU - Lin, D-Yin AU - Lin DY AUID- ORCID: 0000-0002-0813-3161 AD - Flinders Medical Centre, Department of Anaesthesia and Pain Medicine, Adelaide, Australia. AD - Flinders University College of Medicine and Public Health, Adelaide, Australia. FAU - Endlich, Yasmin AU - Endlich Y AUID- ORCID: 0000-0002-8804-4168 AD - Royal Adelaide Hospital, Department of Anaesthesia and Pain Medicine, Adelaide, Australia. AD - The University of Adelaide, Faculty of Medicine, Adelaide, Australia. LA - eng PT - Journal Article DEP - 20250327 PL - United States TA - Anaesth Intensive Care JT - Anaesthesia and intensive care JID - 0342017 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Australia MH - Diabetes Mellitus, Type 2/drug therapy MH - New Zealand MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects OTO - NOTNLM OT - Airway OT - anaesthesia OT - aspiration OT - gastric emptying OT - glucagon-like peptide 1 agonist OT - perioperative anaesthesia OT - webAIRS COIS- Declaration of conflicting interestsYE is the Medical Director of webAIRs. EDAT- 2025/03/27 13:16 MHDA- 2025/07/03 06:27 CRDT- 2025/03/27 07:03 PHST- 2025/07/03 06:27 [medline] PHST- 2025/03/27 13:16 [pubmed] PHST- 2025/03/27 07:03 [entrez] AID - 10.1177/0310057X241311597 [doi] PST - ppublish SO - Anaesth Intensive Care. 2025 Jul;53(4):220-230. doi: 10.1177/0310057X241311597. Epub 2025 Mar 27. PMID- 40140836 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20260127 IS - 1472-6963 (Electronic) IS - 1472-6963 (Linking) VI - 25 IP - 1 DP - 2025 Mar 26 TI - Real world initiation of newly funded empagliflozin and dulaglutide under special authority for patients with type 2 diabetes in New Zealand. PG - 433 LID - 10.1186/s12913-025-12601-3 [doi] LID - 433 AB - BACKGROUND: Type 2 diabetes (T2D) is sub-optimally managed for many in Aotearoa New Zealand, and disproportionately affects Maori and Pacific peoples. In February 2021, SGLT2i/GLP1RA agents were funded for use for the first time with prioritisation for Maori, Pacific and those with cardiovascular and/or renal disease or risk (CVRD). This study evaluates the impact of health system factors on initiation of SGLT2i/GLP1RA therapy. METHODS: Primary care data was collected for patients with T2D aged 18-75 years from four primary care organisations (302 general practices) in the Auckland / Waikato region of New Zealand (Feb 2021 - July 2022). Initiation of SGLT2i/GLP1RA therapy was reviewed by patient (age, gender, ethnicity, CVRD status) and health system variables (funding, provider type, staffing, patient numbers, rurality, after-hours access). Logistic regression was used to estimate the odds ratio of a patient being dispensed SGLT2i/GLP1RA. RESULTS: Of 57,743 patients with T2D, 22,331 were eligible for funded SGLT2i/GLP1RA access and 10,272 of those (46.0%) were prescribed. Initiation of therapy was highest in Maori (50.8%) and Pacific (48.8%) patients (vs. 36.2-40.7% of other ethnic groups; P < 0.001), but was comparable in those with and without CVRD (47.1% vs. 48.9%; P = 0.2). Prescribing was highest in practices with higher doctor/patient numbers, low-cost fees, Maori health providers and clinics without after-hours access. CONCLUSION: Prioritised access for SGLT2i/GLP1RA appears to be associated with a reduced health equity gap for Maori and Pacific patients with T2D in NZ, but work is required to improve prescribing for patients with CVRD. CI - (c) 2025. The Author(s). FAU - Chepulis, Lynne AU - Chepulis L AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. Lynnec@waikato.ac.nz. FAU - Rodrigues, Mark AU - Rodrigues M AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. FAU - Gan, Han AU - Gan H AD - School of Computing and Mathematical Scienes, University of Waikato, Hamilton, New Zealand. FAU - Keenan, Rawiri AU - Keenan R AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. FAU - Kenealy, Tim AU - Kenealy T AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Murphy, Rinki AU - Murphy R AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. AD - Health New Zealand / Te Whatu Ora Te Toka Tumai, Auckland, New Zealand. FAU - Karu, Leanne Te AU - Karu LT AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Scott-Jones, Jo AU - Scott-Jones J AD - Midlands Health Network, Hamilton, New Zealand. FAU - Clark, Penny AU - Clark P AD - Northcare Medical Centre, Hamilton, New Zealand. FAU - Moffitt, Allan AU - Moffitt A AD - Procare Health Limited, Auckland, New Zealand. FAU - Mustafa, Sara AU - Mustafa S AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. FAU - Lawrenson, Ross AU - Lawrenson R AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. FAU - Paul, Ryan AU - Paul R AD - Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand. AD - Health New Zealand / Te Whatu Ora Waikato, Hamilton, New Zealand. LA - eng GR - 21/839/Health Research Council of New Zealand/ PT - Journal Article DEP - 20250326 PL - England TA - BMC Health Serv Res JT - BMC health services research JID - 101088677 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - HDC1R2M35U (empagliflozin) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucosides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - New Zealand MH - Male MH - Middle Aged MH - Female MH - Adult MH - Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - Adolescent MH - *Glucosides/therapeutic use/economics MH - *Recombinant Fusion Proteins/therapeutic use/economics MH - Young Adult MH - *Benzhydryl Compounds/therapeutic use/economics MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/economics MH - *Hypoglycemic Agents/therapeutic use/economics MH - Primary Health Care MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments PMC - PMC11938655 OTO - NOTNLM OT - GLP1RA OT - Health system access OT - SGLT2i OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was approved by the Health and Disability Ethics Committee of New Zealand (ref: 19/CEN/8). Consent for publication: Not applicable. Only deidentified data was analysed. Competing interests: The authors declare no competing interests. EDAT- 2025/03/27 06:28 MHDA- 2025/03/27 06:29 PMCR- 2025/03/26 CRDT- 2025/03/27 00:50 PHST- 2024/02/27 00:00 [received] PHST- 2025/03/17 00:00 [accepted] PHST- 2025/03/27 06:29 [medline] PHST- 2025/03/27 06:28 [pubmed] PHST- 2025/03/27 00:50 [entrez] PHST- 2025/03/26 00:00 [pmc-release] AID - 10.1186/s12913-025-12601-3 [pii] AID - 12601 [pii] AID - 10.1186/s12913-025-12601-3 [doi] PST - epublish SO - BMC Health Serv Res. 2025 Mar 26;25(1):433. doi: 10.1186/s12913-025-12601-3. PMID- 40138849 OWN - NLM STAT- MEDLINE DCOM- 20250413 LR - 20260731 IS - 1873-3360 (Electronic) IS - 0306-4530 (Linking) VI - 176 DP - 2025 Jun TI - The effect of GLP-1RAs on mental health and psychotropics-induced metabolic disorders: A systematic review. PG - 107415 LID - S0306-4530(25)00138-6 [pii] LID - 10.1016/j.psyneuen.2025.107415 [doi] AB - BACKGROUND: Mental illnesses and psychotropic drug use are associated with an increased risk of weight gain and metabolic disorders. Growing evidence suggests that agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) might be safe and effective weight loss medications. However, the current evidence for the use of GLP-1RAs in individuals with obesity and mental illness is limited. OBJECTIVE: Evaluation of the safety and the impact of GLP-1RAs on mental health and psychotropics-induced metabolic disorders such as obesity and type 2 diabetes (T2D). METHODS: A literature search from January 1st, 2010 to August 31st, 2024 was conducted using PubMed and Cochrane Library online databases. Studies comprising adults with obesity or/and T2D and mental illness were included. Studies that examined individuals with obesity or/and T2D without mental illness and completed psychiatric questionnaires before and after GLP-1RAs treatment were also included. RESULTS: From the 36 included studies 18 examined the weight-reducing effect of GLP-1RAs in patients with mental disorders and the other studies examined patients without mental illness. GLP-1RAs lead to a significant weight loss and improvement of glycemic control in patients with mental illness on psychotropics. They showed a beneficial effect on mental health in patients with and without mental disorders and were not associated with a worsening of mental state, suicidality, new-onset mental illness, or increased psychiatric admissions. CONCLUSION: GLP-1RAs are safe and effective weight loss treatments for individuals with obesity and mental illness exerting a positive effect on mental state and quality of life. There is a need for RCTs with larger sample sizes, a longer treatment duration and longer follow-up periods to evaluate the long-term effect of GLP-1RAs. It would be of great interest to conduct studies investigating the use of GLP-1RAs with the purpose to treat mental illness in order to directly assess their use in improving mental health. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Breit, Sigrid AU - Breit S AD - Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. Electronic address: sigrid.breit@unibe.ch. FAU - Hubl, Daniela AU - Hubl D AD - Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250320 PL - England TA - Psychoneuroendocrinology JT - Psychoneuroendocrinology JID - 7612148 RN - 0 (Psychotropic Drugs) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Psychotropic Drugs/adverse effects MH - Obesity/drug therapy MH - *Mental Disorders/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Metabolic Diseases/chemically induced/drug therapy MH - Mental Health MH - Weight Loss/drug effects MH - Adult OTO - NOTNLM OT - GLP-1RAs OT - Mental illness OT - Obesity OT - Quality of life OT - T2D COIS- Declaration of Competing Interest We declare no conflicts of interest. EDAT- 2025/03/27 16:08 MHDA- 2025/04/14 00:25 CRDT- 2025/03/26 19:04 PHST- 2024/11/14 00:00 [received] PHST- 2025/02/17 00:00 [revised] PHST- 2025/02/22 00:00 [accepted] PHST- 2025/04/14 00:25 [medline] PHST- 2025/03/27 16:08 [pubmed] PHST- 2025/03/26 19:04 [entrez] AID - S0306-4530(25)00138-6 [pii] AID - 10.1016/j.psyneuen.2025.107415 [doi] PST - ppublish SO - Psychoneuroendocrinology. 2025 Jun;176:107415. doi: 10.1016/j.psyneuen.2025.107415. Epub 2025 Mar 20. PMID- 40132747 OWN - NLM STAT- MEDLINE DCOM- 20250611 LR - 20260822 IS - 1097-6833 (Electronic) IS - 0022-3476 (Print) IS - 0022-3476 (Linking) VI - 282 DP - 2025 Jul TI - Metabolic and Bariatric Surgery Utilization in the Era of Glucagon-Like Peptide-1 Receptor Agonists among Adolescents versus Adults. PG - 114564 LID - S0022-3476(25)00104-0 [pii] LID - 10.1016/j.jpeds.2025.114564 [doi] AB - This cross-sectional study analyzed adolescent metabolic and bariatric surgery (MBS) utilization before and after glucagon-like peptide-1 receptor agonist (GLP-1RA) medication approval, comparing trends across race and ethnic groups. Although both MBS and GLP-1RA are effective weight management strategies, adolescent MBS utilization increased, while adult rates declined from 2021 through 2023. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Messiah, Sarah E AU - Messiah SE AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX; Children's Health System of Texas, Children's and UTSW, Dallas, TX. Electronic address: Sarah.Messiah@UTSouthwestern.edu. FAU - Ernest, Deepali K AU - Ernest DK AD - University of Texas Health Science Center at Houston, School of Public Health, Houston, TX. FAU - Atem, Folefac D AU - Atem FD AD - University of Texas Health Science Center at Houston, School of Public Health, Houston, TX. FAU - Qureshi, Faisal G AU - Qureshi FG AD - Children's Health System of Texas, Children's and UTSW, Dallas, TX; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Mathew, M Sunil AU - Mathew MS AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX; Children's Health System of Texas, Children's and UTSW, Dallas, TX. FAU - Francis, Jackson M AU - Francis JM AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX; Children's Health System of Texas, Children's and UTSW, Dallas, TX. FAU - Wheelington, Alicia AU - Wheelington A AD - Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Allicock, Marlyn A AU - Allicock MA AD - University of Texas Health Science Center at Houston, School of Public Health, Houston, TX. FAU - Cartwright, Bethany R AU - Cartwright BR AD - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX; Children's Health System of Texas, Children's and UTSW, Dallas, TX; Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Schneider, Benjamin E AU - Schneider BE AD - Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Cruz-Munoz, Nestor de la AU - Cruz-Munoz N AD - Dewitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. FAU - Lipshultz, Steven E AU - Lipshultz SE AD - Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY. FAU - Lingvay, Ildiko AU - Lingvay I AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX; Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Almandoz, Jaime P AU - Almandoz JP AD - Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Barlow, Sarah E AU - Barlow SE AD - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX; Children's Health System of Texas, Children's and UTSW, Dallas, TX. LA - eng GR - U01 HD052104/HD/NICHD NIH HHS/United States GR - R01 HL087000/HL/NHLBI NIH HHS/United States GR - F31 HL094100/HL/NHLBI NIH HHS/United States GR - P30 DK127984/DK/NIDDK NIH HHS/United States GR - R01 CA127642/CA/NCI NIH HHS/United States GR - K12 HD028820/HD/NICHD NIH HHS/United States GR - R01 HL095127/HL/NHLBI NIH HHS/United States GR - T32 HL007188/HL/NHLBI NIH HHS/United States GR - R01 HL053392/HL/NHLBI NIH HHS/United States GR - R01 HL072705/HL/NHLBI NIH HHS/United States GR - R21 HD105129/HD/NICHD NIH HHS/United States GR - R01 HL111459/HL/NHLBI NIH HHS/United States GR - R01 HL078522/HL/NHLBI NIH HHS/United States GR - R01 HL109090/HL/NHLBI NIH HHS/United States GR - U01 HD052102/HD/NICHD NIH HHS/United States GR - R13 HL087708/HL/NHLBI NIH HHS/United States GR - K30 HL004537/HL/NHLBI NIH HHS/United States GR - R01 MD011686/MD/NIMHD NIH HHS/United States GR - U01 AI050274/AI/NIAID NIH HHS/United States GR - P01 CA068484/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20250323 PL - United States TA - J Pediatr JT - The Journal of pediatrics JID - 0375410 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Bariatric Surgery/statistics & numerical data/trends MH - Adolescent MH - Cross-Sectional Studies MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Young Adult MH - *Diabetes Mellitus, Type 2/drug therapy PMC - PMC12184987 MID - NIHMS2086556 OTO - NOTNLM OT - adolescents OT - adults OT - bariatric surgery OT - prevalence COIS- Declaration of Competing Interest All phases of this study were supported by NICHD grant R21HD105129. The National Institute of Child Health and Human Development had no role in the study design, data collection, and analysis. S.E.M. is funded by the National Institutes of Health, National Institute on Minority Health and Health Disparities (grant #R01MD011686) and the National Institute of Child Health and Human Development (grant #R21HD105129). B.R.C. Cartwright reported receiving grant from the American Diabetes Association (grant #7-23-JDFT2DY-05). S.E.L. is supported in part by the US Department of Health and Human Services Health Resources and Services Administration, Rockville, MD (HRSA-C76HF15614-10679 Pediatric Integrative Medicine Research Center), the National Center for Toxicological Research (NCTR-E0728711), the National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, CA127642, CA068484, HD052102, HD052104, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL109090, HL111459, HL095127, HD80002, HD028820), the Laura Coulter-Jones Foundation (Division of Pediatric Clinical Research), the Batchelor Foundation (Batchelor Children's Research Institute), the Children's Cardiomyopathy Foundation, Sofia's Hope, Inc, the Kyle John Rymiszewski Foundation, the Children's Hospital of Michigan Foundation, the Scott Howard Fund, and the Michael Garil Fund. EDAT- 2025/03/26 13:06 MHDA- 2025/06/12 00:38 PMCR- 2025/07/01 CRDT- 2025/03/25 20:27 PHST- 2024/12/21 00:00 [received] PHST- 2025/02/25 00:00 [revised] PHST- 2025/03/19 00:00 [accepted] PHST- 2025/06/12 00:38 [medline] PHST- 2025/03/26 13:06 [pubmed] PHST- 2025/03/25 20:27 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - S0022-3476(25)00104-0 [pii] AID - 10.1016/j.jpeds.2025.114564 [doi] PST - ppublish SO - J Pediatr. 2025 Jul;282:114564. doi: 10.1016/j.jpeds.2025.114564. Epub 2025 Mar 23. PMID- 40128152 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20260127 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 109 IP - 9 DP - 2025 Sep 1 TI - Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients. PG - e501-e507 LID - 10.1097/TP.0000000000005361 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), initially approved for the management of diabetes, have demonstrated a wide range of metabolic benefits. However, their benefit and safety profile in liver transplant (LT) recipients remain poorly defined. METHODS: This study retrospectively analyzed adults who had undergone LT and had concomitant type 2 diabetes mellitus. Thirty-eight post-LT recipients treated with GLP-1RA for type 2 diabetes mellitus were matched with patients treated with insulin therapy 1:1 using propensity scoring for age, sex, ethnicity, cause of cirrhosis, and immunosuppression. This matching aimed to assess the metabolic effects and safety profile of GLP-1RA after LT. RESULTS: The 2 groups were similar at baseline with regard to clinical characteristics, except that time from LT was greater in patients who were on GLP-1RA. Semaglutide was the most commonly used GLP-1RA. LT recipients who received GLP-1RA lost approximately 8% of body weight during 12 mo, whereas patients on insulin therapy gained approximately 10% of body weight during the same period. Patients on GLP-1RA were less likely to have hepatic steatosis compared with patients on insulin therapy post-LT. Both GLP-1 and insulin were well tolerated, with no significant impact on renal function, immunosuppression, or rejection. GLP-1RA was stopped in only 1 patient due to persistent nausea. CONCLUSIONS: GLP-1RA therapy is safe after LT and is well tolerated. Aside from glycemic control, metabolic benefits of GLP-1RA included weight loss and lower prevalence of steatosis in LT recipients. The study findings provide much-needed safety data for GLP-1RA in LT patients and foundational data to design prospective trials to evaluate metabolic benefits of GLP-1RA. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Yakubu, Idris AU - Yakubu I AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Spengler, Joseph AU - Spengler J AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA. FAU - Taylor, Perry AU - Taylor P AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - LaPorte, Michael AU - LaPorte M AD - Virginia Commonwealth University School of Pharmacy, Richmond, VA. FAU - Brown, Andrew AU - Brown A AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Sterling, Sara AU - Sterling S AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Agegnehu, Bem AU - Agegnehu B AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Iaria, Aoife AU - Iaria A AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Marks, Ryan AU - Marks R AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Sprague, Taylor AU - Sprague T AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Pontinha, Vasco AU - Pontinha V AD - Virginia Commonwealth University School of Pharmacy, Richmond, VA. FAU - Patel, Vaishali AU - Patel V AD - Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA. FAU - Patidar, Kavish R AU - Patidar KR AD - Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX. AD - Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX. FAU - Siddiqui, Mohammad Shadab AU - Siddiqui MS AD - Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA. LA - eng PT - Journal Article DEP - 20250325 PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - *Liver Transplantation/adverse effects MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Aged MH - Insulin/therapeutic use MH - Adult MH - Blood Glucose/metabolism/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Time Factors MH - Weight Loss/drug effects MH - *End Stage Liver Disease/complications/surgery MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/25 06:25 MHDA- 2025/08/31 19:52 CRDT- 2025/03/25 00:02 PHST- 2025/08/31 19:52 [medline] PHST- 2025/03/25 06:25 [pubmed] PHST- 2025/03/25 00:02 [entrez] AID - 00007890-990000000-01034 [pii] AID - 10.1097/TP.0000000000005361 [doi] PST - ppublish SO - Transplantation. 2025 Sep 1;109(9):e501-e507. doi: 10.1097/TP.0000000000005361. Epub 2025 Mar 25. PMID- 40127835 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 3 DP - 2025 May TI - Renoprotective mechanisms of glucagon-like peptide-1 receptor agonists. PG - 101641 LID - S1262-3636(25)00036-9 [pii] LID - 10.1016/j.diabet.2025.101641 [doi] AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone, secreted from gut endocrine cells, which acts to potentiate nutrient-induced insulin secretion. Activation of its receptor, GLP-1R, decreases glucagon secretion and gastric emptying, thereby decreasing blood glucose and body weight. It is largely through these mechanisms that Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the treatment of type 2 diabetes. More recently, preclinical and clinical studies have reported that these agents have potent extra-pancreatic effects, exhibiting cardioprotective and renoprotective actions. The recent FLOW trial was the first multicentre clinical trial investigating the effect of GLP-1RAs on a primary renal outcome and reported robust evidence that GLP-1RAs are renoprotective. Studies in rodent models of renal injury have shown that gain and loss of GLP-1R signalling improves or deteriorates kidney function. However, the precise mechanisms responsible for renal benefits of GLP-1RAs are not yet fully understood. While prolonged activation of GLP-1 receptors (GLP-1R) has been shown to reverse diabetes-related disruptions in gene expression across various renal cell populations, GLP-1R expression in both rodent and human kidneys is thought to be primarily confined to certain vascular smooth muscle cells. This review discusses recent advances in our understanding of the effects of GLP-1 medicines on the kidney with a focus on indirect and direct mechanisms of action. CI - Copyright (c) 2025. Published by Elsevier Masson SAS. FAU - Chen, J AU - Chen J AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, 3004, Victoria, Australia. FAU - Cooper, M E AU - Cooper ME AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, 3004, Victoria, Australia. FAU - Coughlan, M T AU - Coughlan MT AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, 3004, Victoria, Australia; Baker Heart and Diabetes Institute, Melbourne, 3004, Victoria, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Science, Monash University Parkville Campus, 381 Royal Parade, Parkville, 3052, Victoria, Australia. Electronic address: melinda.coughlan@monash.edu. LA - eng PT - Journal Article PT - Review DEP - 20250322 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Kidney/drug effects/metabolism MH - *Diabetic Nephropathies/prevention & control/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Diabetic nephropathy OT - Glucagon OT - Glucagon-like protein-1 OT - Kidney OT - Renal COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/25 00:38 MHDA- 2025/05/01 12:29 CRDT- 2025/03/24 20:33 PHST- 2024/12/06 00:00 [received] PHST- 2025/03/18 00:00 [revised] PHST- 2025/03/20 00:00 [accepted] PHST- 2025/05/01 12:29 [medline] PHST- 2025/03/25 00:38 [pubmed] PHST- 2025/03/24 20:33 [entrez] AID - S1262-3636(25)00036-9 [pii] AID - 10.1016/j.diabet.2025.101641 [doi] PST - ppublish SO - Diabetes Metab. 2025 May;51(3):101641. doi: 10.1016/j.diabet.2025.101641. Epub 2025 Mar 22. PMID- 40119283 OWN - NLM STAT- MEDLINE DCOM- 20250514 LR - 20260612 IS - 2731-4553 (Electronic) IS - 2731-4553 (Linking) VI - 26 IP - 1 DP - 2025 Mar 21 TI - Optimizing SGLT2 inhibitor and GLP-1 RA prescribing in high-risk patients with diabetes: a Department of Veterans Affairs quality improvement intervention. PG - 78 LID - 10.1186/s12875-025-02709-0 [doi] LID - 78 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 (SGLT2) inhibitors have dramatic clinical benefits, but many appropriate patients do not receive them. We developed a quality improvement (QI) intervention to increase the adoption of these drugs in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and/or heart failure (HF). The purpose of this study was to examine whether the intervention increased the use of SGLT2 inhibitors and GLP-1 RAs. METHODS: The intervention included: (1) education, academic detailing (1:1 pharmacist to clinician coaching), and audit and feedback directed at providers and allied health professionals at the Veterans Affairs Ann Arbor Healthcare System (VAAAHS); (2) outreach and inreach to patients with T2D and ASCVD, CKD, and/or HF who were not on GLP-1 RAs or SGLT2 inhibitors at baseline. Patients were identified and outcomes evaluated using existing VA national reports. We performed a difference-in-difference analysis of the change in GLP-1 RA and SGLT2 inhibitor prescribing rates before, during, and after the intervention, comparing rates in VAAAHS to rates in the same VA region (called a Veterans Integrated Service Network (VISN)) and the VA nationally to determine whether the rates of prescribing increased faster in VAAAHS than the VISN or VA nationally. RESULTS: Home telehealth nurses and clinical pharmacy practitioners (CPPs) provided outreach to 445 patients; 48% (n = 215) of whom initiated SGLT2 inhibitors or GLP-1 RAs. Four CPPs provided 101 academic detailing sessions to 72 providers. Prior to the intervention, the prescribing rate was 22.7% in VAAAHS, 20.3% in the VISN 10 region, and 18.7% in VA nationally. At the end of the 12-month intervention, the prescribing rate had increased to 37.9% in VAAAHS, 28.4% in the VISN 10 region, and 26.5% in VA nationally. Six-months post-intervention, the prescribing rate continued to increase to 42.4% in VAAAHS, 32.2% in the VISN 10 region, and 30.2% in VA nationally. The rate of prescribing growth in VAAAHS was significantly faster than in the VISN or VA nationally (p < 0.001). CONCLUSION: Our multidisciplinary QI intervention increased SGLT2 inhibitor and GLP-1 RA prescribing approximately 8% points faster than the national average. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Yun, Shira AU - Yun S AD - VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. AD - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. FAU - Hurren, Kathryn AU - Hurren K AD - VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. FAU - Holleman, Rob AU - Holleman R AD - VA Center for Clinical Management Research, Ann Arbor, MI, USA. FAU - Klamerus, Mandi AU - Klamerus M AD - VA Center for Clinical Management Research, Ann Arbor, MI, USA. FAU - Tremblay, Adam AU - Tremblay A AD - VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. AD - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. FAU - Sussman, Jeremy B AU - Sussman JB AD - VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. jeremysu@med.umich.edu. AD - VA Center for Clinical Management Research, Ann Arbor, MI, USA. jeremysu@med.umich.edu. AD - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. jeremysu@med.umich.edu. AD - Institute for Healthcare Policy and Innovation, Ann Arbor, MI, USA. jeremysu@med.umich.edu. AD - , 2800 Plymouth Road, Building 16, Room 335E, Ann Arbor, USA. jeremysu@med.umich.edu. LA - eng PT - Journal Article DEP - 20250321 PL - England TA - BMC Prim Care JT - BMC primary care JID - 9918300889006676 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - United States MH - *Quality Improvement/organization & administration MH - United States Department of Veterans Affairs MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Renal Insufficiency, Chronic/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Heart Failure/drug therapy MH - *Practice Patterns, Physicians'/statistics & numerical data PMC - PMC11927310 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - Medication therapy management OT - Quality improvement OT - Sodium glucose cotransporter-2 (SGLT2) inhibitor OT - Type 2 diabetes OT - Veterans COIS- Declarations. Ethics approval and consent to participate: Not applicable. The VA Ann Arbor Healthcare System's (VAAAHCS) Quality Safety Value and Risk (QSVR) department designated this project as non-research. Thus, obtaining consent from clinicians and patients was not required. All authors and the VAAAHCS Director have attested that the findings reported in this publication were not derived from activities constituting research as described in VHA Program Guide 1200.21. The project generating these findings was a non-research operations activity. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/03/22 20:46 MHDA- 2025/03/22 20:47 PMCR- 2025/03/21 CRDT- 2025/03/22 00:36 PHST- 2024/04/09 00:00 [received] PHST- 2025/01/08 00:00 [accepted] PHST- 2025/03/22 20:47 [medline] PHST- 2025/03/22 20:46 [pubmed] PHST- 2025/03/22 00:36 [entrez] PHST- 2025/03/21 00:00 [pmc-release] AID - 10.1186/s12875-025-02709-0 [pii] AID - 2709 [pii] AID - 10.1186/s12875-025-02709-0 [doi] PST - epublish SO - BMC Prim Care. 2025 Mar 21;26(1):78. doi: 10.1186/s12875-025-02709-0. PMID- 40117955 OWN - NLM STAT- MEDLINE DCOM- 20250409 LR - 20260722 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 5 DP - 2025 May TI - Effectiveness of adding glucagon-like peptide-1 receptor agonist on diabetes complications and mortality among basal insulin-treated people with type 2 diabetes: A real-world Korean study. PG - 108983 LID - S1056-8727(25)00036-4 [pii] LID - 10.1016/j.jdiacomp.2025.108983 [doi] AB - AIMS: To compare the effectiveness of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) on composite of diabetes-related complications and mortality with that of adding short-acting insulin (SAI) or shifting to premixed insulin among basal insulin (BI)-treated individuals with type 2 diabetes mellitus (T2DM) in South Korea. METHODS: From the Health Insurance Review and Assessment Service database, individuals with T2DM who initiated BI treatment and had advanced their treatment regimen from July 1, 2012, to December 31, 2018. RESULTS: A total of 38,634 individuals with T2DM were included in this study. Compared to adding SAI to BI, adding GLP-1RA was associated with decreased risks of cardiovascular complications (hazard ratio 0.56; 95 % confidence interval 0.43-0.72), severe microvascular complications (0.30; 0.19-0.48), diabetes-related hospitalization (0.62; 0.53-0.73), and all-cause mortality (0.27; 0.13-0.57). Compared to switching to premixed insulin, adding GLP-1RA was also associated with lower risk of cardiovascular complications (0.65; 0.51-0.84), severe microvascular complications (0.36; 0.22-0.58), diabetes-related hospitalization (0.62; 0.53-0.73), and all-cause mortality (0.32; 0.15-0.67). CONCLUSIONS: In this real-world Korean study, adding GLP-1RA to BI reduced risks of diabetes complications and all-cause mortality than adding SAI or shifting to premixed insulin. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ha, Kyoung Hwa AU - Ha KH AD - Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Kim, Won AU - Kim W AD - Medical Affairs, Sanofi Korea, Seoul, Republic of Korea. FAU - Kim, Dong Han AU - Kim DH AD - Medical Affairs, Sanofi Korea, Seoul, Republic of Korea. FAU - Kim, Dae Jung AU - Kim DJ AD - Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: djkim@ajou.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250226 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Female MH - Republic of Korea/epidemiology MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Insulin/therapeutic use MH - *Diabetes Complications/mortality/epidemiology/prevention & control MH - Drug Therapy, Combination MH - Adult MH - Treatment Outcome MH - Retrospective Studies MH - Cardiovascular Diseases/prevention & control/mortality OTO - NOTNLM OT - Basal insulin OT - Diabetes complications OT - GLP-1RA OT - Intensification OT - Mortality OT - Type 2 diabetes mellitus COIS- Declaration of competing interest Won Kim and Dong Han Kim are employees of Sanofi. The other authors declare there are no potential conflicts of interest relevant to this article. EDAT- 2025/03/22 00:41 MHDA- 2025/04/10 00:20 CRDT- 2025/03/21 19:09 PHST- 2024/09/30 00:00 [received] PHST- 2025/02/07 00:00 [revised] PHST- 2025/02/25 00:00 [accepted] PHST- 2025/04/10 00:20 [medline] PHST- 2025/03/22 00:41 [pubmed] PHST- 2025/03/21 19:09 [entrez] AID - S1056-8727(25)00036-4 [pii] AID - 10.1016/j.jdiacomp.2025.108983 [doi] PST - ppublish SO - J Diabetes Complications. 2025 May;39(5):108983. doi: 10.1016/j.jdiacomp.2025.108983. Epub 2025 Feb 26. PMID- 40117297 OWN - NLM STAT- MEDLINE DCOM- 20250514 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 5 DP - 2025 May TI - FRONTIER: FReeStyle Libre system use in Ontario among people with diabetes in the IC/ES database-Evidence from real-world practice: Patients on basal insulin, glucagon-like peptide 1 receptor agonist or oral therapies. PG - 2637-2646 LID - 10.1111/dom.16266 [doi] AB - AIM: We aimed to investigate glycated haemoglobin (HbA1c) levels and healthcare resource utilization (HCRU; emergency department [ED] visits or hospitalization) before and after adoption of FreeStyle Libre sensor-based glucose monitoring systems (FSL) by people with type 2 diabetes mellitus (T2DM) on basal insulin without glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy, basal insulin with GLP-1 RA therapy, GLP-1 RA therapy without insulin or oral therapy alone. MATERIALS AND METHODS: Routinely collected administrative health data (housed at IC/ES, formerly the Institute for Clinical Evaluative Sciences) in Ontario, Canada were used to identify 20 253 people with T2DM who had a first FSL claim between 16 September 2019 and 31 August 2020 (index date) and remained active on FSL for 24 months' follow-up. HCRU was measured for 12 months before the index date and the last 12 months of the 24-month follow-up period. HbA1c data were taken from the latest tests in each period. RESULTS: Mean HbA1c was statistically significantly reduced after FSL acquisition among people aged 65 years in all four treatment groups (range, 0.3-0.8% reduction). After FSL acquisition, ED visits and hospitalization were statistically significantly reduced in the oral therapy only group and in some basal insulin subgroups (without GLP-1 RA, all except hospitalization aged /= 30% eGFR decline. RESULTS: The incidence of renal composite outcomes in the SGLT2i-preceding and GLP1Ra (dulaglutide or liraglutide)-preceding groups was not significantly different. It also did not differ between the dulaglutide and liraglutide users. The incidence of >/= 30% eGFR decline was more frequent in liraglutide users, with an odds ratio of 2.63 (95% confidence interval: 1.07-6.45, p = 0.04), with a significantly larger decrease in albuminuria in liraglutide users, with an odds ratio of 0.44 (95% confidence interval: 0.04-0.85, p = 0.03). CONCLUSIONS: Dulaglutide and liraglutide may have different effects on albuminuria and the kidney function in combination with SGLT2i. FAU - Muta, Yoshimi AU - Muta Y FAU - Kobayashi, Kazuo AU - Kobayashi K FAU - Toyoda, Masao AU - Toyoda M FAU - Tsukamoto, Shunichiro AU - Tsukamoto S FAU - Tsuriya, Daisuke AU - Tsuriya D FAU - Takashi, Yuichi AU - Takashi Y FAU - Yokomizo, Hisashi AU - Yokomizo H FAU - Takeshita, Kei AU - Takeshita K FAU - Hashimoto, Takuya AU - Hashimoto T FAU - Kimura, Moritsugu AU - Kimura M FAU - Tamura, Kouichi AU - Tamura K FAU - Kanasaki, Keizo AU - Kanasaki K FAU - Kawanami, Daiji AU - Kawanami D AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan. kawanami@fukuoka-u.ac.jp. LA - eng PT - Journal Article DEP - 20250420 PL - Japan TA - Tokai J Exp Clin Med JT - The Tokai journal of experimental and clinical medicine JID - 7704186 RN - WTT295HSY5 (dulaglutide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/administration & dosage/adverse effects/therapeutic use MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/administration & dosage MH - Male MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Middle Aged MH - Aged MH - Treatment Outcome MH - Glomerular Filtration Rate/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Albuminuria/etiology/epidemiology MH - *Hypoglycemic Agents/administration & dosage MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - Disease Progression EDAT- 2025/03/19 12:31 MHDA- 2025/03/19 12:32 CRDT- 2025/03/19 08:13 PHST- 2024/10/29 00:00 [received] PHST- 2024/11/20 00:00 [accepted] PHST- 2025/03/19 12:32 [medline] PHST- 2025/03/19 12:31 [pubmed] PHST- 2025/03/19 08:13 [entrez] PST - epublish SO - Tokai J Exp Clin Med. 2025 Apr 20;50(1):1-9. PMID- 40100584 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20261010 IS - 1535-1645 (Electronic) IS - 1523-3812 (Linking) VI - 27 IP - 5 DP - 2025 May TI - Sex Differences in Obesity and Its Treatment. PG - 278-285 LID - 10.1007/s11920-025-01601-z [doi] AB - PURPOSE OF REVIEW: Researchers and clinicians have increasingly recognized the importance of investigating and considering sex differences in obesity treatment. In this narrative review, we first summarized sex differences in select obesity-related conditions that have been the focus of studies of second-generation anti-obesity medications (i.e., semaglutide and tirzepatide) including type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure. We next described sex differences related to obesity treatments with a focus on the second-generation anti-obesity medications, semaglutide and tirzepatide. RECENT FINDINGS: Type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure demonstrated sex-specific pathways influenced by factors such as hormones and body composition. Lifestyle modification, on average, resulted in larger weight losses in males. In contrast, second-generation AOMs produced higher mean weight losses among females. Females reported more adverse events (e.g., nausea, vomiting) with second-generation anti-obesity medications. The few studies that have performed analyses of changes in obesity-related comorbidities stratified by sex have shown consistent improvements between males and females in heart failure and cardiovascular outcomes. Studies are needed to evaluate the effect of sex on the efficacy of anti-obesity medications including on mental health, investigate the mechanisms underlying these effects, and develop interventions to improve the availability and access of these medications. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ghanta, Aleena AU - Ghanta A AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. AD - University of Pennsylvania School of Nursing, Philadelphia, PA, USA. FAU - Wilson, Elizabeth AU - Wilson E AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. FAU - Chao, Ariana M AU - Chao AM AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. Ariana.Chao@jhu.edu. AD - University of Pennsylvania School of Nursing, Philadelphia, PA, USA. Ariana.Chao@jhu.edu. LA - eng GR - R56NR020466/NR/NINR NIH HHS/United States GR - R56NR020466/NR/NINR NIH HHS/United States PT - Journal Article PT - Review DEP - 20250318 PL - United States TA - Curr Psychiatry Rep JT - Current psychiatry reports JID - 100888960 RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Obesity/drug therapy/therapy MH - Female MH - Male MH - *Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Sex Factors MH - *Sex Characteristics MH - Sleep Apnea, Obstructive/drug therapy OTO - NOTNLM OT - Anti-obesity medication OT - GLP-1 receptor agonists OT - Obesity treatment OT - Sex differences OT - Weight loss COIS- Declarations. Competing Interests: AMC has served on advisory boards for Eli Lilly and Company and Boehringer Ingelheim and received grant support, on behalf of the University of Pennsylvania, from Eli Lilly and Company. Disclosures: AMC has served on advisory boards for Eli Lilly and Company and Boehringer Ingelheim and received grant support, on behalf of the University of Pennsylvania, from Eli Lilly and Company. EDAT- 2025/03/18 18:22 MHDA- 2025/04/16 18:24 CRDT- 2025/03/18 12:21 PHST- 2025/03/04 00:00 [accepted] PHST- 2025/04/16 18:24 [medline] PHST- 2025/03/18 18:22 [pubmed] PHST- 2025/03/18 12:21 [entrez] AID - 10.1007/s11920-025-01601-z [pii] AID - 10.1007/s11920-025-01601-z [doi] PST - ppublish SO - Curr Psychiatry Rep. 2025 May;27(5):278-285. doi: 10.1007/s11920-025-01601-z. Epub 2025 Mar 18. PMID- 40098267 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in type 2 diabetes according to baseline glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor use: A post hoc analysis of ONWARDS 1-5. PG - 3165-3175 LID - 10.1111/dom.16328 [doi] AB - AIMS: To assess the treatment effects of once-weekly insulin icodec (icodec) versus once-daily basal insulin comparators in individuals with type 2 diabetes (T2D) according to baseline glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) use. MATERIALS AND METHODS: This post hoc analysis of the randomized ONWARDS 1-5 trials of individuals with T2D assessed treatment outcomes by trial according to baseline GLP-1RA and/or SGLT2i use. RESULTS: At screening, 21.3% (801/3765) and 36.9% (1388/3765) of participants in ONWARDS 1-5 were treated with a GLP-1RA or an SGLT2i, respectively. Baseline characteristics were broadly similar across treatment arms irrespective of GLP-1RA/SGLT2i use; GLP-1RA users had numerically higher body mass indices than non-users. Across trials, there were no statistically significant treatment interactions by GLP-1RA or SGLT2i subgroups with respect to: change in glycated haemoglobin (HbA1c) and body weight from baseline to end of treatment (except for body weight change by SGLT2i use in ONWARDS 5); weekly basal insulin dose during the last 2 weeks of treatment (except SGLT2i use in ONWARDS 5); and achievement of HbA1c less than 7% without clinically significant or severe hypoglycaemia. Irrespective of GLP-1RA/SGLT2i use, the rates of clinically significant or severe hypoglycaemia were less than one episode per patient-year of exposure across all trials except ONWARDS 4 (basal-bolus trial). CONCLUSIONS: The efficacy and hypoglycaemia profile of icodec versus once-daily comparators was generally consistent across ONWARDS trials irrespective of background GLP-1RA and/or SGLT2i use. CI - (c) 2025 Novo Nordisk A/S and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Fu, Ariel AU - Fu A AUID- ORCID: 0009-0007-0220-5877 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kellerer, Monika AU - Kellerer M AUID- ORCID: 0000-0002-9834-5976 AD - Marienhospital, Department of Diabetes and Endocrinology, Stuttgart, Germany. FAU - Kumar, Bharath AU - Kumar B AUID- ORCID: 0009-0006-8691-6926 AD - Novo Nordisk India Private Limited, Bangalore, India. FAU - Sogaard, Stinne Byrholdt AU - Sogaard SB AUID- ORCID: 0000-0002-1611-4585 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Goldenberg, Ronald AU - Goldenberg R AUID- ORCID: 0000-0002-1788-3255 AD - LMC Diabetes and Endocrinology, Concord, Ontario, Canada. LA - eng GR - N/A/Novo Nordisk A/S/ PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20250317 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - *Hypoglycemia/chemically induced/epidemiology/prevention & control MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - Drug Administration Schedule MH - *Insulin/administration & dosage/adverse effects MH - Aged MH - Glycated Hemoglobin/analysis MH - Blood Glucose/drug effects PMC - PMC12046478 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - basal insulin OT - glycaemic control OT - hypoglycaemia OT - type 2 diabetes COIS- Tina Vilsboll has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot/Roche, Eli Lilly, Gilead, GSK, Mundipharma, Novo Nordisk, Sanofi, Sun Pharmaceuticals and Zealand Pharma. Ariel Fu and Stinne Byrholdt Sogaard are employees of Novo Nordisk and hold stock in Novo Nordisk. Monika Kellerer has received consulting fees from Abbott, Bayer AG, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and honoraria for lectures, presentations, speakers' bureaus and educational events from Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim, Eli Lilly, MedLearning, MSD, Novartis, Novo Nordisk and SCIARC. Bharath Kumar is an employee of Novo Nordisk India Private Limited. Ronald Goldenberg has received research fees from Eli Lilly, Novo Nordisk and Sanofi (paid to their institution), as well as consultancy and lecture honoraria from Eli Lilly, Novo Nordisk and Sanofi. EDAT- 2025/03/18 06:22 MHDA- 2025/05/03 22:27 PMCR- 2025/05/02 CRDT- 2025/03/18 01:23 PHST- 2025/02/17 00:00 [revised] PHST- 2024/11/29 00:00 [received] PHST- 2025/03/02 00:00 [accepted] PHST- 2025/05/03 22:27 [medline] PHST- 2025/03/18 06:22 [pubmed] PHST- 2025/03/18 01:23 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16328 [pii] AID - 10.1111/dom.16328 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3165-3175. doi: 10.1111/dom.16328. Epub 2025 Mar 17. PMID- 40098249 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260818 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. PG - 3094-3103 LID - 10.1111/dom.16316 [doi] AB - AIMS: To investigate the putative association between semaglutide and non-arteritic anterior ischaemic optic neuropathy (NAION). MATERIALS AND METHODS: Data from national health registries in Denmark (2018-2024) and Norway (2018-2022) were used to compare NAION risk in individuals with type 2 diabetes initiating semaglutide versus sodium-glucose co-transporter 2 inhibitors (SGLT-2is). A supplementary self-controlled analysis examined NAION risk among all semaglutide users. National estimates were pooled using a fixed-effects model. RESULTS: We identified 44 517 users of semaglutide for the management of type 2 diabetes in Denmark and 16 860 in Norway, with a total of 32 NAION events observed. The unadjusted incidence rate of NAION was 2.19/10 000 person-years among Danish semaglutide initiators, compared to 1.18 among SGLT-2i initiators. In Norway, the corresponding rates were 2.90 and 0.92, respectively. After adjustment, the pooled hazard ratio (HR) was 2.81 (95% confidence interval [CI] 1.67-4.75), and the incidence rate difference (IRD) was +1.41 (95% CI +0.53 to +2.29) per 10 000 person-years. Estimates were consistent across both countries but higher and less precise in Norway (HR 7.25; 95% CI 2.34-22.4) compared to Denmark (HR 2.17; 95% CI 1.20-3.92). Results remained consistent across sensitivity and supplementary analyses, with a stronger association observed in a post hoc per-protocol analysis (HR 6.35; 95% CI 2.88-14.0). In the supplementary self-controlled study, symmetry ratios (SRs) for NAION were 1.14 (95% CI 0.55-2.36) in Denmark and 2.67 (95% CI 0.91-8.99) in Norway. CONCLUSIONS: The use of semaglutide for managing type 2 diabetes is associated with an increased risk of NAION compared with the use of SGLT-2is. However, the absolute risk remains low. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Simonsen, Emma AU - Simonsen E AUID- ORCID: 0000-0002-0254-0479 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Lund, Lars Christian AU - Lund LC AUID- ORCID: 0000-0001-8651-6072 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Ernst, Martin Thomsen AU - Ernst MT AUID- ORCID: 0000-0001-9003-3823 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Hjellvik, Vidar AU - Hjellvik V AUID- ORCID: 0000-0002-2379-9906 AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Hegedus, Laszlo AU - Hegedus L AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Hamann, Steffen AU - Hamann S AUID- ORCID: 0000-0003-4318-2716 AD - Department of Ophthalmology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Jorstad, Oystein Kalsnes AU - Jorstad OK AUID- ORCID: 0000-0003-1259-0653 AD - Department of Ophthalmology, Oslo University Hospital, Oslo, Norway. AD - Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Gulseth, Hanne Lovdal AU - Gulseth HL AUID- ORCID: 0000-0001-5057-4449 AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Karlstad, Oystein AU - Karlstad O AUID- ORCID: 0000-0003-1204-787X AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng GR - 2025-00052B/Danmarks Frie Forskningsfond/ PT - Journal Article DEP - 20250317 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Denmark/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Middle Aged MH - Norway/epidemiology MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - Aged MH - Incidence MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Cohort Studies MH - Registries MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046482 OTO - NOTNLM OT - SGLT2 inhibitor OT - antidiabetic drug OT - antiobesity drug OT - pharmaco-epidemiology OT - semaglutide OT - type 2 diabetes COIS- Lars Christian Lund has taught a full-day course in epidemiological methods in drug safety surveillance at Novo Nordisk, with funds paid to the University of Southern Denmark (no personal fees). Vidar Hjellvik reports participation in research projects funded by Novo Nordisk and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees), and with no relation to the work reported in this paper. Steffen Hamann has received grants from Rigshospitalet and the VELUX Foundation. None of these grants has any relation to the work reported in this paper. Oystein Kalsnes Jorstad has received a grant from Roche for developing an educational application. He receives royalties from SJJ Solutions for a syringe used in intravitreal injections. He has received consulting fees from SJJ Solutions and Oslo Economics. He has also received lecture fees from Allergan, Bayer, and Chiesi Farmaceutici, as well as support for meetings, travel, and attendance from SJJ Solutions. He holds patents for a needle for intravitreal injections and a glaucoma stent. Jorstad is also a member of the advisory boards for Allergan, Bayer, and Roche. None of these relationships has any relation to the work reported in this paper. Oystein Karlstad reports participation in research projects funded by Sanofi, Bristol Myers Squibb, Novo Nordisk, and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees) and with no relation to the work reported in this paper. Anton Pottegard reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Servier, and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees). Further, his research group has received one unrestricted grant from Novo Nordisk. None of these grants has any relation to the work reported in this paper. The remaining authors report no conflicts of interest. EDAT- 2025/03/18 06:22 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/03/18 01:22 PHST- 2025/02/21 00:00 [revised] PHST- 2025/01/12 00:00 [received] PHST- 2025/02/23 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/03/18 06:22 [pubmed] PHST- 2025/03/18 01:22 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16316 [pii] AID - 10.1111/dom.16316 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3094-3103. doi: 10.1111/dom.16316. Epub 2025 Mar 17. PMID- 40088335 OWN - NLM STAT- MEDLINE DCOM- 20250920 LR - 20260127 IS - 1432-1912 (Electronic) IS - 0028-1298 (Print) IS - 0028-1298 (Linking) VI - 398 IP - 9 DP - 2025 Sep TI - Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats. PG - 11919-11931 LID - 10.1007/s00210-025-03920-7 [doi] AB - Pre-existing diabetes raises the likelihood of Parkinson's disease (PD), according to epidemiological and animal research. Our study aimed to investigating the likely neuroprotective effect of metformin (Met) and/or semaglutide (Sem) in model of PD in male diabetic rats and the possible underlying mechanism. Type 2 diabetes (T2DM) was induced by giving high-fat diet (HFD) for 3 weeks followed by a single streptozotocin (STZ) injection (40 mg/kg, i.p., once dose) followed by injection of 9 doses of rotenone every 48 +/- 2 h for induction of PD. Met and/or Sema were administered to DM+PD via gastric gavage once daily for 4 weeks. In comparison with the DM+PD group, Met and/or Sem significantly lowered blood glucose levels, HOMA-IR, HbA1C, cholesterol, triglycerides, and LDL with significantly increased insulin and HDL levels. In addition, there was enhanced brain antioxidant status with lower oxidative-inflammatory stress biomarkers associated with improved rat cognitive, locomotor, and olfactory functions. A significant downregulation of caspase 3 and GFAP with concomitant upregulation of NRF2 protein expressions were observed in treated groups. Overall, co-treatment with Met and Sem elicited more efficacy than that of the individual regimen. When combined, the results of this study have demonstrated for the first time that Met and Sem work in concert to create neuroprotection in PD model of male diabetic rats compared to when taken separately. The study's findings indicate that Met and/or Sem have a restorative effect on T2DM and PD-induced changes in neurobehavioral and biochemical/molecular indices ascribed to the improvement of endogenous antioxidant systems, decreased lipid peroxidation, suppression of oxidative/inflammatory stress, and-most importantly-regulation of Nrf2 and caspase 3. CI - (c) 2025. The Author(s). FAU - Salem, Esraa A AU - Salem EA AD - Department of Medical Physiology, Faculty of Medicine, Menoufia University, Shebeen ElKom, 32511, Egypt. FAU - Alqahtani, Saad Misfer AU - Alqahtani SM AD - Department of Pathology, College of Medicine, The University Hospital, Najran University, Najran, Saudi Arabia. FAU - El-Shoura, Ehab A M AU - El-Shoura EAM AUID- ORCID: 0000-0003-2448-7549 AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt. ehabel-shoura@azhar.edu.eg. FAU - Zaghlool, Sameh S AU - Zaghlool SS AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University of Technology and Information (MTI), Mokattam, Cairo, 11571, Egypt. FAU - Abdelzaher, Lobna A AU - Abdelzaher LA AD - Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. FAU - Mohamed, Sally A M AU - Mohamed SAM AD - Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt. FAU - Alalhareth, Ibrahim S AU - Alalhareth IS AD - College of Pharmacy, The University Hospital, Najran University, Najran, Saudi Arabia. FAU - Sheref, Alzahraa A M AU - Sheref AAM AD - Department of Medical Physiology, Faculty of Medicine, Menoufia University, Shebeen ElKom, 32511, Egypt. LA - eng PT - Journal Article DEP - 20250315 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 9100L32L2N (Metformin) RN - 0 (Neuroprotective Agents) RN - 03L9OT429T (Rotenone) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (NF-E2-Related Factor 2) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Nfe2l2 protein, rat) SB - IM MH - Animals MH - Male MH - *Metformin/pharmacology/therapeutic use MH - *Neuroprotective Agents/pharmacology/therapeutic use MH - *Rotenone/toxicity MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism/blood MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Rats MH - Oxidative Stress/drug effects MH - *Behavior, Animal/drug effects MH - Blood Glucose/drug effects MH - Hypoglycemic Agents/pharmacology MH - Brain/drug effects/metabolism MH - Rats, Wistar MH - Diet, High-Fat MH - NF-E2-Related Factor 2 MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12449337 OTO - NOTNLM OT - CX3Cl1, Nrf2 OT - Diabetes OT - GFAP OT - Metformin OT - Parkinson OT - Semaglutide COIS- Declarations. Competing interest: The authors declare no competing interests. EDAT- 2025/03/16 11:18 MHDA- 2025/09/20 06:31 PMCR- 2025/03/15 CRDT- 2025/03/15 12:15 PHST- 2024/11/02 00:00 [received] PHST- 2025/02/11 00:00 [accepted] PHST- 2025/09/20 06:31 [medline] PHST- 2025/03/16 11:18 [pubmed] PHST- 2025/03/15 12:15 [entrez] PHST- 2025/03/15 00:00 [pmc-release] AID - 10.1007/s00210-025-03920-7 [pii] AID - 3920 [pii] AID - 10.1007/s00210-025-03920-7 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep;398(9):11919-11931. doi: 10.1007/s00210-025-03920-7. Epub 2025 Mar 15. PMID- 40087651 OWN - NLM STAT- MEDLINE DCOM- 20250315 LR - 20260924 IS - 1471-2415 (Electronic) IS - 1471-2415 (Linking) VI - 25 IP - 1 DP - 2025 Mar 14 TI - Anterior ischemic optic neuropathy in patients treated with semaglutide: report of four cases with a possible association. PG - 132 LID - 10.1186/s12886-025-03958-4 [doi] LID - 132 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used worldwide for its cardiometabolic benefits. However, it has recently been associated with nonarteritic anterior ischemic optic neuropathy (NAION). This report presents four clinical cases and explores a possible association. CASE PRESENTATION: Four male patients were diagnosed with NAION during semaglutide treatment, with treatment durations of less than one year in three cases. All presented with significant optic disc edema and intraretinal fluid on optical coherence tomography, along with crowded optic disc and small Bruch's membrane opening diameters (< 1.4 mm in three cases). One patient exhibited optic disc drusen. Visual field defects corresponded with ganglion cell layer atrophy on optical coherence tomography. Systemic risk factors varied; two patients had only obesity. CONCLUSIONS: Our observation suggests that individuals with small Bruch's membrane opening diameter may be at risk of developing NAION during semaglutide treatment. CI - (c) 2025. The Author(s). FAU - Ahmadi, Hamid AU - Ahmadi H AD - Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, Valdemar Hansens vej, 13, 2600, Glostrup, Denmark. hamid.ahmadi.01@regionh.dk. FAU - Hamann, Steffen AU - Hamann S AD - Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, Valdemar Hansens vej, 13, 2600, Glostrup, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark. LA - eng PT - Case Reports PT - Journal Article DEP - 20250314 PL - England TA - BMC Ophthalmol JT - BMC ophthalmology JID - 100967802 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Phenylpropionates) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Glucagon-Like Peptides/adverse effects MH - Middle Aged MH - Aged MH - Tomography, Optical Coherence MH - *Hypoglycemic Agents/adverse effects MH - Visual Fields MH - *Phenylpropionates/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Visual Acuity MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11908077 OTO - NOTNLM OT - Semaglutide OT - case-series. OT - nonarteritic anterior ischemic optic neuropathy COIS- Declarations. Ethics approval and consent to participate: Ethics committee approval was not required as the study utilized data obtained through standard patient care practices. The authors declare that they adhered to the CARE guidelines/methodology. Consent for publication: Informed written consent for publication was obtained from the patients. Competing interests: The authors declare no competing interests. EDAT- 2025/03/16 11:16 MHDA- 2025/03/16 11:17 PMCR- 2025/03/14 CRDT- 2025/03/15 00:40 PHST- 2025/01/20 00:00 [received] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/03/16 11:17 [medline] PHST- 2025/03/16 11:16 [pubmed] PHST- 2025/03/15 00:40 [entrez] PHST- 2025/03/14 00:00 [pmc-release] AID - 10.1186/s12886-025-03958-4 [pii] AID - 3958 [pii] AID - 10.1186/s12886-025-03958-4 [doi] PST - epublish SO - BMC Ophthalmol. 2025 Mar 14;25(1):132. doi: 10.1186/s12886-025-03958-4. PMID- 40086589 OWN - NLM STAT- MEDLINE DCOM- 20250421 LR - 20260526 IS - 1095-8584 (Electronic) IS - 0022-2828 (Linking) VI - 202 DP - 2025 May TI - Advances in incretin therapies for targeting cardiovascular disease in diabetes. PG - 102-115 LID - S0022-2828(25)00047-1 [pii] LID - 10.1016/j.yjmcc.2025.03.007 [doi] AB - The global prevalence of obesity is skyrocketing at an alarming rate, with recent data estimating that one-in-eight people are now living with the disease. Obesity is a chronic metabolic disorder that shares underlying pathophysiology with other metabolically-linked diseases such as type 2 diabetes mellitus, cardiovascular disease and diabetic cardiomyopathy. There is a distinct correlation between type 2 diabetes status and the likelihood of heart failure. Of note, there is an apparent sexual dimorphism, with women disproportionately affected with respect to the degree of severity of the cardiac phenotype of diabetic cardiomyopathy that results from diabetes. The current pharmacotherapies available for the attenuation of hyperglycaemia in type 2 diabetes are not always effective, and have varying degrees of efficacy in the setting of heart failure. Insulin can worsen heart failure prognosis whereas metformin, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and more recently, glucagon-like peptide-1 receptor agonists (GLP-1RAs), have demonstrated cardioprotection with their administration. This review will highlight the advancement of incretin therapies for individuals with diabetes and heart failure and explore newly-reported evidence of the clinical usefulness of GLP-1R agonists in this distinct phenotype of heart failure. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Roberts, Timothy D AU - Roberts TD AD - Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. FAU - Hutchinson, Dana S AU - Hutchinson DS AD - Metabolic G Protein-Coupled Receptor Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. FAU - Wootten, Denise AU - Wootten D AD - Metabolic G Protein-Coupled Receptor Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia. FAU - De Blasio, Miles J AU - De Blasio MJ AD - Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. Electronic address: Miles.deblasio@monash.edu. FAU - Ritchie, Rebecca H AU - Ritchie RH AD - Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. Electronic address: Rebecca.ritchie@monash.edu. LA - eng PT - Journal Article PT - Review DEP - 20250312 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Cardiovascular Diseases/drug therapy/etiology/metabolism MH - Hypoglycemic Agents/therapeutic use MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Failure/drug therapy OTO - NOTNLM OT - Cardiomyopathy OT - Diabetes OT - GLP-1R agonists OT - Heart failure OT - Incretin therapies OT - Obesity OT - Sex-differences COIS- Declaration of competing interest Nothing to disclose. EDAT- 2025/03/15 00:38 MHDA- 2025/04/22 00:26 CRDT- 2025/03/14 20:14 PHST- 2024/11/01 00:00 [received] PHST- 2025/02/12 00:00 [revised] PHST- 2025/03/11 00:00 [accepted] PHST- 2025/04/22 00:26 [medline] PHST- 2025/03/15 00:38 [pubmed] PHST- 2025/03/14 20:14 [entrez] AID - S0022-2828(25)00047-1 [pii] AID - 10.1016/j.yjmcc.2025.03.007 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2025 May;202:102-115. doi: 10.1016/j.yjmcc.2025.03.007. Epub 2025 Mar 12. PMID- 40086043 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 3 DP - 2025 Mar TI - Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5-15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials. PG - 103212 LID - S1871-4021(25)00029-3 [pii] LID - 10.1016/j.dsx.2025.103212 [doi] AB - BACKGROUND AND AIMS: Both semaglutide 2.4 mg and tirzepatide have been recently approved for chronic use in obesity. There is a lack of literature comparing the efficacy and safety of both these agents in people with obesity/overweight with or without type 2 diabetes (T2D). We systematically reviewed Phase 3 randomized controlled trials (RCTs) conducted with two agents to synthesize the comparative efficacy and safety outcomes. METHODS: We systematically searched PubMed electronic databases until December 15, 2024, using selected keywords and Boolean "AND." Subsequently, we compared the most closely matched trials conducted with semaglutide 2.4 mg and tirzepatide through an adjusted (if baseline imbalance in treatment outcome modifiers present) or unadjusted (in the absence of baseline imbalance) indirect treatment comparison method. RESULTS: We identified one trial each of semaglutide 2.4 mg (STEP-1) and tirzepatide 5, 10, and 15 mg (SURMOUNT-1) in obese or overweight people without T2D and one trial each of semaglutide 2.4 mg (STEP-2) and tirzepatide 10 and 15 mg (SURMOUNT-2) in overweight people with T2D that were almost entirely comparable concerning baseline outcome modifier characteristics. Our unadjusted analysis without individual patients' data found relatively higher (4 and 5.4 % additional) weight loss, HbA1c (-0.4 % additional) reduction, and fewer gastrointestinal side effects (GI S/E) with tirzepatide 10 and 15 mg, respectively, than with semaglutide 2.4 mg, in the intention-to-treat analysis. CONCLUSION: Tirzepatide 10 and 15 mg are more effective and have fewer GI S/E than semaglutide 2.4 mg. A well-powered head-to-head RCT is currently needed to confirm these findings. CI - Copyright (c) 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Singh, Akriti AU - Singh A AD - KPC Medical College & Hospital, Jadavpur, Kolkata, West Bengal, India. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - G. D Hospital & Diabetes Institute, Kolkata, West Bengal, India; Sun Valley Hospital & Diabetes Research Center, Guwahati, Assam, India; Horizon Life Line Multispecialty Hospital, Kolkata, West Bengal, India; Institute of Medical Science & SUM Hospital, Bhubaneswar, Odisha, India. Electronic address: drawadheshkumarsingh@gmail.com. FAU - Singh, Ritu AU - Singh R AD - Horizon Life Line Multispecialty Hospital, Kolkata, West Bengal, India. FAU - Misra, Anoop AU - Misra A AD - Diabetes Foundation (India), New Delhi, India; National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India; Fortis C-DOC Hospital for Diabetes & Allied Sciences, New Delhi, India. LA - eng PT - Comparative Study PT - Journal Article PT - Systematic Review DEP - 20250308 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/drug therapy/complications MH - Clinical Trials, Phase III as Topic MH - *Tirzepatide/therapeutic use/administration & dosage MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Efficacy OT - Obesity OT - Safety OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest Akriti Singh and Ritu Singh has no competing interests. Awadhesh Kumar Singh and Anoop Misra have received speaker's honoraria from Novo Nordisk and Eli Lilly. EDAT- 2025/03/15 00:38 MHDA- 2025/05/22 00:28 CRDT- 2025/03/14 19:02 PHST- 2025/01/27 00:00 [received] PHST- 2025/02/27 00:00 [revised] PHST- 2025/03/01 00:00 [accepted] PHST- 2025/05/22 00:28 [medline] PHST- 2025/03/15 00:38 [pubmed] PHST- 2025/03/14 19:02 [entrez] AID - S1871-4021(25)00029-3 [pii] AID - 10.1016/j.dsx.2025.103212 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Mar;19(3):103212. doi: 10.1016/j.dsx.2025.103212. Epub 2025 Mar 8. PMID- 40083081 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Time spent in glycaemic control with sustained body weight reduction with tirzepatide: A post hoc analysis of the SURPASS clinical trial programme. PG - 3223-3232 LID - 10.1111/dom.16337 [doi] AB - AIMS: This participant-level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions with tirzepatide treatment in participants with type 2 diabetes (T2D) from the SURPASS programme. MATERIALS AND METHODS: Participants (N = 6246) from SURPASS 1-5 were randomized to once weekly tirzepatide (5, 10 or 15 mg) or comparator (once weekly placebo, once weekly semaglutide 1 mg, insulin degludec or insulin glargine). Continuous time spent with HbA1c < 7.0% (53 mmol/mol), /=5% body weight reduction and combined HbA1c /=5% body weight reduction were assessed through 40 weeks (SURPASS-1, -2, and -5) or 52 weeks (SURPASS-3 and -4). The non-parametric Wilcoxon rank sum test was used to compare the median duration of continuous time spent in control, and logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period. RESULTS: Median time spent with HbA1c < 7.0% (53 mmol/mol) was 80% (tirzepatide) versus 70% (semaglutide) and 0% (placebo) of the treatment duration in 40-week studies, and 77%-85% (tirzepatide) versus 62% (insulin degludec) and 23% (insulin glargine) of the treatment duration in 52-week studies (p < 0.001). Time spent with HbA1c < 7.0% (53 mmol/mol) was generally similar across all tirzepatide doses in each study. Dose-dependent increases in time spent with >/=5% body weight reduction were observed with tirzepatide (median time spent: 20%-77% with tirzepatide versus 25% with semaglutide 1 mg) (p < 0.001). Tirzepatide-treated participants experienced longer time spent with HbA1c /=5% body weight reduction versus semaglutide (median: 35%-60% vs. 7%) (p < 0.001). CONCLUSIONS: In this post hoc analysis, people with T2D experienced substantially longer continuous time in glycaemic control and more sustained body weight reductions with tirzepatide versus placebo and active comparators. CI - (c) 2025 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bergman, Brandon K AU - Bergman BK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas, Texas, USA. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Batterham, Rachel L AU - Batterham RL AD - Eli Lilly and Company, Indianapolis, Indiana, USA. AD - Centre for Obesity Research, Department of Medicine, University College London, London, UK. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Liu, Minzhi AU - Liu M AD - Tigermed-BDM Inc., Somerset, New Jersey, USA. FAU - Sharma, Palash AU - Sharma P AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Karanikas, Chrisanthi A AU - Karanikas CA AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thieu, Vivian T AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250313 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin, Long-Acting) RN - OYN3CCI6QE (Tirzepatide) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - 54Q18076QB (insulin degludec) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glycemic Control MH - Glycated Hemoglobin/analysis/metabolism MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Tirzepatide MH - Insulin Glargine/administration & dosage/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Aged MH - Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Time Factors MH - Drug Administration Schedule MH - Double-Blind Method MH - Treatment Outcome MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046485 OTO - NOTNLM OT - body weight control OT - glycaemic control OT - tirzepatide OT - type 2 diabetes COIS- JR reports clinical research grants from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Pfizer and Sanofi; served on scientific advisory boards; received honorarium or consulting fees from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharma and Zealand; and received honoraria for lectures from Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk and Sanofi during the conduct of the study. WTG has served as a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand and Merck and as a site principal investigator for multicentred clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens and Pfizer. RLB is an employee and shareholder of Eli Lilly and Company and reports research grant support from Novo Nordisk, consultancy with Boehringer Ingelheim, Eli Lilly and Company, Gila Therapeutics Inc., GSK, Novo Nordisk, Pfizer and Rhythm Pharmaceuticals. ML was a contracted employee of Eli Lilly and Company at the time of this analysis. BKB, YC, PS, CAK and VTT are employees and shareholders of Eli Lilly and Company. EDAT- 2025/03/14 11:16 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/03/14 01:23 PHST- 2025/03/03 00:00 [revised] PHST- 2024/12/20 00:00 [received] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/03/14 11:16 [pubmed] PHST- 2025/03/14 01:23 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16337 [pii] AID - 10.1111/dom.16337 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3223-3232. doi: 10.1111/dom.16337. Epub 2025 Mar 13. PMID- 40081498 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20260529 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 187 DP - 2025 May TI - Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. PG - 171380 LID - S0196-9781(25)00041-5 [pii] LID - 10.1016/j.peptides.2025.171380 [doi] AB - Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and 'real-world' studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025). CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Bailey, Clifford J AU - Bailey CJ AD - Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. FAU - Conlon, J Michael AU - Conlon JM AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. Electronic address: jmconlon1@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20250311 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Incretins/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Comorbidity MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular OT - Incretin OT - Multiagonist OT - Obesity OT - Renal OT - Type 2 diabetes COIS- Conflict of Interest CJB has served on steering committees for clinical trials and advisory boards for several pharmaceutical companies. PRF and JMC are named on patents held by Ulster University for peptide therapeutics and have served as advisor to several pharmaceutical companies. EDAT- 2025/03/14 11:19 MHDA- 2025/04/05 15:58 CRDT- 2025/03/13 20:13 PHST- 2025/01/27 00:00 [received] PHST- 2025/03/03 00:00 [revised] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/04/05 15:58 [medline] PHST- 2025/03/14 11:19 [pubmed] PHST- 2025/03/13 20:13 [entrez] AID - S0196-9781(25)00041-5 [pii] AID - 10.1016/j.peptides.2025.171380 [doi] PST - ppublish SO - Peptides. 2025 May;187:171380. doi: 10.1016/j.peptides.2025.171380. Epub 2025 Mar 11. PMID- 40080656 OWN - NLM STAT- MEDLINE DCOM- 20250313 LR - 20260916 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 2 DP - 2025 Mar-Apr TI - The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study. PG - 14791641251322909 LID - 10.1177/14791641251322909 [doi] LID - 14791641251322909 AB - IntroductionDiabetes related foot ulcers (DFUs) are common complications of type 2 diabetes mellitus (T2DM), affecting 15-25% of individuals living with diabetes and significantly contributing to healthcare costs ($9-13 billion annually in the U.S.). Without effective management, these wounds often lead to severe outcomes like amputations. This study aims to examine the association of semaglutide on DFU management.MethodsThis retrospective cohort study utilized TriNetX US Research Network data to assess the impact of semaglutide, a GLP-1 receptor agonist, on DFU outcomes between 2013 and 2023. The study compared outcomes between semaglutide users with DFU (Cohort A, N = 6329) and non-users with DFU (Cohort B, N = 118,821) across 64 healthcare organizations. We matched participants by age, gender, race, and ethnicity; however, we excluded patients with certain co-morbidities. Statistical analysis, such as chi-square analysis and risk ratio, using TriNetX software evaluated different complication outcomes.ResultsSemaglutide users with DFU demonstrated lower relative risks for complications compared to non-users. Within 1 year, semaglutide users were associated with lower relative risks for wound healing complications (0.19% vs 0.38%), chronic non-healing wounds (0.75% vs 1.23%), chronic pain (4.44% vs 8.06%), wound care (2.42% vs 4.86%), wound dehiscence (0.26% vs 0.56%), and amputation (2.34% vs 5.21%) (p < .05). Similar trends persisted over 5 years. While these findings highlight potential benefits of semaglutide with patients with DFU, causation cannot be inferred due to the study's observational design.ConclusionSemaglutide use was associated with favorable outcomes in patients with diabetes-related foot ulcers, including reductions in wound-related complications. While these findings suggest potential benefits of semaglutide as an adjunct in DFU management, further research is needed to confirm these associations and to better understand the mechanisms involved. FAU - Lewis, Joshua E AU - Lewis JE AUID- ORCID: 0009-0001-4785-2011 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Omenge, Diana K AU - Omenge DK AUID- ORCID: 0009-0000-8116-4290 AD - Tilman J. Fertitta College of Medicine, University of Houston School of Medicine, Houston, TX, USA. FAU - Patterson, Amani R AU - Patterson AR AUID- ORCID: 0009-0006-3082-8986 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Anwaegbu, Ogechukwu AU - Anwaegbu O AUID- ORCID: 0009-0008-8776-5941 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Tabukum, Nangah N AU - Tabukum NN AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Lewis, Jimmie E 3rd AU - Lewis JE 3rd AD - School of Podiatric Medicine, Barry University, Miami, FL, USA. FAU - Lee, Wei-Chen AU - Lee WC AD - Department of Family Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng GR - UL1 TR001439/TR/NCATS NIH HHS/United States GR - D34HP49234/HRSA/HRSA HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20250313 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - *Wound Healing/drug effects MH - *Diabetic Foot/diagnosis/drug therapy/physiopathology/epidemiology MH - Retrospective Studies MH - Middle Aged MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/complications MH - Aged MH - Databases, Factual MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - United States/epidemiology MH - Risk Factors MH - Risk Assessment MH - Amputation, Surgical MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11907515 OTO - NOTNLM OT - Diabetes related foot ulcers OT - GLP-1 receptor agonists OT - diabetes complications OT - semaglutide OT - wound healing COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/03/14 11:17 MHDA- 2025/03/14 11:18 PMCR- 2025/03/13 CRDT- 2025/03/13 14:52 PHST- 2025/03/14 11:18 [medline] PHST- 2025/03/14 11:17 [pubmed] PHST- 2025/03/13 14:52 [entrez] PHST- 2025/03/13 00:00 [pmc-release] AID - 10.1177_14791641251322909 [pii] AID - 10.1177/14791641251322909 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Mar-Apr;22(2):14791641251322909. doi: 10.1177/14791641251322909. Epub 2025 Mar 13. PMID- 40074942 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20260430 IS - 1432-1041 (Electronic) IS - 0031-6970 (Print) IS - 0031-6970 (Linking) VI - 81 IP - 5 DP - 2025 May TI - Prescribing patterns of glucagon-like peptide-1 receptor agonists in the Swedish capital region-a register-based cross-sectional study. PG - 739-753 LID - 10.1007/s00228-025-03823-9 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained considerable media attention, but there is limited knowledge about those receiving the drugs. This study aimed to assess demographic characteristics and previous diagnoses in patients dispensed GLP-1 RAs in Region Stockholm, Sweden, between 2019 and 2023, with a focus on off-label prescribing. METHODS: This was a register-based cross-sectional study including all inhabitants in Region Stockholm, Sweden, who were dispensed a GLP-1 RA between 2019 and 2023. Patient characteristics were assessed through record linkage with administrative healthcare data on demographics, healthcare consultations, diagnoses, and other dispensed drugs. RESULTS: The prevalence proportion of GLP-1 RA dispensations in Region Stockholm increased from 4.7 patients/1000 inhabitants in 2019 to 17.5 patients/1000 inhabitants in 2023, and the incidence proportion from 1.8 patients/1000 inhabitants in 2019 to 7.4 patients/1000 inhabitants in 2023. GLP-1 RAs have become more common among a younger and female population, with women constituting 47% of incident patients in 2019 compared to 53% in 2023. The most common diagnosis shifted from type 2 diabetes mellitus (T2DM) (82% in 2019) to obesity (47% in 2023). During the same period, obesity without T2DM notably increased from 10 to 31%. Almost one-third (31%) of all patients dispensed the drugs in 2023 had no recorded diagnosis of either diabetes or obesity, compared to 8% in 2019. CONCLUSION: This study showed an increase in the dispensation of GLP-1 RA, with characteristics of patients changing towards a higher degree of off-label use. The effectiveness and safety of the increasing prescriptions warrant future studies. CI - (c) 2025. The Author(s). FAU - Fors, Alice AU - Fors A AD - Department of Pharmacy, Faculty of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden. FAU - Forslund, Tomas AU - Forslund T AUID- ORCID: 0000-0002-2001-7710 AD - Department of Healthcare Development, Stockholm Region, Public Healthcare Services Committee, Stockholm, Sweden. AD - Academic Primary Health Care Centre, Stockholm Region, Stockholm, Sweden. AD - Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden. FAU - Sundstrom, Anders AU - Sundstrom A AUID- ORCID: 0000-0003-2337-3371 AD - Department of Pharmacy, Faculty of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden. AD - Division of Use and Information, Swedish Medical Products Agency, Uppsala, Sweden. FAU - Wettermark, Bjorn AU - Wettermark B AUID- ORCID: 0000-0003-0531-2516 AD - Department of Pharmacy, Faculty of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden. bjorn.wettermark@uu.se. LA - eng PT - Journal Article DEP - 20250313 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Eur J Clin Pharmacol. 2026 Apr 27;82(5):132. doi: 10.1007/s00228-026-04055-1. PMID: 42036491 MH - Humans MH - Female MH - Sweden/epidemiology MH - Male MH - Cross-Sectional Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Registries MH - *Hypoglycemic Agents/therapeutic use MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Adult MH - Off-Label Use/statistics & numerical data MH - Aged, 80 and over MH - Young Adult MH - Adolescent PMC - PMC12003583 OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Prescribing patterns OT - Sweden COIS- Declarations. Ethics approval: All patient data accessed by the researchers were fully pseudonymized. Consequently, it was not possible to identify individual patients or healthcare providers. Informed consent was not requested, in agreement with the Swedish legislation for conducting registry studies. The study was approved by the Regional Ethical Review Board in Stockholm (registration numbers EPN 2015/579-31/2 and 2023-01601-02). Competing interests: The authors declare no competing interests. EDAT- 2025/03/13 06:27 MHDA- 2025/04/16 14:35 PMCR- 2025/03/13 CRDT- 2025/03/13 00:22 PHST- 2024/12/07 00:00 [received] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/04/16 14:35 [medline] PHST- 2025/03/13 06:27 [pubmed] PHST- 2025/03/13 00:22 [entrez] PHST- 2025/03/13 00:00 [pmc-release] AID - 10.1007/s00228-025-03823-9 [pii] AID - 3823 [pii] AID - 10.1007/s00228-025-03823-9 [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2025 May;81(5):739-753. doi: 10.1007/s00228-025-03823-9. Epub 2025 Mar 13. PMID- 40069849 OWN - NLM STAT- MEDLINE DCOM- 20250403 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 5 DP - 2025 May TI - Efficacy and safety of once-weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial. PG - 2540-2551 LID - 10.1111/dom.16253 [doi] AB - AIM: To evaluate the efficacy and safety of semaglutide 2.4 mg versus placebo for weight management in a population of Chinese adults with overweight or obesity. MATERIALS AND METHODS: In STEP 7 (NCT04251156), a double-blind, phase 3a trial, adults from a predominantly East Asian population with overweight or obesity, with or without type 2 diabetes, were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 44 weeks as an adjunct to a reduced-calorie diet and increased physical activity. This prespecified analysis evaluated Chinese participants in STEP 7. The primary endpoints were percentage change in body weight from baseline to Week 44 and the proportion of participants who achieved >/=5% reduction in body weight from baseline. RESULTS: Overall, 195 Chinese participants were randomized to semaglutide 2.4 mg and 105 to placebo. Estimated change in mean body weight from baseline to Week 44 was -11.8% with semaglutide 2.4 mg versus -3.5% with placebo (estimated treatment difference -8.3%; 95% confidence interval [CI] -10.2, -6.4; p < 0.0001). At Week 44, a greater proportion of participants treated with semaglutide 2.4 mg achieved >/=5% body weight loss versus placebo (85.4% vs. 26.8%): odds ratio 16.1; 95% CI 8.4, 30.9; p < 0.0001. Adverse events were reported by 92.3% of semaglutide-treated participants and 82.9% of placebo-treated participants, the most common of which were gastrointestinal disorders (126/195, 64.6% vs. 35/105, 33.3%). CONCLUSIONS: These data demonstrate beneficial effects of semaglutide 2.4 mg versus placebo, supporting its use in an adult Chinese population with overweight or obesity. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gu, Weijun AU - Gu W AUID- ORCID: 0000-0001-8690-645X AD - Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Lu, Yibing AU - Lu Y AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ye, Xinhua AU - Ye X AD - Department of Endocrinology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China. FAU - Yuan, Guoyue AU - Yuan G AUID- ORCID: 0000-0003-0822-6066 AD - Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liu, Dongmei AU - Liu D AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Zu, Ning AU - Zu N AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Mu, Yiming AU - Mu Y AUID- ORCID: 0000-0002-3344-3540 AD - Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. LA - eng GR - Novo Nordisk A/S/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250311 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Double-Blind Method MH - China/epidemiology MH - *Obesity/drug therapy/complications/therapy MH - Adult MH - Weight Loss/drug effects MH - *Overweight/drug therapy/complications/therapy MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications MH - Drug Administration Schedule MH - *Anti-Obesity Agents/administration & dosage/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11964988 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - clinical trial OT - phase III study OT - semaglutide OT - weight management COIS- Dongmei Lui, Ning Zu and Zewei Shen are employees of Novo Nordisk and own Novo Nordisk stock. Yiming Mu has received speaker honorarium or consultancy fees in advisory boards from Eli Lilly, Novo Nordisk and Sanofi. Weijun Gu, Yibing Lu, Xinhua Ye and Guoyue Yuan have no conflicts of interest to disclose. EDAT- 2025/03/12 11:34 MHDA- 2025/04/04 00:25 PMCR- 2025/04/03 CRDT- 2025/03/12 00:49 PHST- 2025/01/23 00:00 [revised] PHST- 2024/10/31 00:00 [received] PHST- 2025/01/29 00:00 [accepted] PHST- 2025/04/04 00:25 [medline] PHST- 2025/03/12 11:34 [pubmed] PHST- 2025/03/12 00:49 [entrez] PHST- 2025/04/03 00:00 [pmc-release] AID - DOM16253 [pii] AID - 10.1111/dom.16253 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 May;27(5):2540-2551. doi: 10.1111/dom.16253. Epub 2025 Mar 11. PMID- 40064382 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260127 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 674 DP - 2025 Apr 15 TI - Regulation of nanoparticle exocytosis direction via receptors transfer: A novel strategy to enhance therapeutic efficacy of semaglutide. PG - 125439 LID - S0378-5173(25)00275-3 [pii] LID - 10.1016/j.ijpharm.2025.125439 [doi] AB - Coumaric acid (CA) is a typical nutrient required in relatively high quantities by the body. It has been proved CA could specifically bind to monocarboxylate Transporter-1 (MCT-1) receptors, a transporter protein expressed on the surface of intestinal epithelial cells, to facilitate its cellular uptake. Although our preliminary research demonstrated semaglutide (SEM) loaded CA modified nanoparticles (SEM@CNP) could improve the absorption of SEM to some extent, the oral bioavailability still remained suboptimal owing to the lysosomal degradation. To address this issue, INF-7 (peptide chain GLFEAIEGFIENGWEGMIDGWYG) and chloroquine (CQ), two lysosomal escape agents (LEAs) with different mechanisms of action, were incorporated with SEM@CNP for oral delivery (SEM@CNP + INF-7, SEM@CNP + CQ). In type II diabetes mice models, SEM@CNP + CQ effectively inhibited postprandial glucose rise with a relative pharmacological bioavailability of 20.63 +/- 2.99 %, 1.73 times higher than SEM@CNP (11.90 +/- 4.56 %). Mechanistic studies revealed that: 1) after adding LEAs, the exocytosis preference of nanoparticles was altered, tending towards basolateral exocytosis apparently. Regulated exocytosis directionality was linked to the spatial redistribution of MCT-1 receptors. 2) among the two LEAs, CQ demonstrated superior efficacy compared to INF-7. This superiority was attributed to the earlier onset of action and more pronounced degree of membrane disruption induced by CQ. This research provided new insights for the design of oral delivery systems for peptidic drugs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Wang, Yating AU - Wang Y AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Ni, Mingjie AU - Ni M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Minyi AU - Huang M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Xing, Liyun AU - Xing L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Liu, Xi AU - Liu X AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Jia, Fuya AU - Jia F AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Yuan AU - Huang Y AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: huangyuan0@163.com. LA - eng PT - Journal Article DEP - 20250308 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Monocarboxylic Acid Transporters) RN - 886U3H6UFF (Chloroquine) RN - 0 (Symporters) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Monocarboxylate Transport Protein 1) SB - IM MH - Animals MH - *Nanoparticles/chemistry/administration & dosage MH - Mice MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/chemistry/pharmacology MH - Male MH - *Exocytosis/drug effects MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/chemistry/pharmacology MH - Biological Availability MH - Monocarboxylic Acid Transporters/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Administration, Oral MH - Diabetes Mellitus, Experimental/drug therapy/blood MH - Humans MH - Chloroquine/administration & dosage/chemistry MH - Symporters/metabolism MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - Monocarboxylate Transport Protein 1 OTO - NOTNLM OT - Basolateral exocytosis OT - Coumaric acid OT - Lysosomal escape agents OT - Oral OT - Semaglutide OT - Type II diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/11 00:25 MHDA- 2025/04/18 00:25 CRDT- 2025/03/10 20:15 PHST- 2024/12/22 00:00 [received] PHST- 2025/02/15 00:00 [revised] PHST- 2025/03/06 00:00 [accepted] PHST- 2025/04/18 00:25 [medline] PHST- 2025/03/11 00:25 [pubmed] PHST- 2025/03/10 20:15 [entrez] AID - S0378-5173(25)00275-3 [pii] AID - 10.1016/j.ijpharm.2025.125439 [doi] PST - ppublish SO - Int J Pharm. 2025 Apr 15;674:125439. doi: 10.1016/j.ijpharm.2025.125439. Epub 2025 Mar 8. PMID- 40058653 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 222 DP - 2025 Apr TI - Drug adherence, glycemic control, and weight reduction with subcutaneous semaglutide in real-world management of type 2 diabetes. PG - 112086 LID - S0168-8227(25)00100-7 [pii] LID - 10.1016/j.diabres.2025.112086 [doi] AB - BACKGROUND: We describe changes in HbA1c and body-weight and the relationship between drug adherence and clinical response in a large real-world cohort of patients with type 2 diabetes (T2D) treated with subcutaneous semaglutide for up to three years. METHODS: We included adults with T2D registered at Maccabi Healthcare Services, Israel, who initiated subcutaneous semaglutide (August 2019 - June 2022). Adherence, assessed as Proportion of Days Covered (PDC), was based on drug's dispensation. We assessed the absolute change in HbA1c and the relative change in body-weight from baseline. RESULTS: The 23,442 participants (11,513 women) had a mean age of 62.2 years, HbA1c of 7.6 %, and BMI of 33.7 kg/m(2). Compared to baseline, the mean reductions in HbA1c were 0.77 [95 %CI 0.75-0.78], 0.57 [0.53-0.61], and 0.35 [0.27-0.44] %-points at 6 months, 2 years, and 3 years, respectively. The respective body-weight reductions were 4.9 % [4.8-5.0], 5.3% [5.1-5.5], and 4.5 % [3.7-5.2]. Among 6049 patients with >/=2 years of potential follow-up, median PDC between 0-6 months was 83.9 %, and remained relatively stable thereafter, reaching 74.6 % between 18-24 months. Higher PDC was associated with more pronounced HbA1c and body-weight reductions. CONCLUSIONS: Long-term real-world adherence with semaglutide was relatively stable. Semaglutide use was associated with sustained glycemic control and weight reduction in patients with T2D and relatively good baseline glycemic control, especially among those with high adherence, supporting its use for long-term management of T2D. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Melzer Cohen, Cheli AU - Melzer Cohen C AD - Maccabi Institute for Research and Innovation, Tel-Aviv, Israel. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Regeneron Pharmaceuticals Inc., New York, NY, USA. FAU - Aharonovich, Alona AU - Aharonovich A AD - Novo Nordisk, Israel. FAU - Karasik, Avraham AU - Karasik A AD - Maccabi Institute for Research and Innovation, Tel-Aviv, Israel; Tel Aviv University, Tel Aviv, Israel. FAU - Schechter, Meir AU - Schechter M AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: meir.schechter@mail.huji.ac.il. LA - eng PT - Journal Article DEP - 20250308 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Weight Loss/drug effects MH - *Glycemic Control/statistics & numerical data MH - Aged MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis/drug effects MH - Injections, Subcutaneous MH - *Medication Adherence MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glycemic control OT - Real-world evidence OT - Semaglutide OT - Type 2 diabetes OT - Weight management COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Avraham Karasik reports financial support for this study was provided by Novo Nordisk. Meir Schechter reports a relationship with Novo Nordisk that includes: travel reimbursement. Ofri Mosenzon reports a relationship with Novo Nordisk that includes: consulting or advisory, funding grants, and speaking and lecture fees. Ofri Mosenzon reports a relationship with Eli Lilly that includes: board membership, consulting or advisory, and speaking and lecture fees. Ofri Mosenzon reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with Merck Sharp & Dohme Corp that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with Boehringer Ingelheim that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with AstraZeneca that includes: consulting or advisory, funding grants, and speaking and lecture fees. Ofri Mosenzon reports a relationship with BoL Pharma that includes: consulting or advisory. Ofri Mosenzon reports a relationship with Regeneron Pharmaceuticals Inc that includes: employment. Alona Aharonovich reports a relationship with Novo Nordisk that includes: employment. Avraham Karasik reports a relationship with AstraZeneca that includes: funding grants and speaking and lecture fees. Avraham Karasik reports a relationship with Novo Nordisk that includes: funding grants and speaking and lecture fees. Avraham Karasik reports a relationship with Boehringer Ingelheim that includes: funding grants and speaking and lecture fees. Meir Schechter reports a relationship with AstraZeneca that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/10 07:59 MHDA- 2025/03/29 16:15 CRDT- 2025/03/09 20:17 PHST- 2024/11/28 00:00 [received] PHST- 2025/02/14 00:00 [revised] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/03/29 16:15 [medline] PHST- 2025/03/10 07:59 [pubmed] PHST- 2025/03/09 20:17 [entrez] AID - S0168-8227(25)00100-7 [pii] AID - 10.1016/j.diabres.2025.112086 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Apr;222:112086. doi: 10.1016/j.diabres.2025.112086. Epub 2025 Mar 8. PMID- 40057872 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260926 IS - 1942-5546 (Electronic) IS - 0025-6196 (Print) IS - 0025-6196 (Linking) VI - 100 IP - 4 DP - 2025 Apr TI - Prescribing Patterns of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Patients With Type 2 Diabetes at Cardiology, Endocrinology, and Primary Care Visits. PG - 647-656 LID - S0025-6196(24)00463-4 [pii] LID - 10.1016/j.mayocp.2024.08.026 [doi] AB - OBJECTIVE: To determine the prescribing rates of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) at cardiology, endocrinology, and primary care visits in a community health system. PATIENTS AND METHODS: A cross-sectional study using electronic health record data from Bon Secours Mercy Health outpatient clinics across Virginia (2019, 2020, 2021) included patients 18 years and older with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD), and one or more outpatient visits. Adults with type 1 diabetes, stage 4/5 CKD, end-stage kidney disease, dialysis treatment, pregnancy, or hospice or palliative care were excluded. Prescribing rates were compared overall and for each subgroup among cardiology, endocrinology, and primary care visits using generalized linear mixed modeling with a random practice-level effect. RESULTS: The 22,060 included patients had a mean age of 68 years, 50% were female (n=11,030), 41.3% were Black race (n=9,100), and 74.8% were Medicare beneficiaries (n=16,498). In addition, 17,724 patients (80.3%) had ASCVD, 5276 (23.9%) CKD, and 5,965 (27.0%) HF. Overall, prescriptions for either drug class occurred in 17.4% of eligible patients (n=3,849). Cardiology visits had the lowest prescribing rates overall and for each diagnosis subgroup compared with endocrinology and primary care visits in the raw, unadjusted, and adjusted models. CONCLUSION: Overall prescribing rates for SGLT2i and GLP-1 RA were low among adults with type 2 diabetes and ASCVD, HF, or CKD. Additional research is warranted to identify barriers, and potential solutions, to improve prescribing of these therapies. CI - Copyright (c) 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. FAU - Dixon, Dave L AU - Dixon DL AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. Electronic address: DLDixon@vcu.edu. FAU - Salgado, Teresa M AU - Salgado TM AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. FAU - Robinson, Amanda AU - Robinson A AD - C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, Virginia, USA. FAU - Carbone, Salvatore AU - Carbone S AD - Department of Kinesiology and Health Sciences, Virginia Commonwealth University College of Humanities and Sciences, Richmond, Virginia, USA. FAU - Wagner, Tyler D AU - Wagner TD AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA. FAU - Hyder, Haroon AU - Hyder H AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Kirschner, Bryan AU - Kirschner B AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Musselman, Kerri T AU - Musselman KT AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Buffington, Tonya M AU - Buffington TM AD - Bon Secours Mercy Health, Richmond, Virginia, USA. FAU - Sabo, Roy T AU - Sabo RT AD - Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA; Department of Biostatistics, Virginia Commonwealth University School of Public Health, Richmond, Virginia, USA. LA - eng GR - UM1 TR004360/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20250307 PL - England TA - Mayo Clin Proc JT - Mayo Clinic proceedings JID - 0405543 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Primary Health Care/statistics & numerical data MH - Aged MH - Cross-Sectional Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Middle Aged MH - Cardiology/statistics & numerical data MH - Endocrinology/statistics & numerical data MH - Virginia MH - Hypoglycemic Agents/therapeutic use MH - Renal Insufficiency, Chronic PMC - PMC13094883 MID - NIHMS2164053 EDAT- 2025/03/09 19:22 MHDA- 2025/04/04 00:25 PMCR- 2026/04/20 CRDT- 2025/03/09 11:28 PHST- 2024/02/08 00:00 [received] PHST- 2024/08/20 00:00 [revised] PHST- 2024/08/23 00:00 [accepted] PHST- 2025/04/04 00:25 [medline] PHST- 2025/03/09 19:22 [pubmed] PHST- 2025/03/09 11:28 [entrez] PHST- 2026/04/20 00:00 [pmc-release] AID - S0025-6196(24)00463-4 [pii] AID - 10.1016/j.mayocp.2024.08.026 [doi] PST - ppublish SO - Mayo Clin Proc. 2025 Apr;100(4):647-656. doi: 10.1016/j.mayocp.2024.08.026. Epub 2025 Mar 7. PMID- 40057763 OWN - NLM STAT- MEDLINE DCOM- 20250308 LR - 20260721 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Mar 8 TI - Potential benefits of GLP-1 receptor agonist in dialysis patients with type 2 diabetes: the need for comprehensive pharmacokinetic and hemodialysis analyses. PG - 110 LID - 10.1186/s12933-024-02543-1 [doi] LID - 110 AB - The 2022 KDIGO guideline for diabetes management in patients with chronic kidney disease (CKD) had endorsed the use of GLP-1 receptor agonists (GLP-1RAs) for patients with CKD and type 2 diabetes who did not achieve optimal glycemic target with maximally tolerated metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitor. Our study revealed the potential benefits of GLP-1RAs in patients with dialysis-requiring acute kidney disease possibly owing to pleiotropic effects of the medicine. Nonetheless, pharmacokinetics and dialysis dose were omitted in our subgroup analyses. Herein, we would like to raise our concern regarding neglecting these important confounders in our analyses and the impact to the findings of the study. CI - (c) 2024. The Author(s). FAU - Lai, Hsuan-Wen AU - Lai HW AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan. AD - Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Primary Aldosteronism Centre of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. AD - NSARF (National Taiwan University Hospital Study Group of ARF), and CAKS (Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan. FAU - See, Chun Yin AU - See CY AD - Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University , Tainan, Taiwan. seechunyin99@gmail.com. LA - eng PT - Comment PT - Letter DEP - 20250308 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM CON - Cardiovasc Diabetol. 2024 Jul 29;23(1):277. doi: 10.1186/s12933-024-02364-2. PMID: 39080745 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Dialysis/adverse effects MH - Treatment Outcome MH - *Renal Insufficiency, Chronic/diagnosis/therapy/blood MH - *Blood Glucose/metabolism/drug effects MH - *Diabetic Nephropathies/diagnosis/therapy/blood MH - Biomarkers/blood MH - *Incretins/pharmacokinetics/adverse effects/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Aged MH - *Glycemic Control/adverse effects MH - *Hypoglycemic Agents/pharmacokinetics/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11890503 OTO - NOTNLM OT - Dialysis OT - GLP-1 receptor agonist OT - Pharmacokinetics OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/03/09 15:11 MHDA- 2025/03/09 15:12 PMCR- 2025/03/08 CRDT- 2025/03/08 23:26 PHST- 2024/11/24 00:00 [received] PHST- 2024/12/10 00:00 [accepted] PHST- 2025/03/09 15:12 [medline] PHST- 2025/03/09 15:11 [pubmed] PHST- 2025/03/08 23:26 [entrez] PHST- 2025/03/08 00:00 [pmc-release] AID - 10.1186/s12933-024-02543-1 [pii] AID - 2543 [pii] AID - 10.1186/s12933-024-02543-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Mar 8;24(1):110. doi: 10.1186/s12933-024-02543-1. PMID- 40057043 OWN - NLM STAT- MEDLINE DCOM- 20250328 LR - 20250527 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 222 DP - 2025 Apr TI - SGLT2 inhibitors and nephrolithiasis risk in patients with type 2 diabetes: A cohort study and meta-analysis. PG - 112088 LID - S0168-8227(25)00102-0 [pii] LID - 10.1016/j.diabres.2025.112088 [doi] AB - AIMS: This study aimed to evaluate the relationship between sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and nephrolithiasis risk. METHODS: In this real-world cohort study, we analyzed electronic health records from the TriNetX Analytics Network, which includes patients from 64 U.S. healthcare organizations. Adult patients with type 2 diabetes (T2D) who initiated SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP4is), or glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2015 and December 2023 were included. Comparisons were made between SGLT2is and DPP4is and between SGLT2is and GLP-1RAs. Patients were followed-up for up to 5 years. A meta-analysis was further conducted to synthesize available evidence. RESULTS: The cohort study included 500,000 patients (250,000 pairs) for SGLT2is vs. DPP4is comparisons and 482,284 patients (241,142 pairs) for SGLT2is vs. GLP-1Ras comparisons. The risk of nephrolithiasis was significantly lower in SGLT2i users compared with DPP4i (HR: 0.86; 95% CI: 0.83-0.90) and GLP-1RA users (HR: 0.90; 95% CI: 0.86-0.94). A meta-analysis combining our study with four additional real-world studies further supported these findings. CONCLUSIONS: This study suggests that SGLT2is may provide benefits beyond glycemic control by reducing nephrolithiasis risk, offering an advantage when selecting glucose-lowering therapies for patients with T2D. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Yeh, Jia-Ai AU - Yeh JA AD - School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Liu, Yu-Chang AU - Liu YC AD - Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Huang, Amy Huaishiuan AU - Huang AH AD - Department of Internal Medicine, the University of Connecticut School of Medicine, Farmington, USA. FAU - Peng, Carol Chiung-Hui AU - Peng CC AD - Division of Metabolism and Endocrinology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. FAU - Loh, Ching-Hui AU - Loh CH AD - School of Medicine, Tzu Chi University, Hualien, Taiwan; Center for Healthy Longevity, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. FAU - Munir, Kashif M AU - Munir KM AD - Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Huang, Huei-Kai AU - Huang HK AD - School of Medicine, Tzu Chi University, Hualien, Taiwan; Center for Clinical Epidemiology and Biostatistics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Family Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. Electronic address: drhkhuang@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250306 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Nephrolithiasis/epidemiology/chemically induced MH - Male MH - Female MH - Middle Aged MH - Cohort Studies MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult OTO - NOTNLM OT - Diabetes OT - Kidney stones OT - Nephrolithiasis OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/09 15:08 MHDA- 2025/03/29 16:15 CRDT- 2025/03/08 19:16 PHST- 2025/02/16 00:00 [received] PHST- 2025/03/03 00:00 [revised] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/03/29 16:15 [medline] PHST- 2025/03/09 15:08 [pubmed] PHST- 2025/03/08 19:16 [entrez] AID - S0168-8227(25)00102-0 [pii] AID - 10.1016/j.diabres.2025.112088 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Apr;222:112088. doi: 10.1016/j.diabres.2025.112088. Epub 2025 Mar 6. PMID- 40056927 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260502 IS - 2213-8595 (Electronic) IS - 2213-8587 (Print) IS - 2213-8587 (Linking) VI - 13 IP - 5 DP - 2025 May TI - GLP-1 receptor agonists in kidney transplant recipients with pre-existing diabetes: a retrospective cohort study. PG - 374-383 LID - S2213-8587(24)00371-1 [pii] LID - 10.1016/S2213-8587(24)00371-1 [doi] AB - BACKGROUND: Given the cardiovascular, renal, and survival benefits of GLP-1 receptor agonists for diabetes, these agents could be effective among kidney transplant recipients. However, kidney transplant recipients are distinct from GLP-1 receptor agonist trial participants, with longer diabetes duration and severity, greater end-organ damage, increased cardiovascular risk, and multimorbidity. We examined GLP-1 receptor agonist real-world effectiveness and safety in kidney transplant recipients with diabetes. METHODS: This USA-based retrospective cohort study included kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance from a national registry linked with Medicare claims. Post-transplantation GLP-1 receptor agonist use was identified through Medicare claims. Death-censored graft loss was estimated using the Fine-Gray sub-distribution hazard model and extended Cox models were used for mortality and safety endpoints. Models incorporated inverse probability of treatment weights. To further test whether bias could affect the main results, a cohort was created in which each GLP-1 receptor agonist user was matched with a kidney transplant recipient who had not started a GLP-1 receptor agonist, was alive with a functioning graft, and had accrued the same amount of post-transplant survival time. FINDINGS: Between Jan 1, 2013 and Dec 31, 2020, we identified 44 536 first time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. 24 192 patients were excluded as they did not have type 2 diabetes. 2328 patients were ineligible (1916 had missing values and 412 used GLP-1 receptor agonists before transplantation). The primary cohort thus consisted of 18 016 kidney transplant recipients with diabetes. Of these patients, 1969 (10.9%) had at least one GLP-1 receptor agonist prescription filled post-transplant. Compared with patients who had not received a GLP-1 receptor agonist, GLP-1 receptor agonist users were younger (median age at transplant 57 years [IQR 49-64] vs 60 years [51-66], p<0.0001) and more likely to be female (786 [39.9%] vs 5645 [35.2%], p<0.0001). Among GLP-1 receptor agonist users, 552 [28.0%] were non-Hispanic White, 703 [35.7%] were non-Hispanic Black, and 568 [28.8%] were Hispanic. The 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 receptor agonist initiation was 6.0% for GLP-1 receptor agonist users and 10.7% for non-users (Gray's test p=0.004). The 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 receptor agonist initiation was 17.0% for GLP-1 receptor agonist users and 25.8% for non-users (log-rank p=0.0006). The 5-year unadjusted cumulative incidence for mortality was 13.5% for GLP-1 receptor agonist users and 19.9% for non-users (log-rank p<0.0001). GLP-1 receptor agonist use was associated with a 49% lower incidence of death-censored graft loss (adjusted subhazard ratio [aSHR] 0.51, 95% CI 0.36-0.71; p=0.0001) and 31% lower mortality (adjusted hazard ratio [aHR] 0.69, 95% CI 0.55-0.86; p=0.001). Inferences were robust when matched on survival time (death-censored graft loss aSHR 0.53, 95% CI 0.37-0.75; p=0.0005; mortality aHR 0.70, 95% CI 0.55-0.88; p=0.003). Safety endpoints were rare and not associated with GLP-1 receptor agonists, with the exception of diabetic retinopathy (aHR 1.49, 1.11-2.00; p=0.008). INTERPRETATION: GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings. FUNDING: National Institutes of Health. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Orandi, Babak J AU - Orandi BJ AD - Departments of Surgery, New York University, New York, NY, USA; Department of Medicine, New York University, New York, NY, USA. Electronic address: babak.orandi@nyulangone.org. FAU - Chen, Yusi AU - Chen Y AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Li, Yiting AU - Li Y AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Metoyer, Garyn T AU - Metoyer GT AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Lentine, Krista L AU - Lentine KL AD - Department of Medicine, Saint Louis University, St Louis, MO, USA. FAU - Weintraub, Michael AU - Weintraub M AD - Department of Medicine, New York University, New York, NY, USA. FAU - Bae, Sunjae AU - Bae S AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Ali, Nicole M AU - Ali NM AD - Department of Medicine, New York University, New York, NY, USA. FAU - Lonze, Bonnie E AU - Lonze BE AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Ren-Fielding, Christine J AU - Ren-Fielding CJ AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Lofton, Holly AU - Lofton H AD - Department of Medicine, New York University, New York, NY, USA. FAU - Gujral, Akash AU - Gujral A AD - Departments of Surgery, New York University, New York, NY, USA. FAU - Segev, Dorry L AU - Segev DL AD - Departments of Surgery, New York University, New York, NY, USA; Department of Population Health, New York University, New York, NY, USA. FAU - McAdams-DeMarco, Mara AU - McAdams-DeMarco M AD - Departments of Surgery, New York University, New York, NY, USA; Department of Population Health, New York University, New York, NY, USA. LA - eng GR - R01 DK120518/DK/NIDDK NIH HHS/United States GR - K02 AG076883/AG/NIA NIH HHS/United States GR - R01 AG077888/AG/NIA NIH HHS/United States GR - K01 DK132490/DK/NIDDK NIH HHS/United States GR - K24 AI144954/AI/NIAID NIH HHS/United States GR - R01 DK114074/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250305 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Lancet Diabetes Endocrinol. 2025 May;13(5):356-357. doi: 10.1016/S2213-8587(24)00399-1. PMID: 40056924 EIN - Lancet Diabetes Endocrinol. 2025 Jun;13(6):e9. doi: 10.1016/S2213-8587(25)00128-7. PMID: 40318681 MH - Humans MH - *Kidney Transplantation MH - Retrospective Studies MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Transplant Recipients/statistics & numerical data MH - Adult MH - Medicare PMC - PMC12171561 MID - NIHMS2066201 COIS- Declaration of interests BJO has served on an advisory board for Boehringer Ingelheim. KLL is a senior scientist of theScientific Registry of Transplant Recipients, and reports consulting fees form CareDx and speaker honoraria from Sanofi. HL has served on an advisory board for and received speaker honoraria and research funding from Novo Nordisk, received research funding from Eli Lilly, and served on an advisory board for Currax. DLS is a consultant to AstraZeneca, Novavax, Novartis, CareDx, Transmedics, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and ThermoFisher Scientific; has received honoraria from Sanofi, AstraZeneca, Optum, CareDx and Novartis, and has received grant support from the National Institutes of Health, all unrelated to the present work. MM-D has received a speaker honorarium from Chiesi. All other authors report no competing interests. EDAT- 2025/03/09 15:10 MHDA- 2025/04/25 13:45 PMCR- 2026/05/01 CRDT- 2025/03/08 18:52 PHST- 2024/08/27 00:00 [received] PHST- 2024/11/21 00:00 [revised] PHST- 2024/11/27 00:00 [accepted] PHST- 2025/04/25 13:45 [medline] PHST- 2025/03/09 15:10 [pubmed] PHST- 2025/03/08 18:52 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - S2213-8587(24)00371-1 [pii] AID - 10.1016/S2213-8587(24)00371-1 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 May;13(5):374-383. doi: 10.1016/S2213-8587(24)00371-1. Epub 2025 Mar 5. PMID- 40056372 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260929 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 5 DP - 2025 May TI - Safety of iGlarLixi in Japanese People with Type 2 Diabetes: A Post-marketing Database Study. PG - 2168-2189 LID - 10.1007/s12325-025-03135-5 [doi] AB - INTRODUCTION: In this post-marketing study in Japan, the occurrence of hospital-treated hypoglycaemia and severe hyperglycaemia requiring inpatient treatment was evaluated in various cohorts of people with type 2 diabetes (T2D) newly switched to iGlarLixi, a titratable, once-daily, fixed-ratio combination of long-acting insulin glargine 100 U/mL (iGlar-100) and a glucagon-like peptide-1 receptor agonist (GLP-1 RA, lixisenatide). METHODS: In this retrospective, observational study, acute-care hospital data from adults with T2D were analysed from the Medical Data Vision database. In Cohort 1, the incidence rate of hospital-treated hypoglycaemia following newly prescribed iGlarLixi versus iGlar-100 was assessed. Cohort 2 was subdivided to evaluate the incidence rate of hospital-treated hypoglycaemia and severe hyperglycaemia requiring inpatient treatment in people switched to iGlarLixi from either a GLP-1 RA +/- oral antidiabetic drugs (OADs) or OADs alone (Cohort 2A) or from a GLP-1 RA and long-acting insulin +/- OADs or long-acting insulin +/- OADs (Cohort 2B). RESULTS: Of the 438 people in the iGlarLixi group and 9295 people in the iGlar-100 group in Cohort 1, who had a median follow-up duration of 52 and 44 days, respectively, there were zero and 0.011 (95% CI 0.006-0.018) events per person-year of hospital-treated hypoglycaemia, respectively. Cohort 2A included 201 people each in the GLP-1 RA +/- OADs and OADs alone groups, with a median follow-up duration of 76 and 101 days, respectively, and Cohort 2B included 255 people in the GLP-1 RA and long-acting insulin +/- OADs group and 623 people in the long-acting insulin +/- OADs group, with a median follow-up duration of 73 and 62 days, respectively; no cases of hospital-treated hypoglycaemia or severe hyperglycaemia requiring inpatient treatment were observed. CONCLUSION: Consistent with clinical trials, this post-marketing database study observed that newly prescribed iGlarLixi has a low risk of serious hypoglycaemia or hyperglycaemia in Japanese people with T2D, irrespective of prior antidiabetic drug treatment. CI - (c) 2025. The Author(s). FAU - Kaneto, Hideaki AU - Kaneto H AUID- ORCID: 0000-0001-7898-1943 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Hatanaka, Makiko AU - Hatanaka M AD - Post Authorization Regulatory Study, Medical Affairs, Sanofi K.K., Tokyo, Japan. FAU - Morimoto, Yukiko AU - Morimoto Y AD - Real World Evidence Generation Partnering, Medical Affairs, Sanofi K.K., Tokyo, Japan. FAU - Takahashi, Yoko AU - Takahashi Y AUID- ORCID: 0000-0003-2481-9574 AD - General Medicine Medical, Sanofi K.K., Opera City Tower 3-20-2, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 163-1488, Japan. Yoko.Takahashi@sanofi.com. FAU - Terauchi, Yasuo AU - Terauchi Y AUID- ORCID: 0000-0002-8872-3697 AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250308 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Retrospective Studies MH - Female MH - Male MH - Japan/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemia/chemically induced/epidemiology MH - *Insulin Glargine/administration & dosage/adverse effects/therapeutic use MH - Product Surveillance, Postmarketing MH - *Peptides/administration & dosage/adverse effects/therapeutic use MH - Hyperglycemia/chemically induced/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Databases, Factual MH - Adult MH - Glucagon-Like Peptide-2 Receptor MH - East Asian People PMC - PMC12006214 OAB - The goal of type 2 diabetes (T2D) treatment is to manage blood glucose levels and to reduce the risk of diabetes-related complications. In addition to oral antidiabetic drugs (OADs), T2D can be effectively managed using combination therapy with an insulin and a glucagon-like peptide-1 receptor agonist (GLP-1 RA), such as insulin glargine 100 U/mL plus lixisenatide (also known as iGlarLixi); however, these injectable drugs carry risks of hypoglycaemia and hyperglycaemia. In this study, these risks were evaluated in people who were newly prescribed iGlarLixi in Japan and enrolled in a large hospital database. Individuals were divided into various groups; in Cohort 1, hospital-treated hypoglycaemia following newly prescribed iGlarLixi versus insulin glargine 100 U/mL (iGlar-100), with or without OADs, was assessed; in Cohort 2, we evaluated hospital-treated hypoglycaemia and severe hyperglycaemia in people who switched to iGlarLixi from a GLP-1 RA with/without OADs or OADs alone (Cohort 2A), or from a GLP-1 RA and long-acting insulin with/without OADs or long-acting insulin with/without OADs (Cohort 2B). In Cohort 1, hospital-treated hypoglycaemia occurred in none of the 438 people in the iGlarLixi group and 14 of the 9295 people in the iGlar-100 group after a median follow-up of 52 and 44 days, respectively. In Cohort 2A (402 people) and Cohort 2B (878 people), there were no occurrences of hospital-treated hypoglycaemia or hyperglycaemia after a median follow-up of 101 and 73 days, respectively. We concluded that newly prescribed iGlarLixi has a low risk of serious hypoglycaemia or hyperglycaemia in Japanese people with T2D, irrespective of their prior antidiabetic treatment. OABL- eng OTO - NOTNLM OT - Database analysis OT - Hyperglycaemia OT - Hypoglycaemia OT - IGlarLixi OT - Japan OT - Post-marketing surveillance OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Hideaki Kaneto has received lecture fees from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., Novo Nordisk Pharma Ltd., Sumitomo Pharma Co., Ltd., Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. and AstraZeneca K.K.; research expenses or grants from Taisho Pharmaceutical Co., Ltd., Summit Pharma Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; scholarship (incentive) donations, etc. from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., Novo Nordisk Pharma Ltd., Sumitomo Pharma Co., Ltd., Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. and Abbott Japan LLC. Yasuo Terauchi has received lecture fees from MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sanofi K.K., Sumitomo Pharma Co., Ltd., AstraZeneca K.K., Astellas Pharma Inc., and Kowa Company, Ltd.; and scholarship (incentive) donations, etc. from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Makiko Hatanaka, Yukiko Morimoto and Yoko Takahashi are employees of Sanofi K.K. Makiko Hatanaka is a shareholder of Sanofi K.K. Ethical Approval: The study was conducted in accordance with the Japanese Ministerial Ordinance on Good Post-Marketing Study Practice (Ministry of Health, Labour and Welfare Ordinance No. 171, December 20, 2004) and the ethical guidelines for medical and health research involving human subjects. Under these Japanese regulations, this study was conducted without the review or approval by the ethics committee of the participating medical institutions. All data were collected from the MDV database; the authors had no access to individuals' medical records. EDAT- 2025/03/09 15:08 MHDA- 2025/04/17 12:27 PMCR- 2025/03/08 CRDT- 2025/03/08 11:23 PHST- 2024/11/05 00:00 [received] PHST- 2025/02/04 00:00 [accepted] PHST- 2025/04/17 12:27 [medline] PHST- 2025/03/09 15:08 [pubmed] PHST- 2025/03/08 11:23 [entrez] PHST- 2025/03/08 00:00 [pmc-release] AID - 10.1007/s12325-025-03135-5 [pii] AID - 3135 [pii] AID - 10.1007/s12325-025-03135-5 [doi] PST - ppublish SO - Adv Ther. 2025 May;42(5):2168-2189. doi: 10.1007/s12325-025-03135-5. Epub 2025 Mar 8. PMID- 40055951 OWN - NLM STAT- MEDLINE DCOM- 20250812 LR - 20260127 IS - 1755-3768 (Electronic) IS - 1755-375X (Print) IS - 1755-375X (Linking) VI - 103 IP - 6 DP - 2025 Sep TI - Semaglutide and non-arteritic anterior ischaemic optic neuropathy: Review and interpretation of reported association. PG - 615-621 LID - 10.1111/aos.17473 [doi] AB - This review covers a seminal study of the relation between exposure to the glucagon-like peptide 1 (GLP-1) agonist semaglutide and incident non-arteritic anterior ischaemic optic neuropathy (NAION) in a neuro-ophthalmology clinic setting, subsequent studies in unselected populations, a meta-analysis of clinical trials and pathophysiology studies of the optic disc and retina that may help elucidate the relation between semaglutide and NAION in patients with diabetes or obesity. In the matched cohort study of neuro-ophthalmology patients, those treated using agents other than semaglutide had NAION rates, orders of magnitude higher than a background population, presumably because referral patterns led to the enrichment of the study populations with patients at high risk of NAION. With semaglutide, the rates of NAION were 4.28 and 7.64 times higher for type 2 diabetes (T2D) and obesity, respectively, and onset of NAION was within 14 months of treatment initiation, whereas non-semaglutide NAION was evenly distributed over the 3 years of follow-up. Of four health care registry studies, each covering more than 100 000 patients, two found relative rates of NAION two to three times higher with semaglutide than without semaglutide, one found a trend towards semaglutide being associated with NAION in patients with type 2 diabetes only, and one found statistically insignificant imbalances between the two alternatives. The meta-analysis of various GLP-1 receptor agonists versus placebo or active comparator found no significant difference in rates of NAION. Prior reports of long-term glycaemia reduction being associated with early worsening of retinopathy and with NAION indicate that semaglutide may promote such events in proportion to its antihyperglycaemic potency. The association of NAION with small, crowded discs, optic disc oedema and peripapillary exudation suggests that semaglutide-related NAION may result from changes in perfusion that lead to venous dilation and, presumably, to venous congestion during relative hypoglycaemia. Given the retrospective nature of the epidemiological studies, causality cannot be inferred, but a cautious approach to the use of semaglutide and other powerful glycaemia-reducing agents seems warranted, particularly in patients with crowded optic discs, a characteristic that can be identified by proactive eye examination for disc-at-risk characteristics by the use of optical coherence tomography. CI - (c) 2025 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation. FAU - Amini, Abdullah AU - Amini A AUID- ORCID: 0009-0003-1345-364X AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. FAU - Hamann, Steffen AU - Hamann S AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. FAU - Larsen, Michael AU - Larsen M AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Grosserer Christian Andersen og hustru Ingeborg Ovidia Signe Andersen, fodt Schmidts Legat/ GR - Synoptik Foundation/ PT - Journal Article PT - Review DEP - 20250308 PL - England TA - Acta Ophthalmol JT - Acta ophthalmologica JID - 101468102 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Global Health MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12340176 OTO - NOTNLM OT - diabetic retinopathy OT - non-arteritic anterior ischemic optic neuropathy OT - semaglutide COIS- AA and SH declare no conflicts of interest. ML has consulted for Novo Nordisk, Bayer, Roche, Stoke, Janssen, Novartis. EDAT- 2025/03/09 15:10 MHDA- 2025/08/12 06:27 PMCR- 2025/08/12 CRDT- 2025/03/08 04:33 PHST- 2024/11/04 00:00 [received] PHST- 2025/02/25 00:00 [accepted] PHST- 2025/08/12 06:27 [medline] PHST- 2025/03/09 15:10 [pubmed] PHST- 2025/03/08 04:33 [entrez] PHST- 2025/08/12 00:00 [pmc-release] AID - AOS17473 [pii] AID - 10.1111/aos.17473 [doi] PST - ppublish SO - Acta Ophthalmol. 2025 Sep;103(6):615-621. doi: 10.1111/aos.17473. Epub 2025 Mar 8. PMID- 40054529 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20250613 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 31 IP - 6 DP - 2025 Jun TI - Benefits of Glucagon-like Peptide-1 Receptor Agonists After Kidney Transplantation. PG - 798-804 LID - S1530-891X(25)00068-0 [pii] LID - 10.1016/j.eprac.2025.02.020 [doi] AB - OBJECTIVE: Benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in kidney transplant (KT) recipients have not been adequately studied. METHODS: We retrospectively examined the effects of GLP-1 RA on mortality, kidney outcomes and metabolic parameters in KT recipients with type 2 diabetes mellitus (T2DM) treated versus not treated with GLP-1 RA. A reference group of KT recipients not treated with GLP-1 RA was used for comparison. Data were analyzed using analysis of variance, chi2 tests, and generalized estimating equation models. GLP-1 RA was used as a time-dependent model in Cox regression modeling. For survival analysis, the final model fitting was stratified by race-ethnicity. RESULTS: Seventy-seven KT recipients with T2DM were treated with GLP-1 RA for at least 12 months. Reference group included 2094 patients not on GLP-1 RA. The mean (SD) age at transplant was 57.9 (9.5) and 60.8 (9.5) years for the treatment and reference groups, respectively. Median follow-up time from the index date for mortality was 1.5 (IQR 0.99, 2.4) in the treatment and 5.8 (IQR 3.4, 9.1) years in the reference group. GLP-1 RA use was associated with improved survival (P = .049), decreased urine albumin to creatinine ratio (net reduction of 10.62 mg/g per year, P = .003), slower estimated glomerular filtration rate decline (1.04 vs 1.56 mL/min/1.73 m(2) per year, P = .04), and lower troponin levels. CONCLUSIONS: GLP-1 RA in KT recipients with T2DM was associated with reduced mortality, and improved kidney function compared to the reference group. Larger, prospective studies are needed to fully evaluate the risks and benefits of GLP-1 RA therapy in KT recipients. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Sahi, Sukhdeep S AU - Sahi SS AD - Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota. FAU - Garcia Valencia, Oscar AU - Garcia Valencia O AD - Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota. FAU - Na, Jie AU - Na J AD - Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. FAU - Lemke, Adley AU - Lemke A AD - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota. FAU - Duffy, Dustin AU - Duffy D AD - Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. FAU - Smith, Byron AU - Smith B AD - Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. FAU - Navratil, Pavel AU - Navratil P AD - Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Department of Urology, University Hospital Hradec Kralove, Czechia; Charles University, Faculty of Medicine in Hradec Kralove, Czechia. FAU - Budhiraja, Pooja AU - Budhiraja P AD - Department of Internal Medicine Division of Nephrology and Transplant, Mayo Clinic, Phoenix, Arizona. FAU - Diwan, Tayyab S AU - Diwan TS AD - Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota; Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota. FAU - Issa, Naim AU - Issa N AD - Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota. FAU - Stegall, Mark D AU - Stegall MD AD - Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota; Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota. FAU - Denic, Aleksandar AU - Denic A AD - Department of Nephrology and Hypertension Research, Mayo Clinic, Rochester, Minnesota. FAU - Abdelrheem, Ahmed A AU - Abdelrheem AA AD - Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota. FAU - Wadei, Hani M AU - Wadei HM AD - Department of Transplant, Mayo Clinic, Jacksonville, Florida. FAU - Park, Walter D AU - Park WD AD - Department of Cardiovascular Surgery Research, Mayo Clinic, Rochester, Minnesota. FAU - Shah, Pankaj AU - Shah P AD - Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, & Nutrition, Mayo Clinic Rochester, Minnesota. FAU - Kudva, Yogish C AU - Kudva YC AD - Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota; Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, & Nutrition, Mayo Clinic Rochester, Minnesota. FAU - Kukla, Aleksandra AU - Kukla A AD - Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota. Electronic address: kukla.aleksandra@mayo.edu. LA - eng PT - Journal Article DEP - 20250305 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Kidney Transplantation/mortality MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Aged MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonist OT - kidney transplantation OT - post-transplant diabetes mellitus COIS- Disclosure Aleksandra Kukla participated in NovoNordisk Advisory Board in 2020; received no personal compensation. EDAT- 2025/03/09 15:09 MHDA- 2025/06/14 16:47 CRDT- 2025/03/07 19:13 PHST- 2024/12/11 00:00 [received] PHST- 2025/02/26 00:00 [revised] PHST- 2025/02/28 00:00 [accepted] PHST- 2025/06/14 16:47 [medline] PHST- 2025/03/09 15:09 [pubmed] PHST- 2025/03/07 19:13 [entrez] AID - S1530-891X(25)00068-0 [pii] AID - 10.1016/j.eprac.2025.02.020 [doi] PST - ppublish SO - Endocr Pract. 2025 Jun;31(6):798-804. doi: 10.1016/j.eprac.2025.02.020. Epub 2025 Mar 5. PMID- 40050929 OWN - NLM STAT- MEDLINE DCOM- 20250307 LR - 20260127 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 20 IP - 1 DP - 2025 Mar 6 TI - Effects of semaglutide in patients with chronic ankle instability: evidence from a prospective cohort. PG - 243 LID - 10.1186/s13018-025-05664-9 [doi] LID - 243 AB - BACKGROUND: Whether patients with chronic ankle instability (CAI) can benefit from weight loss yielded by using glucagon-like peptide-1 receptor agonists (GLP1-RAs) has remained unclear. METHODS: In this observational study, we recruited more than 2000 adults with CAI according to the selection criteria proposed by International Ankle Consortium with at least two-year follow up from three medical centers. The primary endpoint was the change from baseline of the Foot and Ankle Ability Measure (FAAM) sports subscale at the last follow up. Secondary endpoints included the change from baseline of Foot and Ankle Outcome Score (FAOS)/ Cumberland Ankle Instability Tool (CAIT)/ FAAM activities of daily living (ADL) subscale, number of ankle sprains during study period, incident ankle surgery in treatment of CAI. RESULTS: In this study, 71 out of 2018 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss during the study period. After controlling baseline characteristics, the adjusted mean difference in change from baseline was 16.3 for FAAM sports subscale and 9.3 for FAAM ADL subscale. Likewise, the adjusted analysis of five subscales of FAOS showed similar results, all consistently favoring semaglutide group. For CAIT, patients in the semaglutide group had achieved statistically significant improvement compared with control group. The association of semaglutide exposure with improvement in FAAM sports and ADL subscales was mediated by the weight loss measured by BMI (mediation proportion: FAAM sports subscale, 31.2% [22.2-41.2%]; FHSQ ADL subscale, 34.1% [24.4-44.8%]). We also observed statistically significant decreases in number of recurrent ankle sprains during study period. For incident ankle surgery, 1 out of 71 patients (1.4%) and 151 out of 1947 patients (7.8%) received ankle surgeries in semaglutide and control groups, respectively (P = 0.047). CONCLUSIONS: Semaglutide may show potential benefits as a supplementary intervention in treatment of CAI by improving patient-reported outcomes and preventing recurrent ankle sprains. Further randomized trial is warranted by the current study to further confirm our findings. TRIAL REGISTRATION: researchregistry10716. CI - (c) 2025. The Author(s). FAU - Zhang, Jieyuan AU - Zhang J AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Wang, Cheng AU - Wang C AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Wang, Jiazheng AU - Wang J AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Gu, Wenqi AU - Gu W AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital East Campus, Shanghai, 201306, China. FAU - Wang, Haiqing AU - Wang H AD - Department of Orthopedic Surgery, Ningbo No. 6 hospital, Ningbo, 315040, China. FAU - Zhu, Hongyi AU - Zhu H AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. 420308955@qq.com. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. 420308955@qq.com. FAU - Ma, Xin AU - Ma X AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. maxin@sjtu.edu.cn. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. maxin@sjtu.edu.cn. FAU - Shi, Zhongmin AU - Shi Z AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. szm1972@sjtu.edu.cn. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. szm1972@sjtu.edu.cn. LA - eng GR - 82402855/National Natural Science Foundation of China/ GR - YG2022ZD018/Medical Engineering Cross Research Fund of Shanghai Jiao Tong University/ GR - 23SHS03600/Application Demonstration Project of Innovative Medical Devices in Shanghai in 2023/ GR - 23015820500/Science and Technology Commission of Shanghai Municipality/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250306 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Joint Instability/drug therapy MH - Female MH - Male MH - Prospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - Adult MH - *Ankle Joint/drug effects/physiopathology MH - Chronic Disease MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome MH - Follow-Up Studies MH - Weight Loss/drug effects MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11884071 OTO - NOTNLM OT - Ankle sprain OT - Chronic ankle instability OT - GLP-1 receptor agonist OT - Semaglutide OT - Weight loss COIS- Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Ethics Committee of Shanghai Sixth People's Hospital (approval no. 2019-084). Moreover, this study complied with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for research involving humans. Written consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/03/07 00:21 MHDA- 2025/03/07 06:21 PMCR- 2025/03/06 CRDT- 2025/03/06 23:44 PHST- 2025/01/14 00:00 [received] PHST- 2025/02/27 00:00 [accepted] PHST- 2025/03/07 06:21 [medline] PHST- 2025/03/07 00:21 [pubmed] PHST- 2025/03/06 23:44 [entrez] PHST- 2025/03/06 00:00 [pmc-release] AID - 10.1186/s13018-025-05664-9 [pii] AID - 5664 [pii] AID - 10.1186/s13018-025-05664-9 [doi] PST - epublish SO - J Orthop Surg Res. 2025 Mar 6;20(1):243. doi: 10.1186/s13018-025-05664-9. PMID- 40048723 OWN - NLM STAT- MEDLINE DCOM- 20250601 LR - 20250601 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 103 IP - 6 DP - 2025 May 1 TI - Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review. PG - 182-192 LID - 10.1139/cjpp-2024-0384 [doi] AB - The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardiorenal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardiometabolic pathologies. FAU - Pop, Andrea S K AU - Pop A AD - Doctoral School Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. RINGGOLD: 162271 AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Danila, Maria D AU - Danila M AUID- ORCID: 0000-0003-3700-8228 AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Giuchici, Silvia AU - Giuchici S AD - Doctoral School Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. RINGGOLD: 162271 AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Buriman, Darius G AU - Buriman D AD - Doctoral School Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. RINGGOLD: 162271 AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Lolescu, Bogdan M AU - Lolescu B AD - Doctoral School Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. RINGGOLD: 162271 AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Sturza, Adrian AU - Sturza A AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Muntean, Danina M AU - Muntean D AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Lascu, Ana AU - Lascu A AD - Centre for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Department of Functional Sciences - Chair of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. AD - Institute of Cardiovascular Diseases, Timisoara, Romania. LA - eng PT - Journal Article PT - Review DEP - 20250306 PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Incretins/therapeutic use/metabolism/pharmacology MH - *Adipose Tissue/drug effects/metabolism/pathology MH - *Pericardium/drug effects/metabolism/pathology MH - Animals MH - *Cardiovascular Diseases/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Metabolic Diseases/drug therapy/metabolism MH - Receptors, Gastrointestinal Hormone/metabolism/agonists MH - Epicardial Adipose Tissue OTO - NOTNLM OT - cardiovascular protection OT - diabetes OT - glucose-dependent insulinotropic polypeptide OT - heart failure OT - obesity OT - single and dual receptor agonists COIS- All authors declare no conflict of interest. EDAT- 2025/03/06 18:27 MHDA- 2025/06/02 03:17 CRDT- 2025/03/06 16:42 PHST- 2025/06/02 03:17 [medline] PHST- 2025/03/06 18:27 [pubmed] PHST- 2025/03/06 16:42 [entrez] AID - 10.1139/cjpp-2024-0384 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2025 May 1;103(6):182-192. doi: 10.1139/cjpp-2024-0384. Epub 2025 Mar 6. PMID- 40047207 OWN - NLM STAT- MEDLINE DCOM- 20250326 LR - 20260127 IS - 1473-6543 (Electronic) IS - 1062-4821 (Linking) VI - 34 IP - 3 DP - 2025 May 1 TI - Glucagon-like peptide-1 receptor agonists to improve cardiorenal outcomes: data from FLOW and beyond. PG - 232-240 LID - 10.1097/MNH.0000000000001066 [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP1RA), initially approved for glycemic control in type 2 diabetes mellitus (T2DM), have emerged as agents for weight loss, cardiovascular and kidney protection. This review summarizes the evidence supporting the benefits of these therapies on cardiorenal outcomes. RECENT FINDINGS: Clinical trials have consistently demonstrated reductions in major adverse cardiovascular events with GLP1RA treatments. Recently, the FLOW trial revealed that semaglutide reduced the composite outcome of kidney failure, at least 50% decline in estimated glomerular filtration rate, kidney or cardiovascular mortality by 24% in patients with T2DM, thereby establishing GLP1RA as a pillar of therapy in this population. New evidence suggests favorable effects on kidney endpoints in nondiabetic individuals with overweight or obesity. Dedicated trials have also provided evidence for reduction in the risk for heart failure hospitalization and improvement in symptoms in individuals with heart failure with preserved ejection fraction. Subgroup analyses have suggested that GLP1RAs confer additive cardiorenal benefits irrespective of background medication use. SUMMARY: There is increasing evidence that GLP1RA reduces the risk for cardiovascular events, chronic kidney disease progression, and heart failure hospitalizations. Further data on the effect of dual and triple GLP1-based therapies on cardiorenal outcomes is required. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Faruque, Labib AU - Faruque L AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Yau, Kevin AU - Yau K AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20250306 PL - England TA - Curr Opin Nephrol Hypertens JT - Current opinion in nephrology and hypertension JID - 9303753 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/mortality/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Incretins/therapeutic use/adverse effects MH - *Kidney/drug effects/physiopathology MH - *Cardiovascular Diseases/prevention & control/mortality MH - *Heart Failure/prevention & control/physiopathology/mortality MH - Glucagon-Like Peptides/therapeutic use MH - *Renal Insufficiency, Chronic/physiopathology/prevention & control/mortality MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/06 12:32 MHDA- 2025/03/26 13:06 CRDT- 2025/03/06 06:33 PHST- 2025/03/26 13:06 [medline] PHST- 2025/03/06 12:32 [pubmed] PHST- 2025/03/06 06:33 [entrez] AID - 00041552-990000000-00218 [pii] AID - 10.1097/MNH.0000000000001066 [doi] PST - ppublish SO - Curr Opin Nephrol Hypertens. 2025 May 1;34(3):232-240. doi: 10.1097/MNH.0000000000001066. Epub 2025 Mar 6. PMID- 40045764 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260818 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Effectiveness and safety of daily oral semaglutide in people with type 2 diabetes mellitus switching from sulfonylureas: A real-world retrospective study. PG - 3084-3093 LID - 10.1111/dom.16314 [doi] AB - BACKGROUND: Hypoglycaemia is a serious side effect in the treatment of type 2 diabetes mellitus (T2DM), especially when using insulin and insulin secretagogues such as sulfonylureas. Current guidelines recommend reducing or discontinuing these medications in high-risk populations. This study assessed the real-world effectiveness and safety of oral semaglutide in T2DM patients who suspended or reduced sulfonylurea dosages in favour of oral semaglutide. METHODS: In this retrospective, multicentre cohort study, the primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to an average follow-up period of 37 weeks. Secondary endpoints included changes in fasting blood glucose, body weight, the proportion of patients achieving HbA1c /=1%) and body weight (>/=5%). Safety and exploratory endpoints were also evaluated. RESULTS: The study included 104 patients (mean age: 68.9 +/- 9.9 years). Treatment discontinuation occurred in 9.6% of patients, and 12.5% reported adverse events, primarily gastrointestinal; no hypoglycaemic events were reported. HbA1c significantly decreased from 7.62% to 7.42% (p = 0.04, mean reduction of 0.22%) and the proportion of patients achieving HbA1c /=69 mmol/mol), all-cause mortality, major adverse cardiovascular events or heart failure (MACE-HF) outcomes, renal progression, and microvascular complications using Cox proportional hazards regression adjusting for relevant demographic and clinical covariates. FINDINGS: The five-drug class model was developed from 100 107 drug initiations in CPRD. In the overall CPRD cohort (combined development and validation cohorts), 32 305 (15.2%) of 212 166 drug initiations were of the model-predicted optimal therapy. In model-concordant groups, mean observed 12-month HbA(1c) benefit was 5.3 mmol/mol (95% CI 4.9-5.7) in the CPRD geographical validation cohort (n=24 746 drug initiations, n=12 373 matched pairs) and 5.0 mmol/mol (4.3-5.6) in the CPRD temporal validation cohort (n=9682 drug initiations, n=4841 matched pairs) compared with matched model-discordant groups. Predicted HbA(1c) differences were well calibrated with observed HbA(1c) differences in the three clinical trials in pairwise drug class comparisons, and in pairwise comparisons of the five drug classes in CPRD. 5-year risk of glycaemic failure was lower in model-concordant versus model-discordant groups in CPRD (adjusted hazard ratio [aHR] 0.62 [95% CI 0.59-0.64]). For long-term non-glycaemic outcomes, model-concordant versus model-discordant groups had a similar 5-year risk of all-cause mortality (aHR 0.95 [0.83-1.09]) and lower risks of MACE-HF outcomes (aHR 0.85 [0.76-0.95]), renal progression (aHR 0.71 [0.64-0.79]), and microvascular complications (aHR 0.86 [0.78-0.96]). INTERPRETATION: We have developed a five-drug class model that uses routine clinical data to identify optimal glucose-lowering therapies for people with type 2 diabetes. Individuals on model-predicted optimal therapy had lower 12-month HbA(1c), were less likely to need additional glucose-lowering therapy, and had a lower risk of diabetes complications than individuals on non-optimal therapy. With setting-specific optimisation, the use of routinely collected parameters means that the model is easy to introduce to clinical care in most countries worldwide. FUNDING: UK Medical Research Council. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Dennis, John M AU - Dennis JM AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. Electronic address: j.dennis@exeter.ac.uk. FAU - Young, Katherine G AU - Young KG AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Cardoso, Pedro AU - Cardoso P AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Gudemann, Laura M AU - Gudemann LM AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - McGovern, Andrew P AU - McGovern AP AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Farmer, Andrew AU - Farmer A AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Holman, Rury R AU - Holman RR AD - Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. FAU - McKinley, Trevelyan J AU - McKinley TJ AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Pearson, Ewan R AU - Pearson ER AD - Division of Diabetes, Endocrinology and Reproductive Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. FAU - Jones, Angus G AU - Jones AG AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Shields, Beverley M AU - Shields BM AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. FAU - Hattersley, Andrew T AU - Hattersley AT AD - Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK. CN - MASTERMIND Consortium LA - eng SI - ClinicalTrials.gov/NCT00622284 SI - ClinicalTrials.gov/NCT01167881 PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20250225 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) SB - IM CIN - Lancet. 2025 Mar 1;405(10480):672-674. doi: 10.1016/S0140-6736(24)02844-7. PMID: 40020701 MH - Adolescent MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use/classification MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Randomized Controlled Trials as Topic COIS- Declaration of interests JMD is supported by a Wellcome Trust Early-Career Award (227070/Z/23/Z). KGY and TJM were previously supported by Research England's Expanding Excellence in England (E3) fund. APM declares previous research funding from Eli Lilly, Pfizer, and AstraZeneca. ERP declares personal fees from Illumina, Eli Lilly, and Novo Nordisk. RRH is an Emeritus National Institute for Health and Care Research (NIHR) Senior Investigator, and reports personal fees from AstraZeneca, Eli Lilly, and Novartis. NS declares personal fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi, and grants to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. ATH and BMS are supported by the NIHR Exeter Clinical Research Facility and AF is supported by the NIHR Oxford Biomedical Research Centre. AGJ was previously supported by an NIHR Clinician Scientist Fellowship (CS-2015-15-018) and declares research funding to his university from the UK Medical Research Council, Diabetes UK, Breakthrough T1D (formerly JDRF), the European Foundation for the Study of Diabetes, and the Novo Nordisk Foundation. PC and LMG declare no competing interests. Representatives from GSK, Takeda, Janssen, Quintiles, AstraZeneca, and Sanofi attended meetings as part of the industry group involved with the MASTERMIND Consortium. No industry representatives were involved in the writing of the manuscript or analysis of data. For all authors, all aforementioned declarations are outside the submitted work; all authors declare that there are no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2025/03/01 14:39 MHDA- 2025/03/03 00:57 CRDT- 2025/02/28 18:53 PHST- 2024/10/03 00:00 [received] PHST- 2024/11/25 00:00 [revised] PHST- 2024/11/27 00:00 [accepted] PHST- 2025/03/03 00:57 [medline] PHST- 2025/03/01 14:39 [pubmed] PHST- 2025/02/28 18:53 [entrez] AID - S0140-6736(24)02617-5 [pii] AID - 10.1016/S0140-6736(24)02617-5 [doi] PST - ppublish SO - Lancet. 2025 Mar 1;405(10480):701-714. doi: 10.1016/S0140-6736(24)02617-5. Epub 2025 Feb 25. PMID- 40017057 OWN - NLM STAT- MEDLINE DCOM- 20250415 LR - 20260716 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 104 IP - 3 DP - 2025 Apr TI - Effect of diabetes medications on the risk of developing dementia, mild cognitive impairment, or cognitive decline: A systematic review and meta-analysis. PG - 627-648 LID - 10.1177/13872877251319054 [doi] AB - Background: Diabetes is a risk factor for dementia, but we do not know whether specific diabetes medications ameliorate this risk. Objective: To systematically review and meta-analyze such medication's effect on the risk of developing dementia, mild cognitive impairment (MCI), or cognitive decline. Methods: We searched three databases until 21 November 2023. We included randomized controlled trials (RCT), cohort, and case-control studies assessing association between antidiabetic medication and future dementia, MCI, or cognitive decline. We meta-analyzed studies separately for individual drug classes and their comparators (no medication, placebo, or another drug). We appraised study quality using the Newcastle-Ottawa Scale and Physiotherapy Evidence Database Scale. Results: 42 studies fulfilled inclusion criteria. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus placebo reduced dementia risk by 53% in three RCTs (n = 15,820, RR = 0.47[0.25, 0.86]) and 27% in three case-control studies (n = 312,856, RR = 0.73[0.54, 0.99], I(2 )= 96%). Repaglinide was superior to glibenclamide by 0.8 points on the Mini-Mental State Examination scale in another RCT. Meta-analysis of seven longitudinal studies showed glitazones (n = 1,081,519, RR = 0.78[0.76, 0.81], I(2 )= 0%) were associated with reduced dementia risk. Metformin (n = 999,349, RR = 0.94[0.79, 1.13], I(2 )= 98.4%), sulfonylureas (RR = 0.98[0.78, 1.22], I(2 )= 83.3%), dipeptidyl peptidase-IV inhibitors (DPP-1V) (n = 192,802, RR = 0.86[0.65, 1.15], I(2 )= 92.9%) and insulin (n = 571,274, RR = 1.09[0.95, 1.25], I(2 )= 94.8%) were not. Most studies were observational and limited by confounding by indication. Conclusions: In people with diabetes, RCTs consistently showed GLP-RAs reduce future dementia risk. Glitazones consistently showed protective effects, without heterogeneity, suggesting potential generalizability of these results. Metformin, sulfonylureas, insulin, and DPP-1V studies had inconsistent findings. If information is available future studies should consider dosage, severity, and duration. FAU - Hui, Esther K AU - Hui EK AUID- ORCID: 0000-0001-7815-5473 AD - Division of Psychiatry, University College London, London, UK. FAU - Mukadam, Naaheed AU - Mukadam N AUID- ORCID: 0000-0001-8635-9521 AD - Division of Psychiatry, University College London, London, UK. FAU - Kohl, Gianna AU - Kohl G AUID- ORCID: 0000-0002-8913-1247 AD - Division of Psychology and Language Sciences, University College London, London, UK. FAU - Livingston, Gill AU - Livingston G AUID- ORCID: 0000-0001-6741-5516 AD - Division of Psychiatry, University College London, London, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20250227 PL - United States TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - *Cognitive Dysfunction/epidemiology/prevention & control MH - *Dementia/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Metformin/therapeutic use PMC - PMC12231844 OTO - NOTNLM OT - Alzheimer's disease OT - cognitive decline OT - cognitive impairment OT - dementia OT - diabetes OT - prevention OT - risk factors COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/02/28 06:22 MHDA- 2025/04/15 06:24 PMCR- 2025/07/07 CRDT- 2025/02/28 01:53 PHST- 2025/04/15 06:24 [medline] PHST- 2025/02/28 06:22 [pubmed] PHST- 2025/02/28 01:53 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - 10.1177_13872877251319054 [pii] AID - 10.1177/13872877251319054 [doi] PST - ppublish SO - J Alzheimers Dis. 2025 Apr;104(3):627-648. doi: 10.1177/13872877251319054. Epub 2025 Feb 27. PMID- 40016997 OWN - NLM STAT- MEDLINE DCOM- 20250510 LR - 20250510 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 34 IP - 3 DP - 2025 Mar TI - The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists. PG - 169-195 LID - 10.1080/13543784.2025.2473062 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon receptor agonists have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control and weight are well-established, clinicians may be unfamiliar with other potential benefits of this class. AREAS COVERED: We examined the pleiotropic effects of GLP-1RAs and how they relate to gastroenterologists for MASLD/MASH treatment. Our narrative review of English articles included four GLP-1RAs (subcutaneous semaglutide, liraglutide, dulaglutide, and efpeglenatide), a dual GLP-1/GIP agonist (tirzepatide), a dual GLP-1/glucagon receptor agonist (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes and landscape. EXPERT OPINION: In Phase I - III trials, GLP-1RAs are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis. Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes. Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions. FAU - Alkhouri, Naim AU - Alkhouri N AD - Department of Hepatology, Arizona Liver Health, Phoenix, AZ, USA. FAU - Charlton, Michael AU - Charlton M AD - Transplant Institute, Center for Liver Diseases, University of Chicago Biological Sciences, Chicago, IL, USA. FAU - Gray, Meagan AU - Gray M AD - Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Noureddin, Mazen AU - Noureddin M AD - Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA. LA - eng PT - Journal Article PT - Review DEP - 20250317 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Fatty Liver/drug therapy/physiopathology/etiology MH - Animals MH - Hypoglycemic Agents/pharmacology MH - *Metabolic Diseases/drug therapy/physiopathology/complications MH - Diabetes Mellitus, Type 2/drug therapy/complications OTO - NOTNLM OT - Cardiometabolic risk factors OT - GLP-1 OT - GLP-1RA OT - MASH OT - MASLD OT - safety OT - treatment landscape EDAT- 2025/02/28 06:21 MHDA- 2025/03/20 06:24 CRDT- 2025/02/28 01:12 PHST- 2025/03/20 06:24 [medline] PHST- 2025/02/28 06:21 [pubmed] PHST- 2025/02/28 01:12 [entrez] AID - 10.1080/13543784.2025.2473062 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2025 Mar;34(3):169-195. doi: 10.1080/13543784.2025.2473062. Epub 2025 Mar 17. PMID- 40015951 OWN - NLM STAT- MEDLINE DCOM- 20250407 LR - 20250421 IS - 1468-3288 (Electronic) IS - 0017-5749 (Linking) VI - 74 IP - 5 DP - 2025 Apr 7 TI - Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies. PG - 815-824 LID - 10.1136/gutjnl-2024-334591 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain. OBJECTIVE: We performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D). DESIGN: We systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs). RESULTS: 11 retrospective cohort studies with aggregate data on 1 467 220 patients with T2D (647 903 GLP-1RA new users, 819 317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR 0.71, 95% CI 0.57 to 0.88) and hepatic decompensation (IRR 0.70, 95% CI 0.52 to 0.94). Association with reduced risk of HCC was also observed (IRR 0.82, 95% CI 0.61 to 1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87 to 0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR 0.74, 95% CI 0.66 to 0.83) and versus insulin therapy in preventing HCC (IRR 0.32, 95% CI 0.13 to 0.80). CONCLUSIONS: GLP-1RA use is associated with a lower risk of liver-related complications and hepatic decompensation in people with T2D. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects. CI - (c) Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Celsa, Ciro AU - Celsa C AUID- ORCID: 0000-0002-5662-2162 AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. AD - Department of Surgery & Cancer, Imperial College London, London, UK. FAU - Pennisi, Grazia AU - Pennisi G AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Tulone, Adele AU - Tulone A AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Ciancimino, Giacinta AU - Ciancimino G AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Vaccaro, Marco AU - Vaccaro M AD - University of Palermo, Palermo, Italy. FAU - Infantino, Giuseppe AU - Infantino G AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Di Maria, Gabriele AU - Di Maria G AD - Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Pinato, David J AU - Pinato DJ AD - Department of Surgery & Cancer, Imperial College London, London, UK. AD - Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy. FAU - Cabibbo, Giuseppe AU - Cabibbo G AUID- ORCID: 0000-0002-0946-3859 AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Enea, Marco AU - Enea M AD - Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Mantovani, Alessandro AU - Mantovani A AUID- ORCID: 0000-0002-7271-6329 AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. FAU - Tilg, Herbert AU - Tilg H AUID- ORCID: 0000-0002-4235-2579 AD - Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria. FAU - Targher, Giovanni AU - Targher G AUID- ORCID: 0000-0002-4325-3900 AD - Department of Medicine, University of Verona, Verona, Italy. AD - Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella (VR), Italy. FAU - Camma, Calogero AU - Camma C AUID- ORCID: 0000-0002-9224-1914 AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy. FAU - Petta, Salvatore AU - Petta S AUID- ORCID: 0000-0002-0822-9673 AD - Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy salvatore.petta@unipa.it. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250407 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Observational Studies as Topic MH - Liver Neoplasms/prevention & control/epidemiology MH - Carcinoma, Hepatocellular/prevention & control/epidemiology MH - *Liver Diseases/prevention & control/etiology/epidemiology OTO - NOTNLM OT - CIRRHOSIS OT - DIABETES MELLITUS OT - FATTY LIVER OT - HEPATOCELLULAR CARCINOMA COIS- Competing interests: HT is an Associate Editor of the journal, and GT is an Editorial board member of the journal. The authors did not report any disclosure related to this work. EDAT- 2025/02/28 00:20 MHDA- 2025/04/08 00:24 CRDT- 2025/02/27 21:13 PHST- 2024/12/13 00:00 [received] PHST- 2025/02/16 00:00 [accepted] PHST- 2025/04/08 00:24 [medline] PHST- 2025/02/28 00:20 [pubmed] PHST- 2025/02/27 21:13 [entrez] AID - gutjnl-2024-334591 [pii] AID - 10.1136/gutjnl-2024-334591 [doi] PST - epublish SO - Gut. 2025 Apr 7;74(5):815-824. doi: 10.1136/gutjnl-2024-334591. PMID- 40015592 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260813 IS - 1879-1891 (Electronic) IS - 0002-9394 (Print) IS - 0002-9394 (Linking) VI - 274 DP - 2025 Jun TI - The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy. PG - 24-31 LID - S0002-9394(25)00094-7 [pii] LID - 10.1016/j.ajo.2025.02.025 [doi] AB - PURPOSE: The association between GLP-1 receptor agonists (GLP-1RA) and nonarteritic anterior ischemic optic neuropathy (NAION) remains unclear. Given the debilitating sequelae of NAION and rapid increase of GLP-1RA use, further research is essential to investigate this potential relationship. This study seeks to determine the risk of NAION and ischemic optic neuropathy (ION) in patients prescribed GLP-1RAs. DESIGN: Retrospective matched cohort study. SETTING: TriNetX United States collaborative network. PARTICIPANTS: Patients >/=12 years old with type 2 diabetes (T2DM) and considered overweight or obese (high BMI), with at least one ophthalmology or neurology visit. Among T2DM patients, approximately 120,000 patients with a semaglutide prescription and 220,000 prescribed any GLP-1RA were compared to matched T2DM controls. Among high BMI patients, approximately 58,000 on semaglutide and 66,000 on any GLP-1RA were compared to matched controls. METHODS: Patients prescribed semaglutide or any GLP-1RA were compared with those on non-GLP-1RA medications. Populations were propensity matched (1:1) on various demographic and risk factors to balance baseline cohorts. MAIN OUTCOMES AND MEASURES: Cumulative incidence and risk of NAION and ION. Risk ratios (RR) with 95% confidence intervals (CI) were reported, with significance defined as CI <0.9 or > 1.1. RESULTS: In T2DM patients prescribed semaglutide, the risk of NAION (RR = 0.7, 95% CI: 0.523-0.937) and ION (RR = 0.788, 95% CI: 0.609-1.102) after 5 years was not significantly increased compared to matched T2DM controls. Similarly, T2DM patients on any GLP-1RA demonstrated no significant difference in the risk of NAION (RR = 0.887, 95% CI: 0.735-1.071) or ION (RR = 0.969, 95% CI: 0.813-1.154) compared to controls. Furthermore, no increased risk of either outcome was found in the high BMI groups prescribed semaglutide or any GLP-1RA. The cumulative 5-year risk of NAION and ION in T2DM patients on semaglutide was 0.065% and 0.08%, respectively. In those with high BMI prescribed semaglutide, the risk of NAION and ION after 2 years was 0.038% and 0.404%, respectively. CONCLUSIONS: There was no significant increase in risk of NAION or ION in patients taking semaglutide or GLP-1RAs compared to T2DM or high BMI controls. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Abbass, Nadia J AU - Abbass NJ AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Nahlawi, Raya AU - Nahlawi R AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Shaia, Jacqueline K AU - Shaia JK AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Allan, Kevin C AU - Allan KC AD - Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Departments of Internal Medicine, Pediatrics and Population and Quantitative Health Sciences, Case Western Reserve University (D.C.K.), Cleveland, Ohio, USA; The Center for Clinical Informatics Research and Education (D.C.K.), The MetroHealth System, Cleveland, Ohio, USA. FAU - Talcott, Katherine E AU - Talcott KE AD - Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA. FAU - Singh, Rishi P AU - Singh RP AD - Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Martin Hospitals (R.P.S.), Cleveland Clinic Florida, Stuart, Florida, USA. Electronic address: singhr@ccf.org. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - UL1 TR002548/TR/NCATS NIH HHS/United States GR - P30 EY025585/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20250225 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Risk Factors MH - Incidence MH - Adult MH - Body Mass Index MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC13110070 MID - NIHMS2163178 EDAT- 2025/02/28 00:20 MHDA- 2025/05/01 12:31 PMCR- 2026/04/25 CRDT- 2025/02/27 19:35 PHST- 2025/01/14 00:00 [received] PHST- 2025/02/19 00:00 [revised] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/05/01 12:31 [medline] PHST- 2025/02/28 00:20 [pubmed] PHST- 2025/02/27 19:35 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - S0002-9394(25)00094-7 [pii] AID - 10.1016/j.ajo.2025.02.025 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Jun;274:24-31. doi: 10.1016/j.ajo.2025.02.025. Epub 2025 Feb 25. PMID- 40014091 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 9 DP - 2025 Sep TI - Long-term efficacy of daily oral semaglutide as add-on or switch therapy in adults with type 2 diabetes: a 12-month real-world retrospective study. PG - 1469-1478 LID - 10.1007/s00592-025-02475-6 [doi] AB - AIMS: To evaluate the efficacy of oral semaglutide, either as an add-on or replacement therapy, in improving glycemic control, body weight, and cardiovascular parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: This real-world study evaluated changes in glycated hemoglobin (HbA1c), body weight, and parameters of cardiovascular risk from baseline to a 12-month follow-up visit. The primary endpoint was the change in HbA1c between baseline and follow-up. Secondary endpoints included changes in body weight, the proportion of patients achieving HbA1c /= 1%) and body weight (>/= 5%). Exploratory endpoints were evaluated as well. RESULTS: Data from 950 patients, predominantly female (63.7%) and with a mean age of 68.3 +/- 10.1 years, were included in the study. Prior to starting semaglutide, most patients were on sulfonylureas, either as monotherapy or in combination with metformin or basal insulin. At baseline, mean HbA1c was 8.0 +/- 1.3% (64.0 +/- 14.2 mmol/mol), and body weight was 82.5 kg. Following 12 months of oral semaglutide treatment, HbA1c decreased significantly of -0.84% (p < 0.001) and 53% of patients achieved HbA1c /= 1% reduction in HbA1c and >/= 5% in body weight. Diastolic blood pressure and LDL levels decreased significantly (p < 0.001), while systolic blood pressure and eGFR remained stable. CONCLUSIONS: When used as an add-on or replacement therapy, oral semaglutide significantly improves glycemic control, body weight, renal and cardiovascular risk factors in T2DM patients. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Sansone, Daniela AU - Sansone D AUID- ORCID: 0009-0002-5494-9580 AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. daniela.sansone@aslcittaditorino.it. FAU - Garino, Francesca AU - Garino F AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Gottero, Cristina AU - Gottero C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Gauna, Carlotta AU - Gauna C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Clerico, Alessandra AU - Clerico A AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Corneli, Ginevra AU - Corneli G AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Di Noi, Fabiana AU - Di Noi F AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Mainolfi, Alessandra Rita AU - Mainolfi AR AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Rossi, Claudio AU - Rossi C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Marafetti, Lisa AU - Marafetti L AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Matteoda, Cristina AU - Matteoda C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Balbo, Marcella Libera AU - Balbo ML AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Petraroli, Giuliana AU - Petraroli G AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Bonelli, Nadia AU - Bonelli N AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Toscano, Claudia Chiara M AU - Toscano CCM AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Visconti, Licia AU - Visconti L AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Oleandri, Salvatore AU - Oleandri S AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. LA - eng PT - Journal Article DEP - 20250227 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - Glycated Hemoglobin/metabolism/analysis MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - Drug Therapy, Combination MH - Body Weight/drug effects MH - Treatment Outcome MH - Metformin/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Body weight OT - Cardiovascular risk OT - GLP1-RA OT - HbA1c OT - Oral semaglutide OT - Real-word evidence OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: All authors have nothing to declare. Ethical statement: The study was approved by the relevant ethics committee and adhered to the Good Clinical Practice guidelines concerning clinical investigations on human subjects and the Declaration of Helsinki. Informed consent: All participants provided written informed consent to participate in the study. EDAT- 2025/02/27 12:29 MHDA- 2025/09/16 13:03 CRDT- 2025/02/27 11:14 PHST- 2024/12/04 00:00 [received] PHST- 2025/02/13 00:00 [accepted] PHST- 2025/09/16 13:03 [medline] PHST- 2025/02/27 12:29 [pubmed] PHST- 2025/02/27 11:14 [entrez] AID - 10.1007/s00592-025-02475-6 [pii] AID - 10.1007/s00592-025-02475-6 [doi] PST - ppublish SO - Acta Diabetol. 2025 Sep;62(9):1469-1478. doi: 10.1007/s00592-025-02475-6. Epub 2025 Feb 27. PMID- 40010803 OWN - NLM STAT- MEDLINE DCOM- 20250510 LR - 20260624 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 388 DP - 2025 Feb 26 TI - Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study. PG - e080679 LID - 10.1136/bmj-2024-080679 [doi] LID - e080679 AB - OBJECTIVE: To determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with an increased risk of suicidal ideation, self-harm, and suicide among patients with type 2 diabetes compared with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors. DESIGN: Active comparator, new user cohort study. SETTING: Primary care practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics Death Registration databases. PARTICIPANTS: Patients with type 2 diabetes. EXPOSURES: Two cohorts were assembled, with the first composed of patients who started and continued on GLP-1 receptor agonists or DPP-4 inhibitors between 1 January 2007 and 31 December 2020 and the second composed of patients who started and continued on GLP-1 receptor agonists or SGLT-2 inhibitors between 1 January 1 2013 and 31 December 2020. Both cohorts were followed until 29 March 2021. MAIN OUTCOME MEASURES: The primary outcome was suicidality, defined as a composite of suicidal ideation, self-harm, and suicide. Secondary outcomes were each of these events considered separately. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios and 95% confidence intervals (CIs) to estimate the average treatment effect among the treated patients. RESULTS: The first cohort included 36 082 GLP-1 receptor agonist users (median follow-up 1.3 years) and 234 028 DPP-4 inhibitor users (median follow-up 1.7 years). In crude analyses, GLP-1 receptor agonist use was associated with an increased incidence of suicidality compared with DPP-4 inhibitors (crude incidence rates 3.9 v 1.8 per 1000 person years, respectively; hazard ratio 2.08, 95% CI 1.83 to 2.36). This estimate decreased to a null value after confounding factors were accounted for (hazard ratio 1.02, 95% CI 0.85 to 1.23). The second cohort included 32 336 GLP-1 receptor agonist users (median follow-up 1.2 years) and 96 212 SGLT-2 inhibitor users (median follow-up 1.2 years). Similarly, GLP-1 receptor agonist use was associated with an increased risk of suicidality compared with SGLT-2 inhibitors in crude analyses (crude incidence rates 4.3 v 2.7 per 1000 person years; hazard ratio 1.60, 95% CI 1.37 to 1.87) but not after confounding factors were accounted for (0.91, 0.73 to 1.12). Similar findings were observed when suicidal ideation, self-harm, and suicide were analysed separately in both cohorts. CONCLUSIONS: In this large cohort study, the use of GLP-1 receptor agonists was not associated with an increased risk of suicidality compared with the use of DPP-4 inhibitors or SGLT-2 inhibitors in patients with type 2 diabetes. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Shapiro, Samantha B AU - Shapiro SB AUID- ORCID: 0000-0002-7957-508X AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. AD - Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. FAU - Yin, Hui AU - Yin H AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. FAU - Yu, Oriana Hoi Yun AU - Yu OHY AUID- ORCID: 0000-0003-4877-557X AD - Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada. AD - Division of Endocrinology & Metabolism, McGill University, Montreal, QC, Canada. FAU - Rej, Soham AU - Rej S AUID- ORCID: 0000-0002-3908-9124 AD - Department of Psychiatry, Jewish General Hospital, Montreal, QC, Canada. AD - Department of Psychiatry, McGill University, Montreal, QC, Canada. FAU - Suissa, Samy AU - Suissa S AUID- ORCID: 0000-0002-1281-5296 AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. AD - Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. AD - Department of Medicine, McGill University, Montreal, QC, Canada. FAU - Azoulay, Laurent AU - Azoulay L AUID- ORCID: 0000-0001-5162-3556 AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. AD - Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. LA - eng PT - Journal Article DEP - 20250226 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM EIN - BMJ. 2025 Apr 28;389:r845. doi: 10.1136/bmj.r845. PMID: 40294951 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - United Kingdom/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Suicidal Ideation MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Cohort Studies MH - *Suicide/statistics & numerical data MH - Self-Injurious Behavior/epidemiology/chemically induced MH - Risk Factors PMC - PMC11863255 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this study was funded by the Canadian Institutes of Health Research; SR is a shareholder of Aifred Health; SS attended scientific advisory committee meetings or received speaking fees from AstraZeneca, Atara, Boehringer Ingelheim, Bristol-Myers-Squibb, Covis, Novartis, Panalgo, Pfizer, CSL Behring, and Covispharma, all unrelated to this study; LA received speaking and consulting fees from Pfizer, Boehringer Ingelheim, and Roche for work unrelated to this study; no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2025/02/27 05:03 MHDA- 2025/02/27 05:04 PMCR- 2025/02/26 CRDT- 2025/02/26 20:52 PHST- 2025/02/27 05:04 [medline] PHST- 2025/02/27 05:03 [pubmed] PHST- 2025/02/26 20:52 [entrez] PHST- 2025/02/26 00:00 [pmc-release] AID - BMJ-2024-080679.R3 [pii] AID - shas080679 [pii] AID - 10.1136/bmj-2024-080679 [doi] PST - epublish SO - BMJ. 2025 Feb 26;388:e080679. doi: 10.1136/bmj-2024-080679. PMID- 40009763 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20250730 IS - 1473-6578 (Electronic) IS - 0951-7367 (Linking) VI - 38 IP - 5 DP - 2025 Sep 1 TI - Risk of depression and dementia among individuals treated with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. PG - 368-375 LID - 10.1097/YCO.0000000000001001 [doi] AB - PURPOSE OF REVIEW: To review whether sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists decrease the risk of depression, suicidal ideation and cognitive impairment in later life. RECENT FINDINGS: The results of studies using information derived from large registries and administrative health datasets suggest that GLP-1 receptor agonists (RAs) increase the risk of suicidality, although findings have been inconsistent. One nested-case control study reported that SGLT2i decreases the risk of depression among adults with diabetes, and findings from a small trial of the SGLT2i empagliflozin provided supportive evidence. Several observational studies reported that SGLT2i and GLP-1 RAs decrease dementia risk, with a target trial finding greater cognitive benefit associated with the use of GLP-1 RAs compared with other medicines commonly used to manage diabetes. SUMMARY: Recent results from large observational studies suggest that SGLT2i and GLP-1 RA may decrease the risk of cognitive impairment in later life. The effects of these medicines on mood have not been as well explored, but there are concerns about the potential increased risk of suicidality among GLP-1 RA users. Prescription bias could explain some of these associations, so that robust trial evidence is now needed to confirm or dismiss the reported findings. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Almeida, Osvaldo P AU - Almeida OP AD - Institute for Health Research, University of Notre Dame Australia. AD - WA Centre for Health & Ageing, Medical School, University of Western Australia. LA - eng PT - Journal Article PT - Review DEP - 20250219 PL - United States TA - Curr Opin Psychiatry JT - Current opinion in psychiatry JID - 8809880 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Dementia/chemically induced MH - *Depression/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - dementia OT - depression OT - glucagon-like peptide 1 receptor agonist OT - sodium-glucose cotransporter 2 inhibitor OT - suicide EDAT- 2025/02/26 18:17 MHDA- 2025/07/30 12:30 CRDT- 2025/02/26 15:13 PHST- 2025/07/30 12:30 [medline] PHST- 2025/02/26 18:17 [pubmed] PHST- 2025/02/26 15:13 [entrez] AID - 00001504-990000000-00164 [pii] AID - 10.1097/YCO.0000000000001001 [doi] PST - ppublish SO - Curr Opin Psychiatry. 2025 Sep 1;38(5):368-375. doi: 10.1097/YCO.0000000000001001. Epub 2025 Feb 19. PMID- 40008510 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260817 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 14 IP - 5 DP - 2025 Mar 4 TI - Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes. PG - e039129 LID - 10.1161/JAHA.124.039129 [doi] LID - e039129 AB - BACKGROUND: We investigated the effects of the combined treatment with glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on NT-proBNP (N-terminal pro-brain natriuretic peptide), GDF-15 (growth differentiation factor 15), and MOTS-c (mitochondrial-derived peptide-c) in patients with type 2 diabetes (T2D) and high or very high cardiovascular risk. METHODS: We studied 163 consecutive patients with type 2 diabetes who were treated with insulin (n=40), liraglutide (n=41), empagliflozin (n=42), or their combination (GLP-1RA+SGLT-2i) (n=40) and were matched using propensity score analysis. We measured the following at baseline and 4 and 12 months of treatment: (1) NT-proBNP, GDF-15, and MOTS-c; (2) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and (3) left ventricular global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index using speckle-tracking imaging. RESULTS: At 12 months, GLP-1RA, SGLT-2i, and their combination showed a greater reduction of NT-proBNP (-43.1% versus -54.2% versus -56.9% versus -14.7%) and GDF-15 than insulin. Only treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c. GLP-1RA, SGLT-2i, or GLP-1RA+SGLT-2i provided an increase of global longitudinal strain, left atrial strain, and global work index compared with insulin. In all patients, the reduction of NT-proBNP was associated with the improvement of global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index; the decrease of GDF-15 with the increase of ABTS and MOTS-c; and the increase of MOTs-c with improved global longitudinal strain and constructive myocardial work at 12 months (P<0.05). CONCLUSIONS: Twelve-month treatment with combination of GLP-1RA+SGLT-2i was associated with a greater reduction of neurohumoral markers and increase of antioxidant ability than each treatment alone and insulin. SGLT-2i appear more effective in the improvement of neurohumoral and mitochondrial activation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03878706. FAU - Ikonomidis, Ignatios AU - Ikonomidis I AUID- ORCID: 0000-0001-8241-7886 AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Pavlidis, George AU - Pavlidis G AUID- ORCID: 0000-0003-3220-3446 AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Pliouta, Loukia AU - Pliouta L AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece. FAU - Katogiannis, Konstantinos AU - Katogiannis K AUID- ORCID: 0000-0003-1631-5210 AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Maratou, Eirini AU - Maratou E AUID- ORCID: 0000-0002-9982-7942 AD - Laboratory of Clinical Biochemistry, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece. FAU - Thymis, John AU - Thymis J AUID- ORCID: 0000-0002-3916-5350 AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Michalopoulou, Eleni AU - Michalopoulou E AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Prentza, Vasiliki AU - Prentza V AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Katsanaki, Eleni AU - Katsanaki E AUID- ORCID: 0009-0009-1025-9917 AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Vlachomitros, Dimitrios AU - Vlachomitros D AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Kountouri, Aikaterini AU - Kountouri A AUID- ORCID: 0000-0001-5829-7327 AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece. FAU - Korakas, Emmanouil AU - Korakas E AUID- ORCID: 0000-0002-7813-5488 AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece. FAU - Andreadou, Ioanna AU - Andreadou I AD - Laboratory of Pharmacology, Faculty of Pharmacy National and Kapodistrian University of Athens Athens Greece. FAU - Kouretas, Dimitrios AU - Kouretas D AD - Department of Biochemistry and Biotechnology University of Thessaly Larissa Greece. FAU - Parissis, John AU - Parissis J AD - 2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - 2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece. LA - eng SI - ClinicalTrials.gov/NCT03878706 PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250226 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Benzhydryl Compounds) RN - 0 (Biomarkers) RN - HDC1R2M35U (empagliflozin) RN - 0 (GDF15 protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucosides) RN - 0 (Growth Differentiation Factor 15) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 839I73S42A (Liraglutide) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Benzhydryl Compounds/therapeutic use MH - Biomarkers/blood MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/complications MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucosides/therapeutic use MH - Growth Differentiation Factor 15/blood MH - *Hypoglycemic Agents/therapeutic use MH - Insulin/therapeutic use MH - Liraglutide/therapeutic use MH - Natriuretic Peptide, Brain/blood MH - Peptide Fragments/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome PMC - PMC12132653 OTO - NOTNLM OT - N-terminal pro-brain natriuretic peptide OT - glucagon like peptide-1 receptor agonists OT - growth differentiation factor 15 OT - mitochondrial-derived peptide-c OT - sodium-glucose cotransporter-2 inhibitors COIS- None. EDAT- 2025/02/26 12:22 MHDA- 2025/03/04 12:24 PMCR- 2025/03/04 CRDT- 2025/02/26 06:13 PHST- 2025/03/04 12:24 [medline] PHST- 2025/02/26 12:22 [pubmed] PHST- 2025/02/26 06:13 [entrez] PHST- 2025/03/04 00:00 [pmc-release] AID - JAH310660 [pii] AID - 10.1161/JAHA.124.039129 [doi] PST - ppublish SO - J Am Heart Assoc. 2025 Mar 4;14(5):e039129. doi: 10.1161/JAHA.124.039129. Epub 2025 Feb 26. PMID- 39999536 OWN - NLM STAT- MEDLINE DCOM- 20250510 LR - 20260722 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 3 DP - 2025 Mar TI - FIB-4 predicts events in compensated advanced chronic liver disease and type 2 diabetes treated with GLP-1-receptor-agonists. PG - 108978 LID - S1056-8727(25)00031-5 [pii] LID - 10.1016/j.jdiacomp.2025.108978 [doi] AB - BACKGROUND & AIMS: Patients with compensated advanced chronic liver disease (cACLD) and treated type 2 diabetes have an increased risk for liver-related events, but data regarding this population is lacking, particularly, taking into account novel treatments. We assessed the role of Fibrosis-4 index and other variables to predict events. METHODS: First hepatic decompensation, liver transplantation (OLT), death, hepatocellular carcinoma (HCC) and bacterial infections over a follow-up period of 28.7 (16-49.4) months were retrospectively identified from 106 patients with treated type 2 diabetes and liver stiffness measurement >10 kPa suggesting ACLD. We identified predictors of events using Cox regression. Additionally, we evaluated treatment effect with add-on GLP-1 receptor agonists (GLP-1-RA) compared to other antidiabetic medications. RESULTS: FIB-4 was associated with hepatic decompensation, OLT and death (HR 1.517, 95%CI 1.226-1.879, p 2.67 (p = 0.02). CONCLUSION: FIB-4 is a strong prognostic tool to screen patients and refer them to specialists, in cACLD patients and pharmacologically treated type 2 diabetes, irrespective of treatment. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - van Beurden, Wiebke AU - van Beurden W AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. FAU - Mendoza, Yuly P AU - Mendoza YP AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. FAU - Lange, Naomi F AU - Lange NF AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland. FAU - Bosch, Jaime AU - Bosch J AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. FAU - Berzigotti, Annalisa AU - Berzigotti A AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. FAU - Rodrigues, Susana G AU - Rodrigues SG AD - Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. Electronic address: susana.gomesrodrigues@insel.ch. LA - eng PT - Journal Article DEP - 20250221 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Carcinoma, Hepatocellular/epidemiology MH - Liver Neoplasms/epidemiology MH - *Liver Cirrhosis/complications/diagnosis MH - Prognosis MH - Liver Transplantation MH - Predictive Value of Tests OTO - NOTNLM OT - Diabetes mellitus type 2 OT - Fibrosis OT - GLP-1 RA OT - Liver cirrhosis OT - Prognostic factor COIS- Declaration of competing interest The authors disclose no conflicts. EDAT- 2025/02/25 18:24 MHDA- 2025/03/06 05:04 CRDT- 2025/02/25 18:02 PHST- 2024/08/06 00:00 [received] PHST- 2025/02/03 00:00 [revised] PHST- 2025/02/19 00:00 [accepted] PHST- 2025/03/06 05:04 [medline] PHST- 2025/02/25 18:24 [pubmed] PHST- 2025/02/25 18:02 [entrez] AID - S1056-8727(25)00031-5 [pii] AID - 10.1016/j.jdiacomp.2025.108978 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Mar;39(3):108978. doi: 10.1016/j.jdiacomp.2025.108978. Epub 2025 Feb 21. PMID- 39998880 OWN - NLM STAT- MEDLINE DCOM- 20250403 LR - 20250510 IS - 1531-7056 (Electronic) IS - 0267-1379 (Linking) VI - 41 IP - 3 DP - 2025 May 1 TI - Glucagon like peptide-1 receptor agonists as a promising therapeutic option of metabolic dysfunction associated steatotic liver disease and obesity: hitting two targets with one shot. PG - 104-109 LID - 10.1097/MOG.0000000000001083 [doi] AB - PURPOSE OF REVIEW: Obesity and type 2 diabetes mellitus (T2DM) are significant global health challenges, closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in treating T2DM and obesity, but their potential for managing MASLD is still being explored. This review aims to examine the current progress in using GLP-1RAs for MASLD treatment and evaluate emerging dual and triple hormonal agonists as future therapeutic options. RECENT FINDINGS: GLP-1RAs have been effective in controlling blood sugar levels, promoting weight loss, and improving cardiovascular and kidney function. Furthermore, they have shown potential benefits for liver function in patients with MASLD. GLP-1, a key incretin hormone, influences glucose metabolism, appetite, and insulin sensitivity while affecting gastric emptying and potentially reducing fat deposition in the liver. Recent developments in GLP-1RAs include various formulations with different administration and dosing options, expanding their therapeutic use. SUMMARY: GLP-1RAs have become central to the management of T2DM, obesity, and possibly MASLD due to their ability to lower HbA1c, aid in weight reduction, and provide cardiovascular protection. As research continues, dual and triple hormonal agonists are emerging as the next evolution of incretin-based therapies, offering promising new strategies for addressing MASLD in the future. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Kaya, Eda AU - Kaya E AD - Department of Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany. FAU - Syn, Wing-Kin AU - Syn WK AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. AD - Department of Physiology, Faculty of Medicine and Nursing, University of Basque Coubtry UPV/EHU, Viscaya, Spain. FAU - Manka, Paul AU - Manka P AD - Department of Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Review DEP - 20250213 PL - United States TA - Curr Opin Gastroenterol JT - Current opinion in gastroenterology JID - 8506887 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Fatty Liver/drug therapy MH - Incretins/therapeutic use MH - *Non-alcoholic Fatty Liver Disease/drug therapy EDAT- 2025/02/25 12:26 MHDA- 2025/04/03 18:25 CRDT- 2025/02/25 11:54 PHST- 2025/04/03 18:25 [medline] PHST- 2025/02/25 12:26 [pubmed] PHST- 2025/02/25 11:54 [entrez] AID - 00001574-990000000-00181 [pii] AID - 10.1097/MOG.0000000000001083 [doi] PST - ppublish SO - Curr Opin Gastroenterol. 2025 May 1;41(3):104-109. doi: 10.1097/MOG.0000000000001083. Epub 2025 Feb 13. PMID- 39998480 OWN - NLM STAT- MEDLINE DCOM- 20250403 LR - 20260901 IS - 1531-7080 (Electronic) IS - 0268-4705 (Print) IS - 0268-4705 (Linking) VI - 40 IP - 3 DP - 2025 May 1 TI - Mitigating heart failure risk in patients with diabetes and chronic kidney disease. PG - 178-183 LID - 10.1097/HCO.0000000000001208 [doi] AB - PURPOSE OF REVIEW: Patients with chronic kidney disease and diabetes are at high risk of cardiovascular disease, including heart failure. Risk mitigation requires a comprehensive approach with lifestyle modifications, blood pressure management, renin-angiotensin blockade, and sodium-glucose cotransporter 2 inhibitors. Recent trials have shown that nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) should also be components of this approach. This review will discuss the comprehensive approach to mitigating risk in these high-risk patients and highlight the recent trials of ns-MRAs and GLP-1 RA. RECENT FINDINGS: In recent years, large, randomized controlled trials of ns-MRA and GLP-1 RA have shown benefit in kidney and cardiovascular outcomes for patients with chronic kidney disease and diabetes. SUMMARY: The substantial benefits and overall favorable safety profiles for ns-MRA and GLP-1 RA in patients with chronic kidney disease and diabetes demonstrate that these medications should be considered as a part of a comprehensive approach to cardiovascular risk reduction in this high-risk population. Future studies should consider different combination therapies and guide how and when to initiate these therapies. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Kowalczyk, Nicholas S AU - Kowalczyk NS AD - Department of Medicine, University of Chicago, Chicago, Illinois, USA. FAU - Prochaska, Megan AU - Prochaska M LA - eng GR - K23 DK127252/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20250212 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/complications MH - *Heart Failure/prevention & control/etiology MH - *Mineralocorticoid Receptor Antagonists/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors PMC - PMC13528586 MID - NIHMS2203530 OTO - NOTNLM OT - chronic kidney disease OT - diabetes OT - heart failure risk COIS- Conflicts of interest There are no conflicts of interest. EDAT- 2025/02/25 12:26 MHDA- 2025/04/03 18:25 PMCR- 2026/08/31 CRDT- 2025/02/25 10:43 PHST- 2025/04/03 18:25 [medline] PHST- 2025/02/25 12:26 [pubmed] PHST- 2025/02/25 10:43 [entrez] PHST- 2026/08/31 00:00 [pmc-release] AID - 00001573-990000000-00196 [pii] AID - 10.1097/HCO.0000000000001208 [doi] PST - ppublish SO - Curr Opin Cardiol. 2025 May 1;40(3):178-183. doi: 10.1097/HCO.0000000000001208. Epub 2025 Feb 12. PMID- 39996062 OWN - NLM STAT- MEDLINE DCOM- 20250225 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Efficacy and safety of once-weekly semaglutide monotherapy in a young subject with Prader-Willi syndrome, obesity, and type 2 diabetes: a case report. PG - 1533209 LID - 10.3389/fendo.2025.1533209 [doi] LID - 1533209 AB - BACKGROUND: The treatment of obesity and type 2 diabetes (T2D) in Prader-Willi syndrome (PWS) is still a challenge. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are attractive options, since they effectively reduce weight and improve blood glucose, without increasing the risk of hypoglycemia. However, data on their use in PWS are scarce. CASE DESCRIPTION: In 2019, a 27-year-old male came to our Clinic because of first appearance of severe hyperglycemia (fasting plasma glucose 22.5 mmol/L). Based on clinical presentation, PWS was suspected, and diagnosis was confirmed by genetic tests. The patient was discharged on a basal-bolus insulin therapy managed by his parents due to his cognitive impairment. In spite of COVID-19 pandemic, the patient achieved tight glycemic control (HbA1c 41 mmol/mol) with non-severe hypoglycemic events in the face of significant body weight (BW) increase (+ 13 kg vs baseline). Insulin therapy was then discontinued, and once-weekly semaglutide (up to 0,5 mg weekly) was started. At 12-month follow-up, BW dropped from 79 to 73 kg while maintaining excellent glycemic control (HbA1c 40 mmol/mol). At 24-month follow-up, glycemic control remained optimal (HbA1c 38 mmol/mol) with further BW reduction (71 kg). Neither hypoglycemia nor gastro-intestinal or psychiatric adverse events were reported. CONCLUSION: This case supports the potential use of semaglutide for the treatment of subjects with PWS, obesity and T2D. Ad hoc trials are needed to evaluate the long-term efficacy and tolerability in these subjects. CI - Copyright (c) 2025 Dinoi, Daniele, Michelucci, Baldinotti, Campi, Marchetti, Del Prato and Dardano. FAU - Dinoi, Elisa AU - Dinoi E AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Daniele, Giuseppe AU - Daniele G AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. AD - Center for Instrument Sharing of the University of Pisa (CISUP), Pisa, Italy. FAU - Michelucci, Angela AU - Michelucci A AD - Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy. FAU - Baldinotti, Fulvia AU - Baldinotti F AD - Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy. FAU - Campi, Fabrizio AU - Campi F AD - Section of Diabetes and Metabolic Diseases, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Marchetti, Piero AU - Marchetti P AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Del Prato, Stefano AU - Del Prato S AD - Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Dardano, Angela AU - Dardano A AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. AD - Center for Instrument Sharing of the University of Pisa (CISUP), Pisa, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20250210 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Prader-Willi Syndrome/drug therapy/complications MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - Drug Administration Schedule MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11847660 OTO - NOTNLM OT - GLP-1 RA OT - Prader-Willi syndrome OT - case report OT - obesity OT - semaglutide OT - type 2 diabetes mellitus COIS- ED, AD, AM, FB, FC: no duality of interest. GD: Eli lilly Italia. PM: Eli lilly Italia, Novo Nordisk, Gruppo Menarini, Laboratori Guidotti. SDP: Abbott, Amarin Corporation, AstraZeneca, Berlin Chemie AG, Biomea Fusion, Boehringer Ingelheim, Laboratori Guidotti, Menarini International, Novartis Pharmaceuticals Co., Merck Sharpe & Dohme, Eli Lilly and Company, Novo Nordisk, Sanofi, Sun Pharmaceuticals. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/02/25 06:21 MHDA- 2025/02/25 06:22 PMCR- 2025/01/01 CRDT- 2025/02/25 04:44 PHST- 2024/11/23 00:00 [received] PHST- 2025/01/16 00:00 [accepted] PHST- 2025/02/25 06:22 [medline] PHST- 2025/02/25 06:21 [pubmed] PHST- 2025/02/25 04:44 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1533209 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Feb 10;16:1533209. doi: 10.3389/fendo.2025.1533209. eCollection 2025. PMID- 39993818 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20250522 IS - 1488-2329 (Electronic) IS - 0820-3946 (Print) IS - 0820-3946 (Linking) VI - 197 IP - 7 DP - 2025 Feb 23 TI - Sodium-glucose cotransporter 2 (SGLT2) inhibitors and risk of chronic kidney disease-mineral and bone disorders in patients with type 2 diabetes mellitus and stage 1-3 chronic kidney disease. PG - E178-E189 LID - 10.1503/cmaj.240922 [doi] AB - BACKGROUND: In patients with type 2 diabetes mellitus and chronic kidney disease (CKD), sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal outcomes, but may transiently affect biochemical markers of CKD-mineral and bone disorders (CKD-MBD). We sought to evaluate the long-term risk of CKD-MBD associated with use of SGLT2 inhibitors in this patient population. METHODS: We conducted a retrospective cohort study, employing a target trial emulation framework and using electronic medical records of patients from 9 hospitals in Taiwan (2016-2023). We included adults with type 2 diabetes mellitus and stage 1-3 CKD who had newly started either an SGLT2 inhibitor or, as a comparison group, a glucagon-like peptide-1 receptor agonist (GLP-1 RA). The primary outcome was a composite of incident biochemical abnormalities (serum phosphate > 1.5 mmol/L, serum calcium < 2.1 mmol/L, serum intact parathyroid hormone [iPTH] > 6.9 pmol/L, or serum 25-hydroxyvitamin D < 49.9 nmol/L). RESULTS: The cohort included 13 379 patients receiving SGLT2 inhibitors (n = 11 920) or GLP-1 RAs (n = 1459) with a median follow-up of 3.3 years. Compared with GLP-1 RAs, SGLT2 inhibitors were associated with a lower cumulative incidence of the composite primary outcome (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.79-0.86), hyperphosphatemia (HR 0.83, 95% CI 0.76-0.91), hypocalcemia (HR 0.82, 95% CI 0.78-0.86), high serum iPTH levels (HR 0.66, 95% CI 0.57-0.78), and low serum 25-hydroxyvitamin D levels (HR 0.65, 95% CI 0.47-0.90). INTERPRETATION: Use of SGLT2 inhibitors was associated with a lower incidence of biochemical abnormalities related to CKD-MBD than GLP-1 RAs. These agents may be considered to reduce risk of CKD-MBD in patients with type 2 diabetes mellitus and stage 1-3 CKD. CI - (c) 2025 CMA Impact Inc. or its licensors. FAU - Tsai, Daniel Hsiang-Te AU - Tsai DH AD - School of Pharmacy (Tsai, Chuang, Shao, Lai), Institute of Clinical Pharmacy and Pharmaceutical Sciences (Tsai, Chuang, Shao, Lai), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Population Health Data Center (Tsai, Chuang, Shao, Lai), National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine (Liu), and Division of Nephrology (Liu), Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy (Shao), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. FAU - Chuang, Albert Tzu-Ming AU - Chuang AT AD - School of Pharmacy (Tsai, Chuang, Shao, Lai), Institute of Clinical Pharmacy and Pharmaceutical Sciences (Tsai, Chuang, Shao, Lai), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Population Health Data Center (Tsai, Chuang, Shao, Lai), National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine (Liu), and Division of Nephrology (Liu), Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy (Shao), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. FAU - Liu, Kuan-Hung AU - Liu KH AD - School of Pharmacy (Tsai, Chuang, Shao, Lai), Institute of Clinical Pharmacy and Pharmaceutical Sciences (Tsai, Chuang, Shao, Lai), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Population Health Data Center (Tsai, Chuang, Shao, Lai), National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine (Liu), and Division of Nephrology (Liu), Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy (Shao), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. FAU - Shao, Shih-Chieh AU - Shao SC AD - School of Pharmacy (Tsai, Chuang, Shao, Lai), Institute of Clinical Pharmacy and Pharmaceutical Sciences (Tsai, Chuang, Shao, Lai), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Population Health Data Center (Tsai, Chuang, Shao, Lai), National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine (Liu), and Division of Nephrology (Liu), Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy (Shao), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. scshao@cgmh.org.tw. FAU - Lai, Edward Chia-Cheng AU - Lai EC AD - School of Pharmacy (Tsai, Chuang, Shao, Lai), Institute of Clinical Pharmacy and Pharmaceutical Sciences (Tsai, Chuang, Shao, Lai), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Population Health Data Center (Tsai, Chuang, Shao, Lai), National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine (Liu), and Division of Nephrology (Liu), Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacy (Shao), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250223 PL - Canada TA - CMAJ JT - CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne JID - 9711805 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Female MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Renal Insufficiency, Chronic/complications/epidemiology MH - Aged MH - Taiwan/epidemiology MH - *Chronic Kidney Disease-Mineral and Bone Disorder/epidemiology/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Risk Factors PMC - PMC11867598 COIS- Competing interests:: None declared. EDAT- 2025/02/25 00:22 MHDA- 2025/02/25 00:23 PMCR- 2025/02/24 CRDT- 2025/02/24 20:43 PHST- 2025/01/21 00:00 [accepted] PHST- 2025/02/25 00:23 [medline] PHST- 2025/02/25 00:22 [pubmed] PHST- 2025/02/24 20:43 [entrez] PHST- 2025/02/24 00:00 [pmc-release] AID - 197/7/E178 [pii] AID - 197e178 [pii] AID - 10.1503/cmaj.240922 [doi] PST - epublish SO - CMAJ. 2025 Feb 23;197(7):E178-E189. doi: 10.1503/cmaj.240922. PMID- 39993530 OWN - NLM STAT- MEDLINE DCOM- 20250329 LR - 20250528 IS - 1473-4893 (Electronic) IS - 1470-2118 (Print) IS - 1470-2118 (Linking) VI - 25 IP - 2 DP - 2025 Mar TI - GLP-1 receptor agonist therapy and pregnancy: Evolving and emerging evidence. PG - 100298 LID - S1470-2118(25)00016-8 [pii] LID - 10.1016/j.clinme.2025.100298 [doi] LID - 100298 AB - The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in young adults, posing significant risks around pregnancy. Obesity also impacts on fertility and the co-existence of polycystic ovarian syndrome increases the prevalence of cardiovascular metabolic risk factors. There has been a renewed interest in glucagon-like peptide-1 receptor agonists (GLP-1RA) in this context, due to their multi-dimensional impact on the reproductive axis, as well as their ability to simultaneously target weight loss and glycaemic control. There is, however, limited availability of safety data with respect to these newer non-insulin-based diabetes medications from the perspective of fetal development. As GLP-1RA are not licensed for use in pregnancy, with the increasing chances of incidental exposure from pre-conception use for obesity and T2DM, it is imperative that pre-conception counselling should be an integral part of consultation prior to the initiation of these drugs. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Varughese, Maria S AU - Varughese MS AD - University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield S10 2RX, South Yorkshire, UK. FAU - O'Mahony, Fidelma AU - O'Mahony F AD - Department of Obstetrics & Gynaecology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK; School of Medicine, Faculty of Health, Keele University, North Staffordshire, UK. FAU - Varadhan, Lakshminarayanan AU - Varadhan L AD - School of Medicine, Faculty of Health, Keele University, North Staffordshire, UK; Department of Diabetes & Endocrinology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK. Electronic address: L.Varadhan@Keele.ac.uk. LA - eng PT - Journal Article DEP - 20250222 PL - England TA - Clin Med (Lond) JT - Clinical medicine (London, England) JID - 101092853 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Female MH - Humans MH - Pregnancy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Obesity/drug therapy/complications MH - Polycystic Ovary Syndrome PMC - PMC11929868 OTO - NOTNLM OT - Fetal medicine OT - GLP-1 receptor agonist therapy OT - Pregnancy OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/02/25 00:22 MHDA- 2025/03/30 23:02 PMCR- 2025/02/22 CRDT- 2025/02/24 19:27 PHST- 2024/10/29 00:00 [received] PHST- 2025/02/16 00:00 [revised] PHST- 2025/02/19 00:00 [accepted] PHST- 2025/03/30 23:02 [medline] PHST- 2025/02/25 00:22 [pubmed] PHST- 2025/02/24 19:27 [entrez] PHST- 2025/02/22 00:00 [pmc-release] AID - S1470-2118(25)00016-8 [pii] AID - 100298 [pii] AID - 10.1016/j.clinme.2025.100298 [doi] PST - ppublish SO - Clin Med (Lond). 2025 Mar;25(2):100298. doi: 10.1016/j.clinme.2025.100298. Epub 2025 Feb 22. PMID- 39993315 OWN - NLM STAT- MEDLINE DCOM- 20250510 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 178 IP - 3 DP - 2025 Mar TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes : A Target Trial Emulation Study. PG - 315-326 LID - 10.7326/ANNALS-24-01347 [doi] AB - BACKGROUND: Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential antidepressant effects, population studies yield inconsistent results. OBJECTIVE: To compare the risk for depression in older adults with type 2 diabetes (T2D) initiating treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is). DESIGN: Target trial emulation study. SETTING: U.S. National Medicare administrative data from January 2014 to December 2020. PATIENTS: Adults aged 66 years or older with T2D initiating treatment with a GLP-1RA were matched 1:1 on propensity score with those initiating treatment with either an SGLT2i or a DPP4i. MEASUREMENTS: The primary end point was incident depression. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% CI within matched groups. RESULTS: A total of 14 665 matched pairs of older adults were included in the cohort for GLP-1RAs versus SGLT2is; the rate difference of depression between GLP-1RA users and SGLT2i users was 3.48 (95% CI, -0.81 to 7.78) per 1000 person-years, with an HR of 1.07 (CI, 0.98 to 1.18). In the cohort for GLP-1RAs versus DPP4is (13 711 matched pairs), the rate difference was -5.78 (CI, -10.49 to -1.07) per 1000 person-years, with an HR of 0.90 (CI, 0.82 to 0.98). LIMITATION: Unmeasured confounders (such as hemoglobin A(1c) levels and body mass index), outcome misclassification, and limited generalizability to all GLP-1RA users (for example, younger populations or those without T2D receiving the drug for obesity treatment). CONCLUSION: Among older adults with T2D, the incidence of depression was relatively low. Use of GLP-1RAs was associated with a modestly lower risk for depression compared with use of DPP4is, but not SGLT2is. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida (H.T., Y.L.). FAU - Lu, Ying AU - Lu Y AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida (H.T., Y.L.). FAU - Donahoo, William T AU - Donahoo WT AUID- ORCID: 0000-0002-2126-860X AD - Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida (W.T.D.). FAU - Westen, Sarah C AU - Westen SC AUID- ORCID: 0000-0001-9891-4529 AD - Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, Florida (S.C.W.). FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence, University of Pennsylvania; The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine; Leonard Davis Institute of Health Economics; Penn Medicine Center for Evidence-based Practice; and Penn Institute for Biomedical Informatics, Philadelphia, Pennsylvania, and Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida (Y.C.). FAU - Bian, Jiang AU - Bian J AUID- ORCID: 0000-0002-2238-5429 AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida (J.B.). FAU - Guo, Jingchuan AU - Guo J AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, and Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida (J.G.). LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250225 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - *Depression/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - United States/epidemiology MH - Medicare MH - Aged, 80 and over MH - Proportional Hazards Models MH - Propensity Score PMC - PMC12132804 MID - NIHMS2082136 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/02/24 23:04 MHDA- 2025/03/25 12:40 PMCR- 2025/09/01 CRDT- 2025/02/24 17:02 PHST- 2025/03/25 12:40 [medline] PHST- 2025/02/24 23:04 [pubmed] PHST- 2025/02/24 17:02 [entrez] PHST- 2025/09/01 00:00 [pmc-release] AID - 10.7326/ANNALS-24-01347 [doi] PST - ppublish SO - Ann Intern Med. 2025 Mar;178(3):315-326. doi: 10.7326/ANNALS-24-01347. Epub 2025 Feb 25. PMID- 39988205 OWN - NLM STAT- MEDLINE DCOM- 20250409 LR - 20260722 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 285 DP - 2025 Jul TI - Reminders embedded in PCI reports to optimize discharge diabetes mellitus care (REMIND-DM): Rationale, design, and baseline characteristics. PG - 12-20 LID - S0002-8703(25)00019-5 [pii] LID - 10.1016/j.ahj.2025.01.020 [doi] AB - BACKGROUND: Despite the robust clinical evidence base supporting their role for high-risk patients with type 2 diabetes (T2DM) and concomitant cardiovascular disease, prescription of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) remains suboptimal. Clinical encounters occurring in the period post angiography may present a key opportunity to improve implementation in high-risk patients with T2DM. METHODS: Reminders EMbedded IN PCI Reports to Optimize Discharge Diabetes Mellitus Care (REMIND-DM) is a pragmatic, prospective, cluster randomized quality improvement study in patients with type 2 diabetes undergoing angiography and was run as a quality improvement initiative. Following a 6 month "baseline period", REMIND-DM randomized 23 participating percutaneous coronary intervention (PCI) sites (caring for 7,045 patients over the study period) within the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) quality improvement collaborative to either usual care or a quality improvement intervention consisting of a templated PCI report "reminder" of medication eligibility linked to a decision support tool. Sites were followed for a 6 month "evaluation period." The primary outcome is the new prescription of SGLT2 inhibitor or GLP-1RA among eligible patients at discharge after PCI. To examine the effectiveness of the intervention, primary analyses will be conducted using a difference-in-difference design examining changes in new cardioprotective therapy prescription from baseline to the evaluation periods in both arms. CONCLUSIONS: The REMIND-DM implementation trial has enrolled a large, high-risk population of patients with T2DM and will determine the effectiveness of a low touch QI intervention within BMC2 implemented in the post-PCI period to improve timely prescription of risk lowering therapies in high-risk patients with T2DM. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Chatur, Safia AU - Chatur S AD - Division of Cardiovascular Medicine and Center for Cardiometabolic Implementation Science, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Seth, Milan AU - Seth M AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor MI. FAU - Casey, Mary AU - Casey M AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor MI. FAU - Thompson, Michael P AU - Thompson MP AD - Section of Health Services Research and Quality, Department of Cardiac Surgery, Michigan Medicine, Ann Arbor, MI; Institute for Health Care Policy and Innovation, University of Michigan, Ann Arbor, MI. FAU - Qureshi, M Imran AU - Qureshi MI AD - Division of Cardiology, DMC Sinai Grace Hospital, Detroit, MI. FAU - Gupta, Vishal AU - Gupta V AD - Ascension Borgess Heart Institute and Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI. FAU - Qureshi, Mansoor AU - Qureshi M AD - Division of Cardiovascular Medicine, Trinity Health, Ann Arbor, MI. FAU - Samman, Bashar AU - Samman B AD - Division of Cardiovascular Medicine, McLaren Port Huron, Port Huron, MI. FAU - Forest, Annemarie AU - Forest A AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor MI. FAU - Gurm, Hitinder S AU - Gurm HS AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor MI. FAU - Sukul, Devraj AU - Sukul D AD - Frederik Meijer Heart & Vascular Institute, Corewell Health West, Grand Rapids, MI. Electronic address: Devraj.sukul@gmail.com. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AD - Division of Cardiovascular Medicine and Center for Cardiometabolic Implementation Science, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. LA - eng PT - Clinical Trial Protocol PT - Journal Article DEP - 20250221 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Coronary Angiography MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Multicenter Studies as Topic MH - *Patient Discharge MH - *Percutaneous Coronary Intervention MH - Pragmatic Clinical Trials as Topic MH - Prospective Studies MH - Quality Improvement MH - Randomized Controlled Trials as Topic MH - *Reminder Systems MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use COIS- DISCLOSURES Dr. Chatur is supported by the Canadian Arthur J.E. Child's Cardiology Fellowship. Dr. Gurm has no conflict with this work. Outside of this work, he receives salary support from Blue Cross and Blue Shield of Michigan He is the co-founder of, owns equity in, and is a consultant to Amplitude Vascular Systems. He also owns equity in Jiaxing Bossh Medical Technology Partnership. He is the chair of the Clinical Events Committee for the PERFORMANCE trial sponsored by Contego Medical. Dr. Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, BMS, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. All other authors do not report any relevant disclosures related to this trial. Dr. Sukul received salary support for this role in quality improvement for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). All other authors had nothing to disclose. EDAT- 2025/02/24 02:10 MHDA- 2025/04/10 00:20 CRDT- 2025/02/23 19:32 PHST- 2024/09/09 00:00 [received] PHST- 2025/01/30 00:00 [revised] PHST- 2025/01/31 00:00 [accepted] PHST- 2025/04/10 00:20 [medline] PHST- 2025/02/24 02:10 [pubmed] PHST- 2025/02/23 19:32 [entrez] AID - S0002-8703(25)00019-5 [pii] AID - 10.1016/j.ahj.2025.01.020 [doi] PST - ppublish SO - Am Heart J. 2025 Jul;285:12-20. doi: 10.1016/j.ahj.2025.01.020. Epub 2025 Feb 21. PMID- 39986337 OWN - NLM STAT- MEDLINE DCOM- 20250409 LR - 20260726 IS - 1097-6744 (Electronic) IS - 0002-8703 (Print) IS - 0002-8703 (Linking) VI - 285 DP - 2025 Jul TI - Encouraging the prescribing of SGLT2i and GLP-1RA medications to reduce cardiovascular and renal risk in patients with type 2 diabetes: Rationale and design of a randomized controlled trial. PG - 39-51 LID - S0002-8703(25)00038-9 [pii] LID - 10.1016/j.ahj.2025.02.007 [doi] AB - BACKGROUND: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) medications reduce the risk of cardiovascular and renal complications among patients with type 2 diabetes but are underutilized. There are numerous barriers to prescribing including insurance coverage, medication availability, comfort with prescribing, and diffusion of responsibility of prescribing across specialists. Methods are needed to support prescribing in primary care. METHODS: This was a pragmatic, randomized controlled trial testing interventions to increase appropriate SGLT2i and GLP-1RA prescribing. Primary care providers (PCPs) were randomized to 1 of 3 arms: (1) peer champion support (2) peer champion support and information on insurance coverage, or (3) usual care (no intervention). PCPs in both intervention arms received a welcome email and electronic health record (EHR) messages before visits with patients who had sub-optimally controlled diabetes and an indication for 1 of these medications. In the peer champion support only arm the EHR messages included prescribing tips. In the arm that provided peer champion support and information on insurance coverage, EHR messages contained information on medications in each class that would be most affordable for the patient based on their insurance coverage and offered support for prior authorizations if needed. The primary outcome was prescriptions for an SGLT2i or GLP-1RA medication, beginning 3 days before the targeted visit and continuing through 28 days, in each intervention arm compared to control. RESULTS: 191 primary care providers were included in the study. 1,389 patients had at least 1 visit scheduled with their PCP during the 6-month intervention period; of these 1,079 patients attended at least 1 of these visits and will be included in the primary outcome analysis. 66 providers (484 patients) received the peer champion intervention alone, 63 providers (446 patients) received the peer champion intervention and information on insurance coverage, and 62 providers (459 patients) received usual care. On average, patients were 66 years old, 46% were female, 61% were white, and 16% were Hispanic. There were small differences between groups with regards to patient sex, race, ethnicity, partner status, and percent with Medicare insurance. CONCLUSIONS: These medication classes have the potential to reduce cardiovascular and kidney disease among patients with type 2 diabetes. This study tests interventions to support prescribing of these medications in primary care. CLINICAL TRIAL: Clinicaltrials.gov. Unique identifier: (NCT, Registered: NCT05463705). CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Haff, Nancy AU - Haff N AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: nhaff@mgb.org. FAU - Horn, Daniel M AU - Horn DM AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA; Medical Director of Devoted Health, Waltham, MA. FAU - Bhatkhande, Gauri AU - Bhatkhande G AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Sung, Meekang AU - Sung M AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Colling, Caitlin AU - Colling C AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA. FAU - Wood, Wendy AU - Wood W AD - Department of Psychology & Marshall School of Business, University of Southern California, Los Angeles, CA. FAU - Robertson, Ted AU - Robertson T AD - ideas42, New York, NY; Executive Director of the Center for Healthcare Marketplace Innovation at the University of California, Berkeley, CA. FAU - Gaposchkin, Daniel AU - Gaposchkin D AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA. FAU - Simmons, Leigh AU - Simmons L AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA. FAU - Yang, Judy AU - Yang J AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA. FAU - Yeh, James AU - Yeh J AD - Harvard Medical School, Boston, MA; Department of Medicine, Massachusetts General Hospital, Boston, MA. FAU - Crum, Katherine L AU - Crum KL AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Hanken, Kaitlin E AU - Hanken KE AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA. FAU - Lauffenburger, Julie C AU - Lauffenburger JC AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Choudhry, Niteesh K AU - Choudhry NK AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. LA - eng SI - ClinicalTrials.gov/NCT05463705 GR - K23 HL161480/HL/NHLBI NIH HHS/United States GR - P30 AG064199/AG/NIA NIH HHS/United States PT - Clinical Trial Protocol PT - Journal Article DEP - 20250220 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Practice Patterns, Physicians' MH - Primary Health Care MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Pragmatic Clinical Trials as Topic MH - Randomized Controlled Trials as Topic PMC - PMC11981828 MID - NIHMS2066671 COIS- Conflict of interest Dr. Choudhry serves as a consultant to Veracity Healthcare Analytics and holds equity in RxAnte and DecipherHealth; unrelated the current work, Dr. Choudhry has also received unrestricted grant funding payable to Brigham and Women's Hospital from Humana. The remainder of the authors report no conflicts of interest. EDAT- 2025/02/23 00:42 MHDA- 2025/04/10 00:19 PMCR- 2026/07/01 CRDT- 2025/02/22 19:27 PHST- 2024/08/28 00:00 [received] PHST- 2025/02/04 00:00 [revised] PHST- 2025/02/12 00:00 [accepted] PHST- 2025/04/10 00:19 [medline] PHST- 2025/02/23 00:42 [pubmed] PHST- 2025/02/22 19:27 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - S0002-8703(25)00038-9 [pii] AID - 10.1016/j.ahj.2025.02.007 [doi] PST - ppublish SO - Am Heart J. 2025 Jul;285:39-51. doi: 10.1016/j.ahj.2025.02.007. Epub 2025 Feb 20. PMID- 39985672 OWN - NLM STAT- MEDLINE DCOM- 20250527 LR - 20250616 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 5 DP - 2025 May TI - Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis. PG - 589-606 LID - 10.1007/s00592-025-02468-5 [doi] AB - AIM: To systematically assess randomized controlled trials that evaluated the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on fracture incidence, bone mineral density, and bone metabolism markers in individuals with type 2 diabetes. METHODS: From database setup to March 21, 2024, a search was conducted across nine Chinese and English databases. The Cochrane Risk of Bias Tool was applied to assess potential bias. Data analysis was performed using RevMan 5.3 and Stata 14.0. Subgroup analysis and meta regression were employed to explore sources of heterogeneity, and publication bias was evaluated using funnel plots and Egger's test. RESULTS: Twenty-five studies were included. The results of the meta-analysis indicated that GLP-1 receptor agonist was not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41). Additionally, improvement in lumbar spine BMD (MD = 0.07 g/cm(2), 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm(2), 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm(2), 95% CI 0.04 to 0.07, P < 0.00001) was superior to the control group. Similarly, GLP-1 receptor agonists significantly improved P1NP (SMD = 0.33, 95% CI 0.07 to 0.59, P = 0.01), OC (MD = 1.46 ug/L, 95% CI 1.10 to 1.83, P < 0.00001), 25-OH-D (SMD = 0.45, 95% CI 0.06 to 0.83, P = 0.02), and b-ALP (MD = 0.91ug/L, 95% CI 0.19 to 1.63, P = 0.01) while reducing beta-CTX (SMD = - 0.34, 95% CI - 0.54 to - 0.14, P = 0.001). There was no significant impact on other bone metabolism markers, including N-MID-OT (SMD = 0.43, 95% CI 0.01 to 0.86, P = 0.05), ALP (SMD = - 0.00, 95% CI: - 0.25 to 0.25, P = 0.98), Calcium (MD = 0.00 mmol/L, 95% CI - 0.04 to 0.04, P = 0.94) and Phosphate (MD = 0.02 mmol/L, 95% CI - 0.04 to 0.07, P = 0.57). CONCLUSION: This meta-analysis demonstrated no significant effect of GLP-1 receptor agonists on elevated fracture risk. There was a statistically significant improvement in BMD and certain bone turnover markers (beta-CTX, P1NP, OC, b-ALP, and 25-OH-D). However, due to some limitations, further high-quality clinical studies with sufficient follow-up time are needed to draw more definitive conclusions. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Tan, Yimei AU - Tan Y AD - Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China. AD - Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China. FAU - Liu, Shuanghua AU - Liu S AD - Jinan University, No.601, Huangpu Avenue West, Guangzhou, 510632, Guangdong, China. FAU - Tang, Qizhi AU - Tang Q AUID- ORCID: 0009-0009-2669-8690 AD - Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China. QizhiTang@outlook.com. AD - Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China. QizhiTang@outlook.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250222 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Biomarkers/metabolism MH - *Bone and Bones/metabolism/drug effects MH - *Bone Density/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications MH - *Fractures, Bone/epidemiology/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Bone metabolism markers OT - Bone mineral density OT - Fracture OT - GLP-1 receptor agonists OT - Meta-analysis OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: All the authors report no relevant conflicts of interest for this article. EDAT- 2025/02/22 20:10 MHDA- 2025/05/27 12:44 CRDT- 2025/02/22 11:13 PHST- 2024/08/03 00:00 [received] PHST- 2025/02/04 00:00 [accepted] PHST- 2025/05/27 12:44 [medline] PHST- 2025/02/22 20:10 [pubmed] PHST- 2025/02/22 11:13 [entrez] AID - 10.1007/s00592-025-02468-5 [pii] AID - 10.1007/s00592-025-02468-5 [doi] PST - ppublish SO - Acta Diabetol. 2025 May;62(5):589-606. doi: 10.1007/s00592-025-02468-5. Epub 2025 Feb 22. PMID- 39984953 OWN - NLM STAT- MEDLINE DCOM- 20250222 LR - 20260721 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Feb 21 TI - Association of glucagon-like peptide-1 receptor agonists with cardiovascular and kidney outcomes in type 2 diabetic kidney transplant recipients. PG - 87 LID - 10.1186/s12933-025-02649-0 [doi] LID - 87 AB - BACKGROUND: Cardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited. METHODS: This retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs). RESULTS: A total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years; 57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39; 95% CI 0.31-0.50), MACEs (aHR 0.66; 95% CI 0.56-0.79), and MAKEs (aHR 0.66; 95% CI 0.58-0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased. CONCLUSIONS: In KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population. CI - (c) 2025. The Author(s). FAU - Lin, Li-Chun AU - Lin LC AD - Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan. AD - Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Huang, Thomas Tao-Min AU - Huang TT AD - Division of Nephrology, Primary Aldosteronism Center of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. AD - NSARF (National Taiwan University Hospital Study Group of ARF), and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Primary Aldosteronism Center of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. q91421028@ntu.edu.tw. AD - NSARF (National Taiwan University Hospital Study Group of ARF), and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan. q91421028@ntu.edu.tw. AD - Department of Internal Medicine, National Taiwan University Hospital, Room 1555, B4, Clinical Research Building, 7 Chung-Shan South Road, Taipei, 100, Taiwan. q91421028@ntu.edu.tw. LA - eng PT - Journal Article DEP - 20250221 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Kidney Transplantation/adverse effects/mortality MH - Treatment Outcome MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis MH - Aged MH - *Incretins/adverse effects/therapeutic use MH - Time Factors MH - Risk Assessment MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Adult MH - Databases, Factual MH - *Diabetic Nephropathies/mortality/diagnosis MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11846168 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Kidney transplantation OT - Major adverse cardiovascular events OT - Major adverse kidney events OT - Mortality OT - Type 2 diabetes mellitus COIS- Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: All authors declare no competing interest. EDAT- 2025/02/22 00:22 MHDA- 2025/02/22 20:12 PMCR- 2025/02/21 CRDT- 2025/02/21 23:56 PHST- 2025/01/03 00:00 [received] PHST- 2025/02/13 00:00 [accepted] PHST- 2025/02/22 20:12 [medline] PHST- 2025/02/22 00:22 [pubmed] PHST- 2025/02/21 23:56 [entrez] PHST- 2025/02/21 00:00 [pmc-release] AID - 10.1186/s12933-025-02649-0 [pii] AID - 2649 [pii] AID - 10.1186/s12933-025-02649-0 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Feb 21;24(1):87. doi: 10.1186/s12933-025-02649-0. PMID- 39983843 OWN - NLM STAT- MEDLINE DCOM- 20250413 LR - 20260530 IS - 1879-016X (Electronic) IS - 0163-7258 (Linking) VI - 269 DP - 2025 May TI - GLP-1 receptor agonists, are we witnessing the emergence of a paradigm shift for neuro-cardio-metabolic disorders? PG - 108824 LID - S0163-7258(25)00036-1 [pii] LID - 10.1016/j.pharmthera.2025.108824 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as groundbreaking therapeutic agents in managing a spectrum of metabolic disorders, demonstrating remarkable efficacy across multiple organ systems and disease states. These compounds are not only well-established in the treatment of type 2 diabetes (T2D) and obesity-conditions for which they have received widespread approval-but also exhibit promising potential in addressing cardiovascular disease (CVD) and Metabolic dysfunction-associated steatotic liver disease (MASLD). Recent investigations have begun to illuminate the utility of GLP-1RAs in the management of type 1 diabetes (T1D), as well as neurodegenerative disorders such as Alzheimer's and Parkinson's disease and various behavioral disorders. A plethora of clinical trials have consistently validated the capacity of GLP-1RAs to improve glycemic control, promote weight loss, and mitigate cardiovascular risk factors in individuals with T2D and obesity. While their application in T1D remains limited due to safety concerns-particularly regarding the risks of hypoglycemia and hyperglycemic ketoacidosis-emerging data suggest that GLP-1RAs may offer hepatoprotective benefits, potentially reducing liver fat content and decelerating the progression of MASLD. The neuroprotective attributes of GLP-1 RAs have garnered significant interest, with research indicating their potential to alleviate cognitive decline associated with neurodegenerative diseases. Furthermore, preliminary findings highlight the role of GLP-1 RAs in addressing behavioral disorders, emphasizing their extensive therapeutic promise. This comprehensive review synthesizes the current evidence supporting the diverse therapeutic applications of GLP-1RAs, positioning them as "magic drug" therapies for metabolic and neurological disorders. As ongoing research continues to explore innovative applications and combinations of GLP-1RAs, the landscape of disease management in metabolic and neurological contexts is poised for transformative advancements. This review will also critically assess safety considerations and underscore the need for personalized treatment strategies to optimize patient outcomes in these complex and often comorbid conditions. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Arredouani, Abdelilah AU - Arredouani A AD - Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Qatar. Electronic address: aarredouani@hbku.edu.qa. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250219 PL - England TA - Pharmacol Ther JT - Pharmacology & therapeutics JID - 7905840 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Cardiovascular Diseases/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Metabolic Diseases/drug therapy MH - Neurodegenerative Diseases/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy OTO - NOTNLM OT - Diabetes OT - GLP-1 OT - GLP-1 receptor OT - GLP-1 receptor agonists OT - MASLD OT - Neurodegenerative diseases OT - Obesity COIS- Declaration of competing interest The author declares that there are no conflicts of interest. EDAT- 2025/02/22 00:21 MHDA- 2025/04/14 00:25 CRDT- 2025/02/21 19:34 PHST- 2024/08/30 00:00 [received] PHST- 2025/02/07 00:00 [revised] PHST- 2025/02/14 00:00 [accepted] PHST- 2025/04/14 00:25 [medline] PHST- 2025/02/22 00:21 [pubmed] PHST- 2025/02/21 19:34 [entrez] AID - S0163-7258(25)00036-1 [pii] AID - 10.1016/j.pharmthera.2025.108824 [doi] PST - ppublish SO - Pharmacol Ther. 2025 May;269:108824. doi: 10.1016/j.pharmthera.2025.108824. Epub 2025 Feb 19. PMID- 39981788 OWN - NLM STAT- MEDLINE DCOM- 20250312 LR - 20260127 IS - 1445-5994 (Electronic) IS - 1444-0903 (Linking) VI - 55 IP - 3 DP - 2025 Mar TI - Treatment of obesity: will incretin agonists make bariatric surgery a thing of the past? PG - 369-375 LID - 10.1111/imj.16625 [doi] AB - The prevalence of obesity continues to increase worldwide. Obesity is associated with an increased risk of cardiometabolic and other diseases, reduced quality of life and shortened life expectancy. Highly effective therapies are required to achieve meaningful and sustained weight reduction to prevent, slow or reverse disease associated with obesity. Bariatric surgery is a highly effective intervention to induce weight loss, with observational data demonstrating durability of weight loss over 10 or more years. In addition, bariatric surgery improves cardiometabolic risk factors, including hyperglycaemia and type 2 diabetes, hypertension and dyslipidaemia. Observational data have shown a reduction in all-cause mortality, cardiovascular events and mortality and a reduction in cancer risk and mortality in patients who have undergone bariatric surgery compared to matched patients who did not have surgery. The emergence of newer incretin agonists, particularly semaglutide and tirzepatide, have demonstrated remarkable efficacy in inducing and maintaining weight loss with ongoing use. As for bariatric surgery, incretin agonist therapies also improve type 2 diabetes outcomes, cardiovascular mortality and other obesity-related complications, with new evidence emerging and long-term outcome data awaited. This perspective compares bariatric surgery and incretin agonist therapy, assessing their relative efficacies in weight reduction, impact on obesity-related complications, their respective risk profiles and considerations of cost-effectiveness and equity of access. These comparisons seek to evaluate whether these increasingly popular medications could make bariatric surgery a thing of the past. CI - (c) 2025 Royal Australasian College of Physicians. FAU - Lah, Siehoon AU - Lah S AUID- ORCID: 0000-0003-2834-2486 AD - Metabolism and Obesity Service, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. FAU - Hocking, Samantha L AU - Hocking SL AUID- ORCID: 0000-0002-2514-9392 AD - Metabolism and Obesity Service, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. AD - Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia. LA - eng PT - Journal Article PT - Review DEP - 20250221 PL - Australia TA - Intern Med J JT - Internal medicine journal JID - 101092952 RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Bariatric Surgery/trends/methods MH - *Incretins/agonists/therapeutic use MH - *Obesity/drug therapy/surgery/therapy MH - Weight Loss/drug effects/physiology MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Tirzepatide MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 agonist OT - bariatric surgery OT - incretin agonist OT - obesity OT - semaglutide OT - tirzepatide EDAT- 2025/02/21 12:22 MHDA- 2025/03/12 12:32 CRDT- 2025/02/21 07:13 PHST- 2024/09/01 00:00 [received] PHST- 2024/12/09 00:00 [accepted] PHST- 2025/03/12 12:32 [medline] PHST- 2025/02/21 12:22 [pubmed] PHST- 2025/02/21 07:13 [entrez] AID - 10.1111/imj.16625 [doi] PST - ppublish SO - Intern Med J. 2025 Mar;55(3):369-375. doi: 10.1111/imj.16625. Epub 2025 Feb 21. PMID- 39980227 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260524 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 45 IP - 3 DP - 2025 Mar TI - The potential role of GLP-1 receptor agonists in osteoarthritis. PG - 177-186 LID - 10.1002/phar.70005 [doi] AB - Osteoarthritis (OA) is the most common form of arthritis, affecting over 500 million people globally. Current treatments are primarily symptom-focused, with no approved therapies to halt disease progression. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in type 2 diabetes (T2D) and obesity, demonstrate significant weight loss and glucose-lowering effects and have been shown to possess anti-inflammatory properties. Given the central role of inflammation and metabolic dysfunction in OA, this review examines the potential utility of GLP-1 RAs in OA management, focusing on both indirect effects, such as weight reduction, and possible direct effects on inflammatory pathways and cartilage preservation. Clinical studies suggest that GLP-1 RAs may benefit people with OA by reducing weight, improving glycemic control, and modulating inflammatory markers relevant to OA progression. Notable findings include significant weight loss and pain reduction in people with knee OA (KOA) treated with semaglutide in the STEP-9 trial. In other studies, GLP-1 RAs have shown potential to lower oxidative stress and pro-inflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin (IL)-6, with reductions in OA-related pain and functional impairment observed in some cohorts. However, results vary, with some studies showing limited effects, potentially linked to the degree of weight loss achieved. Although some studies report variability in pain relief, likely influenced by the degree of weight loss achieved, GLP-1 RAs have shown overall promise in reducing both OA symptoms and markers associated with disease progression. This emerging evidence supports the utility of GLP-1 RAs as a potential disease-modifying option for OA, offering a dual benefit in metabolic and joint health. Future research should focus on establishing the long-term efficacy and safety and elucidating the mechanism by which GLP-1 RAs influence OA pathology. CI - (c) 2025 Pharmacotherapy Publications, Inc. FAU - Ryan, Mackenzie AU - Ryan M AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Megyeri, Saige AU - Megyeri S AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Nuffer, Wes AU - Nuffer W AUID- ORCID: 0000-0002-3355-4582 AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Trujillo, Jennifer M AU - Trujillo JM AUID- ORCID: 0000-0001-7898-8029 AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. LA - eng PT - Journal Article PT - Review DEP - 20250220 PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoarthritis/drug therapy MH - Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - GLP-1 receptor agonists OT - inflammation OT - osteoarthritis EDAT- 2025/02/21 06:22 MHDA- 2025/03/13 14:06 CRDT- 2025/02/21 01:53 PHST- 2025/01/15 00:00 [revised] PHST- 2024/11/16 00:00 [received] PHST- 2025/01/18 00:00 [accepted] PHST- 2025/03/13 14:06 [medline] PHST- 2025/02/21 06:22 [pubmed] PHST- 2025/02/21 01:53 [entrez] AID - 10.1002/phar.70005 [doi] PST - ppublish SO - Pharmacotherapy. 2025 Mar;45(3):177-186. doi: 10.1002/phar.70005. Epub 2025 Feb 20. PMID- 39977628 OWN - NLM STAT- MEDLINE DCOM- 20250220 LR - 20260813 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 3 DP - 2025 Mar 1 TI - Comparative Efficacy of Glucagon-Like Peptide 1 Receptor Agonists for Cardiovascular Outcomes in Asian Versus White Populations: Systematic Review and Meta-analysis of Randomized Trials of Populations With or Without Type 2 Diabetes and/or Overweight or Obesity. PG - 489-493 LID - 10.2337/dc24-1533 [doi] AB - BACKGROUND: Cardiovascular outcome trials (CVOTs) suggest glucagon-like peptide 1 receptor agonists (GLP-1RAs) provide greater cardiovascular (CV) benefits in Asian compared with White individuals. PURPOSE: Compare CV efficacy of GLP-1RAs between Asian and White individuals. DATA SOURCES: Systematic review of PubMed and ClinicalTrials.gov (1 January 2015 to 1 November 2024). STUDY SELECTION: Randomized placebo-controlled CVOTs of GLP-1RAs. Risk of bias was assessed (RoB 2). DATA EXTRACTION: Ethnicity-specific hazard ratios (HRs) for major adverse cardiovascular events (MACE). DATA SYNTHESIS: Random-effects meta-analyses per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines included eight trials (5,909 Asian individuals, 55,855 White individuals). GLP-1RA-associated MACE HR was 0.69 (95% CI 0.58, 0.83) in Asian people and 0.85 (95% CI 0.79, 0.91) in White people (Pinteraction = 0.045). Absolute MACE risk reduction was 2.9% (95% CI 1.5, 4.2) in Asian people versus 1.4% (0.9, 1.9) in White people. LIMITATIONS: Lack of individual patient-level data precluded detailed subclassification of the Asian group. CONCLUSIONS: GLP-1RAs may offer greater MACE reductions in Asian compared with White individuals. CI - (c) 2025 by the American Diabetes Association. FAU - Lee, Matthew M Y AU - Lee MMY AUID- ORCID: 0000-0001-9213-2067 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Ghouri, Nazim AU - Ghouri N AUID- ORCID: 0000-0002-8263-2591 AD - School of Medicine, University of Glasgow, Glasgow, U.K. AD - Queen Elizabeth University Hospital, Glasgow, U.K. FAU - Misra, Anoop AU - Misra A AUID- ORCID: 0000-0001-5785-5833 AD - Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases, and Endocrinology, New Delhi, India. AD - National Diabetes, Obesity and Cholesterol Foundation (N-DOC), New Delhi, India. AD - Diabetes Foundation of India (DFI), New Delhi, India. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. AD - Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Rutter, Martin K AU - Rutter MK AUID- ORCID: 0000-0001-6380-539X AD - Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, U.K. AD - Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester, U.K. FAU - Gerstein, Hertzel C AU - Gerstein HC AUID- ORCID: 0000-0001-8072-2836 AD - Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX. AD - Parkland Health, Dallas, TX. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, U.K. LA - eng GR - T32 DK007529/DK/NIDDK NIH HHS/United States GR - RE/18/6/34217/British Heart Foundation Centre of Research/ PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Asian People/statistics & numerical data MH - *Cardiovascular Diseases/epidemiology/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *White People/statistics & numerical data PMC - PMC12081317 COIS- Duality of Interest. M.M.Y.L. has received research grants through his institution, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim, and Roche Diagnostics and is a member of a Trial Steering Committee for Cytokinetics and a Clinical Endpoints Committee for Bayer. N.G. has received speaker honoraria from Novo Nordisk (nonpromotional activity) and Boehringer Ingelheim within the past 3 years. A.M. reports consulting/speaker honoraria from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Janssen, Sanofi, Lupin, US Vitamins, Cipla, and Glenmark. M.K.R. reports consulting honoraria from Eli Lilly. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing education grants from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Sanofi, Carbon Brand, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly, Novo Nordisk, Pfizer, Sanofi, Kowa, and Hanmi. D.K.M. has received honoraria for trial leadership from Boehringer Ingelheim, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, CSL Behring, Eidos, and NewAmsterdam and honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Novo Nordisk, Applied Therapeutics, Bayer, Altimmune, Intercept, Alnylam, Amgen, and Neurotronics. N.S. reports consulting/speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi and grants from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/02/20 18:21 MHDA- 2025/02/20 18:22 PMCR- 2026/03/01 CRDT- 2025/02/20 15:13 PHST- 2024/09/03 00:00 [received] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/02/20 18:22 [medline] PHST- 2025/02/20 18:21 [pubmed] PHST- 2025/02/20 15:13 [entrez] PHST- 2026/03/01 00:00 [pmc-release] AID - 157707 [pii] AID - 241533 [pii] AID - 10.2337/dc24-1533 [doi] PST - ppublish SO - Diabetes Care. 2025 Mar 1;48(3):489-493. doi: 10.2337/dc24-1533. PMID- 39976940 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 4 DP - 2025 Apr 1 TI - Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. PG - 304-314 LID - 10.1001/jamaophthalmol.2024.6555 [doi] AB - IMPORTANCE: Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D). OBJECTIVE: To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non-GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals' risks during exposure and nonexposure periods for each drug. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model. EXPOSURES: GLP-1RA and non-GLP-1RAs. MAIN OUTCOMES AND MEASURES: NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific. RESULTS: The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum's deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001). CONCLUSIONS AND RELEVANCE: Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association. FAU - Cai, Cindy X AU - Cai CX AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Hribar, Michelle AU - Hribar M AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland. AD - Casey Eye Institute, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla. AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla. FAU - Goetz, Kerry AU - Goetz K AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland. FAU - Swaminathan, Swarup S AU - Swaminathan SS AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. FAU - Flowers, Alexis AU - Flowers A AD - Vanderbilt Eye Institute, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. AD - Vanderbilt Eye Institute, Department of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Brown, Eric N AU - Brown EN AD - Vanderbilt Eye Institute, Department of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Xu, Benjamin AU - Xu B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Chen, John AU - Chen J AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. AD - Department of Neurology, Mayo Clinic, Rochester, Minnesota. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California. FAU - Lee, Cecilia AU - Lee C AD - Department of Ophthalmology, University of Washington, Seattle. AD - Karalis Johnson Retina Center, Seattle, Washington. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Ehrlich, Joshua R AU - Ehrlich JR AD - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor. AD - Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor. FAU - Barkmeier, Andrew AU - Barkmeier A AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. FAU - Armbrust, Karen R AU - Armbrust KR AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. FAU - Boland, Michael V AU - Boland MV AD - Department of Ophthalmology, Mass Eye and Ear and Harvard Medical School, Boston, Massachusetts. FAU - Dorr, David AU - Dorr D AD - Department of Medical Informatics & Clinical Epidemiology, Portland, Oregon. FAU - Boyce, Danielle AU - Boyce D AD - Johns Hopkins University School of Medicine, Baltimore, Maryland. AD - Tufts University School of Medicine, Boston, Massachusetts. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia. AD - Pharmacy Practice Research Unit, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia. FAU - Swerdel, Joel AU - Swerdel J AD - Janssen Research and Development, Titusville, New Jersey. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles. AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - Schuemie, Martijn AU - Schuemie M AD - Janssen Research and Development, Titusville, New Jersey. AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor. FAU - Sena, Anthony G AU - Sena AG AD - Janssen Research and Development, Titusville, New Jersey. AD - Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Nagy, Paul AU - Nagy P AD - Department of Biomedical Informatics and Data Science, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - DuVall, Scott L AU - DuVall SL AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. AD - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Matheny, Michael AU - Matheny M AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Nashville, Tennessee. FAU - Viernes, Benjamin AU - Viernes B AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - O'Brien, William AU - O'Brien W AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Wilcox, Adam AU - Wilcox A AD - Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Lai, Albert AU - Lai A AD - Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Stocking, Jacqueline C AU - Stocking JC AD - Department of Internal Medicine, University of California Davis, Sacramento. FAU - Takkouche, Sahar AU - Takkouche S AD - Department of Medicine, Division of Diabetes and Endocrinology, Vanderbilt University, Nashville, Tennessee. FAU - Lee, Lok Hin AU - Lee LH AD - Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Xie, Yangyiran AU - Xie Y AD - Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - McCoy, David B AU - McCoy DB AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - Adibuzzaman, Mohammad AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - Areaux, Raymond G Jr AU - Areaux RG Jr AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. FAU - Rojas-Carabali, William AU - Rojas-Carabali W AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. FAU - Brash, James AU - Brash J AD - IQVIA, Real World Solutions, Brighton, United Kingdom. FAU - Lee, David A AU - Lee DA AD - Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston. FAU - Weiskopf, Nicole G AU - Weiskopf NG AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Mawn, Louise AU - Mawn L AD - Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Agrawal, Rupesh AU - Agrawal R AD - Tan Tock Seng Hospital, Singapore. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Ryan, Patrick B AU - Ryan PB AD - Columbia University Irving Medical Center, New York, New York. AD - Johnson & Johnson, Horsham, Pennsylvania. LA - eng GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - K23 EY033440/EY/NEI NIH HHS/United States GR - T15 LM011271/LM/NLM NIH HHS/United States GR - R01 LM013426/LM/NLM NIH HHS/United States GR - K12 EY027720/EY/NEI NIH HHS/United States GR - R01 LM013990/LM/NLM NIH HHS/United States GR - K01 HL168222/HL/NHLBI NIH HHS/United States GR - R01 AG060942/AG/NIA NIH HHS/United States GR - UL1 TR002369/TR/NCATS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Apr 1;143(4):315-316. doi: 10.1001/jamaophthalmol.2025.0005. PMID: 39976950 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis MH - Retrospective Studies MH - Semaglutide PMC - PMC11843465 COIS- Conflict of Interest Disclosures: Dr Cai reported receiving grants from Regeneron Pharmaceuticals outside the submitted work. Dr Baxter reported receiving grants from National Institutes of Health (NIH) and Research to Prevent Blindess, personal fees from Topcon, and nonfinancial support from Optomed outside the submitted work. Dr Swaminathan reported receiving personal fees from AbbVie, Elios Vision, and Lumata Health and grants from Heidelberg Engineering outside the submitted work. Dr Toy reported receiving advisory board fees from Alimera Sciences, Bausch & Lomb, and Regeneron outside the submitted work. Dr C. Lee reported receiving grants from NIH, Centers for Disease Control and Prevention, and the Alzheimer's Disease Drug Foundation outside the submitted work. Dr Leng reported receiving grants from Astellas and personal fees from Topcon, Astellas, Alcon, Boehringer Ingelheim, Iridex, Nanoscope, Regeneron, Genentech/Roche, Virtual Field, Aptitude Medical, Protagonist Therapeutics, Apellis, and Graybug outside the submitted work. Dr Boland reported receiving personal fees from Carl Zeiss Meditec, Topcon Healthcare, Allergan, and Janssen during the conduct of the study. Dr Swerdel reported being an employee and shareholder of Johnson & Johnson outside the submitted work. Dr Suchard reported receiving grants from NIH, US Department of Veterans Affairs, and the US Food and Drug Administration and personal fees from Johnson & Johnson outside the submitted work. Drs Schuemie and Sena reported being and employee and shareholder of Johnson & Johnson outside the submitted work. Dr DuVall reported receiving grants from Alnylam Pharmaceuticals, Astellas Pharma, AstraZeneca, Biodesix, Celgene Corp, Cerner Enviza, GSK, IQVIA, Janssen Pharmaceuticals, Moderna, Novartis International AG, and Parexel International Corp outside the submitted work. Dr Lai reported being a shareholder of Johnson & Johnson outside the submitted work. Dr Brash reported being employed by IQVIA outside the submitted work. Dr Mawn reported receiving grants from Research to Prevent Blindness and consultant fees from Amgen and Genentech. Dr Ryan reported being an employee and shareholder of Johnson & Johnson. No other disclosures were reported. EDAT- 2025/02/20 12:24 MHDA- 2025/04/17 12:26 PMCR- 2025/02/20 CRDT- 2025/02/20 11:33 PHST- 2025/04/17 12:26 [medline] PHST- 2025/02/20 12:24 [pubmed] PHST- 2025/02/20 11:33 [entrez] PHST- 2025/02/20 00:00 [pmc-release] AID - 2830475 [pii] AID - eoi240096 [pii] AID - 10.1001/jamaophthalmol.2024.6555 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Apr 1;143(4):304-314. doi: 10.1001/jamaophthalmol.2024.6555. PMID- 39964295 OWN - NLM STAT- MEDLINE DCOM- 20260601 LR - 20260605 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 25 IP - 6 DP - 2026 Jun TI - Evaluating bowel obstruction and ileus events in patients on GLP-1 receptor agonists: a systematic review and meta-analysis. PG - 1057-1065 LID - 10.1080/14740338.2025.2465870 [doi] AB - INTRODUCTION: This research evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) and bowel obstruction or ileus. METHODS: We searched databases, including Medline, Embase, and Cochrane, for studies on adult patients treated with GLP-1 RA. We included randomized control trials (RCT), cohort, case-control studies, and case reports. We used the Cochrane Risk of Bias tool to evaluate the quality of RCTs and the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS: Out of 317 records identified, 14 studies were included in the systematic review. The meta-analysis included 6 studies with a combined total of 550,426 participants. The use of GLP-1 RA did not show an incremental risk of bowel obstruction or ileus compared to controls (OR 1.95, 95% CI 0.43-8.79). However, the studies had high heterogeneity (I(2) = 94%). A subgroup analysis by specific medication revealed that liraglutide was associated with a significantly high risk of bowel obstruction or ileus (OR 3.0, 95% CI 2.03-4.45; I(2) = 0%). CONCLUSIONS: GLP-1 receptor agonists do not significantly increase the risk of bowel obstruction or ileus. However, liraglutide is associated with a higher risk compared to semaglutide. Clinicians should remain aware of these rare events while recognizing the benefits of GLP-1 receptor agonists for glycemic control and cardiovascular health. PROSPERO REGISTRATION: CRD42024585971. FAU - Alfehaid, Lama AU - Alfehaid L AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Alyami, Majed AU - Alyami M AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Almohareb, Sumaya AU - Almohareb S AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Alshaya, Omar AU - Alshaya O AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Almutairi, Abdulaali AU - Almutairi A AD - Drug Safety and Risk Management, Saudi Food and Drug Authority, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250222 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Ileus/chemically induced/epidemiology MH - *Intestinal Obstruction/chemically induced/epidemiology MH - *Liraglutide/adverse effects/administration & dosage MH - Randomized Controlled Trials as Topic MH - Semaglutide/administration & dosage/adverse effects OTO - NOTNLM OT - Bowel obstruction OT - glucagon-like peptide-1 receptor agonists OT - ileus OT - liraglutide OT - semaglutide EDAT- 2025/02/18 12:25 MHDA- 2026/06/01 12:38 CRDT- 2025/02/18 10:13 PHST- 2026/06/01 12:38 [medline] PHST- 2025/02/18 12:25 [pubmed] PHST- 2025/02/18 10:13 [entrez] AID - 10.1080/14740338.2025.2465870 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2026 Jun;25(6):1057-1065. doi: 10.1080/14740338.2025.2465870. Epub 2025 Feb 22. PMID- 39963952 OWN - NLM STAT- MEDLINE DCOM- 20250218 LR - 20260813 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 2 IP - 2 DP - 2025 Feb 18 TI - Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. PG - CD015849 LID - 10.1002/14651858.CD015849.pub2 [doi] LID - CD015849 AB - BACKGROUND: Approximately 40% of people with diabetes develop kidney failure and experience an accelerated risk of cardiovascular complications. Glucagon-like peptide 1 (GLP-1) receptor agonists are glucose-lowering agents that manage glucose and weight control. OBJECTIVES: We assessed the benefits and harms of GLP-1 receptor agonists in people with chronic kidney disease (CKD) and diabetes. SEARCH METHODS: The Cochrane Kidney and Transplant Register of Studies was searched to 10 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if participants with diabetes and CKD were randomly allocated to a GLP-1 receptor agonist, placebo, standard care or a second glucose-lowering agent. CKD included all stages (from 1 to 5). DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias using the risk of bias assessment tool 2. Pooled analyses using summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and/or hazard ratio (HR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. The primary outcomes included death (all-cause and cardiovascular), 3- and 4-point major adverse cardiovascular events (MACE), kidney failure, composite kidney outcome, and severe hypoglycaemia. The secondary outcomes included non-fatal or fatal myocardial infarction (MI) or stroke, non-fatal peripheral arterial events, heart failure, hospitalisation due to heart failure, estimated glomerular filtration rate or creatinine clearance, doubling of serum creatinine, urine albumin-to-creatinine ratio, albuminuria progression, vascular access outcomes, body weight, body mass index, fatigue, life participation, peritoneal dialysis infection, peritoneal dialysis failure, adverse events, serious adverse events, withdrawal due to adverse events, HbA1c, sudden death, acute MI, ischaemic stroke, and coronary revascularisation. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Forty-two studies involving 48,148 participants were included. All studies were conducted on people with type 2 diabetes, and no studies were carried out on children. The median study age was 66 years. The median study follow-up was 26 weeks. Six studies were conducted in people with CKD stages 1-2, 11 studies in people with CKD stages 3-5, one study in people on dialysis, and the remaining studies included people with both CKD stages 1-2 and 3-5. Risks of bias in the included studies for all the primary outcomes in studies that compared GLP-1 receptor agonists to placebo were low in most methodological domains, except one study that was assessed at high risk of bias due to missing outcome data for death (all-cause and cardiovascular). The overall risk of bias for all-cause and cardiovascular death in studies that reported the treatment effects of GLP-1 receptor agonists compared to standard care, dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT2) inhibitors were assessed as unclear or at high risk of bias due to deviations from intended interventions or missing data. For GLP-1 receptor agonists compared to insulin or another GLP-1 receptor agonist, the risk of bias for all-cause and cardiovascular death was low or unclear. Compared to placebo, GLP-1 receptor agonists probably reduced the risk of all-cause death (RR 0.85, 95% CI 0.74 to 0.98; I(2) = 23%; 8 studies, 17,861 participants; moderate-certainty evidence), but may have little or no effect on cardiovascular death (RR 0.84, 95% CI 0.68 to 1.05; I(2) = 42%; 7 studies, 17,801 participants; low-certainty evidence). Compared to placebo, GLP-1 receptor agonists probably decreased 3-point MACE (RR 0.84, 95% CI 0.73 to 0.98; I(2) = 65%; 4 studies, 19,825 participants; moderate-certainty evidence), and 4-point MACE compared to placebo (RR 0.77, 95% CI 0.67 to 0.89; 1 study, 2,158 participants; moderate-certainty evidence). Based on absolute risks of clinical outcomes, it is likely that GLP-1 receptor agonists prevent all-cause death in 52 people with CKD stages 1-2 and 116 in CKD stages 3-5, cardiovascular death in 34 people with CKD stages 1-2 and 71 in CKD stages 3-5, while 95 CKD stages 1-2 and 153 in CKD stages 3-5 might experience a major cardiovascular event for every 1000 people treated over 1 year. Compared to placebo, GLP-1 receptor agonists probably had little or no effect on kidney failure, defined as starting dialysis or kidney transplant (RR 0.86, 95% CI 0.66 to 1.13; I(2) = 0%; 3 studies, 4,134 participants; moderate-certainty evidence), or on composite kidney outcomes (RR 0.89, 95% CI 0.78 to 1.02; I(2) = 0%; 2 studies, 16,849 participants; moderate-certainty evidence). Compared to placebo, GLP-1 receptor agonists may have little or no effect on the risk of severe hypoglycaemia (RR 0.82, 95% CI 0.54 to 1.25; I(2) = 44%; 4 studies, 6,292 participants; low-certainty evidence). The effects of GLP-1 receptor agonists compared to standard care or other hypoglycaemic agents were uncertain. No studies evaluated treatment on risks of fatigue, life participation, amputation or fracture. AUTHORS' CONCLUSIONS: GLP-1 receptor agonists probably reduced all-cause death but may have little or no effect on cardiovascular death in people with CKD and diabetes. GLP-1 receptor agonists probably lower major cardiovascular events, probably have little or no effect on kidney failure and composite kidney outcomes, and may have little or no effect on the risk of severe hypoglycaemia in people with CKD and diabetes. CI - Copyright (c) 2025 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Natale, Patrizia AU - Natale P AD - Sydney School of Public Health, The University of Sydney, Sydney, Australia. AD - Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy. FAU - Green, Suetonia C AU - Green SC AD - Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. FAU - Tunnicliffe, David J AU - Tunnicliffe DJ AD - Sydney School of Public Health, The University of Sydney, Sydney, Australia. FAU - Pellegrino, Giovanni AU - Pellegrino G AD - Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy. FAU - Toyama, Tadashi AU - Toyama T AD - Department of Nephrology, Kanazawa University, Kanazawa, Japan. AD - Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan. FAU - Strippoli, Giovanni Fm AU - Strippoli GF AD - Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy. AD - Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. AD - Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. LA - eng SI - ClinicalTrials.gov/NCT03496298 SI - ClinicalTrials.gov/NCT01621178 SI - ClinicalTrials.gov/NCT02963766 SI - ClinicalTrials.gov/NCT01761318 SI - ClinicalTrials.gov/NCT02660047 SI - ClinicalTrials.gov/NCT01336023 SI - ClinicalTrials.gov/NCT01392573 SI - ClinicalTrials.gov/NCT01676116 SI - ClinicalTrials.gov/NCT01618162 SI - ClinicalTrials.gov/NCT01952145 SI - ClinicalTrials.gov/NCT01147250 SI - ClinicalTrials.gov/NCT01144338 SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT01798706 SI - ClinicalTrials.gov/NCT01794143 SI - ClinicalTrials.gov/NCT02465515 SI - ClinicalTrials.gov/NCT01394341 SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01098539 SI - ClinicalTrials.gov/NCT02730377 SI - ClinicalTrials.gov/NCT01620489 SI - ClinicalTrials.gov/NCT00097500 SI - ClinicalTrials.gov/NCT01847313 SI - ClinicalTrials.gov/NCT03550378 SI - ClinicalTrials.gov/NCT02827708 SI - ClinicalTrials.gov/NCT02692716 SI - ClinicalTrials.gov/NCT01394952 SI - ClinicalTrials.gov/NCT04515849 SI - ClinicalTrials.gov/NCT04061200 SI - ClinicalTrials.gov/NCT03914326 SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT03136484 SI - ClinicalTrials.gov/NCT03824002 SI - ClinicalTrials.gov/NCT02545738 SI - ClinicalTrials.gov/NCT02690883 SI - ClinicalTrials.gov/NCT00712673 SI - ClinicalTrials.gov/NCT00763451 SI - ClinicalTrials.gov/NCT00707031 SI - ClinicalTrials.gov/NCT05536804 SI - ClinicalTrials.gov/NCT06182891 SI - ClinicalTrials.gov/NCT06555146 SI - ClinicalTrials.gov/NCT04865770 PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250218 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Placebos) SB - IM UOF - doi: 10.1002/14651858.CD015849 MH - Humans MH - Randomized Controlled Trials as Topic MH - *Renal Insufficiency, Chronic/complications/mortality/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemia/chemically induced/epidemiology MH - Cardiovascular Diseases/mortality/epidemiology MH - Bias MH - Liraglutide/therapeutic use/adverse effects MH - Myocardial Infarction/epidemiology MH - Placebos/therapeutic use PMC - PMC11834151 COIS- 1. Patrizia Natale: has declared that they have no conflict of interest. 2. Suetonia Green: has declared that they have no conflict of interest. 3. David Tunnicliffe: has declared that they have no conflict of interest. 4. Giovanni Pellegrino: has declared that they have no conflict of interest. 5. Tadashi Toyama: Mitsubishi Tanabe Pharma Corporation (Independent Contractor - Other); Mitsubishi Tanabe Pharma Corporation (Independent Contractor - Consultant). 6. Giovanni FM Strippoli: has declared that they have no conflict of interest. EDAT- 2025/02/18 12:25 MHDA- 2025/02/18 12:26 PMCR- 2026/02/18 CRDT- 2025/02/18 06:42 PHST- 2025/02/18 12:26 [medline] PHST- 2025/02/18 12:25 [pubmed] PHST- 2025/02/18 06:42 [entrez] PHST- 2026/02/18 00:00 [pmc-release] AID - CD015849.pub2 [pii] AID - 10.1002/14651858.CD015849.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2. PMID- 39963363 OWN - NLM STAT- MEDLINE DCOM- 20250218 LR - 20260127 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2025 DP - 2025 TI - Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors Improve Renal Resistive Index in Patients With Type 2 Diabetes: A 26-Week Prospective Observational Real-Life Study. PG - 8182211 LID - 10.1155/jdr/8182211 [doi] LID - 8182211 AB - Diabetic kidney disease (DKD) is one of the most life-threatening complications of diabetes and a leading cause of chronic kidney disease. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is) appear to improve renal outcome in patients with Type 2 diabetes (T2D). In this context, the renal resistive index (RRI) is a useful doppler measure to study DKD and predict its evolution. The aim of this work was to study the effect of treatment with GLP1-RA or SGLT2i on RRI and the relationship between RRI and glycometabolic parameters. One hundred forty-five patients with T2D were enrolled in the study and treated for 26 weeks with once-weekly GLP1-RA (38 patients with dulaglutide and 39 with semaglutide), SGLT2i (40 patients), or other therapies (28 control patients). Clinical, anthropometric, and hematochemical parameters and RRI were measured at baseline (T0) and after 6 months of treatment (T6). Changes at 6 months were studied and compared by treatment group. Patients were predominantly male (58.6%), overweight (93.0%) or frankly obese (60.0%), with hypertension (90.0%) and high (> 0.64) or pathological (> 0.7) RRI values (82.0% or 37.0%, respectively). At baseline, RRI correlated positively with age, fasting blood glucose, glycated hemoglobin (HbA1c), triglycerides, and albuminuria and negatively with estimated-glomerular filtration rate (e-GFR). At T6, patients treated with either GLP1-RA or SGLT2i showed a significant improvement in RRI but not in albuminuria or e-GFR, compared with homologous at baseline. In particular, RRI normalized in 32% and 30% of patients on therapy with GLP1-RA and SGLT2i, respectively, while remaining almost unchanged in controls. Notably, the RRI improvement was independent of age, gender, diabetes duration, and changes in BMI, waist circumference, HbA1c, and e-GFR. In conclusion, RRI can be used to detect early kidney damage and follow the evolution of DKD. GLP1-RA and SGLT2i improve RRI, demonstrating benefits on cardiovascular risk and renal outcomes. CI - Copyright (c) 2025 Alfredo Vozza et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Vozza, Alfredo AU - Vozza A AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Volpe, Sara AU - Volpe S AUID- ORCID: 0000-0002-6831-0457 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Custodero, Carlo AU - Custodero C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AUID- ORCID: 0009-0004-7322-7705 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lavarra, Valentina AU - Lavarra V AUID- ORCID: 0009-0007-6995-4127 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AUID- ORCID: 0009-0007-9619-8726 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Crudele, Lucilla AU - Crudele L AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Bergamasco, Alessandro AU - Bergamasco A AUID- ORCID: 0009-0008-6387-0560 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Antonica, Gianfranco AU - Antonica G AUID- ORCID: 0009-0009-0693-6751 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Tortorella, Cosimo AU - Tortorella C AUID- ORCID: 0000-0002-4504-9313 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AUID- ORCID: 0000-0003-3221-6562 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20250210 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - *Diabetic Nephropathies/blood/drug therapy/etiology/physiopathology MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glycated Hemoglobin MH - *Kidney/blood supply/diagnostic imaging/drug effects/physiopathology MH - Prospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Treatment Outcome MH - *Vascular Resistance/drug effects MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC11832268 OTO - NOTNLM OT - Type 2 diabetes OT - chronic kidney disease OT - diabetic kidney disease OT - glucagon-like peptide 1 receptor agonists OT - renal Doppler ultrasound OT - renal damage OT - renal hemodynamic OT - renal resistive index OT - sodium-glucose cotransporter 2 inhibitors COIS- The authors declare no conflicts of interest. EDAT- 2025/02/18 06:21 MHDA- 2025/02/18 06:22 PMCR- 2025/02/10 CRDT- 2025/02/18 04:18 PHST- 2024/05/23 00:00 [received] PHST- 2025/01/22 00:00 [accepted] PHST- 2025/02/18 06:22 [medline] PHST- 2025/02/18 06:21 [pubmed] PHST- 2025/02/18 04:18 [entrez] PHST- 2025/02/10 00:00 [pmc-release] AID - 10.1155/jdr/8182211 [doi] PST - epublish SO - J Diabetes Res. 2025 Feb 10;2025:8182211. doi: 10.1155/jdr/8182211. eCollection 2025. PMID- 39961620 OWN - NLM STAT- MEDLINE DCOM- 20250508 LR - 20250508 IS - 1941-2452 (Electronic) IS - 0884-5336 (Linking) VI - 40 IP - 2 DP - 2025 Apr TI - Use of glucagon-like peptide-1 receptor agonists and incretin mimetics for type 2 diabetes and obesity: A narrative review. PG - 327-349 LID - 10.1002/ncp.11279 [doi] AB - Incretin mimetics, including glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists, have become first-line treatment options for the treatment of type 2 diabetes and obesity. Their therapeutic status is attributed to their high level of efficacy as well as positive impact on related comorbidities, such as sleep apnea and heart failure. Multiple incretin mimetics are currently available with different durations of drug action, dosing frequencies, and delivery devices. Patients may benefit from education on the proper drug administration, anticipated adverse effects, and nutrition considerations with treatment. Practitioners must monitor progress and support the patient to achieve maintenance doses for optimal weight reduction and diabetes-related outcomes. This review aims to present the current literature supporting US Food and Drug Administration-approved indications of incretin mimetics, equip healthcare professionals to optimize care for patients who are prescribed these agents, and provide insights into potential future applications, which may include dual- or triple-mechanism agents that are injected or administered orally. Additional studies are anticipated with existing and future incretin mimetics for the treatment of type 2 diabetes, obesity, and related comorbidities in a rapidly developing therapeutic pipeline. CI - (c) 2025 American Society for Parenteral and Enteral Nutrition. FAU - Zupec, Jason AU - Zupec J AUID- ORCID: 0000-0002-4214-3830 AD - Department of Pharmacy Practice, Philadelphia College of Pharmacy at Saint Joseph's University, Philadelphia, Pennsylvania, USA. FAU - Munger, Rebecca AU - Munger R AD - Department of Pharmacy Practice, Philadelphia College of Pharmacy at Saint Joseph's University, Philadelphia, Pennsylvania, USA. FAU - Scaletta, Alice AU - Scaletta A AD - Department of Pharmacy Practice, Philadelphia College of Pharmacy at Saint Joseph's University, Philadelphia, Pennsylvania, USA. FAU - Quinn, Diane H AU - Quinn DH AD - Department of Pharmacy Practice, Philadelphia College of Pharmacy at Saint Joseph's University, Philadelphia, Pennsylvania, USA. LA - eng PT - Journal Article PT - Review DEP - 20250217 PL - United States TA - Nutr Clin Pract JT - Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition JID - 8606733 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 OTO - NOTNLM OT - gip OT - glp 1 OT - nutrition OT - obesity OT - review OT - type 2 diabetes EDAT- 2025/02/18 00:21 MHDA- 2025/03/05 00:22 CRDT- 2025/02/17 20:42 PHST- 2025/01/15 00:00 [revised] PHST- 2024/11/30 00:00 [received] PHST- 2025/01/17 00:00 [accepted] PHST- 2025/03/05 00:22 [medline] PHST- 2025/02/18 00:21 [pubmed] PHST- 2025/02/17 20:42 [entrez] AID - 10.1002/ncp.11279 [doi] PST - ppublish SO - Nutr Clin Pract. 2025 Apr;40(2):327-349. doi: 10.1002/ncp.11279. Epub 2025 Feb 17. PMID- 39961479 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260507 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 3 DP - 2025 May TI - Glucagon-like peptide 1 receptor agonists and renal outcomes in kidney transplant recipients with diabetes mellitus. PG - 101624 LID - S1262-3636(25)00019-9 [pii] LID - 10.1016/j.diabet.2025.101624 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) show reno-protective effects in type 2 diabetes. Limited data is available on their use in post-transplant diabetes mellitus. We aimed to explore the effect of GLP1-RAs on renal outcomes in diabetic kidney transplant recipients (KTR). METHODS: We conducted a cohort retrospective study on adult KTR with diabetes mellitus. KTR treated with GLP1-RAs were matched with non-users. The primary outcome was the first occurrence of graft rejection, start of dialysis, re-transplantation or all-cause mortality. Other outcomes included a composite of the first occurrence of a genitourinary infection or all-cause mortality, and all-cause mortality. Metabolic effects of GLP1-RA treatment and risk for biliopancreatic adverse events were also explored. RESULTS: We included 272 patients (69 % males, average age 58.3 +/- 11.0 years) with a 3.1-year median follow-up. The use of GLP1-RAs lowered the incidence of the composite renal outcome after adjustment for independent risk factors (114 versus 68 events per 1000-patient years in controls versus GLP1-RA users, HR 0.489, 95 % CI 0.271-0.883). GLP-RA users had improved glycemic control, lipid profile and a decrease in body mass index. The treatment was safe without increased genitourinary infections or biliopancreatic events. CONCLUSION: The use of GLP1-RAs decreased the risk of a composite outcome of renal dysfunction and mortality, improved metabolic control and showed safety of use in a large cohort of diabetic KTR, suggesting reno-protective effects in this high-risk population. Prospective data is further needed in KTR who are excluded from large RCTs. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Masson SAS.. All rights reserved. FAU - Diker Cohen, Talia AU - Diker Cohen T AD - Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: proftdc@gmail.com. FAU - Rudman, Yaron AU - Rudman Y AD - Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Turjeman, Adi AU - Turjeman A AD - Research authority, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Akirov, Amit AU - Akirov A AD - Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Steinmetz, Tali AU - Steinmetz T AD - Institute of Nephrology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Calvarysky, Bronya AU - Calvarysky B AD - Pharmacy, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Dotan, Idit AU - Dotan I AD - Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Journal Article DEP - 20250215 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Kidney Transplantation/adverse effects MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Treatment Outcome MH - Graft Rejection/epidemiology/prevention & control MH - *Diabetic Nephropathies OTO - NOTNLM OT - GLP1 receptor agonists OT - Kidney transplantation OT - Post-transplant diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ID has received fees from Astra Zeneca, Novonordisk, Abbott, Boeringham Ingleheimer, Elli Lilly and Sanofi for educational lectures, and participated in advisory boards of Novonordisk, Boeringham Ingleheimer, Sanofi and Novartis that are outside the scope of this work. ID reports a grant from Astra Zeneca that is outside the scope of the submitted work. TDC has received fees from Astra Zeneca for educational lectures that are outside the scope of this work. YR, AT, AA, TS and BC declare no conflicts of interest. EDAT- 2025/02/18 00:22 MHDA- 2025/05/01 06:28 CRDT- 2025/02/17 19:27 PHST- 2024/12/07 00:00 [received] PHST- 2025/02/06 00:00 [revised] PHST- 2025/02/08 00:00 [accepted] PHST- 2025/05/01 06:28 [medline] PHST- 2025/02/18 00:22 [pubmed] PHST- 2025/02/17 19:27 [entrez] AID - S1262-3636(25)00019-9 [pii] AID - 10.1016/j.diabet.2025.101624 [doi] PST - ppublish SO - Diabetes Metab. 2025 May;51(3):101624. doi: 10.1016/j.diabet.2025.101624. Epub 2025 Feb 15. PMID- 39954057 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 9 DP - 2025 Sep TI - Different formulations of semaglutide and oxidative stress in subjects with type 2 diabetes and MASLD: an open-label, real-life study. PG - 1429-1437 LID - 10.1007/s00592-025-02466-7 [doi] AB - AIM: Semaglutide exerts metabolic effects and cardiovascular protection in type 2 diabetes (T2D), also acting on hepatic steatosis and inflammation. No data are, so far, available on the effect of semaglutide on oxidative stress, neither a comparison of injective (InjS) and oral (OrS) formulations has been performed in subjects with T2D and liver steatosis. METHODS: In a real-life, open label, prospective study we compared standard doses of InjS and OrS in targeting liver inflammation and fibrosis and systemic markers of inflammation and oxidative stress by consecutively prescribing InjS or OrS formulation in a 2:1 ratio to sixty T2D + MASLD subjects (T0), observing them for 6 months (T1). Anthropometry, biochemistry and transient elastography (TE) data were collected; hormones, inflammatory cytokines and peroxidation products were measured. RESULTS: At baseline, InjS and OrS subjects were similar, except for waist circumference, liver enzymes and Controlled Attenuation Parameter (CAP), a measure of liver steatosis (InjS > OrS, all p < 0.05). Differences emerged in T0-T1 variation between the formulations in HbA1c, lipid profile, blood pressure. CAP significantly decreased only in InjS. GLP-1 quite similarly increased; insulin, glucagon and GIP did not vary. InjS and OrS did not modify TNFalpha, IL-10 (an anti-inflammatory cytokine) and MCP-1, while IL-18 was reduced only by InjS. When exploring oxidative stress, AGEs were unaffected, Thiobarbituric acid reactive substances decreased in InjS, 4-Hydroxynonenal was reduced in OrS. CONCLUSION: In T2D + MASLD subjects, InjS, better than OrS, improves metabolic control; a significant reduction of IL-18 by InjS, and a mild anti-oxidative effect of both formulations are reported for the first time. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Petralli, Giovanni AU - Petralli G AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Zoppo, Alice Del AU - Zoppo AD AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Rovera, Chiara AU - Rovera C AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Raggi, Francesco AU - Raggi F AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Salvati, Antonio AU - Salvati A AD - Hepatology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. FAU - Moriconi, Diego AU - Moriconi D AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Distaso, Mariarosaria AU - Distaso M AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Brunetto, Maurizia Rossana AU - Brunetto MR AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Solini, Anna AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. anna.solini@unipi.it. AD - Department of Surgical Medical Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, Pisa, 56126, Italy. anna.solini@unipi.it. LA - eng PT - Journal Article DEP - 20250215 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Acta Diabetol. 2025 Oct;62(10):1829. doi: 10.1007/s00592-025-02482-7. PMID: 40105914 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications MH - *Oxidative Stress/drug effects MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Prospective Studies MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Adult MH - Administration, Oral MH - *Fatty Liver/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Injective semaglutide OT - MASLD OT - Oral semaglutide OT - Oxidative stress COIS- Declarations. Conflict of interest: The authors declare no competing financial interest related to the present manuscript. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. EDAT- 2025/02/16 01:30 MHDA- 2025/09/16 06:36 CRDT- 2025/02/15 11:13 PHST- 2024/11/12 00:00 [received] PHST- 2025/02/01 00:00 [accepted] PHST- 2025/09/16 06:36 [medline] PHST- 2025/02/16 01:30 [pubmed] PHST- 2025/02/15 11:13 [entrez] AID - 10.1007/s00592-025-02466-7 [pii] AID - 10.1007/s00592-025-02466-7 [doi] PST - ppublish SO - Acta Diabetol. 2025 Sep;62(9):1429-1437. doi: 10.1007/s00592-025-02466-7. Epub 2025 Feb 15. PMID- 39952607 OWN - NLM STAT- MEDLINE DCOM- 20250301 LR - 20260507 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 2 DP - 2025 Mar TI - Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes. PG - 101623 LID - S1262-3636(25)00018-7 [pii] LID - 10.1016/j.diabet.2025.101623 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce. METHODS: - We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89-0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84-0.95) and AD (HR, 0.90; 95 % CI, 0.86-0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92-0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91-1.01). CONCLUSIONS: In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Sun, Mingyang AU - Sun M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Wang, Xiaoling AU - Wang X AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China. FAU - Lu, Zhongyuan AU - Lu Z AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China. FAU - Yang, Yitian AU - Yang Y AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Lv, Shuang AU - Lv S AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Miao, Mengrong AU - Miao M AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China. FAU - Chen, Wan-Ming AU - Chen WM AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan. FAU - Wu, Szu-Yuan AU - Wu SY AD - Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan; Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: szuyuanwu5399@gmail.com. FAU - Zhang, Jiaqiang AU - Zhang J AD - Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China. Electronic address: zhangjiq@zzu.edu.cn. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250212 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Alzheimer Disease/prevention & control/epidemiology MH - Retrospective Studies MH - *Dementia, Vascular/prevention & control/epidemiology MH - *Dementia/prevention & control/epidemiology MH - Middle Aged MH - Aged, 80 and over MH - Hypoglycemic Agents/therapeutic use MH - Incidence OTO - NOTNLM OT - Dementia prevention OT - GLP-1 receptor agonists OT - Neuroprotection OT - SGLT2 inhibitors OT - Type 2 Diabetes Mellitus COIS- Declaration of competing interest The authors have no potential conflicts of interest to declare. EDAT- 2025/02/15 15:10 MHDA- 2025/03/03 00:54 CRDT- 2025/02/14 19:33 PHST- 2025/01/13 00:00 [received] PHST- 2025/02/05 00:00 [revised] PHST- 2025/02/06 00:00 [accepted] PHST- 2025/03/03 00:54 [medline] PHST- 2025/02/15 15:10 [pubmed] PHST- 2025/02/14 19:33 [entrez] AID - S1262-3636(25)00018-7 [pii] AID - 10.1016/j.diabet.2025.101623 [doi] PST - ppublish SO - Diabetes Metab. 2025 Mar;51(2):101623. doi: 10.1016/j.diabet.2025.101623. Epub 2025 Feb 12. PMID- 39950222 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20260924 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Alternative dosing regimens of GLP-1 receptor agonists may reduce costs and maintain weight loss efficacy. PG - 2251-2258 LID - 10.1111/dom.16229 [doi] AB - AIMS: To discover alternative dosing regimens of incretin mimetics that simultaneously reduce costs and maintain weight loss efficacy. As a secondary objective, we used our results to explore how allocating a limited incretin mimetics budget could affect public health on a national scale. MATERIALS AND METHODS: We used mathematical modelling and simulation of semaglutide and tirzepatide to investigate dosing regimens which have not yet been studied clinically. For semaglutide, we used a recent pharmacokinetic (PK) and pharmacodynamic (PD) model. For tirzepatide, we used a recent PK model and modelled PD by reparameterizing the semaglutide PD model to fit tirzepatide clinical data. RESULTS: Reducing dose frequency does not commensurately reduce weight loss. For example, merely switching from one dose per week (q1wk) to one dose every 2 weeks (q2wk) maintains roughly 75% of the weight loss. Furthermore, if the decrease in dose frequency involves an appropriate increase in dose size, then approximately 100% of the weight loss is maintained. In addition, we compared offering incretin mimetics to (1) a fraction of obese US adults with q1wk dosing versus (2) twice as many obese US adults with q2wk dosing. Though scenarios (1) and (2) require the same budget, our analysis suggests that (2) reduces national obesity and mortality to a much greater degree. CONCLUSION: Our study highlights the potential utility of alternative dosing regimens of incretin mimetics. Compared with standard once-weekly dosing, costs can be halved and weight loss maintained. These cost-saving results have implications for patients, physicians, insurers, and governments. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Cengiz, Anil AU - Cengiz A AUID- ORCID: 0009-0000-3165-7329 AD - Department of Mathematics, University of Utah, Salt Lake City, Utah, USA. FAU - Wu, Calvin C AU - Wu CC AUID- ORCID: 0000-0001-7758-1366 AD - Tono Health, Brooklyn, New York, USA. FAU - Lawley, Sean D AU - Lawley SD AUID- ORCID: 0000-0003-2208-026X AD - Department of Mathematics, University of Utah, Salt Lake City, Utah, USA. LA - eng GR - DMS-1944574/National Science Foundation/ GR - DMS-2325258/National Science Foundation/ PT - Journal Article DEP - 20250214 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/economics/pharmacokinetics/analogs & derivatives MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Tirzepatide/administration & dosage MH - *Obesity/drug therapy/economics MH - *Hypoglycemic Agents/administration & dosage/economics MH - *Incretins/administration & dosage/economics MH - Drug Administration Schedule MH - Drug Costs MH - Cost-Benefit Analysis MH - *Anti-Obesity Agents/administration & dosage/economics MH - Treatment Outcome MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11885104 OTO - NOTNLM OT - GIP OT - GLP-1 OT - cost-effectiveness OT - pharmacodynamics OT - pharmacokinetics OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2025/02/14 06:20 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/02/14 04:33 PHST- 2025/01/23 00:00 [revised] PHST- 2024/11/27 00:00 [received] PHST- 2025/01/23 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/02/14 06:20 [pubmed] PHST- 2025/02/14 04:33 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16229 [pii] AID - 10.1111/dom.16229 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):2251-2258. doi: 10.1111/dom.16229. Epub 2025 Feb 14. PMID- 39947393 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260127 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 5 DP - 2025 May TI - Newer Glucagon-Like Peptide-1 Receptor Agonists Are Associated With Improved Glycemic Control in US Adults With Type 2 Diabetes: A Population-Level Time Series Analysis. PG - 712-719 LID - S1098-3015(25)00059-2 [pii] LID - 10.1016/j.jval.2025.01.018 [doi] AB - OBJECTIVES: The population-level impact of newer glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatments on patients with type 2 diabetes remains unclear. Therefore, this study investigated the association of newer GLP-1 RAs with population-level diabetes-related outcomes in US adults with type 2 diabetes. METHODS: This was a noninterventional, retrospective analysis of administrative insurance claims data obtained from Optum's deidentified Clinformatics(R) Data Mart Database between January 2004 and December 2022. Individual patient data were aggregated into monthly time series at the population level. Associations between the proportion of patients on newer GLP-1 RAs of interest (dulaglutide, once-weekly or oral semaglutide, and tirzepatide) and average hemoglobin A1c (HbA1c), HbA1c <7.0%, and HbA1c <8.0% were assessed using time series regressions. Time-based trends in population-level outcomes were assessed using interrupted time series analyses. All analyses were adjusted for potential confounders. RESULTS: Time series regression analyses demonstrated that a higher proportion of patients taking newer GLP-1 RAs was associated with a lower average HbA1c and a higher proportion of patients with HbA1c <7.0% (after 5 months of treatment) and <8.0% (after 2 months of treatment). Results from the interrupted time series analyses demonstrated that population-level glycemic control has been improving since the first newer GLP-1 RA (dulaglutide) was approved. This trend has persisted, even after the COVID-19 emergency declaration. CONCLUSIONS: A higher percentage of patients receiving newer GLP-1 RAs was associated with significantly improved population-level glycemic control. The newer GLP-1 RA period displayed improved population-level glycemic control compared with the older GLP-1 RA period. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Lv, Lei AU - Lv L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. Electronic address: lzlv@novonordisk.com. FAU - Wang, Yan AU - Wang Y AD - Analysis Group, Inc, Los Angeles, CA, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Zhang, Yuehan AU - Zhang Y AD - Analysis Group, Inc, New York, NY, USA. FAU - Song, Yan AU - Song Y AD - Analysis Group, Inc, Boston, MA, USA. FAU - Rotroff, Daniel M AU - Rotroff DM AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH, USA; Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250211 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - United States/epidemiology MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Adult MH - Blood Glucose/drug effects MH - Tirzepatide/therapeutic use/administration & dosage MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - glycemic control OT - interrupted time series OT - time series analysis OT - type 2 diabetes COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/02/14 00:23 MHDA- 2025/05/09 12:37 CRDT- 2025/02/13 19:31 PHST- 2024/07/10 00:00 [received] PHST- 2025/01/15 00:00 [revised] PHST- 2025/01/24 00:00 [accepted] PHST- 2025/05/09 12:37 [medline] PHST- 2025/02/14 00:23 [pubmed] PHST- 2025/02/13 19:31 [entrez] AID - S1098-3015(25)00059-2 [pii] AID - 10.1016/j.jval.2025.01.018 [doi] PST - ppublish SO - Value Health. 2025 May;28(5):712-719. doi: 10.1016/j.jval.2025.01.018. Epub 2025 Feb 11. PMID- 39945396 OWN - NLM STAT- MEDLINE DCOM- 20250213 LR - 20260625 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 2 DP - 2025 Feb TI - Association of GLP-1 Receptor Agonists With Risk of Suicidal Ideation and Behaviour: A Systematic Review and Meta-Analysis. PG - e70037 LID - 10.1002/dmrr.70037 [doi] LID - e70037 AB - BACKGROUND AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to treat type 2 diabetes and obesity, providing metabolic and cardiovascular benefits. However, concerns have emerged about potential neuropsychiatric side effects, including suicidal ideation and behaviour, prompting investigations by regulatory bodies such as the FDA and EMA. This systematic review and meta-analysis aimed to assess the association between GLP-1RA use and the risk of suicidal ideation or behaviour. METHODS: A systematic literature search was conducted in PubMed, Embase, and Web of Science through September 2024, adhering to PRISMA guidelines. Observational cohort and case-control studies reporting suicidal ideation or behaviour in adults using GLP-1RAs were included. The Modified Newcastle-Ottawa Scale assessed risk of bias, and random-effect models calculated risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I(2) statistic. RESULTS: Of 126 studies, 11 were included from multiple countries with diverse designs. The meta-analysis of four studies showed no statistically significant difference in suicidal outcomes between GLP-1RA users and users of other anti-hyperglycaemic drugs (RR: 0.568, 95% CI: 0.077-4.205). Substantial heterogeneity was observed (I(2) = 98%). Pharmacovigilance studies indicated no disproportionate increase in suicidality, while some observational studies suggested a lower risk. CONCLUSION: This review found no significant link between GLP-1RA use and increased suicidal ideation or behaviour. However, the high heterogeneity and reliance on pharmacovigilance data suggest caution. Clinicians should monitor patients, particularly those with psychiatric conditions, and further research is needed to assess long-term neuropsychiatric safety. CI - (c) 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Bushi, Ganesh AU - Bushi G AUID- ORCID: 0000-0002-0397-7904 AD - School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India. FAU - Khatib, Mahalaqua Nazli AU - Khatib MN AD - Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India. FAU - Rohilla, Shivam AU - Rohilla S AD - Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, India. AD - Evidence for Policy and Learning, Global Center for Evidence Synthesis, Chandigarh, India. FAU - Singh, Mahendra Pratap AU - Singh MP AD - Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India. FAU - Uniyal, Nidhi AU - Uniyal N AD - Department of General Medicine, Graphic Era (Deemed to be University), Dehradun, India. FAU - Ballal, Suhas AU - Ballal S AD - Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, India. FAU - Bansal, Pooja AU - Bansal P AD - Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, India. FAU - Bhopte, Kiran AU - Bhopte K AD - IES Institute of Pharmacy, IES University, Bhopal, India. FAU - Gupta, Manika AU - Gupta M AD - New Delhi Institute of Management, Delhi, India. FAU - Gaidhane, Abhay M AU - Gaidhane AM AD - School of Epidemiology and Public Health, Jawaharlal Nehru Medical College, and Global Health Academy, Datta Meghe Institute of Higher Education, Wardha, India. FAU - Tomar, Balvir S AU - Tomar BS AD - Institute of Pediatric Gastroenterology and Hepatology, NIMS University, Jaipur, India. FAU - Ashraf, Ayash AU - Ashraf A AD - Chandigarh Pharmacy College, Chandigarh Group of College, Mohali, India. FAU - Ravi Kumar, M AU - Ravi Kumar M AD - Department of Chemistry, Raghu Engineering College, Visakhapatnam, India. FAU - Chauhan, Ashish Singh AU - Chauhan AS AD - Division of Research and Innovation, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India. FAU - Sah, Sanjit AU - Sah S AD - Department of Paediatrics, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India. AD - Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, India. FAU - Serhan, Hashem Abu AU - Serhan HA AUID- ORCID: 0000-0002-2953-2188 AD - Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar. FAU - Shabil, Muhammed AU - Shabil M AD - University Center for Research and Development, Chandigarh University, Mohali, India. AD - Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Iraq. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Risk Factors MH - *Suicidal Ideation PMC - PMC11823376 OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes OT - meta-analysis OT - suicidal ideation COIS- The authors declare no conflicts of interest. EDAT- 2025/02/13 12:24 MHDA- 2025/02/13 12:25 PMCR- 2025/02/13 CRDT- 2025/02/13 07:33 PHST- 2024/12/23 00:00 [revised] PHST- 2024/09/16 00:00 [received] PHST- 2025/01/10 00:00 [accepted] PHST- 2025/02/13 12:25 [medline] PHST- 2025/02/13 12:24 [pubmed] PHST- 2025/02/13 07:33 [entrez] PHST- 2025/02/13 00:00 [pmc-release] AID - DMRR70037 [pii] AID - 10.1002/dmrr.70037 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 Feb;41(2):e70037. doi: 10.1002/dmrr.70037. PMID- 39937048 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20250529 IS - 1365-2362 (Electronic) IS - 0014-2972 (Print) IS - 0014-2972 (Linking) VI - 55 IP - 6 DP - 2025 Jun TI - Effects of glucagon-like PEPTIDE-1 receptor agonists on incidence of hepatocellular carcinoma and liver decompensation in patients with diabetes: A systematic review and META-analysis. PG - e70000 LID - 10.1111/eci.70000 [doi] LID - e70000 AB - This systematic review and meta-analysis evaluated the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on hepatocellular carcinoma (HCC) and liver decompensation in patients with type 2 diabetes. Analysing over 641,377 patients, GLP-1RA use was associated with a significant 58% reduction in HCC risk, particularly in patients with cirrhotis. While a trend towards reduced liver decompensation risk was observed, it was not statistically significant. These findings suggest a potential role for GLP-1RAs in HCC risk stratification and prevention strategies. CI - (c) 2025 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation. FAU - Pasta, Andrea AU - Pasta A AUID- ORCID: 0000-0003-1791-4506 AD - Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. FAU - Facciorusso, Antonio AU - Facciorusso A AUID- ORCID: 0000-0002-2107-2156 AD - Gastroenterology Unit, Department of Experimental Medicine, Universita del Salento, Lecce, Italy. FAU - Plaz Torres, Maria Corina AU - Plaz Torres MC AUID- ORCID: 0000-0003-4257-1058 AD - Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. FAU - Giannini, Edoardo G AU - Giannini EG AUID- ORCID: 0000-0001-8526-837X AD - Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. FAU - Sacco, Rodolfo AU - Sacco R AUID- ORCID: 0000-0002-9887-7315 AD - Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250212 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/epidemiology/prevention & control MH - *Liver Neoplasms/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Liver Cirrhosis/epidemiology MH - Incidence PMC - PMC12066890 OTO - NOTNLM OT - diabetes OT - hepatocellular carcinoma OT - liver decompensation OT - metabolic-associated steatotic liver disease OT - treatment COIS- None of the authors have any relevant financial disclosures. EDAT- 2025/02/12 12:25 MHDA- 2025/05/12 06:33 PMCR- 2025/05/12 CRDT- 2025/02/12 09:23 PHST- 2024/11/21 00:00 [received] PHST- 2025/01/23 00:00 [accepted] PHST- 2025/05/12 06:33 [medline] PHST- 2025/02/12 12:25 [pubmed] PHST- 2025/02/12 09:23 [entrez] PHST- 2025/05/12 00:00 [pmc-release] AID - ECI70000 [pii] AID - 10.1111/eci.70000 [doi] PST - ppublish SO - Eur J Clin Invest. 2025 Jun;55(6):e70000. doi: 10.1111/eci.70000. Epub 2025 Feb 12. PMID- 39937036 OWN - NLM STAT- MEDLINE DCOM- 20250310 LR - 20250728 IS - 1365-2362 (Electronic) IS - 0014-2972 (Print) IS - 0014-2972 (Linking) VI - 55 IP - 4 DP - 2025 Apr TI - Pharmacological treatment options for metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus: A systematic review. PG - e70003 LID - 10.1111/eci.70003 [doi] LID - e70003 AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to type 2 diabetes mellitus (T2DM) through a common root in insulin resistance. The more severe stage, metabolic dysfunction-associated steatohepatitis (MASH), increases the risk for cardiovascular complications, liver cirrhosis and hepatocellular carcinoma. Several trials investigating established antidiabetic-drugs in patients with T2DM and MASLD have yielded promising results. Therefore, we aimed to systematically review the effect of T2DM-drug treatment on MALSD parameters. METHODS: Medical databases were searched until January 2025 for controlled trials in patients with T2DM and MASLD/MASH. Studies that evaluated the effect of T2DM-medication on the severity of MASLD/MASH in T2DM patients were included. The quality of the studies was assessed by three independent reviewers using a set of Cochrane risk-of-bias tools. RESULTS: Of 1748 references, 117 studies fulfilled the inclusion-criteria and were assessed for eligibility in full-text. Fifty-two articles were included. Data included a total of 64.708 patients and study populations ranged from 9 to 50.742. Heterogeneity in study-design and analysis hampered the comparability of the results. Most evidence was present for GLP-1 receptor agonists, SGLT2-inhibitors and PPAR-gamma-agonists for regression of liver fibrosis and MASH. CONCLUSION: Studies on the value of T2DM-drug treatment in the improvement of MASLD vary significantly in study design, size and quality. GLP-1 receptor agonists, PPAR-gamma-agonists, SGLT2-inhibitors may all be preferred pharmacological interventions for patients with MASLD/MASH and T2DM. Newer agents like dual GLP-1/GIP or triple GLP-1/GIP/Glucagon agonists will likely play an important role in the treatment of MASLD/MASH in the near future. CI - (c) 2025 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation. FAU - Konings, Laura A M AU - Konings LAM AUID- ORCID: 0009-0005-6555-915X AD - Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. AD - Department of Internal Medicine and Endocrinology, Erasmus MC, Rotterdam, the Netherlands. FAU - Miguelanez-Matute, Lorena AU - Miguelanez-Matute L AD - Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. FAU - Boeren, Anna M P AU - Boeren AMP AD - Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. FAU - van de Luitgaarden, Inge A T AU - van de Luitgaarden IAT AD - Julius Clinical, Zeist, the Netherlands. FAU - Dirksmeier, Femme AU - Dirksmeier F AD - Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. FAU - de Knegt, Rob J AU - de Knegt RJ AD - Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands. FAU - Tushuizen, Maarten E AU - Tushuizen ME AD - Department of Gastroenterology and Hepatology, LUMC, Leiden, the Netherlands. FAU - Grobbee, Diederick E AU - Grobbee DE AD - Julius Clinical, Zeist, the Netherlands. FAU - Holleboom, Adriaan G AU - Holleboom AG AD - Department of Internal Medicine, Amsterdam UMC, Amsterdam, the Netherlands. FAU - Cabezas, Manuel Castro AU - Cabezas MC AD - Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands. AD - Department of Internal Medicine and Endocrinology, Erasmus MC, Rotterdam, the Netherlands. AD - Julius Clinical, Zeist, the Netherlands. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250212 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (PPAR gamma) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Fatty Liver/drug therapy/etiology MH - PPAR gamma/agonists MH - Insulin Resistance PMC - PMC11891831 OTO - NOTNLM OT - MASH OT - MASLD OT - NAFLD OT - NASH OT - T2DM OT - pharmacotherapy COIS- Authors declare no conflicts of interests. EDAT- 2025/02/12 12:25 MHDA- 2025/03/10 12:31 PMCR- 2025/03/10 CRDT- 2025/02/12 09:22 PHST- 2024/11/07 00:00 [received] PHST- 2025/01/24 00:00 [accepted] PHST- 2025/03/10 12:31 [medline] PHST- 2025/02/12 12:25 [pubmed] PHST- 2025/02/12 09:22 [entrez] PHST- 2025/03/10 00:00 [pmc-release] AID - ECI70003 [pii] AID - 10.1111/eci.70003 [doi] PST - ppublish SO - Eur J Clin Invest. 2025 Apr;55(4):e70003. doi: 10.1111/eci.70003. Epub 2025 Feb 12. PMID- 39934020 OWN - NLM STAT- MEDLINE DCOM- 20250408 LR - 20250409 IS - 1879-3061 (Electronic) IS - 1043-2760 (Linking) VI - 36 IP - 4 DP - 2025 Apr TI - Glucagon-like peptide-1 receptor agonism and end-organ protection. PG - 301-315 LID - S1043-2760(25)00002-5 [pii] LID - 10.1016/j.tem.2025.01.002 [doi] AB - Identification of exendin-4 (a glucagon-like peptide-1 receptor agonist, GLP-1RA) in Gila monster venom may be regarded as one of the most serendipitous discoveries of recent times. GLP-1RAs are now an established therapeutic approach in type 2 diabetes (T2D), body weight management, and cardiovascular (CV) risk protection. Furthermore, there is a growing platform of evidence that GLP-1RA has extended benefit in renal, hepatic, respiratory, and neurological diseases. One can speculate on the biological advantage of exendin-4 to the Gila monster, but for humankind GLP-1RAs are peptides with significant potential to improve disease-related outcomes. We report on the latest evidence and mechanisms for GLP-1RA-mediated end-organ protection that uniquely highlight its future development potential across multiple disease areas. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Daniels, Samuel AU - Daniels S AD - Early-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Karlsson, Cecilia AU - Karlsson C AD - Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Schrauwen, Patrick AU - Schrauwen P AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Parker, Victoria E R AU - Parker VER AD - Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. Electronic address: victoria.parker@astrazeneca.com. LA - eng PT - Journal Article PT - Review DEP - 20250210 PL - United States TA - Trends Endocrinol Metab JT - Trends in endocrinology and metabolism: TEM JID - 9001516 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Exenatide MH - Cardiovascular Diseases/drug therapy/prevention & control MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - cardiovascular OT - end-organ protection OT - glucagon-like peptide-1 (GLP-1) OT - kidney OT - liver OT - neurodegenerative OT - respiratory COIS- Declaration of interests S.D., C.K., and V.E.R.P. are employees of and stockholders in AstraZeneca; P.S. has received institutional research funding from AstraZeneca. V.E.R.P. holds patent WO2021140174A1 (Glucagon and GLP-1R co-agonists for the treatment of chronic kidney disease and diabetic kidney disease in type 2 diabetes). EDAT- 2025/02/12 00:20 MHDA- 2025/04/09 10:11 CRDT- 2025/02/11 22:34 PHST- 2024/09/27 00:00 [received] PHST- 2025/01/08 00:00 [revised] PHST- 2025/01/09 00:00 [accepted] PHST- 2025/04/09 10:11 [medline] PHST- 2025/02/12 00:20 [pubmed] PHST- 2025/02/11 22:34 [entrez] AID - S1043-2760(25)00002-5 [pii] AID - 10.1016/j.tem.2025.01.002 [doi] PST - ppublish SO - Trends Endocrinol Metab. 2025 Apr;36(4):301-315. doi: 10.1016/j.tem.2025.01.002. Epub 2025 Feb 10. PMID- 39933762 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20250507 IS - 1658-3175 (Electronic) IS - 0379-5284 (Print) IS - 0379-5284 (Linking) VI - 46 IP - 2 DP - 2025 Feb TI - GLP-1RA and SGLT2i utilization in people with type 2 diabetes with atherosclerotic cardiovascular disease (ASCVD) or at high risk of ASCVD in the Gulf Region: Results from the PACT-MEA studys. PG - 163-170 LID - 10.15537/smj.2025.46.2.20240620 [doi] AB - OBJECTIVES: To provide insights into the real-world usage of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) among individuals with type 2 diabetes (T2D) from Bahrain, Kuwait, and Qatar who either had established atherosclerotic cardiovascular disease (eASCVD) or were at high risk of developing ASCVD. METHODS: This study of 1062 adults diagnosed with T2D from Bahrain, Kuwait, and Qatar is a sub-analysis within the Prevalence and Clinical Management of Atherosclerotic Cardiovascular Diseases in Patients with Type 2 Diabetes across Countries in the Middle East and Africa (PACT-MEA) study, a noninterventional, cross-sectional study. Participants were recruited from 13 primary or secondary care facilities between March and August 2022. Medical records of participants were reviewed to extract relevant data, including demographic characteristics, eASCVD status, ASCVD risk and glucose-lowering treatment. Appropriate descriptive and inferential statistical tests were performed. RESULTS: Among T2D participants with eASCVD, a significantly higher proportion (41.3%) received SGLT2i compared to GLP-1RA (10.5%, p<0.001). There were notable variations in GLP-1RA/SGLT2i utilization across countries (p<0.001): being lowest in Bahrain (2.3%/18.0%), 26.9%/58.2% in Kuwait and 10.5%/67.1% in Qatar. The use of both medications was significantly higher in individuals with body mass index (BMI) >/=30 kg/m(2) (p<0.05). CONCLUSION: Despite these cardioprotective agents being recommended by guidelines, the study findings suggest a suboptimal use of GLP-1RA and SGLT2i in a real-world setting. CI - Copyright: (c) Saudi Medical Journal. FAU - Al-Dahi, Waleed A AU - Al-Dahi WA AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Khalaf, Saeed H AU - Khalaf SH AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - AlRomaihi, Dalal A AU - AlRomaihi DA AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Alamuddin, Naji M AU - Alamuddin NM AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Al Kandari, Hessa M AU - Al Kandari HM AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Abdalla, Doaa K AU - Abdalla DK AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Alfadehla, Hanan Y AU - Alfadehla HY AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Jayyousi, Amin A AU - Jayyousi AA AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Siddique, Mashhood A AU - Siddique MA AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - AlAlami, Usama A AU - AlAlami UA AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Subbarao, Guruprasad C AU - Subbarao GC AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Chetty, Shashikanth J AU - Chetty SJ AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. FAU - Abdulla, Jehan A AU - Abdulla JA AUID- ORCID: 0000-0003-0393-9139 AD - From the Department of Internal Medicine (Al-Dahi), Mubarak Hospital, Al Jairiyah; from the Department of Pediatric Endocrinology (Al Kandari), Farwaniya Hospital; from the Department of Endocrinology (Al Kandari, Abdalla), Dasman Diabetes Institute, Dasma; from the Department of Primary Care (Abdalla, Alfadehla) Yarmouk Primary Health Care Centre, Al Yarmuk; from the Department of Medical Affairs (AlAlami, Subbarao, Chetty), Novo Nordisk Gulf Cluster, Salmiya, Kuwait; from the Department of Endocrinology (Khalaf), Salmaniya Medical Complex, Manama; from the Department of Endocrinology (AlRomaihi), Awali Hospital, Awali; Department of Internal Medicine (Alamuddin), King Hamad University Hospital, Adliya; from the Department of Endocrinology (Abdulla), Bahrain Defence Force Hospital, West Riffa, Bahrain; and from the Department of Endocrinology (Jayyousi, Siddique), Hamad Medical Corporation, Doha, Qatar. LA - eng PT - Journal Article PL - Saudi Arabia TA - Saudi Med J JT - Saudi medical journal JID - 7909441 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Cross-Sectional Studies MH - *Atherosclerosis/epidemiology MH - Kuwait/epidemiology MH - Aged MH - Qatar/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Bahrain/epidemiology MH - Adult MH - Middle East/epidemiology MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use PMC - PMC11822930 OTO - NOTNLM OT - Diabetes mellitus OT - Middle East OT - atherosclerosis OT - cardiovascular diseases OT - hypoglycemic agents OT - type 2 EDAT- 2025/02/12 00:20 MHDA- 2025/02/12 00:21 PMCR- 2025/02/01 CRDT- 2025/02/11 20:42 PHST- 2024/11/19 00:00 [received] PHST- 2025/01/14 00:00 [accepted] PHST- 2025/02/12 00:21 [medline] PHST- 2025/02/12 00:20 [pubmed] PHST- 2025/02/11 20:42 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - 46/2/163 [pii] AID - SaudiMedJ-46-2-163 [pii] AID - 10.15537/smj.2025.46.2.20240620 [doi] PST - ppublish SO - Saudi Med J. 2025 Feb;46(2):163-170. doi: 10.15537/smj.2025.46.2.20240620. PMID- 39932725 OWN - NLM STAT- MEDLINE DCOM- 20250421 LR - 20250911 IS - 1939-327X (Electronic) IS - 0012-1797 (Linking) VI - 74 IP - 5 DP - 2025 May 1 TI - Comparison of the Effects of SGLT-2i Versus GLP-1RA on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes, Based on Baseline Renal Function. PG - 672-681 LID - 10.2337/db24-0688 [doi] AB - Finding no head-to-head research evaluating the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) at different baseline renal function, we performed a network meta-analysis to compare the two drugs indirectly. Systematic literature searches were conducted of the PubMed, Cochrane Library, Web of Science, and Embase databases, covering their inception until 7 January 2025. Randomized controlled trials (RCTs) comparing the effects of SGLT-2i and GLP-1RA in T2D with different glomerular filtration rates (eGFRs) were selected. Results were reported as risk ratios (RRs) with corresponding 95% CIs. Finally, 10 RCTs involving 87,334 patients with T2D were included. In patients with an eGFR >90 mL/min/1.73 m2, GLP-1RA exhibited a superior ability to reduce the risk of all-cause death compared with SGLT-2i (RR 0.75; 95% CI 0.58, 0.97), but it was less effective in reducing the risk of renal outcome (RR 1.80; 95% CI 1.15, 2.84) in patients with an eGFR 60-90 mL/min/1.73 m2. Conversely, in patients with eGFR 30-60 and 60-90 mL/min/1.73 m2, GLP-1RA did not show an advantage in reducing the risk of hospitalization for heart failure (RR 1.87 [95% CI 1.15, 3.04] and 1.37 [95% CI 1.05, 1.78], respectively). CI - (c) 2025 by the American Diabetes Association. FAU - Wang, Yu AU - Wang Y AD - Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. China. AD - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, P.R. China. FAU - Xia, Chao AU - Xia C AD - Department of Cardiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. China. FAU - Li, Manna AU - Li M AD - Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. China. FAU - Xu, Gaosi AU - Xu G AUID- ORCID: 0009-0007-8715-7295 AD - Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. China. LA - eng GR - 20224ACB206008/Key Projects of Jiangxi Natural Science Foundation/ GR - JXSQ2023201030/the "Thousand Talents Plan"? project in Jiangxi Province/ GR - 2024SSY06231/Jiangxi Province Key Laboratory of Molecular Medicine/ GR - 2022efyB01/Key Clinical Research Project of the Second Affiliated Hospital of Nanchang University/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Kidney/drug effects/physiopathology MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases MH - Randomized Controlled Trials as Topic EDAT- 2025/02/11 12:23 MHDA- 2025/04/22 00:26 CRDT- 2025/02/11 11:33 PHST- 2024/08/14 00:00 [received] PHST- 2025/02/06 00:00 [accepted] PHST- 2025/04/22 00:26 [medline] PHST- 2025/02/11 12:23 [pubmed] PHST- 2025/02/11 11:33 [entrez] AID - 157860 [pii] AID - 10.2337/db24-0688 [doi] PST - ppublish SO - Diabetes. 2025 May 1;74(5):672-681. doi: 10.2337/db24-0688. PMID- 39931897 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 Suppl 2 DP - 2025 Apr TI - Novel pharmacotherapies for weight loss: Understanding the role of incretins to enable weight loss and improved health outcomes. PG - 48-65 LID - 10.1111/dom.16247 [doi] AB - Obesity and type 2 diabetes mellitus (T2D) are widespread diseases that significantly impact cardiovascular and renal morbidity and mortality. In the recent years, intensive research has been performed to assess the role of adipose tissue and body fat distribution in the development of metabolic and non-metabolic complications in individuals with obesity. In addition to lifestyle modifications, glucagon-like peptide-1 receptor agonists (GLP-1-RA) have become a meaningful treatment expansion for the management of both disorders. In addition to improving metabolic control and reducing body weight, treatment with GLP-1-RAs reduces cardiovascular and renal events in individuals with obesity with and without diabetes. These important benefits of GLP-1-RAs have triggered new interest in other enteroendocrine and enteropancreatic peptides for treating obesity and its metabolic and non-metabolic consequences. The first peptide dual-agonist targeting glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors has been approved for the treatment of T2D and obesity. GIP/GLP-1 dual-agonism appear to provide better metabolic control and greater weight reduction compared with GLP-1-R mono-agonism. Other peptide and non-peptide co-agonists are in clinical development for obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD) and other metabolic disorders. This narrative review aims to summarize the available data on approved and emerging enteroendocrine and enteropancreatic based treatment approaches for obesity and metabolic disorders. In addition to available clinical efficacy measures, side effects, limitations and open challenges will also be addressed. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Forst, Thomas AU - Forst T AUID- ORCID: 0000-0003-2132-5691 AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - De Block, Christophe AU - De Block C AUID- ORCID: 0000-0002-0679-3203 AD - Department of Endocrinology-Diabetology, Antwerp University Hospital and University of Antwerp, Belgium. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Frias, Juan AU - Frias J AUID- ORCID: 0000-0001-9486-1255 AD - Biomea Fusion, Redwood City, California, USA. FAU - Lautenbach, Anne AU - Lautenbach A AUID- ORCID: 0000-0002-7763-1527 AD - University Medical-Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Ludvik, Bernhard AU - Ludvik B AUID- ORCID: 0009-0003-8717-8396 AD - Landstrasse Clinic and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Vienna, Austria. FAU - Marinez, Marina AU - Marinez M AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - Mathieu, Chantal AU - Mathieu C AUID- ORCID: 0000-0002-4055-5233 AD - Department of Endocrinology, KU Leuven, Leuven, Belgium. FAU - Muller, Timo D AU - Muller TD AUID- ORCID: 0000-0002-0624-9339 AD - Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Munich, Neuherberg, Germany. AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universitat Munchen (LMU), Munich, Germany. FAU - Schnell, Oliver AU - Schnell O AUID- ORCID: 0000-0003-1713-2766 AD - Forschergruppe Diabetes E.V. at the Helmholtz Center Munich, Munich, Germany. LA - eng PT - Journal Article PT - Review DEP - 20250211 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Weight Loss/drug effects MH - *Obesity/drug therapy/complications/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Gastric Inhibitory Polypeptide/agonists MH - *Anti-Obesity Agents/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - adipocytes OT - co-agonists OT - incretins OT - obesity EDAT- 2025/02/11 06:21 MHDA- 2025/04/16 06:19 CRDT- 2025/02/11 05:43 PHST- 2025/01/25 00:00 [revised] PHST- 2024/11/26 00:00 [received] PHST- 2025/01/26 00:00 [accepted] PHST- 2025/04/16 06:19 [medline] PHST- 2025/02/11 06:21 [pubmed] PHST- 2025/02/11 05:43 [entrez] AID - 10.1111/dom.16247 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27 Suppl 2:48-65. doi: 10.1111/dom.16247. Epub 2025 Feb 11. PMID- 39930946 OWN - NLM STAT- MEDLINE DCOM- 20250211 LR - 20260810 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 18 IP - 2 DP - 2025 Feb TI - Once-Weekly Semaglutide Versus Once-Daily Liraglutide for Weight Loss in Adults: A Meta-Analysis of Randomized Controlled Trials. PG - e70127 LID - 10.1111/cts.70127 [doi] LID - e70127 AB - The effectiveness of glucagon-like peptide-1 receptor agonists in facilitating weight loss among patients with diabetes is widely recognized. However, there are limited data available on the relative effectiveness and safety of once-weekly semaglutide versus once-daily liraglutide. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) identified through a comprehensive search of the Cochrane Library, PubMed, and ScienceDirect databases from inception until July 2024. Statistical analysis was conducted using R version 4.4.1 with the "meta" package, employing a random effects model. Three RCTs with a total of 922 patients were included in our meta-analysis. The results indicated that OW semaglutide significantly reduced body weight (WMD: -4.55; 95% CI: -6.43, -2.67, p < 0.01), HbA1c (WMD: -0.46; 95% CI: -0.84, -0.08; p = 0.02), and fasting plasma glucose levels (WMD: -1.23; 95% CI: -1.51, -0.95; p < 0.01) in comparison to OD liraglutide. The risk of severe adverse effects (OR, 1.66; 95% CI, 0.53-5.16; p = 0.38) and gastrointestinal adverse effects (OR, 1.84; 95% CI, 0.82-4.14; p = 0.14) was comparable between both groups. Once-weekly semaglutide therapy results in a more pronounced loss in body weight, HbA1c, and fasting glucose levels compared to once-daily liraglutide. CI - (c) 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Hashmi, Tallal Mushtaq AU - Hashmi TM AUID- ORCID: 0009-0006-6355-3907 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Ahmed, Mushood AU - Ahmed M AUID- ORCID: 0000-0001-9872-8224 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Haider, Ali AU - Haider A AUID- ORCID: 0000-0002-3464-4889 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Naseem, Salman AU - Naseem S AUID- ORCID: 0009-0003-8755-6799 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Jafar, Uzair AU - Jafar U AUID- ORCID: 0000-0003-0737-7444 AD - Department of Cardiology, King Edward Medical University, Lahore, Pakistan. FAU - Hussain, Munir AU - Hussain M AUID- ORCID: 0009-0001-8883-3810 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Iqbal, Javed AU - Iqbal J AUID- ORCID: 0000-0003-2627-685X AD - Hamad Medical Corporation, Doha, Qatar. FAU - Ali, Waqar AU - Ali W AUID- ORCID: 0009-0008-6727-3819 AD - Department of Endocrinology, King Edward Medical University, Lahore, Pakistan. FAU - Ahmed, Raheel AU - Ahmed R AUID- ORCID: 0000-0003-2814-7314 AD - Department of Cardiology, Royal Brompton Hospital, London, UK. AD - National Heart and Lung Institute, Imperial College London, London, UK. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Liraglutide/administration & dosage/adverse effects MH - Randomized Controlled Trials as Topic MH - *Weight Loss/drug effects MH - Drug Administration Schedule MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glycated Hemoglobin/analysis MH - Blood Glucose/drug effects/analysis MH - Treatment Outcome MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11811509 OTO - NOTNLM OT - diabetes OT - metabolism OT - meta-analysis OT - obesity OT - weight loss COIS- The authors declare no conflicts of interest. EDAT- 2025/02/11 06:21 MHDA- 2025/02/11 06:22 PMCR- 2025/02/11 CRDT- 2025/02/11 03:44 PHST- 2024/12/05 00:00 [revised] PHST- 2024/11/03 00:00 [received] PHST- 2024/12/17 00:00 [accepted] PHST- 2025/02/11 06:22 [medline] PHST- 2025/02/11 06:21 [pubmed] PHST- 2025/02/11 03:44 [entrez] PHST- 2025/02/11 00:00 [pmc-release] AID - CTS70127 [pii] AID - 10.1111/cts.70127 [doi] PST - ppublish SO - Clin Transl Sci. 2025 Feb;18(2):e70127. doi: 10.1111/cts.70127. PMID- 39928811 OWN - NLM STAT- MEDLINE DCOM- 20250210 LR - 20250624 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 104 IP - 6 DP - 2025 Feb 7 TI - Glucagon-like peptide-1 receptor agonists therapy to attenuate the risk of knee osteoarthritis and total knee replacement in type 2 diabetes mellitus: A nation-wide population-based cohort study. PG - e41243 LID - 10.1097/MD.0000000000041243 [doi] LID - e41243 AB - Type 2 diabetes mellitus (T2DM) is an independent risk factor of knee osteoarthritis (KOA). This study was mainly based on data from the Taiwan National Health Insurance Database. Using big data analysis, we showed that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment is helpful for patients with T2DM who have a lower risk of KOA or total knee replacement (TKR). A total of 35,762 patients with T2DM were included in this study. We divided these patients into 988 patients with T2DM without KOA and 372 patients with T2DM with KOA who received GLP-1RA treatment and those who did not receive GLP-1RA treatment. The patients were matched for sex, age, and inclusion date by 1:1 propensity score, which was included in the control group. Cox proportional hazards analyses were performed to compare KOA risk and TKR rate during a maximum follow-up period of 5 years. There were 1976/744 patients with T2DM without/with KOA who received and did not receive GLP-1RA treatment, including 1052/322 men (53.24/43.28%) and 924/422 women (46.76/56.72%). At the end of follow-up, there were 46/39 (4.66/10.48%) patients with T2DM without/with KOA who received GLP-1RA treatment and underwent KOA/TKR were lower than those without GLP-1RA treatment 87/70 (8.81/18.82%). Cox proportional hazard regression analysis showed a lower rate of KOA/TKR among patients with GLP-1RA treatment (adjusted hazard ratio [HR] = .852; 95% confidence interval [CI] = .784-.930, P < .001/ adjusted HR = .913; 95% CI = .885-.977, P = .015, respectively). Kaplan-Meier analysis showed that the cumulative risk of KOA/TKR in patient with/without GLP-1RA was significantly different (log-rank test, P < .001/P < .001, respectively). This study aimed to provide clinicians with the option of GLP-1RA as a treatment for patients with T2DM with or without KOA to reduce the risk of KOA or TKR among such patients. CI - Copyright (c) 2025 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Lin, Chih-Ping AU - Lin CP AUID- ORCID: 0009-0006-0246-1793 AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan, ROC. AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Chung, Chi-Hsiang AU - Chung CH AD - School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC. AD - Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan, ROC. FAU - Lu, Chieh-Hua AU - Lu CH AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Su, Sheng-Chiang AU - Su SC AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Kuo, Feng-Chih AU - Kuo FC AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Liu, Jhih-Syuan AU - Liu JS AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Li, Peng-Fei AU - Li PF AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Huang, Chia-Luen AU - Huang CL AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Ho, Li-Ju AU - Ho LJ AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Chen, Kuan-Chan AU - Chen KC AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Chang, Chun-Yung AU - Chang CY AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, ROC. FAU - Lin, Ming-Shiun AU - Lin MS AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Liu, Yi-Chen AU - Liu YC AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Cheng, An-Che AU - Cheng AC AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Lin, Hong-Han AU - Lin HH AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Kuo, Shi-Wen AU - Kuo SW AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Taipei Tzu Chi Hospital, Taipei, Taiwan, ROC. FAU - Lee, Chien-Hsing AU - Lee CH AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Hsieh, Chang-Hsun AU - Hsieh CH AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Hung, Yi-Jen AU - Hung YJ AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. FAU - Liu, Hsin-Ya AU - Liu HY AD - BeYoung Research Institute, Taipei, Taiwan, ROC. FAU - Guo, Lan-Yuen AU - Guo LY AD - Department of Sports Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. FAU - Chien, Wu-Chien AU - Chien WC AD - School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC. AD - Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Osteoarthritis, Knee/prevention & control/epidemiology/surgery/etiology MH - Male MH - Female MH - *Arthroplasty, Replacement, Knee/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Taiwan/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Propensity Score MH - Cohort Studies MH - Proportional Hazards Models MH - Retrospective Studies PMC - PMC11813052 COIS- The authors have no conflicts of interest to disclose. EDAT- 2025/02/10 18:16 MHDA- 2025/02/10 18:17 PMCR- 2025/02/07 CRDT- 2025/02/10 14:23 PHST- 2025/02/10 18:17 [medline] PHST- 2025/02/10 18:16 [pubmed] PHST- 2025/02/10 14:23 [entrez] PHST- 2025/02/07 00:00 [pmc-release] AID - 00005792-202502070-00054 [pii] AID - MD-D-24-00690 [pii] AID - 10.1097/MD.0000000000041243 [doi] PST - ppublish SO - Medicine (Baltimore). 2025 Feb 7;104(6):e41243. doi: 10.1097/MD.0000000000041243. PMID- 39928303 OWN - NLM STAT- MEDLINE DCOM- 20250407 LR - 20260727 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 185 IP - 4 DP - 2025 Apr 1 TI - Glucose-Lowering Medications and Risk of Chronic Obstructive Pulmonary Disease Exacerbations in Patients With Type 2 Diabetes. PG - 399-410 LID - 10.1001/jamainternmed.2024.7811 [doi] AB - IMPORTANCE: Recent studies have suggested that sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) may benefit patients with chronic obstructive pulmonary disease (COPD). However, clinical evidence is lacking on their comparative association with COPD exacerbations in US patients with type 2 diabetes (T2D). OBJECTIVE: To compare the risk of moderate or severe COPD exacerbations among SGLT-2is, GLP-1RAs, and DPP-4is. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study used data from three 1:1 propensity score-matched cohort studies that emulated 3 target trials comparing patients 40 years or older with T2D and active COPD who initiated treatment with SGLT-2is vs DPP-4is, GLP-1RAs vs DPP-4is, and SGLT-2is vs GLP-1RAs. Data were from 3 US insurance claims databases: the Optum deidentified Clinformatics Data Mart Database (2013-2023), IBM Health MarketScan (2013-2021), and Medicare fee for service (2013-2020). The data analysis was conducted from January to June 2024. EXPOSURES: Initiation of SGLT-2i or DPP-4i, GLP-1RA or DPP-4i, and SGLT-2i or GLP-1RA for the 3 target trials, respectively. MAIN OUTCOMES AND MEASURES: First occurrence of a moderate or severe COPD exacerbation, defined as a filled prescription for oral glucocorticoids in association with an outpatient COPD visit or hospitalization for COPD. Incidence rates, incidence rate differences (IRDs), and hazard ratios (HRs) with 95% CIs were calculated. RESULTS: There were 27 991, 32 107, and 36 218 pairs in the SGLT-2i vs DPP-4i, GLP-1RA vs DPP-4i, and SGLT-2i vs GLP-1RA propensity score-matched cohorts, respectively (mean [SD] age, 70.8 [8.6] and 70.7 [8.8], 70.4 [8.5] and 70.4 [8.2], and 69.8 [8.7] years, respectively; 13 767 [49.2%] and 13 847 [49.5%], 17 622 [54.9%] and 17 620 [54.9%], and 18 807 [51.9%] and 18 854 [52.1%] female individuals, respectively). During a median follow-up of 145 (IQR, 61-355) days of treatment, the risk of moderate or severe COPD exacerbation was lower among those treated with SGLT-2is vs DPP-4is (9.26 vs 11.4 per 100 person-years [PYs]; HR, 0.81; 95% CI, 0.76-0.86; IRD/100 PYs, -2.20; 95% CI, -2.83 to -1.58) and among those treated with GLP-1RAs vs DPP-4is (9.89 vs 11.49 per 100 PYs; HR, 0.86; 95% CI, 0.81-0.91; IRD/100 PYs, -1.60; 95% CI, -2.18 to -1.02), with minimal differences among those treated with SGLT-2is vs GLP-1RAs (9.47 vs 10.00 per 100 PYs; HR, 0.94; 95% CI, 0.89-1.00; IRD/100 PYs, -0.55; 95% CI, -1.09 to -0.01). Results were consistent across sensitivity and subgroup analyses. CONCLUSIONS AND RELEVANCE: The results of this comparative effectiveness research study suggest that SGLT-2is and GLP-1RAs were associated with a reduced risk of moderate or severe COPD exacerbations compared with DPP-4i in adults with T2D and active COPD. This may inform prescribing of glucose-lowering medications among patients with T2D and active COPD. FAU - Ray, Avik AU - Ray A AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Sreedhara, Sushama K AU - Sreedhara SK AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Bykov, Katsiaryna AU - Bykov K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Feldman, William B AU - Feldman WB AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Division of Pulmonary Critical Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. LA - eng GR - K01 AG068365/AG/NIA NIH HHS/United States GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 HL174838/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - JAMA Intern Med. 2025 Apr 1;185(4):410-411. doi: 10.1001/jamainternmed.2024.7812. PMID: 39928327 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Pulmonary Disease, Chronic Obstructive/epidemiology MH - Female MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Middle Aged MH - Aged MH - Disease Progression MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Propensity Score MH - United States/epidemiology MH - Comparative Effectiveness Research PMC - PMC11811870 COIS- Conflict of Interest Disclosures: Dr Wexler reported service on the data monitoring committee for Novo Nordisk outside the submitted work. Dr Bykov reported grants from the National Institutes of Health during the conduct of the study. Dr Feldman reported grants from the National Institutes of Health during the conduct of the study as well as personal fees from Alosa Health and service as an expert witness in litigation against inhaler manufacturers outside the submitted work. Dr Patorno reported grants from the National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, US Food and Drug Administration, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported. EDAT- 2025/02/10 12:23 MHDA- 2025/04/07 13:17 PMCR- 2026/02/10 CRDT- 2025/02/10 11:32 PHST- 2025/04/07 13:17 [medline] PHST- 2025/02/10 12:23 [pubmed] PHST- 2025/02/10 11:32 [entrez] PHST- 2026/02/10 00:00 [pmc-release] AID - 2829731 [pii] AID - ioi240095 [pii] AID - 10.1001/jamainternmed.2024.7811 [doi] PST - ppublish SO - JAMA Intern Med. 2025 Apr 1;185(4):399-410. doi: 10.1001/jamainternmed.2024.7811. PMID- 39922760 OWN - NLM STAT- MEDLINE DCOM- 20250222 LR - 20260518 IS - 1871-403X (Print) IS - 1871-403X (Linking) VI - 19 IP - 1 DP - 2025 Jan-Feb TI - Semaglutide: Nonarteritic Anterior Ischemic Optic Neuropathy in the FDA adverse event reporting system - A disproportionality analysis. PG - 77-79 LID - S1871-403X(25)00017-1 [pii] LID - 10.1016/j.orcp.2025.01.011 [doi] AB - Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used for type 2 diabetes (T2D) and approved for obesity by the FDA in 2022 and in Europe in 2023. Its increasing use has raised concerns about access for T2D patients and potential adverse events (AE), such as Nonarteritic Anterior Ischemic Optic Neuropathy (NAION). This study investigates the association between semaglutide and these AE using the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using FAERS data. AE were identified using MedDRA Preferred Terms (PTs) and related terms. OpenVigil 2.1 was used for data extraction and analysis. This system is a spontaneous safety surveillance database for drugs. The participants are patients who reported AE related to GLP-1 receptor agonists in the FAERS database from January 1, 2004, to September 30, 2024. Reporting Odds Ratios (ROR) and Proportional Reporting Ratios (PRR) were calculated to assess the association between GLP-1 receptor agonists and the AE. Semaglutide showed a significant ROR and PRR for NAION, suggesting a stronger association compared to other GLP-1 receptor agonists. The findings suggest a disproportionate reporting signal for semaglutide and NAION. The mechanisms behind these associations are not fully understood but may involve effects on the hypothalamus and vascular health. Further research is necessary to confirm these findings ensure the safe use of semaglutide, given the potential risk associated with this rare but severe adverse event. CI - Copyright (c) 2025 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. FAU - Azab, Marina AU - Azab M AD - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan 20156, Italy. Electronic address: marina.azab@marionegri.it. FAU - Pasina, Luca AU - Pasina L AD - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan 20156, Italy. LA - eng PT - Journal Article DEP - 20250207 PL - Netherlands TA - Obes Res Clin Pract JT - Obesity research & clinical practice JID - 101303911 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - United States MH - United States Food and Drug Administration MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Nonarteritic Anterior Ischemic Optic Neuropathy OT - Obesity OT - Semaglutide COIS- Declaration of Competing Interest The authors have no conflicts of interest that are directly relevant to the content of this article. EDAT- 2025/02/09 06:20 MHDA- 2025/02/23 00:42 CRDT- 2025/02/08 21:57 PHST- 2025/01/30 00:00 [received] PHST- 2025/01/31 00:00 [accepted] PHST- 2025/02/23 00:42 [medline] PHST- 2025/02/09 06:20 [pubmed] PHST- 2025/02/08 21:57 [entrez] AID - S1871-403X(25)00017-1 [pii] AID - 10.1016/j.orcp.2025.01.011 [doi] PST - ppublish SO - Obes Res Clin Pract. 2025 Jan-Feb;19(1):77-79. doi: 10.1016/j.orcp.2025.01.011. Epub 2025 Feb 7. PMID- 39922304 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260502 IS - 1524-4733 (Electronic) IS - 1098-3015 (Print) IS - 1098-3015 (Linking) VI - 28 IP - 5 DP - 2025 May TI - Capturing the Additional Cardiovascular Benefits of SGLT2 Inhibitors and GLP-1 Receptor Agonists Beyond the Control of Traditional Risk Factors in People With Diabetes. PG - 762-768 LID - S1098-3015(25)00042-7 [pii] LID - 10.1016/j.jval.2025.01.015 [doi] AB - OBJECTIVES: This study aimed to quantify the additional cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond the traditional risk factors control in individuals with type 2 diabetes. This helps calibrate the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model to capture the total cardiovascular benefits of new diabetes medications accurately. METHODS: We extracted patient characteristics and treatment efficacy data from 4 cardiovascular outcome trials (CVOTs) of SGLT2is and 4 CVOTs of GLP-1RAs completed before May 2023. Using the BRAVO diabetes simulation model, we translated reductions in traditional risk factors (ie, glycated hemoglobin, systolic blood pressure, low-density lipids, and body mass index) from the newer drugs into risk reductions in cardiovascular outcomes (ie, myocardial infarction [MI], stroke, congestive heart failure [CHF], and mortality), assuming that the drug-associated risk reductions were only driven by traditional risk factors. Then, we compared the simulated risk-factor-driven risk reductions of cardiovascular outcomes with observed risk reductions from the trials and calculated drug-specific incremental benefits (DIB). RESULTS: After accounting for the cardiovascular effects from traditional risk factors control, SGLT2is was associated with an additional 19% risk reduction in CHF (DIB: 0.81, 95% CI 0.72-0.90). Furthermore, the uncalibrated model predicted a risk reduction in stroke with SGLT2is, which was not observed in CVOTs. This discrepancy highlights the need for an SGLT2i-specific calibrator to align the simulation results with the observed outcomes. In contrast, no additional cardiovascular benefit was associated with GLP-1RAs after controlling for traditional risk factors. CONCLUSIONS: Our study revealed that SGLT2is could further reduce CHF risk beyond the control of traditional risk factors but may offer additional pathways to offset the overall benefits of traditional risk factor control in stroke risk. No additional cardiovascular benefits were observed for GLP-1RAs beyond traditional risk factor control. The BRAVO model calibration enhances cardiovascular outcome prediction with these newer antidiabetic therapies. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Niu, Shu AU - Niu S AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA. FAU - Guan, Dawei AU - Guan D AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA. FAU - Shi, Lizheng AU - Shi L AD - Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. FAU - Fonseca, Vivian AU - Fonseca V AD - Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, LA, USA. FAU - Svensson, Mikael AU - Svensson M AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; School of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Ali, Mohammed K AU - Ali MK AD - Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Family and Preventive Medicine, School of Medicine, Emory University, Atlanta, GA, USA. FAU - Sun, Yan V AU - Sun YV AD - Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. FAU - Hu, Xin AU - Hu X AD - Department of Radiation Oncology, School of Medicine, Emory University, Atlanta, GA, USA. FAU - Su, Chang AU - Su C AD - Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA. FAU - Yang, Carl AU - Yang C AD - Department of Computer Science, College of Art and Sciences, Emory University, Atlanta, GA, USA. FAU - Shao, Hui AU - Shao H AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Family and Preventive Medicine, School of Medicine, Emory University, Atlanta, GA, USA. Electronic address: hui.shao@emory.edu. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250206 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Male MH - Middle Aged MH - Female MH - Aged MH - Risk Factors MH - Hypoglycemic Agents/therapeutic use MH - Heart Disease Risk Factors MH - Computer Simulation PMC - PMC12147311 MID - NIHMS2061795 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - cardiovascular benefits OT - microsimulation model COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. Dr Shi is an editor of Value in Health and had no role in the peer-review process of this article. EDAT- 2025/02/09 06:20 MHDA- 2025/05/09 12:37 PMCR- 2026/05/01 CRDT- 2025/02/08 19:31 PHST- 2024/04/11 00:00 [received] PHST- 2024/12/19 00:00 [revised] PHST- 2025/01/14 00:00 [accepted] PHST- 2025/05/09 12:37 [medline] PHST- 2025/02/09 06:20 [pubmed] PHST- 2025/02/08 19:31 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - S1098-3015(25)00042-7 [pii] AID - 10.1016/j.jval.2025.01.015 [doi] PST - ppublish SO - Value Health. 2025 May;28(5):762-768. doi: 10.1016/j.jval.2025.01.015. Epub 2025 Feb 6. PMID- 39921523 OWN - NLM STAT- MEDLINE DCOM- 20250219 LR - 20260723 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 14 IP - 4 DP - 2025 Feb 18 TI - Comparative Outcomes of Glucagon-Like Peptide-1 Receptor Agonists to Dipeptidyl Peptidase 4 Inhibitors in Patients With Heart Failure and Type 2 Diabetes. PG - e037510 LID - 10.1161/JAHA.124.037510 [doi] LID - e037510 AB - BACKGROUND: Clinical trials showed that glucagon-like peptide-1 receptor agonist (GLP1-RA) significantly improved the control of diabetes and reduced body weight compared with dipeptidyl peptidase 4 inhibitor (DPP-4i). However, it is unclear whether GLP1-RA is effective compared with DPP-4i in patients with heart failure (HF) with type 2 diabetes (T2D). The purpose of this study was to evaluate the risk of GLP1-RA compared with DPP-4i in all-cause death and hospitalization in patients with HF and T2D. METHODS: This multicenter retrospective observational study using TriNetX, a global health care data and analytics platform, included patients with HF and T2D who had received GLP1-RA or DPP-4i from January 1, 2018, to December 31, 2022. Primary outcome was 12-month incidence of all-cause death. Secondary outcome was hospitalization. We used odds ratios (ORs) and 95% CIs to evaluate outcome measures. RESULTS: Among 1 005 097 patients with HF and T2D, 57 965 initiated GLP1-RA and 77 098 initiated DPP-4i. After propensity score matching, the number of participants in both the GLP1-RA group and the DPP-4i group was 36 557. The proportion of 12-month incidence of all-cause death was lower in the GLP1-RA group than in the DPP-4i group (5.9% [2140/36 557] versus 8.5% [3103/36 557]; OR, 0.67 [95% CI, 0.63-0.71]).The proportion of 12-month incidence of hospitalization was also lower in the GLP1-RA group than in the DPP-4i group (42.3% [15 455/36 557] versus 48.5% [17 733/36 557]; OR, 0.78 [95% CI, 0.76-0.80]). CONCLUSIONS: Use of GLP1-RA for patients with HF and T2D was associated with reduced 12-month incidence of all-cause death and hospitalization compared with DPP-4i. FAU - Kishimori, Takefumi AU - Kishimori T AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine Kyoto University Graduate School of Medicine Kyoto Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. FAU - Okada, Masaharu AU - Okada M AUID- ORCID: 0000-0001-6455-772X AD - Department of Cardiovascular Medicine Omi Medical Center Kusatsu Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250208 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Heart Failure/drug therapy/mortality/complications MH - Male MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - Middle Aged MH - Hospitalization/statistics & numerical data MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use PMC - PMC12074738 OTO - NOTNLM OT - dipeptidyl peptidase 4 inhibitor OT - glucagon-like peptide-1 receptor agonist OT - heart failure OT - type 2 diabetes COIS- None. EDAT- 2025/02/08 19:52 MHDA- 2025/02/19 06:22 PMCR- 2025/02/18 CRDT- 2025/02/08 05:43 PHST- 2025/02/19 06:22 [medline] PHST- 2025/02/08 19:52 [pubmed] PHST- 2025/02/08 05:43 [entrez] PHST- 2025/02/18 00:00 [pmc-release] AID - JAH310602 [pii] AID - 10.1161/JAHA.124.037510 [doi] PST - ppublish SO - J Am Heart Assoc. 2025 Feb 18;14(4):e037510. doi: 10.1161/JAHA.124.037510. Epub 2025 Feb 8. PMID- 39921267 OWN - NLM STAT- MEDLINE DCOM- 20250228 LR - 20260917 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 20 IP - 2 DP - 2025 Mar TI - Oral versus subcutaneous semaglutide weight loss outcomes after two years among patients with type 2 diabetes in a real-world database. PG - 163-168 LID - 10.1080/17446651.2025.2462100 [doi] AB - BACKGROUND: Interest has grown in glucagon-like peptide-1 receptor-agonist (GLP-1 RA) semaglutide long-term outcomes. This retrospective cohort study compared effectiveness of oral and subcutaneous semaglutide for weight loss outcomes in adults with type 2 diabetes (T2D) over a 2-year treatment period. RESEARCH DESIGN AND METHODS: Weight loss was evaluated through mean percentage change from baseline, proportion achieving at least 5% weight loss and at least 10% weight loss comparing subcutaneous (n = 310) versus oral users (n = 57) and by age group. RESULTS: Subcutaneous users experienced a mean percentage weight loss of 7.5% (16.7 pounds) with 58.7% and 32.9% achieving >/=5% and >/=10% loss, respectively. Oral users lost 4.4% (8.7 pounds) with 50.9% and 17.5% achieving >/=5% and >/=10% loss, respectively. Significant differences existed between formulations in mean percentage weight change (p-value <0.01) and proportion achieving >/=10% loss (p-value = 0.03), but not in proportion achieving >/=5% loss (p-value = 0.34). Outcomes differed by age within oral semaglutide (p-value = 0.02). Regression analyses adjusted for confounders yielded similar findings. CONCLUSION: Subcutaneous users achieved superior weight loss compared to oral users. Older oral users experienced better weight loss compared to younger users. However, no differences were observed between subcutaneous users. FAU - Kwon, Jimmy AU - Kwon J AD - Department of Statistics, UC Irvine Donald Bren School of Information and Computer Sciences, Irvine, USA. FAU - Thiara, Diana AU - Thiara D AD - Department of Medicine, UCSF School of Medicine, San Francisco, CA, USA. FAU - Watanabe, Jonathan H AU - Watanabe JH AD - Department of Clinical Pharmacy, UCSF School of Pharmacy, San Francisco, CA, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250207 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Administration, Oral MH - Injections, Subcutaneous MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Treatment Outcome MH - Databases, Factual MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP OT - Type 2 diabetes OT - long-term OT - semaglutide OT - weight loss EDAT- 2025/02/08 19:52 MHDA- 2025/02/28 18:22 CRDT- 2025/02/08 01:52 PHST- 2025/02/28 18:22 [medline] PHST- 2025/02/08 19:52 [pubmed] PHST- 2025/02/08 01:52 [entrez] AID - 10.1080/17446651.2025.2462100 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2025 Mar;20(2):163-168. doi: 10.1080/17446651.2025.2462100. Epub 2025 Feb 7. PMID- 39919872 OWN - NLM STAT- MEDLINE DCOM- 20250506 LR - 20260614 IS - 1558-4410 (Electronic) IS - 0889-8529 (Linking) VI - 54 IP - 1 DP - 2025 Mar TI - Treatment of Type 2 Diabetes in Patients with Obesity: A Review. PG - 163-173 LID - S0889-8529(24)00084-7 [pii] LID - 10.1016/j.ecl.2024.10.004 [doi] AB - Type 2 diabetes and obesity have some overlapping pathophysiology. This has allowed for the creation of therapies which are highly effective in treating both conditions. Weekly subcutaneous incretin agonists are preferred agents as they provide significant improvement in glycemic parameters, weight, and other comorbidities, like heart failure and reduce major adverse cardiovascular event. Bariatric surgery continues to show the most durable benefits for patients with both type 2 diabetes mellitus and obesity and should be considered in patients who are unable to meet goals with pharmacotherapy and lifestyle. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Guzman, Heidi AU - Guzman H AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. FAU - Hasan, Leen Z AU - Hasan LZ AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. FAU - Reid, Tirissa J AU - Reid TJ AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: tjr2122@cumc.columbia.edu. LA - eng PT - Journal Article PT - Review DEP - 20241112 PL - United States TA - Endocrinol Metab Clin North Am JT - Endocrinology and metabolism clinics of North America JID - 8800104 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy/drug therapy MH - *Obesity/complications/therapy/surgery MH - Bariatric Surgery MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use OTO - NOTNLM OT - Obesity OT - Pharmacotherapy OT - Semaglutide OT - Tirzepatide OT - Treatment OT - Type 2 diabetes mellitus COIS- Disclosure None of the authors have any commercial or financial conflicts of interest or funding sources to disclose. EDAT- 2025/02/08 00:30 MHDA- 2025/02/08 00:31 CRDT- 2025/02/07 21:20 PHST- 2025/02/08 00:31 [medline] PHST- 2025/02/08 00:30 [pubmed] PHST- 2025/02/07 21:20 [entrez] AID - S0889-8529(24)00084-7 [pii] AID - 10.1016/j.ecl.2024.10.004 [doi] PST - ppublish SO - Endocrinol Metab Clin North Am. 2025 Mar;54(1):163-173. doi: 10.1016/j.ecl.2024.10.004. Epub 2024 Nov 12. PMID- 39918190 OWN - NLM STAT- MEDLINE DCOM- 20250506 LR - 20250506 IS - 2146-8427 (Electronic) IS - 1304-0855 (Linking) VI - 23 IP - 1 DP - 2025 Jan TI - Safety and Efficacy of Tirzepatide in Solid-Organ Transplant Recipients: Experience of a Quaternary Care Center in the Middle East. PG - 12-20 LID - 10.6002/ect.2024.0284 [doi] AB - OBJECTIVES: Diabetes constitutes a prevalent condition posttransplant, imposing a substantial burden on solid organ transplant recipients, including increased risk of graft loss and reduced overall survival. Consequently, the implementation of effective glycemic control strategies is vital. Tirzepatide, the first dual glucosedependent insulinotropic polypeptide/glucagon-like peptide-1 receptor coagonist, represents a novel therapeutic option in the general population; however, further data are needed to support its use in solid-organ transplant recipients. MATERIALS AND METHODS: In this retrospective chart review, we examined a cohort of 41 heterogenous patients who were undergoing tirzepatide therapy after solid-organ transplant in Abu Dhabi, United Arab Emirates, from January 2017 to January 2024. RESULTS: Within our study cohort, the median time elapsed from transplant to tirzepatide therapy commencement was 2.91 years (range, 1.04-4.38 y), with use that lasted for a median follow-up duration of 11 months (range, 7-13 mo) until date of data collection. Tirzepatide facilitated optimal glycemic control, elicited significant weight reductions, and improved renal function without adversely affecting graft function or patient survival, showing an adverse effect profile similar to that of the general population, as shown in the literature. CONCLUSIONS: Tirzepatide represents a promising therapeutic avenue for management of posttransplant diabetes mellitus and type 2 diabetes mellitus in solidorgan transplant recipients. FAU - El Khatib, Omar AU - El Khatib O AD - From the Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, UAE. FAU - Chiha, Maguy AU - Chiha M FAU - Hijazi, Rabih AU - Hijazi R FAU - Jarad, Ola AU - Jarad O FAU - Salloum, Cynthia AU - Salloum C FAU - El Baba, Khaled AU - El Baba K FAU - Dajani, Ruba AU - Dajani R FAU - Al Shaqfa, Salma AU - Al Shaqfa S FAU - El Hajj, Sandra AU - El Hajj S LA - eng PT - Journal Article PL - Turkey TA - Exp Clin Transplant JT - Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation JID - 101207333 RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - *Organ Transplantation/adverse effects/mortality MH - Middle Aged MH - Treatment Outcome MH - Adult MH - United Arab Emirates MH - Time Factors MH - *Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - *Diabetes Mellitus/drug therapy/blood/diagnosis/mortality MH - *Incretins/adverse effects/therapeutic use MH - Graft Survival/drug effects MH - Risk Factors MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Young Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis MH - Tirzepatide EDAT- 2025/02/07 12:25 MHDA- 2025/02/07 12:26 CRDT- 2025/02/07 08:03 PHST- 2025/02/07 12:26 [medline] PHST- 2025/02/07 12:25 [pubmed] PHST- 2025/02/07 08:03 [entrez] AID - 10.6002/ect.2024.0284 [doi] PST - ppublish SO - Exp Clin Transplant. 2025 Jan;23(1):12-20. doi: 10.6002/ect.2024.0284. PMID- 39911047 OWN - NLM STAT- MEDLINE DCOM- 20250602 LR - 20260522 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis. PG - 422-429 LID - 10.1089/dia.2024.0533 [doi] AB - The objective of this study is to quantitatively compare the weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adult patients with no diabetes and type 2 diabetes (T2D). PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase have been used as data sources from database inception to January 6, 2024. A total of 137 trials, encompassing 310 treatment arms, 17 GLP-1RAs, and 56,683 patients, were included in the analysis. The included trials were divided into three groups based on the characteristics of the populations: nondiabetic overweight or obesity group (NDOOG), type 2 diabetes Caucasian group (T2DCG), and type 2 diabetes Asian group (T2DAG). The effects of covariates were further evaluated, patients with a higher baseline body weight tend to have better weight loss outcomes, and patients with a higher baseline glycated hemoglobin (HbA1c) tend to achieve better blood sugar control. Five mathematical models were subjected to longitudinal analysis. In terms of Delta body weight, retatrutide (12 mg qw) was the most effective treatment (mean difference = -26.56% [95% confidence interval: -43.89% to -3.01%]). Tirzepatide (15 mg qw) demonstrated good weight loss ability in all three DeltaBW models, DeltaBW-NDOOG (-22.76% [-26.45% to -18.50%]), DeltaBW-T2DCG (-11.09% [-12.39% to -9.44%])), and DeltaBW-T2DAG (-4.97% [-5.84% to -4.12%]). In the aspect of DeltaHbA1c, tirzepatide (10 mg qw) and oral orforglipron (10 mg qd) were the most effective drug, respectively. GLP-1RAs demonstrated effective weight management in both nondiabetic and T2D populations. Retatrutide achieved the most pronounced weight reduction, followed by tirzepatide. GLP-1RAs also significantly improved glycemic control for patients with T2D, with tirzepatide performing the best for glycemic control. FAU - Zhang, Shaolong AU - Zhang S AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. AD - Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China. FAU - Yu, Boran AU - Yu B AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Xu, Jiamin AU - Xu J AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. AD - Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China. FAU - Jin, Siyao AU - Jin S AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. FAU - Li, Yanming AU - Li Y AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Bing, Hao AU - Bing H AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Li, Jueyu AU - Li J AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. FAU - Ma, Xiangyu AU - Ma X AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Xianhua AU - Zhang X AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. AD - Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China. FAU - Zhao, Libo AU - Zhao L AUID- ORCID: 0000-0002-4968-6045 AD - Department of Pharmacy, Peking University Third Hospital, Beijing, China. AD - Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20250206 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Obesity/drug therapy MH - Glycated Hemoglobin/analysis MH - Overweight/drug therapy MH - Blood Glucose OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - glycemic control OT - model-based meta-analysis OT - systematic review OT - weight loss EDAT- 2025/02/06 06:20 MHDA- 2025/06/02 12:31 CRDT- 2025/02/06 03:44 PHST- 2025/06/02 12:31 [medline] PHST- 2025/02/06 06:20 [pubmed] PHST- 2025/02/06 03:44 [entrez] AID - 10.1089/dia.2024.0533 [doi] PST - ppublish SO - Diabetes Technol Ther. 2025 Jun;27(6):422-429. doi: 10.1089/dia.2024.0533. Epub 2025 Feb 6. PMID- 39910752 OWN - NLM STAT- MEDLINE DCOM- 20250306 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Comparison of the efficacy and safety of GLP-1 receptor agonists on cardiovascular events and risk factors: A review and network meta-analysis. PG - 1735-1751 LID - 10.1111/dom.16228 [doi] AB - OBJECTIVE: This study aims to systematically evaluate and perform a systematic review and network meta-analysis comparing the comprehensive cardiovascular protective effects of various glucagon-like peptide-1 receptor agonists (GLP-1RAs), focusing on cardiovascular events and risk factors. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to December 15, 2024. Included studies were published randomized controlled trials (RCTs) comparing GLP-1RAs to placebo or other GLP-1RAs. Missing data were standardized, and network meta-analysis was performed using Stata 17.0. Study heterogeneity, publication bias and evidence quality were assessed using the Cochrane Risk of Bias tool and Confidence in Network Meta-Analysis (CINeMA). RESULTS: As of December 15, 2024, a total of 18 313 articles were retrieved. Based on the inclusion and exclusion criteria, 156 high-quality studies were included, incorporating 144 782 patients and 14 different GLP-1RAs. The network meta-analysis demonstrated low heterogeneity, ensuring the reliability of the results. Comprehensive analysis revealed the following: Efpeglenatide was the most effective in reducing major adverse cardiovascular events. Oral semaglutide shows more significant advantages in reducing all-cause mortality and cardiovascular mortality. Orforglipron excelled in glycaemic control and weight reduction. SC-Semaglutide showed the greatest efficacy in lowering both systolic blood pressure and diastolic blood pressure, Liraglutide showed the greatest efficacy in lowering total cholesterol, Noiiglutide in triglycerides and Taspoglutide in low-density lipoprotein cholesterol, but no GLP-1RAs in high-density lipoprotein cholesterol. GLP-1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo. CONCLUSION: This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors. However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution. Future large-scale, high-quality clinical trials are needed to validate these findings and further optimize comprehensive cardiovascular management strategies for patients. CI - (c) 2025 John Wiley & Sons Ltd. FAU - An, Xuedong AU - An X AUID- ORCID: 0000-0002-2787-1645 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Sun, WenJie AU - Sun W AUID- ORCID: 0009-0009-0861-2443 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Wen, Zhige AU - Wen Z AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Duan, LiYun AU - Duan L AD - Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhang, YueHong AU - Zhang Y AD - Fangshan Hospital Beijing University of Chinese Medicine, Beijing, China. FAU - Kang, Xiaomin AU - Kang X AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Ji, Hangyu AU - Ji H AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Sun, Yuting AU - Sun Y AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Jiang, Linlin AU - Jiang L AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Zhao, Xuefei AU - Zhao X AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Gao, Qing AU - Gao Q AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Lian, Fengmei AU - Lian F AUID- ORCID: 0000-0003-2222-7487 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. LA - eng GR - 82305205/National Natural Science Foundation of China/ GR - CACM-2023-QNRC2-A05/Young Elite Scientists Sponsorship Program by CACM/ GR - HLCMHPP2023084/High Level Chinese Medical Hospital Promotion Project/ GR - GAMHH9324001/Escort Project of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250205 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular events OT - cardiovascular risk factors OT - network meta-analysis OT - systematic review EDAT- 2025/02/06 06:20 MHDA- 2025/03/07 00:21 CRDT- 2025/02/06 00:42 PHST- 2025/01/07 00:00 [revised] PHST- 2024/09/11 00:00 [received] PHST- 2025/01/21 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/02/06 06:20 [pubmed] PHST- 2025/02/06 00:42 [entrez] AID - 10.1111/dom.16228 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1735-1751. doi: 10.1111/dom.16228. Epub 2025 Feb 5. PMID- 39908666 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20260127 IS - 1748-605X (Electronic) IS - 1748-6041 (Linking) VI - 20 IP - 3 DP - 2025 Mar 18 TI - Chitosan hydrochloride coated and nonionic surfactant modified niosomes: a better way for oral administration of semaglutide. LID - 10.1088/1748-605X/adb2cf [doi] AB - Diabetes is now a global chronic disease, with the number of people with diabetes expected to reach 643 million by the end of 2030. Semaglutide, a human glucagon-like peptide-1 (GLP-1) analogue with 94% similarity to human GLP-1, can promote insulin secretion and repress glucagon secretion in a glucose concentration-dependent manner, resulting in substantial improvement of blood glucose levels and reducing the risk of hypoglycemia in patients with type 2 diabetes. To improve the absorption efficiency of semaglutide in oral delivery, we developed chitosan hydrochloride-coated and nonionic surfactant-modified niosomes (CS.HCL-NSPEs-NIO) as a new way to encapsulate it. The results showed that CS.HCL-NSPEs-NIO could efficiently penetrate the cell junctions in the intestinal endothelium and therefore promote drug absorbance. In addition, gastrointestinal distribution studies revealed that CS. HCL-NSPEs-NIO could stay in the intestine for more than 4 h, thus allowing for long-term glucose regulation. Effective reduction of blood glucose levels and weight loss were observed in db/db mice while no toxicity was detected in major organs. On the whole, our recommendation is that CS.HCL-NSPEs-NIO shows promise as an oral delivery tool for enhancing the hypoglycemic effects of semaglutide. CI - (c) 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved. FAU - Wang, Ben AU - Wang B AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Su, Zhengxing AU - Su Z AD - Sichuan Kelun Pharmaceutical Research Institute Co., Ltd, Chengdu 611138, Sichuan, People's Republic of China. AD - Hunan Kelun Pharmaceutical Research Co. Ltd, Yueyang 414000, Hunan, People's Republic of China. FAU - Kuang, Meiyan AU - Kuang M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Luo, Yi AU - Luo Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Xu, Minhao AU - Xu M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Sun, Meng AU - Sun M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Liu, Xingyou AU - Liu X AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Guo, Yue AU - Guo Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Bai, Lu AU - Bai L AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Wang, Yu AU - Wang Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Yan, Xinlei AU - Yan X AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Xie, Jing AU - Xie J AUID- ORCID: 0000-0001-8517-3549 AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Tang, Yaqin AU - Tang Y AUID- ORCID: 0009-0003-6395-9235 AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. LA - eng PT - Journal Article DEP - 20250318 PL - England TA - Biomed Mater JT - Biomedical materials (Bristol, England) JID - 101285195 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9012-76-4 (Chitosan) RN - 0 (Surface-Active Agents) RN - 0 (Liposomes) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/administration & dosage/chemistry/pharmacokinetics MH - Administration, Oral MH - *Chitosan/chemistry MH - Mice MH - *Surface-Active Agents/chemistry MH - Humans MH - *Liposomes/chemistry MH - Blood Glucose MH - Hypoglycemic Agents/administration & dosage/chemistry MH - Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Mice, Inbred C57BL MH - Diabetes Mellitus, Experimental/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - diabetes OT - oral delivery OT - penetration enhancers OT - semaglutide EDAT- 2025/02/06 00:20 MHDA- 2025/03/18 06:22 CRDT- 2025/02/05 18:03 PHST- 2024/07/26 00:00 [received] PHST- 2025/02/05 00:00 [accepted] PHST- 2025/03/18 06:22 [medline] PHST- 2025/02/06 00:20 [pubmed] PHST- 2025/02/05 18:03 [entrez] AID - 10.1088/1748-605X/adb2cf [doi] PST - epublish SO - Biomed Mater. 2025 Mar 18;20(3). doi: 10.1088/1748-605X/adb2cf. PMID- 39908569 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20250609 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 9 IP - 10 DP - 2025 May 27 TI - Glucagon-like peptide 1 receptor agonists and venous thromboembolism in type 2 diabetes: a target trial emulation. PG - 2410-2418 LID - 10.1182/bloodadvances.2025015871 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP1-RA) are antidiabetic agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxane-induced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation (TTE) using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity score matched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 (International Classification of Diseases, Tenth Revision) codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540 258 patients with 270 129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs 7.6 events per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.73-0.83). This was similar for pulmonary embolism (2.9 vs 3.8 events per 1000 patient-years; HR, 0.74; 95% CI, 0.68-0.82) and deep vein thrombosis (3.9 vs 4.7 events per 1000 patient-years; HR, 0.81; 95% CI, 0.75-0.88). In this propensity score-matched, TTE study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at 1 year compared with patients who received DPP4i. CI - (c) 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Chiang, Cho-Han AU - Chiang CH AUID- ORCID: 0000-0002-5757-6161 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA. FAU - Song, Junmin AU - Song J AUID- ORCID: 0000-0002-6150-6529 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY. FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Medicine, Danbury Hospital, Danbury, CT. FAU - Osataphan, Soravis AU - Osataphan S AD - Division of Hematology and Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. FAU - Lee, Yu-Che AU - Lee YC AUID- ORCID: 0000-0001-8418-7228 AD - Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Buffalo, NY. FAU - Chang, Ko-Yun AU - Chang KY AUID- ORCID: 0009-0005-1041-4797 AD - Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Buffalo, NY. FAU - Chi, Kuan-Yu AU - Chi KY AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY. FAU - Chiang, Cho-Hung AU - Chiang CH AUID- ORCID: 0000-0002-7910-2338 AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Dua, Anahita AU - Dua A AD - Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. FAU - Lake, Leslie AU - Lake L AD - National Blood Clot Alliance, Philadelphia, PA. FAU - Lauw, Mandy N AU - Lauw MN AUID- ORCID: 0000-0003-0398-3164 AD - Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. FAU - Bauer, Kenneth A AU - Bauer KA AD - Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. FAU - Kazi, Dhruv S AU - Kazi DS AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. FAU - Patell, Rushad AU - Patell R AUID- ORCID: 0000-0002-8426-3398 AD - Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. LA - eng PT - Journal Article PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Venous Thromboembolism/etiology/epidemiology/drug therapy/prevention & control MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors PMC - PMC12142527 COIS- Conflict-of-interest disclosure: K.A.B. reports consulting fees from Sanofi, outside the submitted work. R.P. reports consulting fees from Merck Research, outside the submitted work. The remaining authors declare no competing financial interests. EDAT- 2025/02/05 18:20 MHDA- 2025/05/15 12:36 PMCR- 2025/02/07 CRDT- 2025/02/05 17:13 PHST- 2025/01/18 00:00 [accepted] PHST- 2025/01/10 00:00 [received] PHST- 2025/05/15 12:36 [medline] PHST- 2025/02/05 18:20 [pubmed] PHST- 2025/02/05 17:13 [entrez] PHST- 2025/02/07 00:00 [pmc-release] AID - 535457 [pii] AID - 10.1182/bloodadvances.2025015871 [doi] PST - ppublish SO - Blood Adv. 2025 May 27;9(10):2410-2418. doi: 10.1182/bloodadvances.2025015871. PMID- 39907981 OWN - NLM STAT- MEDLINE DCOM- 20250705 LR - 20260127 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 25 IP - 4 DP - 2025 Jul TI - Cardiovascular Effects of Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. PG - 461-467 LID - 10.1007/s40256-025-00721-4 [doi] AB - BACKGROUND: Semaglutide has emerged as an effective medication for treating type 2 diabetes mellitus (DM). However, the cardiovascular effects and safety of this agent in patients with heart failure with preserved ejection fraction (HFpEF) are unclear. OBJECTIVE: This systematic review and meta-analysis aimed to assess the clinical and laboratory effects of semaglutide compared to placebo in patients with HFpEF. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and non-randomized cohorts, from inception to July 2024, comparing semaglutide versus placebo in patients with HFpEF. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were pooled across trials. RESULTS: This meta-analysis included three studies, two RCTs and one non-randomized cohort, reporting data on 1463 patients. The follow-up time of the studies was 52 weeks. Compared to placebo, the use of semaglutide was associated with a significant increase in the 6-min walk distance (MD 16.20; 95% CI 10.19-22.21; p < 0.01; I(2) = 0%). Additionally, reductions were observed in systolic blood pressure (MD -2.22; 95% CI -3.60 to -0.83; p < 0.01; I(2) = 0%), C-reactive protein level (MD 0.59; 95% CI 0.49-0.70; p < 0.01; I(2) = 51%), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (MD 0.81; 95% CI 0.74-0.89; p < 0.01; I(2) = 0%). CONCLUSION: These findings suggest that the use of semaglutide is associated with clinical and laboratory benefits in patients with HFpEF. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Sobral, Milene Vitoria Sampaio AU - Sobral MVS AUID- ORCID: 0009-0001-5754-6472 AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Rodrigues, Livia Kneipp AU - Rodrigues LK AD - Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Barbosa, Abner Macola Pacheco AU - Barbosa AMP AD - Sao Paulo State University, Botucatu, Brazil. FAU - da Rocha, Naila Camila AU - da Rocha NC AD - Sao Paulo State University, Botucatu, Brazil. FAU - Moulaz, Isac Ribeiro AU - Moulaz IR AD - Federal University of Espirito Santo, Vitoria, Brazil. FAU - Dos Santos, Joao Pedro Pereira AU - Dos Santos JPP AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Oliveira, Bruno Henrique Couto AU - Oliveira BHC AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Moreira, Joao Lucas de Magalhaes Leal AU - Moreira JLML AD - State University of Feira de Santana, Feira de Santana, Brazil. FAU - Pacagnelli, Francis Lopes AU - Pacagnelli FL AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Guida, Camila Mota AU - Guida CM AD - Dante Pazzanese Institute of Cardiology, Av. Dante Pazzanese, Sao Paulo, 500, Brazil. camila.mguida@hotmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250205 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/adverse effects MH - *Stroke Volume/drug effects MH - Randomized Controlled Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy MH - Natriuretic Peptide, Brain/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declarations. Funding: None. Conflict of interest: All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: As this is a systematic review with meta-analysis, there is no database; for data extracted from other articles, see Table 1. Code availability: Not applicable. Author contributions: MS carried out the idealization of the work as well as the screening, risk-of-bias assessments, writing of the article, and coordination and supervision of the work. LR, carried out the idealization of the work as well the risk-of-bias assessments and writing the article. AB carried out the collection of outcomes and was involved in writing the article. NR carried out the collection of outcomes and was involved in writing the article. IM took part in writing the article. JS produced Table 1 and wrote the article. BO carried out the screening and was involved in writing the article. JM took part in writing the article. FP was involved in the supervision and coordination of the research group. CG participated in the writing of the article and supervision and coordination of the research group. EDAT- 2025/02/05 12:24 MHDA- 2025/07/05 20:46 CRDT- 2025/02/05 11:24 PHST- 2025/01/19 00:00 [accepted] PHST- 2025/07/05 20:46 [medline] PHST- 2025/02/05 12:24 [pubmed] PHST- 2025/02/05 11:24 [entrez] AID - 10.1007/s40256-025-00721-4 [pii] AID - 10.1007/s40256-025-00721-4 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2025 Jul;25(4):461-467. doi: 10.1007/s40256-025-00721-4. Epub 2025 Feb 5. PMID- 39905643 OWN - NLM STAT- MEDLINE DCOM- 20250306 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Effect of iGlarLixi on continuous glucose monitoring-measured time in range in insulin-naive adults with suboptimally controlled type 2 diabetes. PG - 2173-2182 LID - 10.1111/dom.16214 [doi] AB - AIMS: People with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) >/=9% may benefit from fixed-ratio combination therapies such as iGlarLixi (insulin glargine 100 U/mL and lixisenatide 33 mug/mL). Use of continuous glucose monitoring (CGM) is recommended, but data are lacking to assess the impact of iGlarLixi in individuals with HbA1c >/=9%. MATERIALS AND METHODS: Soli-CGM (NCT05114590) was a 16-week, multicentre, open-label study evaluating the efficacy of once-daily iGlarLixi using blinded CGM-based metrics in insulin-naive adults with HbA1c >/=9%-13% who were receiving >/=2 oral antihyperglycaemic agents (OADs) +/- glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The primary outcome was the change from baseline to week 16 in percent time in range (TIR; 70-180 mg/dL). Secondary outcomes included change in mean daily blood glucose (BG), maximum postprandial glucose 4 h post-breakfast (PPG-4 h), and time above range (TAR; >180 mg/dL). On-treatment hypoglycaemia was assessed. RESULTS: The study enrolled 124 participants (mean age, 55.6 years; HbA1c, 10.2%). Sixteen weeks of treatment with iGlarLixi improved TIR (+26.2%), mean BG (-52.5 mg/dL), maximum PPG-4 h (-73.7 mg/dL), and TAR (-28.7%); all p < 0.001. Rates of American Diabetes Association level 1 (BG <70 but >/=54 mg/dL) and level 2 (BG <54 mg/dL) hypoglycaemia were reported as 1.4 and 0.6 events per person-year, respectively. No level 3 events (requiring assistance) were reported. CONCLUSIONS: In people with T2D suboptimally controlled on >/=2 OADs +/- GLP-1 RAs, 16 weeks of treatment with iGlarLixi significantly improved TIR and reduced TAR without severe hypoglycaemia. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Frias, Juan P AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - Biomea Fusion, Redwood City, California, USA. FAU - Ratzki-Leewing, Alexandria AU - Ratzki-Leewing A AUID- ORCID: 0000-0002-9474-7900 AD - University of Maryland Institute for Health Computing, Bethesda, Maryland, USA. AD - Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA. AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. FAU - Dex, Terry AU - Dex T AD - Sanofi, Bridgewater, New Jersey, USA. FAU - Meneghini, Luigi AU - Meneghini L AD - Sanofi, Bridgewater, New Jersey, USA. FAU - Rodrigues, Amelie AU - Rodrigues A AD - Ividata, Paris, France. FAU - Shah, Viral N AU - Shah VN AD - Indiana University School of Medicine, Indianapolis, Indiana, USA. AD - Indiana University Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, Indiana, USA. LA - eng GR - Sanofi/ PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study DEP - 20250204 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis/drug effects/metabolism MH - Blood Glucose Self-Monitoring MH - Continuous Glucose Monitoring MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin/analysis MH - Glycemic Control MH - Hypoglycemia/chemically induced/prevention & control MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - *Insulin Glargine/administration & dosage/therapeutic use/adverse effects MH - *Peptides/administration & dosage/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-2 Receptor PMC - PMC11885071 OTO - NOTNLM OT - continuous glucose monitoring OT - fixed-ratio combination OT - sulphonylureas OT - type 2 diabetes COIS- JPF is an employee of and stockholder in Biomea Fusion, Inc. He reports research support from Akero, Altimmune, Boehringer Ingelheim, 89bio, Eli Lilly, Intercept, IONIS, Janssen, Madrigal, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Sanofi, and Shionogi; has participated in advisory boards and provided consultancy for Akero, Altimmune, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Echosens, 89bio, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, and Sanofi; and has attended speakers bureau for Eli Lilly. ARL has received research support from Sanofi; has been a consultant for Dexcom, Novo Nordisk, and Sanofi; has participated in advisory boards for Sanofi; and has given paid presentations for Abbott, the American Diabetes Association, Dexcom, Diabetes Canada, Eli Lilly, Novo Nordisk, and Sanofi. TD and LM are employees of Sanofi and hold stock options/stock in Sanofi. AR is an employee of Ividata, contracted by Sanofi. VNS reports receiving grant/research support from Alexion, Dexcom, Enable Bioscience, and Novo Nordisk and has received honoraria from Ascensia Diabetes Care, Dexcom, Embecta, Insulet, Genomelink, LumosFit, Novo Nordisk, Sanofi, and Tandem Diabetes Care for speaking, consulting, or advisory work. EDAT- 2025/02/05 06:20 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/02/05 00:38 PHST- 2025/01/10 00:00 [revised] PHST- 2024/10/14 00:00 [received] PHST- 2025/01/13 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/02/05 06:20 [pubmed] PHST- 2025/02/05 00:38 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16214 [pii] AID - 10.1111/dom.16214 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):2173-2182. doi: 10.1111/dom.16214. Epub 2025 Feb 4. PMID- 39900263 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20250525 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 221 DP - 2025 Mar TI - Evolution of myocardial steatosis in high cardiovascular risk T2DM patients treated by GLP1 receptor agonists: LICAS study. PG - 112017 LID - S0168-8227(25)00031-2 [pii] LID - 10.1016/j.diabres.2025.112017 [doi] AB - BACKGROUND: We hypothesized that the reduction of intramyocardial fat content may be involved in the cardioprotective effect of glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2D). Therefore, we aimed to evaluate the change in intramyocardial triglyceride content in T2D patients treated with GLP1-RA. METHODS: This monocentric proof-of-concept cohort study included patients with unbalanced T2D prior to the introduction of GLP1-RA. Patients underwent cardiac magnetic resonance imaging (MRI) coupled with nuclear magnetic resonance (NMR) spectroscopy at baseline and six months after the introduction (M6) of a GLP1-RA to assess changes in intramyocardial triglyceride levels and morphological, functional, and cardiac tissue parameters. The relative delta (Delta(r)) between baseline and M6 was calculated and analyzed by Student test or sign test. RESULTS: Twenty-six patients (mean age = 62.2 +/- 6.7 years, median HbA1c = 9.1 %) fulfilled inclusion criteria and had both NMR measures. Compared with baseline, relative intramyocardial triglyceride levels significantly decreased after six months of treatment (mean Delta(r) = -26 % [95 %CI:-39; -13]p = 0.003), as well as glycated hemoglobin (HbA1c) (median Delta(r) = -26 % [IQR:25], p < 0.0001), body mass index (BMI) (mean Delta(r) = -6% [-9; -4], p < 0.0001) and left ventricular mass (mean Delta(r) = -6 [-12; -1] p = 0.02). The relative evolution of intramyocardial triglyceride content was not correlated with the relative evolution of HbA1c (r = 0.10) and BMI (r = -0.02). CONCLUSIONS: We demonstrate a significant reduction in intramyocardial triglyceride content in patients with T2D after six months of treatment with GLP1-RA. The lack of correlation with reductions in HbA1c and BMI suggests a specific effect of GLP1-RA on myocardial steatosis, which might contribute to their previously demonstrated cardiovascular benefits. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Houbachi, Lina AU - Houbachi L AD - Department of Endocrinology and Diabetology, CHU Dijon 21000 Dijon, France. FAU - Walker, Paul Michael AU - Walker PM AD - Medical Imaging Department, CHU Dijon / ICMUB Laboratory, CNRS UMR 6302, University of Burgundy, France. FAU - Fournel, Isabelle AU - Fournel I AD - CHU Dijon Bourgogne, INSERM, Universite de Bourgogne, CIC 1432, Module Epidemiologique Clinique F21000 Dijon, France. FAU - Ksiazek, Elea AU - Ksiazek E AD - CHU Dijon Bourgogne, INSERM, Universite de Bourgogne, CIC 1432, Module Epidemiologique Clinique F21000 Dijon, France. FAU - Petit, Jean-Michel AU - Petit JM AD - Department of Endocrinology and Diabetology, CHU Dijon 21000 Dijon, France; INSERM Research Center U1231, Team Padys 21000 Dijon, France; University of Burgundy 21000 Dijon, France. FAU - Cochet, Alexandre AU - Cochet A AD - Medical Imaging Department, CHU Dijon / ICMUB Laboratory, CNRS UMR 6302, University of Burgundy, France. FAU - Leclercq, Thibault AU - Leclercq T AD - Cardiology Department, CHU Dijon 21000 Dijon, France. FAU - Roger, Antoine AU - Roger A AD - Cardiology Department, CHU Dijon 21000 Dijon, France. FAU - Simoneau, Isabelle AU - Simoneau I AD - Department of Endocrinology and Diabetology, CHU Dijon 21000 Dijon, France. FAU - Bouillet, Benjamin AU - Bouillet B AD - Department of Endocrinology and Diabetology, CHU Dijon 21000 Dijon, France; INSERM Research Center U1231, Team Padys 21000 Dijon, France; University of Burgundy 21000 Dijon, France. FAU - Guenancia, Charles AU - Guenancia C AD - Cardiology Department, CHU Dijon 21000 Dijon, France; Epidemiology of Cerebro- and Cardiovascular Diseases (EA 7460), UFR Science de Sante, Universite de Bourgogne 21000 Dijon, France. Electronic address: charles.guenancia@chu-dijon.fr. LA - eng PT - Journal Article DEP - 20250201 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Triglycerides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Triglycerides/metabolism MH - *Cardiovascular Diseases MH - *Myocardium/pathology/metabolism MH - Magnetic Resonance Imaging MH - Cohort Studies OTO - NOTNLM OT - Cardiac MRI OT - GLP1 receptor agonists OT - Intramyocardial triglyceride OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Charles Guenancia reports personal fees from Abbott, Amgen, Astra-Zeneca, BMS, Boston Scientific, MicroPort CRM, Medtronic, NovoNordisk, Pfizer outside the submitted work. Benjamin Bouillet reports personal fees from Abbott, Amgen, Astra-Zeneca, BMS, Lilly, NovoNordisk, Pfizer, UrgoMedical outside the submitted work]. EDAT- 2025/02/04 00:20 MHDA- 2025/02/28 00:20 CRDT- 2025/02/03 19:28 PHST- 2024/11/26 00:00 [received] PHST- 2025/01/10 00:00 [revised] PHST- 2025/01/21 00:00 [accepted] PHST- 2025/02/28 00:20 [medline] PHST- 2025/02/04 00:20 [pubmed] PHST- 2025/02/03 19:28 [entrez] AID - S0168-8227(25)00031-2 [pii] AID - 10.1016/j.diabres.2025.112017 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Mar;221:112017. doi: 10.1016/j.diabres.2025.112017. Epub 2025 Feb 1. PMID- 39899440 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20250513 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 5 DP - 2025 May TI - Population profile and glycemic control following initiation or switch of injectable therapies in Tianjin, China: A real-world retrospective cohort study of adults with type 2 diabetes. PG - 842-851 LID - 10.1111/jdi.14415 [doi] AB - AIMS: To evaluate characteristics and glycemic outcomes in individuals with type 2 diabetes using injectable therapies in real-world clinical practice in Tianjin, China. MATERIALS AND METHODS: Data from inpatients and outpatients receiving injectable therapies between January 2015 and December 2019 were collected from the Tianjin regional electronic medical records and retrospectively analyzed. Seven cohorts were identified, including individuals initiating injectable therapies (premixed insulin [n = 4,687], basal insulin [4,177], or glucagon-like peptide-1 receptor agonists [541]) or switching injectable therapies (premixed insulin to basal insulin [1,298], basal insulin to premixed insulin [1,457], basal insulin to basal + bolus insulin [1,772], or glucagon-like peptide-1 receptor agonists to basal insulin +/- glucagon-like peptide-1 receptor agonists [82]). RESULTS: In participants initiating therapy, glycated hemoglobin and fasting plasma glucose were highest in the basal insulin cohort, while among participants switching therapy, the highest values were in the basal insulin +/- glucagon-like peptide-1 receptor agonists cohort. Initiating therapy with premixed or basal insulin and switching from basal insulin to basal + bolus insulin improved glycemic control over 12 months. A mean delay in initiating therapy of up to 13 months after oral glucose-lowering drug failure was observed, with 60% having a delay of >6 months. This delay was associated with a lower proportion achieving glycemic control 3 months after initiation. CONCLUSIONS: Effectiveness was not observed at all time points in all cohorts, suggesting some treatments were not used in the appropriate population. Delays in initiating injectable therapies were observed and were associated with poor glycemic control. CI - (c) 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Zhang, Qiumei AU - Zhang Q AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Fan, Yaqing AU - Fan Y AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Liu, Xixi AU - Liu X AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Zhang, Minlu AU - Zhang M AD - Sanofi Investment Co., Ltd., Shanghai, China. FAU - Zhang, Jiewen AU - Zhang J AD - Sanofi Investment Co., Ltd., Shanghai, China. FAU - Du, Qin AU - Du Q AD - Sanofi Investment Co., Ltd., Shanghai, China. FAU - Kang, Lei AU - Kang L AD - Sanofi Investment Co., Ltd., Shanghai, China. FAU - Chen, Liming AU - Chen L AUID- ORCID: 0000-0002-5682-2340 AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. LA - eng GR - Sanofi China Investment Company/ PT - Journal Article DEP - 20250203 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - China/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glycemic Control/statistics & numerical data MH - Blood Glucose/analysis MH - Aged MH - Glycated Hemoglobin/analysis MH - *Insulin/administration & dosage/therapeutic use MH - Adult MH - Injections MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Follow-Up Studies MH - Prognosis PMC - PMC12057371 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Hypoglycemic agents OT - Insulins EDAT- 2025/02/03 18:20 MHDA- 2025/05/07 12:31 PMCR- 2025/02/03 CRDT- 2025/02/03 12:44 PHST- 2025/01/06 00:00 [revised] PHST- 2024/08/21 00:00 [received] PHST- 2025/01/16 00:00 [accepted] PHST- 2025/05/07 12:31 [medline] PHST- 2025/02/03 18:20 [pubmed] PHST- 2025/02/03 12:44 [entrez] PHST- 2025/02/03 00:00 [pmc-release] AID - JDI14415 [pii] AID - 10.1111/jdi.14415 [doi] PST - ppublish SO - J Diabetes Investig. 2025 May;16(5):842-851. doi: 10.1111/jdi.14415. Epub 2025 Feb 3. PMID- 39899304 OWN - NLM STAT- MEDLINE DCOM- 20250325 LR - 20250805 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 333 IP - 12 DP - 2025 Mar 25 TI - Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis. PG - 1062-1073 LID - 10.1001/jama.2024.27402 [doi] AB - IMPORTANCE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors improve hyperglycemia, and SGLT2 inhibitors and GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACEs) among individuals with type 2 diabetes. It is not clear whether efficacy varies by age or sex. OBJECTIVE: To assess whether age or sex are associated with differences in the efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP4 inhibitors. DATA SOURCES AND STUDY SELECTION: The MEDLINE and Embase databases and US and Chinese clinical trial registries were searched for articles published from inception to November 2022; in August 2024, the search was updated to capture the trial results. Two reviewers screened for randomized clinical trials of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP4 inhibitors vs a placebo or active comparator in adults with type 2 diabetes. DATA EXTRACTION AND SYNTHESIS: Individual participant data and aggregate data were used to estimate age x treatment interactions and sex x treatment interactions in multilevel network meta-regression models. MAIN OUTCOME AND MEASURES: Hemoglobin A1c (HbA1c) and MACEs. RESULTS: Of the 601 eligible trials identified (592 trials with 309 503 participants reported HbA1c; mean age, 58.9 [SD, 10.8] years; 42.3% were female and 23 trials with 168 489 participants reported MACEs; mean age, 64.0 [SD, 8.6] years; 35.3% were female), individual participant data were obtained for 103 trials (103 reported HbA1c and 6 reported MACEs). The use of SGLT2 inhibitors (vs placebo) was associated with less HbA1c lowering with increasing age for monotherapy (absolute reduction [AR], 0.24% [95% credible interval CrI, 0.10% to 0.38%] per 30-year increment in age), for dual therapy (AR, 0.17% [95% CrI, 0.10% to 0.24%]), and for triple therapy (AR, 0.25% [95% CrI, 0.20% to 0.30%]). The use of GLP-1 receptor agonists was associated with greater HbA1c lowering with increasing age for monotherapy (AR, -0.18% [95% CrI, -0.31% to -0.05%] per 30-year increment in age) and for dual therapy (AR, -0.24% [95% CrI, -0.40% to -0.07%]), but not for triple therapy (AR, 0.04% [95% CrI, -0.02% to 0.11%]). The use of DPP4 inhibitors was associated with slightly better HbA1c lowering in older people for dual therapy (AR, -0.09% [95% CrI, -0.15% to -0.03%] per 30-year increment in age), but not for monotherapy (AR, -0.08% [95% CrI, -0.18% to 0.01%]) or triple therapy (AR, -0.01% [95% CrI, -0.06% to 0.05%]). The relative reduction in MACEs with use of SGLT2 inhibitors was greater in older vs younger participants per 30-year increment in age (hazard ratio, 0.76 [95% CrI, 0.62 to 0.93]), and the relative reduction in MACEs with use of GLP-1 receptor agonists was less in older vs younger participants (hazard ratio, 1.47 [95% CrI, 1.07 to 2.02]). There was no consistent evidence for sex x treatment interactions with use of SGLT2 inhibitors and GLP-1 receptor agonists. CONCLUSIONS AND RELEVANCE: The SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower risk of MACEs. Analysis of age x treatment interactions suggested that SGLT2 inhibitors were more cardioprotective in older than in younger people despite smaller reductions in HbA1c; GLP-1 receptor agonists were more cardioprotective in younger people. FAU - Hanlon, Peter AU - Hanlon P AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Butterly, Elaine AU - Butterly E AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Wei, Lili AU - Wei L AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Wightman, Heather AU - Wightman H AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Almazam, Saleh Ali M AU - Almazam SAM AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Alsallumi, Khalid AU - Alsallumi K AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Crowther, Jamie AU - Crowther J AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - McChrystal, Ryan AU - McChrystal R AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Rennison, Heidi AU - Rennison H AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Hughes, Katherine AU - Hughes K AD - Department of Diabetes, Glasgow Royal Infirmary, NHS of Greater Glasgow and Clyde, Glasgow, Scotland. FAU - Lewsey, Jim AU - Lewsey J AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Lindsay, Robert AU - Lindsay R AD - BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. FAU - McGurnaghan, Stuart AU - McGurnaghan S AD - Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland. FAU - Petrie, John AU - Petrie J AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. FAU - Tomlinson, Laurie A AU - Tomlinson LA AD - Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England. FAU - Wild, Sarah AU - Wild S AD - Usher Institute, University of Edinburgh, Edinburgh, Scotland. FAU - Adler, Amanda AU - Adler A AD - Diabetes Trials Unit, University of Oxford, Oxford, England. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland. FAU - Phillippo, David M AU - Phillippo DM AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England. FAU - Dias, Sofia AU - Dias S AD - Centre for Reviews and Dissemination, University of York, York, England. FAU - Welton, Nicky J AU - Welton NJ AD - Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England. FAU - McAllister, David A AU - McAllister DA AD - School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. LA - eng GR - MR/W016648/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Age Factors MH - Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Randomized Controlled Trials as Topic MH - Sex Factors MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects MH - Treatment Outcome MH - Glycemic Control/adverse effects/methods/statistics & numerical data MH - Adult MH - Aged, 80 and over MH - Drug Therapy, Combination/adverse effects/methods MH - Incidence PMC - PMC11791772 MID - EMS203121 COIS- Conflict of Interest Disclosures: Dr Lewsey reported receiving grants from the University of Glasgow. Dr Lindsay reported having a meeting registration paid for by Novo Nordisk. Dr Petrie reported receiving personal fees from Merck KGaA, Novo Nordisk, IQVIA, and Boehringer Ingelheim and receiving nonfinancial support from AstraZeneca, Novo Nordisk, and Sanofi. Dr Adler reported that her trials unit is undertaking a trial funded by Novo Nordisk. Dr Sattar reported receiving grant funding from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics and receiving personal fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi. Dr Welton reported receiving honoraria from the Association for the British Pharmaceutical Industry. No other disclosures were reported. EDAT- 2025/02/03 12:23 MHDA- 2025/03/25 12:39 PMCR- 2025/08/03 CRDT- 2025/02/03 11:33 PHST- 2025/03/25 12:39 [medline] PHST- 2025/02/03 12:23 [pubmed] PHST- 2025/02/03 11:33 [entrez] PHST- 2025/08/03 00:00 [pmc-release] AID - 2829848 [pii] AID - joi240156 [pii] AID - 10.1001/jama.2024.27402 [doi] PST - ppublish SO - JAMA. 2025 Mar 25;333(12):1062-1073. doi: 10.1001/jama.2024.27402. PMID- 39892787 OWN - NLM STAT- MEDLINE DCOM- 20250316 LR - 20260127 IS - 2405-4577 (Electronic) IS - 2405-4577 (Linking) VI - 66 DP - 2025 Apr TI - Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 564-572 LID - S2405-4577(25)00057-9 [pii] LID - 10.1016/j.clnesp.2025.01.056 [doi] AB - BACKGROUND & AIMS: Semaglutide has demonstrated efficacy in both glycemic control and weight loss. This systematic review and meta-analysis aimed to assess the efficacy and safety of the combined use of semaglutide and basal insulin in individuals diagnosed with type 2 diabetes mellitus (T2DM). METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to identify relevant publications. The primary outcome measure was the change in HbA1c levels. Secondary outcome measures encompassed change in body weight, fluctuations in FPG levels, occurrence of adverse events, serious adverse events, hypoglycemic episodes, and gastrointestinal reactions including nausea, vomiting, and diarrhea. Mean differences (MDs) and relative risk (RR) with confidence intervals (CI) of 95 % were used to analyze the deference. RESULTS: 7 RCTs with 2354 patients were incorporated into the study. Compared to placebo or other active treatment, the addition of semaglutide to basal insulin demonstrated significant reductions in hemoglobin A1c (HbA1c) [mean differences (MD): -1.17 %, P < 0.00001], body weight [MD -5.99 kg, P < 0.00001], and fasting blood glucose (FPG) [MD -1.08 %, P < 0.00001]. No evidence indicated a higher risk of adverse events [RR 1.46, P = 0.13]. However, it did result in increased rates of gastrointestinal adverse events, including nausea, vomiting and diarrhea. CONCLUSIONS: The combination treatment of semaglutide and basal insulin demonstrates significant improvements in glycemic control and reduction in body weight, without an increased risk of hypoglycemia. Our findings provided support for the utilization of a combination therapy involving semaglutide and basal insulin in T2DM. CI - Copyright (c) 2025. Published by Elsevier Ltd. FAU - Chen, Binbin AU - Chen B AD - Department of Gastroenterology, Xijing Hospital,Air Force Medical University, Xi'an 710032, China. Electronic address: 2407633730@qq.com. FAU - Tao, Lanqiu AU - Tao L AD - Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China. Electronic address: 2359367759@qq.com. FAU - Tian, Min AU - Tian M AD - State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, Air Force Medical University, Chang Le Road & 169, Xi'an City, Shaanxi, 710032, PR China. Electronic address: epidemiology@fmmu.edu.cn. FAU - Ji, Zhaohua AU - Ji Z AD - Department of Epidemiology, School of Public Health, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Chang Le Road & 169, Xi'an City, Shaanxi, 710032, PR China. Electronic address: epidemiology@fmmu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250130 PL - England TA - Clin Nutr ESPEN JT - Clinical nutrition ESPEN JID - 101654592 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis/metabolism MH - Drug Therapy, Combination MH - Blood Glucose/drug effects MH - *Insulin/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - Body Weight/drug effects MH - Randomized Controlled Trials as Topic MH - *Insulin Glargine/therapeutic use MH - Hypoglycemia/chemically induced MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - HbA1c OT - Insulin OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare no competing interests. EDAT- 2025/02/02 05:11 MHDA- 2025/03/17 00:42 CRDT- 2025/02/01 19:20 PHST- 2024/01/13 00:00 [received] PHST- 2025/01/16 00:00 [revised] PHST- 2025/01/27 00:00 [accepted] PHST- 2025/03/17 00:42 [medline] PHST- 2025/02/02 05:11 [pubmed] PHST- 2025/02/01 19:20 [entrez] AID - S2405-4577(25)00057-9 [pii] AID - 10.1016/j.clnesp.2025.01.056 [doi] PST - ppublish SO - Clin Nutr ESPEN. 2025 Apr;66:564-572. doi: 10.1016/j.clnesp.2025.01.056. Epub 2025 Jan 30. PMID- 39892489 OWN - NLM STAT- MEDLINE DCOM- 20250520 LR - 20250520 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 138 IP - 6 DP - 2025 Jun TI - Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation. PG - 934-940 LID - S0002-9343(25)00059-2 [pii] LID - 10.1016/j.amjmed.2025.01.021 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation. This review explores the mechanisms underlying GLP-1 RA-induced weight loss, focusing on central and peripheral pathways. Centrally, GLP-1 RAs modulate brain regions controlling appetite, influencing neurotransmitter and peptide release to regulate hunger and energy expenditure. Peripherally, GLP-1 RAs improve glycemic control by enhancing insulin secretion, reducing glucagon release, delaying gastric emptying, and regulating gut hormones. They also reduce triglycerides and low-density lipoprotein cholesterol, mitigate adipose tissue inflammation, and minimize ectopic fat deposition, promoting overall metabolic health. Emerging dual and triple co-agonists, targeting GLP-1 alongside glucose-dependent insulinotropic polypeptide, and glucagon pathways, may enhance weight loss and metabolic flexibility. Understanding these mechanisms is crucial as the therapeutic landscape evolves, offering clinicians and researchers insights to optimize the efficacy of current and future obesity treatments. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Moiz, Areesha AU - Moiz A AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada. FAU - Filion, Kristian B AU - Filion KB AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada. FAU - Tsoukas, Michael A AU - Tsoukas MA AD - Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Yu, Oriana Hy AU - Yu OH AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Peters, Tricia M AU - Peters TM AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Eisenberg, Mark J AU - Eisenberg MJ AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Cardiology, Jewish General Hospital/McGill University, Canada. Electronic address: mark.eisenberg@ladydavis.ca. LA - eng PT - Journal Article PT - Review DEP - 20250131 PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Energy Metabolism/drug effects MH - *Obesity/drug therapy/metabolism MH - *Appetite/drug effects MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Appetite OT - Glucagon-like peptide-1 receptor agonist OT - Metabolism OT - Obesity OT - Semaglutide OT - Tirzepatide OT - Weight loss EDAT- 2025/02/02 05:11 MHDA- 2025/05/20 06:28 CRDT- 2025/02/01 19:14 PHST- 2025/01/23 00:00 [received] PHST- 2025/01/24 00:00 [accepted] PHST- 2025/05/20 06:28 [medline] PHST- 2025/02/02 05:11 [pubmed] PHST- 2025/02/01 19:14 [entrez] AID - S0002-9343(25)00059-2 [pii] AID - 10.1016/j.amjmed.2025.01.021 [doi] PST - ppublish SO - Am J Med. 2025 Jun;138(6):934-940. doi: 10.1016/j.amjmed.2025.01.021. Epub 2025 Jan 31. PMID- 39891379 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20250525 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 61 IP - 8 DP - 2025 Apr TI - Impact of GLP-1 Receptor Agonists on Alcohol-Related Liver Disease Development and Progression in Alcohol Use Disorder. PG - 1343-1356 LID - 10.1111/apt.70007 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes in patients with alcohol use disorder (AUD) remains unclear. We investigated the association between GLP-1RAs and the development and progression of alcohol-related liver disease (ArLD) in patients with AUD. METHODS: Using the TriNetX Research Network, we conducted two retrospective cohort studies comparing GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. The first cohort included patients with AUD but without ArLD (n = 7132 after propensity score matching), while the second comprised patients with established ArLD (n = 1896 after matching). Primary outcomes were incident ArLD in the AUD cohort and hepatic decompensation in the ArLD cohort. RESULTS: In the AUD cohort (median follow-up: 63.2 months), GLP-1RA users showed significantly lower risks of developing ArLD compared to DPP-4i users (incidence rate: 6.0 vs. 8.7 per 1000 person-years; HR: 0.62, 95% CI: 0.44-0.87, p = 0.006). GLP-1RAs were also associated with reduced risks of all-cause mortality (HR: 0.53, p < 0.001). In the ArLD cohort (median follow-up: 28.2 months), GLP-1RA users demonstrated lower risks of hepatic decompensation (incidence rate: 39.5 vs. 51.4 per 1000 person-years; HR: 0.66, 95% CI: 0.51-0.85, p = 0.001) and all-cause mortality (HR: 0.53, p < 0.001) compared to DPP-4i users. CONCLUSIONS: GLP-1RAs were associated with reduced risks of developing and progressing ArLD in patients with AUD, suggesting potential therapeutic benefits in this population. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Kuo, Chia-Chih AU - Kuo CC AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Li, Chun-Hsien AU - Li CH AD - Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Hsing-Tao AU - Kuo HT AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. LA - eng PT - Journal Article DEP - 20250131 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Female MH - Retrospective Studies MH - Disease Progression MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Adult MH - *Alcoholism/drug therapy/complications MH - *Liver Diseases, Alcoholic/prevention & control MH - Aged MH - Cohort Studies OTO - NOTNLM OT - alcohol use disorder OT - alcohol-related liver disease OT - glucagon-like peptide-1 receptor agonists OT - mortality OT - real-world evidence EDAT- 2025/02/01 20:42 MHDA- 2025/03/28 06:25 CRDT- 2025/02/01 01:22 PHST- 2024/12/18 00:00 [revised] PHST- 2024/11/26 00:00 [received] PHST- 2025/01/23 00:00 [accepted] PHST- 2025/03/28 06:25 [medline] PHST- 2025/02/01 20:42 [pubmed] PHST- 2025/02/01 01:22 [entrez] AID - 10.1111/apt.70007 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2025 Apr;61(8):1343-1356. doi: 10.1111/apt.70007. Epub 2025 Jan 31. PMID- 39888616 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 1 DP - 2025 Jan 2 TI - Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. PG - e2457349 LID - 10.1001/jamanetworkopen.2024.57349 [doi] LID - e2457349 AB - IMPORTANCE: Adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is important for their effectiveness. Discontinuation and reinitiation patterns are not well understood. OBJECTIVE: To describe rates of and factors associated with discontinuation and subsequent reinitiation of GLP-1 RAs among adults with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, 125 474 adults with overweight or obesity newly initiated treatment with a dual-labeled GLP-1 RA (liraglutide, semaglutide, or tirzepatide) between January 1, 2018, and December 31, 2023, with a baseline body mass index of 27 or more, an available weight measurement within 60 days before initiation, and regular care in the year before initiation were identified using electronic health record data from a collective of US health care systems. Patients were followed up for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation. EXPOSURE: Patients were stratified by presence of type 2 diabetes at baseline. MAIN OUTCOMES AND MEASURES: Proportions of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations of sociodemographic characteristics, health factors, weight changes, and gastrointestinal adverse events with discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards regression models. All analyses were conducted separately for patients with and patients without type 2 diabetes. RESULTS: In this cohort study of 125 474 adults (mean [SD] age, 54.4 [13.1] years; 82 063 women [65.4%]), 76 524 (61.0%) had type 2 diabetes. One-year discontinuation was significantly higher for patients without type 2 diabetes (64.8% [95% CI, 64.4%-65.2%]) compared with those with type 2 diabetes (46.5% [95% CI, 46.2%-46.9%]). Higher weight loss (1% reduction in weight from baseline was associated with a 3.1% [95% CI, 2.9%-3.2%] lower hazard of discontinuation for patients with type 2 diabetes and a 3.3% [95% CI, 3.2%-3.5%] lower hazard of discontinuation for patients without type 2 diabetes) and higher income (type 2 diabetes only; >$80 000: hazard ratio [HR], 0.72 [95% CI, 0.69-0.76]) were significantly associated with lower rates of discontinuation, while moderate or severe incident gastrointestinal adverse events were associated with a higher hazard of discontinuation (with type 2 diabetes: HR, 1.38 [95% CI, 1.31-1.45]; without type 2 diabetes: HR, 1.19 [95% CI, 1.12-1.27]). Of 41 792 patients who discontinued and had a discontinuation weight measurement available, 1-year reinitiation was lower for those without type 2 diabetes (36.3% [95% CI, 35.6%-37.0%]) compared with those with type 2 diabetes (47.3% [95% CI, 46.6%-48.0%]). Weight regain of 1% from discontinuation was significantly associated with increased hazards of reinitiation of 2.3% (95% CI, 1.9%-2.8%) for patients with type 2 diabetes and 2.8% (95% CI, 2.4%-3.2%) for patients without type 2 diabetes. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with overweight or obesity discontinued GLP-1 RA therapy within 1 year, but those without type 2 diabetes had higher discontinuation rates and lower reinitiation rates. Inequities in access and adherence to effective treatments have the potential to exacerbate disparities in obesity. FAU - Rodriguez, Patricia J AU - Rodriguez PJ AD - Truveta Inc, Bellevue, Washington. FAU - Zhang, Vincent AU - Zhang V AD - Healthcare Transformation Institute, Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. FAU - Gratzl, Samuel AU - Gratzl S AD - Truveta Inc, Bellevue, Washington. FAU - Do, Duy AU - Do D AD - Truveta Inc, Bellevue, Washington. FAU - Goodwin Cartwright, Brianna AU - Goodwin Cartwright B AD - Truveta Inc, Bellevue, Washington. FAU - Baker, Charlotte AU - Baker C AD - Truveta Inc, Bellevue, Washington. FAU - Gluckman, Ty J AU - Gluckman TJ AD - Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence Health System, Portland, Oregon. FAU - Stucky, Nicholas AU - Stucky N AD - Truveta Inc, Bellevue, Washington. FAU - Emanuel, Ezekiel J AU - Emanuel EJ AD - Healthcare Transformation Institute, Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250102 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Adult MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - *Overweight/drug therapy MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11786232 COIS- Conflict of Interest Disclosures: Dr Emanuel reported receiving personal fees from the University of California San Francisco, Advocate Aurora Health, Cain Brothers, Bowdoin College, The Suntory Foundation, Ontario Hospital Association, University of Oklahoma, Sanford Health, Health Plan Alliance, Emory Health Care, and Employer Direct Health Care; nonfinancial support from Galien Foundation, Hlth Inc, National University of Singapore, Hawaii Medical Services Association, Tel Aviv University, The Quadrangle, Lazard, University of Bergen, University of Virginia, New York Historical Society, Amangiri, Forerunner Conference, BCEPS International Symposium, Future of Science, Cell and Gene Therapy, and Arendalsuka Meeting during the conduct of the study; and serving as a member of the Board of Advisors for Cellares Corp, advisor for Clarify Health Solutions, advisor for Notable Health, member of the Advisory Board for JSL Health, member of the Advisory Board for Peterson Center of Healthcare, special advisor to the Director General of the World Health Organization (WHO), member of the Expert Advisory Group WHO COVID-19 committee, member of the Advisory Board of the HIEx Health Innovation Exchange Partnership sponsored by the United Nations, member of the WHO Expert Group on Ethics & Governance of Outbreaks/Emergencies, member of the WHO Guideline Development Group on the Use and Indications of GLP-1s for Adults Living With Obesity, member of the Internal Advisory Board of The Penn Parity Center, advisor for Link Health Technologies, advisor for Nuna Health, member of the Board of Advisors of Alto Pharmacy, consultant for Korro/Coach AI, consultant for Aberdeen Inc, member of the Advisory Board of FeelBetter Inc, member of the Advisory Board of Biden's Transition COVID-19 Committee, and member of the JAMA Editorial Board. No other disclosures were reported. EDAT- 2025/01/31 12:24 MHDA- 2025/01/31 12:25 PMCR- 2025/01/31 CRDT- 2025/01/31 11:35 PHST- 2025/01/31 12:25 [medline] PHST- 2025/01/31 12:24 [pubmed] PHST- 2025/01/31 11:35 [entrez] PHST- 2025/01/31 00:00 [pmc-release] AID - 2829779 [pii] AID - zoi241605 [pii] AID - 10.1001/jamanetworkopen.2024.57349 [doi] PST - epublish SO - JAMA Netw Open. 2025 Jan 2;8(1):e2457349. doi: 10.1001/jamanetworkopen.2024.57349. PMID- 39887855 OWN - NLM STAT- MEDLINE DCOM- 20250306 LR - 20260812 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Comparative effectiveness of insulin glargine, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in veterans with type 2 diabetes. PG - 2120-2130 LID - 10.1111/dom.16207 [doi] AB - AIMS: To compare the risk of all-cause death and cardiovascular events in new users of insulin glargine, glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP-1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023. Inverse probability weighted Cox regression models were used for treatment comparisons on all-cause deaths and cardiovascular events in the entire cohort and above subgroups. RESULTS: There were 20 788 cardiovascular events/414 414 person-years and 15 268 all-cause deaths/446 458 person-years. Insulin glargine had a higher hazard of all-cause death compared to GLP-1RA (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.48-1.67) or SGLT2i (HR 1.55, 95% CI 1.48-1.61) in the entire cohort and across subgroups, especially in those with HbA1C levels <9.0%. Results were similar for secondary outcomes. Compared to GLP-1RA, SGLT2i had similar risk of all-cause death (HR 1.03, 95% CI 0.97-1.10) but higher hazard of cardiovascular events (HR 1.13, 95% CI 1.08-1.19). Across subgroups, GLP-1RA and SGLT2i had generally similar effects, with SGLT2i showing a slightly higher risk in some cases. CONCLUSIONS: Insulin glargine might be deleterious particularly in those with HbA1C <9.0%. There was no clear evidence for prioritization of SGLT2i versus GLP-1RA across subgroups. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Shen, Jincheng AU - Shen J AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Sarwal, Amara AU - Sarwal A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Singh, Ravinder AU - Singh R AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Hartsell, Sydney E AU - Hartsell SE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Wei, Guo AU - Wei G AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Nevers, McKenna AU - Nevers M AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Informatics Decision Enhancement and Surveillance (IDEAS) Center, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah, USA. FAU - Christensen, Jesse C AU - Christensen JC AD - Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah, USA. AD - Department of Physical Therapy and Athletic Training, University of Utah College of Health, Salt Lake City, Utah, USA. FAU - Takyi, Augustine AU - Takyi A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Katkam, Niharika AU - Katkam N AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Derington, Catherine G AU - Derington CG AD - Division of Cardiology, Department of Medicine, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Deshmukh, Vikrant G AU - Deshmukh VG AD - Data Science Services, University of Utah Health, Salt Lake City, Utah, USA. FAU - Boucher, Robert E AU - Boucher RE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Drakos, Stavros G AU - Drakos SG AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Greene, Tom AU - Greene T AD - Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Beddhu, Srinivasan AU - Beddhu S AUID- ORCID: 0000-0002-3312-315X AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Cardio-Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City, Utah, USA. AD - Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah, USA. LA - eng GR - UL1 RR025764/RR/NCRR NIH HHS/United States GR - UM1 TR004409/TR/NCATS NIH HHS/United States GR - R01 AG074592/AG/NIA NIH HHS/United States GR - R01 DK128640/DK/NIDDK NIH HHS/United States GR - UL1 TR000105/TR/NCATS NIH HHS/United States GR - Veterans Health Administration Office of Rural Health/ GR - UL1 TR001067/TR/NCATS NIH HHS/United States GR - UM1TR004409/TR/NCATS NIH HHS/United States GR - T35 DK103596/AG/NIA NIH HHS/United States GR - T32 HL007576/HL/NHLBI NIH HHS/United States GR - T35 DK103596/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20250130 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Insulin Glargine/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Veterans/statistics & numerical data MH - Aged MH - Glycated Hemoglobin/analysis MH - Cardiovascular Diseases/epidemiology/mortality MH - Metformin/therapeutic use MH - Treatment Outcome PMC - PMC11885103 OTO - NOTNLM OT - GLP-1 OT - SGLT2 inhibitor OT - cardiovascular disease OT - database research OT - insulin therapy OT - type 2 diabetes COIS- SB received research support from Bayer, Novo Nordisk and Boehringer Ingelheim. SGD is a consultant with Abbott and receives research support from Novartis. The other authors declare no conflicts of interest. EDAT- 2025/01/31 12:24 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/01/31 10:32 PHST- 2024/12/31 00:00 [revised] PHST- 2024/10/17 00:00 [received] PHST- 2025/01/09 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/31 12:24 [pubmed] PHST- 2025/01/31 10:32 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16207 [pii] AID - 10.1111/dom.16207 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):2120-2130. doi: 10.1111/dom.16207. Epub 2025 Jan 30. PMID- 39886945 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 55 IP - 4 DP - 2025 Apr TI - Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. LID - 56 [pii] LID - 10.3892/ijmm.2025.5497 [doi] AB - The aim of the present study was to investigate the neuroprotective effects of semaglutide in diabetes‑associated cognitive decline (DACD), while also exploring the underlying mechanisms targeting anti‑oxidative effects. The present study evaluated the antioxidant properties of semaglutide using a DACD model of inflammation. To investigate the underlying mechanisms, omics technologies were employed. Comprehensive transcriptomic and proteomic analysis of the cells was conducted to identify the pathways responsible for the observed antioxidant effects. Semaglutide demonstrated the potential to enhance learning and memory functions while mitigating hippocampal pathological damage. RNA‑sequencing and data‑independent acquisition proteomics analyses identified 13,511 differentially expressed genes and 588 differentially expressed proteins between the control and type 2 diabetes mellitus (T2DM) groups. In addition, 1,378 genes and 2,394 proteins exhibited a differential expression between the T2DM and semaglutide (10 microg/kg) treatment groups. A combined transcriptomic and proteomic analysis unveiled 40 common pathways. Acyl‑CoA oxidase 1 (ACOX1) was observed to be activated during oxidative stress and subsequently suppressed by semaglutide. Of note, the antioxidant and anti‑apoptotic properties of semaglutide in high glucose (HG) conditions were partially reversed upon ACOX1 overexpression. Overall, the present data provided molecular evidence to elucidate the physiological connections between semaglutide and neuronal function, and contribute to clarifying the role of semaglutide in combating oxidative stress and HG‑induced cognitive impairment. FAU - Yang, Ying AU - Yang Y AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Song, Lulu AU - Song L AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Yu, Liping AU - Yu L AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Zhang, Jinping AU - Zhang J AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Zhang, Bo AU - Zhang B AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. LA - eng PT - Journal Article DEP - 20250131 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antioxidants) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Proteomics/methods MH - *Antioxidants/pharmacology/therapeutic use MH - *Cognitive Dysfunction/drug therapy/metabolism/genetics/etiology MH - Mice MH - Male MH - *Diabetes Mellitus, Experimental/complications/genetics/metabolism/drug therapy MH - *Transcriptome/drug effects MH - Oxidative Stress/drug effects MH - Hippocampus/drug effects/metabolism/pathology MH - Gene Expression Profiling MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/complications/genetics/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11819768 OTO - NOTNLM OT - cognitive OT - diabetes OT - oxidative stress OT - proteomic OT - transcriptomic COIS- The authors declare that they have no competing interests. EDAT- 2025/01/31 12:23 MHDA- 2025/01/31 12:24 PMCR- 2025/01/30 CRDT- 2025/01/31 07:12 PHST- 2024/10/16 00:00 [received] PHST- 2025/01/16 00:00 [accepted] PHST- 2025/01/31 12:24 [medline] PHST- 2025/01/31 12:23 [pubmed] PHST- 2025/01/31 07:12 [entrez] PHST- 2025/01/30 00:00 [pmc-release] AID - 56 [pii] AID - ijmm-55-04-05497 [pii] AID - 10.3892/ijmm.2025.5497 [doi] PST - ppublish SO - Int J Mol Med. 2025 Apr;55(4):56. doi: 10.3892/ijmm.2025.5497. Epub 2025 Jan 31. PMID- 39883468 OWN - NLM STAT- MEDLINE DCOM- 20250320 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 3 DP - 2025 Mar 1 TI - Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide. PG - 215-220 LID - 10.1001/jamaophthalmol.2024.6058 [doi] AB - IMPORTANCE: Nearly 2% of the US population received a prescription for semaglutide in 2023. There has been a recent concern that this drug and other similar medications may be associated with ophthalmic complications. OBJECTIVE: To report ophthalmic complications associated with the use of semaglutide or tirzepatide. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case series. All patients were initially seen in a community setting. Patients experiencing an ophthalmic complication in association with the use of semaglutide or tirzepatide were included in this analysis. EXPOSURES: Patients described were using either semaglutide or tirzepatide. MAIN OUTCOMES AND MEASURES: Visual acuity and visual field defects. RESULTS: A total of 9 patients (mean [SD] age, 57.4 [11.6] years; age range, 37-77 years; 5 female [56%]; 4 male [44%]) were included in this study. Seven patients with nonarteritic ischemic anterior optic neuropathy, 1 patient with bilateral papillitis, and 1 patient with paracentral acute middle maculopathy were reported. Atypical features included sequential ischemic optic neuropathy, bilateral disc swelling at presentation, and progressive vision loss. CONCLUSIONS AND RELEVANCE: In this case series study, it was not possible to determine if there is a causal link between these drugs and the ophthalmic complications reported. In some cases, it is hypothesized that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported. FAU - Katz, Bradley J AU - Katz BJ AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. FAU - Lee, Michael S AU - Lee MS AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis. FAU - Lincoff, Norah S AU - Lincoff NS AD - Department of Neurology, Jacobs School of Medicine & Biological Sciences, The State University of New York at Buffalo, Buffalo. FAU - Abel, Anne S AU - Abel AS AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis. FAU - Chowdhary, Somya AU - Chowdhary S AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Ellis, Brian D AU - Ellis BD AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Najafi, Ahmad AU - Najafi A AD - Spectrum Eye Care Inc, Findlay, Ohio. FAU - Nguyen, John AU - Nguyen J AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Seay, Meagan D AU - Seay MD AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. FAU - Warner, Judith E A AU - Warner JEA AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. AD - George E. Whalen Department of Veteran's Affairs Medical Center, Salt Lake City, Utah. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Mar 1;143(3):220-221. doi: 10.1001/jamaophthalmol.2024.6181. PMID: 39883452 EIN - JAMA Ophthalmol. 2026 Sep 1;144(9):882. doi: 10.1001/jamaophthalmol.2026.2772. PMID: 42424048 MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/adverse effects MH - Aged MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Visual Acuity/drug effects MH - Visual Fields/drug effects MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Vision Disorders/chemically induced/physiopathology/diagnosis MH - Diabetes Mellitus, Type 2/drug therapy MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11783245 COIS- Conflict of Interest Disclosures: Dr Katz reported having an equity interest in and is a consultant for Avulux. Dr Lee reported receiving consultant fees from Eli Lilly and Panbela, grants from Invex, advisory board fees from Viridian, and personal fees from Horizon outside the submitted work. Dr Najafi reported previously being affiliated with Spectrum Eye Care Inc, where the information for this study was gathered, but has since left that institution and is currently a cornea and external disease fellow at University of Minnesota. No other disclosures were reported. EDAT- 2025/01/30 12:36 MHDA- 2025/03/20 12:34 PMCR- 2026/01/30 CRDT- 2025/01/30 11:33 PHST- 2025/03/20 12:34 [medline] PHST- 2025/01/30 12:36 [pubmed] PHST- 2025/01/30 11:33 [entrez] PHST- 2026/01/30 00:00 [pmc-release] AID - 2829326 [pii] AID - eoi240088 [pii] AID - 10.1001/jamaophthalmol.2024.6058 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Mar 1;143(3):215-220. doi: 10.1001/jamaophthalmol.2024.6058. PMID- 39882599 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 28 IP - 1 DP - 2025 Dec TI - Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes. PG - 268-278 LID - 10.1080/13696998.2025.2459529 [doi] AB - AIMS: The cardioprotective effects of semaglutide 2.4 mg reported in the SELECT cardiovascular (CV) outcomes trial (ClinicalTrials.gov NCT03574597) provide clinical benefit for subjects with overweight or obesity and established CV disease without type 2 diabetes (T2D). We assessed cost-effectiveness of semaglutide 2.4 mg in this population against the American College of Cardiology/American Heart Association value framework. MATERIALS AND METHODS: A cohort-level Markov-state cost-effectiveness model using trial-derived data with outcomes from a healthcare sector perspective measured over a lifetime horizon was developed. Treatment costs were based on US list prices; scenario analyses used literature-reported estimated rebates. Healthcare costs and benefits were discounted at 3.0%. A simulated cohort of 100,000 subjects was aligned to the SELECT trial population baseline characteristics and time-on-treatment. Subjects received either semaglutide 2.4 mg or placebo in addition to standard of care (SoC). Modelled outcomes included clinical events (CV events, progression to T2D, chronic kidney disease [CKD]) and health economic measures, including direct costs and quality-adjusted life years (QALYs). RESULTS: Mean semaglutide 2.4 mg treatment duration was 2.79 years. Per 100,000 subjects, treatment avoided 2,791 non-fatal myocardial infarctions, 3,000 coronary revascularizations, 487 non-fatal strokes, and 115 CV deaths over the modeled lifetime horizon. Average per-subject lifetime treatment costs were $47,353; savings arose from avoided T2D ($14,431), CKD ($2,074), and CV events ($1,512). Semaglutide 2.4 mg was associated with increased lifetime costs ($29,767), additional QALYs gained (0.218) and an incremental cost-effectiveness ratio of $136,271/QALY at list price; a scenario using an empirically estimated 48% rebate predicted $32,219/QALY. LIMITATIONS: The generalizability of observations from SELECT to a broader US population is unknown. Our model does not capture all outcomes nor costs that may be affected by weight loss. Modeling assumptions may present limitations. CONCLUSIONS: Semaglutide 2.4 mg use as in SELECT is cost-effective at list price, using a $150,000/QALY willingness-to-pay threshold. FAU - McEwan, Phil AU - McEwan P AUID- ORCID: 0000-0001-7488-9058 AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Bog, Martin AU - Bog M AUID- ORCID: 0000-0001-6431-8307 AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Faurby, Mads AU - Faurby M AUID- ORCID: 0000-0001-6464-9958 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Foos, Volker AU - Foos V AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine (Endocrinology Division) and Peter O'Donnel Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Lubker, Christopher AU - Lubker C AUID- ORCID: 0000-0003-3220-801X AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Miller, Ryan AU - Miller R AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Toliver, Joshua C AU - Toliver JC AUID- ORCID: 0000-0002-9159-2587 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Yeates, Florian AU - Yeates F AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Lincoff, A Michael AU - Lincoff AM AUID- ORCID: 0000-0001-8175-2121 AD - Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study DEP - 20250212 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control/drug therapy/complications MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - Markov Chains MH - *Obesity/drug therapy/complications MH - Quality-Adjusted Life Years MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - I00 OT - I10 OT - cost-effectiveness analysis OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - overweight EDAT- 2025/01/30 11:06 MHDA- 2025/02/12 12:27 CRDT- 2025/01/30 04:52 PHST- 2025/02/12 12:27 [medline] PHST- 2025/01/30 11:06 [pubmed] PHST- 2025/01/30 04:52 [entrez] AID - 10.1080/13696998.2025.2459529 [doi] PST - ppublish SO - J Med Econ. 2025 Dec;28(1):268-278. doi: 10.1080/13696998.2025.2459529. Epub 2025 Feb 12. PMID- 39881322 OWN - NLM STAT- MEDLINE DCOM- 20250130 LR - 20260527 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Jan 29 TI - Glucagon like peptide-1 (GLP-1) agonists and cardiometabolic protection: historical development and future challenges. PG - 44 LID - 10.1186/s12933-025-02608-9 [doi] LID - 44 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the treatment of cardiometabolic diseases, extending their therapeutic applications far beyond glycemic control in type 2 diabetes (T2D) and obesity. This editorial synthesizes key milestones, from the discovery of GLP-1 to recent clinical trials highlighting the pleiotropic effects of GLP-1RAs in addressing the interconnected spectrum of cardiometabolic conditions, with a focus on cardiovascular, renal, and hepatic benefits. In addition, as GLP-1RAs continue to reshape the management of cardiometabolic disease and global public health, we discuss future challenges to better elucidate their mechanisms of cardiometabolic protection and maximize their therapeutic potential. CI - (c) 2025. The Author(s). FAU - Westermeier, Francisco AU - Westermeier F AD - Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria. francisco.westermeier@fh-joanneum.at. AD - Centro de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile. francisco.westermeier@fh-joanneum.at. FAU - Fisman, Enrique Z AU - Fisman EZ AD - Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. zfisman@tauex.tau.ac.il. AD - Facultad de Medicina, Universidad del Salvador (USAL), Buenos Aires, Argentina. zfisman@tauex.tau.ac.il. LA - eng PT - Editorial PT - Historical Article DEP - 20250129 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Blood Glucose) SB - IM EIN - Cardiovasc Diabetol. 2025 Mar 12;24(1):118. doi: 10.1186/s12933-025-02647-2. PMID: 40075386 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood MH - *Cardiovascular Diseases/prevention & control/epidemiology/diagnosis MH - *Incretins/therapeutic use/adverse effects/history MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Animals MH - *Glucagon-Like Peptide 1/metabolism MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Signal Transduction/drug effects MH - History, 21st Century MH - Cardiometabolic Risk Factors MH - *Blood Glucose/drug effects/metabolism PMC - PMC11781064 OTO - NOTNLM OT - Cardiometabolic diseases OT - Chronic kidney disease OT - GLP-1 OT - Glucagon-like peptide-1 OT - Metabolic liver disease OT - Obesity OT - Type 2 diabetes COIS- Declarations. Competing interests: Enrique Fisman (EF), Editor-in-Chief, and Francisco Westermeier (FW), Deputy Editor of Cardiovascular Diabetology, are the authors of this editorial. Both authors declare no additional competing interests related to this work. EDAT- 2025/01/30 00:19 MHDA- 2025/01/30 11:06 PMCR- 2025/01/29 CRDT- 2025/01/29 23:39 PHST- 2025/01/22 00:00 [received] PHST- 2025/01/22 00:00 [accepted] PHST- 2025/01/30 11:06 [medline] PHST- 2025/01/30 00:19 [pubmed] PHST- 2025/01/29 23:39 [entrez] PHST- 2025/01/29 00:00 [pmc-release] AID - 10.1186/s12933-025-02608-9 [pii] AID - 2608 [pii] AID - 10.1186/s12933-025-02608-9 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Jan 29;24(1):44. doi: 10.1186/s12933-025-02608-9. PMID- 39878627 OWN - NLM STAT- MEDLINE DCOM- 20250129 LR - 20260127 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 1 DP - 2025 Jan-Feb TI - Changes in food preferences after oral semaglutide administration in Japanese patients with type 2 diabetes: KAMOGAWA-DM cohort. PG - 14791641251318309 LID - 10.1177/14791641251318309 [doi] LID - 14791641251318309 AB - BACKGROUND: This study aimed to investigate the effects of oral semaglutide on the changes in food preference of Japanese patients with type 2 diabetes. METHODS: This retrospective multicenter study included 75 patients with type 2 diabetes who received oral semaglutide. The primary outcome was the change in the score of brief-type self-administered diet history questionnaire (BDHQ) score 3 months after the initiation of oral semaglutide treatment. The secondary outcome was the change in the Control of Eating Questionnaire (CoEQ), HbA1c, and body mass index (BMI) after 3 months. RESULTS: The median age, BMI, and HbA1c of the 23 participants were 64.0 years, 26.9 kg/m(2), and 7.6% (59 mmol/mol). The BDHQ results showed total energy was significantly reduced. Among the individual nutrients, carbohydrates most decreased. The CoEQ results particularly showed declines in cravings for something sweet, chocolate or chocolate flavored foods, and starchy foods, satisfaction at meals, frequency and intensity of food craving, difficulty of resisting the craving for food, and frequency of eating in response to cravings for food were significantly lower after 3 months. The mean HbA1c and BMI significantly decreased. CONCLUSIONS: In Japanese patients with type 2 diabetes, oral semaglutide treatment decreased total energy intake and changed food preferences. FAU - Hironaka, Junya AU - Hironaka J AUID- ORCID: 0000-0002-2970-5333 AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Ushigome, Emi AU - Ushigome E AUID- ORCID: 0000-0003-1031-4380 AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Kondo, Yuriko AU - Kondo Y AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Hashimoto, Yoshitaka AU - Hashimoto Y AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Osaka, Takafumi AU - Osaka T AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Majima, Saori AU - Majima S AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Nakanishi, Naoko AU - Nakanishi N AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Okada, Hiroshi AU - Okada H AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Senmaru, Takafumi AU - Senmaru T AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Hamaguchi, Masahide AU - Hamaguchi M AD - Department of Diabetology, Kameoka Municipal Hospital, Kyoto, Japan. FAU - Yamazaki, Masahiro AU - Yamazaki M AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Fukui, Michiaki AU - Fukui M AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. LA - eng PT - Journal Article PT - Multicenter Study PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/psychology/physiopathology MH - Middle Aged MH - Male MH - Female MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Aged MH - Retrospective Studies MH - Japan MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Glycated Hemoglobin/metabolism MH - Treatment Outcome MH - *Food Preferences/drug effects MH - Time Factors MH - Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - Body Mass Index MH - Energy Intake/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People PMC - PMC11780656 OTO - NOTNLM OT - Appetite depressants OT - glucagon-like peptide 1 OT - type 2 diabetes mellitus COIS- Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Hironaka J received personal fees from Novo Nordisk Pharma Ltd., Kowa Pharmaceutical Co., Ltd., outside the submitted work, and received personal fees from Nippon Boehringer Ingelheim Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Ltd, MSD K.K., Kyowa Hakko Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Sanofi K.K., outside the submitted work. Donated Fund Laboratory of Diabetes therapeutics is an endowment department, supported with an unrestricted grant from Ono Pharmaceutical Co., Ltd., Taiyo Kagaku Co. Ltd. and Taisho Pharmaceutical Co., Ltd. Nakanishi N received personal fees from Kowa Pharmaceutical Co. Ltd., and Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., TERUMO CORPORATION. Okada H received personal fees from Mochida Pharma Co. Ltd., Teijin Pharma Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K, Kyowa Hakko Kirin Company Ltd, Kissei Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Kowa Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., and Sanofi K.K. Senmaru T received personal fees from Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, Daiichi Sankyo Co. Ltd., Kowa Pharma Co., Ltd., Astellas Pharma Inc., Takeda Pharma Co., Ltd., Sanofi K.K., Taisho Toyama Pharma Co., Ltd., Kyowa Kirin Co., Ltd., Kissei Pharma Co., Ltd., MSD K.K., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., TERUMO CORPORATION, Abbott Japan Co. Ltd., outside the submitted work. Hashimoto Y received personal fees from Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Mitsubishi Tanabe Pharma Corp., Kowa Company, Ltd., Taisho Pharma Co., Eli Lilly Japan K.K. and Daiichi Sankyo Co. Yamazaki M received grants from AstraZeneca K.K., Ono Pharma Co. Ltd.,; and received personal fees from MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Kowa Company, Limited, AstraZeneca PLC, Takeda Pharmaceutical Company Limited, Kyowa Hakko Kirin Co., Ltd., Daiichi Sankyo Co., Ltd, Kowa Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted work. Hamaguchi M received grants from AstraZeneca K.K., Ono Pharma Co. Ltd., Kowa Pharma Co. Ltd.; and received personal fees from AstraZeneca K.K., Ono Pharma Co. Ltd., Eli Lilly, Japan, Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., K.K., and Kowa Pharma Co. Ltd. outside of the submitted work. Fukui M received grants from Ono Pharma Co. Ltd., Oishi Kenko inc., Yamada Bee Farm, Nippon Boehringer Ingelheim Co. Ltd., Kissei Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Sanwa Kagagu Kenkyusho CO., Ltd., Eli Lilly, Japan, K.K., Taisho Pharma Co., Ltd., Terumo Corp., Tejin Pharma Ltd., Nippon Chemiphar Co., Ltd., Abbott Japan Co. Ltd., and Johnson & Johnson K.K. Medical Co., TERUMO CORPORATION, and received personal fees from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Taisho Pharma Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., Abbott Japan Co. Ltd., Teijin Pharma Ltd., Arkray Inc., Medtronic Japan Co. Ltd., and Nipro Corp., TERUMO CORPORATION, outside the submitted work. EDAT- 2025/01/29 12:26 MHDA- 2025/01/29 12:27 PMCR- 2025/01/29 CRDT- 2025/01/29 10:04 PHST- 2025/01/29 12:27 [medline] PHST- 2025/01/29 12:26 [pubmed] PHST- 2025/01/29 10:04 [entrez] PHST- 2025/01/29 00:00 [pmc-release] AID - 10.1177_14791641251318309 [pii] AID - 10.1177/14791641251318309 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Jan-Feb;22(1):14791641251318309. doi: 10.1177/14791641251318309. PMID- 39873719 OWN - NLM STAT- MEDLINE DCOM- 20250717 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 398 IP - 7 DP - 2025 Jul TI - Tirzepatide mitigates cognitive decline in zebrafish model of type 2 diabetes mellitus induced by high-fat diet. PG - 8861-8883 LID - 10.1007/s00210-025-03827-3 [doi] AB - In examining the enduring consequences of diabetes, recent research has focused on the anticipated outcomes of the condition. Specifically, cognitive impairment has been linked to diabetes mellitus dating back to the discovery of insulin. This study delves into the neuroprotective effects of TZP, i.e. tirzepatide a dual GIP and GLP-1 receptor agonist that works by mimicking these two gut hormones, against cognitive impairment associated with type 2 diabetes mellitus (T2DM). T2DM-like zebrafish model of varying age groups was created through a 6-week administration of a high-fat diet (HFD). Parameters such as body weight, body mass index, and blood glucose levels were monitored, and behavioural assessments (T-maze, novel tank diving test, and inhibitory avoidance test) were conducted at the conclusion of the protocol to assess learning and memory. Additionally, lipid profile biochemical parameters (MDA, AChEs, and GSH), molecular markers (IL-1beta, IL-10, TNF-alpha, Bcl-2, Bax, GSK-3beta, and AMPK), and histopathological examinations were performed. Treatment with the novel GLP-1 and GIP dual agonist TZP (10 nM/kg, i.p.) significantly ameliorated cognitive impairment, as evidenced by behavioural parameters, and restored antioxidant like GSH (p < 0.05) and catalase (p < 0.05) and anti-inflammatory marker levels, i.e. IL-10 (p < 0.05) compared to the HFD group. TZP also mitigated abnormal glucose (73.2 +/- 5.889) and lipid profiles (TG 0.159 +/- 0.0075 and TC 0.100 +/- 0.0020) in hyperglycaemic zebrafish. This study suggests that the positive effects of TZP on cognition and memory may stem from its neuroprotective capabilities, potentially attributed to its antioxidant, anti-inflammatory, and anti-apoptotic properties, as well as its ability to enhance AMPK levels as GLP-1 agonist has the potential to increase the level of AMPK. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Misra, Sakshi AU - Misra S AD - Department of Pharmacology, ISF College of Pharmacy, Ghal Kalan, GT Road, Moga, 142001, Punjab, India. FAU - Rajput, Prabha AU - Rajput P AD - Department of Pharmacology, ISF College of Pharmacy, Ghal Kalan, GT Road, Moga, 142001, Punjab, India. prabharajput1351991@gmail.com. AD - Department of Pharmacology, School of Pharmacy & Technology Management, SVKM's NMIMS University, Shirpur Campus, Shirpur, India. prabharajput1351991@gmail.com. FAU - Kaur, Amandeep AU - Kaur A AD - Department of Pharmacology, ISF College of Pharmacy, Ghal Kalan, GT Road, Moga, 142001, Punjab, India. LA - eng PT - Journal Article DEP - 20250128 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Animals MH - Zebrafish MH - Diet, High-Fat/adverse effects MH - *Cognitive Dysfunction/drug therapy/etiology/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Neuroprotective Agents/pharmacology/therapeutic use MH - Disease Models, Animal MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Gastric Inhibitory Polypeptide/agonists MH - Behavior, Animal/drug effects MH - Maze Learning/drug effects MH - *Cognition/drug effects MH - Male MH - Blood Glucose/drug effects MH - Tirzepatide OTO - NOTNLM OT - Cognitive impairment OT - Diabetes mellitus OT - Neurodegeneration OT - Tirzepatide OT - Zebrafish COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/01/28 12:35 MHDA- 2025/07/17 06:27 CRDT- 2025/01/28 11:13 PHST- 2024/11/27 00:00 [received] PHST- 2025/01/17 00:00 [accepted] PHST- 2025/07/17 06:27 [medline] PHST- 2025/01/28 12:35 [pubmed] PHST- 2025/01/28 11:13 [entrez] AID - 10.1007/s00210-025-03827-3 [pii] AID - 10.1007/s00210-025-03827-3 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul;398(7):8861-8883. doi: 10.1007/s00210-025-03827-3. Epub 2025 Jan 28. PMID- 39873334 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260917 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 20 IP - 2 DP - 2025 Mar TI - Association between glucagon-like peptide-1 agonists and risk of diabetic retinopathy: a disproportionality analysis using FDA adverse event reporting system data. PG - 147-152 LID - 10.1080/17446651.2025.2459720 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists are commonly prescribed for type 2 diabetes mellitus (T2DM). Concerns have emerged regarding their potential link to diabetic retinopathy (DR). METHODS: To evaluate the association between GLP-1 agonists and DR, a disproportionality analysis was conducted using FDA Adverse Event Reporting System (FAERS) data from Q4/2003 to Q2/2024 via OpenVigil 2.1 software. We focused on GLP-1 agonists and glucose-dependent insulinotropic polypeptide (GIP) agonist: Semaglutide, liraglutide, dulaglutide, lixisenatide, and tirzepatide, as primary suspect drugs. 'Diabetic retinopathy' was the key search term mapped to Medical Dictionary for Regulatory Activities (MedDRA) Lower-Level Terms (LLTs). We calculated Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), with 95% confidence intervals (CI) and the Evans' criteria were applied to check the significant associations. RESULTS: Semaglutide (PRR: 19.43, 95% CI: 15.17-24.88; ROR: 19.48, 95% CI: 15.20-24.96; Chi-square: 1078.08) and dulaglutide (PRR: 9.01, 95% CI: 7.11-11.42; ROR: 9.02, 95% CI: 7.11-11.44; Chi-square: 478.31) showed a strong association with DR. Tirzepatide and liraglutide showed a weaker but significant association while lixisenatide showed no significant association. CONCLUSION: GLP-1 agonists (except lixisenatide) were found to be associated with DR. These findings emphasize the need for close monitoring and further research to clarify these associations. FAU - Singh, Harmanjit AU - Singh H AD - Department of Pharmacology, Government Medical College & Hospital, Chandigarh, India. FAU - Natt, Navreet Kaur AU - Natt NK AD - Department of Health and Family Welfare, CHC Manawala, Amritsar, India. FAU - Nim, Dwividendra Kumar AU - Nim DK AUID- ORCID: 0009-0003-7823-7665 AD - Department of Pharmacology, Moti Lal Nehru Medical College, Allahabad, India. LA - eng PT - Journal Article DEP - 20250128 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 74O62BB01U (lixisenatide) SB - IM MH - Humans MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - United States Food and Drug Administration MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Diabetic Retinopathy/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Peptides/adverse effects MH - Tirzepatide/adverse effects MH - Glucagon-Like Peptide-2 Receptor MH - Semaglutide OTO - NOTNLM OT - FAERS OT - GLP-1 agonists OT - diabetic retinopathy OT - disproportionality analysis OT - liraglutide OT - semaglutide EDAT- 2025/01/28 12:34 MHDA- 2025/02/28 18:22 CRDT- 2025/01/28 07:13 PHST- 2025/02/28 18:22 [medline] PHST- 2025/01/28 12:34 [pubmed] PHST- 2025/01/28 07:13 [entrez] AID - 10.1080/17446651.2025.2459720 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2025 Mar;20(2):147-152. doi: 10.1080/17446651.2025.2459720. Epub 2025 Jan 28. PMID- 39871617 OWN - NLM STAT- MEDLINE DCOM- 20250422 LR - 20250422 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 3 DP - 2025 Mar TI - Perioperative and periprocedural management of GLP-1 receptor-based agonists and SGLT2 inhibitors: narrative review and the STOP-GAP and STOP DKA-2 algorithms. PG - 403-419 LID - 10.1080/03007995.2025.2458538 [doi] AB - The GLP-1 receptor-based agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) are major twenty first century breakthroughs in diabetes and obesity medicine but there are important safety considerations regarding the perioperative and periprocedural management of individuals who are treated with these agents. GLP-1RAs have been linked to an increased risk of retained gastric contents and pulmonary aspiration while SGLT2i can be associated with diabetic ketoacidosis. This manuscript provides a narrative review of the available evidence for perioperative and periprocedural risks in people prescribed GLP-1RAs and SGLT2i. The authors provide expert opinion-driven recommendations and algorithms on how to safely manage GLP-1RAs and SGLT2i under perioperative/periprocedural settings. FAU - Goldenberg, Ronald M AU - Goldenberg RM AUID- ORCID: 0000-0002-1788-3255 AD - LMC Diabetes & Endocrinology, Concord, Canada. FAU - Gilbert, Jeremy D AU - Gilbert JD AUID- ORCID: 0000-0001-7456-9396 AD - Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, Toronto, Canada. AD - Department of Medicine, University of Toronto, Toronto, Canada. FAU - Houlden, Robyn L AU - Houlden RL AUID- ORCID: 0000-0002-2748-4741 AD - Division of Endocrinology and Metabolism, Queen's University, Kingston, Canada. FAU - Khan, Tayyab S AU - Khan TS AUID- ORCID: 0000-0002-1713-8781 AD - Division of Endocrinology and Metabolism, St. Joseph's Healthcare Centre, London, Canada. AD - Department of Medicine, Western University, London, Canada. FAU - Makhija, Sapna AU - Makhija S AUID- ORCID: 0009-0001-6862-072X AD - GI Health Centre, Burlington, Canada. FAU - Mazer, C David AU - Mazer CD AUID- ORCID: 0000-0003-2566-4308 AD - Department of Anesthesia, St. Michael's Hospital of Unity Health Toronto, Toronto, Canada. AD - Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Canada. AD - Department of Physiology, University of Toronto, Toronto, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada. FAU - Trinacty, Jill AU - Trinacty J AUID- ORCID: 0009-0002-1774-9117 AD - LMC Diabetes & Endocrinology, Ottawa, Canada. AD - Department of Medicine, Queensway Carleton Hospital, Ottawa, Canada. AD - Bruyere Continuing Care, Ottawa, Canada. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada. AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, Toronto, Canada. AD - Department of Surgery, University of Toronto, Toronto, Canada. LA - eng PT - Journal Article PT - Review DEP - 20250131 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Curr Med Res Opin. 2025 Mar;41(3):i. doi: 10.1080/03007995.2025.2473240. PMID: 40012208 MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Algorithms MH - *Perioperative Care/methods MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Ketoacidosis/chemically induced/prevention & control OTO - NOTNLM OT - GLP-1RA OT - SGLT2i OT - aspiration OT - ketoacidosis OT - perioperative OT - periprocedure EDAT- 2025/01/28 11:26 MHDA- 2025/04/22 16:24 CRDT- 2025/01/28 03:23 PHST- 2025/04/22 16:24 [medline] PHST- 2025/01/28 11:26 [pubmed] PHST- 2025/01/28 03:23 [entrez] AID - 10.1080/03007995.2025.2458538 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Mar;41(3):403-419. doi: 10.1080/03007995.2025.2458538. Epub 2025 Jan 31. PMID- 39862389 OWN - NLM STAT- MEDLINE DCOM- 20250429 LR - 20260127 IS - 1535-2900 (Electronic) IS - 1079-2082 (Linking) VI - 82 IP - 9 DP - 2025 Apr 29 TI - Allodynia (skin tenderness) associated with semaglutide: A case series. PG - e426-e430 LID - 10.1093/ajhp/zxaf008 [doi] AB - PURPOSE: The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications are widely prescribed for management of diabetes mellitus as well as obesity or weight management. Although there have been rare reports of skin hypersensitivity associated with GLP-1RA medications, no published reports have documented allodynia or skin pain to the touch. SUMMARY: We report 4 cases of allodynia associated with dose escalation of the GLP-1RA medication semaglutide. Each patient was prescribed semaglutide for management of obesity and developed symptoms of allodynia with the 2.4-mg subcutaneous once-weekly dose. Therapy was stopped in 2 patients, both of whom had resolution of symptoms. Two patients opted to continue semaglutide despite the adverse effect, with one experiencing resolution after 4 months. No pharmacological mechanism was identified for this unique adverse drug reaction. There was a clear temporal and dose-response relationship in each of the 4 cases. CONCLUSION: The 4 cases presented had scores of 5 or 6 (probable) on the Naranjo scale. It is not known whether this is a class effect of the GLP-1RA medications or if the adverse effect will consistently resolve or improve with continuation. CI - Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2025. FAU - Stark, Jennifer AU - Stark J AD - Veterans Health Care System of the Ozarks, Fayetteville, AR, USA. FAU - Klass, Marian J AU - Klass MJ AD - Veterans Health Care System of the Ozarks, Springfield, MO, USA. FAU - Owen, Lauren AU - Owen L AD - Veterans Health Care System of the Ozarks, Fayetteville, AR, USA. LA - eng PT - Case Reports PT - Journal Article PL - England TA - Am J Health Syst Pharm JT - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JID - 9503023 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Hyperalgesia/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - adverse drug reaction OT - allodynia OT - glucagon-like peptide-1 receptor agonists OT - semaglutide EDAT- 2025/01/26 00:10 MHDA- 2025/04/29 18:31 CRDT- 2025/01/25 11:33 PHST- 2025/04/29 18:31 [medline] PHST- 2025/01/26 00:10 [pubmed] PHST- 2025/01/25 11:33 [entrez] AID - 7979230 [pii] AID - 10.1093/ajhp/zxaf008 [doi] PST - ppublish SO - Am J Health Syst Pharm. 2025 Apr 29;82(9):e426-e430. doi: 10.1093/ajhp/zxaf008. PMID- 39862040 OWN - NLM STAT- MEDLINE DCOM- 20250125 LR - 20250524 IS - 1759-7390 (Electronic) IS - 1750-8460 (Linking) VI - 86 IP - 1 DP - 2025 Jan 24 TI - Glucagon-Like Peptide-1 Receptor Agonists in the Peri-Operative Period. PG - 1-4 LID - 10.12968/hmed.2024.0566 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging as an important class of drugs in the management of Type 2 Diabetes Mellitus (T2DM) and obesity. There are rising concerns of pulmonary aspiration with these medications due to drug-induced gastroparesis. While definitive association is uncertain, it is essential to be prudent and manage these patients as per the current evidence and recommendations. FAU - Narasimhan, Purnima AU - Narasimhan P AUID- ORCID: 0000-0002-2657-8738 AD - Birmingham School of Anaesthesia, West Midlands, UK. LA - eng PT - Journal Article PT - Review DEP - 20250109 PL - Singapore TA - Br J Hosp Med (Lond) JT - British journal of hospital medicine (London, England : 2005) JID - 101257109 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - *Gastroparesis/chemically induced MH - *Perioperative Care/methods OTO - NOTNLM OT - GLP-1 receptor agonists OT - anaesthesia OT - perioperative EDAT- 2025/01/25 13:53 MHDA- 2025/01/25 13:54 CRDT- 2025/01/25 03:22 PHST- 2025/01/25 13:54 [medline] PHST- 2025/01/25 13:53 [pubmed] PHST- 2025/01/25 03:22 [entrez] AID - 10.12968/hmed.2024.0566 [doi] PST - ppublish SO - Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-4. doi: 10.12968/hmed.2024.0566. Epub 2025 Jan 9. PMID- 39858999 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20250524 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 1 DP - 2024 Dec 26 TI - The Beneficial Effects of GLP-1 Receptor Agonists Other than Their Anti-Diabetic and Anti-Obesity Properties. LID - 10.3390/medicina61010017 [doi] LID - 17 AB - As an incretin hormone, Glucagon-like peptide-1 (GLP-1) has obvious effects on blood glucose regulation and weight loss. GLP-1 receptor (GLP-1R) agonists are synthetic products that have similar effects to GLP-1 but are less prone to degradation, and they are widely used in the treatment of type 2 diabetes and obesity. In recent years, different beneficial effects of GLP-1R agonists were discovered, such as reducing ischemia-reperfusion injury, improving the function of various organs, alleviating substance use disorder, affecting tumorigenesis, regulating bone metabolism, changing gut microbiota composition, and prolonging graft survival. Therefore, GLP-1R agonists have great potential for clinical application in various diseases. Here, we briefly summarized the beneficial effects of GLP-1R agonists other than the anti-diabetic and anti-obesity effects. FAU - Lu, Chenqi AU - Lu C AD - Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China. FAU - Xu, Cong AU - Xu C AD - Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yang, Jun AU - Yang J AD - Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China. LA - eng GR - 81873624/the National Natural Science Foundation of China/ PT - Journal Article PT - Review DEP - 20241226 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Obesity/drug therapy MH - *Anti-Obesity Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptide 1/therapeutic use PMC - PMC11767243 OTO - NOTNLM OT - GLP-1 OT - GLP-1 receptor agonists OT - cardiovascular protection OT - kidney protection OT - liver protection OT - neoplasms OT - neuroprotection COIS- The authors declare no conflicts of interest. EDAT- 2025/01/25 13:53 MHDA- 2025/01/25 13:54 PMCR- 2024/12/26 CRDT- 2025/01/25 01:14 PHST- 2024/11/26 00:00 [received] PHST- 2024/12/18 00:00 [revised] PHST- 2024/12/24 00:00 [accepted] PHST- 2025/01/25 13:54 [medline] PHST- 2025/01/25 13:53 [pubmed] PHST- 2025/01/25 01:14 [entrez] PHST- 2024/12/26 00:00 [pmc-release] AID - medicina61010017 [pii] AID - medicina-61-00017 [pii] AID - 10.3390/medicina61010017 [doi] PST - epublish SO - Medicina (Kaunas). 2024 Dec 26;61(1):17. doi: 10.3390/medicina61010017. PMID- 39858442 OWN - NLM STAT- MEDLINE DCOM- 20250125 LR - 20260407 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 1 DP - 2025 Jan 1 TI - Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial. LID - 10.3390/biom15010046 [doi] LID - 46 AB - Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2-3% of the world's population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM. FAU - Petkovic-Dabic, Jelena AU - Petkovic-Dabic J AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Clinic of Skin and Venereal Diseases, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Binic, Ivana AU - Binic I AD - Faculty of Medicine, University of Nis, 18000 Nis, Serbia. FAU - Caric, Bojana AU - Caric B AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Internal Medicine, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Bozic, Ljiljana AU - Bozic L AUID- ORCID: 0000-0003-1564-2391 AD - Department of Microbiology and Immunology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Umicevic-Sipka, Sanja AU - Umicevic-Sipka S AUID- ORCID: 0009-0009-5460-8568 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Clinic of Skin and Venereal Diseases, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Bednarcuk, Natasa AU - Bednarcuk N AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Dabic, Sasa AU - Dabic S AD - Faculty of Medicine Foca, University of East Sarajevo, 71123 Istocno Sarajevo, Bosnia and Herzegovina. FAU - Situm, Mirna AU - Situm M AD - Department of Dermatology and Venerology, University Hospital Center "Sestre Milosrdnice", University of Zagreb, 10000 Zagreb, Croatia. AD - Croatian Academy of Science and Arts, 10000 Zagreb, Croatia. FAU - Popovic-Pejicic, Snjezana AU - Popovic-Pejicic S AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Internal Medicine, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Academy of Science and Arts of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Stojiljkovic, Milos P AU - Stojiljkovic MP AUID- ORCID: 0000-0001-9431-0736 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Skrbic, Ranko AU - Skrbic R AUID- ORCID: 0000-0002-6643-1781 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Academy of Science and Arts of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pathologic Physiology, First Moscow State Medical University I.M. Sechenov, 119435 Moscow, Russia. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20250101 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 9007-41-4 (C-Reactive Protein) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Psoriasis/drug therapy/complications/pathology/blood MH - *Obesity/complications/drug therapy MH - Adult MH - Metformin/therapeutic use MH - C-Reactive Protein/metabolism MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11763288 OTO - NOTNLM OT - DLQI OT - PASI OT - T2DM OT - cytokine OT - psoriasis OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2025/01/25 13:53 MHDA- 2025/01/25 13:54 PMCR- 2025/01/01 CRDT- 2025/01/25 01:11 PHST- 2024/12/02 00:00 [received] PHST- 2024/12/25 00:00 [revised] PHST- 2024/12/30 00:00 [accepted] PHST- 2025/01/25 13:54 [medline] PHST- 2025/01/25 13:53 [pubmed] PHST- 2025/01/25 01:11 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - biom15010046 [pii] AID - biomolecules-15-00046 [pii] AID - 10.3390/biom15010046 [doi] PST - epublish SO - Biomolecules. 2025 Jan 1;15(1):46. doi: 10.3390/biom15010046. PMID- 39856432 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260813 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 46 IP - 5 DP - 2025 May TI - Semaglutide administration protects cardiomyocytes in db/db mice via energetic improvement and mitochondrial quality control. PG - 1250-1261 LID - 10.1038/s41401-024-01448-9 [doi] AB - Diabetic cardiomyopathy causes end-stage heart failure, resulting in high morbidity and mortality in type 2 diabetes mellitus (T2DM) patients. Long-term treatment targeting metabolism is an emerging field in the treatment of diabetic cardiomyopathy. Semaglutide, an agonist of the glucagon-like peptide 1 receptor, is clinically approved for the treatment of T2DM and provides cardiac benefits in patients. However, the cardioprotective mechanism of semaglutide, especially its direct effects on cardiomyocytes (CMs), is not fully understood. Here, we used 8-week diabetic and obese db/db mice treated with semaglutide (200 mug.kg.d(-1), i.p.) to study its direct effect on CMs and the underlying mechanisms. Our results revealed that the consecutive application of semaglutide improved cardiac function. Increased AMPK and ULK1 phosphorylation levels were detected, accompanied by elevated [Ca(2+)](mito). Seahorse analysis revealed that semaglutide increases ATP production via elevated basal and maximum respiration rates as well as spare respiration capacity in CMs. Transmission electron microscopy revealed improved mitochondrial morphology in the cardiomyocytes of db/db mice. On the other hand, Western blot analysis revealed increased Parkin and LC3 protein expression, indicating mitophagy in CMs. Collectively, our findings demonstrate that semaglutide directly protects CMs from high-glucose damage by promoting AMPK-dependent ATP production as well as ULK1-mediated mitophagy in db/db mice. CI - (c) 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society. FAU - Tian, Meng-Yun AU - Tian MY AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Yang, Ji-Qin AU - Yang JQ AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Hu, Jin-Chuan AU - Hu JC AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Lu, Shan AU - Lu S AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. shnlu@njmu.edu.cn. FAU - Ji, Yong AU - Ji Y AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. yongji@njmu.edu.cn. AD - State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, 150081, China. yongji@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20250124 PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Cardiotonic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Myocytes, Cardiac/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - Mice MH - Male MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Cardiotonic Agents/pharmacology/therapeutic use MH - *Diabetic Cardiomyopathies/drug therapy/metabolism/prevention & control MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - *Mitochondria/drug effects/metabolism MH - Energy Metabolism/drug effects MH - *Mitochondria, Heart/drug effects/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12032422 OTO - NOTNLM OT - db/db mice OT - diabetic cardiomyopathy OT - mitochondrial calcium OT - mitophagy OT - semaglutide COIS- Competing interests: The authors declare no competing interests. EDAT- 2025/01/25 13:52 MHDA- 2025/04/26 16:18 PMCR- 2026/05/01 CRDT- 2025/01/24 23:28 PHST- 2024/08/20 00:00 [received] PHST- 2024/11/27 00:00 [accepted] PHST- 2025/04/26 16:18 [medline] PHST- 2025/01/25 13:52 [pubmed] PHST- 2025/01/24 23:28 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - 10.1038/s41401-024-01448-9 [pii] AID - 1448 [pii] AID - 10.1038/s41401-024-01448-9 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2025 May;46(5):1250-1261. doi: 10.1038/s41401-024-01448-9. Epub 2025 Jan 24. PMID- 39853913 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260307 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 17 IP - 1 DP - 2025 Jan TI - Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice. PG - e70054 LID - 10.1111/1753-0407.70054 [doi] LID - e70054 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement. METHODS: We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 +/- 11.9 years, 51.5% female, diabetes duration of 12.9 +/- 8.3 years, weight of 103.1 +/- 20.7 kg, BMI of 35.7 +/- 7.5 kg/m(2), and A1C of 8.2% +/- 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group. RESULTS: The first tertile experienced an average weight loss of -12.2% +/- 5.7% (p < 0.0001), the second tertile lost -3.5% +/- 1.4% (p < 0.0001), and the third tertile gained +2.8% +/- 3.4% (p < 0.0001). The average changes in A1C were - 0.98 +/- 1.8% (p < 0.0001), -0.56% +/- 1.4% (p < 0.001), and -0.19% +/- 1.9% (p = 0.4), respectively. A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group. CONCLUSIONS: These findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs. CI - (c) 2025 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Al-Badri, Marwa AU - Al-Badri M AUID- ORCID: 0000-0002-4998-9708 AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Dhaver, Shilton AU - Dhaver S AUID- ORCID: 0000-0002-5281-6728 AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Hamdy, Osama AU - Hamdy O AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - P30 DK036836/DK/NIDDK NIH HHS/United States PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Blood Glucose) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Exenatide/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Aged MH - Blood Glucose/metabolism/analysis MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11757277 OTO - NOTNLM OT - GLP-1 receptor agonists OT - glycemic control OT - real-world clinical practice OT - type 2 diabetes OT - weight loss COIS- O.H. receives research support from Eli Lilly and Novo Nordisk and serves on an advisory board for Abbott Nutrition. M.A. and S.D. have no disclosures relevant to this work. EDAT- 2025/01/24 17:38 MHDA- 2025/01/24 18:25 PMCR- 2025/01/23 CRDT- 2025/01/24 11:42 PHST- 2024/12/16 00:00 [received] PHST- 2025/01/10 00:00 [accepted] PHST- 2025/01/24 18:25 [medline] PHST- 2025/01/24 17:38 [pubmed] PHST- 2025/01/24 11:42 [entrez] PHST- 2025/01/23 00:00 [pmc-release] AID - JDB70054 [pii] AID - 10.1111/1753-0407.70054 [doi] PST - ppublish SO - J Diabetes. 2025 Jan;17(1):e70054. doi: 10.1111/1753-0407.70054. PMID- 39848681 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260813 IS - 1473-4257 (Electronic) IS - 0306-6800 (Print) IS - 0306-6800 (Linking) VI - 52 IP - 3 DP - 2026 Feb 27 TI - The Ethics of Ozempic and Wegovy. PG - 185-193 LID - 10.1136/jme-2024-110374 [doi] LID - e110374 AB - Semaglutide, sold under the brand names of Ozempic, Rybelsus and Wegovy, is one of the most popular drugs on the market. Manufactured by Novo Nordisk, semaglutide is the newest in a family of glucagon-like peptide-1 receptor agonists used most commonly to treat type II diabetes. To date, the results of semaglutide for the treatment of type II diabetes have been overwhelmingly positive. It is for the drug's effects on appetite suppression and weight loss, however, that have led its surge in popularity, with many hailing semaglutide as the new 'miracle drug for weight loss'. Despite its popularity, both the governmental and popular reception to the drug has largely been mixed. In this paper, we address a range of ethical concerns and argue that while many are legitimate, they do not provide conclusive reason not to prescribe semaglutide for weight loss. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. FAU - Ryan, Nanette AU - Ryan N AUID- ORCID: 0009-0007-7540-149X AD - National University of Singapore Centre for Biomedical Ethics, Singapore. FAU - Savulescu, Julian AU - Savulescu J AUID- ORCID: 0000-0003-1691-6403 AD - Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore julian.savulescu@philosophy.ox.ac.uk. AD - Uehiro Oxford Institute, University of Oxford, Oxford, UK. LA - eng PT - Journal Article DEP - 20260227 PL - England TA - J Med Ethics JT - Journal of medical ethics JID - 7513619 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13018845 OTO - NOTNLM OT - Ethics OT - Ozempic OT - Semaglutide OT - Weight loss COIS- Competing interests: Julian Savulescu is a Bioethics Committee consultant for Bayer. EDAT- 2025/01/24 00:25 MHDA- 2026/03/06 13:46 PMCR- 2026/03/26 CRDT- 2025/01/23 21:03 PHST- 2024/08/12 00:00 [received] PHST- 2024/11/28 00:00 [accepted] PHST- 2026/03/06 13:46 [medline] PHST- 2025/01/24 00:25 [pubmed] PHST- 2025/01/23 21:03 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - jme-2024-110374 [pii] AID - 10.1136/jme-2024-110374 [doi] PST - epublish SO - J Med Ethics. 2026 Feb 27;52(3):185-193. doi: 10.1136/jme-2024-110374. PMID- 39848268 OWN - NLM STAT- MEDLINE DCOM- 20250227 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 3 DP - 2025 Mar TI - Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA(1c) levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial. PG - 196-209 LID - S2213-8587(24)00304-8 [pii] LID - 10.1016/S2213-8587(24)00304-8 [doi] AB - BACKGROUND: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2.4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA(1c). METHODS: STEP-HFpEF DM, a double-blind, randomised, placebo-controlled trial conducted at 108 clinical research sites across 16 countries in Asia, Europe, and North and South America, included individuals aged 18 years or older with documented HFpEF (left ventricular ejection fraction >/=45%), type 2 diabetes, and obesity (BMI >/=30 kg/m(2)). Participants were randomly assigned (1:1), with a block size of four within each stratum using an interactive web response system, stratified by baseline BMI (<35 kg/m(2)vs >/=35 kg/m(2)), to receive either semaglutide 2.4 mg or placebo subcutaneously. The effects of semaglutide versus placebo on the efficacy endpoints were evaluated by HbA(1c) categories at baseline: low (<6.5%; <48 mmol/mol), medium (6.5% to <7.5%; 48 mmol/mol to <58 mmol/mol), and high (>/=7.5%; >/=58 mmol/mol). The dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline to 52 weeks and were assessed in all randomly assigned participants by intention to treat. Hypoglycaemia events were also analysed to assess safety in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04916470. FINDINGS: Between June 27, 2021 and Sept 2, 2022, 616 participants were enrolled and randomly assigned (mean age 68.4 years [SD 8.9]; 273 [44%] were female, 343 [56%] were male, and 519 [84%] were White). The low baseline HbA(1c) group included 227 participants (112 assigned to semaglutide and 115 to placebo), the medium baseline HbA(1c) group included 226 participants (124 assigned to semaglutide and 102 to placebo), and the high baseline HbA(1c) group included 163 participants (74 assigned to semaglutide and 89 to placebo). The median duration of follow-up in the overall trial was 401 days (IQR 400-405). The change in KCCQ-CSS from baseline to 52 weeks was 12.4 points (95% CI 8.8 to 16.0) with semaglutide versus 5.7 points (2.1 to 9.2) with placebo (mean difference 6.7 points [1.6 to 11.8]) in the low baseline HbA(1c) group, 14.5 points (11.0 to 17.9) versus 8.5 points (4.8 to 12.2; 6.0 points [0.9 to 11.1]) in the medium baseline HbA(1c) group, and 14.5 points (10.0 to 19.0) versus 4.8 points (0.7 to 8.9; 9.6 points [3.5 to 15.7]) in the high baseline HbA(1c) group (p(interaction)=0.64; p(trend)=0.46). The change in bodyweight percentage from baseline to 52 weeks was -10.8 (95% CI -12.1 to -9.5) with semaglutide versus -3.3% (-4.6 to -2.0) with placebo (mean difference -7.5% [-9.4 to -5.6]) in the low baseline HbA(1c) group, -9.6% (-10.8 to -8.3) versus -3.3% (-4.7 to -1.9; -6.3 [-8.2 to -4.4]) in the medium baseline HbA(1c) group, and -8.6% (-10.2 to -7.0) versus -3.6% (-5.2 to -2.1; -5.0 [-7.2 to -2.7]) in the high baseline HbA(1c) group (p(interaction)=0.22; p(trend)=0.083). Hypoglycaemia events occurred in 30 (10%) of 310 participants (70 events; 22.9 events per 100 person-years) in the semaglutide group compared with 21 (7%) of 306 participants in the placebo group (90 events; 29.5 events per 100 person-years). INTERPRETATION: Semaglutide 2.4 mg improved heart failure-related symptoms and physical limitations, and reduced bodyweight in patients with obesity-related HFpEF and type 2 diabetes, all independently of baseline HbA(1c), and resulted in lower rates of hypoglycaemia than placebo, despite a well controlled baseline HbA(1c) and broad use of concomitant glucose-lowering medications. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - van der Meer, Peter AU - van der Meer P AD - Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada. FAU - Patel, Shachi AU - Patel S AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. FAU - Chinnakondepalli, Khaja M AU - Chinnakondepalli KM AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. FAU - Borlaug, Barry A AU - Borlaug BA AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi, Jackson, MS, USA. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Harring, Signe AU - Harring S AD - Novo Nordisk, Soborg, Denmark. FAU - Salsali, Afshin AU - Salsali A AD - Novo Nordisk, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - von Lewinski, Dirk AU - von Lewinski D AD - Medical University of Graz, Graz, Austria. FAU - Abhayaratna, Walter AU - Abhayaratna W AD - College of Health and Medicine, The Australian National University, Canberra, ACT, Australia. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org. CN - STEP-HFpEF Trials Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT04916470 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250120 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM CIN - Lancet Diabetes Endocrinol. 2025 Mar;13(3):169-170. doi: 10.1016/S2213-8587(24)00335-8. PMID: 39848269 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Heart Failure/drug therapy/etiology/metabolism/physiopathology MH - Double-Blind Method MH - Aged MH - Middle Aged MH - *Obesity/complications MH - *Glycated Hemoglobin/analysis/metabolism MH - *Stroke Volume/drug effects MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declarations of interests MJD has been a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; has been an advisory board member for Lexicon, Pfizer, ShouTi Pharma, AstraZeneca, Zealand Pharma, and Medtronic; has been a speaker for AstraZeneca, Napp Pharmaceuticals, Novartis, and Amgen; and has received grants from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen, Sanofi-Aventis, and Eli Lilly. PvdM reports institutional payments for consultancy fees or grants from AstraZeneca, Boehringer Ingelheim, BridgeBio, Ionis, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharma Nord, and Vifor. SV reports speaking honoraria or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. BAB receives research support from the US National Institutes of Health (NIH) and the US Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, NGM, Novo Nordisk, NXT, and VADovations; and is named inventor (US patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. JB is a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. DWK reports receiving honoraria as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Corvia Medical, Ketyo, Novartis, Novo Nordisk, Pfizer, and Rivus, grant funding from AstraZeneca, Bayer, Novartis, Novo Nordisk, Pfizer, and Rivus, and has stock ownership in Gilead Sciences. SJS has received research grants from AstraZeneca, Corvia, and Pfizer, and consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Recor, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. SH, AS, and SR are employees of and shareholders in Novo Nordisk. DvL reports honoraria or consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Recardio, Sanofi, Sanova, and Vaxxinity. WA reports honoraria or consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk. MCP has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novo Nordisk, Novartis, Pharmacosmos, Roche, and SQ Innovations, and served on committees or consulted for AbbVie, Akero, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Cardiorentis, Corvia, Eli Lilly, Horizon Therapeutics, LIB Therapeutics, Moderna, New Amsterdam, Novartis, Novo Nordisk, Pharmacosmos, Siemens, SQ Innovations, Takeda, Teikoku, and Vifor. MNK served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stocks in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received other research support from AstraZeneca. All other authors declare no competing interests. EDAT- 2025/01/24 00:26 MHDA- 2025/02/28 00:20 CRDT- 2025/01/23 18:52 PHST- 2024/06/06 00:00 [received] PHST- 2024/09/09 00:00 [revised] PHST- 2024/09/16 00:00 [accepted] PHST- 2025/02/28 00:20 [medline] PHST- 2025/01/24 00:26 [pubmed] PHST- 2025/01/23 18:52 [entrez] AID - S2213-8587(24)00304-8 [pii] AID - 10.1016/S2213-8587(24)00304-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Mar;13(3):196-209. doi: 10.1016/S2213-8587(24)00304-8. Epub 2025 Jan 20. PMID- 39847346 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260921 IS - 2168-619X (Electronic) IS - 2168-6181 (Print) IS - 2168-6181 (Linking) VI - 151 IP - 3 DP - 2025 Mar 1 TI - GLP-1RA Use and Thyroid Cancer Risk. PG - 243-252 LID - 10.1001/jamaoto.2024.4852 [doi] AB - IMPORTANCE: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RA) demands a better understanding of their association with thyroid cancer. OBJECTIVE: To estimate the risk of incident thyroid cancer among adults with type 2 diabetes being treated with GLP-1RA vs other common glucose-lowering medications. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study using claims data for enrollees in commercial, Medicare Advantage, and Medicare fee-for-service plans across the US. Eligible participants were adults with type 2 diabetes at moderate risk for cardiovascular disease and without history of thyroid cancer who had newly filled prescriptions for GLP-1RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), dipeptidyl peptidase-4 inhibitor (DPP4i), or sulfonylurea from January 1, 2014, to December 31, 2021. Data were analyzed February 1 to October 31, 2024. MAIN OUTCOMES AND MEASURES: Overall and piecewise (<1, 1-2, and >/=2 years since treatment initiation) hazard ratios (HRs) for thyroid cancer with use of GLP-1RA vs the other 3 drug classes were estimated using inverse propensity score weighted Cox proportional hazards models. Modified intention-to-treat (mITT) (primary) and as-treated (sensitivity) analyses were performed. RESULTS: Of 351 913 patients (mean [SD] age, 65.3 [8.5] years; 173 391 [49.3%] females and 178 522 [50.7%] males), 41 112 started treatment with GLP-1RA; 76 093, with DPP4i; 43 499, with SGLT2i; and 191 209, with sulfonylurea therapy. The numbers of patients diagnosed with thyroid cancer were 69 (0.17%) in the GLP-1RA group, 172 (0.23%) in the DPP4i group, 72 (0.17%) in the SGLT2i group, and 381 (0.20%) in the sulfonylurea group. In the mITT analysis, GLP-1RA initiation was not significantly associated with increased overall risk for thyroid cancer compared to the other 3 diabetes drugs (HR, 1.24; 95% CI, 0.88-1.76). However, the risk for thyroid cancer was significantly higher within the first year after GLP-1RA initiation (HR, 1.85; 95% CI, 1.11-3.08) and was amplified in the overall as-treated analysis that censored patients when therapy was discontinued or another medication was added (HR, 2.07; 95% CI, 1.10-3.95). CONCLUSIONS AND RELEVANCE: This secondary analysis of a target trial emulation of a comparative effectiveness study found that despite the low absolute risk of thyroid cancer among patients receiving GLP-1RA therapy, there was an increased risk of new thyroid cancer diagnoses within the first year of GLP-1RA initiation compared to 3 other diabetes drugs. This finding may have been due to enhanced early detection; therefore, further research is necessary to understand the underlying causes of this association. FAU - Brito, Juan P AU - Brito JP AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Herrin, Jeph AU - Herrin J AD - Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. AD - OptumLabs, Eden Prairie, Minnesota. FAU - Singh Ospina, Naykky M AU - Singh Ospina NM AD - Division of Endocrinology, Department of Medicine, University of Florida, Gainesville. FAU - Montori, Victor M AU - Montori VM AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Toro-Tobon, David AU - Toro-Tobon D AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, University of Miami Miller School of Medicine, Miami, Florida. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. AD - OptumLabs, Eden Prairie, Minnesota. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - Shao, Hui AU - Shao H AD - Emory Global Diabetes Research Center of Woodruff Health Sciences Center, Emory University, Atlanta, Georgia. AD - Hubert Department of Global Health, Rollin School of Public Health, Emory University, Atlanta, Georgia. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairie, Minnesota. AD - Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore. AD - University of Maryland Institute for Health Computing, Bethesda. LA - eng SI - ClinicalTrials.gov/NCT05214573 GR - K08 CA248972/CA/NCI NIH HHS/United States GR - P30 DK111024/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - JAMA Otolaryngol Head Neck Surg JT - JAMA otolaryngology-- head & neck surgery JID - 101589542 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - Female MH - Male MH - *Thyroid Neoplasms/epidemiology/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - United States/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Incidence MH - Sulfonylurea Compounds/therapeutic use/adverse effects MH - Risk Factors PMC - PMC11907303 COIS- Conflict of Interest Disclosures: Dr Umpierrez reported grants from Dexcom and Abbott and serving on the advisory boards of GlyCare and Dexcom outside the submitted work. Dr Galindo reported grants from Novo Nordisk and consulting/advisory fees from Eli Lilly and Novo Nordisk outside the submitted work. Dr McCoy reported grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, and the American Diabetes Association, and personal fees from the American Diabetes Association, Yale New Haven Health System, and EmmiEducate outside the submitted work. No other disclosures were reported. EDAT- 2025/01/23 12:36 MHDA- 2025/03/13 14:07 PMCR- 2026/01/23 CRDT- 2025/01/23 11:32 PHST- 2025/03/13 14:07 [medline] PHST- 2025/01/23 12:36 [pubmed] PHST- 2025/01/23 11:32 [entrez] PHST- 2026/01/23 00:00 [pmc-release] AID - 2829462 [pii] AID - ooi240099 [pii] AID - 10.1001/jamaoto.2024.4852 [doi] PST - ppublish SO - JAMA Otolaryngol Head Neck Surg. 2025 Mar 1;151(3):243-252. doi: 10.1001/jamaoto.2024.4852. PMID- 39840515 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260812 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon-like peptide-1 receptor agonist therapy in UK primary care: A retrospective, real-world study. PG - 2086-2095 LID - 10.1111/dom.16201 [doi] AB - AIMS: Evaluate glycated haemoglobin (HbA1c) and weight changes after 6 months of once-weekly (QW) injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in UK primary care. MATERIALS AND METHODS: Retrospective, non-interventional study, using the Clinical Practice Research Datalink Aurum primary care database, identified adults with type 2 diabetes (T2D) newly initiating a QW injectable GLP-1 RA between January 2020 and November 2021. Dual primary outcomes were proportion of patients with (1) HbA1c < 7% (<53 mmol/mol) and (2) weight loss categories (from 0% to 15+%) after 6 months of continuous GLP-1 RA therapy. RESULTS: The study cohort comprised 10 816 adults: mean +/- standard deviation age 58.8 +/- 11.4 years, baseline HbA1c 9.3% +/- 1.7% (78.1 +/- 18.6 mmol/mol) and body mass index 36.6 +/- 7.2 kg/m(2). Of 5236 patients with data, 32.8% achieved HbA1c < 7% after 6 months; this proportion was higher for time since T2D diagnosis <5 years (34.1%) versus longer disease duration: >/=5-<10 years (28.0%), >/=10-<15 years (18.7%) and >/=15 years (19.3%). Of 3963 patients with weight data, 22.0% did not lose weight; 34.0%, 27.0%, 11.4% and 5.6% achieved weight reductions of >0%-<5%, >/=5%-<10%, >/=10%-<15% and >/=15%, respectively. No major differences in weight loss were observed by diabetes duration. CONCLUSIONS: Two thirds of T2D patients receiving QW injectable GLP-1 RA for 6 months did not attain target HbA1c < 7%, and less than half and one-quarter of patients achieved >/=5% and >/=10% weight loss, respectively. Results suggest an unmet need for better clinical management of T2D in UK primary care. CI - (c) 2025 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gulati, Kunal AU - Gulati K AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Wijndaele, Katrien AU - Wijndaele K AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Webb, Joanne AU - Webb J AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - von Arx, Lill-Brith AU - von Arx LB AD - Eli Lilly and Company, Herlev, Denmark. FAU - Seif, Monica AU - Seif M AD - Adelphi Real World, Bollington, UK. FAU - Jennison, Thomas AU - Jennison T AD - Adelphi Real World, Bollington, UK. FAU - Geneidat, Antonia AU - Geneidat A AD - Adelphi Real World, Bollington, UK. FAU - Wild, Rosie AU - Wild R AD - Adelphi Real World, Bollington, UK. FAU - Wood, Robert AU - Wood R AD - Adelphi Real World, Bollington, UK. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK. LA - eng GR - Eli Lilly and Company/ PT - Journal Article DEP - 20250122 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Glycated Hemoglobin/analysis MH - Middle Aged MH - Male MH - Female MH - Primary Health Care MH - United Kingdom/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Weight Loss/drug effects MH - Body Weight/drug effects MH - Adult MH - Drug Administration Schedule MH - Treatment Outcome PMC - PMC11885099 OTO - NOTNLM OT - GLP-1 analogue OT - glycaemic control OT - primary care OT - type 2 diabetes OT - weight control COIS- Kamlesh Khunti has acted as a consultant and speaker for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Napp, Novartis, Novo Nordisk, Roche, Sanofi-Aventis and Servier; has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi-Aventis; and is the UK Study Lead for Oramed Pharmaceuticals and Applied Therapeutics. Joanne Webb, Kunal Gulati, Lill-Brith von Arx and Katrien Wijndaele are full-time employees and stock holders of Eli Lilly and Company. Monica Seif, Thomas Jennison, Antonia Geneidat and Rosie Wild are full-time employees of Adelphi Real-World, which received funds from Eli Lilly and Company to conduct this research. Robert Wood was a full-time employee of Adelphi Real-World at the time this work was conducted and prepared for publication. EDAT- 2025/01/22 06:26 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/01/22 05:33 PHST- 2024/12/18 00:00 [revised] PHST- 2024/09/03 00:00 [received] PHST- 2024/12/24 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/22 06:26 [pubmed] PHST- 2025/01/22 05:33 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16201 [pii] AID - 10.1111/dom.16201 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):2086-2095. doi: 10.1111/dom.16201. Epub 2025 Jan 22. PMID- 39838854 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank. PG - 1845-1858 LID - 10.1111/dom.16178 [doi] AB - AIMS: Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank. MATERIALS AND METHODS: All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self-reported white British (N = 408 774), white European (N = 50 314), South Asian (N = 7667), multiple-ancestry groups (N = 10 437) or African-Caribbean (N = 7641) subsets. All ancestries were subsequently combined in an inverse variance-weighted fixed effects meta-analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants). RESULTS: Associations were identified between GLP1R variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626-G, odds ratio [OR] 0.851 [confidence interval, CI 0.79-0.92], risk-taking behaviour: rs75408972-T, OR 1.05 [CI 1.03-1.08] or chronic pain: rs9296280-C, OR 0.645 [CI 0.54-0.78]). The trans-ancestry meta-analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of GLP1R. CONCLUSIONS: GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hayman, Madeleine M E AU - Hayman MME AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. AD - Deanery of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Edinburgh, UK. FAU - Jones, Waneisha AU - Jones W AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. FAU - Aman, Alisha AU - Aman A AD - College of Medical, Veterinary, and Life Sciences, Graduate School, University of Glasgow, Glasgow, UK. FAU - Ward, Joey AU - Ward J AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. FAU - Anderson, Jana AU - Anderson J AUID- ORCID: 0000-0001-7290-6635 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. FAU - Lyall, Donald M AU - Lyall DM AUID- ORCID: 0000-0003-3850-1487 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. FAU - Pell, Jill P AU - Pell JP AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Welsh, Paul AU - Welsh P AUID- ORCID: 0000-0002-7970-3643 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Strawbridge, Rona J AU - Strawbridge RJ AUID- ORCID: 0000-0001-8506-3585 AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. AD - Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden. LA - eng GR - MRC_/Medical Research Council/United Kingdom GR - MR/S003061/1/Health Data Research UK/ GR - BHF_/British Heart Foundation/United Kingdom GR - Department of Health, UK/ GR - Northwest Regional Development Agency/ GR - WT_/Wellcome Trust/United Kingdom GR - Welsh Assembly Government/ GR - Scottish Government/ PT - Journal Article DEP - 20250122 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Afro-Caribbean people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biological Specimen Banks MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/genetics/drug therapy MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Mental Disorders/genetics/epidemiology MH - Phenotype MH - Polymorphism, Single Nucleotide MH - UK Biobank MH - United Kingdom/epidemiology MH - White People/genetics MH - South Asian People/genetics MH - Caribbean People/genetics PMC - PMC11885074 OTO - NOTNLM OT - cardiovascular disease OT - incretin therapy OT - meta-analysis OT - population study OT - type 2 diabetes COIS- Paul Welsh reports grant income from Roche Diagnostics, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work and speaker fees from Novo Nordisk and Raisio outside the submitted work. Naveed Sattar has received grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics outside the submitted work and has consulted for and/or received speaker honoraria from Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics and Sanofi. The other authors have no conflicts of interest to declare. EDAT- 2025/01/22 06:27 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/01/22 03:03 PHST- 2024/12/18 00:00 [revised] PHST- 2024/10/23 00:00 [received] PHST- 2024/12/27 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/22 06:27 [pubmed] PHST- 2025/01/22 03:03 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16178 [pii] AID - 10.1111/dom.16178 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1845-1858. doi: 10.1111/dom.16178. Epub 2025 Jan 22. PMID- 39833406 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20261010 IS - 1546-170X (Electronic) IS - 1078-8956 (Linking) VI - 31 IP - 3 DP - 2025 Mar TI - Mapping the effectiveness and risks of GLP-1 receptor agonists. PG - 951-962 LID - 10.1038/s41591-024-03412-w [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Xie, Yan AU - Xie Y AUID- ORCID: 0000-0002-2457-9382 AD - Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA. AD - Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA. AD - Division of Pharmacoepidemiology, Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA. AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. FAU - Choi, Taeyoung AU - Choi T AD - Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA. AD - Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA. FAU - Al-Aly, Ziyad AU - Al-Aly Z AUID- ORCID: 0000-0002-2600-0434 AD - Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA. zalaly@gmail.com. AD - Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA. zalaly@gmail.com. AD - Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. zalaly@gmail.com. AD - Nephrology Section, Medicine Service, VA St. Louis Health Care System, St. Louis, MO, USA. zalaly@gmail.com. AD - Institute for Public Health, Washington University in St. Louis, St. Louis, MO, USA. zalaly@gmail.com. LA - eng PT - Journal Article DEP - 20250120 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM EIN - Nat Med. 2025 Mar;31(3):1038. doi: 10.1038/s41591-025-03542-9. PMID: 39891006 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Female MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Middle Aged MH - Sulfonylurea Compounds/therapeutic use/adverse effects MH - Aged MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - United States COIS- Competing interests: Y.X. and Z.A.A. are uncompensated consultants for Pfizer. No other potential competing interests relevant to this article are reported. EDAT- 2025/01/21 09:02 MHDA- 2025/03/20 06:24 CRDT- 2025/01/20 23:24 PHST- 2024/06/14 00:00 [received] PHST- 2024/11/12 00:00 [accepted] PHST- 2025/03/20 06:24 [medline] PHST- 2025/01/21 09:02 [pubmed] PHST- 2025/01/20 23:24 [entrez] AID - 10.1038/s41591-024-03412-w [pii] AID - 10.1038/s41591-024-03412-w [doi] PST - ppublish SO - Nat Med. 2025 Mar;31(3):951-962. doi: 10.1038/s41591-024-03412-w. Epub 2025 Jan 20. PMID- 39828939 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Beyond glycated haemoglobin: Modelling contemporary management of type 2 diabetes with the updated Cardiff model. PG - 1752-1761 LID - 10.1111/dom.16141 [doi] AB - AIMS: Recommendations on the use of newer type 2 diabetes (T2D) treatments (e.g., SGLT2 inhibitors and GLP-1 receptor agonists [RA]) in contemporary clinical guidelines necessitate a change in how T2D models approach therapy selection and escalation. Dynamic, person-centric clinical decision-making considers factors beyond a patient's HbA1c and glycaemic targets, including cardiovascular (CV) risk, comorbidities and bodyweight. This study aimed to update the existing Cardiff T2D health economic model to reflect modern T2D management and to remain fit-for-purpose in supporting decision-making. MATERIALS AND METHODS: The Cardiff T2D model's therapy selection/escalation module was updated from a conventional, glucose-centric to a holistic approach. Risk factor progression equations were updated based on UKPDS90; the cardio-kidney-metabolic benefits of SGLT2i and GLP-1 RA were captured via novel risk equations derived from relevant outcomes trial data. The significance of the updates was illustrated by comparing predicted outcomes and costs for a newly diagnosed T2D population between conventional and holistic approaches to disease management, where the latter represents recent treatment guidelines. RESULTS: A holistic approach to therapy selection/escalation enables early introduction of SGLT2i and GLP-1 RA in modelled pathways in a manner aligned to guidelines and primarily due to elevated CV risk. Compared with a conventional approach, only considering HbA1c, patients experience fewer clinical events and gain additional health benefits. CONCLUSIONS: Predictions based on a glucose-centric approach to therapy are likely to deviate from real-world observations. A holistic approach is more able to capture the nuances of contemporary clinical practice. T2D modelling must evolve to remain robust and relevant. CI - (c) 2025 AstraZeneca and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - McEwan, Phil AU - McEwan P AUID- ORCID: 0000-0001-7488-9058 AD - Health Economics and Outcomes Research Ltd., Cardiff, UK. FAU - Foos, Volker AU - Foos V AD - Health Economics and Outcomes Research Ltd., Cardiff, UK. FAU - Roberts, Geraint AU - Roberts G AUID- ORCID: 0000-0003-2006-4581 AD - Health Economics and Outcomes Research Ltd., Cardiff, UK. FAU - Jenkins, Robert H AU - Jenkins RH AD - Health Economics and Outcomes Research Ltd., Cardiff, UK. FAU - Evans, Marc AU - Evans M AUID- ORCID: 0000-0003-0671-0778 AD - Diabetes Resource Centre, University Hospital Llandough, Cardiff, UK. FAU - Wheeler, David C AU - Wheeler DC AD - UK Centre for Kidney and Bladder Health, University College London, London, UK. FAU - Chen, Jieling AU - Chen J AD - AstraZeneca R&D Pharmaceuticals, Gaithersburg, Maryland, USA. LA - eng GR - AstraZeneca/ PT - Journal Article DEP - 20250119 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/economics/epidemiology MH - *Glycated Hemoglobin/analysis MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Models, Economic MH - Blood Glucose MH - Male MH - Clinical Decision-Making MH - Female MH - Middle Aged MH - Practice Guidelines as Topic MH - Cardiovascular Diseases/prevention & control PMC - PMC11885066 OTO - NOTNLM OT - GLP-1 OT - SGLT2 inhibitor OT - cardiovascular disease OT - health economics OT - pharmaco-economics COIS- JC is an employee of AstraZeneca. PM, VF, GR and RJ are employees of Health Economics and Outcomes Research Ltd., who received fees from AstraZeneca in relation to this study. ME has received consulting fees or honoraria from AstraZeneca, Novo Nordisk, Napp, MSD, Sunovion and Novartis, and lecture/speaker bureau fees from AstraZeneca, Novo Nordisk, Napp, Mundipharma, Sunovion and Novartis. DCW has received consulting fees or honoraria from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eledon, Galderma, GlaxoSmithKline, Janssen, Menarini, Merck, Pharmacosmos, ProKidney, Tricida and Vifor. EDAT- 2025/01/20 22:51 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/01/20 00:33 PHST- 2024/11/29 00:00 [revised] PHST- 2024/08/30 00:00 [received] PHST- 2024/12/08 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/20 22:51 [pubmed] PHST- 2025/01/20 00:33 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16141 [pii] AID - 10.1111/dom.16141 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1752-1761. doi: 10.1111/dom.16141. Epub 2025 Jan 19. PMID- 39828025 OWN - NLM STAT- MEDLINE DCOM- 20250328 LR - 20250606 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 222 DP - 2025 Apr TI - Comparison of the effectiveness and safety of GLP-1 receptor agonists for type 2 diabetes mellitus patients with overweight/obesity: A systematic review and network meta-analysis. PG - 111999 LID - S0168-8227(25)00013-0 [pii] LID - 10.1016/j.diabres.2025.111999 [doi] AB - OBJECTIVE: To evaluate the effectiveness and safety of different Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating type 2 diabetes mellitus (T2DM) with overweight/obesity using a systematic review and network meta-analysis. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science up to December 20, 2024, for randomized controlled trials (RCTs) involving T2DM patients with overweight/obesity treated with GLP-1RAs, with the control group receiving either a placebo or another GLP-1RA. We conducted a network meta-analysis assessed evidence using CINeMA. RESULTS: A total of 4548 articles were retrieved, and 41 RCTs were included, comprising 15,126 patients and 13 different GLP-1RAs. Tirzepatide showed superior effects in lowering blood glucose (Compared with placebo, increased glycated hemoglobin: -1.64 (-1.94, -1.35), increased fasting blood glucose: -2.10 (-2.95, -1.25)) and weight loss (Compared with placebo, increased weight: -9.89 (-11.29, -8.49), rincreased BMI: -3.85 (-4.71, -2.99)). However, clinical efficacy of GLP-1RAs in lipid levels, blood pressure, and pancreatic function was not widely observed. Adverse reactions were significant with GLP-1RAs, but overall acceptable. CONCLUSION: GLP-1RAs demonstrate efficacy and safety in T2DM patients with overweight/obesity, with certain advantages over other drugs. However, due to limitations in the number and quality of included studies, conclusions should be interpreted with caution. CI - Copyright (c) 2025. Published by Elsevier B.V. FAU - Wen, Zhige AU - Wen Z AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Sun, Wenjie AU - Sun W AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Wang, Haoshuo AU - Wang H AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Chang, Ruiting AU - Chang R AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Wang, Jialing AU - Wang J AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Song, Changheng AU - Song C AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. FAU - Zhang, Shan AU - Zhang S AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. Electronic address: 8065@gamyy.cn. FAU - Ni, Qing AU - Ni Q AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. Electronic address: niqing@gamyy.cn. FAU - An, Xuedong AU - An X AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, China. Electronic address: Doctor_anxd@163.com. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250117 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/complications/drug therapy MH - *Overweight/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 Receptor Agonists OT - Network Meta-Analysis OT - Overweight/Obesity OT - Systematic Review OT - Type 2 Diabetes Mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/20 22:54 MHDA- 2025/03/29 16:14 CRDT- 2025/01/19 19:16 PHST- 2024/10/06 00:00 [received] PHST- 2025/01/06 00:00 [revised] PHST- 2025/01/07 00:00 [accepted] PHST- 2025/03/29 16:14 [medline] PHST- 2025/01/20 22:54 [pubmed] PHST- 2025/01/19 19:16 [entrez] AID - S0168-8227(25)00013-0 [pii] AID - 10.1016/j.diabres.2025.111999 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Apr;222:111999. doi: 10.1016/j.diabres.2025.111999. Epub 2025 Jan 17. PMID- 39827023 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 47 IP - 4 DP - 2025 Apr TI - Real-World Treatment Patterns Among US Patients With Type 2 Diabetes Mellitus Initiating Treatment With Once Weekly Semaglutide for Diabetes. PG - 277-283 LID - S0149-2918(24)00418-1 [pii] LID - 10.1016/j.clinthera.2024.12.014 [doi] AB - PURPOSE: Injectable once weekly semaglutide for diabetes (OW sema) is a medication approved in 2017 for the treatment of patients with type 2 diabetes (T2DM). In clinical trials, OW sema has been shown to be effective at helping patients achieve glycemic targets. However, more data are needed to understand how patients who initiate treatment with OW sema are treated in the real world and to aid prescribers in making treatment decisions. This study characterized noninsulin antidiabetic medication use patterns among US patients with T2DM initiating treatment with OW sema. METHODS: In this retrospective, claims-based study, patients (15,588) were included if they had at least 1 claim for OW sema between January 1, 2018 and December 31, 2019, were at least 18 years old, were continuously enrolled in the health plan, and had at least 1 claim indicating a diagnosis of T2DM. All patients had at least 1 line of therapy (LOT) that started on the date of the first fill for OW sema. Data related to pre-index date demographics and clinical characteristics were collected, as were data on patient regimens and LOTs. The length of the LOT was calculated, and the top 10 noninsulin treatment regimens were reported in each LOT. FINDINGS: In the first LOT, OW sema monotherapy was the most common regimen. More than one third (36.5%) of patients had 1 LOT until the end of follow-up and most patients who had a second (52.1%) or third (72.0%) LOT continued it to the end of the study. Among the top 10 regimens, 42.2% of patients with a second LOT and 45.8% of patients with a third LOT had an LOT that included OW sema. IMPLICATIONS: This study describes medication regimens within the first year of OW sema use. Among patients initiating OW sema, monotherapy was the most common regimen. These results provide insight into real-world usage patterns of this medication. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Frazer, Monica AU - Frazer M AD - QualityMetric, Johnston, Rhode Island; Optum, Eden Prairie, Minnesota. FAU - Sargent, Andrew AU - Sargent A AD - Optum, Eden Prairie, Minnesota. FAU - Leszko, Michael AU - Leszko M AD - Optum, Eden Prairie, Minnesota. FAU - Buysman, Erin AU - Buysman E AD - Optum, Eden Prairie, Minnesota. FAU - Gronroos, Noelle N AU - Gronroos NN AD - Optum, Eden Prairie, Minnesota. Electronic address: Noelle.gronroos@optum.com. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk Inc, Plainsboro, New Jersey. LA - eng PT - Journal Article DEP - 20250117 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - United States MH - Aged MH - Drug Administration Schedule MH - Adult MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Blood Glucose/drug effects MH - Glycated Hemoglobin MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - Real-world evidence OT - Semaglutide OT - Treatment patterns COIS- Declaration of competing interest Caroline Swift, Sara Alvarez, Tyler J. Dunn, and Josh Noone are employees of Novo Nordisk. Monica Frazer was an employee of Optum at the time the study was conducted and is currently employed at QualityMetric. Andrew Sargent, Michael Leszko, Noelle N. Gronroos, and Erin Buysman are employees of Optum. EDAT- 2025/01/20 22:53 MHDA- 2025/03/14 11:18 CRDT- 2025/01/18 21:53 PHST- 2024/03/06 00:00 [received] PHST- 2024/12/02 00:00 [revised] PHST- 2024/12/25 00:00 [accepted] PHST- 2025/03/14 11:18 [medline] PHST- 2025/01/20 22:53 [pubmed] PHST- 2025/01/18 21:53 [entrez] AID - S0149-2918(24)00418-1 [pii] AID - 10.1016/j.clinthera.2024.12.014 [doi] PST - ppublish SO - Clin Ther. 2025 Apr;47(4):277-283. doi: 10.1016/j.clinthera.2024.12.014. Epub 2025 Jan 17. PMID- 39826595 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 2 DP - 2025 Mar TI - Use of glucagon-like peptide-1 receptor agonists in people with history of acute pancreatitis: TriNetX analysis. PG - 101613 LID - S1262-3636(25)00009-6 [pii] LID - 10.1016/j.diabet.2025.101613 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in subjects with type 2 diabetes (T2D) and obesity. However, concerns over their association with acute pancreatitis (AP) have emerged. Our aim was to evaluate the risk of recurrence of AP in subjects on GLP-1RAs with a history of AP. METHODS: This retrospective study deployed the TriNetX platform. We identified adult cohorts of subjects with a history of AP and analyzed the impact of individual medications (GLP-1RAs, SGLT2i, or DPP4i) on the risk of recurrence of AP. To adjust for baseline differences, propensity score matching was done in cohorts with and without risk factors for AP. RESULTS: Our analysis of 672,069 patients with a history of AP and T2D revealed significant risk reductions associated with GLP-1RAs compared to other treatments. Over one to five years, GLP-1RAs consistently showed a lower risk of AP recurrence compared to SGLT2i and DPP-4i. Specifically, over a one-year period, GLP-1RAs users had a risk reduction of -0.071 (95 % CI:0.085 to -0.057) (p < 0.001) compared to SGLT2i, and -0.064 (95 % CI:0.080 to -0.048) (p< 0.001) compared to DPP-4i. These trends persisted, with the risk differences further widening by the fifth year to -0.086 and -0.094, respectively. CONCLUSION: Based on our findings, we conclude that GLP-1RAs may be safely used in subjects with a history of acute pancreatitis. While our analysis showed that there was a significantly lower risk of AP recurrence in subjects on GLP-1compared to DPP-IV inhibitors and SGLT2 inhibitors, as this is a retrospective analysis we suggest that these findings need to be confirmed in prospective studies. CI - Copyright (c) 2025. Published by Elsevier Masson SAS. FAU - Nassar, Mahmoud AU - Nassar M AD - Endocrine fellow, Division of Endocrinology, Diabetes and Metabolism University at Buffalo, Buffalo, NY, USA. FAU - Abosheaishaa, Hazem AU - Abosheaishaa H AD - Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Misra, Anoop AU - Misra A AD - Chairman, Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chairman, National Diabetes, Obesity and Cholesterol Foundation (N-DOC), President, Diabetes Foundation (India) (DFI) India. FAU - Dandona, Paresh AU - Dandona P AD - Professor of Medicine, Division of Endocrinology and Metabolism, Jacobs School of Medicine, University at Buffalo, Buffalo, NY, USA. FAU - Ghanim, Husam AU - Ghanim H AD - Diabetes and Endocrinology Research Lab, Research Associate Professor, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA. FAU - Chaudhuri, Ajay AU - Chaudhuri A AD - Professor of Medicine, Division of Endocrinology and Metabolism, Jacobs School of Medicine, University at Buffalo, Buffalo, NY, USA. Electronic address: achaudhu@buffalo.edu. LA - eng PT - Journal Article DEP - 20250117 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Pancreatitis/epidemiology/chemically induced MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Recurrence MH - Acute Disease OTO - NOTNLM OT - DPP-4i OT - GLP-1RAs OT - Pancreatitis OT - SGLT2i OT - T2D OT - TriNetx COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/20 22:54 MHDA- 2025/03/03 00:54 CRDT- 2025/01/18 19:13 PHST- 2024/08/29 00:00 [received] PHST- 2025/01/07 00:00 [revised] PHST- 2025/01/11 00:00 [accepted] PHST- 2025/03/03 00:54 [medline] PHST- 2025/01/20 22:54 [pubmed] PHST- 2025/01/18 19:13 [entrez] AID - S1262-3636(25)00009-6 [pii] AID - 10.1016/j.diabet.2025.101613 [doi] PST - ppublish SO - Diabetes Metab. 2025 Mar;51(2):101613. doi: 10.1016/j.diabet.2025.101613. Epub 2025 Jan 17. PMID- 39824696 OWN - NLM STAT- MEDLINE DCOM- 20250129 LR - 20260417 IS - 1871-403X (Print) IS - 1871-403X (Linking) VI - 18 IP - 6 DP - 2024 Nov-Dec TI - Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis. PG - 457-464 LID - S1871-403X(25)00003-1 [pii] LID - 10.1016/j.orcp.2025.01.002 [doi] AB - OBJECTIVE: To explore the effects of semaglutide versus placebo on body weight (BW) by subgroups of baseline characteristics. METHODS: In STEP 6, Japanese and Korean adults with overweight or obesity were randomized to subcutaneous semaglutide 2.4 mg, semaglutide 1.7 mg, or placebo for 68 weeks. A subset of Japanese participants with type 2 diabetes (T2D) was also included. In this post-hoc analysis, change from baseline in BW (%) was assessed by subgroups of baseline characteristics including baseline BW, body mass index, age, sex, glycemic status, dyslipidemia, and hypertension. RESULTS: Of 401 participants (148 female and 253 male) included, the estimated mean change in BW was clinically relevant across all subgroups for semaglutide 2.4 mg, ranging from -9.40 % to -16.42 %. Estimated treatment differences also favored both semaglutide doses versus placebo. Significant treatment-by-subgroup interactions were observed for sex with semaglutide 1.7 mg and 2.4 mg versus placebo at week 68 (p = 0.0008 and p = 0.0005, respectively). Significant treatment-by-subgroup interactions were also observed for presence of T2D and dyslipidemia at baseline, for semaglutide 2.4 mg versus placebo only (p = 0.0381 and p = 0.0181, respectively). CONCLUSIONS: Semaglutide reduces BW in a wide demographic of people with a range of weight-related comorbidities in an East Asian population. CI - Copyright (c) 2025. Published by Elsevier Ltd. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. Electronic address: kadowaki@toranomon.kkr.or.jp. FAU - Lee, Sang Yeoup AU - Lee SY AD - Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea; Department of Medical Education, Pusan National University School of Medicine, Yangsan, South Korea. FAU - Ogawa, Wataru AU - Ogawa W AD - Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Overvad, Maria AU - Overvad M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tobe, Kazuyuki AU - Tobe K AD - First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. Electronic address: limsoo@snu.ac.kr. CN - STEP 6 investigators LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250116 PL - Netherlands TA - Obes Res Clin Pract JT - Obesity research & clinical practice JID - 101303911 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - East Asian People MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Japan MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy MH - Republic of Korea MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Clinical characteristics OT - GLP-1 OT - Obesity OT - Type 2 diabetes OT - Weight management COIS- Declaration of Competing Interest TK reports honoraria for lectures from Astellas Pharma Inc., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., FUJIFILM Toyama Chemical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.; research grant funding from Asahi Mutual Life Insurance Company, Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; and advisory board consulting fees from Abbott Japan LLC., Medtronic Japan Co., Ltd., and Novo Nordisk Pharma Ltd. SYL reports honoraria for lectures from Novo Nordisk. WO has received lecture fees from Abbott Japan LLC, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd., and Sumitomo Pharma; research funding from Abbott Diabetes Care UK Ltd., Nippon Boehringer Ingelheim, Nippon Eli Lilly Japan K.K., Noster, Novo Nordisk Pharma Ltd., Sumitomo Pharma, and Teijin Pharma; and subsidies or donations from Kowa Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Sumitomo Pharma, Takeda Pharmaceutical, and Teijin Pharma. TN is an employee and shareholder of Novo Nordisk. MO is an employee of Novo Nordisk. KT received lecture fees from Kowa Pharmaceutical Co. Ltd, MSD K.K., and Novo Nordisk Pharma Ltd., and grants from Asahi Kasei Pharma Corporation, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Heiseikai Medical corporation association Sakurai Hospital, Japan Diabetes Foundation Kuwayamakai Medical corporation association Tanbo Hospital, Medical corporation association Shichitokukai, Medical corporation association Shikinokai, Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co. Ltd., Suntory Global Innovation Center Ltd., Takeda, Pharmaceutical Co. Ltd., Teijin Pharma Limited, and The Mitsubishi Foundation. TY has received lecture fees from Abbott Japan LLC, Arkray Marketing, Inc., Astellas Pharma Inc, AstraZeneca K.K., Bayer Holding, Ltd., Boehringer Ingelheim, Cosmic Corporation, Covidien Japan Inc. (Medtronic Japan Co., Ltd.), Dojindo Laboratories, Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., FUJIFILM Toyama Chemical Co., Ltd., Kissei, Kowa Pharmaceutical Co. Ltd., Kyorin Pharmaceutical, Kyowa Kirin, LifeScan Japan, Inc., Mitsubishi Tanabe Pharma Corporation, MSD, Musashino Foods Corporation, Nippon Becton Dickinson, Novartis Pharma K.K., Novo Nordisk, Ono, Roche DC Japan, Sanofi, Sanwa Chemistry Laboratory, Sumitomo Dainippon, Taisho, Takeda, Teijin Healthcare, and Terumo; grants and endowments from Aero Switch Therapeutics, Inc., Asahi Mutual Life Insurance Company, Astellas Pharma Inc., Bayer Holding, Ltd., Daiichi Sankyo Co., Ltd., EA Pharma, Eli Lilly Japan K.K., Kowa Pharmaceutical Co. Ltd., Kyowa Kirin, Minophagen, Mitsubishi Corporation Life Sciences, Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation, Nitto Boseki Co., Ltd., Novartis Pharma K.K., Novo Nordisk, Ono, Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda, and Tosoh Corporation; and consulting fees from Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K., and Viatris Pharmaceutical Japan Inc. SL is an advisory board member for AstraZeneca K.K. and Novo Nordisk Pharma Ltd.; reports honoraria for lectures from AstraZeneca K.K., Boehringer Ingelheim, MSD, Novo Nordisk Pharma Ltd., and Sanofi; and has received research funding from CKD and Eli Lilly Japan K.K. EDAT- 2025/01/18 15:10 MHDA- 2025/01/30 00:19 CRDT- 2025/01/17 21:53 PHST- 2024/07/08 00:00 [received] PHST- 2024/12/19 00:00 [revised] PHST- 2025/01/03 00:00 [accepted] PHST- 2025/01/30 00:19 [medline] PHST- 2025/01/18 15:10 [pubmed] PHST- 2025/01/17 21:53 [entrez] AID - S1871-403X(25)00003-1 [pii] AID - 10.1016/j.orcp.2025.01.002 [doi] PST - ppublish SO - Obes Res Clin Pract. 2024 Nov-Dec;18(6):457-464. doi: 10.1016/j.orcp.2025.01.002. Epub 2025 Jan 16. PMID- 39823186 OWN - NLM STAT- MEDLINE DCOM- 20250206 LR - 20250522 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 31 IP - 2 DP - 2025 Feb 1 TI - Comparing demographic/clinical characteristics, health care resource utilization, and costs among patients with type 2 diabetes and established atherosclerotic cardiovascular disease with and without the use of cardioprotective medications. PG - 117-126 LID - 10.18553/jmcp.2025.24251 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) causes increased health care resource utilization (HCRU) and costs in the United States. People with T2D are more likely to have atherosclerotic cardiovascular disease (ASCVD), which is associated with significant morbidity and mortality. Medical associations recommend cardioprotective antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs), to reduce the risk of cardiovascular events in patients with T2D with established, or a high risk of, ASCVD, but not all eligible patients receive these medications. OBJECTIVE: To describe demographic/clinical characteristics and antidiabetic medication prescription patterns and compare HCRU and costs among patients with T2D and ASCVD with or without SGLT2i and/or GLP-1 RA use. METHODS: We conducted a retrospective cohort study using the Merative MarketScan database of longitudinal US health care claims data with patients enrolled from July 1, 2014, to December 31, 2022. Patients with T2D and ASCVD receiving SGLT2is and/or GLP-1 RAs (case cohort) were compared with patients with T2D and ASCVD not receiving SGLT2is and/or GLP-1 RAs (control cohort) during a 12-month baseline period pre-index and a 12-month follow-up period post-index. The index date was SGLT2i/GLP-1 RA prescription for the case cohort and random health care visit for the control cohort. Baseline patient characteristics are reported before propensity score matching (PSM); HCRU and medical costs are reported after PSM. RESULTS: Before PSM, each cohort included 3,386 patients; after PSM, each cohort included 2,351 patients. Patients in the case cohort were significantly more likely to experience myocardial infarction (case, 26.2%; control, 21.5%; P < 0.001) or peripheral artery disease (case, 28.6%; control, 26.1%; P < 0.024) during the baseline period. Patients in the case cohort had significantly lower baseline Charlson Comorbidity Index scores than patients in the control cohort (case, 1.8; control, 2.1; P < 0.001). Patients in the case cohort had significantly fewer all-cause inpatient visits per patient (case, 0.4; control, 0.6; P < 0.001) and all-cause emergency department visits per patient (case, 0.9; control, 1.0; P = 0.024). Patients in the case cohort had significantly lower all-cause inpatient costs (case, $13,977; control, $22,056; P < 0.001), other all-cause outpatient costs (case, $16,504; control, $24,739; P < 0.001), and all-cause total medical costs including pharmacy costs (case, $51,143; control, $58,648; P = 0.01) in the 12-month follow-up period. CONCLUSIONS: Patients with T2D and ASCVD receiving SGLT2is and/or GLP-1 RAs within 12 months of ASCVD diagnosis may benefit from lower HCRU and costs. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Cao, Yiwen AU - Cao Y AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Mitri, Joanna AU - Mitri J AD - Joslin Diabetes Center, Sequel Med Tech, Boston, MA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250117 PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Cardiotonic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - Aged MH - *Atherosclerosis/economics/drug therapy/epidemiology MH - Hypoglycemic Agents/therapeutic use/economics MH - United States/epidemiology MH - *Cardiotonic Agents/therapeutic use/economics MH - *Health Care Costs/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Patient Acceptance of Health Care/statistics & numerical data MH - Adult MH - Cohort Studies PMC - PMC11852797 COIS- This study was funded by Novo Nordisk Inc. (grant number: not applicable). Several Novo Nordisk Inc. employees are authors on the manuscript and contributed to the study design, conduct, interpretation, and decision to publish. EDAT- 2025/01/17 18:23 MHDA- 2025/02/06 12:21 PMCR- 2025/02/01 CRDT- 2025/01/17 15:12 PHST- 2025/02/06 12:21 [medline] PHST- 2025/01/17 18:23 [pubmed] PHST- 2025/01/17 15:12 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - 10.18553/jmcp.2025.24251 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2025 Feb 1;31(2):117-126. doi: 10.18553/jmcp.2025.24251. Epub 2025 Jan 17. PMID- 39823185 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20250522 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 31 IP - 2 DP - 2025 Feb 1 TI - Addition of continuous glucose monitoring to glucagon-like peptide 1 receptor agonist treatment for type 2 diabetes mellitus - An economic evaluation. PG - 127-136 LID - 10.18553/jmcp.2025.24253 [doi] AB - BACKGROUND: Both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and continuous glucose monitoring (CGM) have been shown to improve glycated hemoglobin A1c (A1c) levels among patients with type 2 diabetes mellitus (T2DM). Recently, a US real-world study found statistically significant improvements in A1c levels among patients using GLP-1 RA and a CGM device, compared with a matched cohort receiving only GLP-1 RA. OBJECTIVES: To assess the cost-effectiveness from a US payer perspective of initiating CGM (FreeStyle Libre Systems) in people living with T2DM using a GLP-1 RA therapy, compared with GLP-1 RA alone. METHODS: A patient-level microsimulation model was run for 10,000 patients over a lifetime horizon with 3.0% discounting for costs and utilities. Patient characteristics were based on the overall population of the US real-world study and the subgroup of patients not using intensive insulin. The effect of CGM was modeled as a persistent reduction in A1c compared with GLP-1 RA alone (overall = 0.37%; patients not using intensive insulin = 0.34%). Costs ($2,023) and disutilities were applied to diabetes complications and acute diabetic events. Outcomes were assessed as quality-adjusted life years (QALYs). RESULTS: The base-case incremental cost-effectiveness ratio (incremental costs/incremental QALYs) for GLP-1 RA plus CGM vs GLP-1 RA alone was $40,968/QALY in the overall cohort (cost = $484,180 vs $473,938; QALYs = 13.37 vs 13.12). Among patients not using intensive insulin, the incremental cost-effectiveness ratio was $43,095/QALY. Scenario analysis showed that the model results were robust to changing assumptions. Probabilistic sensitivity analysis showed that GLP-1 RA plus CGM had a 64% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSIONS: From a US payer perspective, CGM is cost-effective when added to GLP-1 RA therapies for the treatment of T2DM, including for patients not using intensive insulin. FAU - Wright, Eugene E AU - Wright EE AD - South Piedmont Area Health Education Center, Charlotte, NC. FAU - Miller, Eden AU - Miller E AD - Diabetes and Obesity Care LLC, Bend, OR. FAU - Bindal, Anila AU - Bindal A AD - Abbott Diabetes Care, Alameda, CA. FAU - Poon, Yeesha AU - Poon Y AD - Abbott Diabetes Care, Mississauga, Ontario, Canada. LA - eng PT - Journal Article DEP - 20250117 PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics/blood MH - Cost-Benefit Analysis MH - *Hypoglycemic Agents/therapeutic use/economics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Glucose Self-Monitoring/economics/methods MH - Female MH - Middle Aged MH - Male MH - Glycated Hemoglobin/analysis MH - *Blood Glucose/analysis/drug effects MH - Quality-Adjusted Life Years MH - Aged MH - United States MH - Continuous Glucose Monitoring PMC - PMC11852799 COIS- This study, the preparation of the manuscript, and publication fees were funded by Abbott. EDAT- 2025/01/17 18:22 MHDA- 2025/02/06 12:23 PMCR- 2025/02/01 CRDT- 2025/01/17 15:12 PHST- 2025/02/06 12:23 [medline] PHST- 2025/01/17 18:22 [pubmed] PHST- 2025/01/17 15:12 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - 10.18553/jmcp.2025.24253 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2025 Feb 1;31(2):127-136. doi: 10.18553/jmcp.2025.24253. Epub 2025 Jan 17. PMID- 39820580 OWN - NLM STAT- MEDLINE DCOM- 20250327 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 4 DP - 2025 Apr TI - Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial. PG - 739-751 LID - 10.1007/s00125-024-06348-5 [doi] AB - AIMS/HYPOTHESIS: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications. METHODS: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions. Adults with type 2 diabetes (HbA(1c) 53.0-85.8 mmol/mol [7.0-10.0%]) receiving GLP-1 RA therapy with or without additional oral glucose-lowering medications were randomly assigned 1:1 to once-weekly IcoSema or once-weekly semaglutide 1.0 mg. The primary endpoint was change in HbA(1c) from baseline to week 52; superiority of IcoSema to semaglutide 1.0 mg was assessed. Secondary endpoints included change in fasting plasma glucose and body weight (baseline to week 52), and combined clinically significant (level 2; <3.0 mmol/l) or severe (level 3; associated with severe cognitive impairment requiring external assistance for recovery) hypoglycaemia (baseline to week 57). RESULTS: Overall, 683 participants were randomised using a Randomisation and Trial Supply Management system to IcoSema (n=342) or semaglutide 1.0 mg (n=341). Mean +/- SD baseline characteristics were as follows: HbA(1c) 64.0+/-8.2 mmol/mol (8.0+/-0.7%); diabetes duration 12.6+/-6.9 years; and BMI 31.1+/-4.7 kg/m(2). From baseline to week 52, mean change in HbA(1c) was -14.7 mmol/mol (-1.35%-points) in the IcoSema group and -9.88 mmol/mol (-0.90%-points) in the semaglutide group; the estimated treatment difference (ETD) was -4.85 (95% CI -6.13, -3.57) mmol/mol (-0.44 [95% CI -0.56, -0.33]%-points), confirming superiority of IcoSema to semaglutide (p<0.0001). The estimated mean change in fasting plasma glucose from baseline to week 52 was statistically significantly reduced with IcoSema vs semaglutide (-2.48 mmol/l vs -1.43 mmol/l, respectively; ETD -1.05 [95% CI -1.36, -0.75] mmol; p<0.0001). Mean change in body weight from baseline to week 52 was statistically significantly different between groups: +0.84 kg for IcoSema vs -3.70 kg for semaglutide (ETD 4.54 kg [95% CI 3.84, 5.23]; p<0.0001). There was no statistically significant difference in the rate of combined clinically significant or severe hypoglycaemia between IcoSema and semaglutide (0.042 vs 0.036 episodes per person-year of exposure; estimated rate ratio 1.20 [95% CI 0.53, 2.69]; p=0.66). The proportion of participants experiencing gastrointestinal adverse events was similar between treatment groups (IcoSema 31.4%; semaglutide 34.4%). CONCLUSIONS/INTERPRETATION: In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA(1c) reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events. However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg. TRIAL REGISTRATION: ClinicalTrials.gov NCT05259033 FUNDING: This trial was funded by Novo Nordisk. CI - (c) 2025. The Author(s). FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Endocrinology Division, Department of Internal Medicine and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. Ildiko.Lingvay@UTSouthwestern.edu. FAU - Benamar, Malik AU - Benamar M AUID- ORCID: 0009-0001-1820-1527 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chen, Liming AU - Chen L AUID- ORCID: 0000-0002-5682-2340 AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Fu, Ariel AU - Fu A AUID- ORCID: 0009-0007-0220-5877 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jodar, Esteban AU - Jodar E AUID- ORCID: 0000-0002-1234-8560 AD - Universitary Hospital QuironSalud Madrid, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain. FAU - Nishida, Tomoyuki AU - Nishida T AUID- ORCID: 0009-0004-5812-7167 AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Riveline, Jean-Pierre AU - Riveline JP AUID- ORCID: 0000-0001-7991-0741 AD - Department of Endocrinology and Diabetology, Lariboisiere Hospital, APHP, Paris-Cite University Paris, Paris, France. AD - Institut Necker Enfants Malades, Inserm U1151, CNRS UMR 8253, IMMEDIAB Laboratory, Paris, France. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Zueger, Thomas AU - Zueger T AUID- ORCID: 0000-0001-6190-7405 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Kantonsspital Olten, Olten, Switzerland. AD - Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Rea, Rosangela AU - Rea R AUID- ORCID: 0000-0002-2102-0495 AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05259033 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250117 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Diabetologia. 2025 Jul;68(7):1586-1588. doi: 10.1007/s00125-025-06435-1. PMID: 40323333 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/metabolism MH - Adult MH - Drug Administration Schedule MH - Treatment Outcome MH - Drug Therapy, Combination MH - Insulin Glargine/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11950020 OTO - NOTNLM OT - Fixed-ratio combination OT - GLP-1 RA OT - Glycaemic control OT - Hypoglycaemia OT - IcoSema OT - Insulin icodec OT - Once-weekly OT - Safety OT - Semaglutide OT - Type 2 diabetes COIS- Acknowledgements: The authors thank all trial participants and staff. Medical writing support was provided by G. Rogers and J. Geatrell of Oxford PharmaGenesis, Oxford, UK, funded by Novo Nordisk A/S. Data availability: Individual participant data will be shared in data sets in a de-identified/anonymised format. Shared data will include data sets from Novo Nordisk-sponsored clinical research completed after 2001 for product indications approved in both the EU and the USA. The trial protocol and redacted clinical trial report will be made available according to Novo Nordisk data sharing commitments. These data will be available after research completion and approval of product and product use in both the EU and the USA (no end date). Data will be shared with bona fide researchers submitting a research proposal requesting access to data, for use as approved by the Independent Review Board (IRB) according to the IRB charter (see novonordisk-trials.com). These data can be accessed via an access request proposal form; the access criteria can be found at novonordisk-trials.com. The data will be made available on a specialised SAS data platform. The results tables will be made available according to US and EU law, via Clinicaltrials.gov and EU Clinical Trials Register. Clinical trials synopsis will be uploaded to novonordisk-trials.com for clinical projects that have been discontinued. Funding: This trial was funded by Novo Nordisk A/S. Representatives of Novo Nordisk A/S were involved in the design and conduct of the trial; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript. Investigators were responsible for trial-related medical decisions and data collection; Novo Nordisk undertook site monitoring, data collation and analysis. Medical writers (G. Rogers and J. Geatrell from Oxford PharmaGenesis, Oxford, UK), funded by Novo Nordisk, assisted with drafting the manuscript under direction of the authors. Novo Nordisk did not have the right to veto publication or to control the decision regarding the journal to which the manuscript was submitted; these decisions were made by the authors. Authors' relationships and activities: IL has received research funding (paid to the institution they are affiliated with) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer and Sanofi, and has received advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GI Dynamics, Intarcia Therapeutics, Intercept Pharmaceuticals, Johnson & Johnson, MannKind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Valeritas and Zealand Pharma. MB and AF are employees of Novo Nordisk A/S. LC has received research funding (paid to the institution they are affiliated with) from AstraZeneca and Eli Lilly. EJ has received research funding (paid to the institution they are affiliated with) from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Faes Farma, MSD, Novartis and Novo Nordisk, and has received advisory/consulting fees and/or other support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, Technofarma, UCB and Viatris. TN is an employee of Novo Nordisk Pharma Ltd. J-PR is an advisory panel member for Abbott, Air Liquide International, Alphadiab, AstraZeneca, Dexcom, Eli Lilly, Medtronic, MSD, Novo Nordisk and Sanofi, and has received research funding from and provided research support to Abbott, Air Liquide International, Medtronic, Novo Nordisk and Sanofi. DY has received consulting or speaker fees from Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, MSD K.K., Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd and Sumitomo Pharma, and clinically commissioned/received joint research grants from Arklay, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd and Taisho Pharmaceutical. TZ has received research funding (paid to the institution they are affiliated with) from Akero Therapeutics, Novartis and Novo Nordisk, and has received advisory/consulting fees and/or other support (paid to the institution they are affiliated with) from AstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi. RR is an advisory panel member for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Novo Nordisk, has participated in speakers' bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD and Novo Nordisk, and has received research grants from Boehringer Ingelheim, Eli Lilly and Novo Nordisk. Contribution statement: All authors had full access to the data associated with this trial and contributed to interpreting the data and drafting the manuscript. The authors jointly decided to submit the manuscript, approved it before submission and take full responsibility for its content. IL is the guarantor of this work. EDAT- 2025/01/17 18:22 MHDA- 2025/03/27 18:26 PMCR- 2025/01/17 CRDT- 2025/01/17 13:22 PHST- 2024/08/16 00:00 [received] PHST- 2024/11/08 00:00 [accepted] PHST- 2025/03/27 18:26 [medline] PHST- 2025/01/17 18:22 [pubmed] PHST- 2025/01/17 13:22 [entrez] PHST- 2025/01/17 00:00 [pmc-release] AID - 10.1007/s00125-024-06348-5 [pii] AID - 6348 [pii] AID - 10.1007/s00125-024-06348-5 [doi] PST - ppublish SO - Diabetologia. 2025 Apr;68(4):739-751. doi: 10.1007/s00125-024-06348-5. Epub 2025 Jan 17. PMID- 39818039 OWN - NLM STAT- MEDLINE DCOM- 20251222 LR - 20260426 IS - 1578-1283 (Electronic) IS - 0213-9111 (Linking) VI - 39 DP - 2025 TI - Association of glucagon-like peptide-1 receptor agonists with acute pancreatitis and biliary disease in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study. PG - 102444 LID - S0213-9111(24)00102-X [pii] LID - 10.1016/j.gaceta.2024.102444 [doi] AB - OBJECTIVE: To evaluate the risk of acute pancreatitis and biliary disease in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHOD: Population-based, propensity-weighted, new user, active comparator design study including patients with diabetes and obesity initiating treatment with GLP-1 RA or the comparator group sodium-glucose cotransporter 2 inhibitors (SGLT-2i) in the region of Valencia from 2015 to 2021. RESULTS: In adjusted, per protocol main analysis, no risk differences were found for acute pancreatitis (HR: 0.56; 95%CI: 0.17-1.91) nor for biliary disease (HR: 1.12; IC95%: 0.79, 1.58). Secondary analyses yielded similar results. CONCLUSIONS: Despite we did not observe increased risk of gastrointestinal events in GLP-1 RA vs SGLT-2i patients, adherence to approved indications and close monitoring of potential adverse events are warranted to ensure patient safety. CI - Copyright (c) 2024. Publicado por Elsevier Espana, S.L.U. FAU - Robles Cabanillas, Celia AU - Robles Cabanillas C AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Hurtado Navarro, Isabel AU - Hurtado Navarro I AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Garcia-Sempere, Anibal AU - Garcia-Sempere A AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. Electronic address: anibal.garcia@fisabio.es. FAU - Llopis-Cardona, Fran AU - Llopis-Cardona F AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Sanchez-Saez, Francisco AU - Sanchez-Saez F AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Rodriguez-Bernal, Clara AU - Rodriguez-Bernal C AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Sanfelix-Gimeno, Gabriel AU - Sanfelix-Gimeno G AD - Health Services Research and Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain; Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250117 PL - Spain TA - Gac Sanit JT - Gaceta sanitaria JID - 8901623 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Pancreatitis/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - *Obesity/complications/drug therapy MH - Middle Aged MH - *Biliary Tract Diseases/chemically induced/epidemiology MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Propensity Score MH - Cohort Studies MH - Acute Disease MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult OTO - NOTNLM OT - Agonistas del receptor del peptido similar al glucagon tipo 1 OT - Cohort study OT - Comparative study OT - Diabetes mellitus tipo 2 OT - Diabetes mellitus type 2 OT - Enfermedades de la vesicula biliar OT - Estudio comparativo OT - Estudio de cohortes OT - Farmacoepidemiologia OT - Gallbladder diseases OT - Glucagon-like peptide-1 receptor agonists OT - Inhibidores del cotransportador de sodio-glucosa tipo 2 OT - Obesidad OT - Obesity OT - Pancreatitis OT - Pharmacoepidemiology OT - Sodium-glucose cotransporter 2 inhibitors EDAT- 2025/01/17 00:20 MHDA- 2025/12/23 00:27 CRDT- 2025/01/16 18:05 PHST- 2024/09/11 00:00 [received] PHST- 2024/11/25 00:00 [revised] PHST- 2024/12/15 00:00 [accepted] PHST- 2025/12/23 00:27 [medline] PHST- 2025/01/17 00:20 [pubmed] PHST- 2025/01/16 18:05 [entrez] AID - S0213-9111(24)00102-X [pii] AID - 10.1016/j.gaceta.2024.102444 [doi] PST - ppublish SO - Gac Sanit. 2025;39:102444. doi: 10.1016/j.gaceta.2024.102444. Epub 2025 Jan 17. PMID- 39815782 OWN - NLM STAT- MEDLINE DCOM- 20250116 LR - 20260630 IS - 2190-6009 (Electronic) IS - 2190-5991 (Print) IS - 2190-5991 (Linking) VI - 16 IP - 1 DP - 2025 Feb TI - The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review. PG - e13677 LID - 10.1002/jcsm.13677 [doi] LID - e13677 AB - BACKGROUND: Obesity is a chronic disease associated with increased risk of multiple metabolic and mental health-related comorbidities. Recent advances in obesity pharmacotherapy, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have the potential to transform obesity and type 2 diabetes mellitus (T2DM) care by promoting marked weight loss, improving glycaemic control and addressing multiple obesity-related comorbidities, with added cardio-renal benefits. Dual agonists combining GLP-1 with other enteropancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP) have also been developed in recent years, leading to greater weight loss than using GLP-1 RAs alone. However, up to 40% of the weight lost with GLP-1 RAs comes from lean body mass, raising concerns about potential adverse effects on skeletal muscle function. Mitochondrial dysfunction, characterized by reduced mitochondrial size and activity, is prevalent in individuals with obesity and T2DM and is a known contributor to muscle wasting in ageing and some chronic diseases. This systematic review investigates the impact of GLP-1-based therapies on skeletal muscle mitochondrial function in individuals with obesity and T2DM or in related animal and cell models. METHODS: A comprehensive search of MEDLINE, Scopus, CINAHL and clinicaltrials.gov was conducted. Inclusion criteria included randomized controlled trials, randomized crossover trials, cluster randomized control trials and basic science studies involving any GLP-1 RA or GLP-1/GIP dual agonist. Outcomes of interest were skeletal muscle respiratory function either in the form of measurements of mass, number, content, oxidative capacity/respiratory function, mitochondrial dynamics, mitochondrial biogenesis and mitophagy. RESULTS: Eight studies were eligible for analysis; no human studies were identified. All of the included studies used GLP-1 RAs (single agonists) as intervention. The emerging evidence suggests that GLP-1 RAs increase mitochondrial area, number and morphology (i.e., reduces swelling). Data are conflicting on the effect of GLP-1 RAs upon mitochondrial mass, respiration and the expression of uncoupling proteins and PGC-1alpha. Data also demonstrate muscle specific (i.e., soleus vs. extensor digitorum longus) responses to GLP-1 RAs. CONCLUSION: GLP-1 RAs appear to have a positive effect upon mitochondria area, number and morphology, but effects upon other aspects of mitochondrial health remain inconclusive. Data are very limited and solely presented in animal and in vitro models. Future studies should be conducted in human populations in order to begin to understand the effect of GLP-1 RAs and GLP-1-based therapies on human skeletal muscle mitochondria. CI - (c) 2025 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC. FAU - Old, Victoria J AU - Old VJ AD - Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. FAU - Choudhary, Pratik AU - Choudhary P AD - Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. FAU - Watson, Emma L AU - Watson EL AD - Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - Germany TA - J Cachexia Sarcopenia Muscle JT - Journal of cachexia, sarcopenia and muscle JID - 101552883 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Mitochondria, Muscle/metabolism/drug effects MH - *Muscle, Skeletal/cytology/drug effects/metabolism MH - Obesity/drug therapy/metabolism PMC - PMC11735953 OTO - NOTNLM OT - GLP-1 RA OT - mitochondria OT - obesity OT - skeletal muscle COIS- The authors declare no conflicts of interest. EDAT- 2025/01/16 06:22 MHDA- 2025/01/16 06:23 PMCR- 2025/01/16 CRDT- 2025/01/16 03:13 PHST- 2024/11/05 00:00 [revised] PHST- 2024/07/02 00:00 [received] PHST- 2024/11/16 00:00 [accepted] PHST- 2025/01/16 06:23 [medline] PHST- 2025/01/16 06:22 [pubmed] PHST- 2025/01/16 03:13 [entrez] PHST- 2025/01/16 00:00 [pmc-release] AID - JCSM13677 [pii] AID - 10.1002/jcsm.13677 [doi] PST - ppublish SO - J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13677. doi: 10.1002/jcsm.13677. PMID- 39815707 OWN - NLM STAT- MEDLINE DCOM- 20250116 LR - 20250527 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 80 IP - 1 DP - 2025 Jan TI - [Patient with type 2 diabetes and progressive chronic kidney disease]. PG - 63-68 AB - Chronic kidney disease (CKD) is a common and severe complication in patients with type 2 diabetes (T2D). While inhibitors of the renin-angiotensin system remained for a long time the only medications that had proven nephroprotective effects, several other pharmacological classes also recently showed such a benefit : sodium-glucose cotransporter type 2 (SGLT2) inhibitors (gliflozins), glucagon-like peptide-1 receptor agonists (semaglutide), and mineralocorticoid receptor antagonists (MRA, finerenone). This clinical vignette aims at explaining the pharmacotherapy strategy for a patient with T2D who presents a progressive CKD. The interest of prescribing a combination of several medications with complementary actions that had proven a nephroprotection is emphasized. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. FAU - Delanaye, Pierre AU - Delanaye P AD - Service de Nephrologie, Dialyse, Transplantation, CHU Liege, Belgique. LA - fre PT - Case Reports PT - English Abstract PT - Journal Article TT - Vignette therapeutique de l'etudiant. Patient avec un diabete de type 2 et une maladie renale chronique progressive. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Hypoglycemic Agents) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/drug therapy MH - Disease Progression MH - Hypoglycemic Agents/therapeutic use MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy/etiology/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use OTO - NOTNLM OT - Chronic kidney disease OT - Finerenone OT - Gliflozin OT - Renal Insufficiency OT - SGLT2 inhibitor OT - Type 2 diabetes OT - angiotensin blocker EDAT- 2025/01/16 06:21 MHDA- 2025/01/16 06:22 CRDT- 2025/01/16 02:34 PHST- 2025/01/16 06:22 [medline] PHST- 2025/01/16 06:21 [pubmed] PHST- 2025/01/16 02:34 [entrez] PST - ppublish SO - Rev Med Liege. 2025 Jan;80(1):63-68. PMID- 39814031 OWN - NLM STAT- MEDLINE DCOM- 20250228 LR - 20260618 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 40 IP - 1 DP - 2025 Feb TI - Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis. PG - 112-124 LID - 10.3803/EnM.2024.2164 [doi] AB - BACKGRUOUND: Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide. METHODS: RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups. RESULTS: Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma. CONCLUSION: Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk. FAU - Kamrul-Hasan, A B M AU - Kamrul-Hasan ABM AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. FAU - Alam, Muhammad Shah AU - Alam MS AD - Department of Medicine, Army Medical College Cumilla, Cumilla, Bangladesh. FAU - Dutta, Deep AU - Dutta D AD - Department of Endocrinology, CEDAR Superspeciality Clinics, New Delhi, India. FAU - Sasikanth, Thanikai AU - Sasikanth T AD - Department of Endocrinology, National Hospital of Sri Lanka, Colombo, Sri Lanka. FAU - Aalpona, Fatema Tuz Zahura AU - Aalpona FTZ AD - Department of Obstetrics and Gynecology, Atpara Upazila Health Complex, Netrokona, Bangladesh. FAU - Nagendra, Lakshmi AU - Nagendra L AD - Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250115 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 0 (Insulin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Insulin/administration & dosage/adverse effects MH - *Neoplasms/chemically induced/epidemiology/etiology MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - *Tirzepatide/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects PMC - PMC11898313 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Meta-analysis OT - Neoplasms OT - Obesity OT - Pancreatic neoplasms OT - Thyroid neoplasms OT - Tirzepatide COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2025/01/16 00:20 MHDA- 2025/02/28 06:21 PMCR- 2025/02/01 CRDT- 2025/01/15 18:45 PHST- 2024/09/29 00:00 [received] PHST- 2024/11/14 00:00 [accepted] PHST- 2025/02/28 06:21 [medline] PHST- 2025/01/16 00:20 [pubmed] PHST- 2025/01/15 18:45 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - EnM.2024.2164 [pii] AID - enm-2024-2164 [pii] AID - 10.3803/EnM.2024.2164 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2025 Feb;40(1):112-124. doi: 10.3803/EnM.2024.2164. Epub 2025 Jan 15. PMID- 39812791 OWN - NLM STAT- MEDLINE DCOM- 20250825 LR - 20250825 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 8 DP - 2025 Aug TI - Glucagon-like peptide 1 receptor agonists outperform basal insulin in cardiovascular and renal outcomes for type 2 diabetes mellitus: a retrospective cohort study. PG - 1221-1232 LID - 10.1007/s00592-024-02443-6 [doi] AB - PURPOSE: Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and basal insulin are currently used in the treatment of type 2 diabetes mellitus (T2DM) as long-acting injectables. In this study, we aimed to compare the cardiovascular (CV) and renal outcomes of GLP-1 RAs and basal insulin treatment in patients with T2DM. METHOD: We conducted a propensity score-matched cohort study of patients from Chang Gung Memorial Hospital institutions between 2013 and 2021. A diverse patient base from multiple centers was enrolled to enhance the applicability of the findings, including patients with T2DM who were prescribed either GLP-1 RAs or basal insulin. RESULTS: Over a mean follow-up period of 2.2 years, 10,839 patients were collected (mean age = 54.3 years; 54.2% men). Among the propensity score-matched patients, 45 (2.23%) in the GLP-1 RA group (2,854 patients) and 72 (3.56%) in the basal insulin group (7,985 patients) experienced 3-point major adverse cardiovascular events (3P-MACEs; hazard ratio [HR] 0.68, 95% CI 0.47-0.99, P =.44). Additionally, composite renal outcomes were observed in 237 (11.7%) patients in the GLP-1 RA group and 360 (17.8%) in the basal insulin group (HR 0.69, 95% CI 0.59-0.81, P <.001). CONCLUSIONS: In patients with T2DM, GLP-1 RAs were associated with more favorable cardiovascular and renal outcomes than basal insulin, suggesting that GLP-1 RA treatment may be a preferable option for managing T2DM with a lower risk of CV and renal complications. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Chen, Tien-Hsing AU - Chen TH AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Tseng, Chin-Ju AU - Tseng CJ AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Li, Yan-Rong AU - Li YR AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Lin, Yuan AU - Lin Y AD - Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Dong-Yi AU - Chen DY AD - Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Yang, Ning-I AU - Yang NI AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Wang, Te-Hsiung AU - Wang TH AD - Department of Emergency Medicine, Tazuke Kofukai, Medical Research Institute, Kitano Hospital, Osaka, Japan. FAU - Hung, Ming-Jui AU - Hung MJ AD - Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Tsai, Ming-Lung AU - Tsai ML AUID- ORCID: 0000-0002-4199-713X AD - Division of Cardiology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan. mltsai.cgmh@gmail.com. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. mltsai.cgmh@gmail.com. AD - College of Management, Chang Gung University, Taoyuan, Taiwan. mltsai.cgmh@gmail.com. LA - eng GR - CMRPG2N0111/Chang Gung Medical Foundation/ GR - CORPVVP0101, CORPVVP0161/Chang Gung Medical Foundation/ PT - Journal Article DEP - 20250115 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/epidemiology MH - Aged MH - *Insulin/therapeutic use MH - Propensity Score MH - Treatment Outcome MH - Adult OTO - NOTNLM OT - Basal insulin OT - CV outcomes OT - GLP-1 RAs OT - Renal outcomes OT - Type 2 diabetes COIS- Declarations. Conflict of interest: The authors declare that this study was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical approval and institutional review board approval: The Institutional Review Board of CGMH approved the study protocol and waived the requirement for informed consent. Patient information was de-identified and anonymized before analyses were conducted. This study was conducted in accordance with the tenets of the Declaration of Helsinki and the ethical regulations of the Institutional Review Board. This study was conducted in accordance with the tenets of the Declaration of Helsinki. Consent to participate: The Institutional Review Board of CGMH approved the study protocol and waived the requirement for informed consent. Consent for publication: The Institutional Review Board of CGMH approved the study protocol and waived the requirement for informed consent. EDAT- 2025/01/15 12:23 MHDA- 2025/08/31 19:45 CRDT- 2025/01/15 11:13 PHST- 2024/10/22 00:00 [received] PHST- 2024/12/29 00:00 [accepted] PHST- 2025/08/31 19:45 [medline] PHST- 2025/01/15 12:23 [pubmed] PHST- 2025/01/15 11:13 [entrez] AID - 10.1007/s00592-024-02443-6 [pii] AID - 10.1007/s00592-024-02443-6 [doi] PST - ppublish SO - Acta Diabetol. 2025 Aug;62(8):1221-1232. doi: 10.1007/s00592-024-02443-6. Epub 2025 Jan 15. PMID- 39812288 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20250521 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 900-1 DP - 2025 Jan 15 TI - [Nephrology: what's new in 2024 (I)]. PG - 56-58 LID - 10.53738/REVMED.2025.21.900-1.56 [doi] AB - From immunoglobulin A nephropathy to primary focal segmental glomerulosclerosis, sparsentan expands its indications. Complement inhibitors offer new hope for patients with certain poor-prognosis glomerulonephritides. Semaglutide enjoys great success, promising nephro- and cardioprotection for type 2 diabetics. The renal safety of proton pump inhibitors is questioned. Quality of life benefits of hemodiafiltration are confirmed. Vadadustat represents an oral alternative for the treatment of renal anemia. Xenotransplantation offers a glimpse of a future without organ shortages. FAU - Nanchen, Giliane AU - Nanchen G AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Golshayan, Dela AU - Golshayan D AUID- ORCID: 0000-0001-5631-6096 AD - Centre de transplantation d'organes, Departement de medecine, CHUV et Universite de Lausanne, 1011 Lausanne. FAU - Fakhouri, Fadi AU - Fakhouri F AUID- ORCID: 0000-0001-5390-8002 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Nephrologie : ce qui a change en 2024 (I). PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Complement Inactivating Agents) SB - IM MH - Humans MH - Quality of Life MH - *Kidney Diseases/therapy MH - *Nephrology/trends MH - Complement Inactivating Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Transplantation, Heterologous/methods COIS- les auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/01/15 12:23 MHDA- 2025/01/15 12:24 CRDT- 2025/01/15 07:12 PHST- 2025/01/15 12:24 [medline] PHST- 2025/01/15 12:23 [pubmed] PHST- 2025/01/15 07:12 [entrez] AID - RMS0900-1-013 [pii] AID - 10.53738/REVMED.2025.21.900-1.56 [doi] PST - ppublish SO - Rev Med Suisse. 2025 Jan 15;21(900-1):56-58. doi: 10.53738/REVMED.2025.21.900-1.56. PMID- 39812281 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20250521 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 900-1 DP - 2025 Jan 15 TI - [Diabetology : what's new in 2024]. PG - 26-28 LID - 10.53738/REVMED.2025.21.900-1.26 [doi] AB - Diabetology is a continuously evolving discipline, many molecules are developed, and treatment recommendations change regularly according to the latest published studies. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The place of the dual GLP-1/GIP agonist is not defined yet. This article guides the physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2024 novelties in the field of diabetes. FAU - Gariani, Karim AU - Gariani K AD - Service d'endocrinologie et diabetologie, Hopitaux universitaires de Geneve, 1211 Geneve 14. FAU - Jornayvaz, Francois R AU - Jornayvaz FR AD - Service d'endocrinologie et diabetologie, Hopitaux universitaires de Geneve, 1211 Geneve 14. LA - fre PT - English Abstract PT - Journal Article TT - Diabetologie : ce qui a change en 2024. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Metformin/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus/drug therapy COIS- K. Gariani declare des Advisory boards avec Lilly, Novo Nordisk et Bayer. F. R. Jornayvaz declare des Advisory boards avec Lilly, Novo Nordisk et Boehringer-Ingelheim. EDAT- 2025/01/15 12:23 MHDA- 2025/01/15 12:24 CRDT- 2025/01/15 07:12 PHST- 2025/01/15 12:24 [medline] PHST- 2025/01/15 12:23 [pubmed] PHST- 2025/01/15 07:12 [entrez] AID - RMS0900-1-006 [pii] AID - 10.53738/REVMED.2025.21.900-1.26 [doi] PST - ppublish SO - Rev Med Suisse. 2025 Jan 15;21(900-1):26-28. doi: 10.53738/REVMED.2025.21.900-1.26. PMID- 39812010 OWN - NLM STAT- MEDLINE DCOM- 20250212 LR - 20250915 IS - 1130-0108 (Print) IS - 1130-0108 (Linking) VI - 117 IP - 2 DP - 2025 Feb TI - Variability in the management of GLP-1 agonists and endoscopic procedures: an opportunity for standardization. PG - 65-67 LID - 10.17235/reed.2025.11011/2024 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), also known as incretin mimetics, have significantly revolutionized the treatment of type 2 diabetes mellitus (T2DM) and obesity worldwide, far exceeding initial expectations regarding their global prescription. This class of medications has demonstrated weight losses of up to 20 % of baseline body weight. Beyond their proven benefits in T2DM and obesity, GLP-1RAs, as well as dual and triple agonists (GLP-1/GIP/glucagon), are being investigated for their effects on conditions such as metabolic-associated steatotic liver disease, various cardiovascular disorders, neurocognitive impairments, and certain addictions. These emerging effects appear to be linked not only to their metabolic action but also to their ability to modulate the chronic inflammatory state underlying these pathologies. FAU - Crespo, Javier AU - Crespo J AD - Gastroenterologia y Hepatologia, Hospital Universitario Marques de Valdecilla, 39008. FAU - Lopez-Arias, Maria Jesus AU - Lopez-Arias MJ AD - Gastroenterologia y Hepatologia, Hospital Universitario Marques de Valdecilla. FAU - Iruzubieta, Paula AU - Iruzubieta P AUID- ORCID: 0000-0001-9476-1801 AD - Gastroenterologia y Hepatologia, Hospital Universitario Marques de Valdecilla. LA - eng PT - Editorial PL - Spain TA - Rev Esp Enferm Dig JT - Revista espanola de enfermedades digestivas JID - 9007566 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Endoscopy, Gastrointestinal/standards MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy EDAT- 2025/01/15 06:21 MHDA- 2025/02/12 06:21 CRDT- 2025/01/15 05:24 PHST- 2025/02/12 06:21 [medline] PHST- 2025/01/15 06:21 [pubmed] PHST- 2025/01/15 05:24 [entrez] AID - 10.17235/reed.2025.11011/2024 [doi] PST - ppublish SO - Rev Esp Enferm Dig. 2025 Feb;117(2):65-67. doi: 10.17235/reed.2025.11011/2024. PMID- 39809690 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260617 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 19 IP - 2 DP - 2025 Apr TI - Investigating socioeconomic disparities in prescribing new diabetes medications in individuals with type 2 diabetes and very high cardiovascular risk in the Netherlands. PG - 178-183 LID - S1751-9918(24)00246-8 [pii] LID - 10.1016/j.pcd.2024.12.011 [doi] AB - AIMS: This study aims to analyze prescription patterns of new diabetes medication and assess socioeconomic disparities in their initiation among individuals with T2DM with very high cardiovascular risk. METHODS: Individuals diagnosed with T2DM and very high cardiovascular risk were identified (N = 10,768) based on general practitioner's electronic health record data. SGLT-2is and GLP-1RAs prescription patterns were examined. Furthermore, the association between SES and the prescription of SGLT-2is and GLP-1RAs in 2022 was investigated. RESULTS: Despite the increase in prescription rates of SGLT-2is and GLP-1RAs between 2019 and 2022, approximately 85 % and 93 % of eligible individuals did not receive SGLT-2is and GLP-1RAs in 2022, respectively. We found a positive association between SGLT-2is prescription and SES in only the 4th quintile compared to 1st quintile (referent) in the fully adjusted model (OR 1.29 95 % CI:1.08-1.54). CONCLUSIONS: The prescription rates among eligible individuals highlight significant room for improvement in aligning prescribing practices with guidelines. We found no profound socioeconomic gradient in initiation of SGLT-2is and GLP-1RAs. The latter may be due to guidelines' clear indication of the eligible population and GP education. Future development and potential disparities in initiation and maintenance should be monitored to ensure equitable prescribing. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Ardesch, Frank H AU - Ardesch FH AD - Department of Public Health and Primary Care/Health Campus The Hague, Leiden University Medical Center, the Netherlands. Electronic address: F.H.Ardesch@lumc.nl. FAU - Geurten, Rose J AU - Geurten RJ AD - Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands. Electronic address: R.Geurten@maastrichtuniversity.nl. FAU - Struijs, Jeroen N AU - Struijs JN AD - Department of Public Health and Primary Care/Health Campus The Hague, Leiden University Medical Center, the Netherlands; Department of Population Health and Health Services Research, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Electronic address: J.N.Struijs@lumc.nl. FAU - Ruwaard, Dirk AU - Ruwaard D AD - Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands. Electronic address: D.Ruwaard@maastrichtuniversity.nl. FAU - Bilo, Henk J G AU - Bilo HJG AD - Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. Electronic address: H.J.G.Bilo@isala.nl. FAU - Elissen, Arianne M J AU - Elissen AMJ AD - Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands. Electronic address: A.Elissen@maastrichtuniversity.nl. LA - eng PT - Journal Article DEP - 20250114 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/economics MH - Male MH - Female MH - Middle Aged MH - *Healthcare Disparities/economics/trends MH - *Cardiovascular Diseases/epidemiology/diagnosis/prevention & control MH - Netherlands/epidemiology MH - *Practice Patterns, Physicians'/trends/economics MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Socioeconomic Factors MH - Risk Assessment MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Prescriptions MH - Socioeconomic Disparities in Health OTO - NOTNLM OT - GLP-1RAs OT - Health equity OT - SGLT-2i OT - Socioeconomic status OT - Type 2 diabetes mellitus OT - Very high cardiovascular risk COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/15 00:20 MHDA- 2025/03/03 00:56 CRDT- 2025/01/14 22:28 PHST- 2024/07/23 00:00 [received] PHST- 2024/12/20 00:00 [revised] PHST- 2024/12/23 00:00 [accepted] PHST- 2025/03/03 00:56 [medline] PHST- 2025/01/15 00:20 [pubmed] PHST- 2025/01/14 22:28 [entrez] AID - S1751-9918(24)00246-8 [pii] AID - 10.1016/j.pcd.2024.12.011 [doi] PST - ppublish SO - Prim Care Diabetes. 2025 Apr;19(2):178-183. doi: 10.1016/j.pcd.2024.12.011. Epub 2025 Jan 14. PMID- 39806559 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260812 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study. PG - 1980-1991 LID - 10.1111/dom.16191 [doi] AB - AIMS: To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D). MATERIALS AND METHODS: This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models. RESULTS: Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15-1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92-2.97) and heart failure (HR 1.97, 95% CI 1.54-2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding. CONCLUSIONS: The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lin, Chia-Ming AU - Lin CM AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Jo-Ching AU - Chen JC AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Meyerowitz-Katz, Gideon AU - Meyerowitz-Katz G AD - School of Health and Society, University of Wollongong, Wollongong, New South Wales, Australia. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2024-A-018/Chung Shan Medical University Hospital/ GR - CSH-2024-C-004/Chung Shan Medical University Hospital/ PT - Journal Article DEP - 20250113 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - R16CO5Y76E (Aspirin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - *Aspirin/adverse effects/administration & dosage/therapeutic use MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Obesity/complications/drug therapy MH - *Cardiovascular Diseases/chemically induced/epidemiology MH - Propensity Score MH - Drug Therapy, Combination/adverse effects MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Aged MH - Cohort Studies MH - Adult PMC - PMC11885080 OTO - NOTNLM OT - GLP-1 receptor agonists OT - aspirin OT - cardiovascular outcomes OT - obesity OT - type 2 diabetes COIS- The authors have no conflicts of interest to declare. EDAT- 2025/01/14 06:16 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/01/14 00:43 PHST- 2024/12/16 00:00 [revised] PHST- 2024/10/01 00:00 [received] PHST- 2024/12/30 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/14 06:16 [pubmed] PHST- 2025/01/14 00:43 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16191 [pii] AID - 10.1111/dom.16191 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1980-1991. doi: 10.1111/dom.16191. Epub 2025 Jan 13. PMID- 39805811 OWN - NLM STAT- MEDLINE DCOM- 20250113 LR - 20260530 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 34 IP - 1 DP - 2025 Jan TI - Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Among Type 2 Diabetes Patients: Replication and Reliability Assessment Across a Research Network. PG - e70087 LID - 10.1002/pds.70087 [doi] LID - e70087 AB - INTRODUCTION: The aim of this study is to use observational methods to evaluate reliability of evidence generated by a study of the effect of glucagon-like peptide 1 receptor agonists (GLP-1RA) on chronic lower respiratory disease (CLRD) outcomes among Type-2 diabetes mellitus (T2DM) patients. RESEARCH DESIGN AND METHODS: We independently reproduced a study comparing effects of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4-i) on CLRD outcomes among patients with T2DM and prior CLRD. We reproduced inputs and outputs using the original study data (national administrative claims) and evaluated the robustness of results in comparison to alternate design/analysis decisions. To evaluate generalizability, we applied an analysis protocol and conducted a meta-analysis across a research network that includes a diverse array of populations and data sources. We also produced additional analyses evaluating individual drugs within the GLP-1RA class and CLRD outcomes. RESULTS: We confirmed alignment of study inputs and outputs and closely reproduced effect estimates and sensitivity analyses. Adjusted effect estimates were robust to empirical calibration. Network meta-analysis confirmed original findings but indicated weaker effects than originally published. Meta-analysis of drugs within the GLP-1RA class against DPP4-i provided evidence that effects vary within the GLP-1RA class, indicating stronger effects for exenatide and weaker effects of dulaglutide. CONCLUSIONS: This study supports and establishes the reliability of the original study by (1) producing consistent findings in a range of alternate databases and populations, (2) demonstrating effects for multiple drugs within the GLP-1RA class, and (3) independently confirming the reproducibility of the original study and its findings. This reliability evaluation provides the beginnings of a broader framework for using standardized tools and distributed data networks to systematically interrogate the reliability of findings generated using observational data. CI - (c) 2025 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Conover, Mitchell M AU - Conover MM AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Observational Health Data Analytics, Johnson & Johnson, Titusville, New Jersey, USA. FAU - Albogami, Yasser AU - Albogami Y AUID- ORCID: 0000-0002-2816-6526 AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Hardin, Jill AU - Hardin J AUID- ORCID: 0000-0003-2682-2187 AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Observational Health Data Analytics, Johnson & Johnson, Titusville, New Jersey, USA. FAU - Reich, Christian G AU - Reich CG AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Real World Solutions, IQVIA, Cambridge, Massachusetts, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Observational Health Data Analytics, Johnson & Johnson, Titusville, New Jersey, USA. AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. FAU - Ryan, Patrick B AU - Ryan PB AD - Observational Health Data Science and Informatics, New York, New York, USA. AD - Observational Health Data Analytics, Johnson & Johnson, Titusville, New Jersey, USA. AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. CN - Observational Health Data Sciences and Informatics (OHDSI) Research Network LA - eng GR - Observational Health Data Sciences and Informatics (OHDSI) Research Network/ GR - Janssen Research & Development, a Johnson & Johnson Company/ PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Reproducibility of Results MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Male MH - Research Design MH - Female PMC - PMC11730806 OTO - NOTNLM OT - chronic lower respiratory disease OT - common data model OT - glucagon-like peptide 1 receptor agonists OT - pharmacoepidemiology OT - real world data OT - real world evidence OT - reliability OT - replicability OT - reproducibility OT - transparency COIS- Sponsors: Observational Health Data Sciences and Informatics (OHDSI) Research Network, Janssen Research & Development, a Johnson & Johnson Company. Four of the co-authors for this work (M.M.C., J.H., A.O. and P.B.R.) are employed by Janssen Research & Development LLC, a Johnson & Johnson company, which markets products that are used to treat Type-2 diabetes mellitus; however, those products are not evaluated in this study. EDAT- 2025/01/14 00:20 MHDA- 2025/01/14 00:21 PMCR- 2025/01/14 CRDT- 2025/01/13 23:03 PHST- 2024/12/12 00:00 [revised] PHST- 2024/01/31 00:00 [received] PHST- 2024/12/13 00:00 [accepted] PHST- 2025/01/14 00:21 [medline] PHST- 2025/01/14 00:20 [pubmed] PHST- 2025/01/13 23:03 [entrez] PHST- 2025/01/14 00:00 [pmc-release] AID - PDS70087 [pii] AID - 10.1002/pds.70087 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2025 Jan;34(1):e70087. doi: 10.1002/pds.70087. PMID- 39805357 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20250521 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 240 DP - 2025 Apr 1 TI - Effects of Novel Antidiabetic Agents on Contrast-Associated Acute Kidney Injury in Diabetic Patients Undergoing Percutaneous Coronary Intervention. PG - 50-56 LID - S0002-9149(25)00015-3 [pii] LID - 10.1016/j.amjcard.2025.01.007 [doi] AB - Contrast-associated acute kidney injury (CA-AKI) remains a serious complication after percutaneous coronary revascularization (PCI), with limited effective preventive strategies especially for diabetic patients. This study aimed to assess the effects of novel antidiabetic agents (NAD), i.e., glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose transporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP4i), on the occurrence of this outcome in diabetic patients undergoing PCI. We enrolled 293 consecutive diabetic patients receiving NAD at the time of PCI (NAD group) and paired them with 293 diabetic individuals undergoing revascularization who were not on NAD (no-NAD group), matched according to age and sex. CA-AKI was defined as an increase in serum creatinine (SCr) >/=0.3 mg/dl or >50% from baseline within 48 to 72 hours after contrast exposure. A propensity score-adjusted logistic regression analysis was performed to account for potential selection bias. NAD treatment was associated with a significantly reduced incidence of CA-AKI than standard glucose-lowering therapies (4.1 vs. 8.5%, p = 0.023). Furthermore, patients using SGLT2i and GLP-1RAs exhibited a lower incidence of CA-AKI compared to those taking DPP4i. Both multivariate and propensity-score-adjusted regression analyses identified NAD therapy as an independent predictor of CA-AKI (OR 0.45, 95% CI 0.22-0.98, p = 0.040 and OR 0.48, 95% CI 0.23-0.98, p = 0.045). In conclusion, this study is the first to explore the potential benefit of all three NAD classes on CA-AKI incidence. The use of these agents is associated with a lower incidence of renal damage in diabetic patients undergoing PCI, with the greatest benefit observed with SGLT2i and GLP-1RAs use. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Nusca, Annunziata AU - Nusca A AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. Electronic address: a.nusca@policlinicocampus.it. FAU - Di Bitonto, Maria Pia AU - Di Bitonto MP AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Spano, Agostino AU - Spano A AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Bernardini, Federico AU - Bernardini F AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Mangiacapra, Fabio AU - Mangiacapra F AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Ricottini, Elisabetta AU - Ricottini E AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Melfi, Rosetta AU - Melfi R AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Giannone, Sara AU - Giannone S AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Ussia, Gian Paolo AU - Ussia GP AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. FAU - Grigioni, Francesco AU - Grigioni F AD - Research Unit of Cardiac Sciences, Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Roma, Italy; Cardiology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. LA - eng PT - Journal Article DEP - 20250111 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Contrast Media) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Percutaneous Coronary Intervention MH - *Acute Kidney Injury/chemically induced/epidemiology/prevention & control MH - *Contrast Media/adverse effects MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Incidence MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Coronary Artery Disease/surgery/complications MH - Propensity Score MH - Coronary Angiography/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/14 00:20 MHDA- 2025/03/10 07:59 CRDT- 2025/01/13 19:22 PHST- 2024/11/15 00:00 [received] PHST- 2025/01/03 00:00 [revised] PHST- 2025/01/09 00:00 [accepted] PHST- 2025/03/10 07:59 [medline] PHST- 2025/01/14 00:20 [pubmed] PHST- 2025/01/13 19:22 [entrez] AID - S0002-9149(25)00015-3 [pii] AID - 10.1016/j.amjcard.2025.01.007 [doi] PST - ppublish SO - Am J Cardiol. 2025 Apr 1;240:50-56. doi: 10.1016/j.amjcard.2025.01.007. Epub 2025 Jan 11. PMID- 39803696 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1556-9519 (Electronic) IS - 1556-3650 (Linking) VI - 63 IP - 2 DP - 2025 Feb TI - Characterization of glucagon-like peptide-1 (GLP-1) agonist exposures reported to a single United States poison center. PG - 133-136 LID - 10.1080/15563650.2024.2444642 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 agonists have gained attention in recent years due to their efficacy in managing type II diabetes mellitus and their emerging role in weight management. The purpose of this study was to characterize glucagon-like peptide-1 agonist exposures reported to a single United States regional poison center over nine years, including causes of exposure, associated clinical effects, and potential areas for improving patient education and safety. METHODS: This retrospective cohort study analyzed all poison center calls involving glucagon-like peptide-1 agonists submitted to a single United States regional poison center from 14 January 2014 to 1 May 2023. Data were abstracted from the electronic medical record of the poison center, including demographics, call volume, drug involved, type of exposure, frequency of hypoglycemia, and other side effects. RESULTS: Two hundred and thirty-seven cases involving glucagon-like peptide-1 agonists were reported to the poison center. The annual number of cases increased sharply over this period. Most patients (n = 166, 70.0%) were females. Most calls (n = 164, 69.2%) were due to unintentional therapeutic errors. Semaglutide was the most frequently involved medication (n = 72, 36.0%). Hypoglycemia was identified in eight patients (3.4%). The lowest mean (+/-SD) blood glucose concentration in these hypoglycemic patients was 49.6 +/- 23.7 mg/dL (2.76 +/- 1.3 mmol/L). DISCUSSION: Unintentional therapeutic errors were involved in 164 (69.2%) cases. Despite the generally mild clinical effects observed in this study, the occurrence of hypoglycemia in a subset of patients, often requiring hospitalization, is of concern. With reports of the acquisition of these medications through online platforms and poorly regulated compounding sources, this trend may pose public health risks. CONCLUSIONS: This study demonstrates the increasing incidence of glucagon-like peptide-1 agonist exposures reported to a United States regional poison center, predominantly due to unintentional overdoses, which highlights the need for ongoing patient education. FAU - Muschler, Karen AU - Muschler K AD - Rocky Mountain Poison and Drug Safety Center, Denver, CO, USA. FAU - Muschalek, Rachael AU - Muschalek R AD - Denver Health Residency in Emergency Medicine, Denver, CO, USA. FAU - Hoyte, Christopher AU - Hoyte C AD - Rocky Mountain Poison and Drug Safety Center, Denver, CO, USA. AD - Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA. LA - eng PT - Journal Article DEP - 20250113 PL - England TA - Clin Toxicol (Phila) JT - Clinical toxicology (Philadelphia, Pa.) JID - 101241654 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Poison Control Centers/statistics & numerical data MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide 1/agonists MH - Adult MH - United States/epidemiology MH - *Hypoglycemic Agents/poisoning MH - Aged MH - Hypoglycemia/chemically induced/epidemiology MH - Young Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Adolescent MH - Glucagon-Like Peptides MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 agonists OT - hypoglycemia OT - liraglutide OT - overdose OT - semaglutide EDAT- 2025/01/13 06:16 MHDA- 2025/02/18 12:26 CRDT- 2025/01/13 05:49 PHST- 2025/02/18 12:26 [medline] PHST- 2025/01/13 06:16 [pubmed] PHST- 2025/01/13 05:49 [entrez] AID - 10.1080/15563650.2024.2444642 [doi] PST - ppublish SO - Clin Toxicol (Phila). 2025 Feb;63(2):133-136. doi: 10.1080/15563650.2024.2444642. Epub 2025 Jan 13. PMID- 39797952 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20260325 IS - 1758-535X (Electronic) IS - 1079-5006 (Linking) VI - 80 IP - 4 DP - 2025 Mar 7 TI - Exploring the Potential Effect of GLP1R Agonism on Common Aging-Related Diseases via Glucose Reduction: A Mendelian Randomization Study. LID - glaf007 [pii] LID - 10.1093/gerona/glaf007 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in managing type 2 diabetes mellitus and weight control. Their potential in treating aging-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed. METHODS: Using a genetic variant in the GLP1R gene to model the long-term effects of GLP1RAs, this Mendelian randomization (MR) study systematically explored potential causal associations between GLP1R agonism and 12 aging-related diseases and indicators. Genetic summary data sets used in this study were obtained from previous genome-wide association studies. RESULTS: The primary MR analysis results suggested that GLP1R agonism was potentially positively causally associated with appendicular lean mass (Beta = 0.246, 95% confidence interval [CI] = 0.096-0.396), whole-body fat-free mass (Beta = 0.202, 95% CI = 0.048-0.355), and lung function (forced vital capacity [FVC]; Beta = 0.179, 95% CI = 0.152-0.205; p < .05). Additionally, a potential negative causal association was observed with myocardial infarction (odds ratio = 0.430, 95% CI = 0.249-0.745; p < .05). CONCLUSIONS: The present MR study provides exploratory evidence suggesting potential causal associations between GLP1R agonism and appendicular lean mass, whole-body fat-free mass, lung function (FVC), and myocardial infarction. Given the exploratory nature of these findings and the limitations of the MR methodology, further research is needed to validate these results and investigate the underlying biological mechanisms. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Jiang, Wei AU - Jiang W AD - School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. AD - Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Ding, Kaixi AU - Ding K AD - School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Yang, Maoyi AU - Yang M AD - Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Hu, Zhipeng AU - Hu Z AD - Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Yue, Rensong AU - Yue R AD - Department of Clinical Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. LA - eng GR - 82305209/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Gerontol A Biol Sci Med Sci JT - The journals of gerontology. Series A, Biological sciences and medical sciences JID - 9502837 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Blood Glucose) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Aging/genetics MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Aged MH - Genome-Wide Association Study MH - *Blood Glucose MH - Male OTO - NOTNLM OT - Aging-related diseases OT - Causal associations OT - GLP1R agonism OT - Glucagon-like peptide-1 receptor agonists OT - Mediators OT - Mendelian randomization EDAT- 2025/01/11 14:11 MHDA- 2025/03/07 12:24 CRDT- 2025/01/11 11:04 PHST- 2024/09/09 00:00 [received] PHST- 2025/03/07 12:24 [medline] PHST- 2025/01/11 14:11 [pubmed] PHST- 2025/01/11 11:04 [entrez] AID - 7951864 [pii] AID - 10.1093/gerona/glaf007 [doi] PST - ppublish SO - J Gerontol A Biol Sci Med Sci. 2025 Mar 7;80(4):glaf007. doi: 10.1093/gerona/glaf007. PMID- 39796271 OWN - NLM STAT- MEDLINE DCOM- 20250111 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 1 DP - 2025 Jan 6 TI - Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on beta-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study. LID - 10.3390/ijms26010421 [doi] LID - 421 AB - Type 2 diabetes (T2D), the most common form, is marked by insulin resistance and beta-cell failure. beta-cell dysfunction under high-glucose-high-lipid (HG-HL) conditions is a key contributor to the progression of T2D. This study evaluates the comparative effects of 10 nM semaglutide, 10 nM tirzepatide, and 1 mM metformin, both alone and in combination, on INS-1 beta-cell maintenance and function under HG-HL conditions. INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation. The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle. Specifically, the combination treatments demonstrated superior restoration of glucose-stimulated insulin secretion (GSIS) functionality compared to 1 mM metformin, 10 nM semaglutide, and 10 nM tirzepatide. FAU - Gojani, Esmaeel Ghasemi AU - Gojani EG AUID- ORCID: 0009-0003-3168-0379 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Wang, Bo AU - Wang B AUID- ORCID: 0000-0001-7260-1938 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Li, Dongping AU - Li D AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Kovalchuk, Olga AU - Kovalchuk O AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Kovalchuk, Igor AU - Kovalchuk I AUID- ORCID: 0000-0002-8137-6928 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. LA - eng GR - IT28033/Mitacs/ PT - Comparative Study PT - Journal Article DEP - 20250106 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Metformin/pharmacology MH - *Glucagon-Like Peptides/pharmacology MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucose/metabolism/pharmacology MH - Animals MH - Rats MH - *Hypoglycemic Agents/pharmacology MH - Apoptosis/drug effects MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Insulin Secretion/drug effects MH - Cell Line MH - Lipids MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11720205 OTO - NOTNLM OT - HG-HL conditions OT - metformin OT - semaglutide OT - tirzepatide OT - beta-cells COIS- The authors declare no conflicts of interest. EDAT- 2025/01/11 14:03 MHDA- 2025/01/11 14:04 PMCR- 2025/01/06 CRDT- 2025/01/11 01:09 PHST- 2024/12/02 00:00 [received] PHST- 2024/12/31 00:00 [revised] PHST- 2025/01/04 00:00 [accepted] PHST- 2025/01/11 14:04 [medline] PHST- 2025/01/11 14:03 [pubmed] PHST- 2025/01/11 01:09 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - ijms26010421 [pii] AID - ijms-26-00421 [pii] AID - 10.3390/ijms26010421 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jan 6;26(1):421. doi: 10.3390/ijms26010421. PMID- 39793280 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20250620 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 1 DP - 2025 Jan TI - Evaluating the causal effect of using glucagon-like peptide-1 receptor agonists on the risk of autoimmune diseases. PG - 103186 LID - S1871-4021(25)00003-7 [pii] LID - 10.1016/j.dsx.2025.103186 [doi] AB - OBJECTIVE: To investigate the causal association of using glucagon-like peptide-1 receptor (GLP1R) agonists with autoimmune diseases. METHODS: The available cis-eQTLs for drugs target genes (GLP1R) were used as genetic variants for exposure to GLP1R agonists. Type 2 diabetes was used as positive control. Mendelian randomizations (MR) were performed to explore the association of genetically-proxied GLP1R agonists with 11 autoimmune diseases from large-scale consortia. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, we performed MR analysis to examine whether GLP1R agonists affect 731 immune cell phenotypes to clarify the potential mechanism. RESULTS: We observed supportive evidence to support the association of GLP1R agonists with reduced the risk of hypothyroidism (OR [95 %] = 0.89 [0.82-0.95], P < 0.001), but increased risk of ulcerative colitis (OR [95 %] = 1.48 [1.27-1.71], P < 0.001), type 1 diabetes (OR [95 %] = 1.34 [1.21-1.50], P < 0.001), systemic lupus erythematosus (OR [95 %] = 1.61 [1.29-2.02], P < 0.001) and sarcoidosis (OR [95 %] = 1.38 [1.08-1.75], P = 0.008). There was no supporting evidence to verify the association of GLP1R expression with asthma, Crohn's disease, multiple sclerosis and myasthenia gravis (P > 0.05). In addition, we found that GLP1R agonists was positively associated with 221 immune cell phenotypes (P < 0.05, OR > 1), and negatively associated with 317 immune cell phenotypes (P < 0.05, OR < 1). CONCLUSION: GLP1R agonists are causally associated with various autoimmune diseases potentially through the modulation of 731 immune cell phenotypes. CI - Copyright (c) 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Sun, Yuming AU - Sun Y AD - Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, China; Furong Laboratory, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Zhou, Qian AU - Zhou Q AD - Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. FAU - Onzere, Lorraine Edna AU - Onzere LE AD - Department of Oncology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Dian, Yating AU - Dian Y AD - Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. FAU - Meng, Yu AU - Meng Y AD - Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. FAU - Li, Daishi AU - Li D AD - Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. FAU - Zeng, Furong AU - Zeng F AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: zengfurong@csu.edu.cn. FAU - Lei, Shaorong AU - Lei S AD - Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, China. Electronic address: leishaorong@csu.edu.cn. FAU - Deng, Guangtong AU - Deng G AD - Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. Electronic address: dengguangtong@outlook.com. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250107 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Autoimmune Diseases/chemically induced/epidemiology/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Factors MH - Mendelian Randomization Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Prognosis MH - *Hypoglycemic Agents/adverse effects OTO - NOTNLM OT - Autoimmune disease OT - GLP1R agonists OT - Mendelian randomization COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/11 13:57 MHDA- 2025/03/15 00:38 CRDT- 2025/01/10 18:06 PHST- 2024/05/19 00:00 [received] PHST- 2025/01/02 00:00 [revised] PHST- 2025/01/05 00:00 [accepted] PHST- 2025/03/15 00:38 [medline] PHST- 2025/01/11 13:57 [pubmed] PHST- 2025/01/10 18:06 [entrez] AID - S1871-4021(25)00003-7 [pii] AID - 10.1016/j.dsx.2025.103186 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Jan;19(1):103186. doi: 10.1016/j.dsx.2025.103186. Epub 2025 Jan 7. PMID- 39791391 OWN - NLM STAT- MEDLINE DCOM- 20250314 LR - 20250521 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 61 IP - 7 DP - 2025 Apr TI - Glucagon-Like Peptide-1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes. PG - 1163-1174 LID - 10.1111/apt.18502 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated long-term liver benefits in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). However, no direct comparison between these therapies has been conducted. This study aimed to compare major adverse liver outcomes (MALOs) between GLP-1 RAs and SGLT2is in patients with MASLD and T2D. METHODS: Using the TriNetX Research Network, a multinational and multi-institutional database, we identified adults with MASLD and T2D who received their first prescription for either a GLP-1 RA or an SGLT2i between January 2010 and June 2023. We conducted a propensity score-matched (PSM) cohort study comparing new users of GLP-1 RAs and SGLT2is. The primary outcome was the risk of MALOs, a composite endpoint consisting of decompensated cirrhosis events, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included all-cause mortality and individual components of the primary outcome. RESULTS: This study included 15,176 pairs of patients treated with either a GLP-1 RA or a SGLT2i. The adjusted hazard ratio (HR) for MALO associated with GLP-1 RAs relative to SGLT2is was 0.84 (95% confidence interval [CI]: 0.73-0.97; incidence rate: 88.9 versus 105.3 events per 10,000 person-years), primarily driven by reduction in decompensated cirrhosis events (adjusted HR: 0.83, 95% CI: 0.71-0.96). GLP-1 RAs were associated with lower all-cause mortality (adjusted HR: 0.84, 95% CI: 0.75-0.94). CONCLUSION: GLP-1 RAs are associated with better long-term liver outcomes compared to SGLT2is in patients with MASLD and T2D. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Kuo, Chia-Chih AU - Kuo CC AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Li, Chun-Hsien AU - Li CH AD - Department of Physical Medicine and Rehabilitation, Chi Mei Hospital, Tainan, Taiwan. FAU - Tsai, Ya-Wen AU - Tsai YW AD - Center for Integrative Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Hsing-Tao AU - Kuo HT AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. LA - eng PT - Journal Article DEP - 20250110 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Adult MH - Cohort Studies OTO - NOTNLM OT - GLP-1 receptor agonist OT - MASLD OT - SGLT-2 inhibitor OT - major adverse liver outcomes EDAT- 2025/01/10 12:24 MHDA- 2025/03/14 11:19 CRDT- 2025/01/10 06:13 PHST- 2024/12/20 00:00 [revised] PHST- 2024/11/10 00:00 [received] PHST- 2025/01/04 00:00 [accepted] PHST- 2025/03/14 11:19 [medline] PHST- 2025/01/10 12:24 [pubmed] PHST- 2025/01/10 06:13 [entrez] AID - 10.1111/apt.18502 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2025 Apr;61(7):1163-1174. doi: 10.1111/apt.18502. Epub 2025 Jan 10. PMID- 39790030 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20250521 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 63 IP - 4 DP - 2025 Apr TI - Renoprotective effects of dulaglutide, a GLP-1 agonist, involving regulation of epithelial-mesenchymal transition in patients with type 2 diabetes and diabetic kidney disease. PG - 141-153 LID - 10.5414/CP204632 [doi] AB - AIMS: To assess the renoprotective effects of dulaglutide and identify mechanisms of action in patients with type 2 diabetes and diabetic kidney disease (DKD). MATERIALS AND METHODS: Outpatients/ambulant patients at the Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University between October 2021 and July 2023, with type 2 diabetes and DKD, a urinary albumin-to-creatinine ratio (UACR) >/= 3 mg/mmol and who were receiving hypoglycemic agents were prescribed dulaglutide at a dose rate of 0.75 - 1.5 mg once weekly (intervention group; n = 70). Patients receiving hypoglycemic agents other than glucagon-like peptide-1 (GLP-1) receptor agonists and who were not prescribed dulaglutide constituted the control group (n = 65). Observations/outcomes: The primary outcome was a change in the UACR and biomarkers of epithelial-mesenchymal transition (EMT) determined after 12 months of intervention treatment. Adverse events (estimates of tolerability and safety) were recorded during treatment and a follow-up period of 12 months. RESULTS: UACR changes in the intervention group compared to the control group were significantly lower (p < 0.01 at 6 months and p < 0.05 at 12 months). The frequency of gastrointestinal adverse events in the two groups were not significantly different, and there were no significant increases in the number of hypoglycemic events. Dulaglutide significantly increased the epithelial marker E-cadherin and inhibited the mesenchymal marker periostin. CONCLUSION: It is concluded that dulaglutide causes significant reductions in urinary albumin and modulates EMT-related proteins thereby ameliorating the decline in kidney function in patients with type 2 diabetes and DKD. FAU - Jiang, Daoli AU - Jiang D FAU - Meng, Fandong AU - Meng F FAU - Chou, Xiaohua AU - Chou X FAU - Shen, Jiaxin AU - Shen J FAU - Liu, Miaoyan AU - Liu M LA - eng PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Diabetic Nephropathies/prevention & control/drug therapy/physiopathology/etiology/diagnosis MH - Middle Aged MH - *Recombinant Fusion Proteins/adverse effects/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use MH - Aged MH - *Epithelial-Mesenchymal Transition/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Albuminuria/prevention & control MH - Treatment Outcome MH - Kidney/drug effects/physiopathology MH - Biomarkers/urine EDAT- 2025/01/10 06:19 MHDA- 2025/03/31 20:03 CRDT- 2025/01/10 03:53 PHST- 2025/03/25 00:00 [accepted] PHST- 2025/03/31 20:03 [medline] PHST- 2025/01/10 06:19 [pubmed] PHST- 2025/01/10 03:53 [entrez] AID - 191764 [pii] AID - 10.5414/CP204632 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2025 Apr;63(4):141-153. doi: 10.5414/CP204632. PMID- 39789997 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Real-world retrospective study in elderly patients aged 65 years and older with type 2 diabetes mellitus treated with daily oral semaglutide (SEMA-elderly). PG - 1805-1814 LID - 10.1111/dom.16174 [doi] AB - AIM: This real-world, retrospective cohort study aimed to assess the efficacy, safety and tolerability of oral semaglutide-the first GLP-1 receptor agonist available in oral form-in patients aged 65 years and older with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline (V1) to six months (V3). Secondary endpoints included change in body weight, proportion of patients achieving HbA1c <7%, proportion of patients achieving both an HbA1c reduction of >/=1% and a body weight reduction of >/=5%. Exploratory endpoints were also assessed, including evaluations at three months (V2). RESULTS: One hundred and one patients (mean age 74.7 +/- 6.1 years) started oral semaglutide treatment. Mean HbA1c decreased significantly from V1 to V3 (change: -0.44%, p < 0.001), with reductions already evident at V2. The proportion of patients achieving an HbA1c /=1% and a weight loss of >/=5%. Body weight decreased from a baseline mean of 76.8-73.7 kg at V3 (p < 0.001). Body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and systolic blood pressure decreased significantly from V1 to V3, with changes already evident at V2. Eleven patients (10.9%) reported adverse events. Seven patients (6.9%) discontinued treatment. CONCLUSION: Oral semaglutide effectively improves glycaemic control and weight management in elderly patients with T2DM while improving lipid and cardiovascular parameters and proving to be safe and well tolerated. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Fiore, Vincenzo AU - Fiore V AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Carbotta, Giovanni AU - Carbotta G AUID- ORCID: 0000-0003-1348-3489 AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Barraco, Sonia AU - Barraco S AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Falasca, Paolo AU - Falasca P AD - Unit of Internal Medicine, RM6 Hospital, Rome, Italy. FAU - Arico, Concetta Nadia AU - Arico CN AD - U.O.C Diabetologia ed Endocrinologia Grande Ospedale Metropolitano - Reggio Calabria, Italy. FAU - Barucca, Alessandra AU - Barucca A AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. LA - eng PT - Journal Article DEP - 20250110 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - Aged MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Aged, 80 and over MH - Blood Glucose/metabolism/drug effects MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Body Weight/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - HbA1c OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes EDAT- 2025/01/10 06:20 MHDA- 2025/03/07 00:21 CRDT- 2025/01/10 03:43 PHST- 2024/12/17 00:00 [revised] PHST- 2024/10/23 00:00 [received] PHST- 2024/12/24 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/10 06:20 [pubmed] PHST- 2025/01/10 03:43 [entrez] AID - 10.1111/dom.16174 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1805-1814. doi: 10.1111/dom.16174. Epub 2025 Jan 10. PMID- 39788759 OWN - NLM STAT- MEDLINE DCOM- 20250109 LR - 20250129 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 1 DP - 2025 Jan 9 TI - Cardiovascular risk associated with glucagon-like peptide-1 receptor agonists versus other conventional glucose-lowering drugs in patients with type-2 diabetes: protocol for a nationwide observational comparative study in routine care. PG - e087790 LID - 10.1136/bmjopen-2024-087790 [doi] LID - e087790 AB - INTRODUCTION: Several cardiovascular outcome trials have been conducted to assess the cardiovascular safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on cardiorenal outcomes in patients with type-2 diabetes (T2D). However, the strict requirements of randomised controlled trials to avoid most confounding factors are at the expense of external validity. Using national real-world data, we aimed to evaluate the effectiveness of GLP-1RAs in association with metformin especially on cardiovascular events, hospitalisation for heart failure and all-cause death in comparison with other diabetes treatment schemes using dipeptidyl peptidase IV inhibitors, sulfonylureas/glinides or insulin also associated with metformin. Sodium-glucose transport protein 2 inhibitors (SGLT-2i) will be excluded as comparators, as this class of oral hypoglycaemic agents just started in 2020 to be marketed in France. METHODS AND ANALYSIS: The Systeme National des Donnees de Sante is a comprehensive nationwide administrative healthcare database in France that covers approximately 67 million people.Several cohorts of adult patients with T2D initiating any GLP1-RA in dual or triple therapies, as recommended by the French Health authorities, will be identified in this database over the period 2016-2021. These cohorts will be defined by the combination of glucose-lowering drugs prescribed simultaneously with GLP1-RA and diabetes treatment received over a 6-month period before GLP1-RA initiation. They will be first matched with T2D controls (1:3 ratio) based on the year of drug initiation and treatment regimens before and simultaneously with GLP1-RA in the different selected cohorts. Comparative analyses will be conducted versus these control groups, adjusting for cardiovascular event history and a propensity score considering age, sex, area of residence, deprivation index, comorbidities, duration of diabetes, use of lipid-lowering drugs, anticoagulants, antiplatelet therapies and blood pressure-lowering therapies. Comparative analyses will be conducted versus these control groups, using a high-dimensional propensity scores method and fixed baseline characteristics. Treatment effects on the different outcomes measured will be estimated for each GLP1-RA group, through HR and their corresponding CIs (95% CI) using Cox regressions and/or competitive risk regressions when necessary. ETHICS AND DISSEMINATION: The study has been approved by an independent ethics committee (Comite ethique et scientifique pour les recherches, les etudes et les evaluations dans le domaine de la sante, Paris, France; reference: 8699786, dated 2 June 2022) and has been registered with the French National Data Protection Commission (Commission Nationale de l'Informatique et des Libertes, Paris, France; reference: 922161, dated 26 June 2022). The findings of this study will be published in peer-reviewed scientific journals and presented at international conferences. TRIAL REGISTRATION NUMBER: F20220803152803. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Danchin, Nicolas AU - Danchin N AD - Department of Cardiology, Hopital Paris St Joseph and Hopital Europeen Georges-Pompidou, APHP, Paris, France. FAU - Lemesle, Gilles AU - Lemesle G AD - Heart and Lung Institute, Lille University Hospital, University of Lille, Lille, France. AD - FACT (French Alliance for Cardiovascular Trials), Paris, France. AD - Inserm U1011, University of Lille, Lille, France. AD - Institut Pasteur de Lille, Lille, France. FAU - Mazighi, Mikael AU - Mazighi M AD - Department of Neurology, Hopital Lariboisiere, Paris, France. AD - FHU NeuroVasc, INSERM 1144, Paris Cite University, Paris, France. FAU - Mohammedi, Kamel AU - Mohammedi K AD - Neurology and Neuro-Vascular Unit, CHU de Bordeaux, Bordeaux, France. AD - INSERM, BMC, U1034, Universite de Bordeaux, Pessac, France. FAU - Schiele, Francois AU - Schiele F AD - Cardiology and Vascular Diseases, CHU de Besancon Hopital Jean Minjoz, Besancon, France. AD - EA3920, Universite de Franche-Comte, Besancon, France. FAU - Sibon, Igor AU - Sibon I AD - Neurology and Neuro-Vascular Unit, CHU de Bordeaux, Bordeaux, France. FAU - Caron, Alexandre AU - Caron A AUID- ORCID: 0000-0002-9872-0633 AD - CEMKA, Bourg-La-Reine, France alexandre.caron@cemka.fr. FAU - Emery, Corinne AU - Emery C AD - CEMKA, Bourg-La-Reine, France. FAU - Nevoret, Camille AU - Nevoret C AD - CEMKA, Bourg-La-Reine, France. FAU - Vigie, Lucile AU - Vigie L AD - Novo Nordisk, Puteaux, France. FAU - Massien, Christine AU - Massien C AD - Novo Nordisk, Puteaux, France. FAU - Detournay, Bruno AU - Detournay B AUID- ORCID: 0000-0001-7843-4608 AD - CEMKA, Bourg-La-Reine, France. FAU - Fauchier, Laurent AU - Fauchier L AD - Cardiologie, Trousseau Hospital, Chambray-les-Tours, France. AD - Universite Francois-Rabelais de Tours, Tours, France. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250109 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 9100L32L2N (Metformin) RN - 0 (Sulfonylurea Compounds) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/agonists MH - *Cardiovascular Diseases/prevention & control MH - France/epidemiology MH - Observational Studies as Topic MH - Metformin/therapeutic use MH - Heart Disease Risk Factors MH - Sulfonylurea Compounds/therapeutic use MH - Female MH - Male MH - Drug Therapy, Combination MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Research Design MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11751855 OTO - NOTNLM OT - DIABETES & ENDOCRINOLOGY OT - General diabetes OT - Observational Study COIS- Competing interests: ND has received fees for giving talks or participating to advisory boards, or support for attending meetings from: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Bouchara-Recordati, IBSA, Maincare, MSD, NovoNordisk, Pfizer, Servier, UCB and Vifor. GL has received fees and honoraria from Alnylam, Amarin, Amgen, Astra Zeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, MSD, Novartis, Novo Nordisk, Organon, Pfizer, Recordati and Sanofi Aventis. MM has received fees and honoraria from Acticor Biotech, Astra Zeneca, Boehringer Ingelheim, Novartis, Novo Nordisk. KM has received consulting fees from Novo Nordisk; honoraria for lectures, presentations, or speaker bureaus from Novo Nordisk, Astra Zeneca, Boehringer-Ingelheim, Eli Lilly, Sanofi, Lifescan, Abbott, and Bayer; and participation to Advisory Board from Novo Nordisk, Sanofi and Amarin. FS has received research grants from and/or was speaker (with or without lecture fees) on a.o. (CME accredited) meetings sponsored by Amgen, Bayer, Novartis, Novo Nordisk, Sanofi Aventis, Recordati, Servier, Mylan and AstraZeneca. IS has received fees and honoraria from Novonordisk, Sanofi Synthe-Labo, Servier, Boheringer Ingelheim, Astra-Zeneca and Medtronic. AC, CE and CN are employees of CEMKA, a French heath care Clinical Research Organization. LV and CM are employees of NovoNordisk. BD has received fees from Astra-Zeneca, CEMKA, Novo-Nordisk, Abbott, Sanofi Winthrop Industry, Lumanity, Continuum+ and CERBA. LF has received consulting fees from AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Novo and XO, and speaker activities for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Boston Scientific, Medtronic and Zoll. EDAT- 2025/01/10 00:21 MHDA- 2025/01/10 00:22 PMCR- 2025/01/09 CRDT- 2025/01/09 21:53 PHST- 2025/01/10 00:22 [medline] PHST- 2025/01/10 00:21 [pubmed] PHST- 2025/01/09 21:53 [entrez] PHST- 2025/01/09 00:00 [pmc-release] AID - bmjopen-2024-087790 [pii] AID - 10.1136/bmjopen-2024-087790 [doi] PST - epublish SO - BMJ Open. 2025 Jan 9;15(1):e087790. doi: 10.1136/bmjopen-2024-087790. PMID- 39786599 OWN - NLM STAT- MEDLINE DCOM- 20250109 LR - 20260127 IS - 1590-1262 (Electronic) IS - 1124-4909 (Print) IS - 1124-4909 (Linking) VI - 30 IP - 1 DP - 2025 Jan 9 TI - Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes. PG - 2 LID - 10.1007/s40519-024-01711-2 [doi] LID - 2 AB - PURPOSE: To report data on the real-world effectiveness and safety of injectable (IS) and oral (OS) therapies in obese or overweight diabetes (T2DM) patients on glycometabolic control, weight loss (WL) and weight maintenance after the use of semaglutide. METHODS: 175 subjects with obesity or overweight and T2DM were retrospectively assessed. Of these, 129 (75F, 54 M; mean age 61.2 +/- 9.8 years) patients were treated with IS and 46 (24F, 22 M; mean age 65.7 +/- 12.8 years) with OS for T2DM and WL. At baseline, mean weight (mW) was 101.8 +/- 24.6 kg and 95.2 +/- 15.0 kg; mean body mass index (mBMI) was 36.7 +/- 8.7 kg/m(2) and 34.3 +/- 5.3 kg/m(2). RESULTS: After 6 months, in the IS group, 127 patients had a mW and mBMI reduction of - 10.4 +/- 8.1 kg and - 3.9 +/- 3.0 kg/m(2). 46 patients in the OS group had a mW and mBMI reduction of - 6.7 +/- 5.3 kg and - 2.6 +/- 2.1 kg/m(2). After 12 months, 102 patients in the IS group achieved a mW and mBMI reduction of - 9.3 +/- 7.5 kg and - 3.4 +/- 2.6 kg/m(2). 44 patients in the OS group of treatment had a mW and mBMI reduction of - 10.7 +/- 6.5 kg and - 3.9 +/- 2.4 kg/m(2). After 24 months, 92 patients in the IS group of therapy achieved a mW and mBMI reduction of - 15.9 +/- 11.4 kg and - 5.8 +/- 3.7 kg/m(2). There was a mean percentage reduction of glycated hemoglobin (HBA1C) of - 1.9 +/- 1.4%, - 1.5 +/- 1.9%, and - 1.5 +/- 1.7% after 6, 12 and 24 months in the IS group. In the OS group there was a mean reduction of - 1.5 +/- 1.6% after 6 months and of - 0.8 +/- 0.6% after 12 months of therapy. CONCLUSIONS: Semaglutide induces WL maintenance after 12 and 24 months of treatment. Our results show a comparable effectiveness of IS and OS in T2DM patients with obesity or overweight. IS and OS treatment provide significant WL that allows reaching the glycometabolic therapeutic goal in a short time. Level of Evidence Level II. CI - (c) 2024. The Author(s). FAU - Del Prete, Michela AU - Del Prete M AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. michela.delprete@asst-lariana.it. FAU - Gavazzi, Lidia AU - Gavazzi L AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Disoteo, Olga Eugenia AU - Disoteo OE AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Vignati, Federico AU - Vignati F AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Di Sacco, Gianleone AU - Di Sacco G AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Muratori, Fabrizio AU - Muratori F AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. LA - eng PT - Journal Article DEP - 20250109 PL - Germany TA - Eat Weight Disord JT - Eating and weight disorders : EWD JID - 9707113 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - Aged MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Retrospective Studies MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use MH - Body Mass Index MH - Body Weight Maintenance MH - Semaglutide PMC - PMC11717789 OTO - NOTNLM OT - Continuing weight loss OT - Diabetes OT - Obesity OT - Overweight OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: This is a retrospective observational study, and no ethical approval is required. Informed consent was obtained from all the participants of the study. Competing interests: The authors declare no competing interests. EDAT- 2025/01/09 16:59 MHDA- 2025/01/09 18:21 PMCR- 2025/01/09 CRDT- 2025/01/09 11:16 PHST- 2024/11/18 00:00 [received] PHST- 2024/12/23 00:00 [accepted] PHST- 2025/01/09 18:21 [medline] PHST- 2025/01/09 16:59 [pubmed] PHST- 2025/01/09 11:16 [entrez] PHST- 2025/01/09 00:00 [pmc-release] AID - 10.1007/s40519-024-01711-2 [pii] AID - 1711 [pii] AID - 10.1007/s40519-024-01711-2 [doi] PST - epublish SO - Eat Weight Disord. 2025 Jan 9;30(1):2. doi: 10.1007/s40519-024-01711-2. PMID- 39778759 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20250520 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 282 DP - 2025 Apr TI - Type 2 diabetes disease and management patterns across a large, diverse healthcare system: Issues and opportunities for guideline-directed therapies. PG - 114-124 LID - S0002-8703(25)00003-1 [pii] LID - 10.1016/j.ahj.2025.01.003 [doi] AB - BACKGROUND: The prevalence, chronicity and clinical impact of type 2 diabetes (T2D) defines this disease state as a critical determinant in morbidity and mortality, as encountered by individuals, health care systems, and public health in general. The need to understand and optimize T2D identification and management is now further heightened by the advent of medications with established cardiovascular (CV) and kidney benefits in such patients, namely sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA). Prescription rates for these agents have remained low despite guidelines incorporating and emphasizing their use. Better understanding T2D disease and management patterns, including percentage of patients meeting guideline indications, is necessary to address undertreatment, improve patient management, and enable better strategies. We evaluated such issues, including eligibility for and utilization of SGLT2i and GLP-1 RA, in a large health system caring for over 1.5 million patients annually. METHODS: The electronic health record (EHR) at a large health network in the Northeastern United States was queried to identify patients 18 years of age or older with T2D and at least 1 hemoglobin A1c (HbA1c) between January 1, 2020 and January 1, 2023, examining those with T2D and 1) atherosclerotic CV disease (ASCVD), 2) an estimated 10-year ASCVD risk score >/= 10% without known ASCVD, 3) heart failure (HF), and/or 4) chronic kidney disease (CKD) based on EHR listed comorbidities. Demographics, medications, comorbidities, and indications for SGLT2i and/or GLP-1 RA therapy were assessed by 1 or more of the 4 indications above as outlined in society guidelines. RESULTS: Of the 147,338 patients who met inclusion criteria, 47% were female, 28% were non-white, and 14% with a non-English language preference. Of those, 121,508 (83%) had an indication for either SGLT2i or GLP-1 RA based on guideline recommendations: 17% were prescribed an SGLT2i, 22% were prescribed GLP-1 RA, and 6% of patients were prescribed both medications. Only 33% of all eligible patients were prescribed therapy. Of patients eligible for either an SGLT2i or GLP-1 RA therapy not currently receiving either therapy, 49% had 10-year ASCVD risk >/= 10% without known ASCVD, 42% had ASCVD, 52% had CKD, and 14% had HF. CONCLUSIONS: More than 4 out of 5 patients with T2D had a CV or kidney indication for either SGLT2i or GLP-1 RA. However, uptake of SGLT2i/GLP-1 RA in these high-risk populations remains low (just 32%) across this health network. Future studies are needed to identify better strategies to overcome provider, patient, and system-level barriers to the uptake and dissemination of guideline-concordant T2D therapies. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Blood, Alexander J AU - Blood AJ AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Chang, Lee-Shing AU - Chang LS AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Colling, Caitlin AU - Colling C AD - Diabetes Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Stern, Gretchen AU - Stern G AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA. FAU - Gabovitch, Daniel AU - Gabovitch D AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA. FAU - Zelle, David AU - Zelle D AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA. FAU - Zacherle, Emily AU - Zacherle E AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Noone, Joshua AU - Noone J AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Robar, Carey AU - Robar C AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Aronson, Samuel J AU - Aronson SJ AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Mass General Brigham Personalized Medicine, Mass General Brigham, Somerville, MA. FAU - Gaziano, Thomas A AU - Gaziano TA AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Matta, Lina S AU - Matta LS AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA. FAU - Plutzky, Jorge AU - Plutzky J AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA. FAU - Cannon, Christopher P AU - Cannon CP AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA. FAU - Scirica, Benjamin M AU - Scirica BM AD - Accelerator for Clinical Transformation, Brigham and Women's Hospital, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: Bscirica@BWH.Harvard.Edu. LA - eng PT - Journal Article DEP - 20250106 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Practice Guidelines as Topic MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Guideline Adherence MH - *Practice Patterns, Physicians' MH - Disease Management COIS- Declaration of competing interest Dr. Blood, Dr. Cannon, Dr. Plutzky, Daniel Gabovitch, and David Zelle report grant support from Boehringer Ingelheim, Better Therapeutics, Foresite Labs, Milestone Pharmaceutical, Eli Lilly, Novo Nordisk, and Pfizer. In addition, Dr. Blood reports grants from General Electric Health, and recieving personal fees from Alnylam, Milestone Therapeutics, NODE health, Walgreens Health, Medscape, Color Health, Corcept Therapeutics, Nference Inc, Withings, and Arsenal Capital Partners and holding equity in AIwithCare, Knownwell, Porter Health, and Signum Technologies. Dr. Chang reports grant support from Novo Nordisk and participating in clinical trials sponsored by Applied Therapeutics, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Eli Lilly, Fractyl Health, Novo Nordisk, Rhythm Pharmaceuticals, and Sanofi. Ms. Zacherle, Dr. Noone, and Dr. Robar are employees of Novo Nordisk Inc. Mr. Aronson reports personal fees from Nest Genomics and Harvard Medical School and holds equity in AIwithCare. Dr. Gaziano reports grant support from the NIH and Novartis and personal fees from Novartis, Multiply Labs, Amgen, DalCor, and Dimagi. Dr. Plutzky reports grant support from NIH/NIDDK, Boehringer Ingelheim, and Novartis and personal fees from Altimmune, Amgen, Bain Capital, Boehringer Ingelheim, Corcept, Esperion, Kailera, Merck, New Amsterdam, Novo Nordisk, and Toku Eyes. Dr. Cannon reports salary support from Colorado Prevention Center (CPC) Clinical Research which recieves research grant support from Amgen, Bayer, Cleerly, Esperion, Lexicon, and Silence and personal fees from Amryt/Chiesi, Amgen, Ascendia, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, CSL Bhering, Genomadix, Eli Lilly, Janssen, Lexicon, Milestone, Novartis, Pfizer, and Rhoshan and serving on the Data and Safety Monitoring Boards for the Areteia, Novo Nordisk, ROMTherapy Inc., and the Veterans Administration. Dr. Wexler serves on the Data Safety Monitoring Committee for Novo Nordisk's SOUL and FLOW trials. Dr. Scirica reports Amgen, Merck, Verve, and personal fees from AbbVie, AstraZeneca, Bayer, Hanmi, Lexeo, Novo Nordisk, Verve, and Boehringer Ingelheim and having equity in Health at Scale, Aboretun LifeScience, Doximity, and AIwithCare. EDAT- 2025/01/09 00:21 MHDA- 2025/02/24 02:10 CRDT- 2025/01/08 19:21 PHST- 2024/02/16 00:00 [received] PHST- 2025/01/02 00:00 [revised] PHST- 2025/01/03 00:00 [accepted] PHST- 2025/02/24 02:10 [medline] PHST- 2025/01/09 00:21 [pubmed] PHST- 2025/01/08 19:21 [entrez] AID - S0002-8703(25)00003-1 [pii] AID - 10.1016/j.ahj.2025.01.003 [doi] PST - ppublish SO - Am Heart J. 2025 Apr;282:114-124. doi: 10.1016/j.ahj.2025.01.003. Epub 2025 Jan 6. PMID- 39777709 OWN - NLM STAT- MEDLINE DCOM- 20250625 LR - 20260515 IS - 2509-2723 (Electronic) IS - 2509-2715 (Print) IS - 2509-2723 (Linking) VI - 47 IP - 3 DP - 2025 Jun TI - Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types. PG - 4413-4427 LID - 10.1007/s11357-024-01494-5 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. While these agents are well known for their metabolic benefits, there is growing interest in their potential effects on cancer biology. However, the role of GLP-1R agonists in cancer remains complex and not fully understood, particularly across different tumor types. This study aimed to evaluate the prognostic significance of GLP1R expression on overall survival across various cancer types. Using a comprehensive analysis of gene expression data and survival outcomes a large cohorts of different tumor types, we employed Cox proportional hazards survival analyses, coupled with false discovery rate determinations, to explore correlations between GLP1R expression and survival. The integrated database included thousands of cancer specimens with available overall survival time and event data from numerous independent cohorts, providing a robust platform for survival analysis. Our findings reveal that increased GLP1R expression is associated with improved overall survival in cancers such as bladder cancer, breast cancer, esophageal adenocarcinoma, renal clear cell carcinoma, and thyroid carcinoma. Conversely, higher GLP1R expression is linked to poorer survival outcomes in cervical squamous cell carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Additionally, GLP1R expression showed no significant impact on overall survival in cancers such as esophageal squamous cell carcinoma, colon cancer, head-neck squamous cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, ovarian cancer, and pancreatic cancer. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient's cancer risk profile. CI - (c) 2025. The Author(s). FAU - Ungvari, Zoltan AU - Ungvari Z AD - Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA. AD - Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. FAU - Bartha, Aron AU - Bartha A AD - Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary. FAU - Ungvari, Anna AU - Ungvari A AUID- ORCID: 0009-0001-5053-2828 AD - Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. Ungann2004@gmail.com. FAU - Fekete, Monika AU - Fekete M AD - Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. FAU - Bianchini, Giampaolo AU - Bianchini G AD - Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Gyorffy, Balazs AU - Gyorffy B AD - Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary. AD - Dept. of Biophysics, Medical School, University of Pecs, H-7624, Pecs, Hungary. AD - Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary. LA - eng GR - RRF-2.3.1-21-2022-00003/Nemzeti Kutatasi, Fejlesztesi es Innovacios Alap/ PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20250108 PL - Switzerland TA - Geroscience JT - GeroScience JID - 101686284 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/mortality/genetics/drug therapy MH - Prognosis MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Aged PMC - PMC12181560 OTO - NOTNLM OT - Cancer prognosis OT - GLP-1 receptor agonists OT - Gene expression OT - KM plotter OT - Survival analysis OT - Tumor biomarkers OT - Type 2 diabetes treatment COIS- Declarations. Competing interests: Dr. Balazs Gyorffy serves as Associate Editor for GeroScience. Dr. Zoltan Ungvari serves as Editor-in-Chief for GeroScience and has personal relationships with individuals involved in the submission of this paper. All other authors declare no competing interests. EDAT- 2025/01/09 00:23 MHDA- 2025/06/25 06:25 PMCR- 2025/01/08 CRDT- 2025/01/08 18:23 PHST- 2024/09/10 00:00 [received] PHST- 2024/12/17 00:00 [accepted] PHST- 2025/06/25 06:25 [medline] PHST- 2025/01/09 00:23 [pubmed] PHST- 2025/01/08 18:23 [entrez] PHST- 2025/01/08 00:00 [pmc-release] AID - 10.1007/s11357-024-01494-5 [pii] AID - 1494 [pii] AID - 10.1007/s11357-024-01494-5 [doi] PST - ppublish SO - Geroscience. 2025 Jun;47(3):4413-4427. doi: 10.1007/s11357-024-01494-5. Epub 2025 Jan 8. PMID- 39774820 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20250520 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 3 DP - 2025 Mar 1 TI - Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes. PG - 444-454 LID - 10.2337/dc24-1903 [doi] AB - OBJECTIVE: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: With an active comparator, new-user approach, we conducted a cohort study using the U.K. Clinical Practice Research Datalink linked with hospital and national statistics databases. Cox proportional hazards models using propensity score fine stratification weighting were used to calculate hazard ratios (HRs) and 95% CIs for cirrhosis (primary outcome) and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes). RESULTS: In the first cohort comparing 25,516 patients starting GLP-1RAs and 186,752 starting DPP-4 inhibitors, GLP-1RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68-1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46-0.90), as also decompensated cirrhosis (HR 0.74, 95% CI 0.54-1.00), but not with a lower risk of hepatocellular carcinoma or liver-related mortality. CONCLUSIONS: In patients with type 2 diabetes in the U.K., GLP-1RAs were not associated with a lower risk of cirrhosis compared with DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared with DPP-4 inhibitors. CI - (c) 2025 by the American Diabetes Association. FAU - Pradhan, Richeek AU - Pradhan R AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia. FAU - Yin, Hui AU - Yin H AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. FAU - Lu, Sally AU - Lu S AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. FAU - Sebastiani, Giada AU - Sebastiani G AD - Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Canada. AD - Division of Endocrinology, Jewish General Hospital, Montreal, Canada. FAU - Yu, Oriana AU - Yu O AD - Division of Endocrinology, Jewish General Hospital, Montreal, Canada. FAU - Suissa, Samy AU - Suissa S AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. FAU - Azoulay, Laurent AU - Azoulay L AUID- ORCID: 0000-0001-5162-3556 AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada. LA - eng GR - CAPMC/CIHR/Canada PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - *Liver Cirrhosis/prevention & control/epidemiology MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies EDAT- 2025/01/08 18:21 MHDA- 2025/02/20 18:21 CRDT- 2025/01/08 16:27 PHST- 2024/09/05 00:00 [received] PHST- 2024/12/04 00:00 [accepted] PHST- 2025/02/20 18:21 [medline] PHST- 2025/01/08 18:21 [pubmed] PHST- 2025/01/08 16:27 [entrez] AID - 157701 [pii] AID - 10.2337/dc24-1903 [doi] PST - ppublish SO - Diabetes Care. 2025 Mar 1;48(3):444-454. doi: 10.2337/dc24-1903. PMID- 39773332 OWN - NLM STAT- MEDLINE DCOM- 20250108 LR - 20260127 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 30 IP - 1 DP - 2025 Jan 7 TI - Comparative efficacy of GLP-1 RAs/SGLT-2 inhibitors in reducing cardiovascular events in type 2 diabetes according to baseline use of metformin: a systematic review and meta-analysis of randomized controlled trials. PG - 13 LID - 10.1186/s40001-024-02241-4 [doi] LID - 13 AB - BACKGROUND: Sodium-glucose transporters 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are recommended along with metformin for the potential cardiovascular benefits among type 2 diabetes. This meta-analysis aims to evaluate whether the effects of SGLT-2i or GLP-1 RAs on cardiovascular outcomes are consistent with and without baseline metformin use. METHODS: PubMed, Cochrane, Web of Science and Embase were searched for randomized placebo-controlled trials with SGLT-2i or GLP-1 RAs as interventions of type 2 diabetes patients up to June, 2024. The main outcomes were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) or cardiovascular death. Both random-effects model and fixed model were adopted to estimate pooled hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: A total of 81,738 patients (median age: 62-66 years, 53.7-71.5% men, median follow-up: 1.3-5.4 years) from 11 studies (7 studies of SGLT-2i and 4 of GLP-1 RAs) were included in the study. The metformin-naive portions ranged from 28.90% to 81.98%. Among patients using metformin at baseline, SGLT-2i or GLP-1 RAs reduced MACE risk (HR = 0.95, 95% CI 0.91-0.99, P = 0.02). In metformin-naive patients, similar reductions were observed (HR = 0.79, 95% CI 0.65-0.95, P = 0.01). No statistically significant interaction was found between metformin users and non-users for any outcome (all P values for interaction > 0.05), indicating consistent cardiovascular benefits regardless of baseline metformin therapy. CONCLUSIONS: SGLT-2i and GLP-1 RAs have the effects of cardiovascular benefits for T2DM patients regardless of baseline metformin use. CI - (c) 2024. The Author(s). FAU - Zhang, Yuxin AU - Zhang Y AD - Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. FAU - Li, Zhaoji AU - Li Z AD - Peking University Third Hospital, Beijing, China. FAU - Hao, Yongchen AU - Hao Y AD - Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. haoyongchen123@163.com. LA - eng GR - PX2023026/Beijing Municipal Administration of Hospitals Incubating Program/ PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250107 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Metformin/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Randomized Controlled Trials as Topic MH - *Cardiovascular Diseases/prevention & control/etiology/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11706166 OTO - NOTNLM OT - Cardiovascular disease OT - GLP-1 Ras OT - Meta-analysis OT - SGLT-2i OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/01/08 18:22 MHDA- 2025/01/08 18:23 PMCR- 2025/01/07 CRDT- 2025/01/08 15:10 PHST- 2023/08/07 00:00 [received] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/01/08 18:23 [medline] PHST- 2025/01/08 18:22 [pubmed] PHST- 2025/01/08 15:10 [entrez] PHST- 2025/01/07 00:00 [pmc-release] AID - 10.1186/s40001-024-02241-4 [pii] AID - 2241 [pii] AID - 10.1186/s40001-024-02241-4 [doi] PST - epublish SO - Eur J Med Res. 2025 Jan 7;30(1):13. doi: 10.1186/s40001-024-02241-4. PMID- 39772758 OWN - NLM STAT- MEDLINE DCOM- 20250117 LR - 20260705 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 35 IP - 1 DP - 2025 Jan TI - Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study. PG - 69-78 LID - 10.1089/thy.2024.0387 [doi] AB - Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up. FAU - Baxter, Sarah M AU - Baxter SM AD - Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland. FAU - Lund, Lars Christian AU - Lund LC AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Andersen, Jacob H AU - Andersen JH AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Brix, Thomas H AU - Brix TH AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Department of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Hegedus, Laszlo AU - Hegedus L AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Department of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Hsieh, Miyuki Hsing-Chun AU - Hsieh MH AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Su, Chris Tzu-Ting AU - Su CT AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Cheng, Michael Chun-Yuan AU - Cheng MC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Chang, Zoe Chi-Jui AU - Chang ZC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Lai, Edward Chia-Cheng AU - Lai EC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Population Health Data Center, National Cheng Kung University, Tainan, Taiwan. FAU - Hussain, Swaleh AU - Hussain S AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. AD - Women's College Hospital Research Institute, Toronto, Canada. AD - ICES, Toronto, Canada. FAU - Chu, Cherry AU - Chu C AD - Women's College Hospital Research Institute, Toronto, Canada. FAU - Gomes, Tara AU - Gomes T AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. AD - ICES, Toronto, Canada. AD - Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Canada. FAU - Antoniou, Tony AU - Antoniou T AD - ICES, Toronto, Canada. AD - Department of Family and Community Medicine, University of Toronto, Toronto, Canada. FAU - Eskander, Antoine AU - Eskander A AD - ICES, Toronto, Canada. AD - Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, Canada. AD - Department of Otolaryngology, Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Canada. FAU - Bouck, Zachary AU - Bouck Z AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. AD - ICES, Toronto, Canada. FAU - Tadrous, Mina AU - Tadrous M AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. AD - Women's College Hospital Research Institute, Toronto, Canada. AD - ICES, Toronto, Canada. FAU - Bea, Sungho AU - Bea S AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Choi, Eun-Young AU - Choi EY AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. FAU - Shin, Ju-Young AU - Shin JY AD - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. FAU - Modig, Karin AU - Modig K AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Talback, Mats AU - Talback M AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. AD - Division of Use and Information, Swedish Medical Products Agency, Uppsala, Sweden. FAU - Ljung, Rickard AU - Ljung R AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. AD - Division of Use and Information, Swedish Medical Products Agency, Uppsala, Sweden. FAU - Gulseth, Hanne Lovdal AU - Gulseth HL AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Karlstad, Oystein AU - Karlstad O AD - Norwegian Institute of Public Health, Oslo, Norway. FAU - Hicks, Blanaid AU - Hicks B AD - Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland. AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Pottegard, Anton AU - Pottegard A AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Meta-Analysis PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20250108 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Thyroid Neoplasms/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Cohort Studies MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Adult MH - Risk Factors OTO - NOTNLM OT - active comparator OT - dipeptidyl peptidase-4 inhibitors OT - glucagon-like peptide 1 receptor agonists OT - thyroid cancer EDAT- 2025/01/08 18:21 MHDA- 2025/01/17 18:23 CRDT- 2025/01/08 14:46 PHST- 2025/01/17 18:23 [medline] PHST- 2025/01/08 18:21 [pubmed] PHST- 2025/01/08 14:46 [entrez] AID - 10.1089/thy.2024.0387 [doi] PST - ppublish SO - Thyroid. 2025 Jan;35(1):69-78. doi: 10.1089/thy.2024.0387. Epub 2025 Jan 8. PMID- 39763481 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20250915 IS - 2396-9881 (Electronic) IS - 2396-9873 (Print) IS - 2396-9873 (Linking) VI - 10 IP - 3 DP - 2025 Sep TI - Prediabetes and diabetes mellitus type II after ischemic stroke. PG - 822-828 LID - 10.1177/23969873241304301 [doi] AB - INTRODUCTION: The progression of diabetes status in post-stroke patients remains under-investigated, particularly regarding new treatments for type II diabetes mellitus (DM II), like glucagon-like peptide 1 receptor agonists (GLP-1-RA) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, which have not been studied in the post-stroke setting. PATIENTS AND METHODS: Eight hundred eighty-four consecutive ischemic stroke patients recruited to our prospective STROKE-CARD Registry were assessed concerning their glycemic status at baseline (normoglycemia, prediabetes, DM II) and change over time within 1 year follow-up. Multivariate logistic regression was performed to identify factors associated with transitioning from normoglycemia to prediabetes or DM II. Additionally, we reviewed ongoing clinical trials for GLP-1-RA and SGLT-2 inhibitors in the context of acute ischemic stroke. RESULTS: At baseline, 44.6% (n = 394) of individuals had normoglycemia, 33.9% (n = 300) were prediabetic, and 21.5% had DM II (n = 190). After 1 year, normoglycemia decreased by 12.1 percentage points (n = 107), whereas prediabetes and DM II increased by 10.2 percentage (n = 90) points and 1.9 percentage points (n = 17), respectively. Statin therapy was the only significant risk factor for progression. 23.4% (n = 207) of our cohort would have met eligibility criteria for a recent trial on semaglutide in obese non-diabetics with prior cardiovascular disease. However, only one ongoing trial aims at evaluating short-term cardiovascular risk reduction in stroke patients. DISCUSSION: GPrediabetes and DM II are frequent in ischemic stroke patients. Even within an intensified post-stroke disease management setting, a considerable amount of stroke survivors convert to prediabetes or DM II within the first year. Our results demonstrate a notable proportion of patients qualifying inclusion in studies examining the efficacy of GLP-1-RA agonists and SGLT-2 inhibitors in secondary prevention. CONCLUSION: Given the high prevalence and progression of prediabetes and DM II in stroke survivors, there is a need for clinical trials evaluating the use of GLP-1-RA and SGLT-2 inhibitors in this population. FAU - Moelgg, Kurt AU - Moelgg K AUID- ORCID: 0009-0004-3508-3923 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Karisik, Anel AU - Karisik A AUID- ORCID: 0009-0000-3075-5437 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Scherer, Lukas AU - Scherer L AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Buergi, Lucie AU - Buergi L AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Dejakum, Benjamin AU - Dejakum B AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Komarek, Silvia AU - Komarek S AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Granna, Julian AU - Granna J AUID- ORCID: 0000-0003-2645-5129 AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Boehme, Christian AU - Boehme C AUID- ORCID: 0000-0003-1369-418X AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Pechlaner, Raimund AU - Pechlaner R AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Toell, Thomas AU - Toell T AUID- ORCID: 0000-0002-8168-2837 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Knoflach, Michael AU - Knoflach M AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Kaser, Susanne AU - Kaser S AD - Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria. FAU - Egger, Alexander AU - Egger A AD - Central Institute of Clinical Chemistry and Laboratory Medicine, Medical University of Innsbruck, Innsbruck, Austria. FAU - Griesmacher, Andrea AU - Griesmacher A AD - Central Institute of Clinical Chemistry and Laboratory Medicine, Medical University of Innsbruck, Innsbruck, Austria. FAU - Mayer-Suess, Lukas AU - Mayer-Suess L AUID- ORCID: 0000-0002-2856-0101 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. LA - eng PT - Journal Article DEP - 20250107 PL - England TA - Eur Stroke J JT - European stroke journal JID - 101688446 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - *Prediabetic State/epidemiology/drug therapy MH - *Ischemic Stroke/complications/epidemiology MH - Middle Aged MH - Prospective Studies MH - Registries MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Blood Glucose/metabolism MH - Aged, 80 and over MH - Disease Progression PMC - PMC11705302 OTO - NOTNLM OT - Prediabetes OT - antidiabetic therapy OT - cardiovascular risk factors OT - ischemic stroke OT - secondary prevention OT - type II diabetes mellitus COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/01/07 06:22 MHDA- 2025/09/16 00:33 PMCR- 2025/01/07 CRDT- 2025/01/07 04:23 PHST- 2025/09/16 00:33 [medline] PHST- 2025/01/07 06:22 [pubmed] PHST- 2025/01/07 04:23 [entrez] PHST- 2025/01/07 00:00 [pmc-release] AID - 10.1177_23969873241304301 [pii] AID - 10.1177/23969873241304301 [doi] PST - ppublish SO - Eur Stroke J. 2025 Sep;10(3):822-828. doi: 10.1177/23969873241304301. Epub 2025 Jan 7. PMID- 39762971 OWN - NLM STAT- MEDLINE DCOM- 20250206 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis. PG - 1507-1514 LID - 10.1111/dom.16159 [doi] AB - AIMS: To explore the relationship between weight loss and insulin sensitivity in response to tirzepatide or semaglutide. MATERIALS AND METHODS: We conducted a post hoc exploratory analysis of a 28-week, double-blind, randomized trial in people with type 2 diabetes treated with metformin, randomized to tirzepatide 15 mg, semaglutide 1 mg or placebo. We evaluated the relationship between change in body weight and change in insulin sensitivity determined from hyperinsulinemic euglycemic clamp (M value), or from mixed-meal tolerance testing (Matsuda index). RESULTS: Tirzepatide was associated with a greater improvement than semaglutide in insulin sensitivity assessed using hyperinsulinemic euglycemic clamps (p < 0.001). With tirzepatide, improvements in insulin sensitivity were associated with percent change in weight (R = -0.656, p < 0.0001). With semaglutide, change in insulin sensitivity was less strongly correlated with percent change in weight (R = -0.268, p = 0.0820; p = 0.0242 vs. tirzepatide). In regression analyses, the slope of the relationship between change in M value and change in weight was statistically different between semaglutide and tirzepatide (p = 0.0461). These relationships were also assessed using the Matsuda index as the metric of insulin sensitivity, and using change in fat mass as the determinant of change in insulin sensitivity. CONCLUSIONS: Improvement in insulin sensitivity was proportional to weight and fat loss, with greater strength of association with tirzepatide. In regression analysis, tirzepatide was associated with greater improvement in insulin sensitivity per unit weight loss than semaglutide. The greater improvement in insulin sensitivity following treatment with tirzepatide was not simply attributable to greater weight or fat loss. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Mather, Kieren J AU - Mather KJ AUID- ORCID: 0000-0001-8696-7500 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mari, Andrea AU - Mari A AD - Institute of Neuroscience, National Research Council, Padova, Italy. FAU - Weerakkody, Govinda AU - Weerakkody G AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Heise, Tim AU - Heise T AUID- ORCID: 0000-0002-8346-2037 AD - Profil, Neuss, Germany. FAU - DeVries, J Hans AU - DeVries JH AUID- ORCID: 0000-0001-9196-9906 AD - Profil, Neuss, Germany. FAU - Urva, Shweta AU - Urva S AUID- ORCID: 0000-0002-3681-479X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Coskun, Tamer AU - Coskun T AUID- ORCID: 0000-0002-2481-133X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Milicevic, Zvonko AU - Milicevic Z AUID- ORCID: 0000-0002-6746-901X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Haupt, Axel AU - Haupt A AUID- ORCID: 0000-0003-4502-0470 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thomas, Melissa K AU - Thomas MK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20250106 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Insulin Resistance MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Glucose Clamp Technique MH - Metformin/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Aged MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GIP OT - GLP-1 OT - insulin sensitivity OT - tirzepatide OT - weight loss EDAT- 2025/01/07 00:21 MHDA- 2025/02/07 00:20 CRDT- 2025/01/06 23:52 PHST- 2024/12/06 00:00 [revised] PHST- 2024/08/26 00:00 [received] PHST- 2024/12/16 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2025/01/07 00:21 [pubmed] PHST- 2025/01/06 23:52 [entrez] AID - 10.1111/dom.16159 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1507-1514. doi: 10.1111/dom.16159. Epub 2025 Jan 6. PMID- 39757501 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1941-5923 (Electronic) IS - 1941-5923 (Linking) VI - 26 DP - 2025 Jan 6 TI - Severe Hypomagnesemia and Hypocalcemia Linked to Semaglutide in Type 2 Diabetes: A Case Report. PG - e946539 LID - 10.12659/AJCR.946539 [doi] LID - e946539 AB - BACKGROUND Although hypomagnesemia is common in type 2 diabetes, clinical presentations with severe hypomagnesemia are rare. A number of oral blood glucose-lowering medications can reduce serum magnesium concentrations, and several severe cases have been reported in the presence of marked glucagon-like peptide-1 receptor agonist (GLP-1RA)-associated gastrointestinal adverse effects. In the present case, an acute presentation with severe hypomagnesemia was likely due to polypharmacy including semaglutide, albeit with a delayed relationship to discontinuation of this GLP-1RA, due to nausea and vomiting. CASE REPORT A 73-year-old woman with type 2 diabetes treated with several oral medications known to reduce serum magnesium (metformin, gliclazide, sitagliptin, esomeprazole) presented after an unwitnessed collapse at home without premonitory symptoms. She had discontinued low-dose semaglutide (0.25 mg subcutaneous weekly) 2 weeks beforehand, and her gastrointestinal adverse effects had largely resolved. She was found to have an undetectable serum magnesium (<0.3 mmol/L) and hypocalcemia. She responded to electrolyte replacement and was discharged well 2 days later. Three weeks after discharge, her serum magnesium and calcium concentrations were within the reference range, on regular oral supplements of both minerals. She spontaneously reported her longstanding muscle cramps had resolved after discharge. Her clinical features and course suggested she had chronic unrecognized hypomagnesemia associated with polypharmacy that progressed to a clinically severe level, with a likely contribution from recent antecedent semaglutide use. CONCLUSIONS Periodic monitoring of serum magnesium concentrations in at-risk individuals with type 2 diabetes is recommended, since the clinical presentation of severe hypomagnesemia can be sudden and without indicative warning symptoms. FAU - Davis, Timothy Mark Earls AU - Davis TME AD - Medical School, University of Western Australia, Fremantle, Western Australia, Australia. AD - Department of Endocrinology and Diabetes, Fiona Stanley and Fremantle Hospitals, Murdoch, Western Australia, Australia. LA - eng PT - Case Reports PT - Journal Article DEP - 20250106 PL - United States TA - Am J Case Rep JT - The American journal of case reports JID - 101489566 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - I38ZP9992A (Magnesium) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypocalcemia/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Magnesium Deficiency/chemically induced MH - Magnesium/blood MH - Semaglutide PMC - PMC11717150 COIS- Conflict of interest: The author has received lecture fees from NovoNordisk Australia, manufacturers of semaglutide EDAT- 2025/01/06 10:08 MHDA- 2025/01/07 00:21 PMCR- 2025/01/06 CRDT- 2025/01/06 01:23 PHST- 2025/01/07 00:21 [medline] PHST- 2025/01/06 10:08 [pubmed] PHST- 2025/01/06 01:23 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - 946539 [pii] AID - 10.12659/AJCR.946539 [doi] PST - epublish SO - Am J Case Rep. 2025 Jan 6;26:e946539. doi: 10.12659/AJCR.946539. PMID- 39756397 OWN - NLM STAT- MEDLINE DCOM- 20250128 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 2 DP - 2025 Feb TI - Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials. PG - 267-277 LID - 10.1002/oby.24202 [doi] AB - OBJECTIVE: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials. METHODS: Efficacy and safety of semaglutide 2.4 mg were evaluated in the STEP clinical trials. In this post hoc analysis, STEP 1, 3, 6, and 8 (which included people with overweight or obesity) and, separately, STEP 2 and 6 (which included people with overweight or obesity and type 2 diabetes) were pooled for analysis. Changes in antihypertensive or lipid-lowering treatment intensity from randomization to end of treatment were evaluated. RESULTS: In both pooled samples, a higher proportion of participants in the semaglutide 2.4 mg group versus placebo underwent antihypertensive or lipid-lowering treatment intensity reduction by end of treatment. A smaller proportion underwent antihypertensive or lipid-lowering treatment intensification by end of treatment in the semaglutide 2.4 mg group of both samples versus placebo. In participants receiving antihypertensive or lipid-lowering medications in both samples, greater numeric reductions in body weight were observed in the semaglutide 2.4 mg group versus placebo. CONCLUSIONS: These results support a relationship between semaglutide 2.4 mg treatment of overweight and obesity and reduced need for antihypertensive and lipid-lowering treatment, facilitating treatment intensity reduction/discontinuation and abating treatment intensification. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Tchang, Beverly G AU - Tchang BG AUID- ORCID: 0000-0002-2955-8089 AD - Weill Cornell Medicine, New York, New York, USA. FAU - Knight, Michael G AU - Knight MG AD - The George Washington University, Washington, DC, USA. FAU - Adelborg, Kasper AU - Adelborg K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Clements, Jennifer N AU - Clements JN AD - University of South Carolina College of Pharmacy, Columbia, South Carolina, USA. FAU - Iversen, Aske Thorn AU - Iversen AT AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Traina, Andrea AU - Traina A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. LA - eng GR - Novo Nordisk/ GR - Novo Nordisk Inc./ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250105 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Antihypertensive Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypolipidemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Antihypertensive Agents/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Glucagon-Like Peptides/administration & dosage MH - *Hypertension/drug therapy/complications MH - *Hypolipidemic Agents/administration & dosage MH - *Obesity/drug therapy/complications MH - Overweight/drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11774009 COIS- Michael G. Knight has participated in advisory boards and received payment for consulting from Novo Nordisk Inc.; has received support from Novo Nordisk for medical writing; has received payment for educational event participation from Gilead Sciences, Inc.; and is a member of the National Medical Association Board of Trustees (unpaid). Kasper Adelborg is an employee and shareholder of Novo Nordisk A/S and has received support from Novo Nordisk for research, medical writing, fees associated with article publication and travel, and registration fees for conferences/meetings. Jennifer N. Clements is a member and has received payment from the Novo Nordisk Cardiometabolic Speakers Bureau and the Eli Lilly Speakers Bureau. Aske Thorn Iversen is an employee and shareholder of Novo Nordisk A/S and has received support from Novo Nordisk for travel and registration fees for conferences/meetings. Beverly G. Tchang is a shareholder of Novo Nordisk Inc. and an advisor to Novo Nordisk and Palatin Technologies, Inc. Andrea Traina is an employee and shareholder of Novo Nordisk Inc. and has received support from Novo Nordisk for research, medical writing, fees associated with article publication and travel, and registration fees for conferences/meetings. EDAT- 2025/01/06 10:07 MHDA- 2025/01/28 12:35 PMCR- 2025/01/28 CRDT- 2025/01/05 18:33 PHST- 2024/09/26 00:00 [revised] PHST- 2024/05/29 00:00 [received] PHST- 2024/10/20 00:00 [accepted] PHST- 2025/01/28 12:35 [medline] PHST- 2025/01/06 10:07 [pubmed] PHST- 2025/01/05 18:33 [entrez] PHST- 2025/01/28 00:00 [pmc-release] AID - OBY24202 [pii] AID - 10.1002/oby.24202 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Feb;33(2):267-277. doi: 10.1002/oby.24202. Epub 2025 Jan 5. PMID- 39755640 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Jan 4 TI - Long-term prognostic impact of glucagon-like peptide-1 receptor agonist before ST-segment elevation myocardial infarction in patients with type 2 diabetes: a nationwide cohort study. PG - 4 LID - 10.1186/s12933-024-02548-w [doi] LID - 4 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment reduces cardiovascular events in type 2 diabetes. Yet, the impact of GLP-1RA treatment before ST-segment elevation myocardial infarction (STEMI) on long-term prognosis in patients with type 2 diabetes remains unclear. In patients with STEMI and type 2 diabetes, we aimed to investigate the association between long-term prognosis and GLP-1RA treatment before STEMI. METHODS: This nationwide cohort study included consecutive patients admitted with type 2 diabetes and STEMI in Denmark from 2010 to 2016. All data were retrieved from nationwide Danish registries. Type 2 diabetes was defined by prior hospital admission with type 2 diabetes or anti-diabetic prescriptions within one year before STEMI. Dispensed GLP-1RA medication was retrieved within one year before STEMI. RESULTS: Of 1421 patients with STEMI and diabetes, 7% were treated with GLP-1RA before STEMI and 93% were not. Patients treated with GLP-1RA were younger, had more comorbidities, and more often treated with other anti-diabetics. During 8.4 years, 36% patients treated with GLP-1RA died whereas 52% died in the no GLP-1RA group (p = 0.002). In adjusted Cox analysis, GLP-1RA was associated with lower long-term mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.43-0.84). There was no association between GLP-1RA and ischemic stroke (adjusted HR 1.05, 95% CI 0.57-1.94), recurrent myocardial infarction (adjusted HR 0.74, 95% CI 0.48-1.15), or hospitalisation for heart failure (adjusted HR 0.71, 95% CI 0.48-1.05). CONCLUSIONS: In patients with diabetes and STEMI, GLP-1RA treatment prior to STEMI admission was associated with significantly lower long-term mortality. CI - (c) 2025. The Author(s). FAU - Madsen, Jasmine Melissa AU - Madsen JM AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. jasmine.melissa.madsen.01@regionh.dk. FAU - Kjaer, Alexander Kruger AU - Kjaer AK AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. FAU - Lonborg, Jacob Thomsen AU - Lonborg JT AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Kober, Lars AU - Kober L AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Glinge, Charlotte AU - Glinge C AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. FAU - Jabbari, Reza AU - Jabbari R AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. FAU - Engstrom, Thomas AU - Engstrom T AD - Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250104 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/complications MH - Male MH - Denmark/epidemiology MH - Female MH - *ST Elevation Myocardial Infarction/mortality/diagnosis/therapy/drug therapy MH - Aged MH - Middle Aged MH - Time Factors MH - Treatment Outcome MH - *Registries MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Risk Assessment MH - Aged, 80 and over MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11700455 OTO - NOTNLM OT - GLP-1RA OT - Prognosis OT - STEMI OT - Therapeutic targets COIS- Declarations. Competing interests: The salary of JM. Madsen was supported by a grant from the Research Foundation of Rigshospitalet (E-22670-08). T. Engstrom has received speaker fees from Abbott Vascular, Boston Scientific, and Bayer, an advisory board fee from Abbott, Novo Nordisk and partici-pated in Data Safety Monitoring of the INFINITY Trial, unrelated to this topic. J. Lonborg has received an advisory board fee, an unrestricted grant, and speakers fee from Boston Sci-entific and speakers fee from Abbott, unrelated to this topic. All other authors have no con-flicts of interest to disclose. L. Kober has received speaker's honorarium from Novo Nordisk, Astra-Zeneca, Boehringer and Novartis. All other authors have nothing to declare. Ethics approval and consent for publication: All civil registration numbers were encrypted which enabled anonymity in all included patients. All register-based studies in an anonymous setup do not require ethical approval in Denmark. The authors are solely responsible for the design and conduct of this study, all analyses, drafting and editing of the paper and its final contents. EDAT- 2025/01/05 06:13 MHDA- 2025/01/07 00:21 PMCR- 2025/01/04 CRDT- 2025/01/04 23:15 PHST- 2024/10/31 00:00 [received] PHST- 2024/12/16 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2025/01/05 06:13 [pubmed] PHST- 2025/01/04 23:15 [entrez] PHST- 2025/01/04 00:00 [pmc-release] AID - 10.1186/s12933-024-02548-w [pii] AID - 2548 [pii] AID - 10.1186/s12933-024-02548-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Jan 4;24(1):4. doi: 10.1186/s12933-024-02548-w. PMID- 39753963 OWN - NLM STAT- MEDLINE DCOM- 20250121 LR - 20260717 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 31 IP - 1 DP - 2025 Jan TI - Proteomic changes upon treatment with semaglutide in individuals with obesity. PG - 267-277 LID - 10.1038/s41591-024-03355-2 [doi] AB - Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA(1c) at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials. CI - (c) 2025. The Author(s). FAU - Maretty, Lasse AU - Maretty L AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - QIAGEN A/S, Aarhus, Denmark. FAU - Gill, Dipender AU - Gill D AUID- ORCID: 0000-0001-7312-7078 AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. AD - Sequoia Genetics, London, UK. FAU - Simonsen, Lotte AU - Simonsen L AUID- ORCID: 0000-0001-6914-0069 AD - Obesity Research, Novo Nordisk A/S, Malov, Denmark. FAU - Soh, Keng AU - Soh K AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Zagkos, Loukas AU - Zagkos L AUID- ORCID: 0000-0002-7700-8102 AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. FAU - Galanakis, Michael AU - Galanakis M AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - Center for Statistics and Data Science Institute, Hasselt University, Hasselt, Belgium. FAU - Sibbesen, Jonas AU - Sibbesen J AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Iglesias, Miquel Triana AU - Iglesias MT AUID- ORCID: 0000-0003-2161-8355 AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Secher, Anna AU - Secher A AUID- ORCID: 0000-0002-6276-5389 AD - Brain and Adipose Biology, Novo Nordisk A/S, Malov, Denmark. FAU - Valkenborg, Dirk AU - Valkenborg D AD - Center for Statistics and Data Science Institute, Hasselt University, Hasselt, Belgium. FAU - Purnell, Jonathan Q AU - Purnell JQ AUID- ORCID: 0000-0001-5505-6333 AD - Oregon Health & Science University (OHSU), Portland, OR, USA. FAU - Knudsen, Lotte Bjerre AU - Knudsen LB AUID- ORCID: 0000-0002-2439-7116 AD - Chief Scientific Advisor Office, Novo Nordisk A/S, Malov, Denmark. FAU - Tahrani, Abd A AU - Tahrani AA AUID- ORCID: 0000-0001-9037-1937 AD - Medical & Science, Novo Nordisk A/S, Soborg, Denmark. a.a.tahrani@bham.ac.uk. AD - Department of Metabolism and Systems Science, University of Birmingham, Birmingham, UK. a.a.tahrani@bham.ac.uk. FAU - Geybels, Milan AU - Geybels M AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - Genmab A/S, Valby, Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250103 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Proteome) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism/complications MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Glycated Hemoglobin/metabolism MH - *Obesity/drug therapy/blood/metabolism MH - *Proteome/drug effects/metabolism MH - *Proteomics/methods MH - Weight Loss/drug effects MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - Observational Studies as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11750704 COIS- Competing interests: L.S., K.S., M. Galanakis, M.T.I., J.S., A.S., L.B.K. and A.A.T. are employees and shareholders of Novo Nordisk. D.G., L.M. and M. Geybels were employees and shareholders of Novo Nordisk at the time of the analysis. M. Galanakis, M. Geybels and D.V. have received a grant from the Danish Innovation Fund (204000005B). J.Q.P. has received consulting fees from Boehringer Ingelheim and Novo Nordisk. L.Z. declares no competing interests. EDAT- 2025/01/04 00:20 MHDA- 2025/01/22 05:33 PMCR- 2025/01/03 CRDT- 2025/01/03 23:49 PHST- 2024/03/22 00:00 [received] PHST- 2024/10/14 00:00 [accepted] PHST- 2025/01/22 05:33 [medline] PHST- 2025/01/04 00:20 [pubmed] PHST- 2025/01/03 23:49 [entrez] PHST- 2025/01/03 00:00 [pmc-release] AID - 10.1038/s41591-024-03355-2 [pii] AID - 3355 [pii] AID - 10.1038/s41591-024-03355-2 [doi] PST - ppublish SO - Nat Med. 2025 Jan;31(1):267-277. doi: 10.1038/s41591-024-03355-2. Epub 2025 Jan 3. PMID- 39752752 OWN - NLM STAT- MEDLINE DCOM- 20250429 LR - 20250520 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 147 DP - 2025 Feb 6 TI - Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice. PG - 113937 LID - S1567-5769(24)02459-7 [pii] LID - 10.1016/j.intimp.2024.113937 [doi] AB - Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, beta-muricholic acid: beta-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD). CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Hu, Weiting AU - Hu W AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China; Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Gong, Wenyu AU - Gong W AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Yang, Fan AU - Yang F AD - The First Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Cheng, Rui AU - Cheng R AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Zhang, Gerong AU - Zhang G AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Gan, Lu AU - Gan L AD - Department of Emergency Medicine and National Clinical Research Center for Geriatrics, Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu 610000, China. FAU - Zhu, Yikun AU - Zhu Y AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Qin, Weiwei AU - Qin W AD - Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Gao, Ying AU - Gao Y AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Li, Xing AU - Li X AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: 13503504180@163.com. FAU - Liu, Jing AU - Liu J AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: jingliu@sxmu.edu.cn. LA - eng PT - Journal Article DEP - 20250102 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Bile Acids and Salts) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - *Gastrointestinal Microbiome/drug effects MH - *Bile Acids and Salts/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Fatty Liver/drug therapy/metabolism MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - *Tirzepatide/therapeutic use/pharmacology MH - Liver/drug effects/pathology/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Humans OTO - NOTNLM OT - Bile acids OT - GIP/GLP-1 receptor agonist OT - Gut microbiota OT - Hepatic steatosis OT - Tirzepatide COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/04 00:20 MHDA- 2025/01/28 11:26 CRDT- 2025/01/03 18:01 PHST- 2024/10/29 00:00 [received] PHST- 2024/12/14 00:00 [revised] PHST- 2024/12/21 00:00 [accepted] PHST- 2025/01/28 11:26 [medline] PHST- 2025/01/04 00:20 [pubmed] PHST- 2025/01/03 18:01 [entrez] AID - S1567-5769(24)02459-7 [pii] AID - 10.1016/j.intimp.2024.113937 [doi] PST - ppublish SO - Int Immunopharmacol. 2025 Feb 6;147:113937. doi: 10.1016/j.intimp.2024.113937. Epub 2025 Jan 2. PMID- 39751188 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20250520 IS - 1479-6805 (Electronic) IS - 0022-0795 (Linking) VI - 264 IP - 2 DP - 2025 Feb 1 TI - Cardiovascular effects of tirzepatide. LID - e240259 [pii] LID - 10.1530/JOE-24-0259 [doi] AB - Tirzepatide is a first-in-class dual agonist at receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for the treatment of T2D and obesity, with unprecedented efficacy for glycaemic control, reductions in body weight and improvements in blood pressure and lipid profile compared with placebo and GLP-1 receptor agonists. To date, clinical trials of tirzepatide have fulfilled the requirement by regulatory authorities of demonstrated cardiovascular safety in high-risk patients. Whether cardiovascular benefits will be found with dual GLP-1/GIP receptor agonists remains uncertain, and the contribution of GIP receptor activation to cardiovascular risk has not been established. Several ongoing large-scale cardiovascular outcome trials for tirzepatide will provide a clearer understanding of where tirzepatide should be positioned in the treatment of established atherosclerotic cardiovascular disease or in people at high risk, in relation to current standard-of-care cardioprotective agents and approaches. FAU - Sumithran, Priya AU - Sumithran P FAU - Russell, Anthony W AU - Russell AW FAU - Zoungas, Sophia AU - Zoungas S AUID- ORCID: 0000-0003-2672-0949 LA - eng PT - Journal Article PT - Review DEP - 20250116 PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - Tirzepatide MH - Glucagon-Like Peptide 1/analogs & derivatives MH - *Cardiovascular System/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals OTO - NOTNLM OT - GIP OT - GLP-1 OT - cardiovascular disease OT - obesity medications OT - tirzepatide EDAT- 2025/01/03 12:21 MHDA- 2025/01/17 18:22 CRDT- 2025/01/03 10:44 PHST- 2024/08/28 00:00 [received] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/01/17 18:22 [medline] PHST- 2025/01/03 12:21 [pubmed] PHST- 2025/01/03 10:44 [entrez] AID - JOE-24-0259 [pii] AID - 10.1530/JOE-24-0259 [doi] PST - epublish SO - J Endocrinol. 2025 Jan 16;264(2):e240259. doi: 10.1530/JOE-24-0259. Print 2025 Feb 1. PMID- 39746343 OWN - NLM STAT- MEDLINE DCOM- 20250209 LR - 20260720 IS - 1664-5502 (Electronic) IS - 1664-3828 (Print) IS - 1664-5502 (Linking) VI - 15 IP - 1 DP - 2025 TI - Cardiovascular and Kidney Outcomes of Glucagon-Like Peptide 1 Receptor Agonist Therapy in Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis. PG - 98-107 LID - 10.1159/000543149 [doi] AB - INTRODUCTION: The effects of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in patients with diabetes and established chronic kidney disease (CKD) remain unclear. METHODS: We systematically searched PubMed, Embase, and Cochrane Library from inception to May 2024 for randomized controlled trials (RCTs) and respective post hoc studies comparing GLP-1 RAs versus placebo in patients with type 2 diabetes mellitus (T2DM) and established CKD (as per study definition or otherwise defined as having an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and/or urine albumin-to-creatinine ratio more than 30 mg/g). We applied a random-effects model to pool risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS: We included 10 RCTs and post hoc analyses comprising 18,042 patients, of whom 9,164 (50.8%) were treated with GLP-1 RAs. There were significantly lower rates of major adverse kidney events (RR 0.82; 95% CI: 0.74-0.90; p < 0.001; high certainty) and a slightly lower incidence of all-cause mortality (HR 0.84; 95% CI: 0.71-1.00; p = 0.046; moderate certainty) with the use of GLP-1 RAs relative to placebo. This kidney protection remained consistent in patients with stage 3b CKD (RR 0.78; 95% CI: 0.65-0.94; p = 0.009; high certainty). No significant differences were observed in major adverse cardiovascular events (HR 0.89; 95% CI: 0.78-1.02; p = 0.090; low certainty) or cardiovascular mortality (HR 0.80; 95% CI: 0.60-1.09; p = 0.155; very low certainty), possibly due to a lack of statistical power. CONCLUSION: GLP-1 RAs were tied to a lower incidence of all-cause mortality and major adverse kidney events in patients with T2DM and established CKD. CI - (c) 2025 The Author(s). Published by S. Karger AG, Basel. FAU - Felix, Nicole AU - Felix N AD - Department of Medicine, Federal University of Campina Grande, Campina Grande, Brazil. FAU - Gauza, Mateus M AU - Gauza MM AD - Department of Medicine, University of the Region of Joinville, Joinville, Brazil. FAU - Bittar, Vinicius AU - Bittar V AD - Department of Medicine, University Centre of Associated Colleges for Education, Sao Joao da Boa Vista, Brazil. FAU - Nogueira, Alleh AU - Nogueira A AD - Division of Nephrology, Department of Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil. FAU - Costa, Thomaz A AU - Costa TA AD - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA. FAU - Godoi, Amanda AU - Godoi A AD - Department of Medicine, Cardiff University School of Medicine, Cardiff, UK. FAU - Araujo de Lucena, Larissa AU - Araujo de Lucena L AD - Department of Medicine, Federal University of Rio Grande do Norte, Natal, Brazil. FAU - Ribeiro Goncalves, Ocilio AU - Ribeiro Goncalves O AD - Department of Medicine, Federal University of Piaui, Teresina, Brazil. FAU - Santos Pinto, Luis Claudio AU - Santos Pinto LC AD - Post-Graduate Program in Health Sciences, Federal University of Bahia, Salvador, Brazil. FAU - Tramujas, Lucas AU - Tramujas L AD - Hcor Research Institute, Sao Paulo, Brazil. FAU - Moura-Neto, Jose A AU - Moura-Neto JA AD - Division of Nephrology, Department of Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil. FAU - Guimaraes, Maria Gabriela AU - Guimaraes MG AD - Department of Nephrology, Ana Nery Hospital, Salvador, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250102 PL - Switzerland TA - Cardiorenal Med JT - Cardiorenal medicine JID - 101554863 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/epidemiology/etiology MH - Glomerular Filtration Rate MH - Randomized Controlled Trials as Topic PMC - PMC11844710 OTO - NOTNLM OT - Chronic kidney disease OT - Diabetes OT - Glucagon-like peptide 1 receptor agonists OT - Renal insufficiency COIS- All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. EDAT- 2025/01/03 00:20 MHDA- 2025/02/10 00:19 PMCR- 2025/01/02 CRDT- 2025/01/02 18:24 PHST- 2024/10/30 00:00 [received] PHST- 2024/12/11 00:00 [accepted] PHST- 2025/02/10 00:19 [medline] PHST- 2025/01/03 00:20 [pubmed] PHST- 2025/01/02 18:24 [entrez] PHST- 2025/01/02 00:00 [pmc-release] AID - 000543149 [pii] AID - 543149 [pii] AID - 10.1159/000543149 [doi] PST - ppublish SO - Cardiorenal Med. 2025;15(1):98-107. doi: 10.1159/000543149. Epub 2025 Jan 2. PMID- 39745177 OWN - NLM STAT- MEDLINE DCOM- 20250102 LR - 20260813 IS - 1949-0984 (Electronic) IS - 1949-0976 (Print) IS - 1949-0976 (Linking) VI - 17 IP - 1 DP - 2025 Dec TI - Hypoglycemic effect of C. butyricum-pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus. PG - 2447814 LID - 10.1080/19490976.2024.2447814 [doi] LID - 2447814 AB - Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the intestine, has been demonstrated to exert remarkable hypoglycemic effects. However, its limitation lies in its short plasma half-life, necessitating the continuous intravenous injection of GLP-1 drugs to achieve efficacy. Here, we engineered Clostridium butyricum to continuously express and deliver GLP-1 (denoted as Cb-GLP-1), and assessed its therapeutic efficacy in type 2 diabetes mellitus (T2DM) mice. We demonstrated that administration of Cb-GLP-1 effectively lowered blood glucose levels, regulated dyslipidemia, and ameliorated hepatic impairment in T2DM mice. Furthermore, Cb-GLP-1 treatment facilitated insulin secretion by retarding islet cell apoptosis and activating the glucagon-like peptide 1 receptor/adenylate cyclase/protein kinase A (GLP-1 R/AC/PKA) signaling pathway. Gut microbiota analysis revealed that Cb-GLP-1 restored gut homeostasis disrupted in T2DM mice, as indicated by the decreased abundance of Lactobacillus and Providencia genera in response to Cb-GLP-1 treatment. Collectively, the intestinal microbiota regulation and hypoglycemic effect of the engineered strain Cb-GLP-1 presents a promising approach for diabetes management. FAU - Zhou, Dexi AU - Zhou D AD - School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China. AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Li, Shengjie AU - Li S AUID- ORCID: 0000-0002-0680-2667 AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Hu, Gang AU - Hu G AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Wang, Yufan AU - Wang Y AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Qi, Zhanghua AU - Qi Z AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Xu, Xuan AU - Xu X AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Wei, Jing AU - Wei J AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Liu, Qiong AU - Liu Q AUID- ORCID: 0000-0002-8950-6133 AD - Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. FAU - Chen, Tingtao AU - Chen T AUID- ORCID: 0000-0002-0506-8536 AD - School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China. AD - National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China. AD - The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250102 PL - United States TA - Gut Microbes JT - Gut microbes JID - 101495343 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy/microbiology MH - *Glucagon-Like Peptide 1/metabolism MH - *Probiotics/administration & dosage/pharmacology MH - Mice MH - *Clostridium butyricum/metabolism MH - *Gastrointestinal Microbiome/drug effects MH - Male MH - *Blood Glucose/metabolism MH - Mice, Inbred C57BL MH - Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Hypoglycemic Agents/pharmacology MH - Insulin/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism/genetics MH - Humans MH - Signal Transduction/drug effects MH - Apoptosis/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12931707 OTO - NOTNLM OT - Clostridium butyricum OT - GLP-1 OT - Type 2 diabetes mellitus OT - engineering probiotics OT - gut microbiota OT - insulin secretion COIS- No potential conflict of interest was reported by the author(s). EDAT- 2025/01/02 12:24 MHDA- 2025/01/02 12:25 PMCR- 2025/01/02 CRDT- 2025/01/02 08:23 PHST- 2025/01/02 12:25 [medline] PHST- 2025/01/02 12:24 [pubmed] PHST- 2025/01/02 08:23 [entrez] PHST- 2025/01/02 00:00 [pmc-release] AID - 2447814 [pii] AID - 10.1080/19490976.2024.2447814 [doi] PST - ppublish SO - Gut Microbes. 2025 Dec;17(1):2447814. doi: 10.1080/19490976.2024.2447814. Epub 2025 Jan 2. PMID- 39744852 OWN - NLM STAT- MEDLINE DCOM- 20250418 LR - 20250418 IS - 1439-7633 (Electronic) IS - 1439-4227 (Linking) VI - 26 IP - 8 DP - 2025 Apr 14 TI - Strategies to Enhance the Therapeutic Efficacy of GLP-1 Receptor Agonists through Structural Modification and Carrier Delivery. PG - e202400962 LID - 10.1002/cbic.202400962 [doi] AB - Diabetes is a metabolic disorder characterized by insufficient endogenous insulin production or impaired sensitivity to insulin. In recent years, a class of incretin-based hypoglycemic drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs), have attracted great attention in the management of type 2 diabetes mellitus (T2DM) due to their benefits, including stable glycemic control ability, a low risk of hypoglycemia, and weight reduction for patients. However, like other peptide drugs, GLP-1RAs face challenges such as instability, susceptibility to enzymatic degradation, and immunogenicity, which severely limit their clinical application. In recent years, various strategies have been developed to improve the bioavailability and therapeutic efficacy of GLP-1RAs, including structural modification and carrier-mediated delivery. This article briefly introduces the research and application status of several common GLP-1RAs and their limitations. Taking exendin-4 as an example, we focus on the research progress of improving bioavailability and therapeutic efficacy based on structural modification and carrier delivery strategies, aiming to provide reference for the development of new GLP-1RAs treatment systems. CI - (c) 2025 Wiley-VCH GmbH. FAU - Zhang, Tingting AU - Zhang T AD - Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China. FAU - Liu, Sainan AU - Liu S AD - Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China. FAU - He, Suning AU - He S AD - Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China. FAU - Shi, Linqi AU - Shi L AUID- ORCID: 0000-0002-9534-795X AD - Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China. FAU - Ma, Rujiang AU - Ma R AUID- ORCID: 0000-0002-2021-3850 AD - Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China. LA - eng GR - 2022YFA12057000/National Key R&D Program of China/ GR - 51773099/National Natural Science Foundation of China/ GR - 51933006/National Natural Science Foundation of China/ GR - 52103183/National Natural Science Foundation of China/ GR - 23JCYBJC01780/Natural Science Foundation of Tianjin, China/ PT - Journal Article PT - Review DEP - 20250110 PL - Germany TA - Chembiochem JT - Chembiochem : a European journal of chemical biology JID - 100937360 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Drug Carriers) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/chemistry/therapeutic use/pharmacology/administration & dosage MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Drug Carriers/chemistry MH - Animals MH - Exenatide/chemistry MH - *Drug Delivery Systems OTO - NOTNLM OT - Carrier Delivery OT - Diabetes Mellitus OT - Exendin-4 OT - GLP-1 Receptor Agonists OT - Structural Modification EDAT- 2025/01/02 06:19 MHDA- 2025/04/18 12:28 CRDT- 2025/01/02 05:13 PHST- 2024/12/23 00:00 [revised] PHST- 2024/11/25 00:00 [received] PHST- 2025/04/18 12:28 [medline] PHST- 2025/01/02 06:19 [pubmed] PHST- 2025/01/02 05:13 [entrez] AID - 10.1002/cbic.202400962 [doi] PST - ppublish SO - Chembiochem. 2025 Apr 14;26(8):e202400962. doi: 10.1002/cbic.202400962. Epub 2025 Jan 10. PMID- 39740304 OWN - NLM STAT- MEDLINE DCOM- 20250429 LR - 20260818 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 2 DP - 2025 Feb TI - Identifying predictors of sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist use in hospital among adults with diabetes. PG - 108945 LID - S1056-8727(24)00271-X [pii] LID - 10.1016/j.jdiacomp.2024.108945 [doi] AB - AIMS: To identify factors associated with use of novel diabetes medications among patients hospitalized under general internal medicine. METHODS: We conducted a cohort study of patients with type 2 diabetes mellitus (T2DM) hospitalized in Ontario, Canada between 2015 and 2020. We evaluated the patient- and physician-level factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2) and glucagon-like peptide 1 receptor agonist (GLP1R) use using a multivariable logistic regression model. RESULTS: There were 253,152 hospitalizations and 68,126 involved patients who had T2DM. Prior to discharge, 3.7 % (N = 2490) of patients with T2DM received an SGLT2 and 0.2 % (N = 121) received a GLP1R. The strongest predictors for receiving a novel diabetes medication were hemoglobin A1C > 9.0 % (Odds Ratio (OR) = 1.81, 95 % Confidence Interval (CI) 1.28, 2.60) and patients aged 40-60 compared with patients <40 years old (OR = 1.81, 95 % CI 1.33, 2.68). The strongest predictors for not receiving a novel diabetes medication were dementia (OR = 0.47, 95 % CI 0.39, 0.56) and creatinine >/=200 mumol/L (OR = 0.11, 95 % CI 0.08, 0.15). Overall, 46.8 % of patients hospitalized with T2DM not receiving a novel diabetes medication would potentially benefit from an SGLT2 inhibitor. CONCLUSIONS: Novel diabetes medications were rarely continued or initiated during hospitalization despite a high prevalence of cardiovascular disease, raising the concern for systematic under-utilization after discharge. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Raudanskis, Ashley AU - Raudanskis A AD - Sinai Health System, Division of General Internal Medicine, Toronto, Ontario, Canada. FAU - Sarma, Shohinee AU - Sarma S AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, United States of America. FAU - Biering-Sorensen, Tor AU - Biering-Sorensen T AD - Department of Cardiology, Copenhagen University Hospital - Herlev & Gentofte, Copenhagen, Denmark. FAU - Zorcic, Katarina AU - Zorcic K AD - Sinai Health System, Division of General Internal Medicine, Toronto, Ontario, Canada. FAU - Razak, Fahad AU - Razak F AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario; St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Verma, Amol AU - Verma A AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario; St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Jensen, Magnus Thorsten AU - Jensen MT AD - Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Perkins, Bruce A AU - Perkins BA AD - Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Colacci, Michael AU - Colacci M AD - Sinai Health System, Division of General Internal Medicine, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario. FAU - Fralick, Michael AU - Fralick M AD - Sinai Health System, Division of General Internal Medicine, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario. Electronic address: mike.fralick@mail.utoronto.ca. LA - eng PT - Journal Article DEP - 20241220 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood/complications MH - Male MH - Female MH - Middle Aged MH - *Hospitalization/statistics & numerical data MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Ontario/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Cohort Studies MH - Glycated Hemoglobin/analysis OTO - NOTNLM OT - Diabetes OT - Diabetes medication OT - Glucagon-like peptide 1 receptor [GLP1R] agonists OT - Sodium-glucose cotransporter 2 [SGLT2] inhibitors OT - Type 2 diabetes mellitus [T2DM] COIS- Declaration of competing interest Michael Fralick was a consultant for ProofDx, a start-up company creating a point of care diagnostic test for COVID-19. Michael Fralick is an advisor for SIGNAL1, a start-up company deploying machine learned models to improve inpatient care. Tor Biering-Sorensen discloses the following relationships: steering committee member of the Amgen-financed GALACTIC-HF trial, of the Boehringer Ingelheim financed SHARP3 trial, of "LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific's Investigational ICM System" trial; advisory board: Amgen, CSL Seqirus and GSK; chief investigator of the Sanofi Pasteur financed "NUDGE-FLU", "DANFLU-1", and "DANFLU-2" trials; speaker honorarium: Bayer, Novartis, Sanofi Pasteur, GE healthcare and GSK; consultant appointments: Novo Nordisk, IQVIA and Parexel; and research grants: GE Healthcare, AstraZeneca, Novo Nordisk and Sanofi Pasteur. Fahad Razak is a part-time employee of Ontario Health. The development of the GEMINI data platform has been supported with funding from sources such as the Canadian Cancer Society, the Canadian Frailty Network, the Canadian Institutes of Health Research, the Canadian Medical Protective Agency, Green Shield Canada Foundation, the Natural Sciences and Engineering Research Council of Canada, Ontario Health, the St. Michael's Hospital Association Innovation Fund, the University of Toronto Department of Medicine, and in-kind support from partner hospitals and the Vector Institute. Fahad Razak holds a salary award from Canada Research Chairs Program, University of Toronto and the PSI Graham Farquharson Knowledge Translation Fellowship. No funding sources from Fahad Razak influenced the writing of this manuscript. Outside of the submitted work, Amol Verma is a part-time employee of Ontario Health and a co-inventor of an AI-based early warning system for patient deterioration that was acquired by the start-up company Signal1. Magnus Thorsten Jensen is the CEO of Steno Diabetes Center Copenhagen which is funded through a partnership between the Capital Region of Denmark and the Novo Nordisk Foundation. Bruce A. Perkins has received honoraria for educational events from Medtronic, Novo Nordisk, Sanofi, Insulet and Abbott. His research institute has received funding from BMO Bank of Montreal and Novo Nordisk for research support. He has served as an advisor to Boehringer Ingelheim, Sanofi, Insulet, Abbott, and Vertex. Ashley Raudanskis, Shohinee Sarma, Katarina Zorcic, and Michael Colacci have no reported conflicts of interest. EDAT- 2025/01/01 12:42 MHDA- 2025/02/11 00:19 CRDT- 2024/12/31 18:02 PHST- 2024/08/28 00:00 [received] PHST- 2024/12/18 00:00 [revised] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/02/11 00:19 [medline] PHST- 2025/01/01 12:42 [pubmed] PHST- 2024/12/31 18:02 [entrez] AID - S1056-8727(24)00271-X [pii] AID - 10.1016/j.jdiacomp.2024.108945 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Feb;39(2):108945. doi: 10.1016/j.jdiacomp.2024.108945. Epub 2024 Dec 20. PMID- 39732312 OWN - NLM STAT- MEDLINE DCOM- 20250215 LR - 20250529 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 271 DP - 2025 Mar TI - GLP-1 Receptor Agonists Use and Incidence of Glaucoma: A Systematic Review and Meta-Analysis. PG - 488-497 LID - S0002-9394(24)00589-0 [pii] LID - 10.1016/j.ajo.2024.12.024 [doi] AB - PURPOSE: In patients with diabetes, glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) may protect against microvascular alterations and oxidative stress, both of which have been implicated in glaucoma. Multiple studies suggest a possible relation between GLP-1 RA use and the development of glaucoma. This study is a systematic review of the published literature regarding the incidence of glaucoma development in patients with type 2 diabetes treated with GLP-1 RAs compared with a control group. DESIGN: A systematic review and meta-analysis. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane databases from July 1991 to May 2024 for studies comparing the incidence of glaucoma development in GLP-1 RA users versus nonusers. We calculated the pooled hazard ratio for the GLP-1 RA group and control individuals using a random-effects model. RESULTS: One hundred ninety-four studies were identified, of which 5 retrospective studies met the inclusion criteria, with a total of 156,042 participants based on routinely collected electronic data. The meta-analysis revealed no significant statistical difference in glaucoma incidence among GLP-1 RA users compared with control individuals (hazard ratio 0.779 [95% CI 0.585-11.036]; P = .086; I(2) = 86%). During the leave-one-out sensitivity analysis, the inclusion of the study by Shao and associates yielded opposite effects, suggesting that SGLT-2 inhibitors might be as effective as, or potentially more effective than, GLP-1 RAs in preventing glaucoma. When this study was excluded from the analysis, the results demonstrated a significant reduction in the incidence of glaucoma among GLP-1 RA users compared with control individuals, with reduced heterogeneity (hazard ratio 0.71 [95% CI 0.60-0.85], I(2) = 29%). Studies had moderate bias concerns because of confounding factors and intervention classification. CONCLUSION: This systematic meta-analysis found that GLP-1 RA use is associated with reduced glaucoma development in retrospective studies. Future well-designed, long-term studies focusing on GLP-1 RAs and SGLT-2 inhibitors are needed to validate these findings and evaluate their effects on glaucoma progression and vision loss. The overall interpretation should be cautious. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Amaral, Dillan Cunha AU - Amaral DC AD - Faculty of Medicine (D.C.A.), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Guedes, Jaime AU - Guedes J AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: jaimeguedes@gmail.com. FAU - Cruz, Matheus Ribeiro Barbosa AU - Cruz MRB AD - Faculty of Medicine (M.R.B.C.), Varzea Grande University Center, Varzea Grande, Brazil. FAU - Cheidde, Lidia AU - Cheidde L AD - Faculty of Medicine (L.C.), Pontifical Catholic University of Sao Paulo, Sorocaba, Brazil. FAU - Nepomuceno, Matheus AU - Nepomuceno M AD - Faculty of Medicine (M.N.), Anhembi Morumbi University, Sao Paulo, Brazil. FAU - Magalhaes, Pedro Lucas Machado AU - Magalhaes PLM AD - Faculty of Medicine (P.L.M.M.), Institute of Medical Education - IDOMED, Rio de Janeiro, Brazil. FAU - Brazuna, Rodrigo AU - Brazuna R AD - Ophthalmology Department (R.B.), Federal University of State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Mora-Paez, Denisse J AU - Mora-Paez DJ AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. FAU - Huang, Ping AU - Huang P AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. FAU - Razeghinejad, Reza AU - Razeghinejad R AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. FAU - Schuman, Joel S AU - Schuman JS AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Biomedical Engineering (J.S.S.), Drexel School of Biomedical Engineering, Science and Health Systems, Philadelphia, Pennsylvania, USA. FAU - Myers, Jonathan S AU - Myers JS AD - Glaucoma Service (J.G., D.J.M-P., P.H., R.R., J.S.S., J.S.M.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241227 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glaucoma/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Incidence MH - Intraocular Pressure/drug effects EDAT- 2024/12/29 00:20 MHDA- 2025/02/16 01:32 CRDT- 2024/12/28 19:14 PHST- 2024/10/06 00:00 [received] PHST- 2024/12/16 00:00 [revised] PHST- 2024/12/22 00:00 [accepted] PHST- 2025/02/16 01:32 [medline] PHST- 2024/12/29 00:20 [pubmed] PHST- 2024/12/28 19:14 [entrez] AID - S0002-9394(24)00589-0 [pii] AID - 10.1016/j.ajo.2024.12.024 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Mar;271:488-497. doi: 10.1016/j.ajo.2024.12.024. Epub 2024 Dec 27. PMID- 39729347 OWN - NLM STAT- MEDLINE DCOM- 20260424 LR - 20260424 IS - 1555-905X (Electronic) IS - 1555-9041 (Print) IS - 1555-9041 (Linking) VI - 20 IP - 2 DP - 2025 Feb 1 TI - Kidney Outcomes with Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk. PG - 206-217 LID - 10.2215/CJN.0000000587 [doi] AB - KEY POINTS: Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists were superior to dipeptidyl peptidase-4 inhibitor and sulfonylurea for preventing kidney complications in patients with type 2 diabetes at moderate cardiovascular disease risk. Sodium-glucose cotransporter 2 inhibitor therapy compared favorably with glucagon-like peptide-1 receptor agonists for kidney disease outcomes. BACKGROUND: CKD is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. METHODS: This retrospective observational study emulated an idealized target trial using claims data from OptumLabs data warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4i), SGLT2i, GLP-1RA, or sulfonylurea (SU) on a primary kidney composite outcome of incident CKD stages 3-5, kidney failure, or need for KRT in patients with type 2 diabetes and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. RESULTS: A total of 364,714 adults aged 21 years or older initiating treatment with a DPP-4i ( N =78,843), GLP-1RA ( N =42,049), SGLT2i ( N =45,466), or SU ( N =198,356) were identified. Relative to DPP-4i, SGLT2i (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.67 to 0.74; P < 0.001) and GLP-1RA (HR, 0.87; 95% CI, 0.83 to 0.92; P < 0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2i (HR, 0.69; 95% CI, 0.66 to 0.73) and GLP-1RA (HR, 0.86; 95% CI, 0.82 to 0.91) treatment was associated with risk reductions for the primary outcome relative to SU treatment. When comparing SGLT2i with GLP-1RA therapy, SGLT2is were superior for the primary composite outcome (HR, 0.81; 95% CI, 0.75 to 0.86; P < 0.001). Similar findings were observed for the secondary composite outcome across all comparisons. CONCLUSIONS: SGLT2is and GLP-1RAs were superior to DPP-4is and SUs for preventing kidney complications in a type 2 diabetes population with moderate baseline CVD risk. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: NCT05214573 . CI - Copyright (c) 2024 by the American Society of Nephrology. FAU - Neumiller, Joshua J AU - Neumiller JJ AUID- ORCID: 0000-0002-4734-7402 AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington. FAU - Herrin, Jeph AU - Herrin J AUID- ORCID: 0000-0002-3671-3622 AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Division of Health Care Delivery Research, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. AD - OptumLabs, Eden Prairie, Minnesota. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Galindo, Rodolfo J AU - Galindo RJ AUID- ORCID: 0000-0002-9295-3225 AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Deng, Yihong AU - Deng Y AD - Division of Health Care Delivery Research, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. AD - OptumLabs, Eden Prairie, Minnesota. FAU - Ross, Joseph S AU - Ross JS AUID- ORCID: 0000-0002-9218-3320 AD - Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AUID- ORCID: 0009-0004-3664-127 AD - Division of Health Care Delivery Research, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - McCoy, Rozalina G AU - McCoy RG AUID- ORCID: 0000-0002-2289-3183 AD - OptumLabs, Eden Prairie, Minnesota. AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. AD - University of Maryland Institute for Health Computing, North Bethesda, Maryland. LA - eng SI - ClinicalTrials.gov/NCT05214573 GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - DB-2020C2-20306/Patient-Centered Outcomes Research Institute, University of Maryland Institute for Health Computing, Montgomery County Government, University of Maryland, Baltimore, University of Maryland, College Park/ PT - Journal Article PT - Observational Study DEP - 20241008 PL - United States TA - Clin J Am Soc Nephrol JT - Clinical journal of the American Society of Nephrology : CJASN JID - 101271570 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sulfonylurea Compounds) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Sulfonylurea Compounds/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - *Renal Insufficiency, Chronic/prevention & control/etiology MH - *Diabetic Nephropathies/prevention & control/etiology MH - Treatment Outcome MH - Heart Disease Risk Factors PMC - PMC11835155 OTO - NOTNLM OT - CKD OT - SGLT2 OT - cardiovascular disease OT - diabetes OT - kidney failure COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/CJN/C52. EDAT- 2024/12/27 12:20 MHDA- 2026/04/24 12:35 PMCR- 2026/02/01 CRDT- 2024/12/27 11:49 PHST- 2024/06/03 00:00 [received] PHST- 2024/10/02 00:00 [accepted] PHST- 2026/04/24 12:35 [medline] PHST- 2024/12/27 12:20 [pubmed] PHST- 2024/12/27 11:49 [entrez] PHST- 2026/02/01 00:00 [pmc-release] AID - 01277230-202502000-00009 [pii] AID - CJASN-2024-000796 [pii] AID - 10.2215/CJN.0000000587 [doi] PST - ppublish SO - Clin J Am Soc Nephrol. 2025 Feb 1;20(2):206-217. doi: 10.2215/CJN.0000000587. Epub 2024 Oct 8. PMID- 39726212 OWN - NLM STAT- MEDLINE DCOM- 20250306 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Anti-diabetic effects of GLP-1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review. PG - 1648-1659 LID - 10.1111/dom.16136 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for anti-obesity indications. However, little is known of the comparative effect of GLP-1 RAs and their glycemic impact across the different routes of administration, diabetic statuses and durations of prescription. PubMed, EMBASE and CENTRAL were searched from inception to 13 February 2024. Only randomised controlled trials were included in this systematic review and meta-analysis. Adults aged above 18 years old, who were in the overweight/obesity range, with or without type 2 diabetes mellitus (T2DM) were included. Baseline characteristics and changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were obtained. GLP1-RAs demonstrated an overall reduction in HbA1c of -0.72% (95% confidence interval [CI] -0.79 to -0.65, p < 0.01) and in FPG of -1.00 mmol/L (95% CI -1.16 to -0.84, p < 0.01). HbA1c reduction in pre-DM patients was -0.44% (95% CI -0.54 to -0.18, p < 0.01). Patients who were followed up for more than a year experienced a smaller reduction of HbA1c. Meta-regression showed that the GLP-1 RAs are more efficacious at higher HbA1c and lower body mass index. Overall, GLP-1 RAs consistently led to a significant reduction in HbA1c at -0.72% and FPG at -1.00 mmol/L. These effects may be equally efficacious in pre-DM patients with obesity and those at lower BMI. With pre-DM and obesity being risk factors for metabolic syndrome, these findings may provide newer perspectives in expanding indications for GLP-1 RA initiation. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Wong, Hon Jen AU - Wong HJ AUID- ORCID: 0000-0002-9274-0406 AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Lin, Norman H Y AU - Lin NHY AUID- ORCID: 0000-0002-6329-4603 AD - Department of Medicine, National University Hospital, Singapore. FAU - Teo, Yao Hao AU - Teo YH AD - Department of Medicine, National University Hospital, Singapore. FAU - Yeo, Brian S Y AU - Yeo BSY AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Toh, Keith Zhi Xian AU - Toh KZX AD - Department of Medicine, National University Hospital, Singapore. FAU - Teo, Yao Neng AU - Teo YN AD - Department of Medicine, National University Hospital, Singapore. FAU - Chan, Mark Y AU - Chan MY AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre Singapore, Singapore. FAU - Yeo, Leonard L L AU - Yeo LLL AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Division of Neurology, Department of Medicine, National University Hospital, Singapore. FAU - Poh, Kian Keong AU - Poh KK AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre Singapore, Singapore. FAU - Kong, William K F AU - Kong WKF AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre Singapore, Singapore. FAU - Eng, Pei Chia AU - Eng PC AD - Division of Endocrinology, Department of Medicine, National University Hospital, Singapore. FAU - Tan, Benjamin Y Q AU - Tan BYQ AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Division of Neurology, Department of Medicine, National University Hospital, Singapore. FAU - Dalakoti, Mayank AU - Dalakoti M AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre Singapore, Singapore. FAU - Sia, Ching-Hui AU - Sia CH AUID- ORCID: 0000-0002-2764-2869 AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre Singapore, Singapore. LA - eng GR - MOH-001368-00/Singapore Ministry of Health National Medical Research Council's Transition Award/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241226 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Overweight/drug therapy/complications MH - Blood Glucose/drug effects/analysis MH - Randomized Controlled Trials as Topic MH - Female MH - Adult MH - Male OTO - NOTNLM OT - GLP-1 RAs OT - HbA1c OT - glycemic control OT - obesity EDAT- 2024/12/27 06:20 MHDA- 2025/03/07 00:21 CRDT- 2024/12/27 01:23 PHST- 2024/12/06 00:00 [revised] PHST- 2024/08/13 00:00 [received] PHST- 2024/12/06 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2024/12/27 06:20 [pubmed] PHST- 2024/12/27 01:23 [entrez] AID - 10.1111/dom.16136 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1648-1659. doi: 10.1111/dom.16136. Epub 2024 Dec 26. PMID- 39723481 OWN - NLM STAT- MEDLINE DCOM- 20250206 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - Assessing the benefit-risk profile of newer glucose-lowering drugs: A systematic review and network meta-analysis of randomized outcome trials. PG - 1444-1455 LID - 10.1111/dom.16147 [doi] AB - AIM: To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). MATERIALS AND METHODS: A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.g., major adverse cardiovascular events [MACE], stroke, and hospitalization for heart failure [HHF]) were assessed. Data were pooled using population-averaged odds ratios (ORs) with 95% CIs. RESULTS: Twenty-six trials enrolling 198 177 participants were included. GLP-1RAs were most effective in lowering the risks of MACE (OR, 0.85, [95% CI, 0.79 to 0.92]) and stroke (0.84 [0.77, 0.91]), but increased the risk of thyroid cancer (1.58 [1.36, 2.50]). SGLT2i showed the greatest benefits in reducing the risk of HHF (0.68 [0.64, 0.73]) and improving composite renal outcomes (0.67 [0.58, 0.77]), but increased the risk of genital infections (3.11 [2.15, 4.50]). DPP4i were associated with a lower risk of certain psychiatric disorders, Parkinson's disease (0.54 [0.32, 0.92]), and amputation (0.70 [0.86, 0.93]), but an increased risk of neuropathy (1.10 [1.02, 1.18]) and pancreatitis (1.63 [1.40, 1.91]). The weighted origami plot suggested that GLP-1RAs were more suitable for reducing macrovascular and microvascular outcomes, while DPP4i might be better for neurodegenerative diseases and cancer concerns. CONCLUSIONS: Given the distinct benefit-risk profiles, the selection of glucose-lowering drugs should be individualized based on patient characteristics and risk factors. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Donahoo, William T AU - Donahoo WT AD - Division of Endocrinology, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Singh Ospina, Naykky AU - Singh Ospina N AD - Division of Endocrinology, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Kotecha, Pareeta AU - Kotecha P AUID- ORCID: 0009-0009-4864-9662 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Lu, Ying AU - Lu Y AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Tong, Jiayi AU - Tong J AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Smith, Steven M AU - Smith SM AUID- ORCID: 0000-0002-0201-839X AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. FAU - Rosenberg, Eric I AU - Rosenberg EI AD - Division of General Internal Medicine, Department of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Kimmel, Stephen E AU - Kimmel SE AD - Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. FAU - Chen, Yong AU - Chen Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - Leonard Davis Institute of Health Economics, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence-based Practice (CEP), Philadelphia, Pennsylvania, USA. AD - Penn Institute for Biomedical Informatics (IBI), Philadelphia, Pennsylvania, USA. LA - eng GR - K08 CA248972/CA/NCI NIH HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - R01DK133465/Division of Diabetes, Endocrinology, and Metabolic Diseases/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20241226 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Assessment MH - Cardiovascular Diseases/epidemiology/prevention & control MH - Blood Glucose/drug effects PMC - PMC12135018 MID - NIHMS2042370 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 analogue OT - SGLT2 inhibitor OT - meta-analysis OT - type 2 diabetes COIS- JG received consulting fees from Pfizer and received research funding from PhRMA foundation. NSO was supported by the National Cancer Institute of the National Institutes of Health under Award Number K08CA248972. The authors declare that there are no conflicts of interest relevant to this work. EDAT- 2024/12/26 06:20 MHDA- 2025/02/07 00:20 PMCR- 2026/03/01 CRDT- 2024/12/26 04:33 PHST- 2024/12/07 00:00 [revised] PHST- 2024/11/10 00:00 [received] PHST- 2024/12/10 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/12/26 06:20 [pubmed] PHST- 2024/12/26 04:33 [entrez] PHST- 2026/03/01 00:00 [pmc-release] AID - 10.1111/dom.16147 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1444-1455. doi: 10.1111/dom.16147. Epub 2024 Dec 26. PMID- 39719165 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 361 DP - 2025 Jan 15 TI - Semaglutide alleviates the pancreatic beta cell function via the METTL14 signaling and modulating gut microbiota in type 2 diabetes mellitus mice. PG - 123328 LID - S0024-3205(24)00918-4 [pii] LID - 10.1016/j.lfs.2024.123328 [doi] AB - AIMS: Semaglutide, a novel long-acting GLP-1RA, stimulates insulin and suppresses islet-secreted glucagon to reduce glucose levels. It has been unveiled that m6A mRNA modification plays a pivotal role in regulating beta cell function. However, it remains unclear whether semaglutide can elicit protective effects through manipulating m6A modification and the underlying mechanism. We aimed to elucidate the role played by semaglutide in m6A modification, and to explore its specific regulatory targets. Furthermore, we also delve into its effects on gut microbiota. MAIN METHODS: Five-week-old male C57BL/6 mice were assigned to two dietary groups and fed a control or high-fat diet for 4 weeks. Then T2DM was induced in high-fat diet-fed mice via streptozotocin (STZ), the main groups were resampled to include treatment with semaglutide (SEM, 40 mug/kg) for another 4 weeks, totaling three groups: Control, Model (T2DM), T2DM + SEM. Additionally, we elucidated specific regulatory targets and signaling pathways in palmitic acid (PA)-stimulated beta-TC-6 cells. Immunofluorescence, Western blot, and RT-qPCR were used in the study. KEY FINDINGS: Semaglutide mitigated pancreatic damage, enhanced islet cell proliferation, and restored islet size and alpha- and beta-cell masses. It also improved the expression of METTL14, pancreatic duodenal homeobox 1 (PDX-1), and protecting mitochondria, and modulated the PDX1 expression in an m6A-dependent manner. Concurrently, semaglutide significantly decreases the abundance of Firmicutes, Actinobacteriota, and Lactobacillus, while increasing the Bacteroides and norank_f_Muribaculaceae content, and the production of short-chain fatty acids (SCFA). SIGNIFICANCE: Semaglutide positively influences by regulating m6A modifications to alleviate pancreatic beta cell dysfunction and modulate the gut microbiome. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Luo, Yunfei AU - Luo Y AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Li, Jin-E AU - Li JE AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Zeng, Haixia AU - Zeng H AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Zhang, Yuying AU - Zhang Y AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Yang, Shiqi AU - Yang S AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Liu, Jianping AU - Liu J AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang City, Jiangxi Province, China; Branch of National Clinical Research Center for Metabolic Diseases, Nanchang City, Jiangxi Province, China. Electronic address: ndefy14105@ncu.edu.cn. LA - eng PT - Journal Article DEP - 20241222 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.1.1.- (Methyltransferases) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Insulin-Secreting Cells/drug effects/metabolism MH - Male MH - *Glucagon-Like Peptides/pharmacology MH - Mice MH - *Gastrointestinal Microbiome/drug effects MH - *Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - *Signal Transduction/drug effects MH - *Diabetes Mellitus, Experimental/metabolism/drug therapy MH - Methyltransferases/metabolism MH - Diet, High-Fat/adverse effects MH - Hypoglycemic Agents/pharmacology MH - Semaglutide OTO - NOTNLM OT - Gut microbiota OT - METTL3/14 OT - Mitochondrial function OT - Pancreatic beta-cell function OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest No competing financial interests exist. EDAT- 2024/12/25 00:20 MHDA- 2025/01/07 00:21 CRDT- 2024/12/24 19:10 PHST- 2024/10/25 00:00 [received] PHST- 2024/12/09 00:00 [revised] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/12/25 00:20 [pubmed] PHST- 2024/12/24 19:10 [entrez] AID - S0024-3205(24)00918-4 [pii] AID - 10.1016/j.lfs.2024.123328 [doi] PST - ppublish SO - Life Sci. 2025 Jan 15;361:123328. doi: 10.1016/j.lfs.2024.123328. Epub 2024 Dec 22. PMID- 39717105 OWN - NLM STAT- MEDLINE DCOM- 20241224 LR - 20250104 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Risk factor screening and prediction modeling of gastrointestinal adverse reactions caused by GLP-1RAs. PG - 1502050 LID - 10.3389/fendo.2024.1502050 [doi] LID - 1502050 AB - OBJECTIVE: This study aimed to explore the risk factors for gastrointestinal side effects (GISEs) in patients with type 2 diabetes mellitus (T2DM) during treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) based on real-world data and to develop a prediction model for GLP-1RA-related GISEs. METHODS: A total of 855 patients who attended the First Affiliated Hospital of Shandong First Medical University from January 2020 to May 2023 were selected as the study participants, who were divided into the training set (598 cases) and the validation set (297 cases) using a simple random sampling method at a ratio of 7:3. The general information and biochemical indicators of the participants were collected to assess the risk factors for GLP-1RA-related GISEs, and multifactorial logistic regression analysis was used to obtain the best predictors. A nomogram prediction model was constructed. The Hosmer-Lemeshow test was used to assess the differentiation and calibration of the nomogram model, and decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: Age, gender, history of gastrointestinal disorders, and number of combined oral medications were found as risk factors for the occurrence of GISEs in patients with T2DM using GLP-1RAs (p < 0.05). The nomogram prediction model based on these four factors had good discriminability (AUC values of the training and validation sets of 0.855 and 0.836, respectively) and accuracy (Hosmer-Lemeshow test: p > 0.05 for the validation set). DCA showed that the prediction model curve had clinical utility in the threshold probability interval of >5%. CONCLUSIONS: The established nomogram model has an excellent predictive effect on GISEs induced by GLP-1RAs in patients with T2DM. CI - Copyright (c) 2024 Gao, Li, Li, Zhou, Zong and Li. FAU - Gao, Rui AU - Gao R AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. FAU - Li, Yue AU - Li Y AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. AD - Department of Medicine, Qilu Institute of Technology, Jinan, China. FAU - Li, Anan AU - Li A AD - Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhou, Penglin AU - Zhou P AD - Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zong, Huiying AU - Zong H AD - Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Li, Yan AU - Li Y AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. LA - eng PT - Journal Article DEP - 20241205 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors MH - *Gastrointestinal Diseases/chemically induced MH - *Nomograms MH - Aged MH - Hypoglycemic Agents/adverse effects MH - Adult MH - Prognosis MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11664219 OTO - NOTNLM OT - gastrointestinal side effects OT - glucagon-like peptide-1 receptor agonists OT - nomogram OT - risk factors OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/12/24 06:20 MHDA- 2024/12/24 06:21 PMCR- 2024/01/01 CRDT- 2024/12/24 04:36 PHST- 2024/09/26 00:00 [received] PHST- 2024/11/11 00:00 [accepted] PHST- 2024/12/24 06:21 [medline] PHST- 2024/12/24 06:20 [pubmed] PHST- 2024/12/24 04:36 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1502050 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Dec 5;15:1502050. doi: 10.3389/fendo.2024.1502050. eCollection 2024. PMID- 39710901 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20260611 IS - 1536-9617 (Electronic) IS - 0020-8167 (Linking) VI - 65 IP - 1 DP - 2025 Jan 1 TI - Glucagon-like Peptide-1 Receptor Agonists in the Management of Diabetic Retinopathy. PG - 23-26 LID - 10.1097/IIO.0000000000000541 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are a family of drugs, most well known by the third-generation once-weekly subcutaneous semaglutide, that act on the incretin pathway of metabolic, hormonal signaling to modulate pancreatic insulin release, gastric emptying, energy intake, and subjective feelings of satiety. This class of drugs' efficacy and safety in the treatment of type 2 diabetes and obesity have been demonstrated across multiple large randomized controlled trials. These data have propelled GLP-1 receptor agonists to ubiquity in diabetic management and weight loss therapy, leading them to be frequently encountered in ophthalmic practice. The effect of GLP-1 receptor agonists like semaglutide on diabetic retinopathy (DR) is at this point unclear; some studies indicate a worsening of DR with the initiation of GLP-1 agonists, especially semaglutide. Overall, the macrovascular reduction of cardiovascular and stroke risks from GLP-1 receptor agonists should be prioritized over the potential microvascular progression of DR, as long as the patient is regularly followed by ophthalmology. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Samanta, Anindya AU - Samanta A AD - Cullen Eye Institute, Baylor College of Medicine, Houston, TX. FAU - Bordbar, Darius D AU - Bordbar DD FAU - Weng, Christina Y AU - Weng CY FAU - Chancellor, John R AU - Chancellor JR LA - eng PT - Journal Article PT - Review DEP - 20241223 PL - United States TA - Int Ophthalmol Clin JT - International ophthalmology clinics JID - 0374731 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- C.Y.W. discloses the following relationships outside of the submitted work: Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, REGENXBIO, Astellas/Iveric Bio, EyePoint (consultant); DRCR Retina Network, Alimera Sciences, AGTC (research); Springer Publishers (royalties). The remaining authors declare that they have no conflicts of interest to disclose. EDAT- 2024/12/23 06:21 MHDA- 2024/12/23 06:22 CRDT- 2024/12/23 00:33 PHST- 2024/12/23 06:22 [medline] PHST- 2024/12/23 06:21 [pubmed] PHST- 2024/12/23 00:33 [entrez] AID - 00004397-202506510-00005 [pii] AID - 10.1097/IIO.0000000000000541 [doi] PST - ppublish SO - Int Ophthalmol Clin. 2025 Jan 1;65(1):23-26. doi: 10.1097/IIO.0000000000000541. Epub 2024 Dec 23. PMID- 39707717 OWN - NLM STAT- MEDLINE DCOM- 20250428 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 4 DP - 2025 Apr TI - Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes. PG - 608-614 LID - 10.1111/jdi.14391 [doi] AB - AIMS/INTRODUCTION: This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin-related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings. MATERIALS AND METHODS: A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin-related drug-naive (naive), switching from dipeptidyl peptide-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonist (GLP-1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups. Similar analyses were performed in the GLP-1 RAs group between GLP-1RAs before switching. RESULTS: Mean change of HbA1c in DPP-4i and GLP-1 RA groups was -0.67% (95% confidence interval [CI]: -0.79 to -0.54) and -0.13% (95% CI: -0.40 to 0.15), respectively, which were significantly smaller than incretin-related drug-naive group; -0.85% (95% CI: -1.08 to -0.62). Mean change in BW between the naive and DPP-4i groups had no differences; however, these changes were lower in the GLP-1 RA group than in the naive group. Mean change in HbA1c between pretreatment with GLP-1 RAs had no differences; however, the mean change in BW in the dulaglutide group was significantly higher than that in the injectable semaglutide group. CONCLUSION: Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin-related drugs in Japanese participants with type 2 diabetes. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Oya, Junko AU - Oya J AUID- ORCID: 0000-0002-6413-2606 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Shimizu, Mika AU - Shimizu M AUID- ORCID: 0009-0003-8614-4776 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Kubota, Ryo AU - Kubota R AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Suda, Rika AU - Suda R AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Nagkagami, Tomoko AU - Nagkagami T AUID- ORCID: 0000-0003-4376-7212 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20241220 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glycated Hemoglobin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/analogs & derivatives MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Middle Aged MH - *Incretins/therapeutic use/administration & dosage MH - Administration, Oral MH - Glycated Hemoglobin/analysis MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - *Drug Substitution MH - Blood Glucose/analysis MH - Treatment Outcome MH - Follow-Up Studies MH - Body Weight/drug effects MH - *Biomarkers/analysis MH - Prognosis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11970300 OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitor OT - Oral semaglutide OT - Real-world clinical setting COIS- Nakagami received personal fees from Sanwa Kagaku Kenkyusho Co. Ltd., Novo Nordisk Pharma Ltd., Japan; Eli Lily Japan KK, Sanofi K.K., Sumitomo Pharma, and Boehringer Ingelheim Japan Inc. The authors declare no conflicts of interest. Approval of the research protocol: N/A. Informed consent: Informed consent was obtained from all study participants. Registry and registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2024/12/21 16:42 MHDA- 2025/04/04 12:29 PMCR- 2024/12/20 CRDT- 2024/12/21 02:43 PHST- 2024/11/21 00:00 [revised] PHST- 2024/08/20 00:00 [received] PHST- 2024/12/10 00:00 [accepted] PHST- 2025/04/04 12:29 [medline] PHST- 2024/12/21 16:42 [pubmed] PHST- 2024/12/21 02:43 [entrez] PHST- 2024/12/20 00:00 [pmc-release] AID - JDI14391 [pii] AID - 10.1111/jdi.14391 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Apr;16(4):608-614. doi: 10.1111/jdi.14391. Epub 2024 Dec 20. PMID- 39704067 OWN - NLM STAT- MEDLINE DCOM- 20250312 LR - 20260923 IS - 1528-1140 (Electronic) IS - 0003-4932 (Print) IS - 0003-4932 (Linking) VI - 281 IP - 4 DP - 2025 Apr 1 TI - Association of Perioperative Glucagon-like Peptide-1 Receptor Agonist Use and Postoperative Outcomes. PG - 600-607 LID - 10.1097/SLA.0000000000006614 [doi] AB - OBJECTIVE: To assess rates of surgical complications and postoperative readmission in diabetic patients with and without active perioperative prescriptions for glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. BACKGROUND: With the rapid growth of GLP-1 RA use in the United States, it is important to understand the potential effect of these drugs on surgical outcomes broadly. METHODS: In this retrospective, observational cohort analysis, patients with a diagnosis of type 1 or type 2 diabetes undergoing a surgical procedure at a multicenter quaternary-care health care system between February 2020 and July 2023 were included. Propensity score matching was performed between procedures in patients with and without an active GLP-1 RA prescription. The primary outcome was 30-day readmission, and secondary outcomes were documented dehiscence, infection, hematoma, and bleeding within 180 days after surgery. RESULTS: Among 74,425 surgical procedures in 21,772 patients included in the analysis, 27.2% were performed in the setting of an active GLP-1 RA prescription. In 13,129 patients [48.0% men, 52.0% women; median (interquartile range) age, 67 (57, 75)], 35,020 procedures were propensity score matched. After matching, the active GLP-1 RA prescription group had a significantly reduced risk of 30-day readmission [relative risk (RR): 0.883; 95% CI: 0.789-0.987; P = 0.028; number needed to treat (NNT): 219; 95% CI: 191-257], postoperative wound dehiscence (RR: 0.711; 95% CI: 0.577-0.877; P = 0.001; NNT: 266; 95% CI: 202-391), and postoperative hematoma (RR: 0.440; 95% CI: 0.216-0.894; P = 0.023; NNT: 1786; 95% CI: 652-2416). No significant differences were seen in rates of infection and bleeding. CONCLUSIONS: An active perioperative GLP-1 RA prescription in patients with diabetes was associated with significant reductions in risk-adjusted readmission, wound dehiscence, and hematoma, and no difference in infection and bleeding rates. Further study is warranted to elucidate any causal association. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Aschen, Seth Z AU - Aschen SZ AD - Department of Surgery, Weill Cornell Medicine, New York, NY. FAU - Zhang, Ashley AU - Zhang A AD - Department of Surgery, Columbia University Irving Medical Center, New York, NY. FAU - O'Connell, Gillian M AU - O'Connell GM AD - Department of Surgery, Columbia University Irving Medical Center, New York, NY. FAU - Salingaros, Sophia AU - Salingaros S AD - Department of Surgery, Weill Cornell Medicine, New York, NY. FAU - Andy, Caroline AU - Andy C AD - Division of Biostatistics, Department of Population Health Sciences,Weill Cornell Medicine, New York, NY. FAU - Rohde, Christine H AU - Rohde CH AD - Department of Surgery, Columbia University Irving Medical Center, New York, NY. FAU - Spector, Jason A AU - Spector JA AD - Department of Surgery, Weill Cornell Medicine, New York, NY. LA - eng GR - UL1 TR001873/TR/NCATS NIH HHS/United States GR - UL1 TR002384/TR/NCATS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, N.I.H., Extramural DEP - 20241220 PL - United States TA - Ann Surg JT - Annals of surgery JID - 0372354 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - *Postoperative Complications/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Patient Readmission/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Propensity Score MH - *Diabetes Mellitus, Type 1/drug therapy MH - *Perioperative Care PMC - PMC12014183 MID - NIHMS2070262 COIS- The authors report no conflicts of interest. EDAT- 2024/12/20 06:24 MHDA- 2025/03/12 18:17 PMCR- 2025/10/01 CRDT- 2024/12/20 05:04 PHST- 2025/03/12 18:17 [medline] PHST- 2024/12/20 06:24 [pubmed] PHST- 2024/12/20 05:04 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 00000658-990000000-01151 [pii] AID - 10.1097/SLA.0000000000006614 [doi] PST - ppublish SO - Ann Surg. 2025 Apr 1;281(4):600-607. doi: 10.1097/SLA.0000000000006614. Epub 2024 Dec 20. PMID- 39700591 OWN - NLM STAT- MEDLINE DCOM- 20250428 LR - 20260818 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 2 DP - 2025 Feb TI - The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease. PG - 108932 LID - S1056-8727(24)00258-7 [pii] LID - 10.1016/j.jdiacomp.2024.108932 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD. METHODS: This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (gamma-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo). RESULTS: Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59 +/- 5.67 U/L in SAM vs. 25.56 +/- 5.46 U/L in M; AST: 18.97 +/- 3.94 U/L in SAM vs. 20.15 +/- 3.95 U/L in M), reduced fibrosis (FIB-4 index: 1.05 +/- 0.44 in SAM vs. 1.16 +/- 0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18 +/- 1.09 in SAM vs. 4.84 +/- 1.15 in M; DIo: 0.18 +/- 0.06 in SAM vs. 0.16 +/- 0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group. CONCLUSION: The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Ren, Rong AU - Ren R AD - Ward 1, Department of Endocrinology, Shanxi Provincial Integrated TCM And WM Hospital, Taiyuan 030013, China. Electronic address: RenYang_111@163.com. FAU - Pei, Yanxia AU - Pei Y AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. FAU - Kong, Lufei AU - Kong L AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. FAU - Shi, Yixin AU - Shi Y AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. LA - eng PT - Journal Article DEP - 20241209 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Metformin/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Insulin-Secreting Cells/drug effects/physiology MH - Female MH - *Non-alcoholic Fatty Liver Disease/drug therapy/complications/physiopathology MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Drug Therapy, Combination MH - Aged MH - Insulin Resistance MH - Liver/drug effects/pathology MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Insulin sensitivity OT - Liver inflammation OT - Metformin OT - Non-alcoholic fatty liver disease OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/20 00:23 MHDA- 2025/02/11 00:18 CRDT- 2024/12/19 18:01 PHST- 2024/11/04 00:00 [received] PHST- 2024/11/29 00:00 [revised] PHST- 2024/12/05 00:00 [accepted] PHST- 2025/02/11 00:18 [medline] PHST- 2024/12/20 00:23 [pubmed] PHST- 2024/12/19 18:01 [entrez] AID - S1056-8727(24)00258-7 [pii] AID - 10.1016/j.jdiacomp.2024.108932 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Feb;39(2):108932. doi: 10.1016/j.jdiacomp.2024.108932. Epub 2024 Dec 9. PMID- 39697128 OWN - NLM STAT- MEDLINE DCOM- 20241219 LR - 20250121 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 79 IP - 12 DP - 2024 Dec TI - [Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity]. PG - 812-820 AB - Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight. Such weight loss was accompanied by an improvement of comorbidities (as sleep apnea syndrome) and cardiovascular risk factors. Two large cardiovascular outcome trials are ongoing in patients with T2DM (SURPASS-CVOT) and in patients with obesity (SURMOUNT-MMO). FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), ULiege, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Le medicament du mois. Le tirzepatide : resume des etudes cliniques SURPASS dans le diabete de type 2 et SURMOUNT dans l'obesite. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Clinical Trials as Topic MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide OTO - NOTNLM OT - Dual agonist OT - GIP/GLP-1 co-agonist OT - Obesity OT - Tirzepatide OT - Type 2 diabetes EDAT- 2024/12/19 06:22 MHDA- 2024/12/19 06:23 CRDT- 2024/12/19 04:22 PHST- 2024/12/19 06:23 [medline] PHST- 2024/12/19 06:22 [pubmed] PHST- 2024/12/19 04:22 [entrez] PST - ppublish SO - Rev Med Liege. 2024 Dec;79(12):812-820. PMID- 39695549 OWN - NLM STAT- MEDLINE DCOM- 20241219 LR - 20250226 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 24 IP - 1 DP - 2024 Dec 18 TI - Predicting responsiveness to GLP-1 pathway drugs using real-world data. PG - 269 LID - 10.1186/s12902-024-01798-9 [doi] LID - 269 AB - BACKGROUND: Medications targeting the glucagon-like peptide-1 (GLP-1) pathway are an important therapeutic class currently used for the treatment of Type 2 diabetes (T2D). However, there is not enough known about which subgroups of patients would receive the most benefit from these medications. OBJECTIVE: The goal of this study was to develop a predictive model for patient responsiveness to medications, here collectively called GLP-1 M, that include GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors (that normally degrade endogenously-produced GLP-1). Such a model could guide clinicians to consider certain patient characteristics when prescribing second line medications for T2D. METHODS: We analyzed de-identified electronic health records of 7856 subjects with T2D treated with GLP-1 M drugs at Vanderbilt University Medical Center from 2003-2019. Using common clinical features (including commonly ordered lab tests, demographic information, other T2D medications, and diabetes-associated complications), we compared four different models: logistic regression, LightGBM, artificial neural network (ANN), and support vector classifier (SVC). RESULTS: Our analysis revealed that the traditional logistic regression model outperforms the other machine learning models, with an area under the Receiver Operating Characteristic curve (auROC) of 0.77.Our model showed that higher pre-treatment HbA1C is a dominant feature for predicting better response to GLP-1 M, while features such as use of thiazolidinediones or sulfonylureas is correlated with poorer response to GLP-1 M, as assessed by lowering of hemoglobin A1C (HbA1C), a standard marker of glycated hemoglobin used for assessing glycemic control in individuals with diabetes. Among female subjects under 40 taking GLP-1 M, the simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with a greater reduction in HbA1C (0.82 +/- 1.72% vs 0.28 +/- 1.70%, p = 0.008). CONCLUSION: These findings indicate a thorough analysis of real-world electronic health records could reveal new information to improve treatment decisions for the treatment of T2D. The predictive model developed in this study highlights the importance of considering individual patient characteristics and medication interactions when prescribing GLP-1 M drugs. CI - (c) 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Zhu, Xiaodong AU - Zhu X AD - Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Fowler, Michael J AU - Fowler MJ AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Wells, Quinn S AU - Wells QS AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Stafford, John M AU - Stafford JM AD - Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. AD - Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. FAU - Gannon, Maureen AU - Gannon M AD - Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA. Maureen.gannon@vumc.org. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Maureen.gannon@vumc.org. AD - Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. Maureen.gannon@vumc.org. AD - Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. Maureen.gannon@vumc.org. LA - eng GR - I01 BX005459/BX/BLRD VA/United States GR - R01 HL144846/HL/NHLBI NIH HHS/United States GR - DK109102/NH/NIH HHS/United States GR - R01 DK109102/DK/NIDDK NIH HHS/United States GR - HL140074/NH/NIH HHS/United States GR - 17SFRN33520017/American Heart Association/ GR - I01-BX005459/U.S. Department of Veterans Affairs/ GR - DK120626/NH/NIH HHS/United States GR - I01-BX003744/U.S. Department of Veterans Affairs/ GR - P30 DK058404/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20241218 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glycated Hemoglobin) RN - 0 (Biomarkers) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide 1 MH - Aged MH - Glycated Hemoglobin/analysis/metabolism MH - Prognosis MH - Biomarkers/analysis MH - Machine Learning MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11654408 OTO - NOTNLM OT - Electronic health record OT - GLP-1 OT - HbA1c OT - Predictive model OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Vanderbilt University Medical Center IRB Committee/Committee on Human Research Protection. All of the data used in the current study was obtained from a fully deidentified synthetic derivative of the electronic health record from Vanderbilt University Medical Center. Individual informed consent for participation in the current study was waived since subject information is deidentified and specific patients cannot be identified. However, at the time of their visit, patients can opt out of being included in the database. Thus, all subjects in the database chose to be included. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2024/12/19 06:23 MHDA- 2024/12/19 06:24 PMCR- 2024/12/18 CRDT- 2024/12/19 00:02 PHST- 2023/06/29 00:00 [received] PHST- 2024/12/02 00:00 [accepted] PHST- 2024/12/19 06:24 [medline] PHST- 2024/12/19 06:23 [pubmed] PHST- 2024/12/19 00:02 [entrez] PHST- 2024/12/18 00:00 [pmc-release] AID - 10.1186/s12902-024-01798-9 [pii] AID - 1798 [pii] AID - 10.1186/s12902-024-01798-9 [doi] PST - epublish SO - BMC Endocr Disord. 2024 Dec 18;24(1):269. doi: 10.1186/s12902-024-01798-9. PMID- 39694296 OWN - NLM STAT- MEDLINE DCOM- 20250405 LR - 20260415 IS - 1097-6779 (Electronic) IS - 0016-5107 (Linking) VI - 101 IP - 4 DP - 2025 Apr TI - Glucagon-like peptide-1 receptor agonist use and the risk of residual gastric contents and aspiration in patients undergoing GI endoscopy: a systematic review and a meta-analysis. PG - 762-771.e13 LID - S0016-5107(24)03794-5 [pii] LID - 10.1016/j.gie.2024.12.019 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus and obesity, but safety concerns have been raised for users undergoing GI endoscopy because of retained food and aspiration events. We compared the risk of adverse events for GLP-1RA users and nonusers undergoing endoscopy. METHODS: We conducted a systematic review and meta-analysis (PROSPERO registration: CRD42024556732). A systematic search in PubMed, Scopus, Web of Science, and Cochrane Central was performed from their inception until July 1, 2024 (EMBASE from 1974 to June 28, 2024). Double-arm adult human original studies (observational, randomized controlled trial) with a sample size of >/=20 undergoing EGD or endoscopy with no GLP-1RA use in the control arm were searched. Studies were excluded if they were single arm and had any use of GLP-1RA before the procedure in the control arm. Residual gastric contents (RGCs), aspiration pneumonia, and premature endoscopy termination were the main outcomes. The random-effects model was used to pool and get final effect estimates. RESULTS: Twenty-three observational studies were selected consisting of 262,018 patients. GLP-1RA users had a statistically significant increase in the risk of RGCs (odds ratio [OR], 4.54; 95% confidence interval [CI], 3.30-6.24; P < .00001, I(2) = 68%) and premature endoscopy termination (OR, 4.54; 95% CI, 3.05-6.75; P < .00001, I(2) = 0%). There was no significant difference in the risk of aspiration pneumonia (OR, .96; 95% CI, .53-1.75; P = .90, I(2) = 70%). A significant reduction was seen in RGCs when EGD and colonoscopy (OR, .28; 95% CI, .22-.36; P < .00001, I(2) = 0%) were done the same day versus EGD alone. CONCLUSIONS: GLP-1RA use was associated with an increased risk of RGCs and premature endoscopy termination, but no significant difference was found in the risk of aspiration pneumonia in patients undergoing endoscopy. CI - Copyright (c) 2025 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved. FAU - Baig, Muhammad Usman AU - Baig MU AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Piazza, Allison AU - Piazza A AD - Samuel J. Wood Library, Weill Cornell Medicine, New York, New York, USA. FAU - Lahooti, Ali AU - Lahooti A AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Johnson, Kate Elise AU - Johnson KE AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Rangwani, Sean AU - Rangwani S AD - Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Gouda, Zane AU - Gouda Z AD - Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Mahadev, Srihari AU - Mahadev S AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Newberry, Carolyn AU - Newberry C AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Hanscom, Mark AU - Hanscom M AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Sampath, Kartik AU - Sampath K AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Kumar, Sonal AU - Kumar S AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Anca, Diana AU - Anca D AD - Department of Anesthesiology, Weill Cornell Medicine, New York, New York, USA. FAU - Schulman, Allison Raye AU - Schulman AR AD - Division of Gastroenterology and Hepatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Carr-Locke, David Leslie AU - Carr-Locke DL AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. FAU - Sharaiha, Reem Z AU - Sharaiha RZ AD - Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241216 PL - United States TA - Gastrointest Endosc JT - Gastrointestinal endoscopy JID - 0010505 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Endoscopy, Gastrointestinal/adverse effects MH - *Gastrointestinal Contents/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Pneumonia, Aspiration/epidemiology/etiology MH - *Respiratory Aspiration of Gastric Contents/epidemiology COIS- Disclosure The following author disclosed financial relationships: C. Newberry: Consultant: Eli Lilly & Company. All other authors disclosed no financial relationships. EDAT- 2024/12/19 00:20 MHDA- 2025/04/06 04:45 CRDT- 2024/12/18 19:17 PHST- 2024/10/16 00:00 [received] PHST- 2024/11/17 00:00 [revised] PHST- 2024/12/06 00:00 [accepted] PHST- 2025/04/06 04:45 [medline] PHST- 2024/12/19 00:20 [pubmed] PHST- 2024/12/18 19:17 [entrez] AID - S0016-5107(24)03794-5 [pii] AID - 10.1016/j.gie.2024.12.019 [doi] PST - ppublish SO - Gastrointest Endosc. 2025 Apr;101(4):762-771.e13. doi: 10.1016/j.gie.2024.12.019. Epub 2024 Dec 16. PMID- 39692102 OWN - NLM STAT- MEDLINE DCOM- 20241218 LR - 20250103 IS - 1752-2978 (Electronic) IS - 1752-296X (Linking) VI - 32 IP - 1 DP - 2025 Feb 1 TI - GLP-1RA based therapies in the young and old. PG - 26-33 LID - 10.1097/MED.0000000000000900 [doi] AB - PURPOSE OF REVIEW: Obesity is recognized as a "gateway" chronic, progressive disease of dysfunctional adipocytes. Glucagon-like peptide-1 receptor agonist-based therapies (GLP1BTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without glucose-dependent insulinotropic polypeptide (GIP), have demonstrated clinically significant weight loss and health gains in adults, hence interest in using them in younger and older people. Therefore, reviewing the role of GLP1BTs in these populations is pertinent and timely. RECENT FINDINGS: Recent American Pediatric Guidelines emphasize the need for early introduction of obesity-management medication (OMM). This review evaluates the recently published data evaluating use of GLP1BTs in young people with obesity and/or youth onset Type 2 diabetes (YOT2D).Large studies of GLP1BTs in adults included those over 65, however no separate trial has looked at this heterogeneous group. This review translates the evidence, as it pertains to those over 65 where possible. SUMMARY: Newer-generation GLP1BTs specifically target pathways involved in energy balance, glycaemic control and other metabolic functions, heralding a new era for the management of younger people.Published cardiovascular outcome trial (CVOT) data presented in this review support the utility of GLP1BTs in the management of older people living with obesity and/or Type 2 diabetes (T2D), with the reassurance of no new safety signals identified. Maturation of the longer-term data and publication of the additional CVOT data in cohorts of differing health complexity will provide further insights. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Rigas, Georgia AU - Rigas G AD - St George & Sutherland Clinical School, University of New South Wales - Medicine. AD - St George Private Hospital Kogarah. FAU - Alexander, Shirley AU - Alexander S AD - Sydney Children's Hospitals Network. AD - University of Notre Dame, Sydney, New South Wales. FAU - Haywood, Cilla J AU - Haywood CJ AD - Austin Health, Continuing Care. AD - Austin Health, Endocrinology. AD - University of Melbourne, Department of Critical Care, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20241209 PL - England TA - Curr Opin Endocrinol Diabetes Obes JT - Current opinion in endocrinology, diabetes, and obesity JID - 101308636 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Aged MH - Adult MH - Age Factors MH - Adolescent MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/12/18 12:24 MHDA- 2024/12/18 12:25 CRDT- 2024/12/18 06:04 PHST- 2024/12/18 12:25 [medline] PHST- 2024/12/18 12:24 [pubmed] PHST- 2024/12/18 06:04 [entrez] AID - 01266029-202502000-00006 [pii] AID - 10.1097/MED.0000000000000900 [doi] PST - ppublish SO - Curr Opin Endocrinol Diabetes Obes. 2025 Feb 1;32(1):26-33. doi: 10.1097/MED.0000000000000900. Epub 2024 Dec 9. PMID- 39692101 OWN - NLM STAT- MEDLINE DCOM- 20250213 LR - 20250213 IS - 1752-2978 (Electronic) IS - 1752-296X (Linking) VI - 32 IP - 1 DP - 2025 Feb 1 TI - Overview of diabetes agents in cardiovascular disease: it takes an orchestra to play Tchaikovsky in symphony. PG - 3-11 LID - 10.1097/MED.0000000000000892 [doi] AB - PURPOSE OF REVIEW: The aim of this review was to discuss the use and concerns of diabetes agents, clinical targets, and key aspects to be considered in the management of patients with type 2 diabetes mellitus (T2DM), and at high risk or established cardiovascular disease (CVD). RECENT FINDINGS: The recent European and American guidelines recommended SGLT2 inhibitors and GLP-1 receptor agonists as the preferred first-line diabetes agents in patients with T2DM and CVD. This is a paradigm shift from using metformin as first-line therapy. Amid their widespread use, however, there are also concerns about their side effects. With the rapidly growing diabetes regimens available, questions arise about how best to approach the management of patients with T2DM and CVD. SUMMARY: To reduce CVD morbidity and mortality in patients with T2DM and at high or very high risk for CVD, the two key diabetes agents SGLT2i and/or GLP1-based therapies should be offered. Although lacking cardiovascular benefit, other diabetes agents remain necessary for many patients with T2DM for their glucocentric effects; Metformin and pioglitazone are useful in severe insulin resistance, while insulin therapy is often necessary in advanced diabetes; GLP1-RA is cautioned in patients with active gastrointestinal and mental health conditions, while DPP4 inhibitor is likely a well tolerated option in a challenging psychosocial setting. Other important aspects that should be considered include obesity, chronic kidney disease, women's cardiovascular health, and psychosocial factors. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Loh, Wann Jia AU - Loh WJ AD - Department of Endocrinology, Changi General Hospital. AD - Duke-NUS Medical School, Singapore, Singapore. AD - Medical School, University of Western Australia, Perth, Western Australia, Australia. LA - eng PT - Journal Article PT - Review DEP - 20241111 PL - England TA - Curr Opin Endocrinol Diabetes Obes JT - Current opinion in endocrinology, diabetes, and obesity JID - 101308636 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Sodium-Glucose Transporter 2 Inhibitors EDAT- 2024/12/18 12:24 MHDA- 2024/12/18 12:25 CRDT- 2024/12/18 06:04 PHST- 2024/12/18 12:25 [medline] PHST- 2024/12/18 12:24 [pubmed] PHST- 2024/12/18 06:04 [entrez] AID - 01266029-990000000-00113 [pii] AID - 10.1097/MED.0000000000000892 [doi] PST - ppublish SO - Curr Opin Endocrinol Diabetes Obes. 2025 Feb 1;32(1):3-11. doi: 10.1097/MED.0000000000000892. Epub 2024 Nov 11. PMID- 39689782 OWN - NLM STAT- MEDLINE DCOM- 20250428 LR - 20250519 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 31 IP - 3 DP - 2025 Mar TI - The Cardiovascular Outcomes Between Liraglutide and Dulaglutide Among Different Chronic Kidney Disease Stages in Patients With Type 2 Diabetes. PG - 292-297 LID - S1530-891X(24)00866-8 [pii] LID - 10.1016/j.eprac.2024.11.016 [doi] AB - OBJECTIVE: This study aimed to evaluate the effectiveness and safety of 2 glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and dulaglutide, in patients with type 2 diabetes mellitus (T2DM) at various stages of chronic kidney disease (CKD). In addition to analyzing Major Adverse Cardiovascular Events (MACE) as the primary outcome, kidney function deterioration, renal disease, and other drug-related safety events, such as urinary tract infections, pancreatitis, amputations, and cancers were measured. RESEARCH DESIGN AND METHODS: This retrospective analysis included 362 842 T2DM patients from the Chang Gung Research Database between 2011 and 2019, identifying 2830 GLP-1 RAs users. After applying exclusion criteria, 1572 patients (945 on liraglutide, 627 on dulaglutide) were included. The primary outcome was MACE incidence across CKD stages. RESULTS: Of the included patients, 945 used liraglutide, and 627 used dulaglutide. This study found no significant difference in the incidence of MACE between the 2 drugs across varying kidney function levels. However, in patients using liraglutide, a significant increase in MACE incidence was observed with deteriorating kidney function, from an HR of 1.401 (95% CI 0.663-2.958) at an eGFR of 60-89 ml/min/1.73 m(2) to an HR of 4.078 (95% CI 1.111-14.971, P = .0079) at an eGFR of <15 ml/min/1.73 m(2), a trend not observed in dulaglutide users (P = .1906). CONCLUSION: Both liraglutide and dulaglutide are effective GLP-1 RAs in T2DM patients, but their impact on cardiovascular outcomes varies with CKD stage in liraglutide users. In contrast, this trend was not observed with dulaglutide, suggesting a potentially greater cardiovascular benefit of dulaglutide at more advanced CKD stages. CI - Copyright (c) 2024 AACE. Published by Elsevier Inc. All rights reserved. FAU - Cai, Yu-Xuan AU - Cai YX AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan. FAU - Liu, Feng-Hsuan AU - Liu FH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan. FAU - Sun, Jui-Hung AU - Sun JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan. FAU - Lin, Chia-Hung AU - Lin CH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: adronlin@cgmh.org.tw. LA - eng PT - Journal Article DEP - 20241215 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Liraglutide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/complications/epidemiology MH - Middle Aged MH - Retrospective Studies MH - *Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - *Cardiovascular Diseases/epidemiology/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - chronic kidney disease OT - liraglutide OT - type 2 diabetes mellitus COIS- Disclosure The authors have no conflicts of interest to disclose. EDAT- 2024/12/18 00:23 MHDA- 2025/03/06 05:03 CRDT- 2024/12/17 19:12 PHST- 2024/09/20 00:00 [received] PHST- 2024/11/15 00:00 [revised] PHST- 2024/11/25 00:00 [accepted] PHST- 2025/03/06 05:03 [medline] PHST- 2024/12/18 00:23 [pubmed] PHST- 2024/12/17 19:12 [entrez] AID - S1530-891X(24)00866-8 [pii] AID - 10.1016/j.eprac.2024.11.016 [doi] PST - ppublish SO - Endocr Pract. 2025 Mar;31(3):292-297. doi: 10.1016/j.eprac.2024.11.016. Epub 2024 Dec 15. PMID- 39688041 OWN - NLM STAT- MEDLINE DCOM- 20241217 LR - 20260127 IS - 2038-1840 (Electronic) IS - 0034-1193 (Linking) VI - 115 IP - 12 DP - 2024 Dec TI - [Impact of Elon Musk's statements on the use of semaglutide in the Lazio Region: a time series analysis study.]. PG - 593-598 LID - 10.1701/4392.43917 [doi] AB - INTRODUCTION: In recent times, TikTok 'weight loss influencers' have been promoting the use of GLP-1 receptor agonist drugs, with particular emphasis on semaglutide. The popularity of this class of drugs has been amplified by the statements of Elon Musk, who publicly declared in October 2022 that he had lost weight thanks to Wegovy, a semaglutide-based medication launched in the US. In Italy, GLP-1 receptor agonists are mainly indicated for the treatment of type 2 diabetes, but in certain cases they can be prescribed off-label for obesity and overweight. The aim of this study is to assess the impact of Elon Musk's statements on the use of semaglutide within Regional Health Service of the Lazio Region. METHODS: Dispensations of GLP-1 receptor agonist drugs (ATC: A10BJ) within Regional Health Service in the Lazio Region between January 2022 and March 2023 were analysed, identifying those related to semaglutide (ATC: A10BJ06). Monthly time series data on new users (with a 1-year washout period) of semaglutide and other GLP-1 drugs were compared to identify any changes after October 2022. In addition, the proportion of patients for whom it was possible to verify the indication of diabetes through health administrative data was examined. RESULTS: Analysis of the monthly trends for the entire class of GLP-1 receptor agonist drugs showed no difference in the monthly average of incident users between the pre and post Elon Musk statements. However, an increase in incident users was observed for semaglutide (monthly average: from 872 pre to 1,380 post) at the expense of the use of other drugs in the same class (monthly average: from 711 pre to 208 post). The proportion of semaglutide users for whom diabetes could not be confirmed remained stable over time at approximately 9.5%. CONCLUSIONS: Elon Musk's statements seem to have had an impact on the use of semaglutide among patients in the Lazio region. Further analyses are necessary to carefully assess the presence of possible other factors influencing the preference for semaglutide over other GLP-1 receptor agonists. FAU - Belleudi, Valeria AU - Belleudi V AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. FAU - Lopes, Sara AU - Lopes S AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. FAU - Addis, Antonio AU - Addis A AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. LA - ita PT - English Abstract PT - Journal Article TT - Impatto delle dichiarazioni di Elon Musk sull'uso della semaglutide nella Regione Lazio: uno studio di analisi delle serie temporali. PL - Italy TA - Recenti Prog Med JT - Recenti progressi in medicina JID - 0401271 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Humans MH - Italy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use/administration & dosage MH - Obesity/drug therapy MH - Weight Loss/drug effects MH - Overweight/drug therapy MH - Practice Patterns, Physicians'/statistics & numerical data MH - Time Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/12/17 11:49 MHDA- 2024/12/17 12:30 CRDT- 2024/12/17 05:33 PHST- 2024/12/17 12:30 [medline] PHST- 2024/12/17 11:49 [pubmed] PHST- 2024/12/17 05:33 [entrez] AID - 10.1701/4392.43917 [doi] PST - ppublish SO - Recenti Prog Med. 2024 Dec;115(12):593-598. doi: 10.1701/4392.43917. PMID- 39684653 OWN - NLM STAT- MEDLINE DCOM- 20241217 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 23 DP - 2024 Dec 2 TI - Pharmacological Nephroprotection in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus-Clinical Practice Position Statement of the Polish Society of Nephrology. LID - 10.3390/ijms252312941 [doi] LID - 12941 AB - Both chronic kidney disease (CKD) and type 2 diabetes (T2D) are modern epidemics worldwide and have become a severe public health problem. Chronic kidney disease progression in T2D patients is linked to the need for dialysis or kidney transplantation and represents the risk factor predisposing to serious cardiovascular complications. In recent years, important progress has occurred in nephroprotective pharmacotherapy in CKD patients with T2D. In the current position paper, we described a nephroprotective approach in CKD patients with T2D based on the five following pillars: effective antihyperglycemic treatment, SGLT2 inhibitor or semaglutide, antihypertensive therapy, use of RASi (ARB or ACEi), and in selected patients, finerenone, as well as sodium bicarbonate in patients with metabolic acidosis. We thought that the current statement is comprehensive and up-to-date and addresses multiple pathways of nephroprotection in patients with CKD and T2D. FAU - Adamczak, Marcin AU - Adamczak M AD - Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland. FAU - Kurnatowska, Ilona AU - Kurnatowska I AUID- ORCID: 0000-0003-3448-0682 AD - Department of Internal Diseases and Transplant Nephrology, Medical University of Lodz, 90-153 Lodz, Poland. FAU - Naumnik, Beata AU - Naumnik B AUID- ORCID: 0000-0001-7090-8856 AD - 1st Department of Nephrology, Transplantation and Internal Medicine with Dialysis Unit, Medical University of Bialystok, 15-540 Bialystok, Poland. FAU - Stompor, Tomasz AU - Stompor T AD - Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, 10-516 Olsztyn, Poland. FAU - Tylicki, Leszek AU - Tylicki L AD - Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-952 Gdansk, Poland. FAU - Krajewska, Magdalena AU - Krajewska M AUID- ORCID: 0000-0002-2632-2409 AD - Department of Non-Surgical Clinical Sciences, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland. LA - eng GR - Publication cost covering/Polish Society of Nephrology/ PT - Journal Article PT - Practice Guideline PT - Review DEP - 20241202 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antihypertensive Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (finerenone) RN - 0 (Naphthyridines) SB - IM MH - Humans MH - Angiotensin Receptor Antagonists/therapeutic use/pharmacology MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use MH - Antihypertensive Agents/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Diabetic Nephropathies/drug therapy/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Nephrology/standards/methods MH - Poland MH - *Renal Insufficiency, Chronic/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Naphthyridines PMC - PMC11641270 OTO - NOTNLM OT - blood pressure control OT - chronic kidney disease OT - diabetes mellitus type 2 OT - metabolic acidosis OT - nephroprotection OT - renin-angiotensin system OT - sodium-glucose co-transporter type 2 inhibitors COIS- Marcin Adamczak receives speaker's fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Sanprobi, travel grants from AstraZeneca, Sandoz, and Chiesi, and participates in the advisory board for AstraZeneca and Boehringer Ingelheim. Ilona Kurnatowska receives speaker's fees from AstraZeneca, Boehringer Ingelheim, and Bayer and travel grants from AstraZeneca, Boehringer Ingelheim, and Chiesi. Beata Naumnik receives speaker's fees from AstraZeneca, Bayer, Boehringer Ingelheim, Baxter, Sandoz, travel grants from AstraZeneca, participates in advisory boards for AstraZeneca, Boehringer Ingelheim, and FreseniusCabi, and participates in clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Novartis, and Alexion. Tomasz Stompor receives speaker's fees from AstraZeneca, Berlin-Chemie/Menarini, Boehringer Ingelheim, Bayer, and Novo Nordisk, participates in advisory boards for AstraZeneca and Boehringer Ingelheim, and participates in clinical trials sponsored by AstraZeneca and Bayer. Leszek Tylicki declares no conflict of interest. Magdalena Krajewska receives speaker's fees from AstraZeneca, Boehringer Ingelheim, Bayer, Takeda, Amicus, Astellas, Chiesi, Fresenius Kabi and Swixx Pharma; travel grants from AstraZeneca, Sandoz, Chiesi and Boehringer Ingelheim; and participates in the advisory board for AstraZeneca and Boehringer Ingelheim. EDAT- 2024/12/17 11:48 MHDA- 2024/12/17 11:49 PMCR- 2024/12/02 CRDT- 2024/12/17 01:14 PHST- 2024/10/17 00:00 [received] PHST- 2024/11/20 00:00 [revised] PHST- 2024/11/26 00:00 [accepted] PHST- 2024/12/17 11:49 [medline] PHST- 2024/12/17 11:48 [pubmed] PHST- 2024/12/17 01:14 [entrez] PHST- 2024/12/02 00:00 [pmc-release] AID - ijms252312941 [pii] AID - ijms-25-12941 [pii] AID - 10.3390/ijms252312941 [doi] PST - epublish SO - Int J Mol Sci. 2024 Dec 2;25(23):12941. doi: 10.3390/ijms252312941. PMID- 39680313 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260817 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 42 IP - 2 DP - 2025 Feb TI - Long-Term Clinical and Economic Effects of Switching to Once-Weekly Semaglutide from Other GLP-1 RAs Among Patients with Type 2 Diabetes in China: A Modeling Projection Study. PG - 904-917 LID - 10.1007/s12325-024-03082-7 [doi] AB - INTRODUCTION: Previous studies, using clinical trial data, demonstrated that once-weekly (OW) semaglutide is dominant versus other glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in China. This study aims to evaluate the long-term clinical and economic effects of switching to OW semaglutide from other GLP-1 RAs among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to project life expectancy, quality-adjusted life years (QALYs), and total direct medical cost over 40 years from a Chinese healthcare system perspective. Baseline characteristics, clinical effectiveness, and the treatment dose of OW semaglutide were derived from previously real-world studies. Patients were assumed to switch to semaglutide or continue previous GLP-1 RAs for 3 years and change to intensive therapy. Drug prices were based on the median bidding price in January 2024 in China. Costs of other GLP-1 RAs were calculated on the basis of their market share in China. All costs were accounted as 2023 Chinese yuan (CNY). A discount of 5% was applied. One-way sensitivity analyses and probabilistic sensitivity analyses were used to test the robustness of the base-case result. RESULTS: The results show that switching to OW semaglutide from other GLP-1 RAs among patients with T2DM in China can improve life expectancy by 0.02 years and afford an additional 0.12 QALYs per patient. Meanwhile, switching to OW semaglutide is associated with decreased total lifetime direct medical costs of 4204 CNY per patient, mainly resulting from savings in microvascular costs (2214 CNY) and macrovascular costs (1228 CNY). Sensitivity analyses show the robustness of modeling projection findings. CONCLUSION: Based on real-world data from China, this modeling projection study demonstrates that switching to OW semaglutide from other GLP-1 RAs can have better clinical and economic effects for patients with T2DM in China, indicating it as a dominant treatment choice. CI - (c) 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature. FAU - Hu, Ying AU - Hu Y AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Chen, Xianwen AU - Chen X AUID- ORCID: 0009-0008-5903-8368 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. FAU - Zou, Huimin AU - Zou H AUID- ORCID: 0000-0002-6239-3335 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. FAU - Zhang, Hao AU - Zhang H AUID- ORCID: 0000-0003-2180-0122 AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd, Beijing, China. FAU - Ni, Qi AU - Ni Q AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Li, Yijun AU - Li Y AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Ung, Carolina Oi Lam AU - Ung COL AUID- ORCID: 0000-0003-1915-5099 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. AD - Centre for Pharmaceutical Regulatory Sciences, University of Macau, Macao, China. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao, China. FAU - Hu, Hao AU - Hu H AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. haohu@um.edu.mo. AD - Centre for Pharmaceutical Regulatory Sciences, University of Macau, Macao, China. haohu@um.edu.mo. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao, China. haohu@um.edu.mo. FAU - Mu, Yiming AU - Mu Y AUID- ORCID: 0000-0002-3344-3540 AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. muyiming@301hospital.com.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241216 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/administration & dosage/economics/therapeutic use MH - China MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Quality-Adjusted Life Years MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Drug Administration Schedule MH - Cost-Benefit Analysis MH - Life Expectancy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - China OT - Modeling OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of Interest: Hao Zhang is an employee of Novo Nordisk. Ying Hu, Xianwen Chen, Huimin Zou, Hao Zhang, Qi Ni, Yijun Li, Carolina Oi Lam Ung, and Yiming Mu declare that they have no competing interests. Ethics Approval: This article is based on previously conducted clinical trials and does not contain any studies with human participants or animals performed by any authors. EDAT- 2024/12/16 12:27 MHDA- 2025/02/01 20:43 CRDT- 2024/12/16 11:33 PHST- 2024/10/30 00:00 [received] PHST- 2024/11/22 00:00 [accepted] PHST- 2025/02/01 20:43 [medline] PHST- 2024/12/16 12:27 [pubmed] PHST- 2024/12/16 11:33 [entrez] AID - 10.1007/s12325-024-03082-7 [pii] AID - 10.1007/s12325-024-03082-7 [doi] PST - ppublish SO - Adv Ther. 2025 Feb;42(2):904-917. doi: 10.1007/s12325-024-03082-7. Epub 2024 Dec 16. PMID- 39680131 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 7 DP - 2025 Jul TI - Comparing medication persistence with oral and subcutaneous semaglutide in a real-world setting. PG - 1065-1072 LID - 10.1007/s00592-024-02424-9 [doi] AB - AIMS: To compare medication persistence and efficacy of oral and subcutaneous semaglutide, in a real-world setting. MATERIALS AND METHODS: This is a single-center, retrospective observational cohort study. Patients with type 2 diabetes mellitus (T2DM) starting treatment with either formulation of semaglutide between January 1 2019 and July 31 2023 and with at least one follow-up visit were included. The primary endpoint was the difference in the proportion of patients that continued treatment after 6, 12 and 18 months. Main secondary endpoints were change in HbA1c and body weight. RESULTS: We included 242 patients on oral (n = 121) and subcutaneous (n = 121) semaglutide. At baseline, patients in the oral semaglutide group were significantly older (mean age: 67 +/- 11 vs. 63 +/- 11 years, p = 0.002) and had a lower body mass index (BMI: 30.5 +/- 5.6 vs. 33.9 +/- 7.1 kg/m(2), p < 0.001). The proportion of patients persistent to treatment was significantly lower in the oral group at 6 (85.3% vs. 94.8%; p < 0.001), 12 (72.3% vs. 92.4%, p < 0.001) and 18 (46.0% vs. 83.8%; p < 0.001) months. Most common reasons for discontinuation were gastro-intestinal side effects. When adjusted for age and BMI, body weight and HbA1c reduction were not significantly different between the two formulations, as the proportion of patients achieving the composite outcome of weight loss >/= 5% and HbA1c < 7.0%. CONCLUSIONS: The present real-world study suggests that persistence is significantly lower when semaglutide is administered as a once-daily tablet compared with a weekly injection, while there are no differences in efficacy between the two formulations. CI - (c) 2024. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Conti, Matteo AU - Conti M AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Pontiggia, Lorenzo AU - Pontiggia L AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Vergani, Michela AU - Vergani M AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Muraca, Emanuele AU - Muraca E AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Cannistraci, Rosa AU - Cannistraci R AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Perra, Silvia AU - Perra S AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Lattuada, Guido AU - Lattuada G AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Perseghin, Gianluca AU - Perseghin G AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Ciardullo, Stefano AU - Ciardullo S AUID- ORCID: 0000-0003-2422-3041 AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. stefano.ciardullo@policlinicodimonza.it. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. stefano.ciardullo@policlinicodimonza.it. AD - Department of Medicine and Surgery, Department of Medicine and Rehabilitation, Universita degli Studi di Milano Bicocca, Policlinico di Monza, Via Modigliani 10, 20900, Monza, MB, Italy. stefano.ciardullo@policlinicodimonza.it. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20241216 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - Injections, Subcutaneous MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adherence OT - Diabetes OT - Persistence OT - Real-world OT - Semaglutide COIS- Declarations. Conflict of interest: The authors have no conflicts of interest to report. EDAT- 2024/12/16 12:28 MHDA- 2025/07/23 10:54 CRDT- 2024/12/16 11:15 PHST- 2024/10/07 00:00 [received] PHST- 2024/11/23 00:00 [accepted] PHST- 2025/07/23 10:54 [medline] PHST- 2024/12/16 12:28 [pubmed] PHST- 2024/12/16 11:15 [entrez] AID - 10.1007/s00592-024-02424-9 [pii] AID - 10.1007/s00592-024-02424-9 [doi] PST - ppublish SO - Acta Diabetol. 2025 Jul;62(7):1065-1072. doi: 10.1007/s00592-024-02424-9. Epub 2024 Dec 16. PMID- 39656981 OWN - NLM STAT- MEDLINE DCOM- 20241210 LR - 20250103 IS - 1958-5381 (Electronic) IS - 0767-0974 (Linking) VI - 40 IP - 11 DP - 2024 Nov TI - [From the discovery of incretin hormones to GIP / GLP-1 / glucagon double and triple agonists]. PG - 837-847 LID - 10.1051/medsci/2024153 [doi] AB - The concept of treating diabetes with gut hormones was proposed in the early days of endocrinology (1902), but was not put into practice until the early 2000s. The discovery of the incretin effect (potentiation of insulin secretion when glucose is taken orally compared to intravenously) led to the discovery of the two main gut hormones responsible for this effect: GIP and GLP-1. The reduction of the incretin effect is directly involved in the pathogenesis of type 2 diabetes, which has led to the development of a series of innovative therapies such as GLP-1 analogues, GLP-1 receptor agonists, GIP/GLP-1 co-agonists and GIP/GLP-1/glucagon tri-agonists. These therapies, with their potent hypoglycaemic and weight-lowering effects, promote optimal control of excess weight and hyperglycaemia, avoiding the escalation of treatment that was once considered inevitable. CI - (c) 2024 medecine/sciences - Inserm. FAU - Phan, Franck AU - Phan F AD - Service de diabetologie, CHU Pitie-Salpetriere, Paris, France. FAU - Bertrand, Romane AU - Bertrand R AD - Universite Paris-Diderot, Unite de biologie fonctionnelle et adaptative / CNRS UMR 8251, Paris, France. FAU - Amouyal, Chloe AU - Amouyal C AD - Service de diabetologie, CHU Pitie-Salpetriere, Paris, France. FAU - Andreelli, Fabrizio AU - Andreelli F AD - Service de diabetologie, CHU Pitie-Salpetriere, Paris, France. LA - fre PT - English Abstract PT - Historical Article PT - Journal Article PT - Review TT - De la decouverte des hormones incretines aux doubles et triples agonistes GIP / GLP-1 / glucagon. DEP - 20241210 PL - France TA - Med Sci (Paris) JT - Medecine sciences : M/S JID - 8710980 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide 1 MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon/metabolism MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - History, 20th Century MH - Animals MH - History, 21st Century MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/12/15 19:30 MHDA- 2024/12/15 19:31 CRDT- 2024/12/10 15:12 PHST- 2024/12/15 19:31 [medline] PHST- 2024/12/15 19:30 [pubmed] PHST- 2024/12/10 15:12 [entrez] AID - msc240165 [pii] AID - 10.1051/medsci/2024153 [doi] PST - ppublish SO - Med Sci (Paris). 2024 Nov;40(11):837-847. doi: 10.1051/medsci/2024153. Epub 2024 Dec 10. PMID- 39673731 OWN - NLM STAT- MEDLINE DCOM- 20241214 LR - 20260625 IS - 1520-7560 (Electronic) IS - 1520-7552 (Linking) VI - 41 IP - 1 DP - 2025 Jan TI - Searching the Crystal Ball for Tailored GLP-1 Receptor Agonists Treatment in Type 2 Diabetes and Obesity. PG - e70017 LID - 10.1002/dmrr.70017 [doi] AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (RA) are novel agents used in the management of type 2 diabetes (T2D) and obesity. Although highly effective, the response to treatment may vary significantly among patients. OBJECTIVE: This perspective review aims to summarise the current knowledge about markers of poor or good response to GLP-1 RA, highlighting the possibility of tailoring treatment strategies and reducing costs associated with T2D and obesity treatment. METHODS: A comprehensive literature search was conducted using PubMed, NCBI, and Scopus databases, focussing on studies published between 2016 and 2024 that evaluated factors influencing treatment outcomes with GLP-1 RA. RESULTS: Several markers, including baseline HbA1c levels, ghrelin and glucose-dependent insulinotropic polypeptide (GIP) levels, specific gut microbiome composition, b-cell function, and genetic markers, were identified as factors associated with treatment response. CONCLUSION: Understanding predictive markers of response to therapy can enhance precision-based medicine for the selection of patients eligible for GLP-1 RA, improving clinical outcomes and optimising diabetes management. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Saturnino, Asia AU - Saturnino A AD - Campus Bio-Medico University, Rome, Italy. FAU - Maddaloni, Ernesto AU - Maddaloni E AUID- ORCID: 0000-0003-3844-9463 AD - Sapienza University of Rome, Rome, Italy. FAU - Zampetti, Simona AU - Zampetti S AD - Sapienza University of Rome, Rome, Italy. FAU - Buzzetti, Raffaella AU - Buzzetti R AUID- ORCID: 0000-0003-1490-6041 AD - Sapienza University of Rome, Rome, Italy. LA - eng PT - Journal Article PT - Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Biomarkers/analysis MH - Precision Medicine MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor EDAT- 2024/12/14 20:22 MHDA- 2024/12/14 20:23 CRDT- 2024/12/14 13:52 PHST- 2024/11/14 00:00 [revised] PHST- 2024/10/24 00:00 [received] PHST- 2024/12/02 00:00 [accepted] PHST- 2024/12/14 20:23 [medline] PHST- 2024/12/14 20:22 [pubmed] PHST- 2024/12/14 13:52 [entrez] AID - 10.1002/dmrr.70017 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 Jan;41(1):e70017. doi: 10.1002/dmrr.70017. PMID- 39672547 OWN - NLM STAT- MEDLINE DCOM- 20250110 LR - 20260617 IS - 1522-1563 (Electronic) IS - 0363-6143 (Print) IS - 0363-6143 (Linking) VI - 328 IP - 1 DP - 2025 Jan 1 TI - Prevention of cardiovascular disease in women with type 2 diabetes: the role of incretin mimetics and sodium-glucose cotransporter-2 inhibitors. PG - C315-C322 LID - 10.1152/ajpcell.00765.2024 [doi] AB - Cardiovascular disease (CVD) is the leading cause of death among individuals with type 2 diabetes (T2D), with women experiencing a disproportionate risk of events compared with men. Women have an amplified burden of cardiovascular risk factors once T2D is diagnosed. Incretin mimetics now plays a central role in managing cardiovascular risk by improving glycemic control, promoting weight loss, and potentially exerting direct cardioprotective effects. Similarly, sodium-glucose cotransporter-2 inhibitors contribute to CVD prevention through various nonglucose-lowering mechanisms. Both classes of medications are integral to personalized treatment strategies aimed at addressing the heightened cardiovascular risk faced by women with diabetes. This mini-review addresses possible mechanisms underlying the increased cardiovascular risk and explores the role of incretin mimetics and SGLT2 inhibitors in mitigating CVD in women with T2D. Emphasizing personalized and sex-specific approaches in diabetes care is crucial for optimizing treatment outcomes and improving cardiovascular health. CI - Copyright (c) 2025 The Authors. FAU - Ibrahim, Eiman AU - Ibrahim E AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, Missouri, United States. FAU - Burken, Mya AU - Burken M AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, Missouri, United States. FAU - Lastra, Guido AU - Lastra G AUID- ORCID: 0000-0001-9205-1021 AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, Missouri, United States. AD - Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, United States. FAU - Manrique-Acevedo, Camila AU - Manrique-Acevedo C AUID- ORCID: 0000-0001-9341-404X AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, Missouri, United States. AD - Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, United States. AD - NextGen Precision Health, University of Missouri, Columbia, Missouri, United States. LA - eng GR - R01 AG082413/AG/NIA NIH HHS/United States GR - R01 HL142770/HL/NHLBI NIH HHS/United States GR - R21 DK116081/DK/NIDDK NIH HHS/United States GR - R01AG082413/HHS | NIH | National Institute on Aging (NIA)/ GR - R01HL142770/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ GR - 1I01CX002399/U.S. Department of Veterans Affairs (VA)/ GR - I01 CX002399/CX/CSRD VA/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Review DEP - 20241213 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - *Incretins/therapeutic use MH - Female MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Heart Disease Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11901335 MID - NIHMS2086595 OTO - NOTNLM OT - SGLT2 inhibitors OT - cardiovascular disease OT - diabetes OT - incretin mimetics OT - sex differences COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2024/12/14 00:24 MHDA- 2025/01/10 18:20 PMCR- 2026/01/01 CRDT- 2024/12/13 20:13 PHST- 2025/01/10 18:20 [medline] PHST- 2024/12/14 00:24 [pubmed] PHST- 2024/12/13 20:13 [entrez] PHST- 2026/01/01 00:00 [pmc-release] AID - C-00765-2024 [pii] AID - 10.1152/ajpcell.00765.2024 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2025 Jan 1;328(1):C315-C322. doi: 10.1152/ajpcell.00765.2024. Epub 2024 Dec 13. PMID- 39671854 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260818 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 2 DP - 2025 Feb TI - Diabetes mellitus therapy in the light of oxidative stress and cardiovascular complications. PG - 108941 LID - S1056-8727(24)00267-8 [pii] LID - 10.1016/j.jdiacomp.2024.108941 [doi] AB - Type 2 diabetes is a chronic disease requiring comprehensive pharmacological and non-pharmacological interventions to slow its progression and prevent or delay its micro- and macrovascular complications. Oxidative stress contributes to the development and progression of type 2 diabetes as well as to the development of its complications through several mechanisms. Therefore, therapeutic targeting of oxidative stress could aid in managing this disease and its complications. In our study, we have collected information on the most frequently used antidiabetic drugs (metformin, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) in the EU and the USA based on their antioxidant effects. Based on our results, we can conclude that the antioxidant effects of the investigated antidiabetics may contribute significantly to the management of the disease and its complications and may open new therapeutic perspectives in their prevention. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Osman, Alaa A M AU - Osman AAM AD - Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Hungary. FAU - Seres-Bokor, Adrienn AU - Seres-Bokor A AD - Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Hungary. FAU - Ducza, Eszter AU - Ducza E AD - Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Hungary. Electronic address: ducza.eszter@szte.hu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20241210 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Antioxidants) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Oxidative Stress/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Cardiovascular Diseases/prevention & control/etiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Antioxidants/therapeutic use/pharmacology MH - Metformin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Angiopathies/prevention & control OTO - NOTNLM OT - Antidiabetic drugs OT - Cardiovascular complications OT - Glucagon-like peptide 1 receptor agonists OT - Metformin OT - Oxidative stress OT - Sodium-glucose cotransporter 2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/14 00:25 MHDA- 2025/02/11 00:19 CRDT- 2024/12/13 18:07 PHST- 2024/09/13 00:00 [received] PHST- 2024/11/19 00:00 [revised] PHST- 2024/12/09 00:00 [accepted] PHST- 2025/02/11 00:19 [medline] PHST- 2024/12/14 00:25 [pubmed] PHST- 2024/12/13 18:07 [entrez] AID - S1056-8727(24)00267-8 [pii] AID - 10.1016/j.jdiacomp.2024.108941 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Feb;39(2):108941. doi: 10.1016/j.jdiacomp.2024.108941. Epub 2024 Dec 10. PMID- 39667523 OWN - NLM STAT- MEDLINE DCOM- 20250710 LR - 20260413 IS - 1532-8414 (Electronic) IS - 1071-9164 (Linking) VI - 31 IP - 7 DP - 2025 Jul TI - GLP-1 Receptor Agonist in Nonobese Patients with Type 2 Diabetes Mellitus and Heart Failure with Preserved Ejection Fraction. PG - 989-1001 LID - S1071-9164(24)00962-X [pii] LID - 10.1016/j.cardfail.2024.10.448 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) promote weight loss and improve heart failure-related symptoms, quality of life, and functional capacity in patients with obesity and heart failure with preserved ejection fraction (HFpEF). However, their clinical effectiveness in nonobese patients with diabetes and HFpEF is understudied. METHODS: The TriNetX research network was used to identify adult patients (>/=18 years) with type 2 diabetes mellitus (T2DM), heart failure with preserved ejection fraction (left ventricular ejection fraction >/=45%), elevated brain natriuretic peptide (>/= 150 pg/mL) or N-terminal pro-B-type natriuretic peptide(>/= 450 pg/mL) and a body mass index (BMI) <30 kg/m2 on or before August 31, 2022. Patients were divided into two groups based on GLP-1RA use. After propensity score matching, Cox proportional hazard ratios (HRs) were used to compare outcomes over a 12-month follow-up period. RESULTS: The study included 84,990 patients (n= 42,495 per group, mean age 64 years, 49% females, 65% white). Patients on GLP-1RAs were associated with lower incidence of heart failure exacerbation events (HR 0.60, 95% CI 0.58-0.62, p<0.001) and all-cause emergency room visits or hospitalizations (HR, 0.67, 95% CI 0.66-0.69; P < .001) compared with those not on GLP-1RAs. Other outcomes, including acute myocardial infarction, atrial fibrillation, ischemic stroke, pulmonary hypertension, C-reactive protein >/= 5 mg/L, acute kidney injury, and the need for renal replacement therapy, were also significantly less frequent in the GLP-1RA group. These associated benefits persisted even among patients on a sodium-glucose cotransporter-2 inhibitor (SGLT2i). CONCLUSION: GLP-1RA use is associated with improved cardiovascular outcomes in nonobese patients with T2DM and HFpEF and has an associated incremental benefit even among patients on SGLT2i. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Khadke, Sumanth AU - Khadke S AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Kumar, Ashish AU - Kumar A AD - Department of Medicine, Cleveland Clinic, Akron General, Akron, Ohio. FAU - Bhatti, Ammar AU - Bhatti A AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Dani, Sourbha S AU - Dani SS AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Al-Kindi, Sadeer AU - Al-Kindi S AD - Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Cardiovascular Center, Houston, Texas. FAU - Nasir, Khurram AU - Nasir K AD - Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Cardiovascular Center, Houston, Texas. FAU - Virani, Salim S AU - Virani SS AD - Section of Cardiology, Department of Medicine, The Aga Khan University, Karachi, Pakistan; Texas Heart Institute and Baylor College of Medicine, Houston, Texas. FAU - Upadhyay, Jagriti AU - Upadhyay J AD - Division of Endocrinology, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Garcia-Banigan, Dinamarie C AU - Garcia-Banigan DC AD - Division of Endocrinology, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Abraham, Sonu AU - Abraham S AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Husami, Raya AU - Husami R AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Kong, Yixin AU - Kong Y AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Labib, Sherif AU - Labib S AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Venesy, David AU - Venesy D AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Shah, Sachin AU - Shah S AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. FAU - Lenihan, Daniel AU - Lenihan D AD - International Cardio-Oncology Society, Tampa, Florida. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Deswal, Anita AU - Deswal A AD - Division of Internal Medicine, Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Fonarow, Gregg C AU - Fonarow GC AD - Division of Cardiology, Ahmanson-UCLA Cardiomyopathy Center, University of California-Los Angeles, Los Angeles, California. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, Texas; University of Mississippi, Jackson, Mississippi. FAU - Nohria, Anju AU - Nohria A AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri. FAU - Ganatra, Sarju AU - Ganatra S AD - Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts. Electronic address: Sarju.Ganatra@Lahey.org. LA - eng PT - Journal Article DEP - 20241210 PL - United States TA - J Card Fail JT - Journal of cardiac failure JID - 9442138 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Heart Failure/drug therapy/physiopathology/complications MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology/complications MH - Male MH - Middle Aged MH - *Stroke Volume/physiology/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Retrospective Studies MH - Follow-Up Studies MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP-1R agonists OT - SGLT 2 inhibitors OT - heart failure with preserved ejection fraction EDAT- 2024/12/13 00:23 MHDA- 2025/07/11 00:26 CRDT- 2024/12/12 19:25 PHST- 2024/05/27 00:00 [received] PHST- 2024/10/30 00:00 [revised] PHST- 2024/10/30 00:00 [accepted] PHST- 2025/07/11 00:26 [medline] PHST- 2024/12/13 00:23 [pubmed] PHST- 2024/12/12 19:25 [entrez] AID - S1071-9164(24)00962-X [pii] AID - 10.1016/j.cardfail.2024.10.448 [doi] PST - ppublish SO - J Card Fail. 2025 Jul;31(7):989-1001. doi: 10.1016/j.cardfail.2024.10.448. Epub 2024 Dec 10. PMID- 39666879 OWN - NLM STAT- MEDLINE DCOM- 20250205 LR - 20260818 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 1 DP - 2025 Jan TI - Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials. PG - 185-197 LID - 10.1080/03007995.2024.2442027 [doi] AB - BACKGROUND: The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components are unclear. We aim to quantify the lipid lowering effects of GLP1-RAs. METHODS: A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until January 2023. Data extraction and quality assessment were performed, and outcomes were analyzed using a random-effects model to calculate weighted mean differences (MDs) in milligrams per deciliter (mg/dl) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary endpoints included total cholesterol (TC), triglycerides, high density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). Subgroup analyses and meta-regression accounted for covariates. RESULTS: GLP-1RAs modestly reduced LDL-C (MD -2.93, 95% CI (-5.01, -0.85), p = 0.01), consistent across treatment durations: 12 weeks (MD: -2.39, 95% CI (-4.70, -0.007), p = 0.04). GLP-1RA reduced TC by approximately 7 mg/dl. There was no significant reduction in triglycerides (MD = -7.19, 95% CI (-15.01, 0.62), p = 0.07) or VLDL-C (MD = -3.99, 95%, CI (-8.73, 0.75), p = 0.10). GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49), p = 0.69). Weight change did not influence LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, p = 0.67) or TC (tau2 = 93.6, I2 = 99.86, R2 = 0.0, p = 0.92). CONCLUSION: GLP-1RA treatment modestly decreased LDL-C and TC but did not significantly affect triglycerides, VLDL-C, or HDL-C. FAU - Rivera, Frederick Berro AU - Rivera FB AD - Lincoln Medical Center, Bronx, NY, USA. FAU - Chin, Marielle Nicole Cabusas AU - Chin MNC AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Pine, Polyn Luz S AU - Pine PLS AD - Ateneo School of Medicine and Public Health, Pasig, Philippines. FAU - Ruyeras, Monica Marie Jadena AU - Ruyeras MMJ AUID- ORCID: 0009-0009-9795-7979 AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Galang, Danica Janine Cabahug AU - Galang DJC AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Gandionco, Keshia Marice AU - Gandionco KM AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Morales, Benna Lynn Faye D AU - Morales BLFD AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Climaco, Zackaree Michael V AU - Climaco ZMV AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Bantayan, Nathan Ross Baoy AU - Bantayan NRB AD - College of Medicine, University of the Philippines, Manila, Philippines. FAU - Magalong, John Vincent AU - Magalong JV AD - College of Medicine, University of the Philippines, Manila, Philippines. FAU - Mangubat, Gerard Francis AU - Mangubat GF AD - Department of Medicine, Southern Philippines Medical Center, Davao, Philippines. FAU - Ong, Kenneth AU - Ong K AD - Department of Cardiology, Lincoln Medical Center, Bronx, NY, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20241218 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cholesterol, LDL) RN - 97C5T2UQ7J (Cholesterol) RN - 0 (Triglycerides) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cholesterol, LDL/blood MH - Weight Loss/drug effects MH - *Cholesterol/blood MH - Triglycerides/blood MH - *Diabetes Mellitus, Type 2/drug therapy/blood OTO - NOTNLM OT - Dulaglutide OT - Glp-1RA OT - Semaglutide OT - lipids OT - liraglutide EDAT- 2024/12/12 18:23 MHDA- 2025/02/05 06:20 CRDT- 2024/12/12 14:53 PHST- 2025/02/05 06:20 [medline] PHST- 2024/12/12 18:23 [pubmed] PHST- 2024/12/12 14:53 [entrez] AID - 10.1080/03007995.2024.2442027 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Jan;41(1):185-197. doi: 10.1080/03007995.2024.2442027. Epub 2024 Dec 18. PMID- 39666113 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250725 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 62 IP - 7 DP - 2025 Jul TI - The potential of precision diabetology for type 2 diabetes treatment-evidence from a meta-regression for all-cause mortality from large cardiovascular outcome trials. PG - 1073-1080 LID - 10.1007/s00592-024-02425-8 [doi] AB - AIMS: Two prerequisites must be met for the precision treatment approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in case of treatment heterogeneity, clinical predictors to identify people who would benefit from one treatment more than from others must be available. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. We recently applied this approach to the treatment of type 2 diabetes for the clinical outcomes of glycaemic control and body weight and repeat it for the clinical outcome of all-cause mortality. METHODS: We performed a meta-regression analysis using digitalized individual participant information on time to death from 10 large cardiovascular outcome trials (7563 deaths from 99,746 participants) on DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors with respect to the variability of all-cause mortality and its potential predictors after treatment. RESULTS: The adjusted difference in log(SD) values of time to death between the verum and placebo arms was -0.036 (95%-CI: -0.059; -0.013), showing larger variability of time to death in the placebo arms. No clinical predictors were found to explain treatment heterogeneity. CONCLUSIONS: This analysis suggests that the potential of the precision treatment approach in type 2 diabetes is low, at least with regard to improvement of all-cause mortality in population with high cardiovascular risk. This extends our previous findings for the clinical outcomes of glycaemic control and body weight. CI - (c) 2024. The Author(s). FAU - Kuss, Oliver AU - Kuss O AUID- ORCID: 0000-0003-3301-5869 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Dusseldorf, Auf'm Hennekamp 65, 40225, Dusseldorf, Germany. oliver.kuss@ddz.de. AD - Centre for Health and Society, Faculty of Medicine, Heinrich Heine University Dusseldorf, Dusseldorf, Germany. oliver.kuss@ddz.de. AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. oliver.kuss@ddz.de. FAU - Roden, Michael AU - Roden M AUID- ORCID: 0000-0001-8200-6382 AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Dusseldorf, Dusseldorf, Germany. AD - Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Schlesinger, Sabrina AU - Schlesinger S AUID- ORCID: 0000-0003-4244-0832 AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Dusseldorf, Auf'm Hennekamp 65, 40225, Dusseldorf, Germany. AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. FAU - Hoyer, Annika AU - Hoyer A AUID- ORCID: 0000-0002-0241-9951 AD - Biostatistics and Medical Biometry, Medical School OWL, Bielefeld University, Bielefeld, Germany. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20241212 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Cardiovascular Diseases/mortality MH - *Precision Medicine/methods MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Treatment Outcome MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Regression Analysis MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Male PMC - PMC12283822 OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide 1 OT - HbA1c OT - Meta-regression OT - Precision medicine OT - Sodium-glucose transporter 2 inhibitors OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: OK received honouraria for biostatistical education from Berlin-Chemie. SS received a speaker honorarium from Novo Nordisk. MR received personal fees from Allergan, Astra-Zeneca, Bristol-Myers-Squibb, Eli Lilly, Fishawack Group, Gilead Sciences, Intercept Pharma, Inventiva, Novartis, Novo Nordisk, Pfizser, Prosciento, Sanofi US and Target RWE and investigator-initiated research support from Boehringer-Ingelheim, Nutricia/Danone and Sanofi-Aventis. AH declares that there are no relationships or activities that might bias, or be perceived to bias, their work. Ethics approval and consent to participate: This work uses only published and digitalized data that are fully anonymised. We therefore did not seek for ethics approval. Consent for publication: Not applicable. EDAT- 2024/12/12 12:28 MHDA- 2025/07/23 10:54 PMCR- 2024/12/12 CRDT- 2024/12/12 11:20 PHST- 2024/05/27 00:00 [received] PHST- 2024/11/23 00:00 [accepted] PHST- 2025/07/23 10:54 [medline] PHST- 2024/12/12 12:28 [pubmed] PHST- 2024/12/12 11:20 [entrez] PHST- 2024/12/12 00:00 [pmc-release] AID - 10.1007/s00592-024-02425-8 [pii] AID - 2425 [pii] AID - 10.1007/s00592-024-02425-8 [doi] PST - ppublish SO - Acta Diabetol. 2025 Jul;62(7):1073-1080. doi: 10.1007/s00592-024-02425-8. Epub 2024 Dec 12. PMID- 39663847 OWN - NLM STAT- MEDLINE DCOM- 20241220 LR - 20250122 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 33 IP - 12 DP - 2024 Dec TI - Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction. PG - 1167-1176 LID - 10.1080/13543784.2024.2441865 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor (GLP-1 R) agonists have demonstrated remarkable effectiveness in the treatment of obesity and type 2 diabetes. Although these agents provide beneficial effects for metabolic dysfunction-associated steatohepatitis (MASH) through their glucose-lowering and weight-reducing properties, their efficacy in promoting fibrosis regression remains unproven. Survodutide, an investigational dual agonist that simultaneously targets both the glucagon receptor (GCGR) and GLP-1 R, has emerged as a promising therapeutic candidate for the comprehensive management of obesity and MASH. By engaging these two critical receptors, this drug has the potential to offer a broad spectrum of metabolic benefits, addressing multiple pathogenic mechanisms underlying these interrelated disorders. AREAS COVERED: This review examines the pharmacological profile, clinical efficacy, and safety data of survodutide derived from phase 1 and 2 clinical trials. EXPERT OPINION: Survodutide's dual agonism of the GCGR and GLP-1 R may surpass the efficacy of selective GLP-1 R agonists, demonstrating significant potential in resolving MASH and promoting fibrosis regression. The drug is generally well tolerated, with primarily manageable gastrointestinal adverse effects. As survodutide progresses through phase 3 clinical development, its potential to provide a more effective and holistic approach to treating MASH and its comorbidities may significantly improve patient outcomes and quality of life. FAU - Kaya, Eda AU - Kaya E AD - Department of Medicine, Knappschaftskrankenhaus Bochum, Ruhr University, Bochum, Germany. AD - Department of Hepatology, The Global NASH Council, Washington, DC, USA. FAU - Yilmaz, Yusuf AU - Yilmaz Y AD - Department of Hepatology, The Global NASH Council, Washington, DC, USA. AD - Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkiye. FAU - Alkhouri, Naim AU - Alkhouri N AD - Department of Hepatology, The Global NASH Council, Washington, DC, USA. AD - Department of Hepatology, Arizona Liver Health, Chandler, Arizona, USA. LA - eng PT - Journal Article PT - Review DEP - 20241217 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Receptors, Glucagon) RN - 0 (2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid) RN - 0 (Hypoglycemic Agents) RN - 0 (Propionates) RN - 0 (Chalcones) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Animals MH - *Obesity/drug therapy MH - *Fatty Liver/drug therapy MH - Receptors, Glucagon/agonists MH - Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - Hypoglycemic Agents/pharmacology/adverse effects/administration & dosage MH - Drug Development MH - Propionates MH - Chalcones MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Metabolic dysfunction-associated steatotic liver disease OT - diabetes OT - fibrosis OT - metabolic disorders, comorbidities OT - metabolic dysfunction-associated steatohepatitis OT - obesity OT - survodutide EDAT- 2024/12/12 06:23 MHDA- 2024/12/20 12:22 CRDT- 2024/12/12 03:13 PHST- 2024/12/20 12:22 [medline] PHST- 2024/12/12 06:23 [pubmed] PHST- 2024/12/12 03:13 [entrez] AID - 10.1080/13543784.2024.2441865 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2024 Dec;33(12):1167-1176. doi: 10.1080/13543784.2024.2441865. Epub 2024 Dec 17. PMID- 39663564 OWN - NLM STAT- MEDLINE DCOM- 20260124 LR - 20260124 IS - 1558-9455 (Electronic) IS - 1558-9447 (Print) IS - 1558-9447 (Linking) VI - 21 IP - 2 DP - 2026 Feb TI - Guidance on Preoperative Management of Hand Surgery Patients Taking GLP-1 Receptor Agonists. PG - 322-324 LID - 10.1177/15589447241300712 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are medications used to treat type 2 diabetes and may aid in weight loss efforts. The surgical management of patients taking GLP-1 agonists differs from others due to the slowed gastric emptying effects of GLP-1 medications. Patients taking these medications may have a higher risk of pulmonary aspiration during hand surgery than other patients, which affects their presurgical management. This article reviews GLP-1 agonists and their role in diabetes and weight loss, as well as current recommendations for surgical management of patients taking GLP-1 agonists. FAU - Kisiel, Sara C AU - Kisiel SC AUID- ORCID: 0009-0006-2466-8509 AD - The University of Arizona College of Medicine-Phoenix, USA. FAU - Hiredesai, Annika AU - Hiredesai A AD - Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA. FAU - Dhupati, Pooja AU - Dhupati P AD - The University of Arizona College of Medicine-Phoenix, USA. FAU - Noland, Shelley AU - Noland S AD - Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA. LA - eng PT - Journal Article PT - Review DEP - 20241211 PL - United States TA - Hand (N Y) JT - Hand (New York, N.Y.) JID - 101264149 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Preoperative Care MH - *Hand/surgery MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Weight Loss/drug effects PMC - PMC11635785 OTO - NOTNLM OT - anesthesia OT - basic science OT - diagnosis OT - metabolic OT - outcomes OT - research and health outcomes OT - specialty OT - surgery COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2024/12/12 06:23 MHDA- 2026/01/24 12:32 PMCR- 2025/12/11 CRDT- 2024/12/12 00:12 PHST- 2026/01/24 12:32 [medline] PHST- 2024/12/12 06:23 [pubmed] PHST- 2024/12/12 00:12 [entrez] PHST- 2025/12/11 00:00 [pmc-release] AID - 10.1177_15589447241300712 [pii] AID - 10.1177/15589447241300712 [doi] PST - ppublish SO - Hand (N Y). 2026 Feb;21(2):322-324. doi: 10.1177/15589447241300712. Epub 2024 Dec 11. PMID- 39658957 OWN - NLM STAT- MEDLINE DCOM- 20241211 LR - 20250103 IS - 0253-9772 (Print) IS - 0253-9772 (Linking) VI - 46 IP - 12 DP - 2024 Dec TI - The mechanism and related research progress of GLP-1 receptor agonists in treating Alzheimer's disease. PG - 1017-1027 LID - 10.16288/j.yczz.24-178 [doi] AB - GLP-1 receptor agonists are primarily used clinically for the treatment of type 2 diabetes and have the potential for weight loss, while they are currently expanding their horizons in the treatment of hypertension, non-alcoholic liver disease, depression, and neurodegenerative diseases. In particular, in the treatment of Alzheimer's disease, a large number of animal models and a handful of clinical studies have demonstrated the potential efficacy of GLP-1 receptor agonists, making it highly probable that they will become a new entrant in the drug list for Alzheimer's disease. At present, the research on the mechanism of GLP-1 receptor agonist in the treatment of Alzheimer's disease is mainly based on in-depth analysis of the pathogenesis of Alzheimer's disease and exploration of the mechanism of its comorbidity with diabetes. This article mainly reviews the latest advances in the mechanism of GLP-1 receptor agonists in the treatment of Alzheimer's disease, introduces the latest achievements in animal studies and clinical studies, and aims to provide reference for the subsequent relevant basic research and clinical application. FAU - Zhu, Xiao-Cheng AU - Zhu XC AD - Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Yi-Wen AU - Wang YW AD - Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Zhou, Hong-Wen AU - Zhou HW AD - Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. LA - eng PT - Journal Article PT - Review PL - China TA - Yi Chuan JT - Yi chuan = Hereditas JID - 9436478 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Alzheimer Disease/drug therapy MH - Humans MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonists OT - pharmacology EDAT- 2024/12/11 06:25 MHDA- 2024/12/11 06:26 CRDT- 2024/12/11 01:23 PHST- 2024/12/11 06:26 [medline] PHST- 2024/12/11 06:25 [pubmed] PHST- 2024/12/11 01:23 [entrez] AID - 24-178 [pii] AID - 10.16288/j.yczz.24-178 [doi] PST - ppublish SO - Yi Chuan. 2024 Dec;46(12):1017-1027. doi: 10.16288/j.yczz.24-178. PMID- 39654073 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - An exploratory analysis of glucagon-like peptide-1 (GLP-1) agonists and biosimilars: A literature review. PG - 1113-1122 LID - 10.1111/dom.16110 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are at the forefront of treating the global health crisis of diabetes mellitus (DM) and obesity. However, the demand for GLP-1 RAs has far outstripped its supply and comes with a high monthly cost. Thus, the development of GLP-1 RA biosimilars can potentially address these barriers by providing greater access to medications that provide clinical outcomes similar to those of the reference products. A narrative review was conducted to examine the current and future developments for GLP-1 RA biosimilars. Liraglutide and semaglutide are the predominant GLP-1 RAs being investigated for the development of biosimilars. Preliminary liraglutide biosimilar comparisons to reference liraglutide have demonstrated similar clinical efficacy and safety profiles. Semaglutide and beinaglutide biosimilars are currently under investigation as well. With the growing popularity of GLP-1 RAs, accessibility and affordability remain a challenge as monthly costs without insurance for liraglutide, semaglutide and tirzepatide are $1418, $892, and $974 respectively. This trend negatively impacts patients with obesity and DM as well as patients who can utilize it for off-label indications for conditions that benefit from weight loss such as obstructive sleep apnoea and non-alcoholic fatty liver disease. A substantial number of pharmaceutical and healthcare companies worldwide are conducting clinical trials on their GLP-1 RA biosimilars. Preliminary results from liraglutide biosimilars are promising, and several semaglutide biosimilars are currently being investigated. Future research should focus on conducting comparative head-to-head trials to determine the clinical outcomes between biosimilars and reference products. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Adam AU - Razick A AD - Department of Psychology, University of California, Los Angeles, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Daniel AU - Razick D AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Akhtar, Muzammil AU - Akhtar M AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Karabala, Muhammad AU - Karabala M AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. LA - eng PT - Journal Article PT - Review DEP - 20241209 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biosimilar Pharmaceuticals) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Biosimilar Pharmaceuticals/therapeutic use/economics MH - Humans MH - *Hypoglycemic Agents/therapeutic use/economics MH - Glucagon-Like Peptides/therapeutic use/economics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/therapeutic use/economics MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - health economics OT - liraglutide OT - obesity care OT - semaglutide EDAT- 2024/12/10 00:22 MHDA- 2025/02/07 00:20 CRDT- 2024/12/09 23:34 PHST- 2024/11/08 00:00 [revised] PHST- 2024/09/22 00:00 [received] PHST- 2024/11/21 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/12/10 00:22 [pubmed] PHST- 2024/12/09 23:34 [entrez] AID - 10.1111/dom.16110 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1113-1122. doi: 10.1111/dom.16110. Epub 2024 Dec 9. PMID- 39651921 OWN - NLM STAT- MEDLINE DCOM- 20241209 LR - 20260127 IS - 0975-4466 (Electronic) IS - 0256-4947 (Print) IS - 0256-4947 (Linking) VI - 44 IP - 6 DP - 2024 Nov-Dec TI - Efficacy and safety of semaglutide: real-world tertiary care experience from Saudi Arabia. PG - 361-368 LID - 10.5144/0256-4947.2024.361 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1, is an effective antidiabetic drug promoting weight loss and providing cardiovascular protection. The original trials did not include participants from Saudi Arabia; hence, the study's findings are expected to be useful. OBJECTIVES: Explore the efficacy, safety, and favorable effects of once-weekly subcutaneous semaglutide (1 mg) in patients with type 2 diabetes and those who received it as an off-license prescription without having diabetes. DESIGN: Retrospective review of medical records. SETTING: Department of medicine at our institution. PATIENTS AND METHODS: This retrospective observational study evaluated patients receiving the glucagon-like peptide-1 analog semaglutide, with the trade name Ozempic. The weight, height, body mass index, blood pressure, and laboratory data, including serum creatinine and hemoglobin A1c (HbA1c) levels and urine albumin/creatinine ratio, were recorded. Moreover, any history of medical comorbidities, such as cardiovascular diseases, cerebrovascular diseases, and heart failure, was documented before and after drug administration. MAIN OUTCOME MEASURES: Glycemic and weight loss efficacy. SAMPLE SIZE: 1007 patients. RESULTS: The median age of the patients was 57.0 years, comprising 60.28% females. Among them, 955 and 442 patients received the medication for at least 3 and 6 months, respectively. Our results show a 4.4% weight loss and 0.4% improvement in HBA1c in patients with diabetes. Similar results were observed in the patients without diabetes in terms of weight along with a significant decrease in diastolic blood pressure. Our results also show stability in the serum creatinine and urine albumin creatinine ratio. The drug was equally effective in males and females. CONCLUSION: Treatment with once-weekly subcutaneous semaglutide (1 mg) led to clinically significant weight loss and improved HbA1c level and cardiometabolic risk factors such as blood pressure. LIMITATIONS: Retrospective design. FAU - Butt, Muhammad Imran AU - Butt MI AUID- ORCID: 0000-0002-2143-7303 AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Alkhalifah, Khalid Mania AU - Alkhalifah KM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Riazuddin, Muhammad AU - Riazuddin M AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Almuammar, Saud Mohammed AU - Almuammar SM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Almuammar, Salman Mohammed AU - Almuammar SM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Alhifthi, Ghayda Abdulkader AU - Alhifthi GA AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Ahmed, Fahad Wali AU - Ahmed FW AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Al Hashim, Samia Mohamed AU - Al Hashim SM AD - From the Department of Biostatistics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Waheed, Najeeb AU - Waheed N AD - From the Department of Endocrinology, Imperial College London Diabetes Centre, Al Ain, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article PT - Observational Study DEP - 20241205 PL - Saudi Arabia TA - Ann Saudi Med JT - Annals of Saudi medicine JID - 8507355 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Saudi Arabia MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Glycated Hemoglobin/drug effects MH - Aged MH - *Weight Loss/drug effects MH - Adult MH - Treatment Outcome MH - Tertiary Health Care MH - Blood Pressure/drug effects MH - Blood Glucose/drug effects MH - Injections, Subcutaneous MH - Semaglutide PMC - PMC11627033 COIS- None. EDAT- 2024/12/09 17:33 MHDA- 2024/12/09 17:34 PMCR- 2024/11/01 CRDT- 2024/12/09 09:14 PHST- 2024/12/09 17:34 [medline] PHST- 2024/12/09 17:33 [pubmed] PHST- 2024/12/09 09:14 [entrez] PHST- 2024/11/01 00:00 [pmc-release] AID - 0256-4947.2024.361 [pii] AID - 10.5144/0256-4947.2024.361 [doi] PST - ppublish SO - Ann Saudi Med. 2024 Nov-Dec;44(6):361-368. doi: 10.5144/0256-4947.2024.361. Epub 2024 Dec 5. PMID- 39647240 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 44 DP - 2025 Jan TI - Beyond fat: Does semaglutide affect lean mass? PG - 104-108 LID - S0261-5614(24)00445-X [pii] LID - 10.1016/j.clnu.2024.12.004 [doi] AB - This opinion paper aims to discuss the influence of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on lean mass beyond its impact on weight loss. Although significant weight loss is achieved with semaglutide, the impact of this drug on lean mass remains controversial. Several investigations have demonstrated that semaglutide-induced weight loss is linked to decreases in lean mass as well as fat mass; on the other hand, the ratio of lean mass to total body mass rises. Nevertheless, larger clinical trials have reported converse findings and significant reductions in lean mass following treatment with semaglutide. This disparity in research findings emphasizes the necessity for additional studies on this subject because semaglutide use is rising quickly. CI - Copyright (c) 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Jamialahmadi, Tannaz AU - Jamialahmadi T AD - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Eid, Ali H AU - Eid AH AD - Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar. FAU - Gadde, Kishore M AU - Gadde KM AD - Department of Surgery, University of California Irvine Medical Center, Orange, CA, USA. FAU - Almahmeed, Wael AU - Almahmeed W AD - Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. FAU - Kroh, Matthew AU - Kroh M AD - Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Al Zein, Mohammad AU - Al Zein M AD - Faculty of Medical Sciences, Lebanese University, Hadath, Beirut, Lebanon. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amir_saheb2000@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20241204 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/pharmacology MH - Humans MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/pharmacology MH - *Body Composition/drug effects MH - Adipose Tissue/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Body composition OT - Glucagon-like peptide-1 receptor agonist OT - Lean mass OT - Semaglutide COIS- Conflict of interest The authors have no competing interests to disclose. EDAT- 2024/12/09 00:22 MHDA- 2025/01/07 00:21 CRDT- 2024/12/08 18:02 PHST- 2024/08/19 00:00 [received] PHST- 2024/11/28 00:00 [revised] PHST- 2024/12/02 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/12/09 00:22 [pubmed] PHST- 2024/12/08 18:02 [entrez] AID - S0261-5614(24)00445-X [pii] AID - 10.1016/j.clnu.2024.12.004 [doi] PST - ppublish SO - Clin Nutr. 2025 Jan;44:104-108. doi: 10.1016/j.clnu.2024.12.004. Epub 2024 Dec 4. PMID- 39645259 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20250902 IS - 1468-3296 (Electronic) IS - 0040-6376 (Print) IS - 0040-6376 (Linking) VI - 80 IP - 1 DP - 2024 Dec 23 TI - Comparative estimate of glucose-lowering therapies on risk of incident pneumonia and severe sepsis: an analysis of real-world cohort data. PG - 32-41 LID - 10.1136/thorax-2024-221906 [doi] LID - e221906 AB - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis. AIMS: This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis. METHODS: A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies. RESULTS: After propensity score matching, 352 687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331 863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)). CONCLUSION: SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. FAU - Riley, David R AU - Riley DR AUID- ORCID: 0000-0002-0905-6524 AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. FAU - Hydes, Theresa J AU - Hydes TJ AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Ibarburu, Gema H AU - Ibarburu GH AD - TriNetX LLC, Cambridge, Massachusetts, USA. FAU - Frost, Frederick AU - Frost F AD - Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK dan.cuthbertson@liverpool.ac.uk. AD - Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. LA - eng PT - Comparative Study PT - Journal Article DEP - 20241223 PL - England TA - Thorax JT - Thorax JID - 0417353 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - doi: 10.1136/thorax-2024-222540 MH - Humans MH - *Sepsis/drug therapy/epidemiology MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Pneumonia/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Incidence MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11671942 OTO - NOTNLM OT - Bacterial Infection OT - Clinical Epidemiology OT - Infection Control OT - Pneumonia OT - Respiratory Infection COIS- Competing interests: MA receives a fellowship from the Novo Nordisk UK research foundation and JDRF. DJJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool. GHI is an employee of TriNetX LLC. UA has received honoraria from Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance at an educational meeting from Diiachi Sankyo. UA has also received investigator-led funding from Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2024/12/08 01:11 MHDA- 2024/12/24 00:26 PMCR- 2024/12/27 CRDT- 2024/12/07 20:53 PHST- 2024/05/10 00:00 [received] PHST- 2024/10/03 00:00 [accepted] PHST- 2024/12/24 00:26 [medline] PHST- 2024/12/08 01:11 [pubmed] PHST- 2024/12/07 20:53 [entrez] PHST- 2024/12/27 00:00 [pmc-release] AID - thorax-2024-221906 [pii] AID - 10.1136/thorax-2024-221906 [doi] PST - epublish SO - Thorax. 2024 Dec 23;80(1):32-41. doi: 10.1136/thorax-2024-221906. PMID- 39644537 OWN - NLM STAT- MEDLINE DCOM- 20241213 LR - 20260818 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 1 DP - 2025 Jan TI - Glucagon-like Peptide-1 receptor agonists versus dipeptidyl-peptidase 4 inhibitors in advanced chronic kidney disease and end stage kidney disease: Real world effectiveness and persistence of therapy. PG - 108925 LID - S1056-8727(24)00251-4 [pii] LID - 10.1016/j.jdiacomp.2024.108925 [doi] AB - BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of death in people with type 2 diabetes (T2D) and chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular events, improve glycemic control, promote weight loss, and slow progression of nephropathy. Despite these benefits and professional society treatment guidelines recommendations, GLP-1RAs remain under-utilized in people with advanced CKD and ESKD due to tolerability and safety concerns. METHODS: We conducted a retrospective cohort study comparing clinical outcomes and medication use details after initiating GLP-1RA or dipeptidyl-peptidase 4 inhibitor (DPP-4i) in people with T2D and advanced CKD or ESKD. Eligible patients were identified via electronic health record query with extraction of baseline demographics, vital signs, and laboratory values. A manual chart review was undertaken to confirm eligibility, medication use, and extract a detailed account of all side effects. RESULTS: A total of 236 eligible patients (149 in the GLP-1RA group and 87 in the DPP-4i group) were identified. The average duration of treatment was 1036 (+/-909.9) and 1109 (+/-1090.9) days for GLP-1RA and DPP-4i, respectively. The average percentage weight loss from baseline to 36 months of treatment in the GLP-1RA group was -9.6 % (95 % CI, -11.3 to -7.8) versus -2.4 % (95 % CI, -5.4 to 0.5) in the DPP-4i group (estimated treatment difference (ETD) -7.1 (95 % CI, -10.6 to -3.7) percentage-points, p < 0.001). The change in HbA1c from baseline to 36 months of treatment was significantly greater in the GLP-1RA (-1.0 %) compared with the DPP-4i group (0.2 %) (ETD -1.2 (95 % CI, -2.1 to -0.3) percentage-points, p = 0.04). CONCLUSION: In patients with T2D and advanced CKD or ESKD, treatment with GLP-1RAs in a real-world setting had long treatment persistence, and compared to DPP-4is, was associated with greater weight loss and glycemic improvement. CI - Published by Elsevier Inc. FAU - Sidra, F N U AU - Sidra FNU AD - Division of Endocrinology, Dept of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. FAU - Agarwal, Shubham AU - Agarwal S AD - Division of Endocrinology, Dept of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Electronic address: shubhamagarwaldr@gmail.com. FAU - Lockhart Pastor, Paola AU - Lockhart Pastor P AD - Division of Endocrinology, Dept of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. FAU - Xie, Donglu AU - Xie D AD - The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. FAU - Li, Xilong AU - Li X AD - Peter O'Donnell Jr. School of Public Health, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - Division of Endocrinology, Dept of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA; Peter O'Donnell Jr. School of Public Health, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. LA - eng GR - UL1 TR003163/TR/NCATS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20241204 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Kidney Failure, Chronic/epidemiology MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Diabetic Nephropathies/drug therapy MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Cohort Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Monitoring OTO - NOTNLM OT - Advanced CKD OT - DPP-4i OT - Dialysis OT - ESKD OT - GLP-1RA OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donglu Xie reports financial support was provided by National Center for Advancing Translational Sciences. Ildiko Lingvay reports a relationship with Novo Nordisk that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Sanofi that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Merck that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Pfizer that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Mylan that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Boehringer Ingelheim that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Eli Lilly that includes: consulting or advisory. Ildiko Lingvay reports a relationship with AstraZeneca that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Janssen that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Intercept that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Intarcia that includes: consulting or advisory. Ildiko Lingvay reports a relationship with TargetPharma that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Novartis that includes: consulting or advisory. Ildiko Lingvay reports a relationship with GI Dynamics that includes: consulting or advisory. Ildiko Lingvay reports a relationship with MannKind that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Valeritas that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Carmot that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Zealand Pharma that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Shionogi that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Mediflix that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Bayer that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/08 01:11 MHDA- 2024/12/14 00:25 CRDT- 2024/12/07 18:00 PHST- 2024/09/30 00:00 [received] PHST- 2024/11/03 00:00 [revised] PHST- 2024/12/03 00:00 [accepted] PHST- 2024/12/14 00:25 [medline] PHST- 2024/12/08 01:11 [pubmed] PHST- 2024/12/07 18:00 [entrez] AID - S1056-8727(24)00251-4 [pii] AID - 10.1016/j.jdiacomp.2024.108925 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Jan;39(1):108925. doi: 10.1016/j.jdiacomp.2024.108925. Epub 2024 Dec 4. PMID- 39641257 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20250519 IS - 1827-1669 (Electronic) IS - 0026-4806 (Linking) VI - 116 IP - 2 DP - 2025 Apr TI - Type 2 diabetes, heart failure and the treatment of their comorbidity. PG - 141-155 LID - 10.23736/S0026-4806.24.09264-4 [doi] AB - Both heart failure and type 2 diabetes are prevalent conditions and share similar pathogenesis, risk factors, and treatment medications. This review aims to inform clinical practice by summarizing the interaction between heart failure and type 2 diabetes, as well as the medications used to manage them. Novel medications such as Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-likepeptide-1 receptor agonists, and finerenone have been shown to protect patients with type 2 diabetes from hospitalization for heart failure. SGLT2 inhibitors have also proven effective in patients with heart failure, regardless of the presence of type 2 diabetes. When choosing diabetes treatment medications for patients with heart failure and type 2 diabetes, shared decision-making can be helpful in weighing the benefits and harms based on individual scenarios. The selection of guideline-directed medical therapy aligns with patients without type 2 diabetes. Given the rapid evolution of knowledge in this field, clinicians need to stay updated with the latest evidence to provide optimal medical care. FAU - Wang, Si AU - Wang S AD - Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Sheyu AU - Li S AD - Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, China - lisheyu@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20241206 PL - Italy TA - Minerva Med JT - Minerva medica JID - 0400732 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Heart Failure/drug therapy/complications/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Comorbidity MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/12/06 06:24 MHDA- 2025/05/19 12:30 CRDT- 2024/12/06 05:53 PHST- 2025/05/19 12:30 [medline] PHST- 2024/12/06 06:24 [pubmed] PHST- 2024/12/06 05:53 [entrez] AID - S0026-4806.24.09264-4 [pii] AID - 10.23736/S0026-4806.24.09264-4 [doi] PST - ppublish SO - Minerva Med. 2025 Apr;116(2):141-155. doi: 10.23736/S0026-4806.24.09264-4. Epub 2024 Dec 6. PMID- 39639835 OWN - NLM STAT- MEDLINE DCOM- 20250206 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - SGLT2 inhibitors reduce epicardial adipose tissue more than GLP-1 agonists or exercise interventions in patients with type 2 diabetes mellitus and/or obesity: A systematic review and network meta-analysis. PG - 1096-1112 LID - 10.1111/dom.16107 [doi] AB - BACKGROUND: Epicardial adipose tissue (EAT) plays a significant role in several cardiovascular diseases. As a correctable risk factor and potential therapeutic target, reducing EAT has multiple cardiovascular benefits, especially in those with abnormal glucolipid metabolism. The objective of this research was to compare the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and exercise on the thickness of EAT and indicators of glucolipid metabolism in people with type 2 diabetes mellitus (T2DM), obesity, and T2DM with obesity. METHODS: We searched four electronic databases: PubMed, EMBASE, the Cochrane Library, and Web of Science for articles before 31 January 2024, regardless of language. We included randomized controlled trials and a small number of case-control studies in this network meta-analysis. Differences in mean changes in EAT, body mass index, and glucolipid metabolism-related metrics were assessed. RESULTS: A comprehensive analysis was conducted on 16 trials (15 randomized controlled trials and one case-control study), comprising a total of 867 people. SGLT2 inhibitors were significantly better at reducing EAT than placebo (standard mean different [SMD] = -0.85 cm [95% confidence interval (CI) -1.39, -0.31]); a similar result was observed for exercise compared with placebo (SMD = -0.78 cm [95% CI -1.37, -0.18]). SGLT2 inhibitors were also significantly better at reducing EAT than GLP-1 agonists and conventional hypoglycaemic therapy (e.g., metformin or insulin; SMD = -0.74 cm [95% CI -1.45, -0.02] and SMD = -1.69 cm [95% CI -2.38, -0.99], respectively). SGLT2 inhibitors were significantly better than placebo at reducing body mass index (MD = -0.90 kg/m(2) [95% CI -1.14, -0.66]) and glycosylated haemoglobin (MD = -0.52% [95%CI -0.86, -0.18]). A similar result was observed when comparing GLP-1 agonists and placebo (MD = -0.48% [95% CI -0.93, -0.03]). Changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not statistically significant between interventions. CONCLUSION: SGLT2 inhibitors have a distinct advantage over both placebo and other therapies at lowering EAT thickness, a result supported by direct comparisons and surface under the cumulative ranking curve analysis. Therefore, SGLT2 inhibitors should be prioritized as a treatment to reduce EAT in individuals with aberrant glucolipid levels, such as patients with T2DM and/or obesity. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Bao, Yu AU - Bao Y AUID- ORCID: 0009-0000-7306-5057 AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China. FAU - Hu, Yucai AU - Hu Y AD - Department of Cardiovascular Diseases, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China. FAU - Shi, Menglong AU - Shi M AD - Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Zhao, Zhiqiang AU - Zhao Z AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China. LA - eng GR - HSRP-DFCTCM-2023-3-10/Education Department of Henan Province/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20241206 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/therapy/complications/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Obesity/therapy/complications/drug therapy MH - *Adipose Tissue/drug effects MH - *Pericardium/drug effects MH - *Exercise Therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1/agonists MH - Epicardial Adipose Tissue OTO - NOTNLM OT - EAT thickness OT - GLP-1 agonists OT - SGLT-2 inhibitors OT - exercise EDAT- 2024/12/06 06:24 MHDA- 2025/02/07 00:20 CRDT- 2024/12/06 04:23 PHST- 2024/11/04 00:00 [revised] PHST- 2024/07/10 00:00 [received] PHST- 2024/11/11 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/12/06 06:24 [pubmed] PHST- 2024/12/06 04:23 [entrez] AID - 10.1111/dom.16107 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1096-1112. doi: 10.1111/dom.16107. Epub 2024 Dec 6. PMID- 39639039 OWN - NLM STAT- MEDLINE DCOM- 20241205 LR - 20250514 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 15 IP - 1 DP - 2024 Dec 5 TI - Healthcare utilization, mortality, and cardiovascular events following GLP1-RA initiation in chronic kidney disease. PG - 10623 LID - 10.1038/s41467-024-54009-3 [doi] LID - 10623 AB - Treatment with glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) may attenuate kidney disease progression and cardiovascular events but their real-world impact on healthcare utilization and mortality in this population are not well-defined. Here, we emulate a clinical trial that compares outcomes following initiation of GLP1-RA vs Dipeptidyl peptidase-4 inhibitors (DPP4i), as active comparators, in U.S. veterans aged 35 years of older with moderate to advanced CKD during fiscal years 2006 to 2021. Primary outcome was rate of acute healthcare utilization. Secondary outcomes were all-cause mortality and a composite of acute cardiovascular events. After propensity score matching (16,076 pairs) and 2.2 years mean follow-up duration, use of GLP1-RA in patients with moderate to advanced CKD was associated with lower annual rate of acute healthcare utilization and all-cause mortality. There was no significant difference in acute cardiovascular events. CI - (c) 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Zhang, Shuyao AU - Zhang S AD - Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Sidra, Fnu AU - Sidra F AD - Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA. AD - The Jones Center for Diabetes & Endocrine Wellness, Macon, GA, USA. FAU - Alvarez, Carlos A AU - Alvarez CA AD - Department of Pharmacy Practice and Center for Excellence in Real World Evidence, Texas Tech University Health Science Center, Dallas, TX, USA. FAU - Kinaan, Mustafa AU - Kinaan M AD - Endocrinology, Diabetes, and Metabolism Fellowship, UCF HCA Healthcare GME, Orlando, FL, USA. AD - Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL, USA. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA. AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Mansi, Ishak A AU - Mansi IA AUID- ORCID: 0000-0001-6122-3716 AD - Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL, USA. Ishak.mansi@va.gov. AD - Education Services, Orlando VA Healthcare System, Orlando, FL, USA. Ishak.mansi@va.gov. LA - eng PT - Journal Article DEP - 20241205 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/mortality/drug therapy MH - Male MH - Female MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Middle Aged MH - *Cardiovascular Diseases/mortality/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Patient Acceptance of Health Care/statistics & numerical data MH - Adult MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11621321 COIS- Competing interests: I.L. received research funding (paid to institution) from NovoNordisk, Sanofi, Merck, Pfizer, Mylan, Boehringer-Ingelheim. IL received advisory/consulting fees and/or other support from: Novo Nordisk, Eli Lilly, Sanofi, Astra Zeneca, Boehringer-Ingelheim, Cytoki Pharma, Johnson and Johnson, Intercept, TARGETPharma, Merck, Pfizer, Valeritas, Zealand Pharma, Shionogi, Carmot Therapeutics, Structure Therapeutics, Bayer, Translational Medical Academy, Mediflix, Biomea, Metsera, Regeneron, The Comm Group, and WebMD. I.L. serves on the Data Safety Monitoring Board for JAEB. C.A.A. received research funding (paid to the institution) from Merck, Bristol Myers Squibb, and Boehringer-Ingelheim. C.A.A. received funding from the National Institutes of Health National Center for Advancing Translational Sciences (grant #UL1TR003163). S.Z., F.S. and I.A.M. declared no conflict of interest. EDAT- 2024/12/06 05:32 MHDA- 2024/12/06 05:33 PMCR- 2024/12/05 CRDT- 2024/12/05 23:35 PHST- 2024/02/02 00:00 [received] PHST- 2024/10/28 00:00 [accepted] PHST- 2024/12/06 05:33 [medline] PHST- 2024/12/06 05:32 [pubmed] PHST- 2024/12/05 23:35 [entrez] PHST- 2024/12/05 00:00 [pmc-release] AID - 10.1038/s41467-024-54009-3 [pii] AID - 54009 [pii] AID - 10.1038/s41467-024-54009-3 [doi] PST - epublish SO - Nat Commun. 2024 Dec 5;15(1):10623. doi: 10.1038/s41467-024-54009-3. PMID- 39638244 OWN - NLM STAT- MEDLINE DCOM- 20250207 LR - 20250711 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 31 IP - 2 DP - 2025 Feb TI - Dose-Response Relationship of Glucagon-like Peptide-1 Receptor Agonists on HbA1c and Body Weight in Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis. PG - 188-197 LID - S1530-891X(24)00844-9 [pii] LID - 10.1016/j.eprac.2024.11.013 [doi] AB - OBJECTIVE: To explore the dose-response relationship of GLP-1 RAs in reducing glycated hemoglobin (HbA1c), body weight, and incidence of adverse events among type 2 diabetes mellitus (T2DM) patients. METHODS: This systematic review and network meta-analysis followed the PRISMA guidelines. We conducted a systematic search of PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for articles published up to October 20, 2024. Selected studies were randomized controlled trials focusing on adult T2DM patients treated with GLP-1 RAs. Primary outcomes included changes in HbA1c, body weight, and incidence of adverse events. Data extraction was performed by 2 independent researchers. Model-Based Network Meta-Analysis employing a random-effects Bayesian approach was used to synthesize the data. RESULTS: The analysis included 62 trials with 17 140 participants. The study revealed a nonlinear dose-response relationship for various GLP-1 RAs, indicating significant reductions in HbA1c and body weight. Tirzepatide (10 mg/wk) was found to be particularly effective, reducing HbA1c by -1.76% (95% credible intervals: -2.10 to -1.41) and body weight by -8.63 kg (95% credible intervals: -9.84 to -7.39) without a significant increase in adverse events, highlighting its optimal balance between efficacy and safety. Other GLP-1 RAs also showed significant efficacy, underscoring the overall benefits of this class of medications in managing T2DM. CONCLUSION: Our findings indicate a nonlinear dose-response relationship for GLP-1 RAs in managing T2DM. Tirzepatide at a dose of 10 mg/wk is identified as an optimal clinical dose offering a balance between efficacy and safety, contributing to refining T2DM management strategies and potentially enhancing patient outcomes. CI - Copyright (c) 2024 AACE. Published by Elsevier Inc. All rights reserved. FAU - Chen, Qian-Qin AU - Chen QQ AD - Department of Endocrinology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya, China. FAU - Yang, Yong AU - Yang Y AD - Evidence-Based Medicine Research Center, School of Physical Education and Sport, Chaohu University, Hefei, China; Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, China. FAU - Xu, Jian-Ya AU - Xu JY AD - Department of Endocrinology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya, China. FAU - Wang, Junyu AU - Wang J AD - School of Exercise and Health, Shanghai University of Sport, Shanghai, China. FAU - Fang, Tuan-Yu AU - Fang TY AD - Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China. FAU - Yuan, Yuan AU - Yuan Y AD - School of Physical Education, Kunsan National University, Gunsan City, South Korea. FAU - Wang, Chengji AU - Wang C AD - Evidence-Based Medicine Research Center, School of Physical Education and Sport, Chaohu University, Hefei, China. FAU - Zhang, Li AU - Zhang L AD - Department of Endocrinology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya, China. Electronic address: 3656658742@qq.com. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20241203 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Body Weight/drug effects MH - *Glycated Hemoglobin/analysis/metabolism/drug effects MH - Dose-Response Relationship, Drug MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology/adverse effects MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - body weight OT - dose-response OT - glucagon-like peptide-1 receptor agonist OT - glycated hemoglobin OT - type 2 diabetes mellitus COIS- Disclosure The authors have no conflicts of interest to disclose. EDAT- 2024/12/06 05:31 MHDA- 2025/02/08 00:30 CRDT- 2024/12/05 19:19 PHST- 2024/08/22 00:00 [received] PHST- 2024/11/23 00:00 [revised] PHST- 2024/11/27 00:00 [accepted] PHST- 2025/02/08 00:30 [medline] PHST- 2024/12/06 05:31 [pubmed] PHST- 2024/12/05 19:19 [entrez] AID - S1530-891X(24)00844-9 [pii] AID - 10.1016/j.eprac.2024.11.013 [doi] PST - ppublish SO - Endocr Pract. 2025 Feb;31(2):188-197. doi: 10.1016/j.eprac.2024.11.013. Epub 2024 Dec 3. PMID- 39636564 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260814 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 2 DP - 2025 Feb TI - Glucagon-Like Peptide-1 Receptor Agonist-Experienced Adults with Type 2 Diabetes Switching to Once-Weekly Semaglutide in a Real-World Setting: SURE Program Post Hoc Analysis. PG - 788-800 LID - 10.1007/s12325-024-03000-x [doi] AB - INTRODUCTION: To investigate outcomes in adults with type 2 diabetes who switched to once-weekly (OW) semaglutide from another glucagon-like peptide-1 receptor agonist (GLP-1RA) in clinical practice. METHODS: This post hoc analysis used data from the SemaglUtide Real-world Evidence (SURE) program, which included nine observational studies investigating the initiation of OW semaglutide in people with type 2 diabetes in routine clinical practice. Using a random coefficient-adjusted mixed model for repeated measurements, changes in glycosylated hemoglobin (HbA(1c)), body weight, and body mass index were analyzed for GLP-1RA-experienced patients who had at least one documented HbA(1c) value within the 12 weeks before switching to OW semaglutide. In addition, descriptive statistics were used for HbA(1c), body weight target achievement, and safety data. RESULTS: Of the 3,505 patients included in the nine SURE studies, 651 switched to OW semaglutide from another GLP-1RA. GLP-1RA-experienced patients who switched to OW semaglutide demonstrated a 0.67%-point [95% confidence interval (CI) - 0.74; - 0.60, p < 0.0001] reduction in HbA(1c), and a 3.69-kg [95% CI - 3.98; - 3.41, p < 0.0001] reduction in body weight over 30 weeks. A body weight reduction of >/= 5% was achieved by 27.6% of patients, and 33.3% of patients with baseline HbA(1c) >/= 7% achieved HbA(1c) < 7% at end of study. No new safety concerns were identified. CONCLUSIONS: Data from this post hoc analysis suggest that, for those not adequately responding to treatment with other GLP-1RAs, switching to OW semaglutide could provide additional glycemic and weight benefits with the convenience of an OW dosing regimen. CI - (c) 2024. The Author(s). FAU - Rudofsky, Gottfried AU - Rudofsky G AUID- ORCID: 0000-0002-2576-7190 AD - Praxis fur Endokrinologie, Diabetes und Adipositas, Olten, Solothurn, Switzerland. Gottfried.rudofsky@hin.ch. FAU - Menzen, Markus AU - Menzen M AD - Gemeinschaftskrankenhaus, Bonn, Germany. FAU - Potier, Louis AU - Potier L AD - Universite Paris Cite, AP-HP, Bichat Hospital, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades, Paris, France. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Clark, Alice AU - Clark A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Priyadarshini, Prachi AU - Priyadarshini P AD - Novo Nordisk GBS, Bengaluru, India. FAU - Abreu, Cristina AU - Abreu C AD - Endocrinology and Nutrition Unit, Segovia General Hospital, Segovia, Spain. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20241205 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Female MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism/analysis MH - Aged MH - Drug Administration Schedule MH - Body Weight/drug effects MH - Adult MH - Body Mass Index MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11787244 OTO - NOTNLM OT - Body weight OT - GLP-1RA OT - Glucagon-like peptide-1 receptor agonist OT - Glycated hemoglobin OT - Post hoc analysis OT - Real-world OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Gottfried Rudofsky has received support, funding, consulting fees and honoraria from Novo Nordisk, and holds stock in Novo Nordisk. Markus Menzen has received consulting fees from Novo Nordisk, Lilly Deutschland, Ascensia, Boehringer Ingelheim, Bayer AG and Novartis; honoraria from AstraZeneca, Bayer AG, Santis, Boehringer Ingelheim, Novo Nordisk, Lilly Deutschland, Lilly Swiss and Abbott; and support for attending meetings from AstraZeneca, Novo Nordisk and Lilly Deutschland. Louis Potier has received research support from Novo Nordisk; consulting fees from Novo Nordisk, Lilly, Sanofi, Bayer, Boehringer Ingelheim and AstraZeneca; and honoraria from Novo Nordisk, Lilly, Sanofi, Bayer and AstraZeneca. Andrei-Mircea Catarig, Alice Clark and Prachi Priyadarshini are full-time employees of Novo Nordisk A/S. Andrei-Mircea Catarig and Prachi Priyadarshini hold stock in Novo Nordisk A/S. Cristina Abreu has no conflicts of interest. Ethical Approval: The SURE study protocols were conducted in accordance with the Declaration of Helsinki and approved by the institutional review board and ethics committee at each participating center. All participants provided written informed consent. EDAT- 2024/12/05 17:32 MHDA- 2025/02/01 20:41 PMCR- 2024/12/05 CRDT- 2024/12/05 11:20 PHST- 2024/07/25 00:00 [received] PHST- 2024/09/13 00:00 [accepted] PHST- 2025/02/01 20:41 [medline] PHST- 2024/12/05 17:32 [pubmed] PHST- 2024/12/05 11:20 [entrez] PHST- 2024/12/05 00:00 [pmc-release] AID - 10.1007/s12325-024-03000-x [pii] AID - 3000 [pii] AID - 10.1007/s12325-024-03000-x [doi] PST - ppublish SO - Adv Ther. 2025 Feb;42(2):788-800. doi: 10.1007/s12325-024-03000-x. Epub 2024 Dec 5. PMID- 39632534 OWN - NLM STAT- MEDLINE DCOM- 20241231 LR - 20250107 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 1 DP - 2025 Jan TI - Tirzepatide for overweight and obesity management. PG - 31-49 LID - 10.1080/14656566.2024.2436595 [doi] AB - INTRODUCTION: Tirzepatide is a once-weekly dual agonist, acting on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. It is approved at the same doses (5, 10 and 15 mg) for both type 2 diabetes (T2D) and chronic weight management. AREAS COVERED: Following a search in PubMed, clinicaltrials.gov, conference abstracts and Lilly website, we review herein the global phase 3 SURMOUNT program on tirzepatide's safety and efficacy for chronic weight management. Additionally, we discuss findings from the regional SURMOUNT-CN and SURMOUNT-J trials (in East-Asian populations) and the phase 2 SYNERGY-NASH, phase 3 SURMOUNT-OSA and SUMMIT studies on tirzepatide's impact on obesity-related complications. We also explore the clinical implications of SURMOUNT program results, considerations for tirzepatide prescribing for overweight/obesity, ongoing research and evidence gaps. EXPERT OPINION: Tirzepatide marks a new era in overweight/obesity treatment, enabling many to achieve >/= 20% weight loss. It is well-tolerated with a safety profile similar to GLP-1 receptor agonists. Tirzepatide also results in clinically important improvements in multiple obesity-related complications including sleep apnea, metabolic-dysfunction associated steatohepatitis, heart failure with preserved ejection fraction and diabetes prevention. Ongoing trials will provide further data on tirzepatide's long-term safety, efficacy (including cardiovascular outcomes) and potential cost-effectiveness for managing overweight/obesity and/or T2D. FAU - Hamza, Malak AU - Hamza M AUID- ORCID: 0009-0005-8483-8197 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Department of Diabetes and Endocrinology, Kettering General Hospital NHS Trust, Kettering, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. LA - eng PT - Journal Article PT - Review DEP - 20241204 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Anti-Obesity Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Animals MH - Humans MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide-2 Receptor/agonists/metabolism MH - *Obesity/drug therapy/metabolism MH - *Overweight/drug therapy/metabolism MH - Weight Loss/drug effects OTO - NOTNLM OT - GIP OT - GLP-1 OT - Glucose-dependent insulinotropic polypeptide OT - SURMOUNT OT - glucagon-like peptide-1 OT - obesity pharmacotherapy OT - tirzepatide OT - weight loss EDAT- 2024/12/05 06:23 MHDA- 2025/01/01 12:42 CRDT- 2024/12/05 01:43 PHST- 2025/01/01 12:42 [medline] PHST- 2024/12/05 06:23 [pubmed] PHST- 2024/12/05 01:43 [entrez] AID - 10.1080/14656566.2024.2436595 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jan;26(1):31-49. doi: 10.1080/14656566.2024.2436595. Epub 2024 Dec 4. PMID- 39629799 OWN - NLM STAT- MEDLINE DCOM- 20241231 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 1 DP - 2025 Jan TI - Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II. PG - 1-7 LID - 10.1080/14656566.2024.2436593 [doi] AB - INTRODUCTION: A stepwise coordinated multiple therapeutic targeted approach to the treatment of type 2 diabetes includes starting with lifestyle modification, oral antihyperglycemic agents, non-insulin injectables (Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and both short and long-acting insulins. Ultra-long-acting insulins offer more convenient administration. As in any chronic disease, the introduction of a novel medication must balance safety, efficacy, financial cost, as well as improved patient convenience and adherence. AREAS COVERED: This manuscript describes IcoSema - a new investigational fixed-ratio combination of basal insulin icodec and the GLP-1 RA semaglutide. The key trials from the clinical development process of insulin icodec, semaglutide, and IcoSema are reviewed with important endpoints highlighted. EXPERT OPINION: Once-weekly IcoSema offers glycemic efficacy that is non-inferior to glargine+aspart, similar risk of hypoglycemia, significant reduction in body weight, the convenience of use, and favorable safety profile with most adverse events being gastrointestinal. FAU - Siamashvili, Maka AU - Siamashvili M AD - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Davis, Stephen N AU - Davis SN AD - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20241204 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects/analogs & derivatives MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Drug Combinations MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - IcoSema OT - diabetes OT - icodec OT - insulin OT - semaglutide EDAT- 2024/12/04 12:29 MHDA- 2025/01/01 12:41 CRDT- 2024/12/04 07:53 PHST- 2025/01/01 12:41 [medline] PHST- 2024/12/04 12:29 [pubmed] PHST- 2024/12/04 07:53 [entrez] AID - 10.1080/14656566.2024.2436593 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jan;26(1):1-7. doi: 10.1080/14656566.2024.2436593. Epub 2024 Dec 4. PMID- 39620926 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20250517 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 2 DP - 2025 Feb 1 TI - Compounded GLP-1 and Dual GIP/GLP-1 Receptor Agonists: A Statement from the American Diabetes Association. PG - 177-181 LID - 10.2337/dci24-0091 [doi] AB - The use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA (GIP/GLP-1 RA) classes has increased substantially over the past several years for treating type 2 diabetes and obesity. Increased demand for these pharmacotherapies has resulted in temporary product shortages for both GLP-1 RA and dual GIP/GLP-1 RA medications. These shortages, in part, have led to entities producing and marketing compounded formulations that bypass regulatory measures, raising safety, quality, and efficacy concerns. Even as shortages resolve, compounded GLP-1 RA and GIP/GLP-1 RA products continue to be heavily marketed to people with diabetes and obesity. The purpose of this statement by the American Diabetes Association is to guide health care professionals and people with diabetes and/or obesity in these circumstances of medication unavailability to promote optimal care and medication use safety. CI - (c) 2024 by the American Diabetes Association. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, Spokane, WA. FAU - Bajaj, Mandeep AU - Bajaj M AD - Department of Medicine, Baylor College of Medicine, Houston, TX. FAU - Bannuru, Raveendhara R AU - Bannuru RR AUID- ORCID: 0000-0002-8069-5783 AD - American Diabetes Association, Arlington, VA. FAU - McCoy, Rozalina G AU - McCoy RG AUID- ORCID: 0000-0002-2289-3183 AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD. FAU - Pekas, Elizabeth J AU - Pekas EJ AD - American Diabetes Association, Arlington, VA. FAU - Segal, Alissa R AU - Segal AR AD - Massachusetts College of Pharmacy and Health Sciences, Boston, MA. FAU - ElSayed, Nuha A AU - ElSayed NA AUID- ORCID: 0000-0003-1217-4916 AD - American Diabetes Association, Arlington, VA. AD - Harvard Medical School, Boston, MA. LA - eng GR - American Diabetes Association/ PT - Journal Article PT - Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/therapeutic use MH - United States MH - Obesity/drug therapy EDAT- 2024/12/02 12:32 MHDA- 2025/01/22 18:25 CRDT- 2024/12/02 10:03 PHST- 2024/10/15 00:00 [received] PHST- 2024/11/04 00:00 [accepted] PHST- 2025/01/22 18:25 [medline] PHST- 2024/12/02 12:32 [pubmed] PHST- 2024/12/02 10:03 [entrez] AID - 157478 [pii] AID - 10.2337/dci24-0091 [doi] PST - ppublish SO - Diabetes Care. 2025 Feb 1;48(2):177-181. doi: 10.2337/dci24-0091. PMID- 39616020 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 47 IP - 1 DP - 2025 Jan TI - Real-world Evidence on Oral Semaglutide for the Management of Type 2 Diabetes. A Narrative Review for Clinical Practice. PG - 102-110 LID - S0149-2918(24)00330-8 [pii] LID - 10.1016/j.clinthera.2024.11.005 [doi] AB - PURPOSE: Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) available for type 2 diabetes mellitus (T2DM) management, whose effectiveness and tolerability have extensively been demonstrated in the PIONEER clinical trial program. Nevertheless, data from real-world are crucial to evaluate treatment performance under routine care. The aim of this narrative review is to summarize available evidence regarding real-world utilization patterns of oral semaglutide, and discuss efficacy, safety, and dosing regimen data in routine scenarios. METHODS: We searched PubMed for real-world studies evaluating oral semaglutide up to August 2024, and specific search terms were: "oral semaglutide," and "real-world studies" or "observational studies" or "retrospective studies". FINDINGS: 19 real-world studies were included in the narrative review. In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight reduction of 2 to 3 kg) benefits across the spectrum of T2DM, aligning with pre-clinical evidence from the PIONEER program. No new tolerability and safety issue has emerged from oral semaglutide administration in routine clinical practice. IMPLICATIONS: Oral semaglutide constitutes an effective and safe option for T2DM management, and its increased acceptance has the potential to favor the early introduction of GLP-1RAs along the disease course. Nevertheless, continuous evaluation of real-world data is critical to better define the optimal positioning of oral semaglutide along T2DM trajectory and fully exploit its potential in everyday clinical practice. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Marassi, M AU - Marassi M AD - Department of Medicine, University of Padova, Padua, Italy. Electronic address: mare.marassi@gmail.com. FAU - Fadini, G P AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy; Veneto Institute of Molecular Medicine, Padua, Italy. LA - eng PT - Journal Article PT - Review DEP - 20241129 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Administration, Oral MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose/drug effects MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Effectiveness OT - Narrative review OT - Oral semaglutide OT - Real-world OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gian Paolo Fadini reports a relationship with Abbott, AstraZeneca, Boehringer, Lilly, MSD, Novo Nordisk, Novaartis, Sanofi, Servier, Takeda that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/01 15:22 MHDA- 2025/01/11 13:59 CRDT- 2024/11/30 21:57 PHST- 2024/06/05 00:00 [received] PHST- 2024/09/30 00:00 [revised] PHST- 2024/11/02 00:00 [accepted] PHST- 2025/01/11 13:59 [medline] PHST- 2024/12/01 15:22 [pubmed] PHST- 2024/11/30 21:57 [entrez] AID - S0149-2918(24)00330-8 [pii] AID - 10.1016/j.clinthera.2024.11.005 [doi] PST - ppublish SO - Clin Ther. 2025 Jan;47(1):102-110. doi: 10.1016/j.clinthera.2024.11.005. Epub 2024 Nov 29. PMID- 39609879 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials. PG - 710-718 LID - 10.1111/dom.16065 [doi] AB - AIMS: Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide. MATERIALS AND METHODS: This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations. RESULTS: The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change. CONCLUSIONS: People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Armstrong, Matthew J AU - Armstrong MJ AD - Liver Unit, Queen Elizabeth University Hospital, Birmingham, UK. AD - National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. FAU - Okanoue, Takeshi AU - Okanoue T AD - Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan. FAU - Sundby Palle, Mads AU - Sundby Palle M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sejling, Anne-Sophie AU - Sejling AS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tawfik, Mohamed AU - Tawfik M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Roden, Michael AU - Roden M AD - Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany. AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Dusseldorf, Germany. AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20241128 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Weight Loss/drug effects MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiometabolic Risk Factors MH - Fatty Liver/complications/drug therapy MH - Aged MH - Adult MH - Non-alcoholic Fatty Liver Disease/drug therapy/complications MH - Obesity/complications/drug therapy MH - Semaglutide PMC - PMC11701178 OTO - NOTNLM OT - GLP-1 analogue OT - semaglutide OT - type 2 diabetes OT - weight control COIS- MJA: consultancy and sponsored lectures for Norgine and Novo Nordisk. TO: no conflicts of interest to declare. MSP: employee and shareholder of Novo Nordisk. A-SS: employee and shareholder of Novo Nordisk. MT: employee and shareholder of Novo Nordisk. MR: research grants from Boehringer Ingelheim and Novo Nordisk; consulting or advisory boards for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, MSD and Novo Nordisk; speaker fees from AstraZeneca, Madrigal, MSD and Novo Nordisk. EDAT- 2024/11/29 05:20 MHDA- 2025/01/07 04:51 PMCR- 2025/01/06 CRDT- 2024/11/28 23:59 PHST- 2024/10/24 00:00 [revised] PHST- 2024/08/22 00:00 [received] PHST- 2024/10/31 00:00 [accepted] PHST- 2025/01/07 04:51 [medline] PHST- 2024/11/29 05:20 [pubmed] PHST- 2024/11/28 23:59 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - DOM16065 [pii] AID - 10.1111/dom.16065 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):710-718. doi: 10.1111/dom.16065. Epub 2024 Nov 28. PMID- 39608670 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260507 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 1 DP - 2025 Jan TI - Cardiovascular and renal effects of the combination therapy of a GLP-1 receptor agonist and an SGLT2 inhibitor in observational real-life studies. PG - 101594 LID - S1262-3636(24)00086-7 [pii] LID - 10.1016/j.diabet.2024.101594 [doi] AB - BACKGROUND: Combining a glucagon-like peptide-1 receptor agonist (GLP-1RA) and an sodium-glucose cotransporter 2 inhibitor (SGLT2i) improved cardiovascular (and renal) prognosis compared to either monotherapy in several post-hoc exploratory analyses of randomized controlled trials (RCTs) versus placebo carried out in patients with type 2 diabetes (T2DM) and high cardiovascular/renal risk. The aim of the present work is to verify if such a benefit of the combined therapy is also present in real-life clinical practice. METHODS: An extended search of the literature was performed to select observational retrospective studies that compared cardiovascular and/or renal outcomes in patients with T2DM treated with a GLP-1RA/SGLT2i combination versus patients treated with either GLP-1RA monotherapy or SGLT2i monotherapy, in addition to standard of care therapy. RESULTS: Nine observational studies showed that a GLP-1RA/SGLT2i combination is associated with a greater reduction in major adverse cardiovascular events (MACEs), hospitalization for heart failure and all-cause-mortality when compared to either GLP-1RA alone or SGLT2i alone, without obvious differences between the two monotherapies, including regarding heart failure. Results were obtained in different populations, including patients with atherosclerotic cardiovascular disease and/or heart failure. Only three observational studies gave information on renal outcomes, with a greater benefit when the GLP-1RA/SGLT2i combination was compared with GLP-1RA alone or SGLT2i alone. CONCLUSION: In real-life conditions, the GLP-1RA/SGLT2i combination reduced cardiovascular and renal outcomes compared with both GLP-1RA monotherapy and SGLT2i monotherapy. Overall, observational studies confirm the results reported in post-hoc exploratory analyses of RCTs versus placebo. CI - Copyright (c) 2024 Elsevier Masson SAS. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium; Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. Electronic address: andre.scheen@chuliege.be. LA - eng PT - Journal Article PT - Review DEP - 20241126 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Observational Studies as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney/drug effects OTO - NOTNLM OT - Cardiovascular outcome OT - Combined therapy OT - GLP-1 receptor agonist OT - Renal outcome OT - SGLT2 inhibitor COIS- Declaration of competing interest The author declare that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/29 05:21 MHDA- 2025/02/07 00:20 CRDT- 2024/11/28 19:34 PHST- 2024/11/12 00:00 [received] PHST- 2024/11/23 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/11/29 05:21 [pubmed] PHST- 2024/11/28 19:34 [entrez] AID - S1262-3636(24)00086-7 [pii] AID - 10.1016/j.diabet.2024.101594 [doi] PST - ppublish SO - Diabetes Metab. 2025 Jan;51(1):101594. doi: 10.1016/j.diabet.2024.101594. Epub 2024 Nov 26. PMID- 39608381 OWN - NLM STAT- MEDLINE DCOM- 20241226 LR - 20250522 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 1 DP - 2025 Jan TI - Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. PG - 15-28 LID - S2213-8587(24)00271-7 [pii] LID - 10.1016/S2213-8587(24)00271-7 [doi] AB - BACKGROUND: GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. METHODS: For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m(2) or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1.73 m(2)), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. FINDINGS: Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0.82, 95% CI 0.73-0.93; I(2) =26.41%), kidney failure by 16% (HR 0.84, 0.72-0.99; I(2) =0%), MACE by 13% (HR 0.87, 0.81-0.93; I(2) =49.75%), and all-cause death by 12% (HR 0.88, 0.83-0.93; I(2) =0%). The effect on the composite kidney outcome (HR 0.81, 95% CI 0.72-0.92; I(2) =23.11%), kidney failure (HR 0.84, 0.72-0.98; I(2) =0%), MACE (HR 0.86, 0.80-0.92; I(2) =48.9%), and all-cause death (HR 0.87, 0.82-0.91; I(2) =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (p(heterogeneity) >0.05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0.95, 95% CI 0.90-1.01; I(2) =88.5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1.51, 95% CI 1.18-1.94; I(2) =96.3%). INTERPRETATION: We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. FUNDING: None. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Badve, Sunil V AU - Badve SV AD - St George Hospital, Sydney, NSW, Australia; Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia. Electronic address: sbadve@georgeinstitute.org.au. FAU - Bilal, Anika AU - Bilal A AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Lee, Matthew M Y AU - Lee MMY AD - School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Sattar, Naveed AU - Sattar N AD - School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Gerstein, Hertzel C AU - Gerstein HC AD - Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. FAU - Ruff, Christian T AU - Ruff CT AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - McMurray, John J V AU - McMurray JJV AD - School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Bakris, George AU - Bakris G AD - American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany; University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - Colhoun, Helen M AU - Colhoun HM AD - Institute of Genetics and Molecular Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. FAU - Tuttle, Katherine R AU - Tuttle KR AD - University of Washington School of Medicine, Seattle, WA, USA; Providence Inland Northwest Health, Spokane, WA, USA. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Perkovic, Vlado AU - Perkovic V AD - Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia. LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241125 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Lancet Diabetes Endocrinol. 2025 Jan;13(1):2-3. doi: 10.1016/S2213-8587(24)00315-2. PMID: 39608382 MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Declaration of interests SVB reports consulting fees from Bayer, AstraZeneca, GSK, and Vifor Pharma; speaking fees from Bayer, AstraZeneca, Pfizer, and Vifor Pharma (all honoraria paid to his institution); and non-financial research support from Bayer. MMYL reports receiving grants through his employer, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim, and Roche Diagnostics; MMYL is a member of a trial steering committee for Cytokinetics and a clinical endpoints committee for Bayer. NS reports consulting and speaking fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, and ZP Therapeutics; and grants from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics, paid to the University of Glasgow. HCG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing education grants from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Sanofi, Carbon Brand, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly, Novo Nordisk, Pfizer, Sanofi, Kowa, and Hanmi. CTR reports research grants through Brigham and Women's Hospital from Anthos, AstraZeneca, Daiichi Sankyo, Janssen, and Novartis; and has received honoraria for scientific advisory boards and consulting from Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen, and Pfizer. JJVM reports payments to his employer, the University of Glasgow, for work on clinical trials, consulting, lecturing, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; personal lecture fees from Abbott, Hikma, Sun Pharmaceuticals, Servier, and Theracos; and personal payments from Abbott, Hikma, Ionis, Sun Pharmaceuticals, and Servier. PR has received grants to his institution from Novo Nordisk, AstraZeneca, and Bayer; and has received honoraria for scientific advisory boards and steering groups from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Sanofi, Eli Lilly, and Novartis. GB has received honoraria from Bayer, KBP Biosciences, Alnylam, AstraZeneca, Novo Nordisk, and InREGEN. KWM has received grants from AHA, Apple, Bayer, California Institute Regenerative Medicine (CIRM), CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and consulting fees from Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and has equity in Human, Medeloop, Precordior, and Regencor. JFEM reports grants from Novo Nordisk, the EU, and McMaster University (Hamilton, Canada); consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, and has had a leadership role in the Kidney Disease Improving Global Outcomes group. HMC reports serving on advisory panels for Novo Nordisk and Bayer; receiving research funding from Sanofi, Roche, and IQVIA; receiving grants from the Chief Scientist Office, Diabetes UK, the European Commission, JDRF (Breakthrough T1D), and the Medical Research Council; serving on a speaker's bureau for Novo Nordisk; and holding stock in Roche and Bayer. KRT is supported by National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581 and Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Travere Therapeutics, Bayer, and the Doris Duke Charitable Foundation, outside of the submitted work. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Bayer, Eli Lilly, Novo Nordisk, Travere Therapeutics, and Pfizer; and speaker fees from Novo Nordisk. REP reports speaker fees from Eli Lilly and Novo Nordisk; consulting fees from Bayer, Bayer HealthCare Pharmaceuticals, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Intas Pharmaceuticals, Eli Lilly, Novo Nordisk, Pfizer, and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi. VP has received honoraria for roles on steering committees, data monitoring committees, or advisory boards or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UpToDate; and is Board Director for George Clinical, St Vincents Health Australia and several independent medical research institutes. AB declares no competing interests. EDAT- 2024/11/29 05:20 MHDA- 2024/12/26 06:20 CRDT- 2024/11/28 18:53 PHST- 2024/07/24 00:00 [received] PHST- 2024/08/18 00:00 [revised] PHST- 2024/08/18 00:00 [accepted] PHST- 2024/12/26 06:20 [medline] PHST- 2024/11/29 05:20 [pubmed] PHST- 2024/11/28 18:53 [entrez] AID - S2213-8587(24)00271-7 [pii] AID - 10.1016/S2213-8587(24)00271-7 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Jan;13(1):15-28. doi: 10.1016/S2213-8587(24)00271-7. Epub 2024 Nov 25. PMID- 39606869 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20260127 IS - 1876-8784 (Electronic) IS - 0028-2162 (Linking) VI - 168 DP - 2024 Nov 21 TI - [Prescribing semaglutide for overweight: is it allowed?]. LID - D8347 [pii] AB - Semaglutide is registered in the Netherlands as a treatment for type 2 diabetes. If semaglutide is prescribed off-label as slimming agent, in principle, patient's costs are not reimbursed by health insurers. With the entry of the Geneesmiddelenwet (Gnw), regulations were provided for off-label prescription of medication. Based on article 68, paragraph 1 Gnw, off-label prescribing is allowed when protocols or standards have been developed. So far, this has not been the case in the Netherlands regarding semaglutide. When protocols and standards are under development, consultation must take place between doctor and pharmacist. The term "protocols or standards under development" is open to multiple interpretations, as shown by case law. Regardless of the chosen interpretation, the scientific evidence for semaglutide as slimming agent seems insufficient. In conclusion does off-label prescribing of semaglutide as slimming agent not meet the requirements of article 68, paragraph 1 Gnw and is therefore not permitted. FAU - Rijk, Paul C AU - Rijk PC AD - Medisch Centrum Leeuwarden, afd. Orthopedie, Leeuwarden. AD - Contact: p.rijk@mcl.nl. LA - dut PT - English Abstract PT - Journal Article TT - Semaglutide voorschrijven als afslankmiddel: mag dat? DEP - 20241121 PL - Netherlands TA - Ned Tijdschr Geneeskd JT - Nederlands tijdschrift voor geneeskunde JID - 0400770 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Netherlands MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Off-Label Use MH - Hypoglycemic Agents/therapeutic use MH - Overweight/drug therapy MH - Semaglutide EDAT- 2024/11/28 06:35 MHDA- 2024/11/28 12:20 CRDT- 2024/11/28 05:53 PHST- 2024/11/28 12:20 [medline] PHST- 2024/11/28 06:35 [pubmed] PHST- 2024/11/28 05:53 [entrez] AID - D8347 [pii] PST - epublish SO - Ned Tijdschr Geneeskd. 2024 Nov 21;168:D8347. PMID- 39605940 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20261027 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Glucagon-like peptide-1 receptor agonists and the risk of erectile dysfunction: a drug target Mendelian randomization study. PG - 1448394 LID - 10.3389/fendo.2024.1448394 [doi] LID - 1448394 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used for type 2 diabetes (T2D) and weight management. However, the causal relationship of GLP-1RAs with erectile dysfunction (ED) was still unclear. METHODS: Mendelian randomization (MR) analysis was conducted to reveal the association of genetically proxied GLP-1RAs with ED. The proportion of potential mediators mediating GLP-1RAs to ED was also assessed by two-step MR. Finally, a series of sensitivity analyses and Two-Sep cis-MR (TSCMR) were performed to evaluate the robustness of the results. RESULTS: MR evidence suggested that genetically proxied GLP-1RAs reduced the risk of ED [odds ratio (OR): 0.493; 95% confidence interval (95% CI): 0.430 to 0.565; P<0.001]. Further mediation analysis via two-step MR showed that this effect was partly mediated through reduced T2D, obesity, hypertension and cardiovascular disease (CVD), with mediated proportions of 2.89% (95% CI: 1.28% to 4.49%), 6.83% (95% CI: 2.25% to 11.41%), 3.22% (95% CI: 1.21% to 5.23%), and 3.06% (95% CI: 0.51% to 5.62%), respectively. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of ED, and to a lesser extent, T2D, obesity, hypertension and CVD mediated this effect. Nevertheless, the potential implications of our results for ED prevention policies required validation in further clinical randomized controlled trials. CI - Copyright (c) 2024 An, Xie and Gan. FAU - An, Hongjin AU - An H AD - Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China. FAU - Xie, Kexin AU - Xie K AD - Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China. FAU - Gan, Huatian AU - Gan H AD - Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. AD - Department of Gastroenterology and Laboratory of Inflammatory Bowel Disease, the Center for Inflammatory Bowel Disease, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. LA - eng PT - Journal Article DEP - 20241113 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - *Erectile Dysfunction/epidemiology/genetics MH - *Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - *Diabetes Mellitus, Type 2/complications/genetics/drug therapy MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Factors MH - Polymorphism, Single Nucleotide MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11600104 OTO - NOTNLM OT - Mendelian randomization OT - erectile dysfunction OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/11/28 06:36 MHDA- 2024/11/28 06:37 PMCR- 2024/01/01 CRDT- 2024/11/28 04:57 PHST- 2024/06/13 00:00 [received] PHST- 2024/10/22 00:00 [accepted] PHST- 2024/11/28 06:37 [medline] PHST- 2024/11/28 06:36 [pubmed] PHST- 2024/11/28 04:57 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1448394 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Nov 13;15:1448394. doi: 10.3389/fendo.2024.1448394. eCollection 2024. PMID- 39604324 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Early combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA in type 2 diabetes. PG - 468-481 LID - 10.1111/dom.16077 [doi] AB - Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-Like peptide-1 receptor agonists (GLP-1 RA) are recommended in people with type 2 diabetes (T2D) for glycaemic control and for people with high cardiovascular risk. However, current guidelines do not specifically address the role of initial early combination therapy with SGLT2i and GLP-1 RA or dual gastric inhibitory polypeptide (GIP)/GLP-1 RA, but rather sequential initiation with either in T2D. This review synthesizes the available evidence on the use of SGLT2i and GLP-1-based therapies for T2D and provides a rationale for their combination. The combination of SGLT2i with GLP-1-based therapies addresses complementary pathophysiological mechanisms and enhances efficacy in achieving target haemoglobin A1C (HbA1c) levels. SGLT2i and GLP-1 RA also have been shown to prevent complications of T2D. While both classes reduce adverse cardiorenal events, SGLT2i has a predominant effect on prevention of kidney dysfunction and heart failure, whereas GLP-1 RA has a more marked effect on the risk of atherosclerotic cardiovascular disease. Both drug classes have favourable safety profiles. Finally, weight loss with combination therapy may have disease-modifying effects that may reverse T2D progression. We propose that the combination of SGLT2i with GLP-1 RA or dual GIP/GLP-1 RA should be considered for most patients with T2D who do not have contraindications. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Vale, Catarina AU - Vale C AUID- ORCID: 0000-0001-9213-7490 AD - Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. FAU - Lourenco, Ines Mariana AU - Lourenco IM AUID- ORCID: 0000-0003-0752-0802 AD - Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. FAU - Jordan, Gabriela AU - Jordan G AD - Scripps Health in San Diego, San Diego, California, USA. FAU - Golovaty, Ilya AU - Golovaty I AD - General Medicine Service, VA Puget Sound Health Care System, Seattle, Washington, USA. AD - Division of General Internal Medicine, University of Washington School of Medicine, Seattle, Washington, USA. FAU - Torres, Hugo AU - Torres H AD - David Geffen School of Medicine, University of California, Los Angeles, California, USA. FAU - Moin, Tannaz AU - Moin T AD - David Geffen School of Medicine, University of California, Los Angeles, California, USA. AD - HSR&D Center for the Study of Healthcare Innovation, Implementation & Policy, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA. FAU - Buysschaert, Martin AU - Buysschaert M AD - Department of Endocrinology and Diabetology, Universite Catholique de Louvain, University Clinic Saint-Luc, Brussels, Belgium. FAU - Neves, Joao Sergio AU - Neves JS AUID- ORCID: 0000-0002-8173-8255 AD - Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. FAU - Bergman, Michael AU - Bergman M AD - Holman Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Population Health, VA New York Harbor Healthcare System, New York University Grossman School of Medicine, New York, New York, USA. LA - eng GR - R01DK124503/National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)/ GR - R01DK127733/National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)/ GR - R18DK122372/National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)/ GR - U18DP006535/National Institute of Diabetes and Digestive and Kidney diseases (NIDDK) / Centers for Disease Control and Prevention (CDC)/ GR - U18 DP006708/DP/NCCDPHP CDC HHS/United States GR - University of California, Los Angeles (UCLA)/ GR - UCOP/ GR - QUE20-028/VA/VA/United States GR - CSP#2002/VA/VA/United States GR - CSP NODES0017/VA/VA/United States GR - U18 DP006708/DP/NCCDPHP CDC HHS/United States GR - QUE20-028/VA/VA/United States GR - CSP#2002/VA/VA/United States GR - CSP NODES0017/VA/VA/United States PT - Journal Article PT - Review DEP - 20241127 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - *Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/drug effects/metabolism/analysis MH - Cardiovascular Diseases/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - combination therapy OT - dual GIP/GLP-1 receptor agonists OT - type 2 diabetes EDAT- 2024/11/28 06:36 MHDA- 2025/01/07 00:21 CRDT- 2024/11/28 02:35 PHST- 2024/10/31 00:00 [revised] PHST- 2024/08/12 00:00 [received] PHST- 2024/11/06 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/11/28 06:36 [pubmed] PHST- 2024/11/28 02:35 [entrez] AID - 10.1111/dom.16077 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):468-481. doi: 10.1111/dom.16077. Epub 2024 Nov 27. PMID- 39603373 OWN - NLM STAT- MEDLINE DCOM- 20250124 LR - 20260901 IS - 1873-2763 (Electronic) IS - 1873-2763 (Linking) VI - 192 DP - 2025 Mar TI - Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials. PG - 117338 LID - S8756-3282(24)00327-2 [pii] LID - 10.1016/j.bone.2024.117338 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures. PURPOSE: The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes. METHODS: A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed. RESULTS: A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61-0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for >78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61-0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21-0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments. CONCLUSION: GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Zhang, Yuan AU - Zhang Y AD - Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China. FAU - Chen, Guanhua AU - Chen G AD - Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China. FAU - Wang, Weimin AU - Wang W AD - Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China; Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. FAU - Yang, Donghui AU - Yang D AD - Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China; Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. FAU - Zhu, Dalong AU - Zhu D AD - Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China; Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: zhudalong@nju.edu.cn. FAU - Jing, Yali AU - Jing Y AD - Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China. Electronic address: jingyalidr@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20241126 PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Fractures, Bone/epidemiology MH - Risk Factors MH - Hypoglycemic Agents/therapeutic use MH - Publication Bias OTO - NOTNLM OT - Fracture OT - GLP-1 RAs OT - RCTs OT - T2DM OT - meta-analysis COIS- Declaration of competing interest We declare no competing interests. EDAT- 2024/11/28 00:24 MHDA- 2025/01/25 13:53 CRDT- 2024/11/27 19:27 PHST- 2024/08/09 00:00 [received] PHST- 2024/10/29 00:00 [revised] PHST- 2024/11/20 00:00 [accepted] PHST- 2025/01/25 13:53 [medline] PHST- 2024/11/28 00:24 [pubmed] PHST- 2024/11/27 19:27 [entrez] AID - S8756-3282(24)00327-2 [pii] AID - 10.1016/j.bone.2024.117338 [doi] PST - ppublish SO - Bone. 2025 Mar;192:117338. doi: 10.1016/j.bone.2024.117338. Epub 2024 Nov 26. PMID- 39602568 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260109 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 33 IP - 1 DP - 2026 Jan 6 TI - Albiglutide and atrial fibrillation in patients with Type 2 diabetes and established cardiovascular disease: insights from the Harmony Outcomes trial. PG - 30-41 LID - 10.1093/eurjpc/zwae379 [doi] AB - AIMS: Atrial fibrillation and flutter (AF) are common in patients with Type 2 diabetes and are associated with worse outcomes. METHODS AND RESULTS: Harmony Outcomes was a multi-centre, event-driven, double-blind, placebo-controlled trial comparing the effects of albiglutide, a glucagon-like peptide-1 receptor agonist, with placebo on a composite of major adverse cardiac events (MACEs; non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) in 9463 patients aged >40 years with Type 2 diabetes and established cardiovascular disease. Herein, the cardiovascular effects of albiglutide in patients with and without AF, as well as the effects on AF events during follow-up, were analysed. Patients with a history of AF (8.9%) exhibited a higher event rate for the primary composite MACE endpoint during 1.6 years of follow-up 12.7 vs. 6.3 events/100 person-years, adjusted hazard ratio [aHR] 1.41 [95% confidence interval (CI) 1.14-1.74], P = 0.001. Treatment with albiglutide reduced the occurrence of the primary endpoint irrespective of history of AF at baseline (history of AF: aHR 0.83 [0.58-1.19], no history of AF: aHR 0.77 [0.66-0.90]; Pinteraction = 0.71). During follow-up, 239 patients (2.5%) experienced an AF event. Overall, albiglutide was associated with numerically fewer AF events [108 vs. 131; hazard ratio 0.82 (0.63-1.06), P = 0.12], irrespective of baseline history of AF (Pinteraction = 0.92). CONCLUSION: In patients with Type 2 diabetes, treatment with albiglutide, compared with placebo, reduced the risk of cardiovascular events irrespective of history of AF. Further, albiglutide treatment did not increase AF adverse events but was associated with a trend to a lower rate of AF events during follow-up without reaching statistical significance. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Krychtiuk, Konstantin A AU - Krychtiuk KA AUID- ORCID: 0000-0001-7792-2837 AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Marquis-Gravel, Guillaume AU - Marquis-Gravel G AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Murphy, Shannon AU - Murphy S AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Chiswell, Karen AU - Chiswell K AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Green, Jennifer B AU - Green JB AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Leiter, Lawrence A AU - Leiter LA AUID- ORCID: 0000-0002-1040-6229 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital, 38 Shuter St, University of Toronto, Toronto, ON M5B 1A6, Canada. FAU - Lopes, Renato D AU - Lopes RD AUID- ORCID: 0000-0003-2999-4961 AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Del Prato, Stefano AU - Del Prato S AD - Section on Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. AD - Sant'Anna School of Advanced Studies, Piazza Martiri della Liberta, 33, 56127 Pisa, Italy. FAU - McMurray, John J V AU - McMurray JJV AD - British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Pl, Glasgow G12 8TA, UK. FAU - Hernandez, Adrian F AU - Hernandez AF AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. FAU - Granger, Christopher B AU - Granger CB AD - Duke Clinical Research Institute, 300 W Morgan Street, Durham, NC 27701, USA. LA - eng GR - Max Kade Foundation/ GR - GSK/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 5E7U48495E (rGLP-1 protein) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Eur J Prev Cardiol. 2026 Jan 6;33(1):42-43. doi: 10.1093/eurjpc/zwaf242. PMID: 40300803 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/complications/blood MH - *Atrial Fibrillation/mortality/drug therapy/diagnosis/epidemiology MH - Male MH - Female MH - Middle Aged MH - Double-Blind Method MH - Treatment Outcome MH - Aged MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use/adverse effects MH - Time Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Factors OAB - Many patients with Type 2 diabetes suffer from atrial fibrillation (AF), a certain rhythm disorder.Treatment with a certain diabetes medication from the class of glucagon-like peptide-1 receptor agonists reduces heart and vessel events in patients with and without AF.Treatment with this antidiabetic medication may also reduce future events resulting from AF. OABL- eng OTO - NOTNLM OT - Albiglutide OT - Atrial fibrillation OT - Diabetes OT - GLP-1 receptor agonist COIS- Conflict of interest: K.A.K.: speaker fees: Zoll Medical and Daiichi Sankyo; travel support: Amgen; consulting fees: Novartis and Amarin. G.M.-G.: consulting fees: Novartis, JAMP Pharma, Boston Scientific, KYE, Pendopharm, and HLS; speaker fees: Novartis, Bayer, Boston Scientific, JAMP Pharma, Pendopharm, HLS, KYE, and CIS. J.B.G.: grants/contracts: Merck, Roche, Boehringer Ingelheim, Lilly, Sanofi/Lexicon; consulting fees: Astra Zeneca, Bayer, Boehringer Ingelheim, Lilly, Novo Nordisk, Pfizer, Anji, Valo, and Vertex; lecture fees: Boehringer Ingelheim. L.A.L.: grants/contracts: Lexicon; consulting fees: Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Pfizer, and Sanofi; lecture fees: Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Servier. R.D.L.: grants/contracts: BMS, GSK, Medtronic, Pfizer, and Sanofi; consulting fees: Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Portola, Glaxo Smith Kline, Medtronic, Merck, Pfizer, and Sanofi; travel support: BMS and GSK. S.D.P.: grants/contracts: Astra Zeneca and Boehringer Ingelheim; consulting fees: Abbott, Amarin Corporation, Applied Therapeutics, Eli Lilly & Co, Hengrui Pharmaceuticals, Menarinii International, Novo Nordisk, Sun Pharmaceuticals, and Evaharma; lecture fees: AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co, Merck Sharpe & Dohme, Novartis Pharmaceuticals, Novo Nordisk, Sanofi, and Laboratori Guidotti. J.J.V.M.: grants: British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217; fees for consulting and other activities: Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; personal lecture fees: Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, and Global Clinical Trial Partners (GCTP). A.F.H.: research grants: Merck, Astra Zeneca, Novartis, and Verily; honoraria: Merck, Bayer, Amgen, Astra Zeneca, and Novartis. C.B.G.: consulting fees: Abbvie, Abiomed, Alnylam, Anthos, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardionomic, Celecor Therapeutics, Hengrui USA, Janssen, Medscape, Medtronic, Merck, NephroSynergy, Novo Nordisk, NIH, Novartis, Pfizer, Philips, and REATA; grants/contracts: Boehringer Ingelheim, Bristol Myers Squibb, FDA, Janssen, Lilly, Novartis, Pfizer, and Philips; equity: Tenac.io. The remaining authors declare no conflict of interest. EDAT- 2024/11/27 18:25 MHDA- 2026/01/06 19:17 CRDT- 2024/11/27 14:23 PHST- 2024/05/30 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/11/18 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2024/11/27 18:25 [pubmed] PHST- 2024/11/27 14:23 [entrez] AID - 7909733 [pii] AID - 10.1093/eurjpc/zwae379 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2026 Jan 6;33(1):30-41. doi: 10.1093/eurjpc/zwae379. PMID- 39602049 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20261010 IS - 1936-0541 (Electronic) IS - 1936-0533 (Linking) VI - 19 IP - 2 DP - 2025 Apr TI - Semaglutide and the risk of adverse liver outcomes in patients with nonalcoholic fatty liver disease and type 2 diabetes: a multi-institutional cohort study. PG - 395-404 LID - 10.1007/s12072-024-10752-9 [doi] AB - BACKGROUND: Semaglutide has shown potential liver benefits in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). However, no direct comparisons have been made between semaglutide and other antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), thiazolidinediones (TZD), and dipeptidyl peptidase-4 inhibitors (DPP-4i), regarding liver outcomes in patients with both NAFLD and T2D. METHODS: This retrospective cohort study utilized the TriNetX electronic health record database, a multinational and multi-institutional database. Adults with NAFLD and T2D who received their first prescription for either semaglutide or other antidiabetic medications were included. New users of semaglutide were matched 1:1 via propensity score matching with users of SGLT2i, DPP-4i, and TZD. The primary outcome was major adverse liver outcome (MALO), a composite end point consisting of decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included the individual components of MALO and all-cause mortality. RESULTS: A total of 648,070 adult patients with T2D and NAFLD were identified, and patients were categorized into three different comparison groups based on their drug of interest. Semaglutide was associated with a lower risk of MALO compared to SGLT2i (adjusted hazard ratio [aHR], 0.73; 95% CI 0.60-0.88), DPP-4i (aHR, 0.72; 95% CI 0.56-0.86), and TZD (aHR, 0.76; 95% CI 0.56-0.99). Additionally, semaglutide was linked to a lower risk of all-cause mortality compared to SGLT2i (aHR, 0.62; 95% CI 0.53-0.72), DPP-4i (aHR, 0.42; 95% CI 0.36-0.49), and TZD (aHR, 0.67; 95% CI 0.54-0.83). CONCLUSION: Semaglutide is associated with better liver outcomes and a lower risk of all-cause mortality compared to SGLT2i, DPP-4i, and TZD in patients with NAFLD and T2D. CI - (c) 2024. Asian Pacific Association for the Study of the Liver. FAU - Kuo, Chia-Chih AU - Kuo CC AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Li, Chun-Hsien AU - Li CH AD - Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Hsing-Tao AU - Kuo HT AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. kht@mail.chimei.org.tw. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. kht@mail.chimei.org.tw. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. dtmed141@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. dtmed141@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241127 PL - United States TA - Hepatol Int JT - Hepatology international JID - 101304009 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiazolidinediones) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Adult MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Thiazolidinediones/therapeutic use MH - Liver Transplantation/statistics & numerical data MH - Carcinoma, Hepatocellular/epidemiology MH - Liver Neoplasms/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - Major adverse liver outcomes OT - Nonalcoholic fatty liver disease OT - Semaglutide COIS- Declarations. Competing interests: The authors state that they have no conflicts of interest. Ethics approval and consent to participate: The Institutional Review Board of the Chi Mei Medical Center approved the study protocol. Written informed consent was not required because TriNetX contains anonymized data. Consent for publication: All authors consent to the publishing of this article. EDAT- 2024/11/27 12:34 MHDA- 2025/04/16 14:35 CRDT- 2024/11/27 11:22 PHST- 2024/09/30 00:00 [received] PHST- 2024/11/09 00:00 [accepted] PHST- 2025/04/16 14:35 [medline] PHST- 2024/11/27 12:34 [pubmed] PHST- 2024/11/27 11:22 [entrez] AID - 10.1007/s12072-024-10752-9 [pii] AID - 10.1007/s12072-024-10752-9 [doi] PST - ppublish SO - Hepatol Int. 2025 Apr;19(2):395-404. doi: 10.1007/s12072-024-10752-9. Epub 2024 Nov 27. PMID- 39596946 OWN - NLM STAT- MEDLINE DCOM- 20241127 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 60 IP - 11 DP - 2024 Oct 27 TI - The Influence of GLP1 on Body Weight and Glycemic Management in Patients with Diabetes-A Scientometric Investigation and Visualization Study. LID - 10.3390/medicina60111761 [doi] LID - 1761 AB - Diabetes medications can affect weight and cardiovascular health. Some medications can aid in weight management, while others may lead to weight gain. Patients must be monitored and receive appropriate care to manage weight and prevent cardiovascular complications. Despite advancements in diabetes treatments that can influence weight and cardiovascular outcomes, ongoing research is necessary in this intricate field. Long-term effects, individual variations, and combination therapies are still subjects of uncertainty and ongoing investigation. The major objective of the research is to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on body weight in diabetic patients through a scientometric assessment. Methodology: Research data were gathered from the Web of Science Core Collection (WoSCC) database by searching for the keywords "Body Weight", dulaglutide, and semaglutide, identifying 60 relevant articles in the field. While there are advantages in managing diseases in which the cardiovascular system is implicated, there are also clinical considerations for personalized medicine and shared decision-making. The scientometric analysis of the articles revealed important insights into how dulaglutide and semaglutide impact weight management and their potential benefits for managing cardiovascular diseases in individuals with diabetes. Conclusions: Semaglutide shows superior outcomes compared to other commercially available GLP-1RAs, particularly in improving blood sugar control, lowering body weight, and addressing other cardio-metabolic risk factors in individuals with type 2 diabetes (T2DM). The findings suggest that GLP-1 RAs have the potential to provide cardiovascular protection by influencing various physiological factors such as blood pressure, pulse rate, glycated hemoglobin (HbA1c) levels, and the urinary albumin-to-creatinine ratio (RAC). The development and validation of the 4GI model provides a sophisticated tool for evaluating the complex interactions involved in diabetes treatments, offering insights into the mechanisms of action of various medications. FAU - Pantea, Ileana AU - Pantea I AD - Department of Basic, Preventive and Clinical Sciences, Transilvania University, 500036 Brasov, Romania. FAU - Repanovici, Angela AU - Repanovici A AUID- ORCID: 0000-0002-8748-5332 AD - Faculty of Product Design and Environment, Transilvania University, 500036 Brasov, Romania. FAU - Andreescu, Oana AU - Andreescu O AD - Department of Basic, Preventive and Clinical Sciences, Transilvania University, 500036 Brasov, Romania. LA - eng PT - Journal Article PT - Review DEP - 20241027 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/analogs & derivatives MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glycemic Control/methods MH - Glucagon-Like Peptide 1 MH - Blood Glucose/analysis MH - Semaglutide PMC - PMC11596011 OTO - NOTNLM OT - body weight OT - diabetes OT - dulaglutide OT - scientometric analyses OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2024/11/27 06:20 MHDA- 2024/11/27 06:21 PMCR- 2024/10/27 CRDT- 2024/11/27 01:26 PHST- 2024/07/26 00:00 [received] PHST- 2024/10/19 00:00 [revised] PHST- 2024/10/23 00:00 [accepted] PHST- 2024/11/27 06:21 [medline] PHST- 2024/11/27 06:20 [pubmed] PHST- 2024/11/27 01:26 [entrez] PHST- 2024/10/27 00:00 [pmc-release] AID - medicina60111761 [pii] AID - medicina-60-01761 [pii] AID - 10.3390/medicina60111761 [doi] PST - epublish SO - Medicina (Kaunas). 2024 Oct 27;60(11):1761. doi: 10.3390/medicina60111761. PMID- 39592891 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - Why does GLP-1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP-1 agonist alone in obese adults without type 2 diabetes? PG - 1079-1095 LID - 10.1111/dom.16106 [doi] AB - Obesity is a chronic condition demanding effective treatment strategies, among which pharmacotherapy plays a critical role. As glucagon-like peptide-1 (GLP-1) agonist approved by the Food and Drug Administration (FDA) for long-term weight management in adults with obesity, liraglutide and semaglutide have great weight loss effect through reducing food intake and delaying gastric emptying. The emergence of unimolecular polypharmacology, which utilizes single molecules to simultaneously target multiple receptors or pathways, marked a revolutionary improvement in GLP-1-based obesity pharmacotherapy. The dual agonist tirzepatide activates both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors and has shown enhanced potency for weight loss compared to conventional GLP-1 mono agonist. Furthermore, emerging data suggests that unimolecular GLP-1/glucagon (GCG) dual agonist, as well as GLP-1/GIP/GCG triple agonist, may offer superior weight loss efficacy over GLP-1 agonist. This review summarizes the comprehensive mechanisms underlying the pronounced advantages of GLP-1/GIP dual agonist, GLP-1/GCG dual agonist and GLP-1/GIP/GCG triple agonist over GLP-1 mono agonist in weight reduction in obese adults without type 2 diabetes. A deeper understanding of these unimolecular multitargeting GLP-1-based agonists will provide insights for their clinical application and guide the development of new drugs for obesity treatment. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Jiang, Yuchen AU - Jiang Y AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. FAU - Zhu, Huijuan AU - Zhu H AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. FAU - Gong, Fengying AU - Gong F AUID- ORCID: 0000-0002-6361-3811 AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. LA - eng GR - 2022-I2M-2-002/the CAMS Innovation Fund for Medical Sciences (CIFMS)/ GR - 82270913/the National Natural Science Foundation of China/ GR - 7222137/the Beijing Natural Science Foundation/ GR - the National Key Clinical Specialty Capacity Improvement Project/ GR - 2023-PT320-10/the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ GR - pumch-2013-020/the PUMCH Foundation/ PT - Journal Article PT - Review DEP - 20241126 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - *Gastric Inhibitory Polypeptide/agonists MH - Liraglutide/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use MH - Drug Therapy, Combination MH - Tirzepatide MH - Receptors, Gastrointestinal Hormone/agonists MH - *Anti-Obesity Agents/therapeutic use MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide OTO - NOTNLM OT - GIP OT - GLP-1 OT - antiobesity drug OT - drug mechanism OT - glucagon OT - weight management EDAT- 2024/11/27 00:21 MHDA- 2025/02/07 00:20 CRDT- 2024/11/26 23:50 PHST- 2024/10/21 00:00 [revised] PHST- 2024/08/23 00:00 [received] PHST- 2024/10/29 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/11/27 00:21 [pubmed] PHST- 2024/11/26 23:50 [entrez] AID - 10.1111/dom.16106 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1079-1095. doi: 10.1111/dom.16106. Epub 2024 Nov 26. PMID- 39592207 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20250517 IS - 1468-3288 (Electronic) IS - 0017-5749 (Linking) VI - 74 IP - 3 DP - 2025 Feb 6 TI - Recent advances in incretin-based therapy for MASLD: from single to dual or triple incretin receptor agonists. PG - 487-497 LID - 10.1136/gutjnl-2024-334023 [doi] AB - Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed for the treatment of type 2 diabetes mellitus and obesity, they were one of the first drug classes to be examined in individuals with MASLD/MASH. Successful phase 2 randomised clinical trials with these agents have resulted in progression to phase 3 clinical trials (principally testing the long-term efficacy of subcutaneous semaglutide). Over the last few years, in addition to GLP-1RAs, newer agents with glucose-dependent insulinotropic peptide and/or glucagon receptor agonist functions have been tested, with increasing evidence from phase 2 randomised clinical trials of histological improvements in MASLD/MASH, as well as benefits on MASLD-related extrahepatic complications. Based on this background of evidence, single, dual or triple incretin receptor agonists are becoming an attractive and promising treatment option for MASLD or MASH, particularly in individuals with coexisting obesity or type 2 diabetes mellitus. In this narrative review, we examine the rapidly expanding body of clinical evidence supporting a role of incretin-based pharmacotherapies in delaying or reversing MASH progression. We also discuss the biology of incretins and the putative hepatoprotective mechanisms of incretin-based pharmacotherapies for managing MASLD or MASH. CI - (c) Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Targher, Giovanni AU - Targher G AUID- ORCID: 0000-0002-4325-3900 AD - Metabolic Diseases Research Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy giovanni.targher@univr.it. FAU - Mantovani, Alessandro AU - Mantovani A AUID- ORCID: 0000-0002-7271-6329 AD - Endocrinology and Metabolism, University of Verona Faculty of Medicine and Surgery, Verona, Italy. FAU - Byrne, Christopher D AU - Byrne CD AUID- ORCID: 0000-0001-6322-7753 AD - Southampton General Hospital, Southampton, UK. FAU - Tilg, Herbert AU - Tilg H AUID- ORCID: 0000-0002-4235-2579 AD - Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria. LA - eng PT - Journal Article PT - Review DEP - 20250206 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Fatty Liver/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - LIVER OT - NONALCOHOLIC STEATOHEPATITIS OT - PHARMACOTHERAPY COIS- Competing interests: HT is an associate editor of the journal, and GT is an editorial board member of the journal. The authors do not have other potential conflicts of interest to disclose. EDAT- 2024/11/27 00:21 MHDA- 2025/02/07 00:20 CRDT- 2024/11/26 21:03 PHST- 2024/10/03 00:00 [received] PHST- 2024/11/03 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/11/27 00:21 [pubmed] PHST- 2024/11/26 21:03 [entrez] AID - gutjnl-2024-334023 [pii] AID - 10.1136/gutjnl-2024-334023 [doi] PST - epublish SO - Gut. 2025 Feb 6;74(3):487-497. doi: 10.1136/gutjnl-2024-334023. PMID- 39588627 OWN - NLM STAT- MEDLINE DCOM- 20241126 LR - 20260127 IS - 1972-6481 (Electronic) IS - 1827-6806 (Linking) VI - 25 IP - 12 DP - 2024 Dec TI - [ANMCO Statement: semaglutide in cardio-nephro-metabolic disorders]. PG - 891-899 LID - 10.1714/4372.43702 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a pivotal therapeutic agent in the management of the cardio-renal-metabolic continuum. Initially developed for glycemic control in type 2 diabetes mellitus, its benefits extend far beyond glucose regulation. Clinical trials have demonstrated semaglutide's potential to reduce major adverse cardiovascular events, particularly in overweight/obese patients with high cardiovascular risk, as well as improving functional capacity in patients suffering from heart failure with preserved left ventricular function. Additionally, it has shown promise in improving renal outcomes, such as slowing the progression of albuminuria and reducing the risk of chronic kidney disease in diabetic populations. These effects are likely due to its multifaceted mechanisms, including anti-inflammatory properties, weight reduction, blood pressure lowering, and direct renal protection. This review synthesizes current evidence on semaglutide's role in the interrelated domains of cardiovascular, renal, and metabolic health. FAU - De Luca, Leonardo AU - De Luca L AD - S.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Fondazione IRCCS Policlinico San Matteo, Pavia. FAU - Bilato, Claudio AU - Bilato C AD - U.O.C. Cardiologia, Ospedali dell'Ovest Vicentino, Azienda ULSS 8 Berica, Vicenza. FAU - Navazio, Alessandro AU - Navazio A AD - S.O.C. Cardiologia Ospedaliera, Presidio Ospedaliero Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia - IRCCS, Reggio Emilia. FAU - Corda, Marco AU - Corda M AD - S.C. Cardiologia, Azienda Ospedaliera "G. Brotzu", Cagliari. FAU - Milli, Massimo AU - Milli M AD - Cardiologia Firenze 1, Ospedali S. Maria Nuova e Nuovo San Giovanni di Dio, Azienda USL Toscana Centro, Firenze. FAU - Scicchitano, Pietro AU - Scicchitano P AD - U.O. Cardiologia-UTIC, Ospedale "F. Perinei", Altamura (BA). FAU - Di Marco, Massimo AU - Di Marco M AD - U.O.C. Cardiologia-UTIC, Ospedale Santo Spirito, Pescara. FAU - Riccio, Carmine AU - Riccio C AD - U.O.S.D. Follow-up del Paziente Post-Acuto, Dipartimento Cardio-Vascolare, AORN Sant'Anna e San Sebastiano, Caserta. FAU - Geraci, Giovanna AU - Geraci G AD - U.O.C. Cardiologia, Ospedale Sant'Antonio Abate, Trapani. FAU - Iacovoni, Attilio AU - Iacovoni A AD - SSD Chirurgia dei Trapianti e del Trattamento Chirurgico dello Scompenso, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo. FAU - Pascale, Vittorio AU - Pascale V AD - UTIC-Emodinamica e Cardiologia Interventistica, Ospedale Civile Pugliese, Catanzaro. FAU - Tizzani, Emanuele AU - Tizzani E AD - Dipartimento di Cardiologia, Ospedale degli Infermi, Rivoli (TO). FAU - Gabrielli, Domenico AU - Gabrielli D AD - U.O.C. Cardiologia, Dipartimento di Scienza Cardio-Toraco-Vascolari, Azienda Ospedaliera San Camillo Forlanini, Roma. FAU - Grimaldi, Massimo AU - Grimaldi M AD - U.O.C. Cardiologia-UTIC, Ospedale Miulli, Acquaviva delle Fonti (BA). FAU - Colivicchi, Furio AU - Colivicchi F AD - U.O.C. Cardiologia Clinica e Riabilitativa, Presidio Ospedaliero San Filippo Neri - ASL Roma 1, Roma. FAU - Oliva, Fabrizio AU - Oliva F AD - Cardiologia 1-Emodinamica, Dipartimento Cardio-Toraco-Vascolare "A. De Gasperis", ASST Grande Ospedale Metropolitano Niguarda, Milano. LA - ita PT - English Abstract PT - Journal Article PT - Review TT - Statement ANMCO: la semaglutide nel continuum cardio-nefro-metabolico. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use MH - Metabolic Diseases/prevention & control/drug therapy MH - Obesity/complications/drug therapy MH - Kidney Diseases/prevention & control MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/11/26 06:35 MHDA- 2024/11/26 06:36 CRDT- 2024/11/26 04:53 PHST- 2024/11/26 06:36 [medline] PHST- 2024/11/26 06:35 [pubmed] PHST- 2024/11/26 04:53 [entrez] AID - 10.1714/4372.43702 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2024 Dec;25(12):891-899. doi: 10.1714/4372.43702. PMID- 39584713 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20260919 IS - 1522-1598 (Electronic) IS - 0022-3077 (Linking) VI - 133 IP - 1 DP - 2025 Jan 1 TI - Impact of glucagon-like peptide-1 receptor agonists on axonal function in diabetic peripheral neuropathy. PG - 14-21 LID - 10.1152/jn.00228.2024 [doi] AB - Diabetic peripheral neuropathy (DPN) affects approximately half of the 500 million people with type 2 diabetes worldwide. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) receptors in the peripheral nervous system may be a suitable target for DPN treatment. Fourteen participants were consecutively recruited after being prescribed either semaglutide or dulaglutide as part of standard clinical care for type 2 diabetes. Participants underwent clinical assessment, nerve conduction studies, and axonal excitability assessment at baseline and at 3 mo following commencement of GLP-1 receptor agonist (GLP-1RA) therapy. These data were combined with 10 participants who had previously received exenatide therapy, and mathematical modeling of excitability data was undertaken. Clinical neuropathy scores improved at 3 mo following commencement of GLP-1 (baseline TNS 3.7 +/- 4.5, posttreatment TNS 2.3 +/- 3.4, P = 0.005). Nerve conduction studies demonstrated an improvement in sural amplitude at 3 mo (baseline 11.9 +/- 8.5 muV, posttreatment 14.2 +/- 9.2 muV; P = 0.013). Axonal excitability studies revealed changes consistent with improvements in Na(+)/K(+)-ATPase pump function and Na(+) permeability, and this was supported by mathematical modeling. GLP-1RA therapy improves clinical and neurophysiological outcomes in DPN. Treatment with GLP-1RA may reverse axonal dysfunction by improving Na(+)/K(+)-ATPase pump function.NEW & NOTEWORTHY Diabetic peripheral neuropathy is known to be relentlessly progressive and irreversible. Prospective studies in 24 participants with diabetic peripheral neuropathy (DPN) treated with glucagon-like peptide-1 receptor agonists (GLP-1RA) demonstrated improvements in clinical neuropathy scores, nerve conduction studies, and axonal excitability recordings. Analysis of axonal excitability recordings revealed the mechanism for GLP-1RA improvement in DPN were changed consistent with improvements in Na(+)/K(+)-ATPase pump function, and this was supported by mathematical modeling. CI - Copyright (c) 2025 The Authors. FAU - Dhanapalaratnam, Roshan AU - Dhanapalaratnam R AUID- ORCID: 0000-0002-7684-0976 AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. AD - Department of Neurology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Issar, Tushar AU - Issar T AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Poynten, Ann M AU - Poynten AM AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Milner, Kerry-Lee AU - Milner KL AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Kwai, Natalie C G AU - Kwai NCG AD - School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia. FAU - Krishnan, Arun V AU - Krishnan AV AUID- ORCID: 0000-0001-8883-8825 AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. AD - Department of Neurology, Prince of Wales Hospital, Sydney, New South Wales, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241125 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetic Neuropathies/drug therapy/physiopathology MH - Male MH - Female MH - Middle Aged MH - *Axons/drug effects/physiology MH - Aged MH - *Neural Conduction/drug effects MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/analogs & derivatives MH - Immunoglobulin Fc Fragments/pharmacology/administration & dosage MH - Recombinant Fusion Proteins/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Hypoglycemic Agents/pharmacology MH - Sodium-Potassium-Exchanging ATPase/metabolism MH - Exenatide/pharmacology/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - axonal excitability OT - diabetes OT - glucagon-like peptide-1 OT - glucagon-like peptide-1 receptor agonist OT - peripheral nerve OT - peripheral neuropathy EDAT- 2024/11/25 12:31 MHDA- 2024/12/23 12:21 CRDT- 2024/11/25 08:13 PHST- 2024/12/23 12:21 [medline] PHST- 2024/11/25 12:31 [pubmed] PHST- 2024/11/25 08:13 [entrez] AID - 10.1152/jn.00228.2024 [doi] PST - ppublish SO - J Neurophysiol. 2025 Jan 1;133(1):14-21. doi: 10.1152/jn.00228.2024. Epub 2024 Nov 25. PMID- 39583077 OWN - NLM STAT- MEDLINE DCOM- 20241125 LR - 20261022 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 12 DP - 2024 TI - Benchmarking the medication efficiency and technological progress of diabetes drugs. PG - 1396832 LID - 10.3389/fpubh.2024.1396832 [doi] LID - 1396832 AB - BACKGROUND: Diabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments' benefits and harms. OBJECTIVE: This study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency. METHODS: To derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications. RESULTS: The paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness. CI - Copyright (c) 2024 Zhang, Wang, Xu, Liu, Ban, Liu, Yan and Han. FAU - Zhang, Hongwei AU - Zhang H AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Chen AU - Wang C AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xu, Ting AU - Xu T AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Liu, Lin AU - Liu L AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ban, Xuyan AU - Ban X AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Liu, Weijie AU - Liu W AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Yan, Chenli AU - Yan C AD - Technological Economics and Management, School of Business Administration, Capital University of Economics and Business, Beijing, China. FAU - Han, Xiaodong AU - Han X AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20241108 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Benchmarking MH - United States MH - United States Food and Drug Administration PMC - PMC11582034 OTO - NOTNLM OT - DEA OT - diabetes OT - directional distance model OT - efficiency change OT - frontier OT - medication efficiency OT - technological progress COIS- The author(s) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/11/25 11:34 MHDA- 2024/11/25 11:35 PMCR- 2024/11/08 CRDT- 2024/11/25 05:06 PHST- 2024/03/06 00:00 [received] PHST- 2024/10/23 00:00 [accepted] PHST- 2024/11/25 11:35 [medline] PHST- 2024/11/25 11:34 [pubmed] PHST- 2024/11/25 05:06 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - 10.3389/fpubh.2024.1396832 [doi] PST - epublish SO - Front Public Health. 2024 Nov 8;12:1396832. doi: 10.3389/fpubh.2024.1396832. eCollection 2024. PMID- 39582250 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260618 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 40 IP - 1 DP - 2025 Feb TI - Metabolic Consequences of Glucagon-Like Peptide-1 Receptor Agonist Shortage: Deterioration of Glycemic Control in Type 2 Diabetes. PG - 156-160 LID - 10.3803/EnM.2024.2150 [doi] AB - In the context of a global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, we assessed the impact of discontinuing dulaglutide on metabolic control in individuals with type 2 diabetes. Our analysis included data from 69 individuals and revealed a significant deterioration in glycemic control following the discontinuation. Specifically, the average hemoglobin A1c level increased from 7.0%+/-0.9% to 8.1%+/-1.4% (P<0.001), and fasting glucose levels rose from 129+/-31 to 156+/-50 mg/dL (P<0.001) within 3 months after stopping the medication. Alternative treatments such as dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporter- 2 inhibitors were insufficient substitutes, highlighting the essential role of continuous GLP-1 receptor agonist therapy in maintaining metabolic health. FAU - Choe, Hun Jee AU - Choe HJ AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea. FAU - Nauck, Michael A AU - Nauck MA AD - Institute of Clinical Chemistry and Laboratory Medicine, University Greifswald, Greifswald, Germany. AD - Diabetes, Endocrinology, Metabolism Section, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr-University, Bochum, Germany. FAU - Moon, Joon Ho AU - Moon JH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. LA - eng PT - Journal Article DEP - 20241125 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Recombinant Fusion Proteins) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - *Glycemic Control MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/supply & distribution MH - Blood Glucose/analysis/drug effects MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/supply & distribution MH - Glycated Hemoglobin/analysis MH - Aged MH - *Recombinant Fusion Proteins/therapeutic use/supply & distribution PMC - PMC11898308 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Glycemic control COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2024/11/25 11:34 MHDA- 2025/02/28 06:21 PMCR- 2025/02/01 CRDT- 2024/11/25 02:15 PHST- 2024/08/19 00:00 [received] PHST- 2024/10/07 00:00 [accepted] PHST- 2025/02/28 06:21 [medline] PHST- 2024/11/25 11:34 [pubmed] PHST- 2024/11/25 02:15 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - EnM.2024.2150 [pii] AID - enm-2024-2150 [pii] AID - 10.3803/EnM.2024.2150 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2025 Feb;40(1):156-160. doi: 10.3803/EnM.2024.2150. Epub 2024 Nov 25. PMID- 39581734 OWN - NLM STAT- MEDLINE DCOM- 20241124 LR - 20250103 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 14 IP - 11 DP - 2024 Nov 24 TI - Effectiveness of glucagon-like peptide-1 receptor agonists for reduction of body mass index and blood glucose control in patients with type 2 diabetes mellitus and obesity: A retrospective cohort study and difference-in-difference analysis. PG - e086424 LID - 10.1136/bmjopen-2024-086424 [doi] LID - e086424 AB - OBJECTIVE: This study aimed to evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) in reducing body mass index (BMI) and blood glucose levels in individuals with type 2 diabetes mellitus (T2DM) using the difference-in-differences (DID) technique. RESEARCH DESIGN AND METHODS: This retrospective cohort study included patients with T2DM, receiving GLP1-RA or other second-line antidiabetic treatments between 2010 and 2023. A linear mixed-effect regression with heterogeneous augmented inverse probability weighting DID analysis was used to compare the effectiveness of GLP-1RA and other second-line treatments in reducing BMI, fasting plasma glucose (FPG) and haemoglobin A1C (HbA1c) in patients with T2DM. An average treatment effect on the treated (ATET) for each outcome was estimated. RESULTS: 1000 patients with T2DM (GLP-1RA=220, non-GLP-1RA=880) were included. Compared with other second-line drugs, GLP-1RA significantly reduced BMI by approximately 1.02 kg/m(2) (95% CI -1.46 to -0.58) over 24 months of treatment. Additionally, GLP-1RA significantly decreased FPG and HbA1c levels, compared with other second-line treatments with overall ATETs (95% CI) of -21.34 mg/dL (-29.53 to -13.15) and -0.58% (-0.77% to -0.38%), respectively. CONCLUSIONS: Our results indicate that patients with T2DM treated with GLP-1RA had a significantly greater reduction in BMI, FPG and HbA1C levels compared with those receiving other second-line antidiabetic therapies. As such, GLP-1RA might be considered the preferred treatment for obese patients with T2DM who fail to sufficiently respond to metformin monotherapy. CI - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Siriyotha, Sukanya AU - Siriyotha S AD - Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. FAU - Anothaisintawee, Thunyarat AU - Anothaisintawee T AUID- ORCID: 0000-0003-1002-8536 AD - Department of Family Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand thunyarat.ano@mahidol.ac.th. FAU - Looareesuwan, Panu AU - Looareesuwan P AD - Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. FAU - Nimitphong, Hataikarn AU - Nimitphong H AD - Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. FAU - McKay, Gareth J AU - McKay GJ AUID- ORCID: 0000-0001-8197-6280 AD - Centre for Public Health, Queen's University Belfast, Northern Ireland, UK. FAU - Attia, John AU - Attia J AUID- ORCID: 0000-0001-9800-1308 AD - Division of Medicine, John Hunter Hospital, New Lambton, New South Wales, Australia. FAU - Thakkinstian, Ammarin AU - Thakkinstian A AD - Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. LA - eng PT - Journal Article DEP - 20241124 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Body Mass Index MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy/complications MH - *Blood Glucose/drug effects/metabolism MH - *Glycated Hemoglobin/analysis MH - Aged MH - Glycemic Control/methods MH - Treatment Outcome MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11590856 OTO - NOTNLM OT - Body Mass Index OT - Diabetes Mellitus, Type 2 OT - Obesity COIS- Competing interests: None declared. EDAT- 2024/11/25 01:25 MHDA- 2024/11/25 01:26 PMCR- 2024/11/24 CRDT- 2024/11/24 21:23 PHST- 2024/11/25 01:26 [medline] PHST- 2024/11/25 01:25 [pubmed] PHST- 2024/11/24 21:23 [entrez] PHST- 2024/11/24 00:00 [pmc-release] AID - bmjopen-2024-086424 [pii] AID - 10.1136/bmjopen-2024-086424 [doi] PST - epublish SO - BMJ Open. 2024 Nov 24;14(11):e086424. doi: 10.1136/bmjopen-2024-086424. PMID- 39580054 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 65 IP - 1 DP - 2025 Jan-Feb TI - An analysis of national news coverage of semaglutide for weight loss. PG - 102297 LID - S1544-3191(24)00328-5 [pii] LID - 10.1016/j.japh.2024.102297 [doi] AB - BACKGROUND: Glucagon-like peptide 1 (GLP-1) agonists like semaglutide have risen significantly in use in recent years as a therapeutic option for the management of obesity. Popular media serves as an information source for many patients, and depending on the content, may influence how a patient views a particular therapy. OBJECTIVE: To describe the content of online/print news articles published about semaglutide for weight loss. METHODS: Online websites and databases were used to access 8 major U.S. online/print news outlets, including the New York Times, Wall Street Journal, Washington Post, USA Today, Fox News, CNN, ABC News, and CBS News. Sources were searched for articles focusing on semaglutide and weight loss published in 2023. Articles were excluded if they focused on: (1) type 2 diabetes, (2) company press releases, or were (3) videos or transcripts of oral broadcasts/podcasts. A random sample of articles was chosen with equitable distribution across sources. Articles were assessed for the presence of data across 9 domains and 30 different content codes, stratified by news source. RESULTS: A total of 127 articles were analyzed, split almost equally between print (n = 63) and online (n = 64) sources. The vast majority of articles were news articles/analyses (122; 96.1%). The most popular primary focus of articles were social/popular aspects of GLP-1 agonists (22; 17.3%), followed by basic medication information (20; 15.8%), harms of the medication (20; 15.8%), and benefits of the medication (17; 13.4%). Print sources were more likely to report on the cash price (55.6% Vs. 28.1%, P = 0.002), lack of insurance (61.9% Vs. 21.9%, P < 0.001), and cost-effectiveness (11.1% Vs. 1.6%, P = 0.027) of the medication compared to online sources. CONCLUSION: Online/print news articles regarding semaglutide for weight loss provide a variety of information about the medication, commonly focusing on social aspects of treatment. CI - Copyright (c) 2024 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Gionfriddo, Michael R AU - Gionfriddo MR FAU - Owens, Katelyn M AU - Owens KM FAU - Banks, Hannah AU - Banks H FAU - Sherigar, Anwitha AU - Sherigar A FAU - Covvey, Jordan R AU - Covvey JR LA - eng PT - Journal Article DEP - 20241122 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Loss/drug effects MH - *Obesity/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - United States MH - *Mass Media/statistics & numerical data MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosure The authors declare no relevant conflicts of interest or financial relationships. EDAT- 2024/11/24 00:44 MHDA- 2025/02/20 00:21 CRDT- 2024/11/23 19:16 PHST- 2024/09/13 00:00 [received] PHST- 2024/11/07 00:00 [revised] PHST- 2024/11/14 00:00 [accepted] PHST- 2025/02/20 00:21 [medline] PHST- 2024/11/24 00:44 [pubmed] PHST- 2024/11/23 19:16 [entrez] AID - S1544-3191(24)00328-5 [pii] AID - 10.1016/j.japh.2024.102297 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2025 Jan-Feb;65(1):102297. doi: 10.1016/j.japh.2024.102297. Epub 2024 Nov 22. PMID- 39571323 OWN - NLM STAT- MEDLINE DCOM- 20241214 LR - 20260618 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 35 IP - 1 DP - 2025 Jan TI - Adverse event reporting of combining SGLT2 inhibitor and GLP1 receptor agonist: A real-world study from FAERS. PG - 103758 LID - S0939-4753(24)00377-6 [pii] LID - 10.1016/j.numecd.2024.09.028 [doi] AB - BACKGROUND AND AIMS: We evaluate whether the combination of sodium-glucose cotransporter-2 inhibitor(SGLT2i) and glucagon-like peptide-1 receptor agonist(GLP1RA) disproportionally increases the reporting of adverse events compared with SGLT2i or GLP1RA monotherapy in the FDA adverse event reporting system (FAERS). METHODS AND RESULTS: Adverse events related to SGLT2i and GLP1RA were screened and selected, then data from the FAERS was underwent thorough disproportionality analysis. The proportional reporting ratio(PRR) of SGLT2i-related adverse events were compared between patients using SGLT2i alone and those using both SGLT2i and GLP1RA. Similarly, the PRR of GLP1RA-related adverse events were compared between patients using GLP1RA alone and those using both SGLT2i and GLP1RA. The results showed that the PRR of SGLT2i-related adverse events including diabetic ketoacidosis(DKA), ketosis, reproductive tract adverse events, urinary tract infection, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using SGLT2i alone, and the signal of fracture was not detected. Likewise, the PRR of GLP1RA-related adverse events including gastrointestinal adverse events, gallbladder and biliary tract disease, pancreatitis, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using GLP1RA alone, the PRR of hyperlipasaemia and hyperamylasaemia increased in the combination therapy and no signal of depression, suicidal and self-injurious behaviour was detected. CONCLUSION: Adverse events reporting are not disproportionally higher among those using both SGLT-2i and GLP1RA compared with SGLT2i or GLP1RA monotherapy. CI - Copyright (c) 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Tian, Chunyan AU - Tian C AD - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2863219917@qq.com. FAU - Yang, Zheng AU - Yang Z AD - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhao, Subei AU - Zhao S AD - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhang, Ping AU - Zhang P AD - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Rong AU - Li R AD - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: rongli@hospital.cqmu.edu.cn. LA - eng PT - Comparative Study PT - Journal Article DEP - 20240927 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - *Adverse Drug Reaction Reporting Systems MH - United States/epidemiology MH - Male MH - Female MH - *United States Food and Drug Administration MH - Risk Factors MH - Middle Aged MH - Incretins/adverse effects/therapeutic use MH - Risk Assessment MH - Treatment Outcome MH - Databases, Factual MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Pharmacovigilance MH - Hypoglycemic Agents/adverse effects MH - Adult MH - Time Factors MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Adverse events OT - Combination therapy OT - FAERS OT - GLP1RA OT - Pharmacovigilance OT - SGLT2i COIS- Declaration of competing interest No potential conflicts of interest relevant to this article were reported. EDAT- 2024/11/22 00:22 MHDA- 2024/12/15 00:42 CRDT- 2024/11/21 18:05 PHST- 2024/04/12 00:00 [received] PHST- 2024/08/15 00:00 [revised] PHST- 2024/09/26 00:00 [accepted] PHST- 2024/12/15 00:42 [medline] PHST- 2024/11/22 00:22 [pubmed] PHST- 2024/11/21 18:05 [entrez] AID - S0939-4753(24)00377-6 [pii] AID - 10.1016/j.numecd.2024.09.028 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2025 Jan;35(1):103758. doi: 10.1016/j.numecd.2024.09.028. Epub 2024 Sep 27. PMID- 39569871 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20250517 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 2 DP - 2025 Feb TI - Enhanced renoprotective effects of combined glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus: Real-world evidence. PG - 204-214 LID - 10.1111/jdi.14361 [doi] AB - INTRODUCTION: Developing a more effective treatment for the global impact of diabetic kidney disease is crucial. This study examined the renoprotective effects of combining glucagon-like peptide-1 receptor agonists (GLP-1 RA) with sodium-glucose cotransporter 2 inhibitors (SGLT2i) compared to SGLT2is alone in type 2 diabetes (DM). MATERIALS AND METHODS: This retrospective cohort study used data from the TriNetX Global Collaborative Network. Type 2 DM patients with estimated glomerular filtration rates >/=60 mL/min/1.73 m(2) who used GLP-1 RA or SGLT2i between January 1, 2013, and December 31, 2023. Propensity score matching balanced baseline characteristics, resulting in 71,186 patients in each group (combined GLP-1 RA and SGLT2i therapy vs SGLT2i alone). Cox regression model was adopted to compare outcomes over a 5-year period, including major adverse kidney events (MAKE), acute kidney injury (AKI), end-stage kidney disease (ESKD), and all-cause mortality. RESULTS: After matching, the average age was 57.1 +/- 10.8 years for the GLP-1 RA plus SGLT2i group and 57.2 +/- 11.7 years for the SGLT2i-only group. The GLP-1 RA plus SGLT2i group had significantly lower risk of MAKE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.69-0.77), AKI (HR: 0.82, 95% C0I: 0.77-0.87), ESKD (HR: 0.61, 95% CI: 0.47-0.78), and all-cause mortality (HR: 0.54, 95% CI: 0.50-0.58) compared to the SGLT2i-only group. Moreover, subgroup analyses showed consistent benefits across different subgroups. CONCLUSIONS: Dual therapy with GLP-1 RA and SGLT2i is supported to enhance renal outcomes and address the growing burden of diabetic kidney disease. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Jhu, Jian-Yu AU - Jhu JY AD - Division of Endocrinology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Fang, Yu-Wei AU - Fang YW AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Huang, Chung-Yen AU - Huang CY AD - Division of Endocrinology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Liou, Hung-Hsiang AU - Liou HH AD - Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan. FAU - Chen, Mon-Ting AU - Chen MT AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. FAU - Tsai, Ming-Hsien AU - Tsai MH AUID- ORCID: 0000-0003-3561-4689 AD - Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. AD - Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. LA - eng GR - 2023SKHADR036/Shin Kong Wu Ho-Su Memorial Hospital/ PT - Journal Article DEP - 20241121 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Middle Aged MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetic Nephropathies/prevention & control/etiology MH - Aged MH - Drug Therapy, Combination MH - Glomerular Filtration Rate MH - *Hypoglycemic Agents/therapeutic use MH - Follow-Up Studies MH - Acute Kidney Injury/prevention & control MH - Prognosis PMC - PMC11786168 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse kidney events OT - Sodium-glucose cotransporter 2 inhibitors COIS- There are no relevant conflicts of interest to disclose. Approval of the research protocol: This study was approved by Shin Kong Wu Ho-Su Memorial Hospital's Ethics Review Board. Informed consent: The informed consent was waived by Shin Kong Wu Ho-Su Memorial Hospital's Ethics Review Board because all personal information was deidentified in this study. Approval date of registry and the registration no. of the study/trial: The approval date is August 2, 2024, and the Protocol number is 20240728R. Animal studies: N/A. EDAT- 2024/11/21 12:24 MHDA- 2025/02/01 20:43 PMCR- 2024/11/21 CRDT- 2024/11/21 08:03 PHST- 2024/10/28 00:00 [revised] PHST- 2024/08/18 00:00 [received] PHST- 2024/11/10 00:00 [accepted] PHST- 2025/02/01 20:43 [medline] PHST- 2024/11/21 12:24 [pubmed] PHST- 2024/11/21 08:03 [entrez] PHST- 2024/11/21 00:00 [pmc-release] AID - JDI14361 [pii] AID - 10.1111/jdi.14361 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Feb;16(2):204-214. doi: 10.1111/jdi.14361. Epub 2024 Nov 21. PMID- 39568409 OWN - NLM STAT- MEDLINE DCOM- 20241210 LR - 20260127 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 166 IP - 1 DP - 2024 Nov 26 TI - Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility. LID - 10.1210/endocr/bqae155 [doi] LID - bqae155 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (eg, hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Jalleh, Ryan J AU - Jalleh RJ AUID- ORCID: 0000-0003-4969-4771 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Marathe, Chinmay S AU - Marathe CS AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Rayner, Christopher K AU - Rayner CK AUID- ORCID: 0000-0003-2950-343X AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. FAU - Jones, Karen L AU - Jones KL AUID- ORCID: 0000-0002-1155-5816 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Umapathysivam, Mahesh M AU - Umapathysivam MM AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Southern Adelaide Diabetes and Endocrine Service, Flinders Medical Centre, Bedford Park, SA 5042, Australia. FAU - Wu, Tongzhi AU - Wu T AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Quast, Daniel R AU - Quast DR AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany. FAU - Plummer, Mark P AU - Plummer MP AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. FAU - Horowitz, Michael AU - Horowitz M AUID- ORCID: 0000-0002-0942-0306 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. LA - eng PT - Journal Article PT - Review PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1 MH - *Gastrointestinal Motility/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Gastric Emptying/drug effects MH - Incretins/therapeutic use/pharmacology MH - Biliary Tract/drug effects/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11630531 OTO - NOTNLM OT - biliary OT - gastric emptying OT - glucagon-like peptide-1 OT - hypoglycemia OT - physiology OT - small intestinal motility EDAT- 2024/11/21 06:20 MHDA- 2024/12/11 00:23 PMCR- 2024/11/21 CRDT- 2024/11/21 04:13 PHST- 2024/07/02 00:00 [received] PHST- 2024/12/11 00:23 [medline] PHST- 2024/11/21 06:20 [pubmed] PHST- 2024/11/21 04:13 [entrez] PHST- 2024/11/21 00:00 [pmc-release] AID - 7906037 [pii] AID - bqae155 [pii] AID - 10.1210/endocr/bqae155 [doi] PST - ppublish SO - Endocrinology. 2024 Nov 26;166(1):bqae155. doi: 10.1210/endocr/bqae155. PMID- 39568391 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - One or two? Comparison of the cardiorenal effects between combination therapy and monotherapy with SGLT2i or GLP1RA. PG - 806-815 LID - 10.1111/dom.16078 [doi] AB - OBJECTIVE: This study aimed to evaluate the cardiorenal effect of combining sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) when compared with monotherapy of either agent in patients with type 2 diabetes (T2D). METHODS: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were systematically searched from inception to June 2024. Eligible studies included randomised controlled trials and observational studies assessing that compared with SGLT2i or GLP-1RA monotherapy, the risk of cardiorenal outcomes in patients with T2D who treated with combination therapy. Pooled relative risk (RR) and 95% confidence intervals (CIs) were computed in random-effects model. RESULTS: In all, five RCTs, 10 post hoc analyses and one observational study were included. The reduced risk of the composite cardiovascular outcome was observed in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.57, 95% CI 0.38-0.86, p = 0.008) or GLP-1RA monotherapy (RR = 0.77, 95% CI 0.65-0.91, p = 0.002). Likewise, the composite renal adverse events were less frequent in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.69, 95% CI 0.59-0.82, p < 0.001) or GLP-1RA monotherapy (RR = 0.66, 95% CI 0.53-0.83, p < 0.001). Compared with GLP-1RA monotherapy, the combination therapy of SGLT2i and GLP-1RA was associated with lower risks of heart failure-related outcomes (RR = 0.63, 95% CI 0.51-0.77, p < 0.001) and all-cause mortality (RR = 0.66, 95% CI 0.50-0.88, p = 0.004) in patients with T2D. CONCLUSION: The cardiorenal benefits might be magnified with the combination therapy of SGLT2i and GLP-1RA when compared with monotherapy of either agent. Further investigations are needed to validate the findings. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Zhang, Mengqing AU - Zhang M AUID- ORCID: 0009-0006-0104-0890 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lin, Chu AU - Lin C AUID- ORCID: 0000-0002-2365-9831 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Cai, Xiaoling AU - Cai X AUID- ORCID: 0000-0002-7881-0543 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Jiao, Ruoyang AU - Jiao R AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Bai, Shuzhen AU - Bai S AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Li, Zonglin AU - Li Z AUID- ORCID: 0000-0002-8949-9455 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lv, Fang AU - Lv F AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Wenjia AU - Yang W AUID- ORCID: 0000-0003-0610-5121 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Liu, Geling AU - Liu G AD - Department of Endocrinology (Section 1), Tangshan Gongren Hospital, Tangshan, China. FAU - Yang, Xiaolin AU - Yang X AD - Department of Endocrinology (Section 1), Tangshan Gongren Hospital, Tangshan, China. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. LA - eng GR - 81970698/National Natural Science Foundation of China/ GR - 81970708/National Natural Science Foundation of China/ GR - 7202216/Natural Science Foundation of Beijing Municipality/ PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241121 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Therapy, Combination MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Cardiovascular Diseases/prevention & control/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RA OT - SGLT2i OT - cardiorenal benefit OT - combination therapy EDAT- 2024/11/21 06:21 MHDA- 2025/01/07 00:21 CRDT- 2024/11/21 03:59 PHST- 2024/10/25 00:00 [revised] PHST- 2024/08/19 00:00 [received] PHST- 2024/11/03 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/11/21 06:21 [pubmed] PHST- 2024/11/21 03:59 [entrez] AID - 10.1111/dom.16078 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):806-815. doi: 10.1111/dom.16078. Epub 2024 Nov 21. PMID- 39561332 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260721 IS - 1939-327X (Electronic) IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 74 IP - 2 DP - 2025 Feb 1 TI - Activation of the HPA Axis Does Not Explain Nonresponsiveness to GLP-1R Agonist Treatment in Individuals With Type 2 Diabetes. PG - 212-222 LID - 10.2337/db24-0463 [doi] AB - It is unclear why some individuals with type 2 diabetes are unresponsive to treatment with glucagon-like peptide 1 receptor (GLP-1R) agonists, but hypothalamic-pituitary-adrenal (HPA) axis activation could play a role. We used [68Ga]Ga-NODAGA-exendin-4 positron emission tomography/computed tomography to compare pituitary GLP-1R expression between responders and nonresponders to treatment with GLP-1R agonists. Pituitary GLP-1R expression and HPA axis activation did not differ between responders and nonresponders to GLP-1R agonist treatment. In addition, pituitary radiolabeled exendin uptake was markedly higher in men than in women. Further study is required to explain treatment differences and understand sex differences in pituitary radiolabeled exendin uptake. CI - (c) 2024 by the American Diabetes Association. FAU - Tokgoz, Sevilay AU - Tokgoz S AUID- ORCID: 0009-0009-7597-8170 AD - Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Boss, Marti AU - Boss M AD - Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Netherlands Heart Institute, Utrecht, the Netherlands. FAU - Jansen, Theodorus J P AU - Jansen TJP AD - Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Meijer, Rick AU - Meijer R AD - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Frielink, Cathelijne AU - Frielink C AD - Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - van Bon, Arianne C AU - van Bon AC AD - Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands. FAU - Tack, Cees J AU - Tack CJ AD - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - de Galan, Bastiaan E AU - de Galan BE AD - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands. AD - Cardiovascular Research Institute Maastricht School for Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands. FAU - Gotthardt, Martin AU - Gotthardt M AD - Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands. LA - eng GR - 459001019/Diabetes Fonds/ GR - ZONMW_/ZonMw/Netherlands PT - Journal Article PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/diagnostic imaging MH - Male MH - *Hypothalamo-Hypophyseal System/drug effects/metabolism/diagnostic imaging MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pituitary-Adrenal System/drug effects/metabolism/diagnostic imaging MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Exenatide MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Aged MH - Positron Emission Tomography Computed Tomography MH - Pituitary Gland/metabolism/diagnostic imaging/drug effects PMC - PMC11755685 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2024/11/19 18:22 MHDA- 2025/01/22 05:33 PMCR- 2024/11/19 CRDT- 2024/11/19 16:32 PHST- 2024/06/04 00:00 [received] PHST- 2024/11/13 00:00 [accepted] PHST- 2025/01/22 05:33 [medline] PHST- 2024/11/19 18:22 [pubmed] PHST- 2024/11/19 16:32 [entrez] PHST- 2024/11/19 00:00 [pmc-release] AID - 157480 [pii] AID - 240463 [pii] AID - 10.2337/db24-0463 [doi] PST - ppublish SO - Diabetes. 2025 Feb 1;74(2):212-222. doi: 10.2337/db24-0463. PMID- 39557200 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260416 IS - 1097-6779 (Electronic) IS - 0016-5107 (Linking) VI - 101 IP - 5 DP - 2025 May TI - Quality of bowel preparation for colonoscopy in patients on glucagon-like peptide-1 receptor agonists. PG - 1068-1072.e1 LID - S0016-5107(24)03734-9 [pii] LID - 10.1016/j.gie.2024.11.024 [doi] AB - BACKGROUND AND AIMS: We aimed to assess the quality of bowel preparation in a matched cohort of patients actively using and not using glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in a large health system in the United States. METHODS: We performed a retrospective review of adult patients undergoing colonoscopy in 22 endoscopy units across 18 sites in the United States. RESULTS: Our cohort comprised 6235 patients (3344 case patients and 2891 control patients). Baseline variables causing suboptimal bowel preparation were setting of procedure (inpatient), sex (male), body mass index (higher), type 2 diabetes mellitus, inflammatory bowel disease, opioid medications, heart failure, and cirrhosis. Total Boston Bowel Preparation Scale was significantly higher in control patients even after controlling for the mentioned variables (P < .01). Case patients were significantly more likely to meet the definition of inadequate bowel preparation. There was no significant difference between different classes of GLP-1 RAs. CONCLUSIONS: Patients using GLP-1 RAs are more likely to have inadequate bowel preparation during colonoscopy, even accounting for other comorbidities. CI - Copyright (c) 2025 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved. FAU - Gala, Khushboo AU - Gala K AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Tome, June AU - Tome J AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Krall, Mary AU - Krall M AD - Division of Health Care Delivery Research, Mayo Clinic, Rochester, Minnesota, USA. FAU - Tian, Devin AU - Tian D AD - Division of Health Care Delivery Research, Mayo Clinic, Rochester, Minnesota, USA. FAU - League, John B AU - League JB AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Vargas, Eric J AU - Vargas EJ AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Pardi, Darrell S AU - Pardi DS AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Johnson, Amanda M AU - Johnson AM AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Coelho-Prabhu, Nayantara AU - Coelho-Prabhu N AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: coelhoprabhu.nayantara@mayo.edu. LA - eng PT - Journal Article DEP - 20241116 PL - United States TA - Gastrointest Endosc JT - Gastrointestinal endoscopy JID - 0010505 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cathartics) RN - 0 (Analgesics, Opioid) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Colonoscopy/methods MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Cathartics MH - Diabetes Mellitus, Type 2/drug therapy MH - Adult MH - United States MH - Analgesics, Opioid/therapeutic use MH - Inflammatory Bowel Diseases MH - Case-Control Studies MH - *Hypoglycemic Agents/therapeutic use COIS- Disclosure All authors disclosed no financial relationships. EDAT- 2024/11/19 00:22 MHDA- 2025/04/26 16:09 CRDT- 2024/11/18 19:24 PHST- 2024/04/21 00:00 [received] PHST- 2024/10/05 00:00 [revised] PHST- 2024/11/10 00:00 [accepted] PHST- 2025/04/26 16:09 [medline] PHST- 2024/11/19 00:22 [pubmed] PHST- 2024/11/18 19:24 [entrez] AID - S0016-5107(24)03734-9 [pii] AID - 10.1016/j.gie.2024.11.024 [doi] PST - ppublish SO - Gastrointest Endosc. 2025 May;101(5):1068-1072.e1. doi: 10.1016/j.gie.2024.11.024. Epub 2024 Nov 16. PMID- 39556224 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250722 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 7 DP - 2025 Jul TI - Fracture events associated with GLP-1 receptor agonists in FDA adverse events reporting system. PG - 1009-1021 LID - 10.1007/s00592-024-02415-w [doi] AB - AIMS: Diabetes patients are at a higher risk of fractures, and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to positively impact on bone metabolism. We aim to provide a comprehensive assessment of fracture events associated with GLP-1RAs based on pharmacovigilance data. METHODS: In this study, fracture-related adverse events (AEs) associated with GLP-1RAs and other commonly used glucose-lowering drugs were identified from Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2022). The reporting odds ratio (ROR) and adjusted ROR (adj. ROR) were used to compare the reporting of fracture-related AEs associated with insulin, GLP-1RAs, and Non GLP-1RAs, in patients with diabetes through two scenarios. This involved separately comparing each glucose-lowering drug to all other medications used in diabetic patients and reiterating after excluding insulin cases. RESULTS: A total of 490,107 AE reports for patients with diabetes were identified and 98, 625 of them were for GLP-1RAs. Among all diabetes drugs, GLP-1RAs had the lowest reporting of any fracture-related AEs [adj. ROR = 0.44 (0.40-0.47)], consistent across osteoporotic fracture [adj. ROR = 0.39 (0.34-0.45)] and hip fracture [adj. ROR = 0.34 (0.28-0.41)]. Among GLP-1RA agents, albiglutide was associated with the lowest adj. ROR [0.11 (0.05-0.21)] for any fracture-related AEs. After excluded all insulin reports, GLP-1RAs retained a significantly lower adj. ROR towards any fracture [adj. ROR = 0.45 (0.40-0.50)], osteoporotic fracture [adj. ROR = 0.44 (0.37-0.52)], and hip fracture [adj. ROR = 0.43 (0.33-0.54)]. CONCLUSION: In a real-world pharmacovigilance setting, GLP-1RAs were associated with lower reporting of fracture-related AEs, indicating the protective effect of GLP-1RAs against fractures. CI - (c) 2024. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Xiao, Yao AU - Xiao Y AD - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China. FAU - Zhou, Min AU - Zhou M AD - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China. FAU - Xiao, Wenfeng AU - Xiao W AUID- ORCID: 0009-0008-9385-4609 AD - Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China. Xiaowf11@sina.com. AD - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, 410008, Hunan, China. Xiaowf11@sina.com. LA - eng PT - Journal Article DEP - 20241118 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - United States Food and Drug Administration MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States/epidemiology MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Fractures, Bone/epidemiology/chemically induced MH - Male MH - Female MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Middle Aged MH - Pharmacovigilance MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Diabetes OT - FAERS OT - Fracture OT - GLP-1RAs OT - Statistical methods COIS- Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval: All data are available from public resources, and ethical approval was waived. Informed consent: For this type of study, formal consent is not required. EDAT- 2024/11/18 12:31 MHDA- 2025/07/23 10:53 CRDT- 2024/11/18 11:14 PHST- 2024/03/26 00:00 [received] PHST- 2024/11/10 00:00 [accepted] PHST- 2025/07/23 10:53 [medline] PHST- 2024/11/18 12:31 [pubmed] PHST- 2024/11/18 11:14 [entrez] AID - 10.1007/s00592-024-02415-w [pii] AID - 10.1007/s00592-024-02415-w [doi] PST - ppublish SO - Acta Diabetol. 2025 Jul;62(7):1009-1021. doi: 10.1007/s00592-024-02415-w. Epub 2024 Nov 18. PMID- 39551761 OWN - NLM STAT- MEDLINE DCOM- 20241117 LR - 20250103 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 24 IP - 1 DP - 2024 Nov 18 TI - Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis. PG - 246 LID - 10.1186/s12902-024-01775-2 [doi] LID - 246 AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, with increased prevalence in individuals with chronic liver conditions and type 2 diabetes mellitus (T2DM). Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) have shown promise in diabetes management and may influence liver disease progression. This systematic review and meta-analysis aimed to assess the efficacy of GLP-1 RAs in reducing the risk of HCC in patients with T2DM. METHODS: We conducted a literature search of PubMed, EMBASE, and Web of Science up to August 1, 2024. Studies that evaluated the incidence of HCC in T2DM patients treated with GLP-1 RAs compared to other therapies were included. Meta-analyses were performed using a random-effects model to compute pooled hazard ratios (HRs) and 95% confidence intervals (CIs), and heterogeneity was assessed using the I(2) statistic. All statistical analyses were performed in R software version 4.3. RESULTS: Eight studies met the inclusion criteria. The pooled analysis demonstrated that GLP-1 RA treatment was associated with a significant reduction in HCC risk compared to insulin or no GLP-1 RA treatment (pooled HR = 0.41, 95% CI: 0.28 to 0.55), with considerable heterogeneity (I(2) = 74%). Compared to metformin and DPP-4 inhibitors, GLP-1 RAs did not significantly alter HCC risk (HR = 0.99, 95% CI: 0.79 to 1.27 for metformin; HR = 1.05, 95% CI: 0.80 to 1.39 for DPP-4 inhibitors). However, GLP-1 RAs were associated with a reduced risk compared to sulfonylureas (HR = 0.78, 95% CI: 0.65 to 0.93). CONCLUSION: GLP-1 RAs may offer protective benefits against HCC in T2DM patients compared to insulin or no GLP-1 RAs, but not significantly over other antidiabetic medications. This review indicates the need for further randomized controlled trials to clarify the role of GLP-1 RAs in HCC risk mitigation and to explore their mechanistic pathways in liver disease management. CI - (c) 2024. The Author(s). FAU - Shabil, Muhammed AU - Shabil M AD - University Center for Research and Development, Chandigarh University, Mohali, Punjab, India. AD - Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, 51001, Iraq. FAU - Khatib, Mahalaqua Nazli AU - Khatib MN AD - Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, City: Wardha, India. FAU - Ballal, Suhas AU - Ballal S AD - Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India. FAU - Bansal, Pooja AU - Bansal P AD - Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India. FAU - Tomar, Balvir S AU - Tomar BS AD - Institute of Pediatric Gastroenterology and Hepatology, NIMS University, Jaipur, India. FAU - Ashraf, Ayash AU - Ashraf A AD - Chandigarh Pharmacy College, Chandigarh Group of College, City: Jhanjeri, Mohali, 140307, Punjab, India. FAU - Kumar, M Ravi AU - Kumar MR AD - Department of Chemistry, Raghu Engineering College, Visakhapatnam, 531162, Andhra Pradesh, India. FAU - Sinha, Aashna AU - Sinha A AD - School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India. FAU - Rawat, Pramod AU - Rawat P AD - Department of Biotechnology, Graphic Era (Deemed to be University, Dehradun, 248002, India. AD - Department of Allied Sciences, Graphic Era Hill University Clement Town, City: Dehradun, 248002, India. FAU - Gaidhane, Abhay M AU - Gaidhane AM AD - Global Health Academy, School of Epidemiology and Public Health, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, City: Wardha, India. abhay.psm@dmiher.edu.in. FAU - Sah, Sanjit AU - Sah S AD - Department of Paediatrics, Hospital and Research Centre, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India. AD - Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India. FAU - Daniel, Afukonyo Shidoiku AU - Daniel AS AD - Global Health and Infectious Diseases Control Institute, Nasarawa State University, Keffi, Nigeria. afukonyoshidoiku@tsuniversity.edu.ng. FAU - Yappalparvi, Ambanna AU - Yappalparvi A AD - School of Pharmaceutical Sciences, 16 Lovely Professional University, Phagwara, India. FAU - Bushi, Ganesh AU - Bushi G AD - Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospital, Saveetha University, Chennai, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241118 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular MH - *Liver Neoplasms/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11571652 OTO - NOTNLM OT - Glucagon-like Peptide-1 receptor agonists OT - Hepatocellular carcinoma OT - Meta-analysis OT - Type 2 diabetes mellitus COIS- Declarations Ethical approval Not required. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. EDAT- 2024/11/18 00:31 MHDA- 2024/11/18 00:32 PMCR- 2024/11/18 CRDT- 2024/11/17 23:15 PHST- 2024/08/30 00:00 [received] PHST- 2024/11/04 00:00 [accepted] PHST- 2024/11/18 00:32 [medline] PHST- 2024/11/18 00:31 [pubmed] PHST- 2024/11/17 23:15 [entrez] PHST- 2024/11/18 00:00 [pmc-release] AID - 10.1186/s12902-024-01775-2 [pii] AID - 1775 [pii] AID - 10.1186/s12902-024-01775-2 [doi] PST - epublish SO - BMC Endocr Disord. 2024 Nov 18;24(1):246. doi: 10.1186/s12902-024-01775-2. PMID- 39549371 OWN - NLM STAT- MEDLINE DCOM- 20241124 LR - 20260627 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 12 DP - 2024 Dec TI - Exploring the antioxidant properties of semaglutide: A comprehensive review. PG - 108906 LID - S1056-8727(24)00232-0 [pii] LID - 10.1016/j.jdiacomp.2024.108906 [doi] AB - Patients with diabetes commonly experience an aberrant production of free radicals and weakened antioxidative defenses, making them highly susceptible to oxidative stress development. This, in turn, can induce and promote diabetic complications. Therefore, utilizing antidiabetic agents with antioxidative properties can offer dual benefits by addressing hyperglycemia and reducing oxidative damage. Semaglutide, a recently approved oral form of glucagon-like peptide-1 (GLP-1) analogues, has shown potent antidiabetic effects. Additionally, recent studies have suggested that it possesses antioxidative properties. However, the exact effects and the molecular pathways involved are not well understood. In this review, we present the latest findings on the antioxidative impacts of semaglutide and draw conclusions about the mechanisms involved. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Yaribeygi, Habib AU - Yaribeygi H AD - Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran. Electronic address: habib.yari@yahoo.com. FAU - Maleki, Mina AU - Maleki M AD - Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Forouzanmehr, Behina AU - Forouzanmehr B AD - Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran. FAU - Kesharwani, Prashant AU - Kesharwani P AD - Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. FAU - Jamialahmadi, Tannaz AU - Jamialahmadi T AD - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Karav, Sercan AU - Karav S AD - Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale 17100, Turkey. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amir_saheb2000@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20241112 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antioxidants) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Humans MH - *Antioxidants/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Oxidative Stress/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Animals MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - GLP-1 agonist OT - NRF2 OT - Oxidative stress OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/17 04:19 MHDA- 2024/11/25 01:26 CRDT- 2024/11/16 18:02 PHST- 2024/07/27 00:00 [received] PHST- 2024/10/02 00:00 [revised] PHST- 2024/11/09 00:00 [accepted] PHST- 2024/11/25 01:26 [medline] PHST- 2024/11/17 04:19 [pubmed] PHST- 2024/11/16 18:02 [entrez] AID - S1056-8727(24)00232-0 [pii] AID - 10.1016/j.jdiacomp.2024.108906 [doi] PST - ppublish SO - J Diabetes Complications. 2024 Dec;38(12):108906. doi: 10.1016/j.jdiacomp.2024.108906. Epub 2024 Nov 12. PMID- 39549228 OWN - NLM STAT- MEDLINE DCOM- 20241216 LR - 20261010 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 63 IP - 12 DP - 2024 Dec TI - Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis. PG - 1679-1688 LID - 10.1007/s40262-024-01449-1 [doi] AB - OBJECTIVE: Our objective was to quantify the efficacy of subcutaneous once-weekly semaglutide in treating type 2 diabetes mellitus (T2DM) over time. METHODS: Based on a literature search of the PubMed, Embase, Cochrane, and Web of Science databases, a modified maximum effect (E(max)) model including rebound effects was built using model-based meta-analysis with change from baseline in glycated hemoglobin as the efficacy endpoint. This was combined with the covariate model to form a final model, and then theoretical values of E(max) and time to reach 50% of E(max) (ET(50)) were obtained for each dose. Model fit and prediction were assessed using goodness-of-fit plots and visual prediction checking. RESULTS: E(max) and ET(50) were influenced by the proportion of males and the baseline values, respectively. There was no evidence of a placebo effect with semaglutide. The efficacy of other doses became more significant over time, and a rebound effect was observed after maximum efficacy, at a rate of 0.018. Simulation of the typical efficacy at the different doses yielded a maximum efficacy of -1.58% with 0.5 mg and a maximum efficacy of -1.87% with 1 mg. In addition, the six simulated doses (0, 0.1, 0.2, 0.5, 1, and 2 mg) showed a dose-dependent relationship between dose and efficacy except for 0.4 mg and 0.8 mg. A higher dose would result in greater efficacy and a faster onset of action. CONCLUSION: The efficacy of semaglutide in glucose control was investigated using the model-based meta-analysis method, which yields new insights into the treatment of T2DM with semaglutide. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Zhang, Ke AU - Zhang K AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. FAU - Zhao, Aiping AU - Zhao A AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Wang, Zhen AU - Wang Z AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. FAU - Ye, Kaihe AU - Ye K AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Xu, Zhaosi AU - Xu Z AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Gong, Xiao AU - Gong X AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. x.gong@foxmail.com. FAU - Zhu, Guanghu AU - Zhu G AUID- ORCID: 0000-0002-1416-1476 AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. ghzhu@guet.edu.cn. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. ghzhu@guet.edu.cn. LA - eng GR - 2024GXNSFAA010475/Natural Science Foundation of Guangxi Province/ GR - CRKL210106/Director Fund Project of the Ministry of Education Key Laboratory of Cognitive Radio and Information Processing/ GR - Guike AD23023002/Science and Technology Project of Guangxi/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20241116 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Blood Glucose/drug effects/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/pharmacology MH - Glycated Hemoglobin/drug effects/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology MH - Models, Biological MH - Treatment Outcome MH - Semaglutide COIS- Declarations. Funding: The work was jointly supported by Guangxi Natural Science Foundation (2024GXNSFAA010475), the Science and Technology Project of Guangxi (Guike AD23023002), and the Director Fund Project of the Ministry of Education Key Laboratory of Cognitive Radio and Information Processing (CRKL210106). Conflict of Interest Statement: All authors declare that they have no conflicts of interest to disclose. Ethics Approval: Not applicable. Data Availability: Data availability is not applicable to this article as no new data were created in this study. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Not applicable. Authors' Contributions: KZ, XG, and GZ wrote the original draft. KZ, AZ, and ZW extracted the data and assessed the quality of the literature. KZ and AZ performed the pharmacodynamic analyses. KY, ZX, and XG provided resources and software. All authors reviewed the manuscript and approved the final version. EDAT- 2024/11/16 22:29 MHDA- 2024/12/16 18:18 CRDT- 2024/11/16 11:21 PHST- 2024/10/24 00:00 [accepted] PHST- 2024/12/16 18:18 [medline] PHST- 2024/11/16 22:29 [pubmed] PHST- 2024/11/16 11:21 [entrez] AID - 10.1007/s40262-024-01449-1 [pii] AID - 10.1007/s40262-024-01449-1 [doi] PST - ppublish SO - Clin Pharmacokinet. 2024 Dec;63(12):1679-1688. doi: 10.1007/s40262-024-01449-1. Epub 2024 Nov 16. PMID- 39548626 OWN - NLM STAT- MEDLINE DCOM- 20241116 LR - 20250103 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 74 IP - 11 DP - 2024 Nov TI - Physio-Friendly Remission-Facilitating Pharmacotherapy (PRP) in Type 2 Diabetes. PG - 2012-2013 LID - 10.47391/JPMA.24-89 [doi] AB - This brief communication describes the concept of physiofriendly pharmacotherapy for type 2 diabetes mellitus. Physio-friendly therapy is defined as that which restores metabolic, including glycaemic and weight homoeostasis, to near normal levels. Drugs such as glucagon like peptide 1 receptor agonists (GLP1RA), sodium glucose cotransporter- 2 inhibitors (SGLT2i), and alfa glucosidase inhibitors, along with metformin, work in a physio-friendly manner and may facilitate remission. Thus, they can also be termed as remission-facilitating drugs. FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital, Karnal, India; University Center for Research & Development, Chandigarh University, Mohali, India. FAU - Verma, Suneet AU - Verma S AD - Department of Medicine, Alchemist Hospital, Panchkula, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India; Non-communicable disease unit, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Metformin/therapeutic use MH - Remission Induction/methods MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes, relapse, remission, person centred care, type 2 diabetes EDAT- 2024/11/16 20:04 MHDA- 2024/11/16 20:05 CRDT- 2024/11/16 00:13 PHST- 2024/11/16 20:05 [medline] PHST- 2024/11/16 20:04 [pubmed] PHST- 2024/11/16 00:13 [entrez] AID - 10.47391/JPMA.24-89 [doi] PST - ppublish SO - J Pak Med Assoc. 2024 Nov;74(11):2012-2013. doi: 10.47391/JPMA.24-89. PMID- 39548500 OWN - NLM STAT- MEDLINE DCOM- 20241116 LR - 20250113 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Nov 15 TI - Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives. PG - 410 LID - 10.1186/s12933-024-02500-y [doi] LID - 410 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy. CI - (c) 2024. The Author(s). FAU - Sawami, Kosuke AU - Sawami K AD - Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. FAU - Tanaka, Atsushi AU - Tanaka A AD - Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. tanakaa2@cc.saga-u.ac.jp. FAU - Node, Koichi AU - Node K AD - Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. LA - eng PT - Journal Article PT - Review DEP - 20241115 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (finerenone) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Incretins) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Naphthyridines) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Treatment Outcome MH - *Drug Therapy, Combination MH - *Kidney/drug effects/physiopathology MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Cardiovascular System/drug effects/physiopathology MH - Incretins/therapeutic use/adverse effects MH - Risk Factors MH - Risk Assessment MH - Mineralocorticoid Receptor Antagonists/therapeutic use/adverse effects MH - Kidney Diseases/prevention & control/physiopathology/chemically induced MH - Blood Glucose/drug effects/metabolism MH - Diabetic Nephropathies/drug therapy/prevention & control/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Naphthyridines PMC - PMC11568621 OTO - NOTNLM OT - Cardiovascular and kidney outcomes OT - Combination therapy OT - Finerenone OT - Glucagon-like peptide-1 receptor agonist OT - Sodium-glucose cotransporter 2 inhibitor COIS- Declarations Ethical approval and consent to participate Not applicable. Consent for publication All authors have read and approved the submission of the manuscript. The manuscript has not been published and is not being considered for publication elsewhere, in whole or in part, in any language. If the manuscript is accepted, we will approve it for publication in Cardiovascular Diabetology. Competing interests KS declares nothing to disclose. AT has received honoraria from Boehringer Ingelheim Japan, Mochida, and Amgen; research funding from GlaxoSmithKline, Takeda, Bristol-Myers Squibb, and Novo Nordisk. KN has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, and Otsuka; research grant from Astellas, Bayer, Boehringer Ingelheim Japan, Fuji, Mochida, and Novartis; scholarship from Abbott Medical, Boehringer Ingelheim Japan, Daiichi Sankyo Healthcare, Mitsubishi Tanabe, and Teijin. EDAT- 2024/11/16 22:18 MHDA- 2024/11/16 22:19 PMCR- 2024/11/15 CRDT- 2024/11/16 00:08 PHST- 2024/07/16 00:00 [received] PHST- 2024/11/02 00:00 [accepted] PHST- 2024/11/16 22:19 [medline] PHST- 2024/11/16 22:18 [pubmed] PHST- 2024/11/16 00:08 [entrez] PHST- 2024/11/15 00:00 [pmc-release] AID - 10.1186/s12933-024-02500-y [pii] AID - 2500 [pii] AID - 10.1186/s12933-024-02500-y [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Nov 15;23(1):410. doi: 10.1186/s12933-024-02500-y. PMID- 39536977 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 218 DP - 2024 Dec TI - Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years. PG - 111928 LID - S0168-8227(24)00838-6 [pii] LID - 10.1016/j.diabres.2024.111928 [doi] AB - AIM: Data on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness of OS in a real world setting with a large >/=75 year old population. METHODS: This study includes all type 2 diabetic patients who started OS between October 2021 and December 2023 in seven diabetes centers. Data were collected at baseline, 6 (T6) and 12 (T12) months. Effectiveness measures were assessed on the total sample and by patient age (<65, 65-75, >75 years). RESULTS: Overall 1824 patients started OS, of those 18.7 % were over 75 years (>75 yr). OS resulted in a significant reduction in rate of patients using sulphonylureas, rapid and basal insulin therapy, HbA1c reduced by 0.87 % at T6 and at T12 (both p < 0.0001), body weight by 2.78 Kg (p < 0.0001) at T6 and 3.89 Kg (p < 0.0001) at T12. Similarly, >75 yr showed HbA1c reduction at T6 (p < 0.0001) and T12 (p = 0.0003), body weight significantly reduced (p for interaction 0.005) both at T6 (-1.57 Kg; p = 0.0003) and T12 (-2.74 Kg; p < 0.0001). CONCLUSION: In our study, OS results efficacy in non-elderly and elderly patients, making it an effective treatment option also for very elderly type 2 diabetic patients. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Baronti, Walter AU - Baronti W AD - Diabetic and Metabolic Diseases Unit, Health Local Unit South-East Tuscany, Grosseto Hospital, Italy. Electronic address: walter.baronti@uslsudest.toscana.it. FAU - Lencioni, Cristina AU - Lencioni C AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. FAU - Occhipinti, Margherita AU - Occhipinti M AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. FAU - Nicolucci, Antonio AU - Nicolucci A AD - Coresearch-Centre for Outcome Research and Clinical Epidemiology, Pescara, Italy. FAU - Cianni, Graziano Di AU - Cianni GD AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. CN - Tuscany Study Group- Italian Diabetologists Association AMD LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241112 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Female MH - Aged, 80 and over MH - *Glycated Hemoglobin/metabolism/analysis MH - Administration, Oral MH - Treatment Outcome MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - Semaglutide OTO - NOTNLM OT - BMI OT - Elderly Type 2 diabetic patients OT - HbA1c OT - Oral-semaglutide OT - Real world COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/14 03:56 MHDA- 2024/12/13 00:23 CRDT- 2024/11/13 19:26 PHST- 2024/09/09 00:00 [received] PHST- 2024/11/05 00:00 [revised] PHST- 2024/11/08 00:00 [accepted] PHST- 2024/12/13 00:23 [medline] PHST- 2024/11/14 03:56 [pubmed] PHST- 2024/11/13 19:26 [entrez] AID - S0168-8227(24)00838-6 [pii] AID - 10.1016/j.diabres.2024.111928 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Dec;218:111928. doi: 10.1016/j.diabres.2024.111928. Epub 2024 Nov 12. PMID- 39536238 OWN - NLM STAT- MEDLINE DCOM- 20250305 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 392 IP - 10 DP - 2025 Mar 6 TI - Tirzepatide for Obesity Treatment and Diabetes Prevention. PG - 958-971 LID - 10.1056/NEJMoa2410819 [doi] AB - BACKGROUND: Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. METHODS: We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. RESULTS: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. CONCLUSIONS: Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.). CI - Copyright (c) 2024 Massachusetts Medical Society. FAU - Jastreboff, Ania M AU - Jastreboff AM AUID- ORCID: 0000-0003-1446-0991 AD - Y-Weight Yale Obesity Research Center, Section of Endocrinology and Metabolism, Department of Medicine, Yale School of Medicine, New Haven, CT. AD - Section of Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, CT. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, University College Dublin, Dublin. FAU - Stefanski, Adam AU - Stefanski A AD - Eli Lilly, Indianapolis. FAU - Aronne, Louis J AU - Aronne LJ AD - Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York. FAU - Halpern, Bruno AU - Halpern B AUID- ORCID: 0000-0003-0973-5065 AD - Hospital 9 de Julho, Sao Paulo. FAU - Wharton, Sean AU - Wharton S AD - University of Toronto, Toronto. AD - Wharton Weight Management Clinic, Toronto. FAU - Wilding, John P H AU - Wilding JPH AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. FAU - Perreault, Leigh AU - Perreault L AD - University of Colorado School of Medicine, Aurora. FAU - Zhang, Shuyu AU - Zhang S AD - Eli Lilly, Indianapolis. FAU - Battula, Ramakrishna AU - Battula R AD - Eli Lilly, Indianapolis. FAU - Bunck, Mathijs C AU - Bunck MC AD - Eli Lilly, Indianapolis. FAU - Ahmad, Nadia N AU - Ahmad NN AD - Eli Lilly, Indianapolis. FAU - Jouravskaya, Irina AU - Jouravskaya I AD - Eli Lilly, Indianapolis. CN - SURMOUNT-1 Investigators LA - eng SI - ClinicalTrials.gov/NCT04184622 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20241113 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Anti-Obesity Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - N Engl J Med. 2025 Jun 26;392(24):2491-2492. doi: 10.1056/NEJMc2504728. PMID: 40561543 CIN - N Engl J Med. 2025 Jun 26;392(24):2492. doi: 10.1056/NEJMc2504728. PMID: 40561544 CIN - N Engl J Med. 2025 Jun 26;392(24):2492-2493. doi: 10.1056/NEJMc2504728. PMID: 40561545 MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Anti-Obesity Agents/administration & dosage/adverse effects MH - *Diabetes Mellitus, Type 2/epidemiology/etiology/prevention & control MH - Disease Progression MH - Double-Blind Method MH - *Obesity/complications/diagnosis/drug therapy MH - *Prediabetic State/drug therapy/etiology MH - *Tirzepatide/administration & dosage/adverse effects MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Body Weight/drug effects MH - Gastrointestinal Diseases/chemically induced/epidemiology MH - Dose-Response Relationship, Drug FIR - Connery, Lisa IR - Connery L FIR - Tran, Hien IR - Tran H FIR - Blevins, Thomas IR - Blevins T FIR - Gangi, Sumana IR - Gangi S FIR - Welch, Michelle IR - Welch M FIR - Nunez, Lazaro IR - Nunez L FIR - Shea, Heidi IR - Shea H FIR - Bhargava, Anuj IR - Bhargava A FIR - Kutner, Mark IR - Kutner M FIR - Nardandrea, John IR - Nardandrea J FIR - Willingham, Katherine IR - Willingham K FIR - Forman, Seth IR - Forman S FIR - True, David IR - True D FIR - Lillestol, Michael IR - Lillestol M FIR - Smith, Timothy IR - Smith T FIR - Detweiler, Robert IR - Detweiler R FIR - Hartley, Paul IR - Hartley P FIR - Rohlf, Jane IR - Rohlf J FIR - Davis, Matthew IR - Davis M FIR - Murray, Alexander IR - Murray A FIR - Santiago, Rica IR - Santiago R FIR - Byars, William IR - Byars W FIR - Fried, David IR - Fried D FIR - Soufer, Joseph IR - Soufer J FIR - Yacoub, Tamer IR - Yacoub T FIR - Block, Bradley IR - Block B FIR - Barranco Santana, Elizabeth IR - Barranco Santana E FIR - Bressler, Peter IR - Bressler P FIR - Cortes-Maisonet, Gregorio IR - Cortes-Maisonet G FIR - Rivera Colon, Luis IR - Rivera Colon L FIR - Ortiz-Carrasquillo, Ramon IR - Ortiz-Carrasquillo R FIR - Gonzalez-Bossolo, Alex IR - Gonzalez-Bossolo A FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Chang, Anna IR - Chang A FIR - Essink, Beal IR - Essink B FIR - Lofton, Holly IR - Lofton H FIR - Recknor, Chris IR - Recknor C FIR - Norwood, Paul IR - Norwood P FIR - Livingston, Michael IR - Livingston M FIR - Vaughn, Michael IR - Vaughn M FIR - Shelton, Courtney IR - Shelton C FIR - Herman, Lee IR - Herman L FIR - Palal, Betsy IR - Palal B FIR - Mohseni, Rizwana IR - Mohseni R FIR - Van, Joanna IR - Van J FIR - McCartney, Michael IR - McCartney M FIR - Audish, Hanid IR - Audish H FIR - Guzman, David IR - Guzman D FIR - Steil, Kenneth IR - Steil K FIR - Arora, Samir IR - Arora S FIR - Toth, Phillip IR - Toth P FIR - McKenzie, Mark IR - McKenzie M FIR - Fraser, Neil IR - Fraser N FIR - O'Neil, Patrick IR - O'Neil P FIR - Bays, Harold IR - Bays H FIR - Rhea, Margaret IR - Rhea M FIR - Ghorbani, Tahereh IR - Ghorbani T FIR - Aronne, Louis IR - Aronne L FIR - Jastreboff, Ania IR - Jastreboff A FIR - Rosenstock, Julio IR - Rosenstock J FIR - Cheng, ZhiFeng IR - Cheng Z FIR - Yu, Yerong IR - Yu Y FIR - Xiao, Jianzhong IR - Xiao J FIR - Li, Ya IR - Li Y FIR - Pang, Shuguang IR - Pang S FIR - Li, Li IR - Li L FIR - Xu, Lan IR - Xu L FIR - Lei, Tao IR - Lei T FIR - Lu, Yi Bing IR - Lu YB FIR - Lin, Jingna IR - Lin J FIR - Drapkina, Oxana IR - Drapkina O FIR - Chazova, Irina IR - Chazova I FIR - Zrazhevskiy, Konstantin IR - Zrazhevskiy K FIR - Troshina, Ekaterina IR - Troshina E FIR - Shutemova, Elena IR - Shutemova E FIR - Voevoda, Mikhail IR - Voevoda M FIR - Ezhov, Andrei IR - Ezhov A FIR - Shalaev, Sergey IR - Shalaev S FIR - Gordeev, Ivan IR - Gordeev I FIR - Rafalskiy, Vladimir IR - Rafalskiy V FIR - Russo, Luis IR - Russo L FIR - Franco, Denise IR - Franco D FIR - Alves, Breno Balabem IR - Alves BB FIR - Akerman Augusto, Gustavo IR - Akerman Augusto G FIR - Vidotti, Maria Helena IR - Vidotti MH FIR - Cercato, Cintia IR - Cercato C FIR - Santos, Queulla IR - Santos Q FIR - Saraiva, Jose IR - Saraiva J FIR - Gelersztein, Elizabeth IR - Gelersztein E FIR - Fretes, Jose IR - Fretes J FIR - Lisandro Gutnisky, Lucas IR - Lisandro Gutnisky L FIR - Perez Manghi, Federico IR - Perez Manghi F FIR - Costanzo, Pablo IR - Costanzo P FIR - Sernia, Virginia IR - Sernia V FIR - Vico, Marisa IR - Vico M FIR - Abalos, Franklin IR - Abalos F FIR - Montana, Oscar IR - Montana O FIR - Serra, Leonardo IR - Serra L FIR - Aizenberg, Diego IR - Aizenberg D FIR - Alpizar-Salazar, Melchor IR - Alpizar-Salazar M FIR - Herrera Marmolejo, Marisol IR - Herrera Marmolejo M FIR - Garcia, Pedro IR - Garcia P FIR - Sauque, Leobardo IR - Sauque L FIR - Nevarez, Luis IR - Nevarez L FIR - Aguilar Espinoza, Luis Horacio IR - Aguilar Espinoza LH FIR - Crespo, Mariana IR - Crespo M FIR - Virgen Carrillo, Luis IR - Virgen Carrillo L FIR - de Los Rios Ibarra, Manuel Odin IR - de Los Rios Ibarra MO FIR - Lopez Maldonado, Francisco IR - Lopez Maldonado F FIR - Kumar, Harish IR - Kumar H FIR - Sethi, Bipin IR - Sethi B FIR - Vikram, Naval IR - Vikram N FIR - Aggarwal, Ajay IR - Aggarwal A FIR - Goyal, Ghanshyam IR - Goyal G FIR - Deshmukh, Vaishali IR - Deshmukh V FIR - Julka, Sandeep IR - Julka S FIR - Gada, Jugal IR - Gada J FIR - Gupta, Hemant IR - Gupta H FIR - Shah, Parag IR - Shah P FIR - Yamada, Masamichi IR - Yamada M FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Inoue, Satoshi IR - Inoue S FIR - Yamasaki, Yoshimitsu IR - Yamasaki Y FIR - Fukushima, Yasushi IR - Fukushima Y FIR - Huang, Kuo-Chin IR - Huang KC FIR - Lin, Wen-Yuan IR - Lin WY FIR - Tien, Kai-Jen IR - Tien KJ FIR - Huang, Chien-Ning IR - Huang CN FIR - Yang, Yi-Ching IR - Yang YC EDAT- 2024/11/14 03:59 MHDA- 2025/03/05 18:20 CRDT- 2024/11/13 15:34 PHST- 2025/03/05 18:20 [medline] PHST- 2024/11/14 03:59 [pubmed] PHST- 2024/11/13 15:34 [entrez] AID - 10.1056/NEJMoa2410819 [doi] PST - ppublish SO - N Engl J Med. 2025 Mar 6;392(10):958-971. doi: 10.1056/NEJMoa2410819. Epub 2024 Nov 13. PMID- 39532398 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260918 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D). PG - 642-651 LID - 10.1111/dom.16057 [doi] AB - AIMS: The study aims to examine the outcome of replacement of prandial insulin with once-weekly subcutaneous semaglutide in people with type 2 diabetes reasonably controlled on multiple daily insulin injections (MDI). MATERIALS AND METHODS: This single-centre, randomised, open-label trial enrolled a statistically predetermined sample of 60 adults with HbA1c 50%, 97.5% stopped prandial insulin and 45% lost >10% body weight. Participant treatment satisfaction scores trended higher with semaglutide. Hypoglycaemia frequency was similar between groups. CONCLUSIONS: In people with type 2 diabetes well controlled (HbA(1c) /=6 weeks experienced significantly greater weight loss compared to those using it for shorter periods (6.3 +/- 6.43 vs 1.65 +/- 1.69; P < .001). GI-related adverse events were reported in 57.8% of patients. Over 95% of patients discontinued G1RA due to insufficient weight loss and/or adverse effects. Patients reaching the maximal recommended dose exhibited significantly greater weight loss versus patients who did not reach it for both Liraglutide (5.9 +/- 4.98 kg vs. 3.9 +/- 5.53 kg; P = .03) and Semaglutide (6.5 +/- 7.8 kg vs. 2.5 +/- 3.8 kg; P = .016). CONCLUSION: Pre-MBS G1RA utilization and failure are prevalent among MBS candidates. Our study underscores the need for further research to understand the role of G1RA therapy in obesity management and the development of guidelines for its appropriate use in MBS candidates. CI - Copyright (c) 2025 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved. FAU - Rayman, Shlomi AU - Rayman S AD - Department of General Surgery, Assuta Ashdod Public Hospital, Affiliated with Faculty of Health and Science and Ben-Gurion University, Ashdod, Israel. Electronic address: shlomir@assuta.co.il. FAU - Morduch, Evyatar AU - Morduch E AD - Faculty of Health and Science, Ben-Gurion University, Be'er-Sheva, Israel. FAU - Reiner-Benaim, Anat AU - Reiner-Benaim A AD - Department of Epidemiology, Biostatistics and Community Health Sciences, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel. FAU - Catzman, Netta-Lee AU - Catzman NL AD - Department of Epidemiology, Biostatistics and Community Health Sciences, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel. FAU - Carmeli, Idan AU - Carmeli I AD - Department of General Surgery, Assuta Ashdod Public Hospital, Affiliated with Faculty of Health and Science and Ben-Gurion University, Ashdod, Israel. FAU - Froylich, Dvir AU - Froylich D AD - Surgery department, Carmel Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel. FAU - Goitein, David AU - Goitein D AD - Department of General Surgery, Chaim Sheba Medical Center, Ramat Gan, Israel; Affiliated with the School of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241009 PL - United States TA - Surg Obes Relat Dis JT - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JID - 101233161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Bariatric Surgery/statistics & numerical data MH - Female MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Liraglutide/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Israel MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonists OT - Semaglutide OT - Weight loss OT - liraglutide COIS- Disclosure The authors have no commercial associations that might be a conflict of interest in relation to this article. EDAT- 2024/11/13 13:48 MHDA- 2025/01/20 22:54 CRDT- 2024/11/08 21:58 PHST- 2024/02/28 00:00 [received] PHST- 2024/08/15 00:00 [revised] PHST- 2024/09/21 00:00 [accepted] PHST- 2025/01/20 22:54 [medline] PHST- 2024/11/13 13:48 [pubmed] PHST- 2024/11/08 21:58 [entrez] AID - S1550-7289(24)00815-3 [pii] AID - 10.1016/j.soard.2024.09.010 [doi] PST - ppublish SO - Surg Obes Relat Dis. 2025 Feb;21(2):121-126. doi: 10.1016/j.soard.2024.09.010. Epub 2024 Oct 9. PMID- 39515454 OWN - NLM STAT- MEDLINE DCOM- 20250215 LR - 20250613 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 271 DP - 2025 Mar TI - Sodium-Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Glaucoma in Patients With Type 2 Diabetes: A Target Trial Emulation. PG - 286-298 LID - S0002-9394(24)00506-3 [pii] LID - 10.1016/j.ajo.2024.10.029 [doi] AB - PURPOSE: Pleiotropic cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) due to vascular remodeling effects have been demonstrated in patients with type 2 diabetes mellitus. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study was to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes. DESIGN: Target trial emulation using observational data from multiple healthcare organizations. METHODS: This population-based cohort study included adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. Propensity score matching was conducted to control for sociodemographic characteristics comorbidities, and concomitant use of medications. The exposure considered was treatment with SGLT2i for type 2 diabetes, and the outcomes were new-onset glaucoma and its subtypes after initiation of antidiabetic treatments. Subgroup analyses were performed to evaluate the effect of individual SGLT2i on incident glaucoma. RESULTS: After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Patients on SGLT2i, compared with those on DPP4i, had a lower risk of glaucoma (hazard ratio [HR] 0.815, 95% confidence interval [CI] 0.794, 0.837), including open-angle glaucoma (HR 0.755, 95% CI 0.729, 0.781) and primary angle-closure glaucoma (HR 0.702, 95% CI 0.636, 0.781). Among all SGLT2i, ertugliflozin (HR 0.668, 95% CI 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR 0.727, 95% CI 0.696, 0.759), dapagliflozin (HR 0.814, 95% CI 0.774, 0.855), and canagliflozin (HR 0.893, 95% CI 0.862, 0.926). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR 0.932, 95% CI 0.906, 0.959). CONCLUSIONS: Patients on SGLT2i, including canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i. SGLT2i demonstrated a protective effect for both open-angle glaucoma and angle-closure glaucoma. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Eng, Kathleen AU - Eng K AD - From Harvard Medical School (K.E.), Boston, Massachusetts. Electronic address: kathleen_eng@hms.harvard.edu. FAU - Zebardast, Nazlee AU - Zebardast N AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts. FAU - Boland, Michael V AU - Boland MV AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts; Glaucoma Center of Excellence (M.V.B. and D.S.F.), Boston, Massachusetts. FAU - Lo, Jui-En AU - Lo JE AD - Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University (J.L.), Cleveland, Ohio. FAU - Swaminathan, Swarup S AU - Swaminathan SS AD - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine (S.S.S.), Miami, Florida. FAU - Friedman, David S AU - Friedman DS AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts; Glaucoma Center of Excellence (M.V.B. and D.S.F.), Boston, Massachusetts. Electronic address: david_friedman@meei.harvard.edu. FAU - Ma, Kevin Sheng-Kai AU - Ma KS AD - Center for Global Health, Perelman School of Medicine, University of Pennsylvania (K.S.M.), Philadelphia, Pennsylvania. Electronic address: kevinskma1@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20241106 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Propensity Score MH - *Primary Prevention/methods MH - Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incidence MH - Retrospective Studies MH - *Glaucoma/prevention & control/epidemiology EDAT- 2024/11/13 14:01 MHDA- 2025/02/16 01:32 CRDT- 2024/11/08 19:25 PHST- 2024/04/20 00:00 [received] PHST- 2024/10/20 00:00 [revised] PHST- 2024/10/28 00:00 [accepted] PHST- 2025/02/16 01:32 [medline] PHST- 2024/11/13 14:01 [pubmed] PHST- 2024/11/08 19:25 [entrez] AID - S0002-9394(24)00506-3 [pii] AID - 10.1016/j.ajo.2024.10.029 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Mar;271:286-298. doi: 10.1016/j.ajo.2024.10.029. Epub 2024 Nov 6. PMID- 39514688 OWN - NLM STAT- MEDLINE DCOM- 20241108 LR - 20260127 IS - 2175-8239 (Electronic) IS - 0101-2800 (Print) IS - 0101-2800 (Linking) VI - 46 IP - 4 DP - 2024 Oct-Dec TI - Kidney effects of Glucagon-Like Peptide 1 (GLP1): from molecular foundations to a pharmacophysiological perspective. PG - e20240101 LID - S0101-28002024000400405 [pii] LID - 10.1590/2175-8239-JBN-2024-0101en [doi] LID - e20240101 AB - GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature. FAU - Rico-Fontalvo, Jorge AU - Rico-Fontalvo J AUID- ORCID: 0000-0002-2852-1241 AD - Asociacion Colombiana de Nefrologia e HTA, Comite de Rinon, Diabetes y Metabolismo, Bogota, Colombia. AD - Universidad Simon Bolivar, Facultad de Ciencias de la Salud, Departamento de Nefrologia, Barranquilla, Colombia. FAU - Reina, Maricely AU - Reina M AUID- ORCID: 0000-0002-1262-1555 AD - Fundacion Universitaria de Ciencias de la Salud, Hospital San Jose, Departamento de Nefrologia, Bogota, Colombia. FAU - Soler, Maria Jose AU - Soler MJ AUID- ORCID: 0000-0003-3621-0766 AD - Hospital Universitario Vall de Hebron, Servicio de Nefrologia, Barcelona, Espana. AD - Nephrology and Transplantation Research Group, Vall d'Hebron Institut de Recerca (VHIR), Nephrology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain. Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud de Espana (CSUR), Barcelona, Espana. AD - Redes de Investigacion Cooperativa Orientadas a Resultados en Salud (RICORS), Instituto de Salud Carlos III (RD21/0005/0031), Spain. FAU - Unigarro-Palacios, Mario AU - Unigarro-Palacios M AUID- ORCID: 0000-0002-7753-6079 AD - Fundacion Universitaria de Ciencias de la Salud, Hospital San Jose, Departamento de Endocrinologia, Bogota, Colombia. FAU - Castaneda-Gonzalez, Juan Pablo AU - Castaneda-Gonzalez JP AUID- ORCID: 0000-0001-5400-9068 AD - Fundacion Universitaria de Ciencias de la Salud, Instituto de Investigaciones, Bogota, Colombia. FAU - Quintero, Javier Jimenez AU - Quintero JJ AUID- ORCID: 0009-0007-5150-7580 AD - Universidad Militar Nueva Granada, Bogota, Colombia. FAU - Raad-Sarabia, Maria AU - Raad-Sarabia M AUID- ORCID: 0000-0002-7080-7024 AD - Universidad del Sinu, Departamento de Medicina Interna, Cartagena, Colombia. FAU - Moraes, Thyago Proenca de AU - Moraes TP AUID- ORCID: 0000-0002-2983-3968 AD - Pontificia Universidade de Catolica do Parana (PUCPR), Curitiba, PR, Brazil. FAU - Daza-Arnedo, Rodrigo AU - Daza-Arnedo R AUID- ORCID: 0000-0002-6295-4972 AD - Asociacion Colombiana de Nefrologia e HTA, Comite de Rinon, Diabetes y Metabolismo, Bogota, Colombia. LA - eng LA - por PT - Journal Article PT - Review PL - Brazil TA - J Bras Nefrol JT - Jornal brasileiro de nefrologia JID - 9426946 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Glucagon-Like Peptide 1 MH - Kidney/drug effects/metabolism/physiology MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11548866 COIS- Conflict of Interest The authors declare that they have no conflict of interest related to the publication of this manuscript. Jorge Rico Fontalvo declares that he has received honoraria for conferences from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Lilly, Sanofi, Novartis, Abbvie, Merck y Bayer. And participated on Advisory Board for AZ, Boehringer Ingelheim, Bayer y Novo Nordisk. Maria Jose Soler declares that she has received honoraria for conferences and consulting fees from Novo Nordisk, Jansen, Mundipharma, AstraZeneca, Esteve, Fresenius, Eli Lilly, Boehringer-Ingelheim, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare, GSK and Otsuka. She is also one of the former Editors-in-Chief of CKJ. Current editorial board of American Society of Nephrology (ASN) journals. Thyago Moraes declares that he has received honoraria for conferences from AstraZeneca, Baxter, Bayer, Boehringer, Lilly, Novo Nordisk and Takeda; and participated on advisory board for AstraZeneca, Baxter, Bayer, Boehringer and Lilly. Rodrigo Daza Arnedo declares that he has received honoraria for conferences from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk y Bayer. Participated in Advisory Board for AZ, Boehringer Ingelheim, Bayer y Novo Nordisk. The other authors declare no conflict of interest. EDAT- 2024/11/13 13:55 MHDA- 2024/11/14 03:56 PMCR- 2024/11/08 CRDT- 2024/11/08 14:22 PHST- 2024/06/02 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/11/14 03:56 [medline] PHST- 2024/11/13 13:55 [pubmed] PHST- 2024/11/08 14:22 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - S0101-28002024000400405 [pii] AID - 10.1590/2175-8239-JBN-2024-0101en [doi] PST - ppublish SO - J Bras Nefrol. 2024 Oct-Dec;46(4):e20240101. doi: 10.1590/2175-8239-JBN-2024-0101en. PMID- 39514094 OWN - NLM STAT- MEDLINE DCOM- 20241221 LR - 20260701 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 1 DP - 2025 Jan TI - Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013-2019. PG - 94-104 LID - 10.1007/s00125-024-06321-2 [doi] AB - AIMS/HYPOTHESIS: The aim of this study was to investigate racial and ethnic disparities in the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) among older adults with type 2 diabetes and cardiorenal conditions. METHODS: Using Medicare fee-for-service data (2013-2019), this retrospective cohort study identified older adults (>/=65 years) with type 2 diabetes initiating second-line therapies (SGLT2is, GLP1-RAs, dipeptidyl peptidase-4 inhibitors [DPP4is] and sulfonylureas [SUs]) with (1) heart failure (HF), (2) atherosclerotic cardiovascular disease (ASCVD), (3) chronic kidney disease (CKD) and (4) no recorded cardiorenal conditions. Participants were classified as non-Hispanic White, non-Hispanic Black and Hispanic. Multinomial regressions, adjusting for sociodemographic, clinical and county-level characteristics, were used to model the odds of initiating SGLT2is or GLP-1RAs within each cohort. RESULTS: Black participants with HF, ASCVD, CKD or no recorded cardiorenal conditions had 35% (adjusted OR 0.65 [95% CI 0.61, 0.68]), 33% (0.67 [0.64, 0.69]), 32% (0.68 [0.64, 0.72]) and 24% (0.76 [0.74, 0.79]) lower odds of initiating SGLT2is, respectively, than White participants. Disparities ameliorated from 50-60% lower odds in 2013 to 17-18% in 2019. Similar patterns were observed for GLP-1RA uptake among Black participants. By contrast, Hispanic participants had similar odds of SGLT2i initiation in the HF and CKD cohorts as White participants, but 6% (0.94 [0.91, 0.98]) lower odds in the ASCVD cohort. Notable disparities for Hispanic participants compared with White participants were observed for GLP-1RA uptake in the HF, ASCVD, CKD and no cardiorenal conditions cohorts: 11% (0.89 [0.84, 0.94]), 16% (0.84 [0.81, 0.87]), 16% (0.84 [0.80, 0.89]) and 25% (0.75 [0.72, 0.78]) lower odds, respectively. Participants had greater odds than White participants of initiating DPP4is, which confer no cardiorenal benefits, across all cohorts (HF 1.25 [1.19, 1.31]; ASCVD 1.36 [1.32, 1.40]; CKD 1.32 [1.26, 1.38). Adjustment for social determinants of health did not meaningfully change the study findings. CONCLUSIONS/INTERPRETATION: Compared with White participants, disparities in the uptake of SGLT2is were evident for Black participants, and in the uptake of GLP-1RAs for both Black and Hispanic participants. This study highlights how type 2 diabetes management is evolving, while underscoring historical imbalances that have shown signs of abatement. CI - (c) 2024. The Author(s). FAU - Wang, Eric AU - Wang E AUID- ORCID: 0000-0002-9937-9959 AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA. ewang@dsi.com. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Khosrow-Khavar, Farzin AU - Khosrow-Khavar F AUID- ORCID: 0000-0003-3636-8918 AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA. AD - Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA. FAU - Crystal, Stephen AU - Crystal S AUID- ORCID: 0000-0003-0366-7583 AD - Center for Health Services Research, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA. AD - Rutgers School of Social Work, Rutgers University, New Brunswick, NJ, USA. FAU - Dave, Chintan V AU - Dave CV AUID- ORCID: 0000-0002-7160-9345 AD - Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA. cdave@ifh.rutgers.edu. AD - Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA. cdave@ifh.rutgers.edu. LA - eng GR - L30 AG069245/AG/NIA NIH HHS/United States GR - R01 DK139163/DK/NIDDK NIH HHS/United States GR - R01 HL163163/HL/NHLBI NIH HHS/United States GR - 1R01HL163163/GF/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20241108 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Aged, 80 and over MH - Female MH - Humans MH - Male MH - *Atherosclerosis/ethnology/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - Ethnicity/statistics & numerical data MH - Healthcare Disparities/ethnology MH - *Heart Failure/ethnology/drug therapy MH - *Medicare MH - *Renal Insufficiency, Chronic/ethnology/drug therapy MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - United States/epidemiology MH - White MH - Black or African American MH - Hispanic or Latino MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11663158 OTO - NOTNLM OT - CVD OT - Chronic kidney disease OT - Diabetes OT - Disparities OT - GLP-1 receptor agonist OT - Heart failure OT - Medicare OT - Older people OT - SGLT2 inhibitor COIS- Data availability: The authors declare that the raw data used in the manuscript are not publicly available to share due to data user agreements in place with the Centers for Medicare and Medicaid Services (CMS). Raw data may be acquired individually through the CMS. Funding: This study was conducted with the support of a grant from the National Heart, Lung, and Blood Institute (NHLBI; 1R01HL163163). Authors' relationships and activities: EW is an employee of Daiichi Sankyo. CVD is the principal investigator on grants from the NHLBI (1R01HL163163) and JDRF (3-SRA-2022-1257-S-B) and reports consulting fees from the US Food and Drug Administration (FDA) and Takeda. EP has received research grants from the Patient-Centered Outcomes Research Institute (DB-2020C2-20326) and the US FDA (5U01FD007213) that are not related to the topic of this work. She is the principal investigator on a research grant to the Brigham and Women's Hospital from Boehringer Ingelheim that is not related to the topic of this work. Contribution statement: All authors were involved in the conception, design and conduct of the study. All authors were involved in the interpretation of the results. EW and CVD wrote the first draft of the manuscript and all authors edited, reviewed and approved the final version of the manuscript. EW and CVD are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2024/11/13 13:52 MHDA- 2024/12/22 00:27 PMCR- 2024/11/08 CRDT- 2024/11/08 11:13 PHST- 2024/05/06 00:00 [received] PHST- 2024/10/13 00:00 [accepted] PHST- 2024/12/22 00:27 [medline] PHST- 2024/11/13 13:52 [pubmed] PHST- 2024/11/08 11:13 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - 10.1007/s00125-024-06321-2 [pii] AID - 6321 [pii] AID - 10.1007/s00125-024-06321-2 [doi] PST - ppublish SO - Diabetologia. 2025 Jan;68(1):94-104. doi: 10.1007/s00125-024-06321-2. Epub 2024 Nov 8. PMID- 39514091 OWN - NLM STAT- MEDLINE DCOM- 20241210 LR - 20260729 IS - 2515-5091 (Electronic) IS - 2515-5091 (Linking) VI - 8 IP - 6 DP - 2024 Nov 1 TI - Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes. LID - 10.1093/jncics/pkae095 [doi] LID - pkae095 AB - BACKGROUND: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes. METHODS: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad. RESULTS: Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P = .02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P = .03). CONCLUSIONS: For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use. CI - (c) The Author(s) 2024. Published by Oxford University Press. FAU - Grandhi, Nikhil AU - Grandhi N AUID- ORCID: 0009-0007-7901-5131 AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. FAU - Liu, Lawrence AU - Liu L AUID- ORCID: 0000-0001-8559-7739 AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - City of Hope Comprehensive Cancer Center, Duarte, CA, USA. FAU - Wang, Mei AU - Wang M AUID- ORCID: 0000-0002-3560-9460 AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. FAU - Thomas, Theodore AU - Thomas T AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. FAU - Schoen, Martin AU - Schoen M AUID- ORCID: 0000-0001-6388-5553 AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Department of Medicine, Saint Louis University School of Medicine, St Louis, MO, USA. FAU - Sanfilippo, Kristen AU - Sanfilippo K AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. FAU - Gao, Feng AU - Gao F AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. FAU - Colditz, Graham A AU - Colditz GA AUID- ORCID: 0000-0002-7307-0291 AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. FAU - Carson, Kenneth R AU - Carson KR AUID- ORCID: 0000-0001-7471-9542 AD - Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Janakiram, Murali AU - Janakiram M AD - City of Hope Comprehensive Cancer Center, Duarte, CA, USA. FAU - Chang, Su-Hsin AU - Chang SH AUID- ORCID: 0000-0001-5872-9556 AD - Research Service, St Louis VA Medical Center, St Louis, MO, USA. AD - Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. LA - eng GR - U01 CA265735/CA/NCI NIH HHS/United States GR - R01 CA253475/NH/NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - Siteman Cancer Center/ GR - R01 CA253475/CA/NCI NIH HHS/United States PT - Journal Article PL - England TA - JNCI Cancer Spectr JT - JNCI cancer spectrum JID - 101721827 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Multiple Myeloma/drug therapy/complications MH - *Monoclonal Gammopathy of Undetermined Significance/complications MH - *Disease Progression MH - Male MH - Aged MH - Female MH - Middle Aged MH - Cohort Studies MH - Proportional Hazards Models MH - Incidence MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus/drug therapy MH - Veterans/statistics & numerical data MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11643351 COIS- None declared. EDAT- 2024/11/13 13:57 MHDA- 2024/12/11 00:23 PMCR- 2024/11/08 CRDT- 2024/11/08 11:13 PHST- 2024/09/22 00:00 [accepted] PHST- 2024/02/29 00:00 [received] PHST- 2024/08/26 00:00 [revised] PHST- 2024/12/11 00:23 [medline] PHST- 2024/11/13 13:57 [pubmed] PHST- 2024/11/08 11:13 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - 7887568 [pii] AID - pkae095 [pii] AID - 10.1093/jncics/pkae095 [doi] PST - ppublish SO - JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae095. doi: 10.1093/jncics/pkae095. PMID- 39511836 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism. PG - 519-528 LID - 10.1111/dom.16042 [doi] AB - AIMS: To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity. MATERIALS AND METHODS: We designed a randomised open-label trial in 25 men with type 2 diabetes (aged 50 [46-60] years, BMI 35.9 [32.8-38.7] kg/m(2)) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10-12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS). RESULTS: The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF-15 score significantly improved only in the TRT group. CONCLUSION: Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity-related FH who desire fertility. CLINICAL TRIAL REGISTRATION NUMBER: NCT06489457, www. CLINICALTRIALS: gov. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gregoric, Nadan AU - Gregoric N AUID- ORCID: 0000-0001-5511-0934 AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Sikonja, Jaka AU - Sikonja J AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AUID- ORCID: 0000-0002-6594-5254 AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Jensterle, Mojca AU - Jensterle M AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. LA - eng SI - ClinicalTrials.gov/NCT06489457 GR - P3-0298/Javna Agencija za Raziskovalno Dejavnost RS/ GR - P3-0343/Javna Agencija za Raziskovalno Dejavnost RS/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20241107 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 3XMK78S47O (Testosterone) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - H16A5VCT9C (testosterone undecanoate) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/pharmacology/administration & dosage MH - *Testosterone/therapeutic use/administration & dosage/analogs & derivatives MH - *Obesity/complications/drug therapy MH - *Hypogonadism/drug therapy/complications MH - Spermatozoa/drug effects MH - Semen Analysis MH - Hormone Replacement Therapy/methods MH - Hypoglycemic Agents/therapeutic use MH - Sperm Count MH - Semaglutide PMC - PMC11701185 OTO - NOTNLM OT - functional hypogonadism OT - obesity OT - semaglutide OT - sperm OT - type 2 diabetes COIS- NG has received lecture honoraria from Novo Nordisk, Eli Lilly, BioMarin, Genesis Pharm and Boehringer Ingelheim. AJ has served as a consultant and is on speaker bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Abbott, Novo Nordisk, Medtronic and Sanofi. MJ has received lecture honoraria from Novo Nordisk, Eli Lilly, Pfizer, Amgen, Novartis and Sanofi, and is an advisory board member of Novo Nordisk, Eli Lilly, Amgen and Pfizer. JS declares no conflict of interest. EDAT- 2024/11/13 13:59 MHDA- 2025/01/07 04:51 PMCR- 2025/01/06 CRDT- 2024/11/08 01:13 PHST- 2024/10/13 00:00 [revised] PHST- 2024/08/31 00:00 [received] PHST- 2024/10/16 00:00 [accepted] PHST- 2025/01/07 04:51 [medline] PHST- 2024/11/13 13:59 [pubmed] PHST- 2024/11/08 01:13 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - DOM16042 [pii] AID - 10.1111/dom.16042 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):519-528. doi: 10.1111/dom.16042. Epub 2024 Nov 7. PMID- 39496174 OWN - NLM STAT- MEDLINE DCOM- 20241118 LR - 20260704 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 177 IP - 11 DP - 2024 Nov TI - In T2D, SGLT-2 inhibitor effects on CV and kidney outcomes were consistent regardless of GLP-1 receptor agonist use. PG - JC124 LID - 10.7326/ANNALS-24-02849-JC [doi] AB - Apperloo EM, Neuen BL, Fletcher RA, et al. Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2024;12:545-557. 38991584. FAU - Maher, Michelle AU - Maher M AD - Galway University Hospitals and University of Galway, Galway, Ireland (M.M., S.D.). FAU - Dinneen, Sean AU - Dinneen S AUID- ORCID: 0000-0002-6636-0493 AD - Galway University Hospitals and University of Galway, Galway, Ireland (M.M., S.D.). LA - eng PT - Journal Article DEP - 20241105 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Meta-Analysis as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2024/11/04 18:23 MHDA- 2024/11/18 18:23 CRDT- 2024/11/04 17:03 PHST- 2024/11/18 18:23 [medline] PHST- 2024/11/04 18:23 [pubmed] PHST- 2024/11/04 17:03 [entrez] AID - 10.7326/ANNALS-24-02849-JC [doi] PST - ppublish SO - Ann Intern Med. 2024 Nov;177(11):JC124. doi: 10.7326/ANNALS-24-02849-JC. Epub 2024 Nov 5. PMID- 39496023 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 44 DP - 2024 Nov 1 TI - Effect of GLP-1 receptor agonists on weight and cardiovascular outcomes: A review. PG - e40364 LID - 10.1097/MD.0000000000040364 [doi] LID - e40364 AB - Diet and lifestyle modifications remain the foundation of obesity treatment, but they have historically proven insufficient for significant, long-term weight loss. As a result, there is a high demand for new pharmacologic treatments to promote weight loss and prevent life-threatening diseases associated with obesity. Researchers are particularly interested in 1 type of drug, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), because of its promising potential in addressing the limitations of non-pharmacologic treatments. In addition to their role in weight loss, these drugs have shown promising early evidence of cardiovascular benefits in obese patients, further enhancing their clinical relevance. Semaglutide and liraglutide, which were initially approved for the treatment of type 2 diabetes, have since been approved by the Food and Drug Administration as weight loss medications due to their effectiveness in promoting significant and sustained weight loss. In this narrative review, we will explore the mechanism of GLP-1 RAs, their effects on weight loss, cardiovascular risk factors and outcomes, common adverse effects, and strategies for managing these effects. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Raza, Fatima Ali AU - Raza FA AUID- ORCID: 0000-0001-6889-2197 AD - Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan. FAU - Altaf, Rafiya AU - Altaf R AD - Department of Surgery, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan. FAU - Bashir, Talha AU - Bashir T AD - Department of Medicine, Karachi Institute of Medical Sciences, Combined Military Hospital Malir, Karachi City, Pakistan. FAU - Asghar, Fatima AU - Asghar F AD - Department of Medicine, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Altaf, Rabiya AU - Altaf R AD - Department of Medicine, Mersey and West Lancashire Teaching Hospitals NHS Trust, Prescot, United Kingdom. FAU - Tousif, Sohaib AU - Tousif S AD - Department of Medicine, Ziauddin University, Karachi City, Pakistan. FAU - Goyal, Aman AU - Goyal A AD - Department of Medicine, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India. FAU - Mohammed, Aisha AU - Mohammed A AD - Department of Medicine, Comanche County Memorial Hospital, Lawton, OK. FAU - Mohammad, Mahnoor Faisal AU - Mohammad MF AD - Department of Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan. FAU - Anan, Mahfuza AU - Anan M AUID- ORCID: 0009-0004-9176-4782 AD - Department of Medicine, Bangladesh Medical College, Dhaka, Bangladesh. FAU - Ali, Sajjad AU - Ali S AUID- ORCID: 0000-0002-8024-5942 AD - Department of Medicine, Ziauddin University, Karachi City, Pakistan. LA - eng PT - Journal Article PT - Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Obesity/drug therapy/complications MH - *Liraglutide/therapeutic use/pharmacology MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Heart Disease Risk Factors MH - Hypoglycemic Agents/therapeutic use MH - Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11537668 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2024/11/04 22:24 MHDA- 2024/11/04 22:25 PMCR- 2024/11/01 CRDT- 2024/11/04 15:33 PHST- 2024/11/04 22:25 [medline] PHST- 2024/11/04 22:24 [pubmed] PHST- 2024/11/04 15:33 [entrez] PHST- 2024/11/01 00:00 [pmc-release] AID - 00005792-202411010-00056 [pii] AID - MD-D-24-09777 [pii] AID - 10.1097/MD.0000000000040364 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Nov 1;103(44):e40364. doi: 10.1097/MD.0000000000040364. PMID- 39495965 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20260923 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 1 DP - 2025 Jan TI - Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE-1 and -2). PG - 67-77 LID - 10.1002/oby.24184 [doi] AB - OBJECTIVE: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2). METHODS: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.6 or 6.0 mg, and dose flexibility is permitted. Participants (n = 726) in SYNCHRONIZE-1 (NCT06066515) have a baseline BMI >/= 30 kg/m(2) or >/=27 kg/m(2) with at least one obesity-related complication but without T2D; participants (n = 755) in SYNCHRONIZE-2 (NCT06066528) have a baseline BMI >/= 27 kg/m(2) and T2D. The primary endpoints are percentage change in body weight and proportion of participants achieving >/=5% body weight reduction from baseline to week 76. Secondary endpoints include change in systolic blood pressure and measures of glycemia. A SYNCHRONIZE-1 substudy is evaluating changes in body composition and liver fat content using magnetic resonance imaging. CONCLUSIONS: These trials are designed to provide robust evaluation of the efficacy, safety, and tolerability of survodutide for the treatment of obesity in the presence or absence of T2D. CI - (c) 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - McMaster University, Hamilton, Ontario and University of Toronto, Toronto, Ontario, Canada. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin, Ireland. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AUID- ORCID: 0000-0002-3750-9789 AD - Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri, USA. FAU - Platz, Elke AU - Platz E AUID- ORCID: 0000-0002-8604-0710 AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Brueckmann, Martina AU - Brueckmann M AUID- ORCID: 0000-0003-1215-0746 AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. AD - First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Jastreboff, Ania M AU - Jastreboff AM AUID- ORCID: 0000-0003-1446-0991 AD - Section of Endocrinology (Internal Medicine & Pediatrics) and Yale Obesity Research Center (Y-Weight), Yale School of Medicine, New Haven, Connecticut, USA. FAU - Ajaz Hussain, Samina AU - Ajaz Hussain S AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Pedersen, Sue D AU - Pedersen SD AUID- ORCID: 0000-0002-4355-1764 AD - C-ENDO Diabetes and Endocrinology Clinic and University of Calgary, Calgary, Alberta, Canada. FAU - Borowska, Luiza AU - Borowska L AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Unseld, Anna AU - Unseld A AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany. FAU - Kloer, Isabel M AU - Kloer IM AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Kaplan, Lee M AU - Kaplan LM AUID- ORCID: 0000-0002-6301-2696 AD - Section of Obesity Medicine and Center for Digestive Health, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. CN - SYNCHRONIZE-1 and -2 trial committees and investigators LA - eng GR - P30 DK045735/DK/NIDDK NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - Boehringer Ingelheim/ PT - Clinical Trial Protocol PT - Journal Article DEP - 20241104 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 9007-92-5 (Glucagon) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - Body Weight/drug effects MH - *Clinical Trials, Phase III as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Glucagon MH - Hypoglycemic Agents/therapeutic use MH - Injections, Subcutaneous MH - *Obesity/drug therapy MH - *Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Multicenter Studies as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11664303 COIS- Sean Wharton reports research funding from Novo Nordisk and Bausch Health Canada. He reports honoraria for academic talks and advisory board from Amgen, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Regeneron, Bausch Health Canada, Merck, iNova and Currax. Carel W. le Roux has received personal fees from Boehringer Ingelheim, GI Dynamics, Herbalife, Johnson & Johnson, Keyron, Eli Lilly, and Novo Nordisk outside the submitted work. Mikhail N. Kosiborod reports research grants (payments to institution) from Astra Zeneca, Boehringer Ingelheim, and Pfizer. He reports serving as a consultant on advisory boards (payments to institution) for 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, Astra Zeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Regeneron, Sanofi, Pharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics. He reports other research support (Data Analytic Center Fees - payments to institution) from Astra Zeneca and Vifor Pharma. He reports receiving honoraria (payments to institution) from Astra Zeneca, Boehringer Ingelheim, and Novo Nordisk. He reports stock options (personal) from Artera Health and Saghmos Therapeutics. Elke Platz's employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals. She has received research support from AstraZeneca, and she serves on the clinical trial steering committee of the SYNCHRONIZE-1 and -2 trials and SYNCHRONIZE-CVOT funded by Boehringer Ingelheim. Martina Brueckmann, Samina Ajaz Hussain, Luiza Borowska, Anna Unseld, and Isabel M. Kloer are employees of Boehringer Ingelheim. Ania M. Jastreboff conducts multicenter trials with Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals and serves on scientific advisory boards for Amgen, AstraZeneca, Biohaven, Boehringer Ingelheim, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron Pharmaceuticals, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals, WeightWatchers, and Zealand Pharma. Sue D. Pedersen declares personal fees for advisory board membership and speaking from Novo Nordisk, Janssen, Eli Lilly, Merck, Bausch Health, AstraZeneca, Abbott, Boehringer Ingelheim, Sanofi, HLS Therapeutics, and Dexcom; consulting fees from Novo Nordisk, Janssen, AstraZeneca, Abbott, HLS Therapeutics, and Dexcom; fees for clinical trials from Novo Nordisk, Eli Lilly, AstraZeneca, Sanofi, Prometic, and Pfizer; and grants from Eli Lilly, AstraZeneca, Abbott, Boehringer Ingelheim, and Sanofi. Lee M. Kaplan reports serving as a consultant to Altimmune, Amgen, AstraZeneca, Bain Capital, Boehringer Ingelheim, Cytoki, Gelesis, Gilead Sciences, Glyscend, Intellihealth, Johnson & Johnson, Kallyope, Eli Lilly, Novo Nordisk, Optum Health, Perspectum, Pfizer, Sidekick Health, Skye Bioscience, twenty30.health, Xeno Biosciences, and Zealand Pharma. EDAT- 2024/11/04 18:23 MHDA- 2024/12/23 06:21 PMCR- 2024/12/23 CRDT- 2024/11/04 15:33 PHST- 2024/10/04 00:00 [revised] PHST- 2024/09/06 00:00 [received] PHST- 2024/10/07 00:00 [accepted] PHST- 2024/12/23 06:21 [medline] PHST- 2024/11/04 18:23 [pubmed] PHST- 2024/11/04 15:33 [entrez] PHST- 2024/12/23 00:00 [pmc-release] AID - OBY24184 [pii] AID - 10.1002/oby.24184 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Jan;33(1):67-77. doi: 10.1002/oby.24184. Epub 2024 Nov 4. PMID- 39495435 OWN - NLM STAT- MEDLINE DCOM- 20250312 LR - 20261010 IS - 1573-2584 (Electronic) IS - 0301-1623 (Linking) VI - 57 IP - 4 DP - 2025 Apr TI - Effect of GLP-1 receptor agonists on prostate cancer risk reduction: a systematic review and meta-analysis. PG - 1039-1049 LID - 10.1007/s11255-024-04266-4 [doi] AB - BACKGROUND: Prostate cancer is one of the most prevalent malignancies among men globally. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), primarily used for type 2 diabetes mellitus (T2DM) management, have been investigated for their potential effects on cancer risks. This systematic review and meta-analysis aimed to assess the association between GLP-1 RA use and risk reduction of prostate cancer. METHODS: A comprehensive literature search was conducted across PubMed, Embase, and Web of Science up to July 30, 2024. Studies that met the inclusion criteria randomized controlled trials, cohort studies, case-control studies, and observational studies assessing the incidence of prostate cancer in GLP-1 RA-treated patients were included. The quality of studies was evaluated using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Meta-analysis was performed using a random effects model. RESULTS: A total of five studies were included, analyzing data from diverse international contexts. The included studies showed a reduced risk of prostate cancer with both adjusted and unadjusted effect estimates with GLP-1 RAs. The meta-analysis revealed an RR of 0.72 (95% CI: 0.610 to 0.832), indicating a statistically significant 28% reduction in prostate cancer risk associated with GLP-1 RA use compared to placebo or other antidiabetic drugs. Moderate heterogeneity was observed (I(2) = 51%). Sensitivity analysis confirmed the results. CONCLUSION: The findings suggest a significant protective association between GLP-1 RA use and reduced prostate cancer risk in men, particularly those with T2DM. This supports the potential of GLP-1 RAs not only in diabetes management but also as a strategy to mitigate cancer risk. Further research is required to confirm these findings and explore the underlying mechanisms, considering different dosages, durations of therapy, and patient subgroups based on demographic and metabolic characteristics. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Sharma, Nikhil AU - Sharma N AD - Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, 781101, India. FAU - Khatib, Mahalaqua Nazli AU - Khatib MN AD - Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India. FAU - Balaraman, Ashok Kumar AU - Balaraman AK AD - Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia. FAU - Roopashree, R AU - Roopashree R AD - Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India. FAU - Kaur, Mandeep AU - Kaur M AD - Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India. FAU - Srivastava, Manish AU - Srivastava M AD - Department of Endocrinology, NIMS University, Jaipur, India. FAU - Barwal, Amit AU - Barwal A AD - Chandigarh Pharmacy College, Chandigarh Group of College, Jhanjeri, Mohali, 140307, Punjab, India. FAU - Prasad, G V Siva AU - Prasad GVS AD - Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, 531162, India. FAU - Rajput, Pranchal AU - Rajput P AD - School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India. FAU - Syed, Rukshar AU - Syed R AD - IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, 462044, India. FAU - Sharma, Gajendra AU - Sharma G AD - New Delhi Institute of Management, Delhi, India. FAU - Kumar, Sunil AU - Kumar S AD - Department of Microbiology, Graphic Era (Deemed to Be University), Clement Town, Dehradun, 248002, India. FAU - Singh, Mahendra Pratap AU - Singh MP AD - Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India. FAU - Bushi, Ganesh AU - Bushi G AD - School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India. FAU - Chilakam, Nagavalli AU - Chilakam N AD - Noida Institute of Engineering and Technology (Pharmacy Institute), Greater, Noida, India. FAU - Pandey, Sakshi AU - Pandey S AD - Centre of Research Impact and Outcome, Chitkara University, Rajpura, 140417, Punjab, India. FAU - Brar, Manvinder AU - Brar M AD - Chitkara Centre for Research and Development, Chitkara University, Rajpura, Himachal Pradesh, 174103, India. FAU - Mehta, Rachana AU - Mehta R AD - Clinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, 121004, India. AD - Dr Lal PathLabs - Nepal, Chandol-4, Maharajgunj, Kathmandu, 44600, Nepal. FAU - Sah, Sanjit AU - Sah S AD - Department of Paediatrics, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India. AD - Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India. FAU - Gaidhane, Abhay M AU - Gaidhane AM AD - School of Epidemiology and Public Health, Jawaharlal Nehru Medical College, and Global Health Academy, Datta Meghe Institute of Higher Education, Wardha, India. FAU - Shabil, Muhammed AU - Shabil M AD - University Center for Research and Development, Chandigarh University, Mohali, Punjab, India. mohdshabil99@gmail.com. AD - Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001, Hillah, Babil, Iraq. mohdshabil99@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241104 PL - Netherlands TA - Int Urol Nephrol JT - International urology and nephrology JID - 0262521 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - *Prostatic Neoplasms/prevention & control/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Meta-analysis OT - Prostate cancer OT - Systematic review COIS- Declarations. Conflicts of interest: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent to participate: Not applicable since this is a review and not involved any human. EDAT- 2024/11/04 12:24 MHDA- 2025/03/12 18:17 CRDT- 2024/11/04 11:19 PHST- 2024/10/08 00:00 [received] PHST- 2024/10/24 00:00 [accepted] PHST- 2025/03/12 18:17 [medline] PHST- 2024/11/04 12:24 [pubmed] PHST- 2024/11/04 11:19 [entrez] AID - 10.1007/s11255-024-04266-4 [pii] AID - 10.1007/s11255-024-04266-4 [doi] PST - ppublish SO - Int Urol Nephrol. 2025 Apr;57(4):1039-1049. doi: 10.1007/s11255-024-04266-4. Epub 2024 Nov 4. PMID- 39495140 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist. PG - 551-562 LID - 10.1111/dom.16047 [doi] AB - AIMS: GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA. MATERIALS AND METHODS: ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human beta-cell line and non-human primates (NHPs). To evaluate safety, ECC5004 was orally administered to NHPs for 9 months and a phase I, double-blind, placebo-controlled FIH study was conducted. This study evaluated single doses of ECC5004 (1-300 mg) in healthy volunteers, and multiple daily doses (5, 10, 30 and 50 mg) in patients with T2DM for 28 days. RESULTS: ECC5004 bound to the hGLP-1R (IC(50) = 2.4 nM) augmented cAMP signalling without beta-arrestin-2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC-betaH5 cells (EC(50) = 5.9 nM) and in vivo in NHPs (EC(50) = 0.022 nM). Dose-dependent body weight changes compared to control were seen in the 9-month NHP toxicity study. In the first-in-human study, ECC5004 was well tolerated with no serious adverse events. Dose-dependent reductions in glucose and body weight were observed with a dose-proportional exposure at doses >/=25 mg. CONCLUSION: ECC5004 engaged the GLP-1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP-1 RAs, along with a pharmacokinetic profile compatible with once-daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. CLINICAL TRIAL REGISTRATION: NCT05654831. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Haggag, Amina Z AU - Haggag AZ AD - Anaheim Clinical Trials LLC, Anaheim, California, USA. FAU - Xu, Jianfeng AU - Xu J AD - Eccogene Inc., Cambridge, Massachusetts, USA. FAU - Butcher, Laurie AU - Butcher L AD - Eccogene Inc., Cambridge, Massachusetts, USA. FAU - Pagnussat, Sandra AU - Pagnussat S AD - QPS MRA LLC, Miami, Florida, USA. FAU - Davies, Graeme AU - Davies G AD - Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Lundqvist, Sara AU - Lundqvist S AD - Assays, Profiling and Cell Sciences, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Wang, Wenyu AU - Wang W AD - Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Van Zuydam, Natalie AU - Van Zuydam N AD - Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Nelander, Karin AU - Nelander K AD - Cardiovascular, Renal and Metabolism Biometrics, Late Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Jha, Aruni AU - Jha A AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Yu, Hongtao AU - Yu H AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Boianelli, Alessandro AU - Boianelli A AD - DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Lindmark, Bosse AU - Lindmark B AD - DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Ollerstam, Anna AU - Ollerstam A AD - Cardiovascular, Renal and Metabolism Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. FAU - Sun, Xuefeng AU - Sun X AD - Eccogene (Shanghai) Co. Ltd., Shanghai, China. FAU - Wang, Fan AU - Wang F AD - Eccogene (Shanghai) Co. Ltd., Shanghai, China. FAU - Pan, Xiaoliang AU - Pan X AD - Eccogene (Shanghai) Co. Ltd., Shanghai, China. FAU - Liu, Haihui AU - Liu H AD - Eccogene (Shanghai) Co. Ltd., Shanghai, China. FAU - Chen, Wengang AU - Chen W AD - Eccogene Inc., Cambridge, Massachusetts, USA. FAU - Xu, Jianfeng AU - Xu J AD - Eccogene (Shanghai) Co. Ltd., Shanghai, China. FAU - Wallenius, Kristina AU - Wallenius K AD - Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Zhou, Jingye AU - Zhou J AUID- ORCID: 0000-0002-8767-3878 AD - Eccogene Inc., Cambridge, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT05654831 GR - Eccogene and AstraZeneca/ PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20241104 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Small Molecule Libraries) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) SB - IM MH - Adult MH - Animals MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Hypoglycemic Agents/pharmacology/administration & dosage MH - Insulin Secretion/drug effects MH - Insulin-Secreting Cells/drug effects/metabolism MH - Macaca fascicularis MH - *Small Molecule Libraries/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11701199 OTO - NOTNLM OT - AZD5004 OT - ECC5004 OT - GLP-1 OT - GLP-1 RA OT - obesity OT - overweight OT - small molecule OT - type 2 diabetes mellitus COIS- AZH and SP have no conflicts of interest. JX, LB, XS, FW, XP, HL, WC, JX and JZ are employees and equity holders of Eccogene. GD, SL, WW, NVZ, KN, AJ, HY, AB, BL, AO and KW are employees and stockholders of AstraZeneca. EDAT- 2024/11/04 12:24 MHDA- 2025/01/07 04:51 PMCR- 2025/01/06 CRDT- 2024/11/04 10:03 PHST- 2024/10/18 00:00 [revised] PHST- 2024/09/20 00:00 [received] PHST- 2024/10/20 00:00 [accepted] PHST- 2025/01/07 04:51 [medline] PHST- 2024/11/04 12:24 [pubmed] PHST- 2024/11/04 10:03 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - DOM16047 [pii] AID - 10.1111/dom.16047 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):551-562. doi: 10.1111/dom.16047. Epub 2024 Nov 4. PMID- 39493783 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20250103 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Anti-atherosclerotic effect of incretin receptor agonists. PG - 1463547 LID - 10.3389/fendo.2024.1463547 [doi] LID - 1463547 AB - Incretin receptor agonists (IRAs), primarily composed of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs), work by mimicking the actions of the endogenous incretin hormones in the body. GLP-1RAs have been approved for use as monotherapy and in combination with GIPRAs for the management of type 2 diabetes mellitus (T2DM). In addition to their role in glucose regulation, IRAs have demonstrated various benefits such as cardiovascular protection, obesity management, and regulation of bone turnover. Some studies have suggested that IRAs not only aid in glycemic control but also exhibit anti-atherosclerotic effects. These agents have been shown to modulate lipid abnormalities, reduce blood pressure, and preserve the structural and functional integrity of the endothelium. Furthermore, IRAs have the ability to mitigate inflammation by inhibiting macrophage activation and promoting M2 polarization. Research has also indicated that IRAs can decrease macrophage foam cell formation and prevent vascular smooth muscle cell (VSMC) phenotype switching, which are pivotal in atheromatous plaque formation and stability. This review offers a comprehensive overview of the protective effects of IRAs in atherosclerotic disease, with a focus on their impact on atherogenesis. CI - Copyright (c) 2024 Wang, Yang, Qi, Fan, Zhou, Peng and Yang. FAU - Wang, Xin AU - Wang X AD - Department of Metabolism and Endocrinology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. FAU - Yang, Xin AU - Yang X AD - Department of Metabolism and Endocrinology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. FAU - Qi, Xiaoyan AU - Qi X AD - Department of Metabolism and Endocrinology, Shenzhen Nanshan People's Hospital; The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China. FAU - Fan, Gang AU - Fan G AD - Department of Urology, Shenzhen Nanshan People's Hospital; The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China. FAU - Zhou, Lingzhi AU - Zhou L AD - Department of pediatrics, Shenzhen Nanshan People's Hospital; The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China. FAU - Peng, Zhengliang AU - Peng Z AD - Department of Emergency, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. FAU - Yang, Jing AU - Yang J AD - Department of Metabolism and Endocrinology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. AD - Department of Metabolism and Endocrinology, Shenzhen Nanshan People's Hospital; The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, China. LA - eng PT - Journal Article PT - Review DEP - 20241018 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Atherosclerosis/drug therapy/metabolism/prevention & control MH - *Incretins/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Receptors, Gastrointestinal Hormone/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11527663 OTO - NOTNLM OT - atherosclerosis OT - cardiovascular disease OT - incretin receptor agonists OT - type 2 diabetes mellitus OT - vasculoprotective effects COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/11/04 06:24 MHDA- 2024/11/04 12:25 PMCR- 2024/01/01 CRDT- 2024/11/04 05:09 PHST- 2024/07/12 00:00 [received] PHST- 2024/09/30 00:00 [accepted] PHST- 2024/11/04 12:25 [medline] PHST- 2024/11/04 06:24 [pubmed] PHST- 2024/11/04 05:09 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1463547 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Oct 18;15:1463547. doi: 10.3389/fendo.2024.1463547. eCollection 2024. PMID- 39491755 OWN - NLM STAT- MEDLINE DCOM- 20250322 LR - 20260608 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 132 IP - 4 DP - 2025 Apr TI - Association between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study. PG - 381-388 LID - S0161-6420(24)00685-7 [pii] LID - 10.1016/j.ophtha.2024.10.030 [doi] AB - PURPOSE: To investigate whether semaglutide increases the risk of nonarteritic anterior ischemic optic neuropathy (NAION) in the general population. DESIGN: This retrospective cohort study used a deidentified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. PARTICIPANTS: This study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight-loss medications other than glucagon-like peptide receptor agonists. METHODS: Patient data were obtained from 160 health care organizations across 21 countries. Outcomes were evaluated at 1, 2, and 3 years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The occurrence of NAION. RESULTS: The final analysis included 37 314 participants with T2DM only, 129 690 participants with obesity only, and 130 216 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1-year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1-year follow-up: HR, 0.41; 95% CI, 0.08-2.09; 2 years: HR, 0.67; 95% CI, 0.20-2.24; 3 years: HR, 0.72; 95% CI, 0.24-2.16), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82). CONCLUSIONS: The findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted because its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. CI - Copyright (c) 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Chou, Chien-Chih AU - Chou CC AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. FAU - Pan, Ssu-Yu AU - Pan SY AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Sheen, Yi-Jing AU - Sheen YJ AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Center for Quantitative Imaging in Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Jun-Fu AU - Lin JF AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Ching-Heng AU - Lin CH AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Lin, Hui-Ju AU - Lin HJ AD - Eye Center, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. FAU - Wang, I-Jong AU - Wang IJ AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. FAU - Weng, Chien-Hsiang AU - Weng CH AD - Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island; Coastal Medical Lifespan, Providence, Rhode Island. Electronic address: chien-hsiang_weng@brown.edu. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20241102 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - *Glucagon-Like Peptides/adverse effects MH - Retrospective Studies MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Aged MH - Obesity/complications/drug therapy/epidemiology MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Follow-Up Studies MH - Incidence MH - Glycated Hemoglobin/metabolism MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Nonarteritic anterior ischemic optic neuropathy OT - Semaglutide OT - Stroke EDAT- 2024/11/04 06:23 MHDA- 2025/03/23 16:51 CRDT- 2024/11/04 01:23 PHST- 2024/09/12 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/10/24 00:00 [accepted] PHST- 2025/03/23 16:51 [medline] PHST- 2024/11/04 06:23 [pubmed] PHST- 2024/11/04 01:23 [entrez] AID - S0161-6420(24)00685-7 [pii] AID - 10.1016/j.ophtha.2024.10.030 [doi] PST - ppublish SO - Ophthalmology. 2025 Apr;132(4):381-388. doi: 10.1016/j.ophtha.2024.10.030. Epub 2024 Nov 2. PMID- 39491749 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1878-1632 (Electronic) IS - 1529-9430 (Linking) VI - 25 IP - 3 DP - 2025 Mar TI - Semaglutide utilization associated with reduced 90-day postoperative complications following single-level posterior lumbar fusion for patients with type II diabetes. PG - 485-493 LID - S1529-9430(24)01093-3 [pii] LID - 10.1016/j.spinee.2024.10.011 [doi] AB - BACKGROUND CONTEXT: Semaglutide (the active agent in medications such as Ozempic) has emerged as an increasingly popular medication in the management of diabetes due to its superior clinical efficacy compared with other medications. Patients undergoing surgery, such as posterior lumbar fusion (PLF), may be on these medications for type II diabetes mellitus (T2DM). While the correlation of T2DM with inferior PLF outcomes is known, considering the potential impact of semaglutide on the odds of postoperative complications has not previously been characterized. PURPOSE: To investigate the potential correlation of semaglutide on 90-day postoperative adverse events following single-level PLF for those with T2DM who are or are not concurrently taking insulin. STUDY DESIGN/SETTING: A retrospective cohort study utilizing the 2010 to Q2 2022 M161Ortho PearlDiver Mariner Patient Claims Database. PATIENT SAMPLE: T2DM patients (with or without concurrent insulin use) undergoing single-level PLF (with or without interbody fusion) were identified using Current Procedural Terminology (CPT) codes. Exclusion criteria included: patients less than 18 years of age, those undergoing concurrent cervical, thoracic, anterior, or multilevel fusion procedures, and those with trauma, neoplasm, or infection diagnosed within three months of surgery. OUTCOME MEASURES: Incidence of 90-day aggregated any, severe, and minor adverse events (AAE, SAE, and MAE, respectively), emergency department (ED) visits, and hospital readmissions. METHODS: Patients with a prior diagnosis of T2DM not using insulin (T2DM-insulin) and T2DM concurrently using insulin (T2DM+insulin) undergoing PLF were identified. Patients within each group who utilized semaglutide in the year prior to surgery were identified and matched 1:4 with nonsemaglutide T2DM-insulin and nonsemaglutide T2DM+insulin patients, respectively, based on age, sex, Elixhauser Comorbidity Index (ECI), obesity, tobacco use, metformin use, and sodium-glucose transport protein 2 inhibitor (SGLT2i) use. The incidence of 90-day adverse events between groups was compared by univariate and multivariate analyses. Bonferroni correction was utilized to reduce the risk of type I error. RESULTS: Of all T2DM patients undergoing PLF, semaglutide use was noted for 227 (0.73%) of T2DM-insulin patients, and 244 (2.17%) of T2DM+insulin patients. Once matched, there were 191 and 148 in the semaglutide groups, respectively. For the PLF T2DM-insulin analysis, those using semaglutide were at significantly lower odds of AAE (odds ratio [OR] 0.43), MAE (OR 0.45), and ED visits (OR 0.34) (p<.001 for all), but not of SAEs or readmissions. For the PLF T2DM+insulin analysis, those using semaglutide were at significantly lower odds of AAE (OR 0.40, p<.001), SAE (OR 0.43, p=.004), MAE (OR 0.34, p<.001), and ED visits (OR 0.26, p<.001), but not readmissions. CONCLUSIONS: The current study found consistent reductions in aggregated 90-day adverse events, but similar odds of hospital readmission for T2DM patients undergoing PLF taking semaglutide preoperatively. These encouraging findings of reduced postoperative complications suggest further prospective analysis, as the observed findings suggest clinical benefit to semaglutide being utilized by the studied patient population. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Vasudevan, Rajiv S AU - Vasudevan RS AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Dhodapkar, Meera M AU - Dhodapkar MM AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Jabbouri, Sahir S AU - Jabbouri SS AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Varthi, Arya G AU - Varthi AG AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Rubio, Daniel R AU - Rubio DR AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. Electronic address: jonathan.grauer@yale.edu. LA - eng PT - Journal Article DEP - 20241102 PL - United States TA - Spine J JT - The spine journal : official journal of the North American Spine Society JID - 101130732 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Spinal Fusion/adverse effects/methods MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Postoperative Complications/epidemiology/prevention & control MH - *Lumbar Vertebrae/surgery MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse events OT - Ozempic OT - Posterior lumbar fusion OT - Semaglutide OT - Spine surgery OT - Type II diabetes COIS- Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms. EDAT- 2024/11/04 06:24 MHDA- 2025/02/16 01:32 CRDT- 2024/11/04 01:22 PHST- 2024/02/29 00:00 [received] PHST- 2024/09/09 00:00 [revised] PHST- 2024/10/27 00:00 [accepted] PHST- 2025/02/16 01:32 [medline] PHST- 2024/11/04 06:24 [pubmed] PHST- 2024/11/04 01:22 [entrez] AID - S1529-9430(24)01093-3 [pii] AID - 10.1016/j.spinee.2024.10.011 [doi] PST - ppublish SO - Spine J. 2025 Mar;25(3):485-493. doi: 10.1016/j.spinee.2024.10.011. Epub 2024 Nov 2. PMID- 39490542 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260901 IS - 1526-3231 (Electronic) IS - 0749-8063 (Linking) VI - 41 IP - 2 DP - 2025 Feb TI - Lower Risk of Postoperative Complications and Rotator Cuff Retear Associated With Semaglutide Use in Patients with Type II Diabetes Mellitus Undergoing Arthroscopic Rotator Cuff Repair. PG - 199-206 LID - S0749-8063(24)00838-7 [pii] LID - 10.1016/j.arthro.2024.09.057 [doi] AB - PURPOSE: To investigate the potential impact of preoperative semaglutide use (the active agent in Ozempic and Wegovy) on 90-day postoperative outcomes and 2-year rotator cuff retear after arthroscopic rotator cuff repair (ARCR) in patients with type II diabetes mellitus (T2DM). METHODS: Patients with T2DM undergoing primary ARCR were identified from the PearlDiver database using administrative billing codes. Exclusion criteria included patients <18 years old; previous RCR; concurrent nonrotator cuff-related arthroscopic shoulder procedures; any traumatic, neoplastic, or infectious diagnoses within 90 days before surgery; and <90-days follow-up. Patients with T2DM using semaglutide within 1 year of ARCR ([+]semaglutide) were matched 1:4 with patients with T2DM who did not ([-]semaglutide) by age, sex, Elixhauser Comorbidity Index, diabetes complications, obesity, tobacco, insulin, and metformin use. Occurrence of any adverse events (AAE), severe adverse events (SAE), and minor adverse events (MAE) within 90 days were compared by multivariable logistic regression. The 2-year retear was assessed by Kaplan-Meier survival analysis and compared by log-rank test. RESULTS: There were 1,094 ARCR (+)semaglutide and 4,110 ARCR (-)semaglutide patients meeting inclusion criteria after matching. The incidence of AAE for the ARCR (-)semaglutide versus ARCR (+)semaglutide patients was 27.4% versus 11.0%, SAE was 10.5% versus 3.5%, and MAE was 22.0% versus 8.5%, respectively (P < .001 for all). ARCR (-)semaglutide patients had a greater odds ratio of AAE (3.65, P < .001) and SAE (3.62, P < .001), including surgical-site infection (2.22, P = .049), venous thromboembolism (3.10, P < .001), sepsis (3.87, P < .001), and cardiac events (3.96, P < .001), as well as greater odds of MAE (3.59, P < .001), including urinary tract infection (3.27), pneumonia (3.88), acute kidney injury (3.91), and emergency department visits (2.51) (P < .001 for all). In addition, (-)semaglutide patients revealed greater 2-year retear vs (+)semaglutide patients (18.3% vs 12.5%, respectively) (P < .001). CONCLUSIONS: Preoperative semaglutide use for patients with T2DM undergoing ARCR was associated with decreased odds of minor and serious 90-day adverse events and lower 2-year rotator cuff retear. LEVEL OF EVIDENCE: Level III, retrospective comparative study. CI - Copyright (c) 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Moran, Jay AU - Moran J AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Garbis, Nickolas G AU - Garbis NG AD - Department of Orthopaedic Surgery and Rehabilitation, Loyola University Chicago, Maywood, Illinois, U.S.A. FAU - Salazar, Dane H AU - Salazar DH AD - Department of Orthopaedic Surgery and Rehabilitation, Loyola University Chicago, Maywood, Illinois, U.S.A. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Jimenez, Andrew E AU - Jimenez AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A.. Electronic address: andrew.jimenez@yale.edu. LA - eng PT - Journal Article DEP - 20241026 PL - United States TA - Arthroscopy JT - Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association JID - 8506498 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Arthroscopy/adverse effects/methods MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Middle Aged MH - *Postoperative Complications/epidemiology/prevention & control/etiology MH - *Rotator Cuff Injuries/surgery/complications MH - Aged MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.E.J. reports consulting or advisory for Arthrex and member of the editorial board of The Journal Arthroscopy. D.H.S. reports consulting or advisory for Zimmer, Arthrex, and Stryker; and board membership, American Shoulder and Elbow Surgeons and American Orthopaedic Association that includes. J.N.G. reports board membership, North American Spine Society and Editor-in-Chief, North American Spine Society Journal. N.G.G. reports consulting or advisory for Medacta USA; speaking and lecture fees from Enovis Corporation and Arthrex; and equity or stocks from Additive Implants and Aevumed. All other authors (A.E.S., J.M., M.J.G.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/04 00:31 MHDA- 2025/01/24 00:26 CRDT- 2024/11/03 23:53 PHST- 2024/07/17 00:00 [received] PHST- 2024/09/11 00:00 [revised] PHST- 2024/09/23 00:00 [accepted] PHST- 2025/01/24 00:26 [medline] PHST- 2024/11/04 00:31 [pubmed] PHST- 2024/11/03 23:53 [entrez] AID - S0749-8063(24)00838-7 [pii] AID - 10.1016/j.arthro.2024.09.057 [doi] PST - ppublish SO - Arthroscopy. 2025 Feb;41(2):199-206. doi: 10.1016/j.arthro.2024.09.057. Epub 2024 Oct 26. PMID- 39488821 OWN - NLM STAT- MEDLINE DCOM- 20241114 LR - 20260127 IS - 1179-1918 (Electronic) IS - 1173-2563 (Print) IS - 1173-2563 (Linking) VI - 44 IP - 11 DP - 2024 Nov TI - Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus. PG - 849-861 LID - 10.1007/s40261-024-01405-8 [doi] AB - BACKGROUND AND OBJECTIVE: IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM). METHODS: In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose. RESULTS: Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC(0-t): ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (C(max)): 1.12 [1.06; 1.18]. Semaglutide AUC(0-t) was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide C(max) was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone. CONCLUSION: The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema. CLINICAL TRIAL: ClinicalTrials.gov identifier: NCT03789578. CI - (c) 2024. The Author(s). FAU - Westergaard, Lisbet AU - Westergaard L AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Alifrangis, Lene AU - Alifrangis L AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Buckley, Stephen T AU - Buckley ST AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Coester, Hans Veit AU - Coester HV AD - Profil, Neuss, Germany. FAU - Klitgaard, Thomas AU - Klitgaard T AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Kristensen, Niels R AU - Kristensen NR AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Nishimura, Erica AU - Nishimura E AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Norgreen, Lea AU - Norgreen L AD - Novo Nordisk, Development, Aalborg, Denmark. FAU - Rocha, Thais M P AU - Rocha TMP AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Steensgaard, Dorte B AU - Steensgaard DB AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Vegge, Andreas AU - Vegge A AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Plum-Morschel, Leona AU - Plum-Morschel L AD - Profil, Neuss, Germany. leona.plum-moerschel@profil.com. LA - eng SI - ClinicalTrials.gov/NCT03789578 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20241103 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Drug Combinations) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Middle Aged MH - *Cross-Over Studies MH - Male MH - Adult MH - Female MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics MH - Double-Blind Method MH - Young Adult MH - Adolescent MH - Drug Combinations MH - Injections, Subcutaneous MH - Drug Administration Schedule MH - Insulin/administration & dosage/pharmacokinetics MH - Semaglutide PMC - PMC11564230 COIS- Declarations Funding This study was funded by Novo Nordisk. Conflicts of interest L.W., L.A., S.T.B., T.K., N.R.K., E.N., L.N., T.M.P.R., D.B.S. and A.V. are employees and shareholders of Novo Nordisk. H.V.C. has no conflicts of interest to disclose. L.P.-M. is an employee and shareholder of Profil. Profil received research funds from Adocia, AstraZeneca, Betagenon, Biocon, Bioton, Crinetics, Eli Lilly, Genova, Nanexa, NeoDyne, Novo Nordisk, Sanofi, Spiden and Zealand Pharma. L.P.-M. received speaker honoraria from Eli Lilly, Gan and Lee Pharmaceuticals and Novo Nordisk. Availability of data and material Individual participant data will be shared in data sets in a de-identified/anonymised format. Datasets from Novo Nordisk sponsored clinical research completed after 2001 for product indications approved in both the EU and USA will be shared. Study protocol and redacted clinical study report will be available according to Novo Nordisk data sharing commitments. The data will be available permanently after research completion and approval of product and product use in both EU and USA. There is no end date. Data will be shared with bona fide researchers submitting a research proposal requesting access to data for use as approved by the independent review board according to the independent review board charter (see novonordisk-trials.com). The data will be made available on a specialised SAS data platform. Individual data from animal studies and in vitro studies will be shared upon reasonable request. Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The clinical study was approved by an independent ethics committee (Arztekammer Nordrhein, Dusseldorf, Germany; approval ID 2018242; approval date 12 November 2018). Animal studies were performed according to the Danish Act on Experiments on Animals, the Appendix A of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123), and European Union Directive 2010/63. The animal studies were performed under licenses granted by the Danish national Animal Experiments Inspectorate (no. 2010/561-1786 and no. 2015-15-0201-00540). Consent to participate Informed consent was obtained from all individual participants included in the clinical study. Consent for publication Not applicable. Code availability Not applicable. Author contributions L.W., N.R.K., L.N. and T.M.P.R. contributed to clinical study data analysis, critical manuscript revision and final manuscript approval; L.A., S.T.B., T.K., E.N., D.B.S. and A.V. contributed to animal and in vitro study design, data analysis, critical manuscript revision and final manuscript approval; H.V.C. and L.P.-M. contributed to clinical study data collection, critical manuscript revision and final manuscript approval. EDAT- 2024/11/03 12:23 MHDA- 2024/11/14 18:30 PMCR- 2024/11/03 CRDT- 2024/11/03 11:04 PHST- 2024/10/14 00:00 [accepted] PHST- 2024/11/14 18:30 [medline] PHST- 2024/11/03 12:23 [pubmed] PHST- 2024/11/03 11:04 [entrez] PHST- 2024/11/03 00:00 [pmc-release] AID - 10.1007/s40261-024-01405-8 [pii] AID - 1405 [pii] AID - 10.1007/s40261-024-01405-8 [doi] PST - ppublish SO - Clin Drug Investig. 2024 Nov;44(11):849-861. doi: 10.1007/s40261-024-01405-8. Epub 2024 Nov 3. PMID- 39487881 OWN - NLM STAT- MEDLINE DCOM- 20250130 LR - 20260623 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 1 DP - 2025 Jan TI - Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes Mellitus in France and Italy: A Retrospective Cohort Study. PG - 174-192 LID - 10.1007/s12325-024-03002-9 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with several treatment options. Some glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the European Medicines Agency include dulaglutide, subcutaneous (s.c.) semaglutide, and oral semaglutide. This study examines dulaglutide and semaglutide dosing patterns for T2DM in France and Italy. METHODS: IQVIA Longitudinal Prescription Data identified adults with T2DM prescribed dulaglutide or semaglutide between August 1, 2020 and December 31, 2022. Cohort 1 (incident) and cohort 2 (prevalent) users were followed for 12 months. RESULTS: In France and Italy, 255,571 and 350,853 patients, respectively, received at least one study GLP-1 RA. Most dulaglutide-naive patients in France (62%) and approximately half in Italy (49%) started on 1.5 mg and remained on this dose for up to 12 months (France: 66% cohort 1, 88% cohort 2; Italy: 73% cohort 1, 87% cohort 2). In cohort 1, s.c. semaglutide users mostly started on 0.25 mg (France, 78%; Italy, 61%). At 12 months, s.c. semaglutide 1.0 mg was most prescribed (France: 58% cohort 1, 75% cohort 2; Italy: 59% cohort 2), with cohort 1 in Italy mostly receiving 0.5 mg (57%). Most oral semaglutide users in Italy started on 3.0 mg (78% cohort 1; 68% cohort 2), which was increased to 7.0 mg (62% cohort 1) and 14.0 mg (48% cohort 2) at 12 months. CONCLUSIONS: GLP-1 RA dosing patterns, although similar between France and Italy, were heterogeneous over time. As oral semaglutide and higher dulaglutide doses are recent to the market, additional real-world evidence is required to evaluate utilization patterns. Graphical abstract available for this article. CI - (c) 2024. The Author(s). FAU - Khare, Swarna AU - Khare S AD - Eli Lilly and Company, 8 Arlington Square West, Bracknell, RG12 1PU, UK. FAU - Osumili, Beatrice AU - Osumili B AUID- ORCID: 0000-0002-5862-9325 AD - Eli Lilly and Company, Indianapolis, IN, USA. osumili_beatrice@lilly.com. FAU - Debackere, Nele AU - Debackere N AD - Eli Lilly and Company, Brussels, Belgium. FAU - Keapoletswe, Karabo AU - Keapoletswe K AD - IQVIA Inc., London, UK. FAU - Falato, Serena AU - Falato S AD - IQVIA Inc., Milan, Italy. FAU - Raoul, Thomas AU - Raoul T AD - IQVIA Inc., Paris, France. FAU - Coles, Briana AU - Coles B AD - IQVIA Inc., London, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241102 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Recombinant Fusion Proteins/administration & dosage MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage MH - France MH - Italy MH - Retrospective Studies MH - Aged MH - *Immunoglobulin Fc Fragments/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11782337 OTO - NOTNLM OT - Dulaglutide OT - Observational study OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of Interest: Swarna Khare, Beatrice Osumili, and Nele Debackere are employees and shareholders of Eli Lilly and Company. Briana Coles, Karabo Keapoletswe, Serena Falato, and Thomas Raoul are employees of IQVIA, which was contracted by Eli Lilly and Company to conduct the study. Briana Coles is the Vice Chair of the trial steering committee for the United Kingdom Early Detection Initiative (UK-EDI). Ethical Approval: The authors had permission to access and use the data from both the IQVIA LRx databases, and ethical approval was not required for secondary use of the data. This study was conducted in accordance with all relevant regulatory requirements, including, where applicable, the Declaration of Helsinki (and its amendments) and the Guidelines for Good Pharmacoepidemiology Practices (ISPE). EDAT- 2024/11/03 00:06 MHDA- 2025/01/30 18:21 PMCR- 2024/11/02 CRDT- 2024/11/02 12:14 PHST- 2024/07/08 00:00 [received] PHST- 2024/09/16 00:00 [accepted] PHST- 2025/01/30 18:21 [medline] PHST- 2024/11/03 00:06 [pubmed] PHST- 2024/11/02 12:14 [entrez] PHST- 2024/11/02 00:00 [pmc-release] AID - 10.1007/s12325-024-03002-9 [pii] AID - 3002 [pii] AID - 10.1007/s12325-024-03002-9 [doi] PST - ppublish SO - Adv Ther. 2025 Jan;42(1):174-192. doi: 10.1007/s12325-024-03002-9. Epub 2024 Nov 2. PMID- 39480988 OWN - NLM STAT- MEDLINE DCOM- 20260423 LR - 20260423 IS - 1555-905X (Electronic) IS - 1555-9041 (Print) IS - 1555-9041 (Linking) VI - 20 IP - 2 DP - 2025 Feb 1 TI - The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials. PG - 159-168 LID - 10.2215/CJN.0000000584 [doi] AB - KEY POINTS: This is an updated meta-analysis about glucagon-like peptide-1 receptor agonists (GLP-1 RAs) incorporating findings from the recently published FLOW and SELECT studies. Our findings show that GLP-1 RAs reduce kidney disease progression in patients with type 2 diabetes or overweight/obesity status, with or without CKD. Our meta-analysis supports the use of GLP-1 RAs for reducing the risk of adverse kidney outcomes across different populations. BACKGROUND: Recent data indicate a potential benefit of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on the progression of kidney disease among patients with CKD. Our aim was to evaluate the effect of GLP-1 RAs on the risk of worsening kidney function across different populations. METHODS: We conducted a meta-analysis of randomized controlled trials that tested GLP-1 RA treatment versus placebo in individuals with type 2 diabetes or with overweight/obesity status, with or without CKD, with kidney events reported as primary or secondary end points. The primary outcome was the occurrence of worsening kidney function, defined as either a doubling of serum creatinine or a >/=40% or >/=50% decline in eGFR, according to each study report. Secondary outcomes included development of persistent macroalbuminuria and a composite of worsening kidney function or the development of persistent macroalbuminuria. Subgroup analyses were performed by eGFR and albuminuria categories. The results are presented as risk ratios with 95% confidence intervals. RESULTS: Eight trials were eligible, including a total of 68,572 patients, of whom 34,042 (49.6%) received GLP-1 RA treatment. During follow-up, 1028 participants receiving GLP-1 RA (3.0%) and 1150 participants receiving placebo (3.5%) experienced worsening kidney function. Treatment with GLP-1 RAs (versus placebo) resulted in a reduction in the risk of worsening kidney function (risk ratios, 0.84; 95% confidence interval, 0.77 to 0.91; P < 0.001). In addition, treatment with GLP-1 RAs significantly reduced the risk of developing persistent macroalbuminuria and the risk of the composite outcome of worsening kidney function or development of persistent macroalbuminuria. The results were consistent in patients with and without CKD. CONCLUSIONS: In conclusion, our meta-analysis suggests that GLP-1 RA reduce kidney disease progression in type 2 diabetes or overweight/obesity regardless of CKD status. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2025_02_14_CJASNFeb20.2.2142025.mp3. CI - Copyright (c) 2024 by the American Society of Nephrology. FAU - Mendonca, Luis AU - Mendonca L AUID- ORCID: 0000-0003-1951-3941 AD - Unit of Cardiovascular Research and Development - Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal. AD - Department of Nephrology, ULS Sao Joao, Porto, Portugal. FAU - Moura, Henrique AU - Moura H AUID- ORCID: 0009-0006-0578-3982 AD - Unit of Cardiovascular Research and Development - Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal. FAU - Chaves, Paulo Castro AU - Chaves PC AUID- ORCID: 0000-0001-8388-4312 AD - Unit of Cardiovascular Research and Development - Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal. AD - Department of Medicine, ULS Sao Joao, Porto, Portugal. FAU - Neves, Joao Sergio AU - Neves JS AUID- ORCID: 0000-0002-8173-8255 AD - Unit of Cardiovascular Research and Development - Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. FAU - Ferreira, Joao Pedro AU - Ferreira JP AUID- ORCID: 0000-0002-2304-6138 AD - Unit of Cardiovascular Research and Development - Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal. AD - Centre d'Investigations Cliniques Plurithematique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. LA - eng SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT03574597 SI - ClinicalTrials.gov/NCT04865770 PT - Journal Article PT - Meta-Analysis DEP - 20241008 PL - United States TA - Clin J Am Soc Nephrol JT - Clinical journal of the American Society of Nephrology : CJASN JID - 101271570 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/physiopathology/drug therapy/complications MH - Obesity/complications MH - Disease Progression MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - *Diabetic Nephropathies/prevention & control/etiology/physiopathology MH - *Kidney/physiopathology/drug effects MH - Overweight/complications PMC - PMC11835157 OTO - NOTNLM OT - GFR OT - albuminuria OT - diabetes mellitus OT - obesity COIS- Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/CJN/C54. EDAT- 2024/11/03 04:19 MHDA- 2026/04/23 18:34 PMCR- 2026/02/01 CRDT- 2024/10/31 14:22 PHST- 2024/06/27 00:00 [received] PHST- 2024/10/02 00:00 [accepted] PHST- 2026/04/23 18:34 [medline] PHST- 2024/11/03 04:19 [pubmed] PHST- 2024/10/31 14:22 [entrez] PHST- 2026/02/01 00:00 [pmc-release] AID - 01277230-990000000-00472 [pii] AID - CJASN-2024-000934 [pii] AID - 10.2215/CJN.0000000584 [doi] PST - ppublish SO - Clin J Am Soc Nephrol. 2025 Feb 1;20(2):159-168. doi: 10.2215/CJN.0000000584. Epub 2024 Oct 8. PMID- 39487697 OWN - NLM STAT- MEDLINE DCOM- 20250317 LR - 20250527 IS - 1469-0756 (Electronic) IS - 0032-5473 (Linking) VI - 101 IP - 1194 DP - 2025 Mar 16 TI - Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis. PG - 330-350 LID - 10.1093/postmj/qgae148 [doi] AB - BACKGROUND: Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. METHODS: We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. RESULTS: All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25 mg (13.64; 0.26, 27.01) compared to Canagliflozin 100 mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10 mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50 mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100 mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10 mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100 mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5 mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10 mg (0.45; 0.25, 0.82) and Empagliflozin 10 mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8 mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10 mg (0.81; 0.66, 0.98) compared to Vildagliptin 50 mg; the cardiovascular death of Albiglutide 30 mg (0.49; 0.28, 0.86) compared to Exenatide 2 mg; and the arrhythmic events of Liraglutide 1.8 mg (0.49; 0.26, 0.90) compared to Empagliflozin 10 mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. CONCLUSIONS: GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Song, Ruirui AU - Song R AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. FAU - Liu, Fang AU - Liu F AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. FAU - Shi, Xiaojing AU - Shi X AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. FAU - Sun, Songtao AU - Sun S AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. FAU - Chen, Jun AU - Chen J AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. FAU - Gao, Hongmei AU - Gao H AUID- ORCID: 0000-0002-6426-473X AD - Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - England TA - Postgrad Med J JT - Postgraduate medical journal JID - 0234135 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Benzhydryl Compounds) RN - HDC1R2M35U (empagliflozin) RN - 0 (Glucosides) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Benzhydryl Compounds/therapeutic use MH - Glucosides/therapeutic use MH - Stroke Volume/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Ventricular Function, Left/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - DPP4i OT - GLP-1RA OT - SGLT2i OT - heart failure EDAT- 2024/11/02 23:14 MHDA- 2025/03/17 18:30 CRDT- 2024/11/02 05:13 PHST- 2023/10/13 00:00 [received] PHST- 2024/03/08 00:00 [revised] PHST- 2024/10/12 00:00 [accepted] PHST- 2025/03/17 18:30 [medline] PHST- 2024/11/02 23:14 [pubmed] PHST- 2024/11/02 05:13 [entrez] AID - 7863358 [pii] AID - 10.1093/postmj/qgae148 [doi] PST - ppublish SO - Postgrad Med J. 2025 Mar 16;101(1194):330-350. doi: 10.1093/postmj/qgae148. PMID- 39487060 OWN - NLM STAT- MEDLINE DCOM- 20250210 LR - 20260617 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 19 IP - 1 DP - 2025 Feb TI - Trends in type 2 diabetes medication use and guideline adherence in Belgian primary care (2019-2023). PG - 29-34 LID - S1751-9918(24)00205-5 [pii] LID - 10.1016/j.pcd.2024.10.007 [doi] AB - AIMS: To assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) in Belgium. To analyze trends in medication use and adherence to guidelines from 2019 to 2023. METHODS: We conducted a retrospective cross-sectional analysis using data from the Intego primary care database, encompassing records from 431 general practitioners. We identified adults with T2D through diagnostic codes and glycated hemoglobin levels and analyzed subgroups with ASCVD, HF, and CKD for trends in medication use, particularly SGLT2 inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP-1). RESULTS: The T2D population increased from 20,766 in 2019 to 21,764 in 2023. The prevalence of ASCVD, HF, and CKD among T2D patients slightly increased to 27 %, 6.7 %, and 23.7 % by 2023 (from 25.2 %, 4.9 % and 21.5 % respectively). Medication prescription trends showed a tripling of SGLT2-i and GLP-1 prescribing in the study period to 6.2 % and 11.5 % respectively. Despite these increases, only 7.5 % of eligible patients received these medications as of 2023. CONCLUSION: The study highlights a growing burden of ASCVD, HF, and CKD among T2D patients in Belgium and an increase in the use of guideline-recommended medications. However, there remains a substantial gap in the optimal use of these therapies, indicating a need for improved implementation of clinical guidelines in primary care. CI - Copyright (c) 2024. Published by Elsevier Ltd. FAU - Raat, Willem AU - Raat W AD - Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. Electronic address: willem.raat@kuleuven.be. FAU - Mamouris, Pavlos AU - Mamouris P AD - Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. FAU - Mathieu, Chantal AU - Mathieu C AD - Department of Chronic Diseases and Metabolism, University Hospitals Leuven, KU Leuven, Belgium. FAU - Goderis, Geert AU - Goderis G AD - Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. FAU - Vaes, Bert AU - Vaes B AD - Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241031 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/diagnosis/blood MH - Belgium/epidemiology MH - *Guideline Adherence/trends/standards MH - Cross-Sectional Studies MH - Male MH - *Primary Health Care/trends/standards MH - Female MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Practice Patterns, Physicians'/trends/standards MH - Practice Guidelines as Topic/standards MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Prevalence MH - *Hypoglycemic Agents/therapeutic use MH - Renal Insufficiency, Chronic/epidemiology/diagnosis MH - Heart Failure/epidemiology/diagnosis MH - Time Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Incretins/therapeutic use OTO - NOTNLM OT - Type 2 diabetes - cardiovascular disease - heart failure - chronic kidney disease - medication use - guidelines EDAT- 2024/11/02 23:14 MHDA- 2025/02/11 00:18 CRDT- 2024/11/01 22:54 PHST- 2024/09/19 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/10/22 00:00 [accepted] PHST- 2025/02/11 00:18 [medline] PHST- 2024/11/02 23:14 [pubmed] PHST- 2024/11/01 22:54 [entrez] AID - S1751-9918(24)00205-5 [pii] AID - 10.1016/j.pcd.2024.10.007 [doi] PST - ppublish SO - Prim Care Diabetes. 2025 Feb;19(1):29-34. doi: 10.1016/j.pcd.2024.10.007. Epub 2024 Oct 31. PMID- 39486576 OWN - NLM STAT- MEDLINE DCOM- 20250328 LR - 20250630 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 49 IP - 1 DP - 2025 Feb TI - Glucagon-like Peptide-1 Receptor Agonist Use in Hospital: A Multicentre Observational Study. PG - 37-43 LID - S1499-2671(24)00376-9 [pii] LID - 10.1016/j.jcjd.2024.10.011 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications for type 2 diabetes mellitus (T2DM) and obesity, yet their uptake among individuals most likely to benefit has been slow. METHODS: We conducted a cross-sectional analysis of medication exposure in adults hospitalized at 16 hospitals in Ontario, Canada, between 2015 and 2022. We estimated the proportions of those with T2DM, obesity, and cardiovascular disease. We identified the frequency of GLP-1RA use and conducted multivariable logistic regression to identify factors associated with their use. RESULTS: Across 1,278,863 hospitalizations, 396,084 (31%) patients had T2DM and approximately 327,844 (26%) had obesity. GLP-1RA use (n=1,274) was low among those with a diagnosis of T2DM (0.3%) or obesity (0.7%), despite a high prevalence of cardiovascular disease (36%). In contrast, the use of diabetes medications lacking cardiovascular benefit was high during inpatient hospitalizations related to diabetes: 60% (n=236,612) received insulin and 14% (n=54,885) received a sulfonylurea. Apart from T2DM (odds ratio [OR]=29.6, 95% confidence interval [CI] 23.5 to 37.2), characteristics associated with greater odds of receiving a GLP-1RA were seen in those 50 to 70 years of age (OR=1.71, 95% CI 1.38 to 2.11) compared with those <50 years of age, glycated hemoglobin >9% (OR=1.83, 95% CI 1.36 to 2.47) compared with <6.5%, and highest income quintile (OR=1.73, 95% CI 1.45 to 2.07) compared with lowest income quintile. CONCLUSION: Knowledge translation interventions are needed to address the low adoption of GLP-1RAs among hospitalized patients with T2DM and obesity, who are the most likely to benefit from this treatment. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Ray, Prachi AU - Ray P AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada; Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. FAU - Moggridge, Jason A AU - Moggridge JA AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada. FAU - Weisman, Alanna AU - Weisman A AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Tadrous, Mina AU - Tadrous M AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Women's College Research Institute, Toronto, Ontario, Canada. FAU - Drucker, Daniel J AU - Drucker DJ AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada; Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. FAU - Perkins, Bruce A AU - Perkins BA AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada; Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Fralick, Michael AU - Fralick M AD - Department of Medicine, Sinai Health System, Toronto, Ontario, Canada; Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: mike.fralick@mail.utoronto.ca. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20241030 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Hospitalization/statistics & numerical data MH - *Obesity/drug therapy/epidemiology MH - Ontario/epidemiology MH - Adult MH - Follow-Up Studies OTO - NOTNLM OT - agoniste du recepteur du peptide-1 de type glucagon OT - cardiovascular disease OT - diabete de type 2 OT - exposition aux medicaments OT - glucagon-like peptide-1 receptor agonist OT - maladie cardiovasculaire OT - medication exposure OT - obesity OT - obesite OT - type 2 diabetes EDAT- 2024/11/02 23:13 MHDA- 2025/03/29 16:14 CRDT- 2024/11/01 20:29 PHST- 2024/07/16 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/10/23 00:00 [accepted] PHST- 2025/03/29 16:14 [medline] PHST- 2024/11/02 23:13 [pubmed] PHST- 2024/11/01 20:29 [entrez] AID - S1499-2671(24)00376-9 [pii] AID - 10.1016/j.jcjd.2024.10.011 [doi] PST - ppublish SO - Can J Diabetes. 2025 Feb;49(1):37-43. doi: 10.1016/j.jcjd.2024.10.011. Epub 2024 Oct 30. PMID- 39486470 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260701 IS - 1532-8406 (Electronic) IS - 0883-5403 (Linking) VI - 40 IP - 6 DP - 2025 Jun TI - Glucagon-Like Peptide-1 Receptor Agonist Use Is Not Associated With Increased Complications After Total Hip Arthroplasty in Patients Who Have Type 2 Diabetes. PG - 1413-1418.e1 LID - S0883-5403(24)01139-2 [pii] LID - 10.1016/j.arth.2024.10.099 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists have emerged as a powerful diabetic treatment adjunct; however, their effects on outcomes following total hip arthroplasty (THA) are not well known. This study aimed to compare the risk of complications in patients who had type 2 diabetes mellitus (DM) who were on GLP-1 agonists with those who were not on these medications. METHODS: In total, 14,065 patients who had type 2 DM undergoing primary THA between 2016 and 2021 were retrospectively reviewed using a national database. Propensity score matching was employed at a 1:4 ratio to match patients who used GLP-1 agonists (n = 812) to those who did not (n = 3,248). Patients were matched on age, sex, insulin status, presence of other diabetic medications, comorbidities, and smoking status. Multivariable logistic regressions were performed to examine 90-day and 1-year THA outcomes between groups. RESULTS: Patients who were not on GLP-1 agonists exhibited increased rates of extended hospital stays (>/=3 days) (odds ratio 1.25, P = 0.01). Patients who were on GLP-1 agonists exhibited no significant differences in surgical or medical complication rates at 90 days compared to those not on GLP-1 agonists. There were also no significant differences in rates of all-cause revision THA, aseptic revision THA, or periprosthetic joint infection during the 1-year postoperative period. CONCLUSIONS: This study demonstrated that GLP-1 agonists were not associated with increased risks for medical or surgical complications in patients who had DM undergoing THA and were associated with lower rates of extended hospital stays after surgery. This study provides additional evidence regarding the association of GLP-1 agonist use before THA with postoperative outcomes. Given the potential for increased glycemic control and weight loss, more data are needed to delineate the role of GLP-1 agonists in the optimization of patients who have DM before THA to minimize postoperative complications. LEVEL OF EVIDENCE: Level III, retrospective cohort. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Heo, Kevin Y AU - Heo KY AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Goel, Rahul K AU - Goel RK AD - Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, North Carolina. FAU - Woltemath, Alyssa AU - Woltemath A AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Fuqua, Andrew AU - Fuqua A AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Hrudka, Bryce T AU - Hrudka BT AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Syed, Omar AU - Syed O AD - Department of Orthopaedic Surgery, New York Medical College, Valhalla, New York. FAU - Arellano, Emilio AU - Arellano E AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Premkumar, Ajay AU - Premkumar A AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. FAU - Wilson, Jacob M AU - Wilson JM AD - Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241030 PL - United States TA - J Arthroplasty JT - The Journal of arthroplasty JID - 8703515 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Hip/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Postoperative Complications/epidemiology/etiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Propensity Score OTO - NOTNLM OT - GLP-1 receptor agonist OT - glucagon-like peptide-1 receptor agonist OT - surgical complications OT - total hip arthroplasty OT - type 2 diabetes mellitus EDAT- 2024/11/02 23:14 MHDA- 2025/05/12 06:32 CRDT- 2024/11/01 20:26 PHST- 2024/07/11 00:00 [received] PHST- 2024/10/19 00:00 [revised] PHST- 2024/10/22 00:00 [accepted] PHST- 2025/05/12 06:32 [medline] PHST- 2024/11/02 23:14 [pubmed] PHST- 2024/11/01 20:26 [entrez] AID - S0883-5403(24)01139-2 [pii] AID - 10.1016/j.arth.2024.10.099 [doi] PST - ppublish SO - J Arthroplasty. 2025 Jun;40(6):1413-1418.e1. doi: 10.1016/j.arth.2024.10.099. Epub 2024 Oct 30. PMID- 39486172 OWN - NLM STAT- MEDLINE DCOM- 20241207 LR - 20250103 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 143 IP - Pt 3 DP - 2024 Dec 25 TI - Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study. PG - 113537 LID - S1567-5769(24)02059-9 [pii] LID - 10.1016/j.intimp.2024.113537 [doi] AB - BACKGROUND: GLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. OBJECTIVE: To evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. METHODS: This comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. RESULTS: Obese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer's disease (RR = 0.627, 95 %CI = 0.481-0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462-0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327-0.588). The risk reduction for Parkinson's disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580-1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369-0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493-0.558). CONCLUSION: This study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Siddeeque, Nabeela AU - Siddeeque N AD - Tulane University School of Medicine, New Orleans, LA, 70112, USA. FAU - Hussein, Mohammad H AU - Hussein MH AD - Ochsner Clinic Foundation, New Orleans, LA 70112, USA. FAU - Abdelmaksoud, Ahmed AU - Abdelmaksoud A AD - Department of Internal Medicine, University of California, Riverside, CA 92521, USA. FAU - Bishop, Julia AU - Bishop J AD - Tulane University School of Medicine, New Orleans, LA, 70112, USA. FAU - Attia, Abdallah S AU - Attia AS AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA. FAU - Elshazli, Rami M AU - Elshazli RM AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA; Biochemistry and Molecular Genetic Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University - Egypt, New Damietta 34517, Egypt; Department of Biological Sciences, Faculty of Science, New Mansoura University, New Mansoura City 35742, Egypt. FAU - Fawzy, Manal S AU - Fawzy MS AD - Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia; Center for Health Research, Northern Border University, Arar 1321, Saudi Arabia. FAU - Toraih, Eman A AU - Toraih EA AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA; Medical Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Ismailia 41522, Egypt. Electronic address: etoraih@tulane.edu. LA - eng PT - Journal Article DEP - 20241031 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Neurodegenerative Diseases/drug therapy MH - Male MH - *Neuroprotective Agents/therapeutic use/pharmacology MH - Female MH - Retrospective Studies MH - Middle Aged MH - Aged MH - Obesity/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Cohort Studies MH - Propensity Score MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonists OT - Neurodegenerative disorders OT - Neuroprotection OT - Obesity OT - Parkinson's disease COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/02 23:13 MHDA- 2024/12/07 14:47 CRDT- 2024/11/01 19:04 PHST- 2024/09/04 00:00 [received] PHST- 2024/10/27 00:00 [revised] PHST- 2024/10/28 00:00 [accepted] PHST- 2024/12/07 14:47 [medline] PHST- 2024/11/02 23:13 [pubmed] PHST- 2024/11/01 19:04 [entrez] AID - S1567-5769(24)02059-9 [pii] AID - 10.1016/j.intimp.2024.113537 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113537. doi: 10.1016/j.intimp.2024.113537. Epub 2024 Oct 31. PMID- 39478377 OWN - NLM STAT- MEDLINE DCOM- 20241031 LR - 20250103 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 20 IP - 893 DP - 2024 Oct 30 TI - [Prescription of GLP-1 receptor agonists and iSGLT2 in geriatrics, is there a risk?]. PG - 1983-1987 LID - 10.53738/REVMED.2024.20.893.1983 [doi] AB - The use of GLP-1 receptor agonists and iSGLT2 is becoming increasingly common, in line with new guidelines issued by the learned societies of cardiology, nephrology and diabetology. However, the enthusiasm aroused by these new drugs needs to be tempered and their use in the very elderly and/or frail needs to be carefully considered by the lack of scientific studies in this population category, , and their prescription requires a comprehensive geriatric assessment before initiating this type of treatment. FAU - Moro, Davide AU - Moro D AD - Service de geriatrie, Hopital de Martigny, Centre hospitalier du Valais romand, 1920 Martigny. FAU - Jean, Michele AU - Jean M AD - Service de geriatrie, Hopital de Martigny, Centre hospitalier du Valais romand, 1920 Martigny. FAU - Coutaz, Martial AU - Coutaz M AUID- ORCID: 0000-0001-6775-6820 AD - Service de geriatrie, Hopital de Martigny, Centre hospitalier du Valais romand, 1920 Martigny. LA - fre PT - English Abstract PT - Journal Article TT - Agonistes du recepteur GLP-1 et des iSGLT2 en geriatrie : quels risques ? PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Geriatric Assessment/methods MH - Practice Guidelines as Topic MH - Geriatrics/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- les auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2024/10/31 10:18 MHDA- 2024/10/31 10:19 CRDT- 2024/10/31 03:43 PHST- 2024/10/31 10:19 [medline] PHST- 2024/10/31 10:18 [pubmed] PHST- 2024/10/31 03:43 [entrez] AID - RMS0893-004 [pii] AID - 10.53738/REVMED.2024.20.893.1983 [doi] PST - ppublish SO - Rev Med Suisse. 2024 Oct 30;20(893):1983-1987. doi: 10.53738/REVMED.2024.20.893.1983. PMID- 39477370 OWN - NLM STAT- MEDLINE DCOM- 20241030 LR - 20260624 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 387 DP - 2024 Oct 30 TI - Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies. PG - e080035 LID - 10.1136/bmj-2024-080035 [doi] LID - e080035 AB - OBJECTIVE: To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator. DESIGN: Target trial emulation studies. SETTING: Canadian population database, January 2014 to June 2022. PARTICIPANTS: 20 146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high risk group. INTERVENTIONS: Initiation of an SGLT-2 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist, with a dipeptidyl peptidase-4 (DPP-4) inhibitor as alternative comparator. MAIN OUTCOME MEASURES: The primary outcome was recurrent nephrolithiasis events ascertained from diagnoses during emergency department visits, hospital admissions, or outpatient visits. Secondary outcomes included nephrolithiasis resulting in hospital admission or emergency department visits and flare-up of gout, as well as a positive control outcome (genital infection) and negative control outcomes (osteoarthritis encounter and appendicitis). Poisson and Cox proportional hazards regression models were used (primary analyses), as well as overlap weighting. RESULTS: After inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14 456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio was 0.67 (95% confidence interval (CI) 0.57 to 0.79) and rate difference was -51 (95% CI -63 to -40) per 1000 person years, with a number needed to treat (NNT) of 20. Among those with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). Protective associations persisted for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and when an SGLT-2 inhibitor was compared with a DPP-4 inhibitor (rate ratio 0.73 (0.68 to 0.78), rate difference -38 (-46 to -29) per 1000 person years (NNT of 26)). Protective associations also persisted among patients with nephrolithiasis and concomitant gout, with a rate ratio of 0.67 (0.57 to 0.79) and rate difference of -53 (95% CI -78 to -27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and 0.63 (0.55 to 0.72) and-62 (-81 to -42) per 1000 person years, respectively, versus a DPP-4 inhibitor (NNT of 16). Furthermore, SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio 0.72, 0.54 to 0.95, rate difference -16, -31 to -1 per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and -21, -33 to -9 per 1000 person years) compared with DPP-4 inhibitors. SGLT-2 inhibitor initiators showed higher risk of genital infection (eg, hazard ratio 2.21, 95% CI 1.68 to 2.90, and rate difference 13 per 1000 person years), but no altered risk of osteoarthritis encounter (0.87, 0.68 to 1.1, and -2 per 1000 person years) or appendicitis (1.07, 0.69 to 1.67, and 1 per 1000 person years). Results were similar when propensity score overlap weighting was applied. CONCLUSIONS: The benefits associated with SGLT-2 inhibitor for patients with nephrolithiasis in these target trial emulations suggest they may be a useful addition to current treatments to simultaneously manage nephrolithiasis recurrence and comorbidities, including gout. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - McCormick, Natalie AU - McCormick N AD - Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA. AD - The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. AD - Arthritis Research Canada, Vancouver, BC, Canada. FAU - Yokose, Chio AU - Yokose C AD - Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA. AD - The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. FAU - Lu, Na AU - Lu N AD - Arthritis Research Canada, Vancouver, BC, Canada. FAU - Wexler, Deborah J AU - Wexler DJ AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. AD - Diabetes Center, Massachusetts General Hospital, Boston, MA, USA. FAU - Avina-Zubieta, J Antonio AU - Avina-Zubieta JA AD - Arthritis Research Canada, Vancouver, BC, Canada. AD - Division of Rheumatology, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada. FAU - De Vera, Mary A AU - De Vera MA AD - Arthritis Research Canada, Vancouver, BC, Canada. AD - Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada. FAU - Chigurupati, Saiajay AU - Chigurupati S AD - Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA. AD - The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Tan, Kiara AU - Tan K AD - Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA. AD - The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Chen, Chixiang AU - Chen C AD - Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA. AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - McCoy, Rozalina AU - McCoy R AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. AD - University of Maryland Institute for Health Computing, Bethesda, MD, USA. AD - Division of Gerontology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Curhan, Gary C AU - Curhan GC AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. AD - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Choi, Hyon K AU - Choi HK AUID- ORCID: 0000-0002-2862-0442 AD - Rheumatology and Allergy Clinical Epidemiology Research Center, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA hchoi@mgh.harvard.edu. AD - The Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. AD - Department of Medicine, Harvard Medical School, Boston, MA, USA. AD - Arthritis Research Canada, Vancouver, BC, Canada. LA - eng GR - R00 AR080243/AR/NIAMS NIH HHS/United States GR - R01 AR065944/AR/NIAMS NIH HHS/United States GR - K99 AR080243/AR/NIAMS NIH HHS/United States GR - K23 AR081425/AR/NIAMS NIH HHS/United States GR - P50 AR060772/AR/NIAMS NIH HHS/United States GR - P30 DK135043/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20241030 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Nephrolithiasis/drug therapy MH - Male MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Recurrence MH - *Gout/drug therapy/complications MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Canada/epidemiology MH - Treatment Outcome MH - Hospitalization/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11524131 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health and Canadian Institutes of Health Research; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. DW reports serving on data monitoring committees for Novo Nordisk, not related to the topic of this work. RM has received support from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), National Institute on Aging of the NIH, Patient Centered Outcomes Research Institute, National Center for Advancing Translational Sciences, and the American Diabetes Association. She also serves as a consultant to Emmi (Wolters Kluwer) on developing patient education materials related to diabetes, and to Yale-New Haven Health System's Center For Outcomes Research and Evaluation on developing quality measures related to diabetes. GCC is the Chief Medical Officer at OM1 and reports research support from GSK. HKC reports research support from Horizon, and consulting fees from Ani, LG, Horizon, Shanton, and Protalix. EDAT- 2024/10/31 04:20 MHDA- 2024/10/31 04:21 PMCR- 2024/10/30 CRDT- 2024/10/30 21:03 PHST- 2024/10/31 04:21 [medline] PHST- 2024/10/31 04:20 [pubmed] PHST- 2024/10/30 21:03 [entrez] PHST- 2024/10/30 00:00 [pmc-release] AID - bmj-2024-080035.R1 [pii] AID - mccn080035 [pii] AID - 10.1136/bmj-2024-080035 [doi] PST - epublish SO - BMJ. 2024 Oct 30;387:e080035. doi: 10.1136/bmj-2024-080035. PMID- 39471690 OWN - NLM STAT- MEDLINE DCOM- 20241127 LR - 20250103 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 143 IP - Pt 2 DP - 2024 Dec 25 TI - Tirzepatide's role in targeting adipose tissue macrophages to reduce obesity-related inflammation and improve insulin resistance. PG - 113499 LID - S1567-5769(24)02021-6 [pii] LID - 10.1016/j.intimp.2024.113499 [doi] AB - BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are significant global health challenges, with adipose tissue inflammation being a pivotal contributor to metabolic dysfunction. The involvement of adipose tissue macrophages (ATMs) in obesity-associated inflammation is well recognized, yet the therapeutic strategies specifically targeting ATM-mediated inflammation remain limited. OBJECTIVE: This study aims to explore the effects of tirzepatide, a novel dual GLP-1 and GIP receptor agonist, on ATMs, adipose tissue inflammation, and insulin resistance in the context of obesity. METHODS: Obese mouse models were established through high-fat diet feeding and subsequently treated with tirzepatide at a dose of 1.2 mg/kg twice weekly for 12 weeks. The study assessed the impact on ATM phenotype, inflammatory markers, and key metabolic indicators. RESULTS: Tirzepatide treatment significantly mitigated the infiltration of pro-inflammatory M1 ATMs within adipose tissue and concurrently reduced levels of inflammatory cytokines, thereby enhancing insulin sensitivity. Tirzepatide demonstrated therapeutic efficacy through its modulation of the ERK signaling pathway and promotion of M1-type macrophage apoptosis. CONCLUSION: Tirzepatide's potential as a therapeutic strategy for addressing metabolic diseases associated with obesity and T2DM by targeting ATM activity and mitigating obesity-associated inflammation. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Xia, Yin AU - Xia Y AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Jin, Jing AU - Jin J AD - Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China. FAU - Sun, Yaqin AU - Sun Y AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Kong, Xiaocen AU - Kong X AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Shen, Ziyang AU - Shen Z AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Yan, Rengna AU - Yan R AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Huang, Rong AU - Huang R AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Liu, Xiaomei AU - Liu X AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Xia, Wenqing AU - Xia W AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Ma, Jingjing AU - Ma J AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. FAU - Zhu, Xudong AU - Zhu X AD - Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China. Electronic address: zhuxudong@njmu.edu.cn. FAU - Li, Qian AU - Li Q AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. Electronic address: shygu@njmu.edu.cn. FAU - Ma, Jianhua AU - Ma J AD - Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. LA - eng PT - Journal Article DEP - 20241029 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Cytokines) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Insulin Resistance MH - *Obesity/drug therapy/metabolism MH - *Macrophages/drug effects/immunology/metabolism MH - *Adipose Tissue/drug effects/metabolism MH - Male MH - Mice MH - *Mice, Inbred C57BL MH - *Inflammation/drug therapy MH - *Diet, High-Fat MH - Diabetes Mellitus, Type 2/drug therapy/metabolism/immunology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Receptors, Gastrointestinal Hormone/metabolism MH - Cytokines/metabolism MH - Humans MH - Disease Models, Animal MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Adipose tissue inflammation OT - ERK signaling pathway OT - Macrophages OT - Obesity OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/10/30 04:20 MHDA- 2024/11/27 06:19 CRDT- 2024/10/29 19:06 PHST- 2024/05/01 00:00 [received] PHST- 2024/09/09 00:00 [revised] PHST- 2024/10/22 00:00 [accepted] PHST- 2024/11/27 06:19 [medline] PHST- 2024/10/30 04:20 [pubmed] PHST- 2024/10/29 19:06 [entrez] AID - S1567-5769(24)02021-6 [pii] AID - 10.1016/j.intimp.2024.113499 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113499. doi: 10.1016/j.intimp.2024.113499. Epub 2024 Oct 29. PMID- 39471265 OWN - NLM STAT- MEDLINE DCOM- 20241029 LR - 20250103 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 30 IP - 11 DP - 2024 Nov TI - Social determinants of health and newer glucose-lowering drugs adoption among US Medicare beneficiaries with type 2 diabetes. PG - 1298-1307 LID - 10.18553/jmcp.2024.30.11.1298 [doi] AB - BACKGROUND: Two classes of newer glucose-lowering drugs (GLDs), sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, improve cardiovascular and renal outcomes among patients with type 2 diabetes (T2D). However, racial and ethnic minority groups carry higher cardiovascular risks but have lower access to newer GLDs. Contextual-level social determinants of health (SDOH) may be the underlying factor associated with newer GLD adoption. OBJECTIVE: To identify the association between contextual-level SDOH and real-world adoption of newer GLDs among Medicare beneficiaries and to examine the nonstationarity in the associations. METHODS: Data were from 15% random samples of January 2017 to December 2018 nationwide Medicare beneficiaries. We identified patients with T2D who did not use newer GLDs in the year before the index date-January 1, 2018-and followed the cohort for 1 year to record their status of initiating a newer GLD. We used a geographically weighted multivariable Poisson regression model to determine to what extent the SDOH-newer GLD initiation association (beta coefficient) varied geographically. RESULTS: We identified 795,469 eligible Medicare beneficiaries with T2D during the study period from our dataset. Of the study cohort, mean age was 73.1 (SD = 10.5) years, 424,312 (53.3%) were female, 562,994 (70.8%) were non-Hispanic White, 96,891 (12.2%) were non-Hispanic Black, 84,744 (10.6%) were Hispanic, and 29,645 (3.7%) were Asian/Pacific Islander. Newer GLD initiation was negatively associated with the percentage of the population reporting non-Hispanic Black race, Hispanic ethnicity, and unemployment, as revealed by nonspatial regression analyses. The county-level median household income was also associated with higher newer GLD initiation. The spatial analysis presented distinct distributions of local parameter estimates for each contextual-level SDOH. CONCLUSIONS: We identified key contextual-level SDOH associated with real-world adoption of newer GLDs and explored their geographic variation through spatially explicit, data-driven analytical approaches. Identifying areas of strong association between SDOH and newer GLD initiation is crucial for policymakers to allocate resources and develop interventions that address structural inequities. FAU - Chen, Wei-Han AU - Chen WH AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. FAU - Li, Yujia AU - Li Y AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. FAU - Chen, Aokun AU - Chen A AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville. FAU - Allen, John M AU - Allen JM AD - Department of Pharmacotherapy & Translational Research, College of Pharmacy, University of Florida, Orlando. FAU - Guo, Yi AU - Guo Y AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety (CoDES), College of Pharmacy, University of Florida, Gainesville. FAU - Bilello, Lori AU - Bilello L AD - Department of Surgery, University of Florida College of Medicine-Jacksonville. FAU - Smith, Steven M AU - Smith SM AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety (CoDES), College of Pharmacy, University of Florida, Gainesville. AD - Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville. FAU - Yang, Lanting AU - Yang L AD - Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA. FAU - Goodin, Amie J AU - Goodin AJ AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety (CoDES), College of Pharmacy, University of Florida, Gainesville. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville. AD - Center for Drug Evaluation and Safety (CoDES), College of Pharmacy, University of Florida, Gainesville. AD - Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - United States/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - *Social Determinants of Health MH - Aged MH - *Medicare MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Middle Aged MH - Aged, 80 and over MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11522454 COIS- Dr Guo received research funding from the PhRMA Foundation and consulting fees from the Pfizer Foundation, both outside the current work. The remaining authors have no disclosures to report. EDAT- 2024/10/29 22:27 MHDA- 2024/10/29 22:28 PMCR- 2024/11/01 CRDT- 2024/10/29 14:33 PHST- 2024/10/29 22:28 [medline] PHST- 2024/10/29 22:27 [pubmed] PHST- 2024/10/29 14:33 [entrez] PHST- 2024/11/01 00:00 [pmc-release] AID - 10.18553/jmcp.2024.30.11.1298 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2024 Nov;30(11):1298-1307. doi: 10.18553/jmcp.2024.30.11.1298. PMID- 39471057 OWN - NLM STAT- MEDLINE DCOM- 20241112 LR - 20250507 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 18 IP - 45 DP - 2024 Nov 12 TI - Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic. PG - 31274-31285 LID - 10.1021/acsnano.4c10248 [doi] AB - Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.g., semaglutide) has transformed the standard of care in recent years for treating type 2 diabetes and reversing obesity. The native GLP-1 sequence has a very short half-life, and therapeutic advances have come from molecular engineering to alter the pharmacokinetic profile of synthetic GLP-1 receptor agonists to enable once-weekly administration, reduce the frequency of injection, and improve adherence. Efforts to further extend this profile would offer additional convenience or enable entirely different treatment modalities. Here, an injectable GLP-1 receptor agonist depot is engineered through integration of a prosthetic self-assembling peptide motif to enable supramolecular nanofiber formation and hydrogelation. This supramolecular GLP-1 receptor agonistic (PA-GLP1) offers sustained release in vitro for multiple weeks, supporting long-lasting therapy. Moreover, in a rat model of type 2 diabetes, a single injection of the supramolecular PA-GLP1 formulation achieved sustained serum concentrations for at least 40 days, with an overall reduction in blood glucose levels and reduced weight gain, comparing favorably to daily injections of semaglutide. The general and modular approach is also extensible to other next-generation peptide therapies. Accordingly, the formation of supramolecular nanofiber depots offers a more convenient and long-lasting therapeutic option to manage diabetes and treat metabolic disorders. FAU - Chen, Weike AU - Chen W AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Xian, Sijie AU - Xian S AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Webber, Bernice AU - Webber B AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - DeWolf, Emily L AU - DeWolf EL AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Schmidt, Connor R AU - Schmidt CR AUID- ORCID: 0000-0002-6514-8757 AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Kilmer, Rory AU - Kilmer R AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Liu, Dongping AU - Liu D AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Power, Elizabeth M AU - Power EM AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Webber, Matthew J AU - Webber MJ AUID- ORCID: 0000-0003-3111-6228 AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241029 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Glucagon-Like Peptide 1/chemistry/metabolism MH - *Nanofibers/chemistry MH - Rats MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Male MH - Hypoglycemic Agents/chemistry/administration & dosage/pharmacology/pharmacokinetics MH - Rats, Sprague-Dawley MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - drug delivery OT - hydrogels OT - nanotechnology OT - self-assembly OT - supramolecular chemistry EDAT- 2024/10/29 18:22 MHDA- 2024/11/13 13:55 CRDT- 2024/10/29 12:43 PHST- 2024/11/13 13:55 [medline] PHST- 2024/10/29 18:22 [pubmed] PHST- 2024/10/29 12:43 [entrez] AID - 10.1021/acsnano.4c10248 [doi] PST - ppublish SO - ACS Nano. 2024 Nov 12;18(45):31274-31285. doi: 10.1021/acsnano.4c10248. Epub 2024 Oct 29. PMID- 39465848 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20250103 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 41 DP - 2024 Oct 11 TI - Effect of glucagon-like peptide-1 receptor agonists on prostate cancer: A review. PG - e39956 LID - 10.1097/MD.0000000000039956 [doi] LID - e39956 AB - Glucagon-like peptide-1 receptor agonist (GLP-1RA) is widely used in the treatment of type 2 diabetes mellitus (T2DM) for its significant hypoglycemic effect, weight loss and small side effects. Some studies have shown that GLP-1RA has an inhibitory effect on prostate cancer, and its application will produce adverse effects associated with an increased or decreased risk of some tumors. GLP-1R is widely expressed by various types of cells and tissues in the human body, so GLP-1RA has attracted wide clinical attention to the occurrence, development and prognosis of tumors, which brings more new directions and hopes for the treatment of prostate cancer. This paper describes the expression of glucagon-like peptide-1 receptor (GLP-1R) in prostate cancer and the effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) on prostate cancer. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Yu, Xu AU - Yu X AD - Linyi People's Hospital of Shandong Second Medical University, Weifang, Shandong, China. FAU - Liu, Jie AU - Liu J AD - Linyi People's Hospital, Linyi, Shandong, China. LA - eng PT - Journal Article PT - Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - *Prostatic Neoplasms/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11479428 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2024/10/28 12:26 MHDA- 2024/10/28 12:27 PMCR- 2024/10/11 CRDT- 2024/10/28 08:13 PHST- 2024/10/28 12:27 [medline] PHST- 2024/10/28 12:26 [pubmed] PHST- 2024/10/28 08:13 [entrez] PHST- 2024/10/11 00:00 [pmc-release] AID - 00005792-202410110-00066 [pii] AID - MD-D-24-07287 [pii] AID - 10.1097/MD.0000000000039956 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Oct 11;103(41):e39956. doi: 10.1097/MD.0000000000039956. PMID- 39464183 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20261021 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies. PG - 1410883 LID - 10.3389/fendo.2024.1410883 [doi] LID - 1410883 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world. METHODS: A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures. RESULTS: In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%. CONCLUSION: Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42023448720. CI - Copyright (c) 2024 Mostafa and Alrasheed. FAU - Mostafa, Mohamed E A AU - Mostafa MEA AD - Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. AD - Department of Anatomy, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Alrasheed, Tariq AU - Alrasheed T AD - Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20241011 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Fractures, Bone/epidemiology/chemically induced MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cohort Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11502341 OTO - NOTNLM OT - DPP-4 inhibitors OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - T2DM OT - bone fracture COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/10/28 06:22 MHDA- 2024/10/28 06:23 PMCR- 2024/01/01 CRDT- 2024/10/28 05:14 PHST- 2024/04/02 00:00 [received] PHST- 2024/09/04 00:00 [accepted] PHST- 2024/10/28 06:23 [medline] PHST- 2024/10/28 06:22 [pubmed] PHST- 2024/10/28 05:14 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1410883 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Oct 11;15:1410883. doi: 10.3389/fendo.2024.1410883. eCollection 2024. PMID- 39462543 OWN - NLM STAT- MEDLINE DCOM- 20241117 LR - 20250108 IS - 1881-784X (Electronic) IS - 1881-7831 (Linking) VI - 18 IP - 5 DP - 2024 Nov 15 TI - Effect of switching from dulaglutide to tirzepatide on blood glucose and renal function. PG - 323-324 LID - 10.5582/ddt.2024.01061 [doi] AB - The case reports a woman in her 70s, with type 2 diabetes and chronic kidney disease in G4 stage. The patient had elevated HbA1c, and she was switched from linagliptin, a dipeptidyl peptidase 4 inhibitor, to dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). Thereafter, the HbA1c level decreased; however, since the dulaglutide supply became a problem, the patient was switched to tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA. To date, no clinical studies have evaluated the efficacy and safety of switching from GLP-1RA to GIP/GLP-1RA, but we report this case because efficacy was observed in this patient. The therapeutic effects after switching to tirzepatide included decrease in HbA1c, increase in eGFR, and decrease in BUN, when compared to when dulaglutide was used. A change from dulaglutide to tirzepatide, could inhibit renal impairment progression and improve renal function. FAU - Ishimura, Atsushi AU - Ishimura A AD - Division of Practical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan. FAU - Kumakura, Hiroyoshi AU - Kumakura H AD - Pharmaceutical Department, Ina Hospital, Saitama, Japan. LA - eng PT - Case Reports PT - Journal Article DEP - 20241028 PL - Japan TA - Drug Discov Ther JT - Drug discoveries & therapeutics JID - 101493809 RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Blood Glucose) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 3X29ZEJ4R2 (Linagliptin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/pharmacology MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use/pharmacology MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Aged MH - *Blood Glucose/drug effects MH - *Hypoglycemic Agents/pharmacology/therapeutic use/adverse effects MH - Glycated Hemoglobin/drug effects MH - Renal Insufficiency, Chronic/drug therapy MH - Drug Substitution MH - Linagliptin/therapeutic use/adverse effects/pharmacology MH - Glomerular Filtration Rate/drug effects MH - Kidney/drug effects MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - chronic kidney disease OT - dulaglutide OT - tirzepatide EDAT- 2024/10/28 00:46 MHDA- 2024/11/18 00:31 CRDT- 2024/10/27 21:32 PHST- 2024/11/18 00:31 [medline] PHST- 2024/10/28 00:46 [pubmed] PHST- 2024/10/27 21:32 [entrez] AID - 10.5582/ddt.2024.01061 [doi] PST - ppublish SO - Drug Discov Ther. 2024 Nov 15;18(5):323-324. doi: 10.5582/ddt.2024.01061. Epub 2024 Oct 28. PMID- 39460581 OWN - NLM STAT- MEDLINE DCOM- 20250201 LR - 20250604 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 2 DP - 2025 Feb TI - Incretin hormones: Revolutionizing the treatment landscape for kidney and liver diseases in type 2 diabetes and obesity. PG - 183-186 LID - 10.1111/jdi.14336 [doi] AB - Several ongoing trials are evaluating incretin-based therapies, including GLP-1 receptor agonists, for their effects on CKD and MASLD. These studies will offer insights into their potential for metabolic diseases in people with type 2 diabetes and obesity. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Bae, Jae Hyun AU - Bae JH AUID- ORCID: 0000-0002-1384-6123 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. FAU - Cho, Young Min AU - Cho YM AUID- ORCID: 0000-0002-2331-6126 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article DEP - 20241026 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/drug therapy/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Incretins/therapeutic use MH - *Liver Diseases/drug therapy/etiology MH - *Obesity/complications/drug therapy PMC - PMC11786174 COIS- Young Min Cho, as an Editorial Board member of the Journal of Diabetes Investigation, was excluded from all editorial decisions regarding the acceptance of this article to avoid potential conflicts of interest. The authors declare no other conflicts of interest. EDAT- 2024/10/26 19:24 MHDA- 2025/02/01 20:42 PMCR- 2024/10/26 CRDT- 2024/10/26 05:53 PHST- 2024/10/07 00:00 [revised] PHST- 2024/10/01 00:00 [received] PHST- 2024/10/09 00:00 [accepted] PHST- 2025/02/01 20:42 [medline] PHST- 2024/10/26 19:24 [pubmed] PHST- 2024/10/26 05:53 [entrez] PHST- 2024/10/26 00:00 [pmc-release] AID - JDI14336 [pii] AID - 10.1111/jdi.14336 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Feb;16(2):183-186. doi: 10.1111/jdi.14336. Epub 2024 Oct 26. PMID- 39457081 OWN - NLM STAT- MEDLINE DCOM- 20241026 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 20 DP - 2024 Oct 21 TI - Glucagon-like Peptide 1 Receptor Agonists in Cardio-Oncology: Pathophysiology of Cardiometabolic Outcomes in Cancer Patients. LID - 10.3390/ijms252011299 [doi] LID - 11299 AB - Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis. FAU - Quagliariello, Vincenzo AU - Quagliariello V AUID- ORCID: 0000-0002-4557-5401 AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. FAU - Canale, Maria Laura AU - Canale ML AD - U.O.C. Cardiologia, Ospedale Versilia, 55041 Lido di Camaiore, Italy. FAU - Bisceglia, Irma AU - Bisceglia I AUID- ORCID: 0000-0002-0689-0695 AD - Servizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00148 Rome, Italy. FAU - Iovine, Martina AU - Iovine M AUID- ORCID: 0000-0001-5871-4098 AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. FAU - Giordano, Vienna AU - Giordano V AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. FAU - Giacobbe, Ilaria AU - Giacobbe I AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. FAU - Scherillo, Marino AU - Scherillo M AD - Division of Cardiology, Hospital San Pio Benevento (BN), 82100 Benevento, Italy. FAU - Gabrielli, Domenico AU - Gabrielli D AUID- ORCID: 0000-0003-3392-0527 AD - U.O.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy. FAU - Maurea, Carlo AU - Maurea C AD - Department of Medicine, University of Salerno, 84084 Fisciano, Italy. FAU - Barbato, Matteo AU - Barbato M AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. FAU - Inno, Alessandro AU - Inno A AUID- ORCID: 0000-0001-6331-6908 AD - Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, 37024 Negrar di Valpolicella, Italy. FAU - Berretta, Massimiliano AU - Berretta M AUID- ORCID: 0000-0002-9837-9148 AD - Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Tedeschi, Andrea AU - Tedeschi A AUID- ORCID: 0000-0003-0315-3304 AD - Cardiology Unit of Emergency Department, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy. FAU - Oliva, Stefano AU - Oliva S AD - UOSD Cardiologia di Interesse Oncologico IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy. FAU - Greco, Alessandra AU - Greco A AUID- ORCID: 0000-0002-3130-0079 AD - Divisione di Cardiologia, Fondazione IRCCS San Matteo Hospital, Viale Golgi 19, 27100 Pavia, Italy. FAU - Maurea, Nicola AU - Maurea N AUID- ORCID: 0000-0003-3704-0092 AD - Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy. LA - eng GR - This research was funded by Ricerca Corrente Grant, Ministero della Salute, Linea 6/1 "Cardi-otossicita da chemioterapie, targeted therapies e immunoterapie, diagnosi precoce e cardiopro-tezione. Ricerca preclinica e clinica"/Ministero della Salute/ PT - Journal Article PT - Review DEP - 20241021 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Neoplasms/drug therapy/complications/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Animals MH - Cardiovascular Diseases/etiology/drug therapy/metabolism MH - Atherosclerosis/drug therapy/metabolism MH - Heart Failure/drug therapy/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Cardio-Oncology MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11508560 OTO - NOTNLM OT - GLP-1 receptor OT - cancer OT - cardio-oncology OT - cardioprotection OT - inflammation OT - metabolism COIS- The authors declare no conflicts of interest. EDAT- 2024/10/26 19:22 MHDA- 2024/10/26 19:23 PMCR- 2024/10/21 CRDT- 2024/10/26 01:07 PHST- 2024/09/06 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/10/17 00:00 [accepted] PHST- 2024/10/26 19:23 [medline] PHST- 2024/10/26 19:22 [pubmed] PHST- 2024/10/26 01:07 [entrez] PHST- 2024/10/21 00:00 [pmc-release] AID - ijms252011299 [pii] AID - ijms-25-11299 [pii] AID - 10.3390/ijms252011299 [doi] PST - epublish SO - Int J Mol Sci. 2024 Oct 21;25(20):11299. doi: 10.3390/ijms252011299. PMID- 39455729 OWN - NLM STAT- MEDLINE DCOM- 20250122 LR - 20261010 IS - 1546-170X (Electronic) IS - 1078-8956 (Linking) VI - 31 IP - 1 DP - 2025 Jan TI - Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. PG - 278-285 LID - 10.1038/s41591-024-03327-6 [doi] AB - Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) >/=25 ml min(-1) 1.73 m(-)(2) and urine albumin-to-creatinine ratio (UACR) >/=30 and <3,500 mg g(-1)) and body mass index >/=27 kg m(-)(2). Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g(-1) (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min(-1) 1.73 m(-)(2); and mean body mass index was 36.2 (s.d. 5.6) kg m(-)(2). Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 . CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Apperloo, Ellen M AU - Apperloo EM AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Gorriz, Jose L AU - Gorriz JL AD - Department of Nephrology, University Clinical Hospital, INCLIVA, University of Valencia, Valencia, Spain. FAU - Soler, Maria Jose AU - Soler MJ AD - Department of Nephrology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain. FAU - Cigarran Guldris, Secundino AU - Cigarran Guldris S AUID- ORCID: 0000-0001-9043-992X AD - Nephrology Service Hospital Ribera-Polusa Lugo, Lugo, Spain. FAU - Cruzado, Josep M AU - Cruzado JM AUID- ORCID: 0000-0003-1388-8558 AD - Department of Nephrology, Hospital Universitari Bellvitge, Bellvitge Biomedical Research Institute, University of Barcelona, Barcelona, Spain. FAU - Puchades, Maria Jesus AU - Puchades MJ AD - Department of Nephrology, University Clinical Hospital, INCLIVA, University of Valencia, Valencia, Spain. FAU - Lopez-Martinez, Marina AU - Lopez-Martinez M AD - Department of Nephrology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain. FAU - Waanders, Femke AU - Waanders F AUID- ORCID: 0000-0003-4417-7732 AD - Department of Internal Medicine, Isala, Zwolle, The Netherlands. FAU - Laverman, Gozewijn D AU - Laverman GD AUID- ORCID: 0000-0002-8716-7115 AD - Department of Internal Medicine, ZiekenhuisGroep Twente, Almelo, The Netherlands. FAU - van der Aart-van der Beek, Annemarie AU - van der Aart-van der Beek A AD - Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands. FAU - Hoogenberg, Klaas AU - Hoogenberg K AD - Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands. FAU - van Beek, Andre P AU - van Beek AP AUID- ORCID: 0000-0002-0335-8177 AD - Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Verhave, Jacobien AU - Verhave J AD - Department Internal Medicine, Rijnstate Ziekenhuis, Arnhem, The Netherlands. FAU - Ahmed, Sofia B AU - Ahmed SB AUID- ORCID: 0000-0003-3000-2229 AD - Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada. FAU - Schmieder, Roland E AU - Schmieder RE AUID- ORCID: 0000-0003-2356-5883 AD - Department of Nephrology and Hypertension, University Hospital Erlangen Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Wanner, Christoph AU - Wanner C AUID- ORCID: 0000-0001-9507-5301 AD - Division of Nephrology, Department of Medicine, University Hospital Wurzburg, Wurzburg, Germany. FAU - Cherney, David Z I AU - Cherney DZI AUID- ORCID: 0000-0003-4164-0429 AD - Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. FAU - Jongs, Niels AU - Jongs N AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AUID- ORCID: 0000-0002-3126-3730 AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.j.lambers.heerspink@umcg.nl. LA - eng SI - ClinicalTrials.gov/NCT04889183 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20241025 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Female MH - Male MH - *Renal Insufficiency, Chronic/drug therapy/complications/physiopathology MH - Middle Aged MH - Double-Blind Method MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Glomerular Filtration Rate/drug effects MH - Albuminuria/drug therapy MH - Aged MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Competing interests: E.M., F.W., J.M.C., M.L.-M., J.V., K.H. and A.v.d.A. report no conflicts of interest. J.L.G. declares funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk (all to the INCLIVA Research Institute); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk; and payment of honoraria for lectures from AstraZeneca, Novo Nordisk, Bayer, Menarini, Boehringer Ingelheim and Eli Lilly. N.J. received travel support from AstraZeneca. S.C.G. declares funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk (all to the FIDES Research Foundation) and payment of honoraria for lectures from AstraZeneca, Novo Nordisk, Baxter, Chiesi, ChemoCentrix, Clarion and Boehringer Ingelheim. M.J.P. received board speaker fees and travel expenses from AstraZeneca, NovoNordisk, Boehringer Ingelheim, Eli Lilly, Bayer and Menarini. G.D.L. received lecture fees from Sanofi, AstraZeneca and Janssen and has served as a consultant for AbbVie, Sanofi, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Merck Sharp & Dohme. A.v.B. declares being contracted via the University of Groningen (no personal payment) to undertake consultancy for Novo Nordisk, Eli Lilly and Boehringer Ingelheim. D.Z.I.C. has received honoraria from Boehringer Ingelheim, Eli Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, AbbVie, Janssen, Bayer, Prometic, Bristol Myers Squibb, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene and Novo Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim, Eli Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. S.B.A. reports no conflicts of interest. She receives research support from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. R.E.S. received grants to the institution from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim and NovoNordisk and speaker and advisor honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Servier and TAD. C.W. has received grants and served on steering committees for Boehringer Ingelheim; served on advisory boards for Boehringer Ingelheim, Merck Sharp & Dohme and Bayer; and received lecture fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, Merck Sharp & Dohme, Novo Nordisk and Bayer. H.J.L.H. is a consultant for AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, CSL-Behring, DIMERIX, Eli Lilly, Gilead, Janssen, Novartis, Novo Nordisk, Roche, Travere Pharmaceuticals and VIFOR Pharma. He received research support through his institution from AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk. He received lecture fees from AstraZeneca, Bayer and Novo Nordisk. EDAT- 2024/10/26 19:24 MHDA- 2025/01/22 06:27 CRDT- 2024/10/25 23:41 PHST- 2024/09/03 00:00 [received] PHST- 2024/09/30 00:00 [accepted] PHST- 2025/01/22 06:27 [medline] PHST- 2024/10/26 19:24 [pubmed] PHST- 2024/10/25 23:41 [entrez] AID - 10.1038/s41591-024-03327-6 [pii] AID - 10.1038/s41591-024-03327-6 [doi] PST - ppublish SO - Nat Med. 2025 Jan;31(1):278-285. doi: 10.1038/s41591-024-03327-6. Epub 2024 Oct 25. PMID- 39450504 OWN - NLM STAT- MEDLINE DCOM- 20241118 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 17 IP - 11 DP - 2024 Nov TI - SGLT2i and GLP1RA effects in patients followed in a hospital diabetology consultation. PG - 1081-1088 LID - 10.1080/17512433.2024.2421872 [doi] AB - BACKGROUND: We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice. RESEARCH DESIGN AND METHODS: A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c). RESULTS: Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (p = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (p = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (p < 0.0001), with a higher percentage of patients achieving >/= 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores (p = 0.004 and p = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (p = 0.010 and p = 0.002, respectively). CONCLUSIONS: Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM. FAU - Lopes, Antonio Cabral AU - Lopes AC AD - Pharmaceutical Services Local Health Unit of Guarda (ULS da Guarda), Guarda, Portugal. AD - Pharmaceutical Services Local Health Unit of Aveiro Region (ULS da Regiao de Aveiro), Aveiro, Portugal. AD - Faculty of Health Sciences, FCS-UBI, University of Beira Interior, Covilha, Portugal. FAU - Lourenco, Olga AU - Lourenco O AD - Faculty of Health Sciences, FCS-UBI, University of Beira Interior, Covilha, Portugal. AD - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilha, Portugal. FAU - Morgado, Manuel AU - Morgado M AD - Faculty of Health Sciences, FCS-UBI, University of Beira Interior, Covilha, Portugal. AD - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilha, Portugal. AD - Pharmaceutical Services, Local Health Unit of Cova da Beira (ULS Cova da Beira), Covilha, Portugal. AD - Clinical Academic Center of Beiras (CACB), UBImedical, Covilha, Portugal. LA - eng PT - Journal Article DEP - 20241027 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Middle Aged MH - *Glycated Hemoglobin MH - Aged MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - *Glomerular Filtration Rate MH - *Blood Pressure/drug effects/physiology MH - Cardiovascular Diseases/prevention & control MH - Weight Loss/drug effects MH - Heart Disease Risk Factors MH - Body Weight/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular risk OT - GLP1 RA OT - HbA1c OT - SGLT2i OT - obesity OT - renal function EDAT- 2024/10/25 06:23 MHDA- 2024/11/18 06:22 CRDT- 2024/10/25 05:03 PHST- 2024/11/18 06:22 [medline] PHST- 2024/10/25 06:23 [pubmed] PHST- 2024/10/25 05:03 [entrez] AID - 10.1080/17512433.2024.2421872 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2024 Nov;17(11):1081-1088. doi: 10.1080/17512433.2024.2421872. Epub 2024 Oct 27. PMID- 39445607 OWN - NLM STAT- MEDLINE DCOM- 20250103 LR - 20260909 IS - 1473-5598 (Electronic) IS - 0263-6352 (Linking) VI - 43 IP - 2 DP - 2025 Feb 1 TI - Effects of glucagon-like peptide-1 receptor agonists on blood pressure in overweight or obese patients: a meta-analysis of randomized controlled trials. PG - 290-300 LID - 10.1097/HJH.0000000000003903 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists are novel medications with proven efficacy in treating type 2 diabetes mellitus, and are increasingly being used for weight loss. They may potentially have benefit in treating metabolic disorders; however, evidence is sparse with regards to treating high blood pressure (BP). We performed a systematic review, meta-analysis and meta-regression investigating the efficacy of GLP-1 RAs in lowering BP in obese or overweight patients. METHODS: Three electronic databases (PubMed, EMBASE, and CENTRAL) were systematically searched for randomized controlled trials (RCTs) published from inception to 13 February 2024. Pair-wise meta-analysis and random effects meta-regression models were utilized. Fixed effects meta-analysis was used to unify treatment effects across different GLP-1 RA doses. RESULTS: We included a total of 30 RCTs with a combined population of 37 072 patients. GLP-1 RAs demonstrated a mean systolic BP (SBP) reduction of -3.37 mmHg [95% confidence interval (CI) -3.95 to -2.80] and a mean diastolic BP (DBP) reduction of -1.05 mmHg (95% CI -1.46 to -0.65) compared with placebo. This effect was consistent across subgroups for diabetic status, formulation of GLP-1 RA, follow-up duration and route of administration for both SBP and DBP, with the exception of subgroups investigating exenatide. Meta-regression suggested no significant correlation between BP reduction and baseline characteristics such as age, percentage of male patients, HbA1c, weight, BMI, and percentage of patients with hypertension. CONCLUSION: Our meta-analysis suggests significant BP reduction benefits from GLP-1 RA use in obese or overweight patients, consistent across diabetic status, duration of treatment, and across route of administration. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Wong, Hon Jen AU - Wong HJ AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. FAU - Toh, Keith Zhi Xian AU - Toh KZX AD - Department of Medicine, National University Hospital. FAU - Teo, Yao Hao AU - Teo YH AD - Department of Cardiology, National University Heart Centre Singapore. FAU - Teo, Yao Neng AU - Teo YN AD - Department of Cardiology, National University Heart Centre Singapore. FAU - Chan, Mark Y AU - Chan MY AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. AD - Department of Cardiology, National University Heart Centre Singapore. FAU - Yeo, Leonard L L AU - Yeo LLL AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. AD - Division of Neurology. FAU - Eng, Pei Chia AU - Eng PC AD - Division of Endocrinology, Department of Medicine, National University Hospital, Singapore. FAU - Tan, Benjamin Y Q AU - Tan BYQ AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. AD - Division of Neurology. FAU - Zhou, Xin AU - Zhou X AD - Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China. FAU - Yang, Qing AU - Yang Q AD - Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China. FAU - Dalakoti, Mayank AU - Dalakoti M AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. AD - Department of Cardiology, National University Heart Centre Singapore. FAU - Sia, Ching-Hui AU - Sia CH AD - Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. AD - Department of Cardiology, National University Heart Centre Singapore. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20241015 PL - Netherlands TA - J Hypertens JT - Journal of hypertension JID - 8306882 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/agonists MH - *Randomized Controlled Trials as Topic MH - *Obesity/drug therapy/complications/physiopathology MH - *Overweight/drug therapy/complications MH - *Blood Pressure/drug effects MH - Exenatide/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypertension/drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/10/24 16:21 MHDA- 2025/01/03 06:21 CRDT- 2024/10/24 07:03 PHST- 2024/07/20 00:00 [received] PHST- 2024/09/30 00:00 [accepted] PHST- 2025/01/03 06:21 [medline] PHST- 2024/10/24 16:21 [pubmed] PHST- 2024/10/24 07:03 [entrez] AID - 00004872-990000000-00567 [pii] AID - 10.1097/HJH.0000000000003903 [doi] PST - ppublish SO - J Hypertens. 2025 Feb 1;43(2):290-300. doi: 10.1097/HJH.0000000000003903. Epub 2024 Oct 15. PMID- 39445596 OWN - NLM STAT- MEDLINE DCOM- 20241224 LR - 20260414 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 20 IP - 12 DP - 2024 Dec TI - Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. PG - 8661-8672 LID - 10.1002/alz.14313 [doi] AB - INTRODUCTION: Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking. METHODS: We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups. DISCUSSION: These findings support further studies to assess semaglutide's potential in preventing AD. HIGHLIGHTS: Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD. CI - (c) 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Wang, QuangQiu AU - Wang Q AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Qi, Xin AU - Qi X AD - Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Gurney, Mark AU - Gurney M AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Perry, George AU - Perry G AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Department of Neuroscience, Development and Regenerative Biology, College of Sciences, The University of Texas at San Antonio, San Antonio, Texas, USA. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Drug Abuse, National Institutes of Health, Maryland, USA. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Ohio, USA. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076051/AG/NIA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG074346/AG/NIA NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - AG057557 AG061388 AG062272 AG076649/AG/NIA NIH HHS/United States GR - R01 AG065240/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20241024 PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Alzheimer Disease/drug therapy MH - Female MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - United States MH - Middle Aged MH - Aged, 80 and over MH - Semaglutide PMC - PMC11667504 OTO - NOTNLM OT - Alzheimer's disease OT - emulation target trial OT - patient electronic health records OT - prevention OT - real-world data OT - semaglutide OT - type 2 diabetes COIS- All authors declare no competing interests. Author disclosures are available in the Supporting Information. EDAT- 2024/10/24 16:21 MHDA- 2024/12/24 12:21 PMCR- 2024/10/24 CRDT- 2024/10/24 07:03 PHST- 2024/09/10 00:00 [revised] PHST- 2024/07/29 00:00 [received] PHST- 2024/09/12 00:00 [accepted] PHST- 2024/12/24 12:21 [medline] PHST- 2024/10/24 16:21 [pubmed] PHST- 2024/10/24 07:03 [entrez] PHST- 2024/10/24 00:00 [pmc-release] AID - ALZ14313 [pii] AID - 10.1002/alz.14313 [doi] PST - ppublish SO - Alzheimers Dement. 2024 Dec;20(12):8661-8672. doi: 10.1002/alz.14313. Epub 2024 Oct 24. PMID- 39443282 OWN - NLM STAT- MEDLINE DCOM- 20250424 LR - 20250516 IS - 2233-6087 (Electronic) IS - 2233-6079 (Print) IS - 2233-6079 (Linking) VI - 49 IP - 1 DP - 2025 Jan TI - Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus. PG - 49-59 LID - 10.4093/dmj.2024.0105 [doi] AB - BACKGRUOUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort. METHODS: This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years. RESULTS: After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group. CONCLUSION: There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers. FAU - Kim, Mijin AU - Kim M AD - Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea. AD - Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. FAU - Kim, Seung Chan AU - Kim SC AD - Department of Biostatistics, Clinical Trial Center, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. FAU - Kim, Jinmi AU - Kim J AD - Department of Biostatistics, Clinical Trial Center, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. FAU - Kim, Bo Hyun AU - Kim BH AD - Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea. AD - Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. LA - eng GR - 20220025/Pusan National University Hospital/ PT - Journal Article DEP - 20241024 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Incidence MH - *Neoplasms/epidemiology/chemically induced MH - Aged MH - Republic of Korea/epidemiology MH - Adult MH - Risk Factors PMC - PMC11788542 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide-1 receptor agonists OT - Pancreatic neoplasms OT - Thyroid cancer, medullary OT - Thyroid neoplasms COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. EDAT- 2024/10/24 00:23 MHDA- 2025/01/20 22:54 PMCR- 2025/01/01 CRDT- 2024/10/23 21:59 PHST- 2024/03/04 00:00 [received] PHST- 2024/05/13 00:00 [accepted] PHST- 2025/01/20 22:54 [medline] PHST- 2024/10/24 00:23 [pubmed] PHST- 2024/10/23 21:59 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - dmj.2024.0105 [pii] AID - dmj-2024-0105 [pii] AID - 10.4093/dmj.2024.0105 [doi] PST - ppublish SO - Diabetes Metab J. 2025 Jan;49(1):49-59. doi: 10.4093/dmj.2024.0105. Epub 2024 Oct 24. PMID- 39443044 OWN - NLM STAT- MEDLINE DCOM- 20241023 LR - 20260211 IS - 1878-0415 (Electronic) IS - 0737-6146 (Linking) VI - 42 IP - 1 DP - 2024 Dec TI - Perioperative Considerations for Patients on GLP1 Agonists. PG - 1-26 LID - S0737-6146(24)00002-9 [pii] LID - 10.1016/j.aan.2024.07.002 [doi] AB - GlP-1 receptor agonists are a class of medications that are becoming increasingly popular. Large trials have shown that their use provides reliable weight loss in obese patients and improved glycemic control in diabetic patients. Its use also has broader implications for overall metabolic health and has been shown to improve cardiovascular outcomes in high-risk populations. Glucagon-like peptide 1 receptors cause multiple effects in the body through stimulation of receptors expressed in a broad range of tissues including the pancreas, liver, gastrointestinal tract, kidneys, heart, endothelium, muscle, and brain. For the anesthesia professionals the effects of these medications on gastric emptying is important. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - VanderWielen, Beth A AU - VanderWielen BA AD - Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA. FAU - Brian Beam, William AU - Brian Beam W AD - Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA. Electronic address: beam.william@mayo.edu. LA - eng PT - Journal Article PT - Review DEP - 20240828 PL - United States TA - Adv Anesth JT - Advances in anesthesia JID - 8409340 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Perioperative Care/methods MH - *Hypoglycemic Agents/pharmacology/administration & dosage/therapeutic use MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - Gastric Emptying/drug effects/physiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Aspiration OT - GLP-1 receptor agonists OT - Gastric ultrasound OT - Perioperative patients COIS- Disclosure The authors have nothing to disclose. EDAT- 2024/10/24 00:23 MHDA- 2024/10/24 00:24 CRDT- 2024/10/23 20:58 PHST- 2024/10/24 00:24 [medline] PHST- 2024/10/24 00:23 [pubmed] PHST- 2024/10/23 20:58 [entrez] AID - S0737-6146(24)00002-9 [pii] AID - 10.1016/j.aan.2024.07.002 [doi] PST - ppublish SO - Adv Anesth. 2024 Dec;42(1):1-26. doi: 10.1016/j.aan.2024.07.002. Epub 2024 Aug 28. PMID- 39442257 OWN - NLM STAT- MEDLINE DCOM- 20241124 LR - 20260627 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 12 DP - 2024 Dec TI - REAL life study of subcutaneous SEMaglutide in patients with type 2 diabetes in SPain: Ambispective, multicenter clinical study. Results in the GLP1-experienced cohort. PG - 108874 LID - S1056-8727(24)00200-9 [pii] LID - 10.1016/j.jdiacomp.2024.108874 [doi] AB - OBJECTIVE: To evaluate the efficacy of switching to once-weekly subcutaneous semaglutide in patients with type 2 diabetes mellitus (T2DM) who were previously treated with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in a real-world setting in Spain. METHODS: The REAL Life study of SEMaglutide in Patients with Type 2 diabetes in Spain (REALSEM-SP) was conducted in four endocrinology departments in Madrid, Spain. Adult patients with T2DM who were prescribed once-weekly (OW) subcutaneous semaglutide and had been previously treated with other GLP-1 RAs were included. Baseline characteristics, including demographic, anthropometric, and laboratory variables, were recorded at baseline and at 6 +/- 3 and 12 +/- 3 months of follow-up. The primary outcome was the change in HbA(1c) at 12 +/- 3 months of follow-up, with secondary outcomes including changes in weight, BMI, and other glycemic parameters. RESULTS: A total of 267 patients were included in the analysis, with a mean age of 61.6 years and a mean T2DM duration of 11.3 years. The majority of patients had grade 1 or 2 obesity at baseline. Switching to OW-semaglutide was associated with a significant reduction in HbA(1c) from baseline to 13 months (-0.35 % +/- 0.81). Patients who reached the 1.0 mg OW-dose showed a significant reduction in HbA(1c) compared to those on the /=18 years) with type 2 diabetes who used a GLP-1 receptor agonist or SGLT-2 inhibitor within 30 days before upper gastrointestinal endoscopy. MAIN OUTCOME MEASURES: The primary outcome was pulmonary aspiration on the day of or the day after endoscopy, defined using diagnostic codes. The secondary outcome was discontinuation of endoscopy. Risk ratios and corresponding 95% confidence intervals (CIs) were estimated after fine stratification weighting based on propensity score. RESULTS: After weighting, 24 817 adults used a GLP-1 receptor agonist (mean age 59.9 years; 63.6% female) and 18 537 used an SGLT-2 inhibitor (59.8 years; 63.7% female). Among users of GLP-1 receptor agonists and SGLT-2 inhibitors, the weighted risk per 1000 people was, respectively, 4.15 and 4.26 for pulmonary aspiration and 9.79 and 4.91 for discontinuation of endoscopy. Compared with SGLT-2 inhibitor use, GLP-1 receptor agonist use was not associated with an increased risk of pulmonary aspiration (pooled risk ratio 0.98, 95% CI 0.73 to 1.31), although it was associated with a higher risk for discontinuation of endoscopy (1.99, 1.56 to 2.53). CONCLUSIONS: In this comparative cohort study, no increased risk of pulmonary aspiration during upper gastrointestinal endoscopy was observed among adults with type 2 diabetes using GLP-1 receptor agonists compared with SGLT-2 inhibitors within 30 days of the procedure; however, GLP-1 receptor agonists were associated with a higher risk of discontinuation of endoscopy, possibly owing to a higher risk of retained gastric content. In the absence of evidence from randomized trials, these findings could inform future practice recommendations on the preprocedural protocol for patients requiring endoscopy. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Alkabbani, Wajd AU - Alkabbani W AUID- ORCID: 0000-0002-7030-0442 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Suissa, Karine AU - Suissa K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Gu, Kristine D AU - Gu KD AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Cromer, Sara J AU - Cromer SJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA. FAU - Bykov, Katsiaryna AU - Bykov K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Hobai, Ion AU - Hobai I AD - Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Thompson, Christopher C AU - Thompson CC AD - Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA epatorno@bwh.harvard.edu. LA - eng GR - K01 AG068365/AG/NIA NIH HHS/United States GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20241022 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Endoscopy, Gastrointestinal MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - *Respiratory Aspiration/etiology MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Cohort Studies MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Risk Factors MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11494456 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: SJC has a close family member employed by a Johnson & Johnson company and reports consultancy for Wolters-Kluwer and Alexion Pharmaceuticals. DJW reports consultancy for Novo Nordisk and serving as a data monitoring committee member for SOUL and FLOW trials. EP is principal investigator of a research grant to the Brigham and Women's Hospital from Boehringer Ingelheim, not related to the topic of this work. CCT reports the following activities: Apollo Endosurgery - consultant/research support (consulting fees/institutional research grants); Bariendo - Founder/Board Member/Ownership Interest; BlueFlame Healthcare Venture Fund - Founder/General Partner; Boston Scientific - consultant (consulting fees)/research support (institutional research grant); Medtronic - consultant (consulting fees); ELLES - founder/board member/ownership interest; Endoquest Robotics - consultant, institutional research grant; Enterasense - founder, consultant, board member, ownership interest; EnVision Endoscopy - founder, board member, consultant, ownership interest; ERBE - institutional research grant; Fractyl - consultant/advisory board member (consulting fees)/research support; FujiFilm - consultant/institutional research grant; GI Dynamics - consultant (consulting fees)/ research support (institutional research grant); GI Windows - founder, board member, ownership interest; Lumendi - consultant/institutional research grant; Olympus/Spiration - consultant (consulting fees)/research support (Equipment Loans); Society for Metabolic and Bariatric Endoscopy (SMBE) - founder/president/ownership interest; Softac - consultant/ownership interest; USGI Medical - consultant (consulting fees)/advisory board member (consulting fees)/research support (institutional research grant); Xenter - consultant/SAB/ownership interest. EDAT- 2024/10/23 04:22 MHDA- 2024/10/23 04:23 PMCR- 2024/10/22 CRDT- 2024/10/22 20:43 PHST- 2024/10/23 04:23 [medline] PHST- 2024/10/23 04:22 [pubmed] PHST- 2024/10/22 20:43 [entrez] PHST- 2024/10/22 00:00 [pmc-release] AID - bmj-2024-080340.R2 [pii] AID - alkw080340 [pii] AID - 10.1136/bmj-2024-080340 [doi] PST - epublish SO - BMJ. 2024 Oct 22;387:e080340. doi: 10.1136/bmj-2024-080340. PMID- 39438027 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20260127 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 38 IP - 3 DP - 2025 Jun TI - Great Expectations: Semaglutide as Antidiabetic Weight Management in a Psychiatric Hospital. PG - 351-356 LID - 10.1177/08971900241294122 [doi] AB - This report explores the potential role of glucagon-like peptide 1 (GLP-1) receptor agonists in minimizing the metabolic side effects of psychotropic medications in patients with underlying type 2 diabetes (T2D) in inpatient psychiatric settings. The introduction of novel antidiabetic medications such as GLP-1 receptor agonists has broadened the options for managing metabolic disorders, particularly T2D. These medications not only offer effective glycemic control but also provide cardiovascular and renal benefits and help with weight management. Given the tendency of psychotropic medications to cause weight gain and metabolic complications, this report presents 2 cases where weekly doses of semaglutide improved blood glucose levels and prevented weight gain in patients receiving chronic psychotropic medications. Integrating GLP-1 receptor agonists into inpatient psychiatric care can help mitigate the metabolic adverse effects of psychotropic medications. However, considerations such as cost, accessibility, and institutional formulary restrictions are essential to ensure comprehensive patient care. FAU - Shannon, Krysta AU - Shannon K AUID- ORCID: 0000-0001-6173-9018 AD - Clinical Pharmacy Manager, NewYork-Presbyterian Hospital, New York, NY, USA. RINGGOLD: 25065 FAU - Shyh, Grace AU - Shyh G AD - Clinical Pharmacy Manager, NewYork-Presbyterian Hospital, New York, NY, USA. RINGGOLD: 25065 LA - eng PT - Case Reports PT - Journal Article DEP - 20241022 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Psychotropic Drugs) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Male MH - Female MH - *Hospitals, Psychiatric/trends MH - *Weight Gain/drug effects MH - Blood Glucose/drug effects MH - Psychotropic Drugs/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide 1 (GLP-1) receptor agonists OT - metabolic disorders OT - psychotropic medication COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2024/10/23 04:22 MHDA- 2025/05/05 06:27 CRDT- 2024/10/22 20:23 PHST- 2025/05/05 06:27 [medline] PHST- 2024/10/23 04:22 [pubmed] PHST- 2024/10/22 20:23 [entrez] AID - 10.1177/08971900241294122 [doi] PST - ppublish SO - J Pharm Pract. 2025 Jun;38(3):351-356. doi: 10.1177/08971900241294122. Epub 2024 Oct 22. PMID- 39435881 OWN - NLM STAT- MEDLINE DCOM- 20241022 LR - 20250103 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 16 IP - 10 DP - 2024 Oct TI - The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agonist on patients with type 2 diabetes: A population-based study. PG - e70013 LID - 10.1111/1753-0407.70013 [doi] LID - e70013 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. METHODS: We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. RESULTS: Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (>/=12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. CONCLUSION: Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations. CI - (c) 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Cheng, Zhiyuan AU - Cheng Z AUID- ORCID: 0000-0003-4694-4843 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Wang, Shuang AU - Wang S AD - Shenzhen Health Development Research and Data Management Center, Shenzhen, China. FAU - Li, Fu-Rong AU - Li FR AUID- ORCID: 0000-0002-0399-7489 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Jin, Cheng AU - Jin C AUID- ORCID: 0000-0002-0903-1685 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Mo, Chunbao AU - Mo C AUID- ORCID: 0000-0003-0738-7773 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Zheng, Jing AU - Zheng J AD - Shenzhen Health Development Research and Data Management Center, Shenzhen, China. FAU - Li, Xia AU - Li X AUID- ORCID: 0000-0003-1922-7152 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. AD - School of Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Liang, Fengchao AU - Liang F AUID- ORCID: 0000-0003-2088-0722 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. AD - School of Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Yang, Jinkui AU - Yang J AUID- ORCID: 0000-0003-1040-3412 AD - Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Gu, Dongfeng AU - Gu D AUID- ORCID: 0000-0002-2781-7825 AD - School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China. AD - Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China. AD - School of Medicine, Southern University of Science and Technology, Shenzhen, China. LA - eng GR - 2023K0610/R&D project of Pazhou Lab (Huangpu)/ GR - 12126602/National Natural Science Foundation of China/ GR - 42107465/National Natural Science Foundation of China/ GR - 82030102/National Natural Science Foundation of China/ GR - ZDSYS20200810171403013/Shenzhen Science and Technology Innovation Committee/ GR - 2022YFC3702703/National Science and Technology Major Project/ GR - C2302001/Shenzhen Medical Academy of Research and Translation/ PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - China/epidemiology MH - Metformin/therapeutic use/adverse effects MH - Insulin/therapeutic use MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11494487 OTO - NOTNLM OT - GLP-1 receptor agonists OT - clinical adverse outcomes OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2024/10/22 16:24 MHDA- 2024/10/22 16:25 PMCR- 2024/10/22 CRDT- 2024/10/22 07:53 PHST- 2024/08/22 00:00 [revised] PHST- 2024/04/19 00:00 [received] PHST- 2024/09/07 00:00 [accepted] PHST- 2024/10/22 16:25 [medline] PHST- 2024/10/22 16:24 [pubmed] PHST- 2024/10/22 07:53 [entrez] PHST- 2024/10/22 00:00 [pmc-release] AID - JDB70013 [pii] AID - 10.1111/1753-0407.70013 [doi] PST - ppublish SO - J Diabetes. 2024 Oct;16(10):e70013. doi: 10.1111/1753-0407.70013. PMID- 39433216 OWN - NLM STAT- MEDLINE DCOM- 20241113 LR - 20250114 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 217 DP - 2024 Nov TI - The impact of glucagon-like peptide-1 receptor agonist on the gastric residue in upper endoscopy. PG - 111900 LID - S0168-8227(24)00810-6 [pii] LID - 10.1016/j.diabres.2024.111900 [doi] AB - AIM: We aimed to investigate the association between Glucagon-like-peptide-1 receptors agonists (GLP1-RA) use and gastric residue on esophagogastroduodenoscopy (EGD). METHODS: A multicenter, retrospective study included all EGDs conducted across seven gastroenterology departments. EGDs with the diagnosis of "poor preparation" or described as a poor preparation in the endoscopist's report were considered as gastric residue. RESULTS: 120,879 EGDs were included in the analysis. Of these, 1671 patients treated with GLP1-RA were compared to 119,208 without GLP1-RA treatment. Of the GLP1-RA group, 93 (5.6 %) had gastric residue compared to 2327 (2.0 %) among the non-GLP1-RA group (p < 0.001). Sup-group analysis: 71 (6.2 %) of the 1141 DM patients treated with GLP1-RA compared to 307 (3.0 %) of the 10,152 DM patients without GLP1-RA treatment (p < 0.001). Additionally, 22 (4.2 %) of 503 non-DM patients treated with GLP1-RA had gastric residue compared to 2065 (2.0 %) of the non-DM non-GLP1-RA group (n = 109,056) (p < 0.001). In multivariate analysis, DM and GLP1-RA were both found to be independent risk factors for excess gastric residue. CONCLUSION: Our results may have important clinical relevance for EGD preparation among GLP1-RA treated patients, either requiring a longer fasting time prior to EGD or holding the medication prior to EGD according to the half-life of the drug. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Abu-Freha, Naim AU - Abu-Freha N AD - Assuta Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: naima@assuta.co.il. FAU - Levi, Zohar AU - Levi Z AD - Department of Gastroenterology, Beilinson Medical Center, Petah Tikva Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Nevo-Shor, Anat AU - Nevo-Shor A AD - The Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. FAU - Guterman, Revital AU - Guterman R AD - Assuta Medical Center, Beer-Sheva, Israel. FAU - Elhayany, Ruhama AU - Elhayany R AD - Assuta Medical Center, Beer-Sheva, Israel. FAU - Yitzhak, Avraham AU - Yitzhak A AD - Assuta Medical Center, Beer-Sheva, Israel. FAU - Zelnik Yovel, Dana AU - Zelnik Yovel D AD - Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, Faculty of Medicine, Tel Aviv University, Zerifin, Israel. FAU - Cohen, Daniel L AU - Cohen DL AD - Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, Faculty of Medicine, Tel Aviv University, Zerifin, Israel. FAU - Shirin, Haim AU - Shirin H AD - Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, Faculty of Medicine, Tel Aviv University, Zerifin, Israel. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241019 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - *Endoscopy, Digestive System MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology MH - Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - *Stomach/surgery OTO - NOTNLM OT - Diabetes mellitus OT - EGD OT - GLP1 OT - Gastric residue OT - Upper endoscopy COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/10/22 04:57 MHDA- 2024/11/14 03:55 CRDT- 2024/10/21 19:13 PHST- 2024/09/10 00:00 [received] PHST- 2024/10/03 00:00 [revised] PHST- 2024/10/16 00:00 [accepted] PHST- 2024/11/14 03:55 [medline] PHST- 2024/10/22 04:57 [pubmed] PHST- 2024/10/21 19:13 [entrez] AID - S0168-8227(24)00810-6 [pii] AID - 10.1016/j.diabres.2024.111900 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Nov;217:111900. doi: 10.1016/j.diabres.2024.111900. Epub 2024 Oct 19. PMID- 39431844 OWN - NLM STAT- MEDLINE DCOM- 20241021 LR - 20260320 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 16 IP - 10 DP - 2024 Oct TI - Major adverse cardiovascular events' reduction and their association with glucose-lowering medications and glycemic control among patients with type 2 diabetes: A retrospective cohort study using electronic health records. PG - e13604 LID - 10.1111/1753-0407.13604 [doi] LID - e13604 AB - BACKGROUND: Cardiovascular diseases are a common cause of death among patients with type 2 diabetes (T2DM). Major adverse cardiovascular event (MACE) risks can be significantly reduced under adequate glycemic control (GC). This study aims to identify factors that influence MACE risk among patients with T2DM, including Hemoglobin A1c variability score (HVS) and early use of MACE-preventive glucose-lowering medications (GLMs). METHODS: We conducted a longitudinal cohort study to retrospectively review electronic health records between 2011 and 2022. Patients with T2DM >/=18 years without previous stroke or acute myocardial infarction (AMI) were included. Cox regression was utilized to investigate MACE risk factors and compare MACE risk reduction associated with early use of MACE-preventive GLMs. RESULTS: A total of 19 685 subjects were included, with 5431 having MACE, including 4453 strokes, 977 AMI, and 1 death. There were 11 123 subjects with good baseline GC. Subjects with good baseline GC had 0.837 (confidence interval [CI]: 0.782-0.895) times lower MACE risk than their counterpart. Subjects with a single MACE-preventive GLM at baseline with continuous use >365 days showed a decreased MACE hazard ratio (0.681; CI: 0.635-0.731). Among all MACE-preventive GLMs, semaglutide provided a more significant MACE-preventive effect. CONCLUSIONS: This study identified that GLM, early GC, and HVS are MACE determinants among patients with T2DM. Novel GLM, adequate GC, and reduction of HVS can benefit MACE outcomes. CI - (c) 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Hsu, Haowen AU - Hsu H AUID- ORCID: 0009-0007-7422-9544 AD - Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. AD - Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. FAU - Kocis, Paul Thomas AU - Kocis PT AD - Department of Pharmacy, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. AD - Department of Pharmacology, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. FAU - Pichardo-Lowden, Ariana AU - Pichardo-Lowden A AD - Department of Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, USA. FAU - Hwang, Wenke AU - Hwang W AD - Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. LA - eng GR - UL1 TR002014/TR/NCATS NIH HHS/United States GR - Patient-Centered Outcomes Research Institute through PCORnet Clinical Research Network Infrastructure 1259/ PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Female MH - Retrospective Studies MH - Male MH - *Electronic Health Records/statistics & numerical data MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology/mortality MH - *Glycemic Control MH - Aged MH - *Blood Glucose/analysis/metabolism MH - Longitudinal Studies MH - Glycated Hemoglobin/analysis/metabolism MH - Risk Factors PMC - PMC11492400 OTO - NOTNLM OT - glucose-lowering medications OT - glycemic control OT - major adverse cardiovascular events OT - primary prevention OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2024/10/21 16:17 MHDA- 2024/10/21 16:18 PMCR- 2024/10/21 CRDT- 2024/10/21 09:14 PHST- 2024/06/16 00:00 [revised] PHST- 2024/04/20 00:00 [received] PHST- 2024/06/30 00:00 [accepted] PHST- 2024/10/21 16:18 [medline] PHST- 2024/10/21 16:17 [pubmed] PHST- 2024/10/21 09:14 [entrez] PHST- 2024/10/21 00:00 [pmc-release] AID - JDB13604 [pii] AID - 10.1111/1753-0407.13604 [doi] PST - ppublish SO - J Diabetes. 2024 Oct;16(10):e13604. doi: 10.1111/1753-0407.13604. PMID- 39431379 OWN - NLM STAT- MEDLINE DCOM- 20241205 LR - 20260623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 1 DP - 2025 Jan TI - Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis. PG - 259-267 LID - 10.1111/dom.16012 [doi] AB - AIM: Diabetes is an independent risk factor for muscle mass loss, with possible mechanisms including impaired insulin signalling and chronic inflammation. The use of a glucagon-like peptide 1 (GLP-1) receptor-based agonist could lead to weight reduction, which might result from the loss of both fat and skeletal muscle. However, the body composition-modifying effects of GLP-1 receptor-based agonists have not been systematically characterized. METHODS: PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to October 2023. Randomized controlled trials of GLP-1 receptor agonist or glucose-dependent insulinotropic polypeptide/GLP-1 receptor dual agonist, which reported the changes of body composition, were included. The results were computed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) in a random-effects model. RESULTS: In all, 19 randomized controlled trials were included. When compared with controls, substantial reductions in fat body mass were observed in patients using GLP-1 receptor-based agonist treatment (WMD = -2.25 kg, 95% CI -3.40 to -1.10 kg), with decrease in areas of both subcutaneous fat (WMD = -38.35 cm(2), 95% CI, -54.75 to -21.95 cm(2)) and visceral fat (WMD = -14.61 cm(2), 95% CI, -23.77 to -5.44 cm(2)). Moreover, greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users compared with non-users (WMD = -1.02 kg, 95% CI, -1.46 to -0.57 kg), while the changes in lean mass percentage were comparable between GLP-1 receptor-based agonist users and non-users. CONCLUSION: Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in lean mass percentage were comparable between the users and non-users. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Jiao, Ruoyang AU - Jiao R AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lin, Chu AU - Lin C AUID- ORCID: 0000-0002-2365-9831 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Cai, Xiaoling AU - Cai X AUID- ORCID: 0000-0002-7881-0543 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Jingxuan AU - Wang J AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Yuan AU - Wang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lv, Fang AU - Lv F AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Wenjia AU - Yang W AUID- ORCID: 0000-0003-0610-5121 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. LA - eng GR - 81970698/National Natural Science Foundation of China/ GR - 81970708/National Natural Science Foundation of China/ GR - 7202216/Natural Science Foundation of Beijing Municipality/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20241021 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Female MH - Humans MH - Male MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Randomized Controlled Trials as Topic MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - fat mass OT - glucagon-like peptide 1 OT - lean mass OT - sarcopenia OT - type 2 diabetes EDAT- 2024/10/21 16:17 MHDA- 2024/12/05 06:23 CRDT- 2024/10/21 06:19 PHST- 2024/09/18 00:00 [revised] PHST- 2024/07/02 00:00 [received] PHST- 2024/09/28 00:00 [accepted] PHST- 2024/12/05 06:23 [medline] PHST- 2024/10/21 16:17 [pubmed] PHST- 2024/10/21 06:19 [entrez] AID - 10.1111/dom.16012 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jan;27(1):259-267. doi: 10.1111/dom.16012. Epub 2024 Oct 21. PMID- 39429118 OWN - NLM STAT- MEDLINE DCOM- 20241118 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 17 IP - 11 DP - 2024 Nov TI - Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire! PG - 1009-1012 LID - 10.1080/17512433.2024.2418398 [doi] AB - Tobacco use represents the leading preventable risk factor for premature deaths worldwide. A meta-analysis of 74 epidemiological studies, including 3.2 million individuals with type 2 diabetes mellitus (T2DM) from 33 countries, reported a pooled prevalence of smoking of 20.8% among individuals with T2DM. Cigarette smoking further aggravates existing deleterious vascular effects of T2DM. Namely, chronic hyperglycemia and exposure to cigarette smoke cause additive injurious effect on the endothelium, leading to an acceleration of vascular complications seen in persons with T2DM and tobacco use disorders (TUD). In a recent study, Wang and colleagues found that semaglutide use was associated with a significantly lower risk for medical encounters for TUD, when compared to other antidiabetic drug classes; indeed, this effect was strongest compared with insulins and weakest compared with other glucagon-like peptide-1 receptor agonists. Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed irrespective of the presence of obesity. Therefore, semaglutide use might be useful in terms of smoking cessation among individuals with T2DM, thus offering an additional benefit for this constantly growing population. However, those interesting findings should be confirmed through dedicated, large-scale randomized controlled trials. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Karakasis, Paschalis AU - Karakasis P AUID- ORCID: 0000-0002-3561-5713 AD - Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece. FAU - Ruza, Ieva AU - Ruza I AUID- ORCID: 0000-0002-3998-3548 AD - Department of Endocrinology, Riga Eastern Clinical University Hospital, Riga, Latvia. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. LA - eng PT - Journal Article DEP - 20241021 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/adverse effects MH - *Hypoglycemic Agents/pharmacology/administration & dosage/adverse effects MH - Risk Factors MH - Smoking/adverse effects/epidemiology MH - *Smoking Cessation/methods MH - Tobacco Use Disorder/complications MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - semaglutide OT - smoking cessation OT - tobacco use disorders OT - type 2 diabetes mellitus EDAT- 2024/10/21 10:51 MHDA- 2024/11/18 06:22 CRDT- 2024/10/21 04:54 PHST- 2024/11/18 06:22 [medline] PHST- 2024/10/21 10:51 [pubmed] PHST- 2024/10/21 04:54 [entrez] AID - 10.1080/17512433.2024.2418398 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2024 Nov;17(11):1009-1012. doi: 10.1080/17512433.2024.2418398. Epub 2024 Oct 21. PMID- 39425977 OWN - NLM STAT- MEDLINE DCOM- 20241019 LR - 20241218 IS - 1651-2006 (Electronic) IS - 1401-7431 (Linking) VI - 58 IP - 1 DP - 2024 Dec TI - Cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs according to baseline blood pressure in type 2 diabetes: a systematic meta-analysis of cardiovascular outcome trials. PG - 2418086 LID - 10.1080/14017431.2024.2418086 [doi] AB - Using a systematic meta-analysis, we investigated if patients with type 2 diabetes (T2D) and with varying baseline blood pressure (BP) differ in the cardiorenal benefits received from sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs). Design: Randomized, placebo-controlled, cardiovascular outcome trials (CVOTs) of SGLT-2is and GLP-1RAs were identified from MEDLINE, Embase, and the Cochrane Library up to April 2024. Hazard ratios (HRs) with 95% CIs were pooled. The differential treatment effect by baseline BP category within each trial was estimated as the ratio of the HR (RHR) and pooled. Results: Seventeen publications based on 9 unique CVOTs (4 SGLT-2is and 5 GLP-1RAs) were eligible. In participants with normal baseline BP, comparing SGLT-2is with placebo, the HRs (95% CIs) were 0.88 (0.79-0.97) for major adverse cardiovascular events (MACE), 0.73 (0.59-0.91) for heart failure (HF) hospitalization, 0.78 (0.65-0.94) for composite CVD death/HF hospitalization, and 0.55 (0.41-0.73) for composite renal outcome. The corresponding estimates for participants with higher baseline BP were 0.88 (0.81-0.96), 0.67 (0.57-0.79), 0.73 (0.65-0.82), and 0.61 (0.48-0.77), respectively. In participants with normal baseline BP, GLP-RAs had no strong effect on MACE, stroke and nephropathy, but reduced stroke and nephropathy risk in those with higher baseline BP. Estimated RHRs showed no statistical evidence that baseline BP modified the cardiorenal benefits of SGLT-2is and GLP-1RAs. Conclusions: In patients with T2D, the cardiorenal benefits of treatment with SGLT2-Is and GLP1-RAs were similar in patients with normal baseline BP compared to those with a higher baseline BP. FAU - Kunutsor, Setor K AU - Kunutsor SK AUID- ORCID: 0000-0002-2625-0273 AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, England. AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Seidu, Samuel AU - Seidu S AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, England. AD - Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Dey, Richard S AU - Dey RS AD - Department of Medicine, University of Ghana Hospital, Legon, Ghana. FAU - Baidoo, Isaac K AU - Baidoo IK AD - Nova Surgery Center, Accra, Ghana. FAU - Oulhaj, Abderrahim AU - Oulhaj A AD - Department of Epidemiology and Population Health, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241019 PL - England TA - Scand Cardiovasc J JT - Scandinavian cardiovascular journal : SCJ JID - 9708377 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Blood Pressure/drug effects MH - *Cardiovascular Diseases/diagnosis/etiology/mortality/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy/mortality MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects MH - Time Factors MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects OTO - NOTNLM OT - GLP-1RA OT - SGLT-2i OT - blood pressure OT - cardiovascular disease OT - kidney disease OT - randomized controlled trial OT - type 2 diabetes EDAT- 2024/10/19 22:17 MHDA- 2024/10/19 22:18 CRDT- 2024/10/19 14:23 PHST- 2024/10/19 22:18 [medline] PHST- 2024/10/19 22:17 [pubmed] PHST- 2024/10/19 14:23 [entrez] AID - 10.1080/14017431.2024.2418086 [doi] PST - ppublish SO - Scand Cardiovasc J. 2024 Dec;58(1):2418086. doi: 10.1080/14017431.2024.2418086. Epub 2024 Oct 19. PMID- 39424598 OWN - NLM STAT- MEDLINE DCOM- 20250111 LR - 20260611 IS - 2055-6845 (Electronic) IS - 2055-6837 (Print) VI - 10 IP - 8 DP - 2025 Jan 11 TI - Design and baseline characteristics of the STRIDE trial: evaluating semaglutide in people with symptomatic peripheral artery disease and type 2 diabetes. PG - 728-737 LID - 10.1093/ehjcvp/pvae071 [doi] AB - BACKGROUND: People with lower extremity peripheral artery disease (PAD) suffer from a high burden of symptoms and significant functional impairment. There are few therapies that improve function and reduce symptoms in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycaemic control, reduce body weight, and reduce the risk of major adverse cardiovascular events in people with atherosclerotic cardiovascular disease and type 2 diabetes (T2D). METHODS AND RESULTS: STRIDE (NCT04560998) is a randomized, placebo-controlled, double-blind phase 3b trial evaluating 1 mg once-weekly subcutaneous semaglutide (GLP-1 RA) vs. placebo, in people with symptomatic PAD (Fontaine IIa claudication) and T2D. Eligible participants were >/=18 years, had haemodynamically stable PAD, had no planned intervention, and were not receiving a GLP-1 RA. The primary endpoint is change in maximum walking distance on a constant-load treadmill (CLT). Secondary endpoints include quality of life and cardiometabolic assessments. A total of 792 participants were randomized in 20 countries. Participants' median age was 68 and median T2D duration 12 years. Risk factors included 25.6% current smokers, 87.9% with hypertension, and 42.7% with coronary heart disease. The mean BMI was 29.6 kg/m2 and the mean HbA1C was 7.3%. Participants exhibited baseline functional impairment with a median maximum walking distance of 186 m on a CLT. CONCLUSION: STRIDE has enrolled participants with symptomatic PAD and T2D, frequent risk factors and comorbidities, and functional impairment. The trial will provide evidence for the functional outcomes with semaglutide in people with PAD and T2D. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Bonaca, Marc P AU - Bonaca MP AUID- ORCID: 0000-0002-9860-3584 AD - CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, CO, USA. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Yasemin AU - Hansen Y AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AUID- ORCID: 0000-0002-1600-4415 AD - Department of Vascular Surgery, Lillebaelt Hospital. AD - Department of Regional Health Research, University of Southern Denmark, Denmark. FAU - Ramesh, Chethana Kalmady AU - Ramesh CK AD - Novo Nordisk GBS India, Bangalore, India. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute for Obesity and Metabolic Disorders Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AUID- ORCID: 0000-0002-2670-2268 AD - Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. FAU - Rasouli, Neda AU - Rasouli N AUID- ORCID: 0000-0003-1269-3580 AD - School of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Aurora, CO, USA. FAU - Sourij, Harald AU - Sourij H AUID- ORCID: 0000-0003-3510-9594 AD - Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Division of Cardiovascular Surgery, St. Michael's Hospital, University of Toronto, Toronto, Canada. LA - eng GR - Novo Nordisk/ PT - Clinical Trial Protocol PT - Journal Article PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - *Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology/physiopathology MH - Double-Blind Method MH - Exercise Tolerance/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Incretins/adverse effects/administration & dosage MH - Injections, Subcutaneous MH - *Intermittent Claudication/drug therapy/physiopathology/diagnosis MH - *Peripheral Arterial Disease/drug therapy/diagnosis/physiopathology/epidemiology MH - Quality of Life MH - Recovery of Function MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Walk Test MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11724141 OTO - NOTNLM OT - GLP1 agonist OT - Maximal walking distance OT - PAD OT - Peripheral artery disease OT - Semaglutide EDAT- 2024/10/19 16:23 MHDA- 2025/01/12 04:19 PMCR- 2025/10/18 CRDT- 2024/10/18 22:23 PHST- 2024/08/06 00:00 [received] PHST- 2024/09/08 00:00 [revised] PHST- 2025/01/12 04:19 [medline] PHST- 2024/10/19 16:23 [pubmed] PHST- 2024/10/18 22:23 [entrez] PHST- 2025/10/18 00:00 [pmc-release] AID - 7826783 [pii] AID - pvae071 [pii] AID - 10.1093/ehjcvp/pvae071 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2025 Jan 11;10(8):728-737. doi: 10.1093/ehjcvp/pvae071. PMID- 39422964 OWN - NLM STAT- MEDLINE DCOM- 20241018 LR - 20260713 IS - 1875-8908 (Electronic) IS - 1387-2877 (Linking) VI - 101 IP - s1 DP - 2024 TI - Incretin Mimetics as Potential Disease Modifying Treatment for Alzheimer's Disease. PG - S357-S370 LID - 10.3233/JAD-240730 [doi] AB - Alzheimer's disease is a devastating neurodegenerative condition that exerts a significant global burden. Despite recent efforts, disease modifying therapies remain extremely limited, with a tremendous proportion of patients having to rely on symptomatic treatment only. Epidemiological and pathological overlaps exist between Alzheimer's disease and diabetes mellitus type 2, with people with diabetes mellitus type 2 at a significantly increased risk of developing Alzheimer's disease in the future. Incretin mimetics, also known as GLP-1/GIP receptor agonists, are useful tools licensed for the treatment of diabetes mellitus type 2 which have recently been the subject of news coverage for their off-label use as weight loss medications. Emerging evidence highlights the possible neuroprotective function of incretin mimetics in models of Alzheimer's disease as well as in clinical studies. This review details the pre-clinical and clinical studies that have explored the effectiveness of incretin mimetics to alleviate Alzheimer's disease associated pathology and cognitive impairment, while also highlighting the progress made to examine the effectiveness of these molecules in Parkinson's disease. Should clinical trials prove effective, incretin mimetics may be able to be repurposed and become useful novel tools as disease-modifying treatments for Alzheimer's disease and other neurodegenerative diseases. FAU - Crook, Harry AU - Crook H AD - Faculty of Medicine, Imperial College London, London, UK. FAU - Edison, Paul AU - Edison P AD - Faculty of Medicine, Imperial College London, London, UK. AD - Cardiff University, Cardiff, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Incretins) RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Alzheimer Disease/drug therapy MH - *Incretins/therapeutic use MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Neuroprotective Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - drug repositioning OT - gastric inhibitory polypeptide OT - glucagon-like peptide-1 OT - type 2 diabetes mellitus EDAT- 2024/10/18 12:25 MHDA- 2024/10/18 18:22 CRDT- 2024/10/18 11:43 PHST- 2024/10/18 18:22 [medline] PHST- 2024/10/18 12:25 [pubmed] PHST- 2024/10/18 11:43 [entrez] AID - JAD240730 [pii] AID - 10.3233/JAD-240730 [doi] PST - ppublish SO - J Alzheimers Dis. 2024;101(s1):S357-S370. doi: 10.3233/JAD-240730. PMID- 39421913 OWN - NLM STAT- MEDLINE DCOM- 20260922 LR - 20260923 IS - 1130-0108 (Print) IS - 1130-0108 (Linking) VI - 118 IP - 9 DP - 2026 Sep TI - Pulmonary aspiration during upper endoscopy in a patient prescribed semaglutide. PG - 532-533 LID - 10.17235/reed.2024.10844/2024 [doi] AB - The past decade has witnessed an increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) owing to robust evidence of its benefits in type 2 diabetes and obesity. However, delay gastric emptying effect of GLP-1RAs has raised concerns for risk of gastric food retention and pneumonia aspiration during upper endoscopy. There have been observation studies reporting an increased incidence of gastric food retention among patients on GLP-1RAs, especially long-acting one like semaglutide. But the association between GLP-1RAs use and pneumonia aspiration during EGD remains unclear due to lack of high-level evidence. We report a case of pulmonary aspiration during EGD in a patient prescribed semaglutide. FAU - Dong, Tao AU - Dong T AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Wang, Lan AU - Wang L AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Wang, Hanying AU - Wang H AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Xiao, Jun AU - Xiao J AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, China. LA - eng PT - Case Reports PT - Letter PL - Spain TA - Rev Esp Enferm Dig JT - Revista espanola de enfermedades digestivas JID - 9007566 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Pneumonia, Aspiration/etiology/diagnostic imaging EDAT- 2024/10/18 06:23 MHDA- 2026/09/22 12:41 CRDT- 2024/10/18 04:53 PHST- 2026/09/22 12:41 [medline] PHST- 2024/10/18 06:23 [pubmed] PHST- 2024/10/18 04:53 [entrez] AID - 10.17235/reed.2024.10844/2024 [doi] PST - ppublish SO - Rev Esp Enferm Dig. 2026 Sep;118(9):532-533. doi: 10.17235/reed.2024.10844/2024. PMID- 39420429 OWN - NLM STAT- MEDLINE DCOM- 20241018 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Oct 17 TI - Non-alcoholic fatty liver disease risk with GLP-1 receptor agonists and SGLT-2 inhibitors in type 2 diabetes: a nationwide nested case-control study. PG - 367 LID - 10.1186/s12933-024-02461-2 [doi] LID - 367 AB - BACKGROUND: Non-alcoholic fatty liver diseases (NAFLDs)/non-alcoholic steatohepatitis (NASH) are the most common liver disorders among patients with type 2 diabetes. Newer classes of glucose-lowering agents (GLAs), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), have been shown to improve liver-related biomarkers. However, their effects on the development of NAFLD/NASH remain inconclusive. METHODS: A nested case-control study was conducted using Taiwan's National Health Insurance Research Database for 2011-2018. Patients aged >/= 40 years, diagnosed with type 2 diabetes, having stable non-insulin GLA use, and without NAFLD/NASH history were included. Patients with incident NAFLD/NASH were matched up to 10 randomly sampled controls based on individual's age, gender, cohort entry date, type 2 diabetes diagnosis date, and disease risk score. Conditional logistic regression analyses were employed to estimate the association between liver risk and treatment exposure. Dose-response analysis was also performed. RESULTS: There were 621,438 study patients included for analysis. During 1.8 years of median follow-up, the incidence of NAFLD/NASH was 2.7 per 1000 person-years. After matching, 5,730 incident NAFLD cases (mean age: 57.6 years, male: 53.2%) and 45,070 controls (57.7 years, 52.7%) were identified. Using GLP-1RAs or SGLT2is was associated with an insignificantly lower NAFLD/NASH risk (i.e., odds ratios [95% CIs]: 0.84 [0.46-1.52] and 0.85 [0.63-1.14], respectively) and increased cumulative SGLT2i doses were significantly associated with a reduced NAFLD/NASH risk (0.61 [0.38-0.97]). CONCLUSION: GLP-1RA and SGLT2i therapies in type 2 diabetes patients might prevent NAFLD/NASH development, with a significantly lower risk related to greater treatment exposure. CI - (c) 2024. The Author(s). FAU - Chang, Kai-Cheng AU - Chang KC AD - Department of Pharmacy, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. FAU - Kuo, Fan-Chi AU - Kuo FC AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. FAU - Yang, Chen-Yi AU - Yang CY AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. FAU - Yang, Chun-Ting AU - Yang CT AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. FAU - Ou, Huang-Tz AU - Ou HT AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. huangtz@mail.ncku.edu.tw. AD - Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. AD - School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. FAU - Kuo, Shihchen AU - Kuo S AD - School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan. AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. LA - eng GR - CDRPG3N0041/The Chang Gung Medical Foundation/ GR - 112-2628-B-006-008-MY3/The Ministry of Science and Technology in Taiwan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241017 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/epidemiology/diagnosis/drug therapy/blood MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/diagnosis/blood MH - Male MH - Middle Aged MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Risk Factors MH - Taiwan/epidemiology MH - Aged MH - Risk Assessment MH - Incidence MH - *Databases, Factual MH - Treatment Outcome MH - Time Factors MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Incretins/therapeutic use/adverse effects MH - Case-Control Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11487834 OTO - NOTNLM OT - Glucagon-like peptide-1 agonists OT - Non-alcoholic fatty liver disease OT - Non-alcoholic steatohepatitis OT - Sodium-glucose co-transporter-2 inhibitors OT - Type 2 diabetes COIS- The authors declare no competing interests. EDAT- 2024/10/18 06:23 MHDA- 2024/10/18 06:24 PMCR- 2024/10/17 CRDT- 2024/10/18 00:02 PHST- 2024/07/24 00:00 [received] PHST- 2024/10/03 00:00 [accepted] PHST- 2024/10/18 06:24 [medline] PHST- 2024/10/18 06:23 [pubmed] PHST- 2024/10/18 00:02 [entrez] PHST- 2024/10/17 00:00 [pmc-release] AID - 10.1186/s12933-024-02461-2 [pii] AID - 2461 [pii] AID - 10.1186/s12933-024-02461-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Oct 17;23(1):367. doi: 10.1186/s12933-024-02461-2. PMID- 39418202 OWN - NLM STAT- MEDLINE DCOM- 20250424 LR - 20251018 IS - 1460-2105 (Electronic) IS - 0027-8874 (Print) IS - 0027-8874 (Linking) VI - 117 IP - 3 DP - 2025 Mar 1 TI - Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data. PG - 476-485 LID - 10.1093/jnci/djae260 [doi] AB - BACKGROUND: Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status. METHODS: This retrospective cohort included patients with type 2 diabetes mellitus who were prescribed GLP-1RAs or other nonglucagon-like peptide-1 receptor agonist antidiabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other nonglucagon-like peptide-1 receptor agonist antidiabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio and 95% confidence interval calculated. RESULTS: The study population comprised 1 636 056 eligible patients including 167 091 prescribed GLP-1RAs and 1 468 965 prescribed other antidiabetes medications. GLP-1RAs were associated with a statistically significant decreased risk for pancreatic cancer incidence compared with each of 6 nonglucagon-like peptide-1 receptor agonist antidiabetes medications with hazard ratios ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with type 2 diabetes mellitus. Further studies and trials are needed to explore mechanisms and confirm causal effects. CI - (c) The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Wang, Lindsey AU - Wang L AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States. FAU - Wang, QuanQiu AU - Wang Q AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States. FAU - Li, Li AU - Li L AUID- ORCID: 0000-0003-1802-9517 AD - Department of Family Medicine, University of Virginia, Charlottesville, VA 22903, United States. AD - University of Virginia Comprehensive Cancer Center, University of Virginia, Charlottesville, VA 22908, United States. FAU - Kaelber, David C AU - Kaelber DC AUID- ORCID: 0000-0001-7855-9515 AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH 44109, United States. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States. AD - Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - TR004528/TR/NCATS NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - R25 CA221718/CA/NCI NIH HHS/United States GR - 15-20-27-XU/Landon Foundation-AACR/ GR - DP2 HD084068/HD/NICHD NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - National Institute of Health/ GR - CA221718/National Cancer Institute Case Comprehensive Cancer Center/ GR - DP2HD084068/Director's New Innovator/ GR - AG057557/AG/NIA NIH HHS/United States GR - RSG-16-049-01-MPC/American Cancer Society/ GR - AA029831/AA/NIAAA NIH HHS/United States PT - Journal Article PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM CIN - doi: 10.1093/jnci/djae324 MH - Humans MH - *Pancreatic Neoplasms/epidemiology/etiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Incidence MH - Obesity/epidemiology/complications MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11884861 COIS- None declared. EDAT- 2024/10/18 07:19 MHDA- 2025/03/07 04:52 PMCR- 2025/10/17 CRDT- 2024/10/17 13:03 PHST- 2024/08/09 00:00 [received] PHST- 2024/09/16 00:00 [revised] PHST- 2024/10/14 00:00 [accepted] PHST- 2025/03/07 04:52 [medline] PHST- 2024/10/18 07:19 [pubmed] PHST- 2024/10/17 13:03 [entrez] PHST- 2025/10/17 00:00 [pmc-release] AID - 7825367 [pii] AID - djae260 [pii] AID - 10.1093/jnci/djae260 [doi] PST - ppublish SO - J Natl Cancer Inst. 2025 Mar 1;117(3):476-485. doi: 10.1093/jnci/djae260. PMID- 39418085 OWN - NLM STAT- MEDLINE DCOM- 20241217 LR - 20260613 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 110 IP - 1 DP - 2024 Dec 18 TI - Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide. PG - 1-15 LID - 10.1210/clinem/dgae719 [doi] AB - CONTEXT: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. DATA ACQUISITION: We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. DATA SYNTHESIS: Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. CONCLUSION: Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Jalleh, Ryan J AU - Jalleh RJ AUID- ORCID: 0000-0003-4969-4771 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Plummer, Mark P AU - Plummer MP AUID- ORCID: 0000-0002-9640-1911 AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. FAU - Marathe, Chinmay S AU - Marathe CS AUID- ORCID: 0000-0002-8086-2449 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Umapathysivam, Mahesh M AU - Umapathysivam MM AUID- ORCID: 0000-0001-8959-5239 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Southern Adelaide Diabetes and Endocrine Service, Flinders Medical Centre, Bedford Park, SA 5042, Australia. FAU - Quast, Daniel R AU - Quast DR AUID- ORCID: 0000-0003-4357-6846 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany. FAU - Rayner, Christopher K AU - Rayner CK AUID- ORCID: 0000-0002-5527-256X AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. AD - Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. FAU - Jones, Karen L AU - Jones KL AUID- ORCID: 0000-0002-1155-5816 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Wu, Tongzhi AU - Wu T AUID- ORCID: 0000-0003-1656-9210 AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Horowitz, Michael AU - Horowitz M AUID- ORCID: 0000-0002-0942-0306 AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. AD - Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. LA - eng GR - Mary Overton postdoctoral fellowship/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM EIN - J Clin Endocrinol Metab. 2025 Sep 16;110(10):e3556. doi: 10.1210/clinem/dgaf387. PMID: 40638456 MH - Humans MH - *Gastric Emptying/drug effects/physiology MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Gastroparesis/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide PMC - PMC11651700 OTO - NOTNLM OT - GLP-1 receptor agonists OT - GLP-1/GIP dual receptor agonists OT - aspiration OT - gastric emptying OT - incretin mimetics OT - retained gastric content OT - tachyphylaxis EDAT- 2024/10/17 12:23 MHDA- 2024/12/18 06:16 PMCR- 2024/10/17 CRDT- 2024/10/17 11:53 PHST- 2024/06/10 00:00 [received] PHST- 2024/12/18 06:16 [medline] PHST- 2024/10/17 12:23 [pubmed] PHST- 2024/10/17 11:53 [entrez] PHST- 2024/10/17 00:00 [pmc-release] AID - 7824836 [pii] AID - dgae719 [pii] AID - 10.1210/clinem/dgae719 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2024 Dec 18;110(1):1-15. doi: 10.1210/clinem/dgae719. PMID- 39415416 OWN - NLM STAT- MEDLINE DCOM- 20250108 LR - 20260610 IS - 1360-0443 (Electronic) IS - 0965-2140 (Print) IS - 0965-2140 (Linking) VI - 120 IP - 2 DP - 2025 Feb TI - The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. PG - 236-250 LID - 10.1111/add.16679 [doi] AB - AIMS: This study aimed to estimate the strength of association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP-1 RA and substance use-outcome association among patients with comorbid type 2 diabetes and obesity. DESIGN: A retrospective cohort study analyzing de-identified electronic health record data from the Oracle Cerner Real-World Data. SETTING: About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022. PARTICIPANTS: The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older. MEASUREMENTS: The exposure indicated the presence (one or more) or absence of GIP/GLP-1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors. FINDINGS: Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43-0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40-0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD. CONCLUSIONS: Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity. CI - (c) 2024 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. FAU - Qeadan, Fares AU - Qeadan F AUID- ORCID: 0000-0002-3376-220X AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. FAU - McCunn, Ashlie AU - McCunn A AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. FAU - Tingey, Benjamin AU - Tingey B AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. LA - eng PT - Journal Article DEP - 20241016 PL - England TA - Addiction JT - Addiction (Abingdon, England) JID - 9304118 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Adult MH - Middle Aged MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - *Opioid-Related Disorders/epidemiology MH - *Alcoholism/epidemiology MH - *Gastric Inhibitory Polypeptide MH - United States/epidemiology MH - Opiate Overdose/epidemiology MH - Alcoholic Intoxication/epidemiology MH - Obesity/epidemiology MH - Comorbidity MH - Incidence MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11707322 OTO - NOTNLM OT - AUD OT - GIP/GLP-1 RA OT - OUD OT - dulaglutide OT - intoxication OT - overdose OT - semaglutide COIS- None. EDAT- 2024/10/17 10:05 MHDA- 2025/01/09 04:53 PMCR- 2025/01/08 CRDT- 2024/10/17 01:04 PHST- 2023/12/30 00:00 [received] PHST- 2024/08/29 00:00 [accepted] PHST- 2025/01/09 04:53 [medline] PHST- 2024/10/17 10:05 [pubmed] PHST- 2024/10/17 01:04 [entrez] PHST- 2025/01/08 00:00 [pmc-release] AID - ADD16679 [pii] AID - 10.1111/add.16679 [doi] PST - ppublish SO - Addiction. 2025 Feb;120(2):236-250. doi: 10.1111/add.16679. Epub 2024 Oct 16. PMID- 39415344 OWN - NLM STAT- MEDLINE DCOM- 20241205 LR - 20260923 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 1 DP - 2025 Jan TI - Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study. PG - 215-227 LID - 10.1111/dom.16005 [doi] AB - AIM: The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. MATERIALS AND METHODS: A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. RESULTS: In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). CONCLUSIONS: The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. CLINICALTRIALS: GOV: NCT05579977. CI - (c) 2024 Pfizer,Inc. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Amin, Neeta B AU - Amin NB AD - Internal Medicine, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Frederich, Robert AU - Frederich R AD - Clinical Development and Operations, Pfizer Research & Development, Groton, Connecticut, USA. FAU - Tsamandouras, Nikolaos AU - Tsamandouras N AD - Clinical Pharmacology, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Haggag, Amina Z AU - Haggag AZ AD - Anaheim Clinical Trials, Anaheim, California, USA. FAU - Schuster, Tilman AU - Schuster T AD - Clinical Development and Operations, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Zmuda, Witold AU - Zmuda W AD - Medicome Sp. Z O.O., Oswiecim, Poland. FAU - Palmer, Alexandra AU - Palmer A AD - Internal Medicine, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Vasas, Szilard AU - Vasas S AD - Borbanya Praxis Eu KFT, Nyiregyhaza, Hungary. FAU - Buckley, Gina AU - Buckley G AD - Clinical Development and Operations, Pfizer Research & Development, Groton, Connecticut, USA. AD - Clinical Development and Operations, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Smith, Timothy R AU - Smith TR AD - StudyMetrix Research, LLC, St Peters, Missouri, USA. FAU - DuBrava, Sarah J AU - DuBrava SJ AD - Clinical Statistics, Pfizer Research & Development, Cambridge, Massachusetts, USA. FAU - Zhu, Qi AU - Zhu Q AD - Worldwide Safety, Pfizer Research & Development, Shanghai, China. FAU - Johnson, Margot AU - Johnson M AD - Internal Medicine, Pfizer Research & Development, Cambridge, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT05579977 GR - Pfizer/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20241016 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (hemoglobin A1c protein, human) RN - 5E7U48495E (rGLP-1 protein) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - *Obesity/drug therapy/complications MH - Double-Blind Method MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - *Glycated Hemoglobin/analysis/drug effects MH - *Dose-Response Relationship, Drug MH - Adult MH - Aged MH - Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Treatment Outcome MH - Administration, Oral MH - Blood Glucose/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11618248 OTO - NOTNLM OT - HbA1c OT - PF-07081532 OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - lotiglipron OT - obesity OT - phase 2 study OT - weight loss COIS- Neeta B. Amin, Gina Buckley, Robert Frederich, Alexandra Palmer, Tilman Schuster, Nikolaos Tsamandouras and Qi Zhu are full-time employees of Pfizer and may own shares/stock options in Pfizer. Sarah J. DuBrava and Margot Johnson were full-time employees of Pfizer at the time of this study and may own shares/stock options in Pfizer. Amina Z. Haggag was a primary investigator and owns Pfizer stock. Szilard Vasas was a primary investigator of this study and others sponsored by Novo Nordisk, IONIS Pharma, Arrowhead Pharmaceuticals and New Amsterdam. Timothy R. Smith was a primary investigator of this study and others sponsored by Lilly, Amgen, Novo Nordisk, Novartis, Boehringer Ingelheim, AbbVie, Reata and Vertex. Witold Zmuda was a primary investigator and reports no other conflicts of interest. EDAT- 2024/10/17 10:05 MHDA- 2024/12/05 06:23 PMCR- 2024/12/05 CRDT- 2024/10/17 00:33 PHST- 2024/09/25 00:00 [revised] PHST- 2024/06/24 00:00 [received] PHST- 2024/09/25 00:00 [accepted] PHST- 2024/12/05 06:23 [medline] PHST- 2024/10/17 10:05 [pubmed] PHST- 2024/10/17 00:33 [entrez] PHST- 2024/12/05 00:00 [pmc-release] AID - DOM16005 [pii] AID - 10.1111/dom.16005 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jan;27(1):215-227. doi: 10.1111/dom.16005. Epub 2024 Oct 16. PMID- 39412809 OWN - NLM STAT- MEDLINE DCOM- 20241016 LR - 20250715 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 10 DP - 2024 Oct 1 TI - Characterizing GLP-1 Receptor Agonist Use in Preadolescent and Adolescent Populations. PG - e2439887 LID - 10.1001/jamanetworkopen.2024.39887 [doi] LID - e2439887 FAU - Miller, Margaret G AU - Miller MG AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Terebuh, Pauline AU - Terebuh P AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Kaelber, David C AU - Kaelber DC AD - Departments of Medicine, Pediatrics, and Population and Quantitative Health Sciences and the Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Adolescent MH - Child MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11581558 OAB - This cross-sectional study examines the characteristics of preadolescent and adolescent populations who received glucagon-like peptide-1 (GLP-1) receptor agonists. OABL- eng COIS- Conflict of Interest Disclosures: Dr Terebuh reported receiving grants from National Institutes of Health during the conduct of the study. Dr Kaelber reported receiving grants from the National Center for Advancing Translational Sciences of the National Institutes of Health during the conduct of the study. No other disclosures were reported. EDAT- 2024/10/16 12:24 MHDA- 2024/10/16 12:25 PMCR- 2024/10/16 CRDT- 2024/10/16 11:34 PHST- 2024/10/16 12:25 [medline] PHST- 2024/10/16 12:24 [pubmed] PHST- 2024/10/16 11:34 [entrez] PHST- 2024/10/16 00:00 [pmc-release] AID - 2824918 [pii] AID - zld240187 [pii] AID - 10.1001/jamanetworkopen.2024.39887 [doi] PST - epublish SO - JAMA Netw Open. 2024 Oct 1;7(10):e2439887. doi: 10.1001/jamanetworkopen.2024.39887. PMID- 39400355 OWN - NLM STAT- MEDLINE DCOM- 20241209 LR - 20250110 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 55 IP - 1 DP - 2025 Jan TI - Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease. PG - e14330 LID - 10.1111/eci.14330 [doi] AB - BACKGROUND: Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease. RESULTS AND CONCLUSION: Glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors are two novel classes of glucose-lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon-like peptide-1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well-established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity. CI - (c) 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. FAU - Kanbay, Mehmet AU - Kanbay M AUID- ORCID: 0000-0002-1297-0675 AD - Department of Internal Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey. FAU - Copur, Sidar AU - Copur S AD - Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Guldan, Mustafa AU - Guldan M AD - Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Ozbek, Lasin AU - Ozbek L AD - Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey. FAU - Mallamaci, Francesca AU - Mallamaci F AD - Nephrology, Dialysis and Transplantation Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy. AD - CNR-IFC, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Institute of Clinical Physiology, Reggio Calabria, Italy. FAU - Zoccali, Carmine AU - Zoccali C AUID- ORCID: 0000-0002-6616-1996 AD - Renal Research Institute, New York, New York, USA. AD - Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy. AD - Associazione Ipertensione Nefrologia Trapianto Renale (IPNET), Grande Ospedale Metropolitano, Reggio Calabria, Italy. LA - eng PT - Journal Article PT - Review DEP - 20241013 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 9007-92-5 (Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon/metabolism MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Glomerular Filtration Rate/drug effects MH - Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - diabetes mellitus OT - fatty kidney OT - glucagon OT - glucagon-like peptide-1 OT - metabolically associated fatty liver disease EDAT- 2024/10/14 16:18 MHDA- 2024/12/10 00:22 CRDT- 2024/10/14 10:45 PHST- 2024/07/29 00:00 [received] PHST- 2024/09/24 00:00 [accepted] PHST- 2024/12/10 00:22 [medline] PHST- 2024/10/14 16:18 [pubmed] PHST- 2024/10/14 10:45 [entrez] AID - 10.1111/eci.14330 [doi] PST - ppublish SO - Eur J Clin Invest. 2025 Jan;55(1):e14330. doi: 10.1111/eci.14330. Epub 2024 Oct 13. PMID- 39400314 OWN - NLM STAT- MEDLINE DCOM- 20250424 LR - 20260127 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 55 IP - 2 DP - 2025 Feb TI - Exploring omics signature in the cardiovascular response to semaglutide: Mechanistic insights and clinical implications. PG - e14334 LID - 10.1111/eci.14334 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits. RESULTS: This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These "omics" approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility. CONCLUSION: Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes. CI - (c) 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. FAU - Vitorino, Rui AU - Vitorino R AUID- ORCID: 0000-0003-3636-5805 AD - Department of Medical Sciences, Institute of Biomedicine iBiMED, University of Aveiro, Aveiro, Portugal. AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. LA - eng GR - UIDB/04501/2020/European Union, QREN, FEDER, and COMPETE for funding Institute of Biomedicine (iBiMED)/ GR - POCI-01-0145-FEDER-007628/European Union, QREN, FEDER, and COMPETE for funding Institute of Biomedicine (iBiMED)/ GR - UIDP/00051/2020/Cardiovascular R&D Centre-UnIC@RISE/ GR - Fundacao para a Ciencia e a Tecnologia/ PT - Journal Article PT - Review DEP - 20241014 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Metabolomics MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Proteomics MH - *Cardiovascular Diseases/prevention & control/metabolism MH - Lipid Metabolism/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular diseases OT - endothelial function OT - inflammation pathways OT - lipid metabolism OT - molecular mechanisms OT - personalized medicine OT - proteomic biomarkers OT - semaglutide OT - therapeutic strategies EDAT- 2024/10/14 12:23 MHDA- 2025/01/20 22:54 CRDT- 2024/10/14 10:43 PHST- 2024/05/05 00:00 [received] PHST- 2024/10/01 00:00 [accepted] PHST- 2025/01/20 22:54 [medline] PHST- 2024/10/14 12:23 [pubmed] PHST- 2024/10/14 10:43 [entrez] AID - 10.1111/eci.14334 [doi] PST - ppublish SO - Eur J Clin Invest. 2025 Feb;55(2):e14334. doi: 10.1111/eci.14334. Epub 2024 Oct 14. PMID- 39400117 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20250519 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 110 IP - 6 DP - 2025 May 19 TI - Approach to the Patient With Thyroid Nodules: Considering GLP-1 Receptor Agonists. PG - e2080-e2087 LID - 10.1210/clinem/dgae722 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP1RAs) have rapidly changed the landscape of diabetes and obesity treatment. Enthusiasm for their use is tempered with concerns regarding their risk for inducing C-cell tumors based on preclinical studies in rodents. A black-box warning from the US Food and Drug Administration recommends against using GLP1RA in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A or 2B (MEN2), providing clear guidance regarding this cohort of patients. However, emerging data also suggest an increased incidence of differentiated thyroid cancer (DTC) in patients treated with these agents. Other studies, though, have not confirmed an association between GLP1RAs and DTC. With conflicting results concerning thyroid cancer risk, there is no clear consensus regarding the optimal approach to screening patients prior to initiating the medications and/or evaluating for thyroid cancer during GLP1RA treatment. Within the context of patient cases, this review will summarize the existing data, describe ongoing controversies, and outline future areas for research regarding thyroid cancer risk with GLP1RA use. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Kelly, Clare A AU - Kelly CA AD - Division of Endocrinology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106 USA. FAU - Sipos, Jennifer A AU - Sipos JA AUID- ORCID: 0000-0001-6745-7353 AD - Division of Endocrinology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - Thyroid cancer, medullary SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Thyroid Nodule/drug therapy/chemically induced MH - *Thyroid Neoplasms/chemically induced/epidemiology/diagnosis MH - Carcinoma, Neuroendocrine/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - calcitonin OT - differentiated thyroid cancer OT - glucagon-like peptide 1 OT - glucagon-like peptide 1 receptor agonist OT - medullary thyroid cancer OT - thyroid cancer EDAT- 2024/10/14 16:18 MHDA- 2025/05/19 06:26 CRDT- 2024/10/14 08:43 PHST- 2024/06/17 00:00 [received] PHST- 2025/05/19 06:26 [medline] PHST- 2024/10/14 16:18 [pubmed] PHST- 2024/10/14 08:43 [entrez] AID - 7821115 [pii] AID - 10.1210/clinem/dgae722 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 May 19;110(6):e2080-e2087. doi: 10.1210/clinem/dgae722. PMID- 39397557 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260127 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 79 IP - 10 DP - 2024 Oct TI - [New outcome studies with injectable semaglutide in different at risk populations]. PG - 676-682 AB - Injectable semaglutide at a dose of 1 mg once weekly has been shown to be the most efficacious glucagon-like peptide-1 receptor agonist when considering both the improvement in blood glucose control and the reduction in body weight in patients with type 2 diabetes (T2D). After the SUSTAIN-6 study, published in 2016, which demonstrated not only the good safety but also already the cardiovascular (CV) efficacy of semaglutide in patients with T2D and high CV risk, several large placebo-controlled randomised trials have confirmed improved prognosis with semaglutide in different at risk populations : patients with T2D and chronic kidney disease (FLOW trial), subjects with obesity and heart failure with preserved ejection fraction, with or without T2D (STEP-HFpEF trial) and people with overweight or obesity (but without T2D) and a confirmed atheromatous cardiovascular disease (SELECT trial). Studies performed in patients with obesity used a higher dose of 2.4 mg/week. These positive results, based upon major clinically relevant outcomes, extend the therapeutic possibilities with semaglutide among at high risk patients of cardiovascular and/or renal diseases. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques et Unite de Pharmacologie clinique, CHU Liege, ULiege, Belgique. FAU - Delanaye, Pierre AU - Delanaye P AD - Service de Nephrologie, Dialyse et Transplantation, CHU Liege, Belgique. FAU - Lancellotti, Patrizio AU - Lancellotti P AD - Service de Cardiologie, CHU Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - L'etude clinique du mois. Nouvelles etudes cliniques avec le semaglutide injectable dans differentes populations a risque. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Obesity/drug therapy/complications MH - Treatment Outcome MH - Injections MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1 OT - Obesity OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/10/14 10:17 MHDA- 2024/10/14 10:18 CRDT- 2024/10/14 04:13 PHST- 2024/10/14 10:18 [medline] PHST- 2024/10/14 10:17 [pubmed] PHST- 2024/10/14 04:13 [entrez] PST - ppublish SO - Rev Med Liege. 2024 Oct;79(10):676-682. PMID- 39396098 OWN - NLM STAT- MEDLINE DCOM- 20241231 LR - 20261010 IS - 1476-5497 (Electronic) IS - 0307-0565 (Linking) VI - 49 IP - 1 DP - 2025 Jan TI - Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis. PG - 21-30 LID - 10.1038/s41366-024-01646-9 [doi] AB - BACKGROUND: Semaglutide is a GLP-1 receptor agonist that provides a reduction in glycated hemoglobin and weight. The objective was to evaluate whether the use of semaglutide, in individuals with overweight or obesity, reduces cardiovascular outcomes and adverse effects (AE). METHODS: The data bases Pubmed, Lilacs, Scielo, Scopus, Web of Science and Cochrane Library were surveyed. RESULTS: Initially, 3333 articles were found, of which 19 articles were included. An additional search included 19 studies, totaling 38 articles. Relative risk (RR) values were significant for hospitalization due to heart failure (HF) 0.24 95% CI 0.12-0.57 (n = 2; 1045 participants; I(2) = 0.18), death due to cardiovascular causes 0.83 95% CI 0.71-0.98 (n = 3; 24 084 participants; I(2) = 0.21), death from any cause 0.79 95% CI 0.70-0.89 (n = 3; 24 084 participants; I(2) = 0.07), coronary revascularization 0.76 95% CI 0.69-0.85 (n = 2;20 951 participants; I(2) = 0.41), and non-fatal myocardial infarction 0.76 95%CI 0.66-0.88 (n = 3; 24 084 participants; I(2) = 0.21), with a difference between the subgroups (p = 0.05), favoring the subcutaneous administration route. The RR of stroke was 0.65 95% CI 0.44-0.97 for patients with diabetes (n = 2; 6480 participants; I(2) = 0.66). There was no difference between the frequency of constipation and routes of administration, as well as between doses of oral semaglutide. The RR of adverse effects was only not significant for discontinuation of treatment for oral semaglutide. CONCLUSION: The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any cause, 24% non-fatal myocardial infarction, 24% coronary revascularization and 35% stroke (in patients with diabetes). The use of semaglutide was associated with a higher relative risk and frequency of most adverse effects evaluated. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Cleto, Andre Saad AU - Cleto AS AUID- ORCID: 0009-0008-7272-9083 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. andresaad8@gmail.com. FAU - Schirlo, Joao Matheus AU - Schirlo JM AUID- ORCID: 0009-0005-2886-7700 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Beltrame, Mayara AU - Beltrame M AUID- ORCID: 0009-0008-8359-1657 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Gomes, Victor Hugo Oliveira AU - Gomes VHO AUID- ORCID: 0009-0008-9307-3108 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Acras, Isabela Hellmann AU - Acras IH AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Neiverth, Guinter Sponholz AU - Neiverth GS AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Silva, Breno Bach AU - Silva BB AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Juliatto, Beatriz Moreira Salles AU - Juliatto BMS AUID- ORCID: 0000-0002-1442-5646 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Machozeki, Janete AU - Machozeki J AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Martins, Camila Marinelli AU - Martins CM AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241012 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/complications/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Overweight/complications/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome MH - Semaglutide COIS- Competing interests: The authors declare no competing interests. EDAT- 2024/10/13 00:30 MHDA- 2025/01/01 12:42 CRDT- 2024/10/12 23:27 PHST- 2024/06/09 00:00 [received] PHST- 2024/09/27 00:00 [accepted] PHST- 2024/09/24 00:00 [revised] PHST- 2025/01/01 12:42 [medline] PHST- 2024/10/13 00:30 [pubmed] PHST- 2024/10/12 23:27 [entrez] AID - 10.1038/s41366-024-01646-9 [pii] AID - 10.1038/s41366-024-01646-9 [doi] PST - ppublish SO - Int J Obes (Lond). 2025 Jan;49(1):21-30. doi: 10.1038/s41366-024-01646-9. Epub 2024 Oct 12. PMID- 39393444 OWN - NLM STAT- MEDLINE DCOM- 20241120 LR - 20260804 IS - 1874-1754 (Electronic) IS - 0167-5273 (Print) IS - 0167-5273 (Linking) VI - 418 DP - 2025 Jan 1 TI - Glucagon-like peptide-1 receptor agonists improve outcomes in individuals with type 2 diabetes with and without heart failure. PG - 132611 LID - S0167-5273(24)01233-6 [pii] LID - 10.1016/j.ijcard.2024.132611 [doi] AB - BACKGROUND: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice. METHODS: Using the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics. RESULTS: A total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80-0.85], p < 0.001), mortality (HR 0.66 [0.63-0.69]) and new diagnosis of HF (HR 0.92 [0.88-0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65-0.76], p < 0.001). Results were consistent across subgroups. CONCLUSIONS: In this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Horiuchi, Yu AU - Horiuchi Y AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. Electronic address: yooouyou@gmail.com. FAU - Wettersten, Nicholas AU - Wettersten N AD - Division of Cardiovascular Medicine, San Diego Veterans Affairs Medical Center, San Diego, California, USA; Division of Cardiovascular Medicine, University of California, San Diego/La Jolla, California, USA. FAU - Asami, Masahiko AU - Asami M AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Yahagi, Kazuyuki AU - Yahagi K AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Komiyama, Kota AU - Komiyama K AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Yuzawa, Hitomi AU - Yuzawa H AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Tanaka, Jun AU - Tanaka J AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Aoki, Jiro AU - Aoki J AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. FAU - Tanabe, Kengo AU - Tanabe K AD - Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. LA - eng GR - IK2 CX002105/CX/CSRD VA/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20241010 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - Female MH - *Heart Failure/drug therapy/mortality/epidemiology MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Sitagliptin Phosphate/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12107941 MID - NIHMS2069646 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure OT - Prognosis OT - Type 2 diabetes mellitus COIS- Declaration of competing interest Yu Horiuchi received honoraria from TriNetX, Nippon Boehringer Ingelheim, Ono Pharmaceutical Company, AstraZeneca, Kyowa Kirin, Sanofi and Eli Lilly Japan. Nicholas Wettersten received grants from Department of Veterans Affairs National Institutes of Health, consulting fees from Guidepoint and honoraria from San Diego Heart Failure Symposium. Masahiko Asami received honoraria from Astellas, Daiichi Sankyo, AstraZeneca and Kyowa Kirin. Kazuyuki Yahagi received honoraria from Daiichi Sankyo and Nippon Boehringer Ingelheim. Hitomi Yuzawa received honoraria from Daiichi Sankyo. Kota Komiyama received honoraria from Astellas, Daiichi Sankyo, Ono Pharmaceutical and Kowa. Jun Tanaka received honoraria from Eli Lilly Japan, Novo Nordisk and Daiichi Sankyo. Jiro Aoki received honoraria from Daiichi Sankyo, Ono Pharmaceutical and Kowa, and has stock of Eli Lilly and Novo Nordisk. Kengo Tanabe received honoraria from Eli Lilly Japan, Novo Nordisk, Daiichi Sankyo, Ono Pharmaceutical, Industry, AstraZeneca and Kowa. EDAT- 2024/10/12 13:18 MHDA- 2024/11/21 00:22 PMCR- 2026/01/01 CRDT- 2024/10/11 19:17 PHST- 2024/07/20 00:00 [received] PHST- 2024/09/12 00:00 [revised] PHST- 2024/09/30 00:00 [accepted] PHST- 2024/11/21 00:22 [medline] PHST- 2024/10/12 13:18 [pubmed] PHST- 2024/10/11 19:17 [entrez] PHST- 2026/01/01 00:00 [pmc-release] AID - S0167-5273(24)01233-6 [pii] AID - 10.1016/j.ijcard.2024.132611 [doi] PST - ppublish SO - Int J Cardiol. 2025 Jan 1;418:132611. doi: 10.1016/j.ijcard.2024.132611. Epub 2024 Oct 10. PMID- 39389007 OWN - NLM STAT- MEDLINE DCOM- 20250625 LR - 20260802 IS - 1744-5086 (Electronic) IS - 0928-6586 (Print) IS - 0928-6586 (Linking) VI - 32 IP - 4 DP - 2025 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy. PG - 390-393 LID - 10.1080/09286586.2024.2399764 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. METHODS: A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. RESULTS: A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92-1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95-1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58-1.12, p = 0.20). CONCLUSION: We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR. FAU - Tauqeer, Zujaja AU - Tauqeer Z AD - Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Associated Retinal Consultants, Royal Oak, MI, USA. FAU - Bracha, Peter AU - Bracha P AD - Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Wolfe Eye Clinic, Des Moines, IA, USA. FAU - Hua, Peiying AU - Hua P AD - Center for Preventative Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Yu, Yinxi AU - Yu Y AUID- ORCID: 0000-0003-3820-1257 AD - Center for Preventative Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Cui, Qi N AU - Cui QN AD - Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - VanderBeek, Brian L AU - VanderBeek BL AUID- ORCID: 0000-0003-4953-118X AD - Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Center for Pharmacoepidemiology Research and Training, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Leonard Davis Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. LA - eng GR - K23 EY025729/EY/NEI NIH HHS/United States GR - P30 EY001583/EY/NEI NIH HHS/United States GR - R01 EY034115/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20241010 PL - England TA - Ophthalmic Epidemiol JT - Ophthalmic epidemiology JID - 9435674 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Retinopathy/epidemiology/chemically induced/diagnosis MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Disease Progression MH - Aged MH - *Macular Edema/epidemiology/chemically induced MH - Risk Factors MH - Adult PMC - PMC11982348 MID - NIHMS2023582 OTO - NOTNLM OT - Diabetes OT - diabetic macular edema OT - diabetic retinopathy OT - non-proliferative diabetic retinopathy OT - retina COIS- None of the authors have any proprietary interests or conflicts of interest related to this submission. EDAT- 2024/10/11 07:19 MHDA- 2025/06/25 06:25 PMCR- 2026/08/01 CRDT- 2024/10/10 18:13 PHST- 2025/06/25 06:25 [medline] PHST- 2024/10/11 07:19 [pubmed] PHST- 2024/10/10 18:13 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - 10.1080/09286586.2024.2399764 [doi] PST - ppublish SO - Ophthalmic Epidemiol. 2025 Aug;32(4):390-393. doi: 10.1080/09286586.2024.2399764. Epub 2024 Oct 10. PMID- 39379059 OWN - NLM STAT- MEDLINE DCOM- 20250117 LR - 20250515 IS - 1439-3646 (Electronic) IS - 0947-7349 (Linking) VI - 133 IP - 1 DP - 2025 Jan TI - Novel Treatment Options in Patients with Maturity-Onset Diabetes of the Young. PG - 51-58 LID - 10.1055/a-2436-7723 [doi] AB - Maturity-onset diabetes of the young (MODY) is the most common monogenetic form of diabetes with an autosomal dominant inheritance pattern. MODY is caused by mutations in genes important for the development and function of pancreatic beta cells, resulting in impaired insulin secretion capacity. To date, 14 different types have been described. While glucokinase (GCK)-MODY (formerly MODY-2) generally requires no drug therapy, other forms of MODY, such as hepatocyte nuclear factor-1-alpha (HNF1A)-MODY (formerly MODY-3) and HNF4A (formerly MODY-1), usually respond very well to sulfonylurea therapy. However, these MODY forms are characterised by a progressive course, meaning that insulin therapy is often required as the disease progresses. Both sulfonylurea therapy and insulin therapy are associated with an increased risk of hypoglycaemia and frequent weight gain. Newer blood glucose-lowering therapies, such as SGLT2 inhibitors (SGLT2i), DPP-4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP-1RA), have a much lower risk of hypoglycaemia and usually have a favourable effect on body weight. This review aims to provide an overview of the treatment of MODY patients with SGLT2i, DPP4i and GLP-1RA on the basis of previously published clinical studies, case series and case reports. CI - Thieme. All rights reserved. FAU - Mussig, Karsten AU - Mussig K AUID- ORCID: 0000-0003-0107-1196 AD - Department of Internal Medicine, Gastroenterology and Diabetology, Franziskus Hospital Harderberg, Niels Stensen Hospitals, Georgsmarienhutte, Germany. LA - eng PT - Journal Article PT - Review DEP - 20241008 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- The author declares that he has no conflict of interest. EDAT- 2024/10/09 00:23 MHDA- 2025/01/17 18:22 CRDT- 2024/10/08 20:03 PHST- 2025/01/17 18:22 [medline] PHST- 2024/10/09 00:23 [pubmed] PHST- 2024/10/08 20:03 [entrez] AID - 10.1055/a-2436-7723 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2025 Jan;133(1):51-58. doi: 10.1055/a-2436-7723. Epub 2024 Oct 8. PMID- 39371922 OWN - NLM STAT- MEDLINE DCOM- 20241007 LR - 20250103 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Glucagon-like peptide-1 receptor agonists in neoplastic diseases. PG - 1465881 LID - 10.3389/fendo.2024.1465881 [doi] LID - 1465881 AB - Glucagon-like peptide-1 receptor agonist (GLP-1RA), a novel hypoglycemic agent for the treatment of type 2 diabetes, has well-known effects such as lowering blood sugar, ameliorating inflammation, reducing weight, and lowering blood lipids. It has also been shown that it can influence the proliferation and survival of cells and has a certain effect on the prognosis of some neoplastic diseases. In this study, the potential effects of GLP-1RAs on the occurrence and development of tumors were reviewed to provide new ideas for the prevention and treatment of tumors in patients. CI - Copyright (c) 2024 Ji, He, Min, Yang, Wu, Xu, Chen and Mei. FAU - Ji, Lisan AU - Ji L AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. FAU - He, Xianzhen AU - He X AD - Children's Medical Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China. FAU - Min, Xinwen AU - Min X AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. FAU - Yang, Handong AU - Yang H AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. FAU - Wu, Wenwen AU - Wu W AD - School of Public Health, Hubei University of Medicine, Shiyan, Hubei, China. FAU - Xu, Hao AU - Xu H AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. FAU - Chen, Jun AU - Chen J AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. AD - Virology Key Laboratory of Shiyan City, Hubei University of Medicine, Shiyan, China. FAU - Mei, Aihua AU - Mei A AD - Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, China. LA - eng PT - Journal Article PT - Review DEP - 20240920 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Neoplasms/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11449759 OTO - NOTNLM OT - GLP-1RA OT - agonists OT - function OT - mechanism OT - tumor diseases COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/10/07 11:22 MHDA- 2024/10/07 11:23 PMCR- 2024/01/01 CRDT- 2024/10/07 05:39 PHST- 2024/07/18 00:00 [received] PHST- 2024/08/28 00:00 [accepted] PHST- 2024/10/07 11:23 [medline] PHST- 2024/10/07 11:22 [pubmed] PHST- 2024/10/07 05:39 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1465881 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Sep 20;15:1465881. doi: 10.3389/fendo.2024.1465881. eCollection 2024. PMID- 39366881 OWN - NLM STAT- MEDLINE DCOM- 20241122 LR - 20250711 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 18 IP - 6 DP - 2024 Dec TI - Cardiovascular effectiveness of newer glucose-lowering agents, with and without baseline lipid-lowering therapy in type 2 diabetes: A systematic meta-analysis of cardiovascular outcome trials and real-world evidence. PG - 589-598 LID - S1751-9918(24)00195-5 [pii] LID - 10.1016/j.pcd.2024.09.007 [doi] AB - BACKGROUND: Whether the cardiovascular treatment benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D). METHODS: We identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95 % confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial. RESULTS: Twenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95 % CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95 % CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs. CONCLUSIONS: Aggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status. PROSPERO Registration: CRD42024498939. CI - Copyright (c) 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Kunutsor, Setor K AU - Kunutsor SK AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK. FAU - Seidu, Borenyi S AU - Seidu BS AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK; The University of Manchester, Manchester, UK. FAU - Seidu, Samuel AU - Seidu S AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK. Electronic address: sis11@leicester.ac.uk. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20241003 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Hypolipidemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis/mortality MH - *Cardiovascular Diseases/prevention & control/mortality/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Treatment Outcome MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Risk Assessment MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Female MH - Male MH - Blood Glucose/drug effects/metabolism MH - Clinical Trials as Topic MH - Middle Aged MH - Aged MH - Hypolipidemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - GLP-1RA OT - Randomised controlled trial OT - SGLT-2i OT - Statins OT - Type 2 diabetes COIS- Declaration of Competing Interest SS is in receipt of speaker honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, MSD, Abbott, Novo Nordisk, SB Communications, OmniaMed Communications, Roche, Napp Pharmaceuticals, NB Medical and Amgen; advisory board honoraria from AstraZeneca, Lilly, Boehringer Ingelheim, Janssen, Abbott, MSD, Novo Nordisk, Takeda and Sanofi; educational grants from Boehringer Ingelheim, Lilly, Novo Nordisk, and Takeda; and conference registration and subsistence from Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, Abbott and Takeda. BSS and SKK have no conflicts EDAT- 2024/10/06 07:18 MHDA- 2024/11/23 11:14 CRDT- 2024/10/04 21:56 PHST- 2024/09/15 00:00 [received] PHST- 2024/09/21 00:00 [accepted] PHST- 2024/11/23 11:14 [medline] PHST- 2024/10/06 07:18 [pubmed] PHST- 2024/10/04 21:56 [entrez] AID - S1751-9918(24)00195-5 [pii] AID - 10.1016/j.pcd.2024.09.007 [doi] PST - ppublish SO - Prim Care Diabetes. 2024 Dec;18(6):589-598. doi: 10.1016/j.pcd.2024.09.007. Epub 2024 Oct 3. PMID- 39366717 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260728 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 12 IP - 5 DP - 2024 Oct 4 TI - Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA. LID - 10.1136/bmjdrc-2024-004431 [doi] LID - e004431 AB - INTRODUCTION: This study aimed to assess recent trends in the US use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD), including incident use following newly diagnosed ASCVD. RESEARCH DESIGN AND METHODS: This real-world, retrospective observational study used de-identified data from the TriNetX Dataworks-USA network. A longitudinal analysis of cross-sectional data (interval: January 01, 2018 to December 31, 2022) assessed the yearly prevalent use of GLP-1 RA and SGLT2i. A nested cohort study (January 01, 2017 to January 31, 2023) assessed the proportions of patients with T2D newly prescribed GLP-1 RAs and SGLT2is after incident ASCVD diagnosis. RESULTS: Prevalent use of GLP-1 RA and/or SGLT2i increased from 9.2% of patients in 2018 to 27.1% in 2022, with eligible annual patient numbers ranging from 279,474 to 348,997. GLP-1 RA-alone use rose from 5.2% to 9.9% and SGLT2i-alone use rose from 2.8% to 12.2% over this interval. Incident use of GLP-1 RA and/or SGLT2i within the year following ASCVD diagnosis increased from 5.9% to 17.0% (2018-2022). For GLP-1 RA alone, this increase was from 3.6% to 7.8%, while for SGLT2i alone, it was from 1.8% to 7.0%. CONCLUSIONS: Use of GLP-1 RAs/SGLT2is in patients with T2D and ASCVD has increased in recent years in the USA, but remains suboptimal given the prevalence of ASCVD and its high morbidity and mortality. CI - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - King, Aaron AU - King A AD - MedFirst Primary Care - Quarry, Baptist Health System Physicians Network, San Antonio, Texas, USA. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Dhopeshwarkar, Neil AU - Dhopeshwarkar N AD - TriNetX LLC, Cambridge, Massachusetts, USA. FAU - Bohn, Rhonda AU - Bohn R AD - Bohn Epidemiology LLC, Boston, Massachusetts, USA. FAU - Dea, Katherine AU - Dea K AD - Statlog Econometrics, Montreal, Quebec, Canada. FAU - Leonard, Charles E AU - Leonard CE AUID- ORCID: 0000-0002-5092-9657 AD - Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - de Havenon, Adam AU - de Havenon A AUID- ORCID: 0000-0001-8178-8597 AD - Department of Neurology, Yale University, New Haven, Connecticut, USA adam.dehavenon@yale.edu. LA - eng GR - UL1 TR001863/TR/NCATS NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20241004 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - Retrospective Studies MH - *Atherosclerosis/epidemiology MH - Middle Aged MH - United States/epidemiology MH - Aged MH - Cross-Sectional Studies MH - Hypoglycemic Agents/therapeutic use MH - Longitudinal Studies MH - Follow-Up Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11459310 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Glucagon-Like Peptide 1 COIS- Competing interests: AK: Paid speaker and clinical advisor for Astellas Pharma, Abbott, Dexcom, Eli Lilly, MannKind and Novo Nordisk. XT: Employee of Novo Nordisk. ND: Employee of TriNetX LLC. RB: No conflicts of interest. KD: Consultant of TriNetX LLC. CEL: CEL reports NIH funding. CEL is a special government employee of the US Food and Drug Administration. CEL recently received honoraria from the American College of Clinical Pharmacy Foundation and the Consortium for Medical Marijuana Clinical Outcomes Research. CEL consults for Novo Nordisk and TriNetX, LLC. CEL's spouse is employed by Merck; neither she nor he own stock in the company. AdH: AdH reports NIH funding, consultant fees from Novo Nordisk, royalty fees from UpToDate, and has equity in Titin KM and Certus. EDAT- 2024/10/06 07:18 MHDA- 2024/10/06 07:19 PMCR- 2024/10/04 CRDT- 2024/10/04 20:43 PHST- 2024/06/27 00:00 [received] PHST- 2024/09/11 00:00 [accepted] PHST- 2024/10/06 07:19 [medline] PHST- 2024/10/06 07:18 [pubmed] PHST- 2024/10/04 20:43 [entrez] PHST- 2024/10/04 00:00 [pmc-release] AID - 12/5/e004431 [pii] AID - bmjdrc-2024-004431 [pii] AID - 10.1136/bmjdrc-2024-004431 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2024 Oct 4;12(5):e004431. doi: 10.1136/bmjdrc-2024-004431. PMID- 39367214 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260127 IS - 2731-0590 (Electronic) IS - 2731-0590 (Linking) VI - 3 IP - 10 DP - 2024 Oct TI - Semaglutide may reduce cardiovascular disease and heart failure. PG - 1180 LID - 10.1038/s44161-024-00556-3 [doi] FAU - Korda, Michelle AU - Korda M AD - Nature Cardiovascular Research, . michelle.korda@nature.com. LA - eng PT - News PL - England TA - Nat Cardiovasc Res JT - Nature cardiovascular research JID - 9918284280206676 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Treatment Outcome MH - Semaglutide EDAT- 2024/10/05 11:43 MHDA- 2024/10/15 00:20 CRDT- 2024/10/04 23:33 PHST- 2024/10/15 00:20 [medline] PHST- 2024/10/05 11:43 [pubmed] PHST- 2024/10/04 23:33 [entrez] AID - 10.1038/s44161-024-00556-3 [pii] AID - 10.1038/s44161-024-00556-3 [doi] PST - ppublish SO - Nat Cardiovasc Res. 2024 Oct;3(10):1180. doi: 10.1038/s44161-024-00556-3. PMID- 39366019 OWN - NLM STAT- MEDLINE DCOM- 20250101 LR - 20260815 IS - 1547-5646 (Electronic) IS - 1547-5646 (Linking) VI - 42 IP - 1 DP - 2025 Jan 1 TI - Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease. PG - 1-8 LID - 10.3171/2024.6.SPINE24141 [doi] AB - OBJECTIVE: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. METHODS: Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (/= 42 mmol/mol. GLP-1 RA initiators were matched to metformin initiators in a ratio of 1:1 to assess outcomes in prediabetes and diabetes. Main outcomes analyzed were 1-year risk of add-on glucose-lowering medication and 1-year risk of nonadherence. One-year risks were estimated with multiple logistic regression and standardized. Multiple linear regression was used to estimate the average differences in biomarker changes. RESULTS: In total, 1778 individuals initiating GLP-1 RA and metformin were included. After standardizing for various factors, GLP-1 RA compared with metformin was associated with reduced 1-year risk of add-on glucose-lowering treatment in patients with prediabetes (1-year risk ratio [RR]: 0.27, 95% confidence interval [CI]: 0.10-0.44) and diabetes (RR: 0.67, 95% CI: 0.37-0.98). GLP-1 RA was associated with higher 1-year risk of nonadherence among patients with prediabetes (RR: 1.60, 95% CI: 1.45-1.75), but no difference in patients with diabetes (RR: 0.88, 95% CI: 0.70-1.06). Compared to metformin, GLP-1 RA was associated with greater HbA1c reduction (prediabetes: -2.59 mmol/mol 95% CI: -3.10 to -2.09, diabetes: -3.79 mmol/mol, 95% CI: -5.28 to -2.30). CONCLUSIONS: GLP-1 RA was associated with a reduced risk of additional glucose-lowering medication, achieving better glycated hemoglobin control overall. However, among patients with prediabetes, metformin was associated with better adherence. CI - (c) 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Sorensen, Kathrine Kold AU - Sorensen KK AUID- ORCID: 0000-0002-9402-1317 AD - Department of Cardiology, Nordsjaelland Hospital, Hillerod, Denmark. FAU - Gerds, Thomas Alexander AU - Gerds TA AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Kober, Lars AU - Kober L AD - The Heart Centre, University Hospital of Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Loldrup Fosbol, Emil AU - Loldrup Fosbol E AD - The Heart Centre, University Hospital of Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Poulsen, Henrik Enghusen AU - Poulsen HE AD - Department of Endocrinology, University Hospital Copenhagen, Frederiksberg, Denmark. FAU - Moller, Amalie Lykkemark AU - Moller AL AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. AD - Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. AD - Cancer Surveillance and Pharmacoepidemiology, Danish Cancer Institute, Copenhagen, Denmark. FAU - Andersen, Mikkel Porsborg AU - Andersen MP AD - Department of Cardiology, Nordsjaelland Hospital, Hillerod, Denmark. FAU - Pedersen-Bjergaard, Ulrik AU - Pedersen-Bjergaard U AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Endocrinology and Nephrology, North Zealand University Hospital, Hillerod and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Torp-Pedersen, Christian AU - Torp-Pedersen C AD - Department of Cardiology, Nordsjaelland Hospital, Hillerod, Denmark. AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. FAU - Zareini, Bochra AU - Zareini B AUID- ORCID: 0000-0002-3891-5957 AD - Department of Cardiology, Nordsjaelland Hospital, Hillerod, Denmark. AD - Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Comparative Study PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Denmark/epidemiology MH - Aged MH - *Glycated Hemoglobin/analysis/metabolism MH - Cohort Studies MH - Blood Glucose/analysis/drug effects/metabolism MH - Prediabetic State/drug therapy/blood/epidemiology MH - Adult MH - Registries MH - Biomarkers/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Monitoring PMC - PMC11450598 COIS- CT-P reports grants from Bayer and Novo Nordisk unrelated to the current study. UPB has served on advisory boards for Novo Nordisk, Sanofi, and Vertex and has received lecture fees from Novo Nordisk and Sanofi. LK reports speakers' honorariums from AstraZeneca, Bayer, Boehringer, Novartis, and Novo. All other authors declare no competing interests. EDAT- 2024/10/04 12:42 MHDA- 2024/10/04 12:43 PMCR- 2024/10/04 CRDT- 2024/10/04 07:23 PHST- 2024/07/08 00:00 [revised] PHST- 2024/04/08 00:00 [received] PHST- 2024/07/31 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/10/04 12:42 [pubmed] PHST- 2024/10/04 07:23 [entrez] PHST- 2024/10/04 00:00 [pmc-release] AID - JDB70000 [pii] AID - 10.1111/1753-0407.70000 [doi] PST - ppublish SO - J Diabetes. 2024 Oct;16(10):e70000. doi: 10.1111/1753-0407.70000. PMID- 39360358 OWN - NLM STAT- MEDLINE DCOM- 20241114 LR - 20250103 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 40 IP - 11 DP - 2024 Nov TI - A discrete choice experiment to understand preferences of patients with type 2 diabetes about the attributes of GLP1 receptor agonists in Spain. PG - 1841-1846 LID - 10.1080/03007995.2024.2407960 [doi] AB - OBJECTIVE: To determine the preferences regarding injection, medication frequency and complexity of GLP1 receptor agonists among patients with type 2 diabetes, treatment-naive for such drugs in Spain. Additionally, patients' willingness to pay according to these attributes was evaluated. METHODS: A discrete-choice experiment survey designed to evaluate patients' preferences over three attributes discriminating by age, sex and patients experience with previous injectable treatment was fulfilled by patients. The resulting model was analyzed using a conditional (fixed-effects) logistic regression. RESULTS: A total of 180 patients (63.35 +/- 11.49 years, 63.28% men, 48.41% with previous cardiovascular disease, 54.69% with a time of evolution of diabetes >10 years) recruited from 5 health care centers in Spain completed the survey. Patients viewed positively weekly injections (vs daily injections), but rated negatively a complex preparation of the dose (vs simple preparation). Whereas naive patients for injectable medications did not consider administration timing of importance, no naive patients considered it relevant. No relevant differences were observed according to age or gender. Patients were willing to pay 83.25eurofor a "no preparation required" dose. No naive and naive patients were willing to pay 34.61euro and 14.35euro; p = 0.000, to change daily injection for a weekly injection. CONCLUSIONS: Patients highly valued the avoidance of injections, with weekly dosing clearly preferred over daily dosing, as well as reducing the treatment complexity. These findings may provide a better understanding of what patients prefer and value in their treatment and provide guidance for clinicians making therapeutic decisions regarding treatments of patients with type 2 diabetes. FAU - San Jose, Patricia AU - San Jose P AD - Endocrine Unit, Hospital Universitari de Bellvitge-IDIBELL and CIBERDEM, L'Hospitalet de Llobregat, Spain. FAU - Monteagudo, Ana AU - Monteagudo A AD - Educadora de Diabetes, Hospital de Elda, Alicante, Spain. FAU - Pico, Antonio AU - Pico A AD - Servicio de Endocrinologia, Hospital General de Alicante, Alicante. Departamento de Medicina Clinica, Universidad Miguel Hernandez y Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL), Spain. FAU - Sequera, Miren AU - Sequera M AD - Departamento Medico, AstraZeneca, Madrid, Spain. FAU - Medina, Jesus AU - Medina J AD - Departamento Medico, AstraZeneca, Madrid, Spain. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241008 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Choice Behavior MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Patient Preference MH - Spain MH - Surveys and Questionnaires MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Discrete choice experiment OT - Spain OT - health technology assessment OT - patient preference OT - type 2 diabetes OT - willingness to pay EDAT- 2024/10/03 06:58 MHDA- 2024/11/14 18:30 CRDT- 2024/10/03 04:43 PHST- 2024/11/14 18:30 [medline] PHST- 2024/10/03 06:58 [pubmed] PHST- 2024/10/03 04:43 [entrez] AID - 10.1080/03007995.2024.2407960 [doi] PST - ppublish SO - Curr Med Res Opin. 2024 Nov;40(11):1841-1846. doi: 10.1080/03007995.2024.2407960. Epub 2024 Oct 8. PMID- 39358879 OWN - NLM STAT- MEDLINE DCOM- 20241003 LR - 20241102 IS - 2639-9636 (Print) IS - 2639-9636 (Linking) VI - 39 IP - 10 DP - 2024 Oct 1 TI - Geriatric Pharmacotherapy Case Series: Medications for Diabetes-A Focus on Secondary Stroke Prevention. PG - 350-359 LID - 10.4140/TCP.n.2024.350 [doi] AB - This report addresses evidence for efficacy of diabetes medications with a focus on stroke risk reduction. The cardiovascular benefits of SGLT-2 inhibitors and GLP-1 receptor agonists have been well-established; however, clinical trials to date have examined composite cardiovascular endpoints that include, but do not specifically focus on, stroke. The purpose of this case review is to examine the evidence for the various diabetes medications in reducing the risk for stroke. This literature review was inspired by a patient seen in a geriatric day hospital program with diabetes and a history of multiple strokes. Our goal was to select a diabetes management regimen that would provide both glycemic control and stroke risk reduction. As diabetes and cerebrovascular disease commonly coexist and are important contributors to morbidity and mortality in older individuals, appropriate management must incorporate both current evidence as well as consideration for patient-specific factors that may influence the treatment plan. This patient case illustrates the importance of both. FAU - Warren, Sabrina AU - Warren S AD - College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - McKee, Shayla AU - McKee S AD - College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Yakiwchuk, Erin AU - Yakiwchuk E AD - College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. LA - eng PT - Case Reports PT - Journal Article PT - Review PL - United States TA - Sr Care Pharm JT - The Senior care pharmacist JID - 101737969 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Aged, 80 and over MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Secondary Prevention/methods MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Stroke/prevention & control/etiology EDAT- 2024/10/03 06:58 MHDA- 2024/10/03 06:59 CRDT- 2024/10/03 00:43 PHST- 2024/10/03 06:59 [medline] PHST- 2024/10/03 06:58 [pubmed] PHST- 2024/10/03 00:43 [entrez] AID - 10.4140/TCP.n.2024.350 [doi] PST - ppublish SO - Sr Care Pharm. 2024 Oct 1;39(10):350-359. doi: 10.4140/TCP.n.2024.350. PMID- 39358806 OWN - NLM STAT- MEDLINE DCOM- 20241003 LR - 20260923 IS - 1758-9193 (Electronic) VI - 16 IP - 1 DP - 2024 Oct 2 TI - Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial. PG - 212 LID - 10.1186/s13195-024-01573-x [doi] LID - 212 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists are a viable option for the prevention of Alzheimer's disease (AD) but the mechanisms of this potential disease modifying action are unclear. We investigated the effects of once-weekly exenatide (EQW) on AD associated proteomic clusters. METHODS: The Exenatide Study of Cardiovascular Event Lowering study compared the cardiovascular effects of EQW 2 mg with placebo in 13,752 people with type 2 diabetes mellitus. 4,979 proteins were measured (Somascan V0.4) on baseline and 1-year plasma samples of 3,973 participants. C-reactive protein (CRP), ficolin-2 (FCN2), plasminogen activator inhibitor 1 (PAI-1), soluble vascular cell adhesion protein 1 (sVCAM1) and 4 protein clusters were tested in multivariable mixed models. RESULTS: EQW affected FCN2 (Cohen's d -0.019), PAI-1 (Cohen's d -0.033), sVCAM-1 (Cohen's d 0.035) and a cytokine-cytokine cluster (Cohen's d 0.037) significantly compared with placebo. These effects were sustained in individuals over the age of 65 but not in those under 65. CONCLUSIONS: EQW treatment was associated with significant change in inflammatory proteins associated with AD. TRIAL REGISTRATION: EXSCEL is registered on ClinicalTrials.gov: NCT01144338 on 10th of June 2010. CI - (c) 2024. The Author(s). FAU - Koychev, Ivan AU - Koychev I AUID- ORCID: 0000-0001-6813-8493 AD - Department of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, UK. ivan.koychev@psych.ox.ac.uk. FAU - Reid, Graham AU - Reid G AUID- ORCID: 0000-0002-6079-9323 AD - Department of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, UK. FAU - Nguyen, Maggie AU - Nguyen M AD - Duke Center for Precision Health, Duke University School of Medicine, Durham, NC, USA. FAU - Mentz, Robert J AU - Mentz RJ AD - Duke Clinical Research Institute, Durham, NC, USA. FAU - Joyce, Dan AU - Joyce D AD - Department of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, UK. FAU - Shah, Svati H AU - Shah SH AD - Duke Center for Precision Health, Duke University School of Medicine, Durham, NC, USA. AD - Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Holman, Rury R AU - Holman RR AD - Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. LA - eng SI - ClinicalTrials.gov/NCT01144338 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20241002 PL - England TA - Alzheimers Res Ther JT - Alzheimer's research & therapy JID - 101511643 RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Alzheimer Disease/drug therapy/blood MH - Male MH - Female MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Exenatide/therapeutic use MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use MH - Double-Blind Method MH - Plasminogen Activator Inhibitor 1/blood MH - C-Reactive Protein/analysis/metabolism MH - Inflammation/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11448378 OTO - NOTNLM OT - Alzheimer's disease OT - Glucagon-like peptide-1 receptor agonists OT - Proteomics COIS- IK received research support and honoraria from Novo Nordisk. He is a paid medical advisor for biotechnology (cfdx Ltd) and digital healthcare companies working in dementia (Five Lives SAS, Cognetivity, Mantrah Ltd). RJM received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Rocket Pharmaceuticals, Sanofi, Verily, Vifor, Windtree Therapeutics, and Zoll. RRH reports personal fees from Anji Pharmaceuticals, AstraZeneca, and Novartis. EDAT- 2024/10/03 00:42 MHDA- 2024/10/03 07:18 PMCR- 2024/10/02 CRDT- 2024/10/02 23:49 PHST- 2024/05/21 00:00 [received] PHST- 2024/09/09 00:00 [accepted] PHST- 2024/10/03 07:18 [medline] PHST- 2024/10/03 00:42 [pubmed] PHST- 2024/10/02 23:49 [entrez] PHST- 2024/10/02 00:00 [pmc-release] AID - 10.1186/s13195-024-01573-x [pii] AID - 1573 [pii] AID - 10.1186/s13195-024-01573-x [doi] PST - epublish SO - Alzheimers Res Ther. 2024 Oct 2;16(1):212. doi: 10.1186/s13195-024-01573-x. PMID- 39353727 OWN - NLM STAT- MEDLINE DCOM- 20241016 LR - 20250715 IS - 1468-3296 (Electronic) IS - 0040-6376 (Linking) VI - 79 IP - 11 DP - 2024 Oct 16 TI - Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD. PG - 1017-1023 LID - 10.1136/thorax-2023-221040 [doi] AB - BACKGROUND: Clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary outcomes and mortality between GLP-1 RA use and no use in patients with type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD). METHODS: The study identified 8060 matched GLP-1 RA users and non-users from Taiwan's National Health Insurance Research Database from 1 January 2008 to 31 December 2019. Cox proportional hazards models were used to determine the risk of cardiopulmonary outcomes between GLP-1 RA users and non-users. RESULTS: The mean follow-up time was 2.51 and 2.46 years for GLP-1 RA users and non-users, respectively. In the matched cohorts, GLP-1 RA users had a significantly lower risk of mortality (adjusted HR (aHR) 0.46, 95% CI 0.38 to 0.56), cardiovascular events (aHR 0.73, 95% CI 0.65 to 0.82), non-invasive positive pressure ventilation (aHR 0.66, 95% CI 0.47 to 0.93), invasive mechanical ventilation (aHR 0.64, 95% CI 0.51 to 0.8) and bacterial pneumonia (aHR 0.76, 95% CI 0.65 to 0.88) than GLP-1 RA non-users. The subsequent analyses for various subgroup and medication duration also showed that GLP-1 RA was associated with a significantly lower risk of mortality, cardiovascular events, ventilation support and bacterial pneumonia than non-GLP-1 RA. CONCLUSION: This nationwide cohort study showed that GLP-1 RA had a lower risk of cardiopulmonary outcomes and all-cause mortality than non-GLP-1 RA in patients with T2D and COPD. GLP-1 RA may help manage diabetes in people with COPD. CI - (c) Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr Yen's Clinic, Taoyuan, Taiwan. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Tsai, Fuu-Jen AU - Tsai FJ AD - China Medical University College of Chinese Medicine, Taichung, Taiwan. FAU - Huang, Yuhan AU - Huang Y AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Yu, Teng-Shun AU - Yu TS AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. FAU - Hwu, Chii-Min AU - Hwu CM AUID- ORCID: 0000-0002-8209-9627 AD - Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan chhwu@vghtpe.gov.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241016 PL - England TA - Thorax JT - Thorax JID - 0417353 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Pulmonary Disease, Chronic Obstructive/drug therapy/complications MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Middle Aged MH - Taiwan/epidemiology MH - Longitudinal Studies MH - Cardiovascular Diseases/mortality MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Assisted Ventilation OT - COPD Exacerbations OT - Emphysema OT - Lung Cancer OT - Non invasive ventilation OT - Pneumonia COIS- Competing interests: None declared. EDAT- 2024/10/03 03:38 MHDA- 2024/10/17 10:03 CRDT- 2024/10/01 21:32 PHST- 2023/10/04 00:00 [received] PHST- 2024/09/13 00:00 [accepted] PHST- 2024/10/17 10:03 [medline] PHST- 2024/10/03 03:38 [pubmed] PHST- 2024/10/01 21:32 [entrez] AID - thorax-2023-221040 [pii] AID - 10.1136/thorax-2023-221040 [doi] PST - epublish SO - Thorax. 2024 Oct 16;79(11):1017-1023. doi: 10.1136/thorax-2023-221040. PMID- 39356547 OWN - NLM STAT- MEDLINE DCOM- 20241015 LR - 20260127 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 18 IP - 41 DP - 2024 Oct 15 TI - Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model. PG - 28406-28424 LID - 10.1021/acsnano.4c11172 [doi] AB - The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule Z(FcRn) that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner. These FcRn-targeted ligands were selected over the endogenous ligands of the receptor (albumin and IgG) due to their smaller size and simpler structure, which could facilitate the transport of functionalized NPs through the tissues. The capacity of FcRn-targeted semaglutide-NPs in controlling the blood glucose levels was evaluated in an hFcRn transgenic mice model, where type 2 diabetes mellitus (T2DM) was induced via intraperitoneal injection of nicotinamide followed by streptozotocin. The encapsulation of semaglutide into FcRn-targeted NPs was translated in an improved glucoregulatory effect in T2DM-induced mice when compared to the oral free semaglutide or nontargeted NP groups, after daily oral administrations for 7 days. Notably, a similar glucose-lowering response was observed between both FcRn-targeted NPs and the subcutaneous semaglutide groups. An increase in insulin pancreatic content and a recovery in beta cell mass were visualized in the mice treated with FcRn-targeted semaglutide-NPs. The biodistribution of fluorescently labeled NPs through the gastrointestinal tract demonstrated that the nanosystems targeting the hFcRn are retained longer in the ileum and colorectum, where the expression of FcRn is more prevalent, than nontargeted NPs. Therefore, FcRn-targeted nanocarriers proved to be an effective platform for improving the pharmacological effect of semaglutide in a T2DM-induced mice model. FAU - Pinto, Soraia AU - Pinto S AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. AD - Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, Porto 4050-313, Portugal. FAU - Viegas, Juliana AU - Viegas J AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. FAU - Cristelo, Cecilia AU - Cristelo C AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. AD - Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, Porto 4050-313, Portugal. FAU - Pacheco, Catarina AU - Pacheco C AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. AD - Instituto Universitario de Ciencias da Saude (IUCS-CESPU), Rua Central de Gandra 1317, Gandra 4585-116, Portugal. FAU - Barros, Sofia AU - Barros S AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. AD - Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, Porto 4050-313, Portugal. FAU - Buckley, Stephen T AU - Buckley ST AUID- ORCID: 0000-0001-9804-7242 AD - Global Research Technologies, Novo Nordisk, Novo Nordisk Park 1, Malov 2760, Denmark. FAU - Garousi, Javad AU - Garousi J AD - Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Roslagstullsbacken 21, Stockholm 114 17, Sweden. AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75185, Sweden. FAU - Graslund, Torbjorn AU - Graslund T AUID- ORCID: 0000-0002-5391-600X AD - Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Roslagstullsbacken 21, Stockholm 114 17, Sweden. FAU - Santos, Helder A AU - Santos HA AUID- ORCID: 0000-0001-7850-6309 AD - Department of Biomaterials and Biomedical Technology, University Medical Center Groningen, University of Groningen, AV Groningen 9713, the Netherlands. AD - Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, Helsinki FI-00014, Finland. FAU - Sarmento, Bruno AU - Sarmento B AUID- ORCID: 0000-0001-5763-7553 AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal. AD - Instituto Universitario de Ciencias da Saude (IUCS-CESPU), Rua Central de Gandra 1317, Gandra 4585-116, Portugal. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241002 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Receptors, Fc) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Histocompatibility Antigens Class I) RN - 53AXN4NNHX (Semaglutide) RN - TW3XAW0RCY (Fc receptor, neonatal) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/chemistry MH - *Receptors, Fc/metabolism MH - Mice MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Humans MH - Nanomedicine MH - Blood Glucose/drug effects/metabolism MH - Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Nanoparticles/chemistry MH - Hypoglycemic Agents/administration & dosage/pharmacology/chemistry/pharmacokinetics MH - Mice, Transgenic MH - Histocompatibility Antigens Class I/metabolism MH - Male MH - Semaglutide OTO - NOTNLM OT - gastrointestinal distribution OT - glucoregulatory effect OT - neonatal Fc receptor-targeted ligands OT - polymeric nanocarriers OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2024/10/02 12:42 MHDA- 2024/10/15 06:22 CRDT- 2024/10/02 11:43 PHST- 2024/10/15 06:22 [medline] PHST- 2024/10/02 12:42 [pubmed] PHST- 2024/10/02 11:43 [entrez] AID - 10.1021/acsnano.4c11172 [doi] PST - ppublish SO - ACS Nano. 2024 Oct 15;18(41):28406-28424. doi: 10.1021/acsnano.4c11172. Epub 2024 Oct 2. PMID- 39356417 OWN - NLM STAT- MEDLINE DCOM- 20241216 LR - 20261010 IS - 1724-6059 (Electronic) IS - 1121-8428 (Linking) VI - 37 IP - 8 DP - 2024 Nov TI - Management of acute kidney disease in type 2 diabetes: the potential role of GLP-1 RAs and SGLT2-Is. PG - 2347-2350 LID - 10.1007/s40620-024-02107-2 [doi] AB - Acute kidney disease (AKD) is defined as subacute damage and/or loss of kidney function occurring 7 to 90 days after acute kidney injury (AKI), and bearing a high risk of progression to chronic kidney disease. Current management of AKD is non-specific and includes prevention of repeated AKI, early and regular follow-up by a nephrologist, resumption and dose adjustment of statins and renin-angiotensin system inhibitors, optimization of blood pressure control, nutrition management, and nephrotoxin avoidance. Recently, SGLT2i and GLP1- RAs have emerged as potential therapeutic tools preventing the transition from acute to chronic kidney disease due to their efficacy in preserving renal function. CI - (c) 2024. The Author(s) under exclusive licence to Italian Society of Nephrology. FAU - Giugliano, Dario AU - Giugliano D AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - De Nicola, Luca AU - De Nicola L AUID- ORCID: 0000-0001-8532-0182 AD - Nephrology Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Piazza L. Miraglia 2, 80138, Naples, Italy. luca.denicola@unicampania.it. LA - eng PT - Journal Article PT - Review DEP - 20241002 PL - England TA - J Nephrol JT - Journal of nephrology JID - 9012268 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Acute Kidney Injury/drug therapy/prevention & control MH - *Renin-Angiotensin System/drug effects/physiology MH - Diabetic Nephropathies/drug therapy/physiopathology MH - Glucagon-Like Peptide 1 MH - Disease Progression MH - Incretins/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Acute kidney disease OT - Acute kidney injury OT - Chronic kidney disease OT - Diabetes mellitus type 2 OT - Therapy COIS- Declarations. Conflict of interest: KE has been member on advisory boards for Eli Lilly & Co., NovoNordisk, Lifescan, Roche, GSK, Bayer and has received honoraria from these activities; LDN has participated in the advisory boards for AstraZeneca and Bayer and has received honoraria for this activity; DG has no conflicts of interest to declare. Ethical approval: Not applicable (no original data). Informed consent to participate: Not applicable (no original data). EDAT- 2024/10/02 12:42 MHDA- 2024/12/17 05:31 CRDT- 2024/10/02 11:07 PHST- 2024/08/05 00:00 [received] PHST- 2024/09/01 00:00 [accepted] PHST- 2024/12/17 05:31 [medline] PHST- 2024/10/02 12:42 [pubmed] PHST- 2024/10/02 11:07 [entrez] AID - 10.1007/s40620-024-02107-2 [pii] AID - 10.1007/s40620-024-02107-2 [doi] PST - ppublish SO - J Nephrol. 2024 Nov;37(8):2347-2350. doi: 10.1007/s40620-024-02107-2. Epub 2024 Oct 2. PMID- 39351253 OWN - NLM STAT- MEDLINE DCOM- 20241001 LR - 20260127 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 30 IP - 36 DP - 2024 Sep 28 TI - Glucagon-like peptide-1 receptor agonists: Exploring the mechanisms from glycemic control to treatment of multisystemic diseases. PG - 4036-4043 LID - 10.3748/wjg.v30.i36.4036 [doi] AB - This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani, which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for metabolic dysfunction-associated fatty liver disease. We provide supplementary insights to their research, highlighting the broader systemic implications of GLP-1RAs, synthesizing the current understanding of their mechanisms and the trajectory of research in this field. GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond. Beyond glycemic control, GLP-1RAs demonstrate cardiovascular and renal protective effects, offering potential in managing diabetic kidney disease al-ongside renin-angiotensin-aldosterone system inhibitors. Their role in bone metabolism hints at benefits for diabetic osteoporosis, while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling. Additionally, they improve hormonal and metabolic profiles in polycystic ovary syndrome. This editorial highlights the multifaceted mechanisms of GLP-1RAs, emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases. CI - (c)The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved. FAU - Kong, Mo-Wei AU - Kong MW AD - Department of Cardiology, Southwest Medical University, Luzhou 646000, Sichuan Province, China. FAU - Yu, Yang AU - Yu Y AD - Department of Cardiology, Southwest Medical University, Luzhou 646000, Sichuan Province, China. FAU - Wan, Ying AU - Wan Y AD - School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, China. FAU - Gao, Yu AU - Gao Y AD - Department of Endocrinology, The Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China. FAU - Zhang, Chun-Xiang AU - Zhang CX AD - Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China. AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou 646000, Sichuan Province, China. zhangchx999@163.com. LA - eng PT - Editorial PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - *Glycemic Control/methods MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Signal Transduction/drug effects MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11439120 OTO - NOTNLM OT - Bone metabolism OT - Cardiovascular protection OT - Glucagon-like peptide-1 receptor agonists OT - Glycemic control OT - Mechanism of action OT - Multisystem diseases OT - Neuroprotection OT - Non-alcoholic fatty liver disease OT - Polycystic ovary syndrome OT - Renal disease COIS- Conflict-of-interest statement: The authors declare that they have no competing interests. EDAT- 2024/10/01 06:55 MHDA- 2024/10/01 06:56 PMCR- 2024/09/28 CRDT- 2024/10/01 04:22 PHST- 2024/07/27 00:00 [received] PHST- 2024/08/08 00:00 [revised] PHST- 2024/09/05 00:00 [accepted] PHST- 2024/10/01 06:56 [medline] PHST- 2024/10/01 06:55 [pubmed] PHST- 2024/10/01 04:22 [entrez] PHST- 2024/09/28 00:00 [pmc-release] AID - 10.3748/wjg.v30.i36.4036 [doi] PST - ppublish SO - World J Gastroenterol. 2024 Sep 28;30(36):4036-4043. doi: 10.3748/wjg.v30.i36.4036. PMID- 39347905 OWN - NLM STAT- MEDLINE DCOM- 20250131 LR - 20261010 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 48 IP - 2 DP - 2025 Feb TI - The blood pressure-lowering property of subcutaneous semaglutide: a systematic review, meta-analysis, and meta-regression. PG - 283-294 LID - 10.1007/s40618-024-02459-3 [doi] AB - PURPOSE: Semaglutide is a glucagon-like peptide (GLP1) receptor agonist with unprecedented weight-lowering and anti-hyperglycemic properties. Recent clinical trials reported that subcutaneous semaglutide can modulate blood pressure; however, its effect on blood pressure widely varied in different studies and different subgroups of patients. METHODS: PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched from the inception to July 18, 2024. Due to high heterogeneity, a random-effects model was adopted to pool data. RESULTS: Twenty clinical trials with 15,312 participants in the placebo group and 18,231 participants in the semaglutide group were included in this study. Subcutaneous semaglutide significantly decreased both systolic (WMD - 3.71 mmHg, 95% CI (-4.29, -3.13), I(2): 50.2%) and diastolic (WMD - 1.10 mmHg, 95% CI (-1.58, -0.63), I(2): 69.7%) blood pressure. Subgroup analyses indicated that the blood pressure-lowering property of subcutaneous semaglutide was greater among patients without diabetes, with lower baseline hemoglobin A1c (HbA1c), baseline body mass index (BMI) greater than 35 kg/m(2), dose of semaglutide more than 1 mg/week, baseline systolic blood pressure equal or less than 130 mmHg, weight loss greater than 10 kg, and BMI reduction greater than 3 kg/m(2). In addition, a treatment length of 50 to 100 weeks was associated with greater blood pressure-lowering effects in subgroup analysis. After adjusting for other factors, meta-regression revealed that placebo-adjusted weight change was independently correlated with the effect of semaglutide on systolic and diastolic blood pressure. CONCLUSION: Subcutaneous semaglutide can significantly decrease systolic and diastolic blood pressure, particularly in selected groups of patients. CI - (c) 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Ala, Moein AU - Ala M AUID- ORCID: 0000-0001-5951-4864 AD - Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. moinala75@yahoo.com. FAU - Moheb Aleaba, Mohammadreza AU - Moheb Aleaba M AD - Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240930 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - *Blood Pressure/drug effects MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Injections, Subcutaneous MH - *Hypertension/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Blood pressure OT - Diabetes OT - Meta-analysis OT - Obesity OT - Semaglutide OT - Weight loss COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors of this manuscript declare no conflict of interest. EDAT- 2024/09/30 12:47 MHDA- 2025/01/31 12:24 CRDT- 2024/09/30 11:08 PHST- 2024/05/06 00:00 [received] PHST- 2024/08/22 00:00 [accepted] PHST- 2025/01/31 12:24 [medline] PHST- 2024/09/30 12:47 [pubmed] PHST- 2024/09/30 11:08 [entrez] AID - 10.1007/s40618-024-02459-3 [pii] AID - 10.1007/s40618-024-02459-3 [doi] PST - ppublish SO - J Endocrinol Invest. 2025 Feb;48(2):283-294. doi: 10.1007/s40618-024-02459-3. Epub 2024 Sep 30. PMID- 39344853 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, exhibits favourable effects on pancreatic beta-cells and hepatic steatosis in obese type 2 diabetic db/db mice. PG - 5982-5994 LID - 10.1111/dom.15972 [doi] AB - AIM: Tirzepatide, a dual agonist of glucagon-like peptide receptor and glucose-dependent insulinotropic polypeptide receptor, is expected to exhibit high clinical efficacy in obese type 2 diabetic patients. We evaluated the effects of tirzepatide on pancreatic beta-cells and the liver, an insulin-target organ, in a mouse model of obese type 2 diabetes mellitus. MATERIALS AND METHODS: Obese type 2 diabetic db/db mice (BKS.Cg-/+ Leprdb/+ Leprdb/Jcl*) were used in this study. Starting at 7 weeks of age, mice were treated with tirzepatide (30 nmol/kg, subcutaneous injection twice a week) or semaglutide (200 nmol/kg, subcutaneous injection twice a week). The control group received phosphate-buffered saline (40-50 muL/subcutaneous injection twice a week). After 4 weeks of drug administration, pancreatic beta-cells and the liver were removed and examined. RESULTS: Compared to the control group, blood glucose and body weight were significantly reduced in the group that received either tirzepatide or semaglutide (p < 0.001 and p < 0.05, respectively). Fasting insulin was significantly higher in the semaglutide and tirzepatide groups compared to the control group (p < 0.001). beta-Cell mass and quality of insulin granules in beta-cells similarly increased in the semaglutide and tirzepatide groups compared to the control group (p < 0.05 and p < 0.001, respectively). The fat staining area in the liver in oil red O staining and the liver-spleen ratio in computed tomography showed improvement only in the tirzepatide group (p < 0.001 and p < 0.005, respectively). Liver macrophage M1/M2 ratio similarly improved with semaglutide and tirzepatide (p < 0.05). CONCLUSION: Tirzepatide and semaglutide exhibited similar potent glucose-lowering effects. At concentrations used in the present experiments, tirzepatide exhibited more beneficial effects on beta-cell-related gene expression, insulin granule count and glucose-stimulated insulin secretion compared to semaglutide. In addition, tirzepatide exhibited a stronger favourable effect on hepatic fat deposition and improved inflammation in the liver. This is the first report showing that tirzepatide, a novel diabetes drug, exhibits a superior effect on pancreatic beta-cells and the liver of obese type 2 diabetic mice. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Iwamoto, Yuichiro AU - Iwamoto Y AUID- ORCID: 0000-0001-8162-359X AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Kimura, Tomohiko AU - Kimura T AUID- ORCID: 0000-0003-3986-9494 AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Dan, Kazunori AU - Dan K AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Iwamoto, Hideyuki AU - Iwamoto H AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Sanada, Junpei AU - Sanada J AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Fushimi, Yoshiro AU - Fushimi Y AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Katakura, Yukino AU - Katakura Y AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Shimoda, Masashi AU - Shimoda M AUID- ORCID: 0000-0002-4223-9613 AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Yamasaki, Yuki AU - Yamasaki Y AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Nogami, Yuka AU - Nogami Y AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Shirakiya, Yoshiko AU - Shirakiya Y AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Nakanishi, Shuhei AU - Nakanishi S AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Mune, Tomoatsu AU - Mune T AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan. LA - eng PT - Journal Article DEP - 20240930 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Mice MH - *Glucagon-Like Peptides/pharmacology/analogs & derivatives/therapeutic use MH - *Blood Glucose/metabolism/drug effects MH - Male MH - Fatty Liver/drug therapy MH - Liver/metabolism/drug effects MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Obesity/complications/drug therapy/metabolism MH - Mice, Obese MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GIP receptor OT - GLP-1 receptor OT - pancreatic beta-cells OT - steatosis OT - type 2 diabetes mellitus EDAT- 2024/09/30 12:45 MHDA- 2024/11/04 18:23 CRDT- 2024/09/30 06:53 PHST- 2024/09/03 00:00 [revised] PHST- 2024/06/21 00:00 [received] PHST- 2024/09/08 00:00 [accepted] PHST- 2024/11/04 18:23 [medline] PHST- 2024/09/30 12:45 [pubmed] PHST- 2024/09/30 06:53 [entrez] AID - 10.1111/dom.15972 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5982-5994. doi: 10.1111/dom.15972. Epub 2024 Sep 30. PMID- 39344838 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps. PG - 5503-5518 LID - 10.1111/dom.15913 [doi] AB - Excess adiposity is at the root of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as first-line treatments for T2D based on significant weight loss results. The composition of weight loss using most diets consists of <25% fat-free mass (FFM) loss, with the remainder from fat stores. Higher amounts of weight loss (achieved with metabolic bariatric surgery) result in greater reductions in FFM. Our aim was to assess the impact that GLP-1RA-based treatments have on FFM. We analysed studies that reported changes in FFM with the following agents: exenatide, liraglutide, semaglutide, and the dual incretin receptor agonist tirzepatide. We performed an analysis of various weight loss interventions to provide a reference for expected changes in FFM. We evaluated studies using dual-energy X-ray absorptiometry (DXA) for measuring FFM (a crude surrogate for skeletal muscle). In evaluating the composition of weight loss, the percentage lost as fat-free mass (%FFML) was equal to DeltaFFM/total weight change. The %FFML using GLP-1RA-based agents was between 20% and 40%. In the 28 clinical trials evaluated, the proportion of FFM loss was highly variable, but the majority reported %FFML exceeding 25%. Our review was limited to small substudies and the use of DXA, which does not measure skeletal muscle mass directly. Since FFM contains a variable amount of muscle (approximately 55%), this indirect measure may explain the heterogeneity in the data. Assessing quantity and quality of skeletal muscle using advanced imaging (magnetic resonance imaging) with functional testing will help fill the gaps in our current understanding. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Dubin, Robert L AU - Dubin RL AUID- ORCID: 0000-0002-7378-9650 AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. FAU - Heymsfield, Steven B AU - Heymsfield SB AUID- ORCID: 0000-0003-1127-9425 AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. FAU - Ravussin, Eric AU - Ravussin E AUID- ORCID: 0000-0003-2129-547X AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. FAU - Greenway, Frank L AU - Greenway FL AUID- ORCID: 0000-0002-1766-6111 AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. LA - eng PT - Journal Article PT - Review DEP - 20240930 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/therapeutic use MH - *Exenatide/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Absorptiometry, Photon MH - Obesity/drug therapy MH - Body Composition/drug effects MH - Female MH - Male MH - Adiposity/drug effects MH - Bariatric Surgery MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/09/30 12:45 MHDA- 2024/11/04 18:23 CRDT- 2024/09/30 06:53 PHST- 2024/08/15 00:00 [revised] PHST- 2024/06/10 00:00 [received] PHST- 2024/08/16 00:00 [accepted] PHST- 2024/11/04 18:23 [medline] PHST- 2024/09/30 12:45 [pubmed] PHST- 2024/09/30 06:53 [entrez] AID - 10.1111/dom.15913 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5503-5518. doi: 10.1111/dom.15913. Epub 2024 Sep 30. PMID- 39343145 OWN - NLM STAT- MEDLINE DCOM- 20241113 LR - 20250103 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 217 DP - 2024 Nov TI - A post-hoc pooled analysis to evaluate efficacy and safety of insulin glargine 300 U/mL in insulin-naive people with type 2 diabetes with/without prior use of glucagon-like peptide-1 receptor agonist therapy. PG - 111871 LID - S0168-8227(24)00781-2 [pii] LID - 10.1016/j.diabres.2024.111871 [doi] AB - AIMS: To evaluate treatment advancement with insulin glargine 300 U/mL (Gla-300), with or without prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in type 2 diabetes (T2D). METHODS: Efficacy and safety outcomes of insulin-naive patients intensifying with Gla-300, with/without prior GLP-1 RA therapy, were evaluated in three analyses (N = 3562): a pooled analysis of seven interventional studies, a subanalysis comparing participants who stopped GLP-1 RA therapy and initiated Gla-300 with those who received add-on Gla-300, and an expanded analysis including two observational studies. RESULTS: Glycaemic outcomes, including HbA1c improvement and fasting plasma glucose, were similar between groups with/without prior GLP-1 RA use. HbA1c least squares mean change from baseline was - 1.7 % and - 1.6 % with and without prior GLP-1 RA, respectively. Glycaemic outcomes were similar between participants who stopped GLP-1 RA therapy when initiating Gla-300 and those who received add-on Gla-300, although more participants receiving add-on Gla-300 achieved HbA1c targets. The expanded analysis yielded similar results. Incidence of hypoglycaemia was low with no clinically relevant weight changes in all analyses. CONCLUSIONS: Treatment advancement with Gla-300 in patients with T2D, with/without prior GLP-1 RA therapy, improved glycaemic outcomes with no relevant impact on weight, while maintaining a low hypoglycaemia risk. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, ON, Canada; Trilium Health Partners & Unity Health, Toronto, Canada. Electronic address: Alice.Cheng@unityhealth.to. FAU - Mauricio, Didac AU - Mauricio D AD - Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau CIBERDEM, Barcelona, Spain. FAU - Ritzel, Robert AU - Ritzel R AD - Division of Endocrinology, Diabetes and Angiology, Klinikum Schwabing and Klinikum Bogenhausen, Stadtisches Klinikum Munchen GmbH, Munich, Germany. FAU - Al-Sofiani, Mohammed E AU - Al-Sofiani ME AD - Division of Endocrinology, Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University, Baltimore, MD, USA. FAU - Bailey, Timothy AU - Bailey T AD - AMCR Institute, Escondido, CA, USA. FAU - Aileen Mabunay, Maria AU - Aileen Mabunay M AD - Sanofi, Global Medical, Singapore, Singapore. FAU - Bonnemaire, Mireille AU - Bonnemaire M AD - Sanofi, Paris, France. FAU - Melas-Melt, Lydie AU - Melas-Melt L AD - Ividata Life Sciences, Levallois-Perret, France. FAU - Mimouni, Safia AU - Mimouni S AD - Pierre & Marie Curie Center, University of Algiers, Algiers, Algeria. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Leicester, UK. LA - eng PT - Journal Article DEP - 20240927 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Insulin Glargine/therapeutic use/adverse effects/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Male MH - Female MH - Middle Aged MH - *Blood Glucose/drug effects/analysis MH - *Glycated Hemoglobin/metabolism/analysis MH - Aged MH - Treatment Outcome MH - Hypoglycemia/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 RA OT - Gla-300 OT - Insulin glargine OT - Insulin-naive OT - Type 2 diabetes COIS- Declaration of competing interest All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All authors participated in the interpretation of the data, the writing, reviewing, and editing of the manuscript, and had final responsibility for approving the published version. A. Cheng: Advisory board member for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Eisai, Eli Lilly, Insulet, HLS Therapeutics, Janssen, Novo Nordisk, Sanofi and Takeda. Speaking honoraria for Abbott Diabetes Care, Amgen, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, GSK, Insulet, HLS Therapeutics, Janssen, Medtronic, Novo Nordisk, Pfizer and Sanofi. Consulting fees from Abbott Diabetes Care, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Eisai, Insulet, HLS Therapeutics, Janssen, Novo Nordisk, Sanofi and Takeda. D. Mauricio: Advisory and/or speaking fees from AB-Biotics, Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, MSD, Novo Nordisk and Sanofi. Research grants to the institution from MSD, Novo Nordisk and Sanofi. R. Ritzel: Consultant for Sanofi, Novo Nordisk, Merck (MSD) and Eli Lilly, and has served on Speaker's bureau for Sanofi, Novo Nordisk, Novartis, Eli Lilly, Merck (MSD), Bristol-Myers Squibb and AstraZeneca. M. E. Al-Sofiani: Has served on an advisory panel for Abbott, Medtronic, Insulet, VitalAire, and Sanofi. Honoraria for speaking/consultancy from Abbott, Eli Lilly, Medtronic, Novo Nordisk, Sanofi and VitalAire. T. Bailey: Research support from Abbott Diabetes, Abbott Rapid Diagnostics, Biolinq, Capillary Biomedical, Dexcom, Eli Lilly, Kowa, Livongo, Mannkind, Medtronic, Novo Nordisk, REMD, Sanofi, Sanvita, Senseonics, Viacyte, vTv Therapeutics and Zealand Pharma. Consulting honoraria from Abbott, CeQur, Lifescan, Mannkind, Medtronic, Novo Nordisk, Sanofi, Abbott Rapid Diagnostics, HagarTech, Intuity Medical, Perspirion, SequelMedTech and Ypsomed. Speaking honoraria from BD, Medtronic and Sanofi. Expert testimony consulting fees from Medtronic Diabetes. Travel/meeting support from Sanofi. M. A.Mabunay & M. Bonnemaire: Employees of Sanofi, may hold stocks/shares in Sanofi. L. Melas-Melt: Employee of Ividata Life Sciences, contracted to provide services to Sanofi. S.Mimouni: Advisory board member and speaker for Eli Lilly, Novo Nordisk and Sanofi. M. Davies: Has acted as a consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; an advisory board member for Lexicon, Pfizer, AstraZeneca, Zealand Pharma and Medtronic; and as a speaker for AstraZeneca. Grants received from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen, Sanofi-Aventis, Eli Lilly and NIHR Leicester Biomedical Research Centre (which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester). EDAT- 2024/09/30 04:18 MHDA- 2024/11/14 03:59 CRDT- 2024/09/29 19:19 PHST- 2024/06/07 00:00 [received] PHST- 2024/09/11 00:00 [revised] PHST- 2024/09/24 00:00 [accepted] PHST- 2024/11/14 03:59 [medline] PHST- 2024/09/30 04:18 [pubmed] PHST- 2024/09/29 19:19 [entrez] AID - S0168-8227(24)00781-2 [pii] AID - 10.1016/j.diabres.2024.111871 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Nov;217:111871. doi: 10.1016/j.diabres.2024.111871. Epub 2024 Sep 27. PMID- 39342279 OWN - NLM STAT- MEDLINE DCOM- 20240929 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Sep 28 TI - Association of semaglutide treatment with coronary artery inflammation in type 2 diabetes mellitus patients: a retrospective study based on pericoronary adipose tissue attenuation. PG - 348 LID - 10.1186/s12933-024-02445-2 [doi] LID - 348 AB - BACKGROUND: The pericoronary fat attenuation index (FAI) has emerged as a novel and sensitive biomarker reflecting the degree of coronary artery inflammation. Semaglutide has been demonstrated to exert a cardiovascular protective effect independent of hypoglycemia; however, its impact on coronary artery inflammation remains elusive. This study aimed to investigate the association between semaglutide treatment and coronary artery inflammation based on FAI in patients with type 2 diabetes mellitus (T2DM). METHODS: This study enrolled 497 T2DM patients who underwent coronary computed tomography angiography (CCTA) at Hebei General Hospital, of whom 93 treated with semaglutide (Sema+) and 404 did not (Sema-). Clinical data, laboratory indicators, and CCTA parameters were collected and compared between the two groups at baseline. Propensity score matching (PSM) was used to adjust for confounders, and pericoronary FAI was compared. Multivariate linear regression models were used to analyze the association between semaglutide treatment and pericoronary FAI. RESULTS: Before PSM, pericoronary FAI of the LAD and LCX was lower in patients treated with semaglutide than those without semaglutide treatment. The results of the PSM analysis revealed a lower FAI in all three major coronary arteries in the Sema + group compared to the Sema- group. Multivariate linear regression analyses revealed an independent association between semaglutide treatment and reduced FAI in all three major coronary arteries. This association varied across T2DM patients of differing profiles. CONCLUSION: Semaglutide treatment may be associated with lower coronary artery inflammation in patients with T2DM, which might partially explain its cardiovascular protective mechanism. CI - (c) 2024. The Author(s). FAU - Li, Yanhong AU - Li Y AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. AD - Department of Internal Medicine, Graduate School of Hebei Medical University, Shijiazhuang, China. FAU - Yao, Wenjing AU - Yao W AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. FAU - Wang, Tianxing AU - Wang T AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. FAU - Yang, Qian AU - Yang Q AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. yangqian8411@163.com. FAU - Song, Kexin AU - Song K AD - Department of Internal Medicine, Graduate School of Hebei Medical University, Shijiazhuang, China. FAU - Zhang, Feifei AU - Zhang F AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. FAU - Wang, Fan AU - Wang F AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. FAU - Dang, Yi AU - Dang Y AD - Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, China. dangyiemail@126.com. LA - eng GR - No. 18277791D/Key Research and Development Program of Hebei Province/ GR - No. GZ2023013/Hebei Province Medical Technology Tracking Project/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240928 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Coronary Artery Disease/diagnostic imaging/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Treatment Outcome MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Coronary Angiography MH - Computed Tomography Angiography MH - Adiposity/drug effects MH - China/epidemiology MH - Risk Assessment MH - Adipose Tissue/drug effects/diagnostic imaging MH - Epicardial Adipose Tissue MH - Semaglutide PMC - PMC11439223 OTO - NOTNLM OT - Coronary artery OT - Pericoronary adipose tissue OT - Semaglutide OT - Type 2 diabetes mellitus OT - Vascular inflammation COIS- The authors declare no competing interests. EDAT- 2024/09/29 00:43 MHDA- 2024/09/29 10:18 PMCR- 2024/09/28 CRDT- 2024/09/28 23:42 PHST- 2024/08/11 00:00 [received] PHST- 2024/09/17 00:00 [accepted] PHST- 2024/09/29 10:18 [medline] PHST- 2024/09/29 00:43 [pubmed] PHST- 2024/09/28 23:42 [entrez] PHST- 2024/09/28 00:00 [pmc-release] AID - 10.1186/s12933-024-02445-2 [pii] AID - 2445 [pii] AID - 10.1186/s12933-024-02445-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Sep 28;23(1):348. doi: 10.1186/s12933-024-02445-2. PMID- 39342059 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 84 IP - 11 DP - 2024 Nov TI - GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy. PG - 1347-1364 LID - 10.1007/s40265-024-02090-9 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven efficacy and safety in randomized clinical trials and observational real-life studies. Besides improving glucose control, reducing body weight, and lowering arterial blood pressure (surrogate endpoints), the breakthroughs were the demonstration of a significant reduction in cardiovascular and renal events in patients with type 2 diabetes at high risk. GLP-1RAs reduce events linked to atherogenic cardiovascular disease (especially ischemic stroke) and also renal outcomes (FLOW trial with semaglutide), with a limited effect on heart failure. The most striking protective effects of SGLT2is were a marked reduction in hospitalization for heart failure and a remarkable reduced progression of chronic kidney disease. These benefits have been attributed to numerous pleiotropic effects beyond glucose-lowering action. Underlying mechanisms contributing to cardiovascular and renal protection are at least partially different between GLP-1RAs (mainly anti-atherogenic and vascular effects) and SGLT2is (mainly systemic and intrarenal hemodynamic changes). Thus, patients at high risk may benefit from complementary actions when being treated with a GLP-1RA/SGLT2i combination. Such combination has proven its efficacy on surrogate endpoints. Furthermore, post hoc subgroup analyses of cardiovascular outcome trials have suggested a greater cardiorenal protection in patients treated with a combination versus either monotherapy. The benefits of a combined therapy have been confirmed in a few retrospective cohort studies. A dedicated prospective trial comparing a combined therapy versus either monotherapy is ongoing (PRECIDENTD); however, several challenges still remain, especially the higher cost of a combined therapy and the worldwide underuse of either GLP-1RAs or SGLT2is in clinical practice, even in patients at high cardiorenal risk. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Scheen, Andre J AU - Scheen AJ AUID- ORCID: 0000-0001-9743-4371 AD - Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium. andre.scheen@chuliege.be. AD - Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. andre.scheen@chuliege.be. LA - eng PT - Journal Article PT - Review DEP - 20240928 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Declarations. Funding: No sources of funding were used to assist in the preparation of this manuscript. Conflict of interest: Andre J. Scheen has no conflicts of interest to declare that may be relevant to the contents of this article. Availability of data and material: Not applicable. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Code availability: Not applicable. Author contributions: Andre J. Scheen as the only author. Disclosures: Andre J. Scheen has received lecturer/scientific advisor/clinical investigator fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, and NovoNordisk, and has worked as a clinical investigator in the EMPA-REG OUTCOME, CANVAS-R, DECLARE-TIMI 58, LEADER and HARMONY Outcomes cardiovascular outcome trials. EDAT- 2024/09/29 00:42 MHDA- 2024/11/28 06:37 CRDT- 2024/09/28 23:31 PHST- 2024/08/25 00:00 [accepted] PHST- 2024/11/28 06:37 [medline] PHST- 2024/09/29 00:42 [pubmed] PHST- 2024/09/28 23:31 [entrez] AID - 10.1007/s40265-024-02090-9 [pii] AID - 10.1007/s40265-024-02090-9 [doi] PST - ppublish SO - Drugs. 2024 Nov;84(11):1347-1364. doi: 10.1007/s40265-024-02090-9. Epub 2024 Sep 28. PMID- 39332263 OWN - NLM STAT- MEDLINE DCOM- 20241204 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 18 IP - 9 DP - 2024 Sep TI - Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study. PG - 103116 LID - S1871-4021(24)00177-2 [pii] LID - 10.1016/j.dsx.2024.103116 [doi] AB - BACKGROUND: Acute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. OBJECTIVES: Our objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. METHODS: We conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. RESULTS: GLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). CONCLUSIONS: GLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans. CI - Copyright (c) 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Nassar, Mahmoud AU - Nassar M AD - Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; American Society for Inclusion, Diversity, and Equity in Healthcare (ASIDE), Delaware, USA. Electronic address: Dr.Nassar@aucegypt.edu. FAU - Nassar, Omar AU - Nassar O AD - Williamsville East High School, Buffalo, NY, USA. Electronic address: omarmfn2000@gmail.com. FAU - Abosheaishaa, Hazem AU - Abosheaishaa H AD - Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, NY, New York, USA. Electronic address: hazemabosheaishaa@gmail.com. FAU - Misra, Anoop AU - Misra A AD - Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, National Diabetes, Obesity and Cholesterol Foundation (N-DOC), Diabetes Foundation (India) (DFI) India, India. Electronic address: anoopmisra@gmail.com. LA - eng PT - Journal Article DEP - 20240919 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Male MH - Female MH - *Pancreatitis/epidemiology/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Middle Aged MH - *Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Recurrence MH - Follow-Up Studies MH - Prognosis MH - Databases, Factual MH - Aged MH - Risk Factors MH - Propensity Score MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Acute pancreatitis OT - GLP-1 receptor agonists OT - Recurrence risk OT - Retrospective cohort study OT - Semaglutide OT - Tirzepatide OT - TriNetX COIS- Declaration of competing interest and Funding The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. No funding was required for this study. EDAT- 2024/09/28 13:18 MHDA- 2024/12/05 05:30 CRDT- 2024/09/27 18:07 PHST- 2024/07/02 00:00 [received] PHST- 2024/09/02 00:00 [revised] PHST- 2024/09/04 00:00 [accepted] PHST- 2024/12/05 05:30 [medline] PHST- 2024/09/28 13:18 [pubmed] PHST- 2024/09/27 18:07 [entrez] AID - S1871-4021(24)00177-2 [pii] AID - 10.1016/j.dsx.2024.103116 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2024 Sep;18(9):103116. doi: 10.1016/j.dsx.2024.103116. Epub 2024 Sep 19. PMID- 39331877 OWN - NLM STAT- MEDLINE DCOM- 20240927 LR - 20250503 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 39 DP - 2024 Sep 27 TI - GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report. PG - e39799 LID - 10.1097/MD.0000000000039799 [doi] LID - e39799 AB - RATIONALE: Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA). PATIENT CONCERNS: The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department. DIAGNOSES: LADA and DKA. INTERVENTIONS: Changed from dulaglutide to insulin therapy. OUTCOMES: After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal. LESSONS: This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Zhang, Jiaming AU - Zhang J AUID- ORCID: 0009-0000-2673-975 AD - Department of Endocrinology and. FAU - Ma, Ying AU - Ma Y AD - Office of Academic Research, Affiliated Hospital of Hebei University, Baoding, China. FAU - Zu, Qianhe AU - Zu Q AD - Hebei University School of Basic Medical Sciences, Baoding, China. FAU - Wang, Xiaohui AU - Wang X AD - Department of Endocrinology and. FAU - Zhang, Yao AU - Zhang Y AD - Department of Endocrinology and. LA - eng PT - Case Reports PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Diabetic Ketoacidosis/chemically induced/drug therapy MH - *Recombinant Fusion Proteins/adverse effects/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Latent Autoimmune Diabetes in Adults/drug therapy MH - Insulin/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11441871 COIS- The authors have no conflicts of interest to disclose. EDAT- 2024/09/27 18:53 MHDA- 2024/09/27 18:54 PMCR- 2024/09/27 CRDT- 2024/09/27 16:22 PHST- 2024/09/27 18:54 [medline] PHST- 2024/09/27 18:53 [pubmed] PHST- 2024/09/27 16:22 [entrez] PHST- 2024/09/27 00:00 [pmc-release] AID - 00005792-202409270-00020 [pii] AID - MD-D-24-03955 [pii] AID - 10.1097/MD.0000000000039799 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Sep 27;103(39):e39799. doi: 10.1097/MD.0000000000039799. PMID- 39327045 OWN - NLM STAT- MEDLINE DCOM- 20250203 LR - 20260628 IS - 1442-9071 (Electronic) IS - 1442-6404 (Linking) VI - 53 IP - 1 DP - 2025 Jan-Feb TI - Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome. PG - 67-75 LID - 10.1111/ceo.14445 [doi] AB - BACKGROUND: To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). METHODS: A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP-1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta-analysis was pooled using a random-effects model. RESULTS: Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP-1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP-1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). CONCLUSION: Our findings indicate no elevated risk of incidence of DR linked to GLP-1RA compared to insulin. In fact, GLP-1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP-1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c - a phenomenon not specific to GLP-1RA and warrants further investigation. CI - (c) 2024 Royal Australian and New Zealand College of Ophthalmologists. FAU - Kapoor, Ishani AU - Kapoor I AD - Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. FAU - Sarvepalli, Swara M AU - Sarvepalli SM AD - Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. FAU - D'Alessio, David A AU - D'Alessio DA AD - Department of Endocrinology, Duke University, Durham, North Carolina, USA. FAU - Hadziahmetovic, Majda AU - Hadziahmetovic M AUID- ORCID: 0000-0003-4676-1844 AD - Department of Ophthalmology, Duke University, Durham, North Carolina, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240926 PL - Australia TA - Clin Exp Ophthalmol JT - Clinical & experimental ophthalmology JID - 100896531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Incidence MH - *Retina/pathology/drug effects MH - Disease Progression OTO - NOTNLM OT - diabetic retinopathy OT - diabetic retinopathy complications OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes EDAT- 2024/09/27 00:42 MHDA- 2025/02/04 00:20 CRDT- 2024/09/26 21:14 PHST- 2024/08/17 00:00 [revised] PHST- 2024/05/27 00:00 [received] PHST- 2024/09/07 00:00 [accepted] PHST- 2025/02/04 00:20 [medline] PHST- 2024/09/27 00:42 [pubmed] PHST- 2024/09/26 21:14 [entrez] AID - 10.1111/ceo.14445 [doi] PST - ppublish SO - Clin Exp Ophthalmol. 2025 Jan-Feb;53(1):67-75. doi: 10.1111/ceo.14445. Epub 2024 Sep 26. PMID- 39325334 OWN - NLM STAT- MEDLINE DCOM- 20241011 LR - 20261010 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 24 IP - 12 DP - 2024 Dec TI - Comparative Effects of GLP-1 Agonists, Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Diabetes Mellitus Outcomes. PG - 273-289 LID - 10.1007/s11892-024-01554-2 [doi] AB - PURPOSE OF REVIEW: The purpose of this review is to assess the effects of glucagon-like peptide-1 (GLP-1) agonists, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus (T2DM) remission. This review explores the efficacy, safety, and durability of these surgical and medical modalities of diabetes management. RECENT FINDINGS: Studies have shown that GLP-1 agonists achieve higher rates of T2DM remission compared to standard glucose-lowering medications and lifestyle changes. In addition to weight loss, bariatric surgery has been found to be highly effective in treating and inducing remission of T2DM. Studies suggest that post-surgical patients see enhanced glycemic control. Both surgical interventions and GLP1 agonists are effective in achieving T2DM remission. Long-term follow-up and randomized controlled trials comparing bariatric surgery and GLP-1 agonists are necessary to evaluate their relative effectiveness in T2DM control. Further research is also needed to assess the combined effects of these treatment modalities. CI - (c) 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Essop, Tasiyah AU - Essop T AD - Norton College of Medicine, State University of New York Upstate Medical University, 750 E Adams St, 13210, Syracuse, NY, United States. FAU - Tran, Kyle AU - Tran K AD - College of Osteopathic Medicine, Pacific Western University of Health Sciences, 309 E 2nd St, 91766, Pomona, CA, United States. FAU - Purdy, Amanda C AU - Purdy AC AD - Department of Surgery, University of California Irvine, 3800 W Chapman Ave, 92868, Orange, CA, USA. FAU - Daly, Shaun C AU - Daly SC AD - Department of Surgery, University of California Irvine, 3800 W Chapman Ave, 92868, Orange, CA, USA. shaund@hs.uci.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20240926 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - *Gastrectomy/methods MH - *Gastric Bypass/methods MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use OTO - NOTNLM OT - Bariatric surgery OT - Diabetes remission OT - GLP-1 agonist OT - Gastric bypass OT - Sleeve gastrectomy EDAT- 2024/09/26 12:43 MHDA- 2024/10/11 12:27 CRDT- 2024/09/26 11:19 PHST- 2024/09/06 00:00 [accepted] PHST- 2024/10/11 12:27 [medline] PHST- 2024/09/26 12:43 [pubmed] PHST- 2024/09/26 11:19 [entrez] AID - 10.1007/s11892-024-01554-2 [pii] AID - 10.1007/s11892-024-01554-2 [doi] PST - ppublish SO - Curr Diab Rep. 2024 Dec;24(12):273-289. doi: 10.1007/s11892-024-01554-2. Epub 2024 Sep 26. PMID- 39322970 OWN - NLM STAT- MEDLINE DCOM- 20250127 LR - 20250711 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 40 IP - 1 DP - 2025 Jan TI - Influence of glucagon-like peptide-1 receptor agonists on hepatic events in type 2 diabetes: a systematic review and meta-analysis. PG - 67-77 LID - 10.1111/jgh.16752 [doi] AB - BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is intrinsically linked to various etiologies of liver disease, with 69% of patients having concomitant metabolic dysfunction-associated steatotic liver disease (MASLD). Studies suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorating liver disease. With this analysis, we address the gap in knowledge about the effectiveness of these agents in preventing different major adverse liver outcomes (MALOs). METHODS: PubMed, Embase, and The Cochrane Central of Trials were searched for articles reporting MALOs in T2DM patients. Publication bias-identifying methods, quality assessment and sensitivity analyses (subgroup analyses, leave-one-out meta-analyses, and meta-regression) were employed. Statistical analyses were performed in R using the "meta" and "metafor" packages. RESULTS: Nine cohort studies from 535 identified articles encompassing 579 256 T2DM patients were included in the main analyses. GLP-1RA use was associated with reduced risks of hepatocellular carcinoma (HR 0.74, 95% CI 0.56-0.96) and cirrhosis decompensation (HR 0.68, 95% CI 0.65-0.72). Within the latter, variceal bleeding and hepatic encephalopathy prevention were found to be significantly reduced. Egger's test, Begg's test, and funnel-plot analysis yielded no publication bias. No significant differences were observed in preventing cirrhosis or hepatic failure. Meta-regression analysis revealed a positive correlation between hepatocellular carcinoma incidence and both male sex and longer follow-up duration. CONCLUSIONS: This meta-analysis improves our understanding of the hepatoprotective effects of GLP-1RAs in T2DM patients and supports existing research, exhibiting superiority over other antidiabetic medications for hepatoprotection in this subgroup. Additional long-term follow-up studies are necessary to further validate these findings. CI - (c) 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Passos, Pedro Robson Costa AU - Passos PRC AUID- ORCID: 0009-0007-9049-0996 AD - Center of Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil. FAU - Filho, Valbert Oliveira Costa AU - Filho VOC AUID- ORCID: 0009-0003-2864-0966 AD - Biomedical Research Center (NUBIMED), Federal University of Ceara, Fortaleza, Ceara, Brazil. FAU - Noronha, Mariana Macambira AU - Noronha MM AUID- ORCID: 0000-0003-0889-7425 AD - Biomedical Research Center (NUBIMED), Federal University of Ceara, Fortaleza, Ceara, Brazil. FAU - Hyppolito, Elodie Bomfim AU - Hyppolito EB AUID- ORCID: 0000-0002-6622-6585 AD - Walter Cantidio University Hospital (HUWC), Fortaleza, Ceara, Brazil. FAU - Saldanha, Erick Figueiredo AU - Saldanha EF AUID- ORCID: 0000-0001-7972-4244 AD - Division of Medical Oncology and Hematology, Princess Mzargaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. FAU - Motta, Rodrigo Vieira AU - Motta RV AUID- ORCID: 0000-0002-6633-9133 AD - Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240925 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Liver Neoplasms/prevention & control/etiology/epidemiology MH - Carcinoma, Hepatocellular/prevention & control/etiology/epidemiology MH - Male MH - Liver Cirrhosis/prevention & control/etiology MH - Female MH - *Liver Diseases/prevention & control/etiology OTO - NOTNLM OT - hepatocellular carcinoma OT - liver cirrhosis OT - metabolic dysfunction-associated steatotic liver disease OT - type 2 diabetes EDAT- 2024/09/26 00:42 MHDA- 2025/01/27 06:20 CRDT- 2024/09/25 23:42 PHST- 2024/09/04 00:00 [revised] PHST- 2024/07/03 00:00 [received] PHST- 2024/09/11 00:00 [accepted] PHST- 2025/01/27 06:20 [medline] PHST- 2024/09/26 00:42 [pubmed] PHST- 2024/09/25 23:42 [entrez] AID - 10.1111/jgh.16752 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2025 Jan;40(1):67-77. doi: 10.1111/jgh.16752. Epub 2024 Sep 25. PMID- 39322888 OWN - NLM STAT- MEDLINE DCOM- 20240925 LR - 20260805 IS - 1613-3560 (Electronic) IS - 1438-3276 (Linking) VI - 166 IP - 16 DP - 2024 Oct TI - [Not Available]. PG - 30 LID - 10.1007/s15006-024-4310-8 [doi] FAU - Rogal, Kristina AU - Rogal K AD - ZIEL - Institute for Food & Health, Technische Universitat Munchen, Gregor-Mendel-Str. 2, 85354, Freising, Deutschland. LA - ger PT - Comment PT - Journal Article TT - Schilddrusenkarzinome wegen GLP-1-RA? PL - Germany TA - MMW Fortschr Med JT - MMW Fortschritte der Medizin JID - 100893959 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CON - Diabetes Obes Metab. 2024 Mar;26(3):891-900. doi: 10.1111/dom.15382. PMID: 38018310 MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - *Thyroid Neoplasms/pathology/diagnosis MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/09/26 00:42 MHDA- 2024/09/26 00:43 CRDT- 2024/09/25 23:23 PHST- 2024/09/26 00:43 [medline] PHST- 2024/09/26 00:42 [pubmed] PHST- 2024/09/25 23:23 [entrez] AID - 10.1007/s15006-024-4310-8 [pii] AID - 10.1007/s15006-024-4310-8 [doi] PST - ppublish SO - MMW Fortschr Med. 2024 Oct;166(16):30. doi: 10.1007/s15006-024-4310-8. PMID- 39320894 OWN - NLM STAT- MEDLINE DCOM- 20240925 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 9 DP - 2024 Sep 3 TI - Semaglutide and Opioid Overdose Risk in Patients With Type 2 Diabetes and Opioid Use Disorder. PG - e2435247 LID - 10.1001/jamanetworkopen.2024.35247 [doi] LID - e2435247 FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. AD - Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland. FAU - Wang, QuangQiu AU - Wang Q AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Berger, Nathan A AU - Berger NA AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20240903 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Opiate Overdose/epidemiology MH - *Opioid-Related Disorders MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Adult MH - Semaglutide PMC - PMC11425147 OAB - This cohort study uses emulation target trial methods to evaluate whether semaglutide is associated with lower rates of opioid overdose among patients with type 2 diabetes (T2D) and opioid use disorder (OUD). OABL- eng COIS- Conflict of Interest Disclosures: None reported. EDAT- 2024/09/25 12:44 MHDA- 2024/09/25 18:59 PMCR- 2024/09/25 CRDT- 2024/09/25 11:33 PHST- 2024/09/25 18:59 [medline] PHST- 2024/09/25 12:44 [pubmed] PHST- 2024/09/25 11:33 [entrez] PHST- 2024/09/25 00:00 [pmc-release] AID - 2824054 [pii] AID - zld240158 [pii] AID - 10.1001/jamanetworkopen.2024.35247 [doi] PST - epublish SO - JAMA Netw Open. 2024 Sep 3;7(9):e2435247. doi: 10.1001/jamanetworkopen.2024.35247. PMID- 39316289 OWN - NLM STAT- MEDLINE DCOM- 20241015 LR - 20260317 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 41 IP - 11 DP - 2024 Nov TI - PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes. PG - 4266-4281 LID - 10.1007/s12325-024-02973-z [doi] AB - INTRODUCTION: Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. METHODS: The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34-44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA(1C)) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA(1C) < 7% (53 mmol/mol) at EOS and proportion of participants with >/= 1%-point HbA(1C) reduction and body weight reduction of >/= 3% or >/= 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. RESULTS: Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA(1C) by an estimated change of - 1.1%-points (95% CI - 1.27 to - 0.96; P < 0.0001) or - 12.2 mmol/mol (CI - 13.87 to - 10.47; P < 0.0001). Estimated change in body weight was - 4.8 kg (CI - 5.47 to - 4.12; P < 0.0001). At EOS, an HbA(1C) level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A >/= 1%-point reduction in HbA(1C) combined with a >/= 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a >/= 1%-point reduction in HbA(1C) and a >/= 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. CONCLUSION: People living with T2D in the UK experienced a meaningful decrease in HbA(1C) and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article. CI - (c) 2024. The Author(s). FAU - Saravanan, Ponnusamy AU - Saravanan P AUID- ORCID: 0000-0002-9566-2626 AD - Warwick Applied Health, Warwick Medical School, University of Warwick, Coventry, UK. P.Saravanan@warwick.ac.uk. AD - Department of Diabetes, Endocrinology and Metabolism, George Eliot Hospital NHS Trust, Nuneaton, UK. P.Saravanan@warwick.ac.uk. AD - Warwick Centre for Global Health, University of Warwick, Coventry, UK. P.Saravanan@warwick.ac.uk. FAU - Bell, Heather AU - Bell H AD - Old School Surgery, Greenisland, Northern Ireland, UK. FAU - Braae, Uffe Christian AU - Braae UC AUID- ORCID: 0000-0002-2743-4584 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Collins, Edward AU - Collins E AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Deinega, Alisa AU - Deinega A AUID- ORCID: 0000-0001-6314-0471 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Dhatariya, Ketan AU - Dhatariya K AUID- ORCID: 0000-0003-3619-9579 AD - Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. AD - Norwich Medical School, University of East Anglia, Norwich, UK. FAU - Machell, Alena AU - Machell A AUID- ORCID: 0009-0007-1962-6061 AD - Egremont Medical Centre, Wallasey, UK. FAU - Trent, Antonia AU - Trent A AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Strzelecka, Anna AU - Strzelecka A AD - Diabetic Services, Whiteabbey Hospital, Northern Health and Social Care Trust, Newtownabbey, UK. LA - eng SI - ClinicalTrials.gov/NCT04862923 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20240924 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Administration Schedule MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Glycated Hemoglobin/analysis/drug effects MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Patient Satisfaction MH - Prospective Studies MH - Treatment Outcome MH - United Kingdom MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11480173 OAB - PIONEER REAL UK investigated the use of a tablet form of the medicine semaglutide in people living with type 2 diabetes in the UK. The purpose was to determine how well the tablet works for blood sugar control and weight loss in everyday clinical practice. The study followed 333 participants whose doctors had given them semaglutide tablets. Their blood sugar levels and body weight were measured before and after taking the semaglutide tablet for 34-44 weeks. The participants were also asked to fill out questionnaires about their treatment satisfaction and how it changed when taking the semaglutide tablet. The participants' blood sugar levels dropped a lot, and body weight was lowered by an average of 4.8 kg during the 34-44 weeks of the study. The participants were also more satisfied with their treatment at the end of the study than before taking the semaglutide tablet. Doctors treating the participants found the treatment to be a success in more than two-thirds of participants. The study also found that the semaglutide tablet was not associated with cases of too low blood sugar and was generally well tolerated. In summary, the semaglutide tablet is a good option for people living with type 2 diabetes who need better blood sugar control and would benefit from weight loss. The treatment is generally well tolerated, and people are very satisfied with it. OABL- eng OTO - NOTNLM OT - Body weight OT - GLP-1 receptor agonist OT - Glucose-lowering medication OT - Glycaemic control OT - HbA1C OT - Incretin therapy OT - Real-world evidence OT - Semaglutide OT - Type 2 diabetes COIS- The authors disclose the following competing interests: Ponnusamy Saravanan: honoraria or travel support from Novo Nordisk and Abbott, UK; an unrestricted educational grant from Novo Nordisk A/S to set up an international Doctoral Training Partnership. Heather Bell: honoraria, travel support or fees for advisory boards from Abbott, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Menarini, Novo Nordisk, PCDS, Roche. Uffe Christian Braae: employee and shareholder of Novo Nordisk A/S. Edward Collins: employee and shareholder of Novo Nordisk A/S. Alisa Deinega: employee of Novo Nordisk A/S. Ketan Dhatariya: honoraria, travel support or fees for advisory boards from AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Eli Lilly, Abbott Diabetes, Menarini, Sanofi. Alena Machell: honoraria, travel support or fees for advisory boards from Novo Nordisk, Abbott. Antonia Trent: employee of Novo Nordisk A/S. Anna Strzelecka: honoraria from Astra Zeneca, Boehringer Ingelheim, Janssen, Lilly, MSD, Novo Nordisk, NAPP. EDAT- 2024/09/24 12:44 MHDA- 2024/10/15 12:24 PMCR- 2024/09/24 CRDT- 2024/09/24 11:23 PHST- 2024/07/17 00:00 [received] PHST- 2024/08/14 00:00 [accepted] PHST- 2024/10/15 12:24 [medline] PHST- 2024/09/24 12:44 [pubmed] PHST- 2024/09/24 11:23 [entrez] PHST- 2024/09/24 00:00 [pmc-release] AID - 10.1007/s12325-024-02973-z [pii] AID - 2973 [pii] AID - 10.1007/s12325-024-02973-z [doi] PST - ppublish SO - Adv Ther. 2024 Nov;41(11):4266-4281. doi: 10.1007/s12325-024-02973-z. Epub 2024 Sep 24. PMID- 39311884 OWN - NLM STAT- MEDLINE DCOM- 20240923 LR - 20260831 IS - 1550-5022 (Electronic) IS - 1078-4659 (Linking) VI - 30 IP - 6 DP - 2024 Nov-Dec 01 TI - What Is the Role of Public Health in the Era of GLP-1 Receptor Agonists. PG - 775-776 LID - 10.1097/PHH.0000000000002064 [doi] FAU - Moore, Justin B AU - Moore JB AUID- ORCID: 0000-0003-4059-0538 AD - Author Affiliation: Department of Implementation Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina. LA - eng PT - Journal Article DEP - 20240920 PL - United States TA - J Public Health Manag Pract JT - Journal of public health management and practice : JPHMP JID - 9505213 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Public Health/methods/trends MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- The authors declare no conflicts of interest. EDAT- 2024/09/23 12:48 MHDA- 2024/09/23 12:49 CRDT- 2024/09/23 11:03 PHST- 2024/09/23 12:49 [medline] PHST- 2024/09/23 12:48 [pubmed] PHST- 2024/09/23 11:03 [entrez] AID - 00124784-202411000-00001 [pii] AID - 10.1097/PHH.0000000000002064 [doi] PST - ppublish SO - J Public Health Manag Pract. 2024 Nov-Dec 01;30(6):775-776. doi: 10.1097/PHH.0000000000002064. Epub 2024 Sep 20. PMID- 39309109 OWN - NLM STAT- MEDLINE DCOM- 20240923 LR - 20261019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Non-functional alpha-cell hyperplasia with glucagon-producing NET: a case report. PG - 1405835 LID - 10.3389/fendo.2024.1405835 [doi] LID - 1405835 AB - INTRODUCTION: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented. CASE REPORT: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and (68)Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative (68)Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis. DISCUSSION AND CONCLUSION: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome. CI - Copyright (c) 2024 Cidade-Rodrigues, Santos, Calheiros, Santos, Matos, Moreira, Inacio, Souteiro, Oliveira, Jacome, Pereira, Henrique, Torres and Monteiro. FAU - Cidade-Rodrigues, Catarina AU - Cidade-Rodrigues C AD - Hospital Padre Americo, Unidade Local de Saude do Tamega e Sousa, Penafiel, Portugal. FAU - Santos, Ana Paula AU - Santos AP AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. AD - Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal. FAU - Calheiros, Raquel AU - Calheiros R AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Santos, Sara AU - Santos S AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Matos, Catarina AU - Matos C AD - Hospital de Braga, Unidade Local de Saude de Braga, Braga, Portugal. FAU - Moreira, Ana Paula AU - Moreira AP AD - Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal. FAU - Inacio, Isabel AU - Inacio I AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Souteiro, Pedro AU - Souteiro P AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Oliveira, Joana AU - Oliveira J AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Jacome, Manuel AU - Jacome M AD - Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Pereira, Sofia S AU - Pereira SS AD - Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. AD - Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal. FAU - Henrique, Rui AU - Henrique R AD - Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal. AD - Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. AD - Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. FAU - Torres, Isabel AU - Torres I AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Monteiro, Mariana P AU - Monteiro MP AD - Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. AD - Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240906 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 9007-92-5 (Glucagon) SB - IM MH - Humans MH - Male MH - Aged MH - *Hyperplasia/metabolism/pathology MH - *Glucagon-Secreting Cells/metabolism/pathology MH - *Glucagon/metabolism MH - *Neuroendocrine Tumors/metabolism/pathology/diagnosis MH - *Pancreatic Neoplasms/metabolism/pathology/diagnosis MH - Diabetes Mellitus, Type 2/metabolism/complications PMC - PMC11412808 OTO - NOTNLM OT - alpha-cell OT - glucagon-producing NET OT - hyperplasia OT - neuroendocrine tumors OT - pancreas COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2024/09/23 07:29 MHDA- 2024/09/23 12:48 PMCR- 2024/01/01 CRDT- 2024/09/23 05:43 PHST- 2024/03/23 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/09/23 12:48 [medline] PHST- 2024/09/23 07:29 [pubmed] PHST- 2024/09/23 05:43 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1405835 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Sep 6;15:1405835. doi: 10.3389/fendo.2024.1405835. eCollection 2024. PMID- 39302577 OWN - NLM STAT- MEDLINE DCOM- 20250131 LR - 20261010 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 48 IP - 2 DP - 2025 Feb TI - Comparative outcomes of systemic diseases in people with type 2 diabetes, or obesity alone treated with and without GLP-1 receptor agonists: a retrospective cohort study from the Global Collaborative Network : Author list. PG - 483-497 LID - 10.1007/s40618-024-02466-4 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored. OBJECTIVE: This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity. METHODS: We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers. RESULTS: In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001). CONCLUSIONS: GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms. CI - (c) 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Nassar, Mahmoud AU - Nassar M AUID- ORCID: 0000-0002-5401-9562 AD - Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA. Dr.Nassar@Aucegypt.edu. FAU - Nassar, Omar AU - Nassar O AD - Williamsville East High School, Buffalo, NY, USA. FAU - Abosheaishaa, Hazem AU - Abosheaishaa H AD - Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Misra, Anoop AU - Misra A AD - Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India. AD - National Diabetes, Obesity and Cholesterol Foundation (N-DOC), New Delhi, India. AD - Diabetes Foundation (India) (DFI) India, New Delhi, India. LA - eng PT - Comparative Study PT - Journal Article DEP - 20240920 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications/epidemiology MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Follow-Up Studies MH - Treatment Outcome MH - Adult OTO - NOTNLM OT - Bronchial asthma OT - Crohn's disease OT - Dementia OT - Lupus OT - Obesity OT - Osteoporosis. OT - Pancreatic cancer OT - Retrospective cohort study OT - Rheumatoid arthritis OT - Systemic diseases OT - Systemic sclerosis OT - TriNetX OT - Type 2 diabetes OT - Ulcerative colitis COIS- Declarations. Conflict of Interest Statement: On behalf of all authors, the corresponding author states that there is no conflict of interest. EDAT- 2024/09/20 13:00 MHDA- 2025/01/31 12:24 CRDT- 2024/09/20 11:20 PHST- 2024/06/26 00:00 [received] PHST- 2024/09/04 00:00 [accepted] PHST- 2025/01/31 12:24 [medline] PHST- 2024/09/20 13:00 [pubmed] PHST- 2024/09/20 11:20 [entrez] AID - 10.1007/s40618-024-02466-4 [pii] AID - 10.1007/s40618-024-02466-4 [doi] PST - ppublish SO - J Endocrinol Invest. 2025 Feb;48(2):483-497. doi: 10.1007/s40618-024-02466-4. Epub 2024 Sep 20. PMID- 39295084 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Glycaemic and weight effects of metabolic surgery or semaglutide in diabetes dosage for patients with type 2 diabetes. PG - 5812-5818 LID - 10.1111/dom.15952 [doi] AB - AIM: To compare weight and glucometabolic outcomes of semaglutide and metabolic and bariatric surgery (MBS) for patients with type 2 diabetes and obesity. MATERIALS AND METHODS: Patients treated with either semaglutide for a duration of >/=2 years or MBS in Sweden were identified within the Scandinavian Obesity Surgery Registry and the National Diabetes Registry and matched in a 1:1-2 ratio using a propensity score matching with a generalized linear model, including age, sex, glycated haemoglobin before treatment, duration of type 2 diabetes, use of insulin, presence of comorbidities and history of cancer, with good matching results but with a remaining imbalance for glomerular filtration rate and body mass index, which were then adjusted for in the following analyses. Main outcomes were weight loss and glycaemic control. RESULTS: The study included 606 patients in the surgical group matched to 997 controls who started their treatment from 2018 until 2020. Both groups improved in weight and glucometabolic control. At 2 years after the intervention, mean glycated haemoglobin was 42.3 +/- 11.18 after MBS compared with 50.7 +/- 12.48 after semaglutide treatment (p < 0.001) with 382 patients (63.0%) and 139 (13.9%), respectively, reaching complete remission without other treatment than the intervention (p < 0.001). Mean total weight loss reached 26.4% +/- 8.83% after MBS compared with 5.2% +/- 7.87% after semaglutide (p < 0.001). CONCLUSION: Semaglutide and MBS were both associated with improvements in weight and improved glycaemic control at 2 years after the start of the intervention, but MBS was associated with better weight loss and glucometabolic control. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Stenberg, Erik AU - Stenberg E AUID- ORCID: 0000-0001-9189-0093 AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Cao, Yang AU - Cao Y AUID- ORCID: 0000-0002-3552-9153 AD - Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. AD - Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Ottosson, Johan AU - Ottosson J AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Hedberg, Suzanne AU - Hedberg S AD - Department of Surgery (Ostra Sjukhuset), Sahlgrenska University Hospital, Gothenburg, Sweden. AD - Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Naslund, Erik AU - Naslund E AD - Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. LA - eng GR - Stockholm Lans Landsting/ GR - Strategic Research Programme in Diabetes/ GR - OLL-939106/Region Orebro Lan/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240918 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Weight Loss/drug effects MH - *Bariatric Surgery MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Blood Glucose/metabolism/drug effects MH - Adult MH - Sweden/epidemiology MH - Glycemic Control/methods MH - Obesity/surgery/complications MH - Registries MH - Treatment Outcome MH - Aged MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - bariatric surgery OT - cohort study OT - glucagon-like peptide-1 OT - glycaemic control OT - weight management EDAT- 2024/09/19 06:42 MHDA- 2024/11/04 12:23 CRDT- 2024/09/19 01:03 PHST- 2024/08/22 00:00 [revised] PHST- 2024/07/22 00:00 [received] PHST- 2024/08/31 00:00 [accepted] PHST- 2024/11/04 12:23 [medline] PHST- 2024/09/19 06:42 [pubmed] PHST- 2024/09/19 01:03 [entrez] AID - 10.1111/dom.15952 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5812-5818. doi: 10.1111/dom.15952. Epub 2024 Sep 18. PMID- 39293069 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260429 IS - 1536-3708 (Electronic) IS - 0148-7043 (Linking) VI - 94 IP - 1 DP - 2025 Jan 1 TI - Glucagon-Like Peptide-1 Agonists: A Practical Overview for Plastic and Reconstructive Surgeons. PG - 121-127 LID - 10.1097/SAP.0000000000004089 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, effectively manage type 2 diabetes by promoting insulin release, suppressing glucagon secretion, and enhancing glucose metabolism. They also aid weight reduction and cardiovascular health, potentially broadening their therapeutic scope. In plastic surgery, they hold promise for perioperative weight management and glycemic control, potentially impacting surgical outcomes. METHODS: A comprehensive review was conducted to assess GLP-1 agonists' utilization in plastic surgery. We analyzed relevant studies, meta-analyses, and trials to evaluate their benefits and limitations across surgical contexts, focusing on weight reduction, glycemic control, cardiovascular risk factors, and potential complications. RESULTS: Studies demonstrate GLP-1 agonists' versatility, spanning weight management, cardiovascular health, neurological disorders, and metabolic dysfunction-associated liver diseases. Comparative analyses highlight variations in glycemic control, weight loss, and cardiometabolic risk. Meta-analyses reveal significant reductions in hemoglobin A1C levels, especially with high-dose semaglutide (2 mg) and tirzepatide (15 mg). However, increased dosing may lead to gastrointestinal side effects and serious complications like pancreatitis and bowel obstruction. Notably, GLP-1 agonists' efficacy in weight reduction and glycemic control may impact perioperative management in plastic surgery, potentially expanding surgical candidacy for procedures like autologous flap-based breast reconstruction and influencing outcomes related to lymphedema. Concerns persist regarding venous thromboembolism and delayed gastric emptying, necessitating further investigation into bleeding and aspiration risk with anesthesia. CONCLUSIONS: GLP-1 agonists offer advantages in perioperative weight management and glycemic control in plastic surgery patients. They may broaden surgical candidacy and mitigate lymphedema risk but require careful consideration of complications, particularly perioperative aspiration risk. Future research should focus on their specific impacts on surgical outcomes to optimize their integration into perioperative protocols effectively. Despite challenges, GLP-1 agonists promise to enhance surgical outcomes and patient care in plastic surgery. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Stanton, Eloise W AU - Stanton EW AUID- ORCID: 0000-0003-0063-8584 FAU - Manasyan, Artur AU - Manasyan A AD - From the Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Banerjee, Rakhi AU - Banerjee R AD - From the Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Hong, Kurt AU - Hong K AD - Division of Internal Medicine, Keck School of Medicine of USC, Los Angeles, CA. FAU - Koesters, Emma AU - Koesters E FAU - Daar, David A AU - Daar DA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240904 PL - United States TA - Ann Plast Surg JT - Annals of plastic surgery JID - 7805336 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/agonists MH - Plastic Surgery Procedures/methods MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Weight Loss COIS- Conflicts of interest and sources of funding: none declared. EDAT- 2024/09/18 18:45 MHDA- 2024/12/12 12:28 CRDT- 2024/09/18 17:03 PHST- 2024/12/12 12:28 [medline] PHST- 2024/09/18 18:45 [pubmed] PHST- 2024/09/18 17:03 [entrez] AID - 00000637-990000000-00551 [pii] AID - 10.1097/SAP.0000000000004089 [doi] PST - ppublish SO - Ann Plast Surg. 2025 Jan 1;94(1):121-127. doi: 10.1097/SAP.0000000000004089. Epub 2024 Sep 4. PMID- 39292847 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260127 IS - 1536-3686 (Electronic) IS - 1075-2765 (Linking) VI - 31 IP - 5 DP - 2024 Sep-Oct 01 TI - Mazdutide Versus Dulaglutide for Weight Loss and Diabetes Management: Meta-Analysis of Randomized Clinical Trials. PG - e619-e622 LID - 10.1097/MJT.0000000000001756 [doi] FAU - Ayesh, Hazem AU - Ayesh H AUID- ORCID: 0000-0001-8231-705 AD - Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN. FAU - Ayesh, Suhail AU - Ayesh S AD - Gene Medical Labs, Gaza, Palestine. FAU - Niswender, Kevin AU - Niswender K AD - Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN. LA - eng PT - Comparative Study PT - Letter PT - Meta-Analysis PL - United States TA - Am J Ther JT - American journal of therapeutics JID - 9441347 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - WTT295HSY5 (dulaglutide) RN - MB76Z4IBZ5 (mazdutide) RN - 0 (Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Peptides COIS- The authors have no conflicts of interest to declare. EDAT- 2024/09/18 18:45 MHDA- 2024/09/18 18:46 CRDT- 2024/09/18 14:23 PHST- 2024/09/18 18:46 [medline] PHST- 2024/09/18 18:45 [pubmed] PHST- 2024/09/18 14:23 [entrez] AID - 00045391-202410000-00024 [pii] AID - 10.1097/MJT.0000000000001756 [doi] PST - ppublish SO - Am J Ther. 2024 Sep-Oct 01;31(5):e619-e622. doi: 10.1097/MJT.0000000000001756. PMID- 39291515 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20250103 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 72 IP - 9 DP - 2024 Sep TI - Improved Clinical Outcomes with the Combination Therapy of a Glucagon-like Peptide-1 Receptor Agonists and a Sodium-glucose Cotransporter-2 Inhibitor in Overweight/Obese People with Type 2 Diabetes: Real-world Evidence from the Indian Subcontinent. PG - 37-42 LID - 10.59556/japi.72.0644 [doi] AB - OBJECTIVE: Type 2 diabetes (T2D) mellitus is increasing exponentially in India, with overweight/obesity being prime contributors. This study aimed at assessing the clinical impact of the combination therapy of a glucagon-like peptide-1 receptor agonist (GLP-1RA) injection (inj.) and a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in overweight/obese patients from the Indian subcontinent. METHODS: In two real-world evidence (RWE) studies (RWE1 and 2), we retrospectively observed the effect of the combination therapy of a GLP-1RA, injection dulaglutide (DU) 1.5 mg/week, and an SGLT-2i, canagliflozin (CAN) 100 mg/day at weeks 16, 32, and 52 on HbA1c, body weight (weight), systolic blood pressure (SBP), lipids, change in doses of antidiabetic agents (ADA) and antihypertensive agents (AHA) in overweight/obese Asian Indian subjects with T2D, who had suboptimal glycemic control. RESULTS: A total of 95 T2D patients [51 males (M), 44 females (F)] completed the two RWE studies. In RWE 1, 40 patients (20 M/20 F), mean [standard deviation (SD)] age 49.4 (10.7) years (Y), weight 92.6 (6.6) kg, body mass index (BMI) 30.6 (2.3) kg/m(2), duration of T2D 8.1 (3.2) Y, completed the study. At week 32, the mean (SD) reduction in A1c (%) was -1.3% [8.4 (0.7) to 7.1 (0.3); p < 0.01] and mean (SD) weight (kg) loss was -5.5 [92.6 (6.6) to 87.9 (7.02); p < 0.00001]. This group was then followed up until week 52. In RWE 2, 55 patients (31 M/24 F), age 51 (5.8) Y, weight 92.6 +/- 3.4 kg, BMI 31.1 +/- 2.1 kg/m(2), SBP 142.4 +/- 3.9 mm Hg, estimated glomerular filtration rate (eGFR) 62 +/- 5 mL/minute/1.73 m(2), with 8.4 +/- 3.3 Y duration of diabetes met the inclusion criteria. In 71% of subjects, A1c decreased by -1.4% [8.5 +/- 0.4 to 7.1 +/- 0.2; p < 0.0001] at week 16 and was 6.8 +/- 0.3 (p = 0.0002) in 18% at week 32. CONCLUSION: A statistically significant (SS) improvement in glycemic control, weight, and improvement in cardiovascular (CV) risk factors was observed with the GLP-1RA/SGLT-2i combination, which was well tolerated. CI - (c) Journal of the Association of Physicians of India 2024. FAU - Nigam, Anant AU - Nigam A AD - Director, Nigam Diabetes Center, Jaipur, Rajasthan, India, Corresponding Author. LA - eng PT - Journal Article PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0SAC974Z85 (Canagliflozin) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Middle Aged MH - India MH - *Drug Therapy, Combination MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Canagliflozin/therapeutic use/administration & dosage MH - Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Adult MH - Retrospective Studies MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments EDAT- 2024/09/18 06:42 MHDA- 2024/09/18 12:51 CRDT- 2024/09/18 05:42 PHST- 2024/09/18 12:51 [medline] PHST- 2024/09/18 06:42 [pubmed] PHST- 2024/09/18 05:42 [entrez] AID - 10.59556/japi.72.0644 [doi] PST - ppublish SO - J Assoc Physicians India. 2024 Sep;72(9):37-42. doi: 10.59556/japi.72.0644. PMID- 39289244 OWN - NLM STAT- MEDLINE DCOM- 20250423 LR - 20261010 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 87 IP - 2 DP - 2025 Feb TI - The possible effect of anti-diabetic agents GLP-1RA and SGLT-2i on the respiratory system function. PG - 378-388 LID - 10.1007/s12020-024-04033-6 [doi] AB - Type 2 Diabetes (T2D) is a chronic disease with increasing incidence and prevalence and serious chronic complications, especially from cardiovascular system. However, other organs can be affected too. Several studies have associated T2D, especially when poorly controlled, with multiple pulmonary diseases. T2D is a common comorbidity among patients with asthma, Chronic Obstructive Pulmonary Disease (COPD), and Obstructive Sleep Apnea Syndrome (OSAS), and it is related to higher respiratory infection incidence, prevalence and severity. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are novel antihyperglycaemic agents with established cardiovascular benefits. There are also limited studies indicating their potential benefit in respiratory function. The aim of this article is to review data on the impact of GLP-1RA and SGLT-2i on respiratory function and describe the possible clinical benefits. Key findings indicate that GLP-1RA significantly improve lung function in patients with COPD, evidenced by improvements in spirometry measurements. Additionally, both GLP-1RA and SGLT-2i are associated with a decreased risk of severe and moderate exacerbations in COPD patients and have shown potential in reducing the incidence of respiratory disorders, including asthma and pneumonia. The mechanisms underlying these benefits are not yet fully understood and include multiple effects, such as anti-inflammatory action and oxidative stress reduction. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Kantreva, Kanella AU - Kantreva K AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. AD - Department of Endocrinology, Diabetes Centre, Endo ERN member, Evangelismos General Hospital, Athens, Greece. FAU - Katsaounou, Paraskevi AU - Katsaounou P AD - Department of Critical Care Medicine, Evangelismos Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Saltiki, Katerina AU - Saltiki K AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Trakada, Georgia AU - Trakada G AD - Respiratory Medicine Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Ntali, Georgia AU - Ntali G AD - Department of Endocrinology, Diabetes Centre, Endo ERN member, Evangelismos General Hospital, Athens, Greece. FAU - Stratigou, Theodora AU - Stratigou T AD - Department of Endocrinology, Diabetes Centre, Endo ERN member, Evangelismos General Hospital, Athens, Greece. FAU - Tzanela, Marinella AU - Tzanela M AD - Department of Endocrinology, Diabetes Centre, Endo ERN member, Evangelismos General Hospital, Athens, Greece. FAU - Psaltopoulou, Theodora AU - Psaltopoulou T AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. FAU - Paschou, Stavroula A AU - Paschou SA AD - Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. s.a.paschou@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20240917 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Pulmonary Disease, Chronic Obstructive/drug therapy MH - *Respiratory System/drug effects/physiopathology OTO - NOTNLM OT - Diabetes OT - GLP-1RA OT - Lungs OT - Pulmonary function OT - SGLT-2i COIS- Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. EDAT- 2024/09/18 00:48 MHDA- 2025/02/10 12:23 CRDT- 2024/09/17 23:14 PHST- 2024/05/14 00:00 [received] PHST- 2024/09/03 00:00 [accepted] PHST- 2025/02/10 12:23 [medline] PHST- 2024/09/18 00:48 [pubmed] PHST- 2024/09/17 23:14 [entrez] AID - 10.1007/s12020-024-04033-6 [pii] AID - 10.1007/s12020-024-04033-6 [doi] PST - ppublish SO - Endocrine. 2025 Feb;87(2):378-388. doi: 10.1007/s12020-024-04033-6. Epub 2024 Sep 17. PMID- 39284788 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20250807 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Treatment trajectories for Danish individuals with type 2 diabetes in the era of emerging glucose-lowering therapies. PG - 4996-5004 LID - 10.1111/dom.15912 [doi] AB - AIM: To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023. MATERIALS AND METHODS: We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes. RESULTS: We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively. CONCLUSIONS: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Andersen, Jacob H AU - Andersen JH AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Sondergaard, Jens AU - Sondergaard J AD - Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense and Esbjerg, Denmark. FAU - Rasmussen, Lotte AU - Rasmussen L AUID- ORCID: 0000-0001-5962-6647 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Kildegaard, Helene AU - Kildegaard H AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Research, Steno Diabetes Centre Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Thomsen, Reimar W AU - Thomsen RW AD - Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark. LA - eng GR - Novo Nordisk (unrestricted grant)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Denmark/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - *Metformin/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Registries MH - Glycated Hemoglobin/analysis/metabolism MH - Blood Glucose/drug effects/metabolism MH - Adult MH - Insulin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - antidiabetic drug OT - database research OT - pharmaco-epidemiology OT - type 2 diabetes EDAT- 2024/09/17 10:43 MHDA- 2024/10/04 12:43 CRDT- 2024/09/16 22:42 PHST- 2024/08/08 00:00 [revised] PHST- 2024/06/12 00:00 [received] PHST- 2024/08/15 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/17 10:43 [pubmed] PHST- 2024/09/16 22:42 [entrez] AID - 10.1111/dom.15912 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4996-5004. doi: 10.1111/dom.15912. Epub 2024 Sep 16. PMID- 39284357 OWN - NLM STAT- MEDLINE DCOM- 20240916 LR - 20251001 IS - 1439-3999 (Electronic) IS - 0023-2165 (Linking) VI - 241 IP - 9 DP - 2024 Sep TI - Glucagon-like Peptide 1 Receptor Agonist: Balancing Alarm and Caution. PG - 1021-1022 LID - 10.1055/a-2369-9085 [doi] FAU - Ziemssen, Focke AU - Ziemssen F AUID- ORCID: 0000-0002-3873-0581 FAU - Hammes, Hans-Peter AU - Hammes HP AUID- ORCID: 0000-0003-3456-1757 FAU - Helbig, Horst AU - Helbig H LA - eng LA - ger PT - Editorial TT - GLP-1-Rezeptoragonisten: Im Spannungsfeld zwischen Vorsicht und Alarm. DEP - 20240916 PL - Germany TA - Klin Monbl Augenheilkd JT - Klinische Monatsblatter fur Augenheilkunde JID - 0014133 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Focke Ziemssen hat Honorare fur Beratungs- und Referententatigkeit von Abbvie/Allergan, Alimera, Apellis, Bayer Healthcare, Biogen, Boehringer, Johnson & Johnson, NovoNordisk, Novartis, MSD Sharp & Dohme, Sanofi, Stada and Roche/Genentech. Studientatigkeit wurde von Acelyrin, Clearside, Kodiak, Johnson & Johnson, Novartis, Regeneron, Roche und Sandoz finanziert. Horst Helbig hat fur Referentatigkeit und Advisory Boards Honorare von Abbvie/Allergan, Alcon, Apellis, Astellas, Bayer, Novartis, Roche and Theapharm erhalten./Focke Ziemssen received lecture fees and consultation honoraria from Abbvie/Allergan, Alimera, Apellis, Bayer Healthcare, Biogen, Boehringer, Johnson & Johnson, NovoNordisk, Novartis, MSD Sharp & Dohme, Sanofi, Stada and Roche/Genentech. Study financing was provided by Acelyrin, Clearside, Kodiak, Johnson & Johnson, Novartis, Regeneron, Roche and Sandoz. Horst Helbig received lecture fees and consultation honoraria from Abbvie/Allergan, Alcon, Apellis, Astellas, Bayer, Novartis, Roche and Theapharm. EDAT- 2024/09/17 10:44 MHDA- 2024/09/17 10:45 CRDT- 2024/09/16 19:03 PHST- 2024/09/17 10:45 [medline] PHST- 2024/09/17 10:44 [pubmed] PHST- 2024/09/16 19:03 [entrez] AID - 10.1055/a-2369-9085 [doi] PST - ppublish SO - Klin Monbl Augenheilkd. 2024 Sep;241(9):1021-1022. doi: 10.1055/a-2369-9085. Epub 2024 Sep 16. PMID- 39284335 OWN - NLM STAT- MEDLINE DCOM- 20240922 LR - 20260313 IS - 2666-7568 (Electronic) IS - 2666-7568 (Linking) VI - 5 IP - 9 DP - 2024 Sep TI - SGLT2 inhibitors and GLP-1 receptor agonists: which is the best anti-frailty drug? PG - 100632 LID - S2666-7568(24)00158-2 [pii] LID - 10.1016/j.lanhl.2024.08.001 [doi] FAU - Mone, Pasquale AU - Mone P AD - Department of Medicine and Health Sciences "Vincenzo Tiberio", Campobasso 86100, Italy; Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, USA; Casa di Cura Montevergine, Mercogliano (Avellino), Italy. Electronic address: pasquale.mone@unimol.it. FAU - Ciccarelli, Michele AU - Ciccarelli M AD - Department of Medicine, Surgery, and Dentistry, University of Salerno, Baronissi (Salerno), Italy. FAU - Jankauskas, Stanislovas S AU - Jankauskas SS AD - Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, USA. FAU - Guerra, Germano AU - Guerra G AD - Department of Medicine and Health Sciences "Vincenzo Tiberio", Campobasso 86100, Italy; International Translational Research and Medical Education Consortium (ITME), Academic Research Unit, Naples, Italy. FAU - Vecchione, Carmine AU - Vecchione C AD - Department of Medicine, Surgery, and Dentistry, University of Salerno, Baronissi (Salerno), Italy. FAU - Visco, Valeria AU - Visco V AD - Department of Medicine, Surgery, and Dentistry, University of Salerno, Baronissi (Salerno), Italy. FAU - Santulli, Gaetano AU - Santulli G AD - Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, USA; International Translational Research and Medical Education Consortium (ITME), Academic Research Unit, Naples, Italy; Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy. LA - eng GR - R01 DK123259/DK/NIDDK NIH HHS/United States GR - R01 HL146691/HL/NHLBI NIH HHS/United States PT - Comment PT - Journal Article DEP - 20240913 PL - England TA - Lancet Healthy Longev JT - The lancet. Healthy longevity JID - 101773309 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CON - Lancet Healthy Longev. 2024 Sep;5(9):100621. doi: 10.1016/j.lanhl.2024.07.004. PMID: 39284334 MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Frailty/drug therapy MH - Aged MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11472278 MID - NIHMS2024540 COIS- We declare no conflicting interests. EDAT- 2024/09/17 10:44 MHDA- 2024/09/23 04:20 PMCR- 2024/10/14 CRDT- 2024/09/16 18:53 PHST- 2024/07/25 00:00 [received] PHST- 2024/08/01 00:00 [revised] PHST- 2024/08/02 00:00 [accepted] PHST- 2024/09/23 04:20 [medline] PHST- 2024/09/17 10:44 [pubmed] PHST- 2024/09/16 18:53 [entrez] PHST- 2024/10/14 00:00 [pmc-release] AID - S2666-7568(24)00158-2 [pii] AID - 10.1016/j.lanhl.2024.08.001 [doi] PST - ppublish SO - Lancet Healthy Longev. 2024 Sep;5(9):100632. doi: 10.1016/j.lanhl.2024.08.001. Epub 2024 Sep 13. PMID- 39284334 OWN - NLM STAT- MEDLINE DCOM- 20240922 LR - 20260313 IS - 2666-7568 (Electronic) IS - 2666-7568 (Linking) VI - 5 IP - 9 DP - 2024 Sep TI - Effect of frailty on effectiveness and safety of GLP-1 receptor agonists versus SGLT2 inhibitors in people with type 2 diabetes in Taiwan: a retrospective, nationwide, longitudinal study. PG - 100621 LID - S2666-7568(24)00137-5 [pii] LID - 10.1016/j.lanhl.2024.07.004 [doi] AB - BACKGROUND: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status. METHODS: In this retrospective, nationwide, longitudinal study, we identified people (aged >/=20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model. FINDINGS: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57.7 years [SD 13.9], 11 338 [49.4%] were female, and 11 630 [50.6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58.8 years [12.3], 107 988 [42.0%] were female, and 149 207 [58.0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1.25 [95% CI 1.13-1.38]; p<0.0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2.43 [1.82-3.23]; p<0.0001), mild frailty (3.93 [3.03 -5.09]; p<0.0001), and moderate or severe frailty (2.60 [2.03-3.31]; p<0.0001) subgroups. INTERPRETATION: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes. FUNDING: Ministry of Education, Taiwan. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Hsiao, Fei-Yuan AU - Hsiao FY AD - Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. FAU - Tan, Elise Chia-Hui AU - Tan EC AD - Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan. FAU - Meng, Lin-Chieh AU - Meng LC AD - Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Yi-Chin AU - Lin YC AD - Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Chen, Ho-Min AU - Chen HM AD - Health Data Research Center, National Taiwan University, Taipei, Taiwan. FAU - Guan, Shang-Ting AU - Guan ST AD - Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Tarng, Der-Cherng AU - Tarng DC AD - Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Wang, Chih-Yuan AU - Wang CY AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Chen, Liang-Kung AU - Chen LK AD - Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; Taipei Municipal Gan-Dau Hospital (Managed by Taipei Veterans General Hospital), Taipei, Taiwan. Electronic address: lkchen2@vghtpe.gov.tw. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240913 PL - England TA - Lancet Healthy Longev JT - The lancet. Healthy longevity JID - 101773309 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Lancet Healthy Longev. 2024 Sep;5(9):100632. doi: 10.1016/j.lanhl.2024.08.001. PMID: 39284335 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Taiwan/epidemiology MH - Retrospective Studies MH - Longitudinal Studies MH - Middle Aged MH - Aged MH - *Frailty/epidemiology MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Declaration of interests F-YH, EC-HT, and C-YW have received a research grant, awarded to the National Taiwan University, from Novo Nordisk. All other authors declare no competing interests. EDAT- 2024/09/17 10:47 MHDA- 2024/09/23 03:01 CRDT- 2024/09/16 18:53 PHST- 2024/02/20 00:00 [received] PHST- 2024/07/01 00:00 [revised] PHST- 2024/07/12 00:00 [accepted] PHST- 2024/09/23 03:01 [medline] PHST- 2024/09/17 10:47 [pubmed] PHST- 2024/09/16 18:53 [entrez] AID - S2666-7568(24)00137-5 [pii] AID - 10.1016/j.lanhl.2024.07.004 [doi] PST - ppublish SO - Lancet Healthy Longev. 2024 Sep;5(9):100621. doi: 10.1016/j.lanhl.2024.07.004. Epub 2024 Sep 13. PMID- 39283612 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260725 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 184 IP - 11 DP - 2024 Nov 1 TI - GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease. PG - 1314-1323 LID - 10.1001/jamainternmed.2024.4661 [doi] AB - IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD. OBJECTIVE: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first. EXPOSURES: Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline. MAIN OUTCOMES AND MEASURES: For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality. RESULTS: Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis. CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course. FAU - Kanwal, Fasiha AU - Kanwal F AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. AD - Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. AD - Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. FAU - Kramer, Jennifer R AU - Kramer JR AD - Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. FAU - Li, Liang AU - Li L AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston. FAU - Yang, Yu-Xiao AU - Yang YX AD - Center for Health Equity Research and Promotion, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. FAU - Cao, Yumei AU - Cao Y AD - Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. FAU - Yu, Xian AU - Yu X AD - Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. FAU - Samuel, Ronald AU - Samuel R AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. FAU - Ali, Basim AU - Ali B AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. FAU - Desiderio, Roxanne AU - Desiderio R AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. FAU - Cholankeril, George AU - Cholankeril G AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. FAU - Bajaj, Mandeep AU - Bajaj M AD - Section of Endocrinology, Baylor College of Medicine, Houston, Texas. FAU - El-Serag, Hashem B AU - El-Serag HB AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas. AD - Center for Innovations in Quality, Effectiveness and Safety (IQuESt), US Department of Veterans Affairs Health Services Research and Development Service, Houston, Texas. AD - Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. FAU - Asch, Steven M AU - Asch SM AD - Center for Innovation to Implementation (Ci2i), VA Palo Alto Health Care System, Palo Alto, California. AD - Division of Primary Care and Population Health, Department of Medicine, Stanford University, Stanford, California. LA - eng GR - P01 CA263025/CA/NCI NIH HHS/United States GR - P30 DK056338/DK/NIDDK NIH HHS/United States GR - R01 CA186566/CA/NCI NIH HHS/United States GR - U01 CA230997/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - *Liver Cirrhosis/complications MH - Middle Aged MH - Retrospective Studies MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - United States/epidemiology MH - Fatty Liver MH - Liver Neoplasms MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11406452 MID - NIHMS2023717 COIS- Conflict of Interest Disclosures: Dr Kramer reported grants from the National Institutes of Health during the conduct of the study. Dr Li reported grants from the National Institutes of Health during the conduct of the study. Dr Yang reported grants from AbbVie paid to the Philadelphia Research and Education Foundation, a nonprofit foundation supporting research at the Corporal Michael J. Crescenz VA Medical Center, outside the submitted work. Dr Asch reported grants from the US Department of Veterans Affairs during the conduct of the study. Dr El-Serag reported grants from Gilead, Merck, Wako, Glycotest, and the Cancer Prevention and Research Institute of Texas, as well as consulting fees from Madrigal Pharmaceuticals outside the submitted work. No other disclosures were reported. EDAT- 2024/09/17 10:43 MHDA- 2024/11/04 12:24 PMCR- 2025/09/16 CRDT- 2024/09/16 11:34 PHST- 2024/11/04 12:24 [medline] PHST- 2024/09/17 10:43 [pubmed] PHST- 2024/09/16 11:34 [entrez] PHST- 2025/09/16 00:00 [pmc-release] AID - 2823685 [pii] AID - ioi240059 [pii] AID - 10.1001/jamainternmed.2024.4661 [doi] PST - ppublish SO - JAMA Intern Med. 2024 Nov 1;184(11):1314-1323. doi: 10.1001/jamainternmed.2024.4661. PMID- 39282819 OWN - NLM STAT- MEDLINE DCOM- 20240916 LR - 20260612 IS - 1477-1128 (Electronic) IS - 1463-4236 (Print) IS - 1463-4236 (Linking) VI - 25 DP - 2024 Sep 16 TI - General practitioner and nurse experiences of type 2 diabetes management and prescribing in primary care: a qualitative review following the introduction of funded SGLT2i/GLP1RA medications in Aotearoa New Zealand. PG - e34 LID - 10.1017/S1463423624000264 [doi] LID - e34 AB - AIM: To explore the views of general practitioners (GPs) and nurses on type 2 diabetes (T2D) management, including the use of recently funded T2D medications in New Zealand (NZ) and their perceived barriers to providing optimal care. BACKGROUND: T2D is a significant health concern in NZ, particularly among Maori and Pacific adults. Characterised by prolonged hyperglycaemia, T2D is generally a progressive condition requiring long-term care. METHODS: Semi-structured interviews were conducted between July and December 2022 with 21 primary care clinicians (10 GPs and 11 nurses/nurse prescribers) from nine different general practice clinics across the Auckland and Waikato regions of NZ. Framework analysis was conducted to identify common themes in clinicians' perceptions and experiences with T2D management. FINDINGS: Three themes were identified: health-system factors, new medications, and solution-based approaches. Lack of clinician time, healthcare funding, staff shortages, and burn-out were identified as barriers to T2D management under health-system factors. The two newly funded medications, empagliflozin and dulaglutide, were deemed to be a positive change for T2D care in that they improved patient satisfaction and clinical outcomes, but several clinicians were hesitant to prescribe these medications. Participants suggested that additional education and specialist diabetes support would be helpful to inform optimal medication prescribing and that better use of a multi-disciplinary team (clinical and support staff) could support T2D care by reducing workload, addressing cultural gaps in healthcare delivery, and reducing burnout. An improved primary care work environment, including appropriate professional development to support prescribing of new medications and the value of collaboration with a non-regulated workforce, may be required to facilitate optimal T2D management in primary care. Future research should focus on interventions to increase support for both clinical teams and patients while adopting a culturally appropriate approach to increase patient satisfaction and improve health outcomes. FAU - Norman, Kimberley AU - Norman K AUID- ORCID: 0000-0003-4278-5451 AD - School of Primary and Allied Health Care, Monash University, Melbourne, Australia. FAU - Mustafa, Sara Tareq AU - Mustafa ST AUID- ORCID: 0000-0001-5902-5622 AD - Medical Research Centre, Te Huataki Waiora School of Health, University of Waikato, Hamilton, New Zealand. FAU - Cassim, Shemana AU - Cassim S AD - School of Psychology, Massey University, Auckland, New Zealand. FAU - Mullins, Hilde AU - Mullins H AD - Department of Nursing, Te Huataki Waiora School of Health, University of Waikato, Hamilton, New Zealand. FAU - Clark, Penny AU - Clark P AD - Northcare Medical Centre, Hamilton, New Zealand. FAU - Keenan, Rawiri AU - Keenan R AUID- ORCID: 0000-0001-8312-8525 AD - Medical Research Centre, Te Huataki Waiora School of Health, University of Waikato, Hamilton, New Zealand. FAU - Te Karu, Leanne AU - Te Karu L AUID- ORCID: 0000-0002-8645-3937 AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Murphy, Rinki AU - Murphy R AUID- ORCID: 0000-0002-0043-2423 AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Paul, Ryan AU - Paul R AD - Medical Research Centre, Te Huataki Waiora School of Health, University of Waikato, Hamilton, New Zealand. AD - Te Whatu Ora Health New Zealand, Hamilton, New Zealand. FAU - Kenealy, Tim AU - Kenealy T AD - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Chepulis, Lynne AU - Chepulis L AUID- ORCID: 0000-0002-9661-4669 AD - Medical Research Centre, Te Huataki Waiora School of Health, University of Waikato, Hamilton, New Zealand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Prim Health Care Res Dev JT - Primary health care research & development JID - 100897390 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Attitude of Health Personnel MH - *Diabetes Mellitus, Type 2/drug therapy MH - General Practitioners/psychology MH - Hypoglycemic Agents/therapeutic use MH - Interviews as Topic MH - New Zealand MH - Nurses/psychology MH - Practice Patterns, Physicians'/statistics & numerical data MH - Primary Health Care MH - Qualitative Research MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11464800 OTO - NOTNLM OT - medication OT - primary health care OT - qualitative research OT - type 2 diabetes COIS- None. EDAT- 2024/09/17 10:43 MHDA- 2024/09/17 10:44 PMCR- 2024/09/16 CRDT- 2024/09/16 06:53 PHST- 2024/09/17 10:44 [medline] PHST- 2024/09/17 10:43 [pubmed] PHST- 2024/09/16 06:53 [entrez] PHST- 2024/09/16 00:00 [pmc-release] AID - S1463423624000264 [pii] AID - 10.1017/S1463423624000264 [doi] PST - epublish SO - Prim Health Care Res Dev. 2024 Sep 16;25:e34. doi: 10.1017/S1463423624000264. PMID- 39279647 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Impact of baseline characteristics on the efficacy of once-weekly subcutaneous semaglutide among participants with type 2 diabetes: A post hoc analysis of SUSTAIN China. PG - 5312-5324 LID - 10.1111/dom.15888 [doi] AB - AIMS: To investigate the impact of baseline characteristics on the efficacy of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg in participants with type 2 diabetes (T2D) from the SUSTAIN China trial. METHODS: In this post hoc analysis, data for semaglutide 0.5 and 1.0 mg versus sitagliptin 100 mg were analysed in the total (n = 868) and Chinese-only (n = 605) populations. Changes from baseline to end of treatment (EOT) in glycated haemoglobin (HbA1c) and body weight were analysed by baseline age, sex, body mass index, HbA1c, diabetes duration, and homeostatic model assessment of beta-cell function (HOMA-beta) tertile. Proportions of participants achieving HbA1c <7.0% (53 mmol/mol) by baseline HbA1c, change from baseline to EOT in standard deviation of seven-point self-monitored plasma glucose (SMPG), derived time-in-range (dTIR) of seven-point SMPG at Week 30, and HOMA-beta ratio to baseline at Week 30 were assessed for both populations. RESULTS: In both populations the efficacy of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg versus sitagliptin was not significantly affected by most of the baseline characteristics studied. The proportion of participants achieving the target HbA1c <7% was not affected by baseline HbA1c (p(interaction) > 0.05). SMPG fluctuation and dTIR indicated less glucose variability in participants treated with semaglutide 0.5 and 1.0 mg versus sitagliptin, and the HOMA-beta ratios to baseline at EOT were greater with semaglutide 0.5 and 1.0 mg versus sitagliptin (p < 0.05). CONCLUSIONS: These results support the effectiveness of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg across a broad range of baseline characteristics, in participants with T2D from SUSTAIN China. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Peking University People's Hospital, Beijing, China. FAU - Lu, Yibing AU - Lu Y AD - The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Hu, Ping AU - Hu P AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Zhang, Qiu AU - Zhang Q AUID- ORCID: 0000-0002-0204-3528 AD - First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Shi, Bimin AU - Shi B AD - The First Affiliated Hospital of Soochow University, Jiangsu, China. LA - eng GR - Novo Nordisk Shanghai Ltd./ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - *Sitagliptin Phosphate/administration & dosage/therapeutic use MH - *Glycated Hemoglobin/analysis/drug effects MH - China/epidemiology MH - Injections, Subcutaneous MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Blood Glucose/drug effects MH - Treatment Outcome MH - Aged MH - Drug Administration Schedule MH - Double-Blind Method MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - glycaemic control OT - incretin therapy OT - type 2 diabetes EDAT- 2024/09/16 06:22 MHDA- 2024/10/04 12:42 CRDT- 2024/09/16 05:03 PHST- 2024/07/30 00:00 [revised] PHST- 2024/05/13 00:00 [received] PHST- 2024/08/04 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/16 06:22 [pubmed] PHST- 2024/09/16 05:03 [entrez] AID - 10.1111/dom.15888 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5312-5324. doi: 10.1111/dom.15888. Epub 2024 Sep 16. PMID- 39279639 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants. PG - 5805-5811 LID - 10.1111/dom.15951 [doi] AB - AIMS: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. MATERIALS AND METHODS: This was a double-blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once-weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time-matched change from baseline in Fridericia heart rate-corrected QT interval (QTcF) at 12-, 24-, 48- and 72 h after the last cagrilintide 4.5-mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two-sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400-mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross-over fashion. RESULTS: A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5-mg dose; the upper limits of the two-sided 90% CIs of the placebo-adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control. CONCLUSIONS: Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gabe, Maria B N AU - Gabe MBN AUID- ORCID: 0000-0003-2559-862X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Fuhr, Rainard AU - Fuhr R AD - Parexel International GmbH, Berlin, Germany. FAU - Sinn, Angela AU - Sinn A AD - Parexel International GmbH, Berlin, Germany. FAU - Eliasen, Astrid AU - Eliasen A AUID- ORCID: 0000-0002-2261-0323 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Berthelsen, Kasper K AU - Berthelsen KK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kuhlman, Anja B AU - Kuhlman AB AUID- ORCID: 0000-0001-8893-8498 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Nejad, Ayna B AU - Nejad AB AUID- ORCID: 0000-0003-4688-7877 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT05804162 GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - U188XYD42P (Moxifloxacin) RN - 0 (Islet Amyloid Polypeptide) RN - 53AXN4NNHX (Semaglutide) RN - AO43BIF1U8 (cagrilintide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Electrocardiography/drug effects MH - Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Healthy Volunteers MH - Heart Rate/drug effects MH - Hypoglycemic Agents/adverse effects/administration & dosage MH - Long QT Syndrome/chemically induced MH - Moxifloxacin/adverse effects/administration & dosage MH - *Islet Amyloid Polypeptide/adverse effects MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - antiobesity drug OT - clinical trial OT - drug development OT - randomized trial EDAT- 2024/09/16 06:22 MHDA- 2024/11/04 12:25 CRDT- 2024/09/16 05:03 PHST- 2024/08/27 00:00 [revised] PHST- 2024/07/30 00:00 [received] PHST- 2024/08/29 00:00 [accepted] PHST- 2024/11/04 12:25 [medline] PHST- 2024/09/16 06:22 [pubmed] PHST- 2024/09/16 05:03 [entrez] AID - 10.1111/dom.15951 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5805-5811. doi: 10.1111/dom.15951. Epub 2024 Sep 16. PMID- 39276017 OWN - NLM STAT- MEDLINE DCOM- 20240914 LR - 20260917 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 45 IP - 35 DP - 2024 Sep 14 TI - The fascinating story of lipid-lowering drugs, sodium-glucose co-transporter 2 inhibitors and GLP1-R agonists: new light shed on their beneficial effects. PG - 3187-3191 LID - 10.1093/eurheartj/ehae586 [doi] FAU - Crea, Filippo AU - Crea F AUID- ORCID: 0000-0002-9482-411X AD - Center of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy. AD - Catholic University of the Sacred Heart, Rome, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Hypolipidemic Agents/therapeutic use MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Cardiovascular Diseases/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/09/14 15:46 MHDA- 2024/09/14 15:47 CRDT- 2024/09/14 07:53 PHST- 2024/09/14 15:47 [medline] PHST- 2024/09/14 15:46 [pubmed] PHST- 2024/09/14 07:53 [entrez] AID - 7756980 [pii] AID - 10.1093/eurheartj/ehae586 [doi] PST - ppublish SO - Eur Heart J. 2024 Sep 14;45(35):3187-3191. doi: 10.1093/eurheartj/ehae586. PMID- 39271004 OWN - NLM STAT- MEDLINE DCOM- 20241204 LR - 20250714 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 50 IP - 6 DP - 2024 Nov TI - A very rare cause of markedly elevated CA 19-9: Glucagon-like peptide-1 receptor agonists. PG - 101578 LID - S1262-3636(24)00070-3 [pii] LID - 10.1016/j.diabet.2024.101578 [doi] AB - AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-RAs) are commonly used to treat type 2 diabetes mellitus (T2DM). Various adverse reactions have been gradually reported. This case presents a rare phenomenon in which a GLP1-RA caused a marked elevation in carbohydrate antigen 19-9(CA 19-9) without evidence of a tumor. METHODS: A mixed-methods approach was utilized, incorporating medical history obtained from regular outpatient consultations and follow-up visits, along with ancillary examinations derived from laboratory tests and imaging. RESULTS: The use of a GLP1-RA for treating T2DM resulted in an increase in CA 19-9 without evidence of a tumor, which gradually normalized after discontinuation of the drug. CONCLUSION: GLP1-RAs may lead to elevated levels of tumor markers during the treatment of T2DM, necessitating monitoring during therapy. Antidiabetic management should be adjusted on an individual basis as needed. CI - Copyright (c) 2024 Elsevier Masson SAS. All rights reserved. FAU - Liang, Rongyue AU - Liang R AD - Department of Geriatrics, Peking University First Hospital, Beijing, China. FAU - Fu, Zhifang AU - Fu Z AD - Department of Geriatrics, Peking University First Hospital, Beijing, China. FAU - Chen, Long AU - Chen L AD - Department of Geriatrics, Peking University First Hospital, Beijing, China. FAU - Zhou, Shuang AU - Zhou S AD - Department of Pharmacy, Peking University First Hospital, Beijing, China. FAU - Jiao, Hongmei AU - Jiao H AD - Department of Geriatrics, Peking University First Hospital, Beijing, China. Electronic address: jiaohm@139.com. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240911 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (CA-19-9 Antigen) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *CA-19-9 Antigen/blood MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Female MH - Male MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Carbohydrate antigen 19-9 OT - Case report OT - Glucagon-like peptide-1 receptor agonists OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/09/14 10:42 MHDA- 2024/12/05 05:31 CRDT- 2024/09/13 19:28 PHST- 2024/07/18 00:00 [received] PHST- 2024/08/08 00:00 [revised] PHST- 2024/08/19 00:00 [accepted] PHST- 2024/12/05 05:31 [medline] PHST- 2024/09/14 10:42 [pubmed] PHST- 2024/09/13 19:28 [entrez] AID - S1262-3636(24)00070-3 [pii] AID - 10.1016/j.diabet.2024.101578 [doi] PST - ppublish SO - Diabetes Metab. 2024 Nov;50(6):101578. doi: 10.1016/j.diabet.2024.101578. Epub 2024 Sep 11. PMID- 39269759 OWN - NLM STAT- MEDLINE DCOM- 20240913 LR - 20260923 IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 13 DP - 2024 Sep 13 TI - Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults With Overweight and Insulin Resistance: Protocol for an Open-Labeled Randomized Controlled Trial. PG - e62667 LID - 10.2196/62667 [doi] LID - e62667 AB - BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. OBJECTIVE: This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. METHODS: This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m(2)) and prediabetes or well-controlled T2DM (hemoglobin A(1c) 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors alpha, and beta galactosidase staining. RESULTS: The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. CONCLUSIONS: Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/62667. CI - (c)Tiffany M Cortes, Libia Vasquez, Monica C Serra, Ronna Robbins, Allison Stepanenko, Kevin Brown, Hannah Barrus, Annalisa Campos, Sara E Espinoza, Nicolas Musi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.09.2024. FAU - Cortes, Tiffany M AU - Cortes TM AUID- ORCID: 0000-0002-8971-9542 AD - Division of Endocrinology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - San Antonio Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, United States. FAU - Vasquez, Libia AU - Vasquez L AUID- ORCID: 0009-0005-2857-4852 AD - Texas Diabetes Institute, University Health System, San Antonio, TX, United States. FAU - Serra, Monica C AU - Serra MC AUID- ORCID: 0000-0002-2466-4675 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - San Antonio Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, United States. AD - Division of Geriatrics, Gerontology & Palliative Medicine, Department of Medicine, University of Texas Health Science San Antonio, San Antonio, TX, United States. FAU - Robbins, Ronna AU - Robbins R AUID- ORCID: 0000-0002-2787-9727 AD - Department of Nutrition and Food Science, Texas Woman's University, Denton, TX, United States. FAU - Stepanenko, Allison AU - Stepanenko A AUID- ORCID: 0009-0009-0350-7716 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Brown, Kevin AU - Brown K AUID- ORCID: 0000-0003-4327-5090 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Barrus, Hannah AU - Barrus H AUID- ORCID: 0009-0006-2454-5656 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Campos, Annalisa AU - Campos A AUID- ORCID: 0009-0007-9443-0122 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Espinoza, Sara E AU - Espinoza SE AUID- ORCID: 0000-0002-1116-302X AD - Division of Geriatrics, Gerontology & Palliative Medicine, Department of Medicine, University of Texas Health Science San Antonio, San Antonio, TX, United States. AD - Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. AD - Diabetes and Aging Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. FAU - Musi, Nicolas AU - Musi N AUID- ORCID: 0000-0003-4242-2888 AD - Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. AD - Diabetes and Aging Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. LA - eng SI - ClinicalTrials.gov/NCT05786521 GR - P30 AG021332/AG/NIA NIH HHS/United States GR - P30 AG044271/AG/NIA NIH HHS/United States GR - R01 AG052697/AG/NIA NIH HHS/United States PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240913 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Aging/drug effects MH - *Biomarkers/blood MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Insulin Resistance MH - *Overweight/drug therapy MH - Physical Functional Performance MH - Prediabetic State/drug therapy/blood MH - Non-Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC11437224 OTO - NOTNLM OT - biomarkers of aging OT - glucagon-like peptide OT - lean body mass OT - physical function OT - semaglutide COIS- Conflicts of Interest: None declared. EDAT- 2024/09/13 14:45 MHDA- 2024/09/13 18:44 PMCR- 2024/09/13 CRDT- 2024/09/13 11:54 PHST- 2024/05/28 00:00 [received] PHST- 2024/07/11 00:00 [accepted] PHST- 2024/07/01 00:00 [revised] PHST- 2024/09/13 18:44 [medline] PHST- 2024/09/13 14:45 [pubmed] PHST- 2024/09/13 11:54 [entrez] PHST- 2024/09/13 00:00 [pmc-release] AID - v13i1e62667 [pii] AID - 10.2196/62667 [doi] PST - epublish SO - JMIR Res Protoc. 2024 Sep 13;13:e62667. doi: 10.2196/62667. PMID- 39269703 OWN - NLM STAT- MEDLINE DCOM- 20240913 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 9 DP - 2024 Sep 3 TI - One-Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice. PG - e2433326 LID - 10.1001/jamanetworkopen.2024.33326 [doi] LID - e2433326 AB - IMPORTANCE: Limited data are available on long-term weight loss achieved with semaglutide or liraglutide for type 2 diabetes (T2D) or obesity in clinical practice. OBJECTIVE: To document weight loss achieved with injectable forms of semaglutide or liraglutide and identify factors associated with weight reduction of 10% or greater at 1 year. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health records from a large, integrated health system in Ohio and Florida. Participants included adults with a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of at least 30.0 who initiated treatment with semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up was completed July 28, 2023. EXPOSURE: Injectable forms of semaglutide or liraglutide approved for T2D or obesity. MAIN OUTCOMES AND MEASURES: Percentage weight change and categorical weight reduction of 10% or greater at 1 year. RESULTS: A total of 3389 patients (mean [SD] age, 50.4 [12.2] years; 1835 [54.7%] female) were identified. Of these, 1341 patients received semaglutide for T2D; 1444, liraglutide for T2D; 227, liraglutide for obesity; and 377, semaglutide for obesity. Mean (SD) percentage weight change at 1 year was -5.1% (7.8%) with semaglutide vs -2.2% (6.4%) with liraglutide (P < .001); -3.2% (6.8%) for T2D as a treatment indication vs -5.9% (9.0%) for obesity (P < .001); and -5.5% (7.5%) with persistent medication coverage (ie, a cumulative gap of less than 90 days) at 1 year vs -2.8% (7.0%) with 90 to 275 medication coverage days and -1.8% (6.7%) with fewer than 90 medication coverage days (P < .001). In the multivariable model, semaglutide vs liraglutide (adjusted odds ratio [AOR], 2.19 [95% CI, 1.77-2.72]), obesity as a treatment indication vs T2D (AOR, 2.46 [95% CI, 1.83-3.30]), persistent medication coverage vs 90 medication coverage days (AOR, 3.36 [95% CI, 2.52-4.54]) or 90 to 275 medication coverage days within the first year (AOR, 1.50 [95% CI, 1.10-2.06]), high dosage of the medication vs low (AOR, 1.58 [95% CI, 1.11-2.25]), and female sex (AOR, 1.57 [95% CI, 1.27-1.94]) were associated with achieving a 10% or greater weight reduction at year 1. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of 3389 patients with obesity, weight reduction at 1 year was associated with the medication's active agent, its dosage, treatment indication, persistent medication coverage, and patient sex. Future research should focus on identifying the reasons for discontinuation of medication use and interventions aimed at improving long-term persistent coverage. FAU - Gasoyan, Hamlet AU - Gasoyan H AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Pfoh, Elizabeth R AU - Pfoh ER AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Butsch, W Scott AU - Butsch WS AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240903 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Liraglutide/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged MH - Ohio MH - Body Mass Index MH - Florida MH - Semaglutide PMC - PMC11400221 COIS- Conflict of Interest Disclosures: Dr Gasoyan reported receiving grant funding from the National Cancer Institute outside the submitted work. Dr Butsch reported advisory board fees from Novo Nordisk A/S and research funding from Eli Lilly and Co during the conduct of the study. Dr Rothberg reported receiving personal fees from the Blue Cross Blue Shield Association outside the submitted work. No other disclosures were reported. EDAT- 2024/09/13 14:44 MHDA- 2024/09/13 14:45 PMCR- 2024/09/13 CRDT- 2024/09/13 11:33 PHST- 2024/09/13 14:45 [medline] PHST- 2024/09/13 14:44 [pubmed] PHST- 2024/09/13 11:33 [entrez] PHST- 2024/09/13 00:00 [pmc-release] AID - 2823644 [pii] AID - zoi241001 [pii] AID - 10.1001/jamanetworkopen.2024.33326 [doi] PST - epublish SO - JAMA Netw Open. 2024 Sep 3;7(9):e2433326. doi: 10.1001/jamanetworkopen.2024.33326. PMID- 39268978 OWN - NLM STAT- MEDLINE DCOM- 20241022 LR - 20250103 IS - 1744-7607 (Electronic) IS - 1742-5255 (Linking) VI - 20 IP - 10 DP - 2024 Oct TI - Assessing the therapeutic and toxicological profile of novel GLP-1 receptor agonists for type 2 diabetes. PG - 939-952 LID - 10.1080/17425255.2024.2401589 [doi] AB - INTRODUCTION: GLP-1 receptor agonists provide multiple benefits for patients with type 2 diabetes. Nonetheless, there are also several significant adverse effects associated with these agents. A thorough understanding of both therapeutic and toxicological profiles of GLP-1 receptor agonists is crucial for appropriate utilization of this medication class. A literature search of PubMed and ClinicalTrials.gov was carried out to inform discussion on the topic. AREAS COVERED: This review article discusses the key advantages and disadvantages derived from the use of GLP-1 receptor agonists in the treatment of type 2 diabetes. Landmark trials which helped characterize the cardiovascular and renal benefits of GLP-1 receptor agonists are highlighted. We also discuss key studies still in progress and new formulations under investigation. EXPERT OPINION: GLP-1 receptor agonists provide glycemic and complication-risk reduction benefits for individuals with type 2 diabetes. Current data suggests there is a lot of potential for further applications, even outside of type 2 diabetes management. It would be of particular interest to see the range of benefits conferred from GLP-1 receptor agonists in individuals without type 2 diabetes. Broader application of these medications could be expected given the ongoing development of new oral formulations and combination agents. FAU - Kukova, Lidiya AU - Kukova L AD - Internal Medicine Resident, Department of Internal Medicine, University of Maryland Medical Center, Baltimore, MD, USA. FAU - Munir, Kashif M AU - Munir KM AD - Professor of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland Medical Center, Baltimore, MD, USA. FAU - Sayeed, Ahmed AU - Sayeed A AD - Medical Student, American University of Antigua College of Medicine, Coolidge, Anitgua and Barbuda. FAU - Davis, Stephen N AU - Davis SN AD - Chair, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng PT - Journal Article PT - Review DEP - 20240913 PL - England TA - Expert Opin Drug Metab Toxicol JT - Expert opinion on drug metabolism & toxicology JID - 101228422 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Hypoglycemic Agents/pharmacology/administration & dosage/adverse effects MH - Animals MH - Blood Glucose/drug effects MH - Cardiovascular Diseases MH - Drug Development MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonist OT - PCOS OT - cardiovascular outcomes OT - hepatic system OT - novel formulations OT - renoprotective effects OT - toxicological profile OT - type 2 diabetes mellitus EDAT- 2024/09/13 14:45 MHDA- 2024/10/22 07:22 CRDT- 2024/09/13 08:13 PHST- 2024/10/22 07:22 [medline] PHST- 2024/09/13 14:45 [pubmed] PHST- 2024/09/13 08:13 [entrez] AID - 10.1080/17425255.2024.2401589 [doi] PST - ppublish SO - Expert Opin Drug Metab Toxicol. 2024 Oct;20(10):939-952. doi: 10.1080/17425255.2024.2401589. Epub 2024 Sep 13. PMID- 39265294 OWN - NLM STAT- MEDLINE DCOM- 20240929 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 43 IP - 10 DP - 2024 Oct TI - Very-low calorie diet and Semaglutide: Synergy and long-term impact on type 2 diabetes management. PG - 2350-2351 LID - S0261-5614(24)00319-4 [pii] LID - 10.1016/j.clnu.2024.09.008 [doi] FAU - Zheng, Ziwei AU - Zheng Z AD - Shanghai Eighth People's Hospital, Xu Hui District, Shanghai, China. FAU - Zhao, Kun AU - Zhao K AD - Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China. FAU - Yang, Shaoling AU - Yang S AD - Shanghai Eighth People's Hospital, Xu Hui District, Shanghai, China. Electronic address: drysl@163.com. LA - eng PT - Letter DEP - 20240906 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Caloric Restriction/methods MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Semaglutide OTO - NOTNLM OT - Beta cell function OT - Digital health technology OT - Personalized treatment OT - Synergistic effect COIS- Conflict of interest This statement follows the International Committee of Medical Journal Editors (ICMJE) guidelines. All authors disclose no conflict of interest for this work. EDAT- 2024/09/13 00:46 MHDA- 2024/09/30 00:42 CRDT- 2024/09/12 18:04 PHST- 2024/07/24 00:00 [received] PHST- 2024/09/04 00:00 [accepted] PHST- 2024/09/30 00:42 [medline] PHST- 2024/09/13 00:46 [pubmed] PHST- 2024/09/12 18:04 [entrez] AID - S0261-5614(24)00319-4 [pii] AID - 10.1016/j.clnu.2024.09.008 [doi] PST - ppublish SO - Clin Nutr. 2024 Oct;43(10):2350-2351. doi: 10.1016/j.clnu.2024.09.008. Epub 2024 Sep 6. PMID- 39262368 OWN - NLM STAT- MEDLINE DCOM- 20240912 LR - 20250103 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 79 IP - 9 DP - 2024 Sep TI - [A new era for incretins : from GLP-1 receptor agonists to co-agonists and poly-agonists]. PG - 605-612 AB - Incretin gut hormones, especially glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), raise a huge interest in diabetology. GLP-1 receptor agonists have gained a privileged role in the management of type 2 diabetes (T2D). They improve glucose control without inducing hypoglycaemia, while promoting weight loss. Furthermore, they protect people with T2D against atherosclerotic cardiovascular disease and contribute to reduce the risk of heart failure and chronic kidney disease, two other common complications of T2D. A recent innovation consists in the development of co-agonists that target both GIP and GLP-1 receptors. Whereas the co-infusion of GIP and GLP-1 failed to further reduce hyperglycaemia of T2D compared to GLP-1 single infusion, tirzepatide, an original dual unimolecular biaised GIP/GLP-1 agonist, showed a remarkable improvement of glucose control in the SURPASS programme in patients with T2D. Consequently, it is now commercialized in many countries for the management of T2D. GLP-1/glucagon (GCG) co-agonists and GIP/GLP-1/GCG poly-agonists are currently in development, aiming to benefit from the favourable effects of GCG on energy expenditure and liver lipid metabolism, while mitigating the hyperglycaemic effects of this hormone thanks to balanced effects of GLP-1 and/or GIP. They might occupy in the future an interesting place in the management of obesity and its metabolic complications among which T2D and liver steatosis. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques et Unite de Pharmacologie clinique, CHU Liege, ULiege, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Une nouvelle ere pour les incretines : des agonistes des recepteurs du GLP-1 aux co-agonistes et poly-agonistes. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Incretins/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Gastric Inhibitory Polypeptide/therapeutic use/agonists/pharmacology MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GIP OT - GLP-1 OT - Glucagon OT - Obesity OT - Poly-agonists OT - Tirzepatide OT - Type 2 diabetes EDAT- 2024/09/12 08:43 MHDA- 2024/09/12 08:44 CRDT- 2024/09/12 04:13 PHST- 2024/09/12 08:44 [medline] PHST- 2024/09/12 08:43 [pubmed] PHST- 2024/09/12 04:13 [entrez] PST - ppublish SO - Rev Med Liege. 2024 Sep;79(9):605-612. PMID- 39259460 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 84 IP - 11 DP - 2024 Nov TI - Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now. PG - 1337-1346 LID - 10.1007/s40265-024-02091-8 [doi] AB - Chronic kidney disease (CKD) is the most common co-morbidity in patients with type 2 diabetes (T2D) and its presence substantially amplifies the risk for premature death, adverse cardiovascular events, and faster progression of kidney injury to kidney failure. For nearly two decades, the pharmacological blockade of the renin-angiotensin-system (RAS) was the only pillar of therapy to afford cardiorenal protection in these patients. During the last 5 years, newer novel therapies have been added to our therapeutic armamentarium, offering promise for more effective management of diabetic kidney disease in the future. Large phase 3 clinical trials have demonstrated additive cardiorenal protective benefits of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors, the non-steroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, and glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide relative to placebo in patients with albuminuric CKD and T2D who are receiving standard-of-care treatment with a RAS-blocker. These therapies are likely much more effective when administered in a combined therapeutic algorithm, but the potential additive effects of combination therapy remain to be established in ongoing clinical trials. In this article, we assemble four pillars of therapy for the attenuation of residual cardiorenal risk in patients with CKD associated with T2D. We provide evidence from recent randomized trials and we discuss the concept of combined treatment for maximal cardiorenal protection in this high-risk patient population. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Georgianos, Panagiotis I AU - Georgianos PI AUID- ORCID: 0000-0001-7065-2096 AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. pangeorgi@yahoo.gr. FAU - Vaios, Vasilios AU - Vaios V AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AD - Second Propedeutic Department of Internal Medicine, School of Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Liakopoulos, Vassilios AU - Liakopoulos V AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20240911 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Naphthyridines) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (finerenone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Disease Progression MH - *Mineralocorticoid Receptor Antagonists/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - Naphthyridines/therapeutic use/pharmacology MH - Renin-Angiotensin System/drug effects MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declarations. Conflicts of Interest: The authors (P.I.G., V.V., T.K., V.L.) report no conflicts of interest relevant to this work. Funding: No external funds were used in the preparation of this article. Author Contributions: P.I.G. reviewed the literature and drafted the initial version of the manuscript. V.V., T.K., and V.L. reviewed the literature and edited the manuscript. All authors read and approved the final version of the manuscript. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Not applicable because this is a review article. Code Availability: Not applicable. EDAT- 2024/09/11 12:45 MHDA- 2024/11/28 06:36 CRDT- 2024/09/11 11:21 PHST- 2024/08/26 00:00 [accepted] PHST- 2024/11/28 06:36 [medline] PHST- 2024/09/11 12:45 [pubmed] PHST- 2024/09/11 11:21 [entrez] AID - 10.1007/s40265-024-02091-8 [pii] AID - 10.1007/s40265-024-02091-8 [doi] PST - ppublish SO - Drugs. 2024 Nov;84(11):1337-1346. doi: 10.1007/s40265-024-02091-8. Epub 2024 Sep 11. PMID- 39254740 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 23 DP - 2024 Dec 12 TI - Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment. PG - 2201-2211 LID - 10.1056/NEJMoa2403953 [doi] AB - BACKGROUND: Insulin efsitora alfa (efsitora) is a new basal insulin designed for once-weekly administration. Data on safety and efficacy have been limited to small, phase 1 or phase 2 trials. METHODS: We conducted a 52-week, phase 3, parallel-design, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive efsitora or degludec. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; we hypothesized that efsitora would be noninferior to degludec (noninferiority margin, 0.4 percentage points). Secondary and safety end points included the change in the glycated hemoglobin level in subgroups of participants using and not using glucagon-like peptide-1 (GLP-1) receptor agonists, the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter in weeks 48 through 52, and hypoglycemic episodes. RESULTS: A total of 928 participants underwent randomization (466 to the efsitora group and 462 to the degludec group). The mean glycated hemoglobin level decreased from 8.21% at baseline to 6.97% at week 52 with efsitora (least-squares mean change, -1.26 percentage points) and from 8.24% to 7.05% with degludec (least-squares mean change, -1.17 percentage points) (estimated treatment difference, -0.09 percentage points; 95% confidence interval [CI], -0.22 to 0.04), findings that showed noninferiority. Efsitora was noninferior to degludec with respect to the change in the glycated hemoglobin level in participants using and not using GLP-1 receptor agonists. The percentage of time that the glucose level was within the target range was 64.3% with efsitora and 61.2% with degludec (estimated treatment difference, 3.1 percentage points; 95% CI, 0.1 to 6.1). The rate of combined clinically significant or severe hypoglycemia was 0.58 events per participant-year of exposure with efsitora and 0.45 events per participant-year of exposure with degludec (estimated rate ratio, 1.30; 95% CI, 0.94 to 1.78). No severe hypoglycemia was reported with efsitora; six episodes were reported with degludec. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora was noninferior to once-daily degludec in reducing glycated hemoglobin levels. (Funded by Eli Lilly; QWINT-2 ClinicalTrials.gov number, NCT05362058.). CI - Copyright (c) 2024 Massachusetts Medical Society. FAU - Wysham, Carol AU - Wysham C AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Bajaj, Harpreet S AU - Bajaj HS AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Franco, Denise Reis AU - Franco DR AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Kiyosue, Arihiro AU - Kiyosue A AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Dahl, Dominik AU - Dahl D AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Zhou, Chunmei AU - Zhou C AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Carr, Molly C AU - Carr MC AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Case, Michael AU - Case M AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). FAU - Firmino Goncalves, Livia AU - Firmino Goncalves L AD - From the MultiCare Rockwood Center for Diabetes and Endocrinology, Spokane, WA (C.W.); LMC Diabetes and Endocrinology, Brampton, ON, Canada (H.S.B.); the Interdisciplinary Research Center for Health Science, Sant'Anna School of Advanced Studies, Pisa, Italy (S.D.P.); Centro de Pesquisas Clinicas-Diagnosticos da America, Sao Paulo (D.R.F.); Tokyo-Eki Center-Building Clinic, Tokyo (A.K.); Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany (D.D.); and Eli Lilly, Indianapolis (C.Z., M.C.C., M.C., L.F.G.). CN - QWINT-2 Investigators LA - eng SI - ClinicalTrials.gov/NCT05362058 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study DEP - 20240910 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 54Q18076QB (insulin degludec) RN - 0 (Insulin, Long-Acting) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glycated Hemoglobin/analysis MH - *Hypoglycemia/blood/chemically induced/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - *Insulin, Long-Acting/administration & dosage/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Drug Administration Schedule FIR - Neto, Danilo IR - Neto D FIR - Alves, Breno IR - Alves B FIR - Madeira, Miguel IR - Madeira M FIR - Salim, Camila IR - Salim C FIR - Augusto, Gustavo IR - Augusto G FIR - Franco, Denise IR - Franco D FIR - Leite, Silmara IR - Leite S FIR - Malakieh, Nadia IR - Malakieh N FIR - Ajala, Buki IR - Ajala B FIR - Akhras, Ronald IR - Akhras R FIR - O'Mahony, John IR - O'Mahony J FIR - Bajaj, Harpreet IR - Bajaj H FIR - Aggarwal, Naresh IR - Aggarwal N FIR - Khandwala, Hasnain IR - Khandwala H FIR - Boreky, Fadia IR - Boreky F FIR - Chen, Liming IR - Chen L FIR - Lu, Song IR - Lu S FIR - Yuan, Guoyue IR - Yuan G FIR - Cao, Hongyi IR - Cao H FIR - Li, Li IR - Li L FIR - Guo, Lixin IR - Guo L FIR - Geng, Jianlin IR - Geng J FIR - Li, Qingju IR - Li Q FIR - Kuang, Hongyu IR - Kuang H FIR - Ye, Xinhua IR - Ye X FIR - Li, Yufeng IR - Li Y FIR - Duan, Peng IR - Duan P FIR - Liu, Ming IR - Liu M FIR - Cheng, ZhiFeng IR - Cheng Z FIR - Jiang, Hongwei IR - Jiang H FIR - Huang, Wenlong IR - Huang W FIR - Xu, Lax IR - Xu L FIR - Lei, Tao IR - Lei T FIR - Shi, Bimin IR - Shi B FIR - Ma, Jianhua IR - Ma J FIR - Ran, Xingwu IR - Ran X FIR - Wang, Xiaoyue IR - Wang X FIR - Wu, Tian IR - Wu T FIR - Wang, Kun IR - Wang K FIR - Zhou, Zhiguang IR - Zhou Z FIR - Dong, Xiaolin IR - Dong X FIR - Lu, Yibing IR - Lu Y FIR - Hrdina, Tomas IR - Hrdina T FIR - Vachova, Alena IR - Vachova A FIR - Divinec, Juraj IR - Divinec J FIR - Edelsberger, Tomas IR - Edelsberger T FIR - Bartaskova, Dagmar IR - Bartaskova D FIR - Kopecka, Sarka IR - Kopecka S FIR - Dolezalova, Barbora IR - Dolezalova B FIR - Perakakis, Nikolaos IR - Perakakis N FIR - Kempe, Hans-Peter IR - Kempe HP FIR - Schaefer, Axel IR - Schaefer A FIR - Zeller, Helga IR - Zeller H FIR - Schaum, Thomas IR - Schaum T FIR - Segner, Alexander IR - Segner A FIR - Sauter, Joachim IR - Sauter J FIR - Dahl, Dominik IR - Dahl D FIR - Doupis, John IR - Doupis J FIR - Benroubi, Marianna IR - Benroubi M FIR - Paschou, Stavroula A IR - Paschou SA FIR - Pagkalos, Emmanouil IR - Pagkalos E FIR - Shimizu, Yukari IR - Shimizu Y FIR - Osonoi, Takeshi IR - Osonoi T FIR - Suzuki, Kunihiro IR - Suzuki K FIR - Tosaki, Takahiro IR - Tosaki T FIR - Yamamoto, Naoyuki IR - Yamamoto N FIR - Hasegawa, Atsushi IR - Hasegawa A FIR - Takahashi, Hideo IR - Takahashi H FIR - Fukushima, Yasushi IR - Fukushima Y FIR - Hakoda, Tomomi IR - Hakoda T FIR - Hayashi, Tsutomu IR - Hayashi T FIR - Nishimura, Hideki IR - Nishimura H FIR - Asakura, Taro IR - Asakura T FIR - Inazawa, Takeshi IR - Inazawa T FIR - Yoshimura, Ryohei IR - Yoshimura R FIR - Tomonaga, Osamu IR - Tomonaga O FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Jinnouchi, Hideaki IR - Jinnouchi H FIR - Tokuyama, Takahiko IR - Tokuyama T FIR - Tsuchida, Kenichi IR - Tsuchida K FIR - Abe, Katsushige IR - Abe K FIR - Sato, Nobuyuki IR - Sato N FIR - Nevarez, Luis IR - Nevarez L FIR - Garcia, Pedro IR - Garcia P FIR - Kim, Sang-Wook IR - Kim SW FIR - Lee, Chang IR - Lee C FIR - Lee, Byung IR - Lee B FIR - Connery, Lisa IR - Connery L FIR - Dempsey, Michael IR - Dempsey M FIR - Igbinadolor, Awawu IR - Igbinadolor A FIR - Schultz, David IR - Schultz D FIR - Mohseni, Rizwana IR - Mohseni R FIR - Schultz, James IR - Schultz J FIR - Gabriel, John IR - Gabriel J FIR - Kniery, Paul IR - Kniery P FIR - Gardner, Donald IR - Gardner D FIR - Lucas, Kathryn IR - Lucas K FIR - Ho, Wayne IR - Ho W FIR - Norwood, Paul IR - Norwood P FIR - Cupelo, Robert IR - Cupelo R FIR - Sartore, Joseph IR - Sartore J FIR - Rosenstock, Julio IR - Rosenstock J FIR - Bhargava, Anuj IR - Bhargava A FIR - Park, Jean IR - Park J FIR - Lewis, Matthew IR - Lewis M FIR - Widicus, Diana IR - Widicus D FIR - Otero-Martinez, Juan IR - Otero-Martinez J FIR - Mansilla-Letelier, Paola IR - Mansilla-Letelier P FIR - Gaudiani, Linda IR - Gaudiani L FIR - Gorman, Timothy IR - Gorman T FIR - Berner, Jason IR - Berner J FIR - Gangi, Sumana IR - Gangi S FIR - Sheikh-Ali, Mae IR - Sheikh-Ali M FIR - Vega, Damaris IR - Vega D FIR - Duda, Ralph IR - Duda R FIR - Welch, Michelle IR - Welch M FIR - Clarke, Subha IR - Clarke S FIR - Quinn, Timothy IR - Quinn T FIR - Mayfield, Ronald IR - Mayfield R FIR - Blake, Dwight IR - Blake D FIR - Wysham, Carol IR - Wysham C EDAT- 2024/09/10 12:43 MHDA- 2024/12/12 12:28 CRDT- 2024/09/10 11:04 PHST- 2024/12/12 12:28 [medline] PHST- 2024/09/10 12:43 [pubmed] PHST- 2024/09/10 11:04 [entrez] AID - 10.1056/NEJMoa2403953 [doi] PST - ppublish SO - N Engl J Med. 2024 Dec 12;391(23):2201-2211. doi: 10.1056/NEJMoa2403953. Epub 2024 Sep 10. PMID- 39248221 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20250807 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus. PG - 5661-5668 LID - 10.1111/dom.15934 [doi] AB - AIMS: Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM. METHODS: This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated. RESULTS: A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 +/- 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 +/- 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m(2). Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA. CONCLUSIONS: In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naive compared to patients switched from GLP1-RA to tirzepatide. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kelly, Michael S AU - Kelly MS AUID- ORCID: 0000-0003-4272-8721 AD - Thomas Jefferson College of Pharmacy, Philadelphia, Pennsylvania, USA. AD - Internal Medicine Associates, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. FAU - Scopelliti, Emily M AU - Scopelliti EM AUID- ORCID: 0000-0001-6985-6470 AD - Thomas Jefferson College of Pharmacy, Philadelphia, Pennsylvania, USA. AD - Internal Medicine Associates, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. FAU - Goodson, Kaylee E AU - Goodson KE AD - Thomas Jefferson College of Pharmacy, Philadelphia, Pennsylvania, USA. FAU - Lo, Ching Mann Anne AU - Lo CMA AD - Thomas Jefferson College of Pharmacy, Philadelphia, Pennsylvania, USA. FAU - Nguyen, Huelena X AU - Nguyen HX AD - Thomas Jefferson College of Pharmacy, Philadelphia, Pennsylvania, USA. FAU - Simon, Barbara AU - Simon B AUID- ORCID: 0000-0002-3454-0166 AD - Division of Endocrinology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Diabetes Obes Metab. 2025 Feb;27(2):1021. doi: 10.1111/dom.16083. PMID: 39552537 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Glycated Hemoglobin/drug effects/analysis/metabolism MH - Body Mass Index MH - Treatment Outcome MH - Weight Loss/drug effects MH - Blood Glucose/drug effects/metabolism MH - Body Weight/drug effects MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - glycaemic control OT - tirzepatide OT - type 2 diabetes OT - weight reduction EDAT- 2024/09/09 12:42 MHDA- 2024/11/04 12:25 CRDT- 2024/09/09 07:02 PHST- 2024/08/23 00:00 [revised] PHST- 2024/06/20 00:00 [received] PHST- 2024/08/24 00:00 [accepted] PHST- 2024/11/04 12:25 [medline] PHST- 2024/09/09 12:42 [pubmed] PHST- 2024/09/09 07:02 [entrez] AID - 10.1111/dom.15934 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5661-5668. doi: 10.1111/dom.15934. Epub 2024 Sep 9. PMID- 39248211 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Association of sodium-glucose cotransporter 2 inhibitors with risk of incident dementia and all-cause mortality in older patients with type 2 diabetes: A retrospective cohort study using the TriNetX US collaborative networks. PG - 5420-5430 LID - 10.1111/dom.15918 [doi] AB - BACKGROUND: Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged >/=50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted. RESULTS: Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality). CONCLUSIONS: The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Pai, Yen-Wei AU - Pai YW AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. AD - Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, I-Chieh AU - Chen IC AUID- ORCID: 0000-0002-8345-5304 AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Jun-Fu AU - Lin JF AUID- ORCID: 0009-0006-5287-7893 AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, Xiao-Hui AU - Chen XH AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, Hsin-Hua AU - Chen HH AUID- ORCID: 0000-0002-7304-4587 AD - Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chang, Ming-Hong AU - Chang MH AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. AD - Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Huang, Jin-An AU - Huang JA AD - Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Health Business Administration, Hungkuang University, Taichung, Taiwan. FAU - Lin, Ching-Heng AU - Lin CH AUID- ORCID: 0000-0002-2450-6108 AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. AD - Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan. AD - Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. LA - eng GR - TCVGH-NCHU1137618/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-YM1130105/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-1137315C/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-1127303C/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-112G211/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-113G211/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-NHRI11301/Taichung Veterans General Hospital Research Fund/ GR - TCVGH-YM1120103/Taichung Veterans General Hospital Research Fund/ PT - Journal Article DEP - 20240909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Female MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Retrospective Studies MH - Aged MH - *Dementia/epidemiology/mortality MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Incidence MH - Hypoglycemic Agents/therapeutic use MH - United States/epidemiology MH - Aged, 80 and over MH - Mortality MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - DPP-4 inhibitor OT - GLP-1 RA OT - SGLT-2 inhibitor OT - incident dementia OT - mortality OT - type 2 diabetes EDAT- 2024/09/09 12:44 MHDA- 2024/10/04 12:43 CRDT- 2024/09/09 06:52 PHST- 2024/08/08 00:00 [revised] PHST- 2024/06/12 00:00 [received] PHST- 2024/08/15 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/09 12:44 [pubmed] PHST- 2024/09/09 06:52 [entrez] AID - 10.1111/dom.15918 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5420-5430. doi: 10.1111/dom.15918. Epub 2024 Sep 9. PMID- 39248157 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Semaglutide use in people with obesity and type 2 diabetes from real-world utilization data: An analysis of the All of US Program. PG - 4989-4995 LID - 10.1111/dom.15911 [doi] AB - AIM: To analyse data from the All of Us Research Program to evaluate the real-world application and long-term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population. MATERIALS AND METHODS: We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide. RESULTS: For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m(2) in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events. CONCLUSIONS: Consistent with clinical trial findings, this real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real-world experience and the long-term effectiveness of semaglutide. CI - Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Mayer, Craig S AU - Mayer CS AUID- ORCID: 0000-0002-2705-9550 AD - Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA. FAU - Fontelo, Paul AU - Fontelo P AD - Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA. LA - eng GR - Z99 LM999999/ImNIH/Intramural NIH HHS/United States GR - Lister Hill National Center for Biomedical Communications of the National Library of Medicine (NLM), National Institutes of Health/ PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glycated Hemoglobin/analysis/drug effects/metabolism MH - *Body Mass Index MH - Aged MH - United States/epidemiology MH - Adult MH - Weight Loss/drug effects MH - Treatment Outcome MH - Administration, Oral MH - Semaglutide PMC - PMC11462475 MID - NIHMS2018147 OTO - NOTNLM OT - obesity care OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to report. EDAT- 2024/09/09 12:43 MHDA- 2024/10/04 12:43 PMCR- 2025/11/01 CRDT- 2024/09/09 06:23 PHST- 2024/08/12 00:00 [revised] PHST- 2024/06/06 00:00 [received] PHST- 2024/08/13 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/09 12:43 [pubmed] PHST- 2024/09/09 06:23 [entrez] PHST- 2025/11/01 00:00 [pmc-release] AID - 10.1111/dom.15911 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4989-4995. doi: 10.1111/dom.15911. Epub 2024 Sep 9. PMID- 39245809 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Time-in-range derived from self-measured blood glucose in people with type 2 diabetes advancing to iGlarLixi: A participant-level pooled analysis of three phase 3 LixiLan randomized controlled trials. PG - 5046-5055 LID - 10.1111/dom.15811 [doi] AB - AIM: To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR). METHODS: Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles. RESULTS: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% +/- 3.4%, 0.61% +/- 3.2%, 0.08% +/- 1.0% and 0.0% +/- 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA. CONCLUSIONS: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi. CI - (c) 2024 Sanofi and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Haluzik, Martin AU - Haluzik M AUID- ORCID: 0000-0002-0201-6888 AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. FAU - Al-Sofiani, Mohammed E AU - Al-Sofiani ME AUID- ORCID: 0000-0003-4420-9378 AD - Department of Internal Medicine, King Saud University, Riyadh, Saudi Arabia. AD - Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, Toronto, Canada. FAU - Lauand, Felipe AU - Lauand F AD - Sanofi, Paris, France. FAU - Melas-Melt, Lydie AU - Melas-Melt L AD - IVIDATA Life Sciences, Levallois-Perret, France. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City Dallas, Dallas, Texas, USA. LA - eng GR - Sanofi/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240908 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Blood Glucose/drug effects/metabolism MH - Blood Glucose Self-Monitoring MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Combinations MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-2 Receptor MH - Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Insulin Glargine/therapeutic use MH - *Peptides/therapeutic use/administration & dosage MH - Randomized Controlled Trials as Topic MH - Clinical Trials, Phase III as Topic OTO - NOTNLM OT - derived time-in-range OT - fixed-ratio combination OT - iGlarLixi OT - real-world data OT - type 2 diabetes EDAT- 2024/09/09 00:50 MHDA- 2024/10/04 12:43 CRDT- 2024/09/08 23:52 PHST- 2024/07/04 00:00 [revised] PHST- 2024/02/14 00:00 [received] PHST- 2024/07/04 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/09 00:50 [pubmed] PHST- 2024/09/08 23:52 [entrez] AID - 10.1111/dom.15811 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5046-5055. doi: 10.1111/dom.15811. Epub 2024 Sep 8. PMID- 39243175 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - Adherence and treatment discontinuation of oral semaglutide and once-weekly semaglutide injection at 12 month follow-up: Japanese real-world data. PG - 1578-1584 LID - 10.1111/jdi.14265 [doi] AB - Adherence and treatment continuation rates of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for both oral (O-SEMA) and subcutaneous injection (SEMA-SC) remain unknown in real-world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O-SEMA and once-weekly SEMA-SC in patients with type 2 diabetes using a real-world claims database. SEMA-SC initiators were 1:1 propensity score-matched to O-SEMA initiators. Non-adherence was defined as <0.8 of the proportion of days covered. SEMA-SC had a significantly higher odds ratio (OR) for non-adherence than O-SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O-SEMA as the reference, was 1.45 for SEMA-SC, although the discontinuation rate of O-SEMA was higher during the early stage. O-SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA-SC initiators at 12 months, which could lead to earlier initiation of GLP-1RA treatment. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Horii, Takeshi AU - Horii T AUID- ORCID: 0000-0002-5465-4531 AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Masudo, Chikako AU - Masudo C AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. FAU - Takayanagi, Yui AU - Takayanagi Y AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. FAU - Oikawa, Yoichi AU - Oikawa Y AUID- ORCID: 0000-0003-1524-6751 AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Shimada, Akira AU - Shimada A AUID- ORCID: 0000-0002-3954-4983 AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Mihara, Kiyoshi AU - Mihara K AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20240907 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Follow-Up Studies MH - Administration, Oral MH - Aged MH - Injections, Subcutaneous MH - Japan MH - Withholding Treatment/statistics & numerical data MH - East Asian People MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring MH - Semaglutide PMC - PMC11527826 OTO - NOTNLM OT - Injection OT - Oral OT - Semaglutide COIS- A.S. received lecture fees from Astellas Pharma, Inc., Eli Lilly Japan K.K., Novo Nordisk Pharma, Inc., and Sanofi K.K. The authors declare no conflicts of interest. Approval of the research protocol: The Ethics Board of Musashino University waived the requirement for ethical approval for this study because all available data were completely anonymous with no personal information, which is characteristic of DPC-based clinical databases. This study was conducted in accordance with the Declaration of Helsinki (revised in Fortaleza, Brazil, October 2013) and the Ethical Guidelines for Medical and Health Research Involving Human Subjects. Informed consent: All patient data were anonymized and did not contain personal data; therefore, informed consent was not required. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2024/09/07 14:42 MHDA- 2024/11/01 06:22 PMCR- 2024/09/07 CRDT- 2024/09/07 05:42 PHST- 2024/06/07 00:00 [revised] PHST- 2024/04/26 00:00 [received] PHST- 2024/06/27 00:00 [accepted] PHST- 2024/11/01 06:22 [medline] PHST- 2024/09/07 14:42 [pubmed] PHST- 2024/09/07 05:42 [entrez] PHST- 2024/09/07 00:00 [pmc-release] AID - JDI14265 [pii] AID - 10.1111/jdi.14265 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1578-1584. doi: 10.1111/jdi.14265. Epub 2024 Sep 7. PMID- 39242961 OWN - NLM STAT- MEDLINE DCOM- 20240927 LR - 20261010 IS - 1759-5053 (Electronic) IS - 1759-5045 (Linking) VI - 21 IP - 10 DP - 2024 Oct TI - GLP1 agonists: current and future landscape of clinical trials for patients with metabolic dysfunction. PG - 664-666 LID - 10.1038/s41575-024-00977-2 [doi] FAU - Goldney, Jonathan AU - Goldney J AUID- ORCID: 0000-0001-8553-8296 AD - Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. melanie.davies@uhl-tr.nhs.uk. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK. melanie.davies@uhl-tr.nhs.uk. LA - eng PT - Journal Article PL - England TA - Nat Rev Gastroenterol Hepatol JT - Nature reviews. Gastroenterology & hepatology JID - 101500079 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Clinical Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1/agonists/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Metabolic Diseases/drug therapy MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/09/07 14:42 MHDA- 2024/09/27 07:06 CRDT- 2024/09/06 23:51 PHST- 2024/09/27 07:06 [medline] PHST- 2024/09/07 14:42 [pubmed] PHST- 2024/09/06 23:51 [entrez] AID - 10.1038/s41575-024-00977-2 [pii] AID - 10.1038/s41575-024-00977-2 [doi] PST - ppublish SO - Nat Rev Gastroenterol Hepatol. 2024 Oct;21(10):664-666. doi: 10.1038/s41575-024-00977-2. PMID- 39242193 OWN - NLM STAT- MEDLINE DCOM- 20250117 LR - 20260525 IS - 1468-3288 (Electronic) IS - 0017-5749 (Print) IS - 0017-5749 (Linking) VI - 74 IP - 2 DP - 2025 Jan 17 TI - Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease. PG - 284-294 LID - 10.1136/gutjnl-2024-332687 [doi] LID - e332687 AB - OBJECTIVE: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DESIGN: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged >/=40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs. RESULTS: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69)). CONCLUSIONS: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Bea, Sungho AU - Bea S AUID- ORCID: 0000-0003-2622-6553 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea (the Republic of). FAU - Ko, Hwa Yeon AU - Ko HY AUID- ORCID: 0000-0001-5297-8826 AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea (the Republic of). FAU - Bae, Jae Hyun AU - Bae JH AUID- ORCID: 0000-0002-1384-6123 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea (the Republic of). FAU - Cho, Young Min AU - Cho YM AUID- ORCID: 0000-0002-2331-6126 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of). FAU - Chang, Yoosoo AU - Chang Y AUID- ORCID: 0000-0002-6945-9050 AD - Kangbuk Samsung Hospital, Seoul, Korea (the Republic of). FAU - Ryu, Seungho AU - Ryu S AUID- ORCID: 0000-0002-3927-8646 AD - Center for Cohort Study, Kangbuk Samsung Hospital, Seoul, Korea (the Republic of). FAU - Byrne, Christopher D AU - Byrne CD AUID- ORCID: 0000-0001-6322-7753 AD - Nutrition and Metabolism, University of Southampton, Southampton, UK. FAU - Shin, Ju-Young AU - Shin JY AUID- ORCID: 0000-0003-1010-7525 AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea (the Republic of) shin.jy@skku.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250117 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Thiazolidinediones) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Thiazolidinediones/adverse effects/therapeutic use MH - Aged MH - Republic of Korea/epidemiology MH - Adult MH - *Fatty Liver/complications/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications PMC - PMC11874371 OTO - NOTNLM OT - DIABETES MELLITUS OT - FATTY LIVER COIS- Competing interests: J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience and Pfizer, outside the submitted work. EDAT- 2024/09/07 14:42 MHDA- 2025/01/18 15:09 PMCR- 2025/03/03 CRDT- 2024/09/06 21:22 PHST- 2024/04/18 00:00 [received] PHST- 2024/08/21 00:00 [accepted] PHST- 2025/01/18 15:09 [medline] PHST- 2024/09/07 14:42 [pubmed] PHST- 2024/09/06 21:22 [entrez] PHST- 2025/03/03 00:00 [pmc-release] AID - gutjnl-2024-332687 [pii] AID - 10.1136/gutjnl-2024-332687 [doi] PST - epublish SO - Gut. 2025 Jan 17;74(2):284-294. doi: 10.1136/gutjnl-2024-332687. PMID- 39240512 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20250103 IS - 1573-7403 (Electronic) IS - 1386-341X (Print) IS - 1386-341X (Linking) VI - 27 IP - 5 DP - 2024 Oct TI - GLP-1 receptor agonists may enhance the effects of desmopressin in individuals with AVP deficiency: a case series and proposed mechanism. PG - 731-736 LID - 10.1007/s11102-024-01451-7 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have diverse effects on sodium and water homeostasis. They decrease thirst perception, potentially inhibit arginine vasopressin (AVP) production, and induce natriuresis. We present three cases of AVP deficiency (AVP-D) where GLP-1 RA initiation led to desmopressin dose reduction. CASES: Three patients with AVP-D on stable desmopressin therapy started GLP-1 RAs for type 2 diabetes mellitus or obesity. Following weight loss and decreased thirst, all patients reduced their desmopressin dose while maintaining normal thirst and urine output. DISCUSSION: GLP-1 RAs influence sodium and water homeostasis through various mechanisms. In individuals with intact AVP systems, GLP-1 RAs may directly suppress AVP production and induce natriuresis in the kidney leading to increased water excretion. In AVP-D, with exogenous desmopressin replacing endogenous AVP, the osmotic permeability of collecting ducts is primarily influenced by desmopressin dose. Thus, increased distal fluid delivery may allow for lower desmopressin doses to maintain water balance. CONCLUSION: Our findings indicate a potential interaction between GLP-1 RAs and desmopressin in AVP-D. Clinicians should reassess desmopressin dosage upon initiating GLP-1 RA therapy. CI - (c) 2024. The Author(s). FAU - Nakhleh, Afif AU - Nakhleh A AUID- ORCID: 0000-0003-1206-1516 AD - Maccabi Healthcare Services, Haifa, Israel. anakhleh@gmail.com. AD - Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel. anakhleh@gmail.com. AD - Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. anakhleh@gmail.com. AD - Diabetes and Endocrinology Clinic, Maccabi Healthcare Services, 54 Simcha Golan St., Haifa, Israel. anakhleh@gmail.com. FAU - Shehadeh, Naim AU - Shehadeh N AD - Maccabi Healthcare Services, Haifa, Israel. AD - Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel. AD - Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. FAU - Mansour, Bshara AU - Mansour B AD - Maccabi Healthcare Services, Haifa, Israel. LA - eng PT - Case Reports PT - Journal Article DEP - 20240906 PL - United States TA - Pituitary JT - Pituitary JID - 9814578 RN - ENR1LLB0FP (Deamino Arginine Vasopressin) RN - 113-79-1 (Arginine Vasopressin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Deamino Arginine Vasopressin/pharmacology/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Arginine Vasopressin/metabolism MH - Adult MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11513766 OTO - NOTNLM OT - AVP deficiency OT - Desmopressin OT - GLP-1 RAs OT - Natriuresis COIS- The authors state that they do not have any conflicts of interest to disclose. EDAT- 2024/09/06 12:44 MHDA- 2024/10/28 12:26 PMCR- 2024/09/06 CRDT- 2024/09/06 11:23 PHST- 2024/08/23 00:00 [accepted] PHST- 2024/10/28 12:26 [medline] PHST- 2024/09/06 12:44 [pubmed] PHST- 2024/09/06 11:23 [entrez] PHST- 2024/09/06 00:00 [pmc-release] AID - 10.1007/s11102-024-01451-7 [pii] AID - 1451 [pii] AID - 10.1007/s11102-024-01451-7 [doi] PST - ppublish SO - Pituitary. 2024 Oct;27(5):731-736. doi: 10.1007/s11102-024-01451-7. Epub 2024 Sep 6. PMID- 39237049 OWN - NLM STAT- MEDLINE DCOM- 20241211 LR - 20260102 IS - 1879-1891 (Electronic) IS - 0002-9394 (Print) IS - 0002-9394 (Linking) VI - 269 DP - 2025 Jan TI - Association Between Glucagon-Like Peptide-1 Receptor Agonists Exposure and Intraocular Pressure Change: GLP-1 Receptor Agonists and Intraocular Pressure Change. PG - 255-265 LID - S0002-9394(24)00392-1 [pii] LID - 10.1016/j.ajo.2024.08.030 [doi] AB - PURPOSE: This study evaluates the effects of glucagon-like peptide-1 receptor (GLP-1R) agonists on intraocular pressure (IOP). DESIGN: Retrospective clinical cohort study. METHODS: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. A total of 1247 glaucoma surgery and treatment naive eyes of 626 patientson GLP-1R agonists and 1083 glaucoma surgery and treatment naive eyes of 547 patients on other oral antidiabetics were included. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry records within 365 days of the index date were included. Clinical and laboratory data were extracted. Eyes were excluded upon exposure to glaucoma hypotensive medication or glaucoma surgery. The primary outcome measure was ∆IOP after exposure, which was analyzed using a paired t test and generalized estimating equations (GEE) RESULTS: The median age was 66.2 years [IQR = 18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, hemoglobin A1c, and body mass index were 15.2 mm Hg [IQR = 3.8], 7.5 [IQR = 2.4], and 29.8 [IQR = 9.4], respectively. A total of 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR = 1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics differed between the groups. The mean ∆IOP was -0.4 +/- 2.8 mm Hg (paired t test P < .001) and -0.2 +/- 3.3 mm Hg (paired t test P = .297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of DeltaIOP in multivariable GEE. Sensitivity analyses yielded similar results. CONCLUSIONS: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with DeltaIOP in multivariable GEE. Moreover, the difference in DeltaIOP between the two groups was small. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Hallaj, Shahin AU - Hallaj S AD - From the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science (S.H., W.H., B.G.C., R.N.W., S.L.B.), Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics (S.H., W.H., B.G.C., S.L.B.), University of California, San Diego, California, USA. FAU - Halfpenny, William AU - Halfpenny W AD - From the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science (S.H., W.H., B.G.C., R.N.W., S.L.B.), Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics (S.H., W.H., B.G.C., S.L.B.), University of California, San Diego, California, USA. FAU - Chuter, Benton G AU - Chuter BG AD - From the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science (S.H., W.H., B.G.C., R.N.W., S.L.B.), Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics (S.H., W.H., B.G.C., S.L.B.), University of California, San Diego, California, USA. FAU - Weinreb, Robert N AU - Weinreb RN AD - From the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science (S.H., W.H., B.G.C., R.N.W., S.L.B.), Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, USA. FAU - Baxter, Sally L AU - Baxter SL AD - From the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science (S.H., W.H., B.G.C., R.N.W., S.L.B.), Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics (S.H., W.H., B.G.C., S.L.B.), University of California, San Diego, California, USA. Electronic address: s1baxter@health.ucsd.edu. FAU - Cui, Qi N AU - Cui QN AD - F.M. Kirby Center for Molecular Ophthalmology (Q.N.C.), Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Electronic address: qi.cui@pennmedicine.upenn.edu. LA - eng GR - DP5 OD029610/OD/NIH HHS/United States GR - R01 EY034115/EY/NEI NIH HHS/United States GR - P30 EY022589/EY/NEI NIH HHS/United States GR - OT2 OD032644/OD/NIH HHS/United States GR - P30 EY001583/EY/NEI NIH HHS/United States GR - R01 EY034146/EY/NEI NIH HHS/United States PT - Journal Article DEP - 20240903 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM UOF - medRxiv. 2024 May 06:2024.05.06.24306943. doi: 10.1101/2024.05.06.24306943. PMID: 38765972 MH - Humans MH - *Intraocular Pressure/drug effects/physiology MH - Female MH - Male MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Tonometry, Ocular MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin/metabolism MH - Blood Glucose/metabolism MH - Administration, Oral MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11634659 MID - NIHMS2021009 COIS- Dr. Baxter reports consulting fees from Topcon and equipment support from Topcon and Optomed outside the submitted work. Dr. Cui reports a provisional patent application related to the topic of this study (publication number: US20220193201A1). SH, WH, and BGC: None. Dr. Weinreb reports consulting fees from Abbvie, Alcon, Balance, Editas, Eyenovia, iSTAR Medical, Nicox, and Topcon outside the submitted work. He also has stock options from Balance, Eyenovia, Iantrek, Implandata, and Toku outside the submitted work and intellectual property licensed from UCSD to Toromedes outside the submitted work. EDAT- 2024/09/06 01:02 MHDA- 2024/12/12 05:25 PMCR- 2026/01/01 CRDT- 2024/09/05 19:29 PHST- 2024/05/15 00:00 [received] PHST- 2024/08/17 00:00 [revised] PHST- 2024/08/22 00:00 [accepted] PHST- 2024/12/12 05:25 [medline] PHST- 2024/09/06 01:02 [pubmed] PHST- 2024/09/05 19:29 [entrez] PHST- 2026/01/01 00:00 [pmc-release] AID - S0002-9394(24)00392-1 [pii] AID - 10.1016/j.ajo.2024.08.030 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Jan;269:255-265. doi: 10.1016/j.ajo.2024.08.030. Epub 2024 Sep 3. PMID- 39236411 OWN - NLM STAT- MEDLINE DCOM- 20240911 LR - 20260627 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 10 DP - 2024 Oct TI - Too good to be true: Are GLP-1 receptor agonists the new metformin? PG - 108851 LID - S1056-8727(24)00177-6 [pii] LID - 10.1016/j.jdiacomp.2024.108851 [doi] AB - Recently, a health-care database study showed that persons with type 2 diabetes taking GLP-1 receptor agonists (GLP-1 RA) had a significantly lower risk of 10 out of 13 obesity-related cancers than patients taking insulin (Wang L, et al. JAMA Netw Open. 2024 7: e2421305). For some cancers, hazard ratios <0.5 were reported. This is reminiscent of studies published >10 years ago showing that people with type 2 diabetes taking metformin had a lower risk of many types of cancer than those not taking metformin. In some studies, also risk reductions of >50 % were reported. The strong effects observed in the metformin studies were explained by time-related biases, in particular, immortal time bias. In the current GLP-1 RA study, it was striking that the curves for the cumulative incidence of several cancers in GLP-1 RA and insulin users diverged immediately after therapy onset. This indicates that there is most likely a time-related bias: insulin is given at much later stages of type 2 diabetes than GLP-1 RA. The current study suggests that one should be sceptical about database results when spectacular risk reductions are reported. Time-related bias should always be considered as an alternative explanation. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Kowall, Bernd AU - Kowall B AD - Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Germany. Electronic address: bernd.kowall@uk-essen.de. FAU - Maier, Gregor AU - Maier G AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Germany. FAU - Rathmann, Wolfgang AU - Rathmann W AD - Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Germany. LA - eng PT - Journal Article DEP - 20240830 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Metformin/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Neoplasms/epidemiology MH - Insulin/therapeutic use MH - Incidence MH - Bias MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cancer OT - Diabetes mellitus OT - Glucagon-like peptide-1 receptor agonist OT - Immortal time bias OT - Metformin OT - Time-lag bias COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/09/06 01:02 MHDA- 2024/09/12 00:42 CRDT- 2024/09/05 18:02 PHST- 2024/07/17 00:00 [received] PHST- 2024/08/21 00:00 [revised] PHST- 2024/08/25 00:00 [accepted] PHST- 2024/09/12 00:42 [medline] PHST- 2024/09/06 01:02 [pubmed] PHST- 2024/09/05 18:02 [entrez] AID - S1056-8727(24)00177-6 [pii] AID - 10.1016/j.jdiacomp.2024.108851 [doi] PST - ppublish SO - J Diabetes Complications. 2024 Oct;38(10):108851. doi: 10.1016/j.jdiacomp.2024.108851. Epub 2024 Aug 30. PMID- 39235730 OWN - NLM STAT- MEDLINE DCOM- 20241105 LR - 20260629 IS - 1534-3170 (Electronic) IS - 1523-3782 (Print) IS - 1523-3782 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Impact of Visceral and Hepatic Fat on Cardiometabolic Health. PG - 1297-1307 LID - 10.1007/s11886-024-02127-1 [doi] AB - PURPOSE OF REVIEW: Body fat distribution plays a significant role in the cardiometabolic consequences of obesity. We review the impact of visceral and hepatic fat and highlight important interventions. RECENT FINDINGS: Several epidemiologic studies have established a clear association between visceral fat and cardiovascular disease. The association between hepatic fat and cardiovascular disease is less clear with discordant results. Novel evidence demonstrates sodium glucose co-transporter-2 (SGLT2) inhibitors facilitate modest weight loss and reductions in ectopic fat depots in patient with type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with decreased visceral/hepatic fat and reductions in MACE in populations with type 2 diabetes and with overweight/obesity. Clear associations between visceral fat and cardiometabolic outcomes have been established, whereas the impact of hepatic fat remains less clear. Lifestyle modification and pharmacologic interventions remain the initial therapies, while surgical intervention is associated with improved long-term outcomes. Emerging therapies have demonstrated a profound impact on body fat distribution and cardiometabolic risk. CI - (c) 2024. The Author(s). FAU - Khawaja, Tasveer AU - Khawaja T AD - Harrington Heart and Vascular Institute, University Hospitals Cleveland and Case Western Reserve University, Cleveland, OH, USA. AD - Department of Medicine, University Hospitals Cleveland and Case Western Reserve University, 11100 Euclid Ave. Mailstop Lakeside, Cleveland, OH, USA. FAU - Nied, Matthew AU - Nied M AD - Department of Medicine, University Hospitals Cleveland and Case Western Reserve University, 11100 Euclid Ave. Mailstop Lakeside, Cleveland, OH, USA. FAU - Wilgor, Abigail AU - Wilgor A AD - Department of Medicine, University Hospitals Cleveland and Case Western Reserve University, 11100 Euclid Ave. Mailstop Lakeside, Cleveland, OH, USA. FAU - Neeland, Ian J AU - Neeland IJ AD - Harrington Heart and Vascular Institute, University Hospitals Cleveland and Case Western Reserve University, Cleveland, OH, USA. Ian.Neeland@UHhospitals.org. AD - Department of Medicine, University Hospitals Cleveland and Case Western Reserve University, 11100 Euclid Ave. Mailstop Lakeside, Cleveland, OH, USA. Ian.Neeland@UHhospitals.org. LA - eng PT - Journal Article PT - Review DEP - 20240905 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Intra-Abdominal Fat MH - *Diabetes Mellitus, Type 2/complications/physiopathology MH - *Cardiovascular Diseases/prevention & control MH - *Obesity/complications/physiopathology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Liver/metabolism MH - Cardiometabolic Risk Factors MH - Body Fat Distribution MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11538208 OTO - NOTNLM OT - Cardiometabolic risk OT - GLP-1 RA OT - Hepatic fat OT - Obesity OT - SGLT2i OT - Visceral fat COIS- Dr. Neeland discloses consulting, speaking, and/or advisory board honoraria from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Bayer Pharmaceuticals that was outside this paper. All other authors declare that they have no conflict of interest. EDAT- 2024/09/05 12:44 MHDA- 2024/11/05 17:01 PMCR- 2024/09/05 CRDT- 2024/09/05 11:19 PHST- 2024/08/22 00:00 [accepted] PHST- 2024/11/05 17:01 [medline] PHST- 2024/09/05 12:44 [pubmed] PHST- 2024/09/05 11:19 [entrez] PHST- 2024/09/05 00:00 [pmc-release] AID - 10.1007/s11886-024-02127-1 [pii] AID - 2127 [pii] AID - 10.1007/s11886-024-02127-1 [doi] PST - ppublish SO - Curr Cardiol Rep. 2024 Nov;26(11):1297-1307. doi: 10.1007/s11886-024-02127-1. Epub 2024 Sep 5. PMID- 39235729 OWN - NLM STAT- MEDLINE DCOM- 20241105 LR - 20261010 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - The Role of Obesity as a Cardiac Disease Risk Factor in Patients with Type 2 Diabetes. PG - 1309-1320 LID - 10.1007/s11886-024-02129-z [doi] AB - PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death globally and is closely associated with obesity and type 2 diabetes mellitus (T2DM). This review examines the interplay between obesity, T2DM, and CVD, highlighting the increasing prevalence and economic burden of these conditions. RECENT FINDINGS: Pharmacologic therapies, particularly glucagon-like peptide-1 receptor agonists, show promise in substantial weight loss and subsequent reduction of adverse cardiovascular events in obese individuals with and without diabetes. Obesity significantly contributes to the development of insulin resistance and T2DM, further escalating CVD risk. The common co-occurrence of these three conditions may involve several other pathophysiological mechanisms, such as chronic inflammation, increased visceral adiposity, and endothelial dysfunction. Until recently, lifestyle modifications and bariatric surgery had been the primary methods for weight loss and mitigating obesity-associated cardiovascular risk. Newer pharmacological options have led to a paradigm shift in our approach to obesity management as they provide substantial benefits in weight loss, glycemic control, and cardiovascular risk reduction. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Koirala, Sushant AU - Koirala S AD - Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. FAU - Sunnaa, Michael AU - Sunnaa M AD - Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. FAU - Bernier, Thomas AU - Bernier T AD - Division of Cardiology, Rush University Medical Center, Chicago, IL, 60612, USA. FAU - Oktay, Ahmet Afsin AU - Oktay AA AD - Division of Cardiology, Rush University Medical Center, Chicago, IL, 60612, USA. Ahmet_a_oktay@rush.edu. LA - eng PT - Journal Article PT - Review DEP - 20240905 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/physiopathology MH - *Obesity/complications/physiopathology MH - *Cardiovascular Diseases/etiology/prevention & control MH - *Heart Disease Risk Factors MH - Weight Loss MH - Bariatric Surgery MH - Insulin Resistance MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes Mellitus OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Weight loss EDAT- 2024/09/05 12:45 MHDA- 2024/11/05 17:02 CRDT- 2024/09/05 11:19 PHST- 2024/08/23 00:00 [accepted] PHST- 2024/11/05 17:02 [medline] PHST- 2024/09/05 12:45 [pubmed] PHST- 2024/09/05 11:19 [entrez] AID - 10.1007/s11886-024-02129-z [pii] AID - 10.1007/s11886-024-02129-z [doi] PST - ppublish SO - Curr Cardiol Rep. 2024 Nov;26(11):1309-1320. doi: 10.1007/s11886-024-02129-z. Epub 2024 Sep 5. PMID- 39235379 OWN - NLM STAT- MEDLINE DCOM- 20240905 LR - 20241202 IS - 1365-2168 (Electronic) IS - 0007-1323 (Print) IS - 0007-1323 (Linking) VI - 111 IP - 9 DP - 2024 Aug 30 TI - Cardiovascular and diabetes outcomes among patients with obesity and type 2 diabetes after metabolic bariatric surgery or glucagon-like peptide 1 receptor agonist treatment. LID - 10.1093/bjs/znae221 [doi] LID - znae221 AB - BACKGROUND: With the increasing prevalence of obesity and type 2 diabetes, the availability of different treatment options remains essential. Studies comparing the outcomes of glucagon-like peptide 1 receptor agonists with those of metabolic bariatric surgery in patients with type 2 diabetes and obesity are lacking. METHODS: Using propensity score matching, based on data from several nationwide clinical registries, patients who underwent primary metabolic bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) were matched with patients who received glucagon-like peptide 1 receptor agonists. Outcome measures included the occurrence of major cardiovascular events, microvascular complications, and potential side effects (alcohol/substance abuse, self-harm, and fractures). RESULTS: Over a mean follow-up of 7 years, major cardiovascular events occurred in 191 of 2039 patients (cumulative incidence 14.5%) in the surgery group compared with 247 of 2039 patients (19.6%) in the glucagon-like peptide 1 receptor agonist group (HR 0.75 (95% c.i. 0.62 to 0.91), P = 0.003). Patients in the surgery group had lower haemoglobin A1c values 5 years after treatment (mean difference 9.82 (95% c.i. 8.51 to 11.14) mmol/mol, P < 0.001) and fewer microvascular complications (retinopathy HR 0.88 (95% c.i. 0.79 to 0.99), P = 0.039; nephropathy HR 0.72 (95% c.i. 0.66 to 0.80), P < 0.001; and neuropathy or leg ulcers HR 0.82 (95% c.i. 0.74 to 0.92), P < 0.001), but a higher risk of alcohol/substance abuse (HR 2.56 (95% c.i. 1.87 to 3.50), P < 0.001), self-harm (HR 1.41 (95% c.i. 1.17 to 1.71), P < 0.001), and fractures (HR 1.86 (95% c.i. 1.11 to 3.12), P = 0.019). CONCLUSION: Compared with glucagon-like peptide 1 receptor agonist treatment, metabolic bariatric surgery is associated with superior metabolic outcomes and a lower risk of major cardiovascular events in patients with type 2 diabetes and obesity, but a higher risk of alcohol/substance abuse, self-harm, and fractures. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. FAU - Stenberg, Erik AU - Stenberg E AUID- ORCID: 0000-0001-9189-0093 AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Ottosson, Johan AU - Ottosson J AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Cao, Yang AU - Cao Y AD - Clinical Epidemiology and Biostatistics, School of Medical Sciences, Orebro University, Orebro, Sweden. AD - Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Sundbom, Magnus AU - Sundbom M AD - Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. FAU - Naslund, Erik AU - Naslund E AUID- ORCID: 0000-0002-0166-6344 AD - Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Surg JT - The British journal of surgery JID - 0372553 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/adverse effects MH - *Cardiovascular Diseases/etiology/epidemiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/complications MH - Obesity, Morbid/surgery/complications MH - Postoperative Complications/epidemiology/etiology MH - Propensity Score MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use PMC - PMC11375857 EDAT- 2024/09/05 12:43 MHDA- 2024/09/05 12:44 PMCR- 2024/09/05 CRDT- 2024/09/05 10:22 PHST- 2024/03/05 00:00 [received] PHST- 2024/06/05 00:00 [revised] PHST- 2024/08/07 00:00 [accepted] PHST- 2024/09/05 12:44 [medline] PHST- 2024/09/05 12:43 [pubmed] PHST- 2024/09/05 10:22 [entrez] PHST- 2024/09/05 00:00 [pmc-release] AID - 7749159 [pii] AID - znae221 [pii] AID - 10.1093/bjs/znae221 [doi] PST - ppublish SO - Br J Surg. 2024 Aug 30;111(9):znae221. doi: 10.1093/bjs/znae221. PMID- 39231072 OWN - NLM STAT- MEDLINE DCOM- 20240904 LR - 20250103 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 23 IP - 9 DP - 2024 Sep 1 TI - Cross-Sectional Analysis of Adverse Dermatologic Events Reported to the FDA After Use of GLP-1 Agonists. PG - e181-e182 FAU - Ituarte, Bianca E AU - Ituarte BE FAU - Taylor, Mitchell A AU - Taylor MA FAU - Thomas, Sierra I AU - Thomas SI FAU - Sharma, Divya AU - Sharma D FAU - High, Robin AU - High R FAU - Wysong, Ashley AU - Wysong A FAU - Wei, Erin X AU - Wei EX LA - eng PT - Letter PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *United States Food and Drug Administration MH - United States/epidemiology MH - Cross-Sectional Studies MH - Male MH - Female MH - Middle Aged MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Hypoglycemic Agents/adverse effects/administration & dosage MH - Glucagon-Like Peptide 1/agonists/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Liraglutide/adverse effects/therapeutic use MH - Exenatide/adverse effects/administration & dosage MH - Adult MH - Drug Eruptions/etiology/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/09/04 18:41 MHDA- 2024/09/04 18:42 CRDT- 2024/09/04 13:22 PHST- 2024/09/04 18:42 [medline] PHST- 2024/09/04 18:41 [pubmed] PHST- 2024/09/04 13:22 [entrez] AID - S1545961624P8287X [pii] PST - ppublish SO - J Drugs Dermatol. 2024 Sep 1;23(9):e181-e182. PMID- 39230989 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260410 IS - 1546-3141 (Electronic) IS - 0361-803X (Linking) VI - 223 IP - 6 DP - 2024 Dec TI - Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Receptor Agonist) Therapy. PG - e2431805 LID - 10.2214/AJR.24.31805 [doi] AB - BACKGROUND. The long-acting glucagon-like peptide-1 receptor agonist semaglutide is used to treat type 2 diabetes or obesity in adults. Clinical trials have observed associations of semaglutide with weight loss, improved control of diabetes, and cardiovascular risk reduction. OBJECTIVE. The purpose of this study was to evaluate intrapatient changes in body composition after initiation of semaglutide therapy by applying an automated suite of CT-based artificial intelligence (AI) body composition tools. METHODS. This retrospective study included adult patients who were receiving semaglutide treatment and who, between January 2016 and November 2023, underwent abdominopelvic CT within both 5 years before and 5 years after initiation of semaglutide. An automated suite of previously validated CT-based AI body composition tools was applied to scans obtained before semaglutide initiation (hereafter, presemaglutide scans) and scans obtained after semaglutide initiation (hereafter, postsemaglutide scans) to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, skeletal muscle area and attenuation, intermuscular adipose tissue (IMAT) area, liver volume and attenuation, and trabecular bone mineral density (BMD). Patients with weight loss of 5 kg or more and those with weight gain of 5 kg or more between the scans were compared. RESULTS. The study included 241 patients (151 women and 90 men; mean age, 60.4 +/- 12.4 [SD] years). In the weight-loss group (n = 67), the postsemaglutide scan, compared with the presemaglutide scan, showed a decrease in VAT area (309.4 vs 341.1 cm(2), p < .001), SAT area (371.4 vs 410.7 cm(2), p < .001), muscle area (179.2 vs 193.0, p < .001), and liver volume (2379.0 vs 2578 HU, p = .009) and an increase in liver attenuation (74.5 vs 67.6 HU, p = .03). In the weight-gain group (n = 48), the postsemaglutide scan, compared with the presemaglutide scan, showed an increase in VAT area (334.0 vs 312.8, p = .002), SAT area (485.8 vs 448.8 cm(2), p = .01), and IMAT area (48.4 vs 37.6, p = .009) and a decrease in muscle attenuation (5.9 vs 13.1, p < .001). Other comparisons were not statistically significant (p > .05). CONCLUSION. Patients using semaglutide who lost versus gained weight showed distinct patterns of changes in CT-based body composition measures. Those with weight loss had overall favorable shifts in measures related to cardiometabolic risk. A decrease in muscle attenuation in those with weight gain is consistent with decreased muscle quality. CLINICAL IMPACT. Among patients using semaglutide, automated CT-based AI tools provide biomarkers of changes in body composition beyond those that are evident by standard clinical measures. FAU - Nelson, Leslie W AU - Nelson LW AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Lee, Matthew H AU - Lee MH AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Garrett, John W AU - Garrett JW AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. AD - Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI. AD - Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI. FAU - Pickhardt, Silas G AU - Pickhardt SG AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Warner, Joshua D AU - Warner JD AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Summers, Ronald M AU - Summers RM AD - Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD. FAU - Pickhardt, Perry J AU - Pickhardt PJ AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. AD - Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI. LA - eng PT - Journal Article DEP - 20240904 PL - United States TA - AJR Am J Roentgenol JT - AJR. American journal of roentgenology JID - 7708173 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - AJR Am J Roentgenol. 2024 Dec;223(6):e2432045. doi: 10.2214/AJR.24.32045. PMID: 39291948 CIN - AJR Am J Roentgenol. 2024 Dec;223(6):e2432063. doi: 10.2214/AJR.24.32063. PMID: 39320356 MH - Humans MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - *Body Composition/drug effects MH - *Tomography, X-Ray Computed/methods MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/agonists MH - Obesity/drug therapy MH - Adult MH - Semaglutide OTO - NOTNLM OT - CT OT - artificial intelligence OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - semaglutide EDAT- 2024/09/04 18:42 MHDA- 2025/01/07 00:21 CRDT- 2024/09/04 12:22 PHST- 2025/01/07 00:21 [medline] PHST- 2024/09/04 18:42 [pubmed] PHST- 2024/09/04 12:22 [entrez] AID - 10.2214/AJR.24.31805 [doi] PST - ppublish SO - AJR Am J Roentgenol. 2024 Dec;223(6):e2431805. doi: 10.2214/AJR.24.31805. Epub 2024 Sep 4. PMID- 39226030 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260725 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 184 IP - 11 DP - 2024 Nov 1 TI - GLP-1 Receptor Agonist Use and Risk of Suicide Death. PG - 1301-1312 LID - 10.1001/jamainternmed.2024.4369 [doi] AB - IMPORTANCE: Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm. OBJECTIVE: To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice. DESIGN, SETTING, AND PARTICIPANTS: This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024. EXPOSURE: Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor. MAIN OUTCOMES AND MEASURES: The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis. RESULTS: In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders. CONCLUSIONS AND RELEVANCE: This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years. FAU - Ueda, Peter AU - Ueda P AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Soderling, Jonas AU - Soderling J AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Wintzell, Viktor AU - Wintzell V AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Svanstrom, Henrik AU - Svanstrom H AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Pazzagli, Laura AU - Pazzagli L AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Eliasson, Bjorn AU - Eliasson B AD - The Swedish National Diabetes Register, Vastra Gotalandsregionen, Gothenburg, Sweden. AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Melbye, Mads AU - Melbye M AD - HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Pediatrics, Stanford University School of Medicine, Stanford, California. AD - Danish Cancer Institute, Copenhagen, Denmark. FAU - Hviid, Anders AU - Hviid A AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. AD - Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Pasternak, Bjorn AU - Pasternak B AD - Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - JAMA Intern Med. 2024 Nov 1;184(11):1312-1313. doi: 10.1001/jamainternmed.2024.4320. PMID: 39226047 EIN - JAMA Intern Med. 2024 Nov 1;184(11):1396. doi: 10.1001/jamainternmed.2024.6163. PMID: 39495245 MH - Humans MH - Male MH - Female MH - Middle Aged MH - Denmark/epidemiology MH - Aged MH - Adult MH - *Suicide/statistics & numerical data MH - Sweden/epidemiology MH - Aged, 80 and over MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Young Adult MH - Adolescent MH - Registries MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Cohort Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11372654 COIS- Conflict of Interest Disclosures: Dr Ueda reported grants from the Karolinska Institutet and the Strategic Research Area Epidemiology program during the conduct of the study. Dr Svanstrom reported being a former employee of IQVIA. Dr Pazzagli was supported by a grant from the Swedish Research Council for Health, Working Life, and Welfare. Dr Eliasson reported support from Konung Gustaf V:s and Drottning Victorias Frimurarstiftelse and personal fees from Novo Nordisk, Sanofi, Eli Lilly, Amgen, AstraZeneca, Boehringer Ingelheim, and Abbott outside the submitted work. Dr Melbye was supported by a grant from the Danish Cancer Society. Dr Hviid reported grants from the Novo Nordisk Foundation, the Lundbeck Foundation, and the Denmark Independent Research Fund outside the submitted work. Dr Pasternak reported grants from the Karolinska Institutet during the conduct of the study. No other disclosures were reported. EDAT- 2024/09/03 12:44 MHDA- 2024/11/04 12:24 PMCR- 2024/09/03 CRDT- 2024/09/03 11:33 PHST- 2024/11/04 12:24 [medline] PHST- 2024/09/03 12:44 [pubmed] PHST- 2024/09/03 11:33 [entrez] PHST- 2024/09/03 00:00 [pmc-release] AID - 2823083 [pii] AID - ioi240055 [pii] AID - 10.1001/jamainternmed.2024.4369 [doi] PST - ppublish SO - JAMA Intern Med. 2024 Nov 1;184(11):1301-1312. doi: 10.1001/jamainternmed.2024.4369. PMID- 39224963 OWN - NLM STAT- MEDLINE DCOM- 20241226 LR - 20250104 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 91 IP - 1 DP - 2025 Jan TI - Use of, time to, and type of first add-on anti-hyperglycaemic therapy to metformin in Australia, 2018-2022. PG - 117-126 LID - 10.1111/bcp.16231 [doi] AB - AIMS: The aim of this study was to examine contemporary trends in the use of, time to, and type of first add-on anti-hyperglycaemic therapy to metformin in Australia. METHODS: We used the dispensing records of a 10% random sample of Pharmaceutical Benefits Scheme (PBS) eligible people. We included people aged 40 years and older initiating metformin from 1 January 2018 to 31 December 2020. Our primary outcome was first add-on anti-hyperglycaemic medicine within 2 years of metformin initiation. We analysed time to dispensing of first add-on therapy. All analyses were stratified by metformin initiation year. RESULTS: Overall, 38 747 people aged 40 years and older initiated metformin between 2018 and 2020. Approximately one-third (n = 12 946) of people received add-on therapy with the proportion increasing slightly by year of metformin initiation (32.3% in 2018 to 34.8% in 2020). Amongst people with add-on therapy following metformin initiation, sodium-glucose cotransporter 2 inhibitor (SGLT2i) use increased from 28.8% (2018) to 35.0% (2020), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) increased from 3.0% to 9.6%, respectively. Dipeptidyl peptidase-4 inhibitors and sulfonylureas as first add-on therapy decreased and insulin remained stable. One-third of people with add-on therapy initiated the therapy on the same day metformin was initiated, i.e. initial combination therapy. CONCLUSIONS: Amongst people initiating metformin from 2018 to 2020, there was an increasing proportion of SGLT2i and GLP-1 RA being used as first add-on therapy. However, the overall prevalence of add-on therapy was low. Advocacy to promote add-on therapy with cardiorenal beneficial medicines is critical to reduce type 2 diabetes morbidity and mortality. CI - (c) 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Milder, Tamara Y AU - Milder TY AUID- ORCID: 0009-0002-0538-2661 AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, Australia. AD - Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia. AD - Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia. FAU - Lin, Jialing AU - Lin J AUID- ORCID: 0000-0002-0643-9191 AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - Pearson, Sallie-Anne AU - Pearson SA AUID- ORCID: 0000-0001-7137-6855 AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - Greenfield, Jerry R AU - Greenfield JR AUID- ORCID: 0000-0002-0866-0973 AD - Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, Australia. AD - Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia. FAU - Day, Richard O AU - Day RO AUID- ORCID: 0000-0002-6045-6937 AD - Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia. FAU - Stocker, Sophie L AU - Stocker SL AUID- ORCID: 0000-0002-2114-587X AD - Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia. AD - School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia. AD - School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Australia. FAU - Neuen, Brendon L AU - Neuen BL AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. AD - Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia. FAU - Falster, Michael O AU - Falster MO AUID- ORCID: 0000-0001-6444-7272 AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - de Oliveira Costa, Juliana AU - de Oliveira Costa J AUID- ORCID: 0000-0002-8355-023X AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. LA - eng GR - 1196900/National Health and Medical Research Council/ GR - 105609/WT_/Wellcome Trust/United Kingdom GR - RG181181/National Heart Foundation of Australia/ GR - 2026621/NHMRC Emerging Leader Investigator Grant/ GR - 2023HIG69/Ramaciotti Foundation Health Investment Grant/ GR - 105609/WT_/Wellcome Trust/United Kingdom PT - Journal Article DEP - 20240903 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Australia MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Therapy, Combination MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Adult MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Insulin/therapeutic use MH - Practice Patterns, Physicians'/statistics & numerical data/trends MH - Time Factors MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11671323 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - combination therapy OT - pharmacoepidemiology OT - pharmacotherapy OT - type 2 diabetes COIS- S.A.P. is a member of the Drug Utilization Sub-Committee of the Pharmaceutical Benefits Advisory Committee. The views expressed in this paper do not represent those of the Committee. B.L.N. has received fees for travel support, advisory boards, scientific presentations and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer and Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, Janssen, the limbic, and Medscape, with all honoraria paid to The George Institute for Global Health. EDAT- 2024/09/03 06:43 MHDA- 2024/12/27 00:21 PMCR- 2024/09/03 CRDT- 2024/09/03 04:53 PHST- 2024/07/31 00:00 [revised] PHST- 2024/05/29 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/12/27 00:21 [medline] PHST- 2024/09/03 06:43 [pubmed] PHST- 2024/09/03 04:53 [entrez] PHST- 2024/09/03 00:00 [pmc-release] AID - BCP16231 [pii] AID - 10.1111/bcp.16231 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2025 Jan;91(1):117-126. doi: 10.1111/bcp.16231. Epub 2024 Sep 3. PMID- 39223865 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Beneficial effect of oral semaglutide for type 2 diabetes mellitus in patients with metabolic dysfunction-associated steatotic liver disease: A prospective, multicentre, observational study. PG - 4958-4965 LID - 10.1111/dom.15898 [doi] AB - AIMS: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events. RESULTS: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%). CONCLUSIONS: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Arai, Taeang AU - Arai T AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. FAU - Atsukawa, Masanori AU - Atsukawa M AUID- ORCID: 0000-0003-3374-7111 AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. FAU - Tsubota, Akihito AU - Tsubota A AD - Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan. FAU - Oikawa, Tsunekazu AU - Oikawa T AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Tada, Toshifumi AU - Tada T AD - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan. FAU - Matsuura, Kentaro AU - Matsuura K AD - Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. FAU - Ishikawa, Toru AU - Ishikawa T AD - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. FAU - Abe, Hiroshi AU - Abe H AD - Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan. FAU - Kato, Keizo AU - Kato K AD - Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan. FAU - Morishita, Asahiro AU - Morishita A AD - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Tani, Joji AU - Tani J AD - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Okubo, Tomomi AU - Okubo T AD - Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan. FAU - Nagao, Mototsugu AU - Nagao M AD - Division of Endocrinology, Diabetes and Metabolism, Nippon Medical School, Tokyo, Japan. FAU - Iwabu, Masato AU - Iwabu M AD - Division of Endocrinology, Diabetes and Metabolism, Nippon Medical School, Tokyo, Japan. FAU - Iwakiri, Katsuhiko AU - Iwakiri K AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240902 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Fatty Liver/drug therapy/complications MH - Treatment Outcome MH - Non-alcoholic Fatty Liver Disease/drug therapy/complications MH - Adult MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/analysis/drug effects/metabolism MH - Semaglutide OTO - NOTNLM OT - clinical trial OT - diabetes complications OT - effectiveness OT - liver EDAT- 2024/09/03 06:43 MHDA- 2024/10/04 12:43 CRDT- 2024/09/03 02:03 PHST- 2024/08/04 00:00 [revised] PHST- 2024/06/17 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/03 06:43 [pubmed] PHST- 2024/09/03 02:03 [entrez] AID - 10.1111/dom.15898 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4958-4965. doi: 10.1111/dom.15898. Epub 2024 Sep 2. PMID- 39222642 OWN - NLM STAT- MEDLINE DCOM- 20240907 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 404 IP - 10456 DP - 2024 Sep 7 TI - Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. PG - 949-961 LID - S0140-6736(24)01643-X [pii] LID - 10.1016/S0140-6736(24)01643-X [doi] AB - BACKGROUND: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established. METHODS: We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2.4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1.0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete. FINDINGS: Across the four trials, 3743 (16.8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5.4%] of 1914 in the semaglutide group had events vs 138 [7.5%] of 1829 in the placebo group; hazard ratio [HR] 0.69 [95% CI 0.53-0.89]; p=0.0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2.8%] vs 86 [4.7%]; HR 0.59 [0.41-0.82]; p=0.0019). No significant effect on cardiovascular death alone was seen (59 [3.1%] vs 67 [3.7%]; HR 0.82 [0.57-1.16]; p=0.25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29.9%] vs 708 [38.7%]). INTERPRETATION: In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available. FUNDING: Novo Nordisk. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org. FAU - Deanfield, John AU - Deanfield J AD - Institute of Cardiovascular Science, University College London, London, UK. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Borlaug, Barry A AU - Borlaug BA AD - Mayo Clinic, Rochester, MN, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott & White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK; National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle, WA, USA. FAU - Kahn, Steven E AU - Kahn SE AD - Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA; University of Washington, Seattle, WA, USA. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Wake Forest University School of Medicine, Winston-Salem, NC, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Stanford School of Medicine, Palo Alto, CA, USA. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Plutzky, Jorge AU - Plutzky J AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - Ronnback, Cecilia AU - Ronnback C AD - Novo Nordisk, Soborg, Denmark. FAU - Shah, Sanjiv J AU - Shah SJ AD - Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada. FAU - Weeke, Peter E AU - Weeke PE AD - Novo Nordisk, Soborg, Denmark. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. CN - SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT04916470 SI - ClinicalTrials.gov/NCT03574597 SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT04788511 GR - U01 AG076928/AG/NIA NIH HHS/United States GR - P30 AG021332/AG/NIA NIH HHS/United States GR - U01 HL160272/HL/NHLBI NIH HHS/United States GR - R01 AG018915/AG/NIA NIH HHS/United States GR - R01 AG078153/AG/NIA NIH HHS/United States GR - U24 AG059624/AG/NIA NIH HHS/United States GR - R01 AG045551/AG/NIA NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20240830 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2024 Sep 7;404(10456):909-911. doi: 10.1016/S0140-6736(24)01763-X. PMID: 39222643 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - *Heart Failure/drug therapy/mortality MH - Hospitalization/statistics & numerical data MH - Obesity/drug therapy MH - *Stroke Volume MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Semaglutide COIS- Declaration of interests MNK has served as a consultant for 35Pharma, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Corcept Therapeutics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Regeneron, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has served on a data monitoring board for Applied Therapeutics; has served on an advisory board for Alnylam, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Esperion Therapeutics, Merck (Diabetes and Cardiovascular), Novo Nordisk, and Sanofi; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stocks in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received support for data analyses from AstraZeneca and Vifor. JD has received consulting honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda and research grants from Aegerion, British Heart Foundation, Colgate, UK Medical Research Council, MSD, National Institute for Health and Care Research, Pfizer, Public Health England, and Roche. RP reports speaker fees from Eli Lilly, Lilly USA, and Novo Nordisk; consulting fees from AbbVie, AstraZeneca, Bayer, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA), Intas Pharmaceuticals, Eli Lilly, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi. All grants are directed to RP's institution. Up to Dec 31, 2023, payment for RP's consultant and speaker services was made directly to his employer, AdventHealth, a nonprofit entity; as of Jan 1, 2024, payment was directed to RP personally. BAB receives research support from the US National Institutes of Health and the US Department of Defense, as well as research grant funding from AstraZeneca, Axon Therapies, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; he has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, NGM, Novo Nordisk, NXT, and VADovations; and is named inventor (US patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. JB is a consultant to Abbott, American Regent, Amgen, Applied Therapeutics, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, CardioCell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards Lifesciences, Element Science, Faraday, Foundry, G3P, Imbria, Impulse Dynamics, Innolife, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, PharmaIN, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, scPharmaceuticals, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. MJD has acted as a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; an advisory board member for AstraZeneca, Carmot/Roche, Medtronic, Pfizer, and Zealand Pharma; and a speaker for Amgen and AstraZeneca; and has received grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi-Aventis. SSE has received consulting fees from Amylyx, AstraZeneca, Avillion, Ayala, Bayer, BeiGene, Boehringer Ingelheim, 89 Bio, BioAge, BioAtla, Bristol Meyer Squibb, BridgeBio, Daiichi Sankyo, Denovo, Fore Therapeutics, GlaxoSmithKline, Inovio, Insmed, Ipsen, Karuna, Lilly, Lundbeck, Mirati, Moderna, Novartis, Novavax, Novo Nordisk, National Surgical Adjuvant Breast and Bowel Project, Pfizer, Principia, Reata, Rebiotx, Roche, Sanofi, solvd, Sutro Biopharma, and TG Therapeutics. SEK received consulting fees from Casma Therapeutics, Oramed, and Third Rock Ventures; and served on an advisory board for AltPep, Anji Pharmaceuticals, Bayer, Boehringer Ingelheim, Eli Lilly, Intarcia, Merck, and Novo Nordisk. He has received stock options from AltPep. DK was supported in part by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine and US National Institutes of Health grants U01AG076928, R01AG078153, R01AG045551, R01AG18915, P30AG021332, U24AG059624, and U01HL160272; and received honoraria as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Corvia Medical, Ketyo, Novartis, Novo Nordisk, Pfizer, and Rivus; grant funding from AstraZeneca, Bayer, Novartis, Novo Nordisk, Pfizer, and Rivus; and has stock ownership in Gilead Sciences. IL has received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals, Novo Nordisk, Pfizer, and Sanofi; served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals, Biomea, Boehringer Ingelheim, Carmot, Eli Lilly, Intarcia, Intercept Pharmaceuticals, Janssen Global Services, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, MannKind, Merck, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Valeritas, and Zealand Pharma; and received travel expenses from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, Novo Nordisk, Sanofi, and Zealand Pharma. KWM has received grants from AHA, Apple, Bayer, California Institute for Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google, Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and consulting fees from Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and holds stock options for Human, Medeloop, Precordior, and Regencor. MCP was supported by the British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217; has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, and SQ Innovations; and served on committees or consulted for AbbVie, Akero, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Cardiorentis, Corvia, Eli Lilly, Horizon Therapeutics, LIB Therapeutics, Moderna, New Amsterdam, Novartis, Novo Nordisk, Pharmacosmos, Siemens, SQ Innovations, Takeda, Teikoku, and Vifor. JP has received consulting fees from Altimmune, Amgen, Esperion Therapeutics, Merck, MJH Life Sciences, Novartis, and Novo Nordisk and received a grant, paid to his institution, from Boehringer Ingelheim. CR, SR, and PEW are employees and SR and PEW are shareholders of Novo Nordisk. SJS has received research grants from AstraZeneca, Corvia, and Pfizer; and consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. SV reports speaking honoraria or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. AML has received research grants from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion Therapeutics, and Novartis, paid to his institution; and consulting fees from Akebia Therapeutics, Alnylam Pharmaceuticals, Ardelyx, Eli Lilly, FibroGen, GlaxoSmithKline, Intarcia, Medtronic Vascular, Novartis, Novo Nordisk, Provention Bio, Amgen, and ReCor Medical. All other authors declare no competing interests. EDAT- 2024/09/03 01:42 MHDA- 2024/09/08 13:49 CRDT- 2024/09/02 18:53 PHST- 2024/07/18 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/09/08 13:49 [medline] PHST- 2024/09/03 01:42 [pubmed] PHST- 2024/09/02 18:53 [entrez] AID - S0140-6736(24)01643-X [pii] AID - 10.1016/S0140-6736(24)01643-X [doi] PST - ppublish SO - Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30. PMID- 39219539 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Utilization and cost of non-insulin glucose-lowering drugs in Australia from 2013 to 2023. PG - 4924-4932 LID - 10.1111/dom.15893 [doi] AB - OBJECTIVES: To investigate the utilization and costs of non-insulin glucose-lowering drugs (GLDs) in Australia from 2013 to 2023. MATERIALS AND METHODS: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation. RESULTS: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium-glucose cotransporter-2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon-like peptide-1 receptor agonists (GLP-1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase-4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP-1RAs contributed to 35% of the costs. CONCLUSION: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP-1RA and SGLT2 inhibitor prescribing. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hamblin, Peter S AU - Hamblin PS AUID- ORCID: 0000-0002-6280-865X AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. AD - Department of Endocrinology & Diabetes, Alfred Health, Melbourne, Victoria, Australia. AD - Department of Endocrinology & Diabetes, Western Health, St Albans, Victoria, Australia. FAU - Earnest, Arul AU - Earnest A AUID- ORCID: 0000-0003-2693-5034 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. FAU - Russell, Anthony W AU - Russell AW AUID- ORCID: 0000-0001-7886-8844 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. AD - Department of Endocrinology & Diabetes, Alfred Health, Melbourne, Victoria, Australia. FAU - Talic, Stella AU - Talic S AUID- ORCID: 0000-0001-7739-3381 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. FAU - Zomer, Ella AU - Zomer E AUID- ORCID: 0000-0002-9993-4297 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. FAU - Zoungas, Sophia AU - Zoungas S AUID- ORCID: 0000-0003-2672-0949 AD - School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. LA - eng PT - Journal Article DEP - 20240902 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - *Hypoglycemic Agents/therapeutic use/economics MH - Retrospective Studies MH - Australia/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/economics MH - Drug Costs/statistics & numerical data/trends MH - Drug Utilization/statistics & numerical data/trends/economics MH - Metformin/therapeutic use/economics MH - Male MH - Female MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - database research OT - observational study OT - type 2 diabetes EDAT- 2024/09/02 08:45 MHDA- 2024/10/04 12:42 CRDT- 2024/09/02 05:03 PHST- 2024/07/27 00:00 [revised] PHST- 2024/06/04 00:00 [received] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/02 08:45 [pubmed] PHST- 2024/09/02 05:03 [entrez] AID - 10.1111/dom.15893 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4924-4932. doi: 10.1111/dom.15893. Epub 2024 Sep 2. PMID- 39219442 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Diabetic kidney disease: The fourth pharmacological pillar may be semaglutide. PG - 4813-4815 LID - 10.1111/dom.15892 [doi] FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - De Nicola, Luca AU - De Nicola L AD - Nephrologic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. LA - eng PT - Journal Article DEP - 20240902 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetic Nephropathies/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/09/02 08:45 MHDA- 2024/10/04 12:42 CRDT- 2024/09/02 04:03 PHST- 2024/08/01 00:00 [revised] PHST- 2024/07/11 00:00 [received] PHST- 2024/08/05 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/02 08:45 [pubmed] PHST- 2024/09/02 04:03 [entrez] AID - 10.1111/dom.15892 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4813-4815. doi: 10.1111/dom.15892. Epub 2024 Sep 2. PMID- 39219392 OWN - NLM STAT- MEDLINE DCOM- 20240902 LR - 20250103 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 20 IP - 884 DP - 2024 Aug 28 TI - [Innovative therapeutic drug combination for type 2 diabetes at cardiorenal risk]. PG - 1492-1497 LID - 10.53738/REVMED.2024.20.884.1492 [doi] AB - Both glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiorenal -prognosis of at-risk patients with type 2 diabetes thanks to pleiotropic effects that are either common or specific. This article discusses the clinical efficacy of a combined therapy with the two medications. Data were obtained from post hoc analyses of subgroups of participants to cardiovascular outcome trials and from real-life observational retro-spective cohort studies. The reported superiority of the combination versus either monotherapy should be confirmed in an ongoing large prospective trial (PRECIDENTD). The extra-cost of such a combined therapy as well as the common underuse of each pharmacological class in daily clinical practice deserve attention. FAU - Scheen, Andre J AU - Scheen AJ AUID- ORCID: 0000-0001-9743-4371 AD - Service de diabetologie, nutrition et maladies metaboliques, Departement de medecine, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AUID- ORCID: 0000-0001-7923-2098 AD - Service de diabetologie, nutrition et maladies metaboliques, Departement de medecine, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Combinaison therapeutique innovante pour le diabete type 2 a risque cardiorenal. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Drug Therapy, Combination/methods MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Cardiovascular Diseases/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Les auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2024/09/02 08:45 MHDA- 2024/09/02 08:46 CRDT- 2024/09/02 03:52 PHST- 2024/09/02 08:46 [medline] PHST- 2024/09/02 08:45 [pubmed] PHST- 2024/09/02 03:52 [entrez] AID - RMS0884-010 [pii] AID - 10.53738/REVMED.2024.20.884.1492 [doi] PST - ppublish SO - Rev Med Suisse. 2024 Aug 28;20(884):1492-1497. doi: 10.53738/REVMED.2024.20.884.1492. PMID- 39219391 OWN - NLM STAT- MEDLINE DCOM- 20240902 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 20 IP - 884 DP - 2024 Aug 28 TI - [GLP-1 receptor agonists : impact on diabetic kidney disease]. PG - 1488-1491 LID - 10.53738/REVMED.2024.20.884.1488 [doi] AB - In addition to optimal glycemic control and management of other factors aggravating the pathology (hypertension, dyslipidemia, -obesity), the cornerstone of treatment of diabetic kidney disease (DKD) includes blockers of the renin-angiotensin system, sodium-glucose cotransporter 2 inhibitors or nonsteroidal antagonists of the mineralocorticoid receptor (finerenone). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended in the treatment of high-risk patients with type 2 diabetes (T2DM) to reduce cardiovascular (CV) risk. Data from CV studies indicate a nephroprotective effect of certain GLP-1 RAs in T2DM patients with DKD. The FLOW study published in May 2024, analyzing the impact of semaglutide vs placebo on renal events as primary outcome, confirms this renal protection of GLP-1 RAs. FAU - Wera, Madeleine AU - Wera M AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AUID- ORCID: 0000-0001-7923-2098 AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Agonistes des recepteurs du GLP-1 : -impact sur la maladie renale diabetique. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Cardiovascular Diseases/prevention & control MH - Renin-Angiotensin System/drug effects/physiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- N. Paquot est coinvestigateur principal pour le CHU de Liege dans l'essai SURPASS-CVOT et declare avoir recu des honoraires comme orateur et/ou membre d'un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Lilly, NovoNordisk, Fresenius et Sanofi. EDAT- 2024/09/02 08:46 MHDA- 2024/09/02 08:47 CRDT- 2024/09/02 03:52 PHST- 2024/09/02 08:47 [medline] PHST- 2024/09/02 08:46 [pubmed] PHST- 2024/09/02 03:52 [entrez] AID - RMS0884-009 [pii] AID - 10.53738/REVMED.2024.20.884.1488 [doi] PST - ppublish SO - Rev Med Suisse. 2024 Aug 28;20(884):1488-1491. doi: 10.53738/REVMED.2024.20.884.1488. PMID- 39218393 OWN - NLM STAT- MEDLINE DCOM- 20241122 LR - 20260312 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 106 IP - 6 DP - 2024 Dec TI - A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. PG - 1170-1180 LID - S0085-2538(24)00629-X [pii] LID - 10.1016/j.kint.2024.08.023 [doi] AB - Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m(2) and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 mug, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m(2), geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 mug (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 mug (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 mug were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study. CI - Copyright (c) 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Selvarajah, Viknesh AU - Selvarajah V AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Robertson, Darren AU - Robertson D AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Hansen, Lars AU - Hansen L AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Jermutus, Lutz AU - Jermutus L AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Smith, Kirsten AU - Smith K AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Coggi, Angela AU - Coggi A AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Sanchez, Jose AU - Sanchez J AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Chang, Yi-Ting AU - Chang YT AD - Oncology Biometrics, late Oncology R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Yu, Hongtao AU - Yu H AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parkinson, Joanna AU - Parkinson J AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Khan, Anis AU - Khan A AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Chung, H Sophia AU - Chung HS AD - Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Hess, Sonja AU - Hess S AD - Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Dumas, Richard AU - Dumas R AD - CISSS Laval, Medecine Department, Endocrinology Division, Laval, Quebec, Canada; Centre de recherches cliniques de Laval, Laval, Quebec, Canada. FAU - Duck, Tabbatha AU - Duck T AD - Division of Nephrology, Clinical Research Solutions, Waterloo, Ontario, Canada. FAU - Jolly, Simran AU - Jolly S AD - Department of Arts and Science, McMaster University, Hamilton, Ontario, Canada. FAU - Elliott, Tom G AU - Elliott TG AD - BC Diabetes, Vancouver, British Columbia, Canada. FAU - Baker, John AU - Baker J AD - Aoteoroa Clinical Trials, Middlemore Hospital, Auckland, New Zealand. FAU - Lecube, Albert AU - Lecube A AD - Endocrinology and Nutrition Department, Arnau de Vilanova University Hospital and Obesity, Diabetes and Metabolism (ODIM) Research Group, Institut de Recerca Biomedica de Lleida, University of Lleida, Lleida, Catalonia, Spain. FAU - Derwahl, Karl-Michael AU - Derwahl KM AD - Institute for Clinical Research and Development, Practise of Endocrinology, Berlin, Germany. FAU - Scott, Russell AU - Scott R AD - Clinical Research Ltd., Christchurch, New Zealand. FAU - Morales, Cristobal AU - Morales C AD - CardioRenalMetabolic Health Unit, Vithas Hospital, Seville, Spain. FAU - Peters, Carl AU - Peters C AD - Diabetes Services, Te Whatu Ora Waitemata, Auckland, New Zealand. FAU - Goldenberg, Ronald AU - Goldenberg R AD - LMC Diabetes & Endocrinology, Vaughan, Ontario, Canada. FAU - Parker, Victoria E R AU - Parker VER AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; The George Institute for Global Health, Sydney, Australia. Electronic address: h.j.lambers.heerspink@umcg.nl. CN - study investigators LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240831 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Glucagon) RN - AYI8EX34EU (Creatinine) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - QL6A9B13HW (cotadutide) SB - IM MH - Humans MH - Female MH - Male MH - Aged MH - *Diabetic Nephropathies/drug therapy/diagnosis MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Albuminuria/drug therapy/urine/diagnosis MH - Kidney/drug effects/physiopathology MH - Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Receptors, Glucagon/agonists MH - Creatinine/urine/blood MH - Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - cotadutide OT - diabetic kidney disease OT - type 2 diabetes mellitus EDAT- 2024/09/02 08:44 MHDA- 2024/11/23 11:12 CRDT- 2024/09/01 19:30 PHST- 2024/04/19 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/15 00:00 [accepted] PHST- 2024/11/23 11:12 [medline] PHST- 2024/09/02 08:44 [pubmed] PHST- 2024/09/01 19:30 [entrez] AID - S0085-2538(24)00629-X [pii] AID - 10.1016/j.kint.2024.08.023 [doi] PST - ppublish SO - Kidney Int. 2024 Dec;106(6):1170-1180. doi: 10.1016/j.kint.2024.08.023. Epub 2024 Aug 31. PMID- 39217553 OWN - NLM STAT- MEDLINE DCOM- 20241017 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 17 DP - 2024 Oct 22 TI - Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial. PG - 1615-1628 LID - S0735-1097(24)08116-6 [pii] LID - 10.1016/j.jacc.2024.08.004 [doi] AB - BACKGROUND: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent >/=50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m(2), kidney replacement therapy, and kidney or CV death) by 24%. OBJECTIVES: This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. METHODS: Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. RESULTS: A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. CONCLUSIONS: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153). CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. Electronic address: Richard.pratley.md@adventhealth.com. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Inland Northwest Health, Spokane, Washington, USA; University of Washington School of Medicine, Seattle, Washington, USA. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Perkovic, Vlado AU - Perkovic V AD - University of New South Wales, Sydney, New South Wales, Australia. FAU - Nielsen, Olav Wendelboe AU - Nielsen OW AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany; University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - MacIsaac, Richard J AU - MacIsaac RJ AD - Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; Department of Medicine, Fitzroy, Victoria and Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Parkville, Victoria, Australia. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Kamenov, Zdravko AU - Kamenov Z AD - Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Marco Bo AU - Hansen MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hadjadj, Samy AU - Hadjadj S AD - l'Institut du Thorax, Nantes Universite, Centre Hospitalier Universitaire Nantes, Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Nantes, France. FAU - Bakris, George AU - Bakris G AD - Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois, USA. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA. CN - FLOW Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240830 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Heart Failure/drug therapy/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Double-Blind Method MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - heart failure OT - outcomes OT - semaglutide OT - type 2 diabetes COIS- Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Pratley has received speaker fees paid to his employer, AdventHealth (through December 31, 2023) from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees directed to his institution from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd, Intas Pharmaceuticals, Eli Lilly, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; has received grants directed to his institution from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi; and has received personal fees (from January 1, 2024) from AdventHealth, a nonprofit entity. Dr Tuttle has received support from National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, and from Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, and the Doris Duke Foundation outside of the submitted work; has received consulting fees from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and has received speaker fees from Novo Nordisk. Dr Rossing has received grants from Bayer, AstraZeneca, and Novo Nordisk; has received honoraria paid to the Steno Diabetes Centre Copenhagen from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer; and has received consulting fees from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UptoDate; and is Board Director for George Clinical, St Vincent's Health Australia and several independent medical research institutes. Dr Mann has received grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; has received consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; has received honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, as well as a leadership role in the Kidney Disease: Improving Global Outcomes group. Dr MacIsaac was a FLOW trial investigator and member of the FLOW global expert panel; has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program, and The National Health and Medical Research Council of Australia; has received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, MSD, Novartis, and Boehringer Ingelheim; has been on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, AstraZeneca, and MSD; has received travel support from Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca; and has been a principal investigator for industry-sponsored clinical trials run by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag, and AbbVie. Dr Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Kamenov has received speaker fees from Actavis, AstraZeneca, Bayer-Schering, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, KRKA, Merck, MLD, MSD (Merck), Mundipharma, Mylan, Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, Servier, TEVA Pharmaceuticals, Valentis, Vedra, and Viatris. Dr Hadjadj has received grants from Asdia, Asten, AstraZeneca, Homeperf, LVL, Nestle Home Care, Pierre Fabre, and VitalAire; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier, and Valbiotis; has received speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Sante, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, and Valbiotis; and has received meeting invitations from AstraZeneca, Abbott, Dino Sante, Eli Lilly, and Novo Nordisk. Dr Bakris has received consulting fees from Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Novo Nordisk, and Dia Medica Therapeutics. Dr Mahaffey has received grants from the American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson and Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson and Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, and Theravance; and holds equity in Human, Medeloop, Precordior and Regencor. Drs Rasmussen, Nielsen, Idorn, Hansen, and Baeres are employees of and shareholders in Novo Nordisk. EDAT- 2024/09/01 16:19 MHDA- 2024/10/17 10:20 CRDT- 2024/09/01 10:33 PHST- 2024/07/13 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/09 00:00 [accepted] PHST- 2024/10/17 10:20 [medline] PHST- 2024/09/01 16:19 [pubmed] PHST- 2024/09/01 10:33 [entrez] AID - S0735-1097(24)08116-6 [pii] AID - 10.1016/j.jacc.2024.08.004 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Oct 22;84(17):1615-1628. doi: 10.1016/j.jacc.2024.08.004. Epub 2024 Aug 30. PMID- 39217501 OWN - NLM STAT- MEDLINE DCOM- 20241007 LR - 20260918 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 45 IP - 38 DP - 2024 Oct 7 TI - Quantifying antihypertensive effects of GLP-1 agonists. PG - 4135-4137 LID - 10.1093/eurheartj/ehae520 [doi] FAU - Cohen, Jordana B AU - Cohen JB AUID- ORCID: 0000-0003-4649-079X AD - Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, 831 Blockley, Philadelphia, PA 19104, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Bress, Adam P AU - Bress AP AUID- ORCID: 0000-0002-2259-5039 AD - Intermountain Healthcare Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA. LA - eng PT - Comment PT - Editorial PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Antihypertensive Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CON - Eur Heart J. 2024 Oct 7;45(38):4124-4134. doi: 10.1093/eurheartj/ehae564. PMID: 39217502 MH - Humans MH - *Antihypertensive Agents/therapeutic use MH - *Hypertension/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Blood Pressure/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/09/01 16:15 MHDA- 2024/10/08 00:23 CRDT- 2024/09/01 09:03 PHST- 2024/10/08 00:23 [medline] PHST- 2024/09/01 16:15 [pubmed] PHST- 2024/09/01 09:03 [entrez] AID - 7745624 [pii] AID - 10.1093/eurheartj/ehae520 [doi] PST - ppublish SO - Eur Heart J. 2024 Oct 7;45(38):4135-4137. doi: 10.1093/eurheartj/ehae520. PMID- 39217337 OWN - NLM STAT- MEDLINE DCOM- 20240831 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Aug 31 TI - Comparative effects of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors on heart failure with preserved ejection fraction in diabetic patients: a meta-analysis. PG - 324 LID - 10.1186/s12933-024-02415-8 [doi] LID - 324 AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001). CONCLUSIONS: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects. CI - (c) 2024. The Author(s). FAU - Albulushi, Arif AU - Albulushi A AD - Department of Adult Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman. dr.albulushi@gmail.com. AD - Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA. dr.albulushi@gmail.com. AD - Advanced Heart Failure & Transplant Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman. dr.albulushi@gmail.com. FAU - Tanoh, Desmond Boakye AU - Tanoh DB AD - Department of Medicine, Insight Hospital and Medical Center Chicago, Chicago, IL, USA. FAU - Almustafa, Ahmed AU - Almustafa A AD - Heart Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. FAU - Al Matrooshi, Nadya AU - Al Matrooshi N AD - Department of Cardiology, Heart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. FAU - Zolty, Ronald AU - Zolty R AD - Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Lowes, Brian AU - Lowes B AD - Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240831 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Stroke Volume/drug effects MH - *Heart Failure/physiopathology/drug therapy/diagnosis MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology/diagnosis/complications MH - *Ventricular Function, Left/drug effects MH - Treatment Outcome MH - *Randomized Controlled Trials as Topic MH - *Incretins/therapeutic use/adverse effects MH - Male MH - Aged MH - Middle Aged MH - Female MH - Recovery of Function MH - Observational Studies as Topic MH - Hypoglycemic Agents/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Exercise Tolerance/drug effects MH - Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11366143 OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP1 receptor agonists OT - HFpEF OT - SGLT2 inhibitors OT - Type 2 diabetes mellitus COIS- The authors declare no competing interests. EDAT- 2024/09/01 16:17 MHDA- 2024/09/01 16:18 PMCR- 2024/08/31 CRDT- 2024/08/31 23:28 PHST- 2024/07/22 00:00 [received] PHST- 2024/08/19 00:00 [accepted] PHST- 2024/09/01 16:18 [medline] PHST- 2024/09/01 16:17 [pubmed] PHST- 2024/08/31 23:28 [entrez] PHST- 2024/08/31 00:00 [pmc-release] AID - 10.1186/s12933-024-02415-8 [pii] AID - 2415 [pii] AID - 10.1186/s12933-024-02415-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Aug 31;23(1):324. doi: 10.1186/s12933-024-02415-8. PMID- 39215626 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Adherence to glucagon-like peptide-1 receptor agonist treatment in type 2 diabetes mellitus: A nationwide registry study. PG - 5239-5250 LID - 10.1111/dom.15872 [doi] AB - AIMS: To assess the level of adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment using real-world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP-1RAs. METHODS: First-time users of GLP-1RAs with type 2 diabetes mellitus (T2DM), aged >/=18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow-up. Adherence to GLP-1RA therapy (medication possession ratio >0.80) and discontinuation of GLP-1RA therapy was estimated at 6- and 12-month follow-ups. Multivariable cause-specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation. RESULTS: In total, 44 343 first-time users of GLP-1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP-1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9-14.6) and 21.2% (95% CI 20.8-21.5) within 12 months. At 6 months, 50.4% were adherent to GLP-1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP-1RA treatment. CONCLUSION: Approximately one in five patients discontinued GLP-1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP-1RA treatment. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Lassen, Mats C H AU - Lassen MCH AUID- ORCID: 0000-0002-2255-582X AD - Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, University of Copenhagen, Copenhagen, Denmark. AD - Centre for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Johansen, Niklas Dyrby AU - Johansen ND AD - Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, University of Copenhagen, Copenhagen, Denmark. AD - Centre for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Modin, Daniel AU - Modin D AD - Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, University of Copenhagen, Copenhagen, Denmark. AD - Centre for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Vistisen, Bodil Kjeldgaard AU - Vistisen BK AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Amadid, Hanan AU - Amadid H AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Zimmermann, Esther AU - Zimmermann E AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Gislason, Gunnar AU - Gislason G AD - Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, University of Copenhagen, Copenhagen, Denmark. FAU - Biering-Sorensen, Tor AU - Biering-Sorensen T AD - Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, University of Copenhagen, Copenhagen, Denmark. AD - Centre for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Steno Diabetes Centre Copenhagen, Copenhagen, Denmark. AD - Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - 21-R149-A10082-22194/Hjerteforeningen/ GR - Novo Nordisk/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240831 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Female MH - Male MH - Middle Aged MH - *Registries MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Denmark/epidemiology MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring OTO - NOTNLM OT - GLP-1 OT - adherence OT - discontinuation OT - registry OT - type 2 diabetes EDAT- 2024/09/01 16:18 MHDA- 2024/10/04 12:42 CRDT- 2024/08/31 06:03 PHST- 2024/07/28 00:00 [revised] PHST- 2024/05/20 00:00 [received] PHST- 2024/07/29 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/01 16:18 [pubmed] PHST- 2024/08/31 06:03 [entrez] AID - 10.1111/dom.15872 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5239-5250. doi: 10.1111/dom.15872. Epub 2024 Aug 31. PMID- 39212980 OWN - NLM STAT- MEDLINE DCOM- 20240924 LR - 20241112 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 332 IP - 12 DP - 2024 Sep 24 TI - GLP-1 Medication Use for Type 2 Diabetes Has Soared. PG - 952-953 LID - 10.1001/jama.2024.18219 [doi] FAU - Hegland, Thomas A AU - Hegland TA AD - Economist, Division of Research and Modelling, Center for Financing, Access and Cost Trends, Agency for Healthcare Research and Quality. FAU - Fang, Zhengyi AU - Fang Z AD - Survey Statistician, Office of the Director, Center for Financing, Access and Cost Trends, Agency for Healthcare Research and Quality. FAU - Bucher, Karen AU - Bucher K AD - Manager and Senior Medical Illustrator, Editorial Graphics, JAMA and JAMA Network. LA - eng PT - News PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/economics/therapeutic use MH - *Drug Prescriptions/economics/history/statistics & numerical data MH - Health Expenditures/statistics & numerical data/trends MH - History, 21st Century MH - Medicaid/economics/statistics & numerical data/trends MH - Insurance Coverage MH - Insurance, Health/economics/statistics & numerical data/trends MH - United States OAB - This JAMA Data Brief discusses new data from the Medical Expenditure Panel Survey, or MEPS, Household Component, a household survey sponsored by the Agency for Healthcare Research and Quality. OABL- eng EDAT- 2024/08/31 09:43 MHDA- 2024/09/24 18:51 CRDT- 2024/08/30 11:33 PHST- 2024/09/24 18:51 [medline] PHST- 2024/08/31 09:43 [pubmed] PHST- 2024/08/30 11:33 [entrez] AID - 2823270 [pii] AID - 10.1001/jama.2024.18219 [doi] PST - ppublish SO - JAMA. 2024 Sep 24;332(12):952-953. doi: 10.1001/jama.2024.18219. PMID- 39211948 OWN - NLM STAT- MEDLINE DCOM- 20250324 LR - 20260127 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 46 IP - 12 DP - 2025 Mar 24 TI - Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial. PG - 1096-1108 LID - 10.1093/eurheartj/ehae613 [doi] AB - BACKGROUND AND AIMS: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. METHODS: Participants were randomized to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorized by estimated glomerular filtration rate < or >/=60 mL/min/1.73 m2, urine albumin-to-creatinine ratio < or >/=300 mg/g, or Kidney Disease Improving Global Outcomes (KDIGO) risk classification. RESULTS: Three thousand, five hundred and thirty-three participants were randomized with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.8%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% [hazard ratio (HR) 0.82 (95% confidence interval 0.68-0.98); P = .03], with consistency across estimated glomerular filtration rate categories, urine albumin-to-creatinine ratio levels, and KDIGO risk classification (all P-interaction > .13). Death due to any cause was reduced by 20% [HR 0.80 (0.67-0.95); P = .01], with consistency across estimated glomerular filtration rate categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by urine albumin-to-creatinine ratio was .01 [<300 mg/g HR 1.17 (0.83-1.65); >/=300 mg/g HR 0.70 (0.57-0.85)]. CONCLUSIONS: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with type 2 diabetes. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, Palo Alto, CA 94305, USA. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. FAU - Arici, Mustafa AU - Arici M AD - Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bakris, George AU - Bakris G FAU - Charytan, David M AU - Charytan DM AD - Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. FAU - Cherney, David Z I AU - Cherney DZI AD - Division of Nephrology, University of Toronto, Toronto, ON, Canada. FAU - Chernin, Gil AU - Chernin G AD - Kaplan Medical Center, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Correa-Rotter, Ricardo AU - Correa-Rotter R AD - National Institute of Medical Sciences and Nutrition, Salvador Zubiran, Mexico City, Mexico. FAU - Gumprecht, Janusz AU - Gumprecht J AD - Department of Clinical and Molecular Medicine, Medical University of Silesia, Katowice, Poland. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pugliese, Giuseppe AU - Pugliese G AUID- ORCID: 0000-0003-1574-0397 AD - Department of Clinical and Molecular Medicine, La Sapienza University, Rome, Italy. FAU - Rasmussen, Ida Kirstine Bull AU - Rasmussen IKB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Sokareva, Ekaterina AU - Sokareva E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany. AD - Department of Nephrology, Hypertension and Rheumatology, University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL, USA. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1093/eurheartj/ehae744 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - *Renal Insufficiency, Chronic/complications/mortality/drug therapy MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - *Cardiovascular Diseases/mortality/prevention & control MH - Glomerular Filtration Rate MH - Double-Blind Method MH - *Diabetic Nephropathies/drug therapy/mortality MH - Treatment Outcome MH - Stroke/mortality/prevention & control MH - Myocardial Infarction/mortality/prevention & control MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11931213 OTO - NOTNLM OT - Cardiovascular outcomes OT - Chronic kidney disease OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/08/31 09:46 MHDA- 2025/03/24 06:30 PMCR- 2024/08/30 CRDT- 2024/08/30 04:32 PHST- 2024/07/01 00:00 [received] PHST- 2024/08/09 00:00 [revised] PHST- 2024/08/22 00:00 [accepted] PHST- 2025/03/24 06:30 [medline] PHST- 2024/08/31 09:46 [pubmed] PHST- 2024/08/30 04:32 [entrez] PHST- 2024/08/30 00:00 [pmc-release] AID - 7745056 [pii] AID - ehae613 [pii] AID - 10.1093/eurheartj/ehae613 [doi] PST - ppublish SO - Eur Heart J. 2025 Mar 24;46(12):1096-1108. doi: 10.1093/eurheartj/ehae613. PMID- 39210781 OWN - NLM STAT- MEDLINE DCOM- 20241125 LR - 20250103 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 150 IP - 22 DP - 2024 Nov 26 TI - Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - 1781-1790 LID - 10.1161/CIRCULATIONAHA.124.071689 [doi] AB - BACKGROUND: GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors both improve cardiovascular and kidney outcomes in people with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors. METHODS: We searched MEDLINE and Embase databases from inception until July 12, 2024, for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data. We estimated treatment effects by baseline SGLT2 inhibitor use using inverse variance-weighted meta-analysis. The main cardiovascular outcomes were major adverse cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure. Kidney outcomes included a composite of >/=50% reduction in estimated glomerular filtration rate, kidney failure or death caused by kidney failure, and annualized rate of decline in estimated glomerular filtration rate (estimated glomerular filtration rate slope). Serious adverse events and severe hypoglycemia were also evaluated. This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024565765). RESULTS: We identified 3 trials with 1743 of 17 072 (10.2%) participants with type 2 diabetes receiving an SGLT2 inhibitor at baseline. GLP-1 receptor agonists reduced the risk of major adverse cardiovascular events by 21% (hazard ratio [HR], 0.79 [95% CI, 0.71-0.87]), with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline (HR, 0.77 [95% CI, 0.54-1.09] and HR, 0.79 [95% CI, 0.71-0.87], respectively; P-heterogeneity=0.78). The effect on hospitalization for heart failure was similarly consistent regardless of SGLT2 inhibitor use (HR, 0.58 [95% CI, 0.36-0.93] and HR, 0.73 [95% CI, 0.63-0.85]; P-heterogeneity=0.26). Effects on the composite kidney outcome (risk ratio, 0.79 [95% CI, 0.66-0.95]) and estimated glomerular filtration rate slope (0.78 mL/min/1.73 m(2)/y [95% CI, 0.57-0.98]) also did not vary according to SGLT2 inhibitor use (P-heterogeneity=0.53 and 0.94, respectively). Serious adverse effects and severe hypoglycemia were also similar regardless of SGLT2 inhibitor use (P-heterogeneity=0.29 and 0.50, respectively). CONCLUSIONS: In people with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use. FAU - Neuen, Brendon L AU - Neuen BL AUID- ORCID: 0000-0001-9276-8380 AD - George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia. AD - Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia (B.L.N., L.H., A.P.). FAU - Fletcher, Robert A AU - Fletcher RA AUID- ORCID: 0000-0002-0885-1788 AD - George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia. FAU - Heath, Lauren AU - Heath L AUID- ORCID: 0000-0001-9866-0805 AD - Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia (B.L.N., L.H., A.P.). FAU - Perkovic, Adam AU - Perkovic A AUID- ORCID: 0000-0001-7582-5611 AD - Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia (B.L.N., L.H., A.P.). FAU - Vaduganathan, Muthiah AU - Vaduganathan M AUID- ORCID: 0000-0003-0885-1953 AD - Division of Cardiovascular Medicine, Center for Cardiometabolic Implementation Science, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.V.). AD - Department of Renal Medicine, St George Hospital, Sydney, Australia (M.V.). FAU - Badve, Sunil V AU - Badve SV AUID- ORCID: 0000-0003-2269-312X AD - George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia. AD - Faculty of Medicine and Health (S.V.B.), University of New South Wales, Sydney, Australia. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle (K.R.T.). AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA (K.R.T.). FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Gerstein, Hertzel C AU - Gerstein HC AUID- ORCID: 0000-0001-8072-2836 AD - Population Health Research Institute, Hamilton Health Sciences and McMaster University, Canada (H.C.G.). FAU - Perkovic, Vlado AU - Perkovic V AUID- ORCID: 0000-0002-4257-7620 AD - George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia. AD - Division of the Vice Chancellor and President (V.P.), University of New South Wales, Sydney, Australia. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AUID- ORCID: 0000-0002-3126-3730 AD - George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia. AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands (H.J.L.H.). LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240830 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Cardiovascular Diseases MH - Kidney/drug effects/physiopathology MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Glomerular Filtration Rate MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - cardiovascular diseases OT - diabetes type 2 OT - glomerular filtration rate OT - glucagon-like peptide-1 receptor agonists OT - kidney OT - renal insufficiency, chronic OT - sodium glucose cotransporter 2 OT - treatment outcome COIS- B.L.N. reports fees for travel support, advisory boards, scientific presentations, and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, Janssen, the limbic, Medscape, Novo Nordisk, and Travere Therapeutics. R.A.F. has received studentship awards from the HDR-UK-Turing Wellcome Programme in Health Data Science. M.V. has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. S.V.B. reports consulting fees from Bayer, AstraZeneca, GlaxoSmithKline, and Vifor Pharma; speaking fees from Bayer, AstraZeneca, Pfizer, and Vifor Pharma (all honoraria paid to his institution); and nonfinancial research support from Bayer. K.R.T. is supported by National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, and Centers for Disease Control and Prevention project Nos. 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Travere Therapeutics, Bayer, and the Doris Duke Charitable Foundation. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Travere Therapeutics, and Pfizer; and speaker fees from Novo Nordisk. R.E.P. declares speaker fees from Lilly and Novo Nordisk; consulting fees from Bayer AG, Bayer HealthCare Pharmaceuticals, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Intas Pharmaceuticals, Lilly, Novo Nordisk, Pfizer, and Sun Pharmaceutical Industries; and research grants from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Lilly, Novo Nordisk, and Sanofi. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing education grants from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Sanofi, Carbon Brand, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly, Novo Nordisk, Pfizer, Sanofi, Kowa, and Hanmi. V.P. serves as a board director for St Vincent's Health Australia, Victor Chang Cardiac Research Institute, and Mindgardens; and has received honoraria for steering committee roles, scientific presentations, advisory board attendance, or a combination from Abbvie, Amgen, AstraZeneca, Bayer, Baxter, Boehringer Ingelheim, Chinook, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Otsuka, Pharmalink, Pfizer, Reata, Travere, Relypsa, Roche, Sanofi, Servier, and Tricida. H.J.L.H. has received grants or contracts from AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, CSL Behring, Dimerix, Eli Lilly, Gilead, Janssen, Novo Nordisk, Novartis, and Travere Therapeutics; and payment or honoraria for speaking from AstraZeneca and Novo Nordisk. The other authors report no conflicts. EDAT- 2024/08/31 09:44 MHDA- 2024/11/25 18:26 CRDT- 2024/08/30 03:53 PHST- 2024/11/25 18:26 [medline] PHST- 2024/08/31 09:44 [pubmed] PHST- 2024/08/30 03:53 [entrez] AID - 10.1161/CIRCULATIONAHA.124.071689 [doi] PST - ppublish SO - Circulation. 2024 Nov 26;150(22):1781-1790. doi: 10.1161/CIRCULATIONAHA.124.071689. Epub 2024 Aug 30. PMID- 39207323 OWN - NLM STAT- MEDLINE DCOM- 20241106 LR - 20260827 IS - 2213-1787 (Electronic) IS - 2213-1779 (Linking) VI - 12 IP - 11 DP - 2024 Nov TI - GLP-1 Receptor Agonists Among Patients With Overweight or Obesity, Diabetes, and HFpEF on SGLT2 Inhibitors. PG - 1814-1826 LID - S2213-1779(24)00561-4 [pii] LID - 10.1016/j.jchf.2024.07.006 [doi] AB - BACKGROUND: Although the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. OBJECTIVES: This study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy. METHODS: The authors conducted a retrospective cohort study using the TriNetX research database including patients >/=18 years with type 2 diabetes mellitus, body mass index >/=27 kg/m(2), and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period. RESULTS: A total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use. CONCLUSIONS: GLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits. CI - Copyright (c) 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Patel, Rushin AU - Patel R AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Wadid, Mark AU - Wadid M AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Makwana, Bhargav AU - Makwana B AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Kumar, Ashish AU - Kumar A AD - Department of Internal Medicine, Cleveland Clinic Akron General Hospital, Cleveland, Ohio, USA. FAU - Khadke, Sumanth AU - Khadke S AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Bhatti, Ammar AU - Bhatti A AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Banker, Ahan AU - Banker A AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Husami, Zaid AU - Husami Z AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Labib, Sherif AU - Labib S AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Venesy, David AU - Venesy D AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Fonarow, Gregg AU - Fonarow G AD - Ahmanson-UCLA Cardiomyopathy Center, Division of Cardiology, University of California-Los Angeles, Los Angeles, California, USA. FAU - Kosiborod, Mikhail AU - Kosiborod M AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Al-Kindi, Sadeer AU - Al-Kindi S AD - Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Cardiovascular Center, Houston, Texas, USA. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Dani, Sourbha AU - Dani S AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. FAU - Nohria, Anju AU - Nohria A AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, Texas, USA; and iDepartment of Cardiovascular Medicine, University of Mississippi, Jackson, Mississippi, USA. FAU - Ganatra, Sarju AU - Ganatra S AD - Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. Electronic address: Sarju.Ganatra@Lahey.org. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240828 PL - United States TA - JACC Heart Fail JT - JACC. Heart failure JID - 101598241 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Heart Failure/drug therapy/physiopathology MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Stroke Volume/physiology MH - *Obesity/complications/drug therapy MH - *Overweight/complications MH - Hospitalization/statistics & numerical data MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2is OT - heart failure with preserved ejection fraction OT - obesity OT - overweight COIS- Funding Support and Author Disclosures Dr Bhatt is on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; he is on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); he is a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; he is on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hopitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, Rutgers University (for the National Institutes of Health-funded MINT Trial); he has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee), Clinical Cardiology (Deputy Editor); he is named on a patent for sotagliflozin (assigned to Brigham and Women's Hospital who assigned to Lexicon; neither he nor Brigham and Women's Hospital receive any income from this patent); he has received research funding for Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; he has received royalties from Elsevier (Editor, Braunwald's Heart Disease); he is Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; he is trustee for American College of Cardiology; and he has done unfunded research for FlowCo. Dr Butler has been a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Kosiborod has received research grants from AstraZeneca and Boehringer Ingelheim; and has served as a consultant for Alnylam, AstraZeneca, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor. Dr Fonarow has done consulting for Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2024/08/31 09:53 MHDA- 2024/11/07 00:27 CRDT- 2024/08/29 10:34 PHST- 2024/03/26 00:00 [received] PHST- 2024/07/09 00:00 [revised] PHST- 2024/07/09 00:00 [accepted] PHST- 2024/11/07 00:27 [medline] PHST- 2024/08/31 09:53 [pubmed] PHST- 2024/08/29 10:34 [entrez] AID - S2213-1779(24)00561-4 [pii] AID - 10.1016/j.jchf.2024.07.006 [doi] PST - ppublish SO - JACC Heart Fail. 2024 Nov;12(11):1814-1826. doi: 10.1016/j.jchf.2024.07.006. Epub 2024 Aug 28. PMID- 39205685 OWN - NLM STAT- MEDLINE DCOM- 20240829 LR - 20261019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study. PG - 1395651 LID - 10.3389/fendo.2024.1395651 [doi] LID - 1395651 AB - BACKGROUND: Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. METHOD: This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. RESULTS: Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 +/- 1.8 vs. -2.1 +/- 1.9, p-value= 0.934, respectively), and weight (-6.1 +/- 5 vs. -6.2 +/- 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. CONCLUSION: This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses. CI - Copyright (c) 2024 Alenzi, Alzahrani, Aljaloud, Alanazi and Alarfaj. FAU - Alenzi, Sara AU - Alenzi S AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia. FAU - Alzahrani, Abdullah AU - Alzahrani A AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Aljaloud, Afnan AU - Aljaloud A AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Alanazi, Kamayel AU - Alanazi K AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Alarfaj, Sumaiah J AU - Alarfaj SJ AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240814 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glycated Hemoglobin/analysis MH - Saudi Arabia/epidemiology MH - Adult MH - Aged MH - Treatment Outcome MH - Blood Glucose/drug effects/analysis MH - Cohort Studies MH - Dose-Response Relationship, Drug MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11349510 OTO - NOTNLM OT - Saudi OT - diabetes mellitus OT - glucagon-like peptide 1 analog OT - obesity OT - ozempic OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/08/31 09:49 MHDA- 2024/09/01 16:18 PMCR- 2024/01/01 CRDT- 2024/08/29 04:07 PHST- 2024/03/17 00:00 [received] PHST- 2024/07/08 00:00 [accepted] PHST- 2024/09/01 16:18 [medline] PHST- 2024/08/31 09:49 [pubmed] PHST- 2024/08/29 04:07 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1395651 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Aug 14;15:1395651. doi: 10.3389/fendo.2024.1395651. eCollection 2024. PMID- 39197980 OWN - NLM STAT- MEDLINE DCOM- 20240828 LR - 20250904 IS - 1558-3597 (Electronic) IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 84 IP - 10 DP - 2024 Sep 3 TI - Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM. PG - 904-917 LID - S0735-1097(24)07779-9 [pii] LID - 10.1016/j.jacc.2024.05.069 [doi] AB - BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials. OBJECTIVES: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM. METHODS: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis. RESULTS: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13]). CONCLUSIONS: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD. CI - Copyright (c) 2024 American College of Cardiology Foundation. All rights reserved. FAU - Khera, Rohan AU - Khera R AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA; Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA. Electronic address: rohan.khera@yale.edu. FAU - Aminorroaya, Arya AU - Aminorroaya A AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA. FAU - Dhingra, Lovedeep Singh AU - Dhingra LS AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA. FAU - Thangaraj, Phyllis M AU - Thangaraj PM AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA. FAU - Pedroso Camargos, Aline AU - Pedroso Camargos A AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. FAU - Ding, Xiyu AU - Ding X AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Anand, Tara V AU - Anand TV AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Arshad, Faaizah AU - Arshad F AD - Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA. FAU - Blacketer, Clair AU - Blacketer C AD - Observational Health Data Analytics, Janssen Research and Development, Titusville, New Jersey, USA. FAU - Chai, Yi AU - Chai Y AD - Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. FAU - Chattopadhyay, Shounak AU - Chattopadhyay S AD - Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA. FAU - Cook, Michael AU - Cook M AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Dorr, David A AU - Dorr DA AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, USA. FAU - Duarte-Salles, Talita AU - Duarte-Salles T AD - Fundacio Institut Universitari per a la Recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina, Barcelona, Spain; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - DuVall, Scott L AU - DuVall SL AD - Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - French, Tina E AU - French TE AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, Tennessee, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Hanchrow, Elizabeth E AU - Hanchrow EE AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, Tennessee, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Kaur, Guneet AU - Kaur G AD - Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom. FAU - Lau, Wallis C Y AU - Lau WCY AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China. FAU - Li, Jing AU - Li J AD - Data Transformation, Analytics, and Artificial Intelligence, Real World Solutions, IQVIA, Durham, North Carolina, USA. FAU - Li, Kelly AU - Li K AD - Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA. FAU - Liu, Yuntian AU - Liu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA. FAU - Man, Kenneth K C AU - Man KKC AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China. FAU - Matheny, Michael E AU - Matheny ME AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, Tennessee, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - McLeggon, Jody-Ann AU - McLeggon JA AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - McLemore, Michael F AU - McLemore MF AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, Tennessee, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Minty, Evan AU - Minty E AD - Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada. FAU - Morales, Daniel R AU - Morales DR AD - Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom. FAU - Nagy, Paul AU - Nagy P AD - Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Observational Health Data Analytics, Janssen Research and Development, Titusville, New Jersey, USA. FAU - Pistillo, Andrea AU - Pistillo A AD - Fundacio Institut Universitari per a la Recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Phan, Thanh-Phuc AU - Phan TP AD - School of Pharmacy, Taipei Medical University, Taipei, Taiwan. FAU - Pratt, Nicole AU - Pratt N AD - Quality Use of Medicines and Pharmacy Research Centre, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia. FAU - Reyes, Carlen AU - Reyes C AD - Fundacio Institut Universitari per a la Recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina, Barcelona, Spain. FAU - Richter, Lauren AU - Richter L AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Ross, Joseph S AU - Ross JS AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA; Section of General Medicine and National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Ruan, Elise AU - Ruan E AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Seager, Sarah L AU - Seager SL AD - Data Transformation, Analytics, and Artificial Intelligence, Real World Solutions, IQVIA, London, United Kingdom. FAU - Simon, Katherine R AU - Simon KR AD - Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, Tennessee, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Viernes, Benjamin AU - Viernes B AD - Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. FAU - Yang, Jianxiao AU - Yang J AD - Department of Computational Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. FAU - Yin, Can AU - Yin C AD - Data Transformation, Analytics, and Artificial Intelligence, Real World Solutions, IQVIA, Shanghai, China. FAU - You, Seng Chan AU - You SC AD - Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea; Institute for Innovation in Digital Healthcare, Yonsei University College of Medicine, Seoul, South Korea. FAU - Zhou, Jin J AU - Zhou JJ AD - Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA; Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. FAU - Ryan, Patrick B AU - Ryan PB AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Schuemie, Martijn J AU - Schuemie MJ AD - Epidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, New Jersey, USA. FAU - Krumholz, Harlan M AU - Krumholz HM AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA; Section of Cardiovascular Medicine, Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA; Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA; Department of Biomathematics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. Electronic address: msuchard@ucla.edu. LA - eng GR - R01 HL144644/HL/NHLBI NIH HHS/United States GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HG006139/HG/NHGRI NIH HHS/United States GR - R01 HS022882/HS/AHRQ HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - U01 FD005938/FD/FDA HHS/United States GR - R01 HS025164/HS/AHRQ HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - K23 HL153775/HL/NHLBI NIH HHS/United States GR - T32 HL155000/HL/NHLBI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Multicenter Study PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM UOF - medRxiv. 2024 Feb 08:2024.02.05.24302354. doi: 10.1101/2024.02.05.24302354. PMID: 38370787 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12045554 MID - NIHMS2077495 OTO - NOTNLM OT - cardiovascular diseases OT - comparative effectiveness research OT - glucagon-like peptide-1 receptor agonists OT - hypoglycemic agents OT - sodium-glucose transporter 2 inhibitors OT - type 2 diabetes mellitus COIS- Funding Support and Author Disclosures This study was partially funded through National Institutes of Health grants R01 HL167858, K23 HL153775, R01 LM006910, R01 HG006139, and R01 HL169954 and the U.S. Department of Veterans Affairs under the research priority to "Put VA Data to Work for Veterans" (VA ORD 22-D4V). The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Khera is an associate editor at JAMA; and has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (awards R01 HL167858 and K23 HL153775) and the Doris Duke Charitable Foundation (award 2022060); has received research support, through Yale University, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. provisional patent applications WO2023230345A1, US20220336048A1, 63/346,610, 63/428,569, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, unrelated to the present work; and is a cofounder of Evidence2Health and Ensight-AI, precision health platforms to improve evidence-based cardiovascular care and cardiovascular diagnostics. Dr DuVall has received grants from Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals, Biodesix, Celgene, Cerner Enviza, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis International, and Parexel International through the University of Utah or the Western Institute for Veteran Research (outside the submitted work). Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work). Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, HugoHealth, and Ensight-AI; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and, through Yale University, from Johnson & Johnson. Dr You is chief technology officer of PHI Digital Healthcare. Dr Ross has received research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (grant U01 FD005938), from the Agency for Healthcare Research and Quality (grant R01 HS022882), and from Arnold Ventures; has received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology and from the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants R01 HS025164 and R01 HL144644); and was an expert witness at the request of the relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled September 2022. Dr Thangaraj is a coinventor on provisional patent 63/606,203, unrelated to the present work, and is funded by grant 5T32 HL155000-03. Ms Blacketer, Dr Ostropolets, and Dr Ryan are employees of Johnson & Johnson. Dr Schuemie is an employee and shareholder of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2024/08/31 09:48 MHDA- 2024/08/31 09:49 PMCR- 2025/09/03 CRDT- 2024/08/28 20:59 PHST- 2024/05/15 00:00 [received] PHST- 2024/05/23 00:00 [accepted] PHST- 2024/08/31 09:49 [medline] PHST- 2024/08/31 09:48 [pubmed] PHST- 2024/08/28 20:59 [entrez] PHST- 2025/09/03 00:00 [pmc-release] AID - S0735-1097(24)07779-9 [pii] AID - 10.1016/j.jacc.2024.05.069 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Sep 3;84(10):904-917. doi: 10.1016/j.jacc.2024.05.069. PMID- 39197936 OWN - NLM STAT- MEDLINE DCOM- 20240828 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 386 DP - 2024 Aug 28 TI - Semaglutide's CVD indication could cost US Medicare $145bn extra a year. PG - q1878 LID - 10.1136/bmj.q1878 [doi] FAU - Mahase, Elisabeth AU - Mahase E AD - The BMJ. LA - eng PT - News DEP - 20240828 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - United States MH - Humans MH - *Glucagon-Like Peptides/economics/therapeutic use MH - *Medicare/economics MH - *Cardiovascular Diseases/economics/prevention & control/drug therapy MH - Hypoglycemic Agents/economics/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/economics MH - Drug Costs MH - Semaglutide EDAT- 2024/08/31 09:50 MHDA- 2024/08/31 09:51 CRDT- 2024/08/28 20:43 PHST- 2024/08/31 09:51 [medline] PHST- 2024/08/31 09:50 [pubmed] PHST- 2024/08/28 20:43 [entrez] AID - 10.1136/bmj.q1878 [doi] PST - epublish SO - BMJ. 2024 Aug 28;386:q1878. doi: 10.1136/bmj.q1878. PMID- 39196369 OWN - NLM STAT- MEDLINE DCOM- 20241120 LR - 20260619 IS - 1939-327X (Electronic) IS - 0012-1797 (Linking) VI - 73 IP - 12 DP - 2024 Dec 1 TI - Glucagon Stimulation Test and Insulin Secretory Capacity in the Clinical Assessment of Incretin-Based Therapy for Diabetes. PG - 2078-2083 LID - 10.2337/db24-0518 [doi] AB - Evaluation of insulin secretory capacity is essential to understand the pathophysiologic condition of individuals with diabetes and assess the efficacy of drugs used in the treatment of this disease. The 1-mg i.v. glucagon stimulation test (GST) is widely used to evaluate residual beta-cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs). However, recent reports have indicated that pharmacologic concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The current studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase 4 inhibitors (DPP-4is). Our first study included individuals receiving GLP-1RA treatment, evaluated by the GST before and after treatment. Although the fasting C-peptide response (CPR) levels were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and nonusers, assessed by the GST after propensity score matching. Although the fasting CPR levels were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that the GST might underestimate insulin secretory capacity under incretin-based therapy. CI - (c) 2024 by the American Diabetes Association. FAU - Haraguchi, Takuya AU - Haraguchi T AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism/Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Yamazaki, Yuji AU - Yamazaki Y AUID- ORCID: 0009-0007-5876-8695 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Kuwata, Hitoshi AU - Kuwata H AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Usui, Ryota AU - Usui R AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Seino, Yutaka AU - Seino Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Yabe, Daisuke AU - Yabe D AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism/Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. LA - eng PT - Journal Article PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 9007-92-5 (Glucagon) RN - 0 (Insulin) RN - 0 (Incretins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (C-Peptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon/metabolism MH - Male MH - *Insulin/metabolism MH - Female MH - *Insulin Secretion/drug effects MH - *Incretins/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/pharmacology MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Aged MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Insulin-Secreting Cells/drug effects/metabolism MH - C-Peptide/metabolism/blood MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/08/28 12:42 MHDA- 2024/11/20 18:21 CRDT- 2024/08/28 11:14 PHST- 2024/06/23 00:00 [received] PHST- 2024/08/26 00:00 [accepted] PHST- 2024/11/20 18:21 [medline] PHST- 2024/08/28 12:42 [pubmed] PHST- 2024/08/28 11:14 [entrez] AID - 157164 [pii] AID - 10.2337/db24-0518 [doi] PST - ppublish SO - Diabetes. 2024 Dec 1;73(12):2078-2083. doi: 10.2337/db24-0518. PMID- 39194153 OWN - NLM STAT- MEDLINE DCOM- 20241121 LR - 20260709 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 19 IP - 6 DP - 2024 Nov TI - Tirzepatide: unveiling a new dawn in dual-targeted diabetes and obesity management. PG - 487-505 LID - 10.1080/17446651.2024.2395540 [doi] AB - INTRODUCTION: Incretin-based therapies have emerged as effective treatments for type 2 diabetes (T2D) and obesity. However, not all patients achieve optimal outcomes with existing treatments, highlighting the need for more effective solutions. AREAS COVERED: We present a comprehensive evaluation of Tirzepatide (TZP), a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, for managing obesity and T2D. We conducted a systematic search of Cochrane, PubMed, Scopus, and Web of Science databases from inception to April 2024. The focus of the review is on the development and therapeutic potential of TZP, with detailed exploration on pharmacodynamics, pharmacokinetics, clinical efficacy, and safety. Furthermore, it reviews TZP's impacts on glycemic control, weight management, and its potential cardiovascular (CV) benefits. EXPERT OPINION: TZP represents a significant advancement in the dual-targeted approach to treating T2D and obesity. Its unique mechanism of action offers superior efficacy in reducing glycemic levels and body weight compared to existing therapies. New data suggesting improvements in CV outcomes indicate that TZP could set a new standard in the treatment paradigm. While long-term data on efficacy and safety are still forthcoming, current evidence positions TZP as a promising option for patients who have not reached their therapeutic goals with existing treatments. FAU - Rabbani, Syed Arman AU - Rabbani SA AD - RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - El-Tanani, Mohamed AU - El-Tanani M AD - RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Matalka, Ismail I AU - Matalka II AD - RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. AD - Department of Pathology and Microbiology, Medicine, Jordan University of Science and Technology, Irbid, Jordan. FAU - Rangraze, Imran Rashid AU - Rangraze IR AD - Internal Medicine Department, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Aljabali, Alaa A A AU - Aljabali AAA AD - Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan. FAU - Khan, Mohammad Ahmed AU - Khan MA AD - Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. FAU - Tambuwala, Murtaza M AU - Tambuwala MM AD - Lincoln Medical School, University of Lincoln, Lincoln, UK. LA - eng PT - Journal Article PT - Review DEP - 20240828 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Incretins/therapeutic use MH - Obesity Management/methods MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Tirzepatide OT - glucagon-like peptide-1 (GLP-1) OT - glucose-dependent insulinotropic polypeptide (GIP) OT - obesity OT - type 2 diabetes EDAT- 2024/08/28 12:42 MHDA- 2024/11/21 06:21 CRDT- 2024/08/28 08:33 PHST- 2024/11/21 06:21 [medline] PHST- 2024/08/28 12:42 [pubmed] PHST- 2024/08/28 08:33 [entrez] AID - 10.1080/17446651.2024.2395540 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2024 Nov;19(6):487-505. doi: 10.1080/17446651.2024.2395540. Epub 2024 Aug 28. PMID- 39193839 OWN - NLM STAT- MEDLINE DCOM- 20241215 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 Suppl 7 DP - 2024 Dec TI - Use of continuous glucose monitoring when initiating glucagon-like peptide-1 receptor agonist therapy in insulin-treated diabetes. PG - 17-26 LID - 10.1111/dom.15883 [doi] AB - Glucagon-like peptide-1 receptor agonist (GLP-1RA) medications have been shown to be effective in achieving optimal glucose control and reducing all-cause death, cardiovascular death, nonfatal myocardial infarction, hospitalization for heart failure, and end-stage kidney disease in individuals with type 1 (T1D) and type 2 diabetes (T2D). However, use of these medications has been associated with increased hypoglycaemia risk in patients treated with concomitant antihyperglycaemic medications. The risk is particularly high in patients with T1D due to their loss of glucagon counter-regulatory response. This article reviews the effect of GLP-1RA formulations on the development of hypoglycaemia in individuals with T1D and T2D treated with insulin therapy, discusses the benefits of continuous glucose monitoring with GLP-1RA treatment, and presents strategies for safely initiating GLP-1RA therapy in these individuals. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Hirsch, Irl B AU - Hirsch IB AD - University of Washington School of Medicine, Seattle, Washington, USA. FAU - Parkin, Christopher G AU - Parkin CG AUID- ORCID: 0000-0001-6838-5355 AD - CGParkin Communications, Inc, Henderson, Nevada, USA. FAU - Cavaiola, Tricia Santos AU - Cavaiola TS AD - University of California San Diego School of Medicine, La Jolla, California, USA. FAU - Bergenstal, Richard M AU - Bergenstal RM AUID- ORCID: 0000-0002-9050-5584 AD - International Diabetes Centre, HealthPartners Institute, Minneapolis, Minnesota, USA. LA - eng PT - Journal Article PT - Review DEP - 20240828 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 1/drug therapy/blood/complications MH - *Hypoglycemia/chemically induced/prevention & control MH - *Blood Glucose Self-Monitoring/methods MH - *Insulin/therapeutic use MH - *Blood Glucose/drug effects/metabolism/analysis MH - Continuous Glucose Monitoring MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - CGM OT - GLP-1RA OT - continuous glucose monitoring OT - glucagon-like peptide-1 receptor agonist OT - hypoglycaemia OT - type 1 diabetes OT - type 2 diabetes EDAT- 2024/08/28 12:43 MHDA- 2024/12/16 11:29 CRDT- 2024/08/28 06:12 PHST- 2024/07/31 00:00 [revised] PHST- 2024/05/30 00:00 [received] PHST- 2024/08/02 00:00 [accepted] PHST- 2024/12/16 11:29 [medline] PHST- 2024/08/28 12:43 [pubmed] PHST- 2024/08/28 06:12 [entrez] AID - 10.1111/dom.15883 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26 Suppl 7:17-26. doi: 10.1111/dom.15883. Epub 2024 Aug 28. PMID- 39192531 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Elucidating the role of weight loss and glycaemic control in patients with type 2 diabetes. PG - 5347-5357 LID - 10.1111/dom.15896 [doi] AB - AIMS: To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon-like peptide-1 receptor agonists (GLP-1RAs). MATERIALS AND METHODS: This observational, retrospective cohort study used deidentified electronic health record-derived data from patients evaluated at the Cleveland Clinic (1 January 2000-31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP-1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated. RESULTS: In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 x 10(-4)), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts. CONCLUSIONS: Antidiabetic medication-associated, and specifically GLP-1RA-associated, weight loss and HbA1c reductions independently reduce real-world clinical outcome risk. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Sharma, Anukriti AU - Sharma A AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Mariam, Arshiya AU - Mariam A AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Zacherle, Emily AU - Zacherle E AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Milinovich, Alex AU - Milinovich A AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Bauman, Janine AU - Bauman J AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Sugano, David S AU - Sugano DS AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Rajpura, Jigar R AU - Rajpura JR AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Zimmerman, Robert S AU - Zimmerman RS AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Burguera, Bartolome AU - Burguera B AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Kattan, Michael W AU - Kattan MW AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Misra-Hebert, Anita D AU - Misra-Hebert AD AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Healthcare Delivery and Implementation Science Center, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Pantalone, Kevin M AU - Pantalone KM AUID- ORCID: 0000-0002-3897-4551 AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Rotroff, Daniel M AU - Rotroff DM AUID- ORCID: 0000-0003-0553-3220 AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. LA - eng GR - Novo Nordisk, Inc/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240827 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - *Weight Loss MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Glycemic Control MH - *Hypoglycemic Agents/therapeutic use MH - *Glycated Hemoglobin/analysis/metabolism MH - Aged MH - *Body Mass Index MH - Blood Glucose/metabolism MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - antidiabetic drug OT - observational study OT - real-world evidence OT - type 2 diabetes EDAT- 2024/08/28 08:43 MHDA- 2024/10/04 12:42 CRDT- 2024/08/28 00:53 PHST- 2024/08/06 00:00 [revised] PHST- 2024/04/12 00:00 [received] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/08/28 08:43 [pubmed] PHST- 2024/08/28 00:53 [entrez] AID - 10.1111/dom.15896 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5347-5357. doi: 10.1111/dom.15896. Epub 2024 Aug 27. PMID- 39190662 OWN - NLM STAT- MEDLINE DCOM- 20240923 LR - 20260901 IS - 1550-5022 (Electronic) IS - 1078-4659 (Linking) VI - 30 IP - 6 DP - 2024 Nov-Dec 01 TI - Public Health Responsibilities in the Era of GLP-1 Receptor Agonists. PG - 777-779 LID - 10.1097/PHH.0000000000002039 [doi] FAU - Wang, Grace AU - Wang G AUID- ORCID: 0000-0001-5626-6033 AD - Trinity College of Arts and Sciences, Duke University, Durham, North Carolina (Ms Wang); School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania (Ms Rahim); College of Arts & Sciences, Cornell University, Ithaca, New York (Mr Bari); Trinity College of Arts and Sciences, Duke University, Durham, North Carolina (Ms Haque); Trinity College of Arts and Sciences, Duke University, Durham, North Carolina and DSP Health, Granville, Ohio (Mr Rahim); and DSP Health, Granville, Ohio (Dr Palakodeti). FAU - Rahim, Eshaal AU - Rahim E FAU - Bari, Soham AU - Bari S AUID- ORCID: 0009-0007-8167-2640 FAU - Haque, Huda AU - Haque H FAU - Rahim, Faraan O AU - Rahim FO AUID- ORCID: 0000-0003-1305-0720 FAU - Palakodeti, Sandeep AU - Palakodeti S LA - eng PT - Journal Article DEP - 20240822 PL - United States TA - J Public Health Manag Pract JT - Journal of public health management and practice : JPHMP JID - 9505213 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Public Health/methods/trends MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Conflicts of Interest: The authors declare no conflicts of interest. EDAT- 2024/08/27 18:43 MHDA- 2024/09/23 12:47 CRDT- 2024/08/27 13:53 PHST- 2024/09/23 12:47 [medline] PHST- 2024/08/27 18:43 [pubmed] PHST- 2024/08/27 13:53 [entrez] AID - 00124784-202411000-00002 [pii] AID - 10.1097/PHH.0000000000002039 [doi] PST - ppublish SO - J Public Health Manag Pract. 2024 Nov-Dec 01;30(6):777-779. doi: 10.1097/PHH.0000000000002039. Epub 2024 Aug 22. PMID- 39190488 OWN - NLM STAT- MEDLINE DCOM- 20241021 LR - 20260619 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 47 IP - 11 DP - 2024 Nov 1 TI - Regional Heterogeneity of the Results of Glucagon-Like Peptide 1 Receptor Agonist Trials in Type 2 Diabetes: A Reanalysis of Individual Participant Data. PG - 1949-1957 LID - 10.2337/dca24-0034 [doi] AB - OBJECTIVE: Multiregional trials are designed under the assumption that treatment effect applies to the entire target population, yet several factors may introduce geographic heterogeneity in treatment effect. We explored whether such variations exist in trials assessing the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in major cardiovascular events (MACE) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A systematic search of Medline and the Cochrane Library was conducted from inception until 30 June 2020. We included international randomized controlled trials comparing any GLP-1RA versus placebo, with MACE as a primary end point. Individual participant data were subsequently requested from the sponsor or through data sharing platforms. For each trial, we calculated hazard ratios (HRs) and their 95% CIs for MACE, subgrouped by region. We then performed a random-effects meta-analysis and conducted meta-regressions to assess the influence of predetermined variables of interest on treatment effect. RESULTS: We included six trials including 45,426 patients. Baseline risk of MACE ranged from 2.9 per 100 patient-years in Southern Asia to 7.4 per 100 patient-years in Sub-Saharan Africa. HRs for MACE ranged between 0.25 (95% CI 0.05, 1.12) in Northern Africa to 0.98 (0.79, 1.22) in Western Europe. There was no significant subgroup difference across regions (P = 0.70). Baseline risk of MACE and indexes of development status (i.e., Human Development Index, gross domestic product) were independently associated with GLP-1RA efficacy. CONCLUSIONS: This study does not suggest any regional heterogeneity of GLP-1RA efficacy in MACE. However, a higher baseline risk and lower development status were associated with a greater benefit of these drugs. CI - (c) 2024 by the American Diabetes Association. FAU - Jullien, Ariane AU - Jullien A AD - INSERM, CIC1406, University of Grenoble Alpes, Grenoble, France. FAU - Jambon-Barbara, Clement AU - Jambon-Barbara C AD - INSERM, CIC1406, University of Grenoble Alpes, Grenoble, France. AD - INSERM, U1300, HP2, University of Grenoble Alpes, Grenoble, France. FAU - Cracowski, Jean-Luc AU - Cracowski JL AD - INSERM, CIC1406, University of Grenoble Alpes, Grenoble, France. AD - INSERM, U1300, HP2, University of Grenoble Alpes, Grenoble, France. FAU - Claggett, Brian L AU - Claggett BL AD - Cardiovascular Division, Brigham and Women's Hospital, Boston, MA. FAU - Borel, Anne-Laure AU - Borel AL AD - INSERM, U1300, HP2, University of Grenoble Alpes, Grenoble, France. AD - Endocrinology Diabetology & Nutrition Department, Grenoble Alpes University Hospital, Grenoble, France. FAU - Khouri, Charles AU - Khouri C AD - INSERM, CIC1406, University of Grenoble Alpes, Grenoble, France. AD - INSERM, U1300, HP2, University of Grenoble Alpes, Grenoble, France. FAU - Roustit, Matthieu AU - Roustit M AUID- ORCID: 0000-0003-4475-1626 AD - INSERM, CIC1406, University of Grenoble Alpes, Grenoble, France. AD - INSERM, U1300, HP2, University of Grenoble Alpes, Grenoble, France. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use EDAT- 2024/08/27 18:43 MHDA- 2024/10/22 04:52 CRDT- 2024/08/27 12:03 PHST- 2024/05/31 00:00 [received] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/10/22 04:52 [medline] PHST- 2024/08/27 18:43 [pubmed] PHST- 2024/08/27 12:03 [entrez] AID - 157161 [pii] AID - 10.2337/dca24-0034 [doi] PST - ppublish SO - Diabetes Care. 2024 Nov 1;47(11):1949-1957. doi: 10.2337/dca24-0034. PMID- 39189078 OWN - NLM STAT- MEDLINE DCOM- 20241116 LR - 20261009 IS - 1531-8257 (Electronic) IS - 0885-3185 (Print) IS - 0885-3185 (Linking) VI - 39 IP - 11 DP - 2024 Nov TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study. PG - 1960-1970 LID - 10.1002/mds.29992 [doi] AB - BACKGROUND: Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results. OBJECTIVE: The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D). METHODS: Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged >/=66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users. RESULTS: This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA. CONCLUSION: Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. (c) 2024 International Parkinson and Movement Disorder Society. CI - (c) 2024 International Parkinson and Movement Disorder Society. FAU - Tang, Huilin AU - Tang H AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Lu, Ying AU - Lu Y AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. FAU - Okun, Michael S AU - Okun MS AD - Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Donahoo, William T AU - Donahoo WT AD - Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Ramirez-Zamora, Adolfo AU - Ramirez-Zamora A AD - Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Wang, Fei AU - Wang F AD - Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, New York, USA. FAU - Huang, Yu AU - Huang Y AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Armstrong, Melissa AU - Armstrong M AUID- ORCID: 0000-0002-2163-1907 AD - Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA. FAU - Svensson, Mikael AU - Svensson M AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. FAU - Virnig, Beth A AU - Virnig BA AD - College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - DeKosky, Steven T AU - DeKosky ST AD - Department of Neurology and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA. AD - 1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, Florida, USA. FAU - Bian, Jiang AU - Bian J AD - Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AD - Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States GR - American Foundation for Pharmaceutical Education/ GR - Pharmaceutical Research and Manufacturers of America Foundation/ GR - R01DK133465/DK/NIDDK NIH HHS/United States GR - R01DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240827 PL - United States TA - Mov Disord JT - Movement disorders : official journal of the Movement Disorder Society JID - 8610688 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Parkinson Disease/epidemiology/drug therapy MH - Male MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - Aged MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Cohort Studies MH - *Medicare MH - Aged, 80 and over MH - United States/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11568939 MID - NIHMS2015669 OTO - NOTNLM OT - Parkinson's disease OT - dipeptidyl peptidase 4 inhibitor (DPP4i) OT - glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - type 2 diabetes COIS- Relevant conflicts of interest/financial disclosure: The authors declare no conflicts of interest relevant to this work. EDAT- 2024/08/27 09:48 MHDA- 2024/11/16 22:27 PMCR- 2025/11/01 CRDT- 2024/08/27 04:43 PHST- 2024/07/31 00:00 [revised] PHST- 2024/04/29 00:00 [received] PHST- 2024/08/07 00:00 [accepted] PHST- 2024/11/16 22:27 [medline] PHST- 2024/08/27 09:48 [pubmed] PHST- 2024/08/27 04:43 [entrez] PHST- 2025/11/01 00:00 [pmc-release] AID - 10.1002/mds.29992 [doi] PST - ppublish SO - Mov Disord. 2024 Nov;39(11):1960-1970. doi: 10.1002/mds.29992. Epub 2024 Aug 27. PMID- 39188242 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Effect of semaglutide on primary prevention of diabetic kidney disease in people with type 2 diabetes: A post hoc analysis of the SUSTAIN 6 randomized controlled trial. PG - 5157-5166 LID - 10.1111/dom.15860 [doi] AB - AIM: Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention. METHODS: Participants with type 2 diabetes from the randomized, double-blind, placebo-controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) >/=30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m(2)]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time. RESULTS: Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7. CONCLUSIONS: This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Wang, Jingyu AU - Wang J AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Yang, Juhong AU - Yang J AD - Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Endocrinology Department of Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Jiang, Wenhui AU - Jiang W AUID- ORCID: 0000-0001-9629-6878 AD - Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province, Cangzhou, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (China) Pharmaceutical Company, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (China) Pharmaceutical Company, Beijing, China. FAU - Gao, Zhongai AU - Gao Z AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Chang, Baocheng AU - Chang B AUID- ORCID: 0000-0002-6674-6644 AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240827 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/prevention & control MH - Double-Blind Method MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Primary Prevention/methods MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - diabetic kidney disease OT - prediction model OT - primary prevention OT - semaglutide OT - type 2 diabetes EDAT- 2024/08/27 09:48 MHDA- 2024/10/04 12:42 CRDT- 2024/08/27 04:03 PHST- 2024/07/03 00:00 [revised] PHST- 2024/04/16 00:00 [received] PHST- 2024/07/12 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/08/27 09:48 [pubmed] PHST- 2024/08/27 04:03 [entrez] AID - 10.1111/dom.15860 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5157-5166. doi: 10.1111/dom.15860. Epub 2024 Aug 27. PMID- 39188238 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - A long-acting glucose-dependent insulinotropic polypeptide receptor agonist improves the gastrointestinal tolerability of glucagon-like peptide-1 receptor agonist therapy. PG - 5474-5478 LID - 10.1111/dom.15875 [doi] FAU - Knop, Filip K AU - Knop FK AUID- ORCID: 0000-0002-2495-5034 AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Urva, Shweta AU - Urva S AUID- ORCID: 0000-0002-3681-479X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rettiganti, Mallikarjuna AU - Rettiganti M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Benson, Charles T AU - Benson CT AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Roell, William C AU - Roell WC AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mather, Kieren J AU - Mather KJ AUID- ORCID: 0000-0001-8696-7500 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Haupt, Axel AU - Haupt A AUID- ORCID: 0000-0003-4502-0470 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Pratt, Edward John AU - Pratt EJ AUID- ORCID: 0000-0003-4449-6231 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20240827 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - Receptors, Gastrointestinal Hormone/agonists MH - Gastric Inhibitory Polypeptide/therapeutic use/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GIP OT - GLP-1 OT - antidiabetic drug OT - antiobesity drug OT - clinical trial OT - incretin therapy EDAT- 2024/08/27 09:48 MHDA- 2024/10/04 12:43 CRDT- 2024/08/27 04:03 PHST- 2024/07/19 00:00 [revised] PHST- 2024/05/09 00:00 [received] PHST- 2024/07/29 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/08/27 09:48 [pubmed] PHST- 2024/08/27 04:03 [entrez] AID - 10.1111/dom.15875 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5474-5478. doi: 10.1111/dom.15875. Epub 2024 Aug 27. PMID- 39186788 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 177 IP - 10 DP - 2024 Oct TI - Estimating New Eligibility and Maximum Costs of Expanded Medicare Coverage of Semaglutide for Cardiovascular Risk Prevention. PG - 1440-1442 LID - 10.7326/ANNALS-24-00308 [doi] FAU - Chaitoff, Alexander AU - Chaitoff A AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital, Boston; and Harvard Medical School, Boston, Massachusetts. FAU - Bendicksen, Liam AU - Bendicksen L AD - Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Feldman, William B AU - Feldman WB AD - Harvard Medical School, Boston; Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Zheutlin, Alexander R AU - Zheutlin AR AD - Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. FAU - Lalani, Hussain S AU - Lalani HS AUID- ORCID: 0000-0002-5972-3997 AD - Harvard Medical School, Boston; and Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. LA - eng PT - Letter DEP - 20240827 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/therapeutic use/economics/adverse effects MH - *Cardiovascular Diseases/prevention & control/economics MH - Hypoglycemic Agents/economics/therapeutic use MH - Medicare/economics MH - Eligibility Determination MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy/prevention & control/economics MH - Heart Disease Risk Factors MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2024/08/26 19:50 MHDA- 2024/10/14 19:00 CRDT- 2024/08/26 17:02 PHST- 2024/10/14 19:00 [medline] PHST- 2024/08/26 19:50 [pubmed] PHST- 2024/08/26 17:02 [entrez] AID - 10.7326/ANNALS-24-00308 [doi] PST - ppublish SO - Ann Intern Med. 2024 Oct;177(10):1440-1442. doi: 10.7326/ANNALS-24-00308. Epub 2024 Aug 27. PMID- 39182626 OWN - NLM STAT- MEDLINE DCOM- 20250222 LR - 20260607 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 132 IP - 3 DP - 2025 Mar TI - Comparative Effects of Glucagon-like Peptide 1 Receptor Agonists and Metformin on Glaucoma Risk in Patients with Type 2 Diabetes. PG - 271-279 LID - S0161-6420(24)00515-3 [pii] LID - 10.1016/j.ophtha.2024.08.023 [doi] AB - PURPOSE: To compare effects of glucagon-like peptide 1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes mellitus (T2DM). DESIGN: A retrospective cohort study was conducted using electronic medical records data from an international electronic health record network, covering a period from May 2006-2024. PARTICIPANTS: Patients with a diagnosis of T2DM who were treated with either GLP-1 receptor agonists or metformin. METHODS: Data from 120 health care organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication use. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. MAIN OUTCOME MEASURES: Incidence of POAG, ocular hypertension, and the need for first-line treatments including topical drops and laser trabeculoplasty. RESULTS: After PSM, both groups included 61 998 patients at the 1-year follow-up, 27 414 patients at the 2-year follow-up, and 14 100 patients at the 3-year follow-up. Patients treated with GLP-1 receptor agonists showed a significantly decreased risk of POAG development compared with those receiving metformin at 1 year (RR, 0.59; 95% CI, 0.39-0.88), 2 years (RR, 0.50; 95% CI, 0.32-0.78), and 3 years (RR, 0.59; 95% CI, 0.37-0.94). Similar protective effects were observed for ocular hypertension at 1 year (RR, 0.44; 95% CI, 0.31-0.62), 2 years (RR, 0.43; 95% CI, 0.30-0.62), and 3 years (RR, 0.51; 95% CI, 0.34-0.75). The risk of first-line therapy initiation also was lower in the GLP-1 receptor agonists group at 1 year (RR, 0.63; 95% CI, 0.53-0.74), 2 years (RR, 0.71; 95% CI, 0.59-0.85), and 3 years (RR, 0.75; 95% CI, 0.62-0.91). CONCLUSIONS: Glucagon-like peptide 1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared with metformin in patients with T2DM. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of patients with diabetes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Muayad, Jawad AU - Muayad J AD - School of Medicine, Texas A&M University, Houston, Texas. FAU - Loya, Asad AU - Loya A AD - Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. FAU - Hussain, Zain S AU - Hussain ZS AD - University of Medicine and Health Sciences, New York, New York. FAU - Chauhan, Muhammad Z AU - Chauhan MZ AD - Department of Ophthalmology, Bernice and Harvey Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Alsoudi, Amer F AU - Alsoudi AF AD - Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. FAU - De Francesco, Ticiana AU - De Francesco T AD - Department of Ophthalmology and Vision Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah; Clinica de Olhos De Francesco, Fortaleza, Brazil; Hospital de Olhos Leiria de Andrade, Fortaleza, Brazil. FAU - Ahmed, Iqbal Ike K AU - Ahmed IIK AD - Department of Ophthalmology and Vision Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada; Prism Eye Institute, Mississauga, Canada. Electronic address: ikeahmed@mac.com. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20240823 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Metformin/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - *Glaucoma, Open-Angle/epidemiology/etiology/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Ocular Hypertension/epidemiology MH - Incidence MH - Intraocular Pressure/physiology/drug effects MH - Follow-Up Studies MH - Risk Factors MH - Propensity Score OTO - NOTNLM OT - GLP-1 receptor agonists OT - Metformin OT - Ocular hypertension OT - Primary open-angle glaucoma OT - Type 2 diabetes EDAT- 2024/08/26 12:38 MHDA- 2025/02/23 00:42 CRDT- 2024/08/25 19:25 PHST- 2024/06/20 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/19 00:00 [accepted] PHST- 2025/02/23 00:42 [medline] PHST- 2024/08/26 12:38 [pubmed] PHST- 2024/08/25 19:25 [entrez] AID - S0161-6420(24)00515-3 [pii] AID - 10.1016/j.ophtha.2024.08.023 [doi] PST - ppublish SO - Ophthalmology. 2025 Mar;132(3):271-279. doi: 10.1016/j.ophtha.2024.08.023. Epub 2024 Aug 23. PMID- 39182542 OWN - NLM STAT- MEDLINE DCOM- 20240914 LR - 20250103 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 982 DP - 2024 Nov 5 TI - Beyond insulin: The Intriguing role of GLP-1 in Parkinson's disease. PG - 176936 LID - S0014-2999(24)00625-3 [pii] LID - 10.1016/j.ejphar.2024.176936 [doi] AB - GLP-1 (Glucagon-like peptide 1) serves as both a peptide hormone and a growth factor, is released upon nutrient intake and contributes to insulin secretion stimulated by glucose levels. Also, GLP-1 is synthesized within several brain areas and plays a vital function in providing neuroprotection and reducing inflammation through the activation of the GLP-1 receptor. Parkinson's Disease (PD) is a neurodegenerative illness that worsens with time and is defined by considerable morbidity. Presently, there are few pharmaceutical choices available, and none of the existing therapies are capable of modifying the course of the disease. There is a suggestion that type 2 diabetes mellitus (T2DM) could increase the risk of PD, and the presence of both conditions concurrently might exacerbate PD symptoms and hasten neurodegeneration. GLP-1 receptor (GLP-1R) agonists exhibit numerous implications like enhancement of glucose-dependent insulin release and biosynthesis, suppression of glucagon secretion and gastric emptying. Also, some GLP-1R agonists have received clinical approval for the management of T2DM. Moreover, the use of GLP-1R agonists has demonstrated counter-inflammatory, neurotrophic, and neuroprotective actions in various preclinical models of neurodegenerative disorders. Considering the significant amount of evidence backing the potential of GLP-1R agonists to protect the nervous system across different research settings, this article delves into examining the hopeful prospect of GLP-1R agonists as a treatment option for PD. This review sheds light on combined neuroprotective benefits of GLP-1R agonists and the possible mechanisms driving the protective effects on the PD brain, through the collection of data from various preclinical and clinical investigations. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Verma, Aanchal AU - Verma A AD - Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India. FAU - Goyal, Ahsas AU - Goyal A AD - Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India. Electronic address: ahsasgoyal1990@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20240823 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Insulin) RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Parkinson Disease/metabolism/drug therapy MH - Animals MH - *Glucagon-Like Peptide 1/metabolism MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Insulin/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Neuroprotective Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonist OT - Glucagon-like peptide 1 OT - Neurodegeneration OT - Neuroinflammation OT - Oxidative stress OT - Parkinson's COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/08/26 12:38 MHDA- 2024/09/15 14:09 CRDT- 2024/08/25 19:23 PHST- 2024/04/09 00:00 [received] PHST- 2024/08/12 00:00 [revised] PHST- 2024/08/22 00:00 [accepted] PHST- 2024/09/15 14:09 [medline] PHST- 2024/08/26 12:38 [pubmed] PHST- 2024/08/25 19:23 [entrez] AID - S0014-2999(24)00625-3 [pii] AID - 10.1016/j.ejphar.2024.176936 [doi] PST - ppublish SO - Eur J Pharmacol. 2024 Nov 5;982:176936. doi: 10.1016/j.ejphar.2024.176936. Epub 2024 Aug 23. PMID- 39181497 OWN - NLM STAT- MEDLINE DCOM- 20241226 LR - 20260825 IS - 1097-6868 (Electronic) IS - 0002-9378 (Linking) VI - 232 IP - 1 DP - 2025 Jan TI - Glucagon-like peptide-1 receptor agonist use in pregnancy: a review. PG - 17-25 LID - S0002-9378(24)00864-0 [pii] LID - 10.1016/j.ajog.2024.08.024 [doi] AB - Glucagon-like peptide-1 receptor agonists are peptide analogues that are used to treat type 2 diabetes mellitus and obesity. The first medication in this class, exenatide, was approved in 2005, and these medications, specifically semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there are currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to glucagon-like peptide-1 receptor agonists in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by type 2 diabetes mellitus and compared outcomes from periconceptional exposure to glucagon-like peptide-1 receptor agonists and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking glucagon-like peptide-1 receptor agonists, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of glucagon-like peptide-1 receptor agonists during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking glucagon-like peptide-1 receptor agonists. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Drummond, Rosa F AU - Drummond RF AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. Electronic address: rosa.drummond@umm.edu. FAU - Seif, Karl E AU - Seif KE AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. FAU - Reece, E Albert AU - Reece EA AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. LA - eng PT - Journal Article PT - Review DEP - 20240823 PL - United States TA - Am J Obstet Gynecol JT - American journal of obstetrics and gynecology JID - 0370476 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Female MH - Humans MH - Pregnancy MH - *Abnormalities, Drug-Induced/epidemiology/etiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/therapeutic use MH - *Obesity/drug therapy MH - *Pregnancy in Diabetics/drug therapy MH - Pregnancy Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Semaglutide OTO - NOTNLM OT - PCOS OT - abortion OT - diabetic fetopathy OT - dulaglutide OT - embryonic death OT - exenatide OT - fetal anomalies OT - fetal death OT - fetal growth restriction OT - glucagon-like peptide-1 receptor agonists OT - glycemic control OT - hyperglycemia OT - insulin resistance OT - liraglutide OT - lixisenatide OT - major congenital malformations OT - miscarriage OT - obesity OT - periconceptional use OT - semaglutide OT - teratogenicity OT - tirzepatide OT - type 2 diabetes OT - unplanned pregnancy OT - weight loss EDAT- 2024/08/26 12:39 MHDA- 2024/12/27 00:20 CRDT- 2024/08/24 19:29 PHST- 2024/05/08 00:00 [received] PHST- 2024/07/28 00:00 [revised] PHST- 2024/08/14 00:00 [accepted] PHST- 2024/12/27 00:20 [medline] PHST- 2024/08/26 12:39 [pubmed] PHST- 2024/08/24 19:29 [entrez] AID - S0002-9378(24)00864-0 [pii] AID - 10.1016/j.ajog.2024.08.024 [doi] PST - ppublish SO - Am J Obstet Gynecol. 2025 Jan;232(1):17-25. doi: 10.1016/j.ajog.2024.08.024. Epub 2024 Aug 23. PMID- 39177691 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20250103 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 11 DP - 2024 Nov TI - Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care. PG - 2585-2597 LID - 10.1007/s00125-024-06251-z [doi] AB - AIMS/HYPOTHESIS: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria. METHODS: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching. The primary endpoint, change in eGFR, was analysed using mixed-effects models. Secondary endpoints included categorical eGFR-based outcomes and changes in albuminuria. Subgroup and sensitivity analyses were performed to assess robustness of the findings. RESULTS: After matching, 5701 participants/group were included. Participants were predominantly male, aged 61 years, with a 10 year duration of diabetes, a baseline HbA(1c) of 64 mmol/mol (8.0%) and BMI of 33 kg/m(2). Chronic kidney disease (CKD) was present in 23% of participants. During a median of 2.1 years, from a baseline of 87 ml/min per 1.73 m(2), eGFR remained higher in the SGLT2i group compared with the GLP-1RA group throughout the observation period by 1.2 ml/min per 1.73 m(2). No differences were detected in albuminuria change. The SGLT2i group exhibited lower rates of worsening CKD class and favourable changes in BP compared with the GLP-1RA group, despite lesser HbA(1c) decline. SGLT2i also reduced eGFR decline better than GLP-1RA in participants without baseline CKD. CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes, treatment with SGLT2i was associated with better preservation of renal function compared with GLP-1RA, as evidenced by slower decline in eGFR. These findings reinforce SGLT2i as preferred agents for renal protection in this patient population. CI - (c) 2024. The Author(s). FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy. gianpaolo.fadini@unipd.it. AD - Laboratory of Experimental Diabetology, Veneto Institute of Molecular Medicine, Padova, Italy. gianpaolo.fadini@unipd.it. FAU - Longato, Enrico AU - Longato E AUID- ORCID: 0000-0001-5940-645X AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Morieri, Mario Luca AU - Morieri ML AUID- ORCID: 0000-0001-6864-0547 AD - Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy. FAU - Bonora, Enzo AU - Bonora E AUID- ORCID: 0000-0003-1074-5164 AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy. FAU - Consoli, Agostino AU - Consoli A AUID- ORCID: 0000-0002-1885-451X AD - Department of Medicine and Aging Sciences (DMSI) and Center for Advanced Studies and Technology (CAST), University G. D'Annunzio of Chieti-Pescara, Chieti, Italy. FAU - Fattor, Bruno AU - Fattor B AD - Diabetology Service, Azienda Sanitaria dell'Alto Adige, Bolzano, Italy. FAU - Rigato, Mauro AU - Rigato M AUID- ORCID: 0000-0002-5125-7434 AD - Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy. AD - Diabetology Service, Department of Medicine, Azienda ULSS 2 Marca Trevigiana, Treviso, Italy. FAU - Turchi, Federica AU - Turchi F AD - Metabolic Disease and Diabetology Unit, IRCCS INRCA, Ancona, Italy. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Department of Clinical & Experimental Medicine, University of Pisa and Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy. FAU - Solini, Anna AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. CN - DARWIN-Renal Study Investigators LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240823 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Retrospective Studies MH - *Glomerular Filtration Rate/drug effects MH - Aged MH - Albuminuria MH - Hypoglycemic Agents/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - Renal Insufficiency, Chronic/drug therapy MH - Kidney/drug effects/physiopathology MH - Treatment Outcome MH - Glycated Hemoglobin/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11519175 OTO - NOTNLM OT - Kidney disease OT - Obesity OT - Pharmacoepidemiology OT - Real-world OT - Type 2 diabetes EDAT- 2024/08/23 12:45 MHDA- 2024/10/28 18:23 PMCR- 2024/08/23 CRDT- 2024/08/23 11:04 PHST- 2024/04/18 00:00 [received] PHST- 2024/07/03 00:00 [accepted] PHST- 2024/10/28 18:23 [medline] PHST- 2024/08/23 12:45 [pubmed] PHST- 2024/08/23 11:04 [entrez] PHST- 2024/08/23 00:00 [pmc-release] AID - 10.1007/s00125-024-06251-z [pii] AID - 6251 [pii] AID - 10.1007/s00125-024-06251-z [doi] PST - ppublish SO - Diabetologia. 2024 Nov;67(11):2585-2597. doi: 10.1007/s00125-024-06251-z. Epub 2024 Aug 23. PMID- 39175005 OWN - NLM STAT- MEDLINE DCOM- 20240823 LR - 20260127 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 25 IP - 1 DP - 2024 Aug 22 TI - Patient and public involvement and engagement in the ASCEND PLUS trial: reflections from the design of a streamlined and decentralised clinical trial. PG - 554 LID - 10.1186/s13063-024-08393-2 [doi] LID - 554 AB - INTRODUCTION: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. AIM: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. METHODS: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. RESULTS: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. CONCLUSIONS: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial. CI - (c) 2024. The Author(s). FAU - El-Nayir, Muram AU - El-Nayir M AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Wijesurendra, Rohan AU - Wijesurendra R AUID- ORCID: 0000-0002-8261-8343 AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. rohan.wijesurendra@ndph.ox.ac.uk. FAU - Preiss, David AU - Preiss D AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Mafham, Marion AU - Mafham M AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Tsiotos, Leandros AU - Tsiotos L AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Islam, Sadman AU - Islam S AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Whitehouse, Anne AU - Whitehouse A AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Wilkinson, Sophia AU - Wilkinson S AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Freeman, Hannah AU - Freeman H AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Lee, Ryonfa AU - Lee R AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Brudlo, Wojciech AU - Brudlo W AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Bobby, Genna AU - Bobby G AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Jenkins, Bryony AU - Jenkins B AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Humphrey, Robert AU - Humphrey R AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Mallorie, Amy AU - Mallorie A AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Toal, Andrew AU - Toal A AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Barker, Elnora C AU - Barker EC AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Moylan, Dianna AU - Moylan D AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Thomson, Graeme AU - Thomson G AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Davies, Firoza AU - Davies F AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Khan, Hameed AU - Khan H AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Allotey, Ian AU - Allotey I AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Dickie, Susan AU - Dickie S AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Roberts, John AU - Roberts J AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20240822 PL - England TA - Trials JT - Trials JID - 101263253 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Patient Participation MH - *Research Design MH - Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Patient Selection MH - Community Participation MH - Administration, Oral MH - United Kingdom MH - Stakeholder Participation MH - Glucagon-Like Peptides MH - Semaglutide PMC - PMC11340079 OTO - NOTNLM OT - Clinical trial OT - Diabetes OT - PPIE OT - Patient and public involvement and engagement COIS- The authors declare that they have no competing interests. EDAT- 2024/08/23 00:43 MHDA- 2024/08/23 06:41 PMCR- 2024/08/22 CRDT- 2024/08/22 23:45 PHST- 2024/04/14 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/08/23 06:41 [medline] PHST- 2024/08/23 00:43 [pubmed] PHST- 2024/08/22 23:45 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - 10.1186/s13063-024-08393-2 [pii] AID - 8393 [pii] AID - 10.1186/s13063-024-08393-2 [doi] PST - epublish SO - Trials. 2024 Aug 22;25(1):554. doi: 10.1186/s13063-024-08393-2. PMID- 39172634 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. PG - 1566-1577 LID - 10.1111/jdi.14291 [doi] AB - AIMS/INTRODUCTION: PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. MATERIALS AND METHODS: Adults naive to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34-44 weeks. The primary endpoint was change in glycated hemoglobin (HbA(1c)) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and >/=75 years. RESULTS: A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA(1c) and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA(1c) from baseline was -0.7 percentage points (-0.77, -0.61) overall, -0.8 percentage points (-0.86, -0.67) in the <75 years subgroup and -0.5 percentage points (-0.68, -0.41) in the >/=75 years subgroup (all P < 0.0001). Estimated change (95% CI) in bodyweight was -2.8 (-3.19, -2.50) kg overall, -2.9 (-3.38, -2.49) kg in the <75 years subgroup and - 2.7 (-3.18, -2.14) kg in the >/=75 years subgroup (all P < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and >/=75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation. CONCLUSIONS: In routine clinical practice, HbA(1c) and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged >/=75 years, with no new safety concerns. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for One Medicine Innovative Translational Research, Gifu University, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Kawanami, Daiji AU - Kawanami D AUID- ORCID: 0000-0002-8926-4701 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Amadid, Hanan AU - Amadid H AD - Global Clinical Drug Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Braae, Uffe Christian AU - Braae UC AD - Real-World Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AD - Global Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-2965-6906 AD - Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University, Tokyo, Japan. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study DEP - 20240822 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Male MH - Female MH - Prospective Studies MH - Aged MH - Japan/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Glycated Hemoglobin/analysis MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/analysis MH - Body Weight/drug effects MH - Adult MH - Treatment Outcome MH - East Asian People MH - Semaglutide PMC - PMC11527839 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Oral semaglutide OT - Prospective studies COIS- Daisuke Yabe received consulting/lecture fees from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and research funding/grants from Arkray Inc., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd. and Terumo Corporation. Professor Yabe is an Editorial Board member of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Yoshiyuki Hamamoto received consulting/lecture fees from Novo Nordisk Pharma Ltd. and Sumitomo Pharma Co., Ltd.; and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Dr Hamamoto is an Editorial Board member of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and grants from Bayer Yakuhin Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation and Sumitomo Pharma Co., Ltd. Rimei Nishimura received consulting/lecture fees from Abbott Japan LLC, Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company Ltd., Medtronic Japan Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd. and Teijin Pharma Ltd.; and research funding/grants from Abbott Japan LLC, Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd. and Taisho Pharmaceutical Co., Ltd. Yasuo Terauchi received consulting/lecture fees from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and grants from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Hanan Amadid is employed by, and a shareholder in, Novo Nordisk. Uffe Christian Braae is employed by, and a shareholder in, Novo Nordisk. Atheline Major-Pedersen is employed by, and a shareholder in, Novo Nordisk. Ryo Suzuki received lecture fees from Astellas Pharma Inc., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd. and Teijin Healthcare Ltd; and grants from Nippon Boehringer Ingelheim Co., Ltd. Approval of the research protocol: The protocol for this research project has been approved by suitably constituted ethics committees or institutional review boards of the institutions, and it conforms to the provisions of the Declaration of Helsinki. Ethics committees, institutional review boards and approval numbers are listed in the Supporting Information. Informed consent: All informed consent was obtained from the participants and/or their guardians. Approval date of registry and the registration no. of the study/trial: This study is registered with ClinicalTrials.gov (NCT04878393; first submitted 5 May 2021). Animal studies: N/A. EDAT- 2024/08/22 18:42 MHDA- 2024/11/01 06:21 PMCR- 2024/08/22 CRDT- 2024/08/22 12:43 PHST- 2024/08/14 00:00 [revised] PHST- 2024/04/12 00:00 [received] PHST- 2024/07/29 00:00 [accepted] PHST- 2024/11/01 06:21 [medline] PHST- 2024/08/22 18:42 [pubmed] PHST- 2024/08/22 12:43 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - JDI14291 [pii] AID - 10.1111/jdi.14291 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1566-1577. doi: 10.1111/jdi.14291. Epub 2024 Aug 22. PMID- 39171608 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20241105 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - Application of the integrated data platform combined with dietary management for adults with diabetes: A prospective randomized controlled trial. PG - 1548-1555 LID - 10.1111/jdi.14296 [doi] AB - AIMS: To investigate the efficacy of the integrated data platform of cloud hospital combined with dietary management for adults with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized controlled clinical trial. One hundred eighty patients with type 2 diabetes were randomly allocated into a control group (Group A) and an experimental group (Group B). Routine standard diabetes care was applied to the patients in Group A. The integrated data platform with dietary management was applied to Group B. Individualized diabetes education videos were sent to the patients through the platform. The primary endpoint was the change in HbA1c and change in body weight from baseline to Week 12 during the follow-up. RESULTS: At Week 12, HbA1c was 7.4 +/- 0.7%, 6.9 +/- 0.9% in Groups A and B, P < 0.01. The rate of fasting blood glucose <7 mmol/L, and glycosylated hemoglobin <7% was higher in Group B than in Group A. At Week 12, there was a significant weight loss and body mass index decrease in the overweight or obese patients of the experimental group. Those overweight or obese patients in the experimental group utilizing the appetite suppressant semaglutide achieved the most significant weight loss, with a 13.4% reduction after 12 weeks. CONCLUSIONS: The integrated data platform combined with personalized diabetes education video delivery was verified to be a more effective management mode for diabetes. For overweight or obese adults with diabetes, the use of semaglutide in conjunction with dietary management and the integrated data platform led to greater weight loss. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Liu, Xiyu AU - Liu X AUID- ORCID: 0000-0003-2315-3221 AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Wang, Xiaohong AU - Wang X AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Xie, Mengxun AU - Xie M AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Cao, Lulu AU - Cao L AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. LA - eng GR - 2022-03-029/Grant from the project of Science and Technology of Jinhua/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20240822 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/diet therapy/therapy MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - *Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - Adult MH - Follow-Up Studies MH - Weight Loss MH - Patient Education as Topic MH - Aged MH - Body Mass Index PMC - PMC11527811 OTO - NOTNLM OT - Dietary intervention OT - Digital platform OT - Type 2 diabetes COIS- The authors declare no conflict of interest. Approval of the research protocol: This study conformed to the provisions of the Declaration of Helsinki. It was approved by the Ethics Committee of Dongyang People's Hospital. Informed consent: All participants signed written informed consent before eligibility screening. Registry and the registration no. of the study/trial: The approval date of registry was 30/01/2024, and the registration no. was ChiCTR2400080460. Animal studies: N/A. EDAT- 2024/08/22 12:42 MHDA- 2024/11/01 06:21 PMCR- 2024/08/22 CRDT- 2024/08/22 06:33 PHST- 2024/07/20 00:00 [revised] PHST- 2024/05/14 00:00 [received] PHST- 2024/07/31 00:00 [accepted] PHST- 2024/11/01 06:21 [medline] PHST- 2024/08/22 12:42 [pubmed] PHST- 2024/08/22 06:33 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - JDI14296 [pii] AID - 10.1111/jdi.14296 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1548-1555. doi: 10.1111/jdi.14296. Epub 2024 Aug 22. PMID- 39171569 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study. PG - 5222-5232 LID - 10.1111/dom.15869 [doi] AB - AIM: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. RESULTS: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. CONCLUSIONS: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Liao, Wen-Ling AU - Liao WL AUID- ORCID: 0000-0003-1223-8844 AD - Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. AD - Center for Personalized Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. FAU - Huang, Jing-Yang AU - Huang JY AD - Center for Health Data Science, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Lin, Yu-Jung AU - Lin YJ AUID- ORCID: 0000-0001-5757-1021 AD - Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. AD - School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan. FAU - Yang, Shun-Fa AU - Yang SF AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Huang, Chieh-Chen AU - Huang CC AUID- ORCID: 0000-0002-3739-6315 AD - Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan. FAU - Wang, Chung-Hsing AU - Wang CH AUID- ORCID: 0000-0003-0395-6123 AD - Division of Genetics and Metabolism, Children's Hospital of China Medical University, Taichung, Taiwan. AD - School of Medicine, China Medical University, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AUID- ORCID: 0000-0001-6627-9364 AD - Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2024-C-004 and CSH-2024-C-010/Chung Shan Medical University Hospital/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240822 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Diabetes Obes Metab. 2025 Mar;27(3):1630. doi: 10.1111/dom.16204. PMID: 39803719 MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Obesity/complications/drug therapy MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Aged MH - Cardiovascular Diseases/epidemiology/prevention & control MH - Treatment Outcome MH - Propensity Score MH - Cohort Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - adverse effects OT - cardiovascular disease OT - glucagon-like peptide-1 receptor agonists OT - obesity management OT - thyroid dysfunction EDAT- 2024/08/22 12:44 MHDA- 2024/10/04 12:43 CRDT- 2024/08/22 06:23 PHST- 2024/07/24 00:00 [revised] PHST- 2024/05/21 00:00 [received] PHST- 2024/07/28 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/08/22 12:44 [pubmed] PHST- 2024/08/22 06:23 [entrez] AID - 10.1111/dom.15869 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5222-5232. doi: 10.1111/dom.15869. Epub 2024 Aug 22. PMID- 39168573 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 9 DP - 2024 Aug 27 TI - Effect of Semaglutide on Epicardial Adipose Tissue in Type 2 Diabetes: Insights From the STOP (Semaglutide Treatment effect On coronary atherosclerosis Progression) Randomized Trial. PG - 865-867 LID - S0735-1097(24)07684-8 [pii] LID - 10.1016/j.jacc.2024.05.065 [doi] FAU - Manubolu, Venkat Sanjay AU - Manubolu VS AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Lakshmanan, Suvasini AU - Lakshmanan S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Kinninger, April AU - Kinninger A AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Ahmad, Khadije AU - Ahmad K AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Susarla, Shriraj AU - Susarla S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Seok, Hoon J AU - Seok HJ AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Hamal, Sajad AU - Hamal S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Dahal, Suraj AU - Dahal S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Roy, Sion K AU - Roy SK AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Budoff, Matthew J AU - Budoff MJ AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. Electronic address: mbudoff@lundquist.org. LA - eng PT - Letter PT - Randomized Controlled Trial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Adipose Tissue/drug effects MH - *Coronary Artery Disease/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Disease Progression MH - Epicardial Adipose Tissue MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Pericardium/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Semaglutide EDAT- 2024/08/22 00:42 MHDA- 2024/08/22 00:43 CRDT- 2024/08/21 20:57 PHST- 2024/02/09 00:00 [received] PHST- 2024/05/14 00:00 [revised] PHST- 2024/05/16 00:00 [accepted] PHST- 2024/08/22 00:43 [medline] PHST- 2024/08/22 00:42 [pubmed] PHST- 2024/08/21 20:57 [entrez] AID - S0735-1097(24)07684-8 [pii] AID - 10.1016/j.jacc.2024.05.065 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 27;84(9):865-867. doi: 10.1016/j.jacc.2024.05.065. PMID- 39167822 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20250716 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 8 DP - 2024 Aug 22 TI - Fair Allocation of GLP-1 and Dual GLP-1-GIP Receptor Agonists. Reply. PG - 776 LID - 10.1056/NEJMc2407932#sa3 [pii] LID - 10.1056/NEJMc2407932 [doi] FAU - Persad, Govind AU - Persad G AD - Sturm College of Law, University of Denver, Denver, CO. FAU - Dellgren, Johan L AU - Dellgren JL AD - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. FAU - Emanuel, Ezekiel J AU - Emanuel EJ AD - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM CON - N Engl J Med. 2024 May 30;390(20):1839-1842. doi: 10.1056/NEJMp2400978. PMID: 38630999 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists/supply & distribution/therapeutic use MH - *Health Care Rationing/ethics/statistics & numerical data MH - Healthcare Disparities/ethics/statistics & numerical data MH - Receptors, Gastrointestinal Hormone/agonists MH - Vulnerable Populations/statistics & numerical data EDAT- 2024/08/21 18:41 MHDA- 2024/08/21 18:42 CRDT- 2024/08/21 17:13 PHST- 2024/08/21 18:42 [medline] PHST- 2024/08/21 18:41 [pubmed] PHST- 2024/08/21 17:13 [entrez] AID - 10.1056/NEJMc2407932#sa3 [pii] AID - 10.1056/NEJMc2407932 [doi] PST - ppublish SO - N Engl J Med. 2024 Aug 22;391(8):776. doi: 10.1056/NEJMc2407932. PMID- 39167821 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20250813 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 8 DP - 2024 Aug 22 TI - Fair Allocation of GLP-1 and Dual GLP-1-GIP Receptor Agonists. PG - 775-776 LID - 10.1056/NEJMc2407932#sa2 [pii] LID - 10.1056/NEJMc2407932 [doi] FAU - Gong, Joanna Y AU - Gong JY AD - Baker Heart and Diabetes Institute, Melbourne, VIC, Australia jonathan.shaw@baker.edu.au. FAU - Shaw, Jonathan E AU - Shaw JE AD - Baker Heart and Diabetes Institute, Melbourne, VIC, Australia jonathan.shaw@baker.edu.au. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CON - N Engl J Med. 2024 May 30;390(20):1839-1842. doi: 10.1056/NEJMp2400978. PMID: 38630999 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - Receptors, Gastrointestinal Hormone/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists/supply & distribution/therapeutic use MH - *Health Care Rationing/ethics/statistics & numerical data MH - Healthcare Disparities/ethics/statistics & numerical data MH - Vulnerable Populations/statistics & numerical data EDAT- 2024/08/21 18:41 MHDA- 2024/08/21 18:42 CRDT- 2024/08/21 17:13 PHST- 2024/08/21 18:42 [medline] PHST- 2024/08/21 18:41 [pubmed] PHST- 2024/08/21 17:13 [entrez] AID - 10.1056/NEJMc2407932#sa2 [pii] AID - 10.1056/NEJMc2407932 [doi] PST - ppublish SO - N Engl J Med. 2024 Aug 22;391(8):775-776. doi: 10.1056/NEJMc2407932. PMID- 39167820 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20250813 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 8 DP - 2024 Aug 22 TI - Fair Allocation of GLP-1 and Dual GLP-1-GIP Receptor Agonists. PG - 775 LID - 10.1056/NEJMc2407932#sa1 [pii] LID - 10.1056/NEJMc2407932 [doi] FAU - Mensah, Michael O AU - Mensah MO AD - Yale University, New Haven, CT michael.mensah@yale.edu. FAU - Freitas, Daniel J AU - Freitas DJ AD - San Francisco Department of Public Health, San Francisco, CA. FAU - Cartwright, Joseph R AU - Cartwright JR AD - Alameda Health System, Oakland, CA. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CON - N Engl J Med. 2024 May 30;390(20):1839-1842. doi: 10.1056/NEJMp2400978. PMID: 38630999 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - *Health Care Rationing/ethics/statistics & numerical data MH - Healthcare Disparities/ethics/statistics & numerical data MH - Receptors, Gastrointestinal Hormone/agonists MH - Vulnerable Populations/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists/supply & distribution/therapeutic use EDAT- 2024/08/21 18:41 MHDA- 2024/08/21 18:42 CRDT- 2024/08/21 17:13 PHST- 2024/08/21 18:42 [medline] PHST- 2024/08/21 18:41 [pubmed] PHST- 2024/08/21 17:13 [entrez] AID - 10.1056/NEJMc2407932#sa1 [pii] AID - 10.1056/NEJMc2407932 [doi] PST - ppublish SO - N Engl J Med. 2024 Aug 22;391(8):775. doi: 10.1056/NEJMc2407932. PMID- 39164856 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Early uptake of semaglutide for type 2 diabetes in Scandinavia and characteristics of initiators in Denmark: A register-based drug utilization study. PG - 5479-5482 LID - 10.1111/dom.15876 [doi] FAU - Rasmussen, Lotte AU - Rasmussen L AUID- ORCID: 0000-0001-5962-6647 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Andersen, Jacob Harbo AU - Andersen JH AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Karlstad, Oystein AU - Karlstad O AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Giunta, Diego Hernan AU - Giunta DH AD - Centre for Pharmacoepidemiology, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Linder, Marie AU - Linder M AD - Centre for Pharmacoepidemiology, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Furu, Kari AU - Furu K AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng PT - Letter DEP - 20240820 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Denmark/epidemiology MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Registries MH - Middle Aged MH - Drug Utilization/statistics & numerical data MH - Aged MH - Scandinavian and Nordic Countries/epidemiology MH - Adult MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - database research OT - liraglutide OT - pharmaco-epidemiology OT - semaglutide EDAT- 2024/08/21 11:41 MHDA- 2024/10/04 12:42 CRDT- 2024/08/21 00:42 PHST- 2024/07/04 00:00 [revised] PHST- 2024/04/29 00:00 [received] PHST- 2024/07/07 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/08/21 11:41 [pubmed] PHST- 2024/08/21 00:42 [entrez] AID - 10.1111/dom.15876 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5479-5482. doi: 10.1111/dom.15876. Epub 2024 Aug 20. PMID- 39163055 OWN - NLM STAT- MEDLINE DCOM- 20240820 LR - 20260127 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 72 IP - 8 DP - 2024 Aug TI - Nonarteritic Anterior Ischemic Optic Neuropathy and Semaglutide: What is This All About? PG - 11-12 LID - 10.59556/japi.72.0621 [doi] AB - Nonarteritic anterior ischemic optic neuropathy (NAION) was first documented by a French physician Jean-Pierre Saint-Yves in 1817 (19th century). The clinical description of NAION was not known until 1935 when C. Miller Fischer thoroughly described it. Briefly, NAION is a rare (2.5-11.8 per 1,00,000 cases in men above 50 years) but serious condition that causes sudden painless loss of vision due to ischemia of the optic nerve.(1) It is more common in Caucasians compared with Asians and is associated with various risk factors such as hypertension, type 2 diabetes (T2D), smoking, hyperlipidemia, obesity, obstructive sleep apnea, small optic nerve cup ("disk at risk"), optic nerve drusen, and certain drugs, especially phosphodiesterase type 5 inhibitors (PDE-5I), amiodarone, and cabergoline.(2) Although the clinical development programs and real-world studies of semaglutide [a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for the treatment of T2D and obesity] did not report any significant increase in the risk of NAION, a recent retrospective cohort study suggested a possible link between NAION and semaglutide.(3) This editorial briefly summarizes the current knowledge about NAION and its relation to metabolic disorders, cardiovascular, and antidiabetes drugs and puts a perspective concerning semaglutide. CI - (c) Journal of the Association of Physicians of India 2024. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - Consultant Endocrinologist, Department of Diabetes & Endocrinology, G. D. Hospital & Diabetes Institute, Kolkata, West Bengal, India, Corresponding Author. FAU - Kesavadev, Jothydev AU - Kesavadev J AD - Consultant Physician and Diabetes Specialist, Department of Diabetes & Endocrinology, Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Tiwaskar, Mangesh AU - Tiwaskar M AD - Consultant Physician and Diabetes Specialist, Department of Diabetes & Endocrinology, Shilpa Medical Research Centre, Mumbai, Maharashtra, India. LA - eng PT - Editorial PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Optic Neuropathy, Ischemic/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Semaglutide EDAT- 2024/08/20 12:43 MHDA- 2024/08/20 12:44 CRDT- 2024/08/20 11:39 PHST- 2024/08/20 12:44 [medline] PHST- 2024/08/20 12:43 [pubmed] PHST- 2024/08/20 11:39 [entrez] AID - 10.59556/japi.72.0621 [doi] PST - ppublish SO - J Assoc Physicians India. 2024 Aug;72(8):11-12. doi: 10.59556/japi.72.0621. PMID- 39163050 OWN - NLM STAT- MEDLINE DCOM- 20240820 LR - 20250227 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 8 DP - 2024 Aug 1 TI - GLP-1 Receptor Agonists and Suicidality-Caution Is Needed. PG - e2423335 LID - 10.1001/jamanetworkopen.2024.23335 [doi] FAU - Salvo, Francesco AU - Salvo F AD - Universite de Bordeaux, INSERM, BPH, Team AHeaD, U1219, Bordeaux, France. AD - Service de Pharmacologie Medicale, CHU de Bordeaux, INSERM, U1219, Bordeaux, France. FAU - Faillie, Jean-Luc AU - Faillie JL AD - Desbrest Institute of Epidemiology and Public Health, Department of Medical Pharmacology and Toxicology, INSERM, Universite de Montpellier, Regional Pharmacovigilance Centre, CHU Montpellier, Montpellier, France. LA - eng PT - Journal Article DEP - 20240801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Female MH - Humans MH - Male MH - Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - *Suicidal Ideation MH - Suicide/statistics & numerical data/psychology EDAT- 2024/08/20 12:43 MHDA- 2024/08/20 12:44 CRDT- 2024/08/20 11:34 PHST- 2024/08/20 12:44 [medline] PHST- 2024/08/20 12:43 [pubmed] PHST- 2024/08/20 11:34 [entrez] AID - 2822457 [pii] AID - 10.1001/jamanetworkopen.2024.23335 [doi] PST - epublish SO - JAMA Netw Open. 2024 Aug 1;7(8):e2423335. doi: 10.1001/jamanetworkopen.2024.23335. PMID- 39161072 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Association between glucagon-like peptide-1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database. PG - 5183-5191 LID - 10.1111/dom.15864 [doi] AB - AIM: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data. MATERIALS AND METHODS: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC(025) regarding the association between GLP-1RA use and suicidality. RESULTS: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC(025) -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC(025) -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC(025) -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC(025) 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC(025) 0.01]). CONCLUSIONS: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Kim, Tae Hyeon AU - Kim TH AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Lee, Kyeongmin AU - Lee K AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Regulatory Science, Kyung Hee University, Seoul, South Korea. FAU - Park, Seoyoung AU - Park S AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Cho, Hanseul AU - Cho H AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Park, Jaeyu AU - Park J AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Regulatory Science, Kyung Hee University, Seoul, South Korea. FAU - Jo, Hyesu AU - Jo H AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Regulatory Science, Kyung Hee University, Seoul, South Korea. FAU - Son, Yejun AU - Son Y AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Kim, Soeun AU - Kim S AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Kang, Jiseung AU - Kang J AD - Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. FAU - Smith, Lee AU - Smith L AD - Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK. FAU - Rahmati, Masoud AU - Rahmati M AD - CEReSS-Health Service Research and Quality of Life Centre, Assistance Publique-Hopitaux de Marseille, Aix-Marseille University, Marseille, France. AD - Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran. AD - Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran. FAU - Fond, Guillaume AU - Fond G AD - CEReSS-Health Service Research and Quality of Life Centre, Assistance Publique-Hopitaux de Marseille, Aix-Marseille University, Marseille, France. FAU - Boyer, Laurent AU - Boyer L AD - CEReSS-Health Service Research and Quality of Life Centre, Assistance Publique-Hopitaux de Marseille, Aix-Marseille University, Marseille, France. FAU - Pizzol, Damiano AU - Pizzol D AD - Health Unit Eni, Maputo, Mozambique. AD - Health Unit, Eni, San Donato Milanese, Italy. FAU - Lee, Hayeon AU - Lee H AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Rhee, Sang Youl AU - Rhee SY AUID- ORCID: 0000-0003-0119-5818 AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Regulatory Science, Kyung Hee University, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Hwang, Jiyoung AU - Hwang J AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Sang, Hyunji AU - Sang H AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Seoul, South Korea. FAU - Yon, Dong Keon AU - Yon DK AUID- ORCID: 0000-0003-1628-9948 AD - Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Centre for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Regulatory Science, Kyung Hee University, Seoul, South Korea. AD - Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea. AD - Department of Paediatrics, Kyung Hee University Medical Centre, Kyung Hee University College of Medicine, Seoul, South Korea. LA - eng GR - RS-2023-00248157/National Research Foundation of Korea (NRF)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240819 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Pharmacovigilance MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Suicide/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Databases, Factual MH - Obesity/epidemiology MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - World Health Organization OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - suicidality EDAT- 2024/08/20 06:42 MHDA- 2024/10/04 12:43 CRDT- 2024/08/20 01:24 PHST- 2024/07/15 00:00 [revised] PHST- 2024/05/28 00:00 [received] PHST- 2024/07/25 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/08/20 06:42 [pubmed] PHST- 2024/08/20 01:24 [entrez] AID - 10.1111/dom.15864 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5183-5191. doi: 10.1111/dom.15864. Epub 2024 Aug 19. PMID- 39160334 OWN - NLM STAT- MEDLINE DCOM- 20241023 LR - 20250103 IS - 2522-5812 (Electronic) IS - 2522-5812 (Linking) VI - 6 IP - 10 DP - 2024 Oct TI - GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management. PG - 1866-1885 LID - 10.1038/s42255-024-01113-9 [doi] AB - The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in the treatment of type 2 diabetes and obesity. With normalisation of glycated haemoglobin levels and weight losses around 15-25%, therapeutic goals that were previously unrealistic are now within reach, and clinical trials have documented that these effects are associated with reduced risk of cardiovascular events and premature mortality. Here, I review this remarkable development from the earliest observations of glucose lowering and modest weight losses with native glucagon-like peptide (GLP)-1 and short acting compounds, to the recent development of highly active formulations and new molecules. I will classify these agents as GLP-1-based therapies in the understanding that these compounds or combinations may have actions on other receptors as well. The physiology of GLP-1 is discussed as well as its mechanisms of actions in obesity, in particular, the role of sensory afferents and GLP-1 receptors in the brain. I provide details regarding the development of GLP-1 receptor agonists for anti-obesity therapy and discuss the possible mechanism behind their beneficial effects on adverse cardiovascular events. Finally, I highlight new pharmacological developments, including oral agents, and discuss important questions regarding maintenance therapy. CI - (c) 2024. Springer Nature Limited. FAU - Holst, Jens Juul AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. jjholst@sund.ku.dk. LA - eng PT - Journal Article PT - Review DEP - 20240819 PL - Germany TA - Nat Metab JT - Nature metabolism JID - 101736592 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - Anti-Obesity Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/08/20 00:42 MHDA- 2024/10/23 06:22 CRDT- 2024/08/19 23:26 PHST- 2024/01/30 00:00 [received] PHST- 2024/07/17 00:00 [accepted] PHST- 2024/10/23 06:22 [medline] PHST- 2024/08/20 00:42 [pubmed] PHST- 2024/08/19 23:26 [entrez] AID - 10.1038/s42255-024-01113-9 [pii] AID - 10.1038/s42255-024-01113-9 [doi] PST - ppublish SO - Nat Metab. 2024 Oct;6(10):1866-1885. doi: 10.1038/s42255-024-01113-9. Epub 2024 Aug 19. PMID- 39159651 OWN - NLM STAT- MEDLINE DCOM- 20240831 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 404 IP - 10455 DP - 2024 Aug 31 TI - International coverage of GLP-1 receptor agonists: a review and ethical analysis of discordant approaches. PG - 902-906 LID - S0140-6736(24)01356-4 [pii] LID - 10.1016/S0140-6736(24)01356-4 [doi] FAU - Dellgren, Johan L AU - Dellgren JL AD - Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Bergen Centre for Ethics and Priority Setting, University of Bergen, Bergen, Norway. FAU - Persad, Govind AU - Persad G AD - Sturm College of Law, University of Denver, Denver, CO, USA; Bergen Centre for Ethics and Priority Setting, University of Bergen, Bergen, Norway. FAU - Emanuel, Ezekiel J AU - Emanuel EJ AD - Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Bergen Centre for Ethics and Priority Setting, University of Bergen, Bergen, Norway. Electronic address: zemanuel@upenn.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240816 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor COIS- Declaration of interests GP reports receiving grants from the Greenwall Foundation and personal fees from the ASCO Post for work outside the current manuscript. EJE reports travel reimbursement from the Alliance of Academic Health Centers International Global Innovation Forum, Macalester College, Oak CEO Summit, DPharm, the University of California San Francisco, Cain Brothers, the Galien Foundation, the HLTH 2022 Meeting, the Hawaii Medical Service Association, the Tel Aviv University, the Suntory Foundation, The Quadrangle, the HLTH 2023 Meeting, the University of Virginia, and the New York Historical Society; reports honorarium from the Advocate Aurora Health Summit; reports conference, honorarium, and travel reimbursement from the University of Pittsburgh Medical Center Shadyside and Bowdoin College; reports honorarium and travel reimbursement from the Ontario Hospital Association, Health Plan Alliance, and Emory Health Care; reports a monetary prize and travel reimbursement from the University of Oklahoma; reports lodging covered by the Lazard HC and Amangiri Executive Retreat; reports a leadership summit, honorarium, and travel reimbursement from Sanford Health; reports a leaders retreat, honorarium, and travel reimbursement from Employer Direct Health Care; reports serving on the board of advisors for Cellares and Alto Pharmacy Holdings; is an advisor for Notable Health; is an advisory board member for JSL Health Capital, the Peterson Center on Health Care, Feel Better, HIEX Health Innovation Exchange partnership sponsored by UN Geneva, and Biden's Transition COVID-19 Committee; is an advisor for Clarify Health Solutions, Korro/Coach AI, Link Health Technologies, and Nuna; is a consultant for Health Care Foundry and Aberdeen; is an expert advisory member for the WHO COVID 19 Ethics & Governance Working Group; is a special advisor to the Director General of WHO; is an editorial board member for the Journal of the American Medical Association; is an internal advisory board member for the Penn Parity Center; reports investments in Sunstone Consulting and Aktivate; reports royalties from his books and William Morris Endeavor; and reports the following grants: Hogan Lovells, Mendel Health, the University of Bergen, Janseen Pharmaceuticals, the Schmidt Futures Schwab Charitable Fund, the Laura and John Arnold Foundation, Humana, the University of Miami, Hawaii Medical Services Association, and the Patient Centered Outcomes Research Institute. JLD declares no competing interests. EDAT- 2024/08/20 00:42 MHDA- 2024/09/01 16:18 CRDT- 2024/08/19 18:52 PHST- 2024/04/14 00:00 [received] PHST- 2024/06/13 00:00 [revised] PHST- 2024/06/26 00:00 [accepted] PHST- 2024/09/01 16:18 [medline] PHST- 2024/08/20 00:42 [pubmed] PHST- 2024/08/19 18:52 [entrez] AID - S0140-6736(24)01356-4 [pii] AID - 10.1016/S0140-6736(24)01356-4 [doi] PST - ppublish SO - Lancet. 2024 Aug 31;404(10455):902-906. doi: 10.1016/S0140-6736(24)01356-4. Epub 2024 Aug 16. PMID- 39157881 OWN - NLM STAT- MEDLINE DCOM- 20240827 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 Suppl 4 DP - 2024 Sep TI - Opportunities to optimize lifestyle interventions in combination with glucagon-like peptide-1-based therapy. PG - 3-15 LID - 10.1111/dom.15829 [doi] AB - Obesity is a chronic multi-system disease and major driver of type 2 diabetes and cardiometabolic disease. Nutritional interventions form the cornerstone of obesity and type 2 diabetes management. Some interventions such as Mediterranean diet can reduce incident cardiovascular disease, probably independently of weight loss. Weight loss of 5% or greater can improve many adiposity-related comorbidities. Although this can be achieved with lifestyle intervention, it is often difficult to sustain in the longer term due to adaptive endocrine changes. In recent years glucagon-like-peptide-1 receptor agonists (GLP-1RAs) have emerged as effective treatments for both type 2 diabetes and obesity. Newer GLP-1RAs can achieve average weight loss of 15% or greater and improve cardiometabolic health. There is heterogeneity in the weight loss response to GLP-1RAs, with a substantial number of patients unable to achieve 5% or greater weight. Weight loss, on average, is lower in older adults, male patients and people with type 2 diabetes. Mechanistic studies are needed to understand the aetiology of this variable response. Gastrointestinal side effects leading to medication discontinuation are a concern with GLP-1RA treatment, based on real-world data. With weight loss of 20% or higher with newer GLP-1RAs, nutritional deficiency and sarcopenia are also potential concerns. Lifestyle interventions that may potentially mitigate the side effects of GLP-1RA treatment and enhance weight loss are discussed here. The efficacy of such interventions awaits confirmation with well-designed randomized controlled trials. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Dash, Satya AU - Dash S AUID- ORCID: 0000-0002-5167-2099 AD - Division of Endocrinology, University Health Network & University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20240819 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/therapy MH - *Glucagon-Like Peptide 1/therapeutic use/agonists MH - *Obesity/complications/therapy MH - *Weight Loss/drug effects MH - Hypoglycemic Agents/therapeutic use MH - Life Style MH - Combined Modality Therapy MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 analogue OT - dietary intervention OT - incretin therapy OT - weight control EDAT- 2024/08/19 06:42 MHDA- 2024/08/27 12:45 CRDT- 2024/08/19 05:29 PHST- 2024/06/28 00:00 [revised] PHST- 2024/04/28 00:00 [received] PHST- 2024/07/10 00:00 [accepted] PHST- 2024/08/27 12:45 [medline] PHST- 2024/08/19 06:42 [pubmed] PHST- 2024/08/19 05:29 [entrez] AID - 10.1111/dom.15829 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Sep;26 Suppl 4:3-15. doi: 10.1111/dom.15829. Epub 2024 Aug 19. PMID- 39151204 OWN - NLM STAT- MEDLINE DCOM- 20241022 LR - 20260127 IS - 1539-2864 (Electronic) IS - 0275-004X (Linking) VI - 44 IP - 11 DP - 2024 Nov 1 TI - NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY. PG - 1851-1859 LID - 10.1097/IAE.0000000000004252 [doi] AB - PURPOSE: Novel therapies for diabetes have potent effects on glycemic control, obesity, and cardiovascular risk reduction, but some, including the popular drug semaglutide, have also been implicated in worsening of diabetic retinopathy (DR). Given the ubiquity of these new agents, understanding the risks to vision is important. Here, we review the data for several newly available agents in terms of systemic efficacy and retinal safety. METHODS: Literature review. RESULTS: Novel antihyperglycemic treatments include incretin mimetics and enhancers, sodium-glucose cotransporter inhibitors, long-acting insulins, and insulin delivery systems. All improve glycemic control, and some have been shown to reduce major cardiovascular outcomes. In a pivotal trial, semaglutide was associated with approximately 75% increased risk of DR worsening. The novel long-acting insulin icodec, formulated for once weekly dosing, showed increased risk of DR worsening over a once daily insulin. No other recent antihyperglycemic agent was associated with DR worsening, although following the semaglutide trials, nearly all studies excluded patients with preexisting DR. Cases of DR worsening were rare in all instances. Dedicated safety studies for semaglutide in DR are currently underway. CONCLUSION: For most patients being considered for treatment with a novel antihyperglycemic agent, benefits on systemic metabolic and cardiovascular health are very likely to outweigh potential retinal harms. Although the true risks of the new agents on DR are unclear because their safety data come from secondary end points, the most vulnerable patients are those with preexisting high-risk DR, poor baseline glycemic control, and using insulin. CI - Copyright (c) 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc. FAU - Rajagopal, Rithwick AU - Rajagopal R AUID- ORCID: 0000-0002-3036-2665 AD - Department of Ophthalmology and Visual Sciences, and. FAU - McGill, Janet B AU - McGill JB AD - Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, Saint Louis, Missouri. LA - eng GR - EY034172/National Eye Institute, Horncrest Foundation/ PT - Journal Article PT - Review PL - United States TA - Retina JT - Retina (Philadelphia, Pa.) JID - 8309919 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Blood Glucose/metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage/adverse effects MH - Risk Factors MH - Disease Progression MH - Semaglutide EDAT- 2024/08/16 18:42 MHDA- 2024/10/22 18:22 CRDT- 2024/08/16 17:53 PHST- 2024/10/22 18:22 [medline] PHST- 2024/08/16 18:42 [pubmed] PHST- 2024/08/16 17:53 [entrez] AID - 00006982-990000000-00774 [pii] AID - 10.1097/IAE.0000000000004252 [doi] PST - ppublish SO - Retina. 2024 Nov 1;44(11):1851-1859. doi: 10.1097/IAE.0000000000004252. PMID- 39145614 OWN - NLM STAT- MEDLINE DCOM- 20240928 LR - 20260922 IS - 1479-6805 (Electronic) IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 263 IP - 1 DP - 2024 Oct 1 TI - GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms. LID - 10.1530/JOE-24-0046 [doi] LID - e240046 AB - Cardiovascular outcome trials (CVOTs) in people living with type 2 diabetes mellitus and obesity have confirmed the cardiovascular benefits of glucagon-like peptide 1 receptor agonists (GLP-1RAs), including reduced cardiovascular mortality, lower rates of myocardial infarction, and lower rates of stroke. The cardiovascular benefits observed following GLP-1RA treatment could be secondary to improvements in glycemia, blood pressure, postprandial lipidemia, and inflammation. Yet, the GLP-1R is also expressed in the heart and vasculature, suggesting that GLP-1R agonism may impact the cardiovascular system. The emergence of GLP-1RAs combined with glucose-dependent insulinotropic polypeptide and glucagon receptor agonists has shown promising results as new weight loss medications. Dual-agonist and tri-agonist therapies have demonstrated superior outcomes in weight loss, lowered blood sugar and lipid levels, restoration of tissue function, and enhancement of overall substrate metabolism compared to using GLP-1R agonists alone. However, the precise mechanisms underlying their cardiovascular benefits remain to be fully elucidated. This review aims to summarize the findings from CVOTs of GLP-1RAs, explore the latest data on dual and tri-agonist therapies, and delve into potential mechanisms contributing to their cardioprotective effects. It also addresses current gaps in understanding and areas for further research. FAU - Mullur, Neerav AU - Mullur N AD - The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada. FAU - Morissette, Arianne AU - Morissette A AD - The University of Ottawa Heart Institute, Ottawa, Ontario, Canada. FAU - Morrow, Nadya M AU - Morrow NM AD - The University of Ottawa Heart Institute, Ottawa, Ontario, Canada. AD - Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada. FAU - Mulvihill, Erin E AU - Mulvihill EE AUID- ORCID: 0000-0002-3981-0241 AD - The University of Ottawa Heart Institute, Ottawa, Ontario, Canada. AD - Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20240919 PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Heart Disease Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11466209 OTO - NOTNLM OT - cardiovascular OT - hormone action OT - incretins OT - metabolism OT - nutrition COIS- The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2024/08/15 12:42 MHDA- 2024/09/29 00:43 PMCR- 2024/10/10 CRDT- 2024/08/15 08:44 PHST- 2024/02/15 00:00 [received] PHST- 2024/08/15 00:00 [accepted] PHST- 2024/09/29 00:43 [medline] PHST- 2024/08/15 12:42 [pubmed] PHST- 2024/08/15 08:44 [entrez] PHST- 2024/10/10 00:00 [pmc-release] AID - JOE-24-0046 [pii] AID - 10.1530/JOE-24-0046 [doi] PST - epublish SO - J Endocrinol. 2024 Sep 19;263(1):e240046. doi: 10.1530/JOE-24-0046. Print 2024 Oct 1. PMID- 39142859 OWN - NLM STAT- MEDLINE DCOM- 20240814 LR - 20250103 IS - 1558-7118 (Electronic) IS - 1557-2625 (Linking) VI - 37 IP - 3 DP - 2024 May-Jun TI - GLP-1 RAs and SGLT2-Is to Lower Glucose and Reduce the Risk of Cardiovascular and Diabetic Kidney Disease. PG - 372-382 LID - 10.3122/jabfm.2023.230455R1 [doi] AB - The landscape of diabetes management has changed, such that the goal of pharmacotherapy extends beyond glucose-lowering to prioritize risk reduction of cardiovascular disease and diabetic kidney disease. Two newer classes of medications, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2-Is), have become first line therapies for many patients with type 2 diabetes to reduce cardiovascular and renal complications of type 2 diabetes. This review article will describe the mechanism of action, evidence for cardiovascular and kidney outcomes, contraindications, adverse effects, and risk mitigation strategies for the GLP-1 RA and SGLT2-I drug classes. In addition, we will provide a practical approach for primary care clinicians to prescribe, adjust, and combine these medication classes, while considering patient preference, tolerability, comorbidities, cost, and availability. CI - (c) Copyright 2024 by the American Board of Family Medicine. FAU - Morrison, Leigh AU - Morrison L AD - From the Clinical Assistant Professor, Department of Family Medicine, University of Michigan (LM, JG); Associate Professor, Department of Family Medicine, University of Michigan (LO). morrisol@med.umich.edu. FAU - Gabison, Jonathan AU - Gabison J AD - From the Clinical Assistant Professor, Department of Family Medicine, University of Michigan (LM, JG); Associate Professor, Department of Family Medicine, University of Michigan (LO). FAU - Oshman, Lauren AU - Oshman L AD - From the Clinical Assistant Professor, Department of Family Medicine, University of Michigan (LM, JG); Associate Professor, Department of Family Medicine, University of Michigan (LO). LA - eng PT - Journal Article PT - Review PL - United States TA - J Am Board Fam Med JT - Journal of the American Board of Family Medicine : JABFM JID - 101256526 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetic Nephropathies/prevention & control/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Blood Glucose/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular Risk Factors OT - Diabetic Nephropathies OT - Glucagon-Like Peptide-1 Receptor Agonists OT - Obesity OT - Pharmacology OT - Primary Health Care OT - Sodium-Glucose Transporter 2 Inhibitors OT - Type 2 Diabetes Mellitus COIS- Conflict of interest: None. EDAT- 2024/08/15 00:42 MHDA- 2024/08/15 00:43 CRDT- 2024/08/14 21:33 PHST- 2023/12/06 00:00 [received] PHST- 2023/12/21 00:00 [revised] PHST- 2024/01/17 00:00 [accepted] PHST- 2024/08/15 00:43 [medline] PHST- 2024/08/15 00:42 [pubmed] PHST- 2024/08/14 21:33 [entrez] AID - 37/3/372 [pii] AID - 10.3122/jabfm.2023.230455R1 [doi] PST - ppublish SO - J Am Board Fam Med. 2024 May-Jun;37(3):372-382. doi: 10.3122/jabfm.2023.230455R1. PMID- 39142724 OWN - NLM STAT- MEDLINE DCOM- 20240814 LR - 20260128 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 8 DP - 2024 Aug 20 TI - Kidney and Cardiovascular Outcomes With SGLT2 Inhibitors and/or GLP-1 Receptor Agonists in Type 2 Diabetes. PG - 709-711 LID - S0735-1097(24)07776-3 [pii] LID - 10.1016/j.jacc.2024.07.002 [doi] FAU - Neuen, Brendon L AU - Neuen BL AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia; Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia. FAU - Solomon, Scott D AU - Solomon SD AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: sdsolomon@bwh.harvard.edu. LA - eng PT - Editorial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Cardiovascular Diseases/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - chronic OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - renal insufficiency OT - sodium-glucose cotransporter 2 OT - treatment outcome OT - type 2 COIS- Funding Support and Author Disclosures Dr Neuen has received fees for travel support, advisory board participation, scientific presentations, and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, Janssen, the limbic, Medscape, Novo Nordisk, and Travere Therapeutics, with all honoraria paid to The George Institute for Global Health. Dr Solomon has received research grants from Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GlaxoSmithKline, Ionis, Eli Lilly, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, GlaxoSmithKline, Eli Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. EDAT- 2024/08/15 00:41 MHDA- 2024/08/15 00:42 CRDT- 2024/08/14 20:55 PHST- 2024/07/02 00:00 [received] PHST- 2024/07/08 00:00 [accepted] PHST- 2024/08/15 00:42 [medline] PHST- 2024/08/15 00:41 [pubmed] PHST- 2024/08/14 20:55 [entrez] AID - S0735-1097(24)07776-3 [pii] AID - 10.1016/j.jacc.2024.07.002 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 20;84(8):709-711. doi: 10.1016/j.jacc.2024.07.002. PMID- 39142723 OWN - NLM STAT- MEDLINE DCOM- 20240814 LR - 20260128 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 8 DP - 2024 Aug 20 TI - Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes. PG - 696-708 LID - S0735-1097(24)07627-7 [pii] LID - 10.1016/j.jacc.2024.06.016 [doi] AB - BACKGROUND: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed. OBJECTIVES: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D. METHODS: Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes. RESULTS: The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status. CONCLUSIONS: SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317). CI - Copyright (c) 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Edmonston, Daniel AU - Edmonston D AD - Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA. Electronic address: daniel.edmonston@duke.edu. FAU - Mulder, Hillary AU - Mulder H AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA. FAU - Lydon, Elizabeth AU - Lydon E AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA. FAU - Chiswell, Karen AU - Chiswell K AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA. FAU - Lampron, Zachary AU - Lampron Z AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA. FAU - Shay, Christina AU - Shay C AD - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA. FAU - Marsolo, Keith AU - Marsolo K AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA; Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Shah, Raj C AU - Shah RC AD - Department of Family and Preventive Medicine and the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA. FAU - Jones, W Schuyler AU - Jones WS AD - Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Gordon, Howard AU - Gordon H AD - University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA. FAU - Hwang, Wenke AU - Hwang W AD - Penn State College of Medicine, Hershey, Pennsylvania, USA. FAU - Ayoub, Isabelle AU - Ayoub I AD - The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. FAU - Ford, Daniel AU - Ford D AD - Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Chamberlain, Alanna AU - Chamberlain A AD - Department of Quantitative Health Sciences, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. FAU - Rao, Ajaykumar AU - Rao A AD - Department of Endocrinology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA. FAU - Fonseca, Vivian AU - Fonseca V AD - Tulane University Health Sciences Center, New Orleans, Louisiana, USA. FAU - Chang, Alexander AU - Chang A AD - Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, USA. FAU - Ahmad, Faraz AU - Ahmad F AD - Northwestern Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Hung, Adriana AU - Hung A AD - Division of Nephrology, Department of Medicine at Vanderbilt University School of Medicine, Nashville, Tennessee, USA. FAU - Hunt, Kelly AU - Hunt K AD - Medical University of South Carolina, Charleston, South Carolina, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, Texas, USA. FAU - Bosworth, Hayden B AU - Bosworth HB AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA; Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA; Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham Veterans Affairs Medical Center, Durham, North Carolina, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, USA; Duke University School of Nursing, Durham, North Carolina, USA. FAU - Pagidipati, Neha AU - Pagidipati N AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina USA; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. LA - eng SI - ClinicalTrials.gov/NCT05465317 PT - Comparative Study PT - Journal Article PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Aged MH - *Glomerular Filtration Rate/drug effects MH - Cardiovascular Diseases MH - Hypoglycemic Agents/therapeutic use MH - Kidney Failure, Chronic MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - cardiovascular disease OT - chronic kidney disease OT - diabetes mellitus OT - glucagon-like 1 receptor agonists OT - sodium-glucose cotransporter 2 inhibitors COIS- Funding Support and Author Disclosures This study was funded by the Boehringer Ingelheim & Lilly Diabetes Alliance. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Dr Butler has received consultant honoraria from Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr Pagidipati has received research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland's Best, Eli Lilly, Novartis, Novo Nordisk, and Verily Life Sciences; has served on consultation/advisory panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; has served as an executive committee member for trials sponsored by Novo Nordisk and Amgen; has served on the Data Safety Monitoring Boards for trials sponsored by Johnson and Johnson and Novartis; and has served on the medical advisory board for Miga Health. Dr Fonseca has received research support (to Tulane) from Fractyl and Jaguar Gene Therapy; has received consultant honoraria from Asahi, Bayer, Abbott, Boehringer Ingelheim, and Corcept; has stock or stock options in Mellitus Health, BRAVO4Health, Amgen, and Abbott; and has patents pending for BRAVO risk engine for predicting diabetes complications and PAX4 gene therapy for type 1 diabetes. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2024/08/15 00:42 MHDA- 2024/08/15 00:43 CRDT- 2024/08/14 20:55 PHST- 2024/04/22 00:00 [received] PHST- 2024/05/29 00:00 [revised] PHST- 2024/06/10 00:00 [accepted] PHST- 2024/08/15 00:43 [medline] PHST- 2024/08/15 00:42 [pubmed] PHST- 2024/08/14 20:55 [entrez] AID - S0735-1097(24)07627-7 [pii] AID - 10.1016/j.jacc.2024.06.016 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 20;84(8):696-708. doi: 10.1016/j.jacc.2024.06.016. PMID- 39140772 OWN - NLM STAT- MEDLINE DCOM- 20240912 LR - 20250925 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 67 IP - 17 DP - 2024 Sep 12 TI - Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor. PG - 14820-14839 LID - 10.1021/acs.jmedchem.4c01177 [doi] AB - Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties. FAU - Zhang, Zhimin AU - Zhang Z AUID- ORCID: 0000-0002-9394-9586 AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Pan, Hao AU - Pan H AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Guo, Liubin AU - Guo L AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Cai, Cancan AU - Cai C AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Chen, Tingni AU - Chen T AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Zhang, Zhiping AU - Zhang Z AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Yang, Xu AU - Yang X AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Zheng, Haowen AU - Zheng H AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Jiang, Chunhua AU - Jiang C AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Wang, Zhiyong AU - Wang Z AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Yang, Yacheng AU - Yang Y AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Wang, Zhe AU - Wang Z AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Zhang, Xiaohua AU - Zhang X AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Zhang, Yuchen AU - Zhang Y AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. FAU - Liu, Dongzhou AU - Liu D AD - Global Drug R&D Center, Huadong Medicine Company Limited, Hangzhou 310011, P. R. of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240814 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - Humans MH - Mice MH - *Drug Design MH - Structure-Activity Relationship MH - Male MH - Hypoglycemic Agents/pharmacology/chemical synthesis/chemistry/pharmacokinetics/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Blood Glucose/drug effects/metabolism MH - Receptors, Glucagon/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/08/14 12:43 MHDA- 2024/09/12 08:42 CRDT- 2024/08/14 09:13 PHST- 2024/09/12 08:42 [medline] PHST- 2024/08/14 12:43 [pubmed] PHST- 2024/08/14 09:13 [entrez] AID - 10.1021/acs.jmedchem.4c01177 [doi] PST - ppublish SO - J Med Chem. 2024 Sep 12;67(17):14820-14839. doi: 10.1021/acs.jmedchem.4c01177. Epub 2024 Aug 14. PMID- 39139128 OWN - NLM STAT- MEDLINE DCOM- 20240814 LR - 20250731 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 21 IP - 4 DP - 2024 Jul-Aug TI - Patient-important outcomes in type 2 diabetes: The paradigm of the sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. PG - 14791641241269743 LID - 10.1177/14791641241269743 [doi] LID - 14791641241269743 AB - The newfound knowledge in type 2 diabetes (T2D) during the past decade for the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is wealthy in favorable results for key patient-important outcomes including morbidity, mortality and health-related quality of life (HRQoL). The SGLT-2i and GLP-1RA offer cardiovascular and renal protection beyond their glucose lowering effect, reduce body weight and hypoglycemia and improve diabetes-related distress, physical function and HRQoL. Along with the fixed-ratio combinations of basal insulin/GLP-1RA, they make feasible a regimen simplification and de-escalation from high dose and multiple injections of insulin reducing treatment burden. Besides cardiorenal risk reduction, the SGLT-2i and GLP-1RA reduce the incidence of depression, cognitive decline, respiratory disease, gout, arrhythmias and other co-occurring conditions of T2D, namely multimorbidity, which frequently complicates T2D and adversely affects HRQoL. The alleviation of multimorbidity by the pleiotropic effects of the SGLT-2i and GLP-1RA, could improve patients' HRQoL. The use of the SGLT-2i and GLP-1RA should be increased within a shared decision-making in which they are reframed as cardiorenal risk-reducing medications with the potential to lower blood glucose. By improving outcomes that patients may highly perceive and value, the SGLT-2i and GLP-1RA may facilitate the contemporary person-centered management of T2D. FAU - Kintzoglanakis, Kyriakos AU - Kintzoglanakis K AUID- ORCID: 0000-0003-1265-3351 AD - Department of Primary Care, Local Health-Team Unit of Thebes, Thebes, Greece. FAU - Diamantis, Christos AU - Diamantis C AD - Department of Primary Care, General Hospital of Livadeia, Livadeia, Greece. FAU - Mariolis, Anargiros AU - Mariolis A AD - Department of Primary Care, Health Center of Areopolis, Areopolis, Laconia, Greece. FAU - Paschou, Stavroula A AU - Paschou SA AD - Departement of Endocrinology, Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, Athens, Greece. LA - eng PT - Journal Article PT - Review PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - *Quality of Life MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Blood Glucose/metabolism/drug effects MH - Risk Factors MH - Glycemic Control/adverse effects MH - Incretins/therapeutic use/adverse effects MH - Biomarkers/blood MH - Patient Reported Outcome Measures MH - Risk Assessment MH - Health Status MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11325323 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - fixed ratio combination of basal insulin/glucagon-like peptide-1 receptor agonists OT - glucagon-like peptide-1 receptor agonists OT - health-related quality of life OT - patient-important outcomes OT - sodium-glucose cotransporter-2 inhibitors COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2024/08/14 06:42 MHDA- 2024/08/14 06:43 PMCR- 2024/08/14 CRDT- 2024/08/14 04:03 PHST- 2024/08/14 06:43 [medline] PHST- 2024/08/14 06:42 [pubmed] PHST- 2024/08/14 04:03 [entrez] PHST- 2024/08/14 00:00 [pmc-release] AID - 10.1177_14791641241269743 [pii] AID - 10.1177/14791641241269743 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2024 Jul-Aug;21(4):14791641241269743. doi: 10.1177/14791641241269743. PMID- 39139038 OWN - NLM STAT- MEDLINE DCOM- 20241213 LR - 20250110 IS - 1098-1128 (Electronic) IS - 0198-6325 (Print) IS - 0198-6325 (Linking) VI - 45 IP - 1 DP - 2025 Jan TI - Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future. PG - 29-65 LID - 10.1002/med.22070 [doi] AB - Among newer classes of drugs for type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are incretin-based agents that lower both blood sugar levels and promote weight loss. They do so by activating pancreatic GLP-1 receptors (GLP-1R) to promote glucose-dependent insulin release and inhibit glucagon secretion. They also act on receptors in the brain and gastrointestinal tract to suppress appetite, slow gastric emptying, and delay glucose absorption. Phase 3 clinical trials have shown that GLP-1 RAs improve cardiovascular outcomes in the setting of T2DM or overweight/obesity in people who have, or are at high risk of having atherosclerotic cardiovascular disease. This is largely driven by reductions in ischemic events, although emerging evidence also supports benefits in other cardiovascular conditions, such as heart failure with preserved ejection fraction. The success of GLP-1 RAs has also seen the evolution of other incretin therapies. Tirzepatide has emerged as a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, with more striking effects on glycemic control and weight reduction than those achieved by isolated GLP-1R agonism alone. This consists of lowering glycated hemoglobin levels by more than 2% and weight loss exceeding 15% from baseline. Here, we review the pharmacological properties of GLP-1 RAs and tirzepatide and discuss their clinical effectiveness for T2DM and overweight/obesity, including their ability to reduce adverse cardiovascular outcomes. We also delve into the mechanistic basis for these cardioprotective effects and consider the next steps in implementing existing and future incretin-based therapies for the broader management of cardiometabolic disease. CI - (c) 2024 The Author(s). Medicinal Research Reviews published by Wiley Periodicals LLC. FAU - Psaltis, James P AU - Psaltis JP AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. FAU - Marathe, Jessica A AU - Marathe JA AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. AD - Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia. FAU - Nguyen, Mau T AU - Nguyen MT AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. AD - Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia. FAU - Le, Richard AU - Le R AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. AD - College of Medicine and Public Health, Flinders University, Adelaide, Australia. FAU - Bursill, Christina A AU - Bursill CA AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. FAU - Marathe, Chinmay S AU - Marathe CS AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Department of Endocrinology, Central Adelaide Local Health Network, Adelaide, Australia. FAU - Nelson, Adam J AU - Nelson AJ AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. AD - Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia. FAU - Psaltis, Peter J AU - Psaltis PJ AUID- ORCID: 0000-0003-0222-5468 AD - Adelaide Medical School, The University of Adelaide, Adelaide, Australia. AD - Heart and Vascular Health Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia. AD - Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia. LA - eng GR - FLF106656/National Heart Foundation of Australia/ GR - 2022-CP-Heart-010-83100/Hospital Research Foundation/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240814 PL - United States TA - Med Res Rev JT - Medicinal research reviews JID - 8103150 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Cardiovascular Diseases/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11638809 OTO - NOTNLM OT - atherosclerosis OT - diabetes OT - incretins OT - obesity OT - tirzepatide COIS- James P. Psaltis, Mau T. Nguyen, Richard Le, and Christina A. Bursill have nothing to declare. Jessica A. Marathe has received speaking honoraria from Novartis. Chinmay S. Marathe has received speaking honoraria from Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. Adam J. Nelson has received consulting fees or speaking honoraria from Amgen, Boehringer Ingelheim, GSK, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and VAXXINITY. Peter J. Psaltis has received consulting fees from Amgen, Eli Lilly, and Esperion and speaker honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck Schering-Plough, Novartis, Novo Nordisk, Pfizer, and Sanofi. EDAT- 2024/08/14 06:42 MHDA- 2024/12/13 11:32 PMCR- 2024/12/13 CRDT- 2024/08/14 03:13 PHST- 2024/06/30 00:00 [revised] PHST- 2024/04/16 00:00 [received] PHST- 2024/07/30 00:00 [accepted] PHST- 2024/12/13 11:32 [medline] PHST- 2024/08/14 06:42 [pubmed] PHST- 2024/08/14 03:13 [entrez] PHST- 2024/12/13 00:00 [pmc-release] AID - MED22070 [pii] AID - 10.1002/med.22070 [doi] PST - ppublish SO - Med Res Rev. 2025 Jan;45(1):29-65. doi: 10.1002/med.22070. Epub 2024 Aug 14. PMID- 39137181 OWN - NLM STAT- MEDLINE DCOM- 20240813 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 66 IP - 1708 DP - 2024 Aug 5 TI - Table: GLP-1 and GIP/GLP-1 receptor agonists for type 2 diabetes. PG - e1-e3 LID - 10.58347/tml.2024.1708c [doi] LA - eng PT - Journal Article PT - Review DEP - 20240805 PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage/pharmacology MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Receptors, Gastrointestinal Hormone/agonists MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Bydureon BCise OT - Byetta OT - Mounjaro OT - Ozempic OT - Rybelsus OT - Trulicity OT - Victoza OT - adverse effects OT - dosage OT - drug interactions OT - dulaglutide OT - exenatide OT - lactation OT - liraglutide OT - pregnancy OT - safety OT - semaglutide OT - tirzepatide OT - type 2 diabetes EDAT- 2024/08/13 18:41 MHDA- 2024/08/13 18:42 CRDT- 2024/08/13 13:23 PHST- 2024/08/13 18:42 [medline] PHST- 2024/08/13 18:41 [pubmed] PHST- 2024/08/13 13:23 [entrez] AID - 10.58347/tml.2024.1708c [doi] PST - epublish SO - Med Lett Drugs Ther. 2024 Aug 5;66(1708):e1-e3. doi: 10.58347/tml.2024.1708c. PMID- 39133509 OWN - NLM STAT- MEDLINE DCOM- 20241007 LR - 20260725 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 184 IP - 10 DP - 2024 Oct 1 TI - GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes. PG - 1195-1203 LID - 10.1001/jamainternmed.2024.3806 [doi] AB - IMPORTANCE: Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. OBJECTIVE: To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. EXPOSURES: GLP-1RAs or DPP-4is. MAIN OUTCOMES AND MEASURES: The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). RESULTS: A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. CONCLUSIONS: In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population. FAU - Huang, Tao AU - Huang T AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China. FAU - Bosi, Alessandro AU - Bosi A AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Faucon, Anne-Laure AU - Faucon AL AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Department of Clinical Epidemiology, Centre for Research in Epidemiology and Population Health, Paris-Saclay University, Paris, France. FAU - Grams, Morgan E AU - Grams ME AD - Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York. FAU - Sjolander, Arvid AU - Sjolander A AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Fu, Edouard L AU - Fu EL AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Xu, Yang AU - Xu Y AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China. AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Carrero, Juan Jesus AU - Carrero JJ AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Nephrology Clinic, Danderyd University Hospital, Stockholm, Sweden. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - JAMA Intern Med. 2025 Mar 1;185(3):352. doi: 10.1001/jamainternmed.2024.8059. PMID: 39869346 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hyperkalemia/epidemiology/chemically induced MH - Male MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Middle Aged MH - Aged MH - Renin-Angiotensin System/drug effects MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use/adverse effects MH - Cohort Studies MH - Sweden/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11320332 COIS- Conflict of Interest Disclosures: Dr Carrero reported receiving grants from Novo Nordisk (to Karolinska Institutet) for topics unrelated to the drugs being investigated in this article during the conduct of the study and grants from MSD, Boehringer, AstraZeneca, Astellas, ViroPharma (to Karolinska Institutet) during the last 2 years for pharmacoepidemiolgic work in topics unrelated to and outside the submitted work. No other disclosures were reported. EDAT- 2024/08/12 12:43 MHDA- 2024/10/07 12:57 PMCR- 2025/08/12 CRDT- 2024/08/12 11:34 PHST- 2024/10/07 12:57 [medline] PHST- 2024/08/12 12:43 [pubmed] PHST- 2024/08/12 11:34 [entrez] PHST- 2025/08/12 00:00 [pmc-release] AID - 2821737 [pii] AID - ioi240048 [pii] AID - 10.1001/jamainternmed.2024.3806 [doi] PST - ppublish SO - JAMA Intern Med. 2024 Oct 1;184(10):1195-1203. doi: 10.1001/jamainternmed.2024.3806. PMID- 39133485 OWN - NLM STAT- MEDLINE DCOM- 20240812 LR - 20250303 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 8 DP - 2024 Aug 1 TI - Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes. PG - e2427258 LID - 10.1001/jamanetworkopen.2024.27258 [doi] LID - e2427258 AB - IMPORTANCE: Despite its demonstrated benefits in improving cardiovascular risk profiles, the association of tirzepatide with mortality and cardiovascular and kidney outcomes compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown. OBJECTIVE: To investigate the association of tirzepatide with mortality and adverse cardiovascular and kidney outcomes compared with GLP-1 RAs in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used US Collaborative Network of TriNetX data collected on individuals with type 2 diabetes aged 18 years or older initiating tirzepatide or GLP-1 RA between June 1, 2022, and June 30, 2023; without stage 5 chronic kidney disease or kidney failure at baseline; and without myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation. EXPOSURES: Treatment with tirzepatide compared with GLP-1 RA. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events. All outcomes were analyzed using Cox proportional hazards regression models. RESULTS: There were 14 834 patients treated with tirzepatide (mean [SD] age, 55.4 [11.8] years; 8444 [56.9%] female) and 125 474 treated with GLP-1 RA (mean [SD] age, 58.1 [13.3] years; 67 474 [53.8%] female). After a median (IQR) follow-up of 10.5 (5.2-15.7) months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with lower hazards of all-cause mortality (adjusted hazard ratio [AHR], 0.58; 95% CI, 0.45-0.75), MACEs (AHR, 0.80; 95% CI, 0.71-0.91), the composite of MACEs and all-cause mortality (AHR, 0.76; 95% CI, 0.68-0.84), kidney events (AHR, 0.52; 95% CI, 0.37-0.73), acute kidney injury (AHR, 0.78; 95% CI, 0.70-0.88), and major adverse kidney events (AHR, 0.54; 95% CI, 0.44-0.67). Treatment with tirzepatide was associated with greater decreases in glycated hemoglobin (treatment difference, -0.34 percentage points; 95% CI, -0.44 to -0.24 percentage points) and body weight (treatment difference, -2.9 kg, 95% CI, -4.8 to -1.1 kg) compared with GLP-1 RA. An interaction test for subgroup analysis revealed consistent results stratified by estimated glomerular filtration rate, glycated hemoglobin level, body mass index, comedications, and comorbidities. CONCLUSIONS AND RELEVANCE: In this study, treatment with tirzepatide was associated with lower hazards of all-cause mortality, adverse cardiovascular events, acute kidney injury, and adverse kidney events compared with GLP-1 RA in patients with type 2 diabetes. These findings support the integration of tirzepatide into therapeutic strategies for this population. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Wang, Hsien-Yi AU - Wang HY AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Sports Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Jiang, Zheng-Hong AU - Jiang ZH AD - Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei. LA - eng PT - Journal Article DEP - 20240801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Cardiovascular Diseases/mortality/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide PMC - PMC11320168 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2024/08/12 12:42 MHDA- 2024/08/12 12:43 PMCR- 2024/08/12 CRDT- 2024/08/12 11:33 PHST- 2024/08/12 12:43 [medline] PHST- 2024/08/12 12:42 [pubmed] PHST- 2024/08/12 11:33 [entrez] PHST- 2024/08/12 00:00 [pmc-release] AID - 2822209 [pii] AID - zoi240844 [pii] AID - 10.1001/jamanetworkopen.2024.27258 [doi] PST - epublish SO - JAMA Netw Open. 2024 Aug 1;7(8):e2427258. doi: 10.1001/jamanetworkopen.2024.27258. PMID- 39128378 OWN - NLM STAT- MEDLINE DCOM- 20241113 LR - 20250103 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 18 IP - 8 DP - 2024 Aug TI - Glucagon-like peptide-1 receptor agonists and risk of sight-threatening retinopathy in Taiwanese population: A propensity based cohort study. PG - 103099 LID - S1871-4021(24)00160-7 [pii] LID - 10.1016/j.dsx.2024.103099 [doi] AB - AIMS: To compare the risk of vision-threatening retinopathy between glucagon-like peptide-1 receptor agonists (GLP-1 RA) use and no use in patients with type 2 diabetes. METHODS: Using propensity score matching, we identified 27,506 pairs of GLP-1 RA users and non-users, 3904 pairs of GLP-1 RA and dipeptidyl peptidase-4 inhibitors (DPP-4i) users, 10,985 pairs of GLP-1 RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i) users, 2542 pairs of GLP-1 RA and sulfonylurea, respectively, from Taiwan's National Health Insurance Research Database from January 1, 2009 to December 31, 2018. We used Cox proportional hazards models to compare the risk of vision-threatening retinopathy between GLP-1 RA use and other matched groups. RESULTS: In the matched cohorts, the time-varying exposure analysis showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to GLP-1 RA non-use (aHR 0.96, 95 % CI 0.89-1.03). New-user and active-comparator analyses showed that GLP-1 RA was associated with a significantly lower risk of vision-threatening retinopathy than DPP-4i (aHR 0.8, 95 % CI 0.66-0.97) but had no significant association with this risk compared to SGLT2i (aHR 1.09, 95 % CI 0.96-1.24) or sulfonylureas (aHR 0.79, 95 % CI 0.49-1.06). CONCLUSIONS: This nationwide cohort study showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to non- GLP-1 RA use, and GLP-1 RA could significantly lower the risk of vision-threatening retinopathy than DPP-4i. CI - Copyright (c) 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Yen, Fu-Shun AU - Yen FS AD - Dr. Yen's Clinic, Taoyuan, Taiwan. Electronic address: yenfushun@gmail.com. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address: jccwei@gmail.com. FAU - Shih, Ying-Hsiu AU - Shih YH AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: hsiu.cmuh@gmail.com. FAU - Hung, Yu-Tung AU - Hung YT AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: yutunghung1227@gmail.com. FAU - Hsu, Tzu-Ju AU - Hsu TJ AD - Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: r7r0923.cmuh@gmail.com. FAU - Hsu, Chih-Cheng AU - Hsu CC AD - Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan; Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan. Electronic address: cch@nhri.edu.tw. FAU - Hwu, Chii-Min AU - Hwu CM AD - Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming Chiao Tung University School of Medicine, Taipei, Taiwan. Electronic address: chhwu@vghtpe.gov.tw. LA - eng PT - Journal Article DEP - 20240808 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Diabetic Retinopathy/epidemiology/etiology MH - Taiwan/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Follow-Up Studies MH - Aged MH - Risk Factors MH - Propensity Score MH - Cohort Studies MH - Prognosis MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Incidence MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Active-comparator OT - Dipeptidyl peptidase-4 inhibitors OT - New-user OT - Sodium-glucose cotransporter-2 inhibitors OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chii-Min Hwu reports was provided by Taipei Veterans General Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/08/12 00:41 MHDA- 2024/11/14 03:56 CRDT- 2024/08/11 18:06 PHST- 2023/12/07 00:00 [received] PHST- 2024/08/02 00:00 [revised] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/11/14 03:56 [medline] PHST- 2024/08/12 00:41 [pubmed] PHST- 2024/08/11 18:06 [entrez] AID - S1871-4021(24)00160-7 [pii] AID - 10.1016/j.dsx.2024.103099 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2024 Aug;18(8):103099. doi: 10.1016/j.dsx.2024.103099. Epub 2024 Aug 8. PMID- 39127552 OWN - NLM STAT- MEDLINE DCOM- 20250408 LR - 20250409 IS - 1879-3061 (Electronic) IS - 1043-2760 (Linking) VI - 36 IP - 4 DP - 2025 Apr TI - Cardioprotective benefits of metabolic surgery and GLP-1 receptor agonist-based therapies. PG - 316-329 LID - S1043-2760(24)00193-0 [pii] LID - 10.1016/j.tem.2024.07.012 [doi] AB - Individuals with excessive adipose tissue and type 2 diabetes mellitus (T2DM) face a heightened risk of cardiovascular morbidity and mortality. Metabolic surgery is an effective therapy for people with severe obesity to achieve significant weight loss. Additionally, metabolic surgery improves blood glucose levels and can lead to T2DM remission, reducing major adverse cardiovascular outcomes (MACE). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are a class of medication that effectively reduce body weight and MACE in patients with T2DM. This review explores the potential mechanisms underlying the cardioprotective benefits of metabolic surgery and GLP-1RA-based therapies and discusses recent evidence and emerging therapies in this dynamic area of research. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved. FAU - Morissette, Arianne AU - Morissette A AD - The University of Ottawa Heart Institute, 40 Ruskin Street, H-3229A, Ottawa, Ontario, KIY 4W7, Canada. FAU - Mulvihill, Erin E AU - Mulvihill EE AD - The University of Ottawa Heart Institute, 40 Ruskin Street, H-3229A, Ottawa, Ontario, KIY 4W7, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, The University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada. Electronic address: emulvihi@uottawa.ca. LA - eng PT - Journal Article PT - Review DEP - 20240810 PL - United States TA - Trends Endocrinol Metab JT - Trends in endocrinology and metabolism: TEM JID - 9001516 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/surgery/metabolism MH - *Bariatric Surgery/methods MH - *Cardiovascular Diseases/prevention & control MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - Hypoglycemic Agents/therapeutic use COIS- Declaration of interests The authors have no interests to declare. EDAT- 2024/08/11 04:43 MHDA- 2025/04/09 10:12 CRDT- 2024/08/10 21:55 PHST- 2024/05/10 00:00 [received] PHST- 2024/07/15 00:00 [revised] PHST- 2024/07/17 00:00 [accepted] PHST- 2025/04/09 10:12 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 21:55 [entrez] AID - S1043-2760(24)00193-0 [pii] AID - 10.1016/j.tem.2024.07.012 [doi] PST - ppublish SO - Trends Endocrinol Metab. 2025 Apr;36(4):316-329. doi: 10.1016/j.tem.2024.07.012. Epub 2024 Aug 10. PMID- 39127152 OWN - NLM STAT- MEDLINE DCOM- 20241025 LR - 20260127 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 229 DP - 2024 Nov TI - Peptide GLP-1 receptor agonists: From injection to oral delivery strategies. PG - 116471 LID - S0006-2952(24)00454-4 [pii] LID - 10.1016/j.bcp.2024.116471 [doi] AB - Peptide glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective drugs for treating type 2 diabetes (T2DM) and have been proven to benefit the heart and kidney. Apart from oral semaglutide, which does not require injection, other peptide GLP-1RAs need to be subcutaneously administered. However, oral semaglutide also faces significant challenges, such as low bioavailability and frequent gastrointestinal discomfort. Thus, it is imperative that advanced oral strategies for peptide GLP-1RAs need to be explored. This review mainly compares the current advantages and disadvantages of various oral delivery strategies for peptide GLP-1RAs in the developmental stage and discusses the latest research progress of peptide GLP-1RAs, providing a useful guide for the development of new oral peptide GLP-1RA drugs. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Ke, Zhiqiang AU - Ke Z AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; Hubei Key Laboratory of Diabetes and Angiopathy, National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. FAU - Ma, Qianqian AU - Ma Q AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; School of Pharmaceutical Sciences and Institute of Materia Medica, Xinjiang University, Urumqi 830017, China. FAU - Ye, Xiaonan AU - Ye X AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Wang, Yanlin AU - Wang Y AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Jin, Yan AU - Jin Y AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Zhao, Xinyuan AU - Zhao X AD - Hubei Key Laboratory of Diabetes and Angiopathy, National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. Electronic address: zhaoxinyuan@hbust.edu.cn. FAU - Su, Zhengding AU - Su Z AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; School of Pharmaceutical Sciences and Institute of Materia Medica, Xinjiang University, Urumqi 830017, China. Electronic address: james_su@xju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240808 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage MH - Animals MH - Drug Delivery Systems/methods MH - Glucagon-Like Peptides/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Advanced microbiome delivery OT - Cell penetrating peptides OT - Oral delivery OT - Peptide GLP-1 receptor agonists OT - Pharmaceutical Technology OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/08/11 04:43 MHDA- 2024/10/26 19:25 CRDT- 2024/08/10 19:17 PHST- 2024/04/19 00:00 [received] PHST- 2024/07/20 00:00 [revised] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/10/26 19:25 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 19:17 [entrez] AID - S0006-2952(24)00454-4 [pii] AID - 10.1016/j.bcp.2024.116471 [doi] PST - ppublish SO - Biochem Pharmacol. 2024 Nov;229:116471. doi: 10.1016/j.bcp.2024.116471. Epub 2024 Aug 8. PMID- 39127032 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260603 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 5 IP - 8 DP - 2024 Aug 9 TI - Therapy for HFpEF: A step forward brings new hope for people with obesity and diabetes. PG - 848-851 LID - S2666-6340(24)00257-5 [pii] LID - 10.1016/j.medj.2024.06.011 [doi] AB - The STEP-HFpEF DM trial(1) showed that semaglutide improved body weight, systemic inflammation, and heart failure symptoms in people with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. By addressing both metabolic and cardiovascular risk, semaglutide is a promising therapeutic option for HFpEF in addition to SGLT2i. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Lim, Lee-Ling AU - Lim LL AD - Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Asia Diabetes Foundation, Hong Kong SAR, China. Electronic address: leeling.lim@ummc.edu.my. FAU - Khunti, Kamlesh AU - Khunti K AD - Diabetes Research Centre, University of Leicester, Leicester, UK. LA - eng GR - NIHR, NHS, and Department of Health and Social Care/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/physiopathology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Heart Failure/drug therapy/physiopathology MH - *Stroke Volume/drug effects MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Semaglutide COIS- Declaration of interests L.-L.L. has acted as a consultant, speaker, or received research grants via her institution from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Roche, Servier, Viatris, and Zuellig Pharma Therapeutics. K.K. has acted as a consultant, speaker, or received grants for investigator-initiated studies for AstraZeneca, Bayer, Novo Nordisk, Sanofi-Aventis, Servier, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi-Sankyo, Applied Therapeutics, Embecta, and Nestle Health Science. EDAT- 2024/08/11 04:43 MHDA- 2024/08/11 04:44 CRDT- 2024/08/10 18:18 PHST- 2024/06/20 00:00 [received] PHST- 2024/06/20 00:00 [revised] PHST- 2024/06/20 00:00 [accepted] PHST- 2024/08/11 04:44 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 18:18 [entrez] AID - S2666-6340(24)00257-5 [pii] AID - 10.1016/j.medj.2024.06.011 [doi] PST - ppublish SO - Med. 2024 Aug 9;5(8):848-851. doi: 10.1016/j.medj.2024.06.011. PMID- 39127031 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260603 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 5 IP - 8 DP - 2024 Aug 9 TI - Glucagon-like peptide receptor-1 receptor agonists: The emerging fourth pillar in type 2 diabetes and chronic kidney disease? PG - 845-847 LID - S2666-6340(24)00256-3 [pii] LID - 10.1016/j.medj.2024.06.010 [doi] AB - Previously, no randomized controlled trials investigated the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) as the primary endpoint in patients with diabetes and chronic kidney disease. In the FLOW trial, Perkovic et al. showed that once-weekly semaglutide reduced kidney failure, kidney-related death, and cardiovascular death by 24% as compared with placebo in patients with type 2 diabetes at high risk of renal progression.(1). CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Ling, James AU - Ling J AD - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR. FAU - Chow, Elaine AU - Chow E AD - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR; Phase 1 Clinical Trial Centre, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR. Electronic address: e.chow@cuhk.edu.hk. LA - eng PT - Journal Article PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/administration & dosage MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetic Nephropathies/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declaration of interests The authors declare no competing interests. EDAT- 2024/08/11 04:43 MHDA- 2024/08/11 04:44 CRDT- 2024/08/10 18:18 PHST- 2024/06/19 00:00 [received] PHST- 2024/06/20 00:00 [revised] PHST- 2024/06/20 00:00 [accepted] PHST- 2024/08/11 04:44 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 18:18 [entrez] AID - S2666-6340(24)00256-3 [pii] AID - 10.1016/j.medj.2024.06.010 [doi] PST - ppublish SO - Med. 2024 Aug 9;5(8):845-847. doi: 10.1016/j.medj.2024.06.010. PMID- 39125772 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 15 DP - 2024 Jul 27 TI - Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy. LID - 10.3390/ijms25158202 [doi] LID - 8202 AB - Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials. FAU - Nicze, Michal AU - Nicze M AUID- ORCID: 0000-0003-2181-4356 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Dec, Adrianna AU - Dec A AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Borowka, Maciej AU - Borowka M AUID- ORCID: 0000-0002-2714-208X AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Krzyzak, Damian AU - Krzyzak D AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Boldys, Aleksandra AU - Boldys A AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Buldak, Lukasz AU - Buldak L AUID- ORCID: 0000-0002-2017-5516 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Okopien, Boguslaw AU - Okopien B AUID- ORCID: 0000-0001-7228-2906 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. LA - eng GR - BNW-1-03/N/3/O/Medical University of Silesia/ GR - 2023/07/X/NZ7/01190/National Science Center/ PT - Journal Article PT - Review DEP - 20240727 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Anti-Obesity Agents/therapeutic use/pharmacology MH - Animals MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Gastrointestinal Microbiome/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11311839 OTO - NOTNLM OT - appetite OT - energy expenditure OT - gastrointestinal tract hormones OT - gut-brain axis OT - incretins OT - microbiome OT - obesity OT - retatrutide OT - semaglutide OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2024/08/10 15:47 MHDA- 2024/08/10 15:48 PMCR- 2024/07/27 CRDT- 2024/08/10 01:15 PHST- 2024/06/28 00:00 [received] PHST- 2024/07/22 00:00 [revised] PHST- 2024/07/25 00:00 [accepted] PHST- 2024/08/10 15:48 [medline] PHST- 2024/08/10 15:47 [pubmed] PHST- 2024/08/10 01:15 [entrez] PHST- 2024/07/27 00:00 [pmc-release] AID - ijms25158202 [pii] AID - ijms-25-08202 [pii] AID - 10.3390/ijms25158202 [doi] PST - epublish SO - Int J Mol Sci. 2024 Jul 27;25(15):8202. doi: 10.3390/ijms25158202. PMID- 39125424 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 16 IP - 15 DP - 2024 Aug 3 TI - Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study). LID - 10.3390/nu16152545 [doi] LID - 2545 AB - Although, in randomized clinical trials, once-weekly subcutaneous semaglutide (OW s.c.) has demonstrated superior efficacy in comparison with placebo and active controls in terms of glycemic control and body weight reduction in patients with type 2 diabetes mellitus (T2DM), these results need to be confirmed in a real-world (RW) setting. An RW ambispective study (6 months retrospective and 6 months prospective) was conducted in 10 tertiary hospitals in Spain. We evaluated changes in HbA1c and body weight in patients with T2DM treated with semaglutide OW s.c. Additionally, we analyzed different subgroups of patients treated with semaglutide OW s.c. as an add-on to glucose-lowering therapy. A total of 752 patients with a mean age of 60.2 years, a mean HbA1c level of 8.5%, a mean body weight of 101.6 kg, and a mean T2DM duration of 10 years were included. At 12 months, compared with baseline, there was a mean difference of -2.1% in HbA1c levels (p < 0.001) and a mean difference of 9.2 kg in body weight (p < 0.001). Moreover, there were statistically significant differences (p < 0.001) between baseline and month 12 in both HbA1c and body weight in the four subgroups receiving semaglutide OW s.c. as an add-on to glucose-lowering therapy. Semaglutide OW s.c. was well tolerated, with gastrointestinal disorders being the most commonly reported side effects. In this RW study, 12 months of treatment with semaglutide OW s.c. in patients with T2DM was associated with significant and clinically relevant improvements in glycemic control and weight loss, regardless of the glucose-lowering therapy received, and the overall safety profile was positive. FAU - Caballero Mateos, Irene AU - Caballero Mateos I AUID- ORCID: 0000-0002-2041-1013 AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital and Vithas Hospital, 41009 Sevilla, Spain. FAU - Garcia de Lucas, Maria Dolores AU - Garcia de Lucas MD AD - Internal Medicine Department, Hospital Costa del Sol, 29603 Marbella, Spain. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29016 Malaga, Spain. FAU - Moreno-Moreno, Paloma AU - Moreno-Moreno P AD - Endocrinology and Nutrition Department, Reina Sofia University Hospital, 14004 Cordoba, Spain. FAU - Jimenez-Millan, Ana Isabel AU - Jimenez-Millan AI AD - Endocrinology and Nutrition Department, University Hospital, 11510 Puerto Real, Spain. FAU - Botana-Lopez, Manuel AU - Botana-Lopez M AD - Endocrinology and Nutrition Department, Lucus Augusti University Hospital, 27003 Lugo, Spain. FAU - Merino-Torres, Juan Francisco AU - Merino-Torres JF AUID- ORCID: 0000-0002-0191-4504 AD - Endocrinology and Nutrition Department, La Fe University Hospital, 46026 Valencia, Spain. FAU - Soto-Gonzalez, Alfonso AU - Soto-Gonzalez A AD - Endocrinology and Nutrition Department, A Coruna University Hospital Complex, 15006 A Coruna, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29016 Malaga, Spain. FAU - Morales-Portillo, Cristobal AU - Morales-Portillo C AUID- ORCID: 0000-0003-0348-826X AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital and Vithas Hospital, 41009 Sevilla, Spain. LA - eng GR - INT21/00078/Instituto de Salud Carlos III/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240803 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Glycated Hemoglobin/analysis MH - Glycemic Control/methods MH - *Hypoglycemic Agents/administration & dosage MH - Injections, Subcutaneous MH - Prospective Studies MH - Retrospective Studies MH - Spain MH - Treatment Outcome MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11314012 OTO - NOTNLM OT - body weight OT - glucagon-like peptide-1 receptor agonist OT - glycemic control OT - once weekly semaglutide OT - type 2 diabetes mellitus COIS- J.C.F.-G. has received speaker honoraria from Novo Nordisk, Lilly, Boehringer-Ingelheim, Esteve, Menarini, and AstraZeneca. The rest of the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/08/10 15:43 MHDA- 2024/08/10 15:44 PMCR- 2024/08/03 CRDT- 2024/08/10 01:13 PHST- 2024/07/04 00:00 [received] PHST- 2024/07/24 00:00 [revised] PHST- 2024/08/01 00:00 [accepted] PHST- 2024/08/10 15:44 [medline] PHST- 2024/08/10 15:43 [pubmed] PHST- 2024/08/10 01:13 [entrez] PHST- 2024/08/03 00:00 [pmc-release] AID - nu16152545 [pii] AID - nutrients-16-02545 [pii] AID - 10.3390/nu16152545 [doi] PST - epublish SO - Nutrients. 2024 Aug 3;16(15):2545. doi: 10.3390/nu16152545. PMID- 39121301 OWN - NLM STAT- MEDLINE DCOM- 20240809 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 32 DP - 2024 Aug 9 TI - Real world study of GLP-1 receptor agonists in overweight or obese type 2 diabetes by using repeated measurement analysis of variance. PG - e38879 LID - 10.1097/MD.0000000000038879 [doi] LID - e38879 AB - To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (n = 35) and the experimental group (n = 32) were statistically significant (P < .001), and the intergroup effect of BMI was statistically significant (P < .05). The interaction effect of BMI was statistically significant (P < .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (P < .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (P > .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Yang, Wanying AU - Yang W AUID- ORCID: 0009-0004-7197-2867 AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhou, Xiangming AU - Zhou X AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Miao, Yuanyuan AU - Miao Y AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Wang, Lu AU - Wang L AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhao, Yunhui AU - Zhao Y AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Ke, Tingyu AU - Ke T AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Ban, Lili AU - Ban L AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. LA - eng GR - YNWR-MY-2020-022/Yunnan provincial Talent Work Leading group office/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Middle Aged MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/analogs & derivatives MH - *Glycated Hemoglobin/drug effects/analysis MH - *Obesity/drug therapy/complications MH - *Body Mass Index MH - *Metformin/therapeutic use MH - *Overweight/drug therapy/complications MH - *Blood Glucose/drug effects/analysis MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Analysis of Variance MH - Adult MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC11315522 COIS- The authors have no conflicts of interest to disclose. EDAT- 2024/08/09 18:42 MHDA- 2024/08/09 18:43 PMCR- 2024/08/09 CRDT- 2024/08/09 14:13 PHST- 2024/08/09 18:43 [medline] PHST- 2024/08/09 18:42 [pubmed] PHST- 2024/08/09 14:13 [entrez] PHST- 2024/08/09 00:00 [pmc-release] AID - 00005792-202408090-00058 [pii] AID - MD-D-24-00002 [pii] AID - 10.1097/MD.0000000000038879 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Aug 9;103(32):e38879. doi: 10.1097/MD.0000000000038879. PMID- 39118222 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Real-world safety profile of once-weekly semaglutide in people with type 2 diabetes: Analysis of pooled data from the SemaglUtide Real-world Evidence (SURE) programme. PG - 4429-4440 LID - 10.1111/dom.15794 [doi] AB - AIM: To investigate, through post hoc analysis of nine studies from the SemaglUtide Real-world Evidence (SURE) programme, the safety of once-weekly (OW) semaglutide in adults with type 2 diabetes (T2D) and in subpopulations in routine clinical practice, complementing findings from the phase 3 randomized clinical trial (RCT) SUSTAIN programme. METHODS: The SURE studies had a duration of ~30 weeks and included adults with diagnosed T2D treated with OW semaglutide. Safety information, including hypoglycaemic events, were collected and analysed for the total study population and for patient subgroups based on baseline patient characteristics, baseline co-medication and prescriber specialty. RESULTS: Of the total 3505 patients, 24.3% reported adverse events (AEs), with most patients reporting non-serious (22.3%) and mild (17.1%) AEs. AEs mainly belonged to the gastrointestinal disorders system organ class (16.3% of patients). In total, 5.1% of patients reported AEs that led to treatment discontinuation, 0.5% reported serious adverse drug reactions and 0.2% had an AE with a fatal outcome, reported as unrelated to treatment. Overall, 1.1% and 0.1% of patients reported level 2 and 3 hypoglycaemic events, respectively. A higher rate of level 2 hypoglycaemia was observed in patients with baseline microvascular complications treated with insulin versus those on insulin without these complications. CONCLUSIONS: Safety data reported in the real-world SURE studies were generally consistent with observations in phase 3 OW semaglutide RCTs. No new safety concerns were identified, highlighting that OW semaglutide is well tolerated by adults with T2D and in subpopulations in routine clinical practice. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yale, Jean-Francois AU - Yale JF AUID- ORCID: 0000-0002-7833-9050 AD - McGill University Health Centre, Montreal, Quebec, Canada. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AUID- ORCID: 0000-0002-1755-630X AD - Global Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jain, Rashmi AU - Jain R AD - Novo Nordisk Service Centre India Private Ltd., Bengaluru, India. FAU - Menzen, Markus AU - Menzen M AD - Gemeinschaftskrankenhaus Bonn, Bonn, Germany. FAU - Holmes, Patrick AU - Holmes P AD - St. George's Medical Practice, Darlington, UK. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240808 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Aged MH - *Hypoglycemia/chemically induced/epidemiology MH - Drug Administration Schedule MH - Adult MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - SURE studies OT - glucagon-like peptide-1 receptor agonist OT - real-world data OT - safety OT - semaglutide OT - type 2 diabetes EDAT- 2024/08/09 06:42 MHDA- 2024/09/18 12:51 CRDT- 2024/08/09 00:04 PHST- 2024/06/28 00:00 [revised] PHST- 2024/02/01 00:00 [received] PHST- 2024/06/28 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/08/09 06:42 [pubmed] PHST- 2024/08/09 00:04 [entrez] AID - 10.1111/dom.15794 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4429-4440. doi: 10.1111/dom.15794. Epub 2024 Aug 8. PMID- 39116084 OWN - NLM STAT- MEDLINE DCOM- 20240808 LR - 20260914 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 19 IP - 8 DP - 2024 TI - Mortality and major adverse cardiovascular events after glucagon-like peptide-1 receptor agonist initiation in patients with immune-mediated inflammatory diseases and type 2 diabetes: A population-based study. PG - e0308533 LID - 10.1371/journal.pone.0308533 [doi] LID - e0308533 AB - OBJECTIVE: To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes newly initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is). METHODS: We performed a population-based cohort study using administrative health data from British Columbia. Patients with an IMID (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i between January 1, 2010, and December 31, 2021 were identified using ICD-9/10 codes. The primary outcome was all-cause mortality. Secondary outcomes included MACE and its components (i.e., cardiovascular death, myocardial infarction, and ischemic stroke). Cox proportional hazard regressions were used with propensity score overlap weighting. The analysis was repeated in age- and sex-matched adults without IMIDs. RESULTS: We identified 10,855 adults with IMIDs and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1-RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.31-0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years. Rate of MACE was also lower with GLP-1-RA exposure (HR 0.66 [0.50-0.88], RD -10.5 [-20.4 to -0.8]). Effect sizes were similar in adults without IMIDs. CONCLUSION: In patients with IMIDs and type 2 diabetes, GLP-1-RA exposure is associated with a lower risk of all-cause mortality and MACE compared to a cardioneutral active comparator. CI - Copyright: (c) 2024 Karacabeyli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Karacabeyli, Derin AU - Karacabeyli D AUID- ORCID: 0000-0002-6597-0302 AD - Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - Lacaille, Diane AU - Lacaille D AD - Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - Lu, Na AU - Lu N AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. FAU - McCormick, Natalie AU - McCormick N AUID- ORCID: 0000-0002-4147-8348 AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. FAU - Xie, Hui AU - Xie H AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. AD - Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. FAU - Choi, Hyon K AU - Choi HK AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. FAU - Avina-Zubieta, J Antonio AU - Avina-Zubieta JA AUID- ORCID: 0000-0001-5526-663X AD - Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. AD - Arthritis Research Canada, Vancouver, British Columbia, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240808 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Female MH - Male MH - Middle Aged MH - Aged MH - *Cardiovascular Diseases/mortality MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Adult MH - Inflammation MH - Cohort Studies MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - British Columbia/epidemiology MH - Proportional Hazards Models MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11309412 COIS- The authors have declared that no competing interests exist. HKC reports research support from Horizon and consulting fees from ANI and LG Chem outside of the submitted work. HKC has participated on an advisory board for Shanton, unrelated to the submitted work. EDAT- 2024/08/08 18:42 MHDA- 2024/08/08 18:43 PMCR- 2024/08/08 CRDT- 2024/08/08 13:34 PHST- 2024/03/22 00:00 [received] PHST- 2024/07/24 00:00 [accepted] PHST- 2024/08/08 18:43 [medline] PHST- 2024/08/08 18:42 [pubmed] PHST- 2024/08/08 13:34 [entrez] PHST- 2024/08/08 00:00 [pmc-release] AID - PONE-D-24-11342 [pii] AID - 10.1371/journal.pone.0308533 [doi] PST - epublish SO - PLoS One. 2024 Aug 8;19(8):e0308533. doi: 10.1371/journal.pone.0308533. eCollection 2024. PMID- 39114288 OWN - NLM STAT- MEDLINE DCOM- 20240808 LR - 20261026 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. PG - 1431292 LID - 10.3389/fendo.2024.1431292 [doi] LID - 1431292 AB - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two incretins that bind to their respective receptors and activate the downstream signaling in various tissues and organs. Both GIP and GLP-1 play roles in regulating food intake by stimulating neurons in the brain's satiety center. They also stimulate insulin secretion in pancreatic beta-cells, but their effects on glucagon production in pancreatic alpha-cells differ, with GIP having a glucagonotropic effect during hypoglycemia and GLP-1 exhibiting glucagonostatic effect during hyperglycemia. Additionally, GIP directly stimulates lipogenesis, while GLP-1 indirectly promotes lipolysis, collectively maintaining healthy adipocytes, reducing ectopic fat distribution, and increasing the production and secretion of adiponectin from adipocytes. Together, these two incretins contribute to metabolic homeostasis, preventing both hyperglycemia and hypoglycemia, mitigating dyslipidemia, and reducing the risk of cardiovascular diseases in individuals with type 2 diabetes and obesity. Several GLP-1 and dual GIP/GLP-1 receptor agonists have been developed to harness these pharmacological effects in the treatment of type 2 diabetes, with some demonstrating robust effectiveness in weight management and prevention of cardiovascular diseases. Elucidating the underlying cellular and molecular mechanisms could potentially usher in the development of new generations of incretin mimetics with enhanced efficacy and fewer adverse effects. The treatment guidelines are evolving based on clinical trial outcomes, shaping the management of metabolic and cardiovascular diseases. CI - Copyright (c) 2024 Liu. FAU - Liu, Qiyuan Keith AU - Liu QK AD - MedStar Medical Group, MedStar Montgomery Medical Center, Olney, MD, United States. LA - eng PT - Journal Article PT - Review DEP - 20240724 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - *Glucagon-Like Peptide 1/metabolism/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Incretins/therapeutic use/pharmacology MH - *Receptors, Gastrointestinal Hormone/agonists/metabolism PMC - PMC11304055 OTO - NOTNLM OT - GIP OT - GLP-1 OT - GLP-1RA OT - cardiovascular disease OT - diabetes OT - obesity OT - tirzepatide COIS- The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/08/08 06:42 MHDA- 2024/08/08 06:43 PMCR- 2024/01/01 CRDT- 2024/08/08 04:31 PHST- 2024/05/11 00:00 [received] PHST- 2024/07/08 00:00 [accepted] PHST- 2024/08/08 06:43 [medline] PHST- 2024/08/08 06:42 [pubmed] PHST- 2024/08/08 04:31 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1431292 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Jul 24;15:1431292. doi: 10.3389/fendo.2024.1431292. eCollection 2024. PMID- 39113264 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice. PG - 4613-4621 LID - 10.1111/dom.15820 [doi] AB - AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Reis-Barbosa, Pedro H AU - Reis-Barbosa PH AUID- ORCID: 0000-0002-4731-7422 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Marcondes-de-Castro, Ilitch AU - Marcondes-de-Castro I AUID- ORCID: 0000-0003-3104-4033 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Marinho, Thatiany S AU - Marinho TS AUID- ORCID: 0000-0001-9976-9466 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Aguila, Marcia Barbosa AU - Aguila MB AUID- ORCID: 0000-0003-3994-4589 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Mandarim-de-Lacerda, Carlos A AU - Mandarim-de-Lacerda CA AUID- ORCID: 0000-0003-4134-7978 AD - Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. LA - eng GR - 302215/2022-0/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ GR - 305993/2021-6/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ GR - E-26/200.796/2021/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - E-26/200.936/2021/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - E-26/201.857/2020/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - E-26/205.749/2022/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - Finance code 0001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240807 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Adiponectin) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 0 (Insulin) RN - 0 (Leptin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Female MH - Mice MH - *Adiponectin/blood MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Diet, High-Fat/adverse effects MH - Gastric Inhibitory Polypeptide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptide-2 Receptor MH - *Insulin/blood MH - *Leptin/blood MH - *Menopause/drug effects MH - Mice, Inbred C57BL MH - *Obesity/drug therapy MH - Ovariectomy MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - body weight OT - dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist OT - menopause OT - obesity OT - ontogenetic allometry EDAT- 2024/08/08 06:42 MHDA- 2024/09/18 12:51 CRDT- 2024/08/08 01:13 PHST- 2024/07/05 00:00 [revised] PHST- 2024/05/26 00:00 [received] PHST- 2024/07/07 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/08/08 06:42 [pubmed] PHST- 2024/08/08 01:13 [entrez] AID - 10.1111/dom.15820 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4613-4621. doi: 10.1111/dom.15820. Epub 2024 Aug 7. PMID- 39113258 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Real-world impact of adding a glucagon-like peptide-1 receptor agonist compared with basal insulin on metabolic targets in adults living with type 2 diabetes and chronic kidney disease already treated with a sodium-glucose co-transporter-2 inhibitor: The Impact GLP-1 CKD study. PG - 4674-4683 LID - 10.1111/dom.15834 [doi] AB - AIM: To compare the effectiveness of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with adding basal insulin among adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) already treated with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) and not reaching their glycaemic control targets. METHODS: A retrospective analysis of the Canadian LMC Diabetes Registry was conducted. Adults who initiated a GLP-1 RA were matched 1:1 to adults who initiated basal insulin in a T2D and CKD population. Changes in metabolic outcomes were evaluated at 26-52 weeks following the therapy start date. RESULTS: Propensity score matching was used to match participants who initiated a GLP-1 RA to participants who initiated basal insulin (n = 153/cohort). A significantly greater reduction in HbA1c at 26-52 weeks of follow-up was observed in the GLP-1 RA cohort compared with the basal insulin cohort (-1.3% +/- 1.4% vs. -1.1% +/- 1.4%, P = .03). Weight was significantly reduced (-3.4 +/- 3.7 vs. 2.6 +/- 4.5 kg, P < .001), and the estimated glomerular filtration rate decline slowed significantly (-0.3 +/- 8.2 vs. -2.4 +/- 10.4 mL/min/1.73m(2), P = .02), but the change in albuminuria was not significantly different (-5.7 +/- 38.1 vs. -0.5 +/- 38.3 mg/mmol, P = .47) at follow-up in the GLP-1 RA group compared with the basal insulin group. No differences in self-reported hypoglycaemic events per week and therapy discontinuations were reported between the cohorts. CONCLUSIONS: The study shows the real-world effectiveness of GLP-1 RA therapy for T2D and CKD. GLP-1 RAs provided superior reductions in HbA1c and weight, and greater kidney protection, compared with basal insulin among adults with T2D and CKD already treated with an SGLT2i. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chu, Lisa AU - Chu L AD - LMC Diabetes & Endocrinology, Toronto, Ontario, Canada. FAU - Bradley, Ryan M AU - Bradley RM AD - Novo Nordisk Canada Inc, Mississauga, Ontario, Canada. FAU - Auerbach, Pernille AU - Auerbach P AD - Novo Nordisk Canada Inc, Mississauga, Ontario, Canada. FAU - Abitbol, Alexander AU - Abitbol A AUID- ORCID: 0000-0001-6830-3532 AD - LMC Diabetes & Endocrinology, Toronto, Ontario, Canada. LA - eng SI - ClinicalTrials.gov/NCT06236672 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240807 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Drug Therapy, Combination MH - *Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Insulin/therapeutic use MH - Canada/epidemiology MH - Glycemic Control/methods MH - Diabetic Nephropathies/drug therapy MH - Blood Glucose/drug effects/metabolism MH - Registries MH - Treatment Outcome MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - basal insulin OT - diabetes complications OT - real-world evidence OT - type 2 diabetes EDAT- 2024/08/08 06:42 MHDA- 2024/09/18 12:50 CRDT- 2024/08/08 01:12 PHST- 2024/07/10 00:00 [revised] PHST- 2024/03/28 00:00 [received] PHST- 2024/07/10 00:00 [accepted] PHST- 2024/09/18 12:50 [medline] PHST- 2024/08/08 06:42 [pubmed] PHST- 2024/08/08 01:12 [entrez] AID - 10.1111/dom.15834 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4674-4683. doi: 10.1111/dom.15834. Epub 2024 Aug 7. PMID- 39113013 OWN - NLM STAT- MEDLINE DCOM- 20240807 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Aug 7 TI - Trends in prognosis and use of SGLT2i and GLP-1 RA in patients with diabetes and coronary artery disease. PG - 290 LID - 10.1186/s12933-024-02365-1 [doi] LID - 290 AB - OBJECTIVE: To explore trends in prognosis and use of glucose-lowering drugs (GLD) in patients with diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: All patients with diabetes and CAD undergoing a coronary angiography between 2010 and 2021 according to the Swedish Angiography and Angioplasty Registry were included. Information on GLD (dispended 6 months before or after coronary angiography) was collected from the Swedish Prescribed Drug Registry. Data on major cardiovascular events (MACE; mortality, myocardial infarction, stroke, heart failure) through December 2021 were obtained from national registries. Cox proportional survival analysis was used to assess outcomes where cardioprotective GLD (any of Sodium Glucose Lowering Transport 2 receptor inhibitors [SGLT2i] and Glucagon Like Peptide Receptor Agonists [GLP-1 RA]) served as a reference. RESULTS: Among all patients (n = 38,671), 31% had stable CAD, and 69% suffered an acute myocardial infarction. Mean age was 69 years, 67% were male, and 81% were on GLD. The use of cardioprotective GLD increased rapidly in recent years (2016-2021; 7-47%) and was more common in younger patients (66 vs. 68 years) and men (72.9% vs. 67.1%) than other GLD. Furthermore, compared with other GLD, the use of cardioprotective GLD was more common in patients with a less frequent history of heart failure (5.0% vs. 6.8%), myocardial infarction (7.7% vs. 10.5%) and chronic kidney disease (3.7% vs. 5.2%). The adjusted hazard ratio (HR) (95% CI) for MACE was greater in patients on other GLD than in those on cardioprotective GLD (1.10; 1.03-1.17, p = 0.004). Trend analyses for the years 2010-2019 revealed improved one-year MACE in patients with diabetes and CAD (year 2019 vs. 2010; 0.90; 0.81-1.00, p = 0.045), while 1-year mortality was unchanged. CONCLUSIONS: The prescription pattern of diabetes medication is changing quickly in patients with diabetes and CAD; however, there are worrying signals of inefficient use prioritizing cardioprotective GLD to younger and healthier individuals at lower cardiovascular risk. Despite this, there are improving trends in 1-year morbidity. CI - (c) 2024. The Author(s). FAU - Ritsinger, Viveca AU - Ritsinger V AD - Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. viveca.ritsinger@ki.se. AD - Department of Research and Development, Region Kronoberg, Vaxjo, Sweden. viveca.ritsinger@ki.se. FAU - Avander, Kamila AU - Avander K AD - Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. FAU - Lagerqvist, Bo AU - Lagerqvist B AD - Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. FAU - Lundman, Pia AU - Lundman P AD - Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. FAU - Norhammar, Anna AU - Norhammar A AD - Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. AD - Capio S:t Gorans Hospital, Stockholm, Sweden. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240807 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Incretins) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - Sweden/epidemiology MH - *Coronary Artery Disease/mortality/diagnosis/epidemiology/diagnostic imaging/drug therapy MH - *Registries MH - Middle Aged MH - Time Factors MH - Risk Assessment MH - Treatment Outcome MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Risk Factors MH - Incretins/therapeutic use/adverse effects MH - Practice Patterns, Physicians'/trends MH - Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis/epidemiology MH - Coronary Angiography/trends MH - Aged, 80 and over MH - Blood Glucose/metabolism/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11304712 COIS- V.R. has received honoraria on expert group participation from Astra Zeneca, Novo Nordisk, and Boehringer Ingelheim. A.N. has received honoraria on expert group participation from Astra Zeneca, Eli Lilly and Company, Novo Nordisk, and Boehringer Ingelheim. B.L., P.L. and K.A. reports no conflicts of interest. EDAT- 2024/08/08 00:42 MHDA- 2024/08/08 00:43 PMCR- 2024/08/07 CRDT- 2024/08/07 23:42 PHST- 2024/06/13 00:00 [received] PHST- 2024/07/15 00:00 [accepted] PHST- 2024/08/08 00:43 [medline] PHST- 2024/08/08 00:42 [pubmed] PHST- 2024/08/07 23:42 [entrez] PHST- 2024/08/07 00:00 [pmc-release] AID - 10.1186/s12933-024-02365-1 [pii] AID - 2365 [pii] AID - 10.1186/s12933-024-02365-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Aug 7;23(1):290. doi: 10.1186/s12933-024-02365-1. PMID- 39112571 OWN - NLM STAT- MEDLINE DCOM- 20240807 LR - 20260518 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 14 IP - 1 DP - 2024 Aug 7 TI - Knowledge gap and prescribing patterns of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors among Chinese doctors. PG - 18290 LID - 10.1038/s41598-024-69016-z [doi] LID - 18290 AB - New anti-diabetic medications, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended in guidelines to reduce cardio-renal events in type 2 diabetes mellitus (T2DM), independent of glucose control. Yet they might be underused in real world. This study aims to address the knowledge gap, prescription patterns and barriers faced by Chinese doctors. Cardio-Metabolic Survey was a cross-sectional study conducted among doctors managing diabetic patients in clinical practice, via a designated online questionnaire from May 1st, to Dec. 31th, 2022. A total of 358 doctors from 57 hospitals across Beijing participated in this survey, 34.9% from tertiary hospitals. Only 30-40% doctors demonstrated somewhat understanding of the mechanism and clinical applications of GLP-1RA or SGLT2 inhibitors. There is no difference in understanding of these two medications overall (p = 0.336). However, doctors in tertiary hospitals have a higher understanding of GLP-1RA and SGLT2 inhibitors compared to those in non-tertiary hospitals (p = 0.049, and 0.008, respectively). 40.2% doctors have never prescribed GLP-1RA, and 36.6% for SGLT2 inhibitors. The frequency of prescribing SGLT2 inhibitors was significantly higher than prescribing GLP-1RA (p = 0.005). The main barriers on prescription include high cost, poor adherence, side effects concern, and insufficient knowledge about these medications. Chinese doctors currently have limited understanding and low prescription frequency for GLP-1RA and SGLT2 inhibitors. Multifaceted approaches are needed to improve doctors' knowledge and strengthen their ability to manage T2DM effectively. CI - (c) 2024. The Author(s). FAU - Liu, Jing AU - Liu J AUID- ORCID: 0000-0002-9714-7708 AD - Department of Hypertension, Cardio-Metabolic Laboratory, Peking University People's Hospital, Xicheng District, Beijing, 100044, China. heartcenter@163.com. FAU - Su, Xiaofeng AU - Su X AD - Department of Hypertension, Cardio-Metabolic Laboratory, Peking University People's Hospital, Xicheng District, Beijing, 100044, China. AD - Department of Cardiology, Peking University People's Hospital, Beijing, China. FAU - Hao, Yongchen AU - Hao Y AD - Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Liu, Jing AU - Liu J AUID- ORCID: 0000-0002-3311-0818 AD - Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. jingliu@ccmu.edu.cn. CN - Cardio Metabolic Survey investigators LA - eng GR - BHTPP2022037/Beijing Health Technologies Promotion Program/ PT - Journal Article DEP - 20240807 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Practice Patterns, Physicians'/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cross-Sectional Studies MH - China MH - Male MH - Surveys and Questionnaires MH - Hypoglycemic Agents/therapeutic use MH - Female MH - Physicians MH - Health Knowledge, Attitudes, Practice MH - Adult MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - East Asian People PMC - PMC11306237 OTO - NOTNLM OT - China OT - Drug prescriptions OT - GLP-1RA OT - Knowledge gap OT - SGLT2 inhibitors COIS- The authors declare no competing interests. FIR - Zhang, Yuqing IR - Zhang Y FIR - Zhang, Yan IR - Zhang Y FIR - Zhong, Zhaohui IR - Zhong Z FIR - Li, Jing IR - Li J FIR - Nie, Ying IR - Nie Y FIR - Wang, Yahong IR - Wang Y FIR - Zhang, Hongwei IR - Zhang H EDAT- 2024/08/08 00:42 MHDA- 2024/08/08 00:43 PMCR- 2024/08/07 CRDT- 2024/08/07 23:21 PHST- 2024/02/23 00:00 [received] PHST- 2024/07/30 00:00 [accepted] PHST- 2024/08/08 00:43 [medline] PHST- 2024/08/08 00:42 [pubmed] PHST- 2024/08/07 23:21 [entrez] PHST- 2024/08/07 00:00 [pmc-release] AID - 10.1038/s41598-024-69016-z [pii] AID - 69016 [pii] AID - 10.1038/s41598-024-69016-z [doi] PST - epublish SO - Sci Rep. 2024 Aug 7;14(1):18290. doi: 10.1038/s41598-024-69016-z. PMID- 39111552 OWN - NLM STAT- MEDLINE DCOM- 20240824 LR - 20250103 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 215 DP - 2024 Sep TI - The incidence of acute pancreatitis with GLP-1 receptor agonist therapy in individuals with a known history of pancreatitis. PG - 111806 LID - S0168-8227(24)00716-2 [pii] LID - 10.1016/j.diabres.2024.111806 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been reported to increase the risk of acute pancreatitis (AP). This real-world study did not observe a higher frequency of AP with GLP-1RA exposure in adults with T2D and a prior history of AP regardless of etiology. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Lomeli, Laura D AU - Lomeli LD AD - Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: lomelil@ccf.org. FAU - Kodali, Alimitha M AU - Kodali AM AD - Carolina Health Specialist, Myrtle Beach, SC, USA. Electronic address: akodali@carolina-health.com. FAU - Tsushima, Yumiko AU - Tsushima Y AD - University Hospitals, Cleveland, OH, USA. Electronic address: yumiko.tsushima@uhhospitals.org. FAU - Mehta, Adi E AU - Mehta AE AD - Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: mehtaae@ccf.org. FAU - Pantalone, Kevin M AU - Pantalone KM AD - Department of Endocrinology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: pantalk@ccf.org. LA - eng PT - Journal Article DEP - 20240805 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Pancreatitis/epidemiology/chemically induced MH - Male MH - Female MH - Middle Aged MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Aged MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Acute Disease MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Drug adverse reactions OT - GLP-1RA OT - Pancreatitis OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/08/08 00:42 MHDA- 2024/08/26 12:40 CRDT- 2024/08/07 19:19 PHST- 2024/06/11 00:00 [received] PHST- 2024/08/01 00:00 [revised] PHST- 2024/08/03 00:00 [accepted] PHST- 2024/08/26 12:40 [medline] PHST- 2024/08/08 00:42 [pubmed] PHST- 2024/08/07 19:19 [entrez] AID - S0168-8227(24)00716-2 [pii] AID - 10.1016/j.diabres.2024.111806 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Sep;215:111806. doi: 10.1016/j.diabres.2024.111806. Epub 2024 Aug 5. PMID- 39109559 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260127 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 38 IP - 1 DP - 2025 Feb TI - Problematic Pharmacokinetics: A Case of Recurrent Pancreatitis Post Discontinuation of a Glucagon-Like Peptide 1 Receptor Agonists. PG - 187-192 LID - 10.1177/08971900241273188 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1RA) are guideline recommended agents for the treatment of type 2 diabetes mellitus (T2DM) and select agents (liraglutide and semaglutide) are FDA approved as anti-obesity pharmacotherapy options. These drugs act on the incretin hormone system within the body to revive insulin excretion, delay gastric emptying, and inhibit the production of glucagon from pancreatic alpha cells. Acute pancreatitis is a serious condition that may have a fatal outcome. It has been shown, and is now part of the prescribing information label, that GLP-1RA agents can cause changes in the pancreas that may ultimately lead to pancreatitis. We describe the case of a 53-year-old female patient with uncontrolled type II diabetes mellitus, who experienced multiple episodes of pancreatitis, from what we suspect was due to repeated exposure to the GLP-1 RA agent, semaglutide. After discontinuation of semaglutide, our patient experienced another episode of pancreatitis roughly 15-week later; which we believe may be due to the patient experiencing the effects of a smoldering pancreas brought on by repeated injury and prolonged circulation of semaglutide post-discontinuation. FAU - Morehouse, Zachary P AU - Morehouse ZP AUID- ORCID: 0000-0002-5719-0947 AD - Department of Family Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC, USA. RINGGOLD: 2351 FAU - Ledford, Jack D AU - Ledford JD AUID- ORCID: 0000-0002-1033-1327 AD - Division of Pharmacy, Atrium Health Carolinas Medical Center, Charlotte, NC, USA. AD - Department of Family and Community Medicine, Wake Forest School of Medicine, Charlotte NC, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20240807 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Middle Aged MH - *Pancreatitis/chemically induced MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use/pharmacokinetics MH - Recurrence MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - diabetes OT - pancreatitis OT - semaglutide COIS- Declaration of Conflicting InterestsZPM and JDL are full time employees of Atrium Health Carolinas Medical Center and neither have any relevant financial disclosures or potential conflicts of interest which may have impacted the production or description of this manuscript in any way. EDAT- 2024/08/07 12:42 MHDA- 2024/12/12 12:28 CRDT- 2024/08/07 06:44 PHST- 2024/12/12 12:28 [medline] PHST- 2024/08/07 12:42 [pubmed] PHST- 2024/08/07 06:44 [entrez] AID - 10.1177/08971900241273188 [doi] PST - ppublish SO - J Pharm Pract. 2025 Feb;38(1):187-192. doi: 10.1177/08971900241273188. Epub 2024 Aug 7. PMID- 39109455 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data. PG - 4646-4652 LID - 10.1111/dom.15828 [doi] AB - AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 +/- 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered >/=80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kassem, Sameer AU - Kassem S AD - Department of Internal Medicine, Carmel Medical Center, Haifa, Israel. AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. FAU - Khalaila, Buthaina AU - Khalaila B AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. AD - Department of Clinical Pharmacology and Regulatory Management, Carmel Medical Center, Haifa, Israel. FAU - Stein, Nili AU - Stein N AD - Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. AD - Department of Community Medicine and Epidemiology, Statistical Unit, Lady Davis Carmel Medical Center, Haifa, Israel. FAU - Saliba, Walid AU - Saliba W AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. AD - Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. AD - Translational Epidemiology Unit and Research Authority, Lady Davis Carmel Medical Center, Haifa, Israel. FAU - Zaina, Adnan AU - Zaina A AUID- ORCID: 0000-0001-7482-3104 AD - Division of Endocrinology and Metabolism, Clalit Medical Health Care Services, Haifa, Israel. AD - Division of Endocrinology and Metabolism, Bar-Ilan University, The Azrieli Faculty of Medicine, Safed, Israel. LA - eng PT - Journal Article DEP - 20240807 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Exenatide/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis/metabolism MH - Glycemic Control/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Immunoglobulin Fc Fragments/therapeutic use/administration & dosage MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - Retrospective Studies MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring MH - Semaglutide OTO - NOTNLM OT - database research OT - glucagon-like peptide-1 analogue OT - glycaemic control OT - real-world evidence OT - type 2 diabetes EDAT- 2024/08/07 06:42 MHDA- 2024/09/18 12:52 CRDT- 2024/08/07 05:32 PHST- 2024/07/04 00:00 [revised] PHST- 2024/05/30 00:00 [received] PHST- 2024/07/07 00:00 [accepted] PHST- 2024/09/18 12:52 [medline] PHST- 2024/08/07 06:42 [pubmed] PHST- 2024/08/07 05:32 [entrez] AID - 10.1111/dom.15828 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4646-4652. doi: 10.1111/dom.15828. Epub 2024 Aug 7. PMID- 39103719 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20250103 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 11 DP - 2024 Nov TI - Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study. PG - 2471-2480 LID - 10.1007/s00125-024-06243-z [doi] AB - AIMS/HYPOTHESIS: Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. METHODS: This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. RESULTS: We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI >/=40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. CONCLUSIONS/INTERPRETATION: Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality. CI - (c) 2024. The Author(s). FAU - Hurtado, Isabel AU - Hurtado I AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Robles, Celia AU - Robles C AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Peiro, Salvador AU - Peiro S AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Garcia-Sempere, Anibal AU - Garcia-Sempere A AUID- ORCID: 0000-0002-4313-3976 AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. anibal.garcia@fisabio.es. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. anibal.garcia@fisabio.es. FAU - Sanfelix-Gimeno, Gabriel AU - Sanfelix-Gimeno G AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. LA - eng PT - Journal Article DEP - 20240806 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Obesity/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Cohort Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Self-Injurious Behavior/drug therapy/epidemiology MH - *Suicidal Ideation MH - Adult MH - Liraglutide/therapeutic use MH - Propensity Score MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11519213 OTO - NOTNLM OT - Cohort study OT - Diabetes OT - GLP-1RA OT - Glucose-lowering drugs OT - Obesity OT - SGLT-2i OT - Self-injury OT - Suicidal ideation EDAT- 2024/08/06 00:41 MHDA- 2024/10/28 18:23 PMCR- 2024/08/06 CRDT- 2024/08/05 23:33 PHST- 2024/02/08 00:00 [received] PHST- 2024/06/17 00:00 [accepted] PHST- 2024/10/28 18:23 [medline] PHST- 2024/08/06 00:41 [pubmed] PHST- 2024/08/05 23:33 [entrez] PHST- 2024/08/06 00:00 [pmc-release] AID - 10.1007/s00125-024-06243-z [pii] AID - 6243 [pii] AID - 10.1007/s00125-024-06243-z [doi] PST - ppublish SO - Diabetologia. 2024 Nov;67(11):2471-2480. doi: 10.1007/s00125-024-06243-z. Epub 2024 Aug 6. PMID- 39098317 OWN - NLM STAT- MEDLINE DCOM- 20240822 LR - 20250523 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 12 IP - 9 DP - 2024 Sep TI - Managing insulin resistance: the forgotten pathophysiological component of type 2 diabetes. PG - 674-680 LID - S2213-8587(24)00127-X [pii] LID - 10.1016/S2213-8587(24)00127-X [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread use in the treatment of individuals with type 2 diabetes because of their potent weight loss promoting effect, ability to augment beta-cell function, and cardiovascular protective effects. However, despite causing impressive weight loss, GLP-1 receptor agonists do not normalise insulin sensitivity in people with type 2 diabetes and obesity, and the long-term effects of this class of antidiabetic medication on muscle mass, frailty, and bone density have been poorly studied. Although GLP-1 receptor agonists improve insulin sensitivity secondary to weight loss, the only true direct insulin-sensitising drugs are thiazolidinediones. Because of side-effects associated with type 2 diabetes therapy, these drugs have not gained widespread use. In lieu of the important role of insulin resistance in the cause of type 2 diabetes and in the pathogenesis of atherosclerotic cardiovascular disease in type 2 diabetes, development of potent insulin-sensitising drugs that can be used in combination with GLP-1 receptor agonists remains a large unmet need in the management of individuals with type 2 diabetes. CI - Copyright (c) 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Abdul-Ghani, Muhammad AU - Abdul-Ghani M AD - Diabetes Division, UT Health, San Antonio, TX, USA. FAU - Maffei, Pietro AU - Maffei P AD - University of Padova, Padova, Italy. FAU - DeFronzo, Ralph Anthony AU - DeFronzo RA AD - Diabetes Division, UT Health, San Antonio, TX, USA. Electronic address: defronzo@uthscsa.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240801 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Insulin Resistance/physiology MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Declaration of interests RAD is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Intarcia, Aardvark, Renalytix, CORCEPT, and Alnylam; has received research grants from Boehringer Ingelheim, AstraZeneca, 89Bio, Amgen, Medality, and CORCEPT; and is a member of speakers bureaus for AstraZeneca, CORCEPT, and Renalytix. All other authors declare no competing interests. EDAT- 2024/08/05 00:42 MHDA- 2024/08/23 00:43 CRDT- 2024/08/04 22:12 PHST- 2023/12/14 00:00 [received] PHST- 2024/03/15 00:00 [revised] PHST- 2024/04/29 00:00 [accepted] PHST- 2024/08/23 00:43 [medline] PHST- 2024/08/05 00:42 [pubmed] PHST- 2024/08/04 22:12 [entrez] AID - S2213-8587(24)00127-X [pii] AID - 10.1016/S2213-8587(24)00127-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2024 Sep;12(9):674-680. doi: 10.1016/S2213-8587(24)00127-X. Epub 2024 Aug 1. PMID- 39096914 OWN - NLM STAT- MEDLINE DCOM- 20240907 LR - 20260127 IS - 2468-1253 (Electronic) VI - 9 IP - 10 DP - 2024 Oct TI - Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. PG - 957-964 LID - S2468-1253(24)00188-2 [pii] LID - 10.1016/S2468-1253(24)00188-2 [doi] AB - The availability of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) such as liraglutide and semaglutide, and a GLP-1 and glucose dependent insulinotropic polypeptide coagonist (tirzepatide) represents a paradigm shift in the management of both type 2 diabetes and obesity. There is now considerable attention, including in the public media, on the effect of both long-acting and short-acting GLP-1RAs to delay gastric emptying. Although slowed gastric emptying is integral to reducing post-prandial blood glucose responses in type 2 diabetes, marked slowing of gastric emptying might also increase the propensity for longer intragastric retention of food, with a consequent increased risk of aspiration at the time of surgery or upper gastrointestinal endoscopy. This Personal View summarises current knowledge of the effects of GLP-1 and GLP-1RAs on gastrointestinal physiology, particularly gastric emptying, and discusses the implications for the development of sound pre-operative or pre-procedural guidelines. The development of pre-procedural guidelines is currently compromised by the poor evidence base, particularly in relation to the effect of long-acting GLP-1RAs on gastric emptying. We suggest pre-procedural management pathways for individuals on GLP-1RA-based therapy and discuss priorities for future research. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved. FAU - Jalleh, Ryan J AU - Jalleh RJ AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Rayner, Chris K AU - Rayner CK AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Hausken, Trygve AU - Hausken T AD - Department of Medicine, Haukeland University Hospital, Bergen, Norway. FAU - Jones, Karen L AU - Jones KL AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Camilleri, Michael AU - Camilleri M AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Horowitz, Michael AU - Horowitz M AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. Electronic address: michael.horowitz@adelaide.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240801 PL - Netherlands TA - Lancet Gastroenterol Hepatol JT - The lancet. Gastroenterology & hepatology JID - 101690683 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Gastric Emptying/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Obesity/drug therapy MH - Liraglutide/therapeutic use/pharmacology MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declaration of interests CKR has participated on advisory boards for Glyscend Therapeutics, a company that owns orally administered, gut-targeted polymer therapies and has work underway related to type 2 diabetes and obesity. CKR has received honoraria for lectures from Eli Lilly and Boehringer Ingelheim. KLJ has previously received research funding from Sanofi-Aventis and AstraZeneca; participated on an advisory board for Glyscend Therapeutics (without receipt of payment); and declares stock options, but does not own any stock, in Glyscend Therapeutics. MH declares stocks in Mirum Pharmaceuticals, a company that owns Livmarli (maralixibat), which is approved in the USA and Europe for the treatment of cholestatic pruritus in Alagille syndrome (a genetic liver disorder). Mirum Pharmaceuticals has work underway related to rare liver diseases, but not diabetes or obesity. MH declares stock options, but does not own any stock, in Glyscend Therapeutics; and is a member of the scientific and clinical advisory board for Glyscend Therapeutics. All other authors declare no competing interests. EDAT- 2024/08/04 13:44 MHDA- 2024/09/08 13:50 CRDT- 2024/08/03 18:55 PHST- 2024/04/12 00:00 [received] PHST- 2024/05/28 00:00 [revised] PHST- 2024/05/29 00:00 [accepted] PHST- 2024/09/08 13:50 [medline] PHST- 2024/08/04 13:44 [pubmed] PHST- 2024/08/03 18:55 [entrez] AID - S2468-1253(24)00188-2 [pii] AID - 10.1016/S2468-1253(24)00188-2 [doi] PST - ppublish SO - Lancet Gastroenterol Hepatol. 2024 Oct;9(10):957-964. doi: 10.1016/S2468-1253(24)00188-2. Epub 2024 Aug 1. PMID- 39095227 OWN - NLM STAT- MEDLINE DCOM- 20240920 LR - 20251002 IS - 1878-0210 (Electronic) IS - 1751-9918 (Print) IS - 1878-0210 (Linking) VI - 18 IP - 5 DP - 2024 Oct TI - Trends in utilization patterns of newer glucose-lowering drugs in US adults with type 2 diabetes and a history of coronary heart disease or heart failure: 2005-2019. PG - 561-563 LID - S1751-9918(24)00158-X [pii] LID - 10.1016/j.pcd.2024.07.003 [doi] AB - BACKGROUND: The newer glucose-lowering drugs (GLDs), including Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have demonstrated superior cardio- and renal protective benefits compared to older GLDs in individuals with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). OBJECTIVE: This study examined the trends of the newer GLDs use in people with T2D who had a history of coronary heart disease or heart failure in the United States. METHOD: We used 2005-2019 data from the Medical Expenditure Panel Survey (MEPS). Individuals with self-reported diabetes and CVD history were identified. RESULTS: There was a steady increase in the use of GLP-1RA only from 2008 (3 %) to 2019 (21 %) and SGLT2i only from 2014 (5 %) to 2019 (12 %). Individuals with dual use of both newer GLD classes increased from 0.62 % in 2015 to 6 % in 2019. The overall uptake of these two newer drugs in 2019 was less than 40 %. In other words, 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments. CONCLUSION: The use of GLP-1RA and SGLT2i among individuals with T2D and a history of CVD was low and varied by insurance type. Policy-level interventions are needed to improve the use of these newer treatments further. SUMMARY: We examined how newer glucose-lowering drugs are used among individuals with type 2 diabetes and at high risk for coronary heart disease or heart failure in the US. We found that 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments due to the variation of insurance type. CI - Copyright (c) 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. FAU - Alshehri, Alaa AU - Alshehri A AD - Center for Drug Evaluation and Safety, Department of Pharmaceutical Evaluation and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA; Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia. FAU - Guan, Dawei AU - Guan D AD - Center for Drug Evaluation and Safety, Department of Pharmaceutical Evaluation and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA. FAU - Li, Piaopiao AU - Li P AD - Center for Drug Evaluation and Safety, Department of Pharmaceutical Evaluation and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA. FAU - Zhang, Yichen AU - Zhang Y AD - Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. FAU - Ghayee, Hans K AU - Ghayee HK AD - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Florida College of Medicine, Malcom Randall VA Medical Center, Gainesville, FL, USA. FAU - Jiao, Tianze AU - Jiao T AD - Center for Drug Evaluation and Safety, Department of Pharmaceutical Evaluation and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA. FAU - Shao, Hui AU - Shao H AD - Center for Drug Evaluation and Safety, Department of Pharmaceutical Evaluation and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center of Woodruff Health Sciences Center, Emory University, Atlanta, GA, USA. Electronic address: hui.shao@emory.edu. LA - eng GR - P30 DK111024/DK/NIDDK NIH HHS/United States GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240802 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/diagnosis MH - *Heart Failure/epidemiology/drug therapy MH - Male MH - United States/epidemiology MH - Female MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Coronary Disease/epidemiology/drug therapy MH - Aged MH - *Practice Patterns, Physicians'/trends MH - Adult MH - Time Factors MH - Treatment Outcome MH - Blood Glucose/drug effects/metabolism MH - Incretins/therapeutic use/adverse effects MH - Biomarkers/blood MH - Glycemic Control/trends MH - Health Care Surveys MH - Young Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11616792 MID - NIHMS2015892 OTO - NOTNLM OT - Cardiovascular disease OT - Coronary heart disease OT - Glucagon-like peptide-1 receptor agonists OT - Glucose-lowering drugs OT - Heart failure OT - Sodium-glucose cotransporter-2 inhibitors OT - Trends OT - Type 2 diabetes OT - Utilization rate COIS- Conflict of Interest "All authors of Trends in Utilization Patterns of Newer Glucose-lowering Drugs in US Adults with Type 2 Diabetes and a History of Cardiovascular Disease: 2005-2019 have no Conflict of Interest of publishing this Brief Research." EDAT- 2024/08/03 10:41 MHDA- 2024/09/21 13:19 PMCR- 2025/10/01 CRDT- 2024/08/02 21:52 PHST- 2024/02/02 00:00 [received] PHST- 2024/07/09 00:00 [revised] PHST- 2024/07/24 00:00 [accepted] PHST- 2024/09/21 13:19 [medline] PHST- 2024/08/03 10:41 [pubmed] PHST- 2024/08/02 21:52 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - S1751-9918(24)00158-X [pii] AID - 10.1016/j.pcd.2024.07.003 [doi] PST - ppublish SO - Prim Care Diabetes. 2024 Oct;18(5):561-563. doi: 10.1016/j.pcd.2024.07.003. Epub 2024 Aug 2. PMID- 39094916 OWN - NLM STAT- MEDLINE DCOM- 20250423 LR - 20260416 IS - 1097-6779 (Electronic) IS - 0016-5107 (Linking) VI - 101 IP - 2 DP - 2025 Feb TI - Glucagon-like peptide-1 receptor agonists and capsule endoscopy in patients with diabetes: a matched cohort study. PG - 393-401 LID - S0016-5107(24)03360-1 [pii] LID - 10.1016/j.gie.2024.07.014 [doi] AB - BACKGROUND AND AIMS: Video capsule endoscopy (VCE) is valuable for assessing conditions like GI bleeding, anemia, and inflammatory bowel disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for diabetes and weight loss, with their pharmacologic effects including delayed gastric emptying. This study investigates the impact of GLP-1RA use on VCE outcomes in patients with diabetes. METHODS: This retrospective cohort study involves patients with diabetes undergoing VCE while on GLP-1RAs matched in a 1:1 ratio with control subjects, who are not on GLP-1RAs, based on demographics and diabetes-related factors. The primary outcome was gastric transit time in VCE studies, whereas secondary outcomes were incomplete small-bowel evaluation and small-bowel transit time. RESULTS: In the GLP-1RA cohort with 68 patients, 5 (7%) experienced failure to pass the video capsule through the stomach; all control subjects passed the video capsule successfully (P = .06). GLP-1RA patients had a longer gastric transit time (99.3 +/- 134.2 minutes) compared with control subjects (25.3 +/- 31.6 minutes, P < .001). Multivariate analysis revealed GLP-1RA use was associated with an increased gastric transit time by 74.5 minutes (95% confidence interval, 33.8-115.2; P < .001) compared with control subjects, after adjusting for relevant factors. Sixteen GLP-1RA patients (23.5%) experienced incomplete passage of the video capsule through the small intestine, a significantly higher rate compared with 3 patients in the control group (4.4%, P < .01). CONCLUSIONS: GLP-1RA use is associated with a prolonged gastric transit time and a higher rate of incomplete small-bowel evaluation during VCE. Future studies may be crucial for evaluating strategies to mitigate these effects. CI - Copyright (c) 2025 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved. FAU - Odah, Tarek AU - Odah T AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Vattikonda, Asrita AU - Vattikonda A AD - Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA. FAU - Stark, Mark AU - Stark M AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Brahmbhatt, Bhaumik AU - Brahmbhatt B AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Lukens, Frank J AU - Lukens FJ AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Badurdeen, Dilhana AU - Badurdeen D AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Hashash, Jana G AU - Hashash JG AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Farraye, Francis A AU - Farraye FA AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240731 PL - United States TA - Gastrointest Endosc JT - Gastrointestinal endoscopy JID - 0010505 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Capsule Endoscopy MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Gastrointestinal Transit/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Intestine, Small/physiopathology MH - Gastric Emptying/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Case-Control Studies MH - Cohort Studies COIS- Disclosure The following authors disclosed financial relationships: J. G. Hashash: Advisory board for Bristol Myers Squibb. F. A. Farraye: Consultant for AbbVie, Avalo Therapeutics, Bristol Myers Squibb, Braintree Labs, Fresenius Kabi, GSK, Iterative Health, Janssen, Pfizer, Pharmacosmos, Sandoz Immunology, Sebela, and Viatris; independent contractor for GI Reviewers and IBD Educational Group; Data Safety Monitoring Board for Lilly. All other authors disclosed no financial relationships. EDAT- 2024/08/03 10:41 MHDA- 2025/02/02 05:11 CRDT- 2024/08/02 19:22 PHST- 2024/05/12 00:00 [received] PHST- 2024/07/05 00:00 [revised] PHST- 2024/07/21 00:00 [accepted] PHST- 2025/02/02 05:11 [medline] PHST- 2024/08/03 10:41 [pubmed] PHST- 2024/08/02 19:22 [entrez] AID - S0016-5107(24)03360-1 [pii] AID - 10.1016/j.gie.2024.07.014 [doi] PST - ppublish SO - Gastrointest Endosc. 2025 Feb;101(2):393-401. doi: 10.1016/j.gie.2024.07.014. Epub 2024 Jul 31. PMID- 39093590 OWN - NLM STAT- MEDLINE DCOM- 20240802 LR - 20260827 IS - 2689-0186 (Electronic) IS - 2689-0186 (Linking) VI - 5 IP - 8 DP - 2024 Aug 2 TI - Prescription Fills for Semaglutide Products by Payment Method. PG - e242026 LID - 10.1001/jamahealthforum.2024.2026 [doi] LID - e242026 FAU - Scannell, Christopher AU - Scannell C AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Los Angeles Area Health Service Research Training Program, Fielding School of Public Health, University of California, Los Angeles. FAU - Romley, John AU - Romley J AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Price School of Public Policy, University of Southern California, Los Angeles. AD - Program on Medicines and Public Health, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles. FAU - Myerson, Rebecca AU - Myerson R AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Department of Population Health Sciences, University of Wisconsin, Madison. FAU - Goldman, Dana AU - Goldman D AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Price School of Public Policy, University of Southern California, Los Angeles. FAU - Qato, Dima M AU - Qato DM AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Program on Medicines and Public Health, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles. LA - eng GR - T32 HS000046/HS/AHRQ HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240802 PL - United States TA - JAMA Health Forum JT - JAMA health forum JID - 101769500 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - United States MH - Diabetes Mellitus, Type 2/drug therapy/economics MH - Semaglutide PMC - PMC11297375 OAB - This cross-sectional study examines trends in US prescription fills for semaglutide products by payment method between January 2021 and December 2023. OABL- eng COIS- Conflict of Interest Disclosures: Dr Scannell reported receiving a postdoctoral training grant from the Agency for Healthcare Research and Quality during the conduct of the study. Dr Goldman reported receiving grants from the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study; grants from the American Heart Association, Amgen, Blue Cross Blue Shield of Arizona, Bristol Myers Squibb, the California Hospital Association, Cedars-Sinai Health System, Charles Koch Foundation, Edwards Lifesciences, Gates Ventures, Genentech, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, Novartis, and Pfizer, receiving personal fees from Biogen, the National Railway Labor Conference, and GRAIL, and being a cofounder with equity from EntityRisk outside the submitted work. Dr Qato reported receiving personal fees from Public Citizens Health Research Group and grants from the National Institutes of Health outside the submitted work. No other disclosures were reported. EDAT- 2024/08/02 12:42 MHDA- 2024/08/02 12:43 PMCR- 2024/08/02 CRDT- 2024/08/02 11:33 PHST- 2024/08/02 12:43 [medline] PHST- 2024/08/02 12:42 [pubmed] PHST- 2024/08/02 11:33 [entrez] PHST- 2024/08/02 00:00 [pmc-release] AID - 2821688 [pii] AID - ald240016 [pii] AID - 10.1001/jamahealthforum.2024.2026 [doi] PST - epublish SO - JAMA Health Forum. 2024 Aug 2;5(8):e242026. doi: 10.1001/jamahealthforum.2024.2026. PMID- 39093567 OWN - NLM STAT- MEDLINE DCOM- 20240802 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 8 DP - 2024 Aug 1 TI - Safety and Risk Assessment of No-Prescription Online Semaglutide Purchases. PG - e2428280 LID - 10.1001/jamanetworkopen.2024.28280 [doi] LID - e2428280 FAU - Ashraf, Amir Reza AU - Ashraf AR AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Mackey, Tim K AU - Mackey TK AD - Global Health Program, Department of Anthropology, University of California San Diego, La Jolla. AD - Global Health Policy and Data Institute, San Diego, California. AD - S-3 Research, San Diego, California. FAU - Schmidt, Janos AU - Schmidt J AD - Institute of Biochemistry and Medical Chemistry, Medical School, University of Pecs, Pecs, Hungary. FAU - Kulcsar, Gyozo AU - Kulcsar G AD - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Vida, Robert Gyorgy AU - Vida RG AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Li, Jiawei AU - Li J AD - S-3 Research, San Diego, California. FAU - Fittler, Andras AU - Fittler A AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - Risk Assessment MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Semaglutide PMC - PMC11297364 OAB - This qualitative study assesses the quality, amount of active ingredient, and characteristics associated with counterfeiting of semaglutide purchased from illegal online pharmacies without a prescription. OABL- eng COIS- Conflict of Interest Disclosures: Mr Schmidt reported receiving grant TKP2021-EGA-17 from the Hungarian National Research, Development and Innovation Office outside the submitted work. No other disclosures were reported. EDAT- 2024/08/02 12:44 MHDA- 2024/08/02 18:42 PMCR- 2024/08/02 CRDT- 2024/08/02 11:32 PHST- 2024/08/02 18:42 [medline] PHST- 2024/08/02 12:44 [pubmed] PHST- 2024/08/02 11:32 [entrez] PHST- 2024/08/02 00:00 [pmc-release] AID - 2821882 [pii] AID - zld240127 [pii] AID - 10.1001/jamanetworkopen.2024.28280 [doi] PST - epublish SO - JAMA Netw Open. 2024 Aug 1;7(8):e2428280. doi: 10.1001/jamanetworkopen.2024.28280. PMID- 39093550 OWN - NLM STAT- MEDLINE DCOM- 20240910 LR - 20240924 IS - 2299-5684 (Electronic) IS - 1734-1140 (Linking) VI - 76 IP - 5 DP - 2024 Oct TI - A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment. PG - 981-990 LID - 10.1007/s43440-024-00629-x [doi] AB - Glucagon-like peptide-1 (GLP-1) agonists play a crucial role in treating type 2 diabetes mellitus and obesity by providing glycemic control and aiding weight management. Despite their widespread use, concerns about serious adverse events have prompted extensive research. This review aims to describe the current understanding of serious adverse events associated with GLP-1 agonists. A comprehensive search of PubMed, Google Scholar and Embase databases was performed starting from 2010. Studies reporting evidence of an association between GLP-1 agonists and serious adverse events from 22 articles (5 case reports, 5 randomized controlled trials (RCTs), 9 real-world data cohort analyses, 2 meta-analyses and 1 systematic review and meta-analysis) were included and categorized by the type of adverse event. While some studies reported risks, including anaphylaxis, cardiovascular, gastrointestinal, psychiatric and thyroid-related events, others found no significant associations. The evidence remains mixed, necessitating further research to fully understand the safety profile of GLP-1 agonists and inform clinical practice. CI - (c) 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences. FAU - Tobaiqy, Mansour AU - Tobaiqy M AUID- ORCID: 0000-0002-4292-0900 AD - Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, 45311, Saudi Arabia. mtobaiqy@uj.edu.sa. LA - eng PT - Journal Article PT - Review DEP - 20240802 PL - Switzerland TA - Pharmacol Rep JT - Pharmacological reports : PR JID - 101234999 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects OTO - NOTNLM OT - Glucagon-like peptide 1 (GLP-1) agonists OT - Obesity OT - Review OT - Serious adverse event OT - Type 2 diabetes mellitus EDAT- 2024/08/02 12:43 MHDA- 2024/09/11 00:43 CRDT- 2024/08/02 11:19 PHST- 2024/03/03 00:00 [received] PHST- 2024/07/11 00:00 [accepted] PHST- 2024/07/10 00:00 [revised] PHST- 2024/09/11 00:43 [medline] PHST- 2024/08/02 12:43 [pubmed] PHST- 2024/08/02 11:19 [entrez] AID - 10.1007/s43440-024-00629-x [pii] AID - 10.1007/s43440-024-00629-x [doi] PST - ppublish SO - Pharmacol Rep. 2024 Oct;76(5):981-990. doi: 10.1007/s43440-024-00629-x. Epub 2024 Aug 2. PMID- 39091271 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Semaglutide improves treatment satisfaction and eating behaviour in Japanese patients with type 2 diabetes mellitus. PG - 4787-4790 LID - 10.1111/dom.15823 [doi] FAU - Baba, Yusuke AU - Baba Y AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Watanabe, Suzuka AU - Watanabe S AD - Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. FAU - Hayashi, Saho AU - Hayashi S AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Sakai, Toshiki AU - Sakai T AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Naka, Masamitsu AU - Naka M AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Kami, Saori AU - Kami S AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Hirayama, Kiichi AU - Hirayama K AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Koizumi, Kazuko AU - Koizumi K AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Takahashi, Ai AU - Takahashi A AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Meguro, Miwako AU - Meguro M AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Iga, Ryo AU - Iga R AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Yamanaka, Yoshitaka AU - Yamanaka Y AD - Department of Rehabilitation, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Kataoka, Masaaki AU - Kataoka M AD - Department of Surgery, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Uchida, Daigaku AU - Uchida D AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. AD - Department of Internal Medicine, Hotaruno Central Naika, Chiba, Japan. FAU - Ishibashi, Ryoichi AU - Ishibashi R AUID- ORCID: 0000-0003-2535-5396 AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. AD - Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. LA - eng PT - Journal Article DEP - 20240802 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - East Asian People MH - Feeding Behavior MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Japan/epidemiology MH - *Patient Satisfaction MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - appetite control OT - attitudes OT - semaglutide EDAT- 2024/08/02 06:41 MHDA- 2024/09/18 12:45 CRDT- 2024/08/02 04:23 PHST- 2024/07/09 00:00 [revised] PHST- 2024/05/16 00:00 [received] PHST- 2024/07/09 00:00 [accepted] PHST- 2024/09/18 12:45 [medline] PHST- 2024/08/02 06:41 [pubmed] PHST- 2024/08/02 04:23 [entrez] AID - 10.1111/dom.15823 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4787-4790. doi: 10.1111/dom.15823. Epub 2024 Aug 2. PMID- 39086638 OWN - NLM STAT- MEDLINE DCOM- 20240801 LR - 20240823 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 30 IP - 26 DP - 2024 Jul 14 TI - Is it necessary to stop glucagon-like peptide-1 receptor agonists prior to endoscopic procedure? A retrospective study. PG - 3221-3228 LID - 10.3748/wjg.v30.i26.3221 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective in diabetes and obesity, reducing hyperglycemia by increasing insulin release and delaying gastric emptying. However, they can cause gastroparesis, raising concerns about aspiration during procedures. Recent guidelines advise discontinuing GLP-1 RA before surgery to reduce the risk of pulmonary aspiration. AIM: To evaluate the effect of GLP-1 RAs on gastric residual contents during endoscopic procedures. METHODS: A retrospective chart review at BronxCare Health System, New York, from January 2019 to October 2023, assessed gastric residue and aspiration in GLP-1 RA patients undergoing endoscopic procedures. Two groups were compared based on dietary status before the procedure. Data included demographics, symptoms of gastroparesis, opiate use, hemoglobin A1c, GLP-1 agonist indication, endoscopic details, and aspiration occurrence. IBM SPSS was used for analysis, calculating means, standard deviations, and applying Pearson's chi-square and t-tests for associations, with P < 0.05 as being significant. RESULTS: During the study, 306 patients were included, with 41.2% on a clear liquid/low residue diet and 58.8% on a regular diet before endoscopy. Most patients (63.1%) were male, with a mean age of 60 +/- 12 years. The majority (85.6%) were on GLP-1 RAs for diabetes, and 10.1% reported digestive symptoms before endoscopy. Among those on a clear liquid diet, 1.5% had residual food at endoscopy compared to 10% on a regular diet, which was statistically significant (P = 0.03). Out of 31 patients with digestive symptoms, 13% had residual food, all from the regular diet group (P = 0.130). No complications were reported during or after the procedures. CONCLUSION: The study reflects a significant rise in GLP-1 RA use for diabetes and obesity. A 24-hour liquid diet seems safe for endoscopic procedures without aspiration. Patients with upper gastrointestinal symptoms might have a higher residual food risk, though not statistically significant. Further research is needed to assess risks based on diabetes duration, gastroparesis, and GLP-1 RA dosing, aiming to minimize interruptions in therapy during procedures. CI - (c)The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved. FAU - Ghazanfar, Haider AU - Ghazanfar H AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Javed, Nismat AU - Javed N AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Qasim, Abeer AU - Qasim A AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Sosa, Franklin AU - Sosa F AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Altaf, Faryal AU - Altaf F AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Khan, Shazia AU - Khan S AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Mahasamudram, Jaydeep AU - Mahasamudram J AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Jyala, Abhilasha AU - Jyala A AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Kandhi, Sameer Datta AU - Kandhi SD AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. skandhi@bronxcare.org. FAU - Shin, Dongmin AU - Shin D AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Mantri, Nikhitha AU - Mantri N AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Sun, Haozhe AU - Sun H AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Hanumanthu, Siddarth AU - Hanumanthu S AD - Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Patel, Harish AU - Patel H AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Makker, Jasbir AU - Makker J AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Balar, Bhavna AU - Balar B AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Dev, Anil AU - Dev A AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. FAU - Chilimuri, Sridhar AU - Chilimuri S AD - Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Endoscopy, Gastrointestinal/adverse effects/methods MH - Gastric Emptying/drug effects MH - *Gastroparesis/epidemiology/etiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Retrospective Studies PMC - PMC11287410 OTO - NOTNLM OT - Complications OT - Endoscopic procedures OT - Gastroparesis OT - Glucagon-like peptide-1 agonists OT - Residual food COIS- Conflict-of-interest statement: We have no financial relationships to disclose. EDAT- 2024/08/01 06:42 MHDA- 2024/08/01 06:43 PMCR- 2024/07/14 CRDT- 2024/08/01 04:17 PHST- 2024/03/26 00:00 [received] PHST- 2024/05/14 00:00 [revised] PHST- 2024/06/24 00:00 [accepted] PHST- 2024/08/01 06:43 [medline] PHST- 2024/08/01 06:42 [pubmed] PHST- 2024/08/01 04:17 [entrez] PHST- 2024/07/14 00:00 [pmc-release] AID - 10.3748/wjg.v30.i26.3221 [doi] PST - ppublish SO - World J Gastroenterol. 2024 Jul 14;30(26):3221-3228. doi: 10.3748/wjg.v30.i26.3221. PMID- 39085578 OWN - NLM STAT- MEDLINE DCOM- 20241120 LR - 20260404 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 39 IP - 15 DP - 2024 Nov TI - Disparities in Use of Novel Diabetes Medications by Insurance: A Nationally Representative Cohort Study. PG - 2987-2994 LID - 10.1007/s11606-024-08961-x [doi] AB - BACKGROUND: Minority racial and ethnic populations have the highest prevalence of type 2 diabetes mellitus but lower use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra), novel medications that reduce morbidity and mortality. Observed disparities may be due to differences in insurance coverage, which have variable cost-sharing, prior authorization, and formulary restrictions that influence medication access. OBJECTIVE: To assess whether racial/ethnic differences in SGLT2i and GLP1ra use differ by payer. DESIGN: Cross-sectional analysis of 2018 and 2019 Medical Expenditure Panel Survey data. PARTICIPANTS: Adults >/= 18 years old with diabetes. MAIN MEASURES: We defined insurance as private, Medicare, or Medicaid using >/= 7 months of coverage in the calendar year. We defined race/ethnicity as White (non-Hispanic) vs non-White (including Hispanic). The primary outcome was use of >/= 1 SGLT2i or GLP1ra medication. We used multivariable logistic regression to assess the interaction between payer and race/ethnicity adjusted for cardiovascular, socioeconomic, and healthcare access factors. KEY RESULTS: We included 4997 adults, representing 24.8 million US adults annually with diabetes (mean age 63.6 years, 48.8% female, 38.8% non-White; 33.5% private insurance, 56.8% Medicare, 9.8% Medicaid). In our fully adjusted model, White individuals with private insurance had significantly more medication use versus non-White individuals (16.1% vs 8.3%, p < 0.001), which was similar for Medicare beneficiaries but more attenuated (14.7% vs 11.0%, p = 0.04). Medication rates were similar among Medicaid beneficiaries (10.0% vs 9.0%, p = 0.74). CONCLUSIONS: Racial/ethnic disparities in novel diabetes medications were the largest among those with private insurance. There was no disparity among Medicaid enrollees, but overall prescription rates were the lowest. Given that disparities vary considerably by payer, differences in insurance coverage may account for the observed disparities in SGLT2i and GLP1ra use. Future studies are needed to assess racial/ethnic differences in novel diabetes use by insurance formulary restrictions and out-of-pocket cost-sharing. CI - (c) 2024. The Author(s). FAU - Bepo, Lurit AU - Bepo L AUID- ORCID: 0009-0008-9170-4244 AD - Division of Hospital Medicine, San Francisco General Hospital, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. lurit.bepo@ucsf.edu. AD - UCSF National Clinician Scholars Program, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, CA, USA. lurit.bepo@ucsf.edu. AD - Division of Hospital Medicine, Zuckerberg San Francisco General Hospital, Department of Medicine, University of California, San Francisco, CA, USA. lurit.bepo@ucsf.edu. FAU - Nguyen, Oanh K AU - Nguyen OK AD - Division of Hospital Medicine, San Francisco General Hospital, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. AD - UCSF Philip R. Lee Institute for Health Policy Studies, San Francisco, CA, USA. AD - UCSF Center for Vulnerable Populations, San Francisco, CA, USA. FAU - Makam, Anil N AU - Makam AN AD - Division of Hospital Medicine, San Francisco General Hospital, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. AD - UCSF Philip R. Lee Institute for Health Policy Studies, San Francisco, CA, USA. AD - UCSF Center for Vulnerable Populations, San Francisco, CA, USA. LA - eng GR - K23HL133441/HL/NHLBI NIH HHS/United States GR - K23AG052603/AG/NIA NIH HHS/United States GR - T32HP19025/HRSA/HRSA HHS/United States GR - K23 AG052603/AG/NIA NIH HHS/United States GR - K23 HL133441/HL/NHLBI NIH HHS/United States GR - P30 AG044281/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20240731 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - United States/epidemiology MH - Middle Aged MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology/economics MH - *Healthcare Disparities/ethnology/statistics & numerical data/economics MH - Adult MH - Aged MH - *Hypoglycemic Agents/therapeutic use/economics MH - Medicaid/statistics & numerical data MH - Cohort Studies MH - Medicare/statistics & numerical data MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/economics MH - Insurance Coverage/statistics & numerical data MH - Insurance, Health/statistics & numerical data MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11576692 COIS- Declarations: Conflict of Interest: The authors declare that they do not have a conflict of interest. EDAT- 2024/08/01 00:42 MHDA- 2024/11/20 11:04 PMCR- 2024/07/31 CRDT- 2024/07/31 23:37 PHST- 2024/02/16 00:00 [received] PHST- 2024/07/18 00:00 [accepted] PHST- 2024/11/20 11:04 [medline] PHST- 2024/08/01 00:42 [pubmed] PHST- 2024/07/31 23:37 [entrez] PHST- 2024/07/31 00:00 [pmc-release] AID - 10.1007/s11606-024-08961-x [pii] AID - 8961 [pii] AID - 10.1007/s11606-024-08961-x [doi] PST - ppublish SO - J Gen Intern Med. 2024 Nov;39(15):2987-2994. doi: 10.1007/s11606-024-08961-x. Epub 2024 Jul 31. PMID- 39084842 OWN - NLM STAT- MEDLINE DCOM- 20240731 LR - 20250103 IS - 1557-9859 (Electronic) IS - 0025-7125 (Linking) VI - 108 IP - 5 DP - 2024 Sep TI - Newer Outpatient Diabetes Therapies and Technologies. PG - 923-951 LID - S0025-7125(24)00019-1 [pii] LID - 10.1016/j.mcna.2024.03.002 [doi] AB - New diabetes drugs such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic peptide/GLP-1 RAs have emerged to show hemoglobin A1c (HbA1c) reduction, weight loss, and cardiovascular benefits. Similarly, sodium-glucose cotransporter 2 inhibitors' benefits span from HbA1c decrease to cardiovascular and renoprotective effects. Diabetes technology has expanded to include type 2 diabetes mellitus, with literature supporting its use in T2DM on any insulin regimen. Connected insulin pens and insulin delivery devices have opened new solutions to insulin users and automated insulin delivery systems have become the standard of care therapy for type 1 diabetes mellitus. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Kamal, Nevin AU - Kamal N AD - Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA. FAU - Lee, Kristen AU - Lee K AD - Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA. FAU - Aleppo, Grazia AU - Aleppo G AD - Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA. Electronic address: aleppo@northwestern.edu. LA - eng PT - Journal Article PT - Review DEP - 20240604 PL - United States TA - Med Clin North Am JT - The Medical clinics of North America JID - 2985236R RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Diabetes Mellitus, Type 1/drug therapy MH - Insulin/therapeutic use/administration & dosage MH - Glycated Hemoglobin MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Insulin Infusion Systems MH - Ambulatory Care/methods MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Automated insulin delivery systems OT - Connected insulin pens OT - Continuous glucose monitoring OT - GLP-1 receptor agonists OT - SGLT2 inhibitors COIS- Disclosure N. Kamal and K. Lee have nothing to disclose. G. Aleppo has received consultant fees from Dexcom, Insulet and Medscape. G. Aleppo has received research support to her employer, Northwestern University from Fractyl Health, Insulet, MannKind, Tandem Diabetes, and Welldoc. EDAT- 2024/08/01 00:42 MHDA- 2024/08/01 00:43 CRDT- 2024/07/31 20:58 PHST- 2024/08/01 00:43 [medline] PHST- 2024/08/01 00:42 [pubmed] PHST- 2024/07/31 20:58 [entrez] AID - S0025-7125(24)00019-1 [pii] AID - 10.1016/j.mcna.2024.03.002 [doi] PST - ppublish SO - Med Clin North Am. 2024 Sep;108(5):923-951. doi: 10.1016/j.mcna.2024.03.002. Epub 2024 Jun 4. PMID- 39084830 OWN - NLM STAT- MEDLINE DCOM- 20240731 LR - 20250331 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 6 DP - 2024 Aug 6 TI - Inquiries Into the Mechanisms by Which GLP-1 Receptor Agonists Reduce Cardiovascular Risk in Diabetes. PG - 558-560 LID - S0735-1097(24)07493-X [pii] LID - 10.1016/j.jacc.2024.05.045 [doi] FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology and Metabolism, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address: Silvio.Inzucchi@yale.edu. FAU - Arai, Andrew E AU - Arai AE AD - Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. LA - eng PT - Editorial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Heart Disease Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - NMR spectroscopy OT - cardiac magnetic resonance (CMR) OT - cardiovascular disease OT - type 2 diabetes COIS- Funding Support and Author Disclosures Dr Inzucchi has served on clinical trial committees and/or as an advisor to Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Merck, Pfizer, and Bayer; and has received speakers fees from Boehringer Ingelheim and AstraZeneca. Dr Arai has reported that he has no relationships relevant to the contents of this paper to disclose. EDAT- 2024/08/01 00:42 MHDA- 2024/08/01 00:43 CRDT- 2024/07/31 20:58 PHST- 2024/05/02 00:00 [received] PHST- 2024/05/06 00:00 [revised] PHST- 2024/05/08 00:00 [accepted] PHST- 2024/08/01 00:43 [medline] PHST- 2024/08/01 00:42 [pubmed] PHST- 2024/07/31 20:58 [entrez] AID - S0735-1097(24)07493-X [pii] AID - 10.1016/j.jacc.2024.05.045 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 6;84(6):558-560. doi: 10.1016/j.jacc.2024.05.045. PMID- 39082364 OWN - NLM STAT- MEDLINE DCOM- 20240731 LR - 20260608 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 29 IP - 7 DP - 2024 Jul 24 TI - Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i. PG - 265 LID - 10.31083/j.fbl2907265 [doi] AB - BACKGROUND: Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke. METHODS: DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol. The following groups (n = 15 each) were formed: DM without treatment, treatment with liraglutide, dulaglutide, canagliflozin as well as control group without DM and treatment. After 8 weeks, 10 rats from each group underwent middle cerebral artery occlusion. In the reperfusion period neurological deficit, neuroglial damage markers and brain necrosis were evaluated. Brain slices from the remaining 5 animals in each group were histologically examined for microglial activation and neuronal damage. RESULTS: Brain damage was similar in "DM" and "Control" (17.53 [14.23; 26.58] and 15.87 [13.40; 22.68] % of total brain volume, respectively). All study drugs diminished damage volume comparing with "DM" and "Control" whereas the necrosis volume in "DM+Liraglutide" was smaller than in "DM+Canagliflozin" and did not significantly differ from "DM+Dulaglutide" (2.9 [1.83; 4.71], 6.17 [3.88; 8.88] and 4.57 [3.27; 7.90] %). The neurological deficit was more prominent in "DM" than in "Control", while all the drugs demonstrated similar positive effect. Neurofilament light chains (NLC) did not differ between "DM" and "Control". Dulaglutide and canagliflozin caused a marked decrease in NLC. Protein S100BB level was similar in "DM" and "Control". Liraglutide caused the largest S100BB decrease, while canagliflozin did not influence it. In chronic brain ischaemia, all drugs increased the number of normal neurons, but GLP-1RAs had a more pronounced effect. DM was accompanied by increased number of activated microglial cells in Cornu Ammonis (CA)1 hippocampal region. Both GLP-1RAs reduced the number of Iba-1-positive cells, with dulaglutide being more effective than liraglutide, whereas canagliflozin did not affect this parameter. CONCLUSIONS: GLP-1RAs and SGLT-2i have neuroprotective properties against acute and chronic brain damage in diabetic rats, although the infarct-limiting effect of GLP-1RAs may be more pronounced. GLP-1RAs and SGLT-2i exert their protective effects by directly influencing neuronal survival, whereas GLP-1RAs also affect microglia. CI - (c) 2024 The Author(s). Published by IMR Press. FAU - Simanenkova, Anna AU - Simanenkova A AD - Institution of Endocrinology, Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia. AD - Faculty Therapy Department, Pavlov First St. Petersburg State Medical University, 197022 Saint-Petersburg, Russia. FAU - Fuks, Oksana AU - Fuks O AD - Institution of Endocrinology, Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia. FAU - Timkina, Natalya AU - Timkina N AD - Institution of Endocrinology, Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia. AD - Faculty Therapy Department, Pavlov First St. Petersburg State Medical University, 197022 Saint-Petersburg, Russia. FAU - Islamova, Alina AU - Islamova A AD - Institution of Endocrinology, Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia. FAU - Sufieva, Dina AU - Sufieva D AD - Laboratory of Functional Morphology of Central and Peripheral Nervous System, Institute of Experimental Medicine, 197022 Saint-Petersburg, Russia. FAU - Kirik, capital O, Cyrilliclga AU - Kirik capital O, Cyrillic AD - Laboratory of Functional Morphology of Central and Peripheral Nervous System, Institute of Experimental Medicine, 197022 Saint-Petersburg, Russia. FAU - Korzhevskii, Dmitrii AU - Korzhevskii D AD - Laboratory of Functional Morphology of Central and Peripheral Nervous System, Institute of Experimental Medicine, 197022 Saint-Petersburg, Russia. FAU - Vlasov, Timur AU - Vlasov T AD - Faculty of Pathophysiology, Pavlov First St. Petersburg State Medical University, 197022 Saint-Petersburg, Russia. FAU - Karonova, Tatiana AU - Karonova T AD - Institution of Endocrinology, Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia. AD - Faculty Therapy Department, Pavlov First St. Petersburg State Medical University, 197022 Saint-Petersburg, Russia. LA - eng GR - 124021600064-8/Ministry of Health of Russian Federation/ PT - Journal Article PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - *Diabetes Mellitus, Experimental/pathology/complications/metabolism/drug therapy MH - *Microglia/drug effects/metabolism/pathology MH - Male MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Rats MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism/pathology MH - Rats, Wistar MH - Brain Damage, Chronic/prevention & control/etiology/pathology MH - Liraglutide/pharmacology/therapeutic use MH - Neuroprotective Agents/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RAs OT - SGLT-2i OT - chronic brain damage OT - diabetes mellitus OT - microglia OT - neuroprotection OT - stroke COIS- The authors declare no conflict of interest. EDAT- 2024/07/31 12:43 MHDA- 2024/07/31 12:44 CRDT- 2024/07/31 06:33 PHST- 2024/06/04 00:00 [received] PHST- 2024/07/04 00:00 [revised] PHST- 2024/07/10 00:00 [accepted] PHST- 2024/07/31 12:44 [medline] PHST- 2024/07/31 12:43 [pubmed] PHST- 2024/07/31 06:33 [entrez] AID - S2768-6701(24)01408-4 [pii] AID - 10.31083/j.fbl2907265 [doi] PST - ppublish SO - Front Biosci (Landmark Ed). 2024 Jul 24;29(7):265. doi: 10.31083/j.fbl2907265. PMID- 39082303 OWN - NLM STAT- MEDLINE DCOM- 20250604 LR - 20250604 IS - 1537-1921 (Electronic) IS - 0898-4921 (Linking) VI - 36 IP - 4 DP - 2024 Oct 1 TI - To the Brain and Beyond: Neurological Implications of Glucagon-Like Peptide-1 Receptor Agonists. PG - 278-282 LID - 10.1097/ANA.0000000000000985 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an increasingly popular class of medications commonly used for glycemic control in patients with type 2 diabetes mellitus and for weight loss. GLP-1 RAs also have potential benefits in patients with various neurological diseases independent of their glucose-modulating effect. In this focused review, we explore animal and clinical evidence evaluating the impact of GLP-1 RAs in common neurological diseases. Our aim is to provide a basis for hypothesis generation for future studies to assess the role that GLP-1 RAs may have on the nervous system, including implications for the perioperative period. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Hunter Guevara, Lindsay R AU - Hunter Guevara LR AD - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN. FAU - Beam, W Brian B AU - Beam WBB FAU - Pasternak, Jeffrey J AU - Pasternak JJ LA - eng PT - Journal Article PT - Review DEP - 20240731 PL - United States TA - J Neurosurg Anesthesiol JT - Journal of neurosurgical anesthesiology JID - 8910749 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Nervous System Diseases/drug therapy MH - *Brain/drug effects MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - brain OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonists OT - neuroprotection OT - stroke COIS- J.F.P.: Associate editor for the Journal of Neurosurgical Anesthesiology. The remaining authors declare no conflicts of interest. EDAT- 2024/07/31 12:42 MHDA- 2025/06/04 12:29 CRDT- 2024/07/31 06:22 PHST- 2024/06/16 00:00 [received] PHST- 2024/07/08 00:00 [accepted] PHST- 2025/06/04 12:29 [medline] PHST- 2024/07/31 12:42 [pubmed] PHST- 2024/07/31 06:22 [entrez] AID - 00008506-990000000-00123 [pii] AID - 10.1097/ANA.0000000000000985 [doi] PST - ppublish SO - J Neurosurg Anesthesiol. 2024 Oct 1;36(4):278-282. doi: 10.1097/ANA.0000000000000985. Epub 2024 Jul 31. PMID- 39082103 OWN - NLM STAT- MEDLINE DCOM- 20241107 LR - 20260708 IS - 1473-6535 (Electronic) IS - 0957-9672 (Linking) VI - 35 IP - 6 DP - 2024 Dec 1 TI - Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit? PG - 259-267 LID - 10.1097/MOL.0000000000000949 [doi] AB - PURPOSE OF REVIEW: This review examines the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on lipid profiles in individuals with type 2 diabetes mellitus and/or obesity, crucial for optimizing cardiovascular risk management. RECENT FINDINGS: GLP-1RAs affect lipid levels by reducing intestinal apolipoprotein B48 production and mesenteric lymph flow, while increasing catabolism of apolipoprotein B100. It remains unknown whether these effects are direct or indirect, but the improvements in lipid levels are strongly correlated to the drug-induced weight loss. Clinical trials demonstrate improvements in lipid profiles, with different effects per agent and dose. We deem it unlikely that improved lipid levels are sufficient to explain the beneficial effects of GLP-1RA on cardiovascular risk, especially given the improvement of many other risk factors (body weight, glycemic control, inflammation) while using these agents. Posthoc mediation analyses of large cardiovascular outcome trials may shed some light on the relative importance of each risk factor. SUMMARY: GLP-1RAs improve lipid profiles in clinical trials, but their complete cardiovascular benefits likely involve multifactorial mechanisms beyond lipid modulation. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Alnima, Teba AU - Alnima T AD - Radboud University Medical Center, Department of Internal Medicine, sections Vascular Medicine and Diabetology, Nijmegen. FAU - Smits, Mark M AU - Smits MM AD - Amsterdam University Medical Center, Department of Internal Medicine. FAU - Hanssen, Nordin M J AU - Hanssen NMJ AD - Amsterdam University Medical Center, Department of Internal Medicine. AD - Amsterdam Diabeter Center, Amsterdam UMC, Amsterdam, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240729 PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Lipids) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Lipids/blood MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/07/31 06:41 MHDA- 2024/11/07 06:23 CRDT- 2024/07/31 04:53 PHST- 2024/11/07 06:23 [medline] PHST- 2024/07/31 06:41 [pubmed] PHST- 2024/07/31 04:53 [entrez] AID - 00041433-202412000-00002 [pii] AID - 10.1097/MOL.0000000000000949 [doi] PST - ppublish SO - Curr Opin Lipidol. 2024 Dec 1;35(6):259-267. doi: 10.1097/MOL.0000000000000949. Epub 2024 Jul 29. PMID- 39080745 OWN - NLM STAT- MEDLINE DCOM- 20240731 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Jul 29 TI - Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists. PG - 277 LID - 10.1186/s12933-024-02364-2 [doi] LID - 277 AB - BACKGROUND: Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored. PURPOSE: This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement. METHODS: A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE). RESULTS: Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m(2). GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE. CONCLUSION: Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis. CI - (c) 2024. The Author(s). FAU - Lai, Hsuan-Wen AU - Lai HW AD - Taipei Medical University, Taipei, Taiwan. FAU - See, Chun Yin AU - See CY AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan. FAU - Chen, Jui-Yi AU - Chen JY AD - Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan. AD - Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Wu, Vin-Cent AU - Wu VC AD - Division of Nephrology, Primary Aldosteronism Centre of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. q91421028@ntu.edu.tw. AD - NSARF (National Taiwan University Hospital Study Group of ARF, Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan. q91421028@ntu.edu.tw. AD - Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan. q91421028@ntu.edu.tw. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240729 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM EIN - Cardiovasc Diabetol. 2024 Oct 14;23(1):360. doi: 10.1186/s12933-024-02452-3. PMID: 39402518 CIN - Cardiovasc Diabetol. 2025 Mar 08;24(1):110. doi: 10.1186/s12933-024-02543-1. PMID: 40057763 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - *Cardiovascular Diseases/mortality/diagnosis/epidemiology MH - Cause of Death MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/mortality/diagnosis/drug therapy/therapy/blood MH - *Diabetic Nephropathies/mortality/therapy/diagnosis MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Renal Dialysis/mortality/adverse effects MH - Retrospective Studies MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor PMC - PMC11287940 OTO - NOTNLM OT - Acute kidney injury OT - GLP-1 OT - Major adverse cardiac events OT - Major adverse kidney events OT - Mortality OT - Renal replacement therapy COIS- The authors declare no competing interests. EDAT- 2024/07/31 06:42 MHDA- 2024/07/31 06:43 PMCR- 2024/07/29 CRDT- 2024/07/31 00:04 PHST- 2024/04/26 00:00 [received] PHST- 2024/07/15 00:00 [accepted] PHST- 2024/07/31 06:43 [medline] PHST- 2024/07/31 06:42 [pubmed] PHST- 2024/07/31 00:04 [entrez] PHST- 2024/07/29 00:00 [pmc-release] AID - 10.1186/s12933-024-02364-2 [pii] AID - 2364 [pii] AID - 10.1186/s12933-024-02364-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Jul 29;23(1):277. doi: 10.1186/s12933-024-02364-2. PMID- 39079728 OWN - NLM STAT- MEDLINE DCOM- 20240730 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 386 DP - 2024 Jul 30 TI - Semaglutide: FDA publishes warning amid reports of patients overdosing. PG - q1696 LID - 10.1136/bmj.q1696 [doi] FAU - Mahase, Elisabeth AU - Mahase E AD - The BMJ. LA - eng PT - News DEP - 20240730 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *United States Food and Drug Administration MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Medical Overuse/prevention & control MH - Semaglutide EDAT- 2024/07/31 00:42 MHDA- 2024/07/31 00:43 CRDT- 2024/07/30 20:43 PHST- 2024/07/31 00:43 [medline] PHST- 2024/07/31 00:42 [pubmed] PHST- 2024/07/30 20:43 [entrez] AID - 10.1136/bmj.q1696 [doi] PST - epublish SO - BMJ. 2024 Jul 30;386:q1696. doi: 10.1136/bmj.q1696. PMID- 39078489 OWN - NLM STAT- MEDLINE DCOM- 20241002 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 10 DP - 2024 Oct TI - Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial. PG - 2175-2187 LID - 10.1007/s00125-024-06228-y [doi] AB - AIMS/HYPOTHESIS: The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). METHODS: This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [DeltaADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. RESULTS: Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20x10(-3) mm(2)/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15x10(-3) mm(2)/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05x10(-3) mm(2)/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed DeltaADC significantly from placebo, showing a decrease of -0.13x10(-3) mm(2)/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA(1c). CONCLUSIONS/INTERPRETATION: In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38. CI - (c) 2024. The Author(s). FAU - Vernstrom, Liv AU - Vernstrom L AUID- ORCID: 0000-0003-2875-435X AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. lvh@clin.au.dk. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. lvh@clin.au.dk. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. lvh@clin.au.dk. FAU - Gullaksen, Soren AU - Gullaksen S AUID- ORCID: 0000-0001-8275-1278 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Regional Hospital Horsens, Horsens, Denmark. FAU - Sorensen, Steffen S AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Ringgaard, Steffen AU - Ringgaard S AUID- ORCID: 0000-0001-5353-7379 AD - The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Laustsen, Christoffer AU - Laustsen C AUID- ORCID: 0000-0002-0317-2911 AD - The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Birn, Henrik AU - Birn H AUID- ORCID: 0000-0003-3715-7266 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Biomedicine, Aarhus University, Aarhus, Denmark. FAU - Funck, Kristian L AU - Funck KL AUID- ORCID: 0000-0003-0213-5550 AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AUID- ORCID: 0000-0003-1782-1596 AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. AD - Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark. FAU - Poulsen, Per L AU - Poulsen PL AUID- ORCID: 0000-0001-6468-2715 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. LA - eng GR - 2019-3780/41/Laegeforeningen/ GR - NNF170C0029064/Novo Nordisk Fonden/ GR - A3192/Health Research Fund of Central Denmark Region/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20240730 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Glucosides) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Humans MH - *Glucosides/therapeutic use MH - *Benzhydryl Compounds/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/diagnostic imaging MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - *Kidney/drug effects/diagnostic imaging/pathology MH - Aged MH - Diffusion Magnetic Resonance Imaging MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Drug Therapy, Combination MH - Diabetic Nephropathies/drug therapy/diagnostic imaging MH - Semaglutide PMC - PMC11447057 OTO - NOTNLM OT - Apparent diffusion coefficient OT - Diffusion-weighted magnetic resonance imaging OT - Glucagon-like peptide-1 receptor agonist OT - Magnetic resonance imaging OT - Sodium-glucose cotransporter 2 inhibitors OT - Total kidney volume OT - Type 2 diabetes EDAT- 2024/07/30 12:42 MHDA- 2024/10/02 12:42 PMCR- 2024/07/30 CRDT- 2024/07/30 11:13 PHST- 2024/02/28 00:00 [received] PHST- 2024/05/07 00:00 [accepted] PHST- 2024/10/02 12:42 [medline] PHST- 2024/07/30 12:42 [pubmed] PHST- 2024/07/30 11:13 [entrez] PHST- 2024/07/30 00:00 [pmc-release] AID - 10.1007/s00125-024-06228-y [pii] AID - 6228 [pii] AID - 10.1007/s00125-024-06228-y [doi] PST - ppublish SO - Diabetologia. 2024 Oct;67(10):2175-2187. doi: 10.1007/s00125-024-06228-y. Epub 2024 Jul 30. PMID- 39075666 OWN - NLM STAT- MEDLINE DCOM- 20241121 LR - 20250122 IS - 1708-8267 (Electronic) IS - 1081-5589 (Print) IS - 1081-5589 (Linking) VI - 72 IP - 8 DP - 2024 Dec TI - Glucagon-like peptide-1 receptor agonist therapy effects on glycemic control and weight in a primary care clinic population. PG - 911-919 LID - 10.1177/10815589241270427 [doi] AB - Glucagon-like peptide-1 receptor agonist (GLP-1a) medications have been shown in randomized controlled trials (RCTs) to have consistent and impressive effectiveness in lowering hemoglobin A1c (HbA1c) and weight, but limited data exist on the efficacy of GLP-1a medications in clinical practice. We studied the association between GLP-1a therapy and changes in weight and HbA1c in a real-world patient population. In this retrospective cohort study of patients seen in a primary care clinic between 2012 and 2021, we examined the change in weight and HbA1c over 12 months in a cohort of patients with at least one prescription for a GLP-1a. Within this cohort, treatment was defined as having >/=2 GLP-1a prescriptions at a therapeutic dosage separated by >/=10 months. The cohort included 693 patients of whom 393 (57%) were treated with GLP-1a therapy. The treatment group had a mean change in body mass index (BMI) of -0.83 kg/m(2) (+/-2.88) compared to -0.70 kg/m(2) (+/-2.99) in the without GLP-1a group (p = 0.57). Treated patients had a mean change in HbA1c of -1.00% (+/-2.07) compared to -0.83% (+/-1.92) in the without GLP-1a group (p = 0.27). For treated and without GLP-1a patients, respectively, the proportion of patients with a decrease in BMI was 65 versus 64% (p = 0.86), and the proportion with a decrease in HbA1c was 73 versus 69% (p = 0.28). In clinical practice, GLP-1a therapy was associated with more modest reductions in weight and HbA1c than shown in prior RCTs. As GLP-1a use continues to expand throughout primary care, the real-world impact of this pharmacotherapy will require further evaluation. FAU - Palecek, Eric J AU - Palecek EJ AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Kimzey, Margaret M AU - Kimzey MM AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Zhang, Jingwen AU - Zhang J AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Marsden, Justin AU - Marsden J AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Bays, Chloe AU - Bays C AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Moran, William P AU - Moran WP AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Mauldin, Patrick D AU - Mauldin PD AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. FAU - Schreiner, Andrew D AU - Schreiner AD AD - Division of General Internal Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. LA - eng GR - K23 DK118200/DK/NIDDK NIH HHS/United States GR - R03 DK129558/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240812 PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Primary Health Care MH - *Glycemic Control MH - *Body Weight/drug effects MH - Glycated Hemoglobin/metabolism MH - Aged MH - Retrospective Studies MH - Blood Glucose/metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11581925 MID - NIHMS2016420 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - adult OT - glucagon-like peptide-1 receptor OT - glycated hemoglobin OT - obesity OT - retrospective studies OT - weight loss COIS- Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EJP, MMK, JZ, JM, CB, and WPM report no conflicts of interest with this work. PDM owned Novo Nordisk stock. ADS has consulted for Novo Nordisk and Pfizer. EDAT- 2024/07/30 06:42 MHDA- 2024/11/21 12:25 PMCR- 2024/12/01 CRDT- 2024/07/30 00:22 PHST- 2024/11/21 12:25 [medline] PHST- 2024/07/30 06:42 [pubmed] PHST- 2024/07/30 00:22 [entrez] PHST- 2024/12/01 00:00 [pmc-release] AID - 10.1177/10815589241270427 [doi] PST - ppublish SO - J Investig Med. 2024 Dec;72(8):911-919. doi: 10.1177/10815589241270427. Epub 2024 Aug 12. PMID- 39075285 OWN - NLM STAT- MEDLINE DCOM- 20240912 LR - 20261010 IS - 1759-507X (Electronic) IS - 1759-5061 (Linking) VI - 20 IP - 10 DP - 2024 Oct TI - The GLP-1 receptor agonist revolution comes to nephrology. PG - 637-638 LID - 10.1038/s41581-024-00876-4 [doi] FAU - Thomas, Merlin C AU - Thomas MC AD - Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia. FAU - Cooper, Mark E AU - Cooper ME AUID- ORCID: 0000-0002-5953-642X AD - Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia. Mark.Cooper@monash.edu. LA - eng PT - Journal Article PL - England TA - Nat Rev Nephrol JT - Nature reviews. Nephrology JID - 101500081 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Nephrology MH - Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/07/30 00:42 MHDA- 2024/09/13 00:46 CRDT- 2024/07/29 23:30 PHST- 2024/09/13 00:46 [medline] PHST- 2024/07/30 00:42 [pubmed] PHST- 2024/07/29 23:30 [entrez] AID - 10.1038/s41581-024-00876-4 [pii] AID - 10.1038/s41581-024-00876-4 [doi] PST - ppublish SO - Nat Rev Nephrol. 2024 Oct;20(10):637-638. doi: 10.1038/s41581-024-00876-4. PMID- 39074369 OWN - NLM STAT- MEDLINE DCOM- 20240819 LR - 20260919 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 177 IP - 8 DP - 2024 Aug TI - Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes : Target Trial Emulation Using Real-World Data. PG - 1016-1027 LID - 10.7326/M23-2718 [doi] AB - BACKGROUND: Reports of reduced desire to smoke in patients treated with semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) medication for type 2 diabetes mellitus (T2DM) and obesity, have raised interest about its potential benefit for tobacco use disorders (TUDs). OBJECTIVE: To examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD. DESIGN: Emulation target trial based on a nationwide population-based database of patient electronic health records. SETTING: United States, 1 December 2017 to 31 March 2023. PARTICIPANTS: Seven target trials were emulated among eligible patients with comorbid T2DM and TUD by comparing the new use of semaglutide versus 7 other antidiabetes medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1RAs). MEASUREMENTS: The TUD-related health care measures (medical encounter for diagnosis of TUD, smoking cessation medication prescriptions, and smoking cessation counseling) that occurred within a 12-month follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: The study compared 222 942 new users of antidiabetes medications including 5967 of semaglutide. Semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other antidiabetes medications, and was strongest compared with insulins (hazard ratio [HR], 0.68 [95% CI, 0.63 to 0.74]) and weakest but statistically significant compared with other GLP-1RAs (HR, 0.88 [CI, 0.81 to 0.96]). Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without a diagnosis of obesity. For most of the group comparisons, the differences occurred within 30 days of prescription initiation. LIMITATION: Documentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence. CONCLUSION: Semaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2DM and TUD compared with other antidiabetes medications including other GLP-1Ras, primarily within 30 days of prescription. These findings suggest the need for clinical trials to evaluate semaglutide's potential for TUD treatment. PRIMARY FUNDING SOURCE: National Institutes of Health. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio (W.W., N.A.B.). FAU - Volkow, Nora D AU - Volkow ND AUID- ORCID: 0000-0001-6668-0908 AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland (N.D.V.). FAU - Berger, Nathan A AU - Berger NA AUID- ORCID: 0000-0001-7086-9885 AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio (W.W., N.A.B.). FAU - Davis, Pamela B AU - Davis PB AUID- ORCID: 0000-0002-7113-5338 AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio (P.B.D.). FAU - Kaelber, David C AU - Kaelber DC AUID- ORCID: 0000-0001-7855-9515 AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio (D.C.K.). FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio (R.X.). LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - R25 CA221718/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240730 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Tobacco Use Disorder/drug therapy/complications MH - Aged MH - United States/epidemiology MH - Smoking Cessation MH - Obesity/complications/drug therapy MH - Semaglutide PMC - PMC12721465 MID - NIHMS2123689 COIS- Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2718. EDAT- 2024/07/29 18:42 MHDA- 2024/08/19 18:42 PMCR- 2025/12/23 CRDT- 2024/07/29 17:03 PHST- 2024/08/19 18:42 [medline] PHST- 2024/07/29 18:42 [pubmed] PHST- 2024/07/29 17:03 [entrez] PHST- 2025/12/23 00:00 [pmc-release] AID - 10.7326/M23-2718 [doi] PST - ppublish SO - Ann Intern Med. 2024 Aug;177(8):1016-1027. doi: 10.7326/M23-2718. Epub 2024 Jul 30. PMID- 39072877 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - The role of incretin receptor agonists in the treatment of obesity. PG - 4178-4196 LID - 10.1111/dom.15796 [doi] AB - INTRODRODUCTION: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists. METHODS: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity. RESULTS: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation. CONCLUSIONS: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Forst, Thomas AU - Forst T AUID- ORCID: 0000-0003-2132-5691 AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - De Block, Christophe AU - De Block C AUID- ORCID: 0000-0002-0679-3203 AD - Antwerp University Hospital and University of Antwerp, Antwerp, Belgium. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Armani, Sara AU - Armani S AUID- ORCID: 0009-0009-5209-6474 AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - Frias, Juan AU - Frias J AUID- ORCID: 0000-0001-9486-1255 AD - Biomea Fusion, Redwood City, California, USA. FAU - Lautenbach, Anne AU - Lautenbach A AUID- ORCID: 0000-0002-7763-1527 AD - University Medical-Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Ludvik, Bernhard AU - Ludvik B AUID- ORCID: 0009-0003-8717-8396 AD - Landstrasse Clinic and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Vienna, Austria. FAU - Marinez, Marina AU - Marinez M AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - Mathieu, Chantal AU - Mathieu C AUID- ORCID: 0000-0002-4055-5233 AD - Department of Endocrinology, KU Leuven, Leuven, Belgium. FAU - Muller, Timo D AU - Muller TD AUID- ORCID: 0000-0002-0624-9339 AD - Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Munich, Neuherberg, Germany. AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universitat Munchen (LMU), Munich, Germany. FAU - Schnell, Oliver AU - Schnell O AUID- ORCID: 0000-0003-1713-2766 AD - Forschergruppe Diabetes e.V. at the Helmholtz Center Munich, Munich, Germany. LA - eng GR - Clinical Research Services, Grenadiesrstrasse 1, 68167 Mannheim, Germany/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240729 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Anti-Obesity Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Incretins/therapeutic use MH - *Obesity/drug therapy/complications MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use OTO - NOTNLM OT - dual co-agonists OT - incretins OT - obesity OT - semaglutide OT - tirzepatide EDAT- 2024/07/29 12:44 MHDA- 2024/09/18 12:44 CRDT- 2024/07/29 09:52 PHST- 2024/06/28 00:00 [revised] PHST- 2024/05/03 00:00 [received] PHST- 2024/06/29 00:00 [accepted] PHST- 2024/09/18 12:44 [medline] PHST- 2024/07/29 12:44 [pubmed] PHST- 2024/07/29 09:52 [entrez] AID - 10.1111/dom.15796 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4178-4196. doi: 10.1111/dom.15796. Epub 2024 Jul 29. PMID- 39072740 OWN - NLM STAT- MEDLINE DCOM- 20240729 LR - 20250103 IS - 1462-4753 (Print) IS - 1462-4753 (Linking) VI - 29 IP - 8 DP - 2024 Aug 2 TI - GLP-1 receptor agonists and their role in managing type 2 diabetes. PG - 391-396 LID - 10.12968/bjcn.2024.0089 [doi] AB - Until recently the focus in diabetes care was on managing blood glucose - a glucocentric view. This is changing to a more holistic model aimed at prevention, treatment and management through lifestyle interventions as well as medication. An estimated 5 million people in the UK are living with diabetes, most have type 2 diabetes which is associated with obesity. Type 2 diabetes can be prevented, treated with diet and weight loss, or managed with medication. The number of people with diabetes has reached epidemic proportions. To manage diabetes well and reduce complications of poorly managed diabetes, management of the condition can no longer be restricted to endocrinologists and diabetes specialist nurses. This article provides guidance on how glucagon-like peptide-1 receptor agonists can be used in the management of type 2 diabetes. FAU - Nazarko, Linda AU - Nazarko L AD - Independent Nurse Consultant. LA - eng PT - Journal Article PL - England TA - Br J Community Nurs JT - British journal of community nursing JID - 9815827 RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - United Kingdom MH - Exenatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists (GLP-1) OT - holistic care OT - management OT - remission OT - type 2 diabetes EDAT- 2024/07/29 12:43 MHDA- 2024/07/29 12:44 CRDT- 2024/07/29 09:45 PHST- 2024/07/29 12:44 [medline] PHST- 2024/07/29 12:43 [pubmed] PHST- 2024/07/29 09:45 [entrez] AID - 10.12968/bjcn.2024.0089 [doi] PST - ppublish SO - Br J Community Nurs. 2024 Aug 2;29(8):391-396. doi: 10.12968/bjcn.2024.0089. PMID- 39072425 OWN - NLM STAT- MEDLINE DCOM- 20240830 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 40 IP - 9 DP - 2024 Sep TI - The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide. PG - 1525-1531 LID - 10.1080/03007995.2024.2386047 [doi] AB - INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjogren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations. FAU - Pinheiro, Marcelo Maia AU - Pinheiro MM AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - de Souza, Luciana Gasques AU - de Souza LG AD - UFMT, Universidade Federal de Mato Grosso, Cuiaba, MT, Brazil. FAU - Nunes, Guilherme Pavini AU - Nunes GP AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - Martin, Isis Franco AU - Martin IF AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - de Oliveira, Yasmin Utuari AU - de Oliveira YU AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - Pinheiro, Felipe Moura Maia AU - Pinheiro FMM AD - Hospital das Clinicas, Faculdade de Medicina de Sao Paulo, Universidade de Sao Paulo-USP, Sao Paulo, SP, Brazil. FAU - Costa, Lygia Nazario AU - Costa LN AD - LAPAT Anatomia Patologica e Citopatologia, Cuiaba, MT, Brazil. FAU - Caprio, Massimiliano AU - Caprio M AD - Department of Human Sciences and Promotion of the Quality of Life & Laboratory of Cardiovascular Endocrinology, San Raffaele Open University & San Raffaele Research Institute-IRCCS San Raffaele, Rome, Italy. FAU - Della-Morte, David AU - Della-Morte D AD - Department of Biomedicine and Prevention, Section of Clinical Nutrition and Nutrigenomics, University of Rome Tor Vergata, Rome, Italy. FAU - Infante, Marco AU - Infante M AUID- ORCID: 0000-0003-2032-8735 AD - Section of Diabetes & Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20240802 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Vasculitis, Leukocytoclastic, Cutaneous/chemically induced/drug therapy/pathology MH - Injections, Subcutaneous MH - Hypoglycemic Agents/adverse effects/administration & dosage MH - Semaglutide OTO - NOTNLM OT - glp-1 OT - glp-1ra OT - glucagon-like peptide 1 receptor agonist OT - leukocytoclastic vasculitis OT - once-weekly semaglutide OT - subcutaneous semaglutide OT - type 2 diabetes mellitus EDAT- 2024/07/29 12:45 MHDA- 2024/08/31 09:53 CRDT- 2024/07/29 06:43 PHST- 2024/08/31 09:53 [medline] PHST- 2024/07/29 12:45 [pubmed] PHST- 2024/07/29 06:43 [entrez] AID - 10.1080/03007995.2024.2386047 [doi] PST - ppublish SO - Curr Med Res Opin. 2024 Sep;40(9):1525-1531. doi: 10.1080/03007995.2024.2386047. Epub 2024 Aug 2. PMID- 39072050 OWN - NLM STAT- MEDLINE DCOM- 20240729 LR - 20250103 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2024 DP - 2024 TI - Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review. PG - 8145388 LID - 10.1155/2024/8145388 [doi] LID - 8145388 AB - Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p